Perineal hernia: a case of outlet dysfunction.
This article describes and discusses a successfully treated case of a primary posterior perineal hernia which is a rare cause of outlet dysfunction. A 46-year-old female patient had a 6 cm left para-anal protrusion and a 7-year history of outlet dysfunction. The perineal hernia orifice was closed via an abdominal approach using both a polypropylene mesh and a Parietex Composite Net. A rectopexy to the promontory of the sacrum was then performed. Moreover, after 6 months' follow-up, the patient presented a sense of incomplete evacuation and underwent a prolassectomy to treat a hidden rectal prolapse. This clinical case shows that the surgical treatment of a pelvic pathology can be successful for the correction of a serious functional defect such as outlet dysfunction.


[Mechanisms of regulation and function of G-protein coupled receptor kinases].
G protein-coupled receptor kinases (GRKs) are key modulators of G protein-coupled receptor (GPCR) signaling. They constitute a family of seven mammalian serine-threonine protein kinases that phosphorylate agonist-bound receptor. GRKs-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization. Activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium sensitive proteins. Moreover, GRK phosphorylation by several other kinases and autophosphorylation have recently been shown to modulate its functionality. This review summarize our current knowledge of GRKs regulatory mechanisms and GRKs physiological function.


Knowledge, Attitude and Practices of Diabetic Patients - A Cross Sectional Study in a Tertiary Care Hospital in Mysore.
The prevalence rates of diabetes are rising rapidly both in urban and rural India with the present prevalence in urban India being 12-19% and in rural India 4 - 10% in different published Indian studies.1 All involved in diabetes care agree that patients play a major role in the successful management of diabetes. There is an increasing amount of evidence that patient education is the most effective way to lessen the diabetic complications and its management.2 Education is likely to be effective if we know the characteristics of the patients in terms of knowledge, attitude and practices about diabetes. This study was conducted in Mysore to know the knowledge, attitude and practices of diabetic patients attending JSS Hospital. A total of 900 patients were included in the study. Five hundred sixteen (57.3%) patients were males, while 384 (42.7%) patients were females. Four hundred twenty-three (47%) patients were from urban area, while 477 (53%) were from rural area. Five hundred sixty-five (62.5%) diabetic patients were unaware of the diagnostic criteria for diabetes mellitus, 661 (73.4%) patients about cause of diabetes, 264 (29.3%) patients about common symptoms of diabetes, 256 (28.4%) patients about symptoms of hypoglycemia. Diabetes is a chronic disease which can affect many systems in the body like the heart, eyes, kidneys and nerves contributing to increased morbidity and mortality. 29%, 30.7%, 31.2% and 35.7% of diabetic patients were not aware of the diabetic complications to heart, eyes, kidneys and nerves respectively. Even patients with diabetes for more than 10 years, 18.8% were not aware of the heart complications while 21.5% were not aware of the diabetes complications to eyes, kidneys and nerves. 834 (92.6%) diabetic patients were not aware of HbA1C. 790 (87.7%) diabetic patients did not know that fruits can be eaten by diabetics. Eight hundred seventeen (90.8%) diabetic patients had not attended a formal diabetic education class. This possibly is a major reason for diabetic patients to have poor awareness of different aspects of diabetes. The low awareness in diabetes patients are noted in different studies done in different parts of India. Education is not just a part of diabetes treatment. It is the treatment. According to WHO, education is the cornerstone of diabetes care. For a physician, diabetes is one of the many diseases calling for his attention in his practice. The time constraints prohibit physicians from delivering optimal diabetes care to their patients which include performing all the necessary tests, educating their patients about the disease, its complications and management. Diabetes educator who can be a nurse, a dietician, a social worker or in a more sophisticated centre a qualified diabetes educator can fill up this important void and play a major role in optimal diabetes care. The key aims of diabetes education are to change behavior of people and promote self management. Self management implies that the person with diabetes will understand the importance of factors like food intake, exercise and medications on blood glucose. PACE project study has concluded that through direct public education and mass media campaigns, awareness about diabetes and its complications can be improved.3 To conclude, education has the biggest role to play in containing diabetes epidemic in India. Responsibility should be at every level from individual doctors to organizations to governments. Effective utilization of the limited available resources is critical for a country like India. We in India are blessed with a large youth population and we should not turn this blessing of a vibrant young nation to a curse of an unhealthy young nation.


Characterization of [Nphe(1)]nociceptin(1-13)NH(2), a new selective nociceptin receptor antagonist.
1.. Nociceptin (orphanin FQ) is a novel neuropeptide capable of inducing a variety of biological actions via activation of a specific G-protein coupled receptor. However, the lack of a selective nociceptin receptor antagonist has hampered our understanding of nociceptin actions and the role of this peptide in pathophysiological states. As part of a broader programme of research, geared to the identification and characterization of nociceptin receptor ligands, we report that the novel peptide [Nphe(1)]nociceptin(1-13)NH(2) acts as the first truly selective and competitive nociceptin receptor antagonist and is devoid of any residual agonist activity. 2. [Nphe(1)]nociceptin(1-13)NH(2) binds selectively to recombinant nociceptin receptors expressed in Chinese hamster ovary (CHO) cells (pK(i) 8.4) and competitively antagonizes the inhibitory effects of nociceptin (i) on cyclic AMP accumulation in CHO cells (pA(2) 6.0) and (ii) on electrically evoked contractions in isolated tissues of the mouse, rat and guinea-pig with pA(2) values ranging from 6.0 to 6.4. 3. [Nphe(1)]nociceptin(1-13)NH(2) is also active in vivo, where it prevents the pronociceptive and antimorphine actions of intracerebroventricularly applied nociceptin, measured in the mouse tail withdrawal assay. Moreover, [Nphe(1)]nociceptin(1-13)NH(2) produces per se a dose dependent, naloxone resistant antinociceptive action and, at relatively low doses, potentiates morphine-induced analgesia. 4. Collectively our data indicate that [Nphe(1)]nociceptin(1-13)NH(2), acting as a nociceptin receptor antagonist, may be the prototype of a new class of analgesics.


Anatomy and blood supply of the lower four cranial and cervical nerves: relevance to surgical neck dissection.
This study is a continuation of previous work searching for possible anatomic reasons to explain variable and usually unpredictable postoperative pain and dysfunction after the same nerve losses with similar neck dissection operations. The study consisted of dissections of 19 deceased unpreserved elderly subjects arterially injected with dyed latex. Of the 19 subjects, 14 had brain stem and cervical spinal cord dissections, and all had neck dissections. The findings suggested two possible anatomic reasons for the pain and dysfunction: (i) The intracranial anatomy of the lower four cranial nerves, the glossopharyngeal (IX), the vagus (X), the spinal accessory (XI), and the hypoglossal (XII), was just as variable as the previously reported peripheral spinal accessory nerve plexus; and (ii) Both the intracranial and neck dissections indicated that the blood supply to the lower four cranial and cervical nerves, particularly to the brachial plexus, could be impaired by atherosclerosis and/or neuroforaminal impingement or operative loss. This loss of blood supply theoretically could result in ischemia as another possible cause of postoperative pain and dysfunction. It is concluded that because of the potential importance of each nerve and vessel, often unknown at operation, it is very important to spare as many of them as possible to avoid subsequent painful impairment.


Precision absolute measurements of strong and highly inhomogeneous magnetic fields.
The low-temperature ([similar or less than]4 K) dependence of the photoconductance in n-type silicon on the conduction electron and bound donor electron spin state serves as the basis of a high-precision, wide-range magnetic field measuring probe, which by virtue of its very small dimensions is well suited for spatial mapping of highly inhomogeneous fields produced by superconducting magnets. The probe may also be adapted to power and frequency measurement of microwave sources operating at approximately mW power levels and frequencies up to approximately 500 GHz.


Fully Printed Stretchable and Multifunctional E-Textiles for Aesthetic Wearable Electronic Systems.
Electronic textiles (e-textiles) that combine the wearing comfort of textiles and the functionality of soft electronics are highly demanded in wearable applications. However, fabricating robust high-performance stretchable e-textiles with good abrasion resistance and high-resolution aesthetic patterns for high-throughput manufacturing and practical applications remains challenging. Herein, the authors report a new multifunctional e-textile fabricated via screen printing of the water-based silver fractal dendrites conductive ink. The as-fabricated e-textiles spray-coated with the invisible waterproofing agent exhibit superior flexibility, water resistance, wearing comfort, air permeability, and abrasion resistance, achieving a low sheet resistance of 0.088 Ω sq-1 , high stretchability of up to 154%, and excellent dynamic stability for over 1000 cyclic testing (ε = 100%). The printed e-textiles can be explored as strain sensors and ultralow voltage-driven Joule heaters driven for personalized thermal management. They finally demonstrate an integrated aesthetic smart clothing made of their multifunctional e-textiles for human motion detection and body-temperature management. The printed e-textiles provide new opportunities for developing novel wearable electronics and smart clothing for future commercial applications.


Achieving ultimate anterior esthetics with a new microhybrid composite.
Direct bonding is one of the most commonly used forms of restoration for the conservative esthetic improvement of anterior teeth. The major challenges involve selecting composites that have adequate strength as well as provide lifelike optical properties that render the restoration functionally sound and esthetically pleasing. Properties such as high sculptability, wide shade range, varying opacities and translucency, as well as high polishability are essential for gaining absolute control over the restorative process and the attainment of natural-looking results. This article discusses a new composite restorative system and its application in the direct esthetic and functional rehabilitation of the anterior dentition.


Histone Acetylation Defects in Brain Precursor Cells: A Potential Pathogenic Mechanism Causing Proliferation and Differentiation Dysfunctions in Mitochondrial Aspartate-Glutamate Carrier Isoform 1 Deficiency.
Mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) deficiency is an ultra-rare genetic disease characterized by global hypomyelination and brain atrophy, caused by mutations in the SLC25A12 gene leading to a reduction in AGC1 activity. In both neuronal precursor cells and oligodendrocytes precursor cells (NPCs and OPCs), the AGC1 determines reduced proliferation with an accelerated differentiation of OPCs, both associated with gene expression dysregulation. Epigenetic regulation of gene expression through histone acetylation plays a crucial role in the proliferation/differentiation of both NPCs and OPCs and is modulated by mitochondrial metabolism. In AGC1 deficiency models, both OPCs and NPCs show an altered expression of transcription factors involved in the proliferation/differentiation of brain precursor cells (BPCs) as well as a reduction in histone acetylation with a parallel alteration in the expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, histone acetylation dysfunctions have been dissected in in vitro models of AGC1 deficiency OPCs (Oli-Neu cells) and NPCs (neurospheres), in physiological conditions and following pharmacological treatments. The inhibition of HATs by curcumin arrests the proliferation of OPCs leading to their differentiation, while the inhibition of HDACs by suberanilohydroxamic acid (SAHA) has only a limited effect on proliferation, but it significantly stimulates the differentiation of OPCs. In NPCs, both treatments determine an alteration in the commitment toward glial cells. These data contribute to clarifying the molecular and epigenetic mechanisms regulating the proliferation/differentiation of OPCs and NPCs. This will help to identify potential targets for new therapeutic approaches that are able to increase the OPCs pool and to sustain their differentiation toward oligodendrocytes and to myelination/remyelination processes in AGC1 deficiency, as well as in other white matter neuropathologies.


Human Choice Predicted by Obtained Reinforcers, Not by Reinforcement Predictors.
Macphail (1985) proposed that "intelligence" should not vary across vertebrate species when contextual variables are accounted for. Focusing on research involving choice behavior, the propensity for choosing an option that produces stimuli that predict the presence or absence of reinforcement but that also results in less food over time can be examined. This choice preference has been found multiple times in pigeons (Stagner and Zentall, 2010; Zentall and Stagner, 2011; Laude et al., 2014) and has been likened to gambling behavior demonstrated by humans (Zentall, 2014, 2016). The present experiments used a similarly structured task to examine adult human preferences for reinforcement predictors and compared findings to choice behavior demonstrated by children (Lalli et al., 2000), monkeys (Smith et al., 2017; Smith and Beran, 2020), dogs (Jackson et al., 2020), rats (Chow et al., 2017; Cunningham and Shahan, 2019; Jackson et al., 2020), and pigeons (Roper and Zentall, 1999; Stagner and Zentall, 2010). In Experiment 1, adult human participants showed no preference for reinforcement predictors. Results from Experiment 2 suggest that not only were reinforcement predictors not preferred, but that perhaps reinforcement predictors had no effect at all on choice behavior. Results from Experiments 1 and 2 were further assessed using a generalized matching equation, the findings from which support that adult human choice behavior in the present research was largely determined by reinforcement history. Overall, the present results obtained from human adult participants are different than those found from pigeons in particular, suggesting that further examination of Macphail (1985) hypothesis is warranted.


Aging and health: an examination of differences between older Aboriginal and non-Aboriginal people.
The Aboriginal population in Canada, much younger than the general population, has experienced a trend towards aging over the past decade. Using data from the 2001 Aboriginal Peoples Survey (APS) and the 2000/2001 Canadian Community Health Survey (CCHS), this article examines differences in health status and the determinants of health and health care use between the 55-and-older Aboriginal population and non-Aboriginal population. The results show that the older Aboriginal population is unhealthier than the non-Aboriginal population across all age groups; differences in health status, however, appear to converge as age increases. Among those aged 55 to 64, 7 per cent of the Aboriginal population report three or more chronic conditions compared with 2 per cent of the non-Aboriginal population. Yet, among those aged 75 and older, 51 per cent of the Aboriginal population report three or more chronic conditions in comparison with 23 per cent of the non-Aboriginal population.


Florida hospital cuts failed pediatric sedation rate 98%.
* In a survey of Broward General Medical Center, The Joint Commission found fault with the administration of sedation for pediatric outpatient diagnostic procedures. * There is a great deal of variation among health care facilities on sedatives use and techniques and safety standards used. * Broward's initiative eliminated rescheduled exams and failed procedures by 98%.


[Analysis of the sudden heart death causes in selected sample of dead].
Sudden cardiac death (SCD) is death from cardiac causes within one hour of the onset of symptoms. In the Czech Republic, there is no SCD registry, analyses of SCD causes are rare and there is no functional connection between the results of an autopsy on a person with SCD and examination of relatives who are at risk of a similar disease. The authors reviewed available autopsy records of the Department of Forensic Medicine and Medical Law of the University Hospital Olomouc over a specified period of time to find persons with severe coronary artery disease, heart failure or deaths from unknown causes in a specific age range. Subsequently, the available information about the circumstances of SCD was analyzed.


Distribution and immunochemical specificities of fimbriae of Porphyromonas gingivalis and related bacterial species.
Rabbit polyclonal antibody (Poly-1) and mouse monoclonal antibodies (mAbs) TO-11, TO-14 and TO-M1 specific for Porphyromonas gingivalis 381 fimbriae were prepared. Poly-1 and the 3 mAbs were screened for their reactivity with whole cells oral and nonoral black-pigmented bacterial species by enzyme-linked immunosorbent assay (ELISA) and the binding experiment using [125I]Poly-1 and [125I]mAbs. ELISA revealed that Poly-1 definitely reacted with whole cells of all the 11 strains of P. gingivalis tested. However, 8 of 11 P. gingivalis strains reacted with mAbs TO-11, TO-14 and TO-M1. These results were confirmed by the specific binding of radiolabelled Poly-1 and mAb TO-11 to the 8 strains. The M(r) of the fimbrial subunit protein (fimbrilin) isolated and purified from P. gingivalis strains 381, BH18/10, HW24D-1, 6/26 and OMZ 314 was 41 kDa by sodium dodecylsulfate-polyacrylamide gel electrophoresis. It was found by immunoblotting that mAbs TO-11 and TO-14/TO-M1 recognized different epitopes of fimbrial protein from P. gingivalis strains. Immunoelectron micrographs of whole cells and the purified fimbriae of P. gingivalis strains visualized similar serotype-specific antibody bindings to the fimbriae. These results indicate that 11 strains of P. gingivalis could be divided into at least 2 separate groups based on the immunochemical specificities of the fimbriae.


Overexpression of HOXB4 enhances the hematopoietic potential of embryonic stem cells differentiated in vitro.
Little is known about the molecular mechanisms controlling primitive hematopoietic stem cells, especially during embryogenesis. Homeobox genes encode a family of transcription factors that have gained increasing attention as master regulators of developmental processes and recently have been implicated in the differentiation and proliferation of hematopoietic cells. Several Hox homeobox genes are now known to be differentially expressed in various subpopulations of human hematopoietic cells and one such gene, HOXB4, has recently been shown to positively determine the proliferative potential of primitive murine bone marrow cells, including cells with long-term repopulating ability. To determine if this gene might influence hematopoiesis at the earliest stages of development, embryonic stem (ES) cells were genetically modified by retroviral gene transfer to overexpress HOXB4 and the effect on their in vitro differentiation was examined. HOXB4 overexpression significantly increased the number of progenitors of mixed erythroid/myeloid colonies and definitive, but not primitive, erythroid colonies derived from embryoid bodies (EBs) at various stages after induction of differentiation. There appeared to be no significant effect on the generation of granulocytic or monocytic progenitors, nor on the efficiency of EB formation or growth rate. Analysis of mRNA from EBs derived from HOXB4-transduced ES cells on different days of primary differentiation showed a significant increase in adult beta-globin expression, with no detectable effect on GATA-1 or embryonic globin (beta H-1). Thus, HOXB4 enhances the erythropoietic, and possibly more primitive, hematopoietic differentiative potential of ES cells. These results provide new evidence implicating Hox genes in the control of very early stages in the development of the hematopoietic system and highlight the utility of the ES model for gaining insights into the molecular genetic regulation of differentiation and proliferation events.


Effects of Cryotherapy on Temperature Change in Caudal Thigh Muscles of Dogs.
The aim of the study reported here was to determine the effect of cryotherapy on the caudal thigh muscles of dogs. We hypothesized that temperature changes would be greatest in superficial tissues and decrease with tissue depth. Eight mixed-breed dogs (mean weight 21.2 kg, mean age 3.3 years) were studied. Temperature was measured at the skin surface and at depths of 1.0 and 3.0 cm below the skin using needle thermistor probes that were inserted beneath the site of cold pack application. Treatment consisted of a standard 1.0°C cold pack applied for 20 minutes. Temperature was recorded every minute for the 20 minute cold pack treatment, and for 80 minutes following treatment. Cutaneous temperatures significantly decreased (p < 0.01), with rapid rewarming of the skin following cold pack removal. Tissue cooling was less profound with increasing tissue depths, but was still significant (p < 0.05). There was no significant difference in muscle temperature between haired and clipped limbs. A single application of a cold pack to the caudal thigh muscles of dogs for 20 minutes resulted in significant temperature reduction at all tissue depths (p < 0.05). This decrease persisted for ∼60 minutes. The presence of hair did not have a significant effect on muscle cooling (p > 0.05).


A descriptive survey of long-term residents with epilepsy and intellectual disability at the Chalfont Centre: is there a relationship between maladaptive behaviour and magnetic resonance imaging findings?
The advent of high-resolution magnetic resonance imaging (MRI) has facilitated the identification of subtle, aetiologically relevant structural brain abnormalities in a significant proportion of patients with epilepsy and negative standard neuro-imaging. In the present study of people with intellectual disability (ID), the authors show that a high frequency of cerebral structural abnormalities (72.4%) can be demonstrated by high-resolution MRI in patients with epilepsy and ID. Malformations of cortical development (MCD) were found in 8.7% of people without profound ID. An earlier age of onset of habitual seizures was associated with more severe ID and more severe seizures in adulthood. There was no obvious association between this finding and maladaptive behaviour, but a past history of febrile convulsions was associated with increased irritability and agitation. Since there was no obvious association between a history of febrile convulsions and MRI abnormalities, the reason for the above finding remains unclear. Inevitably, any residential epilepsy centre population is subject to selection biases. The population studied was highly skewed, with only one-third of the sample being female and 80% having mild ID. Thus, the findings of the present study cannot necessarily be generalized to all people with ID.


Preoperative Predictors of Adverse Clinical Outcome in Emergent Repair of Acute Type A Aortic Dissection in 15 Year Follow Up.
Acute type A aortic dissection (AAAD) has high mortality. Improvements in surgical technique have lowered mortality but postoperative functional status and decreased quality of life due to debilitating deficits remain of concern. Our study aims to identify preoperative conditions predictive of undesirable outcome to help guide perioperative management. We performed retrospective analysis of 394 cases of AAAD who underwent repair in our institution between 2001 and 2018. A combined endpoint of parameters was defined as (1) 30-day versus hospital mortality, (2) new neurological deficit, (3) new acute renal insufficiency requiring postoperative renal replacement, and (4) prolonged mechanical ventilation with need for tracheostomy. Total survival/ follow-up time averaged 3.2 years with follow-up completeness of 94%. Endpoint was reached by 52.8%. Those had higher EuroSCORE II (7.5 versus 5.5), higher incidence of coronary artery disease (CAD) (9.2% versus 3.2%), neurological deficit (ND) upon presentation (26.4% versus 11.8%), cardiopulmonary resuscitation (CPR) (14.4% versus 1.6%) and intubation (RF) before surgery (16.9% versus 4.8%). 7-day mortality was 21.6% versus 0%. Hospital mortality 30.8% versus 0%. This 15-year follow up shows, that unfavorable postoperative clinical outcome is related to ND, CAD, CPR and RF on arrival.


Cell penetrating peptide-modified nanoparticles for tumor targeted imaging and synergistic effect of sonodynamic/HIFU therapy.
Theranostics based on multifunctional nanoparticles (NPs) is a promising field that combines therapeutic and diagnostic functionalities into a single nanoparticle system. However, the major challenges that lie ahead are how to achieve accurate early diagnosis and how to develop efficient and noninvasive treatment. Sonodynamic therapy (SDT) utilizing ultrasound combined with a sonosensitizer represents a novel noninvasive modality for cancer therapy. Different ultrasound frequencies have been used for SDT, nevertheless, whether the effect of SDT can enhance synergistic HIFU ablation remains to be investigated. We prepared a nanosystem for codelivery of a sonosensitizer (methylene blue, MB) and a magnetic resonance contrast agent (gadodiamide, Gd-DTPA-BMA) based on hydrophilic biodegradable polymeric NPs composed of poly (lactic-co-glycolic acid) (PLGA). To enhance accumulation and penetration of the NPs at the tumor site, the surface of PLGA NPs was decorated with a tumor-homing and penetrating peptide-F3 and polyethylene glycol (PEG). The physicochemical, imaging and therapeutic properties of F3-PLGA@MB/Gd and drug safety were thoroughly evaluated both in vitro and in vivo. F3-PLGA@MB/Gd was evaluated by both photoacoustic and resonance imaging. F3-PLGA@MB/Gd NPs exhibited higher cellular association than non-targeted NPs and showed a more preferential enrichment at the tumor site. Furthermore, with good drug safety, the apoptosis triggered by ultrasound in the F3-PLGA@MB/Gd group was greater than that in the contrast group. F3-PLGA@MB/Gd can work as a highly efficient theranostic agent, and the incorporation of targeted multimodal and combined therapy could be an encouraging strategy for cancer treatment.


Aging Properties of Phenol-Formaldehyde Resin Modified by Bio-Oil Using UV Weathering.
The aging properties of phenol-formaldehyde resin modified by bio-oil (BPF) were analyzed using ultraviolet (UV) weathering. The variations on bonding strength of BPF were measured, and the changes on microstructure, atomic composition and chemical structure of BPF were characterized by using a scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS) and nuclear magnetic resonance (NMR), respectively. With the increase of aging time, the bonding strength decreased gradually, the resin surface became rougher and the O/C radio of resin surface increased. However, the loss rate of bonding strength of BPFs was 9.6⁻23.0% lower than that of phenol-formaldehyde resin (PF) after aging 960 h. The aging degree of BPF surfaces was smaller in comparison to PF at the same aging time. These results showed that the bio-oil had a positive effect on the anti-aging property. Analytical results revealed that with increasing the aging time, the XPS peak area of C⁻C/C⁻H decreased, while that of C=O and O⁻C=O increased. The intensity of methylene and ether bridges in NMR analysis decreased along with increasing the intensity of aldehydes, ketones, acids and esters. These results indicated that the aging mechanism of BPF was a process of the breakage of molecular chains and formation of oxygen-containing compounds.


The sequenced rat brain transcriptome--its use in identifying networks predisposing alcohol consumption.
A quantitative genetic approach, which involves correlation of transcriptional networks with the phenotype in a recombinant inbred (RI) population and in selectively bred lines of rats, and determination of coinciding quantitative trait loci for gene expression and the trait of interest, has been applied in the present study. In this analysis, a novel approach was used that combined DNA-Seq data, data from brain exon array analysis of HXB/BXH RI rat strains and six pairs of rat lines selectively bred for high and low alcohol preference, and RNA-Seq data (including rat brain transcriptome reconstruction) to quantify transcript expression levels, generate co-expression modules and identify biological functions that contribute to the predisposition of consuming varying amounts of alcohol. A gene co-expression module was identified in the RI rat strains that contained both annotated and unannotated transcripts expressed in the brain, and was associated with alcohol consumption in the RI panel. This module was found to be enriched with differentially expressed genes from the selected lines of rats. The candidate genes within the module and differentially expressed genes between high and low drinking selected lines were associated with glia (microglia and astrocytes) and could be categorized as being related to immune function, energy metabolism and calcium homeostasis, as well as glial-neuronal communication. The results of the present study show that there are multiple combinations of genetic factors that can produce the same phenotypic outcome. Although no single gene accounts for predisposition to a particular level of alcohol consumption in every animal model, coordinated differential expression of subsets of genes in the identified pathways produce similar phenotypic outcomes. The datasets supporting the results of the present study are available at http://phenogen.ucdenver.edu.


Artificial multienzyme supramolecular device: highly ordered self-assembly of oligomeric enzymes in vitro and in vivo.
A strategy for scaffold-free self-assembly of multiple oligomeric enzymes was developed by exploiting enzyme oligomerization and protein-protein interaction properties, and was tested both in vitro and in vivo. Octameric leucine dehydrogenase and dimeric formate dehydrogenase were fused to a PDZ (PSD95/Dlg1/zo-1) domain and its ligand, respectively. The fusion proteins self-assembled into extended supramolecular interaction networks. Scanning-electron and atomic-force microscopy showed that the assemblies assumed two-dimensional layer-like structures. A fluorescence complementation assay indicated that the assemblies were localized to the poles of cells. Moreover, both in vitro and in vivo assemblies showed higher NAD(H) recycling efficiency and structural stability than did unassembled structures when applied to a coenzyme recycling system. This work provides a novel method for developing artificial multienzyme supramolecular devices and for compartmentalizing metabolic enzyme cascades in living cells.


Src family kinases are necessary for cell migration induced by extracellular HMGB1.
HMGB1 is a nuclear protein that signals tissue damage, as it is released by cells dying traumatically or secreted by activated innate immunity cells. Extracellular HMGB1 elicits the migration to the site of tissue damage of several cell types, including inflammatory cells and stem cells. The identity of the signaling pathways activated by extracellular HMGB1 is not known completely: We reported previously that ERK and NF-kappaB pathways are involved, and we report here that Src is also activated. The ablation of Src or inhibition with the kinase inhibitor PP2 blocks migration toward HMGB1. Src associates to and mediates the phosphorylation of FAK and the formation of focal adhesions.


The accuracy and precision of timing of self-paced, repetitive movements in subjects with Parkinson's disease.
In separate experiments, we studied the temporal accuracy and precision of self-paced, repetitive finger-tapping in two groups of 12 patients with Parkinson's disease and a group of 12 controls matched to the patients with respect to age and general cognitive state. One group (I) of patients was studied initially following 12-15 h abstinence from normal levodopa medication ('off') and again, subsequently, approximately 1 h after ingestion of a single normal dose ('on'). A second group (II) of patients, each of whom had bilaterally asymmetrical neurological signs, was tested using 'worse' and 'better' hands separately. Within each session, subjects were tested repeatedly on a tapping task during which they were required to produce a regular series of self-timed inter-tap intervals, the target duration (550 ms) of which had been established previously during an initial period of tapping in synchrony with the beats of a regular metronome. We employed Wing and Kristofferson's (1973) model of control of motor timing to partition the total variance (TV) about the mean inter-response interval (IRI) produced during the self-paced phase of each run into separate components ['clock' variance (CV) and 'motor-delay' variance (MDV)] attributable to hypothetical 'clock' and 'motor-implementation' processes. Although the mean self-paced IRI of parkinsonian patients was generally shorter than that of controls, only during the 'on' medication condition (Group I) was it significantly so. By comparison with control values, and those observed during the 'on' medication condition, values of TV, CV and MDV in Group I were all significantly higher when subjects were 'off' medication. During the 'on' medication condition, only CV was significantly higher than the control value. In Group II, values of TV, CV and MDV associated with use of the 'worse' hand were all significantly higher than both control values and those associated with use of the 'better' hand. Values of these variables when subjects used the 'better' hand did not, however, differ significantly from control values. The theoretical import of these results is discussed in the light of several important procedural, statistical and computational issues and we conclude that TV, CV, and MDV may all vary significantly as a function of the efficacy of dopaminergic transmission in the basal ganglia.


A greener approach for resource recycling: Manganese bioleaching.
In view of unremitting diminution of mineral resources, rising energy economics along with increasing global consumption of Manganese (Mn), development of environment friendly technologies for tapping alternate sources of Mn has gained importance lately. Mn recovery from mining residues using conventional approaches is extremely expensive due to high capital and energy costs involved. However lean grade ores present in millions of tons awaits the development of competent and cost effective extractive process. Mn recovery by biomining with diverse microbes is thereby recommended as a superior and green alternative to the current pyro metallurgical techniques. The synergistic effects of different factors are known to influence microbial leaching of mineral ores which includes microbiological, mineralogical, physicochemical and process parameters. Bacterial bioleaching is mostly due to enzymatic influence, however fungal bioleaching is non enzymatic. Genomic studies on microbial diversity and an insight of its metabolic pathways provides unique dimension to the mechanism of biomining microorganisms. The extraction of Mn has a massive future prospective and will play a remarkable role in altering the situation of ever-decreasing grades of ore. This review aims to encompass the different aspects of Mn bioleaching, the plethora of organisms involved, the mechanisms driving the process and the recent trends and future prospects of this green technology.


Occurrence and multilocus sequence typing of Clostridium perfringens isolated from retail duck products in Tai'an region, China.
Clostridium perfringens is an important zoonotic microorganism, which can cause diseases in animal and human under certain conditions. Contamination of C. perfringens in chicken and pork meat has been reported worldwide, but it is rarely reported in duck products. The current study was undertaken to investigate C. perfringens contamination in duck products from a large retail market in Tai'an region, China and the serotype distribution, antimicrobial resistance and genetic relatedness of the isolates. In total, 173 samples of duck products, 10 samples of environmental origins and 7 samples of fresh faeces from healthy shopkeepers were collected between March and November 2018, of which, 58 (31.69%), 10 (100%) and 7 (100%) samples were determined to be positive for C. perfringens, respectively. Ninety-nine isolates of C. perfringens were recovered, all of which were identified as type A. Beta2 (cpb2) toxin gene was found in 54.30% and 33.30% of the isolates from duck products and healthy shopkeepers, respectively. Antimicrobial susceptibility testing revealed that 90.10% of the isolates from duck products and environment showed multiple antibiotic resistance, among which, 49.40% were resistant to at least 6 classes of commonly used antibiotics. Multilocus sequence typing (MLST) showed that 58 representative isolates were divided into 41 sequences types (STs), among which, ST11 (8.60%) was the most common; 37.90% of all isolates were classified into four clonal complexes (CC1-CC4). The most prolific clonal complex (CC1), accounting for 24.13% of all isolates, contained isolates mainly from carcass, animal intestinal contents and environment of four retail stores. A portion of human isolates and duck isolates was distributed in the same CC or ST. In conclusion, C. perfringens contamination in some duck products in Tai'an retail market was relatively high, and most of the isolates exhibited broad-spectrum antimicrobial resistance. Although all the isolates belong to type A, considerable genetic diversity was observed, and a portion of the strains from human and duck was found to be phylogenetically close. The results indicated that antimicrobial-resistance strains of duck origin pose a potential threat to humans by spreading through the food chain.


[Efficiency of magnetic therapy techniques in the treatment and rehabilitation of patients with joint diseases from the standpoint of evidence-based medicine].
This article provides information on currently proven effective treatment methods for patients with joint diseases, by using magnetic fields with various physical characteristics. A wide range of biotropic parameters allows obtaining various primary physicochemical changes in biological tissues, which was a rationale for including magnetic therapy (MT) in the combination treatment of degenerative-dystrophic and inflammatory diseases. Analysis of scientific publications suggests that there are a large number of randomized, placebo-controlled studies providing evidence for reduced pain, improved joint functional activity and quality of life in patients with knee osteoarthritis under magnetic fields with varying inductions, frequencies, and exposures. There are few randomized clinical trials identifying the efficiency of MT for a number of other joint diseases and after arthroplasty. Despite the fact that there are differences in methodological approaches, it is possible to draw a general conclusion on the scientific validity of using MT in the complex treatment and rehabilitation programs for patients with joint diseases and on the prospects of further developments in this area.


Novel Therapeutic Agents for Rare Diseases of Calcium and Phosphate Metabolism.
The last decade has been revolutionary regarding the management of rare bone diseases caused by impaired calcium and phosphate metabolism. Elucidation of the underlying genetic basis and pathophysiologic alterations has been the determinant factor for the development of new, disease-specific treatment agents. The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) possesses a critical role in the pathogenesis of various hypophosphatemic disorders. Among them, the genetic disorder of X-linked hypophosphatemia and the acquired syndrome of tumor-induced osteomalacia, although very rare, have attracted the scientific community's attention towards designing an FGF23-inhibitor as a potential specific therapy. The monoclonal antibody burosumab was approved for the treatment of children and adult patients with X-linked hypophosphatemia and recently for tumor-induced osteomalacia patients, demonstrating benefits regarding their symptoms, biochemical profile and bone mineralization status. Asfotase alfa is a hydroxyapatite-targeted recombinant alkaline phosphatase, an enzymatic replacement therapy, substituting the defective activity of tissue non-specific alkaline phosphatase, in patients suffering from hypophosphatasia. Promising data regarding its favorable effect on survival rate, bone quality, fracture healing, muscle strength, mobility, respiratory function, and general quality of life have led to the approval of the drug for the treatment of childhood-onset hypophosphatasia. Given the high costs of treatment for both agents and their limited clinical use until now, more data are needed to define patients' characteristics that make them ideal candidates for therapy. Long-term safety issues also need to be clarified.


Global status of lignocellulosic biorefinery: Challenges and perspectives.
The bioprocessing of lignocellulosic biomass to produce bio-based products under biorefinery setup is gaining global attention. The economic viability of this biorefinery would be inclined by the efficient bioconversion of all three major constituents of lignocellulosic biomass i.e. cellulose, hemicellulose, and lignin for value-added biochemicals and biofuels production. Although the lignocellulosic biorefinery setup has a clear value proposition, the commercial success at the industrial scale is still inadequate. This can be attributed mainly to irregular biomass supply chain, market uncertainties, and scale-up challenges. Global research efforts are underway by public and private sectors to get deeper market penetration. A comprehensive account of important factors, limitations, and propositions are worth consideration for the commercial success of lignocellulosic biorefineries. In this article, the importance of integration of lignocellulosic biorefineries with existing petrochemical refineries, the technical challenges of industrialization, SWOT analysis, and future directions have been reviewed.


Fatal complications of bariatric surgery.
Bariatric surgery is an increasingly used method to treat morbid obesity. The mortality rate among patients undergoing bariatric operations is generally quoted as between 0.05-2.0%. Our focus was not on mortality rates but rather on the reasons patients die following the procedures. In New York City, deaths that are due to predictable complications of appropriate therapy are certified as therapeutic complications. We retrospectively reviewed all deaths investigated by the Office of the Chief Medical Examiner in New York City between 1997 and 2005 in which bariatric surgery had been performed. We report the fatal complications, the interval between surgery and death, the type of procedure, and coexisting morbidities. Autopsies were performed on 95% of these fatalities. There were 97 deaths due to therapeutic complications of the operations. The interval between the initial surgery and death ranged from several hours to years. The most common complication was an anastomotic leak with subsequent infection. A high percentage of deaths occurred after discharge (40%) and/or >30 days after surgery (37%). There were 8 deaths from complications of bariatric surgery that occurred >1 year after surgery. Studies that report the mortality rate during hospitalization or within 30 days of surgery, underestimate the actual incidence. Bariatric surgery carries both short- and long-term risks.


Differential effects of statins on endogenous H2S formation in perivascular adipose tissue.
Hydrogen sulfide (H(2)S) is a new gasotransmitter synthesized enzymatically from l-cysteine in cytosol and is oxidized in mitochondria. In the cardiovascular system, H(2)S regulates vascular tone, inhibits atherogenesis, and protects against myocardial ischemia-reperfusion injury. We examined the effect of statins on vascular H(2)S production. Male Wistar rats received pravastatin (40mg/kg/day) or atorvastatin (20mg/kg/day) for 3 weeks and then H(2)S formation was measured in aortic media, periaortic adipose tissue (PAAT) and the liver. Only atorvastatin increased H(2)S production in PAAT whereas both statins stimulated its formation in the liver. Neither statin affected H(2)S production in aortic media. H(2)S formation in post-mitochondrial supernatant was higher than in mitochondria-containing supernatant and was not influenced by statins in any tissue. In addition, oxidation of exogenous H(2)S in isolated liver mitochondria was slower in statin-treated than in control rats. These data indicate that statins increase net H(2)S production by inhibiting its mitochondrial oxidation. Statins had no effect on the activity of H(2)S-metabolizing enzyme, sulfide:quinone oxidoreductase, measured at saturating coenzyme Q concentration. Both statins reduced CoQ(9) concentration in plasma and liver, but only atorvastatin decreased CoQ(9) in PAAT. Atorvastatin attenuated phenylephrine-induced contraction of PAAT+ but not of PAAT- aortic rings. Effects of atorvastatin on net H(2)S production, mitochondrial H(2)S oxidation and aortic contractility were abolished by supplementation of exogenous CoQ(9). In conclusion, lipophilic atorvastatin, but not hydrophilic pravastatin, increases net H(2)S production in perivascular adipose tissue by inhibiting its mitochondrial oxidation. This effect is mediated by statin-induced CoQ(9) deficiency and results in the augmentation of anticontractile effect of perivascular adipose tissue.


3α-Dimethyl-amino-20-(N-methyl-acetamido)-pregn-5-ene.
The title compond, C(26)H(44)N(2)O, is an steroidal alkaloid isolated from the medicinally important plant Sarcococca saligna. The mol-ecule consists of four fused rings (A-D), having chair, half-chair, chair and envelope conformations, respectively. The dimethyl-amino group is axially oriented on ring A, whereas the (N-methyl-acetamido)-ethyl group is attached equatorially on ring D. The crystal structure is stabilized only by van der Waals forces.


Retinal dysplasia of holoprosencephaly.
Retinal dysplasia occurs in the setting of sporadic and syndromic holoprosencephaly, which often has associated ocular malformations. The pathology of this dysplasia, which includes rosettes, has been previously described. However, its funduscopic findings have not been well documented. The authors present the fundus images of a patient with severe holoprosencephaly with retinal dysplasia and bilateral optic nerve colobomas that resulted in death 2 weeks after birth.


COVID-19 pandemic control using restrictions and vaccination.
This work deals with the impact of the vaccination in combination with a restriction parameter that represents non-pharmaceutical interventions measures applied to the compartmental SEIR model in order to control the COVID-19 epidemic. This restriction parameter is used as a control parameter, and the univariate autoregressive integrated moving average (ARIMA) is used to forecast the time series of vaccination of all individuals of a specific country. Having in hand the time series of the population fully vaccinated (real data + forecast), the Levenberg-Marquardt algorithm is used to fit an analytic function that models this evolution over time. Here, it is used two time series of real data that refer to a slow vaccination obtained from India and Brazil, and two faster vaccination as observed in Israel and the United States of America. Together with vaccination, two different control approaches are presented in this paper, which enable reduces the infected people successfully: namely, the feedback and nonfeedback control methods. Numerical results predict that vaccination can reduce the peaks of infections and the duration of the pandemic, however, a better result is achieved when the vaccination is combined with any restrictions or prevention policy.


Cervical myelopathy secondary to omovertebral bone in the pediatric patient with Sprengel deformity.
Sprengel deformity is a congenital anomaly arising mainly in the shoulder girdle, associated with elevation of dysplastic scapula. skeletal anomalies, mainly Klippel-Feil syndrome, hemivertebrae, and omovertebral bone may be present along Sprengel anomaly. The omovertebral bone is an abnormal bone that originates from the superomedial edge of the scapula with different insertion points along the posterior cervical spine, seen in about third of the patients with Sprengel anomaly. While cosmetic to functional impairment is a common presentation to the omovertebral bone, cervical myelopathy is a rare presentation. Here, we described our experience, management and follow up of 13-year-old boy presented with cervical myelopathy secondary to the omovertebral bone.


Systemically induced (hematogenous) contact eczema.
The oral or parenteral application of certain contact allergens may elicit eczematous skin reactions "from the inside" in sensitized individuals; this phenomenon has been called "systemically induced eczema" or "hematogenous contact eczema". Both the clinical morphology and dermatopathology are very similar to classical allergic contact eczema. The distribution of skin lesions is mostly symmetrical and may affect the face or the anogenital area. The pathophysiology involves T-lymphocytes and probably secretion of cytokines similar to the well-known phenomenon of "flare-up". The most important contact allergens known to elicit systemically induced contact eczema are metal salts, drugs, phytoallergens and balsam of Peru. After careful diagnosis, a specific allergen avoidance is the basis of prophylaxis and therapy.


Evaluation of the energize your life! Social marketing campaign pilot study to increase fruit intake among community college students.
In this study, the authors evaluated the effectiveness of the Energize Your Life! social-marketing campaign pilot study to improve knowledge, attitudes, and fruit intake among community college students. The authors used a cross-sectional, quasi-experimental, pre- and posttest design. They randomly selected community college students (N = 1,367) and exposed the intervention campus to fruit fairs to distribute fresh fruit, 100% fruit juice, and fruit smoothie samples and information about fruit to students. The authors also addressed policy change to increase the accessibility of fruit on campus. There was a significant increase in fruit intake between pre- and posttest at the intervention campus. Although students had positive attitudes toward intake, most did not achieve the minimum recommended daily 2 servings of fruit. Approximately 25% of the students had insufficient funds, which affected their food intake. Longer-term social marketing interventions may be an effective means of improving the dietary quality of community college students.


Colorless glasses containing ion-exchanged silver.
Introduction of silver into a silicate glass often leads to reduction and coloration. The electron required for silver reduction is extracted from a nonbridging oxygen atom. The use of high-field-strength ions limits the number of nonbridging oxygens and silver reduction.


Beginners in prescribing practice: Experiences and perceptions of nurses and doctors.
To investigate and compare the experiences and perceptions of nurses and doctors in becoming prescribers. The development of core skills, knowledge and attitudes as a prescriber is among the present foci of current medical education, and the requirements for ongoing mentorship, support and education for novice medical prescribers have been identified as important training components. However, little is known of the prescribing practices of other health professionals who are also new to prescribing, for example, nurse prescribers. This qualitative study was guided by a constructivist narrative approach using a multiple case narrative strategy. A purposive sampling approach was used, with a view to selecting participants to best illuminate the experiences of beginning to prescribe. Individual interviews were conducted, 26 in total, lasting approximately one hour each and were audio-recorded. Common themes were found across prescribing groups: fear and anxiety when taking on prescribing responsibility; the strategy of using a personal list of medicines to support safe practice; how this list was expanded over time; referring to senior colleagues in prescribing decision-making. This study shows that the journeys are similar for nurses and doctors as beginning prescribers. The effort required for a novice prescriber to select the most appropriate medication and write prescriptions can be extensive as development of expertise takes time and occurs over months or years. Medical and nurse prescribers differ in term of educational preparation, their journeys as beginner prescribers share common behaviour and practices. Clinical experience and mentorship important to enhance skill development in prescribing and should be advocated for all prescribers. Beginner prescribers require ongoing education and support when prescribing for high risk patients or when prescribing new drugs.


A review of facial image analysis for delineation of the facial phenotype associated with fetal alcohol syndrome.
The facial anomalies associated with fetal alcohol syndrome (FAS), some of which are also present in individuals with less severe forms of the broader category of fetal alcohol spectrum disorders (FASD), are typically identified with the aid of linear distance measurements taken between facial landmarks. Digital facial imaging methods are increasingly being used in syndrome delineation. Distance measurements derived from stereo-photogrammetry and facial surface imaging have been used to study the FAS facial anomalies. Geometric morphometric methods capture the spatial arrangement between landmarks, providing a statistical platform for comparison of facial shapes, and have been shown to hold promise for characterizing the FAS facial shape. We review the progression in the use of imaging and image analysis methods in studies on the facial phenotype associated with FAS.


The Influencing Legal and Factors of Migrant Children's Educational Integration Based on Convolutional Neural Network.
This research aims to analyze the influencing factors of migrant children's education integration based on the convolutional neural network (CNN) algorithm. The attention mechanism, LSTM, and GRU are introduced based on the CNN algorithm, to establish an ALGCNN model for text classification. Film and television review data set (MR), Stanford sentiment data set (SST), and news opinion data set (MPQA) are used to analyze the classification accuracy, loss value, Hamming loss (HL), precision (Pre), recall (Re), and micro-F1 (F1) of the ALGCNN model. Then, on the big data platform, data in the Comprehensive Management System of Floating Population and Rental Housing, Student Status Information Management System, and Student Information Management System of Beijing city are taken as samples. The ALGCNN model is used to classify and compare related data. It is found that in the MR, STT, and MPQA data sets, the classification accuracy and loss value of the ALGCNN model are better than other algorithms. HL is the lowest (15.2 ± 1.38%), the Pre is second only to the BERT algorithm, and the Re and F1 are both higher than other algorithms. From 2015 to 2019, the number of migrant children in different grades of elementary school shows a gradual increase. Among migrant children, the number of migrant children from other counties in this province is evidently higher than the number of migrant children from other provinces. Among children of migrant workers, the number of immigrants from other counties in this province is also notably higher than the number of immigrants from other provinces. With the gradual increase in the years, the proportion of township-level expenses shows a gradual decrease, whereas the proportion of district and county-level expenses shows a gradual increase. Moreover, the accuracy of the ALGCNN model in migrant children and local children data classification is 98.6 and 98.9%, respectively. The proportion of migrant children in the first and second grades of a primary school in Beijing city is obviously higher than that of local children (p < 0.05). The average final score of local children was greatly higher than that of migrant children (p < 0.05), whereas the scores of migrant children's listening methods, learning skills, and learning environment adaptability are lower, which shows that an effective text classification model (ALGCNN) is established based on the CNN algorithm. In short, the children's education costs, listening methods, learning skills, and learning environment adaptability are the main factors affecting migrant children's educational integration, and this work provides a reference for the analysis of migrant children's educational integration.


[Psychiatry: under the influence].
The history of madness and psychiatry has witnessed the socio-cultural influence of psychiatric disorders in etiological constructs, expression and treatment. After a brief historical overview, the author emphasizes the contemporary socio-politico-economical conditions and their influence on the field of psychiatry. The prevalence of economic values and "econometric process" increasingly penetrates the organization of government, institutions and science, as well as favouring uniformity and fragmentation of its constructs and treatments. In regards to the clinical field, theories on treatment of symptoms without consideration of human or social subjectivity as well as organistic and mecanistic theories of the psychic troubles have gained in importance. In conclusion, the author recalls that dimensions perceived by consumers are the most influential determinants of change and well-being.


The influence of dipper and nondipper blood pressure patterns on left ventricular functions in hypertensive patients: a tissue Doppler study.
We investigated the effect of dipper and non-dipper blood pressure patterns on left ventricular diastolic filling parameters in hypertensive patients. Fifty-five hypertensive patients (37 women, 18 men; mean age 55+/-10 years) were evaluated with echocardiography and ambulatory 24-hour blood pressure monitoring. All the patients received antihypertensive drug therapy for at least three months prior to the evaluations. Tissue Doppler-derived systolic and diastolic parameters were compared. Dipper and nondipper blood pressure patterns were found in 22 patients (40%) and 33 patients (60%), respectively. Both groups had similar left ventricular systolic and diastolic diameters. Dipper patients had significantly lower values for left atrial diameter (p<0.0001), interventricular septum (p=0.001) and posterior wall (p=0.012) thickness, left ventricular mass (p=0.017) and mass index (p=0.021). Both groups had similar mitral E and A waves, E/A ratio, E-wave deceleration time, isovolumetric relaxation time, and tissue Doppler-derived A' wave. Dipper patients had a significantly lower E/E' ratio (10.8+/-3.4 vs. 14.1+/-3.6; p=0.002) and significantly higher systolic (S') (p=0.05) and early diastolic (E') (p=0.027) tissue velocities. Based on the E/E' ratios being <15 or = or >15, the frequency of dipper hypertension was significantly higher in patients with E/E' <15 (48.8% vs. 9.1%; p=0.019). The frequency of dippers was also higher among patients having an E/E' ratio of <8, compared to those having an E/E' ratio of = or >8 to <15 (90% vs. 35.3%; p=0.019). Nondipper blood pressure pattern may be associated with increased left ventricular mass, impaired left ventricular systolic and diastolic dysfunction, and higher left ventricular filling pressures.


Influence of the molecular structure and exposure concentration on the uptake and elimination kinetics, bioconcentration, and biotransformation of anionic and nonionic surfactants.
In vivo experiments with fish (sole) were performed for pure homologs of linear alkylbenzene sulfonates (LAS) and alcohol ethoxylates (AEO), the most widely used anionic and nonionic surfactants. The surfactant concentration measured in the organism was higher than in the experimental water, and increased with the exposure concentration for both compounds. At the exposure levels tested the bioconcentration factors (BCF) for AEO were one order of magnitude higher than for LAS. Two linear relationships for hydrophobicity were established, one with BCF and the other with uptake rate. The influence of the exposure concentration on the uptake (k(1)) and elimination (k(2)) velocities was researched. The value obtained for k(1) for AEO was higher than for LAS, while k(2) was very similar for both compounds, indicating differences in the incorporation and but not in the depuration rate. For the first time, internal degradation products of LAS were identified and quantified in fish and water and the glucuronic conjugate of AEO was detected in an organism. The predominant biotransformation process for these compounds may be different: the results suggest a phase I biotransformation for LAS and phase II for AEO, due to their different molecular structures.


Why are patients with progressive nonfluent aphasia nonfluent?
To investigate the cognitive and neural basis for nonfluent speech in progressive nonfluent aphasia (PNFA). Nonfluent speech is the hallmark feature of PNFA, and this has been attributed to impairments in syntactic processing, motor-speech planning, and executive functioning that also occur in these patients. Patients with PNFA have left inferior frontal atrophy. A large semi-structured speech sample and neuropsychological measures of language and executive functioning were examined in 16 patients with PNFA, 12 patients with behavioral-variant frontotemporal dementia (bvFTD), and 13 age-matched controls. Speech fluency was quantified as words per minute (WPM) in the semi-structured speech sample. Stepwise linear regression analyses were used to relate WPM to grammatic, motor-speech planning, and executive aspects of patient functioning. These measures were then related to cortical thickness in 8 patients with PNFA and 7 patients with bvFTD using structural MRI. WPM was significantly reduced in patients with PNFA relative to controls and patients with bvFTD. Regression analyses revealed that only grammatic measures predicted WPM in PNFA, whereas executive measures were the only significant predictor of WPM in bvFTD. Cortical thinning was significant in PNFA relative to controls in left inferior frontal and anterior-superior temporal regions, and a regression analysis related this area to reduced WPM in PNFA. Significant cortical thinning associated with limited grammatic processing also was seen in the left inferior frontal-superior temporal region in PNFA, and this overlapped with the area of frontal-temporal thinning related to reduced WPM. Nonfluent speech in PNFA may be due in part to difficulty with grammatic processing associated with left inferior frontal and anterior-superior temporal disease.


Improved version of a local contracted configuration interaction of singles and doubles with partial inclusion of triples and quadruples.
A local contracted single and double configuration interaction (LC-CISD) method, which introduces contracted singly and doubly excited vectors within the framework of bond functions, has been recently proposed [P. Reinhardt et al., J. Chem. Phys. 129, 164106 (2008)]. The present work improves this method by introducing a coupled-electron pair approximation (CEPA-3) dressing and by incorporating the leading part of linked effects of triples (T) and quadruples (Q) through a series of local four-electron full CI calculations. Two different ways have been adopted to incorporate this linked TQ effect. One consists of dressing the first column/line of the whole LC-CISD matrix. The other one introduces an additional contracted wave function responsible for the linked effect for each bond pair. The present LC-CEPA-3+TQ treatments have been applied to the evaluation of equilibrium bond lengths and harmonic frequencies of diatomic molecules (HF, BF, CuH, N(2), F(2), and Cl(2)) and single bond breaking in HF, CH(4), ClCH(3), ClSiH(3), n-butane, and F(2) molecules, symmetrical stretching of the two OH bonds in a water molecule, and symmetrical expansion of a triangular Be(3) cluster. The results show that the performance of the LC-CEPA-3+TQs compares favorably with coupled-cluster singles and doubles (CCSD) and CCSD(T) methods, presenting similar behaviors around equilibrium and better ones for stretched geometries. The LC-CEPA-3 method is strictly separable, and the size consistency error of our treatment of triples and quadruples is extremely small. The strict separability can be further achieved by dressing the doubly excited bond functions with the linked TQ effect. The efficiency of truncations on the bielectronic integrals has also been tested.


Rapid and Multiplexed MicroRNA Diagnostic Assay Using Quantum Dot-Based Förster Resonance Energy Transfer.
The detection of next generation microRNA (miRNA) biomarkers has become a highly important aspect for clinical diagnostics. We use multiplexed Förster resonance energy transfer (FRET) between a luminescent Tb complex and three different semiconductor quantum dots (QDs) to sensitively detect three different miRNAs from a single 150 μL sample with ca. 1 nM (subpicomol) detection limits. The rapid and amplification-free mix-and-measure assay format is based on careful design of miRNA base pairing and stacking to selectively detect different miRNAs with very strong sequence homologies. Clinical applicability is demonstrated by sensitive multiplexed quantification of three miRNAs at low (2 to 10 nM) and varying concentrations in samples that contained up to 10% serum.


Antithrombotic actions and pharmacokinetics of heparin fractions and fragments.
During the last few years many reports on the antithrombotic actions of low molecular weight fractions (LMF) have become available and are being tested in the experimental and clinical settings. Although derived from commercial heparins, the mode of antithrombotic actions, pharmacokinetics and physiologic disposition of these agents is distinct from the parent materials. The antithrombotic potency of these fractions is generally assigned in terms of their ability to inhibit serine proteases such as factor Xa and thrombin in the presence of antithrombin III (AT III). However, these agents are also reported to exert their antithrombotic actions via non AT III mediated inhibition of serine proteases (XIIa, IXa), activation of fibrinolysis via the release of plasminogen activators and charge transition on vascular surfaces. In order to evaluate the relative pharmacologic actions of heparin and its derivatives, we utilized defined animal models to obtain data in terms of pharmacologic parameters. Significant differences between heparin and its derivatives were evident. Human studies on the pharmacokinetics and the endogenous actions of these agents confirmed our preclinical findings. These studies suggest that well-defined preclinical studies are an essential element in the development of newer antithrombotic agents.


Deletion of Sox9 in the liver leads to hepatic cystogenesis in mice by transcriptionally downregulating Sec63.
Hepatic cysts are found in heterogeneous disorders with different pathogeneses, of which simple hepatic cysts and polycystic liver diseases are two major types. The process of hepatic cytogenesis for these two diseases is caused by defects in remodelling of the ductal plate during biliary tract development, which is called ductal plate malformation. SOX9 is a transcription factor participating in the process of bile duct development, and thus, its dysregulation may play important roles in hepatic cystogenesis. SEC63 encodes an endoplasmic reticulum membrane protein that is mutated in human autosomal dominant polycystic liver disease. However, the transcriptional regulation of SEC63 is largely unknown. In the present study, a liver-specific Sox9 knockout (Sox9LKO ) mouse was generated to investigate the roles and underlying mechanism of SOX9 in hepatic cystogenesis. We found that hepatic cysts began to be observed in Sox9LKO mice at 6 months of age. The number and size of cysts increased with age in Sox9LKO mice. In addition, the characteristics of hepatic cytogenesis, including the activation of proliferation, absence of primary cilium, and disorder of polarity in biliary epithelial cells, were detected in the livers of Sox9LKO mice. RNAi silencing of SOX9 in human intrahepatic biliary epithelial cells (HIBEpic) resulted in increased proliferation and reduced formation of the primary cilium. Moreover, Sec63 was downregulated in primary biliary epithelial cells from Sox9LKO mice and SEC63 in HIBEpic transfected with siSOX9. Chromatin immunoprecipitation assays and luciferase reporter assays further demonstrated that SOX9 transcriptionally regulated the expression of SEC63 in biliary epithelial cells. Importantly, the overexpression of SEC63 in HIBEpic partially reversed the effects of SOX9 depletion on the formation of primary cilia and cell proliferation. These findings highlight the biological significance of SOX9 in hepatic cytogenesis and elucidate a novel molecular mechanism underlying hepatic cytogenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Doxorubicin Conjugated to Glutathione Stabilized Gold Nanoparticles (Au-GSH-Dox) as an Effective Therapeutic Agent for Feline Injection-Site Sarcomas-Chick Embryo Chorioallantoic Membrane Study.
Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized gold nanoparticles (Au-GSH-Dox) has higher cytotoxic effects than free doxorubicin for feline fibrosarcoma cell lines with high glycoprotein P activity (FFS1, FFS3). The aim of the present study was to assess the effectiveness of intratumoural injection of Au-GSH-Dox on the growth of tumours from the FFS1 and FFS3 cell lines on chick embryo chorioallantoic membrane. This model has been utilized both in human and veterinary medicine for preclinical oncological studies. The influence of intratumoural injections of Au-GSH-Dox, glutathione-stabilized gold nanoparticles and doxorubicin alone on the Ki-67 proliferation marker was also checked. We demonstrated that the volume ratio of tumours from the FFS1 and FFS3 cell lines was significantly (p < 0.01) decreased after a single intratumoural injection of Au-GSH-Dox, which confirms the positive results of in vitro studies and indicates that Au-GSH-Dox may be a potent new therapeutic agent for feline injection-site sarcomas.


Human growth hormone: friend or foe in sports medicine?
The authors discuss the nature and potential of human growth hormone and the possibility that its misuse as a "doping" agent may lead to restrictions and hamper research.


μ-Oxido-bis-[chlorido(4,4'-di-tert-butyl-2,2'-bipyridine-κN,N')dioxido-molybdenum(VI)] 0.2-hydrate.
The title hydrate, [Mo(2)Cl(2)O(5)(C(18)H(24)N(2))(2)]·0.2H(2)O, has been isolated as the oxidation product of [Mo(η(3)-C(3)H(5))Cl(CO)(2)(di-t-Bu-bipy)] (where di-t-Bu-bipy is 4,4'-di-tert-butyl-2,2'-bipyridine). A μ-oxide ligand bridges two similar MoCl(di-t-Bu-bipy)O(2) units, having the terminal oxide ligands mutually cis, and the chloride and μ-oxide trans to each other. In the binuclear complex, the coordination geometries of the metal atoms can be described as highly distorted octa-hedra. Individual complexes co-crystallize with a partially occupied water mol-ecule of crystallization (occupancy factor = 0.20; H atoms not located), with the crystal packing being mediated by the need to effectively fill the available space. A number of weak C-H⋯O and C-H⋯Cl inter-actions are present.


Dissimilarity in adolescent and maternal representations of Type 1 diabetes: exploration of relations to adolescent well-being.
To compare the illness representations of adolescents with Type 1 diabetes and their mothers, and to explore how congruence and incongruence influences adolescent psychological adjustment. A total of 30 adolescents (13-19 years) with Type 1 diabetes completed self-report questionnaires of illness representations and psychological well-being; 26 mothers completed the illness representation questionnaire. t-Test and correlation analyses showed convergence on the majority of the illness representation dimensions with maternal representations differing significantly on only two dimensions: perceiving their adolescent's diabetes to have more serious consequences and to have a greater emotional impact. Computation of dissimilarity scores between mothers and adolescents, showed mothers to maximize the seriousness of diabetes across several dimensions, but no significant associations were found with adolescent psychological well-being. Chronic illness in children and young people exists in a social context and the management of diabetes requires an ongoing supportive relationship between parent and child. The results show a high degree of consistency in the beliefs adolescents and their mothers hold, and such congruence is presumed to benefit psychological well-being. However, the mediators and moderators for family belief processes are unclear and several possibilities are discussed.


Occurrence of Pyruvate Orthophosphate Dikinase in the Succulent Plant, Kalanchoë daigremontiana Hamet. et. Perr.
Pyruvate orthophosphate dikinase was detected from Kalanchoë daigremontiana Hamet. et. Perr., a succulent plant with crassulacean acid metabolism. Enzyme activity was similar to that of maize extracts. Two enzymes demonstrating pyruvate orthophosphate dikinase activity from K. daigremontiana and Zea mays were found to be partially identical from enzyme-inhibition and immunoprecipitin tests with maize enzyme antiserum. A time course study demonstrated that pyruvate orthophosphate dikinase activity in leaf extracts was dependent upon exposure of leaves to light.


The amyloid precursor protein represses expression of acetylcholinesterase in neuronal cell lines.
The toxic role of amyloid β peptides in Alzheimer's disease is well documented. Their generation is via sequential β- and γ-secretase cleavage of the membrane-bound amyloid precursor protein (APP). Other APP metabolites include the soluble ectodomains sAPPα and sAPPβ and also the amyloid precursor protein intracellular domain (AICD). In this study, we examined whether APP is involved in the regulation of acetylcholinesterase (AChE), which is a key protein of the cholinergic system and has been shown to accelerate amyloid fibril formation and increase their toxicity. Overexpression of the neuronal specific isoform, APP695, in the neuronal cell lines SN56 and SH-SY5Y substantially decreased levels of AChE mRNA, protein, and catalytic activity. Although similar decreases in mRNA levels were observed of the proline-rich anchor of AChE, PRiMA, no changes were seen in mRNA levels of the related enzyme, butyryl-cholinesterase, nor of the high-affinity choline transporter. A γ-secretase inhibitor did not affect AChE transcript levels or enzyme activity in SN56 (APP695) or SH-SY5Y (APP695) cells, showing that regulation of AChE by APP does not require the generation of AICD or amyloid β peptide. Treatment of wild-type SN56 cells with siRNA targeting APP resulted in a significant up-regulation in AChE mRNA levels. Mutagenesis studies suggest that the observed transcriptional repression of AChE is mediated by the E1 region of APP, specifically its copper-binding domain, but not the C-terminal YENTPY motif. In conclusion, AChE is regulated in two neuronal cell lines by APP in a manner independent of the generation of sAPPα, sAPPβ, and AICD.


Maternal and neonatal outcomes following in vitro fertilization: A cohort study in Romania.
Although in recent years the number of pregnancies obtained through in vitro fertilization (IVF) has increased significantly, a higher incidence of complications has been identified in this group. The widespread development and use of IVF has led to an increasing rate of multiple pregnancies and thus their associated complications. However, whether these complications occur due to assisted reproduction or infertility problems remains to be elucidated. In the present study, a comparison was made of IVF pregnancies with spontaneous conception, and the risk of obstetric and neonatal complications was assessed. An ambispective observational cohort study was carried out between January 2017 and October 2021 at Elias University Emergency Hospital, Romania. The exposed cohort included 132 IVF pregnancies and the control cohort included 157 spontaneous pregnancies. The IVF group included 110 pregnancies with fresh embryo-transfer and 22 pregnancies with cryopreserved embryo-transfer. Obstetric, perinatal and neonatal complications were analysed by multivariable logistic analysis. The results showed that, IVF pregnancies had a higher risk of pregnancy-induced hypertension (OR=6.42, 95% CI=1.72-23.92) and placental abnormalities (OR=5.49, 95% CI=1.07-28.17). Neonates obtained through IVF had a higher risk of prematurity (OR=6.52, 95% CI=2.99-14.20), low birth weight (LBW) (OR=17.18, 95% CI=7.06-41.87), small for gestational age (OR=4.10, 95% CI=1.95-8.59) and were more frequently hospitalized in the Neonatal Intensive Care Unit (NICU) (OR=11.91, 95% CI=5.72-24.81). Nulliparous women were associated with an increased risk of NICU admission (OR=0.46, 95% CI=0.25-0.88) and risk of LBW (OR=0.37, 95% CI=0.19-0.75). Maternal age ≥35 years had no influence as a confounding variable. In conclusion, this cohort study showed that IVF pregnancies have a higher risk of obstetric and neonatal complications than pregnancies obtained by spontaneous conception.


Angiogenesis-related pathways in the pathogenesis of ovarian cancer.
Ovarian Cancer represents the most fatal type of gynecological malignancies. A number of processes are involved in the pathogenesis of ovarian cancer, especially within the tumor microenvironment. Angiogenesis represents a hallmark phenomenon in cancer, and it is responsible for tumor spread and metastasis in ovarian cancer, among other tumor types, as it leads to new blood vessel formation. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Growth factors have been identified to play key roles in driving angiogenesis and, thus, the formation of new blood vessels that assist in "feeding" cancer. Such molecules include the vascular endothelial growth factor (VEGF), the platelet derived growth factor (PDGF), the fibroblast growth factor (FGF), and the angiopoietin/Tie2 receptor complex. These proteins are key players in complex molecular pathways within the tumor cell and they have been in the spotlight of the development of anti-angiogenic molecules that may act as stand-alone therapeutics, or in concert with standard treatment regimes such as chemotherapy. The pathways involved in angiogenesis and molecules that have been developed in order to combat angiogenesis are described in this paper.


Metformin induces ferroptosis by targeting miR-324-3p/GPX4 axis in breast cancer.
Metformin is a widely prescribed hypoglycemic drug. Many studies have shown its anti-cancer properties. In the present study, we aimed to explore the effect of metformin on breast cancer and clarify the underlying mechanism. Our results showed that metformin induced ferroptosis in MDA-MB-231 cells through upregulating miR-324-3p expression. Overexpression of miR-324-3p inhibited cancer cell viability. miR-324-3p inhibitor promoted cell viability. Further studies showed that the effect of miR-324-3p was mediated by directly targeting glutathione peroxidase 4 (GPX4). miR-324-3p bound to the 3'-UTR of GPX4 and led to the downregulation of GPX4. In vivo studies showed that metformin induced ferroptosis by upregulating miR-324-3p in the xenograft model of breast cancer in mice. Our study suggested that metformin promotes ferroptosis of breast cancer by targeting the miR-324-3p/GPX4 axis. Metformin could act as a potential anti-cancer agent through the induction of ferroptosis.


Lab on a chip phased-array MR multi-platform analysis system.
We present a lab on a chip (LOC) compatible modular platform for magnetic resonance (MR)-based investigation of sub-millimetre samples. The platform combines the advantages offered respectively by microcoils (high resolution at the microscale) and macroscopic surface coils (large field of view) as MR-detectors and consists of a phased array of microcoils (PAMs) providing a flat MR-sensitive area of 18.3 mm(2) with a B(0)-field uniformity better than 0.25 ppm in the sensor centre area. We demonstrate both high-resolution magnetic resonance imaging (MRI) and NMR spectroscopy using this platform. To demonstrate the application for biological samples, we report MR imaging of fish oocytes with an in-plane resolution of 30 × 30 μm(2) and a contrast to noise ratio of 10 for a scan time of only 13 min 39 s. We have also demonstrated high-resolution spectroscopy of a water phantom achieving 11 ppb (4.5 Hz at 400 MHz) linewidth and an SNR of 28 for only 12 s scan time. State of the art automatic wire bonding technology in conjunction with MEMS techniques has been employed to manufacture the platform with potential applications in MR-investigation of planar samples.


NMDA-dependent phase synchronization between septal and temporal CA3 hippocampal networks.
Increasing evidence suggests that synchronization between brain regions is essential for information exchange and memory processes. However, it remains incompletely known which synaptic mechanisms contribute to the process of synchronization. Here, we investigated whether NMDA receptor-mediated synaptic plasticity was an important player in synchronization between septal and temporal CA3 areas of the rat hippocampus. We found that both the septal and temporal CA3 regions intrinsically generate weakly synchronized δ frequency oscillations in the complete hippocampus in vitro. Septal and temporal oscillators differed in frequency, power, and rhythmicity, but both required GABAA and AMPA receptors. NMDA receptor activation, and most particularly the NR2B subunit, contributed considerably more to rhythm generation at the temporal than the septal region. Brief activation of NMDA receptors by application of extracellular calcium dramatically potentiated the septal-temporal coherence for long durations (>40 min), an effect blocked by the NMDA antagonist AP-5. This long-lasting NMDA-receptor-dependent increase in coherence was also associated with an elevated phase locking of spikes locally and across regions. Changes in coherence between oscillators were associated with increases in phase locking between oscillators independent of oscillator amplitude. Finally, although the septal CA3 rhythm preceded the oscillations in temporal regions in control conditions, this was reversed during the NMDA-dependent enhancement in coherence, suggesting that NMDA receptor activation can change the direction of information flow along the septotemporal CA3 axis. These data demonstrate that plastic changes in communication between septal and temporal hippocampal regions can arise from the NMDA-dependent phase locking of neural oscillators.


Optimization of the cryopreservation and thawing protocol for human hepatocytes for use in cell transplantation.
Cryopreservation of human hepatocytes is important for their use in hepatocyte transplantation. On thawing, cryopreserved hepatocytes often have reduced viability and metabolic function in comparison with fresh cells. The aim of this study was to modify the different steps in the standard cryopreservation procedure in an attempt to improve the overall outcome. Human hepatocytes with a viability of 69% +/- SD 16% were isolated from donor livers with a collagenase perfusion technique. Different cell densities, concentrations, rates, and methods of addition of dimethyl sulfoxide were tested for the freezing solution. Modified controlled-rate freezer programs were tested to obtain a linear decrease in the temperature. Once they were frozen, the storage time and thawing method for hepatocytes were investigated. The effects on thawed cell viability and attachment, lactate dehydrogenase release, cytochrome P450 1A1/2 activity, and albumin synthesis were determined. The results were used to produce an improved cryopreservation protocol suitable for good manufacturing practice conditions. With a cell density of 10(7) cells/mL in University of Wisconsin solution containing 300 mM glucose, 10% (vol/vol) dimethyl sulfoxide was added dropwise over 5 minutes, and was immediately frozen. Thawing was done rapidly at 37 degrees C, and dilution was performed with Eagle's minimum essential medium containing 300 mM glucose and 4% human serum albumin. Hepatocytes could be stored at -140 degrees C without significant further loss of function for up to 3 years. With this protocol, hepatocytes had a viability of 52% +/- 9%, an attachment efficiency of 48% +/- 8%, and lactate dehydrogenase leakage of 17% +/- 4%. This protocol is currently in use to cryopreserve hepatocytes for use in cell transplantation at our center.


Pneumococcal infections in HIV infected adults--clinical features, reasons behind the association and future hopes for prevention.
Streptococcus pneumoniae is the most important bacterial cause of pneumonia and meningitis among adults world wide. It is a particularly common cause of these infections and also bacteraemia among HIV infected adults with rates of disease increasing to more than 100 times the normal as HIV infection progresses to AIDS. This article briefly describes the common presentations and outcomes of pneumococcal disease (PD) in HIV infected adult inpatients in Malawi. Factors underlying susceptibility to pneumococcal infection in HIV infected adults are then reviewed, along with the effectiveness of current vaccines. Finally, novel approaches that will be needed to combat PD in HIV afflicted parts of the world are suggested.


The use of soluble fibrin in evaluating the acute and chronic hypercoagulable state.
Soluble fibrin detected in clinical plasma samples includes a variety of complexes consisting of fibrin monomer units, fibrinogen, and various proteolytic derivatives of fibrinogen and fibrin. The advantage of measuring soluble fibrin over fibrinopeptide A to detect thrombin action on fibrinogen is the considerably longer half-life of soluble fibrin in the circulation. Soluble fibrin can be detected by a variety of methods, including paracoagulation and precipitation assays, adsorption of fibrin monomer to insolubilized fibrinogen, functional assays based on the cofactor activity of some soluble fibrin compounds in t-PA-induced plasminogen activation, and by using fibrin-specific antibodies. Fibrin-specific antibodies may react with epitopes generated directly by fibrinopeptide A or B release or with epitopes generated by fibrin polymerization. Epitopes dependent on fibrinopeptide A release are often not accessible in native fibrin complexes and require the disaggregation of fibrin compounds to be reactive, whereas epitopes dependent on fibrinopeptide B release or fibrin polymerization are accessible to the monoclonal antibodies in nondenatured fibrin. Since soluble fibrin assays detect different structural or functional properties of soluble fibrin, no common calibrator for all soluble fibrin assays and, often, little correlation between different assay systems in clinical evaluations exist. Clinical applications of soluble fibrin assays include diagnosis and treatment monitoring of intravascular coagulation processes and prethrombotic states, monitoring anticoagulant treatment, and biocompatibility investigations. Some soluble fibrin assays have been demonstrated to be extremely sensitive indicators of acute fibrin formation. For the exclusion of venous thrombosis, D-dimer assays appear to be more sensitive than current soluble fibrin assays, since D-dimer assays detect freshly formed fibrin and proteolytic fragments of particulate clots. Further clinical studies are needed to establish the clinical utility of specific, soluble fibrin assays. The development of rapid, quantitative soluble fibrin assays for clinical routine use should be encouraged.


Association between nonspecific airway hyperresponsiveness and Arg16Gly beta2-adrenergic receptor gene polymorphism in asymptomatic healthy Japanese subjects.
Nonspecific airway hyperresponsiveness (AHR), a cardinal feature of asthma, is thought to result from several genetic and environmental factors. Asymptomatic AHR in nonasthmatic healthy subjects might be a risk factor for the development of asthma. Genetic variations in codons 16 and 27 of the human beta(2)-adrenergic receptor (beta(2)-AR) alter receptor function in vitro and are associated with various asthma-related phenotypes, including asthma severity and AHR. To date, however, few reports have examined the impact of beta(2)-AR gene polymorphism on AHR in asymptomatic healthy subjects. To determine whether polymorphism of the beta(2)-AR gene (Arg16Gly and Gln27Glu) might influence nonspecific AHR in asymptomatic healthy Japanese subjects. A cohort of 120 asymptomatic healthy subjects was analyzed using a stepwise linear regression model. Nonspecific airway responsiveness was measured using a continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan). We used values of the cumulative dose of inhaled methacholine measured at the inflection point at which respiratory conductance starts to decrease (Dmin) as an index of AHR. Genotyping to identify polymorphisms at codons 16 and 27 was conducted using an assay combining kinetic real-time quantitative polymerase chain reaction with allele-specific amplification. The Gly16Gly genotype was associated with lower Dmin values. The log Dmin value of asymptomatic healthy subjects carrying the Arg16 allele (Arg16/Arg or Arg16/Gly, n = 90) was 1.09 +/- 0.56 (mean +/- SD), while those homozygous for the Gly16 allele (n = 30) yielded a log Dmin value of 0.85 +/- 0.56 (p < 0.05). This study indicates that a specific beta(2)-AR polymorphism at codon 16 might be a genetic determinant of AHR, as judged by methacholine-induced bronchoconstriction in asymptomatic healthy subjects.


Reaction of decabrominated diphenyl ether by zerovalent iron nanoparticles.
Polybrominated diphenyl ethers (PBDEs) recognized as a new class of environmental persistent toxic contaminants have been distributed widely in the world. In this study, the synthesized nanoscale zerovalent iron (NZVI) in the laboratory was used to investigate the removal kinetics and mechanisms of decabrominated diphenyl ether (DBDE) at different pH. Within 40 min 90% of DBDE was rapidly removed by NZVI as compared to around 40 d needed for 24-fold weight of microscale ZVI. The removal by NZVI is much faster than that by microscale ZVI due to its high surface area and reactivity. At a different pH, the pseudo-first-order removal rate constants of DBDE linearly increased from 0.016 to 0.024 min(-1) with the decreasing of aqueous initial pH values from 10 to 5. The degradation of DBDE with NZVI is favorable in an acid condition. The debromination pathways of DBDE with NZVI were proposed on the basis of the identified reaction intermediates ranging from nona- to mono-brominated diphenyl ethers (BDEs) for an acid condition and from nona- to penta-BDEs for an alkaline condition. The debromination of PBDEs from para positions is more difficult than that from meta or ortho positions. Adsorption on NZVI also plays a role on the removal of DBDE. These findings can facilitate the treatment and fate prediction of PBDEs with NZVI in the environment.


CO2 laser heating system for in situ radial x-ray absorption at 16-BM-D at the Advanced Photon Source.
We present a portable CO2 laser heating system for in situ x-ray absorption spectroscopy (XAS) studies at 16-BM-D (High Pressure Collaborative Access Team, Advanced Photon Source, Argonne National Laboratory). Back scattering optical measurements are made possible by the implementation of a Ge beamsplitter. Optical pyrometry is conducted in the near-infrared, and our temperature measurements are free of chromatic aberration due to the implementation of the peak-scaling method [A. Kavner and W. R. Panero, Phys. Earth Planet. Inter. 143-144, 527-539 (2004) and A. Kavner and C. Nugent, Rev. Sci. Instrum. 79, 024902 (2008)] and mode scrambling of the input signal. Laser power stabilization is established using electronic feedback, providing a steady power over second timescales [Childs et al., Rev. Sci. Instrum. 91, 103003 (2020)]-crucial for longer XAS collections. Examples of in situ high pressure-temperature extended x-ray absorption fine structure measurements of ZrO2 are presented to demonstrate this new capability.


Municipal waste landfill as a source of polychlorinated biphenyls releases to the environment.
This study aimed to investigate the impact of municipal waste landfill on polychlorinated biphenyls (PCBs) release to the environment concerning groundwater flow directions. The contents of polychlorinated biphenyls in soils, plants and water were analysed at various distances from the landfill. Thanks to low solubility PCBs in water groundwater flow direction, under the landfill, have an influence on PCBs concentration in groundwater. Strong PCBs' sorption to organic matter caused that no affect groundwater flow directions on PCB content in soils and plants' tissues was observed. The largest PCBs deposition zone was located 50 m from the contamination source (landfill). Tri-CB and tetra-CB homologues were capable of migration deep into the soil profile, which could be related to the geological material from which the soils under study were developed, as well as to the properties of the PCB homologues.


Mathematical investigations of the escape from the Malthusian trap.
"We present a simulation model that synthesizes Malthusian and Boserupian notions of the way population growth and economic development were intertwined. The non-linear stochastic model consists of a system of equations whose dynamics culminate in an industrial revolution after hundreds of iterations. The Industrial Revolution [in Europe] can thus be conceptualized as a permanent 'escape' from the Malthusian trap that occurs once the economy is capable of permanently sustaining an ever growing population. We investigate the conditions for such an escape and their sensitivity to the parameters of the model.... Our results show that the likelihood of an escape is sensitive to the savings rate and to the output elasticities of the two sectors of the economy. When not in a subsistence crisis, the chances that an escape will occur increase for larger values of the ratio of the savings rate to the growth rate of the population. The chances of an escape also increase substantially for larger values of the output elasticities of labor." (SUMMARY IN FRE)


Comparative Investigations on the Metabolism of 2-(2,4-Dichlorophenoxy)Isobutyric Acid in Plants and Cell Suspension Cultures of Lycopersicon esculentum.
The metabolism of [(14)CH(3)]2-(2,4-dichlorophenoxy)isobutyric acid (DIB) was studied in plants and cell suspension cultures of Lycopersicon esculentum Mill. sp. ;Lukullus'. Both plants and cells in suspension culture showed a rapid uptake of DIB from nutrient media. The metabolites, isolated by extraction with methanol and separated by chromatographic methods, were identified by enzymic, chemical, and spectrometric methods. Two conjugates of the carboxyl with 2 and 3 moles glucose per mole DIB and, to a smaller extent, its beta-d-glucopyranosyl ester, were formed in both intact plants and cell suspension cultures, but there were quantitative differences.


Protein fluxes along the filopodium as a framework for understanding the growth-retraction dynamics: the interplay between diffusion and active transport.
We present a picture of filopodial growth and retraction from physics perspective, where we emphasize the significance of the role played by protein fluxes due to spatially extended nature of the filopodium. We review a series of works, which used stochastic simulations and mean field analytical modeling to find the concentration profile of G-actin inside a filopodium, which, in turn, determines the stationary filopodial length. In addition to extensively reviewing the prior works, we also report some new results on the role of active transport in regulating the length of filopodia. We model a filopodium where delivery of actin monomers towards the tip can occur both through passive diffusion and active transport by myosin motors. We found that the concentration profile of G-actin along the filopodium is rather non-trivial, containing a narrow minimum near the base followed by a broad maximum. For efficient enough actin transport, this non-monotonous shape is expected to occur under a broad set of conditions. We also raise the issue of slow approach to the stationary length and the possibility of multiple steady state solutions.