Re-assessment of South African juvenile facial soft tissue thickness data for craniofacial approximation: A comparative analysis using central tendency statistics.
Facial soft tissue thickness (FSTT) data form the basis of craniofacial identification methods such as facial approximation in cases where unknown skeletal remains lack unique identifiers such as fingerprints, DNA and dental records. Appropriate FSTT data are said to be required to produce accurate facial approximations that may be recognised by relatives. This view led to a vast number of studies considering subdivisions of FSTT data according to ancestry, age and sex. The paucity of South African juvenile FSTT standards of particular age groups, sex and ancestry is therefore problematic as "accurate" facial approximations cannot be produced. However, the use of pooled datasets and central tendency statistics offers a unique opportunity to circumvent the problem of small or absent FSTT datasets. The aim of this study was to use central tendency statistics of previously published South African data in order to assess whether it is necessary to subdivide FSTT datasets into different subgroups. In addition, a meta-analysis using central tendency statistics of 11 datasets within the C-table repository using the free open source TDStats programme (available through CRANIOFACIALidentification.com) for midfacial landmarks was performed. These datasets comprised of raw juvenile and adult FSTT data gathered from 1895 to 2015 as measured by a variety of methods Scatter plots showed that FSTT correlation with age is rather weak, while Kernel density plots of FSTT by sex and landmark indicated no difference between South African juvenile males and females. In order to test the practical application of FSTT data, two facial approximations were constructed - one based on the shorth from South African data and C-tables and one based on an American dataset. When comparing the two facial approximations based on different datasets, geometric deviation indicated differences at midline and bilateral landmarks, but the visual presentation of the facial approximations was similar. Therefore it is suggested that differences of less than 3mm at any landmark do not result in profound practical differences in the juvenile face. Subcategorizing juvenile data is not necessary as the same result can be achieved by weighted means as presented in the sub-adult C-tables.


Decision support for malaria-control programmes--a system dynamics model.
Although malaria claims millions of casualties every year there are hardly any recent efforts to model its epidemiology in order to support decision-makers of malaria-control programmes. There have been ample attempts to develop analytical models during the era of WHO malaria eradication programmes (1950-1970), but none of them was detailed enough to honour the high complexity arising from the interdependencies of the environment, the parasite, vector and host system. This paper presents a multi-group system dynamics model of the spread of malaria in an African country. Epidemiological details are included so that the impact of several intervention programmes can be simulated and analysed. The model's basic structure is fully described and some examples of the simulations are presented. It becomes obvious that detailed multi-group system dynamics models are valuable to assess the effectiveness and efficiency of anti-malaria campaigns.


GABA(A) receptors in the central amygdala are involved in memory retention deficits induced by cannabinoids in rats.
The central nucleus of the amygdala (CeA) as the main output of amygdala plays an important role in memory processes. In this study we first evaluated the effects of intra-CeA administrations of different doses of a cannabinoid CB1 agonist, WIN55, 212-2, GABA(A) receptor agonist and antagonist, muscimol and bicuculline, alone on memory retention using passive avoidance learning (PAL) test in rats. Then we examined the effects of GABA(A) receptor agents on the responses induced by intra-CeA microinjection of different doses of WIN55, 212-2. We found that administration of WIN55, 212-2 (0.05, 0.1, 0.2 and 0.4μg/rat) immediately after training impaired memory retrieval in a dose-dependent fashion. Although pre-test intra-CeA administration of muscimol (125, 250 and 500ng/rat) alone had no effect on the step-through latency, its co-administration (125ng/rat) with different doses of WIN55, 212-2 potentiated the amnesic effects of any doses of WIN55, 212-2. The results also showed that pre-test intra-CeA administration of bicuculline (200, 400 and 800ng/rat) alone had no significant effect, but at dose of 200ng/rat disrupted post-training WIN55, 212-2-induced amnesia in the retention test. Furthermore, the additional effect of muscimol (125ng/rat) on memory impairment induced by WIN55, 212-2 (0.1μg/rat) was prevented by intra-CeA co-injection of bicuculline (200ng/rat). We indicated that stimulating or blocking GAGA(A) receptors in the CeA by muscimol and bicuculline interfere with WIN55, 212-2-induced deficits in memory retention in a PAL task and therefore suggests an interaction between cannabinergic and GABAergic systems of the CeA in memory process.


An aptamer-based magnetic flow cytometer using matched filtering.
Facing unprecedented population-ageing, the management of noncommunicable diseases (NCDs) urgently needs a point-of-care (PoC) testing infrastructure. Magnetic flow cytometers are one such solution for rapid cancer cellular detection in a PoC setting. In this work, we report a giant magnetoresistive spin-valve (GMR SV) biosensor array with a multi-stripe sensor geometry and matched filtering to improve detection accuracy without compromising throughput. The carefully designed sensor geometry generates a characteristic signature when cells labeled with magnetic nanoparticles (MNPs) pass by thus enabling multi-parametric measurement like optical flow cytometers (FCMs). Enumeration and multi-parametric information were successfully measured across two decades of throughput (37 - 2730 cells/min). 10-μm polymer microspheres were used as a biomimetic model where MNPs and MNP-decorated polymer conjugates were flown over the GMR SV sensor array and detected with a signal-to-noise ratio (SNR) as low as 2.5 dB due to the processing gain afforded by the matched filtering. The performance was compared against optical observation, exhibiting a 92% detection efficiency. The system achieved a 95% counting accuracy for biomimetic models and 98% for aptamer-based pancreatic cancer cell detection. This system demonstrates the ability to perform reliable flow cytometry toward PoC diagnostics to benefit NCD control plans.


Proteomics Analysis Reveals Non-Controlled Activation of Photosynthesis and Protein Synthesis in a Rice npp1 Mutant under High Temperature and Elevated CO₂ Conditions.
Rice nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) catalyzes the hydrolytic breakdown of the pyrophosphate and phosphodiester bonds of a number of nucleotides including ADP-glucose and ATP. Under high temperature and elevated CO₂ conditions (HT + ECO₂), the npp1 knockout rice mutant displayed rapid growth and high starch content phenotypes, indicating that NPP1 exerts a negative effect on starch accumulation and growth. To gain further insight into the mechanisms involved in the NPP1 downregulation induced starch overaccumulation, in this study we conducted photosynthesis, leaf proteomic, and chloroplast phosphoproteomic analyses of wild-type (WT) and npp1 plants cultured under HT + ECO₂. Photosynthesis in npp1 leaves was significantly higher than in WT. Additionally, npp1 leaves accumulated higher levels of sucrose than WT. The proteomic analyses revealed upregulation of proteins related to carbohydrate metabolism and the protein synthesis system in npp1 plants. Further, our data indicate the induction of 14-3-3 proteins in npp1 plants. Our finding demonstrates a higher level of protein phosphorylation in npp1 chloroplasts, which may play an important role in carbohydrate accumulation. Together, these results offer novel targets and provide additional insights into carbohydrate metabolism regulation under ambient and adverse conditions.


Prediction of Response of Hepatocellular Carcinoma to Radioembolization: Machine Learning Using Preprocedural Clinical Factors and MR Imaging Radiomics.
To create and evaluate the ability of machine learning-based models with clinicoradiomic features to predict radiologic response after transarterial radioembolization (TARE). 82 treatment-naïve patients (65 responders and 17 nonresponders; median age: 65 years; interquartile range: 11) who underwent selective TARE were included. Treatment responses were evaluated using the European Association for the Study of the Liver criteria at 3-month follow-up. Laboratory, clinical, and procedural information were collected. Radiomic features were extracted from pretreatment contrast-enhanced T1-weighted magnetic resonance images obtained within 3 months before TARE. Feature selection consisted of intraclass correlation, followed by Pearson correlation analysis and finally, sequential feature selection algorithm. Support vector machine, logistic regression, random forest, and LightGBM models were created with both clinicoradiomic features and clinical features alone. Performance metrics were calculated with a nested 5-fold cross-validation technique. The performances of the models were compared by Wilcoxon signed-rank and Friedman tests. In total, 1,128 features were extracted. The feature selection process resulted in 12 features (8 radiomic and 4 clinical features) being included in the final analysis. The area under the receiver operating characteristic curve values from the support vector machine, logistic regression, random forest, and LightGBM models were 0.94, 0.94, 0.88, and 0.92 with clinicoradiomic features and 0.82, 0.83, 0.82, and 0.83 with clinical features alone, respectively. All models exhibited significantly higher performances when radiomic features were included (P = .028, .028, .043, and .028, respectively). Based on clinical and imaging-based information before treatment, machine learning-based clinicoradiomic models demonstrated potential to predict response to TARE.


Reduced excretion of vasodilator prostaglandins in preeclampsia.
The role of prostaglandin (PG) system in preeclampsia (pre-E) was investigated. Urinary excretion of PGE2,6-keto PGF1 alpha,2,3 dinor 6-keto PGF1 alpha, TxB2 and 2,3-dinor-TxB2 and kallikrein were determined in 10 normotensive pregnant women and 14 with pre-E. 6-keto PGF1 alpha and 2,3-dinor 6-keto PGF1 alpha (the main renal and extrarenal metabolites of vasodilator PGI2) and PGE2 excretion was lower in pre-E. TxB2 metabolites in urine were similar in the two groups of women. Our data are consistent with the hypothesis of an imbalance between vasodilator and vasoconstrictor PGs in pre-E.


12-month follow-up of an exploratory 'brief intervention' for high-frequency cannabis users among Canadian university students.
One in three young people use cannabis in Canada. Cannabis use can be associated with a variety of health problems which occur primarily among intensive/frequent users. Availability and effectiveness of conventional treatment for cannabis use is limited. While Brief Interventions (BIs) have been shown to result in short-term reductions of cannabis use risks or problems, few studies have assessed their longer-term effects. The present study examined 12-month follow-up outcomes for BIs in a cohort of young Canadian high-frequency cannabis users where select short-term effects (3 months) had previously been assessed and demonstrated. N=134 frequent cannabis users were recruited from among university students in Toronto, randomized to either an oral or a written cannabis BI, or corresponding health controls, and assessed in-person at baseline, 3-months, and 12-months. N=72 (54%) of the original sample were retained for follow-up analyses at 12-months where reductions in 'deep inhalation/breathholding' (Q=13.1; p< .05) and 'driving after cannabis use' (Q=9.3; p< .05) were observed in the experimental groups. Reductions for these indicators had been shown at 3-months in the experimental groups; these reductions were maintained over the year. Other indicators assessed remained overall stable in both experimental and control groups. The results confirm findings from select other studies indicating the potential for longer-term and sustained risk reduction effects of BIs for cannabis use. While further research is needed on the long-term effects of BIs, these may be a valuable - and efficient - intervention tool in a public health approach to high-risk cannabis use.


Velocity measurement of clay intrusion through a sudden contraction step using a tagging pulse sequence.
Magnetic resonance imaging (MRI) with a spatial tagging sequence was used to measure the velocity distribution of clay that was forced past a sudden contraction. A spatial tagging sequence provided magnetic resonance images of clay that allowed measurement of the velocity distribution in the clay, which can provide profound insights on the deformation process of clay during the intrusion process. The experiments were conducted using a specially-designed vessel that could operate at up to 30 MPa. The vessel offers a rectangle test section with a sudden contraction step that had a ratio of contraction of 2:1. The vessel was installed into a commercial magnetic resonance imaging equipment and then the fluid motion of clay flowing into the narrow contracted channel was quantitatively investigated to examine behaviors of flowing clay as non-Newtonian fluid. MRI results are compared with those obtained by computational fluid dynamics (CFD) calculation. Velocity distributions obtained from each tag displacement did not well agree with those predicted by CFD results near the contraction step where the fluid accelerated rapidly. However, a post-processing on calculation results, in which virtual tag displacement is calculated, gave better agreement with experiment and enabled us to compare MRI results with CFD results.


Label-free identification of the microstructure of rat spinal cords based on nonlinear optical microscopy.
The spinal cord is a vital link between the brain and the body and mainly comprises neurons, glial cells and nerve fibres. In this work, nonlinear optical (NLO) microscopy based on intrinsic tissue properties was employed to label-freely analyze the cells and matrix in spinal cords at a molecular level. The high-resolution and high-contrast NLO images of unstained spinal cords demonstrate that NLO microscopy has the ability to show the microstructure of white and grey matter including ventral horn, intermediate area, dorsal horns, ventral column, lateral column and dorsal column. Neurons with various sizes were identified in grey matter by dark spots of nonfluorescent nuclei encircled by cytoplasm-emitting two-photon excited fluorescence signals. Nerve fibres and neuroglias were observed in white matter. Besides, the spinal arteries were clearly presented by NLO microscopy. Using spectral and morphological information, this technique was proved to be an effective tool for label-freely imaging spinal cord tissues, based on endogenous signals in biological tissue. With future development, we foresee promising applications of the NLO technique for in vivo, real-time assessment of spinal cord diseases or injures.


Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults, with emphasis on MRI.
Acute lymphoblastic leukemia (ALL) is the most common of all childhood malignancies. Current remission rates approach 80%. Recurrent disease can present in a wide variety of ways. MR imaging plays a crucial role in the detection of disease relapse. Because other disorders can mimic recurrence of leukemia, it is important for the radiologist to judge recurrence from non-recurrence accurately in order to avoid unnecessary testing and emotional stress on the patient and family.


Possible mechanisms to explain dust overloading of the lungs.
This paper briefly reviews the available evidence on dust overloading of the lungs, a condition which has come to the forefront in many recently reported chronic inhalation studies. A general hypothesis is developed that dust overloading, which is typified by a progressive reduction of particle clearance from the deep lung, reflects a breakdown in alveolar macrophage (AM)-mediated dust removal due to the loss of AM mobility. The inability of the dust-laden AMs to translocate to the mucociliary escalator is correlated to an average composite particle volume per alveolar macrophage in the lung. When this particulate volume exceeds approximately 60 micron3/AM, on the basis of a uniform distribution of particles over the AM pool size (approximately 2.5 X 10(7) cells) in the Fischer 344 rat, the overload effect appears to be initiated. When the distributed particulate volume exceeds approximately 600 micron3 per cell, the evidence suggests that AM-mediated particle clearance virtually ceases and agglomerated particle-laden macrophages remain in the alveolar region. This paper considers possible mechanisms why these particle-laden cells are immobilized, viz., one is based on excessive particle-cell, cell-cell chemotactic interactions, and migratory inhibition factors; the other considers the volumetric increase by phagocytized particles, per se, as leading to an inability of the AM to spread and migrate probably through a competitive requirement for surface membrane and cytoskeleton in both endocytotic and migratory functions.


Event-related potential indices of semantic processing in schizophrenia.
Event-related potentials (ERPs) were recorded while schizophrenic patients and healthy controls read congruous and incongruous sentences in anticipation of a memory test. The schizophrenic group performed more poorly in both recognition memory and cued recall tests. The two groups did not differ in the amplitude of the N400 component of the ERP but the difference between the ERPs to congruous and incongruous sentences persisted longer in the schizophrenic sample. The schizophrenic sample also showed reduced parietal positivity and a reduced effect of congruity on the late positive component that follows N400. Within the schizophrenic sample, measures of attentional impairment and positive thought disorder were correlated with mean amplitude of both the N400 and the subsequent positivity. The results imply that the structure and spread of activation within semantic memory is not impaired in schizophrenia. Rather, impairments appear to lie in processes required to integrate activated information with the current context.


Semimechanistic pharmacokinetic-pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy.
Tripegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) that has been used to prevent chemotherapy-induced neutropenia in adults. This study aimed to establish a pharmacokinetic (PK)-pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed-dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK-PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors. Tripegfilgrastim PK and ANC dynamics were described with a pharmacodynamics-mediated drug disposition model assuming quasi-equilibrium with five transit compartments mimicking neutrophil granulopoiesis. The effect of chemotherapy on neutrophils was included by stimulating the elimination of the G-CSF receptor at the mitotic cells. Healthy adult and pediatric patients showed significantly different value for dissociation constant of the tripegfilgrastim-G-CSF receptor complex (Kd ) and apparent volume of distribution (Vd /F). Patients treated with chemotherapy had a higher Vd /F and 62% lower Kd than healthy adults. As the age increased, the absorption rate of tripegfilgrastim was decreased. Body weight affected the G-CSF receptor-mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G-CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6 mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10-20, 21-30, 31-44, and more than 45 kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight-based treatment with 100 μg/kg.


Costs and effectiveness of interventions in child maltreatment.
There has been increasing awareness of the need to prevent child maltreatment at a time of limited public funds. As a result, cost-effectiveness has become important in the planning of health care and social services. Evaluations of child maltreatment interventions that have been analyzed for their cost-effectiveness are reviewed. There has been relatively little work in this area and much of it has serious methodological flaws. Nevertheless, research suggests that home health visitors, lay group counseling, and family and group therapy are promising interventions. Medical foster care has been shown to substantially reduce costs, but its effectiveness has not been determined. Current knowledge on the effectiveness of interventions in child maltreatment is limited, and this needs to be addressed in order to answer the question of cost-effectiveness. Recommendations are made for future research in the field.


Lifetime complications of drug use in intravenous drug users.
Ninety-two intravenous drug users (IVDUs) were identified from a study of 1,640 relatives of treated alcoholics and felons. Nearly all of the IVDUs (90%) reported a lifetime history of some degree of physical, psychological, or social difficulty related to drug abuse, but only 35% had ever received treatment for drug abuse. Overall, compared to subjects with a history of substantial illicit drug use who had never injected, IVDUs were significantly more likely to report all drug-related problems assessed. Even in populations of drug users not selected through treatment, any history of intravenous (IV) drug use is strongly indicative of a lifetime occurrence of complications of drug use.


[Socialpsychiatry, social psychiatry 1911. On the origins of the concept in the writings of Max Fischer of Wiesloch].
The term "Social Psychiatry" was first used in English in 1917 by E. E. Southard. Six years before, in 1911 Max Fischer, director of Wiesloch Mental Hospital near Heidelberg employed the terms "Sozialpsychiatrie" and "Soziale Psychiatrie" in German.


Homeobox Genes in Odontogenic Lesions: A Scoping Review.
Homeobox genes play crucial roles in tooth morphogenesis and development and thus mutations in homeobox genes cause developmental disorders such as odontogenic lesions. The aim of this scoping review is to identify and compile available data from the literatures on the topic of homeobox gene expression in odontogenic lesions. An electronic search to collate all the information on studies on homeobox gene expression in odontogenic lesions was carried out in four databases (PubMed, EBSCO host, Web of Science and Cochrane Library) with selected keywords. All papers which reported expression of homeobox genes in odontogenic lesions were considered. A total of eleven (11) papers describing expression of homeobox genes in odontogenic lesions were identified. Methods of studies included next generation sequencing, microarray analysis, RT-PCR, Western blotting, in situ hybridization, and immunohistochemistry. The homeobox reported in odontogenic lesions includes LHX8 and DLX3 in odontoma; PITX2, MSX1, MSX2, DLX, DLX2, DLX3, DLX4, DLX5, DLX6, ISL1, OCT4 and HOX C in ameloblastoma; OCT4 in adenomatoid odontogenic tumour; PITX2 and MSX2 in primordial odontogenic tumour; PAX9 and BARX1 in odontogenic keratocyst; PITX2, ZEB1 and MEIS2 in ameloblastic carcinoma while there is absence of DLX2, DLX3 and MSX2 in clear cell odontogenic carcinoma. This paper summarized and reviews the possible link between homeobox gene expression in odontogenic lesions. Based on the current available data, there are insufficient evidence to support any definite role of homeobox gene in odontogenic lesions.


Use of the interposed nerve graft to reduce differences in functional muscle transfer outcome arising from variability in motor input.
Regulation of functional muscle transfer outcome by means of an interposed nerve graft: The gold standard treatment of chronic unilateral facial palsy is a functional muscle transfer (FMT) reinnervated by a branch of the contralateral facial nerve via a cross-facial nerve graft, but clinical outcome varies from underactivity to overactivity of the transferred muscle. Work in an animal model has established that the magnitude of donor motor input received by heterotopically transferred muscle correlates with reinnervation and force production, the corollary being that standardising donor motor input could standardise outcome. We hypothesise that a 'low-capacity' interposed nerve graft could deliver a fixed motor input to an FMT despite variable motor input, thereby standardising force production and clinical outcome. To test this hypothesis, we compared reinnervation and force production by FMTs reinnervated with different-sized motor inputs via high- and low-capacity interposed nerve grafts. Force production was measured in vivo after recovery of transplanted muscle, and reinnervation quantified by both nerve morphometry and intramuscular immunohistochemical staining for protein gene product 9.5. Both reinnervation and force production data suggest that outcome correlates with donor motor nerve magnitude only when a high-capacity interposed nerve graft is used, this correlation being lost when using a low-capacity interposed nerve graft. The implications for human facial reanimation surgery are discussed.


Reduced rat plasma lysophosphatidylglycerol or lysophosphatidic acid level as a biomarker of aristolochic acid-induced renal and adipose dysfunctions.
Food products and diet pills containing aristolochic acid (AA) are responsible for a rapid progression of nephropathy associated with reduced body weight in human beings. In this study, we investigated the relationship of dietary NaCl and lysophospholipid (LPL) plasma levels to body weight gain in AA-treated rats. Male rats receiving a salt-deficient chow, normal salt chow or high salt chow were injected intraperitoneally daily with AA for 15days. Body weight, visceral fat mass, food intake, levels of LPL in plasma and its synthesized enzyme were investigated. Body weight gain, visceral fat mass and daily food intake were smaller in AA-treated rats than those of control rats, regardless of dietary salt concentration. AA treatment decreased plasma levels of major lysophosphatidic acid (LPA) molecular species in rats fed the normal or high-salt chow but not the salt-deficient chow, whereas both the plasma lysophospholipase D activity and kidney mRNA level of autotaxin of AA-treated rats fed chow with defined salt concentrations were lower than those of control rats. Plasma levels of major molecular species of lysophosphatidylglycerol (LPG) in AA-treated rat groups fed chow with defined salt concentrations were lower than those of control rats. Plasma levels of LPG and LPA seem to be relevant to the reduced body weight gain and fat mass due to AA treatment.


Positive contrast visualization of iron oxide-labeled stem cells using inversion-recovery with ON-resonant water suppression (IRON).
In proton magnetic resonance imaging (MRI) metallic substances lead to magnetic field distortions that often result in signal voids in the adjacent anatomic structures. Thus, metallic objects and superparamagnetic iron oxide (SPIO)-labeled cells appear as hypointense artifacts that obscure the underlying anatomy. The ability to illuminate these structures with positive contrast would enhance noninvasive MR tracking of cellular therapeutics. Therefore, an MRI methodology that selectively highlights areas of metallic objects has been developed. Inversion-recovery with ON-resonant water suppression (IRON) employs inversion of the magnetization in conjunction with a spectrally-selective on-resonant saturation prepulse. If imaging is performed after these prepulses, positive signal is obtained from off-resonant protons in close proximity to the metallic objects. The first successful use of IRON to produce positive contrast in areas of metallic spheres and SPIO-labeled stem cells in vitro and in vivo is presented.


Genetic Variants of the NKG2C/HLA-E Receptor-Ligand Axis Are Determinants of Progression-Free Survival and Therapy Outcome in Aggressive B-Cell Lymphoma.
Aggressive B-cell lymphomas account for the majority of non-Hodgkin lymphomas (B-NHL). NK cells govern the responses to anti-CD20 monoclonal antibodies and have emerged as attractive targets for immunotherapy in subtypes of B-NHL. NKG2C and its cognate ligand HLA-E represent key molecules for fine-tuning of NK cell-mediated immune responses. Here, we investigated the impact of genetic variants of NKG2C and HLA-E on clinical outcomes of 441 B-NHL patients. Homozygous deletion of NKG2C (NKG2C-/-) was three-fold increased in patients compared to 192 healthy controls. Among studied patients, NKG2C-/- was more abundant in International Prognostic Index (IPI) high-risk patients compared to patients with a lower IPI (p = 0.013). Strikingly, NKG2C-/- was associated with a significantly reduced 2-year PFS (progression-free survival) (p = 0.0062) and represented an independent risk factor for 2-year PFS in multivariate analysis (p = 0.005). For HLA-E, the cognate ligand of NKG2C, the HLA-E*01:01 allele frequency was increased in B-NHL patients compared to controls (p = 0.033) and was associated with complete remission in univariate (p = 0.034) and multivariate (p = 0.018) analysis. Our data suggest that NKG2C and HLA-E genotyping is a promising tool for both defining risk groups of aggressive B-NHL and predicting response to immune therapeutic approaches.


Interaction patterns between psychiatric aides and patients.
The present study investigated the manner in which psychiatric aides used their time when not involved in staff meetings or off-ward activities. Aides' behaviors on two shifts were observed during times they had the greatest likelihood of interacting with patients. It was found that aides were most likely to be observed in the Nursing Station on both shifts. Aides typically had a specific purpose for interacting with patients when they were on the wards. It was concluded that increased structuring of patient-aide interactions was necessary along with more stringent guidelines regarding the use of the Nursing Station.


Flow Cytometry-Based Assessment of Antibody Function Against Malaria Pre-erythrocytic Infection.
The development of new interventional strategies against pre-erythrocytic malaria is hampered by the lack of standardized approaches to assess inhibition of sporozoite infection of hepatocytes. The following methodology, based on flow cytometry, can be used to quantitatively assess P. falciparum sporozoite infection in vitro in medium throughput. In addition to assessing the efficacy of antibodies, this assay has a wide variety of applications for investigating basic science questions about the malaria liver stage. This approach is easily applied in a variety of laboratory settings, assesses the functionality of antibody responses against malaria sporozoites, and can be adapted for the limited quantities of sample which are typically available from clinical investigations.


Normative data for aquagenic wrinkling of palms in children 1-15 years of age: A cross-sectional study.
Aquagenic wrinkling of palms (AWP) is emerging as a screening test for cystic fibrosis (CF). There is lack of normative data for the same in our population. To generate normative data for AWP in children 1-15 years of age and to describe the factors associated with it. Children aged 1-15 years were enrolled after obtaining informed consent and assent of the parent and child based on age. Information regarding age, gender, anthropometry, indications for visiting hospital and drug intake were noted down. Wrinkling test was done using distilled water maintained in room temperature. Sweat chloride analysis was done using Nano duct sweat analysis system for children having AWP within 3 min. The mean/median time to wrinkle was noted and presented as centile curves after smoothing. The mean (SD) and median (interquartile range [IQR]) aquagenic wrinkling time in children 1-15 years of age was 4.88 (1.066) and 5 (4-5.75) minutes respectively. The mean (SD) and median (IQR) time for AWP was 4.78 (1.076) and 5 (4-5) minutes respectively for boys and 4.98 (1.048) and 5 (4-6) minutes, respectively for girls. The time taken to wrinkle was observed to increase with age. Males have earlier AWP than females. There was no association between AWP and anthropometry or sweat chloride levels. We have estimated the normative data for AWP in children 1-15 years of age which can be used for CF screening in children with typical clinical features from resource limited settings.


A DNA vaccine encoding the 42 kDa C-terminus of merozoite surface protein 1 of Plasmodium falciparum induces antibody, interferon-gamma and cytotoxic T cell responses in rhesus monkeys: immuno-stimulatory effects of granulocyte macrophage-colony stimulating factor.
We have constructed a DNA plasmid vaccine encoding the C-terminal 42-kDa region of the merozoite surface protein 1 (pMSP1(42)) from the 3D7 strain of Plasmodium falciparum (Pf3D7). This plasmid expressed recombinant MSP1(42) after in vitro transfection in mouse VM92 cells. Rhesus monkeys immunized with pMSP1(42) produced antibodies reactive with Pf3D7 infected erythrocytes by IFAT, and by ELISA against yeast produced MSP1(19) (yMSP1(19)). Immunization also induced antigen specific T cell responses as measured by interferon-gamma production, and by classical CTL chromium release assays. In addition, immunization with pMSP1(42) primed animals for an enhanced antibody response to a subsequent boost with the recombinant yMSP1(19). We also evaluated Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) as an adjuvant for pMSP1(42.) We tested both rhesus GM-CSF expressed from a DNA plasmid, and E. coli produced recombinant human GM-CSF. Plasmids encoding rhesus GM-CSF (prhGM-CSF) and human GM-CSF (phuGM-CSF) were constructed; these plasmids expressed bio-active recombinant GMCSF. Co-immunization with a mixture of prhGM-CSF and pMSP1(42) induced higher specific antibody responses after the first dose of plasmid, but after three doses of DNA monkeys immunized with or without prhGM-CSF had the same final antibody titers and T cell responses. In comparison, rhuGM-CSF protein did not lead to accelerated antibody production after the first DNA dose. However, antibody titers were maintained at a slightly higher level in monkeys receiving GM-CSF protein, and they had a higher response to boosting with recombinant MSP1(19). The GM-CSF plasmid or protein appears to be less potent as an adjuvant in rhesus monkeys than each is in mice, and more work is needed to determine if GM-CSF can be a useful adjuvant in DNA vaccination of primates.


The effects of host plant defoliation and fertilizer application on larval growth and oviposition behaviour in cinnabar moth.
Defoliated ragwort plants produced regrowth foliage that was higher in alkaloid, but lower in amino acid concentrations than primary foliage. Total N was not affected. 2) Plants fertilized with nitrogen (as ammonium sulphate) had lower amino acid concentrations than unfertilized control plants, slightly increased alkaloid levels but similar total N concentrations. 3) Ovipositing females laid eggs upon plants with equal probability for controls, regrowth and fertilized foliage (one rosette in 5 received an egg batch). However, the probability of receiving eggs was significantly lower on the primary leaves of 'cut-back' plants that had had their lower leaves removed a few days before egg laying (only one rosette in 13 was selected). 4) Egg batch size was higher on fertilized control foliage than on other treatments. 5) Larvae attained greater final weights when fed a diet of regrowth foliage, despite the higher levels of alkaloid they contained. Larval development rate was not affected by experimental treatment of the foliage. 6) Larval growth was lowest on the leaves of fertilized plants. This was associated with significant reductions in the concentrations of three amino acids (methionine down 29%, tyrosine 33% and lysine 25%).


Medial closing-wedge distal femoral varus osteotomy: Symptoms and functional impact in cases of associated patellofemoral osteoarthritis. A two-year follow-up prospective pilot study.
To date, indications for distal femoral varus osteotomy (FVO) in cases of associated patellofemoral osteoarthritis (PFO) have yet to be clarified. The purpose of this prospective study is to assess the short-term symptoms, functional and radiological impact of a medial closing-wedge femoral varus osteotomy on the patellofemoral joint in patients with valgus deformities who are afflicted with lateral tibiofemoral osteoarthritis (LTFO) associated with PFO. Fourteen patients (15 knees) received a medial closing-wedge femoral varus osteotomy. The functional impact of an FVO on the patellofemoral joint was assessed based on the KOOS-PF (Knee Injury and Osteoarthritis Outcome Score-Patellofemoral Subscale), the Kujala score and the patellofemoral symptoms. Realignment of the patella was measured by the Merchant's patellofemoral congruence angle. The pre- and post-operative symptoms and functional scores were compiled prospectively and compared two years after the surgery. The Kujala patellofemoral functional scores and the KOOS-PF showed considerable improvement with a differential of +37.5 points ± 20.4 and +42.7 points ± 19.3 (p < .01) respectively. The average Merchant's congruence angle went from 8.8° laterally to 3.6° medially, resulting in medialization of the patella, with a significant difference (p < .01). Based on the specific clinical analysis of the patellar joint, preoperative J-sign was identified in 26.7% of patients (n = 4) and was not found during postoperative examination (p = .1). Preoperative apprehension test was identified in 33.3% of patients (n = 5) against 13.3% (n = 2) after surgery (p = .39). Preoperative pain extension test was identified in 40% of patients (n = 6) against 20% during postoperative clinical analysis (p = .43). Although the threshold of significance for patellofemoral symptoms was not reached, the medial closing-wedge femoral varus osteotomy induces a significant medialization of the patella (Merchant's congruence angle) and improves short-term functional results even with co-existing patellofemoral osteoarthritis. Due to the lack of specificity of the patellofemoral scores, patellofemoral osteoarthritis improvement is difficult to determine on its own, but does not represent a contraindication to FVO. III. Prospective clinical study.


Resolution of Hyperreninemia, Secondary Hyperaldosteronism, and Hypokalemia With 177Lu-DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy in a Patient With Pancreatic Neuroendocrine Tumor.
A 54-year-old woman presented with a history of nausea, vomiting, diarrhea, and recurrent episodes of severe hypokalemia requiring hospitalization. Imaging revealed a pancreatic mass with liver metastases, histologically confirmed to be a neuroendocrine tumor. Elevated active renin and aldosterone levels were identified, and the patient was treated with 4 induction cycles of Lu-DOTATATE, which resolved the diarrhea, nausea, and hypokalemia, and normalized the renin and aldosterone levels. After 3 additional maintenance Lu-DOTATATE treatments, the pancreatic tumor had decreased in size, was deemed operable, and was resected. She remains on maintenance Lu-DOTATATE therapy with progression-free survival of 45 months thus far.


Current issues and perspectives in small rodent magnetic resonance imaging using clinical MRI scanners.
Small rodents such as mice and rats are frequently used in animal experiments for several reasons. In the past, animal experiments were frequently associated with invasive methods and groups of animals had to be killed to perform longitudinal studies. Today's modern imaging techniques such as magnetic resonance imaging (MRI) allow non-invasive longitudinal monitoring of multiple parameters. Although only a few institutions have access to dedicated small animal MR scanners, most institutions carrying out animal experiments have access to clinical MR scanners. Technological advances and the increasing field strength of clinical scanners make MRI a broadly available and viable technique in preclinical in vivo research. This review provides an overview of current concepts, limitations, and recent studies dealing with small animal imaging using clinical MR scanners.


Carcinogenic effects of infantile and long-term 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment in the mouse.
An infantile carcinogenesis assay was carried out with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) injections administered intraperitoneally at 0, 1, 30 and 60 micrograms/kg b.w. doses to (C57BL/6J X C3Hf)F1 (B6C3) and to (C57BL/6J X BALB/c)F1 (B6C) mice, starting from the 10th day of life, once weekly repeated 5 times. Animals were then observed until 78 weeks of age. The induction of thymic lymphomas was related to treatment at 60 micrograms/kg dose level in both sexes of both hybrids, and at 30 micrograms/kg dose level in both sexes of B6C mice and in male but not female B6C3 mice. The incidence of hepatocellular adenomas was increased by TCDD treatment at 60 micrograms/kg dose level in B6C3 of both sexes but not in B6C mice. Hepatocellular carcinomas were seen at increased incidence at 30 and 60 micrograms/kg doses in B6C3 males but not in B6C3 females or in B6C mice of both sexes. The incidence of other tumor types was not related to treatment in both hybrids. A long-term carcinogenesis bioassay with TCDD was carried out in B6C3 mice treated by gavage at 0, 2.5 and 5.0 micrograms/kg b.w. doses from 6 weeks of age, once weekly for 52 weeks. The animals were observed until 110 weeks of age. An increased incidence of hepatocellular adenomas and carcinomas was related to treatment, at both doses and in both sexes. The incidence of other tumor types was uniformly low in treated and control groups, without any association with treatment, in both sexes.


Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis.
The insulin-like growth factor (IGF) system influences oligodendrocyte survival, myelination, and immune functions. We examined whether alterations in the circulating IGF system occur in multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. We measured concentrations of IGF-I, IGF-II, and insulin-like growth factor binding proteins -1, -2, and -3 in both serum and cerebrospinal fluid from MS patients and age- and sex-matched controls. IGFBP-1 was not detectable in cerebrospinal fluid. We found no significant differences in any of the other components between patients with MS and controls.


Semen variables of sheep (Ovis aries) experimentally infected with Toxoplasma gondii.
The influence of Toxoplasma gondii on semen variables and sperm morphology of sheep was evaluated in eight reproductive males distributed into three experimental groups: GI, three sheep inoculated with 2.0x10(5) of P strain oocytes; GII, three sheep infected with 1.0x10(6) of RH strain tachyzoites and; GIII two control sheep. Clinical (rectal temperature, cardiac and respiratory frequencies), parasite and serology exams (IIF) were realized. Sperm variables (volume, motility, vigor and concentration) and semen morphology for each sheep were also evaluated. Thus, semen and blood collections were assessed on post-inoculation days (PIDs)-1,3,5,7,11,14 and weekly thereafter up to PID 70. Clinical alterations were observed (hypothermia and anorexia) in infected sheep from groups GI and GII. Parasitic outbreaks were detected in five sheep. All the infected sheep produced antibodies against T. gondii from PID 5 onwards, reaching a peak of 4096 and 8192 for group GI and GII sheep, respectively. Differences (P<0.05) were observed regarding the ejaculate volume between the inoculated groups (oocytes and tachyzoites) and control. Even though experimental toxoplasmic infection resulted in clinical symptomology in the inoculated sheep, the minimal alterations in sperm pathologies could not be directly attributed to T. gondii.


Prevalence of depressive symptoms and associated factors among people who inject drugs in China.
People who inject drugs (PWID) have a high prevalence of mental health problems (e.g., depression) which compromise the effects of HIV prevention. We investigated the prevalence of depression and associated factors among PWID in Dazhou, China. Anonymous face-to-face interviews were administered to eligible participants by well-trained doctors. The Center of Epidemiological Studies Depression Scale (CES-D) was used to measure depression, using hierarchical linear regression models. Among the 257 participants, 7.0%, 11.3%, and 75.1% were probable cases of mild (16 ≤ CES-D < 21), moderate (21 ≤ CES-D < 25), and severe (CES-D ≥ 25) depression, respectively. Hopefulness (standardized β = -0.34, p < 0.001) and emotional family support (β = -0.21, p < 0.001) were negatively associated, whereas severity of drug dependence (β = 0.12, p = 0.034) and unmet service needs (β = 0.20, p < 0.001) were positively associated, respectively, with CES-D scores. The adjusted analysis showed that resilience was negatively associated with CES-D, but it was not selected by the stepwise model containing hopefulness and emotional family support. Protective factors (i.e., hopefulness and emotional family support) and risk factors (i.e., severity of drug dependence and unmet service needs) remained significant in the same regression model. Protective and risk factors were independently associated with depressive symptoms. Integrated interventions covering basic and psychosocial needs for PWID are warranted. Such interventions should strengthen emotional family support and cultivate positive factors such as hopefulness.


CD44 is associated with proliferation in normal and neoplastic human colorectal epithelial cells.
Flash-frozen biopsies obtained from surgical specimens of three adenomatous polyps and 22 colorectal adenocarcinomas (19 primary and three metastatic) were tested by immunohistochemistry for CD44 expression using F10-44-2 monoclonal antibody. CD44 positivity was correlated with proliferative status defined by Ki-67 monoclonal antibody reactivity. In normal colonic mucosa, CD44 was expressed in the proliferative zone of crypts. In tumours, CD44 expression was associated with proliferative areas irrespective of tumour stage or differentiation. Non-proliferating areas of the carcinomatous epithelium did not express CD44 although non-proliferating stromal lymphoid tissue did. There was no apparent association with tumour progression. F10-44-2-defined CD44 is consistently expressed during proliferation by normal colorectal epithelial cells and by both benign and malignant colorectal tumour cells.


From the archives of MD Anderson Cancer Center: Plasmablastic lymphoma presenting as a kidney mass in an immunocompetent patient: Case report and literature review.
Plasmablastic lymphoma (PBL) is a rare, aggressive large B-cell lymphoma with plasmablastic or immunoblastic morphology and a terminally differentiated B-cell immunophenotype. PBL often presents at extranodal sites, commonly the oral cavity of immunocompromised patients with human immunodeficiency virus (HIV) and/or Epstein-Barr virus (EBV) infection. Cases of PBL arising outside the oral cavity in previously healthy immunocompetent patients are rare. We report a 65-year-old HIV- and EBV-negative man who presented with abdominal pain, fatigue, and vomiting. Imaging studies showed a 30 × 18 cm bulky lobulated mass located within the left kidney with surrounding para-aortic lymphadenopathy. Serum and urine protein electrophoresis revealed a monoclonal gammopathy of IgA lambda type. Biopsy of the mass showed PBL. Bone marrow lumbar puncture evaluations also showed evidence of PBL. The patient was treated with chemotherapy and radiation with initial improvement; however, he died 14 months after initial diagnosis. Based on our literature review, this case of PBL is one of the few reported to present as a kidney mass in immunocompetent, HIV- and EBV-negative patient. Distinguishing PBL from plasma cell myeloma (PCM) can be challenging. Knowledge of clinical features including presence of CRAB (hypercalcemia, renal failure, anemia, bone lesions) or bone marrow infiltration by mature clonal plasma cells is helpful to establish a diagnosis of PCM. Genetic features of PCM (typical translocations or mutations) also can be helpful in distinguishing plasmablastic transformation of PCM and from PBL. The case we report also highlights the need for more studies to identify specific immunohistochemical and molecular markers to improve PBL diagnosis in immunocompetent patients.


Regulation of growth and macromolecular synthesis by putrescine and spermidine in Pseudomonas aeruginosa.
Growth of P. aeruginosa, slowed by the addition of monofluoromethylornithine, difluoromethylarginine and dicyclohexylammonium sulfate, could be restored by addition of 0.1 mM putrescine plus 0.1 muM spermidine, or 0.1 mM spermidine or 5 mM putrescine by themselves. Lower concentrations of putrescine (0.1 mM - 1 mM) also partially reversed the growth inhibition. Conversion of putrescine to spermidine continued, although at a markedly reduced ratio, in the drug-inhibited cells, but intracellular spermidine concentrations remained depressed suggesting that reversal of inhibition by putrescine may be a direct effect. There was appreciable back-conversion of any added spermidine to putrescine with a demonstrable increase in total intracellular putrescine levels, making conclusions on the effects of spermidine ambiguous. Spermine (0.1 mM), a polyamine not present in bacteria, was also effective in reversing growth inhibition, probably because of its conversion into spermidine and putrescine. The effects of putrescine, spermidine and spermine were specific in that the non-physiological amines, 1,3-diaminopropane, 1,5-diaminopentane (cadaverine), 1,6-diaminohexane, or 1,7-diaminoheptane could not reverse the effects of the three drugs. Rates of total protein, RNA and DNA synthesis were all slowed to the same extent as growth rate and showed similar recovery with the addition of putrescine or spermidine. A role for putrescine in P. aeruginosa growth processes is suggested.


B cell development and receptor diversity during aging.
Although it is clear that B cell genesis declines with age, the specifics of why this happens are largely unknown. Even less clear is how the age-related decline in B cell development might affect peripheral B cell function. Recent studies have investigated the impact of aging on both B cell genesis in the bone marrow and the resulting peripheral B cell repertoire. On the basis of these studies we propose a model in which the aging of very early B cell progenitors results in shifts in the peripheral B cell repertoire and, consequently, changes in mature B cell function.


[Metabolism of the local anaesthetic fomocaine by rat liver mitochondria (author's transl)].
Fomocaine (Erbocain) is metabolized by different routes in rat and beagle. By highly purified rat liver mitochondria it was metabolized to its N-oxide only. The N-oxide was reduced to fomocaine by a reductase localised in the matrix or in the inner membrane of the mitochondria. C-Hydroxylation with subsequent conjugation reactions as well as oxidative N- or O-dealkylation found in intact animals were not observed in mitochondria.


Insulin-like growth factor-1 (IGF-1) enhances developmental competence of cat embryos cultured singly by modulating the expression of its receptor (IGF-1R) and reducing developmental block.
The aim of this study is to determine the effects of insulin-like growth factor-1 (IGF-1) and the mRNA expression of IGF-1 receptor (IGF-1R) during the in vitro development of cat embryos cultured in groups versus singly. Cumulus-oocyte complexes (COCs) were matured and fertilized in vitro with frozen-thawed semen. Cleaved embryos (48h post-fertilization) were randomly assigned to one of the following treatments: 1) group embryo culture without IGF-1 (10 embryos per 50μl droplet), 2) single-embryo culture without IGF-1, and 3) to 6) single-embryo culture (50μl droplet per embryo) supplemented with different concentrations of IGF-1 (5, 25, 50 and 100ng/ml, respectively). During in vitro culture, the embryos were analyzed for development to the morula, blastocyst and hatching blastocyst stage. Relative mRNA expression of IGF-1R was also examined by qPCR at the morula and blastocyst stages. In addition, the mRNA expression of IGF-1R in morula-stage embryos treated with IGF-1 was determined. The influence of IGF-1 to preimplantation embryo development was then explored by co-incubation with 0.5μM IGF-1R inhibitor (Picropodophyllin; PPP). Group embryo culture led to a significantly higher blastocyst development rate compared with single-embryo culture (P<0.05). The poor development of singly cultured embryos coincided with the significantly lower IGF-1R expression in morulae than in group-cultured morulae. IGF-1 (25 or 50ng/ml) supplementation significantly improved the blastocyst formation rate of single embryos to a level similar to group culture by promoting the morula-to-blastocyst transition. IGF-1 supplementation (25 or 50ng/ml) of singly cultured embryos upregulated the expression of IGF-1R mRNA in morula-stage embryos to the same level as that observed in group-cultured embryos (without IGF-1). The beneficial effects of IGF-1 on singly cultured embryo were (P<0.05) suppressed by PPP even in the group culture embryo without growth factor supplementation. IGF-1 supplementation improves the developmental competence of feline embryos cultured individually and also increases IGF-1R gene expression to levels similar to group-cultured embryos.


A comparative assessment of action plans on antimicrobial resistance from OECD and G20 countries using natural language processing.
Following the launch of the Global Action Plan on antimicrobial resistance (AMR-GAP) in 2015, most OECD and G20 countries developed their own national action plans (AMR-NAPs). This is the first paper that deploys natural language processing (NLP) techniques to systematically measure and compare the extent to which AMR-NAPs from 21 OECD and G20 countries align with the AMR-GAP in terms of the strategic objectives and interventions. We quantify the extent of alignment based on two NLP metrics: term-frequency (TF) and term-frequency-inverse document frequency (TF-IDF). Quantifying TF allows us to compare the relative prominence of strategic objectives and interventions, whereas quantifying TF-IDF enables us to identify interventions that occur more frequently in each AMR-NAP. Similar to the AMR-GAP, in our sample, terms associated with optimizing antimicrobial use in human and animal health have the highest frequency (TF = 0. 287), whereas terms linked to raising AMR awareness and education have the lowest frequency (TF = 0.066). Substantial cross-country variation exists in the distribution of interventions that are distinctly frequent in each AMR-NAP. We also report new evidence on the selected policy design and monitoring and evaluation features of these documents. Our results suggest a high degree of congruence between the AMR-GAP and AMR-NAPs, with notable diversity in the spate of interventions that OECD and G20 countries discuss in their action plans.


Training and education--with a view of the involvement in Germany.
The replies of 15 countries to the questionnaires-training and education-have shown that transfusion medicine teaching and education regarded as a definitely clearly defined specialty with different tones and degrees, is to be considered at different levels relating to teaching basic knowledge of transfusion medicine during the education as well as in the postgraduate training. The reported results may serve as an incentive or impulse to suitable regulations and a common consensus of transfusion medicine curriculum although each European Country has its peculiarities.


Combined deficiency of IL-1beta18, but not IL-1alphabeta, reduces susceptibility to hypoxia-ischemia in the immature brain.
Interleukin (IL)-1 and IL-18 belong to the IL-1 family. IL-18 deficiency has been shown to confer moderate protection after hypoxia-ischemia (HI) in the immature brain, while the contribution of the two isoforms of IL-1 (IL-1alpha and IL-1beta) in neonatal HI brain injury has not been investigated previously. The aim of this study was to examine the contribution of the different members of the IL-1 family to neonatal HI damage. Unilateral HI was induced at postnatal day 9 in IL-1beta, IL-1beta18, and IL-1alphabeta knockout and wild-type mice and brain injury was evaluated 1 week later. IL-1beta18-deficient mice showed 17% reduction in brain injury, while no significant reduction in injury was detected between any of the other groups. These results indicate that IL-18, but not IL-1beta, or the combination of IL-1alpha and IL-1beta, is a contributor to HI injury in the immature brain.


Factors that Influence Acquisition of Lower Extremity Braces in the Pediatric Orthopaedic Population.
Lower extremity brace-wear compliance has been studied in pediatrics, but failure to acquire a prescribed brace has not been included. The purpose of this study was to evaluate brace acquisition as a component of brace-wear compliance. Records of patients (0 to 21 y) prescribed lower extremity braces from 2017 to 2019 were reviewed. Diagnoses included cerebral palsy, spina bifida, short Achilles tendon, clubfoot, and other. Brace type was categorized as clubfoot foot abduction orthosis, ankle-foot orthosis, knee, hip, or custom/other braces. Brace prescription and acquisition dates were recorded. Insurance was classified as government, private, or uninsured. Patient demographics included age, sex, race, and calculated area deprivation index. Of the 1176 prescribed lower extremity braces, 1094 (93%) were acquired while 82 (7%) were not. The odds ratios (OR) of failure to acquire a prescribed brace in Black and Hispanic patients were 1.64 and 2.71 times that in White patients, respectively (95% confidence interval: 1.01-2.71, P=0.045; 1.23-5.6, P=0.015); in patients without insurance, the OR was 8.48 times that in privately insured patients (95% confidence interval: 1.93-31.1, P=0.007). The ORs of failure to acquire were 2.12 (P=0.003) in patients 4 years or more versus 0 to 3 years, 4.17 (P<0.0001) in cerebral palsy versus clubfoot, and 4.12 (P=0.01) in short Achilles tendon versus clubfoot. There was no significant association between sex or area deprivation index and failure of brace acquisition. In our cohort, 7% of prescribed braces were not acquired. Black or Hispanic race, lack of insurance, and older age were associated with failure to acquire prescribed braces. Braces prescribed for clubfoot were acquired more often than for cerebral palsy or short Achilles tendon. Brace-wear compliance is an established factor in treatment success and recurrence. This study identified risk factors for failed brace acquisition, a critical step for improving compliance. These results may help effect changes in the current system that may lead to more compliance with brace wear. Level III-retrospective cohort study.


Realistic and inexpensive ultrasound phantoms to demonstrate aortic aneurysm and aortic dissection.
Using ultrasound to evaluate for the presence of aortic pathology is a common procedure in the emergency department. Phantoms are models that are used to simulate clinical conditions for teaching ultrasound-related skills. To date, no 'homemade' phantom has been created to model aortic aneurysms, and no phantoms exist to model aortic dissection. We used several readily available, inexpensive ingredients to create ultrasound phantoms. These phantoms realistically mimic aortic aneurysm and aortic dissection. These are the first 'homemade' phantoms that demonstrate aortic pathology. We have created realistic, affordable, easily reproducible phantoms for use in teaching clinicians to use ultrasound when evaluating patients for aortic aneurysm and/or aortic dissection.


Huge epithelioid malignant peripheral nerve sheath tumor in the left axilla: a case report.
This report describes a patient with a rare huge epithelioid malignant peripheral nerve sheath tumor (MPNST) in the left axilla. A male in his 70s was admitted to our hospital for evaluation of a growing tumor in his left axilla. The tumor was solid and immovable. Examination of a biopsy specimen resulted in a diagnosis of epithelioid MPNST. Two weeks after the biopsy was performed, the tumor grew to 20 cm and became painful, and the patient was unable to feel pressure on his upper arm. Immediately before surgery to remove the tumor, computed tomography suggested the presence of lung metastases. The patient and his family were informed of his disease state, and they elected surgical treatment to ease the symptoms associated with tumor enlargement. Systemic metastases appeared soon after the surgery, and the patient died within 11 weeks. Comparative genomic hybridization (CGH) analysis showed that this tumor was chromosomally unstable, with impairments in gene expression.


Delivery of hydroxycamptothecin via sonoporation: An effective therapy for liver fibrosis.
Hepatic fibrosis is the common pathway for most chronic liver diseases, characterized by excessive accumulation of extracellular matrix (ECM) proteins. It has been shown that fibrotic ECM significantly hindered passage of nanoparticles. Efforts have been made by decorating degrading enzymes on surfaces of nanosized delivery vehicles to improve drug delivery. However, these strategies are restricted by limiting shelf-life. Inspired by the application of sonoporation in assisting drug delivery through blood-brain barrier and tumor tissues, we investigated whether sonoporation can be an alternative strategy in improving drug delivery for fibrotic diseases. Hydroxycamptothecin (HCPT), a potential drug in treating liver fibrosis, was selected as a model drug to evaluate the drug delivery efficiency and therapeutic effect among three delivery strategies, i.e., (1) injection solution, (2) delivery through liposomes, and (3) delivery via sonoporation. Our study showed that in addition to the improved drug delivery efficiency, the combination of HCPT and sonoporation led to synergistic effect and the mechanisms were investigated. The treatment group of HCPT delivered with sonoporation achieved the most significant attenuation in liver fibrosis among the three delivery strategies.


Design, implementation, and monitoring of HIV service packages for people who inject drugs: An assessment of programs supported by the Global Fund in 46 countries.
People who inject drugs (PWID) are at higher risk of acquiring and transmitting HIV, accounting for an estimated 10% of HIV new infections globally. The World Health Organization (WHO) and other international agencies have clearly outlined the comprehensive package of services that should be available for PWID. This paper summarizes the data and findings from the PWID service packages assessed in 15 countries across different regions. It also provides data on the design of PWID programs in a further 30 countries that identified PWID as a key population in their national HIV strategic documents. A mixed-method approach was used, including desk reviews, key informant interviews, site observations and group interviews with implementers and PWID focus groups. Design of service packages varied considerably between countries while many matched the WHO Comprehensive Package. Only 85% countries (39/46) included needle-syringe exchange programs (NSEP) and 76% included opioid agonist therapy (OAT). Only 17% countries included overdose management in their package design. Across the 46 countries assessed, the average coverage with defined prevention package was 40% among countries for which coverage figures could be derived. Despite some examples of client-based, high-quality services in challenging environments, few countries, which rely primarily on external donor support, are reaching the necessary coverage levels across the full range of PWID HIV prevention, testing and care services. Transition from donor to domestic funding to fund this element of the HIV responses in many countries presents a compelling case to prevent PWID from being further left behind.


A proposal for combined MRI and PET/CT interpretation criteria for preoperative nodal staging in non-small-cell lung cancer.
To determine the positive reading criteria for malignant nodes when interpreting combined MRI and PET/CT images for preoperative nodal staging in non-small-cell lung cancer (NSCLC). Forty-nine patients with biopsy-proven NSCLC underwent both PET/CT and thoracic MRI [diffusion weighted imaging (DWI)]. Each nodal station was evaluated for the presence of metastasis by applying either inclusive (positive if either one read positive) or exclusive (positive if both read positive) criteria in the combined interpretation of PET/CT and MRI. Nodal stage was confirmed pathologically. The combined diagnostic accuracy of PET/CT and MRI was determined on per-nodal station and per-patient bases and compared with that of PET/CT alone. In 49 patients, 39 (19%) of 206 nodal stations harboured malignant cells. Out of 206 nodal stations, 186 (90%) had concordant readings, while the rest (10%) had discordant readings. Inclusive criteria of combined PET/CT and MRI helped increase sensitivity for detecting nodal metastasis (69%) compared with PET/CT alone (46%; P = 0.003), while specificity was not significantly decreased. Inclusive criteria in combined MRI and PET/CT readings help improve significantly the sensitivity for detecting nodal metastasis compared with PET/CT alone and may decrease unnecessary open thoracotomy. Key Points • Combined interpretation of MRI and PET/CT enhances the detection of nodal metastasis. • Inclusive criteria of combined MRI/PET/CT improved the sensitivity for detecting nodal metastasis. • Combined interpretation of MRI and PET/CT may reduce unnecessary open thoracotomies.


Biliary cystadenocarcinoma of the liver. A clinicopathologic and histochemical evaluation of nine cases.
Nine cases of biliary cystadenocarcinoma of the liver were studied, with emphasis on its clinicopathologic features, mucin profiles, and immunohistochemical characteristics. In general, the cystic tumors had protrusions that consisted of well-differentiated papillary adenocarcinoma cells with or without benign-appearing epithelial elements. In invading or metastatic foci, the carcinoma cells tended to show distinctive anaplastic changes. Tumor growth was confined to the cystic lesions in five cases (noninvasive type), whereas in four cases it extended to the hepatic parenchyma or neighboring organs (invasive type). There was a considerable difference between the two groups in terms of prognosis. In fact, the patients included in the group with the noninvasive type had no sign of tumor recurrence after an appropriate surgical procedure. With mucin histochemical and immunohistochemical approaches, positive reactions with carcinoembryonic antigen, tissue polypeptide antigen, carbohydrate 19-9, and Dupan-2 and the predominance of sialomucin were observed in most cases of biliary cystadenocarcinoma, indicating a similar cellular nature of cholangiocarcinoma.


Traditional medicinal knowledge of plants used for cancer treatment by communities of mountainous areas of Fez-Meknes-Morocco.
Since their existence on earth, humans have used herbal medicine to meet their requirements for medication. The aim of the study: This work refers to a study conducted to carry out an ethnopharmacological survey of medicinal plants used for the treatment of cancer in Fez-Meknes region of Morocco. Material and Methods: To achieve this goal, 300 informants including 237 local people and 63 herbalists. They were requested to fill a survey related questionnaire aiming at the collection of data about the addressed objective. Informants were asked about the vernacular names, parts of medicinal plants used, mode of preparation, route of administration, reference area as well as the ecological distribution. The Relative Frequency of Citation (RFC) and Fidelity Level (FL) were calculated to identify the most effective plants recommended by informants for disease treatment. Results: The findings obtained in the present survey revealed that 94 species belonging to 47 families have been used for cancer treatment in the region of Fez-Meknes. Fruits, leaves, and seeds are the most commonly used plant parts, by the time powder and infusion arethe most common methods used fordrug preparations. Conclusion: This work may contribute towards the society as it provides interesting data on traditional medicinal knowledge of medicinal plantsused to fight cancer.


Biomechanical analysis of the ankle anterior drawer test for anterior talofibular ligament injuries.
The effect of sectioning the anterior talofibular ligament on the load-displacement behavior of the ankle was evaluated in vitro during the anterior drawer test using the flexibility approach. Controlled forces were applied across the ankle joint in the anterior-posterior direction, and the resulting displacements were measured at four flexion angles (10 degrees of dorsiflexion, neutral, and 10 degrees and 20 degrees of plantar flexion). The anterior talofibular ligament then was sectioned, and the anterior-posterior loadings were repeated at the four flexion angles. Two parameters were developed to describe the nonlinear load-displacement response of the ankle joint: neutral zone laxity (joint displacement between +/- 2.5 N) and flexibility (a measure of the nonlinear load-displacement response of the ankle between 10 and 50 N of anterior drawer loading). After sectioning the anterior talofibular ligament, significant increases in neutral zone laxity were observed at all angles of ankle flexion. The largest increases in neutral zone laxity were found with the ankle in 10 degrees of plantar flexion (76.3% increase) and 20 degrees of plantar flexion (89.7% increase). After sectioning the ligament, a significant increase (19.3%) in flexibility of the ankle was observed at 10 degrees of dorsiflexion, but no change in flexibility was observed with the ankle in the neutral and plantar flexed positions. These findings indicate that anterior drawer testing of the anterior talofibular ligament-deficient ankle between 10 degrees and 20 degrees of plantar flexion results in the largest increase in neutral zone laxity compared with the normal ankle with intact ligaments.(ABSTRACT TRUNCATED AT 250 WORDS)


Sequencing of the CFTR gene in selected Turkish patients with cystic fibrosis.
Common mutation detection panels are usually used in clinical practice in most of the centers of our country in order to demonstrate mutations of cystic fibrosis (CF) patients. But heterogenicity of CFTR mutations in Turkey makes identification of CFTR mutations extremely difficult while using common mutation detection panels. In this report, we described our experience and findings in offering sequencing of the CFTR gene to 17 patients in which no mutations were identified by common mutation analysis. Overall allele informativity increased from 4/34 (11.76%) to 13/34 (38.2%) after whole exon sequencing of CFTR in our patients. Genotype of CF patients could be entirely described in some of our patients by CFTR sequencing but there is still a group of patients, independently from their clinical classification whose mutations can not be determined by CFTR sequencing.


Familial, atypical hemolytic-uremic syndrome in a premature infant.
The hemolytic-uremic syndrome (HUS) typically presents in toddlers or older children after an episode of bloody diarrhea caused by Escherichia coli O157:H7. However, numerous "atypical" presentations have been described, including familial cases. Here we describe what we believe to be the first report of familial HUS in a premature infant during the neonatal period.


Mating behaviour and parapatry in two species of Australian reptile tick.
Few quantitative studies have examined the ecological consequences of similarities and/or differences in mating behaviour of parapatric species. Reproductive interference occurs between several parapatric species of Australian reptile tick, due to similarities in their mating behaviour (Andrews et al. 1982a). Attempts to determine whether reproductive interference serves to maintain parapatry between Amblyomma limbatum and Aponomma hydrosauri have been hindered because of difficulties in providing conditions conducive to conspecific mating in Amb. limbatum. The present study examined whether off-host and/or onhost temperature influenced the subsequent mating behaviour (i.e. the proportion of females that mate and the time when mating occurs) of these two species. Irrespective of the temperature experienced by ticks prior to host attachment, specific on-host temperatures were needed to induce mating in Amb. limbatum (i.e. host cloacal temperatures >32° C prior to the time of peak mating activity). Significantly more Amb. limbatum females were mated and the time taken by females to mate decreased with increasing on-host temperatures. mating in Ap. hydrosauri occurred over a wider range of on-host temperatures and the time when mating occurred did not alter at different on-host temperatures. In addition, significantly more Ap. hydrosauri males moved and each male made more moves on hosts than did Amb. limbatum males. It is suggested that Ap. hydrosauri may in consequence have a competitive mating advantage over Amb. limbatum at a boundary. Similarities in mating behaviour, on the other hand, increase the probability of reproductive interference, hence reduce the reproductive fitness of colonizing females of both species. We propose that similarities and differences in mating behaviour could play a critical role in the maintenance of parapatric boundaries.


Validity of submaximal exercise testing in adults with athetospastic cerebral palsy.
To examine the validity of the multistage submaximal cycle ergometer test for adults with athetospastic cerebral palsy. Cross-sectional and correlative study. Oxygen uptake and heart rates were recorded while the participants underwent the maximal cycle ergometer test and the multistage submaximal cycle ergometer test. Peak oxygen consumption (Vo(2)peak) was achieved by the maximal cycle test. Maximum oxygen consumption (VO(2)max) was predicted by the multistage submaximal cycle ergometer test. Research laboratory setting. Adults with athetospastic cerebral palsy (N=16; 10 women and 6 men; mean age ± SD, 43.7±14.5y). Not applicable. Peak VO(2) was compared with the predicted VO(2)max. Mean VO(2)peak and the predicted VO(2)max ± SD were 866.9±202.9 mL/min(-1) and 857.4±248.4 mL/min(-1), respectively. There was not a significant difference between VO(2)peak values and the predicted VO(2)max values (r=.28). And there was a significant correlation between VO(2)peak values and the predicted VO(2)max values (r=.94, P<.001). SE of the estimate (or SE for X to Y) was 71.2 mL/min(-1), equivalent to 7.4%. The multistage submaximal cycle ergometer test may provide a valid VO(2)max estimate of adults with athetospastic cerebral palsy.


Phenobarbital inducible UDP-glucuronosyltransferase is responsible for glucuronidation of 3'-azido-3'-deoxythymidine: characterization of the enzyme in human and rat liver microsomes.
Glucuronidation by liver microsomes of 3'-azido-3'-deoxythymidine (AZT) was characterized in human and in various animal species. The glucuronide isolated by HPLC, was identified by mass spectrometry (fast atom bombardment, desorption in chemical ionization), and beta-glucuronidase hydrolysis. AZT glucuronidation reaction in liver microsomes of human and monkey proceeded similarly with an apparent Vmax of 0.98 nmol/min/mg protein and apparent Km of 13 mM. Oleoyl lysophosphatidylcholine activated more than twofold the formation of the glucuronide. Human kidney microsomes could also biosynthesize AZT glucuronide, although to a lower extent (six times less than the corresponding liver). Probenecid, which is administered to AIDS patients, decreased hepatic AZT glucuronidation in vitro (I50 = 1.5 mM), whereas paracetamol did not exert any effect at concentrations up to 21.5 mM. Morphine also inhibited the reaction (I50 = 2.7 mM). AZT glucuronidation presented the highest rate in human and in monkey (0.50 nmol/min/mg protein); pig and rat glucuronidated the drug two and three times less, respectively. In Gunn rat, the specific activity in liver microsomes was similar (0.18 nmol/min/mg protein) to that of the congenic normal strain; this suggests that an isozyme other than bilirubin UDP-glucuronosyltransferase catalyzed the reaction. In rats, AZT glucuronidation was stimulated fourfold by phenobarbital; 3-methylcholanthrene or clofibrate failed to increase this activity. This result was consistent with the bulkiness of the AZT molecule (thickness 6.7 A), which is a critical structural factor for glucuronidation of the drug by phenobarbital-induced isozymes. Altogether, the results strongly indicate that UDP-glucuronosyltransferase (phenobarbital inducible forms) is responsible for AZT glucuronidation.


Anatomic variations of inferior mesenteric artery and left colic artery evaluated by 3-dimensional CT angiography: Insights into rectal cancer surgery - A retrospective observational study.
To demonstrate the clinical applicability of 3-dimensional CT angiography (3D-CTA) in evaluating the anatomic variations of inferior mesenteric artery (IMA) and left colic artery (LCA), to help make pre-operative strategies of rectal cancer surgery. 188 patients with abdominal and pelvic contrast-enhanced CT scan were retrospectively enrolled and 3D-CTA was reconstructed. The origin and branching patterns of IMA, tracking patterns of LCA, intersectional patterns among IMA, LCA and inferior mesenteric vein (IMV) were examined, and their associations with clinical features were analyzed. The origin of IMA was located 42.1 ± 7.7 mm above iliac artery bifurcation, 64.4% within the area of the 3rd lumbar vertebra. 47.3% of LCA arose independently from IMA, 27.1% arose at the root of sigmoid artery (SA), 20.7% shared a common trunk with SA while 4.8% of LCA was absent. As for track of LCA before anastomosis with marginal artery, 53.2% went straight upward while medial to the inner border of left kidney (Type A), 27.1% traveled diagonally across left kidney (Type B) and14.9% went infero-laterally to the lower border of left kidney (Type C). Short IMA trunk was independently associated with type A LCA and lower site of IMA origin. At the horizontal level of IMA origin, 29% of the LCA went distant from IMV, while 71% (21% medial, 50% lateral) were mutually close, and the close type was independently associated with type A LCA. Preoperative understanding of the vascular variations and the mutual relationship among LCA, IMA and IMV could be obtained by 3D-CTA, which would further help surgeons to set detailed plans for laparoscopic rectal cancer surgery.


The mouse neutralization test in comparison with the rapid fluorescent focus inhibition test: differences in the results in rabies antibody determinations.
Sixteen lots of rabies immune globulin (RIG) and six lots of rabies immune horse serum (RIS) from different producers were examined for rabies antibody by the standard mouse neutralization test (MNT) and the rapid fluorescent focus inhibition test (RFFIT). An equine rabies standard serum was assayed in parallel. In comparisons of RIS with this standard the MNT and RFFIT gave comparable results. In comparisons of RIG the antibody values in the MNT was two to ten times higher than that in the RFFIT in 15 out of 16 lots. The MNT and RFFIT are thus not fully comparable when measuring rabies antibodies in RIG. The choice of the titration method is obviously important in the measurement of the antibody concentration in RIG or RIS in IU against an equine rabies reference preparation. The described differences could have consequences for the use of RIG.


Retention reproducibility of basic drugs in high-performance liquid chromatography on a silica column with a methanol-high-pH buffer eluent. Changes in selectivity with the age of the stationary phase.
The long-term reproducibility of the separation of basic drugs by high-performance liquid chromatography using a silica column with a methanol-high-pH eluent was examined. The relative capacity factors of specific tertiary amines changed systematically compared with the other drugs on storage of the columns for 1 year. The changes were enhanced on storing the column in mobile phase and were accelerated by prolonged washing with water. A comparison of freshly packed columns suggested that similar changes also occurred with the dry silica on storage. These effects may be a contributor to previously observed batch-to-batch differences in the silica.


Mealtime emotional climate and child health: A systematic review.
Positive mealtime emotional climate (MEC) has been linked to better nutrition, psychosocial, literacy and academic outcomes, and fewer behavior problems. However, MEC has been defined in a variety of ways across studies, limiting the ability to synthesize findings and plan future research. To identify which child characteristics are associated with MEC and to determine how previous studies have measured MEC. We searched three databases (1980-2020) for peer-reviewed articles measuring MEC. Inclusion criteria required at least one child-level outcome related to physical, nutritional, or developmental health; children aged 0-18 years old; and quantitative data using cohort, case-control, intervention, or experimental designs. We used a previously published taxonomy to categorize child/adolescent characteristics as correlates, non-correlates, unclear, or as having insufficient evidence, according to the amount of evidence linking them to MEC. Additionally, we extracted data about the measures and definitions of MEC from each included article. Out of 668 unique studies identified in the initial search after duplicates removed, 14 met inclusion criteria, and only three used the same measure of MEC. Healthful dietary intake, disordered eating behaviors, and weight/BMI were categorized as correlates of MEC, but links to unhealthy dietary intake are unclear. Several characteristics (e.g. temperament, academic success) were examined in one study only. Future research should examine the relationship between MEC and child psychosocial child outcomes and utilize a preschool age group. These findings aid in conceptualizing how MEC has been defined and measured and illuminate the importance of MEC on children's health.


How to erase memory traces of pain and fear.
Pain and fear are both aversive experiences that strongly impact on behaviour and well being. They are considered protective when they lead to meaningful, adaptive behaviour such as the avoidance of situations that are potentially dangerous to the integrity of tissue (pain) or the individual (fear). Pain and fear may, however, become maladaptive if expressed under inappropriate conditions or at excessive intensities for extended durations. Currently emerging concepts of maladaptive pain and fear suggest that basic neuronal mechanisms of memory formation are relevant for the development of pathological forms of pain and fear. Thus, the processes of erasing memory traces of pain and fear may constitute promising targets for future therapies.


[Ultrasound detection of gastric antrum motility--evaluating a simple semiquantitative method].
This study was carried out to evaluate a simplified sonographic technique for the sonographic analysis of antral motility. For this purpose the percentage of visually complete contractions (estimated reduction of the antral area > 50%)/2 minutes was compared to the mean amplitude (%) and the mean velocity (%/s) of the contractions. The percentage of complete contractions was closely correlated to both the mean amplitude (r = 0.97, p < 0.0001) and the velocity (r = 0.92, p < 0.0001) of the antral contractions. Since the simplified technique is regardless to a postprocessing unit, which is not available in many sonolayers, it could be recommended as a valid routine screening method for the detection of antral motility disorders.


Co-culture of human hair follicles and dermal papillae in a collagen matrix.
Human hair follicles, either alone or in combination with dermal papillae, were cultured in a collagen matrix. When plucked hair follicles were cultured alone, spike-like structures composed of outer root sheath cells started growing around the follicle and then radiated into the gel. When isolated dermal papillae were embedded close to the follicles, spikes started growing earlier and grew more rapidly than without the papillae. In cultures of excised follicles from which the dermal papilla had been removed, epithelial cells (possibly hair bulb cells) started growing out from the bulbous portion and then also formed spikes. In the presence of a papilla, the spikes elongated toward the papilla, finally reaching and surrounding it. These findings suggest that dermal papilla cells produce a factor(s) that enhances growth of follicular epithelial cells and also attracts those cells. In cultures of whole excised follicles, two major characteristic patterns of cellular growth were recognized. When the dermal papilla remained inside the bulb in contact with the hair bulb matrix, the hair matrix cells proliferated and differentiated in the normal manner, resulting in elongation of the hair shaft and follicle. But when the papilla was detached from the hair bulb matrix, epithelial cells proliferated from the bulbous portion and finally formed hair follicle-like structures. Thus, attachment of the dermal papilla to the hair bulb matrix in the bulbous portion appears to be necessary for growth of the hair and follicle in the normal manner. Our model may be useful for examining the interaction between follicular epithelial cells and dermal papillae and for studying the growth of hair and follicles in vitro.


Mitochondrial Targeted Therapies: Where Do We Stand in Mental Disorders?
The neurobiology of psychiatric disorders is still unclear, although changes in multiple neuronal systems, specifically the dopaminergic, glutamatergic, and gamma-aminobutyric acidergic systems as well as abnormalities in synaptic plasticity and neural connectivity, are currently suggested to underlie their pathophysiology. A growing body of evidence suggests multifaceted mitochondrial dysfunction in mental disorders, which is in line with their role in neuronal activity, growth, development, and plasticity. In this review, we describe the main endeavors toward development of treatments that will enhance mitochondrial function and their transition into clinical use in congenital mitochondrial diseases and chronic disorders such as types 1 and 2 diabetes, cardiovascular disorders, and cancer. In addition, we discuss the relevance of mitochondrial targeted treatments to mental disorders and their potential to become a novel therapeutic strategy that will improve the efficiency of the current treatments.


CFD Modeling of Ventilation and Dust Flow Behavior in Polishing and the Design of an Innovative Wet Dust Removal System.
Fine aluminum dust pollution in the polishing process was detected during a field survey. To obtain a fundamental understanding of the airflow patterns and the fine dust dispersion characteristics during a polishing process, computational fluid dynamics simulations were first performed to analyze the data collected in field measurements. The inappropriate ventilation arrangement and lack of effective dust control measures were identified as the main reasons for the high dust exposure levels (in excess of 1000 μg/m3). Simulation results showed that inhalable dust particles (PM10) could be significantly diluted at the operator's breathing level by adding a supply air inlet above the operating area. Moreover, dry dust collection systems create a risk of aluminum dust explosion accidents. An innovative design of wet dust removal system which could mitigate the occurrence of dust explosions was proposed and then implemented on site. An independent field dust assessment showed that a reduction of fine dust particles up to 95% in the worker's breathing area and the fine dust in the vents was reduced to 80%. Therefore, the proposed strategies are implemented immediately to address the combustible dust in the polishing working environment and can provide guidance for operators.


SIGIRR participates in negative regulation of LPS response and tolerance in human bladder epithelial cells.
The innate immune response of urinary tract is critically important in the defense to microbial attack. Toll-like receptor 4 (TLR4) controls initial mucosal response to uropathogenic Escherichia coli (UPEC). However, excessive and dysfunctional TLR signaling may result in severe inflammation and inappropriate tissue damage. Previous studies have demonstrated that single immunoglobulin IL-1R-related receptor/Toll IL-1 receptor 8 (SIGIRR/TIR8) is a member of the toll-interleukin-1 receptor (TIR) family that can negatively modulate TLR4 mediated signaling, but its role in the innate immunity of urinary tract infection remains incompletely defined. In this study, we investigated its cellular distribution and mechanisms involved within the human bladder epithelial cells after LPS stimulation. Immunostaining, reverse transcription PCR and Western blot results showed that SIGIRR was constitutively expressed in the human bladder epithelial cell lines and was downregulated after LPS stimulation. To further define the role of SIGIRR, cells were transiently transfected with SIGIRR siRNA and stimulated with LPS. SIGIRR gene silencing augmented chemokine expression in response to LPS, as indicated by increased levels of IL-6 and IL-8 secretions in the supernatants compared with negative control siRNA. Furthermore, LPS tolerance, a protective mechanism against second LPS stimulation, was significantly reduced in SIGIRR siRNA transfected cells. Moreover, transient gene silencing augmented LPS-induced NF-κB and MAPK activation. In conclusion, our results suggest that SIGIRR plays an important role in the negative regulation of LPS response and tolerance in human bladder epithelial cells, possibly through its impact on TLR-mediated signaling.


Acute-onset chronic inflammatory demyelinating polyneuropathy with cranial nerves and respiratory tract involvement: A case report.
Sixteen percent of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely like acute idiopathic demyelinating polyneuropathy (AIDP) the demyelinating form of GBS, developing in <8 weeks 2. This entity is classified as acute-onset CIDP (A-CIDP) which presents overlapping clinical and electrophysiological findings with GBS during early stages of disease, but followed with a chronic course beyond 2 months. Also, those who have three or more treatment-related fluctuations (TRF) are included under this term. Distinguishing between acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) and acute idiopathic demyelinating polyneuropathy (AIDP) may be difficult during early stages but is crucial in order to guide treatment strategies without delay. These two forms share some overlapping clinical and electrophysiological findings, including some severe clinical features such as cranial nerve and respiratory tract involvement making the diagnosis of A-CIDP more difficult.


Cancer of unknown primary inside the gastric wall identified by endoscopic submucosal dissection.
We report the rare and interesting case of cancer of unknown primary (CUP) detected by endoscopic submucosal dissection (ESD). A 67-year-old man with a gastric adenoma was referred to our hospital for endoscopic treatment. Esophagogastroduodenoscopy revealed a 15-mm submucosal tumor (SMT) at the lesser curvature of the lower gastric body, near the gastric adenoma. Both lesions were resected by ESD. Pathological examination showed that the SMT was a poorly differentiated adenocarcinoma with lymphatic tissue. Additional surgical resection was performed, and the lymph nodes were found to have the same pathological findings as the SMT. These lesions were diagnosed as CUP because the obvious primary site was not detected with additional examination. The patient has been followed up for 24 months without recurrence.


Estimation of doses received in a dry-contaminated residential area in the Bryansk region, Russia, since the Chernobyl accident.
In nuclear preparedness, an essential requirement is the ability to adequately predict the likely consequences of a major accident situation. In this context it is very important to evaluate which contributions to dose are important, and which are not likely to have significance. As an example of this type of evaluation, a case study has been conducted to estimate the doses received over the first 17 years after the Chernobyl accident in a dry-contaminated residential area in the Bryansk region in Russia. Methodologies for estimation of doses received through nine different pathways, including contamination of streets, roofs, exterior walls, and landscape, are established, and best estimates are given for each of the dose contributions. Generally, contaminated soil areas were estimated to have given the highest dose contribution, but a number of other contributions to dose, e.g., from contaminated roofs and inhalation of contaminants during the passage of the contaminated plume, were of the same order of magnitude.


The basis for colored silver-protein complex formation in stained polyacrylamide gels.
Using a modified silver stain of Merril et al. [(1981) Science 211, 1437-1438] for staining polypeptides in sodium dodecyl sulfate-polyacrylamide gels, protein bands reproducibly stain different shades of blue, yellow, red, and gray. The procedure is highly temperature dependent, with optimal color formation at 42 degrees C. The procedure may be completed within 2 h. Color formation is due to silver ion complexes with charged amino acid side chains. The color of the silver-protein complex can be predicted if the amino acid sequence is known, although some exceptions are discussed. This provides another dimension to the characterization of proteins by gel electrophoresis.


A first account of the heterotrophic eukaryote Rabdiophrys Rainer from the fossil record and description of a new species from an ancient Eocene Arctic freshwater lake.
Rotosphaerids are unicellular, heterotrophic, eukayotic protists that have filopodia, an exterior covering consisting of highly ornamented siliceous scales, and are classified in the Rotosphaerida within the opistokont lineage. Given their appearance as relatively large spherical cells with protruding filopodia and a silica scale covering, they are often mistaken for centrohelid heliozoans. Even though these organisms are widely distributed in both marine and freshwater environments, many species are rarely reported, and none have been reported from the fossil record. We report extensive remains of a new species of Rabdiophrys, R. giraffensis, from an ancient waterbody that was situated near the Arctic Circle in northern Canada during the Eocene. The new species has both plate and spine scales that are similar in morphology, but significantly larger than its closest modern congeners, R. monopora and R. anulifera. The waterbody in which the new species grew and thrived is inferred to have been a moderately deep, circumneutral pond, with moderate concentrations of nutrients and dissolved humic material.


Feeding disorders in infants and children.
Feeding disorders are common in infants and children. Multiple interacting behavioral, anatomic, and functional factors all can impact on the feeding process, making the evaluation and treatment of pediatric disorders complex and challenging. Knowledge of the normal process of feeding and swallowing, a careful history, observation of the patient during a feeding session, and selected tests usually provide an understanding of the underlying cause of feeding difficulties. Treatment of underlying pathology and careful balancing of the risks and benefits of oral feeding underlie the selection of an optimal management strategy.


Phenology, productivity, and nutrient accumulation in the post-fire chaparral shrub Lotus scoparius.
Lotus scoparius is a drought-deciduous shrub which is an early and abundant colonizer of sites following fire in southern California chaparral. Productivity, seasonal nutrient concentrations, nutrient accumulations and phenology were studied in a 4-year-old burn site in Adenostoma chaparral in which L. scoparius had established 49% cover. Net aboveground primary production for L. scoparius was 105 g m-2 y-1; leaves accounted for 40% of the annual production. The true increment to biomass was only 17 g m-2 y-1; 83% of the net production entered the litter layer or standing dead components. In response to the Mediterranean climatic regime, most of the annual net production and plant activity occurred from May through June when photoperiod and temperatures were favorable and moisture was available. In July leaf abscission occurred in response to the summer drought conditions. Correlation and principal component analysis suggested consistent seasonal behavior in the foliar concentrations of N, P, Zn, and Mn. Nitrogen, P, K, and Zn were strongly reabsorbed from leaf tissues before abscission. Calcium, Mg, and Fe formed a second functional group of elements which increased in concentration throughout leaf maturation and which were not reabsorbed from senescing foliage. The seasonal pattern of nitrogen-containing organic compounds (chlorophylls and proteins) was most associated with the leaf phenology and water stress. The rapid growth of Lotus scoparius plays a role in conserving nutrients that might be lost through runoff and erosion after fire in the chaparral.