Direct Observation of an Iron-Bound Terminal Hydride in [FeFe]-Hydrogenase by Nuclear Resonance Vibrational Spectroscopy.
[FeFe]-hydrogenases catalyze the reversible reduction of protons to molecular hydrogen with extremely high efficiency. The active site ("H-cluster") consists of a [4Fe-4S]H cluster linked through a bridging cysteine to a [2Fe]H subsite coordinated by CN- and CO ligands featuring a dithiol-amine moiety that serves as proton shuttle between the protein proton channel and the catalytic distal iron site (Fed). Although there is broad consensus that an iron-bound terminal hydride species must occur in the catalytic mechanism, such a species has never been directly observed experimentally. Here, we present FTIR and nuclear resonance vibrational spectroscopy (NRVS) experiments in conjunction with density functional theory (DFT) calculations on an [FeFe]-hydrogenase variant lacking the amine proton shuttle which is stabilizing a putative hydride state. The NRVS spectra unequivocally show the bending modes of the terminal Fe-H species fully consistent with widely accepted models of the catalytic cycle.


Stereoselective [2 + 2] photodimerization: a viable strategy for the synthesis of enantiopure cyclobutane derivatives.
The [2 + 2] photodimerization of cinnamic acid derivatives to afford enantiopure cyclobutanes has been investigated. The use of a chiral auxiliary represents a convenient and straightforward method to exert enantiocontrol on the reaction. By exploiting Evans oxazolidinones, the stereoselective light-driven cyclisation affords a functionalised cyclobutane ring with up to 99% enantiocontrol after removing the chiral auxiliary. In-flow experiments allowed us to improve further the efficiency of the methodology, leading to high conversion and excellent enantioselectivity.


Perceptions of social challenges of adults with autism spectrum disorder.
This study examines perceptions of social challenges by adults with autism spectrum disorder (ASD). The investigators analyzed three separate, regularly scheduled social group meetings attended by a total of 18 adults with ASD where the activity was a discussion of social issues. Participants generated social questions and challenges they had encountered as a result of having autism. The questions were presented to the group for a discussion of potential solutions. Written and audio data were collected and a member check was completed. The data were plumbed for key words and emergent themes to identify major social challenges as viewed by adults with ASD. The emergent themes included relationships at work, developing and maintaining personal relationships, appropriate behaviors around members of the opposite sex, and personal perspectives on having ASD.


General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 4th communication: Effects on gastrointestinal, urinary and reproductive systems and other effects.
A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on the gastrointestinal, urinary and reproductive systems and other tissues were investigated in mice, rats guinea pigs, rabbits and dogs. 1. Gastrointestinal system: SNI-2011 did not cause any effects on the gastrointestinal system, i.e. the intestinal transport of charcoal meal in mice, the secretion of gastric and bile juices, and the formation of ulcer induced by water immersion restraint in rats. 2. Urinary and reproductive systems: SNI-2011 augmented the spontaneous movement of rat pregnant uterus in vivo at 0.3 mg/kg i.v. or higher, and this effect was not observed in the non-pregnant uterus. SNI-2011 increased the spontaneous movement of isolated guinea pig bladder (3 x 10(-6) mol/l or higher) and increased the in vivo spontaneous movement of rat bladder (0.3 mg/kg i.v. or higher). SNI-2011 caused increases in rat urine volume, pH and urinary excretion of Na+ and Cl- at 30 mg/kg p.o. 3. Others: SNI-2011 had no effect on the vascular permeability in mice, hematological parameters and blood coagulation in rats. SNI-2011 had neither hemolytic nor anti-inflammatory effect. These results suggest that SNI-2011 has muscarinic effects on the gastrointestinal, urinary and reproductive systems and other tissues at the doses approximately 10-fold higher than the doses needed for saliva secretion.


Fluorinated carbohydrates as lectin ligands: dissecting glycan-cyanovirin interactions by using 19F NMR spectroscopy.
NMR spectroscopy and isothermal titration calorimetry (ITC) are powerful methods to investigate ligand-protein interactions. Here, we present a versatile and sensitive fluorine NMR spectroscopic approach that exploits the (19)F nucleus of (19)F-labeled carbohydrates as a sensor to study glycan binding to lectins. Our approach is illustrated with the 11 kDa Cyanovirin-N, a mannose binding anti-HIV lectin. Two fluoro-deoxy sugar derivatives, methyl 2-deoxy-2-fluoro-α-D-mannopyranosyl-(1→2)-α-D-mannopyranoside and methyl 2-deoxy-2-fluoro-α-D-mannopyranosyl-(1→2)-α-D-mannopyranosyl-(1→2)-α-D-mannopyranoside were utilized. Binding was studied by (19)F NMR spectroscopy of the ligand and (1)H-(15)N HSQC NMR spectroscopy of the protein. The NMR data agree well with those obtained from the equivalent reciprocal and direct ITC titrations. Our study shows that the strategic design of fluorinated ligands and fluorine NMR spectroscopy for ligand screening holds great promise for easy and fast identification of glycan binding, as well as for their use in reporting structural and/or electronic perturbations that ensue upon interaction with a cognate lectin.


Effects of insulin, glucagon, and epinephrine on the plasma membrane of the white adipose cell: a freeze-fracture study.
A quantitative study of the adipocyte plasma membrane under the influence of lipipolytic or lipogenic hormones has been carried out by freeze-fracture. The number of plasma membrane invaginations (so-called pinocytosis) and of intramembranous particles was evaluated. Under the influence of either insulin, glucogon, or epinephrine, the membrane invaginations were significantly increased with respect to control adipocytes. Insulin was shown to increase the number of intramembranous particles of the plasma membrane whereas glucagon or epinephrine had an opposite effect. These data point to a hormonal modulation of the fine-structural organization of the adipocyte plasma membrane.


Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation.
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy.


Spindle cell carcinoma of the lung: a clinicopathologic presentation of three cases.
Three patients with spindle cell carcinoma located in the lower respiratory tract are presented, including cases of two monophasic and one biphasic tumor. On light microscopic examination, the spindle cell components of the tumors were histologically characterized by sheets of fusiform spindle cells that closely resembled a sarcoma. Keratin expression in the spindle cell components of these tumors, as shown by anti-cytokeratin antibody staining, demonstrated their epithelial nature. It is supposed that the spindle cell component displays a spectrum of phenotypes originating from epithelial cells with varying degrees of mesenchymal transformation. It is difficult to establish a diagnosis of this rare primary pulmonary malignancy prior to surgical intervention. A review of the literature allowed for a summary of the clinicopathologic characteristics of this tumor.


[Avoidable hospital drug prescription in the elderly. A review of the literature].
Elderly persons are particularly exposed to drug reactions, especially drug interactions subsequent to multiple prescriptions. It is also recognized that the drug risk is the leading hospital risk involving 1 to 10% of all hospitalized patients. An analysis of the avoidable nature of drug reactions leads to consideration of a sequence of 4 events leading to drug exposure: prescription, delivery, administration and compliance. Each event in this sequence corresponds to a distinct person: physician, pharmacist, nurse, patient. This suggests that the prevention of drug reactions in hospitalized elderly persons requires implementation of an "alert-causal attributability-avoidability-prevention" system by the healthcare teams where physicians, pharmacists, and nurses work in close coordination with the patient.


Proteomic and functional analyses of Lachesis acrochorda snake venom from the Valle del Cauca Department of Colombia.
Lachesis acrochorda envenomation has a lethality rate of approximately 90%. Despite its high lethality, little is known about its local and systemic effects and its relationship with its protein content. Thus, to increase knowledge of L. acrochorda snake venom from the Southwestern ecoregion of Colombia, we developed a proteomic analysis using a "bottom-up shotgun proteomic profiling" approach. Besides, we evaluated toxinological properties and compared the effects with the Bothrops asper snake venom activities. The RP-HPLC profile showed similarities with the L. acrochorda snake venom from the Northwestern ecoregion of Colombia. However, the results displayed differences in the protein families identified, probably due to the proteomic identification strategy. The in vitro and in vivo tests showed a L. acrochorda snake venom with Phospholipase A2 and metalloproteinase activities related to myotoxic, edematic, and hemorrhagic effects. Nevertheless, the L. acrochorda snake venom displayed a low lethality despite a large amount of inoculated venom. This investigation's results will help us improve the knowledge about the relationship between the clinical manifestations of L. acrochorda envenomation and the venom protein content.


Erythromycin attenuates metalloprotease/anti-metalloprotease imbalance in cigarette smoke-induced emphysema in rats via the mitogen-activated protein kinase/nuclear factor-κB activation pathway.
The present study investigated whether erythromycin (ERY) reduces cigarette smoke (CS)-induced emphysema in rats and aimed to determine the anti-inflammatory effect of ERY, which may identify potential treatments for chronic obstructive pulmonary disease. Furthermore, the current study focused on the potential effects on the imbalance between matrix metalloprotease (MMP) and anti-MMP activity, the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor‑κB (NF‑κB) signaling pathway. Wistar rats were divided into the following three groups (n=12 each): control (ERY vehicle only, without any CS exposure), CS (animals were exposed to CS for 12 weeks) and CS + ERY (animals were exposed to CS for 12 weeks and received 100 mg/kg/day ERY). The recruitment of inflammatory cells into the bronchoalveolar lavage fluid (BALF) and the histopathology of lung tissue from all groups was evaluated to grade the severity of the emphysema. The expression of MMP‑2, MMP‑9 and tissue inhibitor of metalloproteinase‑1 was evaluated by immunohistochemistry and western blotting. The activation of MAPKs, NF‑κB and inhibitor of NF‑κB (IκBα), in lung tissues was examined by western blotting. Treatment with ERY resulted in fewer inflammatory cells and cytokines in the BALF, and fewer emphysema‑associated changes in the lungs compared with control. The stimulus of CS promoted the phosphorylation of extracellular signal‑regulated kinase (ERK)1/2 and p38, but not c‑Jun NH2‑terminal kinase, thereby inducing the activation of the ERK/MAPK signaling pathway in rats. Furthermore, CS exposure increased the expression of NF-κB and decreased the expression of IκBα. The levels of phosphorylated ERK1/2 and p38 were significantly reduced in rats with CS‑induced emphysema when treated with ERY compared with the CS group. The results of the present study therefore indicate that oral administration of ERY may suppress CS‑induced emphysema by regulating inflammatory cytokines and the MMP/anti-MMP imbalance via the MAPK/NF-κB pathway.


Study on the interaction of 6-(2-morpholin-4-yl-ethyl)-6H-indolo [2,3-b]quinoxaline hydrochloride with human serum albumin by fluorescence spectroscopy.
Under physiological conditions, in vitro interaction between the bio-active substance 6-(2-morpholin-4-yl-ethyl)-6H-indolo[2,3-b]quinoxaline hydrochloride (MIQ) and human serum albumin (HSA) was investigated at an excitation wavelength 260 nm and at different temperatures (298 K, 308 K and 313 K) by fluorescence emission spectroscopy. From spectral analysis, MIQ showed a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The binding constant is estimated asK A = 2.55 × 10-4 l · mol-1 at 298 K. Based on the thermodynamic parameters evaluated from the van 't Hoff equation, the enthalpy change (ΔH°) and entropy change (ΔS°) were derived to be negative values. A value of 2.37 nm for the average distance r between MIQ (acceptor) and tryptophan residues of HSA (donor) was derived from the fluorescence resonance energy transfer. UV/vis absorption spectra were used to confirm the quenching mechanism.


Changes in dicot-weeds species composition in spring barley in Latvia during the past 20 years.
Dicot weed populations were assessed in spring barley trials carried out in four three-years periods at 5-year intervals: 1990-1992, 1995-1997; 2001-2003 and 2006-2008. The overall aim of this research was to evaluate the changes in dicot-weed infestations in spring barley in fields of one region (Riga) of Latvia in sod-podzolic loamy sand soil. The results of the trials showed that Galeopsis spp, Stellaoria media, Viola orvensis and Chenopodium album were among the most frequent weed species in the periods of 1990-1992 and 1995-1997. The occurrence of C. album and V. arvensis increased during the periods of 2001-2003 and 2006-2008.


Practices in primary health care oriented toward the harmful consumption of drugs.
Objective To analyze the practices of primary care focused on the harmful consumption of drugs. Method This is a qualitative study, developed with a dialectical-critical approach. Data collection was carried out through semi-structured interviews with 10 employees of a basic health unit (UBS). Results The demands are not accepted, and if they go beyond the barriers shaped by the historical absence of health care practices for drug users and moralistic and preconceived ideologies, they are not reinterpreted as health needs; practices that meet these demands and go beyond the barriers are poor; the functionalist approach, which explains drug use as a disease and considers drug users as deviants, supports the few existing practices. Conclusion primary health care is mistakenly focused on addiction; it lacks structural elements of the production process in health and internal dynamics of the working processes that would foster the development of collective practices.


BODY CONDITION OF EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) EVALUATED BY COMPUTED TOMOGRAPHY.
Conservation efforts determining the health status of individuals can aid in assessing population health and sustainability. Body condition was determined in 65 free-ranging Eastern box turtles (Terrapene carolina carolina) from four locations in Vermilion County, Illinois, in the months of May, July, and September 2014, 2015, and 2016 using computed tomography (CT). Physical examinations were performed to determine morphometric measurements, and CT scans measured body fat. Twenty-three linear models were constructed to determine which morphometric measurements best correlated to fat content. The top two models of body fat included a relationship between mass and carapace width. Fat increases as both mass and carapace width increase. CT, while impractical for daily use, improved on previous methods of measuring body condition and created a calculation that can be applied broadly to Eastern box turtles. By understanding how measurements of mass and carapace width correlate to body condition, practitioners, researchers, and conservationists can evaluate chelonians with increased confidence in the accuracy of their assessment.


Cryptococcal Meningitis Diagnosed With Lumbar Puncture in an Emergency Department Patient With Acute Delirium.
Cryptococcal meningitis is a life-threatening fungal infection of the central nervous system. It primarily affects immunocompromised individuals, particularly those with advanced HIV/AIDS, but can occur in people of all ages. Risk factors include solid organ transplantation, hematological malignancies, immunosuppressive medications, and primary immunodeficiency disorders. We describe a case of a 68-year-old male with atypical risk factors for cryptococcal meningitis who presented acutely delirious with a negative diagnostic workup aside from a positive cerebrospinal fluid (CSF) meningitis screen reporting Cryptococcus neoformans/gattii. While the rate of lumbar puncture (LP) in the ED has drastically decreased over the years, we emphasize the importance of considering its diagnostic value in emergency department settings in patients with atypical presentations.


Genome-wide mapping of transcriptional enhancer candidates using DNA and chromatin features in maize.
While most cells in multicellular organisms carry the same genetic information, in each cell type only a subset of genes is being transcribed. Such differentiation in gene expression depends, for a large part, on the activation and repression of regulatory sequences, including transcriptional enhancers. Transcriptional enhancers can be located tens of kilobases from their target genes, but display characteristic chromatin and DNA features, allowing their identification by genome-wide profiling. Here we show that integration of chromatin characteristics can be applied to predict distal enhancer candidates in Zea mays, thereby providing a basis for a better understanding of gene regulation in this important crop plant. To predict transcriptional enhancers in the crop plant maize (Zea mays L. ssp. mays), we integrated available genome-wide DNA methylation data with newly generated maps for chromatin accessibility and histone 3 lysine 9 acetylation (H3K9ac) enrichment in young seedling and husk tissue. Approximately 1500 intergenic regions, displaying low DNA methylation, high chromatin accessibility and H3K9ac enrichment, were classified as enhancer candidates. Based on their chromatin profiles, candidate sequences can be classified into four subcategories. Tissue-specificity of enhancer candidates is defined based on the tissues in which they are identified and putative target genes are assigned based on tissue-specific expression patterns of flanking genes. Our method identifies three previously identified distal enhancers in maize, validating the new set of enhancer candidates and enlarging the toolbox for the functional characterization of gene regulation in the highly repetitive maize genome.


Postnatal development of synaptic transmission in local networks of L5A pyramidal neurons in rat somatosensory cortex.
The probability of synaptic transmitter release determines the spread of excitation and the possible range of computations at unitary connections. To investigate whether synaptic properties between neocortical pyramidal neurons change during the assembly period of cortical circuits, whole-cell voltage recordings were made simultaneously from two layer 5A (L5A) pyramidal neurons within the cortical columns of rat barrel cortex. We found that synaptic transmission between L5A pyramidal neurons is very reliable between 2 and 3 weeks of postnatal development with a mean unitary EPSP amplitude of approximately 1.2 mV, but becomes less efficient and fails more frequently in the more mature cortex of approximately 4 weeks of age with a mean unitary EPSP amplitude of 0.65 mV. Coefficient of variation and failure rate increase as the unitary EPSP amplitude decreases during development. The paired-pulse ratio (PPR) of synaptic efficacy at 10 Hz changes from 0.7 to 1.04. Despite the overall increase in PPR, short-term plasticity displays a large variability at 4 weeks, ranging from strong depression to strong facilitation (PPR, range 0.6-2.1), suggesting the potential for use-dependent modifications at this intracortical synapse. In conclusion, the transmitter release probability at the L5A-L5A connection is developmentally regulated in such a way that in juvenile animals excitation by single action potentials is efficiently transmitted, whereas in the more mature cortex synapses might be endowed with a diversity of filtering characteristics.


Infantile Colic Is Associated With Low-grade Systemic Inflammation.
Dysbiosis, an imbalance in the taxonomic composition of the gut bacteria occurring during the critical stages of development, induces lasting shifts in the immunological and metabolic phenotype if accompanied by an inflammatory response. Because altered gut microbiota and successful treatment with probiotics have both been demonstrated in cases of colic, we hypothesized here that infants with colic might have low-grade inflammation. In 28 infants with colic and in 12 healthy controls at the age of 1 month, we measured the following serum immunological biomarkers: cytokines interleukin 1β (IL-1β); IL-6; IL-10; tumor necrosis factor α; interferon γ (IFN-γ); chemokines IL-8; monocyte chemotactic protein-1 (MCP-1); macrophage inflammatory protein 1β (MIP-1β) and chemokine (C-X-C motif) ligand 16; and intestinal fatty acid-binding protein, a biomarker of enterocyte damage and zonulin, a biomarker of intestinal permeability. In addition, intestinal microbiota composition was correlated with immunological biomarkers. Infants with colic had increased concentrations of IL-8, MCP-1, and MIP-1β in serum as compared with healthy children. All the other immunological biomarkers were comparable between the groups. Fecal levels of Clostridium leptum correlated negatively with the proinflammatory markers MCP-1 (r = -0.44, P = 0.02), MIP-1β (r = -0.43, P = 0.02), and tumor necrosis factor α (r = -0.38, P = 0.04). In addition, C coccoides group levels correlated negatively with MCP-1 (r = -0.43, P = 0.02) and Bifidobacterium breve levels positively with chemokine (C-X-C motif) ligand 16 (r = 0.38, P = 0.04). In addition to gut microbiota alterations, colic in infants is associated with low-grade systemic inflammation. Specific bacterial species beyond conventional probiotics may have anti-inflammatory properties that may help to modulate microbiota and alleviate colic-related inflammation.


Long-term Outcomes of Primary Intraocular Lens Implantation in Patients Aged 7 to 24 Months.
To report long-term outcomes of primary intraocular lens (IOL) placement in patients aged 7 to 24 months. This was a retrospective study of 27 consecutive patients (28 eyes) aged 7 to 24 months who underwent cataract surgery with primary IOL placement. Average follow-up was 62.7 ± 41.7 months and the mean age of surgery was 14.4 ± 5.6 months. Mean final visual acuity was 1.02 ± 0.72 logMAR (20/209). Adverse events occurred in 7 eyes (25%) and included visual axis opacification in 6 eyes and pupillary block glaucoma in 1 eye. Seven patients (25.9%) required additional intraocular surgery. Strabismus was present in 19 patients (70.4%). Better stereopsis was correlated with better final acuity. Cataract surgery with IOL placement in patients aged 7 to 24 months is associated with few complications. Visual axis opacification is the most frequent adverse event. [J Pediatr Ophthalmol Strabismus. 2017;54(3):149-155.].


[A case of selective short-term memory disturbance due to a glioma in the left temporo-parietal lobe].
We report a patient with selective short-term memory disturbance caused by a glioma in the left temporal-parietal lobe. The patient was a 40-year-old right-handed housewife who complained of difficulty in memorizing series of numbers. She was working as a car dealer. She was well until 6 months prior to the present admission when she noted a difficulty in memorizing series of numbers such when telephone numbers and car registration numbers. She had to write them down as her customers told them to her. On admission, she was alert and oriented to all spheres. She was mentally sound without dementia. She did not show aphasia, apraxia, or agnosia, except for brief periods of seizures in which she became unable to speech. Neuropsychological examination revealed that she had difficulty in repeating and dictating series of numbers and meaningless kana words. However, she could easily pick up the correct series of numbers or kana words among multiple choices presented visually. Thus it was clear that her problem was not the disturbance of auditory input nor expression, but a selective impairment of short-term memory. She could memorize the same stimuli when visually presented. Therefore, her problem was thought to be a disturbance of auditory short-term memory of meaningless words. After resection of her tumor, she developed transient amnesic aphasia, which improved a year later. She was examined again in her memory function. In the task of visual stimuli, we presented her a card in which a series of numbers or a nonsense syllable was written for 5 seconds and asked her to remember them.(ABSTRACT TRUNCATED AT 250 WORDS)


Probable destructive meningioma in an archaeological adult male skull from Alaska.
Several intracranial pathological conditions can affect the bones of the skull. The most common cause of these conditions is tumor, but infection and other diseases are also known to affect the bones of the skull. Distinguishing between the various causes of intracranial skeletal pathology in archaeological human remains is usually a challenging exercise, and a specific diagnosis will often be impossible. Meningiomas are tumors that arise in arachnoid tissues embedded in the outer layer of the dura. Because of this association, they occur almost exclusively in the skull and vertebral column. Usually meningiomas are slow-growing tumors that do not metastasize to other organs and tissues of the body. However, rare cases can be malignant and, even when meningiomas are benign, their presence and growth can adversely affect the nervous and vascular supply to other tissues in the skull and vertebral column. Their effect on adjacent bone tissue varies from stimulating bone-forming lesions to causing highly destructive lesions. A few examples of meningioma have been described in the paleopathological literature. Most of these cases are bone-stimulating meningiomas. The case presented here is a probable example of a highly destructive meningioma of the skull base, with unilateral extension into the left side of the cranium. This case is compared with a modern clinical case of destructive intracranial meningioma that was documented both radiographically and pathologically. Destructive meningiomas can be confused with other pathological conditions, including benign and malignant tumors. Criteria for differentiating the diagnostic options are reviewed.


A comparison of perinatal outcomes in singletons and multiples born after in vitro fertilization or intracytoplasmic sperm injection stratified for neonatal risk criteria.
To compare perinatal singleton and multiple outcomes in a large Dutch in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) population and within risk subgroups. Newborns were assigned to a risk category based on gestational age, birthweight, Apgar score and congenital malformation. Register-based retrospective cohort study. Netherlands Perinatal Registry data. A total of 3041 singletons and 1788 multiple children born from IVF/ICSI in 2003-2005. Student's t-test or Mann-Whitney U-test was used to analyze continuous data, chi-squared analyses were used for categorical data. Multivariate logistic and linear regression analysis was performed to analyze whether the risk stratification criteria were associated with neonatal hospital admission and length of stay. Start of labor, mode of delivery, gestational age, birthweight, 5-min Apgar score, congenital malformation, neonatal hospital admission, neonatal intensive care unit admission and mortality. IVF/ICSI-conceived multiples had considerably poorer outcomes than singletons in terms of cesarean section rate, preterm birth, birthweight, being small-for-gestational-age, Apgar score, neonatal hospital admission, neonatal intensive care unit admission and neonatal mortality. As opposed to the results found in the total study population and the low-risk and moderate-risk populations, high-risk multiples showed better outcomes than high-risk singletons regarding cesarean section rate, birthweight and Apgar score. All risk stratification variables were associated with being hospitalized after birth. Length of stay was associated with all risk stratification criteria except Apgar score. Perinatal outcomes in IVF/ICSI-conceived multiples are considerably poorer than in singletons. This finding mainly pertains to low-risk children. High-risk multiples had significantly better perinatal outcomes than high-risk singletons.


Acceptance of sugar reduction in flavored yogurt.
To investigate what level of sugar reduction is accepted in flavored yogurt, we conducted a hedonic test focusing on the degree of liking of the products and on optimal sweetness and aroma levels. For both flavorings (strawberry and coffee), consumers preferred yogurt containing 10% added sugar. However, yogurt containing 7% added sugar was also acceptable. On the just-about-right scale, yogurt containing 10% sugar was more often described as too sweet compared with yogurt containing 7% sugar. On the other hand, the sweetness and aroma intensity for yogurt containing 5% sugar was judged as too low. A second test was conducted to determine the effect of flavoring concentration on the acceptance of yogurt containing 7% sugar. Yogurts containing the highest concentrations of flavoring (11% strawberry, 0.75% coffee) were less appreciated. Additionally, the largest percentage of consumers perceived these yogurts as "not sweet enough." These results indicate that consumers would accept flavored yogurts with 7% added sugar instead of 10%, but 5% sugar would be too low. Additionally, an increase in flavor concentration is undesirable for yogurt containing 7% added sugar.


Acoustic radiation torque on an irregularly shaped scatterer in an arbitrary sound field.
To eliminate the limitation of the conventional acoustic radiation torque theory, which is only applicable to a disklike scatterer in a plane sound field, a new theory is established to calculate the radiation torque on any irregularly shaped scatterer in any arbitrary sound field. First, with the aid of the conservation law of angular momentum, the acoustic radiation torque is expressed as the angular momentum flux through a spherical surface with the center at the scatterer's centroid. Second, the velocity potential of the scattered field is derived, taking into account the influences of the translational and rotational movements of the scatterer induced by the first order stress of the incident sound field. Finally, a general calculating formula of the acoustic radiation torque is achieved. For a disklike scatterer in a plane sound filed, results from the above formula are well identical with those conventional formulas. By studying the case of a semicircular cylinder scatterer in a standing-wave sound field, it is found that for an irregularly shaped scatterer its rotation velocity is normally nonzero and the radiation torque changes with the spatial attitude.


Novel insight into Chronic Inflammatory Demyelinating Polineuropathy in APECED syndrome: molecular mechanisms and clinical implications in children.
Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE gene mutation. It is characterized by the association of multiple autoimmune diseases, with a classical triad including chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical failure. Its clinical spectrum has significantly enlarged in the last years with the apparence of new entities. One of these novel manifestations is the chronic inflammatory demyelinating polineuropathy (CIDP), that is characterized by involvement of peripheral nervous system, with nerve demyelination, progressive muscular weakness of both arms and legs and sensory loss. The identification of myelin protein zero as an important autoantigen (Ag) in CIDP may suggest the development of Ag-based therapies, such as Ag-specific DNA vaccination or infusion of Ag-coupled cells.


Preparation of a First 18F-Labeled Agonist for M1 Muscarinic Acetylcholine Receptors.
M1 muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer's disease and other CNS pathologies. Consequently, major efforts have been spent in the development of subtype-selective positron emission tomography (PET) tracers for mAChRs resulting in the development of several 11C-labeled probes. However, protocols for the preparation of 18F-labeled mAChR-ligands have not been published so far. Here, we describe a straightforward procedure for the preparation of an 18F-labeled M1 mAChR agonist and its corresponding pinacol boronate radiolabeling precursor and the non-radioactive reference compound. The target compounds were prepared from commercially available aryl fluorides and Boc protected 4-aminopiperidine using a convergent reaction protocol. The radiolabeling precursor was prepared by a modification of the Miyaura reaction and labeled via the alcohol-enhanced Cu-mediated radiofluorination. The developed procedure afforded the radiotracer in a non-decay-corrected radiochemical yield of 17 ± 3% (n = 3) and in excellent radiochemical purity (>99%) on a preparative scale. Taken together, we developed a straightforward protocol for the preparation of an 18F-labeled M1 mAChR agonist that is amenable for automation and thus provides an important step towards the routine production of a 18F-labeled M1 selective PET tracer for experimental and diagnostic applications.


Characterization of novel transcripts of human papillomavirus type 16 using cap analysis gene expression technology.
We have performed cap-analysis gene expression (CAGE) sequencing to identify the regulatory networks that orchestrate genome-wide transcription in human papillomavirus type 16 (HPV16)-positive cervical cell lines of different grades: W12E, SiHa, and CaSki. Additionally, a cervical intraepithelial neoplasia grade 1 (CIN1) lesion was assessed for identifying the transcriptome expression profile. Here we have precisely identified a novel antisense noncoding viral transcript in HPV16. In conclusion, CAGE sequencing should pave the way for understanding a diversity of viral transcript expression.


Changes in body image disturbance in morbidly obese patients 1 year after laparoscopic adjustable gastric banding.
The effectiveness of post-surgical weight loss in improving body image disturbance (BID) in morbidly obese patients is still unclear. Providing multidimensional measures of BID and controlling for the effect of co-morbid eating psychopathology may help to clarify this issue. This preliminary study explores whether 1) BID improves 1 year after laparoscopic adjustable gastric banding (LAGB), and whether 2) such improvement is related to post-surgical BMI and/or eating disorder reduction. BID was multidimensionally assessed by means of the Body Uneasiness Test (BUT). 35 obese subjects (mean BMI 45.5) were evaluated prior to and 1 year after LAGB using the BUT, and a standardized interview and questionnaire to assess eating psychopathology. BID and eating habit changes during follow-up were also investigated. Postoperative BUT values were entered as outcome measures (dependent variables) in a series of stepwise multiple regression analyses; BMI and binge eating reduction, baseline BUT scores, gender, age, and age of onset of obesity were tested as independent variables. Some aspects of BID (body image overconcern and related avoidance behaviors, compulsive self-monitoring, and overall severity of BID) improved following LAGB, while others (weight phobia, depersonalization, and uneasiness toward body parts) did not. The post-surgical lower levels of the former were predicted by the overall decrease in binge eating symptoms, irrespective of BMI reduction, age, gender, and age of onset of obesity. LAGB may ameliorate some BID aspects in morbidly obese patients, and an improvement in eating behaviors may contribute to this effect.


Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea.
It has been suggested that obstructive sleep apnea (OSA)-induced hypoxic stress might contribute to cardiovascular disorders by promoting expression of soluble adhesion molecules. The reported increase of circulating adhesion molecules in patients with OSA remains controversial because confounders such as cardiovascular risk factors and left ventricular function have not been adequately controlled for. We hypothesized that soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and E-selectin levels are correlated with OSA independent of coexisting coronary artery disease (CAD). University-affiliated teaching hospitals. A prospective study of 61 consecutive subjects with angiographically proven CAD deemed to have stable angina. Fifteen patients (mean +/- SD) 61.2 +/- 1.9 years old with moderate-to-severe OSA (apnea-hypopnea index [AHI] > or = 20/h) were matched to a control group (AHI < or = 5/h) for age, gender, body mass index, and severity of CAD. Venous blood samples were collected the morning of the sleep study and assayed for human ICAM-1, VCAM-1, L-selectin, and E-selectin with commercially available enzyme-linked immunosorbent assay kits. All but L-selectin were significantly increased in the OSA group compared to the control subjects (ICAM-1, 367.4 +/- 85.2 ng/mL vs 252.8 +/- 68.4 ng/mL, p = 0.008; VCAM-1, 961.5 +/- 281.7 ng/mL vs 639.1 +/- 294.4 ng/mL, p = 0.004; E-selectin, 81.0 +/- 30.4 ng/mL vs 58.1 +/- 23.2 ng/mL, p = 0.03, respectively). The increased levels of adhesion molecules correlated with the AHI and the oxygen desaturation index but not with the severity of hypoxemia or the frequency of arousals. These findings suggest that OSA modulates the expression of proinflammatory mediators. Further studies should evaluate the influence of adhesion molecules on cardiovascular outcome in CAD patients with OSA.


Dominicans and balneology in the Bohemia and surrounding countries (1650 - 1720).
The paper tackles the question of balneological treatment available for the members of the Order of Preachers in Central Europe between 1650 and 1720. I took advantage of a strict record keeping procedure within the Dominican order, which required that all members obtain a written permission from the Father Provincial before taking any journey beyond local boundaries. As all the records were kept in so called "Provincial books" (Libri provinciae) it was possible to identify travelling permits issued for balneological treatment and collect data about visits to spas from the entire Czech Province.


Genetic improvement of non-conventional Torulaspora delbrueckii for traditional sparkling winemaking by mixing for eventual hybridization with Saccharomyces cerevisiae.
Non-conventional yeasts such as Torulaspora delbrueckii (Td) have been proposed for sparkling winemaking. Unfortunately, this yeast has poor efficiency in completing wine fermentation as compared to Saccharomyces cerevisiae (Sc). New mutants with increased resistance to SO2, ethanol, and high CO2 pressure were previously isolated from spore clones of Td. Although these mutants showed improved capability for base wine fermentation, there is still room for genetic improvement of Td yeasts until the fermentative capacity of Sc is achieved. As an alternative approach, yeast mixture for eventual hybridization of Td with Sc was assayed in this study. The new yeast mixture clones (Sc-mixed Td) showed an intermediate phenotype between both parent yeasts for some relevant biotechnological properties, such as resistance to SO2, ethanol, copper, high CO2 pressure, and high temperature, as well as flocculation potential. These properties varied depending on the specific Sc-mixed Td clone. Several mixture clones showed improved capability for base wine fermentation as compared to the Td parent strain, approaching the fermentation capability of the Sc parent strain. The organoleptic quality of sparkling wine was also improved by using some mixture clones and this improved quality coincided with an increased amount of acetate and ethyl esters. The genetic stability of some Sc-mixed Td clones was good enough for commercial yeast production and winery applications.


A new device for measuring the viscoelastic properties of hydrated matrix gels.
Determinations of the viscoelastic properties of extracellular matrices (ECMs) are becoming increasingly important for accurate predictive modeling of biological systems. Since the interactions of the cells with the ECM and surrounding fluid (e.g., blood, media) each affect cell behavior; it is advantageous to evaluate the ECM's material properties in the presence of the hydrating fluid. Conventional rheometry methods evaluate the bulk material properties of gel materials while displacing the hydrating liquid film. Such systems are therefore nonideal for testing materials such as ECMs, whose properties change with dehydration. The new patent pending, piezoelectrically actuated linear rheometer is designed to eliminate this problem. It uses a single cantilever to apply an oscillating load to the gel and to sense the gel's deflection. Composed of two thin film piezopolymer layers, the cantilever uses one layer as the actuator, and the second piezopolymer layer to measure the lateral movement of its attached probe. The viscoelastic nature of the ECM adds stiffness and damping to the system, resulting in the attenuation and phase shift of the sensor's output voltage. From these parameters, the ECM's shear storage and loss moduli are then determined. Initial tests on the BioMatrix I and type I collagen ECMs reveal that the first prototype of the piezoelectrically actuated linear rheometer is capable of accurately determining the trend and order of magnitude of an ECM's viscoelastic properties. In this paper, details of the rheometer's design and operating principles are described.


Caries Detection on Intraoral Images Using Artificial Intelligence.
Although visual examination (VE) is the preferred method for caries detection, the analysis of intraoral digital photographs in machine-readable form can be considered equivalent to VE. While photographic images are rarely used in clinical practice for diagnostic purposes, they are the fundamental requirement for automated image analysis when using artificial intelligence (AI) methods. Considering that AI has not been used for automatic caries detection on intraoral images so far, this diagnostic study aimed to develop a deep learning approach with convolutional neural networks (CNNs) for caries detection and categorization (test method) and to compare the diagnostic performance with respect to expert standards. The study material consisted of 2,417 anonymized photographs from permanent teeth with 1,317 occlusal and 1,100 smooth surfaces. All the images were evaluated into the following categories: caries free, noncavitated caries lesion, or caries-related cavitation. Each expert diagnosis served as a reference standard for cyclic training and repeated evaluation of the AI methods. The CNN was trained using image augmentation and transfer learning. Before training, the entire image set was divided into a training and test set. Validation was conducted by selecting 25%, 50%, 75%, and 100% of the available images from the training set. The statistical analysis included calculations of the sensitivity (SE), specificity (SP), and area under the receiver operating characteristic (ROC) curve (AUC). The CNN was able to correctly detect caries in 92.5% of cases when all test images were considered (SE, 89.6; SP, 94.3; AUC, 0.964). If the threshold of caries-related cavitation was chosen, 93.3% of all tooth surfaces were correctly classified (SE, 95.7; SP, 81.5; AUC, 0.955). It can be concluded that it was possible to achieve more than 90% agreement in caries detection using the AI method with standardized, single-tooth photographs. Nevertheless, the current approach needs further improvement.


Making the Psychological Dimension of Learning Visible: Using Technology-Based Assessment to Monitor Students' Cognitive Development.
Technology-based assessment offers unique opportunities to collect data on students' cognitive development and to use that data to provide both students and teachers with feedback to improve learning. The aim of this study was to show how the psychological dimension of learning can be assessed in everyday educational practice through technology-based assessment in reading, mathematics and science. We analyzed three related aspects of the assessments: cognitive development, gender differences and vertical scaling. The sample for the study was drawn from primary school students in Grades 1-8 (ages 7 to 14) in Hungary. There were 1500 to 2000 students in each grade cohort. Online tests were constructed from 1638 items from the reading, mathematics, and science domains in the eDia system. The results confirmed that the disciplinary, application and psychological dimensions of learning can be distinguished empirically. Students' cognitive development was the most steady (and effective) in mathematics, where the greatest development occurred in the first years of schooling. Path models suggested that the psychological dimension of learning can be predicted at a moderate level based on students' level of school knowledge consisting of the disciplinary and application dimensions of learning as latent constructs. The predictive power was almost the same in both dimensions. Generally, girls developed faster in the psychological dimension of reading, mathematics and science learning; however, the size of gender differences varied by age and domain. This study (1) provides evidence that the psychological dimension of learning can be made visible even in an educational context, (2) highlights the importance of the explicit development of the psychological dimension of learning during school lessons, and (3) shows that there are gender differences in the developmental level of the psychological dimension of learning in favor of girls but that this varies by grade and domain.


Thoughts on medication and psychoanalysis: a lay analyst's view.
The issues involved in split analytic treatments-where a second person manages the patient's medication-are discussed from the point of view of a developmentalist and lay analyst. Case material is presented to illustrate the interplay of medication with other elements of the psychoanalytic situation. Medication and its effects, it is argued, should be accorded no special status apart from other interventions and enactments in an analysis. Some see medication and psychoanalysis as parallel processes, two separate and unintegrated theoretical systems, and recommend shifting back and forth between models of the mind or becoming "bilingual"; against this view, it is argued that anything the analyst does will affect the patient's thoughts, fantasies, and even physiology in individual ways, and only attention to analytic material can reveal what an intervention means in a specific case. Success in split treatment depends on a collaborative therapeutic alliance among patient, analyst, and consultant. Because there is as yet no theory that bridges psychoanalysis and psychopharmacology, analysts must talk of these matters as incompletely synthesized and regard them as part of the challenges that make psychoanalysis the exciting, impossible profession it is.


Simultaneous transverse colon and sigmoid volvulus.
Colonic volvulus is one of the most common causes of bowel obstruction. It could occur in different parts of the colon. The sigmoid is the most common part, but it rarely occurs in the transverse colon because of the colon's anatomical features. So, simultaneous sigmoid and transverse colon volvulus is a rare phenomenon that could endanger patients' lives due to its rarity, ischemia, necrosis of the colon wall, and the lack of a definite algorithm to approach this disease. So, it is essential to consider this disease as one of the most important differential diagnoses in patients with abdominal pain and distention. In this article, a 45-year-old male presented to the surgical ward with severe prolonged abdominal pain, diagnosed with simultaneous sigmoid and transverse colon volvulus during laparotomy.


HIV associated kidney diseases: Clarifying concordance between renal failure in HIV infection and histopathologic manifestations at kidney biopsy.
Patients with HIV infection have a wide spectrum of renal diseases. Some are known to be the direct effect of the viral infection while others are renal diseases that also occur in uninfected populations. HIV associated nephropathy (HIVAN) is considered to be a subtype of primary focal and segmental glomerulosclerosis that is distinct in HIV infected patients. It is more frequent in the African-American population and associated with mutations of the apolipoprotein L1 (APOL1) gene. HIV associated immune complex kidney disease (HIVICD) encompasses a spectrum of HIV associated renal diseases characterized by the presence of immune complex deposition within glomeruli. Thrombotic microangiopathy (TMA) is a complication of HIV infection that presents with hemolytic anemia, thrombocytopenia, and renal failure. TMA in HIV patients is associated with very high mortality. Lastly, the multitude of antiretroviral drugs used for treatment of HIV infections can result in nephrotoxicity. Although a kidney biopsy may not be the first line study for renal disease, knowledge of the different histopathologic features of HIV-associated and unassociated diseases is of paramount importance in the treatment and subsequent outcome of renal function in HIV infected patients. In this review we will describe the histopathologic features and discuss the pathophysiology of the entities previously named.


Preventing pancreatic fistula after distal pancreatectomy: An invagination method.
Following an increase in the use of the GIA stapler for treating a pancreatic stump, more techniques to prevent postoperative pancreatic juice leakage have been required. We describe one successful case using our new technique of invaginating the cut end of the pancreas into the stomach to prevent a pancreatic fistula (PF) from occurring. A 50-year-old woman with pancreatic cancer in the tail of the pancreas underwent distal pancreatectomy, causing a grade A PF. We resected the distal pancreas without additional reinforcement to invaginate the stump into the gastric posterior wall with single layer anastomosis using a 3-0 absorbable suture. The drain tubes were removed on the third postoperative day. Although a grade A PF was noted, the patient was discharged on foot on the eleventh postoperative day. Our technique may be a suitable method for patients with a pancreatic body and tail tumor.


Ethnicity, religious affiliation and girl-child marriage: a cross-sectional study of nationally representative sample of female adolescents in Nigeria.
The persistently high prevalence of girl-child marriage remains a public health and developmental concern in Nigeria. Despite global campaign against the practice and policy efforts by Nigerian government, the prevalence remains unabated. This study investigates the prevalence and the influence of ethnicity and religious affiliation on the girl-child marriage among female adolescents in Nigeria. Data of 7804 girls aged 15-19 years extracted from the 2013 Nigeria Demographic and Health Survey were used. Ethnic groups were classified into five: major Northern ethnic group (Hausa/Fulani); Northern ethnic minorities; two major Southern ethnic groups (Yoruba and Igbo), and Southern ethnic minorities. The prevalence of girl-child marriage was determined for the five ethnic groups and individually for each ethnic minority group. Relationships between ethnicity and religious affiliation on girl-child marriage were explored using Cox proportional hazard regression models, adjusting for residence, education and wealth quintile. Child marriage was higher for the Northern majority ethnic group of Hausa/Fulani (54.8%) compared to the two major Southern ethnic groups (3.0-3.6%) and aggregated Northern ethnic minorities (25.7%) and Southern minorities (5.9%). However, overall, the less known Northern ethnic minority groups of Kambari (74.9%) and Fulfude (73.8%) recorded the highest prevalence. Compared to the major Southern ethnic group of Yoruba, the adjusted hazard ratio (AHR) of child marriage was significantly higher for Northern ethnic minorities (AHR = 2.50; 95% C.I. = 1.59-3.95) and Northern major ethnicity (AHR = 3.67, 95% C.I. = 2.33-5.77). No significant difference was recorded among Southern ethnic groups. Girls affiliated to other religions (Muslim and traditionalist) had higher child-marriage risks compared to Christians (AHR = 2.10; 95% C.I. = 1.54-2.86). Ethnicity and religion have independent associations with girl-child marriage in Nigeria; interventions must address culturally-laden social norms that vary by ethnic groups as well as religious-related beliefs.


Capillary enzyme immunoassay for rapid detection of herpes simplex virus in clinical specimens.
Capillary enzyme immunosorbent assay (CapELISA) is a modification of the standard enzyme immunosorbent assay which permits rapid detection of viral antigens in clinical specimens. The capillary tube format provides a very large reactive surface relative to the sample size. The close proximity of antigen to antibody in the tube optimizes the reaction, resulting in increased sensitivity and shorter incubation requirements. Sensitivity is further enhanced by use of a biotin-avidin enzyme detector system and a fluorogenic rather than a colorigenic substrate. The assay is performed at ambient temperature and requires less than 2 h. It is read with an inexpensive hand-held black light. Data for the use of CapELISA for the detection of herpes simplex virus in clinical specimens are presented. The results show greater than or equal to 85% sensitivity and 100% specificity when compared with tissue culture tests on the same samples. This new system should be advantageous for the diagnosis, treatment, and management of patients with herpesvirus infections and for the prevention of neonatal herpes acquired by passage of the fetus through an infected birth canal.


Evidence for the formation of singly bonded dimers during the reductive electrochemistry of methanofullerenes.
Four methanofullerene derivatives, with phosphonate or sulfone groups attached to a C(60) core through a Bingel procedure, were synthesized to probe their stability upon electrolytic reduction. Derivatives 1 and 2 are the most stable upon electroreduction and do not exhibit retro-cyclopropanation reactions until more than three electrons per C(60) derivative are transferred. The cyclopropane ring is then removed and C(60)(>CH(2))(n) (n=1-3) products result from reactions of the trianion of C(60) with the solvent, CH(2)Cl(2). The situation with diphosphonate 3 or phosphonatecarboxylate 4 is dramatically different. For 3, quantitative retro-cyclopropanation occurs when 2.8 e(-) per molecule are transferred. In the case of 4, when more than two electrons per molecule are transferred, there is evidence of the reversible formation of a very stable intermediate, which is oxidized at a potential 500 mV more positive than the first fullerene-based reduction of the parent compound. Electrolysis of a simple C(70)-Bingel monoadduct (5) also exhibits the formation of a similar intermediate. On the basis of cyclic voltammetry, ESR spectroscopy, and MALDI analysis of products, the intermediate observed during the electrolysis of compounds 4 and 5 is assigned to a dimeric structure.


A comparison of the size of fenestrations in the internal elastic lamina of young and old porcine aortas as seen with the scanning electron microscope.
The size of the fenestrations (windows) in the internal elastic lamina (IEL) of arteries may be important in the functioning of the blood vessel wall. The fenestrations are filled with collagen, muscle, and (or) ground substance, which must be removed to make the fenestration visible with the scanning electron microscope. All of the nonelastic components are removed with a hot alkali solution. Our experiments were designed to compare the fenestration size in the IEL of the thoracic aorta of young (6-8 weeks) and old (6-9 months) pigs. A protocol for digestion of young pig tissue was developed and showed that fresh young aortas should be digested in 0.1 M NaOH at 75 degrees C for 2 h and fixed tissue should be digested for 5 h. The average area of the fenestrations for young pig thoracic aortas digested for 2 h was 1.8 +/- 0.29 (SE) microns 2 and for the old pig aortas digested for 2 h was 1.7 +/- 0.11 (SE) microns 2. These values were not significantly different (p greater than 0.05), but the IEL from young pigs appeared rougher than the previously reported smooth IEL of the adult pigs.


The mood-stabilizer lithium prevents hippocampal apoptosis and improves spatial memory in experimental meningitis.
Pneumococcal meningitis is associated with high morbidity and mortality rates. Brain damage caused by this disease is characterized by apoptosis in the hippocampal dentate gyrus, a morphological correlate of learning deficits in experimental paradigms. The mood stabilizer lithium has previously been found to attenuate brain damage in ischemic and inflammatory diseases of the brain. An infant rat model of pneumococcal meningitis was used to investigate the neuroprotective and neuroregenerative potential of lithium. To assess an effect on the acute disease, LiCl was administered starting five days prior to intracisternal infection with live Streptococcus pneumoniae. Clinical parameters were recorded, cerebrospinal fluid (CSF) was sampled, and the animals were sacrificed 42 hours after infection to harvest the brain and serum. Cryosections of the brains were stained for Nissl substance to quantify brain injury. Hippocampal gene expression of Bcl-2, Bax, p53, and BDNF was analyzed. Lithium concentrations were measured in serum and CSF. The effect of chronic lithium treatment on spatial memory function and cell survival in the dentate gyrus was evaluated in a Morris water maze and by quantification of BrdU incorporation after LiCl treatment during 3 weeks following infection. In the hippocampus, LiCl significantly reduced apoptosis and gene expression of Bax and p53 while it increased expression of Bcl-2. IL-10, MCP-1, and TNF were significantly increased in animals treated with LiCl compared to NaCl. Chronic LiCl treatment improved spatial memory in infected animals. The mood stabilizer lithium may thus be a therapeutic alternative to attenuate neurofunctional deficits as a result of pneumococcal meningitis.


Crystallographic orientation of ZrB2-ZrC composites manufactured by the spark plasma sintering method.
The crystallographic grain orientation of ZrB2-ZrC composites manufactured using a spark plasma sintering (SPS) method, a new sintering technique in development for poorly sinterable ceramic materials, was analysed by the scanning electron microscopy-electron backscattered diffraction (SEM-EBSD) method. Their crystallographic features have been compared with those of a conventionally sintered specimen using a pressureless sintering (PLS) method. In the composite sintered by PLS, (0001) planes of ZrB2 were orientated in the direction parallel to the specimen surface (RD) but (1010) and (2110) planes randomly orientated. In the case of SPS, (0001) planes of ZrB2 were orientated normal to the specimen surface (ND) and weakly to the RD. In both cases of PLS and SPS, ZrC grains had a randomly orientated grain structure. The distribution of grain boundary misorientation of PLS and SPS-processed composites showed the same tendency that high-angle boundaries were more prevalent than low-angle boundaries. But in the case of ZrC grains in the SPS sample, the proportion of CSL boundaries with low sigma value (3, 5, 7, 9, 11) was relatively larger.


Comparison of non-vitamin K antagonist oral anticoagulants and well-controlled warfarin in octogenarians with non-valvular atrial fibrillation: Real-world data from a single tertiary center.
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, and its prevalence increases with age. Nevertheless, data about the use of oral anticoagulants (OACs) among patients with ≥80 years remains limited. This study aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in octogenarians with non-valvular AF (NVAF). Medical records of 387 patients who were ≥80 years and diagnosed with NVAF in our hospital between January 2017 and December 2019 were evaluated retrospectively. Patients with NVAF were divided into 2 groups (NOACs and warfarin), and the incidence of stroke/systemic embolism and major bleeding were analyzed. A total of 322 patients were included in the study. The median follow-up duration was 10.9 months for the NOACs group and 12.1 months for the warfarin group. The primary efficacy outcome was stroke/systemic embolism, and the primary safety outcome was major bleeding. A total of 220 patients were taking NOACs, and the most preferred NOACs were apixaban (53.6%), rivaroxaban (29.5%), dabigatran (13.2%), and edoxaban (3.6%) in this order. During a mean follow-up of 302.7 patient-years, the incidence of stroke or systemic embolic events was slightly higher among patients with warfarin but the difference was not statistically significant (p=0.862). The incidence rates of major bleeding events were similar between the treatment groups (p=0.824). Our study revealed that the safety and efficacy outcomes are similar between the 2 treatment groups in octogenarians with NVAF.


First Metatarsophalangeal Joint Distraction Arthrodesis With Bicortical Calcaneal Autograft.
First metatarsophalangeal joint (MTPJ) arthrodesis is a surgical treatment option for failed first MTPJ procedures. In cases of failed MTPJ arthroplasty, removal of failed implants and necrotic bone can cause shortening and biomechanical insufficiency of the first ray. Distraction arthrodesis with bone grafting can be used to maintain first ray length. We describe a technique of autograft harvest from the ipsilateral calcaneus. We present a retrospective case series of clinical and radiographic outcomes of distraction arthrodesis with bicortical calcaneal autograft in patients with failed procedures of the first MTPJ. We achieved a 100% osseous union rate. There was an insignificant change in first ray length from preoperative to postoperative (P = .2402). First ray length was maintained with a median autograft length of 10 (range 5 to 14) mm. We were able to correct first ray deformity with a significant reduction in preoperative to postoperative intermetatarsal angle and hallux abduction angle (P = .0156, P = .0068, respectively). Seven (88%) of 8 patients with available subjective follow-up were satisfied with the outcome of the procedure and would undergo the procedure again. Our results indicate that first MTPJ distraction arthrodesis with calcaneal autograft is a viable option for failed first MTPJ procedures. Surgeons who implement our techniques can expect high rates of osseous union, deformity correction, and patient satisfaction.


Evaluation of Internal Construct Validity and Unidimensionality of the Brachial Assessment Tool, A Patient-Reported Outcome Measure for Brachial Plexus Injury.
To evaluate the internal construct validity and dimensionality of a new patient-reported outcome measure for people with traumatic brachial plexus injury (BPI) based on the International Classification of Functioning, Disability and Health definition of activity. Cross-sectional study. Outpatient clinics. Adults (age range, 18-82y) with a traumatic BPI (N=106). There were 106 people with BPI who completed a 51-item 5-response questionnaire. Responses were analyzed in 4 phases (missing responses, item correlations, exploratory factor analysis, and Rasch analysis) to evaluate the properties of fit to the Rasch model, threshold response, local dependency, dimensionality, differential item functioning, and targeting. Not applicable, as this study addresses the development of an outcome measure. Six items were deleted for missing responses, and 10 were deleted for high interitem correlations >.81. The remaining 35 items, while demonstrating fit to the Rasch model, showed evidence of local dependency and multidimensionality. Items were divided into 3 subscales: dressing and grooming (8 items), arm and hand (17 items), and no hand (6 items). All 3 subscales demonstrated fit to the model with no local dependency, minimal disordered thresholds, no unidimensionality or differential item functioning for age, time postinjury, or self-selected dominance. Subscales were combined into 3 subtests and demonstrated fit to the model, no misfit, and unidimensionality, allowing calculation of a summary score. This preliminary analysis supports the internal construct validity of the Brachial Assessment Tool, a unidimensional targeted 4-response patient-reported outcome measure designed to solely assess activity after traumatic BPI regardless of level of injury, age at recruitment, premorbid limb dominance, and time postinjury. Further examination is required to determine test-retest reliability and responsiveness.


pX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250 mutants.
Hepatitis B virus (HBV) infects humans and causes a wide range of clinical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation machinery. Accordingly, the HBV-encoded pX, the only known viral regulator, is a potent transcription coactivator. We investigated the relationship between pX and cellular coactivators. We show that pX restores wild-type activity to inactive TBPAS mutants with poor TAFII250 and activator-binding activity. This pX-mediated recovery, however, is not obtained with inactive TBPAS mutants in binding of other general transcription factors. Remarkably, ts13, a cell line temperature sensitive for TAFII250 function, exhibiting growth arrest and apoptosis at the restrictive temperature, is rescued partially by pX expression, thus generating a pX-dependent cell growth. Collectively, our results suggest that pX suppresses some of the phenotypes of TBP and TAFII250 mutations, implying that pX circumvents the need for a holo-TFIID complex for transcription activation to proceed.


Nationwide survey of radiation therapy in Japan for lung cancer complicated with interstitial lung disease.
The purpose of this study was to clarify the opinions of radiation oncologists in Japan regarding treatment for lung cancer complicated with interstitial lung disease (ILD) by a questionnaire survey, and the risk of acute exacerbation (AE) after radiotherapy. Questionnaires were sent to all of the facilities in which radiation therapy is performed for lung cancer in Japan by using the mailing list of the Japanese Society for Radiation Oncology (JASTRO). The questionnaire survey was conducted to clarify who judges the existence of ILD, the indications for radiation therapy in cases of ILD-combined lung cancer, and the ratio of ILD-combined lung cancer in lung cancer patients treated with radiation therapy. Patients with ILD-combined lung cancer who received radiotherapy during the period from April 2014 to March 2015 were retrospectively analysed. Any cases of AE without any other obvious cause were included. ILD confirmation was performed by central radiologists using computed tomography images. A total of 47 facilities responded to the questionnaire. Radiation therapy was an option in cases of ILD-combined lung cancer in 39 (83%) of the facilities. The indication for radiation therapy was based on image findings in 35 (90%) of the 39 facilities in which radiation therapy was acceptable or was a choice in some cases of ILD. The final indication was based on the opinion of the pulmonologist in 29 (74%) of those 39 facilities. In fiscal year 2014, a total of 2128 patients in 38 facilities received chest irradiation. Seventy-eight (3.7%) of those 2128 patients had ILD-combined lung cancer. Sixty-seven patients were included in patient analysis. AE occurred in 5 patients (7.5%), and one of those 5 patients (20.0%) died from radiation-induced AE. The median period from radiotherapy to AE was 4 months (range, 2-7 months). The following four independent risk factors for AE were identified in univariate analysis: non-advanced age (<75 years), increased C-reactive protein level (≥0.3 mg/dl), adjuvant chemotherapy and ≥ Grade 2 radiation pneumonitis. Radiotherapy was an option for lung cancer even in cases with ILD in 83% (39/47) of the facilities in Japan. Seventy-eight (3.7%) of 2128 patients who received radiation therapy for lung cancer had ILD. Radiotherapy for ILD-combined lung cancer may induce AE at a substantial rate and AE can be life-threatening. Minimizing the risk of radiation pneumonitis might enable the risk of AE to be reduced.


Effect of heparin on the utilization in vitro of labelled glycerides from triglyceride-rich lipoproteins in rat adipose tissue.
Triglyceride-rich lipoproteins from adult rat plasma were labelled in vivo with 3H in the esterified fatty acids and 14C in the labelled glyceride glycerol of neutral lipids by injecting i.v. sodium 9-10 (n)-[3H] palmitate and [U-14C] glycerol, after which the prelabelled lipoproteins were purified by ultracentrifugation and dialysis. The lipoproteins were incubated in vitro, in the presence or not of heparin, with pieces of epididymal fat pads or isolated adipocytes from fed rats. The disappearance of both [3H]- and [14C] lipids from the media was greater when incubations were performed with adipocytes than with fat-pad pieces and it increased with heparin in both preparations. More 3H-label than 14C was found in the tissue lipids, a higher percentage being present in adipocytes than in fat-pad pieces, and the amount of label in tissue lipids was always enhanced by heparin. Some 14C-label appeared as esterified fatty acids in both tissue preparations and it also was enhanced by the presence of heparin. These findings are in agreement with the recognized influence of heparin on the release of lipoprotein lipase and show the direct relationship between heparin action and tissue ability to take up products of lipoprotein triglyceride breakdown. They also demonstrate the ability of adipose tissue to metabolize glycerol coming from the hydrolysis of lipoprotein glycerides.


Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and is upregulated in reactive astrocytes.
Transglutaminase-6 (TGM6), a member of the transglutaminase enzyme family, is found predominantly in central nervous system (CNS) neurons under physiological conditions. It has been proposed as an autoimmune target in cerebral palsy, gluten-sensitive cerebellar ataxia, and schizophrenia. To investigate TGM6 involvement in multiple sclerosis (MS). Antibody levels against TGM6 (TGM6-IgG) were measured in the cerebrospinal fluid (CSF) of 62 primary progressive multiple sclerosis (PPMS), 85 secondary progressive multiple sclerosis (SPMS), and 50 relapsing-remitting multiple sclerosis (RRMS) patients and 51 controls. TGM6 protein expression was analyzed in MS brain autopsy, murine experimental autoimmune encephalomyelitis (EAE), and cultured astrocytes. CSF levels of TGM6-IgG were significantly higher in PPMS and SPMS compared to RRMS and controls. Notably, patients with clinically active disease had the highest TGM6-IgG levels. Additionally, brain pathology revealed strong TGM6 expression by reactive astrocytes within MS plaques. In EAE, TGM6 expression in the spinal cord correlated with disease course and localized in reactive astrocytes infiltrating white matter lesions. Finally, knocking down TGM6 expression in cultured reactive astrocytes reduced their glial fibrillary acidic protein (GFAP) expression. TGM6-IgG may be a candidate CSF biomarker to predict and monitor disease activity in progressive MS patients. Furthermore, TGM6 expression by reactive astrocytes within both human and mouse lesions suggests its involvement in the mechanisms of glial scar formation.


Three ATPase activities have an abnormal developmental time course in trembler sciatic nerves.
Trembler mutant mice are affected by a peripheral neuropathy characterized by hypomyelination, demyelination, and Schwann cell proliferation. In adult mutants, supernumerary Schwann cells form membranous structures known as 'onion-bulb' formations. The activities of the Na+, K+-ATPase and of two ouabain-insensitive Mg2+-ATPases were investigated in sciatic nerves of young and adult mutants. The Na+, K+-ATPase activities were 92 and 76% of the control values in young and adult mutants, respectively. By immunoblot analysis, the alpha-subunit of the Na+, K+-ATPase had an identical apparent molecular weight in controls at both ages and in young mutants. In adult mutants, on the contrary, the alpha-subunit appeared smaller by about 2 kd, similar to that in kidney, indicating that the Na+, K+-ATPase was localized mainly on supernumerary Schwann cells. In addition, in the mutants, the developmental increase of both the mitochondrial and the nonmitochondrial Mg2+-ATPase was abnormally high. We suggest that the abnormal increase of the nonmitochondrial Mg2+-ATPase activity during development reflects an enrichment of that enzyme in 'onion-bulb' formations.


Optical Anapole Metamaterial.
The toroidal dipole is a localized electromagnetic excitation independent from the familiar magnetic and electric dipoles. It corresponds to currents flowing along minor loops of a torus. Interference of radiating induced toroidal and electric dipoles leads to anapole, a nonradiating charge-current configuration. Interactions of induced toroidal dipoles with electromagnetic waves have recently been observed in artificial media at microwave, terahertz, and optical frequencies. Here, we demonstrate a quasi-planar plasmonic metamaterial, a combination of dumbbell aperture and vertical split-ring resonator, that exhibits transverse toroidal moment and resonant anapole behavior in the optical part of the spectrum upon excitation with a normally incident electromagnetic wave. Our results prove experimentally that toroidal modes and anapole modes can provide distinct and physically significant contributions to the absorption and dispersion of slabs of matter in the optical part of the spectrum in conventional transmission and reflection experiments.


Effectiveness of Physical Exercise on Alzheimer's disease. A Systematic Review.
A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life in a population of older people with Alzheimer´s disease. Pubmed, Scopus, PEDro, Web of Science, CINAHL, Cochrane Library, grey literature and a reverse search from inception to April 2021 were searched to identify documents. Publications investigating the effect of any type of physical exercise-based intervention in any of its multiple modalities on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life were searched. The data were extracted into predesigned data extraction tables. Risk of bias was evaluated through the PEDro scale and its internal validity scale. A total of 8 different randomized controlled trials with a total sample of 562 non-overlap Alzheimer disease patients between 50-90 years and a mean age of 75.2 ± 3.9 years were eligible for analyses. Physical-functional capacity was evaluated in 6 of 8 studies and cognitive performance was evaluated in 5 of 8 studies, all of them showed improvements in these variables when compared with the controls, except for two studies in physical-functional capacity and one study for cognitive performance. In the physical-functional capacity and cognitive performance variables, aerobic physical exercise was used in isolation, or in a multimodal way, combining aerobic, strength and balance exercise, from 2 to 7 weekly sessions with doses between 30 and 90 minutes, and a duration of the program comprised of 9 weeks to 6 months. Neuropsychiatric symptoms and quality of life were evaluated in 2 of 8 studies, which the intervention groups experienced significant improvements when compared with the control groups, except for one study that found similar differences in quality of life between both groups. In the neuropsychiatric symptoms and quality of life variables, only aerobic physical exercise was used, in a more homogeneous way, from 2 to 3 weekly sessions with doses of 30 to 60 minutes, and a total program duration of 9 to 16 weeks. Despite the scarcity of studies, especially those based on multimodal proposals, and the heterogeneity in the protocols, this systematic review found moderate to limited evidence that aerobic physical exercise on its own or combined in a multimodal program that also includes strength and balance exercise can be a useful tool in the management of patients with Alzheimer's disease with the aim of maintaining and/or improving physical-functional capacity and cognitive performance. In addition, this review found moderate evidence of the positive impact that aerobic physical exercise could have in reducing neuropsychiatric symptoms and improving quality of life in patients with Alzheimer´s disease. PROSPERO registration number: CRD42021229891.


Analysis of medical expenditure and socio-economic status in patients with ocular chemical burns in East China: a retrospective study.
Little has been known regarding the relationship between ocular chemical injury and victims' medical expenditure, income loss and socio-economic status changes. So we conduct this retrospective cross-sectional study in patients with ocular chemical burns in East China. Fifty-six patients were enrolled and required to complete a self-report questionnaire consisting of the following contents: entire expenditure on medical treatment; the victims' personal and household per capita income, and income loss caused by the injury; and the changes of socioeconomic status as well. The median expense of medical treatment was CNY 40,000 (approximately US$5,900). The medical expenditure rose significantly with increased injury severity, prolonged hospital stay, and increased frequency of surgery. More than half victims (51.8 %, 29/56) paid all or the majority of medical expense by themselves. The expense of only 5 victims was mainly paid by medical insurance, accounting for less than ten percent (8.9 %, 5/56). The victims' personal and household per capita income both decreased significantly after the injury, with the median reduction being CNY 24,000 and CNY 7,800 (approximately US$3600 and US$1200) per year respectively. The reduction amplitude of personal and household per capita income rose with increased injury severity and prolonged time of care required. The injury caused emotional depression or anxiety in 76.8 % (43/56) victims, and the relationship with their relatives got worse in 51.9 % (29/56) patients. Moreover, only 21.4 % (12/56) patients felt that the whole society gave them care and concern after the injury, whereas 46.4 % (26/56) and 28.6 % (16/56) felt indifference or discrimination from society as a whole (X2 = 16.916, P = 0.028). The medical expense was a huge economic burden to most victims of ocular chemical burns, and personal and household per capita income of the victims decreased significantly after injury, both of which had a close relationship with the injury severity. Formal legislation was urgently needed to compel the employer to purchase injury or medical insurance and provide more compulsory protection to the population working in high risk occupations. In addition, psychological counseling and instruction shouldn't be neglected in the aid and treatment of victims.


Radiofrequency ablation of left-sided accessory pathways: transaortic versus transseptal approach.
The aim of this study was to compare the efficacy of transaortic (n = 54) and transseptal (n = 28) techniques during radiofrequency (RF) ablation of left accessory pathways (n = 75) in both left posteroseptal and free-wall locations in 73 consecutive patients (mean age 32 +/- 15 years). The transseptal approach included transseptal puncture and use of a retained long sheath in the left atrium (n = 24) or direct insertion of the mapping/ablation catheter via a patent foramen ovale (n = 4). Transseptal RF ablation was used as the primary method in 23 patients or at a separate session after the transaortic RF ablation failed in 5 patients. Transaortic RF ablation was used as primary method in 50 patients and after failed transseptal ablation in 4 patients. Transaortic ablation was successful in 47 (87%) of 54 procedures, transseptal ablation in 24 (86%) of 28 procedures, with total RF ablation success in 70 (96%) of 73 patients. The transseptal puncture/long sheath method was successful in 23 (96%) of 24 patients. This latter technique resulted in more stable positioning and easier manipulation of the ablation catheter. Switching from transseptal puncture/long sheath to transaortic technique was needed in 1 of 24 patients, from transseptal/patent foramen ovale approach to the transaortic route in 3 of 4 patients, and from the transaortic to the transseptal approach at a separate session in 5 patients. The age of patients and number of RF lesions were similar in the two groups. Fluoroscopy time was lower for the transseptal group (81 +/- 57 vs 121 +/- 81 min; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Temporary chromatopsia and alternate umbropsia in multiple sclerosis.
Uncommon visual symptoms were described in two women with clinically definite, remittent multiple sclerosis. In the first case with right optic atrophy temporary chromatopsia (vision of only blue colour) and left-sided, paroxysmal and alternate "fading out" followed by "brightening up" vision (umbropsia) occurred spontaneously. In the second case with bilateral optic atrophy transient chromatopsia (vision of only green colour) and short-lived "fading out" vision when fixating on a target were noted. Chromatopsia might be associated with impaired function of selected optic nerve fibers conducting impulses from a limited population of retinal ganglion cells. Alternate umbropsia and short-lived "fading out" vision probably depend on paroxysmal, frequency-related intermittent conduction block at the level of optic nerve fibers or synaptic elements.


Application of ureterorenoscope and flexible ureterorenoscope lithotripsy in removing calculus from extracorporeal living donor renal graft: a single-center experience.
Here, we reported our clinical application of ureterorenoscope (URS) and flexible URS lithotripsy in stone removal on 10 cases of excised living donor kidney graft. After the extraction of donor kidney by retroperitoneal laparoscopy, the donor graft was perfused with 4 °C HCA solution. Calculus between 2-4 mm were removed intact with lithotomy forceps under direct vision of URS. Larger calculi of >4 mm were fractured with flexible URS combining holmium laser lithotripsy. Fragments of the calculus were extracted with basket extractor and lithotomy forceps. All operations were successful. The operation time was 14-31 min (average 21.2 ± 6.3 min). The kidneys were then transplanted to the recipients using routine procedure. The transplanted kidneys functioned well after transplantation. Gross hematuria resolved 1-4 d after operation (average 2.6 ± 0.9 d). The transplanted kidneys functioned well without early complications such as functional recovery delay and acute graft rejection. The donors and recipients were followed for 12 months. The size of the transplanted kidneys was normal and new stones or urinary obstruction was not seen upon urinary color Doppler ultrasound examination. In conclusion, we believe it is feasible, safe and effective to use URS or flexible URS combining holmium laser lithotripsy on extracorporeal living donor kidney.


Antidiabetic Effects of Tea.
Diabetes mellitus (DM) is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients consumes a huge budget due to the high frequency of consultations and long hospitalizations, making DM a serious threat to both human health and global economies. Tea contains abundant polyphenols and caffeine which showed antidiabetic activity, so the development of antidiabetic medications from tea and its extracts is increasingly receiving attention. However, the results claiming an association between tea consumption and reduced DM risk are inconsistent. The advances in the epidemiologic evidence and the underlying antidiabetic mechanisms of tea are reviewed in this paper. The inconsistent results and the possible causes behind them are also discussed.


Teaching emergency management students about money: "Without money you ain't doin bupkis".
The objective of this article is to address the glaring deficiency in educating emergency managers with regard to the financial aspects of Emergency Management (EM) and suggest curriculum changes. This article reviews 313 Higher Education Programs in EM located in 189 institutions of higher education in the United States to determine which include courses in the financial aspects of EM. The programs reviewed range from undergraduate certificates to PhD Degrees in EM. Of the 313 EM programs, only 78 [24.8 percent] have any courses discussing accounting, budgeting, economics, or finance either as a required or restricted elective course. Only nine [2.9 percent] courses focus on the financial issues of EM. Based upon the data reported, the author suggests changes in EM education as a starting point in the necessary discussion of what an EM educational program should cover.


Spinal epidural extramedullary haematopoiesis in β-thalassaemia intermedia.
A 22-year-old man known to have β-thalassaemia intermedia since childhood presented with bilateral lower limb weakness after spinal anaesthesia for an elective minor operation of his left leg. MRI and CT scans were performed to rule out acute epidural haematoma; coincidental imaging features of marrow hyperplasia and spinal epidural extramedullary haematopoiesis were found. This article will present and discuss the imaging features, differential diagnosis, management and literature review of the rare occurrence of extramedullary haematopoiesis in the spinal epidural space.


Use of rubber dam and its association with other endodontic procedures in New Zealand.
The use of rubber dam for endodontic treatment in New Zealand was analysed by a national survey of general dental practitioners. The response rate was 79 percent. Rubber dam was used routinely by 57 percent, its use increasing among practitioners graduating since 1969. A greater percentage of practitioners with less than 10 years experience used rubber dam than did more experienced practitioners. Use of rubber dam was associated with sodium hypochlorite and EDTA as canal irrigants. Reamers were the favoured hand instrument of non-users of rubber dam. No significant differences were found in the canal obturation techniques of users and non-users, but rubber dam users used the long-cone paralleling method of radiography significantly more than non-users. Practitioners in solo practice used rubber dam significantly less than those in group practice. Rubber dam users attended significantly more refresher courses in endodontics than non-users.


Visual Interhemispheric and Striate-Extrastriate Cortical Connections in the Rabbit: A Multiple Tracer Study.
Previous studies in rabbits identified an array of extrastriate cortical areas anatomically connected with V1 but did not describe their internal topography. To address this issue, we injected multiple anatomical tracers into different regions in V1 of the same animal and analyzed the topography of resulting extrastriate labeled fields with reference to the patterns of callosal connections and myeloarchitecture revealed in tangential sections of the flattened cortex. Our results extend previous studies and provide further evidence that rabbit extrastriate areas resemble the visual areas in rats and mice not only in their general location with respect to V1 but also in their internal topography. Moreover, extrastriate areas in the rabbit maintain a constant relationship with myeloarchitectonic borders and features of the callosal pattern. These findings highlight the rabbit as an alternative model to rats and mice for advancing our understanding of cortical visual processing in mammals, especially for projects benefiting from a larger brain.


Identification of genomic regions associated with agronomic and biofortification traits in DH populations of rice.
Rice provides energy and nutrition to more than half of the world's population. Breeding rice varieties with the increased levels of bioavailable micronutrients is one of the most sustainable approaches to tackle micronutrient malnutrition. So, high zinc and iron content in the grain are primary targets in rice biofortification breeding. In this study, we conducted QTL mapping using doubled haploid (DH) populations, PSBRc82 x Joryeongbyeo and PSBRc82 x IR69428, phenotyped for agronomic traits and micronutrients during two growing seasons and using genotypic information from analysis with the 6K SNP chip. A number of DH lines were identified as having high grain Zn and Fe content in polished rice. Importantly, we identified 20 QTLs for agronomic traits and 59 QTLs for a number of biofortification traits. Of the 79 QTLs, 12 were large-effect QTLs (>25% PVE), nine QTLs were consistent across seasons in either population, and one QTL was identified in both populations. Moreover, at least two QTLs were clustered in defined regions of chromosomes 1, 2, 3, 4, 5, 7 and 9. Eight epistatic interactions were detected for Cu, Mg, Na, and Zn in population 1. Furthermore, we identified several candidate genes near QTLs for grain Zn (OsNRAMP, OsNAS, OsZIP, OsYSL, OsFER, and OsZIFL family) and grain yield (OsSPL14 and OsSPL16). These new QTLs and candidate genes help to further elucidate the genetic basis for grain micronutrient concentration, and may prove useful for marker assisted breeding for this important trait.


Nonequilibrium thermodynamics of glycolytic traveling wave: Benjamin-Feir instability.
Evolution of the nonequilibrium thermodynamic entities corresponding to dynamics of the Hopf instabilities and traveling waves at a nonequilibrium steady state of a spatially extended glycolysis model is assessed here by implementing an analytically tractable scheme incorporating a complex Ginzburg-Landau equation (CGLE). In the presence of self and cross diffusion, a more general amplitude equation exploiting the multiscale Krylov-Bogoliubov averaging method serves as an essential tool to reveal the various dynamical instability criteria, especially Benjamin-Feir (BF) instability, to estimate the corresponding nonlinear dispersion relation of the traveling wave pattern. The critical control parameter, wave-number selection criteria, and magnitude of the complex amplitude for traveling waves are modified by self- and cross-diffusion coefficients within the oscillatory regime, and their variabilities are exhibited against the amplitude equation. Unlike the traveling waves, a low-amplitude broad region appears for the Hopf instability in the concentration dynamics as the system phase passes through minima during its variation with the control parameter. The total entropy production rate of the uniform Hopf oscillation and glycolysis wave not only qualitatively reflects the global dynamics of concentrations of intermediate species but almost quantitatively. Despite the crucial role of diffusion in generating and shaping the traveling waves, the diffusive part of the entropy production rate has a negligible contribution to the system's total entropy production rate. The Hopf instability shows a more complex and colossal change in the energy profile of the open nonlinear system than in the traveling waves. A detailed analysis of BF instability shows a contrary nature of the semigrand Gibbs free energy with discrete and continuous wave numbers for the traveling wave. We hope the Hopf and traveling wave pattern around the BF instability in terms of energetics and dissipation will open up new applications of such dynamical phenomena.


Non-tuberculous mycobacteria in patients with bronchiectasis.
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Patients with pre-existing lung damage are susceptible to NTM, but their prevalence in bronchiectasis is unknown. Distinguishing between lung colonisation and disease can be difficult. A prospective study of 100 patients with bronchiectasis was undertaken to evaluate the prevalence of NTM in sputum, and a retrospective analysis of clinical, microbiological, lung function and radiology data of our clinic patients with NTM sputum isolates over 11 years was performed. The prevalence of NTM in this population of patients with bronchiectasis was 2%. Patients in the retrospective study were divided into three groups: bronchiectasis+multiple NTM isolates (n=25), bronchiectasis+single isolates (n=23), and non-bronchiectasis+multiple isolates (n=22). Mycobacterium avium complex (MAC) species predominated in patients with bronchiectasis compared with non-bronchiectasis lung disease (72% v 9%, p<0.0001). Single isolates were also frequently MAC (45.5%). Multiple isolates in bronchiectasis were more often smear positive on first sample than single isolates (p<0.0001). NTM were identified on routine screening samples or because of suggestive radiology. No particular bronchiectasis aetiology was associated with an NTM. Pseudomonas aeruginosa and Staphylococcus aureus were frequently co-cultured. Six (25%) of multiple NTM patients had cavities of which five were due to MAC. Half the patients with multiple isolates were treated, mostly due to progressive radiology. NTM are uncommon in non-cystic fibrosis bronchiectasis. Routine screening identifies otherwise unsuspected patients. MAC is the most frequent NTM isolated.


[Differential diagnosis of depressive state].
Depressive state is experienced usually in health subjects as "grief" process or "mourning work" in object loss. Also, subthreshold depression (sD) has been found to be a highly prevalent condition, with a considerable impact on the quality of life of patients, resulting in a strongly increased service utilization, and it has been found to be associated with large-scale economic costs because of disability days. A person can be considered to have sD when he or she has clinically relevant depressive symptoms, without meeting criteria for a full-blown major depressive disorder (MDD). The clinically relevant depressive symptoms in sD can either be operationalized as having a depressed mood with one or more additional symptoms of a mood disorder, or as meeting the criteria of minor depression (mD), as defined in the Appendix of the DSM-IV. Assessing the incidence of MDD in patients exhibiting sD is important for several reasons. First, it is an important indicator for the clinical relevance of sD. Secondly, it is important for understanding the process by which an individual develops MDD and the role of depressive symptoms in the process. Thirdly, the increased risk is important because it may provide a rationale for the development of new interventions that prevent the onset of new cases of MDD. Several recent studies in this area have found evidence that it is indeed possible to reduce the number of new cases of MDD by intervening in subjects with sD.


Robert Hooke (1635-1703), in his own words.
The diaries and other writings of Robert Hooke (1635-1703), as well as those of his contemporaries, are drawn upon to sketch his social and scientific life. An account is presented of his involvement with the Royal Society from its earliest days, and of his relations with notable scientists. In exploring the similarity between combustion and respiration, he established that air is composed of different gases, and that it is not motion of the lungs but a supply of fresh air that is necessary for life.