Mental health status and use of mental health services by California adults.
In 2005, nearly one in five adults in California, about 4.9 million people, said they needed help for a mental or emotional health problem. Approximately one in 25, or over one million Californians, reported symptoms associated with serious psychological distress (SPD). Of those adults with either perceived need or SPD, only one in three reported visiting a mental health professional for treatment. This policy brief, based on data from the 2005 California Health Interview Survey (CHIS 2005), presents the first comprehensive overview of mental health status and service use in California, and highlights differences by age, gender, race/ethnicity, income and insurance status. It also demonstrates the critical need for continued efforts to expand mental health services and threats to such services caused by the ongoing state budget crisis.


Extracranial radial forearm free flap closure of refractory cerebrospinal fluid leaks: a novel hybrid transantral-endoscopic approach.
Although rare, recalcitrant cerebrospinal fluid (CSF) leak after skull base tumor resection or major head trauma is a difficult therapeutic challenge, often complicated by lack of local vascularized tissue in a scarred, radiated field. Craniotomy with a free tissue transfer has been described for CSF leak repair from these complicated skull base defects. : We present our experience with a novel extracranial approach to manage refractory CSF leaks with a radial forearm free flap set in through a transantral and ethmoid sinus approach. Five patients with recalcitrant CSF leaks in the anterior skull base underwent radial forearm free tissue transfer via a hybrid transantral-endoscopic approach. There were 4 female patients and 1 male patient. Average age was 58 years (range, 30-72 years). Four patients had previous neurosurgical anterior skull base tumor resections, and 1 patient had significant head trauma leading to a recalcitrant CSF leak. All 5 patients had undergone multiple prior endoscopic and/or open repairs. All 5 patients had successful resolution of their leak after undergoing radial forearm free tissue transfer. Two of 5 patients required a second minor endoscopic procedure. No patients required a craniotomy. An extracranial transantral-endoscopic approach for the inset of radial forearm free flap is a safe treatment technique that precludes the need for a craniotomy and promotes effective repair of CSF leaks refractory to traditional endoscopic procedures. RFFF, radial forearm free flap.


Dynamic profiling of different ready-to-drink fermented dairy products: A comparative study using Temporal Check-All-That-Apply (TCATA), Temporal Dominance of Sensations (TDS) and Progressive Profile (PP).
Despite the several differences in ingredients, processes and nutritional values, dairy foods as yogurts, fermented milks and milk beverages are widely accepted worldwide, and although they have their sensory profiling normally covered by descriptive analyses, the temporal perception involved during the consumption are rarely considered. In this sense, the present work aimed to assess the dynamic sensory profile of three categories of fermented dairy products using different temporal methodologies: Temporal Dominance of Sensations (TDS), Progressive Profiling (PP), Temporal CATA (TCATA), and compare the results obtained. The findings showed that the different sensory characteristics among the products are basically related to their commercial identity. Regarding the methods, all of them collected the variations between samples with great correlation between data. In addition, to detect differences in intensities, TCATA showed to be the most sensitive method in detecting textural changes. When using PP, a balanced experimental design considering the number of attributes, time intervals, and food matrix must be weighed. The findings are of interest to guide sensory and consumer practitioners involved in the dairy production to formulate/reformulate their products and help them choosing the most suitable dynamic method to temporally evaluate them.


Myocilin mutations in black South Africans with POAG.
Myocilin (MYOC) mutations are associated with primary open-angle glaucoma (POAG) in multiple populations. Here we examined the role of MYOC mutations in a black South African population with primary open-angle glaucoma (POAG). Unrelated black South African subjects with POAG and unaffected controls were recruited from the St. John Eye Hospital (Soweto, Johannesburg, South Africa) and East London Hospital Complex (Eastern Cape, South Africa). A complete eye examination including visual field assessment was performed in all subjects. Blood samples were obtained for DNA extraction. The complete coding region of MYOC was sequenced using the PCR-based Sanger method. Identified mutations were compared to known MYOC mutations. One hundred-thirteen POAG cases and 131 controls were recruited for analysis. A total of 19 variants were observed. Probable glaucoma-causing mutations were observed in 4.4% of POAG cases. A previously reported glaucoma-causing mutation, Tyr453MetfsX11, was observed in three cases and one control. Two other sequence variants, Gly374Val and Lys500Arg, occurred only in cases. Other sequence variants, including 6 novel variants, occurred in at least one control. A small minority of black South Africans with POAG carry MYOC mutations. The Gly374Val mutation might represent a novel glaucoma-causing mutation. The Tyr453MetFSX11 mutation appears to be a glaucoma-causing mutation with incomplete penetrance.


Cloning and expression analysis of two pro-inflammatory cytokines, IL-1 beta and IL-8, in haddock (Melanogrammus aeglefinus).
This paper reports the cloning and sequencing of two pro-inflammatory cytokines, interleukin (IL)-1beta and IL-8, in haddock (Melanogrammus aeglefinus) by homology cloning. The complete transcript of the haddock IL-1beta was sequenced and contained 1043 bp, including a 762 bp open reading frame. The 3' end of the gene includes a polyadenylation signal 13 bp upstream of the poly(A) tail, along with 10 instability motifs. The predicted protein of 253aa revealed the presence of the IL-1 family signature and the absence of an ICE cut site. The cDNA of the chemokine IL-8 was sequenced in haddock and contained 903 bp of which 306 bp are the open reading frame. Interestingly, the predicted protein sequence of 101aa, contains an ELR motif preceding the CXC signature, common in all vertebrate IL-8 molecules but absent in all teleost genes sequenced to date. The expression of both haddock cytokines was studied in four different tissues: head kidney, spleen, liver and gill. Tissues were obtained from both healthy fish and fish stimulated in vivo with four commercial serotypes of LPS, namely Escherichia coli 026:B6, 055:B5, 0111:B4 and 0127:B8 and PMA. Haddock IL-1beta was not constitutively expressed and expression was only observed following stimulation. However, this expression was stimulant dependent and only PMA and LPS 026:B6 induced high levels of expression in the head kidney. The haddock IL-8 gene on the other hand, showed a constitutive expression, that could be up or down-regulated depending on the immunostimulant used, although to a lesser extent than IL-1beta.


Functional near-infrared optical imaging: utility and limitations in human brain mapping.
Although near-infrared spectroscopy (NIRS) was developed as a tool for clinical monitoring of tissue oxygenation, it also has potential for neuroimaging. A wide range of different NIRS instruments have been developed, and instruments for continuous intensity measurements with fixed spacing [continuous wave (CW)-type instruments], which are most readily available commercially, allow us to see dynamic changes in regional cerebral blood flow in real time. However, quantification, which is necessary for imaging of brain functions, is impossible with these CW-type instruments. Over the past 20 years, many different approaches to quantification have been tried, and several multichannel time-resolved and frequency-domain instruments are now in common use for imaging. Although there are still many problems with this technique, such as incomplete knowledge of how light propagates through the head, NIRS will not only open a window on brain physiology for subjects who have rarely been examined until now, but also provide a new direction for functional mapping studies.


Lung Cancer Screening CT: Sex-Specific Conversion Factors to Estimate Effective Radiation Dose From Dose-Length Product.
Effective dose (ED) is used to understand radiation-related cancer risk of CT scans. Currently, ED for low-dose CT (LDCT) lung cancer screening (LCS) is estimated by multiplying the CT scan-reported dose-length product (DLP) by a DLP-to-ED conversion factor (k-factor) for general chest CT imaging, which does not account for sex. The purpose of this study was to calculate sex-specific k-factors for LDCT LCS. This retrospective study evaluated consecutive LCS patients across a large health system from 2016 to 2017. Patient and CT scan-related data were obtained from the radiology information system, the picture archiving and communication system, and a radiation dose index-monitoring system. Each patient's ED was determined by patient-specific Monte-Carlo simulation using Cristy phantoms and divided by study DLP to determine the k-factor. The k-factors were compared vs the standard of 0.014 mSv·mGy⁻1·cm⁻1 for a chest CT scan by using a one-sample Student t test. Bivariate and multivariable analyses were performed for k-factors based on patient and CT scan factors. A total of 1,890 patients were included in the study. The mean k-factor for all patients was 0.0179 mSv·mGy⁻1·cm⁻1, which was 22% greater than the standard value of 0.014 mSv·mGy⁻1·cm⁻1 for a chest CT scan previously applied to LDCT imaging (P < .001). The mean k-factor in women (0.0213 mSv·mGy⁻1·cm⁻1) was 43% greater than in men (0.0149 mSv·mGy⁻1·cm⁻1) in the multivariable model (P < .001). The overall k-factor for LCS is higher than the previously used value for chest CT imaging; when stratified according to sex, it was 43% greater in women than in men. Sex- and LCS-specific k-factors should be used to estimate effective radiation dose in LCS programs.


Importance of Calibration Method in Central Blood Pressure for Cardiac Structural Abnormalities.
Central blood pressure (CBP) independently predicts cardiovascular risk, but calibration methods may affect accuracy of central systolic blood pressure (CSBP). Standard central systolic blood pressure (Stan-CSBP) from peripheral waveforms is usually derived with calibration using brachial SBP and diastolic BP (DBP). However, calibration using oscillometric mean arterial pressure (MAP) and DBP (MAP-CSBP) is purported to provide more accurate representation of true invasive CSBP. This study sought to determine which derived CSBP could more accurately discriminate cardiac structural abnormalities. A total of 349 community-based patients with risk factors (71±5years, 161 males) had CSBP measured by brachial oscillometry (Mobil-O-Graph, IEM GmbH, Stolberg, Germany) using 2 calibration methods: MAP-CSBP and Stan-CSBP. Left ventricular hypertrophy (LVH) and left atrial dilatation (LAD) were measured based on standard guidelines. MAP-CSBP was higher than Stan-CSBP (149±20 vs. 128±15mm Hg, P < 0.0001). Although they were modestly correlated (rho = 0.74, P < 0.001), the Bland-Altman plot demonstrated a large bias (21mm Hg) and limits of agreement (24mm Hg). In receiver operating characteristic (ROC) curve analyses, MAP-CSBP significantly better discriminated LVH compared with Stan-CSBP (area under the curve (AUC) 0.66 vs. 0.59, P = 0.0063) and brachial SBP (0.62, P = 0.027). Continuous net reclassification improvement (NRI) (P < 0.001) and integrated discrimination improvement (IDI) (P < 0.001) corroborated superior discrimination of LVH by MAP-CSBP. Similarly, MAP-CSBP better distinguished LAD than Stan-CSBP (AUC 0.63 vs. 0.56, P = 0.005) and conventional brachial SBP (0.58, P = 0.006), whereas Stan-CSBP provided no better discrimination than conventional brachial BP (P = 0.09). CSBP is calibration dependent and when oscillometric MAP and DBP are used, the derived CSBP is a better discriminator for cardiac structural abnormalities.


Polyamine transport inhibitors: design, synthesis, and combination therapies with difluoromethylornithine.
The development of polyamine transport inhibitors (PTIs), in combination with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high polyamine requirements. The DFMO+PTI combination therapy results in sustained intracellular polyamine depletion and cell death. A series of substituted benzene derivatives were evaluated for their ability to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl human pancreatic cancer cells. Several design features were discovered which strongly influenced PTI potency, sensitivity to amine oxidases, and cytotoxicity. These included changes in (a) the number of polyamine chains appended to the ring system, (b) the polyamine sequence, (c) the attachment linkage of the polyamine to the aryl core, and (d) the presence of a terminal N-methyl group. Of the series tested, the optimal design was N(1),N(1'),N(1″)-(benzene-1,3,5-triyltris(methylene))tris(N(4)-(4-(methylamino)butyl)butane-1,4-diamine, 6b, which contained three N-methylhomospermidine motifs. This PTI exhibited decreased sensitivity to amine oxidases and low toxicity as well as high potency (EC50 = 1.4 μM) in inhibiting the uptake of spermidine (1 μM) in DFMO-treated L3.6pl human pancreatic cancer cells.


The complete amino-acid sequence of elongation factor Tu from Escherichia coli.
The complete primary structure of elongation factor Tu from Escherichia coli has been elucidated. The protein, which is a mixture of two gene products, consists of a single polypeptide chain of 393 residues. After tryptic digestion of S-carboxymethylated protein, 50 tryptic peptides were isolated covering the complete protein chain. Their alignment was established with overlapping peptides obtained by chemical cleavage with cyanogen bromide and subsequent enzymic subdigestion with Staphylococcus aureus protease, chymotrypsin, elastase and thermolysin. Peptides were sequenced by manual dansyl-Edman and direct Edman degradation procedures. The N-terminal amino acid of EF-Tu is serine and is N-acetylated. The lysine residue at positon 56, in the polypeptide chain is partly methylated. The C-terminal residue is a mixture of serine and glycine, and this was the only heterogeneity found in the EF-Tu preparation used in this study.


Therapeutic antibody glycosylation analysis: a contract research organization perspective in the frame of batch release or comparability support.
Glycosylation of the Fc moiety of a monoclonal antibody is a heterogeneous posttranslational process considered as a critical quality attribute of the purified drug substance due to its major impact on safety and efficacy (i.e., immunogenicity, CDC or ADCC effector functions, etc.). Glycosylation should thus be addressed for batch-to-batch comparability and for drug substance characterization, in terms of identity and/or purity testing. We present below a set of efficient, performing and complementary analytical tests that can be used alone or in combination, depending on the information needed and available laboratory instrumentation. The results obtained using these techniques for "global" glycosylation profile, N-glycans profiling, monosaccharides, and sialic acids determination are presented for the Trastuzumab (Herceptin)-humanized mAb produced in CHO.


Normal neurogenesis and scrapie pathogenesis in neural grafts lacking the prion protein homologue Doppel.
The agent that causes prion diseases is thought to be identical to PrPSc, a conformer of the normal prion protein PrPC. Recently a novel protein, termed Doppel (Dpl), was identified that shares significant biochemical and structural homology with PrPC. To investigate the function of Dpl in neurogenesis and in prion pathology, we generated embryonic stem (ES) cells harbouring a homozygous disruption of the Prnd gene that encodes Dpl. After in vitro differentiation and grafting into adult brains of PrPC-deficient Prnp0/0 mice, Dpl-deficient ES cell-derived grafts contained all neural lineages analyzed, including neurons and astrocytes. When Prnd-deficient neural tissue was inoculated with scrapie prions, typical features of prion pathology including spongiosis, gliosis and PrPSc accumulation, were observed. Therefore, Dpl is unlikely to exert a cell-autonomous function during neural differentiation and, in contrast to its homologue PrPC, is dispensable for prion disease progression and for generation of PrPSc.


Cutaneous leukemia inhibitory factor and its potential role in the development of skin tumors.
Leukemia inhibitory factor (LIF) is a polyfunctional cytokine with a variety and a diverse range of biological activities. However, this is a reflection of the fact that the cytokine is expressed in many different tissues, has a wide target cell range, and fulfills different functions in different tissues. The purpose of this article is to examine what is known about LIF expression in the skin and to consider whether LIF plays a role in inflammatory and hyperplastic events in the skin. LIF is strongly expressed in skin tumors, and recent studies indicate that it may affect tumor growth by several different mechanisms. The biological activities of LIF relevant to carcinogenesis, its expression, and signal transduction by the LIF receptor are described. Expression of LIF in normal skin by skin tumors and its induction by ultraviolet radiation and proinflammatory stimuli are discussed, as are possible interactions between LIF, mast cells, and tumor growth. We consider what role LIF and other members of the hemopoietin family of cytokines play in healthy and diseased skin and whether LIF could play a role in hyperplastic skin disorders. LIF appears to be an important cytokine for normal keratinocyte growth and wound healing and may be involved in regulating the proliferation of skin tumors. Accordingly, LIF may be a useful target for anticancer therapy and as a growth factor for normal skin during reconstructive surgery.


Real-world vehicle emissions: a summary of the Seventeenth Coordinating Research Council On-Road Vehicle Emissions Workshop.
The Coordinating Research Council, Inc. (CRC) held its 17th On-Road Vehicle Emissions Workshop in March 2007, where results of the most recent on-road vehicle emissions research were presented. We summarize ongoing work from researchers who are engaged in improving our understanding of the role and contribution of mobile sources to ambient air quality and emission inventories. Participants in the Workshop discussed efforts to improve mobile source emission models, light- and heavy-duty vehicle emissions measurements, on- and off-road emissions measurements, effects of fuels and lubricating oils on emissions, as well as emerging issues and topics for future research.


[Characteristic of structural and functional organization of two-cell mouse embryos exposed to inhibitors of cell proliferation].
Within the framework of studying the "2-cell block in vitro" phenomenon, two variants of inhibitory-induced stoppage of development at a two-cell stage were produced and analysed. Mimosine arrested the cleavage on the G1/S interface, and genistein at G2 stage of the second cell cycle. In the experimentally blocked embryos a detailed study was made of the ultrastructural organization of blastomeres and intracellular localization of mitochondria vitally stained with rhodamine 123. The light and electron microscope observations testify to the viability of the embryos within a 22-24 hour exposure to inhibitors. Adhesive contacts between blastomeres were seen to slack after the treatment with both the inhibitors, resp., but in particular after genistein treatment. At the ultrastructural level no significant destructive modifications in blastomere organization were noticed. The cytoplasm of the control and treated embryo cells displayed diffusely distributed sheets of intermediate filaments, morphologically looking immature mitochondria and numerous aggregated lipid inclusions. The nuclear morphology was similar in both cases. Mitochondria of the treated embryo cells kept their ability to accumulate rhodamine 123, which testifies to their functional activity. However, the character of mitochondrial intracellular distribution was seen to change from diffuse to clustered. Numerous mitochondria clusters were concentrated mainly in the perinuclear area of blastomeres. As in the control ones, in the treated embryos the position of the nuclei was visualized by ring-like concentrations of mitochondria in the central part of blastomeres; in mimosine-treated cells the "rings" were thickened and contained mitochondria clusters. In genistein-treated embryos, mitochondria form numerous tiny clusters uniformly distributed in the cytoplasm; the perinuclear "rings" are still present, though less distinct than in the control embryos. Thus, it may be concluded that although the inhibitory treatment of two-cell embryos truly modified the mitochondrial distribution in these, the eventual pattern of such changes differed considerably from that characteristic of embryos in the state of "2-cell block in vitro". These results support the view on the unique character of morphofunctional modifications that occur in the latter embryos.


Genome-Wide Characterization of Berberine Bridge Enzyme Gene Family in Wheat (Triticum aestivum L.) and the Positive Regulatory Role of TaBBE64 in Response to Wheat Stripe Rust.
Berberine bridge enzymes (BBEs), functioning as carbonate oxidases, enhance disease resistance in Arabidopsis and tobacco. However, the understanding of BBEs' role in monocots against pathogens remains limited. This study identified 81 TaBBEs with FAD_binding_4 and BBE domains. Phylogenetic analysis revealed a separation of the BBE gene family between monocots and dicots. Notably, RNA-seq showed TaBBE64's significant induction by both pathogen-associated molecular pattern treatment and Puccinia striiformis f. sp. tritici (Pst) infection at early stages. Subcellular localization revealed TaBBE64 at the cytoplasmic membrane. Knocking down TaBBE64 compromised wheat's Pst resistance, reducing reactive oxygen species and promoting fungal growth, confirming its positive role. Molecular docking and enzyme activity assays confirmed TaBBE64's glucose oxidation to produce H2O2. Since Pst relies on living wheat cells for carbohydrate absorption, TaBBE64's promotion of glucose oxidation limits fungal growth and resists pathogen infection. This study sheds light on BBEs' role in wheat resistance against biotrophic fungi.


Regulation and Function of ILC3s in Pulmonary Infections.
Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections.


Physicians' attitudes about prescribing and knowledge of the costs of common medications.
Compliance with medical therapy is often compromised because patients cannot afford to pay for medications. Inadequate physician knowledge of drug costs may unwittingly contribute to this problem. To measure attitudes about prescribing and knowledge of medication costs and compare differences among attending physicians and residents. Written survey of internal medicine house staff and general medicine attending physicians in an urban hospital-based primary care center. One hundred thirty-four of 189 physicians responded (71% response rate). Seventy percent of respondents were house officers and 30% were attending physicians. Eighty-eight percent of physicians felt the cost of medicines was an important consideration in the prescribing decision, and 71% were willing to sacrifice some degree of efficacy to make drugs more affordable for their patients. However, 80% often felt unaware of the actual costs. Only 33% had easy access to drug cost data, and only 13% had been formally educated about drug costs. Regarding insurance coverage, 94% of physicians gave strong consideration to the cost of medications when patients were self-paying, 68% when patients had Medicare, and 30% when patients had Medicaid or were participants in a health maintenance organization with a prescription plan. Physicians' estimates of the cost of a month's supply of 33 commonly used medications were accurate in 45% of cases, too low for 40%, and too high for 15%. The costs of brand-name and expensive drugs were most likely to be underestimated. House officers were less cost-conscious than attending physicians. Physicians were predisposed to being cost-conscious in their prescribing habits, but lacked accurate knowledge about actual costs and insurance coverage of drugs. Interventions are needed to educate physicians about drug costs and provide them with reliable, easily accessible cost information in real-world practice.


Recurrent inhibition of alpha-motoneurons in patients with upper motor neuron lesions.
The recurrent inhibition of alpha-motoneurons by Renshaw cells, brought about by a conditioning reflex discharge, was estimated by measuring the amplitude of a test reflex which involved only those soleus motoneurons which had already fired in response to the conditioning volley. The results obtained in 95 patients with upper motor neuron disease and in 31 normal subjects were compared. At rest, there was no evidence for a decrease in the excitability of Renshaw cells: on the contrary, recurrent inhibition, if it changed at all, was increased in 55 out of 95 patients. In most patients the changes in Renshaw cells excitability which occur during postural or voluntary contractions in normal subjects were not found. We conclude that changes in recurrent inhibition are not responsible for the hyperexcitability of the stretch reflex which characterizes human spasticity. On the other hand, the paralysis of the supraspinal control of Renshaw cells, which normally accompanies voluntary movements, could account in part for two difficulties exhibited by spastic patients: in grading the strength of a muscular contraction, and in regulating reciprocal Ia inhibition according to the requirements of a voluntary movement.


Small unrepaired atrial septal defects display impaired exercise capacity compared with healthy peers.
Adult patients with small, unrepaired atrial septal defects have an increased risk of pneumonia, atrial fibrillation, and stroke. Furthermore, they have higher late mortality than the background population. The functional capacity is unknown in these patients. Therefore, our objective was to determine exercise capacity in adult patients diagnosed with an unrepaired atrial septal defect compared to healthy controls. A cross-sectional study. Adult patients with small, unrepaired atrial septal defects, aged 18-65, diagnosed between 1953 and 2011. Cardiopulmonary exercise test was performed using an incremental bicycle test and gas exchange was measured using breath-by-breath technique. Primary outcome was peak oxygen uptake, secondary outcome was maximal workload and ventilatory anaerobic threshold. We included 32 patients previously diagnosed with a small, unrepaired atrial septal defect and 16 healthy, age- and gender-matched controls (age 36.3 ± 13 years). Patients were divided into two groups based on whether the atrial septal defect was open (age 36.3 ± 11 years) or spontaneously closed (age 36.8 ± 14 years) since time of diagnosis. No differences in demographic characteristics or weekly exercise levels were found. Both patient groups reached lower peak oxygen uptake (open: 31.7 ± 11 mL/kg/min; spontaneously closed: 29.7 ± 6.9 mL/kg/min) compared with controls (42.6 ± 6.1 mL/kg/min; P = .0001). Workload (open: 2.6 ± 1.0 watt/kg; spontaneously closed: 2.5 ± 0.6 watt/kg) and aerobic capacity (open: 21.4 ± 8.7 mL/kg/min; spontaneously closed: 22.5 ± 6.5 mL/kg/min) was also poorer in patients compared to controls (workload: 3.5 ± 0.5 watt/kg; P = .0006, aerobic capacity: 31.3 ± 6.8 mL/kg/min; P = .0007). Adult patients with a diagnosis of small, unrepaired atrial septal defect have significantly impaired exercise capacity when compared to healthy controls. The impairment was present even if, by the time of assessment, the defect had closed spontaneously. The pathophysiological mechanisms behind the impaired exercise capacity demonstrated in these patients remain unexplained and will be a target for future work.


Modified Origins of Cortical Projections to the Superior Colliculus in the Deaf: Dispersion of Auditory Efferents.
Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (N = 5, 3 female) with perinatal-onset deafness. The superior colliculus was exposed to a retrograde pathway tracer, and subsequently labeled cells throughout the cerebrum were identified and quantified. Overall, the percentage of cortical projections arising from auditory cortex was substantially increased, not decreased, in early-deaf cats compared with intact animals. Furthermore, the distribution of labeled cortical neurons was no longer localized to a particular cortical subregion of auditory cortex but dispersed across auditory cortical regions. Collectively, these results demonstrate that, although patterns of cortical afferents are stable following perinatal deafness, the patterns of cortical efferents to the superior colliculus are highly mutable.SIGNIFICANCE STATEMENT When a sense is lost, the remaining senses are functionally enhanced through compensatory crossmodal plasticity. In deafness, brain regions that normally process sound contribute to enhanced visual and somatosensory perception. We demonstrate that hearing loss alters connectivity between sensory cortex and the superior colliculus, a midbrain region that integrates sensory representations to guide orientation behavior. Contrasting expectation, the proportion of projections from auditory cortex increased in deaf animals compared with normal hearing, with a broad distribution across auditory fields. This is the first description of changes in cortical efferents following sensory loss and provides support for models predicting an inability to form a coherent, multisensory percept of the environment following periods of abnormal development.


Acute mitral regurgitation with papillary muscle rupture in a dog.
Papillary muscle rupture is uncommon in the dog. Two-dimensional echocardiography provides a rapid, noninvasive test in the diagnosis of acute, severe mitral regurgitation resulting from papillary muscle rupture. This report illustrates the usefulness of echocardiography to determine the cause of acute mitral regurgitation.


Cambodia malaria indicator survey 2020: Implications for malaria elimination.
Cambodia has made significant progress in controlling malaria in the past decade. It now aims to eliminate malaria from the country by 2025. It launched the Malaria Elimination Action Framework (MEAF 2016-2020) in 2015 with strong political commitment targeting appropriate interventions on high-risk populations, particularly mobile and migrant groups. In 2020, the household-level Cambodia Malaria Survey 2020 (CMS 2020) was conducted with the objective to assess the performance of malaria control activities using the indicators outlined in MEAF 2016-2020. The survey used a cross-sectional probability proportional to size approach drawing 4,000 households from 100 villages across the malaria-endemic districts of the country. A total of 3,996 households with 17,415 inhabitants were interviewed. Of the surveyed households, 98.4% owned a long-lasting insecticide-treated bednet or hammock (LLIN/LLIHN). However, only 79.5% of these reported sleeping under a net the previous night, with only 45.7% sleeping under an insecticide treated net (ITN). Given that forest visitors are at the highest risk of getting malaria, the survey also targeted this group. Of the forest visitor respondents, 89.3% brought an ITN along and 88.9% reported to have used a net during their forest stay. About 10.8% of forest goers had received a forest kit for malaria prevention from mobile malaria workers the last time they went to the forest. Knowledge about mosquito repellents was high among forest goers (62.5%) but the actual use thereof during the last visit to the forest was low (22%). While awareness about malaria prevention with LLINs remained high among most respondents, knowledge about malaria diagnosis and treatment was not universal. Source of malaria knowledge and its treatment was usually from a household member, followed by a village malaria worker or a primary health care center staff. Of those who had fever during the previous two weeks, 93.6% sought advice or treatment outside the home, and the most commonly reported source for advice or treatment was private providers (39.4%) followed by health center/district hospital (31.3%). ITN distribution and other malaria prevention interventions have largely benefited the high-risk groups including the forest visitors. Comparing the CMS 2020 results with the 2017 CMS results, it is clear that forest visitors' use of LLIN/LLIHN has improved considerably. However, more needs to be done to ensure forest visitors be protected either through using LLINs or repellents while working and staying in the forest areas. Also, given that sleeping under LLINs has decreased over the past several years among the at-risk populations, the programme will have to develop strategies to ensure that the communities do not lower their guard against malaria as cases further dwindle in malaria prone areas. Heightened awareness amongst the general population will be critical for eliminating malaria in Cambodia without any possibility of malaria re-emergence or re-establishment.


Infection in Shoulder Arthroplasty: Prevention, Diagnosis, and Treatment.
Prosthetic joint infection is a devastating complication following shoulder arthroplasty that can lead to pain, poor function, and poor quality of life. With the increasing number of shoulder arthroplasties performed annually, recognition of prosthetic infection and treatment is necessary. The skin surrounding the shoulder has a unique microbiome, and Cutibacterium acnes is the most commonly encountered bacteria causing prosthetic joint infection. C acnes is a low-virulence organism that resides in the subcutaneous layer of the skin. As a result, the clinical presentation is typically less obvious than prosthetic infections seen in other joints such as the hip and knee. Therefore, diagnosis is not always straightforward, and optimal treatment strategy is unclear. Guidance on prevention, diagnosis, and treatment of shoulder prosthetic joint infection with special emphasis on the consensus definition established at the 2018 International Consensus Meeting is provided.


Development of a LAMP assay for rapid detection of different intimin variants of attaching and effacing microbial pathogens.
Intimin harboured by pathogenic Escherichia coli (E. coli) strains is a key virulence factor involved in host cell adherence and colonization. Twenty-seven intimin-encoding E. coli attaching and effacing (eae) gene variants have been reported according to their 3' binding domain sequences. In our study, we developed a specific and sensitive loop-mediated isothermal amplification (LAMP) assay to detect all known intimin variants. Four primers specific for six regions of eae genes were designed using online software. The eae-LAMP assay was highly specific and detected all 27 tested eae variants; no cross-reactions were observed with genes from enterotoxigenic E. coli (ETEC), E. coli BL21, Salmonella, Shigella, Listeria monocytogenes, or Streptococcus suis type 2 (SS2). With the lowest detection limit of approximately 10 copies per reaction the eae-LAMP assay was 100 times more sensitive than conventional PCR. These results, and the results of tests involving food and faecal samples artificially contaminated with E. coli O157 : H7 (eaeγ+), show that the eae-LAMP assay is a simple, rapid, sensitive and specific tool for detecting intimin variants from pathogenic strains of E. coli. The eae-LAMP assay has great potential for wider applications, not only in the laboratory but also in the field setting, as it does not require specialized equipment.


Orchiectomy versus long-acting D-Trp-6-LHRH in advanced prostatic cancer.
One hundred and four patients were randomised for the study. Fifty-five were entered into the D-Trp-6-LHRH group and 49 into the orchiectomy group. All pre-treatment patient characteristics were similar and testosterone levels at 1 month or later were in the castrate range in both groups. Forty-six patients (83%) in the D-Trp-6-LHRH group and 40 (82%) in the orchiectomy group had a partial remission or stable disease at 3 months or later. There was no significant difference between the groups for response or survival. Three patients in the D-Trp-6-LHRH group had a disease "flare" in the first 10 days of treatment. The flare symptoms resolved by the end of 4 to 8 weeks. The incidence of flushing, decreased libido and impotence was similar in both groups. Although there was less psychological morbidity in the D-Trp-6-LHRH group the difference did not reach statistical significance. Our results indicate that long-acting D-Trp-6-LHRH offers a safe and highly effective alternative to orchiectomy.


Adaptive fuzzy segmentation of magnetic resonance images.
An algorithm is presented for the fuzzy segmentation of two-dimensional (2-D) and three-dimensional (3-D) multispectral magnetic resonance (MR) images that have been corrupted by intensity inhomogeneities, also known as shading artifacts. The algorithm is an extension of the 2-D adaptive fuzzy C-means algorithm (2-D AFCM) presented in previous work by the authors. This algorithm models the intensity inhomogeneities as a gain field that causes image intensities to smoothly and slowly vary through the image space. It iteratively adapts to the intensity inhomogeneities and is completely automated. In this paper, we fully generalize 2-D AFCM to three-dimensional (3-D) multispectral images. Because of the potential size of 3-D image data, we also describe a new faster multigrid-based algorithm for its implementation. We show, using simulated MR data, that 3-D AFCM yields lower error rates than both the standard fuzzy C-means (FCM) algorithm and two other competing methods, when segmenting corrupted images. Its efficacy is further demonstrated using real 3-D scalar and multispectral MR brain images.


Nanolayering around and thermal resistivity of the water-hexagonal boron nitride interface.
The water-hexagonal boron nitride interface was investigated by molecular dynamics simulations. Since the properties of the interface change significantly with the interatomic potential, a new method for calibrating the solid-liquid interatomic potential is proposed based on the experimental energy of the interface. The result is markedly different from that given by Lorentz-Berthelot mixing for the Lennard-Jones parameters commonly used in the literature. Specifically, the extent of nanolayering and interfacial thermal resistivity is measured for several interatomic potentials, and the one calibrated by the proposed method gives the least thermal resistivity.


Pathology and the pathologist in the cancer program.
Cancer as one of the most important human diseases does not present as formidable a problem as infectious disease did a century ago. The diversified cancer program, combining voluntary and governmental agencies in support of research, education and coordinated teamwork in the clinical care of the patient, presents a varied although unified approach to the problem that has never before been available for the study of any single human disease. Pathology, with its applied methods from the basic sciences, has a singular role in the scientific aspect of the cancer program. Representing a new specialty in medicine and embodying an inquiring approach to the study of human disease, pathology has a leading role to play. The pathologist, assuming the new role of "pathologist-physician" brings to the clinical care of the cancer patient the most precise methods of cancer diagnosis. The "pathologist-physician" should be a pivotal member of the "clinical team" in the immediate diagnosis, care and treatment of the cancer patient.


Effects of muscle glycogen on performance of repeated sprints and mechanisms of fatigue.
This study investigated the effect of initial muscle glycogen on performance of repeated sprints and some potential mechanisms for an effect of glycogen on fatigue. Eight subjects performed 2 cycling trials (repeated 60-s sprints) following consumption of either a high carbohydrate (HC) or a low carbohydrate (LC) diet. Muscle biopsies and blood samples were collected at baseline, following a 15% (15% fatigue) and a 30% decline in sprint performance (30% fatigue), when exercise was terminated. Baseline muscle glycogen levels [346 +/- 19 HC (SEM) vs. 222 +/- 19 mmol/kg dw LC] and total exercise time to 30% fatigue were higher following HC than LC (57.5 +/- 10.0 vs. 42.0 +/- 3.6 min; p <.05). Similar significant (p <.05) decreases over the entire exercise bout were seen in muscle glycogen (43%), creatine phosphate (CP; 35%), and sarcoplasmic reticulum (SR) Ca2+-uptake in isolated homogenized muscle (56%) for both trials (p >.05 between trials). The percentage decline in SR Ca2+-release was less for HC than LC (36% and 53%, respectively), but this was not statistically different. In summary, HC delayed fatigue during repeated sprints. As the reductions in muscle glycogen, CP, and SR function during exercise were not different by dietary treatment, these data do not support a link between whole muscle glycogen and SR function or CP reduction during repeated sprint exercise.


Bowel behaviour in young black and white children.
Bowel behaviour was investigated in 81 rural black, 117 urban black, and 77 white children aged 1 to 4 years. The study was undertaken principally because intake of dietary fibre by urban blacks is now lower than that of whites: moreover, that of rural blacks has also fallen. Average daily defecation frequencies in rural and urban black children and white children were 1.9, 1.8, and 1.5, respectively. Black children voided smaller stools and more frequently than white children. In both ethnic groups most stools were soft. Median transit times, determined in 55 rural black, 80 urban black, and 45 white children, were approximately 6.5, 7, and 27 hours, respectively. Median transit times increased little with age in black compared with white children. The higher defecation frequency and the much shorter transit time in black children are not explicable in terms of the levels of fibre intake.


Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway.
Although gastric cancer (GC) is one of the most common cancers, knowledge of its development, and carcinogenesis is limited. The present study explored the involvement of ceramide synthase 6 (CERS6) in GC carcinogenesis and prognosis. RT-PCR, immunoblotting, and immunohistochemistry were used to examine the expression of CERS6. Transfection and small hairpin RNA technology were used to investigate the effect of CERS6 manipulation on cell proliferation and spread as well as the underlying mechanism. Moreover, xenograft proliferation was employed to explore the influence of CERS6 on tumor growth in animals. It was found that overexpression of CERS6 was significantly correlated with several clinicopathologic parameters and poor disease-free survival. The overexpression and silencing of CERS6 in GC cells facilitated and suppressed cell proliferation and spread as well as xenograft proliferation, respectively. Mechanistic studies further revealed that CERS6 influenced cell proliferation and spread by regulating cell cycle control and metastasis-related protein through the SOCS2/JAK2/STAT3 signaling pathway. Collectively, this study suggests that CERS6 overexpression could be a useful biomarker for predicting the outcomes of GC patients and that CERS6 targeting represents a potential modality for treating GC.


Effect of mouse interferon on chemical carcinogenesis in normal rat kidney cells infected with Moloney murine leukemia virus.
The present study was carried out with a normal rat kidney cell clone that was initiated from a single cell infected by only one infectious particle of the non-transforming retrovirus, Moloney murine leukemia virus. Although the parental cells were highly resistant to chemical carcinogenesis, this infected clone was rendered susceptible to transformation by chemical carcinogens. However, when it was exposed to the tested carcinogen at a low subculture passage post-infection, cell transformation was detectable only after many subsequent passages. On the other hand, if it was exposed to the carcinogen at a high passage post-infection, cell transformation was detectable sometimes even without further passage, or in other cases after the first subsequent passage. Mouse interferon could inhibit the transformation by carcinogen employed at the low but not at the high passage post-infection. This inhibitory effect was reversible; if interferon was removed, even after the cells had been passaged many times in its presence, cell transformation became visible at passage 11 after interferon removal, although no treatment with the carcinogen was repeated. Interferon had no effect on the replication or the focus-forming capacity of cells transformed by such chemical-retroviral co-carcinogenesis. The possibility that this carcinogenic process depends on amplification of the integrated provirus DNA, and that this amplification can be inhibited by interferon is discussed.


Explaining transitions over the hypothesized psychosis continuum.
It is crucial to understand the psychological mechanisms that mediate transition from having one or two psychotic symptoms to becoming a patient with a psychotic disorder. This study investigated whether: (i) a delusional interpretation and/or a depressed response to hallucinatory experiences predicts the later onset of clinical psychotic disorder; and (ii) the presence of need for care in relation to psychotic disorder was associated with the use of particular coping strategies. A general population sample of 4672 individuals with no lifetime evidence of any psychotic disorder were interviewed with the Composite International Diagnostic Interview Schedule (CIDI) at baseline and 1 and 3 years later. At year 3, individuals with CIDI evidence of psychotic symptoms were interviewed by clinicians to identify onset of psychotic disorder with need for care. Coping, subjective distress with and perceived control over the psychotic experience were assessed using the Maastricht Assessment of Coping Strategies (MACS). Given the presence of hallucinatory experiences at baseline, the increase in risk on the additive scale of having the psychosis outcome at T2 was higher in the group with delusional ideation at T1 than in those without delusional ideation at T1. Similarly, presence of depressed mood at T1 increased the risk of having the psychosis outcome at T2, but this effect overlapped partly with the risk-increasing effect of delusional ideation. Individuals with a need for care were much more likely to display symptomatic coping, whereas the presence of the other coping types was not different across the groups with and without need for care. Transitions over the psychosis continuum are, at least in part, driven by the emotional, cognitive and behavioural responses to the initial psychotic or psychosis-like experiences. Individuals who react with a delusional interpretation, negative emotional states and/or a symptomatic coping style have an increased risk for developing clinical psychosis.


Phenomenology, psychopathology, and short-term therapeutic outcome of 102 infants aged 0 to 12 months consecutively referred to a community-based 0 to 3 mental health clinic.
Infants ages 0 to 1 year consecutively referred for psychiatric treatment during the year 2005 were followed, and variables associated with diagnosis and short-term outcome were assessed. Infants were evaluated using the Psychiatric Infant Navigator Chart and Evaluation that includes nosological diagnoses [Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, (DC 0-3), Zero to Three, 1994] as well as risk and protective factors, treatment procedure, and outcomes. Seventy-six percent of the infants had an Axis I diagnosis, with anxiety disorders and a mixed disorder of emotional expressiveness being the most frequent. Twenty-five percent had an Axis II diagnosis. Multiple correspondence analyses showed that two dimensions corresponding grossly to DC 0-3 Axes I and II emerged. They emphasized three clinical profiles characterized by (a) good infant functioning, parent's awareness of their own difficulties, and a good outcome; (b) moderate child symptoms, overinvolved relating, and a good/intermediate outcome; (c) severe child symptoms, underinvolved relating, and a less favorable short-term outcome, signaling the risk for developmental disorders. Among the associated risk factors were cumulative parental stress, maternal psychopathology, and family dysfunction. Clinical implications of these findings indicated that infants under the age of 1 year who are referred for mental health evaluation and intervention are a heterogeneous group in terms of both severity and prognosis. Clinicians should differentiate subgroups of young children to detect those infants at risk for persistent psychopathology.


Ugene, a newly identified protein that is commonly overexpressed in cancer and binds uracil DNA glycosylase.
Expression microarrays identified a novel transcript, designated as Ugene, whose expression is absent in normal colon and colon adenomas, but that is commonly induced in malignant colon cancers. These findings were validated by real-time PCR and Northern blot analysis in an independent panel of colon cancer cases. In addition, Ugene expression was found to be elevated in many other common cancer types, including breast, lung, uterus, and ovary. Immunofluorescence of V5-tagged Ugene revealed it to have a nuclear localization. In a pull-down assay, uracil DNA glycosylase 2 (UNG2), an important enzyme in the base excision repair (BER) pathway, was identified as a partner protein that binds to Ugene. Coimmunoprecipitation and Western blot analysis confirmed the binding between the endogenous Ugene and UNG2 proteins. Using deletion constructs, we find that Ugene binds to the first 25 amino acids of the UNG2 NH(2) terminus. We suggest that Ugene induction in cancer may contribute to the cancer phenotype by interacting with the BER pathway.


Effects of oral contraceptive therapy on the circadian patterns of cortisol and thyrotropin (TSH).
The daily variation of serum cortisol and thyrotropin (TSH) has been simultaneously recorded every 30-min. in 4 women taking the same oral contraceptive containing oestrogens and progestogens and in 4 control women. The circadian rhythm of cortisol persisted under contraceptive therapy with about a 2.5 fold elevation of the mean level and amplitude of the basal rhythm. Theoretical equilibrium calculations of the circadian variations of the free, transcortin-bound and albumin-bound cortisol fractions showed that these elevations are explained qualitatively and quantitatively by an oestrogen-induced increase of the same order of the transcortin cortisol-binding sites. As a consequence of the already high saturation of transcortin in normal conditions, the magnitude of the variation of free cortisol level resulting from a burst in cortisol secretion varies with the time of day. The role of albumin as a buffer is thereby emphasized. The early morning maximum, characterizing the normal TSH daily pattern, appeared to be considerably enhanced in women under contraceptive therapy. If the circadian variations of TSH are driven by thyrotropin releasing hormone (TRH), these higher morning peaks probably reflect a higher burst of TRH secretion rather than an increased responsiveness of the pituitary to TRH secretion induced by contraceptive therapy. Finally these results do not support the hypothesis of a regulation of TSH circadian variations by an inhibiotry action of cortisol. Contraceptive therapy does not appear to play a role at the level of the central clock or on the resetting mechanism.


Chemoradiation Including Paclitaxel for Locally Recurrent Muscle-invasive Bladder Cancer in Elderly Patients.
To evaluate outcomes and toxicities of chemoradiation with a less intensive paclitaxel regimen for locally recurrent bladder cancer. Three elderly patients received simultaneous chemoradiation for recurrent muscle-invasive bladder cancer. Chemotherapy included two courses (three times 25 mg/m2 over 1.5 weeks) of paclitaxel. Radiotherapy doses were 59.4 Gy to the bladder and 50.4 Gy to regional lymph nodes. Survival, local control and toxicities were retrospectively evaluated. One patient died after 71 months, two were alive after 69 and 98 months, respectively. No local recurrence was not observed. Five-year survival and local control rates were 100%. Two patients experienced grade 1 acute dysuria, one patient grade 1 diarrhea. Late toxicities were also mild; two patients had grade 1 dysuria. Chemoradiation with a less intensive paclitaxel regimen resulted in excellent 5-year results and was very well tolerated. It may be a reasonable option for elderly patients who cannot tolerate more intensive approaches.


The Automated Bone Scan Index as a Predictor of Response to Prostate Radiotherapy in Men with Newly Diagnosed Metastatic Prostate Cancer: An Exploratory Analysis of STAMPEDE's "M1|RT Comparison".
Prostate radiotherapy (RT) is a first-line option for newly diagnosed men with low-burden metastatic prostate cancer. The current criterion to define this clinical state is based on manual bone metastasis counts, but enumeration of bone metastases is limited by interobserver variations, and it does not account for metastasis volume or lesional coalescence. The automated bone scan index (aBSI) is a quantitative method of evaluating bone metastatic burden in a standardised and reproducible manner. To evaluate whether aBSI has utility as a predictive imaging biomarker to define a newly diagnosed metastatic prostate cancer population that might benefit from the addition of prostate RT to standard of care (SOC) systemic therapy. This is an exploratory analysis of men with newly diagnosed metastatic prostate cancer randomised in a 1:1 ratio to either SOC or SOC + prostate RT within the STAMPEDE "M1|RT comparison". The SOC was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December 2015. Men allocated RT received either a daily or a weekly schedule that was nominated before randomisation. Baseline bone scans were evaluated retrospectively to calculate aBSI. We used overall (OS) and failure-free (FFS) survival as the end points. Treatment-aBSI interaction was evaluated using the multivariable fractional polynomial interaction (MFPI) and subpopulation treatment effect pattern plot. Further analysis was done in aBSI quartiles using Cox regression models adjusted for stratification factors. Baseline bone scans for 660 (SOC: 323 and SOC + RT: 337) of 2061 men randomised within the "M1|RT comparison" met the software requirements for aBSI calculation. The median age was 68 yr, median PSA was 100 ng/mL, median aBSI was 0.9, and median follow-up was 39 mo. Baseline patient characteristics including aBSI were balanced between the treatment groups. Using the MFPI procedure, there was evidence of aBSI-treatment interaction for OS (p = 0.04, MFPI procedure) and FFS (p < 0.01, MFPI procedure). Graphical evaluation of estimated treatment effect plots showed that the OS and FFS benefit from prostate RT was greatest in patients with a low aBSI. Further analysis in quartiles based on aBSI supported this finding. A low automated bone scan index is predictive of survival benefit associated with prostate RT in men with newly diagnosed metastatic prostate cancer. The widely used bone scan can be evaluated using an automated technique to potentially select men with newly diagnosed metastatic prostate cancer who might benefit from prostate radiotherapy.


Admissions for isolated nonoperative mild head injuries: Sharing the burden among trauma surgery, neurosurgery, and neurology.
Isolated nonoperative mild head injuries (INOMHI) occur with increasing frequency in an aging population. These patients often have multiple social, discharge, and rehabilitation issues, which far exceed the acute component of their care. This study was aimed to compare the outcomes of patients with INOMHI admitted to three services: trauma surgery, neurosurgery, and neurology. Retrospective case series (January 1, 2009 to August 31, 2013) at an academic Level I trauma center. According to an institutional protocol, INOMHI patients with Glasgow Coma Scale (GCS) of 13 to 15 were admitted on a weekly rotational basis to trauma surgery, neurosurgery, and neurology. The three populations were compared, and the primary outcomes were survival rate to discharge, neurological status at hospital discharge as measured by the Glasgow Outcome Score (GOS), and discharge disposition. Four hundred eighty-eight INOMHI patients were admitted (trauma surgery, 172; neurosurgery, 131; neurology, 185). The mean age of the study population was 65.3 years, and 58.8% of patients were male. Seventy-seven percent of patients has a GCS score of 15. Age, sex, mechanism of injury, Charlson Comorbidity Index, Injury Severity Score, Abbreviated Injury Scale in head and neck, and GCS were similar among the three groups. Patients who were admitted to trauma surgery, neurosurgery and neurology services had similar proportions of survivors (98.8% vs 95.7% vs 94.7%), and discharge disposition (home, 57.0% vs 61.6% vs 55.7%). The proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to trauma (97.7% vs 93.0% vs 92.4%). In a logistic regression model adjusting for Charlson Comorbidity Index CCI and Abbreviated Injury Scale head and neck scores, patients who were admitted to neurology or neurosurgery had significantly lower odds being discharged with GOS 4 or 5. While the trauma group had the lowest proportion of repeats of brain computed tomography (61.6%), the neurosurgery group had the highest proportion of intensive care unit admission (29.8%), and the neurology group had the longest emergency department stay (7.5 hours), there were no significant differences in duration of hospital stay, in-hospital complications, and readmission within 30 days. Although there were differences in use of health care resources, and the proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to trauma, most clinical outcomes were similar in INOMHI patients admitted to trauma surgery, neurosurgery, or neurology in our institution. A rotational policy of admitting INOMHI patients is feasible among services with expertise in and commitment to the care of these patients. Therapeutic/care management study, level IV.


Discontinuation from Antiretroviral Therapy: A Continuing Challenge among Adults in HIV Care in Ethiopia: A Systematic Review and Meta-Analysis.
Discontinuation of antiretroviral therapy (ART) reduces the immunological benefit of treatment and increases complications related to human immune-deficiency virus (HIV). However, the risk factors for ART discontinuation are poorly understood in developing countries particularly in Ethiopia. This review aimed to assess the best available evidence regarding risk factors for ART discontinuation in Ethiopia. Quantitative studies conducted in Ethiopia between 2002 and 2015 that evaluated factors associated with ART discontinuation were sought across six major databases. Only English language articles were included. This review considered studies that included the following outcome: ART treatment discontinuation, i.e. 'lost to follow up', 'defaulting' and 'stopping medication'. Meta- analysis was performed with Mantel Haenszel method using Revman-5 software. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals at a p-value of <0.05. Nine (9) studies met the criteria of the search. Five (5) were retrospective studies, 3 were case control studies, and 1 was a prospective cohort study. The total sample size in the included studies was 62,156. Being rural dweller (OR = 2.1, 95%CI: 1.5-2.7, I2 = 60%), being illiterate (OR = 1.5, 95%CI: 1.1-2.1), being not married (OR = 1.4, 95%CI: 1.1-1.8), being alcohol drinker (OR = 2.9, 95%CI: 1.9-4.4, I2 = 39%), being tobacco smoker (OR = 2.6, 95%CI: 1.6-4.3, I2 = 74%), having mental illness (OR = 2.7, 95%CI: 1.6-4.6, I2 = 0%) and being bed ridden functional status (OR = 2.3, 95%CI: 1.5-3.4, I2 = 37%) were risk factors for ART discontinuation. Whereas, having HIV positive partner (OR = 0.4, 95%CI: 0.3-0.6, I2 = 69%) and being co-infected with Tb/HIV (OR = 0.6, 95%CI: 0.4-0.9, I2 = 0%) were protective factors. Demographic, behavioral and clinical factors influenced ART treatment discontinuation. Hence, we recommend strengthening decentralization of HIV care services in remote areas, strengthening of ART task shifting, application of seek-test-treat-succeed model, and integration of smoking cession strategies and mental health care into the routine HIV care program.


Crocetin attenuating Urinary tract Infection and adherence of uropathogenic E. coli in NRK-52E cells via an inflammatory pathway.
Urinary tract infections (UTI) are commonly treated with broad-spectrum antibiotics, but treatment has limitation due to causes of nephrotoxicity in uroepithelial cells. Recently, the researcher focuses their research on alternative therapy for the treatment of UTI. This study evaluated the anti-infectious effect of crocetin against adherence of pathogenic [2-14 C]-acetate labeled Escherichia coli (MTCC-729) to rat proximal renal tubular cells (NRK-52E cells) and explores the possible mechanism of action. In vitro cytotoxicity and radio acetate labeled tests were performed on NRK-52E cells. The rats were divided into five different groups as follows: normal control (NC), disease control (DC), and various doses of crocetin (1.25, 2.5, and 5 mg/kg) treated group rats. White blood cells in blood, urine, and bacterial colony counts were estimated at regular intervals. Pro-inflammatory cytokines, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), and interleukin-8 (IL-8), were also estimated. In the current study, we estimated the mRNA expression of toll-like receptor-4 (TLR-4) and toll-like receptor-2 (TLR-2) in the renal and bladder tissues. Crocetin significantly (p < .05) inhibited the adherence of E. Coli in NRK-52E cells. Crocetin suppresses the lipid peroxidation (LPO) 42% in cells treated with H2 O2 cells without crocetin. The white blood cells (WBC) count in blood and urine were augmented and crocetin treatment significantly (p < .05) reduced the WBC in urine and blood. The pro-inflammatory cytokines, such as IL-6, MCP-1, IL-10, and IL-8, significantly (p < .05) increased in the DC group and crocetin significantly (p < .05) reduced the pro-inflammatory cytokines. Dose-dependent treatment of crocetin significantly reduced the mRNA expression of TLR2 and TLR4 in the renal and bladder tissues. Crocetin considerably reduced the bacterial adherence to NRK-52E cells, attenuated the H2 O2 induced toxicity in NRK-52E cells and also improved the renal tubular function, and reduced the inflammatory response via altering the inflammatory and antioxidant markers. As we all know that urinary tract infection is the most common disease worldwide. In this study, we scrutinized the protective effect of crocetin against urinary tract infection. Crocetin treatment considerably reduced the zone of inhibition and improved radioactivity. Crocetin significantly reduced the levels of cytokines and inflammatory mediators. Crocetin can be used as a protective drug in the treatment of urinary tract infections.


Getting out of a sticky situation: targeting the myofibroblast in scleroderma.
There is no treatment for the fibrosis observed in scleroderma (systemic sclerosis, SSc). Although genome-wide expression profiling has suggested that differences in gene expression patters between non-lesional and lesional skin are minimal, phenotypically these areas of tissue are quite different. In fact, lesional areas of scleroderma patients can be distinguished by the presence of a differentiated form of fibroblast, termed the myofibroblast. This cell type expresses the highly contractile protein α-smooth muscle actin (α-SMA). Fibroblasts isolated from SSc lesions excessively synthesize, adhere to and contract extracellular matrix (ECM) and display activated adhesive signaling pathways. Strategies aimed at blocking myofibroblast differentiation, persistence and activity are therefore likely to be useful in alleviating the fibrosis in scleroderma.


Latency of herpes simplex virus in absence of neutralizing antibody: model for reactivation.
Mice inoculated with herpes simplex virus (type 1) by the lip or corneal route and then passively immunized with rabbit antibody to herpes simplex virus developed a latent infection in the trigeminal ganglia within 96 hours. Neutralizing antibody to herpes simplex virus was cleared from the circulation and could not be detected in most of these mice after 2 months. Examination of ganglia from the antibody-negative mice revealed latent virus in over 90 percent of the animals, indicating that serum neutralizing antibody is not necessary to maintain the latent state. When the lips or corneas of these mice were traumatized, viral reactivation occurred in up to 90 percent of the mice, as demonstrated by the appearance of neutralizing antibody. This study provides a model for identifying factors that trigger viral reactivation.


Depressive symptoms and harmful alcohol use in hepatitis C patients: prevalence and correlates.
It is important to understand the characteristics and vulnerabilities of people who have hepatitis C because this disease is currently an important public health problem. The objective of this study was to estimate the prevalence of depressive symptoms and harmful alcohol use in patients with hepatitis C and to study the association between these outcomes and demographic, psychosocial and clinical variables. This cross-sectional, descriptive and analytical study involved 82 hepatitis C patients who were being treated with pegylated interferon and ribavirin at a public university hospital. The primary assessments used in the study were the Alcohol Use Disorders Identification Test and the Beck Depression Inventory. Bivariate analyses were followed by logistic regression. The prevalence of depressive symptoms was 30.5% (n=25), and that of harmful alcohol use was 34.2% (n=28). Logistic regression analysis showed that individuals who were dissatisfied with their social support (OR=4.41; CI=1.00-19.33) and were unemployed (OR=6.31; CI=1.44-27.70) were at a higher risk for depressive symptoms, whereas harmful alcohol use was associated with the male sex (OR=6.78; CI=1.38-33.19) and the use of illicit substances (OR=7.42; CI=1.12-49.00). High prevalence rates of depressive symptoms and harmful alcohol use were verified, indicating vulnerabilities that must be properly monitored and treated to reduce emotional suffering in this population.


Hippocampal synapses depend on hippocampal estrogen synthesis.
Estrogens have been described to induce synaptogenesis in principal neurons of the hippocampus and have been shown to be synthesized and released by exactly these neurons. Here, we have focused on the significance of local estrogen synthesis on spine synapse formation and the synthesis of synaptic proteins. To this end, we reduced hippocampal estrogen synthesis in vitro with letrozole, a reversible nonsteroidal aromatase inhibitor. In hippocampal slice cultures, letrozole treatment resulted in a dose-dependent decrease of 17beta-estradiol as quantified by RIA. This was accompanied by a significant decrease in the density of spine synapses and in the number of presynaptic boutons. Quantitative immunohistochemistry revealed a downregulation of spinophilin, a marker of dendritic spines, and synaptophysin, a protein of presynaptic vesicles, in response to letrozole. Surprisingly, no increase in the density of spines, boutons, and synapses and in spinophilin expression was seen after application of estradiol to the medium of cultures that had not been treated with letrozole. However, synaptophysin expression was upregulated under these conditions. Our results point to an essential role of endogenous hippocampal estrogen synthesis in the maintenance of hippocampal spine synapses.


Genetic dissection of an allotetraploid interspecific CSSLs guides interspecific genetics and breeding in cotton.
The low genetic diversity of Upland cotton limits the potential for genetic improvement. Making full use of the genetic resources of Sea-island cotton will facilitate genetic improvement of widely cultivated Upland cotton varieties. The chromosome segments substitution lines (CSSLs) provide an ideal strategy for mapping quantitative trait loci (QTL) in interspecific hybridization. In this study, a CSSL population was developed by PCR-based markers assisted selection (MAS), derived from the crossing and backcrossing of Gossypium hirsutum (Gh) and G. barbadense (Gb), firstly. Then, by whole genome re-sequencing, 11,653,661 high-quality single nucleotide polymorphisms (SNPs) were identified which ultimately constructed 1211 recombination chromosome introgression segments from Gb. The sequencing-based physical map provided more accurate introgressions than the PCR-based markers. By exploiting CSSLs with mutant morphological traits, the genes responding for leaf shape and fuzz-less mutation in the Gb were identified. Based on a high-resolution recombination bin map to uncover genetic loci determining the phenotypic variance between Gh and Gb, 64 QTLs were identified for 14 agronomic traits with an interval length of 158 kb to 27 Mb. Surprisingly, multiple alleles of Gb showed extremely high value in enhancing cottonseed oil content (SOC). This study provides guidance for studying interspecific inheritance, especially breeding researchers, for future studies using the traditional PCR-based molecular markers and high-throughput re-sequencing technology in the study of CSSLs. Available resources include candidate position for controlling cotton quality and quantitative traits, and excellent breeding materials. Collectively, our results provide insights into the genetic effects of Gb alleles on the Gh, and provide guidance for the utilization of Gb alleles in interspecific breeding.


Evaluation of a clinical decision-making aid for nutrition advice in age-related macular degeneration.
Age-related macular disease (AMD) is a multifactorial degenerative condition affecting the central area of the retina. Patients with AMD report that eye care practitioners are not giving consistent advice regarding nutrition and reported confusion as to what advice, if any, to follow. The aim of this study was to design and conduct a preliminary evaluation of a flowchart to support eye care practitioners in providing accurate, evidence-based nutritional advice to their patients. A flowchart was designed to take practitioners through a decision-making process that would determine whether a patient matched the Age-Related Eye Disease Study (AREDS) 2 eligibility criteria for supplementation. The flowchart was evaluated using a qualified and student optometrist cohort, with both cohorts completing confidence scales and students completing clinical scenarios. Qualified participants showed a significant increase in confidence scores from the initial survey (M = 69.7%, standard deviation [SD] = 16.2%) to the second survey after use of the flowchart for 2 weeks (M = 82.1%, SD = 11.6%; t(45) = 7.33, p < .001; rs = .61, p < .001). The student participants also increased confidence scored after receiving the flowchart (M of first survey = 41.7, SD = 14.6; M of second survey = 69.1, SD = 1.7; t(25) = 7.92, d = .81, p < .001) and increased the number of correct answers on five clinical scenarios. Overall, the flowchart has proved to be useful in boosting the self-efficacy of both qualified practitioners and student practitioners, as well as improving clinical decisions made by student practitioners.


Mucoepidermoid carcinoma of the lung--a case report.
Mucoepidermoid carcinoma is an uncommon primary lung tumor. Mucoepidermoid carcinomas have been reported in all age group and equally in both sexes. A case of mucoepidermoid carcinoma histologically confirmed by biopsy is reported here. The patient is a 15 years old male presented with cough and dyspnoea for 5 days. Chest roentgenography showed segmental consolidation of right lower lobe. Chest computed tomography revealed a soft tissue mass with calcification within the lumen of lower trachea in precarinal location. The patient underwent thoracotomy for endotracheal mass and resection was done. Following operation, the patient is symptom free and follow-up CT scan shows normal tracheal outline.


Ischemic stroke in Greyhounds: 21 cases (2007-2013).
To determine the prevalence of ischemic stroke in Greyhounds and determine whether affected dogs had coagulation abnormalities and hypertension. Multi-institutional, retrospective study. 21 dogs. Medical records (including diagnostic testing results) and MRI images of the brain were reviewed for Greyhounds with ischemic stroke that had been evaluated at 4 institutions. The proportion of Greyhounds with ischemic stroke was compared with the proportion of non-Greyhound dogs with ischemic stroke. Demographic information for dogs evaluated at each institution was obtained to determine the proportion of Greyhounds in the hospital populations. 21 Greyhounds with ischemic stroke were identified. Abnormalities in coagulation were not identified in the 14 Greyhounds that underwent such testing. Systemic hypertension was identified in 6 of 14 Greyhounds that underwent such testing. No other abnormalities were identified by means of other routine diagnostic tests for Greyhounds. For all institutions combined, the prevalence of ischemic stroke in Greyhounds was 0.66% (21/3,161 Greyhounds). Greyhounds were significantly more likely to be evaluated because of ischemic stroke, compared with all other dog breeds combined (OR, 6.6; 95% confidence interval, 4.2 to 10.2). Results of this study suggested that Greyhounds were predisposed to ischemic stroke, compared with all other breeds combined. Coagulation abnormalities did not seem to contribute to ischemic stroke. Hypertension may have contributed to the development of ischemic stroke. Greyhounds with ischemic stroke should undergo measurement of systolic arterial blood pressure. Antihypertensive treatments may be warranted for such dogs.


Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience).
Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.


Cardiovascular disease epidemiology in Asia: an overview.
Cardiovascular disease (CVD) is the leading cause of death in the world and half of the cases of CVD are estimated to occur in Asia. Compared with Western countries, most Asian countries, except for Japan, South Korea, Singapore and Thailand, have higher age-adjusted mortality from CVD. In Japan, the mortality from CVD, especially stroke, has declined continuously from the 1960s to the 2000s, which has contributed to making Japan into the top-ranking country for longevity in the world. Hypertension and smoking are the most notable risk factors for stroke and coronary artery disease, whereas dyslipidemia and diabetes mellitus are risk factors for ischemic heart disease and ischemic stroke. The nationwide approach to hypertension prevention and control has contributed to a substantial decline in stroke mortality in Japan. Recent antismoking campaigns have contributed to a decline in the smoking rate among men. Conversely, the prevalence of dyslipidemia and diabetes mellitus increased from the 1980s to the 2000s and, therefore, the population-attributable risks of CVD for dyslipidemia and diabetes mellitus have increased moderately. To prevent future CVD in Asia, the intensive prevention programs for hypertension and smoking should be continued and that for emerging metabolic risk factors should be intensified in Japan. The successful intervention programs in Japan can be applied to other Asian countries.


Enhanced flow of core-softened fluids through narrow nanotubes.
We investigate through non-equilibrium molecular dynamic simulations the flow of anomalous fluids inside rigid nanotubes. Our results reveal an anomalous increase of the overall mass flux for nanotubes with sufficiently smaller radii. This is explained in terms of a transition from a single-file type of flow to the movement of an ordered-like fluid as the nanotube radius increases. The occurrence of a global minimum in the mass flux at this transition reflects the competition between the two characteristic length scales of the core-softened potential. Moreover, by increasing further the radius, another substantial change in the flow behavior, which becomes more evident at low temperatures, leads to a local minimum in the overall mass flux. Microscopically, this second transition is originated by the formation of a double-layer of flowing particles in the confined nanotube space. These nano-fluidic features give insights about the behavior of confined isotropic anomalous fluids.


Role of the proline knot motif in oleosin endoplasmic reticulum topology and oil body targeting.
An Arabidopsis oleosin was used as a model to study oleosin topology and targeting to oil bodies. Oleosin mRNA was in vitro translated with canine microsomes in a range of truncated forms. This allowed proteinase K mapping of the membrane topology. Oleosin maintains a conformation with a membrane-integrated hydrophobic domain flanked by N- and C-terminal domains located on the outer microsome surface. This is a unique membrane topology on the endoplasmic reticulum (ER). Three universally conserved proline residues within the "proline knot" motif of the oleosin hydrophobic domain were substituted by leucine residues. After in vitro translation, only minor differences in proteinase K protection could be observed. These differences were not apparent in soybean microsomes. No significant difference in incorporation efficiency on the ER was observed between the two oleosin forms. However, as an oleosin-beta-glucuronidase translational fusion, the proline knot variant failed to target to oil bodies in both transient embryo expression and in stably transformed seeds. Fractionation of transgenic embryos expressing oleosin-beta-glucuronidase fusions showed that the proline knot variant accumulated in the ER to similar levels compared with the native form. Therefore, the proline knot motif is not important for ER integration and the determination of topology but is required for oil body targeting. The loss of the proline knot results in an intrinsic instability in the oleosin polypeptide during trafficking.


Genomic structure and chromosomal localization of the novel ETS factor, PE-2 (ERF).
The members of the ETS family of transcription factors are grouped because they share a highly conserved DNA binding domain. These factors are involved in growth factor pathways and regulate both proliferation and differentiation. To identify ETS factors that may be involved in early hematopoietic progenitor regulation, we isolated a novel member of the ETS family by reverse transcriptase-PCR of the conserved DNA binding domain using degenerate oligonucleotides. This gene directs the synthesis of a 2704-nucleotide transcript whose largest open reading frame encodes a 548-amino-acid protein. Northern blot analysis reveals ubiquitous expression in all human tissues and cell lines tested, with highest levels in the testis, ovary, pancreas, and heart. Comparison of this gene with the available databases reveals very significant homology to the ETS factor PE-1 and probable near-identity with the recently cloned factor ERF. The PE-2 gene is composed of four exons spanning over 9 kb of genomic DNA. Sequence analysis of the promoter region reveals a GC-rich sequence without a TATA motif and with putative binding motifs for CREB, c-myb, and AP-1 factors. Using mouse-human somatic hybrids and FISH analysis, the PE-2 gene is localized to human chromosome 19q13.2, a region involved in translocations and deletions in leukemias and several solid tumors, suggesting that this novel ETS factor may play a role in carcinogenesis.


The double-stranded RNA bluetongue virus induces type I interferon in plasmacytoid dendritic cells via a MYD88-dependent TLR7/8-independent signaling pathway.
Dendritic cells (DCs), especially plasmacytoid DCs (pDCs), produce large amounts of alpha/beta interferon (IFN-α/β) upon infection with DNA or RNA viruses, which has impacts on the physiopathology of the viral infections and on the quality of the adaptive immunity. However, little is known about the IFN-α/β production by DCs during infections by double-stranded RNA (dsRNA) viruses. We present here novel information about the production of IFN-α/β induced by bluetongue virus (BTV), a vector-borne dsRNA Orbivirus of ruminants, in sheep primary DCs. We found that BTV induced IFN-α/β in skin lymph and in blood in vivo. Although BTV replicated in a substantial fraction of the conventional DCs (cDCs) and pDCs in vitro, only pDCs responded to BTV by producing a significant amount of IFN-α/β. BTV replication in pDCs was not mandatory for IFN-α/β production since it was still induced by UV-inactivated BTV (UV-BTV). Other inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-12p40, were also induced by UV-BTV in primary pDCs. The induction of IFN-α/β required endo-/lysosomal acidification and maturation. However, despite being an RNA virus, UV-BTV did not signal through Toll-like receptor 7 (TLR7) for IFN-α/β induction. In contrast, pathways involving the MyD88 adaptor and kinases dsRNA-activated protein kinase (PKR) and stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) were implicated. This work highlights the importance of pDCs for the production of innate immunity cytokines induced by a dsRNA virus, and it shows that a dsRNA virus can induce IFN-α/β in pDCs via a novel TLR-independent and Myd88-dependent pathway. These findings have implications for the design of efficient vaccines against dsRNA viruses.


STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin.
The TrkA receptor tyrosine kinase induces death in medulloblastoma cells via an interaction with the cerebral cavernous malformation 2 (CCM2) protein. We used affinity proteomics to identify the germinal center kinase class III (GCKIII) kinases STK24 and STK25 as novel CCM2 interactors. Down-modulation of STK25, but not STK24, rescued medulloblastoma cells from NGF-induced TrkA-dependent cell death, suggesting that STK25 is part of the death-signaling pathway initiated by TrkA and CCM2. CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling. Finally, STK25 expression in tumors is correlated with positive prognosis in neuroblastoma patients. These findings delineate a death-signaling pathway downstream of neurotrophic receptor tyrosine kinases that may provide targets for therapeutic intervention in pediatric tumors of neural origin.


Exercise in pregnancy: effect on fitness and obstetric outcomes-a randomized trial.
A prospective randomized controlled trial was designed to assess the benefits and possible risks of aerobic exercise during pregnancy, using a fitness regimen based on the 2002 American College of Obstetricians and Gynecologists guidelines for exercise during pregnancy. Inactive women were randomized at 12-14 wk gestation to a group that remained sedentary or to a group that performed moderate aerobic exercise 45-60 min, 4 d·wk, through 36 wk gestation. Thirty-one subjects in each group completed the study. Compared with women who remained sedentary, active women improved aerobic fitness (P < 0.05) and muscular strength (P < 0.01), delivered comparable size infants with significantly fewer cesarean deliveries (P < 0.01), and recovered faster postpartum (P < 0.05), at least related to the lower incidence of cesarean section. Active women developed no gestational hypertension (P = 0.16 compared with controls) and reported no injuries related to the exercise regimen. In the active group, there was one premature birth at 33 wk by a woman with a history of premature delivery of twins at 34 wk. There were no differences between groups in the incidence of gestational diabetes, musculoskeletal pains during pregnancy, flexibility on sit-and-reach test, mean length of pregnancy, neonatal Apgar scores, placenta weights, overall length of labor, weight gain during pregnancy, or weight retention postpartum. Previously sedentary women who began exercising at 12-14 wk improved fitness and delivery outcomes.


Fractured strut of Björk-Shiley 70 degrees convexo-concave mitral valve prosthesis found in left coronary artery. Use of a portable transcutaneous cardiopulmonary bypass system for successful valve replacement.
Strut fractures followed by disk escape of Björk-Shiley convexo-concave valve prostheses are a well-known problem. This article discusses the case of a successfully treated patient who was admitted to our institution with extreme and prolonged cardiogenic shock. The strut was dislodged into the main stem of the left coronary artery and the disk into the iuxtarenal abdominal aorta. The intent of this report is, in particular, to illustrate the management problems. Immediately after diagnosis, circulation and oxygenation were ensured by use of a portable cardiopulmonary bypass support (CPS) system whose circulation lines were introduced subcutaneously. Thus the transfer to the operating room and the surgical intervention were able to start under controlled conditions. The disk was removed by Fogarty catheter manoevre without any problems during the same operation, using a transpericardial access to the descending thoracic aorta. In our opinion, the primary insertion of the CPS and the avoidance of an additional laparotomy in disk removal help promote the survival of such critically ill patients.


[Criteria for assessing the efficacy of brachytherapy of uveal melanomas, complications of therapy and there prevention].
The authors assess the efficacy of brachytherapy of uveal melanomas in 954 patients. Strontium ophthalmoapplicators were used in 652, rutenium ones in 302 patients. As a rule, Sr applicators were sutured in patients with tumors up to 3.5 mm thick and Ru ones in cases with tumors thicker than 3.5 mm. A special program was used for individual approach and improving the accuracy of planning. A total of 74.5% of patients have been followed up for at least 3 years, with check-ups every 3-6 months. The effect of brachytherapy was considered positive in cases with complete resorption or at least 50% decrease of the tumor and a stable clinical picture for 9-12 months. In 60% of patients the tumor regressed completely, in 16% partially, and in 24% there were signs of activation of melanoma growth one year after treatment. The frequency of radiation complications was as follows: retinopaty, 3.15%; neuroretinopathy, 1.1%; hemophthalmia, 0.9%; neovascular glaucoma, 1.1%; cataract, 0.63%. The incidence of radiation complications increases with increase of the applicator power and rigidity of exposure. Computer planning of brachytherapy with due consideration for the size of the tumor and the eye and localization of the neoplasm for each case will help decrease the incidence of complications.


Substrate specificity classes and the recognition signal for Salmonella type III flagellar export.
Most flagellar proteins of Salmonella are exported to their assembly destination via a specialized apparatus. This apparatus is a member of the type III superfamily, which is widely used for secretion of virulence factors by pathogenic bacteria. Extensive studies have been carried out on the export of several of the flagellar proteins, most notably the hook protein (FlgE), the hook-capping protein (FlgD), and the filament protein flagellin (FliC). This has led to the concept of two export specificity classes, the rod/hook type and the filament type. However, little direct experimental evidence has been available on the export properties of the basal-body rod proteins (FlgB, FlgC, FlgF, and FlgG), the putative MS ring-rod junction protein (FliE), or the muramidase and putative rod-capping protein (FlgJ). In this study, we have measured the amounts of these proteins exported before and after hook completion. Their amounts in the culture supernatant from a flgE mutant (which is still at the hook-type specificity stage) were much higher than those from a flgK mutant (which has advanced to the filament-type specificity stage), placing them in the same class as the hook-type proteins. Overproduction of FliE, FlgB, FlgC, FlgF, FlgG, or FlgJ caused inhibition of the motility of wild-type cells and inhibition of the export of the hook-capping protein FlgD. We also examined the question of whether export and translation are linked and found that all substrates tested could be exported after protein synthesis had been blocked by spectinomycin or chloramphenicol. We conclude that the amino acid sequence of these proteins suffices to mediate their recognition and export.


Porcine Babesiosis Caused by Babesia sp. Suis in a Pot-Bellied Pig in South Africa.
Babesiosis is a worldwide, tick-borne disease of economic importance in livestock caused by Babesia spp., which are hemoparasitic piroplasms that target the host erythrocytes. Cattle, dogs, small ruminants, and wild ruminants are the species most commonly affected, while in cats, horses, and pigs, it is less frequently reported. Although babesiosis has been observed worldwide, porcine babesiosis remains an uncommon disease with a very limited number of cases reported. Here, we describe a case in a 12-year old pot-bellied pig from South Africa that died after a history of anorexia and reluctance to rise for 2 days. A complete necropsy, blood smear cytology, reverse line blot (RLB) hybridization and 18S rRNA sequencing were performed. Numerous Babesia spp. hemoparasites and a moderate regenerative anemia were identified on blood smear, and a urine dipstick test yielded 4+ heme. Diffuse icterus and splenomegaly were observed upon gross examination. Histopathology revealed hemoglobin casts within renal tubules and collecting ducts, pulmonary edema, splenic congestion, and intrahepatic cholestasis. BLASTN homology of the 18SrRNA sequence revealed a 100% identity to the published sequence of Babesia sp. Suis isolated from pigs in Italy. This case of babesiosis in a pig highlights the clinical manifestations and gross and pathological findings of porcine babesiosis.


Brief Report: Risk-Aversion and Rationality in Autism Spectrum Disorders.
Risk-aversion and rationality have both been highlighted as core features of decision making in individuals with Autism Spectrum Disorders (ASD). This study tested whether risk-aversion is related to rational decision-making in ASD individuals. ASD and matched control adults completed a decision-making task that discriminated between the use of risk-averse and rational strategies. Results showed that overall, ASD participants were more risk-averse than control participants. Specifically, both groups made similar choices when risk-aversion was the less rational strategy but ASD participants chose more rational options than control participants when risk-aversion was the most rational strategy. This study confirmed that risk-aversion is a core feature of ASD and revealed that ASD individuals can switch their decision-making strategy adaptively to avoid negative consequences.