Cardiac MRI to Visualize Myocardial Damage after ST-Segment Elevation Myocardial Infarction: A Review of Its Histologic Validation.
Cardiac MRI is a noninvasive diagnostic tool using nonionizing radiation that is widely used in patients with ST-segment elevation myocardial infarction (STEMI). Cardiac MRI depicts different prognosticating components of myocardial damage such as edema, intramyocardial hemorrhage (IMH), microvascular obstruction (MVO), and fibrosis. But how do cardiac MRI findings correlate to histologic findings? Shortly after STEMI, T2-weighted imaging and T2* mapping cardiac MRI depict, respectively, edema and IMH. The acute infarct size can be determined with late gadolinium enhancement (LGE) cardiac MRI. T2-weighted MRI should not be used for area-at-risk delineation because T2 values change dynamically over the first few days after STEMI and the severity of T2 abnormalities can be modulated with treatment. Furthermore, LGE cardiac MRI is the most accurate method to visualize MVO, which is characterized by hemorrhage, microvascular injury, and necrosis in histologic samples. In the chronic setting post-STEMI, LGE cardiac MRI is best used to detect replacement fibrosis (ie, final infarct size after injury healing). Finally, native T1 mapping has recently emerged as a contrast material-free method to measure infarct size that, however, remains inferior to LGE cardiac MRI. Especially LGE cardiac MRI-defined infarct size and the presence and extent of MVO may be used to monitor the effect of new therapeutic interventions in the treatment of reperfusion injury and infarct size reduction. © RSNA, 2021 Online supplemental material is available for this article.


Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis.
Objective To elucidate the role of hypoxia and inflammatory pathways in the pathogenesis of iatrogenic laryngotracheal stenosis (iLTS). Study Design (1) Examination of mucosal surface gene expression in human iLTS. (2) In vitro comparison of normal and scar laryngotracheal fibroblasts under normoxic and hypoxic conditions. Setting Tertiary care hospital in a research university (2012-2016). Subjects and Methods Brush biopsies were obtained from normal laryngotracheal tissue and scar in iLTS patients; gene expression was compared. Fibroblasts were isolated from normal and scarred trachea and grown in vitro in either a 1% O2 or normoxic environment. Cell growth and gene and protein expression were compared. Statistical analysis utilized a multilevel mixed effects model. Results Expression of IL-6 (fold change = 2.8, P < .01), myofibroblast marker αSMA (fold change = 3.0, P = .01), and MMP13 (fold change = 5.4, P = .02) was significantly increased in scar biopsy samples as compared to normal. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts proliferated significantly faster (n = 8, P < .01 each day). Expression of IL-6 (n = 8, fold change = 2.6, P < .01) increased significantly after 12 hours under hypoxia. Expression of αSMA (n = 8, fold change= 2.0, P = .03), COL1 (n = 8, fold change = 1.1, P = .03), and MMP13 (n = 8, fold change = 1.6, P = .01) increased significantly after 48 hours under hypoxia. Scar fibroblasts also proliferated significantly faster under hypoxic conditions but did not display the same expression profile. Conclusion Human iLTS scar has a myofibroblast phenotype. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts can transdifferentiate into a similar phenotype. These changes may be mediated by IL-6, a fibrosis-related cytokine.


50-km single-ended spontaneous-Brillouin-based distributed-temperature sensor exploiting pulsed Raman amplification.
We demonstrate enhanced performance of a single-ended spontaneous-Brillouin-intensity-based distributed-temperature sensor with a sensing length of 50 km and a spatial resolution of 15 m by use of Raman amplification of the probe pulse within the sensing fiber. The Raman amplification was achieved with a copropagating pump pulse at 1450 nm. The standard deviation error of the temperature resolution was 1 degree C at the front end and increased to less than 13 degrees C at 50 km with Raman pulse amplification.


Association between protein-rich dietary patterns and anthropometric measurements among children aged 6 years.
The associations between types of dietary protein intake and child anthropometric measurements have not been fully studied. Therefore, we examined dietary protein pattern in relation to anthropometric indicators among 6-year-old children. We carried out a cross-sectional study of 788 randomly selected children from health centres in Tehran, Iran. Dietary intake was assessed using a food frequency questionnaire completed by the mothers. Anthropometric measurements were based on standard protocols. Principle component analysis was performed to identify different dietary protein patterns. We used multivariate logistic regression to evaluate how these patterns were associated with child anthropometry. Three dietary protein patterns were identified: pattern 1 (rich in red and processed meats, dairy products and eggs), pattern 2 (rich in fish and poultry) and pattern 3 (rich in soy and legumes). After adjusting for potential confounders (energy intake, socioeconomic status and physical activity), being in the third compared to the first tertiles of pattern 2 was associated with increased (OR = 1.57; 95% CI: 1.09-2.27; P = .01) and decreased (OR = 0.54; 95% CI: 0.32-0.92; P = .02) risk of overweight/obesity and underweight/wasting, respectively. There was no association between other dietary patterns and risk of overweight/obesity or underweight/wasting. The present study showed inverse association between the fish/white meat pattern and underweight/wasting and also a positive association between higher fish/white meat protein intake and higher risk of overweight/obesity. Further studies are needed to confirm these results.


A mitochondrial protein homologous to the mammalian peripheral-type benzodiazepine receptor is essential for stress adaptation in plants.
The cloning of abiotic stress-inducible genes from the moss Physcomitrella patens led to the identification of the gene PpTSPO1, encoding a protein homologous to the mammalian mitochondrial peripheral-type benzodiazepine receptor and the bacterial tryptophane-rich sensory protein. This class of proteins is involved in the transport of intermediates of the tetrapyrrole biosynthesis pathway. Like the mammalian homologue, the PpTSPO1 protein is localized to mitochondria. The generation of PpTSPO1-targeted moss knock-out lines revealed an essential function of the gene in abiotic stress adaptation. Under stress conditions, the PpTSPO1 null mutants show elevated H(2)O(2) levels, enhanced lipid peroxidation and cell death, indicating an important role of PpTSPO1 in redox homeostasis. We hypothesize that PpTSPO1 acts to direct porphyrin precursors to the mitochondria for heme formation, and is involved in the removal of photoreactive tetrapyrrole intermediates.


Teaching empathy to medical students: an updated, systematic review.
Some research shows that empathy declines during medical school. The authors conducted an updated, systematic review of the literature on empathy-enhancing educational interventions in undergraduate medical education. The authors searched PubMed, EMBASE, PsycINFO, CINAHL, Scopus, and Web of Science (January 1, 2004 through March 19, 2012) using key words related to undergraduate medical education and empathy. They independently selected and reviewed all English-language articles that described an educational intervention designed to promote empathy in medical students, assessing the quality of the quantitative studies using the Medical Education Research Study Quality Instrument (MERSQI). The authors identified and reviewed the full texts of 18 articles (15 quantitative and 3 qualitative studies). Included interventions used one or more of the following-patient narrative and creative arts (n=7), writing (n=3), drama (n=1), communication skills training (n=4), problem-based learning (n=1), interprofessional skills training (n=1), patient interviews (n=4), experiential learning (n=2), and empathy-focused training (n=1). Fifteen articles reported significant increases in empathy. Mean effect size was 0.23. Mean MERSQI score was 10.13 (range 6.5-14). These findings suggest that educational interventions can be effective in maintaining and enhancing empathy in undergraduate medical students. In addition, they highlight the need for multicenter, randomized controlled trials, reporting long-term data to evaluate the longevity of intervention effects. Defining empathy remains problematic, and the authors call for conceptual clarity to aid future research.


Problems and perils of prescription medicines.
Most of the advertising material and articles in scientific journals about new drugs focus on their potential benefits. Data on the safety and tolerability of drugs are collected and carefully analysed during clinical trials, but the scope of this information is limited. Safe use of medicines requires a balanced assessment of both risks and benefits. This symposium at the Royal College of Physicians sought to highlight current issues in assessing the risks associated with prescription medicines. The result was a lively and informative debate with insights and challenges for prescribers and drug developers alike. This report focuses on the issues of most interest to drug developers.


Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer's disease.
Lifestyle factors such as intellectual stimulation, cognitive and social engagement, nutrition, and various types of exercise appear to reduce the risk for common age-associated disorders such as Alzheimer's disease (AD) and vascular dementia. In fact, many studies have suggested that promoting physical activity can have a protective effect against cognitive deterioration later in life. Slowing or a deterioration of walking speed is associated with a poor performance in tests assessing psychomotor speed and verbal fluency in elderly individuals. Fitness training influences a wide range of cognitive processes, and the largest positive impact observed is for executive (a.k.a. frontal lobe) functions. Studies show that exercise improves additional cognitive functions such as tasks mediated by the hippocampus, and result in major changes in plasticity in the hippocampus. Interestingly, this exercise-induced plasticity is also pronounced in APOE ε4 carriers who express a risk factor for late-onset AD that may modulate the effect of treatments. Based on AD staging by Braak and Braak (1991) and Braak et al. (1993) we propose that the effects of exercise occur in two temporo-spatial continua of events. The "inward" continuum from isocortex (neocortex) to entorhinal cortex/hippocampus for amyloidosis and a reciprocal "outward" continuum for neurofibrillary alterations. The exercise-induced hypertrophy of the hippocampus at the core of these continua is evaluated in terms of potential for prevention to stave off neuronal degeneration. Exercise-induced production of growth factors such as the brain-derived neurotrophic factor (BDNF) has been shown to enhance neurogenesis and to play a key role in positive cognitive effects. Insulin-like growth factor (IGF-1) may mediate the exercise-induced response to exercise on BDNF, neurogenesis, and cognitive performance. It is also postulated to regulate brain amyloid β (Aβ) levels by increased clearance via the choroid plexus. Growth factors, specifically fibroblast growth factor and IGF-1 receptors and/or their downstream signaling pathways may interact with the Klotho gene which functions as an aging suppressor gene. Neurons may not be the only cells affected by exercise. Glia (astrocytes and microglia), neurovascular units and the Fourth Element may also be affected in a differential fashion by the AD process. Analyses of these factors, as suggested by the multi-dimensional matrix approach, are needed to improve our understanding of this complex multi-factorial process, which is increasingly relevant to conquering the escalating and intersecting world-wide epidemics of dementia, diabetes, and sarcopenia that threaten the global healthcare system. Physical activity and interventions aimed at enhancing and/or mimicking the effects of exercise are likely to play a significant role in mitigating these epidemics, together with the embryonic efforts to develop cognitive rehabilitation for neurodegenerative disorders.


Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions.
Genetic effects on gene expression and splicing can be modulated by cellular and environmental factors; yet interactions between genotypes, cell type, and treatment have not been comprehensively studied together. We used an induced pluripotent stem cell system to study multiple cell types derived from the same individuals and exposed them to a large panel of treatments. Cellular responses involved different genes and pathways for gene expression and splicing and were highly variable across contexts. For thousands of genes, we identified variable allelic expression across contexts and characterized different types of gene-environment interactions, many of which are associated with complex traits. Promoter functional and evolutionary features distinguished genes with elevated allelic imbalance mean and variance. On average, half of the genes with dynamic regulatory interactions were missed by large eQTL mapping studies, indicating the importance of exploring multiple treatments to reveal previously unrecognized regulatory loci that may be important for disease.


Newborn screening for severe combined immunodeficiency (SCID): a review.
Because prompt intervention may prevent complications, early diagnosis is important in many inherited metabolic diseases. Early diagnosis of Severe Combined Immunodeficiency (SCID) is critical - because chances for successful treatment are highest for infants who have not yet experienced severe opportunistic infections. SCID is a rare disease that can be detected in newborn infants (i.e., those more or equal 1 month of age) by automated blood count and manual differential. Early diagnosis of SCID is rare since, because estimates of the incidence rate range from one in 50,000 to 100,000 births, most pediatricians do not routinely count white blood cells in newborns. Tests for T-cell lymphopenia (TCLP) using dried blood spots (DBS) could be used to identify children with SCID - as well as for other immunodeficiencies that would not be apparent until after the child developed an infection. Screening newborns for SCID would allow early diagnosis and treatment -- as well as genetic counseling for the family.


Alterations in the common pathway of coagulation during weight loss induced by gastric bypass in severely obese patients.
The objective of this study was to establish the relationship between the plasminogen activator inhibitor-1 (PAI-1), antithrombin-III (ATIII), fibrinogen, and white blood cell (WBC) levels in severely obese patients. We analyzed various plasma parameters implicated in the intrinsic and extrinsic coagulation pathway from 34 severely obese patients before and 1, 6, and 12 months after gastric bypass. In obese people, ATIII, fibrinogen, and WBC levels were in the upper limit of the normal range, and all were higher and significantly different from nonobese people. After bariatric surgery, the ATIII level continued to be high during the first month and increased until 12 months, while fibrinogen decreased only at that time. PAI-1 plasma protein and PAI-1 mRNA levels in liver and adipose tissue show similar profiles and had a strong positive correlation (r = 0.576, P = 0.0003 in liver; r = 0.433, P = 0.0004 in adipose tissue). They were higher in obese patients compared with nonobese control, but tended to recover normal values 1 month after surgery. Thus, the liver and adipose tissue could be an important source of PAI-1 protein in plasma. Gastric bypass surgery leads to a normalization of the hematological profile and a decrease in PAI-1 levels, which entails a decrease of risk for thromboembolism in severely obese.


Use of Hydroxychloroquine in Hair Disorders.
Hydroxychloroquine (HCQ) is an antimalarial that is utilized to treat a range of dermatologic and autoimmune disorders. With its ability to alter immunologic mechanisms, it has been used to slow or halt the progression of hair loss in conditions secondary to autoimmune dysfunction. Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and alopecia areata (AA) are hair disorders with underlying autoimmune components and no standardized treatment guidelines. We summarized the available literature on the use of HCQ to treat LPP, FFA, and AA. For all three conditions, HCQ showed variable efficacy from halted hair loss to no improvement. While patients did show success with HCQ treatment, there were no clear treatment patterns. Regimens ranged from HCQ monotherapy to combination treatments with other agents like steroids. Overall, HCQ should certainly be considered by clinicians as a treatment option for patient suffering from these hair disorders. While there is no standardized treatment, incorporation of HCQ should take into consideration individual patient characteristics, clinical judgment, and risks of side effects.


Grisel syndrome presenting as hemiplegia in a patient with multifocal staphylococcal sepsis.
Grisel syndrome is a non-traumatic rotary subluxation of C1 on C2 (atlantoaxial subluxation). It is a rare condition predominantly described in paediatric population with previous history of upper respiratory infections orotolaryngeal procedures. The diagnosis is established by the association of clinical and radiologic findings4,6.We report a case of 15-year old boy with Grisel syndrome accompanying multifocal sepsis (pericarditis, septic polyarthritis, pneumonia and pharangytis ), treated surgically - occipital cervical fusion using struts of iliac crest tri-cortical graft wired to the occiput and C3 and C4. To describe a case of non-traumatic atlantoaxial rotatory subluxation (Grisel syndrome) and to review clinical and radiologic aspects, pathophysiology, and treatment of this rare condition, which if left untreated can lead to catastrophic outcomes. Authors are trying to demonstrate the significance of early intervention for improved outcomes, and that physicians should examine patients with multifocal sepsis thoroughly so as not to miss foci of infection and have high index of suspicion of the syndrome in patients that present with neck swelling, and develop torticollis and neurological deficit. This is a case presentation of a 15-year-old boy who presented with an acute history of neck swelling, shortness of breath, orthopnoea, pericardial effusion, right hip and knee swelling. He later developed torticollis and left sided hemiplegia. On admission, he was septicemic. There was no history of head or neck trauma. Cervical spine radiograph showed increased atlantodental index (ADI) and prevertebral soft tissue swelling. Consent was sought from guardian and patient to use images and case notes for submission for publication. The patient was treated with analgesia, drainage of pericardial effusion and intravenous antibiotics. The right knee sepsis was noted on admission and drained on the day pericardial drain was inserted, while the right hip was missed - only to be noted 59 days later with limb length discrepancy. The C1/C2 subluxation was noted 17 days after admission. Reduction was done soon after diagnosis and maintained with a halo-thoracic immobilizer. A week later, he underwent posterior occipital cervical fusion. The hemiplegia resolved fully. Multifocal staphylococcal septicemia can present with unusual foci of infection, which may be missed especially if the patient is very sick. Grisel syndrome with an associated left hemiplegia and septic arthritis of the right hip were diagnosed late in this case. Grisel syndrome patients might end up with catastrophic outcomes if left untreated or mis-diagnosed, but if prompt treatment is initiated, full functional recovery is achievable.


The fluorescent aptamer Squash extensively repurposes the adenine riboswitch fold.
Squash is an RNA aptamer that strongly activates the fluorescence of small-molecule analogs of the fluorophore of green fluorescent protein (GFP). Unlike other fluorogenic aptamers, isolated de novo from random-sequence RNA, Squash was evolved from the bacterial adenine riboswitch to leverage its optimized in vivo folding and stability. We now report the 2.7-Å resolution cocrystal structure of fluorophore-bound Squash, revealing that while the overall fold of the riboswitch is preserved, the architecture of the ligand-binding core is dramatically transformed. Unlike previously characterized aptamers that activate GFP-derived fluorophores, Squash does not harbor a G-quadruplex, sandwiching its fluorophore between a base triple and a noncanonical base quadruple in a largely apolar pocket. The expanded structural core of Squash allows it to recognize unnatural fluorophores that are larger than the simple purine ligand of the parental adenine riboswitch, and suggests that stable RNA scaffolds can tolerate larger variation than has hitherto been appreciated.


Epidural ropivacaine 1% with and without sufentanil addition for Caesarean section.
So far only ropivacaine concentrations of 0.5 and 0.75% have been used for Caesarean section. This prospective double-blind trial evaluated the anaesthetic quality of ropivacaine 1% with and without sufentanil addition. Three groups of patients (n=20 each) scheduled for an elective Caesarean section were studied. The patients received initially 120 mg ropivacaine, or 120 mg ropivacaine plus 10 microg or 20 microg sufentanil. Additional epidural ropivacaine was injected if necessary. Primary outcome parameter was time to achieve sensory block at T4. Moreover, pain intensity at delivery (visual analogue scale, VAS), incidence of maternal side-effects (hypotension, bradycardia, nausea, vomiting, shivering, pruritus), and neonatal outcome (Apgar score, neurologic and adaptive capacity score, umbilical cord blood-gas values) were recorded. The onset time for the sensory block was not significantly different among the groups. Also, VAS scores at delivery did not differ significantly between the plain ropivacaine 1% group (18 +/- 29 mm), the 10-microg sufentanil group (1 +/- 5 mm), and the 20-microg sufentanil group (6 +/- 18 mm). The total dose of ropivacaine was significantly higher in the plain ropivacaine 1% group (145 +/- 19 mg) compared to the patients receiving additional 10 microg sufentanil (130 +/- 15 mg, P = 0.02) or 20 microg sufentanil (129 +/- 16 mg, P = 0.01). The incidence of maternal side-effects and neonatal outcome were similar in all groups. Ropivacaine 1% alone provided sufficient analgesia. Sufentanil addition did not significantly improve the quality of epidural anaesthesia with ropivacaine 1.0% for Caesarean section.


Deep-sea hydrothermal vents: potential hot spots for natural products discovery?
Deep-sea hydrothermal vents are among the most extreme and dynamic environments on Earth. However, islands of highly dense and biologically diverse communities exist in the immediate vicinity of hydrothermal vent flows, in stark contrast to the surrounding bare seafloor. These communities comprise organisms with distinct metabolisms based on chemosynthesis and growth rates comparable to those from shallow water tropical environments, which have been rich sources of biologically active natural products. The geological setting and geochemical nature of deep-sea vents that impact the biogeography of vent organisms, chemosynthesis, and the known biological and metabolic diversity of Eukarya, Bacteria, and Archaea, including the handful of natural products isolated to date from deep-sea vent organisms, are considered here in an assessment of deep-sea hydrothermal vents as potential hot spots for natural products investigations. Of critical importance too are the logistics of collecting deep vent organisms, opportunities for re-collection considering the stability and longevity of vent sites, and the ability to culture natural product-producing deep vent organisms in the laboratory. New cost-effective technologies in deep-sea research and more advanced molecular techniques aimed at screening a more inclusive genetic assembly are poised to accelerate natural product discoveries from these microbial diversity hot spots.


Experience and perceptions of healthcare providers on clinical management and care of near-miss infants: a qualitative content analysis.
Neonatal Near Miss (NNM) refers to neonates with severe complications who almost died but survived immediately after birth. In Ethiopia, the prevalence of NNM has been assessed using a validated Neonatal Near-Miss Assessment Scale. However, understanding the experiences and perceptions of healthcare providers in the clinical management and care of NNM infants remains unexplored. The aim was to investigate the determinants contributing to the survival of neonatal near-miss babies and to identify any barriers encountered, as reported by the experiences of healthcare providers in public hospitals of Amhara Regional State, northwest Ethiopia. Semi structured interviews were used to collect data from 25 midwives, nurses, and pediatricians with at least six months of prior experience in one of the labor wards or neonatal intensive care units at one of the four public health hospitals in the Amhara Regional state of northwest Ethiopia included in a large intervention study assessing a NNM scale. Purposeful sampling was used, selecting participants based on their experiences related to the aim of this study. The participants had a varying level of education and years of experience to care for NNM infants. The average age of the healthcare providers was 31 years, with 7 years of work experience. The transcripts of the interviews with the healthcare providers were analyzed using qualitative content analysis. The experience and perceptions of healthcare providers was described in the main category "A sense of hopelessness when caring for the baby" capturing a broader emotional and professional aspect, while the subcategories "Unclear responsibilities discharging one's mission", "Provision of kangaroo mother care" and "Quick action required at birth" are more specific and practical. Healthcare providers perceived a sense of hopelessness when caring for the NNM infant, particularly providing Kangaroo Mother Care (KMC) and quick actions when required at birth to save the life of the infant. Unclear responsibilities and a sense of hopelessness could have acted as barriers, hindering the ability of healthcare providers to fulfill their mission of taking swift actions and providing KMC to NNM infants, thus impacting their ability to save the lives of these infants. Healthcare providers' and parents' attitudes must be changed towards hope rather than hopelessness when caring for NNM infants.


Aquabacter cavernae sp. nov., a bacterium isolated from cave soil.
A Gram-stain-negative, rod-shaped, non-motile, aerobic, catalase-negative and oxidase-positive bacterium, designated strain Sn-9-2T, was isolated from a cave soil sample collected from Tiandong cave, Guizhou Province, south-west PR China. Growth occurred at 15-40 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum, pH 7.0-8.0) and with 0-1 % NaCl (w/v). The predominant respiration quinone was ubiquinone-10 (Q-10). The major cellular fatty acids were summed feature 8 (C18 : 1ω7c or C18 : 1ω6c; 83.9 %) and C16 : 0 (5.8 %). The major polar lipids were phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine, phosphatidylglycerol, three unidentified phospholipids, two unidentified glycolipids, two unidentified polar lipids and one unidentified aminolipid. The DNA G+C content of strain Sn-9-2T was 67.5 mol%. Based on the results of 16S rRNA gene sequence analysis, the nearest phylogenetic neighbours of strain Sn-9-2T (MF958452) were identified as Aquabacter spiritensis (FR733686) DSM 9035T (97.5 %), Xanthobacter autorophicus (jgi.1053054) DSM 432T (97.2 %) and Xanthobacter tagetidis ATCC 700314T RCTF01000015 (96.9 %). The average nucleotide identity values were 78.0, 77.4 and 77.6 % and the digital DNA-DNA hybridization values were 21.8, 22.0 and 18.8 % between strain Sn-9-2T and A. spiritensis DSM 9035T, X. autotrophicus DSM 432T and X. tagetidis DSM 11105T, respectively. The DNA-DNA hybridization data indicated that strain Sn-9-2T represented a novel genomic species. On the basis of the results of phylogenetic analysis, chemotaxonomic data, physiological characteristics and DNA-DNA hybridization data, strain Sn-9-2T should represent a novel species of the genus Aquabacter, for which the name Aquabactercavernae sp. nov. is proposed. The type strain is Sn-9-2T (=KCTC 62308T=CCTCC AB 2018270T).


From Over-Tourism to Under-Tourism via COVID-19: Lessons for Sustainable Tourism Management.
With various strains of the novel coronavirus emerging during the last few years, there is a need to reinvent and manage the tourism industry by engaging various stakeholders. Industry and policymakers need to observe the shift and curate tourism-related products and offerings accordingly. In light of the increasing demand for innovations and future directions in the post-COVID-19 period, this article conducts a bibliometric analysis for sustainable tourism studies spanning the years 1990-2021. This paper presents an integrative review of tourism, environment and sustainable tourism to reveal geographical, contextual, and methodological directions for future research. The comprehensive analysis includes contributions on topics and methods, country collaborations, and thematic analysis. The findings are consistent with the Sustainable Development Goals of sustainable production and consumption (SDG-12), with a particular emphasis on sustainable tourism to promote local culture and create jobs (SDG-12.b) and on sustainable growth (SDG-13). The study's findings can be used to inform future policies and directions; for example, the findings indicate that the hospitality industry is facing challenges that necessitate new regulations to address its socioeconomic and environmental impacts.


Evaluation of Loopamp™ Leishmania Detection Kit and Leishmania Antigen ELISA for Post-Elimination Detection and Management of Visceral Leishmaniasis in Bangladesh.
With reduced prevalence of visceral leishmaniasis (VL) in the Indian subcontinent (ISC), direct and field deployable diagnostic tests are needed to implement an effective diagnostic and surveillance algorithm for post-elimination VL control. In this regard, here we investigated the diagnostic efficacies of a loop-mediated isothermal amplification (LAMP) assay (Loopamp™ Leishmania Detection Kit, Eiken Chemical CO., Ltd, Japan), a real-time quantitative PCR assay (qPCR) and the Leishmania antigen ELISA (CLIN-TECH, UK) with different sampling techniques and evaluated their prospect to incorporate into post-elimination VL control strategies. Eighty clinically and rK39 rapid diagnostic test confirmed VL cases and 80 endemic healthy controls were enrolled in the study. Peripheral blood and dried blood spots (DBS) were collected from all the participants at the time of diagnosis. DNA was extracted from whole blood (WB) and DBS via silica columns (QIAGEN) and boil & spin (B&S) methods and tested with qPCR and Loopamp. Urine was collected from all participants at the time of diagnosis and was directly subjected to the Leishmania antigen ELISA. 41 patients were followed up and urine samples were collected at day 30 and day 180 after treatment and ELISA was performed. The sensitivities of the Loopamp-WB(B&S) and Loopamp-WB(QIA) were 96.2% (95% CI 89·43-99·22) and 95% (95% CI 87·69-98·62) respectively. The sensitivity of Loopamp-DBS(QIA) was 85% (95% CI 75·26- 92·00). The sensitivities of the qPCR-WB(QIA) and qPCR-DBS(QIA) were 93.8% (95% CI 86·01-97·94) and 72.5% (95% CI 61·38-81·90) respectively. The specificity of all molecular assays was 100%. The sensitivity and specificity of the Leishmania antigen ELISA were 97.5% (95% CI 91·47-99·70) and 91.95% (95% CI 84·12-96·70) respectively. The Leishmania antigen ELISA depicted clinical cure at day 180 in all the followed-up cases. Efficacy and sustainability identify the Loopamp-WB(B&S) and the Leishmania antigen ELISA as promising and minimally invasive VL diagnostic tools to support VL diagnostic and surveillance activities respectively in the post-elimination era.


Construction and expression of a recombinant DNA gene encoding a polyomavirus middle-size tumor antigen with the carboxyl terminus of the vesicular stomatitis virus glycoprotein G.
We constructed a molecular clone encoding the N-terminal 379 amino acids of the polyomavirus middle-size tumor antigen, followed by the C-terminal 60 amino acids of the vesicular stomatitis virus glycoprotein G. This hybrid gene contained the coding region for the C-terminal hydrophobic membrane-spanning domain of the G protein in place of the C-terminal hydrophobic domain of the middle-size tumor antigen. The hybrid gene was expressed in COS-1 cells under the control of the simian virus 40 late promoter. The hybrid protein was located in cell membranes and was associated with a tyrosine-specific protein kinase activity, as was the middle-size tumor antigen. Plasmids encoding the hybrid protein failed to transform mouse NIH 3T3 or rat F2408 cells.


High Catalytic Activity of Co-centered 2D Metal Organic Frameworks toward Bifunctional Oxygen Evolution and Reduction Reactions: Rationalized by Spin Polarization Effect.
CoX4 (X = NH, S, and O) motifs have demonstrated their high catalytic activity in the platforms of metal organic frameworks (MOFs), however, the underlying reason is still unrevealed. Herein, we propose monolayers constructed by linking TMNxO4-x motifs (TM = Fe, Co, Ni, Cu) with trioxotriangulenes (TOTs) as suitable models to clarify the structure-property-performance relationship of 2D MOFs for the oxygen evolution/reduction reaction (OER/ORR). The highly robust catalytic activity of CoNxO4-x for both the OER and the ORR has been confirmed, even surpassing that of most previously reported 2D MOFs and SACs. This activity is attributed to the moderate interaction between Co and the key intermediate species, which can be modulated by the coordinating atoms. We reveal spin momentum as a reliable activity descriptor in rationalizing the OER/ORR activity, which can be extended to many other 2D MOFs. The elucidated structure-activity relationship is significant for the development of effective bifunctional OER/ORR electrocatalysts.


Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity.
Schlemm's canal (SC) is a specialized vascular structure in the eye that functions to drain aqueous humor from the intraocular chamber into systemic circulation. Dysfunction of SC has been proposed to underlie increased aqueous humor outflow (AHO) resistance, which leads to elevated ocular pressure, a factor for glaucoma development in humans. Here, using lymphatic and blood vasculature reporter mice, we determined that SC, which originates from blood vessels during the postnatal period, acquires lymphatic identity through upregulation of prospero homeobox protein 1 (PROX1), the master regulator of lymphatic development. SC expressed lymphatic valve markers FOXC2 and integrin α9 and exhibited continuous vascular endothelial-cadherin (VE-cadherin) junctions and basement membrane, similar to collecting lymphatics. SC notably lacked luminal valves and expression of the lymphatic endothelial cell markers podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Using an ocular puncture model, we determined that reduced AHO altered the fate of SC both during development and under pathologic conditions; however, alteration of VEGF-C/VEGFR3 signaling did not modulate SC integrity and identity. Intriguingly, PROX1 expression levels linearly correlated with SC functionality. For example, PROX1 expression was reduced or undetectable under pathogenic conditions and in deteriorated SCs. Collectively, our data indicate that PROX1 is an accurate and reliable biosensor of SC integrity and identity.


Clinical manifestations of benign prostatic hyperplasia and indications for therapeutic intervention.
The symptomatology of benign prostatic hyperplasia is a complex issue, and the clear-cut indications for therapeutic intervention are few. Overflow incontinence is a clear indication for treatment, and it seems prudent to recommend surgical intervention for patients with large postvoiding residual volumes. Acute urinary retention, recurrent infection, azotemia, and severe hematuria are other strong indications. When the indications are less clear, the patient's perspective on the impact of prostate disease on his life is important.


Identification of Novel Cryptic Multifunctional Antimicrobial Peptides from the Human Stomach Enabled by a Computational-Experimental Platform.
Novel approaches are needed to combat antibiotic resistance. Here, we describe a computational-experimental framework for the discovery of novel cryptic antimicrobial peptides (AMPs). The computational platform, based on previously validated antimicrobial scoring functions, indicated the activation peptide of pepsin A, the main human stomach protease, and its N- and C-terminal halves as antimicrobial peptides. The three peptides from pepsinogen A3 isoform were prepared in a recombinant form using a fusion carrier specifically developed to express toxic peptides in Escherichia coli. Recombinant pepsinogen A3-derived peptides proved to be wide-spectrum antimicrobial agents with MIC values in the range 1.56-50 μM (1.56-12.5 μM for the whole activation peptide). Moreover, the activation peptide was bactericidal at pH 3.5 for relevant foodborne pathogens, suggesting that this new class of previously unexplored AMPs may contribute to microbial surveillance within the human stomach. The peptides showed no toxicity toward human cells and exhibited anti-infective activity in vivo, reducing by up to 4 orders of magnitude the bacterial load in a mouse skin infection model. These peptides thus represent a promising new class of antibiotics. We envision that computationally guided data mining approaches such as the one described here will lead to the discovery of antibiotics from previously unexplored sources.


Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement.
Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with bi-allelic loss-of-function variants in the RBM42 gene. The patient is a two-year-old female with severe central nervous system abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing. Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global alternative splicing to abnormal embryonic development.


Children's memory reports over time: Getting both better and worse.
Injured children (N = 145 between 2 and 13 years of age) were recruited from a hospital emergency room and were interviewed about the injury event soon afterward and then twice more at yearly intervals. Their transcripts were coded three ways: completeness of overall structural components of a prototypical injury event (e.g., who, when, where), amount of narrative detail (specifically unique units of information), and the accuracy of both types of information. Completeness components were also categorized as central or peripheral, and narrative details were coded as pertaining to persons, objects, attributes, locations, or activities. Over time, children maintained consistent completeness scores; that is, the overall structure of the event stayed the same. However, they provided more elaborative detail of all types and especially about attributes and activities. Only accuracy (of both types of information) deteriorated. Thus, different aspects of their interviews changed in different ways over 2 years. Implications for assessing changes over time in child witness reports are discussed.


General principles of irradiation therapy as applied to head and neck cancer.
The general principles of irradiation therapy as applied to head and neck cancer are illustrated by discussion of typical radiation treatment planning for an early glottic carcinoma, carcinoma of the larynx with subglottic extension, a paranasal sinus carcinoma, and a localized tonsillar carcinoma. Each example shows how with modern techniques and careful planning radiation therapy can be directed homogeneously to any desired volume containing tumor but limiting the complications produced in the normal tissues. Homogeneous distribution of the dose of irradiation within the tumor is essential to avoid "cold" spots producing tumor recurrence and "hot" spots producing normal tissue complications. Improvements in technique of irradiation have halved the recurrence rate in T1 glottic cancer and reduced neck node recurrences in T1 supraglottic cancer from 19% to 3%. Techniques of implantation and the concept of therapeutic ratio are also discussed. The concepts of pre vs postoperative irradiation are discussed and the Toronto approach of delayed combined irradiation and surgery, which represents in our view the optimal combination of irradiation and surgery, is reviewed.


Mycobacterial PE12 protein promotes bacterial survival through inhibiting cell apoptosis.
Mycobacterial PE_PGRS family proteins play key roles in pathogen-host interaction. However, the function of most PE_PGRS proteins remains unknown. In this study, we characterized the role of PE12 of Mycobacterium bovis (M. bovis) on bacterial growth, bacterial survival, and host cell apoptosis. Transcriptome sequencing of infected THP-1 cells was also performed. Compared to Ms_Vec, we found that M. bovis PE12 did not alter the colony morphology of M. smegmatis. The survival of Ms_PE12 was obviously higher than that of Ms_Vec. Furthermore, PE12 significantly suppressed the apoptosis of THP-1 induced by M. smegmatis infection. Transcriptome analysis results showed that there were 70 downregulated genes in the Ms_PE12 infection group in comparison with the Ms_Vec infection group, and these differentially expressed genes were enriched in 240 downregulated GO terms and 6 KEGG pathways. The downregulated expression genes are involved in cell adhesion, phagocytosis, apoptosis, inflammatory response, glycolysis and transmembrane transporter activity. Taken together, our study reveals that PE12 can suppress apoptosis and inhibit proinflammatory cytokine response. We propose that PE12 is related to macrophage phagocytosis and apoptosis, providing useful information to the pathogenic mechanisms of M. bovis.


Diversity in the olfactory epithelium of bony fishes: development, lamellar arrangement, sensory neuron cell types and transduction components.
In this study we use a taxon-based approach to examine previous, as well as new findings on several topics pertaining to the peripheral olfactory components in teleost fishes. These topics comprise (1) the gross anatomy of the peripheral olfactory organ, including olfactory sensory neuron subtypes and their functional parameters, (2) the ultrastructure of the olfactory epithelium, and (3) recent findings regarding the development of the nasal cavity and the olfactory epithelium. The teleosts are living ray-finned fish, and include descendants of early-diverging orders (e.g., salmon), specialized descendants (e.g., goldfish and zebrafish), as well as the Acanthopterygii, numerous species with sharp bony rays, including perch, stickleback, bass and tuna. Our survey reveals that the olfactory epithelium lines a multi-lamellar olfactory rosette in many teleosts. In Acanthopterygii, there are also examples of flat, single, double or triple folded olfactory epithelia. Diverse species ventilate the olfactory chamber with a single accessory nasal sac, whereas the presence of two sacs is confined to species within the Acanthopterygii. Recent studies in salmonids and cyprinids have shown that both ciliated olfactory sensory neurons (OSNs) and microvillous OSNs respond to amino acid odorants. Bile acids stimulate ciliated OSNs, and nucleotides activate microvillous OSNs. G-protein coupled odorant receptor molecules (OR-, V1R-, and V2R-types) have been identified in several teleost species. Ciliated OSNs express the G-protein subunit G(alphaolf/s), which activates cyclic AMP during transduction. Localization of G protein subunits G(alpha0) and G(alphaq/11) to microvillous or crypt OSNs, varies among different species. All teleost species appear to have microvillous and ciliated OSNs. The recently discovered crypt OSN is likewise found broadly. There is surprising diversity during ontogeny. In some species, OSNs and supporting cells derive from placodal cells; in others, supporting cells develop from epithelial (skin) cells. In some, epithelial cells covering the developing olfactory epithelium degenerate, in others, these retract. Likewise, there are different mechanisms for nostril formation. We conclude that there is considerable diversity in gross anatomy and development of the peripheral olfactory organ in teleosts, yet conservation of olfactory sensory neuron morphology. There is not sufficient information to draw conclusions regarding the diversity of teleost olfactory receptors or transduction cascades.


Imaging procedures in adrenal pathology.
Imaging plays a vital role in the evaluation of adrenal pathology. The most widely used modalities are computed tomography and magnetic resonance imaging. Alone or in conjunction with appropriate clinical and biochemical data, imaging can provide specific diagnoses that preclude the need for tissue sampling. This article reviews imaging features of normal and diseased adrenals, from both benign and malignant causes.


Genetic modulation of Rpd3 expression impairs long-term courtship memory in Drosophila.
There is increasing evidence that regulation of local chromatin structure is a critical mechanism underlying the consolidation of long-term memory (LTM), however considerably less is understood about the specific mechanisms by which these epigenetic effects are mediated. Furthermore, the importance of histone acetylation in Drosophila memory has not been reported. The histone deacetylase (HDAC) Rpd3 is abundant in the adult fly brain, suggesting a post-mitotic function. Here, we investigated the role of Rpd3 in long-term courtship memory in Drosophila. We found that while modulation of Rpd3 levels predominantly in the adult mushroom body had no observed impact on immediate recall or one-hour memory, 24-hour LTM was severely impaired. Surprisingly, both overexpression as well as RNAi-mediated knockdown of Rpd3 resulted in impairment of long-term courtship memory, suggesting that the dose of Rpd3 is critical for normal LTM.


Adherence to Healthy or Unhealthy Pro-Vegetarian Plant-Based Diets Have Different Impact on Prostate Cancer Severity: Preliminary Findings.
Prostate cancer (PCa) is a prevalent malignancy affecting men worldwide, and plant-based diets have been widely advocated for their health benefits. The aim of this study was to test the association between general, healthy, and unhealthy pro-vegetarian plant-based diets and PCa severity on 118 consecutive patients undergoing prostatectomy in a university hospital in Italy. Food frequency questionnaires were used to calculate scores for dietary patterns. Multivariate logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to test the associations. A general plant-based diet was not associated with cancer severity, while patients reporting a higher adherence to a healthy plant-based diet were less likely to have a more severe PCa (for medium/high vs. low-risk PCa, OR = 0.27, 95% CI: 0.08, 0.88; for high vs. medium/low-risk PCa, OR = 0.09, 95% CI: 0.02, 0.39). Patients resulting in higher adherence to an unhealthy plant-based diet were more likely to be diagnosed with more severe PCa (OR = 6.15, 95% CI: 1.70, 22.24). In conclusion, plant-based dietary patterns may have a different impact on PCa severity depending on the quality of the foods included.


Somatic Coliphages as an Operational Tool to Assess Loss of Bathing Water Quality after Heavy Rain Events.
Rapid population growth and coastal development has led to increased fecal contamination of coastal surface waters worldwide, enhancing the potential risk of waterborne human pathogens in bathing areas. More frequent heavy rainfall events, attributed to global warming, have further exacerbated the problem by causing sometimes sewer overflows into recreational waters. As traditional bacterial indicators have limited accuracy for predicting health risks associated with waterborne viruses, the additional use of viral indicators such as coliphages is recommended. In this study, we compared the behavior of bacterial and viral indicators of water quality at 10 Barcelona beaches during three bathing seasons, in dry conditions, and after four rainstorms that caused specific pollution events due to rain runoff with combined sewer overflows (CSO). Levels of all target indicators increased after the rainstorms, but compared to Escherichia coli and intestinal enterococci, somatic coliphages exhibited a slower decline and higher environmental persistence following a rain event. Daily continuous sampling carried out during the days following a rainstorm allowed not only the determination of the decay kinetics of each target indicator but also the day when the water quality recovered the values established in the current European regulation in approximately 2 -3 days after each CSO. These observations indicate that the combined use of bacterial and viral indicators can enhance the surveillance of microbial quality of bathing waters. Moreover, coliphages can swiftly provide insights into transient fecal pollution linked to rainfall episodes, thanks to available analytical techniques that enable same-day recommendations. The management of urban wastewater and recreational water regulations should consistently employ microbial indicators to address rainwater runoff or sewer overflows resulting from heavy rainfall.


Variations in carotid artery intima-media thickness during the cardiac cycle in children.
There is paucity of research looking at variations in carotid artery intima-media thickness (CIMT) during the cardiac cycle in children. The aim of this study was to ascertain variations, if any, in CIMT during the cardiac cycle in a population of high-risk children. Forty-nine children aged 6 to 19 years with dyslipidemia and other atherosclerosis-promoting risk factors underwent a carotid ultrasound. CIMT was measured using commercially available, semiautomated edge-detection software. The region of interest was the far wall of the common carotid artery. CIMT was measured at various points during the cardiac cycle using the electrocardiogram (EKG) as a reference. CIMT measurements two frames before, during, and after the QRS complex (end diastole) were analyzed separately (designated as "QRS CIMT") from the other CIMT measurements (designated as "non-QRS CIMT"). Demographics, heart rate, blood pressure, anthropometric measures, lumen diameter, family history, and presence of other atherosclerosis-promoting risk factors were documented. "QRS CIMT" was significantly thicker than "non-QRS CIMT" (P = .01), with the age group 10 to 14 years showing the most significant variation between "QRS CIMT" and "non-QRS CIMT" (P = .005). CIMT values between right and left carotid arteries differed by 2.5%. Age, systolic blood pressure, and blood glucose were significant predictors of mean CIMT by simple linear regression; systolic blood pressure was the only significant predictor of mean CIMT by stepwise multiple linear regression analysis. CIMT measurements vary during the cardiac cycle in children. It is thicker during the QRS complex on EKG. Carotid ultrasound should be performed with an EKG, and CIMT should be measured at the same point on the EKG to overcome this variation. Furthermore, we recommend that CIMT be measured at the R-wave on EKG because this is an easily discernible point in the cardiac cycle.


New framework for standardized notation in wastewater treatment modelling.
Many unit process models are available in the field of wastewater treatment. All of these models use their own notation, causing problems for documentation, implementation and connection of different models (using different sets of state variables). The main goal of this paper is to propose a new notational framework which allows unique and systematic naming of state variables and parameters of biokinetic models in the wastewater treatment field. The symbols are based on one main letter that gives a general description of the state variable or parameter and several subscript levels that provide greater specification. Only those levels that make the name unique within the model context are needed in creating the symbol. The paper describes specific problems encountered with the currently used notation, presents the proposed framework and provides additional practical examples. The overall result is a framework that can be used in whole plant modelling, which consists of different fields such as activated sludge, anaerobic digestion, sidestream treatment, membrane bioreactors, metabolic approaches, fate of micropollutants and biofilm processes. The main objective of this consensus building paper is to establish a consistent set of rules that can be applied to existing and most importantly, future models. Applying the proposed notation should make it easier for everyone active in the wastewater treatment field to read, write and review documents describing modelling projects.


Persistence and Progression of Airway Obstruction in Children With Early Onset Scoliosis.
Obstructive lung disease occurs in 30% of children with early onset scoliosis (EOS); changes in degree of airway obstruction over time have not been reported. Longitudinal patterns of incidental, persistent, and progressive airway obstruction were retrospectively analyzed in a cohort of children with EOS with at least 1 forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) value <85% on serial spirometric assessments over a ≥3-year observation period. The prevalence of clinical features and the severity of coronal and sagittal spine deformities for each group at the beginning and end of the study period were compared. Airway obstruction was incidental in 12 (24%) and persistent in 37 (76%) of 49 children with EOS. Twenty of 37 (54%) of those with persistent obstruction developed progressive airway obstruction. The decline in FEV1/FVC over 6±2 years was insignificant in the incidental group (4%±2%) and the persistent nonprogressive group (7%±4%) but significant in the progressive group (13%±4%, t test; P=0.002). In total, 29% of the 49 children at the onset and 57% at the end of the study had airway obstruction. The incidental, persistent nonprogressive, and progressive groups did not differ with regard to age, diagnosis distribution, or sex. The initial coronal curve size, apex, direction of the curve, and degree of kyphosis were statistically similar among the 3 groups. Coronal curve magnitude inversely correlated with FEV1/FVC at the end but not the beginning of the study (r=-0.19, P=0.002). Six of 19 responded to bronchodilator treatment, suggesting concurrent asthma. Airway obstruction did not relate to restrictive pulmonary abnormalities measured by FVC at first or last timepoints [slope=-0.076 (95% confidence interval, -0.99 to 0.038; P=0.19)]. Changes in degrees of airway obstruction and restrictive lung disease over time did not correlate [slope=-0.125 (95% confidence interval, -0.294 to 0.044; P=0.14)]. Children with EOS and progressive airway obstruction represent an important subgroup which may require new surgical and nonsurgical treatment strategies to prevent loss of lung function over time.


Neuron-synapse IC chip-set for large-scale chaotic neural networks.
We propose a neuron-synapse integrated circuit (IC) chip-set for large-scale chaotic neural networks. We use switched-capacitor (SC) circuit techniques to implement a three-internal-state transiently-chaotic neural network model. The SC chaotic neuron chip faithfully reproduces complex chaotic dynamics in real numbers through continuous state variables of the analog circuitry. We can digitally control most of the model parameters by means of programmable capacitive arrays embedded in the SC chaotic neuron chip. Since the output of the neuron is transfered into a digital pulse according to the all-or-nothing property of an axon, we design a synapse chip with digital circuits. We propose a memory-based synapse circuit architecture to achieve a rapid calculation of a vast number of weighted summations. Both of the SC neuron and the digital synapse circuits have been fabricated as IC forms. We have tested these IC chips extensively, and confirmed the functions and performance of the chip-set. The proposed neuron-synapse IC chip-set makes it possible to construct a scalable and reconfigurable large-scale chaotic neural network with 10000 neurons and 10000/sup 2/ synaptic connections.


How well imageability, concreteness, perceptual strength, and action strength predict recognition memory, lexical decision, and reading aloud performance.
We examined how well imageability, concreteness, perceptual strength, and action strength predicted recognition memory, lexical decision, and reading aloud performance. We used our imageability estimates [Cortese, M. J., & Fugett, A. (2004). Imageability ratings for 3,000 monosyllabic words. Behavior Methods and Research, Instrumentation, & Computers, 36(3), 384-387. https://doi.org/10.3758/BF03195585; Schock, J., Cortese, M. J., & Khanna, M. M. (2012a). Imageability ratings for 3,000 disyllabic words. Behavior Research Methods, 44(2), 374-379. https://doi.org/10.3758/s13428-011-0162-0], concreteness norms of Brysbaert and colleagues [Brysbaert, M., Warriner, A. B., & Kuperman, V. (2014). Concreteness ratings for 40 thousand generally known English lemmas. Behavior Research Methods, 46(3), 904-911. https://doi.org/10.3758/s13428-013-0403-5], and perceptual and action strength ratings of Lynott and colleagues [Lynott, D., Connell, L., Brysbaert, M., Brand, J., & Carney, J. (2020). The lancaster sensorimotor norms: Multidimensional measures of perceptual and action strength for 40,000 English words. Behavior Research Methods, 52(3), 1271-1291. https://doi.org/10.3758/s13428-019-01316-z]. Our results indicate imageability is the best predictor, but methodological differences between ratings studies may contribute to the results. Surprisingly, action strength was negatively (albeit weakly) related to recognition memory. Analyses of item zRTs from the English lexicon project indicate these variables were not strong predictors of reading aloud or lexical decision performance. However, there is a small, consistent positive relationship between concreteness and zRTs (i.e., a facilitative abstractness effect). We believe researchers should either employ or control for imageability rather than concreteness, perceptual strength, or action strength when conducting recognition memory experiments. In addition, image-based codes generated at encoding strengthen memory traces but do not provide major inputs into reading aloud and lexical decision processes. Also, the facilitative abstractness effect on lexical decision and reading aloud zRTs may reflect more robust lexical representations for abstract words than concrete words, and that these two constructs are distinct.


Genetic animal models for absence epilepsy: a review of the WAG/Rij strain of rats.
Based on the reviewed literature and the data presented in this paper, conclusions can be drawn with respect to the validity of the WAG/Rij strain of rats as a model for absence epilepsy in humans. The view that the WAG/Rij model has "face validity" is supported by the simultaneous presence of clinical and electroencephalographic signs characterizing absences in rat and humans, by the decrease in responsiveness during the presence of spike-wave discharges in both species, by the agreement between model and patient with respect to the preferential occurrences of spike-wave discharges at transitions in states of vigilance, by the corresponding modulation of spike-wave discharges by physical and mental activities in both and, finally, by the fact that in both humans and rats absence epilepsy is inherited. Against this view, however, argue two points. In rats, absences appear after puberty and are maintained during life, while in humans the seizures occur before puberty and then disappear or convert to more serious forms of epilepsy. The second point is the frequency difference of the spikes and waves in the discharge train: 8-10 Hz in the rat and 3 Hz in the human (though there are no a priori reasons why the frequency of spike waves in the burst must be the same in all species). The absence model also has predictive validity, based on pharmacological data that demonstrate the specificity of certain drugs as being effective in convulsive epilepsies and not in absence epilepsy. So far, all drugs affect spike-wave activity the same way in rats and humans, with lamotrigine being, perhaps, the only exception. Furthermore, sleep deprivation is a powerful provocation for the initiation of spike-wave discharges in both rats and humans. Potential explanations for the presence of absence seizures in rats have been found at the levels of activities in networks and nuclei; of neurons, membrane properties, and ion channels; of proteins and enzymes; and, finally, of genes and chromosomes. Further descriptions of the cellular processes can be found extensively in the literature (e.g., McCormick and Contreras, 2001) and those of the thalamo-cortico-thalamic network in this review as well as in others (Avanzini et al., 1999). Considering the extensive involvement of the phenomena under study with theoretical issues such as the relationship between sleep spindles and spike-wave discharges, and the origin of seizure activity, it can be concluded that the model also has construct validity as far as the present neurobiological theories holding for absence epilepsy in humans are concerned. The WAG/Rij model can therefore be recommended for continued use in evaluating antiepileptic drugs for monotherapy and polytherapy, as well as for the toxicological side effects of putative new antiabsence drugs.


[Changing characteristics of organic matter and pH of cultivated soils in Zhejiang province over the last 50 years].
By comparing the current quality investigation data of cultivated soils in Zhejiang province with the past data, changing characteristics of organic matter and pH value of the soils in this province over last 50 years were analyzed. The results showed that content of organic matter and pH value of the cultivated soils changed greatly during past 50 years, and the changes varied with historical periods and soil types. From 1958 to 1980s, accumulation of soil organic matter was obvious, soil organic matter increased averagely by 40.34%, and the mean pH increased slightly by 0.05 of pH unit. From 1980s to 2008, the mean content of organic matter in paddy soils decreased by 5.58%. The changes of soil organic matter varied with distribution zones of the paddy soils. The mean content of organic matter of paddy soils in valley plain increased with time, and those in plain with water network, hilly area and coastal plain decreased with time. The mean contents of organic matter in fluvio-aquic soil and coastal saline soil in the year 2008 were 29.48% and 14.60% respectively higher than those in 1980s. As compared with those obtained at 1980s, the cultivated soil in this province have been significantly acidified in the past thirty years, the mean pH value declined by 0.25 of pH unit, and the decline of pH value of paddy soils was greater than those of fluvio-aquic soil and saline soil. Changes in fertilization structure and conversion of paddy fields to upland were thought as main causes of the changes in both soil organic matter and pH value.


Prevalence of human papillomaviruses in patients with head and neck squamous cell carcinoma in Lithuania and Belarus.
Overall, head and neck sqamous cell carcinoma accounts for more than 550,000 cases annually worldwide. It is well known that human papillomavirus (HPV) is the main risk factor for cervical cancer development. As the incidence and the mortality of cervical cancer are closely related to the HPV prevalence, we hypothesized that there is the same association between HPV prevalence and head and neck squamous cell carcinoma. Therefore we performed the study aiming to compare the level of HPV infection and HPV type distribution between two groups of Lithuanian and Belarusian patients with head and neck sqamous cell carcinoma. One hundred ninety head and neck sqamous cell carcinoma patients were included in the study, 75 from Lithuania and 115 from Belarus. PCR was used for HPV detection and typing. The distribution of HPV infection among head and neck sqamous cell carcinoma patients was similar in the Lithuanian (20.0%) and Belarusian (18.3%) patient groups, however differences were found in the distribution of HPV types.


Malignant Hyperthermia Versus Thyroid Storm in a Patient With Symptomatic Graves Disease: A Case Report.
Malignant hyperthermia and thyroid storm are intraoperative emergencies with overlapping symptoms but different treatment protocols. We faced this diagnostic dilemma in a 25-year-old patient with symptomatic hyperthyroidism, elevated free T3 and free T4, and low thyroid-stimulating hormone from Graves disease despite treatment with propranolol 80 mg daily and methimazole 40 mg every 8 hours. During thyroidectomy, he developed hyperthermia and hypercarbia without tachycardia. When the rate of rise of PaCO2 and temperature accelerated, we treated the patient for malignant hyperthermia, a diagnosis subsequently confirmed by genetic testing.


CagA and VacA polymorphisms do not correlate with severity of histopathological lesions in Helicobacter pylori-infected Greek children.
The presence of various numbers of EPIYA tyrosine phosphorylation motifs in the CagA protein of Helicobacter pylori has been suggested to contribute to pathogenesis in adults. In this prospective study, we characterized H. pylori isolates from symptomatic children, with reference to the diversity of functional EPIYA motifs in the CagA protein and vacA isotypes, and assessed the potential correlation with the histopathological manifestations of the infection. We analyzed 105 H. pylori isolates from 98 children and determined the diversity of EPIYA motifs in CagA by amplification and sequencing of the 3' variable region of the cagA gene as well as vacA isotypes for the signal, middle, and intermediate regions. CagA phosphorylation and levels of secreted IL-8 were determined following in vitro infection of AGS gastric epithelial cells. Histopathological evaluation of H. pylori colonization, activity, and severity of the associated gastritis was performed according to the updated Sydney criteria. EPIYA A (GLKN[ST]EPIYAKVNKKK), EPIYA B (Q[V/A]ASPEPIY[A/T]QVAKKVNAKI), and EPIYA C (RS[V/A]SPEPIYATIDDLG) motifs were detected in the ABC (46.6%) and ABCC (17.1%) combinations. No isolates harboring more than two EPIYA C motifs in CagA were found. The presence of isogenic strains with variable numbers of CagA EPIYA C motifs within the same patient was detected in seven cases. Occurrence of increasing numbers of EPIYA C motifs correlated strongly with presence of a high-vacuolation (s1 or s2/i1/m1) phenotype and age. A weak positive correlation was observed between vacuolating vacA genotypes and presence of nodular gastritis. However, CagA- and VacA-dependent pathogenicities were not found to contribute to severity of histopathology manifestations in H. pylori-infected children.


Effects of air temperature on the risk of death from COPD in major microregions in Brazil: a time series study.
To evaluate the association between the risk of death from COPD and air temperature events in ten major Brazilian microregions. This was a time series analysis of daily COPD deaths and daily mean air temperatures between 1996 and 2017. Using distributed nonlinear lag models, we estimated the cumulative relative risks of COPD mortality for four temperature percentiles (representing moderate and extreme cold and heat events) in relation to a minimum mortality temperature, with a lag of 21 days, in each microregion. Significant associations were found between extreme air temperature events and the risk of death from COPD in the southern and southeastern microregions in Brazil. There was an association of extreme cold and an increased mortality risk in the following microregions: 36% (95% CI, 1.12-1.65), in Porto Alegre; 27% (95% CI, 1.03-1.58), in Curitiba; and 34% (95% CI, 1.19-1.52), in São Paulo; whereas moderate cold was associated with an increased risk of 20% (95% CI, 1.01-1.41), 33% (95% CI, 1.09-1.62), and 24% (95% CI, 1.12-1.38) in the same microregions, respectively. There was an increased COPD mortality risk in the São Paulo and Rio de Janeiro microregions: 17% (95% CI, 1.05-1.31) and 12% (95% CI, 1,02-1,23), respectively, due to moderate heat, and 23% (95% CI, 1,09-1,38) and 32% (95% CI, 1,15-1,50) due to extreme heat. Non-optimal air temperature events were associated with an increased risk of death from COPD in tropical and subtropical areas of Brazil.


Case-control study on influence of methionine, nitrite, and salt on gastric carcinogenesis in northern Italy.
A new mutagen, 2-chloro-4-methylthiobutanoic acid, has recently been identified from a nitrite-treated Japanese salted fish. Its structure suggests that it derives from methionine in the presence of salt and nitrite. We thus considered the interaction between intake of methionine, salt, and nitrites on gastric cancer risk using data from a case-control study conducted in Northern Italy on 746 cases of incident histologically confirmed gastric cancer and 2,053 controls in hospital for acute nonneoplastic nondigestive tract disorders. Compared with subjects reporting low-methionine and low-salt intake, the odds ratios (ORs) were 2.4 [95% confidence interval (CI) = 1.5 - 4.0] for those reporting low-salt and high-methionine, 1.5 (95% CI = 1.0 - 2.2) for those with high-salt and low-methionine, and 2.8 (95% CI = 1.9 - 4.2) for those with high-salt and high-methionine intake. Likewise, with reference to nitrites, compared with subjects with low-methionine and low-nitrite intake, the ORs were 1.9 (95% CI = 1.3 - 2.6) in the high-methionine and low-nitrite stratum, 1.5 (95% CI = 1.0 - 2.1) in the low-methionine and high-nitrite stratum, and 2.5 (95% CI = 1.9 - 3.2) in the high-methionine and high-nitrite stratum. All these estimates were statistically significant. Thus the present findings from a large case-control study conducted in a relatively high-incidence area for gastric cancer suggest that a diet rich in methionine, salt, and nitrite is associated with increased gastric cancer risk.


Pro-inflammatory gene expression in solid glioblastoma microenvironment and in hypoxic stem cells from human glioblastoma.
Adaptation to hypoxia and consequent pro-inflammatory gene expression of prostate and breast carcinomas have been implicated in the progression toward cancer malignant phenotype. Only partial data are available for the human tumor glioblastoma multiforme (GBM). The aim of our study was to analyze the hypoxic and pro-inflammatory microenvironment in GBMs and to demonstrate that in a stem/progenitor cell line derived from human glioblastoma (GBM-SCs), hypoxia activates a coordinated inflammatory response, evidencing an invasive and migratory phenotype. From each of 10 human solid glioblastomas, clinically and histopathologically characterized, we obtained three surgical samples taken from the center and the periphery of the tumor, and from adjacent host normal tissue. Molecular and morphological analyses were carried out using quantitative real-time PCR and western blot (WB). GBM stem and differentiated cells were incubated under hypoxic conditions and analyzed for pro-inflammatory gene expression and for invasive/migratory behavior. A panel of selected representative pro-inflammatory genes (RAGE and P2X7R, COX2, NOS2 and, PTX3) were analyzed, comparing tumor, peritumor and host normal tissues. Tumors containing leukocyte infiltrates (as assessed using CD45 immunohistochemistry) were excluded. Selected genes were overexpressed in the central regions of the tumors (i.e. in the more hypoxic areas), less expressed in peripheral regions, and poorly expressed or absent in adjacent normal host tissues. Western blot analysis confirmed that the corresponding pro-inflammatory proteins were also differently expressed. Hypoxic stem cell lines showed a clear time-dependent activation of the entire panel of pro-inflammatory genes as compared to differentiated tumor cells. Biological assays showed that invasive and migratory behavior was strengthened by hypoxia only in GBM stem cells. In human solid glioblastoma we have observed a coordinated overexpression of a panel of pro-inflammatory genes as compared to host normal tissue. We have also evidenced a similar pattern of overexpressed genes in GBM-SCs after hypoxic treatment, showing also a gain of invasive and migratory function that was lost when these stem cells differentiated. We suggest that, as has been previously described for prostatic and mammary carcinoma, in human glioblastoma acquisition of a proinflammatory phenotype may be relevant for malignant progression.


Reconstruction of multiple non-line-of-sight objects using back projection based on ellipsoid mode decomposition.
Non-line-of-sight imaging has attracted more attentions for its wide applications. Even though ultrasensitive cameras/detectors with high time-resolution are available, current back-projection methods are still powerless to acquire a satisfying reconstruction of multiple hidden objects due to severe aliasing artifacts. Here, a novel back-projection method is developed to reconstruct multiple hidden objects. Our method considers decomposing all the ellipsoids in a confidence map into several "clusters" belonging to different objects (namely "ellipsoid mode decomposition"), and then reconstructing the objects individually from their ellipsoid modes by filtering and thresholding, respectively. Importantly, the simulated and experimental results demonstrate that this method can effectively eliminate the impacts of aliasing artifacts and exhibits potential advantages in separating, locating and recovering multiple hidden objects, which might be a good base for reconstructing complex non-line-of-sight scenes.


Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation.
Doxorubicin (DOX) is an effective chemotherapeutic agent used to treat a wide variety of malignancies. In addition to its multi-organ toxicity, DOX treatment has been shown to induce systemic inflammation in patients and experimental animals. Inflammation alters the expression of hepatic cytochrome P450 (CYP) enzymes, which play important roles in drug metabolism and DOX-induced toxicity. Significant sex differences have been reported in DOX-induced toxicity; however, sex differences in DOX-induced systemic inflammation and the potential effects on hepatic CYP expression have not been determined. In the current work, male and female C57Bl/6 mice were administered DOX (20 mg/kg by intraperitoneal injection), and groups of mice were sacrificed 24 and 72 h after DOX administration. DOX elicited a systemic inflammatory response in both male and female mice, but the inflammatory response was stronger in male mice. DOX altered the expression of hepatic CYP isoforms in a sex-dependent manner. Most notably, inhibition of Cyp2c29 and Cyp2e1 was stronger in male than in female mice, which paralleled the sex differences in systemic inflammation. Therefore, sex differences in DOX-induced systemic inflammation may lead to sexually dimorphic drug interactions, in addition to contributing to the previously reported sexual dimorphism in specific DOX-induced organ toxicity.


[High-resolution CT of the lung versus thoracic radiography after adjuvant radiotherapy in breast carcinoma].
We examined the lungs of 35 women following postoperative radiotherapy for breast cancer by using high-resolution computed tomography (HR-CT). Radiotherapy was performed on a cobalt 60 unit using a five-field technique. The average interval between the end of radiotherapy and HR-CT examinations was 23.8 months. HR-CT was limited to those lung areas that were at risk for radiation-induced changes. In 40% of patients minimal interstitial damage (e.g. thickened septal lines, curvilinear densities) invisible on chest x-ray was demonstrated by HR-CT. Massive fibrosis as reported by others was not seen in our study. We conclude that in case lung involvement is suspected clinically during or after radiotherapy, HR-CT is the method of choice for demonstrating these morphological changes.


Association of haemorrhagic fever with renal syndrome and weather factors in Junan County, China: a case-crossover study.
Haemorrhagic fever with renal syndrome (HFRS) is a type of vector-borne zoonosis sensitive to climate change. To explore the short-term effect of air temperature and amount of precipitation on HFRS incidence, a total of 13 722 clinically confirmed HFRS cases from January 1977 to December 2001 in Junan County, China were included in this study. According to symmetric bidirectional case-crossover design, the hazard period (the three calendar months preceding the month when the case was diagnosed) and the control period (the same calendar month of the year before and the year after the hazard period) matched and conditional logistic regression was used to examine the effect of monthly mean temperature and precipitation on the risk of HFRS. The results showed the facilitating climatic conditions for HFRS included: condition with moderate mean air temperature (10-25 °C) and abundant precipitation (>120 mm) 3 months before [odds ratio (OR) 1·346, 95% confidence interval (CI) 1·191-1·522] and 2 months before (OR 1·193, 95% CI 1·063-1·339); and condition with temperature >25 °C and abundant precipitation (>120 mm) 3 months before (OR 1·17, 95% CI 1·004-1·363). Temperature of 10-25 °C and moderate precipitation (10-120 mm) in the current month was the most favourable condition for HFRS incidence.


High oxidative capacity due to chronic exercise training attenuates lipid-induced insulin resistance.
Fat accumulation in skeletal muscle combined with low mitochondrial oxidative capacity is associated with insulin resistance (IR). Endurance-trained athletes, characterized by a high oxidative capacity, have elevated intramyocellular lipids, yet are highly insulin sensitive. We tested the hypothesis that a high oxidative capacity could attenuate lipid-induced IR. Nine endurance-trained (age = 23.4 ± 0.9 years; BMI = 21.2 ± 0.6 kg/m(2)) and 10 untrained subjects (age = 21.9 ± 0.9 years; BMI = 22.8 ± 0.6 kg/m(2)) were included and underwent a clamp with either infusion of glycerol or intralipid. Muscle biopsies were taken to perform high-resolution respirometry and protein phosphorylation/expression. Trained subjects had ~32% higher mitochondrial capacity and ~22% higher insulin sensitivity (P < 0.05 for both). Lipid infusion reduced insulin-stimulated glucose uptake by 63% in untrained subjects (P < 0.05), whereas this effect was blunted in trained subjects (29%, P < 0.05). In untrained subjects, lipid infusion reduced oxidative and nonoxidative glucose disposal (NOGD), whereas trained subjects were completely protected against lipid-induced reduction in NOGD, supported by dephosphorylation of glycogen synthase. We conclude that chronic exercise training attenuates lipid-induced IR and specifically attenuates the lipid-induced reduction in NOGD. Signaling data support the notion that high glucose uptake in trained subjects is maintained by shuttling glucose toward storage as glycogen.


Regression-based analysis of combined EEG and eye-tracking data: Theory and applications.
Fixation-related potentials (FRPs), neural responses aligned to the end of saccades, are a promising tool for studying the dynamics of attention and cognition under natural viewing conditions. In the past, four methodological problems have complicated the analysis of such combined eye-tracking/electroencephalogram experiments: (1) the synchronization of data streams, (2) the removal of ocular artifacts, (3) the condition-specific temporal overlap between the brain responses evoked by consecutive fixations, and (4) the fact that numerous low-level stimulus and saccade properties also influence the postsaccadic neural responses. Although effective solutions exist for the first two problems, the latter two are only beginning to be addressed. In the current paper, we present and review a unified regression-based framework for FRP analysis that allows us to deconvolve overlapping potentials while also controlling for both linear and nonlinear confounds on the FRP waveform. An open software implementation is provided for all procedures. We then demonstrate the advantages of this proposed (non)linear deconvolution modeling approach for data from three commonly studied paradigms: face perception, scene viewing, and reading. First, for a traditional event-related potential (ERP) face recognition experiment, we show how this technique can separate stimulus ERPs from overlapping muscle and brain potentials produced by small (micro)saccades on the face. Second, in natural scene viewing, we model and isolate multiple nonlinear effects of saccade parameters on the FRP. Finally, for a natural sentence reading experiment using the boundary paradigm, we show how it is possible to study the neural correlates of parafoveal preview after removing spurious overlap effects caused by the associated difference in average fixation time. Our results suggest a principal way of measuring reliable eye movement-related brain activity during natural vision.


Determination of HIV status of infants born to HIV-infected mothers: a review of the diagnostic methods with special focus on the applicability of p24 antigen testing in developing countries.
In 2009, 2.5 million children under the age of 15 y were living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS); 370,000 were diagnosed with HIV and 260,000 died due to AIDS. More than 90% of the children infected with HIV live in sub-Saharan Africa. Most children infected with HIV contract the infection in utero, during delivery, or via breast milk. This review outlines the current diagnostic methods to determine the HIV status of infants born to HIV-infected mothers. The HIV DNA and RNA polymerase chain reaction (PCR) tests are highly accurate and are recommended as the first-choice diagnostic methods. However, they are expensive and require complex laboratory procedures. Consequently, a search for less costly and complicated methods has led to the testing of p24 antigen analyses as an alternative to the gold-standard PCR tests, with encouraging results. The p24 antigen Perkin Elmer assay currently most often used has a sensitivity of 98.8% and a specificity of 100% (infants 6 weeks of age). Larger-scale studies should be performed in resource-limited settings to confirm these findings.


The properties of mammalian striated myofibrils isolated by an enzymatic method.
A new method for the isolation of large numbers of individual myofibrils from fresh mammalian skeletal and cardiac muscle has been described. Purification of isolated myofibrils was accomplished by differential centrifugation of fresh frozen sections of muscle which had been mechanically agitated after exposure for 30 to 45 minutes at 0 degrees C. to the action of a dilute solution of trypsin in a phosphate buffer solution with a pH of 7.0 and an ionic strength of 0.25. Isolated skeletal myofibrils of the rabbit and man have similar constant solubility properties. They dissolve in an aqueous mixture of 0.5 N potassium chloride and 0.03 N sodium bicarbonate, giving viscous solutions which exhibit conspicuous birefringence of flow. They are soluble in buffer solutions (ionic strength 0.15) on the acid side of pH 4 and alkaline side of pH 10. If the ionic strength of potassium phosphate buffer solutions is increased to 0.5 or if the ionic strength of phosphate-borate buffer solutions is increased to a similar value by addition of potassium chloride, the isolated myofibrils become soluble at neutrality. Hence, it is possible, first to isolate the myofibrils and then dissolve them without deviating appreciably from physiologic ranges of pH. The extent to which myofibrils are modified by the conditions imposed by the method of isolation is unknown. There is no significant change in microscopic structure or optical birefringence. Furthermore, there is retention of a form of physiological reactivity, for when the isolated skeletal myofibrils are immersed in solutions of adenosinetriphosphate, they promptly and irreversibly change from elongated fibrils with distinct structural detail into dense spherical masses without recognizable microscopic structure.


Incidentally detected gallbladder polyps: is follow-up necessary?--Long-term clinical and US analysis of 346 patients.
To determine the natural history of gallbladder (GB) polyps incidentally detected at ultrasonography (US) and to propose management guidelines for these lesions based on polyp size. The HIPAA-compliant study was approved by the institutional review board, and informed consent was waived. A database search for "polyp" in all US examinations of the GB between January 1, 1999, and December 31, 2001, at a single institution was performed. All subsequent US reports were reviewed to determine changes in GB polyp size. The electronic medical record was searched to obtain clinical and pathologic follow-up. Three hundred forty-six patients (mean age, 51.6 years; range, 20-93 years) with GB polyps were included. There were 156 men (45%) and 190 women (55%). US follow-up (mean, 5.4 years; range, 2-11.5 years) was performed in 149 patients (43%). Polyp size was stable in 90 (60%) polyps, decreased in eight (5%), increased in one (1%), and resolved in 50 (34%). Forty-two patients (12%) underwent cholecystectomy, revealing 13 (31%) GBs with polypoid lesions, 24 (57%) with stones and no polyps, and five (12%) with neither a stone nor a polypoid lesion. Clinical follow-up (mean, 8 years; range, 5-10.4 years) was performed in 155 patients (45%). No patient had clinical evidence of GB-related disease. Overall, no cases of GB malignancy were identified in 346 patients. Mean polyp size was 5.0 mm (range, 1-18 mm). No neoplastic polyps were found at 1-6 mm, one neoplastic polyp was seen at 7-9 mm, and two neoplastic polyps were found at 10 mm or larger. The risk of GB malignancy resulting from incidentally detected polyps is extremely low. Incidentally detected GB polyps measuring 6 mm or less may require no additional follow-up. Data are inconclusive regarding polyps 7 mm or greater, and further studies are warranted.


Single active-site histidine in D-xylose isomerase from Streptomyces violaceoruber. Identification by chemical derivatization and peptide mapping.
Group-specific chemical modifications of D-xylose isomerase from Streptomyces violaceruber indicated that complete loss of activity is fully correlated with the acylation of a single histidine. Active-site protection, by the ligand combination of xylitol plus Mg2+, completely blocked diethyl pyrocarbonate derivatization of this particular residue [Vangrysperre, Callens, Kersters-Hilderson & De Bruyne (1988) Biochem. J. 250, 153-160]. Differential peptide mapping between D-xylose isomerase, which has previously been treated with diethyl pyrocarbonate in the presence or absence of xylitol plus Mg2+, allowed specific isolation and sequencing of a peptide containing this active-site histidine. For this purpose we used two essentially new techniques: first, a highly reproducible peptide cleavage protocol for protease-resistant, carbethoxylated proteins with guanidinium hydrochloride as denaturing agent and subtilisin for proteolysis; and second, reverse-phase liquid chromatography with dual-wavelength detection at 214 and 238 nm, and calculation of absorbance ratios. It allowed us to locate the single active-site histidine at position 54 in the primary structure of Streptomyces violaceoruber D-xylose isomerase. The sequence around this residue is conserved in D-xylose isomerases from a diversity of micro-organisms, suggesting that this is a structurally and/or functionally essential part of the molecule.


Dynamic X-ray elastography using a pulsed photocathode source.
X-ray absorption of breast cancers and surrounding healthy tissue can be very similar, a situation that sometimes leads to missed cancers or false-positive diagnoses. To increase the accuracy of mammography and breast tomosynthesis, we describe dynamic X-ray elastography using a novel pulsed X-ray source. This new imaging modality provides both absorption and mechanical properties of the imaged material. We use a small acoustic speaker to vibrate the sample while a synchronously pulsed cold cathode X-ray source images the mechanical deformation. Using these stroboscopic images, we derive two-dimensional stiffness maps of the sample in addition to the conventional X-ray image. In a breast phantom composed of ZrO2 powder embedded in gel, dynamic elastography derived stiffness maps were able to discriminate a hard inclusion from surrounding material with a contrast-to-noise ratio (CNR) of 4.5. The CNR on the corresponding absorption image was 1.1. This demonstrates the feasibility of dynamic X-ray elastography with a synchronously pulsed X-ray source.


The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies.
The novel human coronavirus EMC (hCoV-EMC), which recently emerged in Saudi Arabia, is highly pathogenic and could pose a significant threat to public health. The elucidation of hCoV-EMC interactions with host cells is critical to our understanding of the pathogenesis of this virus and to the identification of targets for antiviral intervention. Here we investigated the viral and cellular determinants governing hCoV-EMC entry into host cells. We found that the spike protein of hCoV-EMC (EMC-S) is incorporated into lentiviral particles and mediates transduction of human cell lines derived from different organs, including the lungs, kidneys, and colon, as well as primary human macrophages. Expression of the known coronavirus receptors ACE2, CD13, and CEACAM1 did not facilitate EMC-S-driven transduction, suggesting that hCoV-EMC uses a novel receptor for entry. Directed protease expression and inhibition analyses revealed that TMPRSS2 and endosomal cathepsins activate EMC-S for virus-cell fusion and constitute potential targets for antiviral intervention. Finally, EMC-S-driven transduction was abrogated by serum from an hCoV-EMC-infected patient, indicating that EMC-S-specific neutralizing antibodies can be generated in patients. Collectively, our results indicate that hCoV-EMC uses a novel receptor for protease-activated entry into human cells and might be capable of extrapulmonary spread. In addition, they define TMPRSS2 and cathepsins B and L as potential targets for intervention and suggest that neutralizing antibodies contribute to the control of hCoV-EMC infection.


Erythrobacter odishensis sp. nov. and Pontibacter odishensis sp. nov. isolated from dry soil of a solar saltern.
Two bacterial strains (JC130(T) and JA747(T)) were isolated from dry soils of a solar saltern. Phylogenetic analysis showed that strain JA747(T) clustered with species of the genus Erythrobacter belonging to the family Erythrobacteraceae of the class Alphaproteobacteria in the phylum Proteobacteria, while strain JC130(T) clustered with species of the genus Pontibacter belonging to the family Cytophagaceae of the phylum Bacteroidetes. Based on 16S rRNA gene sequence analysis, strain JA747(T) had highest similarity with Erythrobacter gangjinensis K7-2(T) (96.7 %) and other members of the genus Erythrobacter (<96 %). Strain JC130(T) had highest sequence similarity with Pontibacter korlensis X14-1(T) (98.1 %), Pontibacter actiniarum KMM 6156(T) (96.9 %) and other members of the genus Pontibacter (<96 %). However, strain JC130(T) showed less than 32 % DNA reassociation value (based on DNA-DNA hybridization) with Pontibacter korlensis NRRL B-51097(T) ( = X14-1(T)) and Pontibacter actiniarum LMG 23027(T) ( = KMM 6156(T)). Strain JA747(T) was positive for catalase and oxidase activity and negative for nitrate reduction, and hydrolysis of starch and casein. Phosphatidylglycerol, diphostatidylglycerol, phosphatidylethanolamine and phosphatidylcholine were the major polar lipids for strain JA747(T). C18 : 1ω7c, C16 : 1ω6c/C16 : 1ω7c, C17 : 1ω6c and C16 : 0 were the major fatty acids of strain JA747(T). Strain JC130(T) was positive for catalase and oxidase, and negative for gelatinase and nitrate reduction. Phosphatidylethanolamine was the major polar lipid of strain JC130(T). Major fatty acids of strain JC130(T) were iso-C15 : 0 and summed feature 4 (anteiso-C17 : 1B/iso I). Based on the phenotypic, chemotaxonomic and molecular evidence presented, strains JA747(T) and JC130(T) are considered to represent two novel species of the genera Erythrobacter and Pontibacter, for which the names Erythrobacter odishensis sp. nov. (type strain JA747(T) = KCTC 23981(T) = NBRC 108930(T)) and Pontibacter odishensis sp. nov. (type strain JC130(T) = KCTC 23982(T) = LMG 26962(T)), respectively, are proposed. Emended descriptions of the genera Erythrobacter and Pontibacter are provided.


Proteome of synaptosome-associated proteins in spinal cord dorsal horn after peripheral nerve injury.
Peripheral nerve injury may lead to neuroadaptive changes of cellular signals in spinal cord that are thought to contribute to central mechanisms underlying neuropathic pain. Here we used a 2-DE-based proteomic technique to determine the global expression changes of synaptosome-associated proteins in spinal cord dorsal horn after unilateral fifth spinal nerve injury (SNI). The fifth lumbar dorsal horns ipsilateral to SNI or sham surgery were harvested on day 14 post-surgery, and the total soluble and synaptosomal fractions were isolated. The proteins derived from the synaptosomal fraction were resolved by 2-DE. We identified 27 proteins that displayed different expression levels after SNI, including proteins involved in transmission and modulation of noxious information, cellular metabolism, membrane receptor trafficking, oxidative stress, apoptosis, and degeneration. Six of the 27 proteins were chosen randomly and further validated in the synaptosomal fraction by Western blot analysis. Unexpectedly, Western blot analysis showed that only one protein in the total soluble fraction exhibited a significant expression change after SNI. The data indicate that peripheral nerve injury changes not only protein expression but also protein subcellular distribution in dorsal horn cells. These changes might participate in the central mechanism that underlies the maintenance of neuropathic pain.


Mouse fitness measures reveal incomplete functional redundancy of Hox paralogous group 1 proteins.
Here we assess the fitness consequences of the replacement of the Hoxa1 coding region with its paralog Hoxb1 in mice (Mus musculus) residing in semi-natural enclosures. Previously, this Hoxa1B1 swap was reported as resulting in no discernible embryonic or physiological phenotype (i.e., functionally redundant), despite the 51% amino acid sequence differences between these two Hox proteins. Within heterozygous breeding cages no differences in litter size nor deviations from Mendelian genotypic expectations were observed in the outbred progeny; however, within semi-natural population enclosures mice homozygous for the Hoxa1B1 swap were out-reproduced by controls resulting in the mutant allele being only 87.5% as frequent as the control in offspring born within enclosures. Specifically, Hoxa1B1 founders produced only 77.9% as many offspring relative to controls, as measured by homozygous pups, and a 22.1% deficiency of heterozygous offspring was also observed. These data suggest that Hoxa1 and Hoxb1 have diverged in function through either sub- or neo-functionalization and that the HoxA1 and HoxB1 proteins are not mutually interchangeable when expressed from the Hoxa1 locus. The fitness assays conducted under naturalistic conditions in this study have provided an ultimate-level assessment of the postulated equivalence of competing alleles. Characterization of these differences has provided greater understanding of the forces shaping the maintenance and diversifications of Hox genes as well as other paralogous genes. This fitness assay approach can be applied to any genetic manipulation and often provides the most sensitive way to detect functional differences.