A systematic review and meta-analysis of the association between poor oral health and substance abuse.
Substance use disorders are associated commonly with comorbid physical illness. There are fewer data on dental disease in these conditions, in spite of high rates of dry mouth (xerostomia), as well as the associated indirect or life-style effects such as poverty and lack of access to care. We compared the oral health of people with substance use disorders (SUDs) with non-using controls. This was a systematic search for studies from the last 35 years of the oral health of people reporting SUDs. We used MEDLINE, PsycInfo, OVID, Google Scholar, EMBASE and article bibliographies. Results were compared with the general population. Oral health was assessed in terms of dental caries and periodontal disease using the following standardized measures: the mean number of decayed, missing and filled teeth (DMFT) or surfaces (DMFS) and probing pocket depth. Non-carious tooth loss was assessed clinically. We identified 28 studies that had sufficient data for a meta-analysis, comprising 4086 SU patients and 28 031 controls. People with SUD had significantly higher mean scores for DMFT [mean difference = 5.15, 95% confidence interval (CI) = 2.61-7.69 and DMFS (mean difference = 17.83, 95% CI = 6.85-28.8]. They had more decayed teeth but fewer restorations, indicating reduced access to dental care. Patients with SUD also exhibited greater tooth loss, non-carious tooth loss and destructive periodontal disease compared to controls. Patients with substance use disorders have greater and more severe dental caries and periodontal disease than the general population, but are less likely to have received dental care.


Global Analysis of miRNA-mRNA Interaction Network in Breast Cancer with Brain Metastasis.
MicroRNAs (miRNAs) have been linked to a number of cancer types including breast cancer. The rate of brain metastases is 10-30% in patients with advanced breast cancer which is associated with poor prognosis. The potential application of miRNAs in the diagnostics and therapeutics of breast cancer with brain metastasis is an area of intense interest. In an initial effort to systematically address the differential expression of miRNAs and mRNAs in primary breast cancer which may provide clues for early detection of brain metastasis, we analyzed the consequent changes in global patterns of gene expression in Gene Expression Omnibus (GEO) data set obtained by microarray from patients with in situ carcinoma and patients with brain metastasis. The miRNA-pathway regulatory network and miRNA-mRNA regulatory network were investigated in breast cancer specimens from patients with brain metastasis to screen for significantly dysregulated miRNAs followed by prediction of their target genes and pathways by Gene Ontology (GO) analysis. Functional coordination of the changes of gene expression can be modulated by individual miRNAs. Two miRNAs, hsa-miR-17-5p and hsa-miR-16-5p, were identified as having the highest associations with targeted mRNAs [such as B-cell lymphoma 2 (BCL2), small body size/mothers against decapentaplegic 3 (SMAD3) and suppressor of cytokine signaling 1 (SOCS1)] and pathways associated with epithelial-mesenchymal transitions and other processes linked with cancer metastasis (including cell cycle, adherence junctions and extracellular matrix-receptor interaction). mRNAs for two genes [HECT, UBA and WWE domain containing 1 (HUWE1) and BCL2] were found to have the highest associations with miRNAs, which were down-regulated in brain metastasis specimens of breast cancer. The change of 11 selected miRNAs was verified in The Cancer Genome Atlas (TCGA) breast cancer dataset. Up-regulation of hsa-miR-17-5p was detected in triple-negative breast cancer tissues in TCGA. Furthermore, a negative correlation of hsa-miR-17-5p with overall survival and phosphatase and tensin homolog (PTEN) and BCL2 target genes was found in TCGA breast cancer specimens. Our findings provide a functionally coordinated expression pattern of different families of miRNAs that may have potential to provide clinicians with a strategy to treat breast cancer with brain metastasis from a systems-rather than a single-gene perspective.


Relation of somal lipid synthesis to the fast axonal transport of protein and lipid.
The role of somal lipid synthesis in the fast axonal transport of protein and lipid was examined in vitro utilizing spinal/sciatic nerve preparations of bullfrog. Inhibition of phospholipid synthesis in dorsal root ganglia by the amphiphilic cation, fenfluramine (0.1-2.0 mM) was monitored as decreased incorporation of [3H]choline into phosphatidyl choline. This inhibition was directly proportional to a decrease in the amount of [3H]protein undergoing fast axonal transport, the two variables being related by a slope close to unity. [3H]Choline-labeled lipid undergoing fast transport in the axon was unaffected by inhibition of somal phospholipid synthesis. Levels of fenfluramine up to 1.0 mM had no effect on uptake or incorporation of [3H]leucine. Selective exposure of desheathed nerve trunks to 1.0 mM fenfluramine had no effect on [3H]protein translocation, indicating that local phospholipid synthesis is not required to maintain ongoing transport in the axon. Inhibition of cholesterol synthesis in the ganglia with the analog 20,25-diazacholesterol also resulted in depression of [3H]protein transport. Since synthesis of both phospholipid and cholesterol are required at the level of the ganglion, it is suggested that the initiation of fast axonal transport of protein is dependent on the assembly of lipoprotein structures in the soma.


Fatal cerebral malaria: a venous efflux problem.
Most Plasmodium falciparum-infected children with cerebral malaria (CM) die from respiratory arrest, but the underlying pathology is unclear. Here we present a model in which the ultimate cause of death from CM is severe intracranial hypertension. Dynamic imaging of mice infected with P. berghei ANKA, an accepted model for experimental CM, revealed that leukocyte adhesion impairs the venous blood flow by reducing the functional lumen of postcapillary venules (PCV). The resulting increase in intracranial pressure (ICP) exacerbates cerebral edema formation, a hallmark of both murine and pediatric CM. We propose that two entirely different pathogenetic mechanisms-cytoadherence of P. falciparum-infected erythrocytes in pediatric CM and leukocyte arrest in murine CM-result in the same pathological outcome: a severe increase in ICP leading to brainstem herniation and death from respiratory arrest. The intracranial hypertension (IH) model unifies previous hypotheses, applies to human and experimental CM alike, eliminates the need to explain any selective recognition mechanism Plasmodium might use to target multiple sensitive sites in the brain, and explains how an intravascular parasite can cause so much neuronal dysfunction.


Interference of high-dose methotrexate in the metabolism of valproate?
A case of tonic-clonic seizure was observed in a child with acute lymphoblastic leukemia a few hours after a 24-hour infusion of high-dose methotrexate (MTX; 5 g/m2). Because of former epileptic symptoms, the child had been treated with valproic acid for several months. During this and the following high-dose MTX infusion, an acute decline of the serum valproate concentration to about 25% of the pre-MTX value was observed. The pathogenesis of the acute decline of serum valproate concentration is discussed.


[The pathology of catecholamine metabolism in cerebrovascular diseases].
Blood catecholamines were investigated with high-performance liquid chromatography and electrochemical detection in 95 patients with cerebrovascular affections. On day 1-3 since ischemic apoplexy blood norepinephrine and dopamine levels increased significantly. This is possibly due to their active release from neurons in brain tissue ischemia. High blood catecholamines are thought an unfavourable factor aggravating the disease and responsible for cardiac sequelae. Ways of cerebral tissue protection in case of ischemia are suggested.


AUNet: a deep learning method for spectral information classification to identify inks.
It is common to tamper with the contents of documents and forge contracts illegally. In this work, we propose a U-shaped network with attention modules (AUNet) and combine it with a hyperspectral system to effectively identify different inks. It provides an effective detection method for illegal tampering with documents and forging contract contents. First, the hyperspectral system obtains the spectral information of different pen inks without destroying the sample. Second, because the hyperspectral system's detection data have the characteristics of small samples, we introduce U-Net to conduct the deep fusion of multi-level spectral information to avoid feature degradation and fully mine the deep features hidden in the spectral information. Finally, spatial and channel attention modules are introduced to focus on the features affecting classification performance. The results show that AUNet effectively realizes the effective classification of ink spectral information and achieves 97.81% accuracy, 98.71% recall, 98.80% precision, and 98.71% F1-score.


Total sleep time as a predictor of suicidal behaviour.
Insomnia symptoms are a known predictor of suicide; however, less is known about the relationship between hypersomnia and suicide, and how total sleep time may better account for suicidal ideation compared with subjective reports of insomnia symptoms. In the present secondary data analysis, a squared term confirmed the importance of both short and long total sleep time on suicidal behaviour. Total sleep time had a significant positive direct effect on suicidal behaviour (b = 0.20, SE = 0.08, P < 0.05), significant negative direct effects on insomnia symptoms (b = -1.67, SE = 0.13, P < 0.0001) and on depressive symptoms (b = -1.76, SE = 0.29, P < 0.0001). Depression had a significant positive effect on suicidal behaviour (b = 0.17, SE = 0.01, P < 0.0001), and significantly mediated the relationship between total sleep time and suicidal behaviour, but insomnia symptoms did not. Total sleep time squared had a significant positive relationship with suicidal behaviour (b = 0.02, SE = 0.01, P < 0.05), significant negative direct effects on insomnia symptoms (b = -0.12, SE = 0.01, P < 0.0001) and on depressive symptoms (b = -0.12, SE = 0.02, P < 0.0001). Depression had a significant positive effect on suicidal behaviour (b = 0.17, SE = 0.01, P < 0.0001), and significantly mediated the relationship between total sleep time and suicidal behaviour. These results suggest the importance of assessing for total sleep time in clinical settings with regard to suicide risk.


Identification of arginine esterase as the major androgen-dependent protein secreted by dog prostate and preliminary molecular characterization in seminal plasma.
This work was undertaken to determine the identity of the major androgen-dependent 15,000 molecular weight protein previously observed on SDS polyacrylamide gel electrophoresis of both dog prostate cytosol and dog seminal plasma. The protein was identified as one of the two chains of arginine esterase on the basis of its ability to bind 3H-diisopropylphosphofluoridate (DFP), an active site titrant of serine proteases. Furthermore, since the other polypeptide chain was heterogeneous, at least five distinct peaks of arginine esterase activity could be separated by chromatofocusing under nonreducing conditions. The molecular weight of the seminal plasma protein was estimated at 29,500 by Sephadex G-100 gel filtration, and at 25,000 by SDS polyacrylamide gel electrophoresis in the absence of mercaptoethanol. In the presence of mercaptoethanol, two major peaks were observed with molecular weights of 15,000 and 14,000. These results show that arginine esterase of dog seminal plasma is a serine protease composed of two different chains linked by disulfide bridges. One of the chains contains the reactive serine group. The other one is probably glycosylated since it presents several isoelectric points.


Nonclinical evaluation of a Vitis vinifera extract towards a novel antiaging cosmetic ingredient.
Skin aging is regulated by multiple physiological processes, such as oxidative stress. Natural products have been considered as a promising source of antioxidant compounds. As a result, few innovative products on the market based on natural products tackle additional underlying mechanisms of skin aging. The present work reports the nonclinical evaluation of a novel extract from the skin of V. vinifera fruits (codified as ACH37 extract), with the aim of supporting its use as an antiaging cosmetic ingredient candidate in clinical trials. We employed enzymatic, phenotypic, and gene expression assays, both in vitro and ex vivo, to investigate the action of the ACH37 extract in different biological processes that could be related to skin aging mechanisms. The ACH37 extract was able to scavenge reactive oxygen species (DPPH, O2 - ), prevent inflammation (LPS- and UV-induced COX-2, IL-1β, and IL-8 expression), modulate extracellular matrix remodeling (inhibiting elastase, MMP-1, MMP-3, and MMP-12, as well as associated expression), increase telomere length, telomerase activity, and reverse the UV-induced suppression of genes involved in skin protection. In addition, the ACH37 extract permeated human skin explants and presented antioxidant efficacy ex vivo. The results indicated that the ACH37 extract acts on multiple targets commonly related to skin aging, being a promising antiaging active ingredient candidate to be further investigated in clinical trials.


OVIPOSITION SITE SELECTION BY DROSOPHILA MELANOGASTER AND DROSOPHILA SIMULANS.
The effects of texture and larval residues in the medium on oviposition site selection (OSS) by Drosophila melanogaster and Drosophila simulans were studied. Drosophila melanogaster laid over 95% of its eggs in sieved medium (vs. unsieved medium); D. simulans laid all of its eggs in sieved medium. Surgical removal of antennal segments, and of fore-, mid-, or hindtarsi did not affect this result, indicating that sense organs involved in discriminating between sieved and unsieved medium are not confined to only one of the tested structures. In a "multiple choice" experiment, females were allowed to lay eggs in sieved medium of three types: unconditioned (fresh) medium, medium conditioned by D. melanogaster larvae (i.e., medium containing larval residues of D. melanogaster), and medium conditioned by D. simulans larvae. This choice experiment was performed with D. melanogaster and with D. simulans, using three densities of females (10, 20, and 40 per experimental unit). Both species laid more eggs in unconditioned medium than in either of the conditioned media, and density had no effect. D. melanogaster laid more eggs near the edges of food patches than in the center, whereas D. simulans showed no preference for edge or center. Under crowded conditions, both species survived at a higher rate in conditioned media (egg-to-adult survival) than in unconditioned medium, leading to the anomalous conclusion that females of these species seem not to maximize the survival of their offspring. This anomaly was partially resolved by the finding that medium already containing larvae gave lower survival rates than unoccupied medium.


The Metabolic Phenotype in Obesity: Fat Mass, Body Fat Distribution, and Adipose Tissue Function.
The current obesity epidemic poses a major public health issue since obesity predisposes towards several chronic diseases. BMI and total adiposity are positively correlated with cardiometabolic disease risk at the population level. However, body fat distribution and an impaired adipose tissue function, rather than total fat mass, better predict insulin resistance and related complications at the individual level. Adipose tissue dysfunction is determined by an impaired adipose tissue expandability, adipocyte hypertrophy, altered lipid metabolism, and local inflammation. Recent human studies suggest that adipose tissue oxygenation may be a key factor herein. A subgroup of obese individuals - the 'metabolically healthy obese' (MHO) - have a better adipose tissue function, less ectopic fat storage, and are more insulin sensitive than obese metabolically unhealthy persons, emphasizing the central role of adipose tissue function in metabolic health. However, controversy has surrounded the idea that metabolically healthy obesity may be considered really healthy since MHO individuals are at increased (cardio)metabolic disease risk and may have a lower quality of life than normal weight subjects due to other comorbidities. Detailed metabolic phenotyping of obese persons will be invaluable in understanding the pathophysiology of metabolic disturbances, and is needed to identify high-risk individuals or subgroups, thereby paving the way for optimization of prevention and treatment strategies to combat cardiometabolic diseases.


Proximal epithelioid sarcomatous dedifferentiation in secondary chondrosarcoma in a known case of multiple osteochondromatosis.
Osteochondroma is the most common benign bone tumor. Approximately 15% of osteochondromas occur as multiple lesions. Multiple osteochondromatosis has a higher risk of developing chondrosarcomas, which are of low grade with good prognosis. About 10% of all chondrosarcomas may undergo dedifferentiated change, which has a poorer prognosis. Dedifferentiated peripheral chondrosarcoma developing within an osteochondroma is extremely rare. Dedifferentiation usually occurs in the form of osteosarcoma, malignant fibrous histiocytoma, fibrosarcoma, or rhabdomyosarcoma. We report a case of proximal epithelioid sarcomatous dedifferentiation in secondary chondrosarcoma in a 39-year-old male with multiple osteochondromatosis in bilateral arm. To the best of our knowledge, epithelioid sarcomatous dedifferentiation has not been described in the literature.


Advanced practice: A clinical or political issue?
Advanced practice is characterized by a greater degree of clinical competence, critical thinking and professional accountability in the areas of organizational management, decision-making and leadership. Advanced practice is praised in clinical and academic settings for its beneficial effects on peoples' health. However, the authors believe that advanced practice also confers specific (corporate) benefits, particularly with respect to acquisition of authority, credibility and legitimacy compared to, and in the eyes of, other health professionals. This article takes a critical look at the specialization phenomena in nursing and encourages dialogue on underlying motivations and the quest for professional status


Respiratory syncytial virus infection in the modern era.
Respiratory syncytial virus (RSV) continues to be a major cause of severe lower respiratory tract infection in infants, young children, and older adults. In this review, changes in the epidemiology of RSV during the coronavirus disease 2019 (COVID-19) pandemic are highlighted together with the role which increased molecular surveillance efforts will have in future in assessing the efficacy of vaccines and therapeutics. The introduction of nonpharmaceutical intervention (NPIs) strategies during the COVID-19 pandemic between 2020 and 2022 resulted in worldwide disruption to the epidemiology of RSV infections, especially with respect to the timing and peak case rate of annual epidemics. Increased use of whole genome sequencing along with efforts to better standardize the nomenclature of RSV strains and discrimination of RSV genotypes will support increased monitoring of relevant antigenic sites in the viral glycoproteins. Several RSV vaccine candidates based on subunit, viral vectors, nucleic acid, or live attenuated virus strategies have shown efficacy in Phase 2 or 3 clinical trials with vaccines using RSVpreF protein currently the closest to approval and use in high-risk populations. Finally, the recent approval and future use of the extended half-life human monoclonal antibody Nirsevimab will also help to alleviate the morbidity and mortality burden caused by annual epidemics of RSV infections. The ongoing expansion and wider coordination of RSV molecular surveillance efforts via whole genome sequencing will be crucial for future monitoring of the efficacy of a new generation of vaccines and therapeutics.


Longitudinal Monitoring of Patients With Chronic Low Back Pain During Physical Therapy Treatment Using the STarT Back Screening Tool.
Study Design Preplanned secondary analysis of a randomized clinical trial. Background The STarT Back Screening Tool (SBST) was developed to screen and to classify patients with low back pain into subgroups for the risk of having a poor prognosis. However, this classification at baseline does not take into account variables that can influence the prognosis during treatment or over time. Objectives (1) To investigate the changes in risk subgroup measured by the SBST over a period of 6 months, and (2) to assess the long-term predictive ability of the SBST when administered at different time points. Methods Patients with chronic nonspecific low back pain (n = 148) receiving physical therapy care as part of a randomized trial were analyzed. Pain intensity, disability, global perceived effect, and the SBST were collected at baseline, 5 weeks, 3 months, and 6 months. Changes in SBST risk classification were calculated. Hierarchical linear regression models adjusted for potential confounders were built to analyze the predictive capabilities of the SBST when administered at different time points. Results A large proportion of patients (60.8%) changed their risk subgroup after receiving physical therapy care. The SBST improved the prediction for all 6-month outcomes when using the 5-week risk subgroup and the difference between baseline and 5-week subgroup, after controlling for potential confounders. The SBST at baseline did not improve the predictive ability of the models after adjusting for confounders. Conclusion This study shows that many patients change SBST risk subgroup after receiving physical therapy care, and that the predictive ability of the SBST in patients with chronic low back pain increases when administered at different time points. Level of Evidence Prognosis, 2b. J Orthop Sports Phys Ther 2017;47(5):314-323. Epub 29 Mar 2017. doi:10.2519/jospt.2017.7199.


The transcription factor MYB110 regulates plant height, lodging resistance, and grain yield in rice.
The high-yielding Green Revolution varieties of cereal crops are characterized by a semi-dwarf architecture and lodging resistance. Plant height is tightly regulated by the availability of phosphate (Pi), yet the underlying mechanism remains obscure. Here, we report that rice (Oryza sativa) R2R3-type MYB transcription factor MYB110 is a Pi-dependent negative regulator of plant height. MYB110 is a direct target of PHOSPHATE STARVATION RESPONSE 2 (OsPHR2) and regulates OsPHR2-mediated inhibition of rice height. Inactivation of MYB110 increased culm diameter and bending resistance, leading to enhanced lodging resistance despite increased plant height. Strikingly, the grain yield of myb110 mutants was elevated under both high- and low-Pi regimes. Two divergent haplotypes based on single nucleotide polymorphisms in the putative promoter of MYB110 corresponded with its transcript levels and plant height in response to Pi availability. Thus, fine-tuning MYB110 expression may be a potent strategy for further increasing the yield of Green Revolution cereal crop varieties.


BK and Kv3.1 potassium channels control different aspects of deep cerebellar nuclear neurons action potentials and spiking activity.
Deep cerebellar nuclear neurons (DCNs) display characteristic electrical properties, including spontaneous spiking and the ability to discharge narrow spikes at high frequency. These properties are thought to be relevant to processing inhibitory Purkinje cell input and transferring well-timed signals to cerebellar targets. Yet, the underlying ionic mechanisms are not completely understood. BK and Kv3.1 potassium channels subserve similar functions in spike repolarization and fast firing in many neurons and are both highly expressed in DCNs. Here, their role in the abovementioned spiking characteristics was addressed using whole-cell recordings of large and small putative-glutamatergic DCNs. Selective BK channel block depolarized DCNs of both groups and increased spontaneous firing rate but scarcely affected evoked activity. After adjusting the membrane potential to control levels, the spike waveforms under BK channel block were indistinguishable from control ones, indicating no significant BK channel involvement in spike repolarization. The increased firing rate suggests that lack of DCN-BK channels may have contributed to the ataxic phenotype previously found in BK channel-deficient mice. On the other hand, block of Kv3.1 channels with low doses of 4-aminopyridine (20 μM) hindered spike repolarization and severely depressed evoked fast firing. Therefore, I propose that despite similar characteristics of BK and Kv3.1 channels, they play different roles in DCNs: BK channels control almost exclusively spontaneous firing rate, whereas DCN-Kv3.1 channels dominate the spike repolarization and enable fast firing. Interestingly, after Kv3.1 channel block, BK channels gained a role in spike repolarization, demonstrating how the different function of each of the two channels is determined in part by their co-expression and interplay.


Comorbidities of epilepsy.
In epilepsy management, control of seizures is the prime objective. However, the quality of life is affected by comorbid conditions that include the neurological, neuropsychiatric, and neurobehavioural disorders. These are not only reactive processes to a chronic condition but also have a bidirectional relationship, sharing common underlying pathogenesis. This article besides addressing these issues also explores the therapeutic management. A systematic search of PubMed from Jan 2006 to August 2016 was undertaken using the terms "comorbidities" and "epilepsy." In addition, articles specifically from India and other original papers were selected based on relevance. In this review, the neuropsychiatric, neurobehavioral (mood disorders, behaviour issues, attention deficits, psychosis), and neurologic [cognitive impairment, migraine, SUDEP-Sudden unexpected death in epilepsy (SUDEP)] comorbidities are covered in relation to epilepsy and its treatment. The incidental disorders such as hypertension, diabetes, and cancer that are mentioned in some reports have not been addressed here. Comorbidities in epilepsy are common but poorly understood and often remain unaddressed. The prevalence of comorbid conditions is considerably higher in epilepsy than seen in the general population and other chronic conditions. There is a wide spectrum of secondary disorders that have a marked impact and significantly increase the burden of the primary epilepsy condition. There is a need to acknowledge, screen, and intervene early in newly diagnosed cases for the optimal management of epilepsy.


Identifying the Optimal Candidate for Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer: Results from a Large, Multi-institutional Analysis.
Salvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients. To identify the optimal candidates for SLND based on preoperative characteristics. The study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga-labeled prostate-specific membrane antigen ligand. SLND. The study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model. Median follow-up was 30 (interquartile range, 16-50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p<0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]: 2.04; p<0.0001), time from RP to PSA rising (HR: 0.99; p=0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p=0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p=0.038), three or more positive spots at PET/CT scan (HR: 1.26; p=0.019), and PSA level at SLND (HR: 1.05; p<0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel'sC index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the "treat-all" option at all the threshold probabilities. We reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach. The risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery.


Acetylation of lysine 564 adjacent to the C-terminal binding protein-binding motif in EVI1 is crucial for transcriptional activation of GATA2.
Ecotropic viral integration site 1 (EVI1) is an important transcription factor for leukemogenesis. EVI1 is a member of a group of transcription factors with C-terminal binding protein (CtBP)-binding motifs that act as transcriptional co-repressors; however, we recently found that EVI1 directly activates GATA2 transcription, which is an important gene for the maintenance of hematopoietic stem cells. We show here that EVI1-activated GATA2 transcripts derive from exon 1S of GATA2, which is specifically activated in neural and hematopoietic cells. EVI1 was acetylated by the histone acetyltransferase p300/CBP association factor (P/CAF) in myeloid leukemia cells and hematopoietic progenitor cells. Acetylation at Lys(564), which is adjacent to the CtBP-binding consensus sequence of EVI1, was found to be important for transcriptional activation of GATA2. Mutation of Lys(564) to alanine (K564A) markedly reduced the ability of EVI1 to bind DNA and activate transcription of GATA2. Furthermore, we confirmed that Lys(564) in EVI1 was specifically acetylated in leukemia and primary hematopoietic cells by using an antibody directed against an acetylated Lys(564) EVI1 peptide. Moreover, co-transfection of P/CAF with EVI1 overcame the suppressive effect of the CtBP co-repressor and resulted in GATA2 transcriptional activation; nonetheless, CtBP2 was still included in the protein complex with EVI1 and P/CAF on the EVI1-binding site in the GATA2 promoter region. Thus, acetylation of EVI1 at Lys(564) by P/CAF enhances the DNA binding capacity of EVI1 and thereby contributes to the activation of GATA2.


Ultrastructure of jaw muscle spindle afferents within the rat trigeminal mesencephalic nucleus.
This study examined the ultrastructures of neuronal elements within trigeminal mesencephalic nucleus by labeling masseteric mesencephalic neurons and masseter motoneurons with injection of horseradish peroxidase into masseteric muscle. Of eight horseradish peroxidase-labeled muscle spindle afferents examined, four terminals showed synaptic contact with labeled dendrites of masseteric motoneurons, two with labeled somata, and the remaining two with unlabeled dendrites. A few of the labeled dendrites showed intimate contact with the somata of the trigeminal mesencephalic nucleus neurons. These results provide morphological evidence of synaptic contact of recurring masseteric muscle spindle afferents with the trigeminal mesencephalic nucleus somata and also suggest the presence of electrical synapses between the somata of the trigeminal mesencephalic nucleus neurons and dendrites of jaw-closing motoneurons.


Multi-center prospective survey of inflammatory bowel diseases in Kerala: More than 2000 cases.
Inflammatory bowel disease (IBD) is considered uncommon in Asia. The aim of this study was to document the demographic characteristics and clinical aspects of ulcerative colitis (UC) and Crohn's disease (CD) in Kerala, India. A survey of IBD in Kerala was performed. All gastroenterologists in the region were invited. From May 2013 to October 2015, data were collected in a standardized pro-forma. Forty-seven doctors in 34 centers contributed data. A total of 2142 patients were analyzed. This is the largest state-wide survey of IBD in India. Ulcerative colitis was diagnosed in 1112 (38 new), Crohn's disease in 980 (53 new), and 50 were unclassified (5 new). The district-wise distribution of IBD cases correlated with the District-wise Gross State Domestic Product (r = 0.69, p < 0.01). Three percent was below the age of 18. Patients with UC had more diarrhea (73% vs. 51%), bleeding PR (79% vs. 34%), and intermittent flares (35% vs. 13%) (all p < 0.01). Patients with CD had more abdominal pain (62% vs. 46%), weight loss (53% vs. 40%), fever (28% vs. 18%), and history of antituberculosis treatment (21% vs. 5%) (all p < 0.01). Compared to adults, children (below 18 years) were more likely to have extensive UC (58% vs. 34%, p < 0.01) and unclassified IBD (15% vs. 2%, p < 0.01). Inflammatory bowel disease is common in Kerala, India. The disease characteristics of patients with IBD are almost similar to those from other parts of the country. Both UC and CD were seen in equal proportion in Kerala.


School-Based Mental Health Practitioners: A Resource Guide for Educational Leaders.
School-based mental health practitioners can offer enhanced support to schools and students; yet their training, roles, and expertise vary. The roles of these professionals are often conflated, misunderstood, or marginalized in their utility throughout the school system. The purpose of this manuscript is to enhance the capacity of educational leaders to make informed hiring, contracting, and role assignment decisions that best fit school and student needs regarding school mental health services. We clarify the landscape of two distinct groups of qualified school mental health professionals-those who are education certified and those who are independently licensed; each group represents professionals from multiple disciplines. We illuminate similarities and differences of these professionals and juxtapose the utility of traditional mental health versus school-based mental health. We then discuss the similarities and differences of qualified school mental health professionals described within the context of traditional and school-based mental health preparation and service delivery. We conclude by contributing three resources for educational leaders to support the process of engaging school-based mental health practitioners. First, we offer a planning guide to understand state variations in certification requirements across professionals. Second, we provide a hiring guide primer that summarizes education requirements and delineates role orientations for school mental health practitioners. Third, we provide an interview guide to help clarify a candidate's experience and skills useful to contemporary school needs. We conclude by offering recommendations for educational leaders to become more effective consumers of school-based mental health services. The online version contains supplementary material available at 10.1007/s12310-022-09530-5.


Design of specific peptide inhibitors for group I phospholipase A2: structure of a complex formed between phospholipase A2 from Naja naja sagittifera (group I) and a designed peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) at 1.9 A resolution reveals unique features.
Phospholipase A(2) (PLA(2)) (E. C. 18.104.22.168) is a common enzyme in the two-way cascade mechanism leading to the production of proinflammatory compounds known as eicosanoids. The binding of phospholipase A(2) to the membrane surface and hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before its cleavage. To regulate the production of proinflammatory compounds, a specific peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) for the group I PLA(2) enzymes has been designed and synthesized. PLA(2) was isolated from Indian cobra (Naja naja sagittifera) venom and purified to homogeneity. The binding studies indicated the K(i) value of 1.02 +/- 0.10 x 10(-8) M. The purified PLA(2) samples and the designed inhibitor VAFRS were cocrystallized. The crystal structure of the complex was determined and refined to 1.9 A resolution. The peptide binds to PLA(2) at the active site and fills the hydrophobic channel completely. However, its placement with respect to the channel is in the opposite direction as compared to those observed in group II PLA(2)'s. Furthermore, the predominant intermolecular interactions involve strong electrostatic interactions between the side chains of peptide Arg and Asp 49 of PLA(2) together with a number of van der Waals interactions with other residues. A good number of observed interactions between the peptide and the protein indicate the significance of a structure-based drug design approach. The novel factor in the present sequence of the peptide is related to the introduction of a positively charged residue at the C-terminal part of the peptide.


Underutilization of Physical and Mental Health Services Prior to Nursing Home Admission.
The authors interviewed the families of 420 nursing home admissions to examine the relationship between patients' need for nursing and mental health services and their use of these services prior to nursing home placement. Although the majority of demented and nondemented patients needed help with activities of daily living, and many needed help with behavioral disorders, fewer than one-third of the families of these patients used community nursing and mental health services for these problems. Increased awareness of the potential value of and improved access to these services may postpone or prevent nursing home placement.


Cu(I) complexes of 3,3'-polymethylene bridged derivatives of 2,2'-bi-1,10-phenanthroline.
A series of 3,3'-polymethylene-2,2'-bi-1,10-phenanthrolines coordinate with Cu(I) to form dinuclear complexes [(CuL)(2)](2+). As the 3,3'-bridge is lengthened from two to four carbons, the ligand becomes more twisted about the 2,2'-bond, favoring dinuclear coordination. The distance between the two copper atoms varies from 2.92 A for the dimethylene-bridged system to 3.59 A for the tetramethylene bridge. Favorable pi-stacking interactions occur between opposing ligands and promote complex formation. Competition experiments indicate that self-recognition is important and only homoleptic complexes are observed. Under equilibrium conditions, formation of the tetramethylene-bridged complex appears to be the most favored while the dimethylene-bridged system is least favored. The intensity of the long wavelength metal-ligand charge-transfer absorption band decreases as the 3,3'-bridge is shortened. Interaction between the two copper centers is evidenced by a splitting of the oxidation wave, and this splitting increases as the Cu-Cu distance is decreased.


The simultaneous perception of auditory-tactile stimuli in voluntary movement.
The simultaneous perception of multimodal information in the environment during voluntary movement is very important for effective reactions to the environment. Previous studies have found that voluntary movement affects the simultaneous perception of auditory and tactile stimuli. However, the results of these experiments are not completely consistent, and the differences may be attributable to methodological differences in the previous studies. In this study, we investigated the effect of voluntary movement on the simultaneous perception of auditory and tactile stimuli using a temporal order judgment task with voluntary movement, involuntary movement, and no movement. To eliminate the potential effect of stimulus predictability and the effect of spatial information associated with large-scale movement in the previous studies, we randomized the interval between the start of movement and the first stimulus, and used small-scale movement. As a result, the point of subjective simultaneity (PSS) during voluntary movement shifted from the tactile stimulus being first during involuntary movement or no movement to the auditory stimulus being first. The just noticeable difference (JND), an indicator of temporal resolution, did not differ across the three conditions. These results indicate that voluntary movement itself affects the PSS in auditory-tactile simultaneous perception, but it does not influence the JND. In the discussion of these results, we suggest that simultaneous perception may be affected by the efference copy.


Subcortical and Cortical Electrophysiological Measures in Children With Speech-in-Noise Deficits Associated With Auditory Processing Disorders.
The aim of this study was to analyze the subcortical and cortical auditory evoked potentials for speech stimuli in children with speech-in-noise (SIN) deficits associated with auditory processing disorder (APD) without any reading or language deficits. The study included 20 children in the age range of 9-13 years. Ten children were recruited to the APD group; they had below-normal scores on the speech-perception-in-noise test and were diagnosed as having APD. The remaining 10 were typically developing (TD) children and were recruited to the TD group. Speech-evoked subcortical (brainstem) and cortical (auditory late latency) responses were recorded and compared across both groups. The results showed a statistically significant reduction in the amplitudes of the subcortical potentials (both for stimulus in quiet and in noise) and the magnitudes of the spectral components (fundamental frequency and the second formant) in children with SIN deficits in the APD group compared to the TD group. In addition, the APD group displayed enhanced amplitudes of the cortical potentials compared to the TD group. Children with SIN deficits associated with APD exhibited impaired coding/processing of the auditory information at the level of the brainstem and the auditory cortex. https://doi.org/10.23641/asha.21357735.


Lentiviral RNA interference-mediated downregulation of Forkhead box M1 expression suppresses growth of oral squamous cell carcinoma in vitro.
Oral squamous cell carcinoma (OSCC) is one of the most fatal types of oral cancer worldwide. Forkhead box M1 (FOXM1) is associated with the occurrence and development of a number of types of human cancer, but its function in OSCC remains unclear. The present study aimed to explore the effect of FOXM1 downregulation using lentivirus-mediated short hairpin (sh)RNA against FOXM1 (LV-shFOXM1) in the cell line Tca8113 in vitro. Infection of Tca8113 cells with LV-shFOXM1 inhibited the mRNA and protein expression level of FOXM1. The downregulation of FOXM1 resulted in cell cycle arrest of Tca8113 cells, and the inhibition of proliferation, migration and invasion. The protein expression level of cyclins B1 and D1 were downregulated, whereas those of p27 and p21 were upregulated following infection with LV-shFOXM1, compared with the blank control and LV-shCON groups. In addition, FOXM1 downregulation decreased the expression of matrix metalloproteinase-2 and LV-shFOXM1 significantly suppressed OSCC cell viability. Therefore, FOXM1 may be a target for the treatment of OSCC.


Short-term pharmacokinetic study of mycophenolate mofetil in neonatal swine.
Mycophenolate mofetil (MMF) is an effective immunosuppressive agent that has been frequently used in laboratory animals including swine; however, the pharmacokinetic properties of MMF in swine have not been studied. This short-term study was designed to evaluate the feasibility and the pharmacokinetic profiles of MMF therapy in neonatal swine. Twelve neonatal pigs were randomized into four groups including one control and three treated groups with oral MMF administered at 0.5, 1, and 2 g/m(2)/d for 4 days, divided by 2 half-doses at 9:00 and 17:00 (except day 4 during which MMF was not administered at 17:00). Blood samples were collected at 9:00 on days 0, 2, 3 and 4 for complete blood count and hepatic/renal function examination; the trough concentration of plasma mycophenolic acid (MPA) was also determined. On days 2 and 4, blood was collected to determine the area under the curve (AUC) of plasma MPA concentration. Animal body-weight growth and manifestations of MMF side-effects such as anorexia, vomiting, and diarrhea were also observed. MMF has no acute hepatic/renal toxicity in newborn pigs; however, less body-weight growth was observed in treated groups. In the control group, a spontaneous increase of lymphocyte count was observed; in contrast, MMF therapy with doses of 1 and 2 g/m(2)/d reduced both lymphocyte and monocyte counts of piglets. Oral MMF had high bioavailability in neonatal swine. MPA-AUC0-12h of doses 0.5, 1, and 2 g/m(2)/d was 22.00 ± 3.32, 57.57 ± 34.30, and 140.00 ± 19.70 μg × h/mL, respectively. Neither MPA trough concentration (MPA-C0), nor MPA maximum concentration (MPA-Cmax) or MPA-AUC0-6h had high correlation with MMF-dose. For surveillance of MPA exposure, MPA-C0 had significant correlation with MPA-AUC0-12h (Spearman's ρ = 0.933, AUC0-12h = 17.882 × C0 + 14.479, r(2) = 0.966). To reach adequate drug exposure and to reduce dose-dependent side effects, an MMF dose of 1 g/m(2)/d is recommended to be used as an initial dose for immunosuppressive therapy in piglets, and MPA-C0 monitoring is the most practical strategy for experimental transplantation study.


Analytical electron microscopic evaluation of the effects of paraformaldehyde pretreatment on the reaction of glutaraldehyde with biogenic amines.
Analytical electron microscopy was used to determine the quantitative effects of paraformaldehyde pretreatment on the formation of the biogenic amine-glutaraldehyde-chrome complex. Pretreatment with paraformaldehyde prevented the glutaraldehyde-chrome reaction with norepinephrine in the rat adrenal medulla. In contrast to the effect of paraformaldehyde on norepinephrine, pretreatment did not prevent the chrome reaction in serotonin-containing argentaffin cells of the gut. X-Ray energy spectrographic analysis revealed a significant decrease in chrome content in the paraformaldehyde treated tissue, but sufficient chrome did react to produce an electron-dense product. Thus by treating tissue with paraformaldehyde prior to the glutaraldehyde chrome procedure, serotonergic sites may be differentiated from catecholaminergic areas at the electron microscopic level.


Hospital-associated funguria: analysis of risk factors, clinical presentation and outcome.
Fungal urinary tract infections are an increasing problem in hospitalized patients. Funguria may be a result of contamination of the urine specimen, colonization of hte urinary tract, or may be indicative of true invasive infection. In this study, we report the risk factors, clinical features, treatments and outcome in a group of 68 hospitalized patients (adults and children) with fungal isolates recovered from 103 urinary samples. Underlying medical conditions were present in most patients. In the pediatric group, urinary tract abnormalities (86%) and prematurity (19%)accounted for the majority of the cases. Diabetes mellitus (28%), nephrolithiasis, and benign prostatic hyperplasia were the most common diseases in adults. Indwelling urethral catheters were noted in 38% of the pediatric patients and in 43% of adults during hospitalization. Candida albicans strains were responsible for 97% and 75% of positive cultures in children and adults, respectively. Symptoms such as fever, dysuria, frequency and flank pain were generally absent in both groups. Fluconazole was the most frequent antifungal utilized (61%) in children and ketoconazole in the adult group (42%). Removing the urinary catheter was attempted in 6 pediatric patients (29%) and in only 8 adults (17%). One patient (4%) in the pediatric group died compared to 10 in the adult group (21%, p=0.04). Successful diagnosis and treatment of funguria depends on a clear understanding of the risk factors and awareness of fungal epidemiology.


Sigma receptor ligands alter concentrations of corticosterone in plasma in the rat.
Both BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol hydrochloride) and gevotroline (WY-47384; 8-fluoro-2,3,4,5-tetrahydro-2-[3-(3-pyridinyl)-propyl]-1H-pyrido[4,3-b] indole hydrochloride) are known to antagonize the psychotomimetic action of N-allyl-normetazocine (NAN; SKF-10047) and exhibit a high affinity for the sigma receptor. Unexpectedly, the putative antagonists BMY-14802 and gevotroline acted like the agonist NAN and increased activity in the hypothalamic-pituitary-adrenal axis to elevate levels of corticosterone in plasma. During the acrophase (peak) of the effects of the circadian rhythm on the hypothalamic-pituitary-adrenal axis, the ED50 was 6.5 mmol/kg for BMY-14802 and 9.6 mmol/kg for gevotroline. The ED50s for BMY-14802 and gevotroline during the low activity phase were 15.8 and 21.2 mmol/kg, respectively. The efficacies during both phases of the circadian rhythm were similar for each drug. Additive effects on the levels of corticosterone in plasma were observed when the animals were pretreated with doses above the respective ED50 values and then subjected to a rotational stress, but a small dose of BMY-14802 (0.5 mg/kg) had the opposite effect and completely inhibited the stress-related increases in corticosterone in plasma. Neither drug, at large doses, altered the increase in levels of corticosterone in plasma generated by the circadian rhythm, but at smaller doses BMY-14802 did lower circadian-related levels of corticosterone. Pretreatment with dexamethasone blocked the gevotroline-related increase in corticosterone in plasma, but not the BMY-14802-related increase. These data suggest that central sigma receptor mechanisms are involved in the regulation of the hypothalamic-pituitary-adrenal axis and that therapeutic agents that affect these receptors may alter the activity in this axis.


Stable Isotope Dilution Assays for Clinical Analyses of Folates and Other One-Carbon Metabolites: Application to Folate-Deficiency Studies.
Folate deficiency is generally accepted as a potential direct or indirect risk factor for diseases including spina bifida, coronary heart diseases, malfunctions of the central nervous system, and cancer. The direct inclusion of folates in the methylation cycle, including the remethylation of homocysteine and regeneration of S-adenosylmethionine, underlines the importance of these vitamins and other components of one-carbon metabolism. Therefore, the aim of the present study was to develop a multiple stable isotope dilution assay (SIDA) for the respective analytes in plasma and tissue samples to allow for a closer look at the interaction between a severe folate deficiency and local folate status, as well as further interactions with circulating S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine. The analytical methods were based on SIDAs coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using the deuterated folates [2H4]-5-methyltetrahydrofolic acid, [2H4]-5-formyltetrahydrofolic acid, [2H4]-tetrahydrofolic acid, [2H4]-10-formylfolic acid, and [2H4]-folic acid and the deuterated one-carbon metabolites [2H4]-homocysteine, [2H4]-S-adenosylhomocysteine, and [2H3]-S-adenosylmethionine as internal standards. Three analytical methods have been developed for the analysis of homocysteine, S-adenosylmethionine, S-adenosylhomocysteine, and six folate vitamers. Validation data for the analysis of C1-metabolites in plasma and tissue samples or folate analysis in tissue samples revealed excellent sensitivity, precision, and recovery for all analytes studied. The miniaturized methods using sample volumes as low as 50 μL and weighed portions of 5-25 mg will allow the assessment of the status of folates and additional biomarkers of impaired one-carbon metabolism during folate deficiency.


Carbon Nanosheets Containing Discrete Co-Nx-By-C Active Sites for Efficient Oxygen Electrocatalysis and Rechargeable Zn-Air Batteries.
Structural and compositional engineering of atomic-scaled metal-N-C catalysts is important yet challenging in boosting their performance for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Here, boron (B)-doped Co-N-C active sites confined in hierarchical porous carbon sheets (denoted as Co-N,B-CSs) were obtained by a soft template self-assembly pyrolysis method. Significantly, the introduced B element gives an electron-deficient site that can activate the electron transfer around the Co-N-C sites, strengthen the interaction with oxygenated species, and thus accelerate reaction kinetics in the 4e- processed ORR and OER. As a result, the catalyst showed Pt-like ORR performance with a half-wave potential (E1/2) of 0.83 V versus (vs) RHE, a limiting current density of about 5.66 mA cm-2, and higher durability (almost no decay after 5000 cycles) than Pt/C catalysts. Moreover, a rechargeable Zn-air battery device comprising this Co-N,B-CSs catalyst shows superior performance with an open-circuit potential of ∼1.4 V, a peak power density of ∼100.4 mW cm-2, as well as excellent durability (128 cycles for 14 h of operation). DFT calculations further demonstrated that the coupling of Co-Nx active sites with B atoms prefers to adsorb an O2 molecule in side-on mode and accelerates ORR kinetics.


Do cheap internet drugs threaten the safety of the doctor-patient relationship?
During traditional office visits, trusted physicians give their patients careful and leisurely diagnostic attention, communicate sound and understandable clinical impressions and, more often than not, write prescriptions that can be filled at convenient neighborhood pharmacies. Or do they? In reality, harried doctors rush through appointments, leaving patients confused about prescriptions they cannot afford, either because their insurance plans do not cover the recommended medication or because they lack the cash to pay out of pocket for obscenely priced products. Internet pharmaceutical acquisition offers a cheap alternative. Or does it?


Thromboembolic complication induced stable occlusion of a ruptured basilar tip aneurysm. Case report and review of the literature.
We describe a case of a ruptured basilar bifurcation aneurysm that thrombosed during preparation for endovascular therapy as a complication of diagnostic angiogaphy, and showed a favorable evolution during long-term follow-up. Endogenous thrombosis of ruptured, non giant aneurysms is uncommon. The persistence of occlusion over time in such cases is not well established. Two weeks after rupture, a 6 x 8 mm basilar bifurcation aneurysm was referred for endovascular treatment. During preparation for endovascular coil occlusion, without having any endovascular material at the level of the basilar artery, a complete thrombotic occlusion of the basilar bifurcation and aneurysm was observed. Given the good collateral circulation for both posterior cerebral arteries no thrombolysis was undertaken. The early follow-up of seven days, three and six months showed a complete recanalization of the basilar artery and remodeling of the basilar bifurcation. The 20 months imaging follow-up demonstrated a small aneurysm regrowth at the prevoius location that remained stable during the follow-up of seven years. Unchanged biological and hemodynamic characteristics. however, may pose an elevated risk of a new aneurysm formation over time, making long-term imaging follow-up, and in case of progression, aneurysm occlusion necessary for the patient.


Bacterial Community Dynamics and Biocement Formation during Stimulation and Augmentation: Implications for Soil Consolidation.
Microbially-induced CaCO3 precipitation (MICP) is a naturally occurring process wherein durable carbonates are formed as a result of microbial metabolic activities. In recent years, MICP technology has been widely harnessed for applications in civil engineering wherein synthesis of calcium carbonate crystals occurs at ambient temperature paving way for low energy biocement. MICP using pure urease (UA) and carbonic anhydrase (CA) producing bacteria has been promising in laboratory conditions. In the current study we enriched ureolytic and carbonic anhydrase communities in calcareous soil under biostimulation and bioaugmentation conditions and investigated the effect of microbial dynamics on carbonate precipitation, calcium carbonate polymorph selection and consolidation of biological sand column under nutrient limited and rich conditions. All treatments for stimulation and augmentation led to significant changes in the composition of indigenous bacterial population. Biostimulation as well as augmentation through the UA route was found to be faster and more effective compared to the CA route in terms of extracellular enzyme production and carbonate precipitation. Synergistic role of augmented cultures along with indigenous communities was recorded via both the routes of UA and CA as more effective calcification was seen in case of augmentation compared to stimulation. The survival of supplemented isolates in presence of indigenous bacterial communities was confirmed through sequencing of total diversity and it was seen that both UA and CA isolate had the potential to survive along with native communities under high nutrient conditions. Nutrient conditions played significant role in determining calcium carbonate polymorph fate as calcitic crystals dominated under high carbon supplementation. Finally, the consolidation of sand columns via stimulation and augmentation was successfully achieved through both UA and CA route under high nutrient conditions but higher consolidation in short time period was noticed in UA route. The study reports that based upon the organic carbon content in native soils, stimulation can be favored at sites with high organic carbon content while augmentation with repeated injections of nutrients can be applied on poor nutrient soils via different enrichment routes of microbial metabolism.


Estimation of seabed properties and range from vector acoustic observations of underwater ship noise.
The Intensity Vector Autonomous Recorder (IVAR) simultaneously measures acoustic particle velocity and pressure. IVAR was deployed during the 2017 Seabed Characterization Experiment (SBCEX) with the primary objective to study sound propagation in fine-grained, muddy sediments. In this study a Bayesian inversion framework is applied to ship underwater noise recorded by IVAR. The data are relative phase of pressure and vertical particle velocity, a quantity that is independent of the ship noise source spectrum. Inversion estimates for the sediment layer and underlying basement properties are in agreement with other reports from SBCEX.


The stromal derived factor-1 mutated allele (SDF1-3'A) is associated with a lower incidence of atherosclerosis in HIV-infected patients.
HIV-infected patients have higher rates of subclinical atherosclerosis. The chemokine stromal derived factor 1 (SDF-1) is the natural ligand for the CXCR4 HIV co-receptor, is highly expressed in atherosclerotic plaques, and the plasma concentration is lower in individuals homozygous for the mutant allele (SDF1-3'A). We tested the influence of SDF1-3'A on atherosclerosis in HIV-infected patients. We performed carotid ultrasonography and determined the SDF1-3'A DNA polymorphism in 183 HIV-infected patients. Classical cardiovascular risk factors and antiretroviral therapy were also recorded. From these patients, we selected a group of 134 patients taking protease inhibitor-based antiretroviral therapy and in whom the lipid profile over an 18-month follow-up was collated. We found atherosclerosis in 113 (61.7%) and a lower number of patients with the SDF-1 mutated allele in the group with carotid atherosclerosis compared to those without (41.6% versus 57.1%; P = 0.04). Using a logistic regression analysis, age and dyslipidaemia were significantly associated with atherosclerosis but the SDF1-3'A allele exerted a protective effect on the development of atherosclerosis (odds ratio, 0.45; 95% confidence interval, 0.14-1.02; P = 0.05). Further, we observed that, in the selected group of patients there were lower plasma low-density lipoprotein cholesterol concentrations [mean +/- SEM, 2.06 +/- 0.34 mmol/l] throughout follow up in those patients without carotid lesions and who also carried the mutated SDF1-3'A allele (P = 0.04). The SDF1-3'A allele is associated with a lower presence of subclinical carotid atherosclerosis in an HIV-infected population.


Tapering the sky response for angular power spectrum estimation from low-frequency radio-interferometric data.
It is important to correctly subtract point sources from radio-interferometric data in order to measure the power spectrum of diffuse radiation like the Galactic synchrotron or the Epoch of Reionization 21-cm signal. It is computationally very expensive and challenging to image a very large area and accurately subtract all the point sources from the image. The problem is particularly severe at the sidelobes and the outer parts of the main lobe where the antenna response is highly frequency dependent and the calibration also differs from that of the phase centre. Here, we show that it is possible to overcome this problem by tapering the sky response. Using simulated 150 MHz observations, we demonstrate that it is possible to suppress the contribution due to point sources from the outer parts by using the Tapered Gridded Estimator to measure the angular power spectrum Cℓ of the sky signal. We also show from the simulation that this method can self-consistently compute the noise bias and accurately subtract it to provide an unbiased estimation of Cℓ.


Specificity of the 3H-triolein assay for pancreatic lipase in blood plasma.
The aim of this study was to investigate the specificity of the 3H-triolein assay and to investigate the recovery of highly purified pancreatic lipase and pancreatic lipase in the form of pure non-activated pig pancreatic juice. Blood plasma from pigs was analysed for pancreatic lipase activity using the 3H-triolein substrate assay, with a method specific for lipoprotein lipase and with a method specific for hepatic lipase. The recovery of pancreatic lipase from pancreatic juice was approximately 100%, while the recovery of highly purified pancreatic lipase in plasma or whole blood was found to be approximately 1%. Preparations of highly concentrated, purified lipoprotein lipase showed activity in the 3H-triolein assay designed for pancreatic lipase, but the activity did not exceed 1% of the activity of this enzyme measured in an assay specific for lipoprotein lipase (samples containing physiological levels of lipoprotein lipase did not show any activity in the assay). Hepatic lipase was not measurable under the conditions of the 3H-triolein assay. In conclusion, the 3H-triolein assay showed pronounced specificity for pancreatic lipase compared with lipoprotein lipase or hepatic lipase.


Learning Transanal Total Mesorectal Excision.
A dynamic evolution is occurring in transanal surgery. Transanal techniques began with intraluminal surgical removal of rectal masses and have progressed to transanal total mesorectal excision (taTME) for rectal cancer. TaTME was first performed in 2009 by Sylla, Rattner, Delgado, and Lacy. This article documents the training pathway followed by pioneers in the taTME technique as well as consensus reports outlining the process of learning the taTME technique. A literature search was performed for taTME training, learning, and technique. Key elements in learning the taTME technique include appropriate indications, cadaver training, and outcomes reporting such as participating in a taTME registry. Consensus reports also agree on the following facets associated with improved outcomes: (1) appropriate case selection of mid and low rectal cancers, (2) prerequisite completion of an accredited training program in laparoscopic colorectal surgery and prior experience in transanal endoscopic surgery, (3) a two-team taTME approach from above and below is ideal, and (4) higher rectal cancer volume surgical practice. The unifying international recommendation for surgeons interested in learning the taTME technique conveys the following message: taTME is an advanced and complex technique that requires dedicated training and experience in TME surgery.


Angiotensin converting enzyme insertion/deletion polymorphism in sporadic and familial Alzheimer's disease and longevity.
A recent, large meta-analysis has reproposed the role of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a risk factor for Alzheimer's disease (AD). To further investigate the proposed association and to better clarify the role of ACE as a risk factor for AD, we analyzed the genotype and allele frequency distribution of ACE I/D and apolipoprotein E (APOE) gene polymorphisms in 235 Italian patients with sporadic AD, 153 with familial AD (FAD), 192 healthy controls and 111 centenarians. Patients with AD were consecutively gathered from among the outpatients from the Neurology Department at the University of Florence. All 691 subjects were genotyped for ACE and APOE polymorphisms. There were no significant differences in ACE genotypes or allele frequencies in all the studied groups, even after stratification for APOE epsilon4 carrier status. Centenarians show the highest allele D frequency, although the value is not significant, thus suggesting a possible implication of the D allele as an epistatic allele that has pleiotropic age-dependent effects. In conclusion, our data suggest that the ACE allelic variant is not a susceptibility factor in sporadic and familial AD (FAD), nor does it mitigate the effect of the APOE epsilon4 allele in the risk of developing AD. Moreover, our data do not suggest a possible involvement of the D allele in longevity.


Malaysian Journal of Medical Sciences' Performance Status in 2016.
This editorial aims to report on the performance of the Malaysian Journal of Medical Sciences (MJMS) in the year 2016. The performance report is based on an analysis of the auto-generated data compiled from the ScholarOne Manuscripts™. It will specifically focus on the pattern of manuscript submission, geographical distribution of contributors, manuscript submission by month and the acceptance-rejection rate of post-review manuscripts. It will also discuss the effects of the decision to raise the article acceptance standards. The MJMS would also like to share the news of its receipt of the 2016 Current Research in Malaysia (CREAM) award. This honour was bestowed upon us by the Ministry of Higher Education (MOHE) of Malaysia, on November 1, 2016.


Position of tianeptine among antidepressive chemotherapies.
The advent of a new antidepressant is always received with both interest and scepticism by clinicians. No new compound has yet been shown to be more efficient than imipramine in the treatment of depression. In determining the position of a compound among the antidepressants, four levels are to be considered: (a) Chemical family: Tianeptine is a tricyclic compound of dibenzothiazepine type. It is the only representative of this subgroup. (b) Biochemical activities: Tianeptine increases the presynaptic uptake of serotonin after single as well as repeated administration; but this action is not linked to any effect on the 5-HT post-synaptic systems. Electrophysiological modifications are observed in the locus coeruleus (noradrenergic) at 2.5 times higher doses; nevertheless, the essential action involves the serotoninergic systems. Tianeptine has no affinity for alpha 1 adrenergic and H1 antihistaminic receptors; this affinity is responsible in a large part for the sedative anxiolytic properties of antidepressants. Tianeptine has no affinity for the muscarinic receptors. It has secured its place among the non-anticholinergic antidepressants. The mechanism of action or the therapeutic profile cannot be inferred from this original biochemical profile. (c) In clinical trials, the double-blind trials confirm the antidepressant efficacy in essentially neurotic depressive syndromes, similar to that of imipramine, nomifensine, amitriptyline. They do not show a shorter onset time of antidepressant activity. The therapeutic profile appears to be neither stimulating nor sedative. Some arguments are in favor of an anxiolytic activity. Others favor a more psychotonic profile. Tianeptine can be classified among the mid-position antidepressants. (d) With respect to clinical acceptability, tianeptine has no anticholinergic effect and no cardiovascular effect.


Preventive effect of SA3443, a novel cyclic disulfide, on glucocorticoid-induced cataract formation of developing chick embryo.
The preventive effect of SA3443 [(4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid] against glucocorticoid-induced cataract of developing chick embryos was studied. When hydrocortisone succinate sodium (HC: 0.25 mumol per egg) was administered to 15-day-old embryos, almost all lenses became opaque (stage I:O%, II: 2.5 +/- 4.6%, III: 5 +/- 5.4%, IV-V 92.5 +/- 7.1%) at 48 hr after the treatment. However, a double application of SA3443 (10 mumol per egg) at 3 and 10 hr after HC treatment effectively prevented the cataract formation (stage I: 52.8 +/- 13.7%, II: 11.6 +/- 6.3%, III: 22.9 +/- 8.9%, IV-V: 13.9 +/- 11.0%) and diminished the decline in glutathione in the lens at 48 hr and in the liver at 24 hr after HC administration. The cleavage of the cyclic disulfide bond of SA3443 did not occur in the lens homogenate but in the liver homogenate. These results suggest that the appearance of sulfhydryl residue in the liver may contribute to the anticataract effects by representing radical scavenger activities.


Evaluation of a Multicomponent Psychosocial Skill Training Program for Junior Physicians in Their First Year at Work: A Pilot Study.
The present study was designed to gather preliminary information regarding the feasibility of implementing a psychosocial resilience program and to assess if the program would potentially promote protective factors (such as resiliency, self-efficacy) and job satisfaction as well as decreasing perceived stress among a sample of German junior physicians. Eighty-two junior physicians in their first year after graduation took part in the project and were randomized in a controlled trial to either an intervention or a control group for 3 months. The intervention group was offered resilience training combined with cognitive behavioral and solution-focused counseling. Primary outcome measures included scales of the PSQ, BRCS, SWOPE, and COPSOQ. Two post-intervention follow-up measurements proved the effectiveness of the intervention. There was a significant improvement between baseline and follow-up intervention scores on measures of resilience, self-efficacy, optimism, and perceived stress observed in the intervention group compared to the control group. Job satisfaction did not significantly differ between baseline and follow-ups. These results indicate that the program to enhance resilience and decrease stress among physicians is feasible to implement as a group training program in a workplace setting. Further, the intervention provides statistically significant improvement in perceptions of distress and strengthens protective factors (such as resiliency).


Biological evaluation of root canal antiseptics using in vitro and in vivo methods.
Five antiseptics commonly used in endodontic treatment were evaluated with regard to cytotoxicity and initial tissue irritating effect. The cytotoxicity was evaluated in a cell culture system using HeLa cells and the initial tissue irritating effect was assessed by application of the antiseptics onto an intact nonepithelialized tissue surface. The cell response was assessed by registering changes in the DNA synthesis of the cells and the tissue response was assessed by registering changes in the oxidoreductase enzyme activity of the tissue. To evaluate the ability of the cells and the tissue to overcome an induced damage, one part of the study included a recovery period before the condition of the cells and the tissue was assessed. The most severe cell and tissue reactions were caused by 5% Chloramine-T whereas no differences in toxicity or tissue irritating effect were found between 0.04% Jodopax, 0.1% Biosept, 0.1% Hibitane, or 0.5% sodium hypochlorite. The HeLa cells showed the best recovery after having been influenced by Jodopax, Chloramine-T or sodium hypochlorite solutions, whereas the best tissue recovery was observed in the experiments with Biosept and Hibitane.


[Adverse reactions to anthrax vaccination in Danish military personnel deployed to Iraq].
On Denmark's decision to join the war in Iraq, it was decided to immunise all personnel to be deployed there with anthrax vaccine. This paper describes the types and frequency of adverse reactions to the vaccine. Between March 2003 and February 2004, 1,899 immunisations against anthrax in 755 personnel were registered at the health care facilities of the Danish Defence. No serious or life-threatening adverse reactions were reported. The data showed a statistically significant decrease in adverse reactions between the four immunisation series. For males, adverse reactions after the second immunisation depended on possible adverse reactions to the first immunisation. In females, this correlation was not found. No differences in the frequency of adverse reactions between males and females were found. None of the vaccinated persons suffered serious or life-threatening adverse reactions. Compared to other studies on self-reported adverse reactions, the overall frequency was low. The data showed a statistically significant decrease in adverse reactions between the four immunisation series. This has been described in comparable studies. The correlation between adverse reactions in the second immunisation being dependent on adverse reactions to the first immunisation has been partly confirmed by other studies. No differences between the sexes were found, probably because only a few females were included in the study. In case of a significant level of threat concerning biological weapons, immunisation against anthrax is considered appropriate.


GENESRCH: a computer program for restriction fragment analysis.
We describe a program GENESRCH which has been written to enable the design of efficient restriction fragment analysis of DNA from patients with hereditary disorders. The program identifies homology of DNA sequences up to 20 base pairs in length, calculates the fragment sizes and indicates the position of enzyme restriction sites within the gene of interest. GENESRCH is written in the BASIC language and will run on any IBM-compatible PC with a parallel printer. A hard disc is recommended for efficient storage and retrieval of data. An example of the use of the program is cited.


Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center.
Development and implementation of robust reporting processes to systematically provide quality data to care teams in a timely manner is challenging. National cancer quality measures are useful, but the manual data collection required is resource intensive, and reporting is delayed. We designed a largely automated measurement system with our multidisciplinary cancer care programs (CCPs) to identify, measure, and improve quality metrics that were meaningful to the care teams and their patients. Each CCP physician leader collaborated with the cancer quality team to identify metrics, abiding by established guiding principles. Financial incentive was provided to the CCPs if performance at the end of the study period met predetermined targets. Reports were developed and provided to the CCP physician leaders on a monthly or quarterly basis, for dissemination to their CCP teams. A total of 15 distinct quality measures were collected in depth for the first time at this cancer center. Metrics spanned the patient care continuum, from diagnosis through end of life or survivorship care. All metrics improved over the study period, met their targets, and earned a financial incentive for their CCP. Our quality program had three essential elements that led to its success: (1) engaging physicians in choosing the quality measures and prespecifying goals, (2) using automated extraction methods for rapid and timely feedback on improvement and progress toward achieving goals, and (3) offering a financial team-based incentive if prespecified goals were met.


NS5A inhibitor resistance-associated polymorphisms in Brazilian treatment-naive patients infected with genotype 1 hepatitis C virus.
Several promising NS5A protein inhibitors for hepatitis C virus (HCV) treatment, showing good antiviral activity, are currently being evaluated in clinical trials. However, viral breakthroughs associated with resistant variants have been observed, especially in patients infected with HCV-1a. We aimed to evaluate the occurrence of potential resistance mutations in the NS5A gene of HCV among Brazilian treatment-naive patients. Direct sequencing of the HCV NS5A gene was performed in serum samples of 106 treatment-naive patients infected with subtypes 1a (n = 52) and 1b (n = 54). The sequence variability, signature patterns in amino acid sequences and variants associated with NS5A inhibitors were evaluated. The M28T and Y93H mutations were found in the subtype 1a sequences of two (3.85%) patients, and seven (13.46%) other patients presented the secondary mutation(s) H58P, E62D or H58P-E62D. For subtype 1b, the Y93H mutation was found in two (3.70%) patients and the substitutions R30Q, L31M, P58S and I280V were found in eight (14.81%) patients. Two distinct HCV-1a clades were distinguished by a phylogenetic analysis performed along with representative HCV-1a sequences and sequences containing HCV NS5A inhibitor resistance mutations retrieved from the Los Alamos database. All Brazilian sequences formed a large group of related sequences inside clade 1. It is noteworthy that 65.85% of sequences with substitution at sites 28, 30, 31 and 93 were found in clade 1. Brazilian HCV-1a sequences presented a peculiar pattern of amino acid composition, mutations and frequencies, which is distinct from other previously characterized sequences from other locations. The association of these findings with the outcome of treatment with NS5A inhibitors awaits further analysis.


The Economic Consequences of AIDS mortality in South Africa.
We quantify the impact of adult deaths on household economic wellbeing, using a large longitudinal dataset spanning more than a decade. Verbal autopsies allow us to distinguish AIDS mortality from that due to other causes. The timing of the lower socioeconomic status observed for households with AIDS deaths suggests that the socioeconomic gradient in AIDS mortality is being driven primarily by poor households being at higher risk for AIDS, rather than AIDS impoverishing the households. Following a death, households that experienced an AIDS death are observed being poorer still. However, the additional socioeconomic loss following an AIDS death is very similar to the loss observed from sudden death. Funeral expenses can explain some of the impoverishing effects of death in the household. In contrast, the loss of an employed member cannot. To date, antiretroviral therapy has not changed the socioeconomic status gradient observed in AIDS deaths.


Urban-rural comparison of HBV and HCV infection prevalence among adult women in Shandong Province, China.
In order to make urban-rural comparison of the prevalence of hepatitis B and C virus (HBV and HCV, respectively) infection in China, a twin survey was conducted in 1996 on two groups (50 subjects each) of 21-55 year-old, apparently healthy women for infection markers and serum enzyme levels; one group (the urban group) was in Jinan, the provincial capital of Shandong Province, and the other (the rural group) was in a farming village in Zhangqiu area some 30 km away from Jinan City. Comparison between the two groups showed that there was no significant (p > 0.10) difference in the prevalence of HBsAg+, anti-HBs+, anti-HBc+ and the cases positive to any of three HBV infection markers (i.e. HBV+). No age-dependent difference was detected within or between the groups. Thus the overall positivity rate was 8% for HBsAg+, 47% for anti-HBs+, 48% for anti-HBc+, and 64% for HBV+. No anti-HCV+ case was found either in the urban group or in the rural group. Liver function remained normal in all cases studied. The results together with perusal of published data suggest the urban-rural difference will not be remarkable, if present, in HBV and HCV infection in the regions studied, and possibly in China as a whole.


Multistage carcinogenesis and the incidence of human cancer.
We consider the implications of multistage carcinogenesis for the incidence of cancer in human populations. When clonal expansion of partially altered cells is properly accounted for, we find it unnecessary to invoke genomic instability as an early event in malignant transformation. Environmental agents that increase the rate of clonal expansion of partially altered cells are efficient carcinogens. As a corollary, intervention strategies that decrease this rate are to be preferred to strategies that decrease the rate of early mutational events in carcinogenesis.


Potential environmental implications of nanoscale zero-valent iron particles for environmental remediation.
Nanoscale zero-valent iron (nZVI) particles are widely used in the field of various environmental contaminant remediation. Although the potential benefits of nZVI are considerable, there is a distinct need to identify any potential risks after environmental exposure. In this respect, we review recent studies on the environmental applications and implications of nZVI, highlighting research gaps and suggesting future research directions. Environmental application of nZVI is briefly summarized, focusing on its unique properties. Ecotoxicity of nZVI is reviewed according to type of organism, including bacteria, terrestrial organisms, and aquatic organisms. The environmental fate and transport of nZVI are also summarized with regards to exposure scenarios. Finally, the current limitations of risk determination are thoroughly provided. The ecotoxicity of nZVI depends on the composition, concentration, size and surface properties of the nanoparticles and the experimental method used, including the species investigated. In addition, the environmental fate and transport of nZVI appear to be complex and depend on the exposure duration and the exposure conditions. To date, field-scale data are limited and only short-term studies using simple exposure methods have been conducted. In this regard, the primary focus of future study should be on 1) the development of an appropriate and valid testing method of the environmental fate and ecotoxicity of reactive nanoparticles used in environmental applications and 2) assessing their potential environmental risks using in situ field scale applications.


Vascular endothelial growth factor modified macrophages transdifferentiate into endothelial-like cells and decrease foam cell formation.
Macrophages are largely involved in the whole process of atherosclerosis from an initiation lesion to an advanced lesion. Endothelial disruption is the initial step and macrophage-derived foam cells are the hallmark of atherosclerosis. Promotion of vascular integrity and inhibition of foam cell formation are two important strategies for preventing atherosclerosis. How can we inhibit even the reverse negative role of macrophages in atherosclerosis? The present study was performed to investigate if overexpressing endogenous human vascular endothelial growth factor (VEGF) could facilitate transdifferentiation of macrophages into endothelial-like cells (ELCs) and inhibit foam cell formation. We demonstrated that VEGF-modified macrophages which stably overexpressed human VEGF (hVEGF165) displayed a high capability to alter their phenotype and function into ELCs in vitro Exogenous VEGF could not replace endogenous VEGF to induce the transdifferentiation of macrophages into ELCs in vitro We further showed that VEGF-modified macrophages significantly decreased cytoplasmic lipid accumulation after treatment with oxidized LDL (ox-LDL). Moreover, down-regulation of CD36 expression in these cells was probably one of the mechanisms of reduction in foam cell formation. Our results provided the in vitro proof of VEGF-modified macrophages as atheroprotective therapeutic cells by both promotion of vascular repair and inhibition of foam cell formation.


A quantitative analysis framework of placenta accreta spectrum: placenta subtype, intraoperative bleeding, and hysterectomy risk evaluation based on magnetic resonance imaging-anatomical-clinical features.
Placenta accreta spectrum (PAS) is a significant contributor to maternal morbidity and mortality. Our objective was to develop a quantitative analysis framework utilizing magnetic resonance imaging (MRI)-anatomical-clinical features to predict 3 clinically significant parameters in patients with PAS: placenta subtype (invasive vs. non-invasive placenta), intraoperative bleeding (≥1,500 vs. <1,500 mL), and hysterectomy risk (hysterectomy vs. non-hysterectomy). A total of 125 pregnant women with PAS from 2 medical centers were enrolled into an internal training set and an external testing set. Some 21 MRI-anatomical-clinical features were integrated as input into the framework. The proposed quantitative analytic framework contains mainly 3 classifiers built by extreme gradient boosting (XGBoost) and their testing in external datasets. We also further compared the accuracy of placenta subtype prediction between the proposed model and 4 radiologists. A quantitative model interpretation method called SHapley Additive exPlanations (SHAP) was conducted to explore the contribution of each feature. The placenta subtype (invasive vs. non-invasive), intraoperative bleeding (≥1,500 vs. <1,500 mL), and hysterectomy risk (hysterectomy vs. non-hysterectomy) demonstrated impressive area under the receiver operating characteristic curve (AUROC) values of 0.93, 0.88, and 0.90, respectively, in the internal validation set. Even in the external testing set, these metrics maintained their strength, achieving AUROC values of 0.91, 0.82, and 0.82, respectively. Comparing our proposed framework to the 4 radiologists, our model exhibited superior accuracy, specificity, and sensitivity in predicting placental subtypes within the external testing cohort. The features associated with intraplacental dark T2 bands played a crucial role in the decision-making process of all 3 prediction models. The quantitative analysis framework can provide a robust method for classification of placenta subtype (invasive vs. non-invasive placenta), intraoperative bleeding (≥1,500 vs. <1,500 mL), and hysterectomy risk (hysterectomy vs. non-hysterectomy) based on MRI-anatomical-clinical features in PAS.


Effects of volatile anesthetics on elastic stiffness in isometrically contracting ferret ventricular myocardium.
The effects of halothane, isoflurane, and sevoflurane on elastic stiffness, which reflects the degree of cross-bridge attachment, were studied in intact cardiac muscle. Electrically stimulated (0.25 Hz, 25 degrees C), isometrically twitching right ventricular ferret papillary muscles (n = 15) at optimal length (L(max)) were subjected to sinusoidal length oscillations (40 Hz, 0.25- 0.50% of L(max) peak to peak). The amplitude and phase relationship with the resulting force oscillations was decomposed into elastic and viscous components of total stiffness in real time. Increasing extracellular Ca(2+) concentration in the presence of anesthetics to produce peak force equal to control increased elastic stiffness during relaxation, which suggests a direct effect of halothane and sevoflurane on cross bridges.


Dorsal dermal sinus presenting as quadriparesis.
Dorsal dermal sinus (DDS) represents the spectrum of spinal dysraphism. Children may present with features of meningitis. A 13-month male child presented with features of meningitis and quadriparesis. Clinical examination revealed a small pit over the thoracic spine. MRI was suggestive of a DDS. Initially, the patient responded to antibiotics and methylprednisolone, which was given for resolving the mass effect. However, he had a recurrence of symptoms and underwent surgical exploration and resection of DSS with resolution of symptoms. Careful examination of the back is extremely essential in children with meningitis. Radiological investigation helps in visualisation of the DSS. Although rare in children, they may present with recurrent meningitis.


Temperamental differences, family relationships, and young children's response to change within the family.
In a longitudinal study of 40 firstborn children, temperamental differences between the children were found to be linked to the emergence and persistence of anxious and unhappy behaviour over the year following the birth of a sibling. Direct observation showed that these temperamental differences were also associated with differences in the children's interactions with their mothers, and with differences in their behaviour towards their mothers when mother and sibling were interacting. In contrast, the wide range of individual differences in the behaviour of the firstborn children to their siblings was not associated with temperamental difference between the children. There was some evidence for continuity in temperamental differences between the assessments before and after the sibling birth, but in many children the behavioural changes were marked. These findings underline the clinical significance of temperamental differences in children's vulnerability to changes in family life; they also indicate that 'temperament' should be considered not as a characteristic of the child independent of his or her particular family relationships but, on the contrary, as closely linked to his or her relationship with the mother, and as susceptible to the effects of marked change in the family environment.


Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion.
Beta-catenin functions both as an adherens junction adhesion protein and as an essential mediator of the canonical Wnt signaling pathway. Wnts stabilize beta-catenin and promote its accumulation in the nucleus, where it regulates transcription of the target genes. Here we show that Smad7 promotes cell-cell adhesion by stabilizing beta-catenin and consequently increases the beta-catenin-E-cadherin complex level at the plasma membrane. A Smad7-Axin interaction disassociates GSK-3beta and beta-catenin from Axin, as well as inhibits the recruitment of Smurf2, an E3 ligase, to beta-catenin, thus protecting beta-catenin from phosphorylation and degradation. Smad7 increases the stabilized beta-catenin to form a complex with E-cadherin and stabilizes the E-cadherin-beta-catenin complex. Thereby, rather than being translocated to the nucleus for regulating the target gene transcription, Smad7-stabilized-beta-catenin is shunted to the E-cadherin complex to modulate cell-cell adhesion.


Immunochemical identification of intermediate-sized filaments in human neoplastic cells. A diagnostic aid for the surgical pathologist.
Forty-three tumors were investigated by means of immunofluorescence with the use of antibodies against the following different classes of intermediate-sized (10 nm) filament proteins: 1) cytokeratins, 2) vimentin, and 3) desmin. In general, the immunologic features of tumor-cell intermediate filaments are those present in their tissue of origin. It can be seen, therefore, that, during neoplastic transformation, there are no major changes in the synthesis of the type of intermediate filament proteins when compared to normal tissues. Immunologic identification of these proteins furnishes the surgical pathologist with a quick and clear-cut way to differentiate tumors of mesenchymal origin from epithelial neoplasms, and in particular to distinguish between malignant lymphomas and lymph node metastases of undifferentiated carcinomas.


CdTe quantum dots as fluorescent probes to study transferrin receptors in glioblastoma cells.
Overexpression of transferrin receptors (TfRs), which are responsible for the intracellular uptake of ferric transferrin (Tf), has been described in various cancers. Although molecular biology methods allow the identification of different types of receptors in cancer cells, they do not provide features about TfRs internalization, quantification and distribution on cell surface. This information can, however, be accessed by fluorescence techniques. In this work, the quantum dots (QDs)' unique properties were explored to strengthen our understanding of TfRs in cancer cells. QDs were conjugated to Tf by covalent coupling and QDs-(Tf) bioconjugates were applied to quantify and evaluate the distribution of TfRs in two human glioblastoma cells lines, U87 and DBTRG-05MG, and also in HeLa cells by using flow cytometry and confocal microscopy. HeLa and DBTRG-05MG cells showed practically the same TfR labeling profile by QDs-(Tf), while U87 cells were less labeled by bioconjugates. Furthermore, inhibition studies demonstrated that QDs-(Tf) were able to label cells with high specificity. HeLa and DBTRG-05MG cells presented a similar and a higher amount of TfR than U87 cells. Moreover, DBTRG-05MG cells are more efficient in recycling the TfR than the other two cells types. This is the first study about TfRs in human glioblastoma cells using QDs. This new fluorescent tool can contribute to our understanding of the cancer cell biology and can help in the development of new therapies targeting these receptors.


Tissue-Preferential Activity and Induction of the Pepper Capsaicin Synthase PUN1 Promoter by Wounding, Heat and Metabolic Pathway Precursor in Tobacco and Tomato Plants.
A promoter is an essential structural component of a gene that controls its transcription activity in different development stages and in response to various environmental stimuli. Knowledge of promoter functionality in heterologous systems is important in the study of gene regulation and biotechnological application. In order to explore the activity of the pepper capsaicin synthase gene (PUN1) promoter, gene constructs of pPUN1::GUS (for β-glucuronidase) and pPUN1::NtKED (for a tobacco wound-responsive protein) were introduced into tobacco and tomato, respectively, and their activities were examined. Higher levels of GUS staining intensity and transcription were detected in ovary, anther and pollen than other tissues or organs in tobacco plants. Likewise, transgenic tomato fruits had a higher level of pPUN1::NtKED gene expression than the leaf and flower. The PUN1-driven gene expression can be transiently induced by wounding, heat (40 °C) and the capsaicinoid biosynthetic pathway precursor phenylalanine. When compared to the reported pPUN1::GUS-expressing Arabidopsis, the PUN1 promoter exhibited a more similar pattern of activities among pepper, tobacco and tomato, all Solanaceae plants. Our results suggest the potential utility of this tissue-preferential and inducible promoter in other non-pungent Solanaceae plants for research of gene function and regulation as well as in the biotechnological applications.


Vibrio fluvialis and Vibrio furnissii isolated from a stool sample of one patient.
Vibrio fluvialis and Vibrio furnissii have been associated with diarrhea but have rarely been isolated in the United States. We received strains of V. fluvialis and V. furnissii that were isolated from the stool of a 1-month-old baby. A description of these two strains and the case history of the patient are given in this report.