Combined mTORC1/mTORC2 inhibition blocks growth and induces catastrophic macropinocytosis in cancer cells.
The mammalian target of rapamycin (mTOR) pathway, which plays a critical role in regulating cellular growth and metabolism, is aberrantly regulated in the pathogenesis of a variety of neoplasms. Here we demonstrate that dual mTORC1/mTORC2 inhibitors OSI-027 and PP242 cause catastrophic macropinocytosis in rhabdomyosarcoma (RMS) cells and cancers of the skin, breast, lung, and cervix, whereas the effects are much less pronounced in immortalized human keratinocytes. Using RMS as a model, we characterize in detail the mechanism of macropinocytosis induction. Macropinosomes are distinct from endocytic vesicles and autophagosomes in that they are single-membrane bound vacuoles formed by projection, ruffling, and contraction of plasma membranes. They are positive for EEA-1 and LAMP-1 and contain watery fluid but not organelles. The vacuoles then merge and rupture, killing the cells. We confirmed the inhibition of mTORC1/mTORC2 as the underpinning mechanism for macropinocytosis. Exposure to rapamycin, an mTORC1 inhibitor, or mTORC2 knockdown alone had little or reduced effect relative to the combination. We further demonstrate that macropinocytosis depends on MKK4 activated by elevated reactive oxygen species. In a murine xenograft model, OSI-027 reduced RMS tumor growth. Molecular characterization of the residual tumors was consistent with the induction of macropinocytosis. Furthermore, relative to the control xenograft tumors, the residual tumors manifested reduced expression of cell proliferation markers and proteins that drive the epithelial mesenchymal transition. These data indicate a role of mTORC2 in regulating tumor growth by macropinocytosis and suggest that dual inhibitors could help block refractory or recurrent RMS and perhaps other neoplasms and other cancer as well.


In vitro approaches to analysis of transcription termination.
Transcription termination is an important event in the transcription cycle that has been exploited in a variety of genetic regulatory mechanisms. Analysis of transcription termination is greatly facilitated by in vitro approaches. We describe a basic protocol for analysis of transcription termination in vitro, and include descriptions of parameters that can be modified for specific types of experimental questions.


Synergistic effects on mesenchymal stem cell-based cartilage regeneration by chondrogenic preconditioning and mechanical stimulation.
Mesenchymal stem cells (MSCs) hold promising translational potential in cartilage regeneration. However, the efficacy of MSC-based tissue engineering is not satisfactory in the treatment of cartilage defect because of the inevitable cellular functional changes during ex vivo cell expansion. How to maintain the chondrogenic capacity of MSCs to improve their therapeutic outcomes remains an outstanding question. Bone marrow-derived MSCs were firstly primed in chondrogenic induction medium which was then replaced with normal growth medium to attain the manipulated cells (M-MSCs). Methacrylated hyaluronic acid (MeHA) was synthesized as a scaffold to encapsulate the cells. The MSC- or M-MSC-laden constructs were treated with dynamic compressive loading (DL) in a bioreactor or with free loading (FL) for 14 days. Afterwards, the constructs were implanted in nude mice or rat models of osteochondral defects to test their efficiency in cartilage regeneration or repair. Data showed that the resulting M-MSCs exhibited superior chondrogenic differentiation potential and survivability compared with untreated MSCs. More importantly, we found that DL significantly promoted neocartilage formation in the MeHA hydrogel encapsulated with M-MSCs after 30 days of implantation in nude mice. Furthermore, the constructs laden with M-MSCs after DL for 14 days significantly enhanced cartilage healing in a rat model of osteochondral defect. Findings from this study highlight the importance of maintaining chondrogenic potential of MSCs by in-vitro chondrogenic preconditioning and a synergistic effect of mechanical stimulation in cartilage engineering, which may shed light on the stem cell-based tissue engineering for cartilage repair.


Spinal dysraphism: a cross-sectional and retrospective multidisciplinary clinic-based study.
Spinal dysraphism is a common birth defect that causes different kinds of secondary impairments, including joint deformities, reduced mobility, and bowel/bladder dysfunction. Due to the diversity in terminology, cultural/ethnic differences, and medical policies, prior study results cannot be generalized to all populations. Therefore, we performed this study to define the characteristics of patients in Taiwan with spinal dysraphism. Patients diagnosed with a myelomeningocele or lipomyelomeningocele were identified from the database of our spinal dysraphism multidisciplinary clinic. A cross-sectional study was conducted by telephone interview and retrospective chart review. Clinical characteristics, such as neurologic level, orthopedic deformities, assistive device use, and level of ambulation, were collected. Spearman's correlation (r) tests were performed between ambulation or neurologic level and other variables. Seventy-eight subjects were included in the current study. Subjects with myelomeningoceles had more severe neurologic involvement, poorer ambulation outcome, and higher rates of orthopedic deformities, assistive device use, lower hand function, and bowel/bladder dysfunction. The correlation test revealed that the level of ambulation was negatively influenced by a higher neurologic level, a history of shunt placement, and various orthopedic deformities. Neurologic level also had widespread influence on history of shunt placement, orthopedic deformities, assistive device use, the need for additional assistive devices, aggressiveness of assistive devices, and bowel/bladder dysfunction. For patients with spinal dysraphism, the neurologic level is the most important prognostic factor for many other clinical characteristics, including ambulation status.


Clinical Usefulness of F-18 FDG PET/CT in Papillary Thyroid Cancer with Negative Radioiodine Scan and Elevated Thyroglobulin Level or Positive Anti-thyroglobulin Antibody.
Elevated thyroglobulin (Tg) levels, along with a negative radioiodine scan, present a clinical problem for the diagnosis of recurrence in papillary thyroid cancer (PTC) patients. The purpose of this study was to assess (1) the usefulness of (18)F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) for PTC patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-thyroglobulin antibody (TgAb), and (2) the effect of endogenous thyroid stimulating hormone (TSH) stimulation (ETS) on detecting recurrence in these circumstances. Eighty-four patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb under ETS were included. Correlation with clinicopathological features and recurrence, detectability of FDG PET/CT and cut-off value of serum Tg for recurrence in PTC patients with these circumstance were assessed. In addition, detectability of F-18 FDG PET/CT under ETS and suppression were compared. In Cox regression analysis, only serum Tg level was significantly associated with recurrence (P < 0.001, HR = 1.13; 95 % CI, 1.061-1.208). The cut-off level of Tg was 21.5 ng/mL (AUC, 0.919; P < 0.001) for discriminating the recurrence in the patients with positive PET/CT finding. The sensitivity, specificity, PPV, NPV, and accuracy of F-18 FDG PET/CT for detecting recurrence were 64 %, 94 %, 86 %, 81 %, and 83 %. In the analysis of F-18 FDG PET/CT under ETS, the sensitivity, specificity, PPV, NPV and accuracy was 64 %, 94 %, 88 %, 81 % and 83 %. Those under TSH suppression were 67 %, 92 %, 80 %, 85 % and 83 %. F-18 FDG PET/CT, although less sensitive, showed high specificity, PPV, NPV, and accuracy and therefore can be useful for the patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb. In addition, FDG PET/CT under ETS does not seem to have an additive role in detecting recurrence in these patients.


Nonapnea Sleep Disorders in Patients Younger than 65 Years Are Significantly Associated with CKD: A Nationwide Population-Based Study.
Nonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan. We conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio. The subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26-1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23-1.84; P<0.01), whereas patients with sleep disturbance had a 49%increased risk of subsequent CKD (95% CI = 1.19-1.87; P<0.001). Younger women (aged < 65 years) were at a high risk of CKD with NASD (adjusted hazard ratio, [HR] = 1.81; 95% CI = 1.35-2.40, p< 0.001). In this nationwide population-based cohort study, patients with NASD, particularly men of all ages and women aged younger than 65 years, were at high risk of CKD.


Iatrogenic fractures in ankylosing spondylitis--a report of two cases.
Two cases of intraoperative, iatrogenic cervical spine fractures in patients with ankylosing spondylitis are reported. To describe the uncommon complication of iatrogenic cervical spine fractures occurring during spine surgery in patients with ankylosing spondylitis. To our knowledge, this is the first report on this rare complication. A 39-year-old patient (1) with ankylosing spondylitis was operated on for cervical stenosis due to C1/2 anterolisthesis. Fifteen hours postoperatively, he developed acute quadriplegia. MRI revealed a fracture/dislocation of C6 on C7 and compression of the spinal cord at this level. Revision was performed with decompression and instrumentation from the occiput to T3. A 55-year-old patient (2) with ankylosing spondylitis and thoracic hyperkyphosis underwent a correction procedure consisting of costotransversectomy, anterior cage implantation at T8/9, and posterior instrumentation from T4 to L1. Halo traction was temporarily applied for correction. At the end of the operation, with the patient still under anesthesia, increased mobility of the cervical spine was noticed. Emergent MRI revealed a fracture of the anterior structures of C6/7. Posterior instrumentation from C5 to T1 was then performed. Quadriplegia persisted in patient 1 until his death secondary to further complications. Patient 2 was mobilized without any neurologic deficits. The fracture healed in good alignment. Iatrogenic fractures of the cervical spine during surgery in ankylosing spondylitis patients are a rare but potentially severe complication. Early diagnosis and therapy are necessary before dislocation, cord compression, and subsequent neurologic impairment occur.


Genetic transformation of Lactobacillus casei by electroporation.
Lactobacillus casei IAM1045 was transformed with a plasmid pAM beta 1-1, a tra deleted derivative of pAM beta 1, by electroporation. Effective transformation was achieved in electroporation buffers of a wide range of pH values, and in all phases of cell growth tested, with highest frequency in the early log phase. Polyethylene glycol increased the transformation frequency, whereas divalent cations such as Mg2+, Ca2+ and Mn2+ at 0.25 mM decreased the frequency by 2 to 3 orders. Highly efficient transformation of approximately 10(-4)/viable cell was achieved under optimal conditions. A plasmid harboring the trpD, C, F, B and A genes from L casei RNL7 was introduced by electroporation into tryptophan auxotrophic L casei JCM1053. The resulting transformant was found to express the trp genes introduced.


Extended polysialic acid chains (n greater than 55) in glycoproteins from human neuroblastoma cells.
Polysialic acid-containing glycoproteins consisting of extended chains of at least 55 sialyl residues (DP55, where DP represents degree of polymerization) are expressed on human neuroblastoma cells, CHP-134. The strategy used for detecting these unique carbohydrate structures was based on the use of two highly specific prokaryotic-derived enzyme systems and an anti-polysialosyl antibody (H.46). These probes were developed for the detection of polysialic acid on neural cell adhesion molecules (Troy, F. A., Hallenbeck, P. C., McCoy, R. D., and Vimr, E. R. (1987) Methods Enzymol. 138, 169-185). Proof for the presence of long chain multimers of sialic acid was based on two types of experiments which utilized: 1) a glycopeptide fraction of CHP-134 cells, labeled metabolically with D-[3H]GlcN and 2) a membrane fraction from CHP-134 cells which served as an exogenous acceptor of [14C] NeuNAc residues in an Escherichia coli K1 sialyltransferase assay. In vitro, this enzyme CMP-NeuNAc:poly-alpha-2,8-sialosyl sialyltransferase catalyzes the transfer of [14C]NeuNAc from CMP-[14C]NeuNAc to exogenous acceptors containing at least 3 sialyl residues. In the first series of experiments, endo-N-acetylneuraminidase (Endo-N), a bacteriophage-derived enzyme specific for hydrolyzing poly-alpha-2,8-sialosyl chains containing a minimum of 5 sialyl residues was used. Limit Endo-N digestion of the 3H-glycopeptides from the [3H] GlcN-labeled cells released short [3H]sialyl oligomers [( 3H]DP1-6) which were degraded to [3H]NeuNAc by exosialidase. Partial Endo-N digestion released a series of [3H]sialyl oligomers extending up to DP55. The longer (DP20-55) and intermediate sized (DP10-20) oligomers were isolated and converted to short oligomers ((3H]DP1-6) by retreating with Endo-N, thus confirming their identity as homo-oligomers of alpha-2,8-linked [3H]NeuNAc residues. In the second series of experiments, a membrane fraction of CHP-134 cells was radiolabeled in vitro with [14C]NeuNAc by E. coli K1 sialyltransferase. The membrane fraction had a major portion of radioactivity that was high Mr and polydisperse (Mr 100,000-250,000) as demonstrated in sodium dodecyl sulfate-polyacrylamide gels. Using Western blotting, pre-existing material of similar size was shown to react with antibody H.46.(ABSTRACT TRUNCATED AT 400 WORDS)


Hemispheric processing of affective and linguistic intonation contours in normal subjects.
In a previous study of the comprehension of linguistic prosody in brain-damaged subjects, S. R. Grant and W. O. Dingwall (1984. The role of the right hemisphere in processing linguistic prosody, presentation at the Academy of Aphasia, 1984) demonstrated that the right hemisphere (RH) of nonaphasic patients plays a prominent role in the processing of stress and intonation. The present study examines laterality for affective and linguistic prosody using the dichotic listening paradigm. Both types of prosody elicited a significant left ear advantage. This advantage was more pronounced for affective than for linguistic prosody. These findings strongly support previously documented evidence of RH involvement in the processing of affective prosody (R. G. Ley & M. P. Bryden, 1982. A dissociation of right and left hemispheric effects for recognizing emotional tone and verbal content, Brain and Cognition, 1, 3-9). They also provide support for the previously mentioned demonstration of RH involvement in the processing of linguistic intonation (S. Blumstein & W. E. Cooper, 1974. Hemispheric processing of intonation contours, Cortex, 10, 146-158; Grant & Dingwall, 1984).


Quetiapine and classical mood stabilizers in the long-term treatment of Bipolar Disorder: a 4-year follow-up naturalistic study.
The aim of this naturalistic study was to compare the effectiveness of quetiapine and classical mood stabilizers, as mono- or combination therapy, in the long-term treatment of Bipolar Disorder (BD). 232 DSM-IV BD I (n=91) or BD II (n=141) patients, treated and followed up for four years, were studied. Mood stabilizers were chosen by the treating psychiatrists on the basis of their clinical judgement. The sample was subdivided into 6 treatment groups: quetiapine (n=41), lithium (n=39), sodium valproate (n=73), lamotrigine (n=31), quetiapine plus lithium (n=25), and quetiapine plus sodium valproate (n=23). Throughout the 4-year follow-up period patients were assessed monthly, or whenever a recurrence occurred, by the administration of HAMD-21 and of the YMRS. Primary outcome measures were the duration of euthymia and the cumulative proportion of subjects who maintained euthymia. Kaplan-Meier survival analyses were done to tabulate and compare the differences in survival distributions across the different treatment groups (Log-Rank Mantel-Cox test). The combined treatments with quetiapine plus lithium or sodium valproate were more effective overall in maintaining euthymia, (percentages of patients who maintained euthymia: 29.3% for quetiapine, 46.2% for lithium, 32.9% for sodium valproate, 41.9% lamotrigine, 80% for quetiapine plus lithium, and 78.3% for quetiapine plus sodium valproate). In addition, quetiapine monotherapy was as effective as lithium monotherapy or combination treatment with lithium or sodium valproate in preventing the recurrence of major depressive episodes. The main limitations of the study are the lack of randomized, controlled conditions and the low doses of quetiapine used. If the results from this study will be replicated, there will be important implications for the use of quetiapine in the long-term treatment of BD.


Stochastic state estimation for neural networks with distributed delays and Markovian jump.
This paper investigates the problem of state estimation for Markovian jump Hopfield neural networks (MJHNNs) with discrete and distributed delays. The MJHNN model, whose neuron activation function and nonlinear perturbation of the measurement equation satisfy sector-bounded conditions, is first considered and it is more general than those models studied in the literature. An estimator that guarantees the mean-square exponential stability of the corresponding error state system is designed. Moreover, a mean-square exponential stability condition for MJHNNs with delays is presented. The results are dependent upon both discrete and distributed delays. More importantly, all of the model transformations, cross-terms bounding techniques and free additional matrix variables are avoided in the derivation, so the results obtained have less conservatism and simpler formulations than the existing ones. Numerical examples are given which demonstrate the validity of the theoretical results.


Neural crest stem cells: discovery, properties and potential for therapy.
Neural crest (NC) cells are a migratory cell population synonymous with vertebrate evolution. They generate a wide variety of cell and tissue types during embryonic and adult development including cartilage and bone, connective tissue, pigment and endocrine cells as well as neurons and glia amongst many others. Such incredible lineage potential combined with a limited capacity for self-renewal, which persists even into adult life, demonstrates that NC cells bear the key hallmarks of stem and progenitor cells. In this review, we describe the identification, characterization and isolation of NC stem and progenitor cells from different tissues in both embryo and adult organisms. We discuss their specific properties and their potential application in cell-based tissue and disease-specific repair.


The blood labyrinthine barrier in the human normal and Meniere's disease macula utricle.
The ultrastructural organization of the blood labyrinthine barrier (BLB) was investigated in the human vestibular endorgan, the utricular macula, using postmortem specimens from individuals with documented normal auditory and vestibular function and surgical specimens from patients with intractable Meniere's disease. Transmission electron microscopic analysis of capillaries located in the normal human utricular stroma showed vascular endothelial cells with few pinocytotic vesicles, covered by a smooth and uniform basement membrane surrounded by pericyte processes. Meniere's disease specimens revealed differential ultrastructural pathological changes in the cellular elements of the microvasculature. With moderate degeneration of the BLB, there were numerous vesicles within the vascular endothelial cells (VECs), with increased numbers at the abluminal face, pericyte process detachment and disruption of the perivascular basement membrane surrounding the VECs. With severe degeneration of the BLB, there was severe vacuolization or frank apparent necrosis of VECs and loss of subcellular organelles. A higher severity of BLB degenerative changes was associated with a higher degree of basement membrane thickening and edematous changes within the vestibular stroma. This study presents the first ultrastructural analysis of the capillaries constituting the BLB in the human vestibular macula utricle from normal and Meniere's disease.


Clinical 'pearls' of maternal critical care Part 2: sickle-cell disease in pregnancy.
The current review outlines the challenges in managing pregnant women with sickle-cell anemia, who are at risk of becoming critically ill during pregnancy. Sickle obstetric patients pose unique challenges to the anesthetist and intensivist. We discuss the role of prophylactic transfusions for specific indications like acute anemia and twin pregnancies. The management and prevention of vaso-occlusive crises and chest crisis are also outlined. The role of the multidisciplinary team cannot be overstated.Massive obstetric hemorrhage in this population is difficult, and unique considerations such as cell-saver technology and tranexamic acid usage are discussed. Secondary complications such as pulmonary hypertension and stroke are also considered, with a summary of the latest treatment guidelines. This is a challenging cohort of pregnant patients who have a significantly increased morbidity and mortality. This review aims to aid management of these patients on the labor ward for both obstetric anesthetists and intensivists.


Reduced magnetic mismatch negativity: a shared deficit in psychosis and related risk.
Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR). Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC). The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP. Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.


Osteopontin drives retinal ganglion cell resiliency in glaucomatous optic neuropathy.
Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, αRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found an ectopic neuronal expression of Osteopontin (Spp1) in other RGCs subject to glaucomatous conditions. This contrasted with the Spp1 downregulation subject to axotomy. αRGC-specific Spp1 elimination led to significant αRGC loss, diminishing their resiliency. Spp1 overexpression led to robust neuroprotection of susceptible RGC subclasses under glaucomatous conditions. In contrast, Spp1 overexpression did not significantly protect RGCs subject to axotomy. Additionally, SPP1 marked adult human RGC subsets with large somata and SPP1 expression in the aqueous humor correlated with glaucoma severity. Our study reveals Spp1's role in mediating neuronal resiliency in glaucoma.


Defining the relative contribution of health care environmental components to patient outcomes in the model of 30-day readmission after coronary artery bypass graft (CABG).
Patient outcomes following health care interventions may be dependent on a variety of factors: patient, surgeon, hospital, information technology, and temporal, cultural, and socioeconomic factors, among others. In this study, we characterize the relative contribution of each of these factors using a model of 30-day readmission following coronary artery bypass graft. The Healthcare Cost and Utilization Project, the American Hospital Association Annual Health Survey Databases, the Healthcare Information and Management Systems Society, and the Distressed Communities Index from 2010 to 2013 were linked for Florida, Iowa, Massachusetts, Maryland, New York, and Washington. Logistic regression, random forest, decision tree, gradient boosting, k-nearest-neighbors classification, and XGBoost tree models were implemented. Modeling results were compared on the basis of predictive accuracy, sensitivity, specificity, and area under the curve. Decision tree performed best and was selected for further analysis. A gradient-boosted model was used to quantify factor contribution. The model had 45,352 patients, 54,096 admissions, and a 16.2% 30-day readmission rate after coronary artery bypass graft. The top 10 predictors were disposition at discharge, number of chronic conditions, total procedures, median household income, adults without high school diplomas, primary payer method, Agency for Healthcare Research and Quality comorbidity: renal failure, patient location (urban-rural), admission type, and age categories. The top 3 socioeconomic predictors were estimated state median household income, adults without high school diplomas, and patient location (urban versus rural designation). The relative contribution of patient/temporal, socioeconomic, hospital information technology, and hospital factors to readmission is 83.45%, 5.71%, 6.34%, and 4.31%, respectively. In this model, the contribution of socioeconomic factors is substantive but lags significantly behind patient/temporal factors. With ever increasing availability of data, identification of contributors to patient outcomes within the overall health care macroenvironment will allow prioritization of interventions.


On reduced size in spiders from marginal habitats.
Four heathland spider species, Agroeca proxima, Centromerita concinna, Theridion simile, and Philodromus histrio, were studied in the Kalmthout National Nature Reserve in northern Belgium. They were caught by pitfall trapping or sweeping in different Calluna heath plots where the vegetation was in varying stages of development after being burnt, mowed, or grazed. Each species proved to thrive in a different plot, its numbers being greater and its size larger (cephalothorax width) in that plot. For the first two species positive correlations were found, for males as well as for females, between average size and numbers caught during a complete year cycle in a particular habitat.In contrast to non-predators, which are smaller when their populations are denser, spiders show a functional response that explains their increase in size with increasing density. It is suggested that in this respect a fundamental difference exists between predators and non-predators.


A systematic selection of the non-aqueous phase in a bacterial two liquid phase bioreactor treating alpha-pinene.
A systematic evaluation of the selection criteria of non-aqueous phases in two liquid phase bioreactors (TLPBs), also named two-phase partitioning bioreactors (TPPBs), was carried out using the biodegradation of alpha-pinene by Pseudomonas fluorescens NCIMB 11671 as a model process. A preliminary solvent screening was thus carried out among the most common non-aqueous phases reported in literature for volatile organic contaminants biodegradation in TLPBs: silicon oil, paraffin oil, hexadecane, diethyl sebacate, dibutyl-phtalate, FC 40, 1,1,1,3,5,5,5-heptamethyltrisiloxane (HMS), and 2,2,4,4,6,8,8-heptamethylnonane (HMN). FC 40, silicone oil, HMS, and HMN were first selected based on its biocompatibility, resistance to microbial attack, and alpha-pinene mass transport characteristics. FC 40, HMS, HMN, and silicone oil at 10% (v/v) enhanced alpha-pinene mass transport from the gas to the liquid phase by a factor of 3.8, 14.8, 11.4, and 8.6, respectively, compared to a single-phase aqueous system. FC 40 and HMN were finally compared for their ability to enhance alpha-pinene biodegradation in a mechanically agitated bioreactor. The use of FC 40 or HMN (both at 10% v/v) sustained non-steady state removal efficiencies (RE) and elimination capacities (EC) approximately 7 and 12 times higher than those achieved in the system without an organic phase, respectively. In addition, preliminary results showed that P fluorescens could uptake and mineralize alpha-pinene directly from the non aqueous phase.


Whole genome sequence of an uncommon G9P[4] species A rotavirus containing DS-1-like (genotype 2) genes in Japan.
Species A rotaviruses (RVAs) have been recognized as one of the leading causes of acute gastroenteritis in humans worldwide. Here, the complete coding sequences of 11 RNA segments of an uncommon G9P[4] RVA strain, which was detected in feces of a diarrheal child in Japan, were determined by next-generation sequencing technology. Its genomic constellation, VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, was determined as G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. This work reports the complete coding sequences of a G9P[4] RVA strain containing DS-1-like (genotype 2) genes that was isolated in Japan in 2013.


Nicotinamide: a potential addition to the anti-psoriatic weaponry.
Psoriasis is an inflammatory disorder characterized by a T helper type 1 cell cytokine pattern. Increased expression of adhesion molecules, prominent neutrophil accumulation, and increased production of nitric oxide are characteristics of this disorder. Moreover, histamine and proteases are supposed to participate in the pathogenesis of psoriasis. Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) that, through enhancement of nuclear kappa B-mediated transcription, plays a pivotal role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Through interaction with CD38 and inhibition of IL-1, IL-12, and TNF-alpha production, nicotinamide produces a mild TH2 bias. Nicotinamide is a potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis and mast cell histamine release. It inhibits nitric oxide synthase mRNA induction and suppresses antigen-induced lymphocyte transformation. Nicotinamide increases the biosynthesis of ceramides, which upon degradation produce sphingosine. Sphingosine inhibits protein kinase C (PKC) and decreases basal cell proliferation dependent on PKC. Taken together, it can be reasoned that nicotinamide could be a useful addition to anti-psoriatic armamentarium. The combination of nicotinamide and thalidomide or methotrexate provided a powerful synergistic inhibition of murine collagen-induced arthritis. Nicotinamide decreased the methotrexate-induced hepatotoxicity. The above combinations may prove to have a powerful anti-psoriatic effect as well. As PARP inhibitors could exert anti-retroviral effect, nicotinamide could also be of special value in the treatment of HIV-infected psoriatics.


Evaluation of the in vivo genotoxicity of Allura Red AC (Food Red No. 40).
Allura Red AC (Food Red No. 40) is a red azo dye that is used for food coloring in beverage and confectionary products. However, its genotoxic properties remain controversial. To clarify the in vivo genotoxicity, we treated mice with Allura Red AC and investigated the induction of DNA damage (liver, glandular stomach), clastogenicity/anuegenicity (bone marrow), and mutagenicity (liver, glandular stomach) using Comet assays, micronucleus tests, and transgenic gene mutation assays, respectively. All studies were conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guideline. Although Allura Red AC was administered up to the maximum doses recommended by the OECD guideline, no genotoxic effect was observed in any of the genotoxic endpoints. These data clearly show no evidence of in vivo genotoxic potential of Allura Red AC administered up to the maximum doses in mice.


Analysis of targeted somatic mutations in pleomorphic carcinoma of the lung using next-generation sequencing technique.
Pleomorphic carcinoma (PC) of the lung is a rare type of lung cancer with aggressive characteristics and a poor prognosis. Because it is rare, the molecular characteristics of PC remain unclear. A gene mutation analysis was performed using next-generation sequencing (NGS) in patients with PC of the lung who had undergone surgical resection. A total of nine patients were enrolled in the study. All the patients were male and eight had a history of smoking. Eight tumors contained spindle cells and three contained giant cells. Mutations considered significant were found in eight of the nine patients: in TP53 in five patients, in MET in two patients, and in ALK, ERBB2, PIK3CA, APC, NF1, and CDKN2A in one patient each. No EGFR mutation was detected in our analysis. Co-mutations were detected in three patients: TP53 with MET and NF1, TP53 with ERBB2, and PIK3CA with CDKN2A. TP53 mutations were detected most frequently in PC of the lung with NGS analysis. Different co-mutations were seen in several specimens. Significant findings of the study This study demonstrates that mutations in the TP53 gene are frequently found and co-mutations are sometimes found in pleomorphic carcinoma of the lung using genomic profiling analysis. What this study adds Our results will help to analogize the genetic characteristics and potential target of molecular-targeted agents of pleomorphic carcinoma of the lung.


Experimental data on the mechanical properties of individual caobilla wood cubes used on control pile systems.
This article contains data on the mechanical properties of individual cubes of caobilla wood (Swietenia humilis Zucc.) used as deformable cell of control piles, which are a special foundation system used to regulate both loads and settlements in buildings. The data were obtained from stress-controlled compression tests considering wooden cubes with different volumetric weight, moisture conditions and fiber orientation. In addition, the correlation of yield stress versus volumetric weight of caobilla wood cubes is presented. The mean values and standard deviations of volumetric weight and yield stress of the tested wooden cubes under dry and wet states are also presented.


Doublecortin is preferentially expressed in invasive human brain tumors.
Doublecortin (DCX) is required for neuroblastic migration during the development of the cerebral cortex. DCX is a microtubule-associated protein that plays a role in cellular motility. These facts led us to hypothesize that DCX is increased in invasive brain tumors. DCX expression was assessed in 69 paraffin-embedded brain tumors of neuroepithelial origin. In addition, mouse brain sections of the subventricular zone and dentate gyrus were used as positive controls for immunostaining, and specificity of antibody staining was demonstrated by peptide neutralization. DCX was highly expressed in both high-grade invasive tumors (glioblastoma, n=11; anaplastic astrocytoma/oligoastrocytoma, n=7; and medulloblastoma/PNET, n=6) and low-grade invasive tumors (oligodendroglioma, n=3; and astrocytoma/oligoastrocytoma, n=5). However, DCX was less intensely expressed in the circumscribed group of tumors (pilocytic astrocytoma, n=6; ependymoma/subependymoma, n=7; dysembryoplastic neuroepithelial tumor, n=4; ganglioglioma, n=2; meningioma, n=9; and schwannoma, n=9). By the Cochran-Mantel-Haenszel statistical test, the circumscribed group was significantly different from both the high-grade invasive group (P<0.0001) and the low-grade invasive group (P<0.0001). We conclude that DCX is preferentially expressed in invasive brain tumors. In addition, DCX immunostaining was stronger at the margin of the tumor than at the center. For a subset of these tumors, we also detected DCX mRNA and protein by Northern and Western blotting. DCX mRNA and protein was detected in glioma cell lines by Northern blotting, immunofluorescence microscopy and Western blotting. Collectively, the immunohistochemistry, Western blots and Northern blots conclusively demonstrate expression of DCX by human brain tumors.


Diagnosis of periorbital gas on ocular ultrasound after facial trauma.
Ocular trauma can occur from isolated facial trauma or in major blunt trauma such as motor vehicle accidents or falls. Despite the etiology of the injury, a thorough evaluation is important but may often be difficult if severe swelling is present. Recently, emergency ultrasound has seen the use of ocular ultrasound to evaluate visual changes and trauma. Literature suggests that unsuspected and difficult to diagnose pathology may be easily detected on ultrasound of the orbit. We present 3 cases of isolated facial trauma in which routine evaluation with ocular ultrasound led to the discovery of periorbital air with one patient having air insufflating the upper lid of the affected side.


From syntactic-semantic tagging to knowledge discovery in medical texts.
In the GALEN project, the syntactic-semantic tagger MultiTALE is upgraded to extract knowledge from natural language surgical procedure expressions. In this paper, we describe the methodology applied and show that out of a randomly selected sample of such expressions coming from the procedure axis of Snomed International, 81% could be analysed correctly. The problems encountered fall in three different categories: unusual grammatical configurations within the Snomed terms, insufficient domain knowledge and different categorisation of concepts and semantic links in the domain and linguistic models used. It is concluded that the Multi-TALE system can be used to attach meaning to words that not have been encountered previously, but that an interface ontology mediating between domain models and linguistic models is needed to arrive at a higher level of independence from both particular languages and from particular domains.


[The prevention of thromboembolic disease by physical means. Use of an external electric stimulator. Initial results obtained during hip surgery].
The authors report their preliminary results using an external electric stimulator in hip surgery. One group received electric stimulation and the control group did not. There were 75 patients in each group and each patient underwent a total hip replacement. In the non-stimulated group, there were 15 DVT's (20%) and in the stimulated group 3 (4%). These results are discussed.


Blood loss is a stronger predictor of iron status in men than C282Y heterozygosity or diet.
To determine the relative importance of HFE gene, diet, lifestyle, and blood loss characteristics for predicting iron status in a sample of men aged 40 years or over. Iron status (serum ferritin, transferrin saturation, soluble transferrin receptor) was measured in 44 C282Y heterozygote and 85 age- and BMI-matched wildtype men aged 40 years or over. Dietary intake of iron (total, heme and non-heme), and components known to influence iron bioavailability, was determined using a validated Meal-Based Intake Assessment Tool. Information on lifestyle and blood loss was obtained by questionnaire. Height and weight were measured to determine Quetelet's body mass index. Linear mixed models were used to determine the extent to which these variables predicted iron status. C282Y heterozygosity was associated with 17% higher transferrin saturation (95% CI: 6%, 29%) but no difference in serum ferritin or soluble transferrin receptor concentrations. Blood donation was negatively associated with transferrin saturation (-13% (- 3%, -22%)) and serum ferritin (-58% (-44%, -68%)), and had a marginally significant positive association with soluble transferrin receptor concentration. Self-reported fecal blood loss was negatively associated with serum ferritin concentration (-35% (-54%, -7%)). Alcohol was the only dietary variable associated with iron status and was associated with all three of the iron status indices. Serum ferritin concentration was positively associated with body mass index (10% per unit increase (6%, 15%)). Blood loss was a stronger predictor of iron status than either C282Y heterozygosity or diet in this population of men aged 40 years and over.


Malignant histiocytoma of the rectum: report of a case.
A case of malignant histiocytoma of the rectum has been described. We believe this is the first report of a case of this type. Other relevant reports are reviewed.


Epidemiologic studies of vitamins and cancer of the lung, esophagus, and cervix.
Epidemiologic studies of the relationships between vitamins and 3 types of cancer are reviewed. First, the widely reported association between vitamin A and beta-carotene and risk of lung cancer is considered. In a large population-based case-control study of lung cancer among white males in New Jersey, increased intake of vegetables, dark green vegetables, dark yellow-orange vegetables, and carotenoids were each associated with reduced risk, but intake of retinol or total vitamin A was not related. The protective effect of vegetables was limited to current and recent cigarette smokers, which suggests that vegetable intake prevents a late-stage event in carcinogenesis. Consumption of dark yellow-orange vegetables was consistently more predictive of reduced risk than either the total carotenoid index or consumption of any other food group, possible because of the high content of beta-carotene in this food group. The results and limitations of other epidemiologic studies of diet and lung cancer are reviewed. Second, the evolving relationship between multiple micronutrient deficiencies and esophageal cancer is discussed. In a death certificate-based case-control study of esophageal cancer in black males in Washington, D.C., several indicators of general nutritional status, including consumption of fresh or frozen meat and fish, dairy products and eggs, and fruit and vegetables, and the number of meals eaten per day, were inversely and independently correlated with the risk of esophageal cancer. Estimates of intake of micronutrients, such as carotenoids, vitamin C, thiamin, and riboflavin, were less strongly associated with reduced risk than were the broad food groups that provide most of each micronutrient. Thus no single micronutrient deficiency was identified. Other studies suggest that generally poor nutrition may partially explain the susceptibility of urban black men to esophageal cancer. Finally, the postulated association between low folacin levels and risk of cervical cancer is examined. Among women who use oral contraceptives, serum and red blood cell folacin levels were reported to be lower among those with cervical dysplasia. In a clinical trial involving oral contraceptive users, cervical dysplasia gradually decreased in the group supplemented with oral folate but remained unchanged in the group given the placebo. Other epidemiologic studies of diet and cervical cancer are discussed.


Antidepressant-drug interactions are potentially but rarely clinically significant.
The salient pharmacologic features of the selective serotonin reuptake inhibitors (SSRIs) discovered in the late 1980s included an in vitro ability to inhibit various cytochrome P450 enzymes (CYPs). Differences in potency among the SSRIs for CYP inhibition formed the basis of a marketing focus based largely on predictions of in vivo pharmacokinetic drug interactions from in vitro data, conclusions derived from case reports, and the extrapolation of the results of pharmacokinetic studies conducted in healthy volunteers to patients. Subsequently introduced antidepressants have undergone a similar post hoc scrutiny for potential drug-drug interactions. Concern for the untoward consequences of drug interactions led the FDA to publish guidance for the pharmaceutical industry in 1997 recommending that in vitro metabolic studies be conducted early in the drug development process to evaluate inhibitory properties toward the major CYPs. However, the prevalence of clinically significant enzyme inhibition interactions occurring during antidepressant treatment remains poorly defined despite millions of exposures. Although lack of evidence does not equate to evidence of absence, sparse epidemiological and post-marketing surveillance data do not substantiate a conclusion that widespread morbidity results from antidepressant-induced drug interactions. This commentary discusses points of uncertainty and controversy in the field of drug interactions, notes areas where inadequate data exist, and suggests explanations for a low prevalence of serious interactions. The conclusion is drawn that drug interactions from CYP inhibition caused by the newer antidepressants are potentially, but rarely, clinically significant.


Neurologic assessment skills for the acute medical surgical nurse.
Practical and efficient neurologic assessment skills are vital for acute care nurses. During an acute neurologic event, the nurse needs a focused assessment of the pertinent history and symptom analysis and an immediate head-to-toe survey, eliciting any abnormal signs to identify and correctly report the medical problem. When a patient requires routine monitoring of neurologic signs, the nurse's role includes a neurologic assessment, collecting and assimilating that data, interpreting the patient problem, notifying the physician when appropriate, and documenting that data. This article presents an overview of a staff nurse's neurologic assessment, explains common neurologic tests performed at the bedside, identifies an efficient way to perform the assessment, and indicates what to include and document when "neuro signs" are ordered.


Effect of cough on heart rate and blood pressure in patients with "cough syncope".
"Cough syncope" is uncommon, and its mechanism remains controversial. This study evaluated susceptibility to cough-triggered neural reflex hypotension-bradycardia among cough syncope patients. We hypothesized that individuals with cough syncope would manifest not only more profound cough-triggered hypotension than do other fainters but also an inappropriate chronotropic response accompanying cough-induced hypotension, thereby supporting the notion that a neural reflex hypotension-bradycardia contributes to the condition. Three patient groups were studied. Group 1 patients (n = 9) had "cough syncope." The remaining patients had recurrent faints of other causes: group 2 (n = 13) had a positive head-up tilt test, and group 3 (n = 18) had a negative tilt test. With cough, group 1 patients exhibited a greater drop in systolic pressure (-51 +/- 19.3 mmHg) than did either group 2 (-23 +/- 11.1 mmHg, P < .04) or group 3 patients (-28 +/- 12.4 mmHg, P < .05). Recovery time to normalization of systolic pressure was greater in group 1 (25 +/- 9.1 seconds) than in group 2 or 3 (8 +/- 2.7 seconds and 9 +/- 6.1 seconds, respectively, both P < .01 vs group 1). The expected positive chronotropic response accompanying cough-induced hypotension was diminished in group 1 patients (0.16 +/- 0.21 bpm/mmHg) compared with that in either group 2 (0.74 +/- 0.60 bpm/mmHg, P < .05 vs group 1) or group 3 (0.33 +/- 0.15 bpm/mmHg, P = .06 vs group 1). Cough syncope patients not only exhibit more pronounced hypotension in response to cough than other fainters, but they also manifest an inappropriate cough-triggered blood pressure-heart rate relationship. These findings argue in favor of the importance of a neurally mediated reflex contribution to symptomatic hypotension in cough syncope.


Salvage treatment for severe upper gastrointestinal bleeding caused by Mallory-Weiss syndrome and myocardial depression after acute myocardial infarction.
Complications related to upper gastrointestinal bleeding (UGIB) after acute myocardial infarction (AMI) and hyperkalemia-induced myocardial depression (MD) are not rare. However, severe UGIB caused by Mallory-Weiss syndrome (MWS) after AMI in patients with hyperkalemia-induced MD after red blood cell (RBC) transfusion has not previously been reported. We report a case of a 44-year-old male patient, presenting with AMI of the anterior wall, who underwent percutaneous coronary intervention (PCI). The patient developed two episodes of hematemesis within 12 h post-operation, the second of which was massive (about 2000 ml). Emergency endoscopy revealed MWS, thus titanium clips were simultaneously placed to stop the bleeding. In addition, the patient received RBC transfusion. One hour later, his blood pressure (BP) suddenly dropped to 63/35 mmHg, with arterial blood gas analyses revealing hyperkalemia. He was treated with bicarbonate, insulin and calcium gluconate to correct hyperkalemia, which lowered serum potassium and returned his cardiac function to normal. This case shows a dilemma in treatment of upper gastrointestinal bleeding caused by MWS after coronary stent implantation, suggesting the need for timely hemostatic endoscopic procedures when this happens. Clinicians are advised to monitor patients' vital signs in order to prevent serious damage caused by transfusion-related complications. This is because complex and uncommon complications may begin with such common symptoms, which can rapidly deteriorate to life-threatening situations if not timely treated.


An experimental investigation into the use of implanted thermocouples and differential thermometry as monitors for microvascular anastomoses.
It has been suggested that direct monitoring of arterial temperature using implanted thermocouples, may have value as a clinical postoperative monitor for vascularized free tissue transfers, including those with no visible surfaces. This study evaluated the technique in experimental animals, using simple, inexpensive equipment. Mean arterial differential temperature changes, with ipsilateral (n = 20) and contralateral (n = 21) references, of 0.6 degrees C and 0.5 degrees C respectively, reliably indicated occlusion of the superficial femoral artery in situ. In epigastric island flaps, arterial occlusion (n = 24) produced mean arterial temperature changes of 0.5 degrees C, but changes after venous occlusion were not significantly greater than unoccluded base line fluctuation. Venous differential temperature did not change significantly after either arterial or venous occlusion. In six epigastric free flaps, success or failure could not be distinguished, as the wide variation in measurements in the four successful flaps overlapped the recordings in the two which failed. It was shown that the nearer to the body core, the less the temperature difference between arterial wall and periarterial tissue. Occlusion of deeply sited arteries produced little or no change in arterial temperature. In view of these findings and because of the invasive nature of the technique, the authors did not pursue it clinically.


[Prognostication of sequelae in Bell's palsy].
Four symptoms of sequelae (abnormal synkinesis, facial spasm, contracture, and crocodile's tear) which persisted or appeared after 6 months from onset were examined with 351 patients with Bell's palsy. The incidence of sequelae were 2% in the group having score (May-Hosomi's modified method, 90 points method) over 40 points within 1 months after onset. Other hand, the incidence of sequelae were 15% in the group having score under 40 points at 1 weeks from onset, 30% in the group having score under 40 points at 2 weeks, 57% in the group having score under 40 points at 3 weeks, and 76% in the group having score under 40 points at 1 month. From these findings, it was seen that the prognostication with a high accuracy was possible by the score.


Circulating antigens in schistosomiasis: detection of 31/32-kDa proteins in sera from patients infected with Schistosoma japonicum, S. mansoni, S. haematobium, or S. intercalatum.
A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect 31/32-kDa schistosome proteins as circulating antigens in sera from schistosomiasis patients. A monoclonal antibody was used as a capture antibody and rabbit antiserum raised against purified 31/32-kDa proteins was the detecting antibody. Positive results were obtained with patients infected with Schistosoma japonicum (88%; n = 69), S. mansoni (80%; n = 56), S. haematobium (100%; n = 40), or S. intercalatum (94%; n = 65). Sera from uninfected Chinese and African individuals and from Chinese patients with trichinosis, cysticercosis, or paragonimiasis did not react in the assay. This ELISA appears to be valuable in diagnosing infections by all major human schistosome species.


Pregnancy outcomes in severe polyhydramnios: no increase in risk in patients needing amnioreduction for maternal pain or respiratory distress.
Polyhydramnios is a common complication of fetal malformations and has been described to have high risk of pregnancy complications such as prematurity and placental abruption. In a subgroup of women severe polyhydramnios may lead to maternal dyspnea or untreatable pain, and amnioreduction is the procedure indicated to relieve those symptoms. There is a lack of information concerning the increase in the risk for the pregnancy when the procedure is indicated. Therefore, this study sought to evaluate the risk of complications in pregnancies with severe polyhydramnios that needed amnioreduction in relation to the basal risk for the pregnancy of having polyhydramnios without the need for the procedure. Patients with singleton pregnancies and severe polyhydramnios followed in our fetal medicine center were evaluated retrospectively. Pregnancy complications (prematurity rate, fetal death, premature rupture of membranes, placental abruption and chorioamnionitis) were studied in the group of patients needing the procedure and their risk was compared to the risk of having a pregnancy with severe polyhydramnios but with no need for the procedure. One hundred and thirty-five patients were evaluated. Forty-four patients (32.6%) needed amnioreduction. There was no increase in the risk of having complications when the procedure was needed OR = 1.4 (CI 0.46-1.26). Amnioreduction performed to relieve maternal symptoms did not statistically increase the risk of pregnancy complications with severe polyhydramnios in single pregnancies.


[Neodymium YAG laser therapy in dermatology].
Because of its optical characteristics, the Neodym-YAG laser is suitable for the treatment of benign, semi-malignant, and malignant skin tumors as well as deep vascular lesions. This kind of laser radiation can be applied rather easily and exactly and allows successful treatment of skin lesions especially in critical locations. We report on first experiences with this technique, which led to good functional and cosmetic results.


Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: a cross-sectional observational study of 565 consecutive patients.
To determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR. Pre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA. Of 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV-V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7-10.6, AUC = 0.759). Focal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV-V VUR and 76% with recurrent UTI had normal DMSA.


[Study on the status and quality of sleep-related influencing factors in medical college students].
To study the status and influencing factors on sleep quality in some medical college students. Stratified sampling, pittsburgh sleep quality index (PSQI), self-evaluation depression scale (SDS), self-evaluation anxiety scale (SAS) and self-developed questionnaire of influencing factors on the quality of sleep in medical college students were used. Cumulative odds logistic model was performed to analyze the related factors on the quality of sleep. 19.17 percent of the medical college students showed poor quality of sleep and the difference between genders was not statistically significant (P > 0.05). Statistically significant (P < 0.05) difference was seen among different years of students and correlation was found between sleep quality and depression or anxiety (P < 0.0001). Factors influencing on the quality of sleep in medical college students would include: worry of sleep, irregular work/rest, worry on examination, stress, relationship with classmates, self-evaluated health condition, environments of the dormitory and late to bed. Influencing factors were identified and comprehensive measures should be taken to improve the quality of sleep.


Increased sensitivity using real-time dPCR for detection of SARS-CoV-2.
A real-time dPCR system was developed to improve the sensitivity, specificity and quantification accuracy of end point dPCR. We compared three technologies - real-time qPCR, end point dPCR and real-time dPCR - in the context of SARS-CoV-2. Some improvement in limit of detection was obtained with end point dPCR compared with real-time qPCR, and the limit of detection was further improved with the newly developed real-time dPCR technology through removal of false-positive signals. Real-time dPCR showed increased linear dynamic range compared with end point dPCR based on quantitation from amplification curves. Real-time dPCR can improve the performance of TaqMan assays beyond real-time qPCR and end point dPCR with better sensitivity and specificity, absolute quantification and a wider linear range of detection.


Reversal-learning deficits in childhood-onset bipolar disorder across the transition from childhood to young adulthood.
Bipolar disorder (BD) is a severe mental illness that can have high costs for youths (<18 years old) and adults. Relative to healthy controls (HC), individuals with BD often show impaired attention, working memory, executive function, and cognitive flexibility (the ability to adapt to changing reward/punishment contingencies). In our study of youths and young adults with BD, we investigated 1) how cognitive flexibility varies developmentally in BD, and 2) whether it is independent of other executive function deficits associated with BD. We measured errors on a reversal-learning task, as well as spatial working memory and other executive function, among participants with BD (N=75) and HC (N=130), 7-27 years old. Regression analyses focused on the effects of diagnosis on reversal-learning errors, controlling for age, gender, IQ, spatial span, and executive function. Similar analyses examined non-reversal errors to rule out general task impairment. Participants with BD, regardless of age, gender, or cognitive ability, showed more errors than HC on the response reversal stages of the cognitive flexibility task. However, participants with BD did not show more errors on non-reversal stages, even when controlling for other variables. Study limitations include the cross-sectional, rather than longitudinal, design; inability to measure non-linear age effects; and inclusion of medicated participants and those with psychiatric comorbidity. Individuals with BD show a specific impairment in reversing a previously rewarded response, which persists across the transition from childhood to young adulthood. Tailored interventions targeting this deficit may be effective throughout this developmentally turbulent time.


Differential requirements for the induction of interleukin 2 responsiveness in L3T4+ and Lyt-2+ T cell subsets.
Minimal requirements for the induction of interleukin 2 (IL-2) responsiveness in purified subsets of murine T lymphocytes have been investigated. Whereas Lyt-2+ cells could be induced to IL-2-dependent growth by lectin, phorbol ester, or calcium ionophore, none of these stimuli was by itself sufficient for L3T4+ cells. The latter cells could, however, be induced to respond to IL-2 by combinations of lectin plus phorbol ester or ionophore plus phorbol ester (but not lectin plus ionophore). Under optimal conditions, growth of L3T4+ cells (like Lyt-2+ cells) was independent of accessory cells and cell-cell contact.


Probe integrated scattering cross sections in the analysis of atomic resolution HAADF STEM images.
The physical basis for using a probe-position integrated cross section (PICS) for a single column of atoms as an effective way to compare simulation and experiment in high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM) is described, and the use of PICS in order to make quantitative use of image intensities is evaluated. It is based upon the calibration of the detector and the measurement of scattered intensities. Due to the predominantly incoherent nature of HAADF STEM, it is found to be robust to parameters that affect probe size and shape such as defocus and source coherence. The main imaging parameter dependencies are on detector angle and accelerating voltage, which are well known. The robustness to variation in other parameters allows for a quantitative comparison of experimental data and simulation without the need to fit parameters. By demonstrating the application of the PICS to the chemical identification of single atoms in a heterogeneous catalyst and in thin, layered-materials, we explore some of the experimental considerations when using this approach.


[Protein arrays and perspectives of medical applications].
Protein microarrays make it possible to detect molecular interactions with various partners (proteins, peptides, nucleic acids, sugars, etc.). Their advantages are crucial for high-throughput analysis of proteomes of different organisms. Moreover, the recent data reveal the performance of microarrays over current immunological methods. Therefore, the antigen and antibody microarrays become indispensable for medical applications, in particular, for diagnosis and prognosis of microbial infections, autoimmune and allergic diseases. The further technological progress might provide the extension of the miniaturized assays for multiparametric monitoring of human pathologies in practical medicine.


Brain damage in a mouse model of global cerebral ischemia. Effect of NMDA receptor blockade.
The importance of particular genes in neuronal death following global cerebral ischemia can readily be studied in genetically modified mice provided a reliable model of ischemia is available. For that purpose, we developed a mouse model of global cerebral ischemia that induces consistent damage to different regions of the brain and with a low mortality rate. Twelve minutes of ischemia was induced in C57BL/6 mice by bilateral common carotid artery occlusion under halothane anesthesia and artificial ventilation. Body and brain temperature were monitored and cortical cerebral blood flow in each hemisphere was measured by laser Doppler flowmeter before, during, and for 5 min after ischemia. Extensive damage was found in the striatum and marked cell damage was observed in the CA1 and CA2 regions of hippocampus and in thalamus. Mild damage was seen in the CA3 region, dentate gyrus and cortex. Hippocampal damage in the CA1 region is delayed and developed over 48 h. Intraischemic hypothermia of 33 degrees C provided a robust neuroprotection. The non-competitive N-methyl-D-aspartate receptor blocker, MK-801, did not provide protection in the hippocampus, cortex, striatum or thalamus when administered 30 min prior to ischemia or 2 h after the end of ischemia, but selectively mitigated damage in the hippocampus, when administered immediately following ischemia. This model of global cerebral ischemia may be useful in pharmacological and genomic studies of ischemic brain damage.


Elliptical specularity detection in endoscopy with application to normal reconstruction.
To detect specularities as elliptical blobs in endoscopy. The rationale is that in the endoscopic setting, specularities are generally small and that knowing the ellipse coefficients allows one to reconstruct the surface normal. In contrast, previous works detect specular masks as free-form shapes and consider the specular pixels as nuisance. A pipeline combining deep learning with handcrafted steps for specularity detection. This pipeline is general and accurate in the context of endoscopic applications involving multiple organs and moist tissues. A fully convolutional network produces an initial mask which specifically finds specular pixels, being mainly composed of sparsely distributed blobs. Standard ellipse fitting follows for local segmentation refinement in order to only keep the blobs fulfilling the conditions for successful normal reconstruction. Convincing results in detection and reconstruction on synthetic and real images, showing that the elliptical shape prior improves the detection itself in both colonoscopy and kidney laparoscopy. The pipeline achieved a mean Dice of 84% and 87% respectively in test data for these two use cases, and allows one to exploit the specularities as useful information for inferring sparse surface geometry. The reconstructed normals are in good quantitative agreement with external learning-based depth reconstruction methods manifested, as shown by an average angular discrepancy of [Formula: see text] in colonoscopy. First fully automatic method to exploit specularities in endoscopic 3D reconstruction. Because the design of current reconstruction methods can vary considerably for different applications, our elliptical specularity detection could be of potential interest in clinical practice thanks to its simplicity and generalisability. In particular, the obtained results are promising towards future integration with learning-based depth inference and SfM methods.


A re-evaluation of the metric diversity within Homo erectus.
Previous work by several researchers has suggested that the cranial sample from Zhoukoudian possesses a unique metric pattern relative to the African and Asian specimens assigned to Homo erectus. The current study readdresses this issue with an expanded fossil sample and a larger and more comprehensive set of cranial measurements. To test the patterns present in the assemblage, canonical variates analysis was performed using a covariance matrix generated from the Howells data set. From this, interindividual Mahalanobis distances were computed for the fossils. Random expectation statistics were then used to measure statistical significance of the Mahalanobis distances. The results show that the Zhoukoudian hominids exhibit a unique metric pattern not shared by the African and Indonesian crania sampled. In these tests the Hexian calvaria resembled the African and Indonesian specimens and differed significantly from the craniometric pattern seen in the Zhoukoudian fossils. The Zhoukoudian specimens are characterized by a wide midvault and relatively narrow occipital and frontal bones, while the African and Indonesian crania (including Hexian) have relatively broad frontal and occipital dimensions compared to their midvaults. These results do not suggest that a multiple-species scenario is necessary to encompass the variation present in the sample. Based on the current evidence it is more probable that this variation reflects polytypism influenced by environmental adaptation and/or genetic drift.


[Audipog perinatal network. Part 1: principal perinatal health indicators, 2004-2005].
To present the principal perinatal indicators for 2004-2005, based on data from the Audipog sentinel network. The database for 2004 and 2005 covers 71,406 pregnancies from 86 maternity units throughout the year. We constructed a random subsample each year by including only the births occurring during a single month for each maternity ward. Our study therefore analyzes 6987 pregnancies in 2004 and 7648 pregnancies in 2005. The number of women working during pregnancy increased between 2004 and 2005 (62.3% versus 66.3%) (p=0.0008) as did the percentage with a postsecondary education (35.1% versus 41.9%) (p<0.0001). The percentage of amniocenteses declined (10.4% versus 7.9%) (p<0.0001). Use of prenatal care improved: more women had prenatal visits before week 14 (30.5% versus 33.9%) (p=0.0002), and fewer women had no prenatal care at all (1.1% versus 0.4%) (p=0.0003). The percentage of preterm deliveries was 6.4% in 2004 and 7% in 2005 (p=0.14) and the percentage of induced preterm deliveries was 37% in 2004 and 41.2% in 2005 (p=0.18). The cesarean rate was essentially stable (19 and 19.2%) and the rate of instrumental intervention in vaginal deliveries fell from 13.1% in 2004 to 11.2% in 2005 (p=0.0015). The rates of cesarean and of preterm deliveries remained stable between 2004 and 2005, but the rate of induced preterm deliveries rose. These indicators are consistent with trends that began earlier.


Pseudoepithelial pattern in smears prepared from fine needle aspirates of plasmacytomas.
A pseudoepithelial pattern was observed in smears prepared from fine needle aspirates (FNA) from three plasmacytomas. In one case cells displayed a markedly granular, 'oncocytic' cytoplasm. Granularity of the cytoplasm was due to a large number of mitochondria as shown by electron microscopy. B-lymphocytic origin of the neoplasms was confirmed by immunocytochemistry.


Ultrasound monitoring of temperature change during radiofrequency ablation: preliminary in-vivo results.
Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion and permits in situ destruction of hepatic tumors. However, local tumor recurrence rates after RF ablative therapy are as high as 34% to 55%, which may be due in part to the inability to monitor accurately temperature profiles in the tissue being ablated, and to visualize the subsequent zone of necrosis (thermal lesion) formed. The goal of the work described in this paper was to investigate methods for the real-time and in vivo monitoring of the spatial distribution of heating and temperature elevation to achieve better control of the degree of tissue damage during RF ablation therapy. Temperature estimates are obtained using a cross-correlation algorithm applied to RF ultrasound (US) echo signal data acquired at discrete intervals during heating. These temperature maps were used to display the initial temperature rise and to continuously update a thermal map of the treated region. Temperature monitoring is currently performed using thermosensors on the prongs (tines) of the RF ablation probe. However, monitoring the spatial distribution of heating is necessary to control the degree of tissue damage produced.


Gryllus bimaculatus extract ameliorates high-fat diet-induced hyperglycemia and hyperlipidemia by inhibiting hepatic lipogenesis through AMPK activation.
Insect-based food is increasingly used and is a sustainable protein source provided by eco-friendly breeding respecting the animal welfare. The cricket Gryllus bimaculatus is an approved edible insect. In this paper, the effects of G. bimaculatus extracts (AE-GBE) on hepatic insulin resistance and the underlying mechanisms were investigated in high fat diet (HFD)-fed C57BL/6J mice. Mice were fed HFD for 6 weeks and some were concomitantly given AE-GBE orally (100 mg/kg/day). AE-GBE significantly improved glucose tolerance and insulin sensitivity by attenuating hepatic lipid accumulation measured by the reduced serum and hepatic lipid contents. Moreover, AE-GBE significantly downregulated the expression of hepatic lipogenesis-related genes and activated the AMPK signaling pathway. Therefore, AE-GBE might improve fatty liver and glucose metabolism disorders as well as insulin resistance by inhibiting the expression of proteins involved in hepatic fatty acid synthesis through AMPK activation. The online version contains supplementary material available at 10.1007/s10068-022-01117-9.


Characterization of the novel dimethyl sulfide-degrading bacterium Alcaligenes sp. SY1 and its biochemical degradation pathway.
Recently, the biodegradation of volatile organic sulfur compounds (VOSCs) has become a burgeoning field, with a growing focus on the reduction of VOSCs. The reduction of VOSCs encompasses both organic emission control and odor control. Herein, Alcaligenes sp. SY1 was isolated from active sludge and found to utilize dimethyl sulfide (DMS) as a growth substrate in a mineral salt medium. Response surface methodology (RSM) analysis was applied to optimize the incubation conditions. The following conditions for optimal degradation were identified: temperature 27.03°C; pH 7.80; inoculum salinity 0.84%; and initial DMS concentration 1585.39 μM. Under these conditions, approximately 99% of the DMS was degraded within 30 h of incubation. Two metabolic compounds were detected and identified by gas chromatography-mass spectrometry (GC-MS): dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS). The DMS degradation kinetics for different concentrations were evaluated using the Haldane-Andrews model and the pseudo first-order model. The maximum specific growth rate and degradation rate of Alcaligenes sp. SY1 were 0.17 h(-1) and 0.63 gs gx(-1)h(-1). A possible degradation pathway is proposed, and the results suggest that Alcaligenes sp. SY1 has the potential to control odor emissions under aerobic conditions.


Dynamic Contrast-Enhanced Perfusion MRI of High Grade Brain Gliomas Obtained with Arterial or Venous Waveform Input Function.
The aim of this study was to evaluate the differences in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) perfusion estimates of high-grade brain gliomas (HGG) due to the use of an input function (IF) obtained respectively from arterial (AIF) and venous (VIF) approaches by two different commercially available software applications. This prospective study includes 20 patients with pathologically confirmed diagnosis of high-grade gliomas. The data source was processed by using two DCE dedicated commercial packages, both based on the extended Toft model, but the first customized to obtain input function from arterial measurement and the second from sagittal sinus sampling. The quantitative parametric perfusion maps estimated from the two software packages were compared by means of a region of interest (ROI) analysis. The resulting input functions from venous and arterial data were also compared. No significant difference has been found between the perfusion parameters obtained with the two different software packages (P-value < .05). The comparison of the VIFs and AIFs obtained by the two packages showed no statistical differences. Direct comparison of DCE-MRI measurements with IF generated by means of arterial or venous waveform led to no statistical difference in quantitative metrics for evaluating HGG. However, additional research involving DCE-MRI acquisition protocols and post-processing would be beneficial to further substantiate the effectiveness of venous approach as the IF method compared with arterial-based IF measurement.


Super typhoon induced high silica export from Arakawa River, Japan.
Dissolved silicate (DSi) and particulate silica (PSi) concentrations were measured at Arakawa River and at sewage treatment plants (STP) during October 2018 to October 2019. These included flooding observations after super Typhoon Hagibis. At ordinary water levels, the STP effluents were found to be the largest source of DSi in the river. Although DSi concentrations during the flooding events (165 μmol L-1) decreased by about 25% compared to that of ordinary water level (221 μmol L-1), PSi was more than sixteen times higher value (301 μmol L-1) compared to that of ordinary water level (18 μmol L-1). Loading amounts of DSi and PSi (± 1 standard error) were 1.5 × 108 (± 0.1 × 108) and 0.15 × 108 (± 0.02 × 108) mol year-1, respectively, excluding the data of Typhoon Hagibis. Loading amounts during flooding events of DSi and PSi were 1.2 × 108 (± 0.1 × 108) and 2.4 × 108 (± 0.4 × 108) mol 15 days-1, respectively. Although the silica loading at ordinary water level was mainly derived from DSi, the silica loading during flooding events was extremely large due to both high level of DSi and PSi; moreover, it was higher than the annual loading amount.


Probing Charge Carrier Transport and Recombination Pathways in Monolayer MoS2/WS2 Heterojunction Photoelectrodes.
Monolayer heterojunctions such as MoS2/WS2 are attractive for solar energy conversion applications because the interfacial electric field spatially separates charge carriers in less than 100 fs. Photoelectrochemical cells represent an intriguing platform to collect the spatially separated carriers. However, the recombination, transport, and interfacial charge transfer processes that take place following the ultrafast charge separation step have not been investigated. Here we demonstrate novel charge recombination and transport pathways in monolayer MoS2/WS2 photoelectrochemical cells by spatially resolving the net collection of carriers (i.e., the photocurrent) at the single nanosheet level. We discovered an excitation-wavelength-dependent recombination pathway that depends on the heterojunction stacking configuration and the carrier generation profile in the heterostructure. Photocurrent mapping measurements revealed that charge transport occurs parallel to the layers over micrometer-scale distances even though the indium tin oxide electrode and liquid electrolyte provide efficient charge extraction pathways via intimate electron- and hole-selective contacts. Our results reveal how composition heterogeneity influences the performance of bulk heterojunction electrodes made from randomly oriented nanosheets and provide critical insight into the design of efficient heterojunction photoelectrodes for solar energy conversion applications.


Detection of GB virus-C/hepatitis G virus genome in peripheral blood mononuclear cells and liver tissue.
The replication site for the GB virus-C/hepatitis G virus (GBV-C/HGV) was investigated by using polymerase chain reaction (PCR)-based assays and in situ hybridisation. A total of 28 patients with consecutive GBV-C/HGV infection were enrolled in this study: Nine patients were being treated with immunosuppressive therapy after liver transplantation, and the remaining 19 patients were not receiving such treatment. GBV-C/HGV RNA was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR) and was quantitated by using competitive RT-PCR in all patients. Positive and negative strands of GBV-C/HGV RNA in liver tissue were detected with in situ hybridisation by using RNA probes that were specific for the GBV-C/HGV genome. Concentrations of GBV-C/HGV RNA in serum were significantly higher (P=0.003) in the nine patients who were receiving immunosuppression (median, 10(7) copy/ml; range, 10(5)-10(7)) than in the 19 patients who were not receiving immunosuppressive therapy (median, 10(4) copy/ml; range, 10(2)-10(7)). In situ hybridisation of GBV-C/ HGV RNA was performed on paraffin-embedded liver tissue that was obtained from six patients with GBV-C/HGV infection. Two of those six patients were receiving immunosuppressive therapy, and four were not. Significant positive signals were observed in the samples from two of the six patients who were infected with GBV-C/HGV, but such signals were not observed in any of the six patients who were without the infection. The two patients with positive signals (both were undergoing immunosuppressive therapy) showed both positive and negative strands of GBV-C/HGV RNA in mononuclear cells that infiltrated into portal areas, but neither of the strands was observed in hepatocytes. Moreover, the GBV-C/HGV replication was analysed in peripheral blood mononuclear cells by using strand-specific PCR (conventional RT-PCR and rTth method). Two of the six patients were positive for negative-strand GBV-C/HGV RNA by using conventional RT-PCR. In conclusion, GBV-C/HGV replication was active under an immunosuppressive state, and it is suggested that GBV-C/HGV replicates in mononuclear cells.


The immune response towards beta-adrenergic ligands and their receptors--VII. Equilibrium and kinetic binding studies of l-alprenolol to a monoclonal anti-alprenolol antibody.
Binding of the catecholamine beta-adrenergic antagonist, l-alprenolol, by the IgGl anti-alprenolol monoclonal antibody 37A4 was examined using the radioligand 3H-dihydroalprenolol as an extrinsic signal and the increase in antibody fluorescence upon l-alprenolol binding as intrinsic signal. Equilibrium binding studies based on both signals indicated that the binding process was exothermic with a positive entropy change. The difference in the affinity constants obtained by radioligand binding studies and by fluorescence analysis could be ascribed to the higher affinity of the hydrogenated tritiated l-dihydroalprenolol compared to the unsaturated l-alprenolol. The association rate constants determined by both signals were 10(4)-10(5)/M/sec and showed a high activation enthalpy (8-10 kcal/mol), thus excluding a diffusion controlled reaction. At low temp (7 degrees C), the fluorescence stopped-flow studies showed non-linear pseudo first order kinetics, indicating the existence of a fast pre-equilibrium of low affinity, followed by a conformational change leading to the tight binding of the ligand. The dissociation rate constants determined using both signals were very similar. Thus, the differences in affinity between the hydrogenated and non-saturated l-alprenolol could be ascribed to the association rate constants. Affinity constants and thermodynamic parameters calculated from the kinetic data were in close agreement with those determined by equilibrium binding. The mechanisms of ligand binding are discussed in terms of the interactions of idiotypes and anti-idiotypes in the anti-catecholamine immune response.


Nel-like Molecule 1 Contributes to the Odontoblastic Differentiation of Human Dental Pulp Cells.
Nel-like molecule-1 (Nell-1) with epidermal cell growth factor-like coding structures is a recently discovered secreted protein that can specifically induce osteoblast differentiation, bone formation, and bone regeneration. The expression and localization of Nell-1 during murine molar development suggest that this protein participates in odontoblastic differentiation. This study aims to assess the expression of Nell-1 in the pulp-dentin complex of human teeth and determine the effect of human recombinant Nell-1 (hrNell-1) on odontoblastic differentiation of cultured human dental pulp cells. Immunohistochemical assay was performed to detect the expression and location of Nell-1 in healthy human teeth. The activity of alkaline phosphatase in human dental pulp cells stimulated by hrNell-1 was examined. Moreover, the expression of related odontoblastic markers was evaluated using quantitative real-time polymerase chain reaction and Western blot. Immunohistochemical results showed that Nell-1 was primarily expressed in the odontoblasts (odontoblastic bodies and processes), pulp fibroblasts, and endothelial cells of the blood vessels in human teeth. In vitro experiments showed that hrNell-1 could increase the activity of alkaline phosphatase and enhance the expression of important odontoblastic markers including osteopontin and dentin matrix protein 1 in cultured human dental pulp cells. Nell-1 plays a role in odontoblastic differentiation of human dental pulp cells and dentin formation.


Diagnostic accuracy and prognostic utility of D Dimer in acute appendicitis in children.
The objective was to determine the uselfulness of D Dimer (DD) as a diagnostic or prognostic marker in acute appendicitis (AA) in children using a prospective observational study in the pediatric emergency department of a tertiary hospital. We enrolled 135 patients aged 1-16 years presenting with abdominal pain consistent with AA, who required laboratory studies. We analyzed clinical, analytical variables and histopathology findings (when they underwent surgery). Statistical analysis was conducted using SPSS. 38.5% of the children were clinically diagnosed with AA (n = 52), confirmed by pathology in 51 patients. 55.8% were gangrenous appendicitis. Leucocyte count, C-reactive protein (CRP), and DD were higher in the AA group and in the gangrenous appendicitis group (p < 0.05), with highest values of DD in the gangrenous group. The area under the receiving operating characteristics (ROC) curve for DD in the diagnosis of AA is 0.66 (95% CI 0.56-0.75). For DD cut-off point of 230 ng/mL, sensitivity (Se) was 0.40, specificity (Sp) 0.80, positive predictive value (PPV) 0.57, and negative predictive value (NPV) 0.66. The area under the ROC curve for DD in children with gangrenous appendicitis is 0.93 (95% CI 0.87-1). A DD cut-off point of 230 ng/mL exhibited: Se = 0.69, Sp = 1, PPV = 1 and NPV = 0.72. DD levels increase in patients with AA. Although it does not constitute a useful diagnostic marker, it could be a good prognostic marker.


Children's early school attendance and stability as a mechanism through which homelessness is associated with academic achievement.
Unfortunately, family homelessness is a crisis in the United States. The majority of families experiencing homelessness are headed by single mothers and half of children who experience homelessness are less than five years of age. In the current study, we investigated whether children's school attendance and stability mediated the association between early experiences of homelessness (in infancy and toddlerhood) with children's school performance on standardized assessments of math and English language arts administered in the spring of third grade in a sample of children of young mothers. We used a person-centered analytic technique (i.e., repeated measures latent class analysis) to identify three classes of children's patterns of school attendance and stability from kindergarten through third grade that consisted of (a) High Absenteeism, (b) Decreasing Absenteeism, and (c) Low Absenteeism classes. Early experiences of homelessness were directly and indirectly associated with math, but not English language arts scores, through the three identified classes. The results of the current study have important implications for young children who experience homelessness and suggest promoting school attendance as one avenue to support academic achievement. In addition, supporting families and children early (i.e., before they begin pre-kindergarten) will be key in ensuring that young children who experience homelessness are successful in educational environments.


Clinical and Therapeutic Aspects of Sideroblastic Anaemia with B-Cell Immunodeficiency, Periodic Fever and Developmental Delay (SIFD) Syndrome: a Systematic Review.
Sideroblastic anaemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD) syndrome is a novel rare autoinflammatory multisystem disorder. We performed a systematic review of the available clinical and therapeutics aspects of the SIFD syndrome. A systematic review according to PRISMA approach, including all articles published before the 30th of July 2021 in Pubmed and EMBASE database, was performed. The search identified 29 publications describing 58 unique patients. To date, 41 unique mutations have been reported. Onset of disease is very early with a median age of 4 months (range 0-252 months). The most frequent manifestations are haematologic such as microcytic anaemia or sideroblastic anaemia (55/58), recurrent fever (52/58), neurologic abnormalities (48/58), immunologic abnormalities in particular a humoral immunodeficiency (48/58), gastrointestinal signs and symptoms (38/58), eye diseases as cataract and retinitis pigmentosa (27/58), failure to thrive (26/58), mucocutaneous involvement (29/58), sensorineural deafness (19/58) and others. To date, 19 patients (35.85%) died because of disease course (16) and complications of hematopoietic cell stems transplantation (3). The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) is dramatically changing the natural history of this disease. SIFD syndrome is a novel entity to consider in a child presenting with recurrent fever, anaemia, B-cell immunodeficiency and neurodevelopmental delay. To date, therapeutic guidelines are lacking but anti-TNFα treatment and/or HCST are attractive and might modify the clinical course of this syndrome.


ABI sequencing analysis. Manipulation of sequence data from the ABI DNA sequencer.
The ABI Sequencing Analysis application is designed specifically for the analysis of data produced by the ABI DNA Sequencer. The ABI sequencer is a laser-based instrument that utilizes fluorescent labels to analyze the products of a sequencing reaction as they migrate through a gel. After the data are collected from a sequencing run, the Analysis program identifies and tracks the sample lanes of the gel and subsequently normalizes and integrates the raw data into a chromatogram of the final sequence. For the user, there are basically two types of files that can be manipulated to potentially improve the analysis results. The Gel File consists of a computer generated image of the sequencing gel with the fluorescent DNA banding patterns. This image allows the user to view and edit the tracking lines generated and used by Analysis to collect data points for each sample. Individual Sample Files are stored for each of the samples analyzed and include the chromatogram, raw data, and annotations and information regarding the sample and sequence run. Generally, the products of a sequencing reaction are easily resolved and the Analysis software interprets the correct nucleotide sequence. Ambiguous base calls tend to occur near the end of the sequence and may be either edited or deleted by the user before exporting the data for further comparisons or alignments. Occasionally the tracking lines within the gel image may need to be adjusted or moved. The sample data are then reextracted from the Gel File and analyzed again. This review explains the general operation of Analysis in terms of viewing and editing a chromatogram, retracking the lanes of a Gel File, and analyzing the final sample data. The three versions 1.2.1, 2.1.2, and 3.3 are discussed.


Effects of unilateral cerebral ischemia on the hippocampal theta depth profile in the ether-anesthetized Mongolian gerbil.
In gerbils (Meriones unguiculatus) unilateral cerebral ischemia of 5 to 15 min resulted in selective destruction of the ipsilateral hippocampal CA1 stratum pyramidale. It also produced an obvious amplitude reduction in both superficial and deep theta rhythms recorded from damaged hippocampal formation. The presence of normal theta in the left normoxic hemisphere showed that the septohippocampal projections, integrity of which is essential for theta appearance, were spared by ischemia. These data have implications in relation to the two generators hypothesis of theta.


Farrerol inhibits IL-6 and IL-8 production in LPS-stimulated human gingival fibroblasts by suppressing PI3K/AKT/NF-κB signaling pathway.
Farrerol, a new type of 2,3-dihydro-flavonoid isolated from rhododendron, has been shown to have anti-bacterial and anti-inflammatory activities. In the present study, we investigated the anti-inflammatory effects of farrerol on the production of IL-6 and IL-8 in human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS). The cytotoxicity of farrerol was determined using the MTT assay. The production of IL-6 and IL-8 was measured using ELISA and qRT-PCR. The effects of farrerol on PI3K, Akt phosphorylation, and NF-κB activation were detected using western blotting analyses. These results showed that farrerol inhibited LPS-induced IL-6 and IL-8 production in a dose dependent manner. LPS-induced NF-κB activation was suppressed by farrerol. Furthermore, farrerol suppressed LPS-induced PI3K and Akt phosphorylation, which are upstream molecules of NF-κB. These results indicated that farrerol attenuated IL-6 and IL-8 production by inhibition of PI3K and AKT phosphorylation, resulting in an inhibition of NF-κB activation. Farrerol may be a therapeutic agent for the treatment of periodontal disease.


Extended indications for median sternotomy in patients requiring pulmonary resection.
We have employed median sternotomy in 9 patients for resection of both benign and malignant lung lesions. The most frequent use of this approach was for bilateral wedge resection, though unilateral resection was done in 2 patients. Our experience supports the previously documented usefulness of median sternotomy for minor bilateral resections and suggests that more complex pulmonary resections are possible when an appropriate indication exists. We compared the effects of median sternotomy with those of lateral thoracotomy on postoperative vital capacity and peak airway flow. Both incisions results in a marked loss of measured lung function, but recovery occurs notably sooner after median sternotomy than ater lateral thoracotomy.


Retracted: Static and Dynamic Demonstration of the Ecological Level of Ethnic Cultural Industries Based on the Internet of Things and Environmental Responsibility.
[This retracts the article DOI: 10.1155/2022/5953522.].


MORPHEUS: An automated tool for unbiased and reproducible cell morphometry.
Here we present a new Fiji/ImageJ2 plugin called Multiparametric Morphometric Analysis of EUcaryotic cellS (MORPHEUS), designed for the automated evaluation of cell morphometry from images acquired by fluorescence microscopy. MORPHEUS works with sampling distributions to learn-in an unsupervised manner and by a nonparametric approach-how to recognize the cells suitable for subsequent analysis. Afterward, the algorithm performs the evaluation of the most relevant cell-shape descriptors over the full set of detected cells. Optionally, also the extraction of nucleus features and a double-scale analysis of orientation can be performed. The whole algorithm is implemented as a one-click procedure, thus minimizing the user's intervention. By reducing biases and errors of human origin, MORPHEUS is intended to be a useful tool to enhance reproducibility in the bioimage analysis.


Early postoperative small bowel obstruction: A review.
Early postoperative small bowel obstruction (ESBO) is a challenging problem. Although it is usually amenable to non-operative management, a significant proportion of patients will require re-operation. Certain causes of ESBO and types of index procedures should prompt consideration for early re-operation. A laparoscopic approach during the index operation, certain barrier agents and closure of mesenteric defects in bariatric surgery may reduce the risk of ESBO. There is no consensus regarding an acceptable length of time for initial non-operative management of ESBO but re-operation beyond two weeks may be associated with increased complications.