[Papillary thyroid carcinoma: clinical manifestations, recurrences and prognosis].
Papillary carcinoma was detected in 2512 cases out of 3048 patients with differentiated thyroid carcinoma who underwent surgery during a 61-year period at the Mayo Clinic. The clinical picture of papillary carcinoma was shown to be interrelated with the appearance of recurrences, metastases and with prognosis for life. Lethality and survival were estimated within 5, 10, 20, 30 and 40 years depending on the stage of the disease that allowed a separation and comparison of groups of low and high risk in connection with the further prognosis. Median follow-up was 14 +/- 0.9 years and the longest follow-up was 60 years. It was shown that if the tumor was confined to the neck and the tumor was grossly resected the survival rate did not differ from the level predicted by an actuarial curve, and the appearance of metastases in regional lymph nodes represented no real threat in low-risk patients.


Status of Selinum spp. L. a Himalayan Medicinal Plant in India: A Review of Its Pharmacology, Phytochemistry and Traditional Uses.
There is a growing trend of herbal medicines in India as well as other parts of the world. The use of herbal medicines alone or alongside prescription drugs for disease management is quite common now. We hereby carry out a review of dominant species of Selinum mainly S. vaginatum C.B. Clarke and S. wallichianum (DC.) Raizada & H.O. Saxena which are potent source of herbal medicine and whose potential is still not exploited. They are found in Northern Himalayas in the states of Kashmir, Himachal Pradesh and Uttarakhand in India, and also distributed in adjoining countries like China, Nepal, and West Pakistan. It is a perennial, primitive, high altitude, therapeutic herbal plant belonging to family Apiaceae (Umbelliferae) traditionally used for various diseases like epilepsy, seizures, and hysteria, etc. The aim of this review was to provide a summary on botanical characterization, traditional uses, phytochemistry and pharmacological activity of Selinum spp. The available information will be further tapped for commercial use of this plant without endangering its status. Based on the available evidence on the species pharmacology and chemistry, we highlight in which their therapeutic potential can be properly harnessed for possible integration into the country's healthcare system and be further passed on globally.


Brief treatment of co-occurring post-traumatic stress and depressive symptoms by use of accelerated resolution therapy(®).
This uncontrolled prospective cohort study evaluated the use of accelerated resolution therapy (ART) for treatment of comorbid symptoms of post-traumatic stress disorder (PTSD) and major depressive disorder. Twenty-eight adult subjects, mean age of 41 years (79% female, 36% Hispanic), received a mean of 3.7 ± 1.1 ART treatment sessions (range 1-5). ART is a new exposure-based psychotherapy that makes use of eye movements. Subjects completed a range of self-report psychological measures before and after treatment with ART including the 17-item PCL-C checklist (symptoms of PTSD) and 20-item Center for Epidemiologic Studies Depression Scale (CES-D). For the PCL-C, the pre-ART mean (±standard deviation) was 62.5 (8.8) with mean reductions of -29.6 (12.5), -30.1 (13.1), and -31.4 (14.04) at post-ART, 2-month, and 4-month follow-up, respectively (p < 0.0001 for comparisons to pre-ART score). Compared to pre-ART status, this corresponded to standardized effect sizes of 2.37, 2.30, and 3.01, respectively. For the CES-D, the pre-ART mean was 35.1 (8.8) with mean reductions of -20.6 (11.0), -18.1 (11.5), and -15.6 (14.4) at post-ART, 2-month, and 4-month follow-up, respectively (p ≤ 0.0001 compared to Pre-ART score). This corresponded to standardized effect sizes of 1.88, 1.58, and 1.09, respectively. Strong correlations were observed at 2-month and 4-month follow-up for post-treatment changes in PTSD and depression symptom scores (r = 0.79, r = 0.76, respectively, p ≤ 0.0002). No serious treatment-related adverse effects were reported. In summary, ART appears to be a promising brief, safe, and effective treatment for adults with clinically significant comorbid symptoms of PTSD and depression. Future controlled and mechanistic studies with this emerging therapy are warranted, particularly given its short treatment duration, and in light of current heightened emphasis on health care cost constraints.


Demographic and attitudinal determinants of protective behaviours during a pandemic: a review.
A new strain of H1N1 influenza, also known as swine flu was confirmed in the UK in May 2009 and has spread to over 100 countries around the world causing the World Health Organization to declare a global flu pandemic. The primary objectives of this review are to identify the key demographic and attitudinal determinants of three types of protective behaviour during a pandemic: preventive, avoidant, and management of illness behaviours, in order to describe conceptual frameworks in which to better understand these behaviours and to inform future communications and interventions in the current outbreak of swine flu and subsequent influenza pandemics. Web of Science and PubMed databases were searched for references to papers on severe acute respiratory syndrome, avian influenza/flu, H5N1, swine influenza/flu, H1N1, and pandemics. Forward searching of the identified references was also carried out. In addition, references were gleaned from an expert panel of the Behaviour and Communications sub-group of the UK Scientific Pandemic Influenza Advisory Group. Papers were included if they reported associations between demographic factors, attitudes, and a behavioural measure (reported, intended, or actual behaviour). Twenty-six papers were identified that met the study inclusion criteria. The studies were of variable quality and most lacked an explicit theoretical framework. Most were cross-sectional in design and therefore not predictive over time. The research shows that there are demographic differences in behaviour: being older, female and more educated, or non-White, is associated with a higher chance of adopting the behaviours. There is evidence that greater levels of perceived susceptibility to and perceived severity of the diseases and greater belief in the effectiveness of recommended behaviours to protect against the disease are important predictors of behaviour. There is also evidence that greater levels of state anxiety and greater trust in authorities are associated with behaviour. The findings from this review can be broadly explained by theories of health behaviour. However, theoretically driven prospective studies are required to further clarify the relationship between demographic factors, attitudes, and behaviour. The findings suggest that intervention studies and communication strategies should focus on particular demographic groups and on raising levels of perceived threat of the pandemic disease and belief in the effectiveness of measures designed to protect against it.


Carotenoid and Tocochromanol Profiles during Kernel Development Make Consumption of Biofortified "Fresh" Maize an Option to Improve Micronutrient Nutrition.
Biofortification is a strategy to reduce micronutrient malnutrition. The aim of this study was to investigate whether consumption of biofortified fresh maize can supply nutritionally meaningful amounts of provitamin A carotenoids (PVA), zinc, lysine, and tryptophan. The accumulation patterns for PVA and tocochromanol compounds in developing grain of 23 PVA hybrids was studied, and nutritionally meaningful amounts of those compounds were found in grain by milk stage, when fresh maize is eaten. The highest PVA and tocochromanol accumulation occurred by physiological maturity. The percent apparent retention in boiled fresh maize was 92%, 117%, 99%, and 66% for PVA, zinc, lysine, and tryptophan, respectively. Consumption of 0.5 to 2 ears of fresh maize daily could supply 33-62.2%, 11-24% and more than 85% of the estimated average requirement of PVA, tryptophan, and zinc, respectively. The results indicate that eating biofortified fresh maize can contribute to improved micronutrient nutrition.


Efficient Wideband Numerical Simulations for Nanostructures Employing a Drude-Critical Points (DCP) Dispersive Model.
A highly efficient numerical approach for simulating the wideband optical response of nano-architectures comprised of Drude-Critical Points (DCP) media (e.g., gold and silver) is proposed and validated through comparing with commercial computational software. The kernel of this algorithm is the subdomain level discontinuous Galerkin time domain (DGTD) method, which can be viewed as a hybrid of the spectral-element time-domain method (SETD) and the finite-element time-domain (FETD) method. An hp-refinement technique is applied to decrease the Degrees-of-Freedom (DoFs) and computational requirements. The collocated E-J scheme facilitates solving the auxiliary equations by converting the inversions of matrices to simpler vector manipulations. A new hybrid time stepping approach, which couples the Runge-Kutta and Newmark methods, is proposed to solve the temporal auxiliary differential equations (ADEs) with a high degree of efficiency. The advantages of this new approach, in terms of computational resource overhead and accuracy, are validated through comparison with well-known commercial software for three diverse cases, which cover both near-field and far-field properties with plane wave and lumped port sources. The presented work provides the missing link between DCP dispersive models and FETD and/or SETD based algorithms. It is a competitive candidate for numerically studying the wideband plasmonic properties of DCP media.


Synthesis of non-natural sequence-encoded polymers using phosphoramidite chemistry.
Sequence-defined non-natural polyphosphates were prepared using iterative phosphoramidite protocols on a polystyrene solid support. Three monomers were used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dipropargyl-propyl) diisopropylphosphoramidite (1'). Phosphoramidite coupling steps allowed rapid synthesis of homopolymers and copolymers. In particular, the comonomers (0, 1), (0, 1'), and (1, 1') were used to synthesize sequence-encoded copolymers. It was found that long encoded sequences could be easily built using phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion chromatography analyses indicated the formation of monodisperse polymers with controlled comonomer sequences. The polymers obtained with the comonomers (0, 1') and (1, 1') were also modified by copper-catalyzed azide-alkyne cycloaddition with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. (1)H and (13)C NMR analysis evidenced quantitative modification of the alkyne side-chains of the monodisperse copolymers. Thus, the molecular structure of the coding monomer units can be easily varied after polymerization. Altogether, the present results open up interesting avenues for the design of information-containing macromolecules.


Impact of personality and depression on quality of life in patients with severe haemophilia in Korea.
Among reports on the psychological variables that influence quality of life (QoL), none has addressed the impact of personality on QoL in patients with haemophilia. We investigated the impact of psychosocial variables including depression and personality on QoL in patients with severe haemophilia. A cross-sectional survey examining psychosocial and clinical characteristics was administered to Korean patients with severe haemophilia. Personality traits were ascertained using the 10-item short version of the Big Five Inventory, which quantifies five personality dimensions including extraversion, agreeableness, conscientiousness, neuroticism and openness. Patient QoL and depression were measured by the World Health Organization Quality of Life-abbreviated version and the Beck Depression Inventory (BDI) respectively. Multivariate linear regression analyses were used for each domain to determine the impact of psychological variables on QoL. Of the 53 subjects who consented to participate, 46 cases were finally analysed. Multivariate linear regression analyses demonstrated that agreeableness was significantly and positively associated with the physical health domain of QoL. Openness was independently and positively associated with the psychological and social relationship domains of QoL. BDI scores were significantly and negatively associated with all four domains of the QoL. Persistent pain and joint impairment showed strong associations with all domains in a univariate analysis, but the impact was attenuated after adjusting for psychosocial variables. Personality and depression had strong impacts on QoL independent of physical status in patients with severe haemophilia. Providing psychological screening and intervention are recommended for enhancing QoL in patients with severe haemophilia.


Autonomous driving in urban environments: approaches, lessons and challenges.
The development of autonomous vehicles for urban driving has seen rapid progress in the past 30 years. This paper provides a summary of the current state of the art in autonomous driving in urban environments, based primarily on the experiences of the authors in the 2007 DARPA Urban Challenge (DUC). The paper briefly summarizes the approaches that different teams used in the DUC, with the goal of describing some of the challenges that the teams faced in driving in urban environments. The paper also highlights the long-term research challenges that must be overcome in order to enable autonomous driving and points to opportunities for new technologies to be applied in improving vehicle safety, exploiting intelligent road infrastructure and enabling robotic vehicles operating in human environments.


Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF.
Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system, regulates numerous inflammatory-proliferative responses in vascular wall cells and is thus involved in atherosclerosis. We have previously shown that pigment epithelium-derived factor (PEDF) inhibits advanced glycation end-product-induced pericyte apoptosis, thereby exerting beneficial effects on diabetic retinopathy. However, a role for PEDF in vascular inflammation and atherosclerosis remains to be elucidated. In this study, we have examined whether PEDF inhibits the Ang-II-induced endothelial cell (EC) activation in vitro and the way that it might achieve this effect. Ang II significantly induced redox-sensitive transcriptional factor NF-kappaB activation and subsequent monocyte chemoattractant protein-1 expression in human umbilical vein ECs (HUVEC), both of which were completely inhibited by PEDF or the anti-oxidant N-acetylcysteine. PEDF or diphenylene iodonium, an inhibitor of NADPH oxidase, inhibited Ang-II-induced intracellular reactive oxygen species (ROS) generation in HUVEC. Furthermore, PEDF inhibited Ang-II-induced up-regulation of mRNA levels of p22phox, Nox4, and gp91phox/Nox2, which are membrane components of NADPH oxidase, and its enzymatic activity in HUVEC. Antisense, but not sense, DNAs against p22phox, Nox4, or gp91phox/Nox2 were found significantly to inhibit Ang-II-induced ROS generation in HUVEC. These results demonstrate that PEDF inhibits Ang-II-induced EC activation by suppressing NADPH-oxidase-mediated ROS generation and that PEDF may play a protective role in the development and progression of atherosclerosis.


Phylogenetic placement of the spider genus Nephila (Araneae: Araneoidea) inferred from rRNA and MaSp1 gene sequences.
The family status of the genus Nephila, which belongs to Tetragnathidae currently but Araneidae formerly, was reexamined based on molecular phylogenetic analyses. In the present study, 12S and 18S rRNA gene fragments of eight species of spiders were amplified and sequenced. In addition, 3'-end partial cDNA of major ampullate spidroin-1 (MaSp1) gene of Argiope amoena was cloned and sequenced, and the 3'-end non-repetitive region's cDNA sequence of MaSp1 gene and the predicted amino acid sequence of C-terminal non-repetitive region of MaSp1 were aligned with some previously known sequences. The resulting phylogeny showed that Araneidae and Tetragnathidae are not a sister group in the superfamily Araneoidea, and the genus Nephila is closer to the genera of the family Araneidae rather than to those of Tetragnathidae. We suggest that the genus Nephila should be transferred back to Araneidae. Or the subfamily Nephilinae might be elevated to family level after it was redefined and redelimited. Furthermore, the study showed that 3'-end non-repetitive region's cDNA sequence of MaSp1 gene and C-terminal non-repetitive region's amino acid sequence of MaSp1 are useful molecular markers for phylogenetic analysis of spiders.


Prognostic Value of Combined Radiomic Features from Follow-Up DWI and T2-FLAIR in Acute Ischemic Stroke.
The biological pathways involved in lesion formation after an acute ischemic stroke (AIS) are poorly understood. Despite successful reperfusion treatment, up to two thirds of patients with large vessel occlusion remain functionally dependent. Imaging characteristics extracted from DWI and T2-FLAIR follow-up MR sequences could aid in providing a better understanding of the lesion constituents. We built a fully automated pipeline based on a tree ensemble machine learning model to predict poor long-term functional outcome in patients from the MR CLEAN-NO IV trial. Several feature sets were compared, considering only imaging, only clinical, or both types of features. Nested cross-validation with grid search and a feature selection procedure based on SHapley Additive exPlanations (SHAP) was used to train and validate the models. Considering features from both imaging modalities in combination with clinical characteristics led to the best prognostic model (AUC = 0.85, 95%CI [0.81, 0.89]). Moreover, SHAP values showed that imaging features from both sequences have a relevant impact on the final classification, with texture heterogeneity being the most predictive imaging biomarker. This study suggests the prognostic value of both DWI and T2-FLAIR follow-up sequences for AIS patients. If combined with clinical characteristics, they could lead to better understanding of lesion pathophysiology and improved long-term functional outcome prediction.


Genetic parameter estimates for bull prolificacy and its relationship with scrotal circumference in a commercial beef cattle population.
The commercial beef cattle industry relies heavily on the use of natural service sires. When artificial insemination is deemed difficult to implement, multisire breeding pastures are used to increase reproductive rates in large breeding herds or to safe-guard against bull injury during the breeding season. Although each bull might be given an equal opportunity to produce offspring, evidence suggest that there is substantial variation in the number of calves sired by each bull in a breeding pasture. With the use of DNA-based paternity testing, correctly assigning calves to their respective sires in multisire pastures is possible and presents an opportunity to investigate the degree to which this trait complex is under genetic control. Field data from a large commercial ranch was used to estimate genetic parameters for calf count (CC; 574 records from 443 sires) and yearling scrotal circumference (SC; n = 1961) using univariate and bivariate animal models. Calf counts averaged 12.2 ± 10.7 and SC averaged 35.4 ± 2.30 cm. Bulls had an average of 1.30 records and there were 23.9 ± 11.1 bulls per contemporary group. The model for CC included fixed effects of age during the breeding season (in years) and contemporary group (concatenation of breeding pasture and year). Random effects included additive genetic and permanent environmental effects, and a residual. The model for SC included fixed effects of age (in days) and contemporary group (concatenation of month and year of measurement). Random effects included an additive genetic effect and a residual. Univariate model heritability estimates for CC and SC were 0.178 ± 0.142 and 0.455 ± 0.072, respectively. Similarly, the bivariate model resulted in heritability estimates for CC and SC of 0.184 ± 0.142 and 0.457 ± 0.072, respectively. Repeatability estimates for CC from univariate and bivariate models were 0.315 ± 0.080 and 0.317 ± 0.080, respectively. The estimate of genetic correlation between CC and SC was 0.268 ± 0.274. Heritability estimates suggest that both CC and SC would respond favorably to selection. Moreover, CC is lowly repeatable and although favorably correlated, SC appears to be weakly associated with CC.


Heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is not only a common but also a potentially serious drug adverse effect. Unlike other drug-induced thrombocytopenias, HIT does not usually cause bleeding, but instead causes thrombosis. Thrombosis in HIT can lead to limb gangrene (requiring leg amputation) or even death. HIT is mediated by an antibody that recognizes an epitope on the platelet factor 4 (PF4)-heparin complex. The antibody-PF4-heparin complex binds to FcgammaRII receptors on the platelet surface and cross-links the receptors. This induces intense platelet activation and platelet aggregation, and simultaneously activates blood-coagulation pathways. These changes are probably the basis of the thrombotic events in HIT. Diagnosis of HIT should be made mainly on clinical criteria but should be confirmed whenever possible by laboratory tests, particularly in patients with comorbid conditions, in whom the diagnosis of HIT cannot be made with certainty without testing. The tests for HIT antibodies are either immunoassays (e.g. ELISA), or functional tests, (e.g. 14C-serotonin release assay). Once a clinical diagnosis of HIT is made, heparin should be ceased immediately and treatment with an alternative anticoagulant (such as danaparoid, r-hirudin or argatroban) commenced. This should continue for at least 5 days unless the diagnosis of HIT is subsequently proven to be incorrect. Warfarin should also be commenced when the patient is clinically stable and thrombosis is under control. There should be an overlap of a few days between warfarin and the alternative anticoagulant therapy.


Transformation-specific cell killing by a cancer-associated galactosyltransferase acceptor and cellular binding.
Cancer-associated galactosyltransferase acceptor (CAGA glycoprotein), a small glycoprotein purified from human malignant effusion that selectively kills transformed cells, was tritiated by reductive methylation in the presence of NaB(3)H(4). CAGA-glycoprotein-sensitive cells (baby-hamster kidney cells transformed by polyoma virus and chick-embryo fibroblasts infected with Ts68 temperature-sensitive mutant of Rous sarcoma virus grown at 37 degrees C, the permissive temperature) bound 3-5-fold more (3)H-labelled CAGA glycoprotein than did their CAGA-glycoprotein-resistant non-transformed counterparts. The Rous-sarcoma-virus-infected chick-embryo fibroblasts grown at non-permissive temperature (41 degrees C) bound an intermediate amount of (3)H-labelled CAGA glycoprotein; however, this intermediate amount appeared to be sufficient to induce inhibition of cell growth when the infected chick-embryo fibroblasts treated at 41 degrees C were switched to 37 degrees C. Binding of (3)H-labelled CAGA glycoprotein was time- and temperature-dependent and was not inhibited by monosaccharide. Binding was completely inhibited by the oligosaccharide liberated by endoglucosaminidase H treatment or by exhaustive Pronase digestion of intact CAGA glycoprotein. However, the isolated oligosaccharide failed to demonstrate the growth-inhibition characteristics of the intact glycopeptide. Binding of (3)H-labelled CAGA glycoprotein was unaffected by co-incubation with the peptide core released by endoglucosaminidase H treatment. (3)H-labelled CAGA glycoprotein bound to intact cells could be removed by trypsin treatment up to 4h after addition of the glycoprotein but not thereafter. This time course paralleled the decreasing reversibility of growth inhibition. However, all (3)H-labelled CAGA glycoprotein was found in the supernatant when cells were first disrupted by sonication followed by trypsin treatment for up to 12h. (3)H-labelled CAGA glycoprotein linked to Sepharose 4B failed to cause growth inhibition in CAGA-glycoprotein-sensitive cells. These findings suggest that binding of CAGA glycoprotein occurs via its oligosaccharide moiety. Binding appears to be a necessary but not sufficient condition to induce cell killing. Growth inhibition appears to depend on internalization of the glycoprotein and the presence of a transformation-specific cell process.


Identification of Fatigue and Sleepiness in Immune and Neurodegenerative Disorders from Measures of Real-World Gait Variability.
Current assessments of fatigue and sleepiness rely on patient reported outcomes (PROs), which are subjective and prone to recall bias. The current study investigated the use of gait variability in the "real world" to identify patient fatigue and daytime sleepiness. Inertial measurement units were worn on the lower backs of 159 participants (117 with six different immune and neurodegenerative disorders and 42 healthy controls) for up to 20 days, whom completed regular PROs. To address walking bouts that were short and sparse, four feature groups were considered: sequence-independent variability (SIV), sequence-dependant variability (SDV), padded SDV (PSDV), and typical gait variability (TGV) measures. These gait variability measures were extracted from step, stride, stance, and swing time, step length, and step velocity. These different approaches were compared using correlations and four machine learning classifiers to separate low/high fatigue and sleepiness.Most balanced accuracies were above 50%, the highest was 57.04% from TGV measures. The strongest correlation was 0.262 from an SDV feature against sleepiness. Overall, TGV measures had lower correlations and classification accuracies.Identifying fatigue or sleepiness from gait variability is extremely complex and requires more investigation with a larger data set, but these measures have shown performances that could contribute to a larger feature set.Clinical relevance- Gait variability has been repeatedly used to assess fatigue in the lab. The current study, however, explores gait variability for fatigue and daytime sleepiness in real-world scenarios with multiple gait-impacted disorders.


Bright Mid-Wave Infrared Resonant-Cavity Light-Emitting Diodes Based on Black Phosphorus.
The mid-wave infrared (MWIR) wavelength range plays a central role in a variety of applications, including optical gas sensing, industrial process control, spectroscopy, and infrared (IR) countermeasures. Among the MWIR light sources, light-emitting diodes (LEDs) have the advantages of simple design, room-temperature operation, and low cost. Owing to the low Auger recombination at high carrier densities and direct bandgap of black phosphorus (bP), it can serve as a high quantum efficiency emitting layer in LEDs. In this work, we demonstrate bP-LEDs exhibiting high external quantum efficiencies and wall-plug efficiencies of up to 4.43 and 1.78%, respectively. This is achieved by integrating the device with an Al2O3/Au optical cavity, which enhances the emission efficiency, and a thin transparent conducing oxide [indium tin oxide (ITO)] layer, which reduces the parasitic resistance, both resulting in order of magnitude improvements to performance.


Respiratory insufficiency associated with acute intermittent porphyria.
Acute intermittent porphyria (AIP) is a disease that may present with gastrointestinal, psychiatric, or neurologic symptoms. We describe two patients in whom AIP was first diagnosed during episodes of acute respiratory insufficiency. The biochemical defects, clinical presentations, pathophysiology, diagnostic criteria, and treatment of AIP are reviewed. We emphasize that AIP should be considered in the differential diagnosis of every patient with unexplained respiratory failure. Once considered, AIP is relatively simple to diagnose and specific therapeutic measures can be instituted.


Development of the middle ear in neonatal chinchillas. I. Birth to 14 days.
Measures of middle-ear function in humans show large differences among neonates, infants, and adults. In contrast, hearing sensitivity is essentially mature at birth. Hypotheses that have been proposed to explain the developmental changes in middle-ear function include: (i) contaminating effects of the immature neonatal ear-canal wall and (ii) persistent fetal tissue in the ear canal, tympanic membrane (TM), and middle-ear space. To better understand the relationships between middle-ear function, hearing sensitivity and the structure of the middle ear, 30 chinchillas, aged 1-14 days, were studied. Middle-ear function was assessed by multifrequency tympanometry with probe tones ranging from 226 to 2,000 Hz. Hearing sensitivity was measured by auditory brainstem response using clicks and 1, 2, 4, and 8 kHz tone bursts. Structural characteristics were analyzed from temporal bone histologic preparations. At all frequencies, the acoustic admittance of the neonatal car is very low and tympanometric patterns are complex and irregular, compared to adult animals. The admittance is essentially constant from 1 to 14 days, indicating that developmental changes occur over a much wider age span than that investigated here. Hearing sensitivity of the chinchilla appears to be mature at birth. Histologic analysis indicated that there were no age-related changes in TM thickness, TM diameter, distance from TM to promontory, and stapes footplate diameter. There were small increases in bone thickness, middle-ear area, mastoid bulla area, and in the perimeters of the middle ear and mastoid bulla. There were no significant amounts of loose mesenchyme or other fetal tissue in the middle-ear space.


BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism.
BRCA-1 is a nuclear protein involved in DNA repair, transcriptional regulation, and cell cycle control. Its involvement in other cellular processes has been described. Here, we aimed to investigate the role of BRCA-1 in macrophages M(LPS), M(IL-4), and tumor cell-induced differentiation. We used siRNAs to knockdown BRCA-1 in RAW 264.7 macrophages exposed to LPS, IL-4, and C6 glioma cells conditioned medium (CMC6), and evaluated macrophage differentiation markers and functional phagocytic activity as well as DNA damage and cell survival in the presence and absence of BRCA-1. LPS and CMC6, but not by IL-4, increased DNA damage in macrophages, and this effect was more pronounced in BRCA-1-depleted cells, including M(IL-4). BRCA-1 depletion impaired expression of pro-inflammatory cytokines, TNF-α and IL-6, and reduced the phagocytic activity of macrophages in response to LPS. In CMC6-induced differentiation, BRCA-1 knockdown inhibited TNF-α and IL-6 expression which was accompanied by upregulation of the anti-inflammatory markers IL-10 and TGF-β and reduced phagocytosis. In contrast, M(IL-4) phenotype was not affected by BRCA-1 status. Molecular docking predicted that the conserved BRCA-1 domain BRCT can interact with the p65 subunit of NF-κB. Immunofluorescence assays showed that BRCA-1 and p65 co-localize in the nucleus of LPS-treated macrophages and reporter gene assay showed that depletion of BRCA-1 decreased LPS and CMC6-induced NF-κB transactivation. IL-4 had no effect upon NF-κB. Taken together, our findings suggest a role of BRCA-1 in macrophage differentiation and phagocytosis induced by LPS and tumor cells secretoma, but not IL-4, in a mechanism associated with inhibition of NF-κB.


Arthroscopic removal of a plastic soft drink bottle cap in the knee: a case report.
We report a rare case of late knee locking after an open knee injury in a polytrauma patient with a pelvic fracture and a contralateral femoral artery injury. Once the life and limb threatening injuries were addressed, debridement and washout of the knee wound was performed. X-rays and subsequent CT revealed only an undisplaced patella fracture. The patient presented 6 months later to a knee surgeon with recurrent locking. An arthroscopy was performed and a 10 mm plastic soft drink bottle cap was retrieved leading to the immediate resolution of symptoms without complications.Open knee injuries require thorough debridement washout and joint assessment. Late locking should raise the suspicion of an intra-articular loose or foreign body. Arthroscopy is an excellent first line tool in the diagnosis and late management of this unusual problem.


Adapting the Quality Maternal and Newborn Care (QMNC) Framework to evaluate models of antenatal care: A pilot study.
Recent evidence indicates that continuity models of maternity care result in improved clinical and psychosocial outcomes, but their causal mechanisms are poorly understood. The recent Lancet Series on Midwifery's Quality Maternal and Newborn Care Framework describes five components of quality care and their associated characteristics. As an initial step in developing this Framework into an evaluation toolkit, we transformed its components and characteristics into a topic guide to assess stakeholder perceptions and experiences of care provided and received. The main purpose of this study was to assess the feasibility of this process. We conducted twelve focus groups in two Scottish health board areas with 13 pregnant women, 18 new mothers, 26 midwives and 12 obstetricians who had experience of a range of different models of maternity care. Transcripts were analysed using a six-phase approach of thematic analysis. We mapped the identified themes and sub-themes back to the Framework. The emerging themes and sub-themes demonstrated the feasibility of using the QMNC framework as a data collection tool, and as a lens for analysing the data. Of the four emerging themes, only Organisation Culture / Work Structure' mapped directly to a single Framework component. The others-'Relationships'; 'Information and support'; and 'Uncertainty'-mapped to between two and five components, illustrating the interconnectedness of the Framework's components. Some negative sub-themes mirrored positive Framework characteristics of care. Some re-phrasing and re-ordering of the topic guides in later focus groups ensured we could cover all aspects of the Framework adequately. Adapting the Quality Maternal and Newborn Care Framework enabled us to focus on aspects of care which worked well and which didn't work well for these key stakeholders. Identifying 'what works for whom and why' in different models of care is a necessary step in reinforcing and replicating the most effective models of care.


The complement inhibitors Crry and factor H are critical for preventing autologous complement activation on renal tubular epithelial cells.
Congenital and acquired deficiencies of complement regulatory proteins are associated with pathologic complement activation in several renal diseases. To elucidate the mechanisms by which renal tubular epithelial cells (TECs) control the complement system, we examined the expression of complement regulatory proteins by the cells. We found that Crry is the only membrane-bound complement regulator expressed by murine TECs, and its expression is concentrated on the basolateral surface. Consistent with the polarized localization of Crry, less complement activation was observed when the basolateral surface of TECs was exposed to serum than when the apical surface was exposed. Furthermore, greater complement activation occurred when the basolateral surface of TECs from Crry(-/-)fB(-/-) mice was exposed to normal serum compared with TECs from wild-type mice. Complement activation on the apical and basolateral surfaces was also greater when factor H, an alternative pathway regulatory protein found in serum, was blocked from interacting with the cells. Finally, we injected Crry(-/-)fB(-/-) and Crry(+/+)fB(-/-) mice with purified factor B (an essential protein of the alternative pathway). Spontaneous complement activation was seen on the tubules of Crry(-/-)fB(-/-) mice after injection with factor B, and the mice developed acute tubular injury. These studies indicate that factor H and Crry regulate complement activation on the basolateral surface of TECs and that factor H regulates complement activation on the apical surface. However, congenital deficiency of Crry or reduced expression of the protein on the basolateral surface of injured cells permits spontaneous complement activation and tubular injury.


Field-scale application of oily food waste and nitrogen fertilizer requirements of corn at different landscape positions.
Oily food waste (FOG; fat + oil + greases) containing high concentrations of fat, oil and grease is produced by the food service, production, and processing industries. It has a high C to N ratio (90:1) and can recycle soil available N through immobilization and remineralization during its decomposition. Experiments were conducted at a farm (Hillsburg fine sandy loam; Typic Hapludalf) having rolling topography (5 and 9% slope) during 1995 and 1996. Objectives of this study were to (i) examine the variability of available N and corn (Zea mays L.) grain yield at different landscape positions of FOG-amended fields and (ii) determine whether N fertilizer management could be improved by considering the spatial variability of soil NO(3)-N at different landscape positions in FOG-amended fields. A spatial and temporal variability in soil NO(3)-N was observed during both years. Corn grain yields at all N fertilizer application rates were affected by slope position and followed the pattern: lower > upper > or = middle. Nitrogen fertilizer requirements for corn production in conjunction with FOG management were also affected by slope position. Essentially no additional fertilizer N was required for corn production at the lower landscape position. It was estimated that site-specific fertilizer N management on FOG-amended fields could result in an average savings of 51 and 63 kg N ha(-1) (with a potential economical savings of US 42 dollars and US 52 dollars ha(-1)) during 1995 and 1996, respectively.


Interfractional Rectal Displacement Requiring Repeated Precaution Did Not Correlate to Biochemical Control and Rectal Toxicity in Patients with Prostate Cancer Treated with Image-guided Intensity-modulated Radiation Therapy.
To investigate the correlation between frequency of action level of interfractional rectal displacement requiring repeated precaution in patients with prostate cancer and late toxicity from image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy. We examined 264 patients who underwent IG-IMRT during 2007-2011. Megavoltage computed tomographic (MVCT) images were acquired before radiation therapy and was examined with soft-tissue matching by comparing treatment planning images within 9,345 fractions. Displacement of the anterior rectal region larger than 5 mm, requiring repeated precaution, was defined as the level of rectal displacement requiring action (ARD). ARD was identified in 815 (7.7%) out of 9,345 fractions and at least once in 82% (216/264) of patients. The highest incidence of ARD (11%) was found during the initial week of treatment (first five and next five fractions), after which the incidence decreased to 6% (p<0.0001). Patients with lean body (lower body mass index (BMI) tended to have a higher incidence of ARD. We identified 16 (6%) cases of gastrointestinal toxicity and 12 (4.5%) genitourinary toxicities as a late adverse reaction (3 months or later after IG-IMRT). There was no correlation between ARD and late toxicity. Prostate-specific antigen (PSA) control was also similar (p=0.12) between those with ARD (96% at 5 year) and those without ARD (88%). ARD occurred predominantly in lean patients, during the initial week of treatment and became less likely over time. ARD was not correlated to late toxicity and PSA control, therefore, IG-IMRT technique was able to adequately control error due to interfractional prostate and rectal motion.


Severe bronchiectasis resulting from chronic bacterial bronchitis and bronchopneumonia in a jungle cat.
Bronchiectasis is irreversible bronchial dilation that can be congenital or acquired secondary to chronic airway obstruction. Feline bronchiectasis is rare and, to our knowledge, has not been reported previously in a non-domestic felid. An ~10-y-old female jungle cat (Felis chaus) was presented for evaluation of an abdominal mass and suspected pulmonary metastasis. The animal died during exploratory laparotomy and was submitted for postmortem examination. Gross examination revealed consolidation of the left caudal lung lobe and hila of the cranial lung lobes. Elsewhere in the lungs were several pale-yellow pleural foci of endogenous lipid pneumonia. On cut section, there was severe distension of bronchi with abundant white mucoid fluid. The remaining lung lobes were multifocally expanded by marginal emphysema. Histologically, ectatic bronchi, bronchioles, and fewer alveoli contained degenerate neutrophils, fibrin, and mucin (suppurative bronchopneumonia) with rare gram-negative bacteria. Aerobic culture yielded low growth of Proteus mirabilis and Escherichia coli. There was chronic bronchitis, marked by moderate bronchial gland hyperplasia, lymphoplasmacytic inflammation, and lymphoid hyperplasia. The palpated abdominal mass was a uterine endometrial polyp, which was considered an incidental, but novel, finding. Chronic bronchitis and bronchopneumonia should be considered as a cause of bronchiectasis and a differential diagnosis for respiratory disease in non-domestic felids.


Incidence and Risk Factors of Moderate to Severe Postoperative Pain Following the Placement of Primary and Secondary Orbital Implants: A Prospective Observational Study.
To prospectively explore the incidence and risk factors of moderate to severe pain after primary and secondary orbital implantation following evisceration or enucleation surgery. One hundred eighteen patients under general anesthesia for orbital implantation were enrolled in this study. In 91 patients, primary orbital implantation followed evisceration, and in 27 patients, the implantation was secondary after previous evisceration or enucleation surgery. Medical interventions for all participants were followed by standardized surgical, anesthetic, and analgesic protocols. Postoperative pain (POP) intensity was quantified by an 11-point numerical rating scale within 72 hours after the surgery, numerical rating scale ≥4 was considered moderate to severe POP. Multivariate logistic regression was utilized to identify the risk factors related to the development of POP. Thirty-five patients (29.7%) displayed moderate to severe POP, particularly within 6 to 24 hours after surgery, which peaked at 24 hours. Of these patients, 26 patients who were unable to tolerate the pain received additional doses of analgesics during in-hospital stay. Logistic regression model revealed that preoperative anxiety (odds ratios = 4.890; p = 0.002), congenital microphthalmia (odds ratios = 14.602; p = 0.038), and surgical time longer than 60 minutes (odds ratios = 5.586; p = 0.001) were significantly associated with moderate to severe POP after orbital implantation. Orbital implantation after evisceration or enucleation surgery is likely to cause moderate to severe pain intensity in the early postoperative period. Preoperative anxiety, prolonged surgical time, and congenital microphthalmia were the risk factors.


Fracture Prospectively Recorded From Prepuberty to Young Adulthood: Are They Markers of Peak Bone Mass and Strength in Males?
Fractures are common in otherwise healthy children and adolescents. They result from trauma of varying severity. Some reflect a greater skeletal fragility. A long-term implication of these fractures is their potentiality to predict adult bone fragility and increased risk of osteoporosis in later life. Using dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and micro-finite element analysis (μFEA) measurements, we previously found in 124 healthy females, followed from the age of 7.9 to 20.4 years, substantial deficits in both structural and strength components of the radius in the 42 girls who sustained a fracture during skeletal development. The objective of the current study was to assess in healthy males the relationship between fracture during development and expression of bone fragility in adulthood. A cohort of 152 boys was followed from age 7.4 ± 04 (mean ± SD) to 22.6 ± 0.7 years, ie, when peak bone mass is attained. Ninety participants (59.2%) sustained at least one fracture during growth, with highest incidence within the 10- to 13-year age range. Forearm was the most frequent site of fractures. At 7.4 years, several bone DXA-measured variables (areal bone mineral density [aBMD], bone mineral content [BMC]) were lower in the group with a positive fracture history during skeletal development compared with the non-fractured group. In contrast, at 22.6 years, no DXA-measured sites, including forearm, indicated a deficit in the fractured group compared with the non-fractured group. Likewise, at 22.6 years, neither HR-pQCT nor μFEA measurements, including distal radius, showed a structural or strength deficit in the fractured group. These results markedly contrast with a similar prospective study using the same technical and clinical design in 124 healthy girls. In conclusion, our prospective studies suggest a sex difference in the predictability of bone fragility in young adults who sustained fractures during childhood and adolescence. This difference might be related to the degree of trauma severity, usually lower in girls than in boys. © 2017 American Society for Bone and Mineral Research.


Art, science and mathematics: new approaches to animal health problems in the agricultural industry.
This article is about change; particularly the prospect for change in veterinary research during the last decade and a half of the 20th century. The title encapsulates the idea that veterinary medicine, if it is to be effective, periodically has to change its approach to solving animal health problems; that over the last century we have witnessed one major change, that from veterinary medicine as an art to veterinary medicine as a science, and that we are probably on the brink of another change, moving from a scientific or more correctly an experimental approach to a mathematical or observational approach.


A qualitative study of childhood cancer families' post-treatment needs and the impact of a community-based organization in a rural, socioeconomically disadvantaged, majority Hispanic/Latino region.
Individual- and population-level socioeconomic disadvantages contribute to unequal outcomes among childhood cancer survivors. Reducing health disparities requires understanding experiences of survivors from historically marginalized communities, including those with non-English language preference. We partnered with a community-based organization (CBO) serving families of children with cancer in a rural region in California with low socioeconomic status and majority Hispanic/Latino (H/L) residents. We interviewed English- and Spanish-speaking adolescent/young adult (AYA) childhood cancer survivors (≥15 years old, ≥5 years from diagnosis), parents, and CBO staff to evaluate post-treatment needs and impact of CBO support. Data were analyzed qualitatively using applied thematic analysis. Themes were refined through team discussions with our community partners. Twelve AYAs (11 H/L, 11 bilingual), 11 parents (eight H/L, seven non-English preferred), and seven CBO staff (five H/L, five bilingual) participated. AYAs (five female, seven male) were of median (min-max) age 20 (16-32) and 9 (5-19) years post diagnosis; parents (nine female, two male) were age 48 (40-60) and 14 (6-23) years post child's diagnosis. Themes included challenges navigating healthcare, communication barriers among the parent-AYA-clinician triad, and lasting effects of childhood cancer on family dynamics and mental health. Subthemes illustrated that language and rurality may contribute to health disparities. CBO support impacted families by serving as a safety-net, fostering community, and facilitating H/L families' communication. Childhood cancer has long-lasting effects on families, and those with non-English language preference face additional burdens. Community-based support buffers some of the negative effects of childhood cancer and may reduce disparities.


The relation of polymer structure of stent used in patients with acute coronary syndrome revascularized by stent implantation with long-term cardiovascular events.
Drug-eluting stents (DES) have revolutionized percutaneous coronary intervention (PCI) by improving event-free survival compared to older stent designs. However, early-generation DES with polymer matrixes have raised concerns regarding late stent thrombosis due to delayed vascular healing. To address these issues, biologically bioabsorbable polymer drug-eluting stents (BP-DES) and polymer-free drug-eluting stents (PF-DES) have been developed. The aim of the present study is to evaluate and compare the long-term effects of different stent platforms in patients with acute coronary syndrome (ACS) undergoing PCI. We conducted a retrospective, observational study involving 1192 ACS patients who underwent urgent PCI. Patients were treated with thin- strut DP-DES, ultra-thin strut BP-DES, or thin-strut PF-DES. The primary endpoint was a composite of cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (CITLR) at 12 months and 4 years. The baseline demographics and clinical characteristics of patients in the three stent subgroups were similar. No significant differences were observed in target lesion failure (TLF), cardiac mortality, TVMI, and stent thrombosis (ST) rates among the three subgroups at both 12 months and 4 years. However, beyond the first year, the rate of CITLR was significantly lower in the ultra-thin strut BP-DES subgroup compared to thin-strut DP-DES, suggesting potential long-term advantages of ultra-thin strut BP-DES. Additionally, both ultra-thin strut BP-DES and thin-strut PF-DES demonstrated lower ST rates after the first year compared to thin-strut DP-DES. Our study highlights the potential advantages of ultra-thin strut BP-DES in reducing CITLR rates in the long term, and both ultra-thin strut BP-DES and thin-strut PF-DES demonstrate lower rates of ST beyond the first year compared to thin-strut DP-DES. However, no significant differences were observed in overall TLF, cardiac mortality and TVMI rates among the three stent subgroups at both 12 months and 4 years.


[Sensitization study of oncological patients to bacterial allergens with the aid of the leukocyte migration inhibition reaction].
The results of studying sensitization of 88 patients with cancer (larynx, esophagus, ovaries) to 7 bacterial allergens (pathogenic and nonpathogenic staphylococcus, hemolytic streptococcus, catarrhal diplococcus, Proteus, Escherichia coli and blue pus bacilli) are reported. These bacilli are most frequently the cause of development of postoperative suppurations. The studies performed (before, during and after the combined therapy) indicated by leucocyte migration inhibition test that during the disease ad therapeutic course there occurs nonspecific sensitization of leucocytes to bacterial allergens which gradually disappears following termination of the therapy. Postoperatively, the sensitization offers grounds for the development of suppurative complications, the latter is associated with the enhanced inhibition of leucocytes migration by an allergen of that microbial species which caused the development of suppurative complications. Therefore, this test with a set of bacterial allergens may be used as a diagnostic adjunct early reveal the postoperative suppurations.


PET study of pointing with visual feedback of moving hands.
This study was conducted to determine where in the human brain visual feedback of hand movements is processed to allow accurate pointing. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H2 15O in nine normal volunteers while performing one control and two reaching tasks. In all tasks, visual stimuli were presented on a head mounted display (HMD). A target board was placed in front of the subjects bearing six red light-emitting diodes (LEDs) aligned on a circle with a green LED at its center. The center green LED and one of the six red LEDs, randomly selected, were repeatedly switched on and off, alternatively. In the control task, subjects were instructed to gaze at the lit LED. In the two reaching tasks, the reaching with visual feedback (RwithF) task and the reaching without visual feedback (RwithoutF) task, they had to point to the lit red LED with their right index fingers. In the RwithF task, their right hands were visible on the HMD before touching the target, whereas in the RwithoutF task, they were not visible. For each subject, subtraction images of each reaching task minus the control and the RwithF task minus the RwithoutF task were calculated after transformation of PET images into the standard brain shape with an adjustable computerized brain atlas. These subtraction rCBF images were then averaged among the subjects, and significant changes of rCBF were identified. Significant increases in rCBF not only in the RwithF task minus control image but also in the RwithF task minus the RwithoutF task image were observed in the supramarginal cortex, the premotor cortex and the posterior cingulate cortex of the left hemisphere, the caudate nucleus and the thalamus of the right hemisphere, and the right cerebellum and vermis. These results indicate that the supramarginal cortex, the premotor cortex, and the posterior cingulate cortex of the left hemisphere and the cerebellum are involved in integrating visual feedback of hand movements and execution of accurate pointing.


Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients.
The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro- and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSH-related antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.


Single-step assembly of homogenous lipid-polymeric and lipid-quantum dot nanoparticles enabled by microfluidic rapid mixing.
A key challenge in the synthesis of multicomponent nanoparticles (NPs) for therapy or diagnosis is obtaining reproducible monodisperse NPs with a minimum number of preparation steps. Here we report the use of microfluidic rapid mixing using hydrodynamic flow focusing in combination with passive mixing structures to realize the self-assembly of monodisperse lipid-polymer and lipid-quantum dot (QD) NPs in a single mixing step. These NPs are composed of a polymeric core for drug encapsulation or a QD core for imaging purposes, a hydrophilic polymeric shell, and a lipid monolayer at the interface of the core and the shell. In contrast to slow mixing of lipid and polymeric solutions, rapid mixing directly results in formation of homogeneous NPs with relatively narrow size distribution that obviates the need for subsequent thermal or mechanical agitation for homogenization. We identify rapid mixing conditions that result in formation of homogeneous NPs and show that self-assembly of polymeric core occurs independent of the lipid component, which only provides stability against aggregation over time and in the presence of high salt concentrations. Physicochemical properties of the NPs including size (35-180 nm) and zeta potential (-10 to +20 mV in PBS) are controlled by simply varying the composition and concentration of precursors. This method for preparation of hybrid NPs in a single mixing step may be useful for combinatorial synthesis of NPs with different properties for imaging and drug delivery applications.


Early discharge following uncomplicated appendicectomy in children.
This cohort evaluation investigated the discharge of 15 children within 12 to 24 hours following an uncomplicated appendicectomy who were subsequently supported by an outreach nurse. By monitoring the child's progress, providing the support the family was expected to require and offering professional back-up for any unforeseen problems the outreach nurse ensured the child's safety and improved quality of care after early discharge from the hospital. The pivotal importance of the outreach nursing input was demonstrated when the expected visit did not materialise for one child.


SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches.
Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species. SAM-VI aptamers selectively bind the cofactor SAM and strongly discriminate against SAH. The consensus sequence and structural model for SAM-VI share some features with the consensus model for the SAM-III riboswitch class, whose members are mainly found in lactic acid bacteria. However, there are sufficient differences between the two classes such that current bioinformatics methods separately cluster representatives of the two motifs. These findings highlight the abundance of RNA structures that can form to selectively recognize SAM, and showcase the ability of RNA to utilize diverse strategies to perform similar biological functions.


Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages.
Inflammation appears to have a major role in the development of atherosclerotic lesions affecting native and transplanted coronary arteries. The subsequent risk of plaque rupture and acute ischemic events correlates with the degree of inflammation and may be modified by aspirin, an anti-inflammatory cyclooxygenase inhibitor. Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) are involved in the inflammatory response via the rapid and exaggerated production of prostanoids and nitric oxide, both of which may have proatherosclerotic effects. These effects may be mediated by the formation of peroxynitrite in the case of nitric oxide and involve "cross talk" between the two enzyme systems. This study aimed to investigate native and transplant atherosclerosis for the presence and distribution of Cox-2 and iNOS. Immunocytochemical studies were performed on atherosclerotic lesions from patients with native (n=12) and transplant (n=5) coronary disease by using antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of peroxynitrite production). Control tissue was obtained from unused donor hearts and at the time of autopsy. Cox-2 and iNOS colocalized predominantly in macrophages/foam cells in both types of atherosclerosis. Cox-2 expression was also detected in medial smooth muscle cells and endothelial cells, including those of the vasa vasorum. Nitrotyrosine was found in the same distribution as that of iNOS and was colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native and transplant atherosclerosis, possibly allowing for interaction between the enzymes and suggesting an alternative mechanism for the benefits of aspirin via inhibition of Cox-2 activity.


Where we've come from, where we might go.
The paper reviews 50 years of research in health sciences education and identifies several recurring controversies-formative versus summative assessment, high and low fidelity simulation, expertise as knowledge versus skills, and the impact of teaching versus curriculum. I then look at the role these may play in the current situation where COVID has necessitated rapid change to distance learning. I then posit an essential role for research in teaching and learning, using multiple methods from qualitative to neuropsychological to better understand the dimensions of effective teaching. The ultimate goal is to operationalize these findings in creation of distance learning modules.


Analysing experienced and inexperienced cyclists' attentional focus and self-regulatory strategies during varying intensities of fixed perceived effort cycling: A mixed method study.
Using a think aloud approach during fixed perceived effort exercise is a unique method to explore the decision-making processes that guide the self-regulation of perceived effort during endurance-based activity. In a two-part study, authors investigated the attentional focus and self-regulatory strategies associated with: Part A - perceived effort corresponding to (RPEGET) and above gas exchange threshold (RPE+15%GET); Part B - between experienced and inexperienced cyclists during fixed perceived effort cycling tasks. Eighteen (15 male, 3 female) healthy, active individuals completed three visits (visit 1 - ramped incremental test and familiarisation, visit 2 and 3-30-min fixed perceived effort cycling). During which, power output, heart rate, lactate, think aloud, and perceptual markers were taken. Random-intercepts linear mixed-effects models assessed the condition, time, and condition × time interactions on all dependent variables. Power output, heart rate, lactate and instances of internal sensory monitoring (t195=2.57,p=.011,β=0.95[0.23,1.68]) and self-regulation (t195=4.14,p=.001,β=1.69[0.89,2.49]) were significantly higher in the RPE+15%GET versus RPEGET trial. No significant differences between inexperienced and experienced cyclists for internal sensory monitoring (t196=-1.78,p=.095,β=-1.73[-3.64,0.18]) or self-regulatory thoughts (t196=-0.39,p=.699,β=-1.06[-6.32,4.21]) were noted but there were significant condition × time interactions for internal monitoring (t196=2.02,p=.045,β=0.44[0.01,0.87]) and self-regulation (t196=3.45,p=.001,β=0.85[0.37,1.33]). Seemingly, experienced athletes associatively attended to internal psychophysiological state and subsequently self-regulate their psychophysiological state at earlier stages of exercise than inexperienced athletes. This is the first study to exhibit the differences in attentional focus and self-regulatory strategies that are activated based on perceived effort intensity and experience level in cyclists.


Persistence, localization, and external control of transgene expression after single injection of adeno-associated virus into injured joints.
A single intra-articular injection of adeno-associated virus (AAV) results in stable and controllable transgene expression in normal rat knees. Because undamaged joints are unlikely to require treatment, the study of AAV delivery in joint injury models is crucial to potential therapeutic applications. This study tests the hypotheses that persistent and controllable AAV-transgene expression are (1) highly localized to the cartilage when AAV is injected postinjury and (2) localized to the intra-articular soft tissues when AAV is injected preinjury. Two AAV injection time points, postinjury and preinjury, were investigated in osteochondral defect and anterior cruciate ligament transection models of joint injury. Rats injected with AAV tetracycline response element (TRE)-luciferase received oral doxycycline for 7 days. Luciferase expression was evaluated longitudinally for 6 months. Transgene expression was persistent and controllable with oral doxycycline for 6 months in all groups. However, the location of transgene expression was different: postinjury AAV-injected knees had luciferase expression highly localized to the cartilage, while preinjury AAV-injected knees had more widespread signal from intra-articular soft tissues. The differential transgene localization between preinjury and postinjury injection can be used to optimize treatment strategies. Highly localized postinjury injection appears advantageous for treatments targeting repair cells. The more generalized and controllable reservoir of transgene expression following AAV injection before anterior cruciate ligament transection (ACLT) suggests an intriguing concept for prophylactic delivery of joint protective factors to individuals at high risk for early osteoarthritis (OA). Successful external control of intra-articular transgene expression provides an added margin of safety for these potential clinical applications.


A rice orthologue of the ABA receptor, OsPYL/RCAR5, is a positive regulator of the ABA signal transduction pathway in seed germination and early seedling growth.
Abscisic acid (ABA) is a phytohormone that positively regulates seed dormancy and stress tolerance. PYL/RCARs were identified an intracellular ABA receptors regulating ABA-dependent gene expression in Arabidopsis thaliana. However, their function in monocot species has not been characterized yet. Herein, it is demonstrated that PYL/RCAR orthologues in Oryza sativa function as a positive regulator of the ABA signal transduction pathway. Transgenic rice plants expressing OsPYL/RCAR5, a PYL/RCAR orthologue of rice, were found to be hypersensitive to ABA during seed germination and early seedling growth. A rice ABA signalling unit composed of OsPYL/RCAR5, OsPP2C30, SAPK2, and OREB1 for ABA-dependent gene regulation was further identified, via interaction assays and a transient gene expression assay. Thus, a core signalling unit for ABA-responsive gene expression modulating seed germination and early seedling growth in rice has been unravelled. This study provides substantial contributions toward understanding the ABA signal transduction pathway in rice.


Therapeutic implications of SARS-CoV-2 dysregulation of the gut-brain-lung axis.
The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19 (COVID-19) pandemic. Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms, including fever, cough, fatigue, and loss of smell and taste. However, many individuals develop pneumonia, acute respiratory distress syndrome, septic shock, and multiorgan dysfunction. In addition to these primarily respiratory symptoms, SARS-CoV-2 can also infiltrate the central nervous system, which may damage the blood-brain barrier and the neuron's synapses. Resultant inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves, leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal functions. Additionally, SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial barrier. As a result, this exacerbates pro-inflammatory responses both locally and systemically, resulting in impaired clinical outcomes. Recent evidence has highlighted the complex interactions that mutually modulate respiratory, neurological, and gastrointestinal function. In this review, we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung axis. We further highlight targeting specific responses to SARS-CoV-2 for the development of novel, urgently needed therapeutic interventions. Finally, we propose a prospective related to the individuals from Low- and Middle-Income countries. Here, the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.


Effects of mutations in potential phosphorylation sites on transcytosis of FcRn.
The neonatal Fc receptor, FcRn, transports immunoglobulin G (IgG) across intestinal epithelial cells of suckling rats and mice from the lumenal surface to the serosal surface. In cell culture models FcRn transports IgG bidirectionally, but there are differences in the mechanisms of transport in the two directions. We investigated the effects of mutations in the cytoplasmic domain of FcRn on apical to basolateral and basolateral to apical transport of Fc across rat inner medullary collecting duct (IMCD) cells. Basolateral to apical transport did not depend upon determinants in the cytoplasmic domain. In contrast, an essentially tailless FcRn was markedly impaired in apical to basolateral transport. Using truncation and substitution mutants, we identified serine-313 and serine-319 as phosphorylation sites in the cytoplasmic domain of FcRn expressed in Rat1 fibroblasts. Mutations at Ser-319 did not affect transcytosis across IMCD cells. FcRn-S313A was impaired in apical to basolateral transcytosis to the same extent as tailless FcRn, whereas FcRn-S313D transported at wild-type levels. FcRn-S313A recycled more Fc to the apical medium than the wild-type receptor, suggesting that Ser-313 is required to allow FcRn to be diverted from an apical recycling pathway to a transcytotic pathway.


Preparation and properties of a calcium(II)-based molecular chain decorated with manganese(II) butterfly-like complexes.
The room temperature reaction of [Mn2O2(bipy)4](ClO4)3 (bipy = 2,2'-bipyridine) with Ca(CHCl2COO)2 in methanol produced a yellow crystalline material. The X-ray determined structure comprises of a multiple calcium(II) carboxylate bridged chain-like structure which is decorated with [Mn(bipy)2(OH2)](2+) subunits. The redox behaviour for the complex in H2O and MeCN is reported. In the latter solvent the oxidation of the manganese ions appears to be facilitated by the presence of the calcium ions. Magnetic susceptibility and low temperature magnetization measurements show that the Mn moment is isotropic, with g = 1.99(1) and S = 5/2, confirming it is in the 2+ oxidation state. A very weak antiferromagnetic interaction is also detected. Frequency-dependent ac measurements evidence slow magnetic relaxation of the Mn(bipy)2 units. Two relaxation mechanisms are identified: a very slow direct process and a faster one caused by the Resonant Phonon Trapping mechanism. This is the first example of field-induced single ion magnet (SIM) behavior in a mononuclear Mn(II) complex.


Calcium accumulation and calcium binding by the cell membranes of cardiomyocytes and smooth muscle of aorta in spontaneously hypertensive rats.
1. The ability of isolated membrane fractions of cardiomyocytes, aortic smooth muscle and erythrocytes from spontaneously hypertensive rats to bind calcium was investigated isotopically. 2. Plasma membranes of aortic smooth muscle and erythrocytes of spontaneously hypertensive rats possess a lower calcium-binding ability than preparations from normotensive controls. 3. Sarcoplasmic reticulum from the myocardium of spontaneously hypertensive rats had a lower ability to accumulate calcium. 4. Changes in the calcium-binding ability of the erythrocyte membrane of spontaneously hypertensive rats was related to the diminution of the amount of exchangeable calcium on the inner part of the membrane. The latter may be the cause of the increase of erythrocyte membrane permeability for sodium in spontaneously hypertensive rats and in patients with essential hypertension.


[Transcatheter hepatic artery infusion chemotherapy and embolization for 60 patients with primary hepatic carcinoma].
Sixty patients with primary hepatic carcinoma (PHC) were treated with transcatheter hepatic artery infusion chemotherapy (TAI) and embolization (TAE) from June 1988 to December 1989. There were 54 males and 6 females. Their age ranged from 22 to 72 years with an average of 52. Course of disease ranged from 1/2 to 12 months. In these 60 cases, 31 had Stage II and 29 Stage III lesions. Using Seldinger's method per femoral artery, conventional hepatic angiography was performed. Afterwards, adriamycin or cisplatin infusion was carried out, followed by chemoembolization therapy of tumor vessels using mixture of ethiodized oil or iophendylate and mitomycin C. Finally, gelatin sponge block was used for proximal arterial embolization. After the treatment procedure, abdominal pain was relieved, tumor reduced in size, AFP, r-GT, AKP and LDH declined to various degrees and the survival time was prolonged. The 3-, 6- and 12-month survival rates were 93.3% (56/60), 67.3% (37/49) and 33.3% (9/27), respectively. It is indicated that TAI and TAE, being safe and effective, is the treatment of choice for patients with unresectable PHC.


An innovative approach in the detection of Toxocara canis excretory/secretory antigens using specific nanobodies.
Human toxocariasis is a zoonosis resulting from the migration of larval stages of the dog parasite Toxocara canis into the human paratenic host. Despite its well-known limitations, serology remains the most important tool to diagnose the disease. Our objective was to employ camelid single domain antibody fragments also known as nanobodies (Nbs) for a specific and sensitive detection of Toxocara canis excretory/secretory (TES) antigens. From an alpaca immune Nb library, we retrieved different Nbs with specificity for TES antigens. Based on ELISA experiments, these Nbs did not show any cross-reactivity with Ascaris lumbricoides, Ascaris suum, Pseudoterranova decipiens, Anisakis simplex and Angiostrongylus cantonensis larval antigens. Western blot and immunocapturing revealed that Nbs 1TCE39, 1TCE52 and 2TCE49 recognise shared epitopes on different components of TES antigen. The presence of disulphide bonds in the target antigen seems to be essential for recognition of the epitopes by these three Nbs. Three separate sandwich ELISA formats, using monovalent and bivalent Nbs, were assessed to maximise the detection of TES antigens in solution. The combination of biotinylated, bivalent Nb 2TCE49 on a streptavidin pre-coated plate to capture TES antigens, and Nb 1TCE39 chemically coupled to horseradish peroxidase for detection of the captured TES antigens, yielded the most sensitive ELISA with a limit of detection of 0.650 ng/ml of TES antigen, spiked in serum. Moreover, the assay was able to detect TES antigens in sera from mice, taken 3 days after the animals were experimentally infected with T. canis. The specific characteristics of Nbs make this ELISA not only a promising tool for the detection of TES antigens in clinical samples, but also for a detailed structural and functional study of TES antigens.


Supporting the Process of Exploring and Interpreting Space-Time Multivariate Patterns: The Visual Inquiry Toolkit.
While many data sets carry geographic and temporal references, our ability to analyze these datasets lags behind our ability to collect them because of the challenges posed by both data complexity and tool scalability issues. This study develops a visual analytics approach that leverages human expertise with visual, computational, and cartographic methods to support the application of visual analytics to relatively large spatio-temporal, multivariate data sets. We develop and apply a variety of methods for data clustering, pattern searching, information visualization, and synthesis. By combining both human and machine strengths, this approach has a better chance to discover novel, relevant, and potentially useful information that is difficult to detect by any of the methods used in isolation. We demonstrate the effectiveness of the approach by applying the Visual Inquiry Toolkit we developed to analyze a data set containing geographically referenced, time-varying and multivariate data for U.S. technology industries.


Decreased susceptibility of mast cell-deficient Kit(W)/Kit(W-v) mice to the development of 1, 2-dimethylhydrazine-induced intestinal tumors.
Administration of 1,2-dimethylhydrazine (DMH) induces intestinal epithelial tumors in mice. Increased numbers of mast cells have been reported to occur both within and near a variety of different neoplasms, including DMH-induced intestinal tumors. We investigated the role of the tyrosine kinase receptor, c-kit, and mast cells, in this model by administering DMH to c-kit mutant mast cell-deficient mice and the congenic normal mice. We attempted to induce colonic tumors by administering DMH (20 mg/kg body weight, s.c., weekly for 20 weeks) to WBB6F1-Kit+/+ (+/+) wild-type mice, the congenic mast cell-deficient WBB6F1-Kit(W)/Kit(W-v) (W/W(v)) mice and W/W(v) mice that had been repaired of their mast cell deficiency by adoptive transfer of bone marrow cells derived from the congenic +/+ mice. The susceptibility to the development of DMH-induced colonic tumors, and the numbers of mast cells associated with these tumors, was evaluated. Normal (+/+) mice exhibited significantly higher numbers of mast cells in DMH-induced intestinal tumors than in macroscopically normal colonic mucosa. Treatment with DMH induced development of colonic tumors in 97% of +/+ mice, but in only 32% of the W/W(v) mice. W/W(v) mice that had been repaired of their mast cell deficiency by transfer of +/+ bone marrow cells expressed susceptibility to the development of colonic tumors that was similar to that of wild-type mice. These results show that genetic impairment of c-kit function reduces the susceptibility of mice to DMH-induced colonic tumors, and that defects in bone marrow-derived cells in the W/W(v) mice contribute significantly to this result. Our findings also are consistent with the possibility that mast cells promote the development of DMH-induced colonic epithelial tumors in mice.


Modulation of the antifungal activity of new medicinal plant extracts active on Candida glabrata by the major transporters and regulators of the pleiotropic drug-resistance network in Saccharomyces cerevisiae.
The increased incidence of drug-resistant fungal infections, a process in which active efflux plays an important role, calls for the development of new treatments. Candida albicans and Candida glabrata are the most frequent human fungal pathogens. The latter, in spite of its increased azole tolerance, is rarely used in medicinal plant screening. Several extracts inhibiting the growth of this pathogenic yeast are identified here. The ethyl acetate extract of the herb Dalea formosa of the American Southwest, not previously known to possess antifungal activity, proved most active against azole-sensitive and azole-resistant isolates. The model yeast Saccharomyces cerevisiae, related to C. glabrata, was used to evaluate the influence of multidrug efflux on the antifungal activity of identified extracts and selected fractions from further purification steps, together with their ability to modulate ketoconazole resistance. The differential involvement of the major pleiotropic drug transporters of the ATP-binding cassette superfamily Pdr5p, Snq2p, and Yor1p as well as their transcriptional activators Pdr1p and Pdr3p in the detoxification of the antifungal constituents of several important medicinal plants is demonstrated. These include Artemisia annua and its widely used antimalarial component artemisinin. This approach revealed the concomitant presence of multidrug efflux pump substrates and modulators in the extract of A. annua and also allowed the identification of an extract not affected by the major pleiotropic drug-resistance genes.


The parasellar region of human infants: cavernous sinus topography and surgical approaches.
In this study the authors analyze the peculiarities of the parasellar anatomy and the topography of surgical approaches to the parasellar region (PSR) in human infants. Forty-nine specimens of the PSR obtained at autopsy were studied using microdissection and histological analysis. Important distances between anatomical landmarks were measured with the aid of a dissecting microscope. One serially sectioned specimen was three-dimensionally reconstructed and analyzed on the computer screen by using the authors' new episcopic reconstruction technique. The anatomy of the infant PSR differs distinctly from that of the adult. The parasellar portion of the internal carotid artery (ICA) does not form a siphon, but takes a straight course, and the venous pathways as well as the cranial and sympathetic nerves have different topographical relationships. Analyses of surgical approaches demonstrate that, in young children, the anterolateral approach can be used to reach the pterygopalatine compartment, the superior ophthalmic vein, and those pathological processes that extend from the orbit into the PSR. The approach via Parkinson's triangle can be used in 45% of cases to access the pathological processes that occur in the voluminous space above and behind the posterior flexure of the parasellar ICA. Taking this route, sympathetic nerve fibers passing through the PSR are not at risk, but some arterial branches that run within the lateral wall of the sinus can complicate this approach. This study presents a guideline that can assist radiologists and neurosurgeons in the planning and performance of interventions within the PSR of neonates and young children.


Musashi-2 (MSI2) regulates epidermal growth factor receptor (EGFR) expression and response to EGFR inhibitors in EGFR-mutated non-small cell lung cancer (NSCLC).
Non-small cell lung cancer (NSCLC) has limited treatment options. Expression of the RNA-binding protein (RBP) Musashi-2 (MSI2) is elevated in a subset of non-small cell lung cancer (NSCLC) tumors upon progression, and drives NSCLC metastasis. We evaluated the mechanism of MSI2 action in NSCLC to gain therapeutically useful insights. Reverse phase protein array (RPPA) analysis of MSI2-depleted versus control KrasLA1/+; Trp53R172HΔG/+ NSCLC cell lines identified EGFR as a MSI2-regulated protein. MSI2 control of EGFR expression and activity in an NSCLC cell line panel was studied using RT-PCR, Western blots, and RNA immunoprecipitation. Functional consequences of MSI2 depletion were explored for cell growth and response to EGFR-targeting drugs, in vitro and in vivo. Expression relationships were validated using human tissue microarrays. MSI2 depletion significantly reduced EGFR protein expression, phosphorylation, or both. Comparison of protein and mRNA expression indicated a post-transcriptional activity of MSI2 in control of steady state levels of EGFR. RNA immunoprecipitation analysis demonstrated that MSI2 directly binds to EGFR mRNA, and sequence analysis predicted MSI2 binding sites in the murine and human EGFR mRNAs. MSI2 depletion selectively impaired cell proliferation in NSCLC cell lines with activating mutations of EGFR (EGFRmut). Further, depletion of MSI2 in combination with EGFR inhibitors such as erlotinib, afatinib, and osimertinib selectively reduced the growth of EGFRmut NSCLC cells and xenografts. EGFR and MSI2 were significantly co-expressed in EGFRmut human NSCLCs. These results define MSI2 as a direct regulator of EGFR protein expression, and suggest inhibition of MSI2 could be of clinical value in EGFRmut NSCLC.


Photonic crystal film with three alternating layers for simultaneous R, G, B multi-mode photonic band-gaps.
We studied 1-dimensional (1-D) photonic crystal (PC) films with three alternating layers to investigate multi-mode photonic band-gaps (PBGs) at red, green, and blue color regions. From simulations, it was shown that PCs with three alternating layered elements of [a/b/c] structure have sharp PBGs at the three color regions with the central wavelengths of 459 nm, 527 nm, and 626 nm, simultaneously. Experimentally, it was proven that red, green, and blue PBGs were generated clearly by the PCs, which were made of multilayers of [SiO(2)/Ta(2)O(5)/TiO(2)], based on the simulation. It was also shown that the measured wavelengths of the PBGs corresponded exactly to those of the simulated results. Moreover, it was demonstrated that a 1-D PC of [a/b/c] structure can be used for making white organic light emitting devices (OLEDs) with improved color rendering index (CRI) for color display or lighting.


Quality of automatic geocoding tools: a study using addresses from hospital record files in Temuco, Chile.
Automatic geocoding methods have become popular in recent years, facilitating the study of the association between health outcomes and the place of living. However, rather few studies have evaluated geocoding quality, with most of them being performed in the US and Europe. This article aims to compare the quality of three automatic online geocoding tools against a reference method. A subsample of 300 handwritten addresses from hospital records was geocoded using Bing, Google Earth, and Google Maps. Match rates were higher (> 80%) for Google Maps and Google Earth compared with Bing. However, the accuracy of the addresses was better for Bing with a larger proportion (> 70%) of addresses with positional errors below 20m. Generally, performance did not vary for each method for different socioeconomic status. Overall, the methods showed an acceptable, but heterogeneous performance, which may be a warning against the use of automatic methods without assessing quality in other municipalities, particularly in Chile and Latin America.


Ficus racemosa is pollinated by a single population of a single agaonid wasp species in continental South-East Asia.
High specificity in the Ficus-agaonid wasp mutualism has lead to the assumption of a mostly 'one-to-one' relationship, albeit with some exceptions. This view has been challenged by new molecular data in recent years, but surprisingly little is known about local and spatial genetic structuring of agaonid wasp populations. Using microsatellite markers, we analysed genetic structuring of Ceratosolen fusciceps, the fig wasp pollinating Ficus racemosa, a fig tree species widely distributed from India to Australia. In sampling stretching from the south of China to the south of Thailand we found evidence for only a single pollinating wasp species in continental South-East Asian mainland. We found no evidence for the co-occurrence of cryptic species within our subcontinent sampling zone. We observed no spatial genetic structure within sites and only limited structuring over the whole sampling zone, suggesting that F. racemosa is pollinated by a single population of a single agaonid wasp species all over continental South-East Asia. An additional sample of wasps collected on F. racemosa in Australia showed clear-cut genetic differentiation from the Asian continent, suggesting allopatric divergence into subspecies or species. We propose that the frequent local co-occurrence of sister species found in the literature mainly stems from contact zones between biogeographic regions, and that a single pollinator species over wide areas might be the more common situation everywhere else.


Experimental development of an endoscopic approach to neck exploration and parathyroidectomy.
Recent advances in minimally invasive surgical technology have the potential to lead to new applications outside body cavities. The purpose of the present study was to develop techniques for obtaining endoscopic exposure and access to the pretracheal space in the neck with the goal of performing neck exploration and parathyroidectomy and to evaluate the safety and efficacy of such an approach experimentally. The technique for endoscopic neck exploration was developed in eight adult mongrel dogs and was further evaluated in a survival dog model and in human cadavers. The pretracheal space was accessed by a 2.5 cm midline incision in the lower neck. This space was expanded with a balloon dissector, and exposure was maintained with an external lift device. A 5 or 10/12 mm midline port and two to four lateral 5 mm cervical ports were placed, and dissection was carried out with pediatric endoscopic instruments and an ultrasonic coagulator. Excised parathyroid tissue was verified histologically. Two-gland parathyroidectomy was successfully completed in five of six dogs; inadequate exposure led to a failed procedure in one animal. Mean operative time was 130 +/- 6 minutes, and there were no operative complications. Serum calcium levels did not change significantly after operation (p = not significant). At autopsy, approximately 20 ml of clear sterile fluid was present in the pretracheal space of every dog. In five human cadavers mean dissection time for attempted four-gland parathyroidectomy was 69 +/- 38 minutes (range, 45 to 135 minutes). Four of four parathyroids were identified and removed in two patients, three of three parathyroids in one patient, three of four parathyroids in one patient, and two of four parathyroids in one patient. Parathyroidectomy may be performed safely and reliably in an animal model with minimally invasive techniques that can be applied to parathyroid dissection in human cadavers. These results suggest that an endoscopic approach to neck exploration and parathyroidectomy is potentially feasible and may warrant further study in clinical trials.


Physiological Changes Differ between Responders and Nonresponders to Pulmonary Rehabilitation in COPD.
Not all patients with chronic obstructive pulmonary disease (COPD) experience similar benefits after pulmonary rehabilitation (PR). This pre-post PR study used a large sample of patients with COPD to determine whether PR-induced changes of oxygen uptake (V˙O2) kinetics and exercise responses of V˙O2, carbon dioxide output (V˙CO2), minute ventilation (V˙E), V˙E/V˙CO2, breathing frequency, and tidal volume differed between responders and nonresponders to PR. Responders to PR were defined as patients with a minimal clinically important increase in endurance time of 105 s. Isotime (=180 s) values of V˙O2, V˙CO2, V˙E, V˙E/V˙CO2, breathing frequency, and tidal volume; gains of V˙O2, V˙CO2, and V˙E; and V˙O2 mean response time of 183 patients with COPD (forced expiratory volume in 1 s: 56% ± 19% predicted) were compared between pre- and post-PR constant work rate tests. After PR, only the group of responders significantly decreased V˙O2 mean response time (P < 0.05), V˙CO2 gain, V˙E gain, and isotime values of V˙CO2, V˙E, and V˙E/V˙CO2 (all, P < 0.001), while also improving their breathing pattern (e.g., decreased breathing frequency isotime value; P < 0.0001). These changes were not observed in the group of nonresponders. Changes in physiological exercise responses were correlated with changes in physical performance (e.g., correlation between changes in V˙O2 mean response time and endurance time: P = 0.0002, r = -0.32). PR-induced changes in physiological exercise responses differed between responders and nonresponders. Physiological changes are relevant to explain the variable improvements of physical performance after PR in patients with COPD.


[Salmonella enteritidis, an emergent pathogen in Chile].
Salmonella enteritidis infections have increased worldwide in the last years. Isolation of this pathogen was remarkably rare in Chile until 1994, when the still ongoing outbreak emerged. To assess the main epidemiological characteristics of the Salmonella enteritidis epidemic in Chile. Cases of clinical infections by Salmonella enteritidis were recorded from bacteriological and demographic notifications obtained at The National Reference Laboratory for Enterobacteria. Infection rates were calculated using the total Chilean population and the population of the different Health Services along the country. Until 1993, 13.67 Salmonella enteritidis strains per year were received at the Reference Laboratory. The figures increased to 478 and 432 in 1994 and 1995, respectively. National rates were 3.41 and 3.04 notifications/100,000 inhabitants in 1994 and 1995 respectively. Northern regions were the most affected and 90% of observed cases during 1994 came from Arica and Antofagasta. At the present time, 20% of cases are observed in Santiago, located in the mid-portion of the country. The outbreak has mainly affected children and young adults (70% of cases). Strains have been isolated from stool cultures, suggesting gastrointestinal infections as the main clinical presentation. More than 98% of strains are susceptible to chloramphenicol, ampicillin, tetracycline, sulfa-trimetroprim, cefotaxime or ciprofloxacin. The obtained data clearly indicate the existence of an epidemic outbreak of Salmonella enteritidis infections, with a geographic progression from North to South.


Paeoniflorin suppressed IL-22 via p38 MAPK pathway and exerts anti-psoriatic effect.
The total glucosides of paeony (TGP) are used to treat psoriasis in the clinic. However, its active components and mechanisms are not clear. Paeoniflorin is the main constituent of TGP. Thus, the anti-psoriasis effect of paeoniflorin was studied, and its mechanism was explored. The effect of paeoniflorin was evaluated using a psoriasis-like model of guinea pigs. The levels of IL-6, IL-17A, IL-22, p38 MAPK, and ERK1/2 in HaCaT cells stimulated by lipopolysaccharide (LPS) were determined using RT-qPCR, enzyme linked immunosorbent assays (ELISAs) and western blot. Compared with the control group, the model group showed edema, redness, and lesions in the ear upon stimulation with propranolol hydrochloride, and the Baker Score increased by 7-fold. Paeoniflorin ameliorated the lesion and decreased the Baker Score by 37% (p<0.05). In vitro, paeoniflorin significantly inhibited the mRNA expression of IL-6, IL-17A and IL-22 at both 2.08 and 10.41μM (p<0.01), and paeoniflorin had a marginal effect on the protein expression of IL-17A and IL-6. However, it inhibited the protein expression of IL-22 significantly, with inhibition ratios of 48.5% and 47.8% at 2.08 and 10.41μM, respectively (p<0.05). This effect was achieved by inhibiting the phosphorylation of p38 MAPK. The results of this work demonstrated that paeoniflorin is the active components of TGP and support its use as a therapeutic compound for psoriasis therapy.


Vaccination for the prevention of equine herpesvirus-1 disease in domesticated horses: A systematic review and meta-analysis.
Equine herpes virus type 1 (EHV-1) infection in horses is associated with respiratory and neurologic disease, abortion, and neonatal death. Vaccines decrease the occurrence of clinical disease in EHV-1-infected horses. A systematic review was performed searching multiple databases to identify relevant studies. Selection criteria were original peer-reviewed research reports that investigated the in vivo use of vaccines for the prevention of disease caused by EHV-1 in domesticated horses. Main outcomes of interest included pyrexia, abortion, neurologic disease, viremia, and nasal shedding. We evaluated risk of bias, conducted exploratory meta-analyses of incidence data for the main outcomes, and performed a GRADE evaluation of the quality of evidence for each vaccine subtype. A total of 1018 unique studies were identified, of which 35 met the inclusion criteria. Experimental studies accounted for 31/35 studies, with the remainder being observational studies. Eight vaccine subclasses were identified including commercial (modified-live, inactivated, mixed) and experimental (modified-live, inactivated, deletion mutant, DNA, recombinant). Risk of bias was generally moderate, often because of underreporting of research methods, and sample sizes were small leading to imprecision in the estimate of the effect size. Several studies reported either no benefit or minimal vaccine efficacy for the primary outcomes of interest. Meta-analyses revealed significant heterogeneity was present, and our confidence in the quality of evidence for most outcomes was low to moderate. Our review indicates that commercial and experimental vaccines minimally reduce the incidence of clinical disease associated with EHV-1 infection.


The oncoprotein SS18-SSX1 promotes p53 ubiquitination and degradation by enhancing HDM2 stability.
Mutations of the p53 gene are uncommon in synovial sarcoma, a high-grade tumor genetically characterized by the chromosomal translocation t:(X;18), which results in the fusion of SS18 with members of SSX gene family. Although implicated in tumorigenesis, the mechanisms by which SS18-SSX promotes tumor growth and cell survival are poorly defined. Here, we show that SS18-SSX1 negatively regulates the stability of the tumor suppressor p53 under basal conditions. Overexpression of SS18-SSX1 enhanced p53 ubiquitination and degradation in a manner dependent on the ubiquitin ligase activity of HDM2. The negative effect of SS18-SSX1 expression on p53 was mediated by its ability to promote HDM2 stabilization through inhibition of HDM2 autoubiquitination. Furthermore, SS18-SSX1 expression altered the induction of p53-regulated genes in response to cellular stress by abrogating the transactivation of HDM2, PUMA, and NOXA but not p21. Our data uncover a novel mechanism whereby SS18-SSX1 can negatively regulate p53 tumor-suppressive function by increasing the stability of its negative regulator HDM2 and suggest that chemical compounds that target the p53-HDM2 regulatory axis may be of therapeutic benefit for the treatment of synovial sarcoma.