A Two-Stage Framework for Automated Malignant Pulmonary Nodule Detection in CT Scans.
This research is concerned with malignant pulmonary nodule detection (PND) in low-dose CT scans. Due to its crucial role in the early diagnosis of lung cancer, PND has considerable potential in improving the survival rate of patients. We propose a two-stage framework that exploits the ever-growing advances in deep neural network models, and that is comprised of a semantic segmentation stage followed by localization and classification. We employ the recently published DeepLab model for semantic segmentation, and we show that it significantly improves the accuracy of nodule detection compared to the classical U-Net model and its most recent variants. Using the widely adopted Lung Nodule Analysis dataset (LUNA16), we evaluate the performance of the semantic segmentation stage by adopting two network backbones, namely, MobileNet-V2 and Xception. We present the impact of various model training parameters and the computational time on the detection accuracy, featuring a 79.1% mean intersection-over-union (mIoU) and an 88.34% dice coefficient. This represents a mIoU increase of 60% and a dice coefficient increase of 30% compared to U-Net. The second stage involves feeding the output of the DeepLab-based semantic segmentation to a localization-then-classification stage. The second stage is realized using Faster RCNN and SSD, with an Inception-V2 as a backbone. On LUNA16, the two-stage framework attained a sensitivity of 96.4%, outperforming other recent models in the literature, including deep models. Finally, we show that adopting a transfer learning approach, particularly, the DeepLab model weights of the first stage of the framework, to infer binary (malignant-benign) labels on the Kaggle dataset for pulmonary nodules achieves a classification accuracy of 95.66%, which represents approximately 4% improvement over the recent literature.


Implant Sonication versus Tissue Culture for the Diagnosis of Spinal Implant Infection.
MINI: We compared the sensitivity and specificity of peri-implant tissue culture to the vortexing-sonication technique for the diagnosis of spinal implant infection (SII). Lower thresholds of sonicate fluid culture positivity showed increased sensitivity with maintained specificity. We recommend a threshold of 20 CFU/10 mL for sonicate culture positivity for the diagnosis of SII. This is a retrospective study comparing the diagnosis of spinal implant infection (SII) by peri-implant tissue culture to vortexing-sonication of retrieved spinal implants. We hypothesized that vortexing-sonication would be more sensitive than peri-implant tissue culture. We previously showed implant vortexing-sonication followed by culture to be more sensitive than standard peri-implant tissue culture for diagnosing of SII. In this follow-up study, we analyzed the largest sample size available in the literature to compare these two culture methods and evaluated thresholds for positivity for sonicate fluid for SII diagnosis. We compared peri-implant tissue culture to the vortexing-sonication technique which samples bacterial biofilm on the surface of retrieved spinal implants. We evaluated different thresholds for sonicate fluid positivity and assessed the sensitivity and specificity of the two culture methods for the diagnosis of SII. A total of 152 patients were studied. With more than 100 colony forming units (CFU)/10 mL as a threshold for sonicate fluid culture positivity, there were 46 patients with SII. The sensitivities of peri-implant tissue and sonicate fluid culture were 65.2% and 79.6%; the specificities were 88.7% and 93.4%, respectively. With more than 50 CFU/10 mL as a threshold, there were 50 patients with SII. The sensitivities of peri-implant tissue and sonicate fluid culture were 68.0% and 76.0%; the specificities were 92.2% for both methods. Finally, with more than or equal to 20 CFU/10 mL as a threshold, there were 52 patients with SII. The sensitivities of peri-implant tissue and sonicate fluid culture were 69.2% and 82.7%; the specificities were 94.0% and 92.0%, respectively. Implant sonication followed by culture is a sensitive and specific method for the diagnosis of SII. Lower thresholds for defining sonicate fluid culture positivity allow for increased sensitivity with a minimal decrease in specificity, enhancing the clinical utility of implant sonication. 4.


A turn-key approach for large-scale identification of complex posttranslational modifications.
The conjugation of complex post-translational modifications (PTMs) such as glycosylation and Small Ubiquitin-like Modification (SUMOylation) to a substrate protein can substantially change the resulting peptide fragmentation pattern compared to its unmodified counterpart, making current database search methods inappropriate for the identification of tandem mass (MS/MS) spectra from such modified peptides. Traditionally it has been difficult to develop new algorithms to identify these atypical peptides because of the lack of a large set of annotated spectra from which to learn the altered fragmentation pattern. Using SUMOylation as an example, we propose a novel approach to generate large MS/MS training data from modified peptides and derive an algorithm that learns properties of PTM-specific fragmentation from such training data. Benchmark tests on data sets of varying complexity show that our method is 80-300% more sensitive than current state-of-the-art approaches. The core concepts of our method are readily applicable to developing algorithms for the identifications of peptides with other complex PTMs.


Pet owners prefer face-to-face consultations, with many being open to considering virtual consultations with veterinarians.
To explore pet owners' use of information and communication technologies (ICTs) during virtual veterinarian-client-patient consultations and to examine pet owners' attitudes toward virtual consultations. 714 pet owners. In an anonymous online survey distributed using snowball sampling, all participants were asked about utilization of ICTs, preferred method of interaction (face-to-face and 5 ICTs), opinion on virtual communication, and demographics. Sentiment toward virtual veterinarian consultations was measured for participants who had experienced a "virtual only" or "combination virtual and face-to-face" consultation in the previous 6 months using the Net Promoter Score. For these participants, multivariable logistic regression was used to explore factors associated with recommending virtual consultations. 92% (583/632) of participants resided in Ontario, Canada. Most (85.6% [611/714]) participants had experience using the telephone for veterinary care, while only 5.2% (37/714) had used live videoconferencing. Participants ranked face-to-face interactions as most preferred (P < .001), followed by telephone and then live videoconferencing. Participants were significantly (P < .001) less confident communicating during virtual consultations, particularly for building rapport. For participants experiencing a virtual consultation in the previous 6 months (n = 348), the overall Net Promoter Score was neutral at -1.43. Participants were divided about recommending virtual consultations, with 33.3% (116/348) being promoters and 34.8% (121/348) being detractors. Age of participant and comfort using videoconferencing were positively associated (P < .05) with recommending virtual consultations. Although participating pet owners significantly preferred face-to-face consultations with veterinarians, many appear willing to consider virtual consultations. Further exploration of pet owners' preferences and concerns around virtual care, including communication, is needed.


Preserved immune functions and controlled leukocyte oxidative stress in naturally long-lived mice: possible role of nuclear factor kappa B.
In order to verify the survival biomarker role of several immune functions, and to determine the oxidation and inflammation mechanisms underlying variability in the aging process, we have investigated a variety of immune functions and oxidative stress parameters as well as activation of the nuclear factor kappa B (NF kappaB) in peritoneal leukocytes from four different age groups of mice, including natural extreme longevity. Immune cells from naturally long-lived animals showed preservation of immune function in response to stimuli and controlled oxidative stress as well as nuclear factor kappa B activation in resting conditions. Moreover, leukocytes from extreme long-lived animals showed increased catalase activity when compared with the adults. In contrast, the old and very old animal groups showed impaired immune function and increased oxidation as well as NF kappaB activation. Our results support preserved immune function as a biomarker of extended survival and point to controlled regulation of NF kappaB activity as a key mechanism restraining oxidative stress in immune cells and contributing to reach longevity.


Effectiveness of Baduanjin (a Type of Qigong) on Physical, Cognitive, and Mental Health Outcomes: A Comprehensive Review.
The aim of this study is to comprehensively review empirical evidence on the effectiveness of Baduanjin exercise, one type of mind-body focused qigong exercise, on individuals' physical, cognitive, and mental well-being; outline potential mechanisms; and, suggest potential implication strategies for using Baduanjin in clinical practices and for future research. Recent randomized-controlled studies and systematic reviews/meta-analyses published in English were searched in PubMed, PsycINFO, and Scopus up to July 2022. The search terms include Baduanjin and sleep, chronic illness, cognition, mental health, etc. We only selected papers that specifically studied the health effects of Baduanjin, excluding those that involved other forms of Qigong or other traditional Chinese medical practices. Since many RCT studies have already been included in the review papers that we selected, only those not covered in the review papers were selected to avoid repetition. 19 recent randomized-controlled studies and 8 systematic reviews were identified. In general, the effectiveness of Baduanjin exercise on individuals' physical, cognitive, and mental health is evident. Baduanjin has proven to be effective in improving sleep quality, including reducing difficulties in getting asleep and reducing daytime sleepiness. It also reduces fatigue and improves the quality of life for patients with other physical health issues, such as cancer, musculoskeletal pain, and chronic illnesses. The effectiveness of Baduanjin exercise is also evident in cognition, improving executive functions, and slowing down age-related cognitive deterioration. Similarly, Baduanjin alleviates various types of mental illnesses, increases patients' social competence, and enhances emotional regulation. There is initial evidence on the safety and efficacy of Baduanjin in improving individuals' various aspects of health and well-being, suggesting that Baduanjin may serve as an effective adjunct to conventional treatments for a variety of clinical health benefits. More research is needed to confirm the efficacy and safety of Baduanjin in other non-Chinese ethnic populations.


Morquio B syndrome: a primary defect in beta-galactosidase.
Fibroblasts from patients with Morquio B syndrome contain normal numbers of beta-galactosidase molecules with normal turnover but strongly reduced activity per enzyme molecule. Various substrate affinities are abnormal: the Km for methylum belliferyl (MU)-beta-galactoside is 4-10-fold elevated and affinity for keratan sulphate and oligosaccharides, isolated from Morquio B urine, was not detectable. In contrast, these substrate affinities are normal for beta-galactosidase in adult type GM1-gangliosidosis fibroblasts. Cell hybridization studies demonstrate that Morquio B syndrome and infantile and adult type GM1-gangliosidosis belong to the same complementation group. From these results we conclude that Morquio B syndrome is caused by a mutation in the structural gene for beta-galactosidase, which is allelic to the mutations in infantile and adult type GM1-gangliosidosis. Urinary excretion of keratan sulphate and oligosaccharides is abnormal in Morquio B syndrome but normal in adult type GM1-gangliosidosis. The catalytic properties of beta-galactosidase in Morquio B syndrome and GM1-gangliosidosis provide a possible explanation for the distinct clinical manifestations in these disorders.


Video-thoracoscopy closure of coronary artery fistula: case report.
The coronary artery fistulas (FAC) are rare and often found occasionally. The conventional treatment can be made by surgical closure with median thoracotomy or with embolization by catheterization. We describe an innovative technique to ligature of FAC, on a full endoscopy. Women, 45 years with symptomatic fistula between coronary artery anterior descending and trunk artery pulmonary, which took thoracoscopy left, pericardiotomy and ligation of fistula with metal clip without thoracotomy. There were no complications, stayed 24 hours in the ICU and was in hospital 4 days. The technique was effective, allows easy accessibility surgical and quick post-operative recovery.


Perspectival reversals of a solid: a phenomenal description.
The paper presents a phenomenal investigation of monocular perception of perspectival reversal of a conical shell. The inverted shell is seen as shorter than the stimulus, and both relative size of elements within it and movement within it appear to be affected by reversal. Similarity of the observed effects to those recorded in studies of afterimages are noted, as is similarity to reversals of Mach's Book.


Sonography of neonatal periventricular leukomalacia: recent experience with a 7.5-MHz scanner.
This study compared the relative efficacy of 5.0- and 7.5-MHz (high-resolution) transducers in the sonographic evaluation of cystic periventricular leukomalacia (PVL). Of 668 premature neonates evaluated by cranial sonography over a 4-year period, 34 were diagnosed as having PVL. Of these 34 neonates, 17 were examined with both 5.0- and 7.5-MHz transducers. Fifty-two neonates with no evidence of PVL also were evaluated by sonography with the two different-frequency transducers to determine the normal appearance of the neonatal brain. Among the neonates with PVL, features of the disease that have not been observed with routine 5.0-MHz transducers were apparent with use of the 7.5-MHz transducer: 7.5-MHz scanning clearly identified small areas of cystic PVL in three (17.6%) of 17 neonates that were not visible using the lower-resolution technique. The higher-resolution scanning also identified widening of the interhemispheric fissure by anechoic cerebrospinal fluid and demonstrated the falx as a distinct structure. The latter two superficial abnormalities were identified in combination with enlargement of the lateral and third ventricles, suggesting that diffuse cerebral atrophy accompanies PVL in most cases. The excellent near-field resolution of 7.5-MHz technology makes it the preferred method for the evaluation of PVL in the preterm neonate.


Improved oral hygiene is associated with decreased risk of new-onset diabetes: a nationwide population-based cohort study.
Inflammation plays an important role in the development of diabetes, a major global health problem. Periodontal disease is also common in the general population. Because periodontal disease and poor oral hygiene can provoke transient bacteraemia and systemic inflammation, we hypothesised that periodontal disease and oral hygiene indicators would be associated with the occurrence of new-onset diabetes. In this study we analysed data collected between 2003 and 2006 on 188,013 subjects from the National Health Insurance System-Health Screening Cohort (NHIS-HEALS) in Korea who had no missing data for demographics, past medical history, oral hygiene indicators or laboratory findings. The presence of periodontal disease was defined on the basis of a modified version of ICD-10 codes (Korean Classification of Disease, sixth edition), if claims for treatment for acute periodontitis (K052), chronic periodontitis (K053) and periodontosis (K054) were made more than two times by a dentist, or if, according to medical records, subjects received treatment by a dentist for periodontal disease with ICD-10 codes K052, K053 or K054. Oral hygiene behaviours (number of tooth brushings, a dental visit for any reason and professional dental cleaning) were collected as self-reported data of dental health check-ups. Number of missing teeth was ascertained by dentists during oral health examination. The incidence of new-onset diabetes was defined according to ICD-10 codes E10-E14. The criterial included at least one claim per year for both visiting an outpatient clinic and admission accompanying prescription records for any glucose-lowering agent, or was based on a fasting plasma glucose ≥7 mmol/l from NHIS-HEALS. Of the included subjects, 17.5% had periodontal disease. After a median follow-up of 10.0 years, diabetes developed in 31,545 (event rate: 16.1%, 95% CI 15.9%, 16.3%) subjects. In multivariable models, after adjusting for demographics, regular exercise, alcohol consumption, smoking status, vascular risk factors, history of malignancy and laboratory findings, the presence of periodontal disease (HR 1.09, 95% CI 1.07, 1.12, p < 0.001) and number of missing teeth (≥15 teeth) remained positively associated with occurrence of new-onset diabetes (HR 1.21, 95% CI 1.09, 1.33, p < 0.001, p for trend <0.001). Frequent tooth brushing (≥3 times/day) was negatively associated with occurrence of new-onset diabetes (HR 0.92, 95% CI 0.89, 0.95, p < 0.001, p for trend <0.001). Frequent tooth brushing may be an attenuating factor and the presence of periodontal disease and an increased number of missing teeth may be augmenting factors for the occurrence of new-onset diabetes. Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes.


An unembalmed cadaveric preparation for simulating pleural effusion: A pilot study of chest percussion involving medical students.
Cadaveric simulations are an effective way to add clinical context to an anatomy course. In this study, unembalmed (fresh) cadavers were uniquely prepared to simulate pleural effusion to teach chest percussion and review thoracic anatomy. Thirty first-year medical students were assigned to either an intervention (Group A) or control group (Group B). Group A received hands-on training with the cadaveric simulations. They were instructed on how to palpate bony landmarks for identifying the diaphragm and lobes of the lungs, as well as on how to properly perform chest percussion to detect abnormal fluid in the pleural space. Students in Group B practiced on each other. Students in Group A benefited from the training in several ways. They had more confidence in their percussive technique (A = mean 4.3/5.0, B = 2.9/5.0), ability to count the ribs on an intact body (A = mean 4.0/5.0, B = 3.0/5.0), and ability to identify the lobes of the lungs on an intact body (A = mean 3.8/5.0, B = 2.3/5.0). They also demonstrated a greater ability to locate the diaphragm on an intact body (A = 100%, B = 60%) and detect abnormal pleural fluid (A = 93%, B = 53%) with greater confidence (A = mean 3.7/5.0, B = 2.5/5.0). Finally, the hands-on training with the unembalmed cadavers created more excitement around learning in Group A compared with Group B. This study shows that simulating pleural effusion in an unembalmed cadaver is a useful way to enhance anatomy education. Anat Sci Educ 10: 160-169. © 2016 American Association of Anatomists.


Effect of Fusobacterium nucleatum on the T and B cell responses to Porphyromonas gingivalis in a mouse model.
T cell cytokine profiles and specific serum antibody levels in five groups of BALB/c mice immunized with saline alone, viable Fusobacterium nucleatum ATCC 25586, viable Porphyromonas gingivalis ATCC 33277, F. nucleatum followed by P. gingivalis and P. gingivalis followed by F. nucleatum were determined. Splenic CD4 and CD8 cells were examined for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma and IL-10 by dual colour flow cytometry and the levels of serum anti-F. nucleatum and anti-P. gingivalis antibodies determined by an ELISA. Both Th1 and Th2 responses were demonstrated by all groups, and while there were slightly lower percentages of cytokine positive T cells in mice injected with F. nucleatum alone compared with the other groups immunized with bacteria, F. nucleatum had no effect on the T cell production of cytokines induced by P. gingivalis in the two groups immunized with both organisms. However, the percentages of cytokine positive CD8 cells were generally significantly higher than those of the CD4 cells. Mice immunized with F. nucleatum alone had high levels of serum anti-F. nucleatum antibodies with very low levels of P. gingivalis antibodies, whereas mice injected with P. gingivalis alone produced anti-P. gingivalis antibodies predominantly. Although the levels of anti-F. nucleatum antibodies in mice injected with F. nucleatum followed by P. gingivalis were the same as in mice immunized with F. nucleatum alone, antibody levels to P. gingivalis were very low. In contrast, mice injected with P. gingivalis followed by F. nucleatum produced equal levels of both anti-P. gingivalis and anti-F. nucleatum antibodies, although at lower levels than the other three groups immunized with bacteria, respectively. Anti-Actinobacillus actinomycetemcomitans, Bacteroides forsythus and Prevotella intermedia serum antibody levels were also determined and found to be negligible. In conclusion, F. nucleatum immunization does not affect the splenic T cell cytokine response to P. gingivalis. However, F. nucleatum immunization prior to that of P. gingivalis almost completely inhibited the production of anti-P. gingivalis antibodies while P. gingivalis injection before F. nucleatum demonstrated a partial inhibitory effect by P. gingivalis on antibody production to F. nucleatum. The significance of these results with respect to human periodontal disease is difficult to determine. However, they may explain in part differing responses to P. gingivalis in different individuals who may or may not have had prior exposure to F. nucleatum. Finally, the results suggested that P. gingivalis and F. nucleatum do not induce the production of cross-reactive antibodies to other oral microorganisms.


Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on rats with persistent inflammation.
Ruxiang, or Gummi olibanum, an herbal medicine derived from the gum resin of Boswellia carterii Birdw. (BC) of the family Burseraceae, has been used traditionally in China to alleviate pain and reduce inflammation. The present study is an investigation of the effects of a BC extract on persistent hyperalgesia and edema in rats with peripheral inflammation. In this randomized, blinded study, the antihyperalgesic and antiedema effects of 3 dosages of BC were compared to a vehicle control. Inflammation was induced in rats by injecting complete Freund's adjuvant (CFA) into one hind paw. A single oral dose of the BC extract was administered daily for 7 days, beginning one day before CFA. Hyperalgesia was assessed using a paw withdrawal latency (PWL) test pre-CFA and 2 hours, 5 hours, 1 day, and 5 days post-CFA. Edema was determined by measuring paw thickness at the same time points. Spinal Fos protein expression was analyzed 2 hours post-CFA. Adverse effects of the extract were monitored by observing the animals closely for unusual behavioral changes. Compared to control, a dosage of 0.45 g/kg BC significantly lengthened PWL and reduced paw edema on day 5 post-CFA. At 0.90 g/kg, BC significantly lengthened PWL at 5 hours, 1 day, and 5 days, and reduced paw edema at 2 hours, 5 hours, 1 day, and 5 days. This dosage also significantly suppressed spinal Fos expression in the medial half of laminae I-II. At 1.80 g/kg, BC significantly lengthened PWL and reduced paw edema at all time points. No noticeable adverse effects were observed in animals given the lower dosages of BC, but adverse effects in some animals were observed at 1.80 g/kg per day. In the acute toxicity study, the maximal single dose of 2.50 g/kg produced no adverse effects in the treated rats during the 14 days of observation. The data suggest that BC produces significant antihyperalgesia and anti-inflammation effects and that the antihyperalgesia may be mediated by suppressed inflammation-induced Fos expression in the spinal dorsal horn neurons.


Long-Delay Arterial Spin Labeling Provides More Accurate Cerebral Blood Flow Measurements in Moyamoya Patients: A Simultaneous Positron Emission Tomography/MRI Study.
Arterial spin labeling (ASL) MRI is a promising, noninvasive technique to image cerebral blood flow (CBF) but is difficult to use in cerebrovascular patients with abnormal, long arterial transit times through collateral pathways. To be clinically adopted, ASL must first be optimized and validated against a reference standard in these challenging patient cases. We compared standard-delay ASL (post-label delay=2.025 seconds), multidelay ASL (post-label delay=0.7-3.0 seconds), and long-label long-delay ASL acquisitions (post-label delay=4.0 seconds) against simultaneous [15O]-positron emission tomography (PET) CBF maps in 15 Moyamoya patients on a hybrid PET/MRI scanner. Dynamic susceptibility contrast was performed in each patient to identify areas of mild, moderate, and severe time-to-maximum (Tmax) delays. Relative CBF measurements by each ASL scan in 20 cortical regions were compared with the PET reference standard, and correlations were calculated for areas with moderate and severe Tmax delays. Standard-delay ASL underestimated relative CBF by 20% in areas of severe Tmax delays, particularly in anterior and middle territories commonly affected by Moyamoya disease (P<0.001). Arterial transit times correction by multidelay acquisitions led to improved consistency with PET, but still underestimated CBF in the presence of long transit delays (P=0.02). Long-label long-delay ASL scans showed the strongest correlation relative to PET, and there was no difference in mean relative CBF between the modalities, even in areas of severe delays. Post-label delay times of ≥4 seconds are needed and may be combined with multidelay strategies for robust ASL assessment of CBF in Moyamoya disease.


Variation at three short tandem repeat (STR) loci in Australians: forensic and ethnic considerations.
We report the results of typing three short tandem repeat (STR) polymorphisms by a multiplex system in three forensically relevant populations of Australia; (i) a general Australian, (ii) a Caucasian, and (iii) an Asian sample. The STRs are tetranucleotide repeats in the following autosomal genes; CSF1PO, TPOX and THO1, and collectively comprise the CTT multiplex (Promega). In all three population samples, each of the loci exhibited genotype frequencies consistent with those expected under Hardy-Weinberg equilibrium, and, further, there was no significant deviation from random association of alleles across separate loci. These two characteristics, plus the high discrimination power values, demonstrate that the CTT multiplex system is a powerful tool for DNA profiling in Australian jurisdictions. Australian Asians and Caucasians exhibit frequencies of alleles at these three STR loci very similar to those in other Asian and Caucasian samples. While most of the variation exists within any single population, there are still considerable differences between Asians and Caucasians. This difference between the two groups is minimal with respect to TPOX and greatest for THO1 alleles.


Unraveling the function of the Rhodospirillum rubrum activator of polyhydroxybutyrate (PHB) degradation: the activator is a PHB-granule-bound protein (phasin).
Efficient hydrolysis of native poly(3-hydroxybutyrate) (nPHB) granules in vitro by soluble PHB depolymerase of Rhodospirillum rubrum requires pretreatment of nPHB with an activator compound present in R. rubrum cells (J. M. Merrick and M. Doudoroff, J. Bacteriol. 88:60-71, 1964). Edman sequencing of the purified activator (17.4 kDa; matrix-assisted laser desorption ionization-time of flight mass spectrometry) revealed identity to a hypothetical protein deduced from a partially sequenced R. rubrum genome. The complete activator gene, apdA (activator of polymer degradation), was cloned from genomic DNA, expressed as a six-His-tagged protein in recombinant Escherichia coli (M(r), 18.3 x 10(3)), and purified. The effect of ApdA on PHB metabolism was studied in vitro and in vivo. In vitro, the activity of the activator could be replaced by trypsin, but recombinant ApdA itself had no protease activity. Comparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the protein patterns of trypsin- and ApdA-treated nPHB granules isolated from different PHB-accumulating bacteria showed that trypsin activated nPHB by removing proteins of the surface layer of nPHB regardless of the origin of nPHB, but ApdA bound to and interacted with the surface layer of nPHB in a nonproteolytic manner, thereby transforming nPHB into an activated form that was accessible to the depolymerase. In vivo, expression of ApdA in E. coli harboring the PHB biosynthetic genes, phaCBA, resulted in significant increases in the number and surface/volume ratio of accumulated PHB granules, which was comparable to the effect of phasin proteins, such as PhaP in Ralstonia eutropha. The amino acid sequence of ApdA was 55% identical to the amino acid sequence of Mms16, a magnetosome-associated protein in magnetotactic Magnetospirillum species. Mms16 was previously reported to be a GTPase with an essential function in magnetosome formation (Y. Okamura, H. Takeyama, and T. Matsunaga, J. Biol. Chem. 276:48183-48188, 2001). However, no GTPase activity of ApdA could be demonstrated. We obtained evidence that Mms16 of Magnetospirillum gryphiswaldense can functionally replace ApdA in R. rubrum. Fusions of apdA and mms16 to gfp or yfp were functionally expressed, and both fusions colocalized with PHB granules after conjugative transfer to R. rubrum. In conclusion, ApdA in vivo is a PHB-bound, phasin-like protein in R. rubrum. The function of Mms16 in magnetotactic bacteria requires further clarification.


A screening test for unstimulated salivary flow measurement.
It is well established that saliva is an important factor for the health of both soft and hard tissues in the oral cavity. This study determined: 1) the correlation between unstimulated salivary flow assessed using the Modified Schirmer tear strip Test (MST), with gravimetric and volumetric measurements and 2) the MST value that would allow the most reliable identification of patients with severe (<0.1 ml/minute) and moderate (<0.2 ml/minute) hyposalivation. A retrospective clinical study was conducted using data from 90 patients seen at the Indiana University School of Dentistry. All patients had a sample of unstimulated whole saliva collected by drooling for five minutes for volumetric/gravimetric assessment, followed by placement of the Schirmer strip in the floor of the mouth for three minutes (MST). Results showed a non-linear association between the MST and volumetric/gravimetric methods, with moderate Spearman correlation coefficients (0.67-0.71). Analysis of ROC-curves suggests that a cutoff screening value of 25 mm/three minutes provides high sensitivity (77%) and positive predictive value (71%) without significantly affecting specificity (80%). In conclusion, this study supports use of the MST test as a screening tool for hyposalivation.


[Rosmarinic acid inhibits high glucose-induced cardiomyocyte hypertrophy by activating Parkin-mediated mitophagy].
To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG). Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 μmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and 3H-leucine labeling were used for determining the level of membrane potential and protein synthesis rate, respectively. The cell surface area was observed by light microscopy. RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I (P < 0.05), promoted the formation of mitochondrail autophagosome, inhibited the production of reactive oxygen species (P < 0.05), restored the activities of mitochondrial respiratory chain complex enzymes and mitochondrial membrane potential (P < 0.05), inhibited apoptosis (P < 0.05), and reduced the cell surface area and protein synthesis rate of H9c2 cells induced by HG exposure (P < 0.05). The protective effects of RA against HG-induced oxidative stress and cardiomyocyte hypertrophy was obviously blocked by inhibition of mitophagy mediated by transfection with Parkin siRNA (P < 0.05). RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.


Urine cultures in a long-term care facility (LTCF): time for improvement.
Urinary tract infections (UTIs) are the most prevalent infections in long-term care facilities (LTCFs). Numerous studies have described the problem of inadequate UTI diagnosis and treatment. We assessed the role of urine cultures in the diagnosis and treatment of UTIs in a LTCF. In a 370-bed non-academic LTCF a retrospective assessment of antibiotic (AB) prescriptions for UTIs and urine cultures was performed from July 2014 to January 2016. The reasons why physicians, including 11 nursing home physicians and 2 junior doctors, ordered urine cultures were recorded using questionnaires. During the study period, 378 residents were prescribed 1672 AB courses; 803 were for UTIs. One hundred and fifty-five urine cultures were obtained from 135 residents; 66 of these cultures were performed on the same day as ABs were prescribed (8% of all prescriptions for UTI), while 89 were not. There was a discrepancy between the actions that seemed logical based on the culture results and the actions that were actually taken in 75% of the cases. In these cases, initial AB treatment was not adjusted when the isolated microorganism was resistant to the AB prescribed, the urine culture was positive and no ABs had previously been administered, or ABs were prescribed and no microorganism was isolated. The most frequent reason for ordering a urine culture was to confirm the diagnosis of a UTI. In the majority of patients, AB therapy was not adjusted when the urine culture results suggested it may be appropriate. The physicians were erroneously convinced that UTIs could be diagnosed by a positive urine culture.


Breast cancer, psychological distress and life events among young women.
Since 1983, studies have suggested an interaction between the severe life events, psychological distress and the etiology of Cancer. However, these associations are still under dispute. The aim of the present study was to examine the relationship between life events, psychological distress and Breast Cancer (BC) among young women. A case control study. The study population included 622 women, under the age of 45 years. 255 were diagnosed for BC, and 367 were healthy women. A validated Brief Symptom Inventory (BSI) and Life Event Questionnaire were used. The cases presented significantly higher scores of depression compared to the controls and significant lower scores of happiness and optimism. A significant difference was found when comparing the groups according to the cumulative number of life events (two or more events). A multivariate analysis suggest that exposure to more than one life event is positively associated with BC [Odds Ratio(OR) :1.62 95% Confidence Interval (CI): 1.09-2.40], and that a general feeling of happiness and optimism has a "protective effect" on the etiology of BC. (OR-0.75, 95% CI:0.64-0.86). Young women who were exposed to a number of life events, should be considered as a risk group for BC and treated accordingly.


Identification of a functional homolog of the mammalian CYP3A4 in locusts.
Insects have been proposed as a new tool in early drug development. It was recently demonstrated that locusts have an efflux transporter localized in the blood-brain barrier (BBB) that is functionally similar to the mammalian P-glycoprotein efflux transporter. Two insect BBB models have been put forward, an ex vivo model and an in vivo model. To use the in vivo model it is necessary to fully characterize the locust as an entire organism with regards to metabolic pathways and excretion rate. In the present study, we have characterized the locust metabolism of terfenadine, a compound that in humans is specific to the cytochrome P450 enzyme 3A4. Using high-resolution mass spectrometry coupled to ultra-high-performance liquid chromatography, we have detected metabolites identical to human metabolites of terfenadine. The formation of human metabolites in locusts was inhibited by ketoconazole, a mammalian CYP3A4 inhibitor, suggesting that the enzyme responsible for the human metabolite formation in locusts is functionally similar to human CYP3A4. Besides the human metabolites of terfenadine, additional metabolites were formed in locusts. These were tentatively identified as phosphate and glucose conjugates. In conclusion, not only may locusts be a model useful for determining BBB permeation, but possibly insects could be used in metabolism investigation. However, extensive characterization of the insect model is necessary to determine its applicability.


MRI safety of Med-El C40/C40+ cochlear implants.
Cochlear implants are an accepted means for the treatment of profound bilateral deafness. Magnetic resonance imaging (MRI) is gaining more and more importance as a diagnostic tool. It is therefore very likely that cochlear implant wearers will, at some point in their life, become MRI candidates. This makes a discussion of MRI safety of cochlear implants a most timely subject. With the C40/C40+ system as an example, all the major and potentially troublesome interactions are discussed, as well as the conditions for the safe conduct of MR examinations with cochlear implant wearers. For the C40/C40+ systems, safe MR imaging is possible with 0.2 Tesla, 1.0 Tesla and 1.5 Tesla scanners.


Switch of rhodopsin expression in terminally differentiated Drosophila sensory neurons.
Specificity of sensory neurons requires restricted expression of one sensory receptor gene and the exclusion of all others within a given cell. In the Drosophila retina, functional identity of photoreceptors depends on light-sensitive Rhodopsins (Rhs). The much simpler larval eye (Bolwig organ) is composed of about 12 photoreceptors, eight of which are green-sensitive (Rh6) and four blue-sensitive (Rh5). The larval eye becomes the adult extraretinal 'eyelet' composed of four green-sensitive (Rh6) photoreceptors. Here we show that, during metamorphosis, all Rh6 photoreceptors die, whereas the Rh5 photoreceptors switch fate by turning off Rh5 and then turning on Rh6 expression. This switch occurs without apparent changes in the programme of transcription factors that specify larval photoreceptor subtypes. We also show that the transcription factor Senseless (Sens) mediates the very different cellular behaviours of Rh5 and Rh6 photoreceptors. Sens is restricted to Rh5 photoreceptors and must be excluded from Rh6 photoreceptors to allow them to die at metamorphosis. Finally, we show that Ecdysone receptor (EcR) functions autonomously both for the death of larval Rh6 photoreceptors and for the sensory switch of Rh5 photoreceptors to express Rh6. This fate switch of functioning, terminally differentiated neurons provides a novel, unexpected example of hard-wired sensory plasticity.


An introduction to critical paths.
A critical path defines the optimal sequencing and timing of interventions by physicians, nurses, and other staff for a particular diagnosis or procedure. Critical paths are developed through collaborative efforts of physicians, nurses, pharmacists, and others to improve the quality and value of patient care. They are designed to minimize delays and resource utilization and to maximize quality of care. Critical paths have been shown to reduce variation in the care provided, facilitate expected outcomes, reduce delays, reduce length of stay, and improve cost-effectiveness. The approach and goals of critical paths are consistent with those of total quality management (TQM) and can be an important part of an organization's TQM process.


Responses to online photographs of non-suicidal self-injury: a thematic analysis.
There is concern that graphic pictures of non-suicidal self-injury (NSSI) may detrimentally impact vulnerable viewers--namely those who may self-injure. How individuals (most who have, but some of whom have not, self-injured) respond to photographs of NSSI is currently unknown. Thematic analysis was used to assess testimony regarding NSSI imagery online. Analysis of testimony regarding NSSI photographs revealed a dichotomy. Individuals reporting positive perceptions said the photographs reduced loneliness and NSSI enactment. People reporting negative perceptions argued photographs reinforce and encourage NSSI. Experiences of being triggered by NSSI images were described by several participants. Photographs of NSSI posted online may have several risks for viewers. It is important to achieve a greater understanding of the effects of various forms of online NSSI content and to develop supportive NSSI resources on the Internet.


Its all about connections: hubs and invasion in habitat networks.
During the early stages of invasion, the interaction between the features of the invaded landscape, notably its spatial structure, and the internal dynamics of an introduced population has a crucial impact on establishment and spread. By approximating introduction areas as networks of patches linked by dispersal, we characterised their spatial structure with specific metrics and tested their impact on two essential steps of the invasion process: establishment and spread. By combining simulations with experimental introductions of Trichogramma chilonis (Hymenoptera: Trichogrammatidae) in artificial laboratory microcosms, we demonstrated that spread was hindered by clusters and accelerated by hubs but was also affected by small-population mechanisms prevalent for invasions, such as Allee effects. Establishment was also affected by demographic mechanisms, in interaction with network metrics. These results highlight the importance of considering the demography of invaders as well as the structure of the invaded area to predict the outcome of invasions.


A bacterium-like particle vaccine displaying protective feline herpesvirus 1 antigens can induce an immune response in mice and cats.
Feline herpesvirus 1 (FHV-1) is a highly transmissible virus that mainly causes ocular and upper respiratory infections in cats and seriously threatens the health of domestic cats and captive or wild cats (such as tigers, cheetahs, and lions). Vaccination is crucial to reduce the incidence rate and mortality of cats infected with FHV-1. In this study, three bacterium-like particles (BLPs) displaying the gB, gC, and gD proteins of FHV-1 were constructed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Indirect immunofluorescence assay, western blot, and electron microscopy results showed that gB, gC or gD protein of FHV-1 was successfully displayed on the surface of GEM particles. Additionally, we designed one more BLPs, designated gB&gC&gD-GEM, which consisted of a mixture of gB-GEM, gC-GEM, and gD-GEM at a protein content ratio of 1:1:1. Mice were immunized with the four BLPs mixed with Gel02 adjuvant, and the results indicated that neutralizing antibody level in the gB&gC&gD-GEM group was superior than those in the other groups. Moreover, gB&gC&gD-GEM significantly increased the secretion of cytokines, as well as the activation and maturation of B cells. It also boosted the production of central memory T cells among CD4 + and CD8 + T cells. Moreover, gB&gC&gD-GEM mixed with Gel02 adjuvant provoked an antibody response in cats. In conclusion, the BLPs vaccine prepared from gB&gC&gD-GEM induced specific humoral and cellular immune responses to FHV-1 and be used as a potential vaccine candidate for the control of FHV-1 infection in cats.


Green Synthesis of Silver Nanoparticles Using Pseudoduganella eburnea MAHUQ-39 and Their Antimicrobial Mechanisms Investigation against Drug Resistant Human Pathogens.
Silver nanoparticles (AgNPs) have shown great promise in biomedical applications. The exact mechanism and mode of action of AgNPs regarding antimicrobial activity are still not well known. Moreover, synthesis of nanoparticles by physical and chemical methods is expensive and not ecofriendly. This study highlights the green, rapid, facile, cost-effective and ecofriendly synthesis of AgNPs using Pseudoduganella eburnea MAHUQ-39 and also investigates their antibacterial mechanisms. The transmission electron microscopy (TEM) image revealed a spherical shape of the AgNPs. The size of the synthesized AgNPs was 8 to 24 nm. The elemental mapping and selected area electron diffraction (SAED) and X-ray diffraction (XRD) patterns revealed the crystalline structure of AgNPs. Fourier-transform infrared spectroscopy (FTIR) analysis identified the functional groups that are involved in the reduction of silver ion to AgNPs. The green synthesized AgNPs exhibited strong antimicrobial activity against multidrug-resistant pathogenic microbes. Minimal inhibitory concentrations (MICs) of Staphylococcus aureus and Pseudomonas aeruginosa were 100 μg/mL and 6.25 μg/mL, respectively, and the minimum bactericidal concentrations (MBCs) of S. aureus and P. aeruginosa were 200 μg/mL and 50 μg/mL, respectively. Our data demonstrated that synthesized AgNPs created structural changes of cells and destroyed the membrane integrity of strains S. aureus and P. aeruginosa. Therefore, AgNPs synthesized by strain MAHUQ-39 can be used as a powerful antimicrobial agent for various therapeutic applications.


Ulcer-free survival days and ulcer healing in patients with diabetic foot ulcers: A prospective cohort study.
Healing rates may not give a complete indication of the effectiveness and management of diabetic foot ulcers because of high recurrence rates. The most important outcome for patients is remaining ulcer-free; however, this has hardly been investigated. The aim of our study was to prospectively investigate ulcer-free survival days and ulcer healing in patients with diabetic foot ulcers. This was a prospective cohort study of all referrals to our diabetic foot expertise centre from December 2014 to April 2017. Outcomes were determined after a minimum follow-up period of 12 months. Primary outcomes were ulcer-free survival days and 12-month healing percentages. Predictors for ulcer-free survival days and healing were investigated in multivariate analyses. A total of 158 patients were included. Median ulcer-free survival days in the healed group were 233 days (interquartile range [IQR] 121-312) and 131 days (IQR 0-298) in the overall population. The healing rate at 12-month follow up was 67% (106/158), and the recurrence rate was 31% (33/106). Independent predictors of ulcer-free survival days were duration of diabetes, peripheral artery disease (PAD), cardiovascular disease, end-stage renal disease (ESRD), and infection. Ulcer-free survival days are related to PAD and cardiovascular disease, and ulcer-free survival days should be the main outcome when comparing the effectiveness of management and prevention of the diabetic foot ulcers.


Motor responses to food of the ileum, proximal colon, and distal colon of healthy humans.
Intraluminal pressures and motility indexes were recorded from ileum, ascending colon, rectosigmoid colon, and rectum of 6 healthy men. Three different test meals were eaten at 5-hour intervals. During fasting, migrating motor complexes were identified in the ileum. In ascending colon, irregular, isolated peaks of pressure were common; when bursts of continuous activity occurred, their predominant frequency was 6/min. Regular contractile activity occurred in distal colon at a frequency of 2.5-3.5/min. although 3 subjects also demonstrated rates of 7/min. There were both synchronous and independent contractions of the rectosigmoid and rectum, and no temporal relationship was obvious between motor activities of ascending and distal colons. When the preprandial hour contained no migrating motor complex, all meals increased the ileal motility index by 50%. The motility index of ascending and rectosigmoid colons were enhanced by solid meals, but not by meals containing amino acids. We conclude that motor patterns in the colon vary regionally, both fasting and after food. Results obtained at one site of the large intestine should not be extrapolated to others.


Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity.
Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus. We studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11β-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies. In adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01-0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01-0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2-3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses). Our findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.


Imaging diagnosis--FDG-PET/CT of a canine splenic plasma cell tumor.
An 8-year-old Shih Tzu developed abdominal pain and hyperglobulinemia. A round splenic mass was noted radiographically and sonographically. The patient was evaluated by fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG-PET/CT). There was no evidence of metastasis or bone marrow involvement on PET/CT images. The standardized uptake value (SUV) of the splenic mass was increased over the reference range (SUV = 4.83). The patient was diagnosed as splenic extramedullary plasmacytoma through immunohistopathologic study. After the splenectomy, the globulin level normalized and the patient is alive without complications.


Diagnosing metabolic syndrome in craniopharyngioma patients: body composition versus BMI.
Craniopharyngioma patients often have poor metabolic profiles due to hypothalamic-pituitary damage. Previously, using BMI as obesity marker, the occurrence of the metabolic syndrome in these patients was estimated at 46%. Our aim was to determine if dual X-ray absorptiometry (DXA) scan in evaluation of obesity and metabolic syndrome would be superior. Retrospective study of craniopharyngioma patients for whom DXA scan results were available. BMI, fat percentage and fat mass index were used to evaluate obesity and as components for obesity in metabolic syndrome. Ninety-five craniopharyngioma patients were included (51% female, 49% childhood-onset disease). Metabolic syndrome occurred in 34-53 (45-51%) subjects (depending on the definition of obesity, although all definitions occurred in higher frequency than in the general population). Metabolic syndrome frequency was higher if obesity was defined by fat percentage (52 vs 42%) or fat mass index (51 vs 43%) compared to BMI. Misclassification appeared in 9% (fat percentage vs BMI) and 7% (fat mass index vs BMI) for metabolic syndrome and 29 and 13% for obesity itself, respectively. For metabolic syndrome, almost perfect agreement was found for BMI compared with fat percentage or fat mass index. For obesity, agreement was fair to moderate (BMI vs fat percentage). Using BMI to evaluate obesity underestimates the true prevalence of metabolic syndrome in patients with craniopharyngioma. Furthermore, fat percentage contributes to a better evaluation of obesity than BMI. The contribution of DXA scan might be limited for identification of the metabolic syndrome.


Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats.
Huntington's disease (HD) is caused by an abnormal expansion of CAG repeats in the gene encoding huntingtin. The development of therapies for HD requires preclinical testing of drugs in animal models that reproduce the dysfunction and regionally specific pathology observed in HD. We have developed a new knock-in mouse model of HD with a chimeric mouse/human exon 1 containing 140 CAG repeats inserted in the murine huntingtin gene. These mice displayed an increased locomotor activity and rearing at 1 month of age, followed by hypoactivity at 4 months and gait anomalies at 1 year. Behavioral symptoms preceded neuropathological anomalies, which became intense and widespread only at 4 months of age. These consisted of nuclear staining for huntingtin and huntingtin-containing nuclear and neuropil aggregates that first appeared in the striatum, nucleus accumbens, and olfactory tubercle. Interestingly, regions with early pathology all receive dense dopaminergic inputs, supporting accumulating evidence for a role of dopamine in HD pathology. Nuclear staining and aggregates predominated in striatum and layer II/III and deep layer V of the cerebral cortex, whereas neuropil aggregates were found in the globus pallidus and layer IV/superficial layer V of the cerebral cortex. The olfactory system displayed early and marked aggregate accumulation, which may be relevant to the early deficit in odor discrimination observed in patients with HD. Because of their early behavioral anomalies and regionally specific pathology, these mice provide a powerful tool with which to evaluate the effectiveness of new therapies and to study the mechanisms involved in the neuropathology of HD.


Fine-needle aspiration cytology of thyroid nodules: experience at the Queen Elizabeth Hospital, Barbados (1998-2002).
Fine-needle aspiration cytology (FNAC) of the thyroid nodule has become part of accepted practice defining the role of surgery. This study assessed a 5-year period comparing cytologic with histopathologic diagnosis in 256 samples from 234 patients (203 women and 31 men). Inadequate cytologic samples were obtained in 21.1% of cases. The sensitivity and positive predictive values for the detection by FNAC of thyroid neoplasms was 21.1% and 30.8%, respectively, with a specificity and negative predictive value of 79.5% and 70.0%, respectively. The overall FNAC accuracy was 61.9%. It is anticipated that improvement in diagnosis will develop from specific cytopathological training in thyroid FNAC, consideration of the cytopathologist performing the aspiration biopsy, and the development of immunohistochemical and molecular techniques applied to the cytologic smears. The principal inherent difficulty with thyroid FNAC is the inability to confidently distinguish hyperplastic follicular adenomas from microinvasive follicular carcinomas.


Optimization design of spectral discriminator for high-spectral-resolution lidar based on error analysis.
Accurate aerosol optical properties could be obtained via the high spectral resolution lidar (HSRL) technique, which employs a narrow spectral filter to suppress the Rayleigh or Mie scattering in lidar return signals. The ability of the filter to suppress Rayleigh or Mie scattering is critical for HSRL. Meanwhile, it is impossible to increase the rejection of the filter without limitation. How to optimize the spectral discriminator and select the appropriate suppression rate of the signal is important to us. The HSRL technology was thoroughly studied based on error propagation. Error analyses and sensitivity studies were carried out on the transmittance characteristics of the spectral discriminator. Moreover, ratwo different spectroscopic methods for HSRL were described and compared: one is to suppress the Mie scattering; the other is to suppress the Rayleigh scattering. The corresponding HSRLs were simulated and analyzed. The results show that excessive suppression of Rayleigh scattering or Mie scattering in a high-spectral channel is not necessary if the transmittance of the spectral filter for molecular and aerosol scattering signals can be well characterized. When the ratio of transmittance of the spectral filter for aerosol scattering and molecular scattering is less than 0.1 or greater than 10, the detection error does not change much with its value. This conclusion implies that we have more choices for the high-spectral discriminator in HSRL. Moreover, the detection errors of HSRL regarding the two spectroscopic methods vary greatly with the atmospheric backscattering ratio. To reduce the detection error, it is necessary to choose a reasonable spectroscopic method. The detection method of suppressing the Rayleigh signal and extracting the Mie signal can achieve less error in a clear atmosphere, while the method of suppressing the Mie signal and extracting the Rayleigh signal can achieve less error in a polluted atmosphere.


Considerations in participatory action research when working cross-culturally.
Professionals from minority world nations are increasingly consulting with majority world nations to develop intervention and educational training programs, yet minority world programs cannot be simply transferred to majority world countries. Participatory action research (PAR) provides a methodology that can be used to facilitate the development of programs that are useful for and sustainable by the majority world communities. This article describes the principles of PAR and gives examples of the ways that cultural values and behaviors may influence interactions between minority and majority world persons. An understanding of these cultural variations in values is essential for the successful implementation of PAR and will reduce miscommunication and incorrect interpretations of behaviors.


Treatment of malignancy-associated hypercalcemia with cinacalcet: a paradigm shift.
Palliation of symptoms related to malignancy-associated hypercalcemia (MAH) is essential and clinically meaningful for patients, given the continued poor prognosis, with high morbidity and mortality associated with this disease process. Historically, agents have been temporizing, having no impact on patient morbidity nor survival. We suggest that cinacalcet can be an efficacious agent to be taken orally, reducing patients' time in the hospital/clinic settings. It is well-tolerated and maintains serum calcium levels in the normal range, while targeted cancer treatments can be employed. This has a direct, major impact on morbidity. Maintaining eucalcemia can increase quality of life, while allowing targeted therapies time to improve survival. Given that our case (and others) showed calcium reduction in MAH, there is promising evidence that cinacalcet can be more widely employed in this setting. Future consideration should be given to studies addressing the efficacy of cinacalcet in calcium normalization, improvement of quality of life, and impact on survival in patients with MAH. Though the exact mechanism of action for cinacalcet's reduction in calcium in this setting is not currently known, we can still afford patients the possible benefit from it.


Observation of the dipole- and quadrupole-bound anions of 1,4-dicyanocyclohexane.
Quadrupole-bound anions are negative ions in which their excess electrons are loosely bound by long-range electron-quadrupole attractions. Experimental evidence for quadrupole-bound anions has been scarce; until now, only trans-succinonitrile had been experimentally confirmed to form a quadrupole-bound anion. In this study, we present experimental evidence for a new quadrupole-bound anion. Our combined Rydberg electron transfer/anion photoelectron spectroscopy study demonstrates that the ee conformer of 1,4-dicyanocyclohexane (DCCH) supports a quadrupole-bound anion state, and that the cis-DCCH conformer forms a dipole-bound anion state. The electron binding energies of the quadrupole- and dipole-bound anions are measured as 18 and 115 meV, respectively, both of which are in excellent agreement with theoretical calculations by Sommerfeld.


Lipid peroxidation and the total antioxidant status in the pathogenesis of age related and diabetic cataracts: a study on the lens and blood.
Cataract is one of the major causes of a visual impairment, which eventually leads to blindness. An oxidative damage to the lens proteins is a major factor which leads to cataract formation. Therefore, we intended to study the relationship between the biochemical markers of oxidative stress and various forms of cataracts. We examined the lenses and the sera of 120 subjects who were aged 50 to 80 years, who were distributed in two groups, viz. the study group (90 patients) and the control group (30 subjects). The oxidative stress was assessed by estimating the lipid peroxidation product in the form of thiobarbituric acid reactive substances (TBARS), the antioxidant status by measuring the levels of vitamin E and the total antioxidant capacity (TAC). The study group patients were further divided into those with nuclear cataracts (30 patients), cortical cataracts (30 patients), and diabetic cataracts (30 patients). In this study, it was found that the levels of TBARS in the study group were significantly high (p<0.001), whereas the TAC (p<0.001) and the vitamin E (p<0.001) levels were significantly low, both in the lenses and the blood of the study group as compared to those of the control group. Thus, the present study suggests that an imbalance between the oxygen free radicals and the antioxidants may lead to lipid peroxidation in the lens. Also, the elevated levels of glucose in the diabetic cataracts lead to the auto-oxidation of glucose and a non-enzymatic glycation of the lens protein. Thereby, the high molecular weight proteins aggregate in the cataract.


Primary cutaneous zygomycosis secondary to minor trauma in an immunocompromised pediatric patient: a case report.
Zygomycosis is an opportunistic infection generally found in immunocompromised individuals. Herein we present a pediatric patient with primary cutaneous mucormycosis that developed at a site of trauma. Diagnosis and treatment are discussed.


Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review.
The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. Among the new emerging biomarkers of sepsis, Presepsin (P-SEP) appears to be the most promising. Several studies have shown that P-SEP plasma levels increase during bacterial sepsis and decline in response to appropriate therapy, with sensitivity and specificity values comparable to those of PCT. In neonatal sepsis, P-SEP compared to PCT has been shown to be more effective in diagnosing and guiding therapy. Since in sepsis the P-SEP plasma levels increase before those of PCT and since the current methods available allow measurement of P-SEP plasma levels within 17 min, P-SEP appears a sepsis biomarker particularly suited to the emergency department and critical care.


Towards Inferring Network Properties from Epidemic Data.
Epidemic propagation on networks represents an important departure from traditional mass-action models. However, the high-dimensionality of the exact models poses a challenge to both mathematical analysis and parameter inference. By using mean-field models, such as the pairwise model (PWM), the high-dimensionality becomes tractable. While such models have been used extensively for model analysis, there is limited work in the context of statistical inference. In this paper, we explore the extent to which the PWM with the susceptible-infected-recovered (SIR) epidemic can be used to infer disease- and network-related parameters. Data from an epidemics can be loosely categorised as being population level, e.g., daily new cases, or individual level, e.g., recovery times. To understand if and how network inference is influenced by the type of data, we employed the widely-used MLE approach for population-level data and dynamical survival analysis (DSA) for individual-level data. For scenarios in which there is no model mismatch, such as when data are generated via simulations, both methods perform well despite strong dependence between parameters. In contrast, for real-world data, such as foot-and-mouth, H1N1 and COVID19, whereas the DSA method appears fairly robust to potential model mismatch and produces parameter estimates that are epidemiologically plausible, our results with the MLE method revealed several issues pertaining to parameter unidentifiability and a lack of robustness to exact knowledge about key quantities such as population size and/or proportion of under reporting. Taken together, however, our findings suggest that network-based mean-field models can be used to formulate approximate likelihoods which, coupled with an efficient inference scheme, make it possible to not only learn about the parameters of the disease dynamics but also that of the underlying network.


Effect of green tea (camellia sinensis l.) leaf extract on reproductive system of adult male albino rats.
Green tea leaf extract (GTLE), used in this experiment has shown great influence on male reproductive system functionally as well as morphologically. The extract was prepared according to the method of Wei. H. et al. The extract was given to two different experimental animal groups with two different doses during 26 consecutive days. After treatment it was found that, the weight of the testis was markedly reduced instead of normal weight gain of all the animals. The sperm count and motility were reduced for the treated groups as compared with control animal group. The enzymes like SGPT and SGOT were as usual and other blood parameters like glucose and protein were also as usual comparing with controlled group. Testosterone level was reduced in the treated groups. FSH and LH levels were also altered accordingly in treated groups. Histological examination showed inhibition of spermatogenesis as evidenced by disintegration of seminiferous tubules of testis. Result of this study showed that GTLE has potent castrative effect on male reproductive system in dose dependent manner.


Autophagy induction sensitizes cancer cells to anti-cancer drugs.
Resistance to anti-cancer therapy is a major challenge for cancer treatment. Many studies revealed that macroautophagy/autophagy inhibition can overcome autophagy-mediated therapy resistance, but these efforts have not yet led to the success of clinical applications. In a recent paper, we established a 37-gene autophagy signature to estimate the autophagy status of approximately 10,000 tumor samples across 33 cancer types from The Cancer Genome Atlas, and muti-omics characterization reveals that autophagy induction may also sensitize cancer cells to anti-cancer drugs. These findings provide a comprehensive resource of molecular alterations associated with autophagy and highlight the potential to utilize drug sensitivity induced by autophagy to overcome the resistance of cancer therapy.


Extracellular Ca2+-Sensing Fluorescent Protein Biosensor Based on a Collagen-Binding Domain.
The importance of extracellular gradients of biomolecules is increasingly appreciated in the processes of tissue development and regeneration, in health and disease. In particular, the dynamics of extracellular calcium concentration is rarely studied. Here, we present a low affinity Ca2+ biosensor based on Twitch-2B fluorescent protein fused with the cellulose- and collagen-binding peptides. These recombinant chimeric proteins can bind cellulose and collagen scaffolds and enable scaffold-based biosensing of Ca2+ in the proximity of cells in live 3D tissue models. We found that the Twitch-2B mutant is compatible with intensity-based ratiometric and fluorescence lifetime imaging microscopy (FLIM) measurement formats, under one- and two-photon excitation modes. Furthermore, the donor fluorescence lifetime of the biosensor displays response to [Ca2+] over a range of ∼2-2.5 ns, making it attractive for multiplexed FLIM assays. To evaluate the performance of this biosensor in physiological measurements, we applied it to the live Lgr5-GFP mouse intestinal organoid culture and measured its responses to the changes in extracellular Ca2+ upon chelation with EGTA. When combined with spectrally resolved FLIM of lipid droplets using Nile red dye, we observed changes in cytoplasmic and basal membrane-associated lipid droplet composition in response to the extracellular Ca2+ depletion, suggesting that the intestinal epithelium can respond to and compensate such treatment. Altogether, our results demonstrate Twitch-2B as a prospective Ca2+ sensor for multiplexed FLIM analysis in a complex 3D tissue environment.


Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells.
The human intracellular enzyme AKR1B1 belongs to the aldo-keto reductase superfamily. The AKR1B1-catalyzed reduction of aldehydes is part of the intracellular inflammatory pathway leading to the activation of NF-κB and the expression of pro-inflammatory genes. The present study is aimed at determining the inhibition of AKR1B1 brought about by an extract of artichoke leaves (bracts), and the effects of this extract and three participating compounds on the expression of AKR1B1, COX-2, and MMP-2 proteins in THP-1 cells. It seeks to identify the ability of the test substances to modulate the lipopolysaccharide (LPS)-induced activation of NF-κB in cells and the intracellular oxidant effect of test substances after incubation with LPS. Low concentrations of the extract inhibit the enzyme AKR1B1. After stimulation by LPS, the extract attenuated the activity of NF-κB in THP-1 cells, but no changes in the expression of AKR1B1 were recorded. The extract diminished the expression of the inflammation-related enzymes COX-2 and MMP-2, probably by inhibiting the activity of NF-κB. The extract significantly diminished the intracellular reactive oxygen species after a brief LPS incubation, which may also have reduced intracellular inflammation. The diminished activity of NF-κB in the cells could be linked to the inhibition of the activity of AKR1B1. Copyright © 2017 John Wiley & Sons, Ltd.


Optimal size threshold for PIRADSv2 category 5 upgrade and its positive predictive value: is it predictive of "very high" likelihood of clinically-significant cancer?
To identify the optimal size metric and threshold for Prostate Imaging Reporting and Data System (PIRADS) 5 upgrade, calculate its positive predictive value (PPV) for clinically-significant prostate cancer (csPCA), and determine if it is indicative of a "very high" likelihood of csPCA. One hundred and forty-three PIRADS 4 or 5 lesions were evaluated. Lesion diameters were used to calculate lesion volume (LV). Pearson correlation between maximum lesion diameter (MLD) and LV was calculated. Area under the curve (AUC) for discriminating csPCA (Gleason grade ≥ 3 + 4) was calculated using MLD and LV. Optimal size thresholds (using Youden index) and highly predictive size thresholds were identified for the whole prostate (WP), peripheral zone (PZ), and transitional zone (TZ). There was high correlation between MLD and LV (r=0.77-0.81), with comparable AUCs for MLD and LV in the identification of csPCA in the WP (0.73, 0.72), PZ (0.73, 0.73), and TZ (0.79, 0.75). Optimal MLD thresholds were 1.4, 1.4, and 1.6 cm in the WP, PZ, and TZ respectively, with PPVs of 76%, 81%, and 69%, respectively. An MLD threshold of 2.7 cm would be needed in the WP to achieve a PPV approaching 90%, with sensitivity decreasing to 10%. There is high correlation between MLD and LV with comparable discrimination of csPCA using each. PIRADSv2's 1.5 cm MLD threshold is near the optimal threshold for PIRADS 5 upgrade but has moderate PPV. A much higher threshold would be needed to increase its PPV, with significant sacrifice in sensitivity.


Midwifery care in eight industrialized countries: how does Canadian midwifery compare?
Much has been written about the status of midwifery in developing countries, yet there is limited knowledge and analysis of the role of midwifery in the provision of maternity care in the developed world. The purpose of this study was to better understand how midwifery in Canada compares with midwifery in other developed countries with particular attention to educational preparation, scope of practice, and the contribution of midwives to the overall provision of maternity care. Eight countries were selected on the basis of comparably low maternal mortality rates (defined as < 10/100,000 live births). Document analysis and a survey of key informants were used to develop an understanding of the role of midwifery in the various jurisdictions. We then undertook an analysis of similarities and differences among models. Variations in models of midwifery exist within and among the countries studied. Midwifery in Canada is most similar to midwifery in the Netherlands and New Zealand with regard to the model of practice, continuity of care, choice of birth place and degree of autonomy. Midwifery in Canada is growing, but offers a relatively small contribution to the national provision of maternity services in comparison with other countries. The growth of midwifery in Canada may play a key role in lowering intervention rates and strengthening maternity care as is evidenced in other industrialized nations where midwifery care is an integral part of maternity services.


Multidisciplinary care improves clinical outcome and reduces medical costs for pre-end-stage renal disease in Taiwan.
Multidisciplinary care (MDC) for patients with chronic kidney disease (CKD) may help to optimize disease care and improve clinical outcomes. Our study aimed to evaluate the effectiveness of pre-end-stage renal disease (ESRD) patients under MDC and usual care in Taiwan. In this 3-year retrospective observational study, we recruited 822 ESRD subjects, aged 18 years and older, initiating maintenance dialysis more than 3 months from five cooperating hospitals. The MDC (n = 391) group was cared for by a nephrologists-based team and the usual care group (n = 431) was cared for by sub-specialists or nephrologists alone more than 90 days before dialysis initiation. Patient characteristics, dialysis modality, hospital utilization, hospitalization at dialysis initiation, mortality and medical cost were evaluated. Medical costs were further divided into in-hospital, emergency services and outpatient visits. The MDC group had a better prevalence in peritoneal dialysis (PD) selection, less temporary catheter use, a lower hospitalization rate at dialysis initiation and 15% reduction in the risk of hospitalization (P < 0.05). After adjusting for gender, age and Charlson Comorbidity Index score, there were lower in-hospital and higher outpatient costs in the MDC group during 3 months before dialysis initiation (P < 0.05). In contrast, medical costs (NT$ 146,038 vs 79,022) and hospitalization days (22.4 vs 15.5 days) at dialysis initiation were higher in the usual care group. Estimated medical costs during 3 months before dialysis till dialysis initiation, the MDC group yielded a reduction of NT$ 59,251 for each patient (P < 0.001). Patient mortality was not significantly different. Multidisciplinary care intervention for pre-ESRD patients could not only significantly improve the quality of disease care and clinical outcome, but also reduce medical costs.


Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers.
To determine the feasibility of delivering inhaled treprostinil during mechanical ventilation and spontaneous unassisted ventilation using the Tyvaso Inhalation System and the vibrating mesh nebulizer. We sought to compare differences in fine particle fraction, and absolute inhaled treprostinil mass delivered to neonatal, pediatric, and adult models affixed with a face mask, conventional, and high-frequency ventilation between Tyvaso Inhalation System and with different nebulizer locations between Tyvaso Inhalation System and vibrating mesh nebulizer. Fine particle fraction was first determined via impaction with both the Tyvaso Inhalation System and vibrating mesh nebulizer. Next, a test lung configured with neonatal, pediatric, and adult mechanics and a filter to capture medication was attached to a realistic face model during spontaneous breathing or an endotracheal tube during conventional ventilation and high-frequency oscillator ventilator. Inhaled treprostinil was then nebulized with both the Tyvaso Inhalation System and vibrating mesh nebulizer, and the filter was analyzed via high-performance liquid chromatography. Testing was done in triplicate. Independent two-sample t tests were used to compare mean fine particle fraction and inhaled mass between devices. Analysis of variance with Tukey post hoc tests were used to compare within device differences. Academic children's hospital aerosol research laboratory. Fine particle fraction was not different between the Tyvaso Inhalation System and vibrating mesh nebulizer (0.78 ± 0.04 vs 0.77 ± 0.08, respectively; p = 0.79). The vibrating mesh nebulizer delivered the same or greater inhaled treprostinil than the Tyvaso Inhalation System in every simulated model and condition. When using the vibrating mesh nebulizer, delivery was highest when using high-frequency oscillator ventilator in the neonatal and pediatric models, and with the nebulizer in the distal position in the adult model. The vibrating mesh nebulizer is a suitable alternative to the Tyvaso Inhalation System for inhaled treprostinil delivery. Fine particle fraction is similar between devices, and vibrating mesh nebulizer delivery meets or exceeds delivery of the Tyvaso Inhalation System. Delivery for infants and children during high-frequency oscillator ventilator with the vibrating mesh nebulizer may result in higher than expected dosages.


The complex problem of the interprosthetic femoral fracture in the elderly patient.
An ageing population and greater number of hip and knee replacements performed have led to an increasing number of patients with ipsilateral hip and knee replacements in situ. This often physiologically suboptimal population is at risk for periprosthetic fracture. An interprosthetic femoral fracture represents a unique challenge to the surgeon and requires a detailed multidisciplinary management strategy involving both fracture fixation and often complex revision. We have identified the largest series to our knowledge of patients presenting for surgical management of an unstable fracture between a hip and knee prosthesis. Institutional approval was granted for prospective study of these patients. We present the detailed management, outcome and review the known literature of the best practice for such a complex surgical case. We have outlined 9 fractures in 8 patients presenting to a single trauma unit. A variety of surgical options, often more than one, were employed. One patient died during the study period. All fractures progressed to union. There was a female preponderance with a mean age of 78 years. All patients had established systemic and metabolic bone morbidity. We believe this fracture pattern presents to the general orthopaedic surgeon a unique challenge, which bridges the expertise of the trauma and revision surgical spectrum. It is obvious that this will become an increasing issue with the median age of the population increasing. This case series highlights the need for ready availability of biological, arthroplasty and trauma systems to address such.


Assessment of fidelity in an educational workshop designed to increase the uptake of a primary care alcohol screening recommendation.
Educational workshops are a commonly used quality improvement intervention. Often delivered by credible local health professionals who do not necessarily have skills in pedagogy, it can be challenging to achieve high intervention fidelity. This paper summarizes the fidelity assessment of a workshop designed to increase the uptake of a primary care alcohol screening recommendation. Delivered in a single health region, the workshop comprised separate sessions delivered by three local health professionals, plus two role plays delivered by a commercial company. Sessions were tailored to local barriers. Meetings were held with presenters and an outline of the barriers was provided. Two researchers attended the workshop, rating the number of specified barriers targeted by presenters and their quality of delivery. Participant responsiveness was measured through attendees' feedback and intervention dose was calculated as the proportion of health professionals who attended and proportion of general practices represented. Exposure was low, with 62 of 545 health professionals from 30 of a possible 80 practices attending. Sixty-five per cent of the specified barriers were targeted. There was variability in quality of delivery and participant responsiveness; challenges included potential mixed messages, overreliance on didactic methods and certain barriers appearing easier to target than others. The framework provided a rounded assessment of intervention fidelity: intervention coverage was low, adherence was moderate and there was variability in the quality of delivery across presenters. Future studies testing the effectiveness of interventions delivered by local experts with and without brief training in pedagogy/behaviour change would be beneficial.


Genome-wide multi-omics analysis reveals the nutrient-dependent metabolic features of mucin-degrading gut bacteria.
The prevalence and occurrence of mucin-degrading (MD) bacteria, such as Akkermansia muciniphila and Ruminococcus gnavus, is highly associated with human health and disease states. However, MD bacterial physiology and metabolism remain elusive. Here, we assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 54 A. muciniphila genes and 296 R. gnavus genes. The reconstructed core metabolic pathways coincided with the growth kinetics and fermentation profiles of A. muciniphila and R. gnavus grown in the presence of mucin and its constituents. Genome-wide multi-omics analyses validated the nutrient-dependent fermentation profiles of the MD bacteria and identified their distinct mucolytic enzymes. The distinct metabolic features of the two MD bacteria induced differences in the metabolite receptor levels and inflammatory signals of the host immune cells. In addition, in vivo experiments and community-scale metabolic modeling demonstrated that different dietary intakes influenced the abundance of MD bacteria, their metabolic fluxes, and gut barrier integrity. Thus, this study provides insights into how diet-induced metabolic differences in MD bacteria determine their distinct physiological roles in the host immune response and the gut ecosystem.


Towards a more effective climate policy on international trade.
In the literature on the attribution of responsibilities for greenhouse gas emissions, two accounting methods have been widely discussed: production-based accounting (PBA) and consumption-based accounting (CBA). It has been argued that an accounting framework for attributing responsibilities should credit actions contributing to reduce global emissions and should penalize actions increasing them. Neither PBA nor CBA satisfy this principle. Adapting classical Ricardian trade theory, we consider ex post measurement and propose a scheme for assigning credits and penalties. Their size is determined by how much CO2 emissions are saved globally due to trade. This leads to the emission responsibility allotment (ERA) for assigning responsibilities. We illustrate the differences between ERA and PBA and CBA by comparing their results for 41 countries and regions between 1995-2009. The Paris Agreement (COP21) proposed new market mechanisms; we argue that ERA is well suited to measure and evaluate their overall mitigation impact.


Placental pathology and neurodevelopment of the infant with intrauterine growth restriction.
The placentas of 68 infants with intrauterine growth restriction (IUGR) were examined for evidence of impaired uteroplacental circulation and compared with those of 65 appropriately grown infants. Infarcts and/or accelerated villous maturation were present in the placentas in 27 (40%) of the infants with IUGR compared with seven (11%) of the infants without IUGR (P<0.001). The infants were followed-up at 4 and 12 months of age and growth parameters recorded. Medical and developmental assessments and neuromotor developmental examinations were also performed. The 23 infants in the IUGR group with placentas with evidence of impaired uteroplacental circulation were compared with the 31 infants with IUGR with normal placentas. There was no difference between the groups in growth, cognitive development, or neuromotor abnormality. It was concluded that IUGR is strongly associated with placental markers of impaired uteroplacental blood flow while it would appear that there is no association between placental pathology and growth or neurodevelopment in the first year.


Effect of trial order and error magnitude on motor learning by observing.
Watching an actor make reaching movements in a perturbing force field provides the observer with information about how to compensate for that force field. Here we asked two questions about the nature of information provided to the observer. Is it important that the observer learn the difference between errant (curved) movements and goal (straight) movements by watching the actor progress in a relatively orderly fashion from highly curved to straight movements over a series of trials? Or is it sufficient that the observer sees only reaching errors in the force field (FF)? In the first experiment, we found that observers performed better if they observed reaches in a FF that was congruent, rather than incongruent, with the FF used in a later test. Observation-trial order had no effect on performance, suggesting that observers understood the goal in advance and perhaps learned about the force-field by observing movement curvature. Next we asked whether observers learn optimally by observing the actor's mistakes (high-error trials), if they learn by watching the actor perform with expertise in the FF (low-error trials), or if they need to see contrast between errant and goal behavior (a mixture of both high- and low-error trials). We found that observers who watched high-error trials were most affected by observation but that significant learning also occurred if observers watched only some high-error trials. This result suggests that observers learn to adapt their reaching to an unpredictable FF best when they see the actor making mistakes.


The association between a polygenic Alzheimer score and cortical thickness in clinically normal subjects.
Late-onset Alzheimer's disease (AD) is 50-70% heritable with complex genetic underpinnings. In addition to Apoliprotein E (APOE) ε4, the major genetic risk factor, recent genome-wide association studies (GWAS) have identified a growing list of sequence variations associated with the disease. Building on a prior large-scale AD GWAS, we used a recently developed analytic method to compute a polygenic score that involves up to 26 independent common sequence variants and is associated with AD dementia, above and beyond APOE. We then examined the associations between the polygenic score and the magnetic resonance imaging-derived thickness measurements across AD-vulnerable cortex in clinically normal (CN) human subjects (N = 104). AD-specific cortical thickness was correlated with the polygenic risk score, even after controlling for APOE genotype and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ(1-42)). Furthermore, the association remained significant in CN subjects with levels of CSF Aβ(1-)(42) in the normal range and in APOE ε3 homozygotes. The observation that genetic risk variants are associated with thickness across AD-vulnerable regions of interest in CN older individuals, suggests that the combination of polygenic risk profile, neuroimaging, and CSF biomarkers may hold synergistic potential to aid in the prediction of future cognitive decline.


Physical activity in Brazil: lessons from ELSA-Brasil. Narrative review.
The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) was conducted among civil servants at six higher education institutions located in six Brazilian state capitals. The objective of this review was to identify the publications produced within the scope of ELSA-Brasil that analyzed the participants' physical activity. Review study using baseline data from ELSA-Brasil. Narrative review of Brazilian studies on physical activity produced using data from ELSA-Brasil participants. The prevalence of leisure-time physical activity (LTPA) among ELSA-Brasil participants was low (44.1% among men and 33.8% among women). The main factors associated were social (higher schooling and family income), environmental (living in places with conditions and opportunities for physical activity) and individual (not being obese, being retired, not smoking and positive perception of body image). The perception of facilities for walking in the neighborhood was positively associated with both LTPA and commuting-related physical activity. An active lifestyle was a protective factor against several cardiometa-bolic variables (hypertension, diabetes, lipid abnormalities and cardiovascular risk over the next 10 years). Comparison between LTPA and commuting-related physical activity showed that only LTPA had a protective effect against arterial hypertension. The prevalence of physical activity among ELSA-Brasil participants was low. The main determinants were social, environmental and personal. LTPA had a greater protective efect on cardio-metabolic outcomes than did commuting-related physical activity.


Preserving the world's tropical forests--a price on carbon may not do.
Climate policy will create both disincentives and incentives for tropical deforestation. Disincentives if the carbon emissions from forest clearing are priced, as is currently being discussed within the United Nations Framework Convention on Climate Change (UNFCCC); incentives as a price on carbon will increase the demand for carbon-neutral energy sources, including bioenergy, making deforestation for biomass cultivation increasingly profitable. The question is whether the increased cost for forest clearing, through the price on carbon emissions, will be enough to counter-balance the increased profitability of deforestation through the escalating value of agricultural land. In an attempt to answer this question we analyze the profitability of tropical deforestation and subsequent bioenergy production, taking oil palm plantations as an illustrative example. We estimate that deforesting for palm oil bioenergy production is likely to remain highly profitable, even in the face of a price on the carbon emissions from forest clearing. Current efforts to include carbon emissions from tropical deforestation in a future international climate regime, while a step in the right direction, may therefore not suffice as protection for the world's tropical forests. Additional, and stronger, protection measures for the world's tropical forests will still be needed.


Dexmedetomidine versus Midazolam in Procedural Sedation. A Systematic Review of Efficacy and Safety.
To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation. We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (≥18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications. We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar. Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar.


Synthesis of the aminocyclitol units of (-)-hygromycin A and methoxyhygromycin from myo-inositol.
Concise and efficient syntheses of the aminocyclitol cores of hygromycin A (HMA) and methoxyhygromycin (MHM) have been achieved starting from readily available myo-inositol. Reductive cleavage of myo-inositol orthoformate to the corresponding 1,3-acetal, stereospecific introduction of the amino group via the azide, and resolution of a racemic cyclitol derivative as its diastereomeric mandelate esters are the key steps in the synthesis. Synthesis of the aminocyclitol core of hygromycin A involved chromatography in half of the total number of steps, and the aminocyclitol core of methoxyhygromycin involved only one chromatography.


Pathoanatomic studies and clinical significance of lumbosacral zygapophyseal (facet) joints.
Low back pain, with or without pain referred to the leg, affects up to 85% of the population at some time during their lives, which places an enormous economic burden upon many world communities and costs the United States in excess of $13 billion per year. The role of the lumbosacral zygapophyseal (facet, interlamina) joints in the low back "facet" syndrome is briefly discussed, including the clinical symptomatology. The main purpose of this article is to provide preliminary morphological findings of histological studies of human cadaveric lower lumbosacral spines, which show some examples of how the zygapophyseal joints may be involved in dysfunction of mechanical origin. Statistical analysis of the frequency of these findings will be published when the histological study currently under way is completed. While it is not possible to correlate morphological changes in cadavers with pain, it appears that the zygapophyseal joints and their associated soft tissues could be a source of low back pain of mechanical origin, with or without referred pain to the leg.