Synthesis and Characterization of Carbon Dots Coated CaCO3 Nanocarrier for Levofloxacin Against Multidrug Resistance Extended-Spectrum Beta-Lactamase Escherichia coli of Urinary Tract Infection Origin.
The multidrug resistance (MDR) Escherichia coli having Extended-Spectrum Beta-Lactamase (ESBL) genes and the capacity to create a biofilm acts as a major reduction in the therapeutic effectiveness of antimicrobials. In search of a novel nanocarrier (NC) for targeted delivery of antibiotics, carbon dots (CDs) coated calcium carbonate nanocarriers (CCNC) from organic chicken eggshells conjugated with levofloxacin (Lvx) were synthesized. Our main objectives were to explore the antimicrobial, antibiofilm, and NC potential of CDs coated CaCO3 Nanocarrier conjugated with levofloxacin (CD-CCNC-Lvx) to combat biofilm-producing MDR ESBL E. coli of urinary tract infection origin. The synthesized NC system was physiochemically characterized, validating the synthesis of CCNC and CD-CCNC-Lvx with a particle size of 56 and 14 nm, respectively. Scanning electron microscopy (SEM) showed rod shape morphology. X-ray diffraction results discovered crystalline and dispersed nanoparticles. In vitro release drug kinetics illustrated sustained release of Lvx. NC system exhibited strong antibacterial and antibiofilm potential against E. coli with a noticeable low minimal inhibitory concentration (MIC). MIC of CCNC was found to be 30 ± 0.1 μg/mL and CD-CCNC-Lvx was 20 ± 0.1 μg/mL for MDR ESBL-producing E. coli. The synergistic effect of NC upon conjugation with Lvx showed incredible activity with 30 mm zone of inhibition and 68% biofilm inhibition. Flow cytometry analysis revealed treated E. coli cells showed 58.69% reduction in cell viability. SEM images of treated bacterial cells showed morphological changes, which were also confirmed by our flow cytometry findings leading to cell membrane damage in E. coli. NC system also downregulated the blaCTX-M gene in E. coli. The hemolytic analysis proved biocompatibility with human red blood cells (RBCs). It is concluded that CCNC has the potential to be used as NC for target delivery of antibiotics and may combat toxicity of antibiotics as the inhibition of E. coli was noticed at low MIC concentration.


Investigation of a Combined Surveying and Scanning Device: The Trimble SX10 Scanning Total Station.
Surveying fields from geosciences to infrastructure monitoring make use of a wide range of instruments for accurate 3D geometry acquisition. In many cases, the Terrestrial Laser Scanner (TLS) tends to become an optimal alternative to total station measurements thanks to the high point acquisition rate it offers, but also to ever deeper data processing software functionalities. Nevertheless, traditional surveying techniques are valuable in some kinds of projects. Nowadays, a few modern total stations combine their conventional capabilities with those of a laser scanner in a unique device. The recent Trimble SX10 scanning total station is a survey instrument merging high-speed 3D scanning and the capabilities of an image-assisted total station. In this paper this new instrument is introduced and first compared to state-of-the-art image-assisted total stations. The paper also addresses the topic of various laser scanning projects and the delivered point clouds are compared with those of other TLS. Directly and indirectly georeferenced projects have been carried out and are investigated in this paper, and a polygonal traverse is performed through a building. Comparisons with the results delivered by well-established survey instruments show the reliability of the Trimble SX10 for geodetic work as well as for scanning projects.


Predictors of Problematic Social Media Use: Personality and Life-Position Indicators.
Given the preponderance of social media in our increasingly saturated media environments, there is a need for greater understanding of how personality traits and states can influence problematic social media use. This study examines whether contextual age indicators (life satisfaction, interpersonal interaction, social activity), the fear of missing out, and the Big Five personality traits are significant predictors of Facebook, Instagram, and Snapchat addictions. A survey of 337 college students reveals that greater social activity is a positive predictor of addiction to Snapchat. Another significant finding is a positive relationship between social media addiction and the fear of missing out, which explained the most variance in addiction scores for Snapchat (16%). An inductive analysis of open-ended responses indicated strong similarities between those who claimed that they were addicted to these social media apps and those said that they were not addicted. Both groups described largely similar usage patterns and media dependency, yet several users did not self-identify as addicted to social media. These patterns indicate that more research is needed to determine how social media users differentiate between normative, heavy, and addicted usage.


Display of the vectorcardiograms with a new complementary loop of formula Z = f (square root X2 + Y2).
It is important in vectorcardiography to be able to determine the position and magnitude of a given vector, e.g., the left maximum spatial vector, or the vector occurring 20 ms after beginning of QRS, etc. In this aim the authors present besides the three classical planar projections , a fourth curve of Lissajous, known asthe "modulus curve" and which corresponds to the formula Z = f (square root X2 + Y2). In general applications, this curve is very simple to use, and several examples of application are given. The technical realization, which involves no great modification of standard equipment, is described.


Inapparent twin malignancy in thyroglossal cyst: Case Report.
BACKGROUND: Although malignancy has been reported in thyroglossal cysts, synchronous occurrence of two malignancies is extremely rare. CASE REPORT: A case of concurrent papillary and squamous carcinoma arising in the thyroglossal cyst is presented here. CONCLUSIONS: Papillary and squamous carcinoma simultaneously occurring in a thyroglossal cyst is rarely diagnosed prior to surgery and pose a therapeutic dilemma. In view of the extreme rarity of the condition, controversies do exist regarding the optimal strategy to be adopted. The ideal procedure needs to be individually tailored and involve a combination of surgery, radio ablation, thyroid suppression and external radiotherapy.


Depression, anxiety and insomnia in Chinese older adults and their family caregivers during the COVID-19 pandemic: an actor-partner interdependence model approach.
This study aimed to explore the dyadic effects of depression and anxiety on insomnia symptoms in Chinese older adults and their caregivers living in a community setting. Data were collected from 1,507 pairs of older adults and their caregivers who were in the Guangdong Mental Health Survey in China. The 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder module 7 (GAD-7), and Insomnia Severity Index (ISI) were used to measure depression, anxiety, and insomnia symptoms. Actor-Partner Interdependence Models (APIM) were used to determine whether anxiety or depression symptoms predicted individual or dyadic insomnia. Older adults' and caregivers' depression and anxiety had significant positive correlations with their own and their caregivers' insomnia symptoms (all P < 0.001). Actor effects were found between depression and insomnia symptoms in both older adults and caregivers (B = 0.695, P < 0.001; B = 0.547, P < 0.001, respectively), with one significant partner effects (B = 0.080, P = 0.007). Actor effects were also found between anxiety and insomnia symptoms in both older adults and caregivers (B = 0.825, P < 0.001; B = 0.751, P < 0.001, respectively), with one significant partner effects (B = 0.097, P = 0.004). However, the caregivers' depression and anxiety were not associated with older adults' insomnia symptoms in the APIM analyses. Older adults and their caregivers had an interrelationship between psychological distress and insomnia. Consequently, healthcare providers might consider involving dyads when designing programs to reduce insomnia and improve psychological distress for family caregivers.


In vitro transformation of epithelial cells by ras oncogenes.
Genes of the ras family of dominant transforming genes are frequently activated by specific point mutations in common human epithelial malignancies and also in many experimental tumour models. Testing of the hypothesis that ras activation is a critical event in tumorigenesis involves reconstruction of genetic events in vitro using appropriate epithelial models. This article reviews experimental transformation of human and rodent epithelial cells by ras oncogenes in vitro, alone and in combination with cooperating oncogenic events.


The Results of a Propensity Score Matching Analysis of the Efficacy of Abdominal Fascia and Skin Closure Using PDS® Plus Antibacterial (Polydioxanone) Sutures on the Incidence of Superficial Incisional Surgical Site Infections after Gastroenterologic Surgery.
Surgical site infections (SSIs) lead to prolonged hospitalization and increased cost of hospital stay after surgery. Therefore, the prevention of SSIs is one of the most critical tasks facing surgeons and nursing staff. In the present study, the efficacy of using triclosan-coated polidioxanone sutures (PDS® Plus Antibacterial Suture, (Ethicon Inc., Somerville, NJ) for abdominal closure was analyzed retrospectively using a propensity score matching analysis. Of 1,768 patients who underwent gastroenterologic surgery at Fukuoka University Hospital between January 2009 and September 2013, 812 underwent abdominal closure using PDS Plus. These patients were compared retrospectively regarding the incidence of SSIs using a propensity score matching method with 956 patients treated in the previous period without abdominal closure using PDS Plus sutures. The propensity score was calculated from the age, gender, body mass index, smoking status, diabetes mellitus, use of steroid medication, malignant or benign disease, organ location, emergency or planned surgery, wound classification, the American Society of Anesthesiologists score, open or laparoscopic surgery, the length of the operation, and blood loss. Nine hundred sixty-six patients (483 matched sets) were enrolled by the propensity score matching method. No parameter used for the propensity score was different between the PDS Plus and control groups. Closure using PDS Plus could reduce the incidence of SSIs compared with that in the control group (p = 0.022). Of the parameters used for the propensity score, malignant disease (p = 0.0002), open surgery (p = 0.0020), a prolonged operation (p < 0.0001), high blood loss (p < 0.0001), the need for a transfusion (p = 0.019), and gastrointestinal tract surgery (p = 0.0059) were significant risk factors for the development of SSIs in the univariable analysis. In a multivariable regression model, open surgery (p < 0.0001), prolonged operation (p < 0.0001), gastrointestinal tract surgery (p = 0.001), and abdominal closure without PDS Plus (p < 0.0001) were the independent risk factors for the development of an SSI. The development of an SSI prolonged the hospital stay (p < 0.0001) and the use of antibiotic medication (p < 0.0001); abdominal closure using PDS Plus affected the antibiotic medication period (p = 0.013) but not the hospital stay (p = 0.40). Although abdominal fascia and skin closure using PDS Plus was compared with variable abdominal closure, the present findings suggest that abdominal fascia and skin closure using PDS Plus sutures could help prevent the development of SSIs after gastroenterologic surgery, as determined by a propensity score matching analysis.


Rosai Dorfman disease of the parotid and submandibular glands: salivary gland scintigraphy and oral findings in two siblings.
Rosai-Dorfman disease (RDD) is an unusual clinical entity characterized by benign pseudolymphomatous proliferation with significant histiocytic infiltration. In the present paper, extranodal RDD of the major salivary glands causing salivary hypofunction and the results of salivary gland scintigraphy and ultrasound are presented in two siblings. Case 1: a 10-year-old boy with bilateral painless masses around the parotid and submandibular glands was referred. Ultrasound examination showed bilateral, well-defined, hypoechoic solid mass lesions within both parotid glands with minimal normal parenchyma in the upper poles. Both submandibular glands were markedly hypoechoic and heterogeneous. Mass lesions within the parotid glands appeared as cold lesions with regular contours on scintigraphy. Dynamic images showed normal uptake and normal response to secretion in the upper poles of the parotid glands, corresponding with ultrasonographically normal parenchyma. Both submandibular glands showed markedly diminished uptake and secretion. Case 2: a 9-year-old boy presented with mass lesions around the submandibular glands. Ultrasound examination showed normal parotid glands and markedly hypoechoic and heterogeneous submandibular glands. Salivary gland scintigraphy showed normal uptake and secretion of parotid glands with markedly diminished uptake and secretion in both submandibular glands. There were severe carious lesions in both patients due to salivary hypofunction. Treatments of the two patients' teeth were performed. Major salivary gland involvement of RDD is important for dentists as it may cause xerostomia and can mimic dental abscess. Functional evaluation of salivary glands with scintigraphy, besides radiological and pathological techniques, will help to explain whether salivary glands are affected or not and improve the diagnostic effectiveness.


Focal adhesion kinases crucially regulate TGFβ-induced migration and invasion of bladder cancer cells via Src kinase and E-cadherin.
Focal adhesion kinase (FAK) is a non-receptor protein-tyrosine kinase that is triggered off by special extracellular signals such as some growth factors and integrins. FAK is found in cell-matrix attachment sites and implicated in cell migration, invasion, movement, gene expression, survival and apoptosis. In this study, we aimed to investigate whether FAK plays a role in invasion and migration of bladder cancer cells. Using an FAK-specific small interfering RNA (siRNA) and an FAK inhibitor PF-228, we found that inhibition of FAK tyrosine phosphorylation or knockdown of FAK suppressed invasion and migration of bladder cancer cells. Src is an important mediator of FAK-regulated migratory and invasive activity. Tyrosine phosphorylation of Src and FAK is mutually dependent and plays a key role in transforming growth factor beta (TGFβ)-induced invasion and migration. E-cadherin acts downstream of FAK and is a critical negative regulator in FAK-regulated invasion and migration of bladder cancer cells. These findings imply that FAK is involved in oncogenic signaling of invasion and migration, which can be a novel therapeutic target to treat patients with bladder cancer.


ENU mutagenesis in the mouse: application to human genetic disease.
Genetic approaches in model organisms provide a powerful means by which to examine the biological basis of human diseases as well as the physiological processes that are affected by them. Although not without its drawbacks, the mouse has become the mammalian species of choice in studying the molecular basis of disease. Targeted mutagenesis approaches in the mouse have led to dramatic increases in our understanding of human disease processes. As a complement to these gene-driven studies, three developments have led to the reassessment of a phenotype-driven approach in the mouse--the accumulation of information that has emerged from human and mouse genome sequencing projects, the use of high-efficiency point mutagens such as N-ethyl-N-nitrosourea (ENU) and the application of systematic hierarchical screening protocols for the mouse. In this paper, progress with existing phenotypic screening programmes is discussed and opportunities for the development of new mouse disease models are presented.


Intertrigo: a practical approach.
Although the precise diagnosis of intertriginous dermatosis is hampered by the unique conditions of the skin folds, there are a few common rules to be considered in the therapeutic approach. Dryness must be reached by changing occlusive conditions, astringent compresses, and absorbing powders. To improve the primary dermatosis, superimposed infection must be treated. With rare exceptions, fluorinated steroids should not be used in occlusive areas. Finally, the skills of a dermatologist may be required to optimize the care of patients with complex dermatoses involving the flexural skin.


Estimation of cyclodextrin affinity to steroids.
A nonlinear spectrometric method for determination of the stability constant (Ks) for cyclodextrin complex with steroid was developed. The method is based on calculation of the parameters of competitive cyclodextrin complexation by simultaneous fitting of two types of curves. Those of the first type are the dependencies of absorbance of methyl orange solution on the cyclodextrin concentration, the second type being the absorption curves of displacement of the dye, by steroid, from the cyclodextrin complex. With the method proposed, Ks values were calculated with standard deviation less than 10%. This method is validated by determination of Ks values using the phase-solubility technique. For neutral steroid molecules, the effect of pH on Ks was found to be insignificant. Ks values for the cyclodextrin-dye complex were determined for randomly methylated beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, carboxymethyl-beta-cyclodextrin and sulfobutylether-beta-cyclodextrin. More hydrophobic steroids were characterised by higher Ks values. Anionic beta-cyclodextrins showed high affinity for the steroids studied. Simple equipment and sufficient computing allowed recommendation of the method for express estimation of cyclodextrin's affinity for hydrophobic substrates.


Family Caregivers of Patients With a High-Grade Glioma: A Qualitative Study of Their Lived Experience and Needs Related to Professional Care.
The poor prognosis and disabling symptoms of a high-grade glioma (HGG) affect not only the patient but place high demands on family caregivers. The objective of this study was to explore the experience of family caregivers of patients with HGG and their needs related to professional care. A qualitative research using semistructured interviews was conducted. Sixteen family caregivers of patients with an HGG who were treated or in follow-up at a Belgian hospital were interviewed. Family caregivers reported experiencing loss of their old life and the patient's old self. They were saddened to see the patient's disabilities and the change in their relationship, which in turn contributed to feelings of loneliness. At the same time, they reported a strong commitment and determination to provide the patient with the best possible care. Many, however, felt unprepared to do so, and they reported feeling insecure. Caregivers expressed the need for information and for consideration and support. The diagnosis of an HGG is disruptive to the life of family caregivers. They strongly commit but at the same time struggle to care for the patient. Professional caregivers should be aware of the subtle balance between family caregivers' wish to care and the burden of caregiving. Professional caregivers can be of great value to family caregivers by providing guidance and assistance for this new caregiving role while being considerate of their commitment and their grief.


Silicon drift detector based X-ray spectroscopy diagnostic system for the study of non-thermal electrons at Aditya tokamak.
Silicon drift detector based X-ray spectrometer diagnostic was developed to study the non-thermal electron for Aditya tokamak plasma. The diagnostic was mounted on a radial mid plane port at the Aditya. The objective of diagnostic includes the estimation of the non-thermal electron temperature for the ohmically heated plasma. Bi-Maxwellian plasma model was adopted for the temperature estimation. Along with that the study of high Z impurity line radiation from the ECR pre-ionization experiments was also aimed. The performance and first experimental results from the new X-ray spectrometer system are presented.


Pharmacokinetic and Pharmacodynamic Variability of Insulin When Administered by Jet Injection.
Jet injection has been shown to accelerate the absorption and action of rapid-acting insulin. In this study, we compared the variability of absorption characteristics between jet injection and conventional administration of the rapid-acting insulin analogue aspart. A total of 30 healthy volunteers were enrolled in this randomized controlled blinded parallel study. On two test days, they received insulin aspart (0.2 units/kg body weight), either by jet injection or conventional pen, followed by a 6-hour euglycemic glucose clamp. Plasma glucose and insulin levels and glucose infusion rates were measured every 5 to 10 minutes to calculate the variability in pharmacological endpoints. Jet injection advanced the times until maximal insulin concentration (T-INSmax) and glucose infusion rate (T-GIRmax) by ~40% (both P < .01). The difference between the two test days for these endpoints did not differ between jet injection and conventional administration (T-INSmax: 7.3 ± 1.9 vs 22.3 ± 6.3 min, P = .074; T-GIRmax: 24.0 ± 3.5 vs 27.3 ± 6.6 min, P = .66). The corresponding intraindividual coefficients of variation for injection by jet or conventional pen were 15.3 ± 3.3 and 22.0 ± 4.6% ( P = .25, Pvariance = .044) for T-INSmax and 34.5 ± 5.1 and 21.2 ± 4.6% for T-GIRmax ( P = .064, Pvariance = .62). The variance in maximal insulin concentration was significantly less after conventional administration ( P = .039). The variance in total glucose-lowering effect and total insulin exposure did not differ ( P = .93 and P = .32) Conclusion: Using a jet injector for insulin administration was associated with slightly altered variability in pharmacokinetic endpoints, but with about similar variability in pharmacodynamic endpoints compared to conventional administration. Variability in these endpoints remains considerable, regardless of the method of insulin administration.


Toxicity of vinyl chloride and poly(vinyl chloride): a critical review.
In 1974, vinyl chloride (VC) was first reported in the open scientific literature to induce angiosarcoma of the liver both in humans and in animals. Additional research has now demonstrated the carcinogenicity of VC to other organs and at lower concentrations. The target organs for VC now clearly include the liver, brain and the lung, and probably the lymphohematopoietic system. The evidence for a carcinogenic risk has been extended to jobs associated with poly(vinyl chloride) exposure. Cases of liver angiosarcoma have been reported among individuals employed in PVC fabrication facilities and an epidemiological study has demonstrated a significant association between exposure to PVC dust and the risk of lung cancer mortality. Cases of angiosarcoma of the liver also have been reported among individuals living in near proximity to vinyl chloride-poly(vinyl chloride) plants. An association between PVC dust and pneumoconiosis also has been demonstrated. On the basis of findings, prudent control of PVC dust in the industrial setting is indicated.


Anaesthetic considerations in chronic renal failure.
This paper discusses the anaesthetic problems presented by patients in chronic renal failure. The anaesthetic agents and techniques used in 181 patients who underwent 941 operations (including 218 renal transplants) are described.


[Leishmaniasis: progress in diagnosis, treatment and prevention].
Visceral leishmaniasis ranks second after malaria in the top 10 fatal parasitic diseases worldwide. Treatment is effective, but most patients live in developing countries where even basic health care is unavailable. Economic factors hamper a targeted approach, which should include the following: preventing transmission by distributing bednets; developing diagnostic tools that can be used in the field without a laboratory; developing new and affordable drugs; and evaluating different drug combinations and treatment schedules that may prevent the development of resistance, as has been done in tuberculosis, HIV and malaria.


Cobalt(II)-Catalyzed Isocyanide Insertion Reaction with Sulfonyl Azides in Alcohols: Synthesis of Sulfonyl Isoureas.
A Co(II)-catalyzed isocyanide insertion reaction with sulfonyl azides in alcohols to form sulfonyl isoureas via nitrene intermediate has been developed. This protocol provides a new, environmentally friendly, and simple strategy for the synthesis of sulfonyl isourea derivatives by employing a range of substrates under mild conditions.


Effect of blood pressure on L-NAME-sensitive component of vasorelaxation in adult rats.
The aim of this study was to investigate nitric oxide (NO) production and L-NAME-sensitive component of endothelium-dependent vasorelaxation in adult normotensive Wistar-Kyoto rats (WKY), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). Blood pressure (BP) of WKY, BHR and SHR (determined by tail-cuff) was 111+/-3, 140+/-4 and 184+/-6 mm Hg, respectively. NO synthase activity (determined by conversion of [(3)H]-L-arginine) was significantly higher in the aorta of BHR and SHR vs. WKY and in the left ventricle of SHR vs. both BHR and WKY. L-NAME-sensitive component of endothelium-dependent relaxation was investigated in the preconstricted femoral arteries using the wire myograph during isometric conditions as a difference between acetylcholine-induced relaxation before and after acute N(G)-nitro-L-arginine methyl ester pre-treatment (L-NAME, 10(-5) mol/l). Acetylcholine-induced vasorelaxation of SHR was significantly greater than that in WKY. L-NAME-sensitive component of vasorelaxation in WKY, BHR and SHR was 20+/-3 %, 29+/-4 % (p<0.05 vs. WKY) and 37+/-3 % (p<0.05 vs. BHR), respectively. There was a significant positive correlation between BP and L-NAME-sensitive component of relaxation of the femoral artery. In conclusion, results suggest the absence of endothelial dysfunction in the femoral artery of adult borderline and spontaneously hypertensive rats and gradual elevation of L-NAME-sensitive component of vasorelaxation with increasing blood pressure.


Cellular basis for genetically determined enhanced resistance of certain mouse strains to listeriosis.
The characteristics of the mononuclear phagocytes mediating resistance to infection with Listeria during the early phase (0 to 48 h) of the response have been investigated in genetically determined susceptible (A/J) and resistant (C57BL/6, B10.A/SgSn) strains of mice. Irradiation immediately before infection profoundly enhanced the bacterial growth in the resistant strain, while having no effect in the susceptible strain, over a wide range (3 x 10(3) to 10(5)) of infective doses. This effect of irradiation is demonstrable at low-dose radiation (200 roentgens) and can be reversed by repopulation with 20 x 10(6) syngeneic nucleated bone marrow cells. Administration of dextran sulfate 500 24 h before infection profoundly enhanced the bacterial growth in the susceptible strain, while having much less effect in the resistant strain. Thus, the genetic advantage of the resistant mouse strains to listerial infection, at least during the early phase of the response, appears to be due to a cellular mechanism that is highly radiosensitive and relatively insensitive to dextran sulfate 500. In the susceptible strain, the early protective cellular mechanism is radioresistant and highly dextran sulfate 500 sensitive.


Amanita phalloides Mushroom Poisonings - Northern California, December 2016.
Amanita phalloides, colloquially known as the "death cap," belongs to the Phalloideae section of the Amanita family of mushrooms and is responsible for most deaths following ingestion of foraged mushrooms worldwide (1). On November 28, 2016, members of the Bay Area Mycological Society notified personnel at the California Poison Control System (CPCS) of an unusually large A. phalloides bloom in the greater San Francisco Bay Area, coincident with the abundant rainfall and recent warm weather. Five days later, CPCS received notification of the first human A. phalloides poisoning of the season. Over the following 2 weeks, CPCS was notified of an additional 13 cases of hepatotoxicity resulting from A. phalloides ingestion. In the past few years before this outbreak, CPCS received reports of only a few mushroom poisoning cases per year. A summary of 14 reported cases is presented here. Data extracted from patient medical charts revealed a pattern of delayed gastrointestinal manifestations of intoxication leading to dehydration and hepatotoxicity. Three patients received liver transplants and all but one recovered completely. The morbidity and potential lethality associated with A. phalloides ingestion are serious public health concerns and warrant medical provider education and dissemination of information cautioning against consuming foraged wild mushrooms.


Pentoxifylline attenuates pulmonary inflammation and neutrophil activation in experimental acute pancreatitis.
Acute pancreatitis (AP) is associated with a systemic inflammatory response. Pentoxifylline (PTX) has been shown to attenuate neutrophil activation and end-organ injury in shock states such as hemorrhage and sepsis. We hypothesized that PTX would down-regulate AP-induced lung injury. Sprague-Dawley rats underwent catheterization of the pancreatic duct. Acute pancreatitis (n = 7) and AP/PTX animals (n = 7) received a retrograde infusion of 3.5% sodium taurocholate and intravenous treatment with normal saline or normal saline and PTX (25 mg/kg), respectively. Pulmonary neutrophil degranulation and sequestration were determined by zymography and detection of myeloperoxidase. Nuclear factor kappa B and mitogen-activated protein kinase phosphorylation was determined by Western blot. Cytokine-induced neutrophil chemoattractant was quantified by enzyme linked immunosorbent assay. Pulmonary histologic injury scores were attenuated in the AP/PTX group (P < 0.05). Plasma amylase levels remained unchanged. Pentoxifylline produced a significant decline in myeloperoxidase content and matrix metalloproteinase activity (P < 0.05). The increase in the phosphorylation of pulmonary nuclear factor kappa B, p38 mitogen-activated protein kinase, and extracellular-related signal kinase 1/2 observed after AP was not demonstrated with PTX (P < 0.05). Pentoxifylline supplementation reduced pulmonary cytokine-induced neutrophil chemoattractant levels by 50% (P < 0.05). Pentoxifylline significantly attenuated histologic lung injury, pulmonary neutrophil activity, and proinflammatory signaling in a severe model of AP. Therefore, PTX may serve as an adjunct for the treatment of the inflammatory complications of severe AP.


Ehlers-Danlos syndrome type VIB with characteristic facies, decreased curvatures of the spinal column, and joint contractures in two unrelated girls.
Two unrelated girls, aged 11 and 14 years, with clinical manifestations of Ehlers-Danlos syndrome (EDS) type VIB, characteristic facies, skeletal abnormalities, and other features are described. They had Marfanoid habitus with pectus excavatum; fragile, hyperextensible, and readily bruisable skin with widened, atrophic scars; recurrent hematomas; generalized joint laxity; hypotonia; scoliosis; and mild delay of gross motor development. Lysyl hydroxylase deficiency was ruled out in Patient 1. Parental consanguinity was present in Patient 2. They both had, in early childhood, down-slanting palpebral fissures, drooping lower eyelids, short nose, small mouth, and long philtrum. Facial features that persisted included thick eyebrows, hypertelorism, strabismus, blue sclerae, low-set, and slanted ears, hypoplastic columella, high-arched palate, and thin upper lip. They had tubular stenosis of the phalanges, metacarpals, and metatarsals; decreased physiological curvatures of the spinal column with tall vertebrae; and joint contractures including talipes equinovarus and progressive talipes valgus. Their hearing of high-pitched sounds was impaired. They had constipation and recurrent cystitis with an enlarged bladder. In view of these findings, we propose that these two girls represent a clinically recognizable subgroup of EDS type VIB.


Hypertension in pregnancy.
Hypertension in pregnancy is still a leading cause of morbidity and mortality in mother and fetus. This review of the literature from 1991 to 1992 focuses on research relating to the causes of preeclampsia and the pathogenesis of the marked vasoconstriction so characteristic of this disease. Reports hypothesizing primary roles for endothelial cell dysfunction, aberrations in prostaglandin synthesis, fatty acid and antioxidant metabolism, as well as for dietary calcium deficiency and the renin-angiotensin system are analyzed; articles regarding clinical trials whose origins derive from some of these hypotheses, such as low-dose aspirin and calcium supplementation to prevent preeclampsia, are appraised. The review concludes by examining several controversies regarding management of pregnant women with chronic hypertension, including the proper way to measure blood pressure in pregnancy, the diastolic level at which treatment with antihypertensive medications should commence, and the choice of drugs that are safe and preferable for use during gestation.


CYP2C19 genotype-guided antiplatelet therapy in a patient with clopidogrel resistance.
We report a switch in antiplatelet medication based on platelet function and CYP2C19 genotype test results in a 74-year-old man with severe coronary arterial disease. Upon bare metal stent implantation at age 66, clopidogrel therapy (75 mg/ day) was initiated to supplement aspirin. Over the next eight years, the patient required multiple percutaneous coronary interventions for de novo coronary stenosis and in-stent restenosis. Platelet reactivity measured while on clopidogrel therapy was high, consistent with clopidogrel resistance. CYP2C19 genotype testing then revealed homozygosity for the *2 null allele. The *2/*2 designation indicates poor metabolizer status, indicating deficient capacity of the cytochrome p450 2C19 enzyme for activation of clopidogrel. A medication switch to prasugrel,which does not rely on activation by the 2C19 enzyme, reduced platelet reactivity by 86%. The patient has suffered no cardiovascular events in the 18 months since initiation of prasugrel therapy.


Paraprofessional versus professional drug abuse counselors: attitudes and expectations of the counselors and their clients.
Three groups of methadone maintenance and drug-free outpatient counselors, ex-addict paraprofessionals (EXAs), non-ex-addict paraprofessionals (NEAs), and degreed professional counselors (PROs), were contrasted in terms of their views of drug abuse and drug treatment, their attitudes toward and expectations for their clients, and in terms of their clients' attitudes toward them. Across groups, counselors agreed on the major cause of drug abuse, the critical factor in treatment, the definition of treatment success, and their expectations for client success. While clients of the three groups viewed their counselors are equally able to understand them and were equally confident of the counselors, the clients of EXAs saw their counselors as more knowledgeable about critical issues of drugs and the street scene, were more willing to bring personal problems to their counselors, and expected and desired more participation from their counselors in both counseling-related and personal problems.


Effect of over-expression of neuropathy target esterase on mammalian cell proliferation.
Neuropathy target esterase (NTE), the human homologue of a protein required for brain development in Drosophila, is expressed primarily in neural cells but is also detected in non-neural cells. Although NTE has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation, the function of NTE has not been defined in neural cells. In this study we have investigated the possible role of NTE in neuroblastoma cells and non-neural cells using an over-expression strategy. Over-expression of NTE in human neuroblastoma SH-SY5Y cells and monkey kidney COS7 cells led to an accumulation of NTE on the cytoplasmic surface of the endoplasmic reticulum and inhibition of cell proliferation. In particular, high levels of NTE arrested COS7 cells at G2/M stage yet was not associated with arrest at a particular phase of the cell cycle in SH-SY5Y cells. Moreover, over-expression of NTE did not induce apoptosis in two kinds of cell lines as assessed by flow cytometry. These results suggest that the role of NTE over-expression in cell proliferation is associated with different mechanisms in different cells.


Consecutive exotropia following surgically corrected cyclic esotropia.
Cyclic esotropia is a rare form of strabismus consisting of regular intervals of esotropia alternating with periods of orthophoria in a rhythmic/cyclic manner. In the vast majority of cases, surgery appears to permanently correct the esotropia, with no sequelae after years of follow-up. We report a case of consecutive exotropia in a patient five years after bilateral medial rectus recessions for cyclic esotropia. A case report involving review of a clinical chart. A two-year-old male presented with right esotropia and mild amblyopia. He was treated with patching and following resolution of the amblyopia he developed a cyclic esotropia. Surgical correction was performed for the full amount measured on a "manifest" day. Following the surgery, he was orthophoric and demonstrated binocular vision. He remained stable for five years, and then returned with occasional diplopia and an intermittent exotropia. Cyclic esotropia is a rare disorder of ocular motility that spontaneously appears and disappears at regular intervals. After surgical correction, the deviation disappears and recurrence of esotropia is very infrequent. We present the first reported case of consecutive exotropia following surgical correction of a cyclic esotropia.


A critical evaluation of genomic control methods for genetic association studies.
Population stratification is an important potential confounder of genetic case-control association studies. For replication studies, limited availability of samples may lead to imbalanced sampling from heterogeneous populations. Genomic control (GC) can be used to correct chi(2) test statistics which are presumed to be inflated by a factor lambda; this may be estimated by a summary chi(2) value (lambda(median) or lambda(mean)) from a set of unlinked markers. Many studies applying GC methods have used fewer than 50 unlinked markers and an important question is whether this can adequately correct for population stratification. We assess the behavior of GC methods in imbalanced case-control studies using simulation. SNPs are sampled from two subpopulations with intra-continental levels of FST (< or =0.005) and sampling schemata ranging from balanced to completely imbalanced between subpopulations. The sampling properties of lambda(median) and lambda(mean) are explored using 6-1,600 unlinked markers to estimate Type 1 error and power empirically. GC corrections based on the chi(2)-distribution (GC(median) or GC(mean)) can be anti-conservative even when more than 100 single nucleotide polymorphisms (SNPs) are genotyped and realistic levels of population stratification exist. The GCF procedure performs well over a wider range of conditions, only becoming anti-conservative at low levels of alpha and with fewer than 25 SNPs genotyped. A substantial loss of power can arise when population stratification is present, but this is largely independent of the number of SNPs used. A literature survey shows that most studies applying GC have used GC(median) or GC(mean), rather than GCF, which is the most appropriate GC correction method.


Alterations in upper gastrointestinal motility in Helicobacter pylori-positive nonulcer dyspepsia.
To study the association between gastrointestinal motility and Helicobacter pylori (HP) among patients with nonulcer dyspepsia (NUD). We examined the gastric emptying and orocecal transit times (OCTT) in patients with NUD who were colonized with Helicobacter pylori (n = 27). NUD was defined as dyspeptic symptoms for at least 3 months in the absence of gastrointestinal pathology as seen on endoscopy and ultrasound. Subjects with diabetes mellitus, thyroid disorder, or abdominal surgery except appendectomy were excluded. The HP-negative patients with NUD (n = 38) served as controls. Solid phase gastric emptying was assessed by radionuclide scintigraphy. OCTT was determined by measuring exhaled breath hydrogen upon administration of lactulose. The two groups were similar with respect to age, sex, race, and history of smoking. Gastric emptying (t1/2) was 64.96 +/- 3.61 min in the HP-negative and 61.0 +/- 6.59 in the HP-positive group (p = NS). The OCTT was 130.9 +/- 17.26 minutes in the HP-negative and 84.28 +/- 11.07 in the HP-positive group (p = 0.03). There was no difference in the prevalence of nonhydrogen producers between the two groups. There was no correlation between gastric emptying and OCTT (p > 0.05). OCTT is faster among HP-positive patients with NUD than among HP-negative patients. However, gastric emptying is similar in the two groups.


The Current State of Peptide Drug Discovery: Back to the Future?
Over the past decade, peptide drug discovery has experienced a revival of interest and scientific momentum, as the pharmaceutical industry has come to appreciate the role that peptide therapeutics can play in addressing unmet medical needs and how this class of compounds can be an excellent complement or even preferable alternative to small molecule and biological therapeutics. In this Perspective, we give a concise description of the recent progress in peptide drug discovery in a holistic manner, highlighting enabling technological advances affecting nearly every aspect of this field: from lead discovery, to synthesis and optimization, to peptide drug delivery. An emphasis is placed on describing research efforts to overcome the inherent weaknesses of peptide drugs, in particular their poor pharmacokinetic properties, and how these efforts have been critical to the discovery, design, and subsequent development of novel therapeutics.


Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
Multiple studies demonstrate significantly better therapeutics outcomes in smokers as compared with never smokers when single-agent immunotherapy is applied. Non-smoker patients usually need a combination of chemoimmunotherapy to achieve comparable or slightly better therapeutic results. This effect is thought to be due to tobacco product-induced upregulation of PD-L1/PD-1 expression and tumor mutational burden score. Genomic transformation, however, cannot entirely explain the upregulation of PD-L1/PL-1 expression in cells following short-term exposure to cytotoxic compounds. Cytotoxic drugs, crude tobacco products, benzo(a)pyrene, nicotine, and multiple other toxic compounds were shown to exhibit rapid PD-L1/PD-1 upregulation. A significant immunomodulatory effect of nicotine via acetylcholine receptors is well documented. However, nicotine activity rapidly subsides when the drug is withdrawn. We hypothesize that smoking cessation might mitigate the benefits of monoimmunotherapy for some patients. Further studies of the nicotinic acetylcholine receptor stimulus of immunocytes are needed and might lead to characterization and clinical implementation of new immunotherapy sensitizer products.


Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28.
Progressive external ophthalmoplegia (PEO) is a common feature in adults with mitochondrial (mt) DNA maintenance disorders associated with somatic mtDNA deletions in muscle, yet the causal genetic defect in many patients remains undetermined. Whole-exome sequencing identified a novel, heterozygous p.(Gly671Trp) mutation in the AFG3L2 gene encoding an mt protease--previously associated with dominant spinocerebellar ataxia type 28 disease--in a patient with indolent ataxia and PEO. Targeted analysis of a larger, genetically undetermined cohort of patients with PEO with suspected mtDNA maintenance abnormalities identified a second unrelated patient with a similar phenotype and a novel, heterozygous p.(Tyr689His) AFG3L2 mutation. Analysis of patient fibroblasts revealed mt fragmentation and decreased AFG3L2 transcript expression. Western blotting of patient fibroblast and muscle showed decreased AFG3L2 protein levels. Our observations suggest that AFG3L2 mutations are another important cause, albeit rare, of a late-onset ataxic PEO phenotype due to a disturbance of mtDNA maintenance.


Linehan's biosocial model applied to emotion dysregulation in autism: a narrative review of the literature and an illustrative case conceptualization.
Emotion dysregulation (ED) is a transdiagnostic difficulty prevalent in autism spectrum condition (ASC). Importantly, recent research has suggested that ED is involved in self-harm and suicidality. Pre-existing models on the etiology of ED in ASC focus mainly on biological factors to ASC features, such as sensory sensitivities, poor flexibility, and sensitivity to change. However, although psychosocial factors seem to play a role in the emergence of ED in ASC as well (e.g., childhood maltreatment and camouflaging), there is a lack of a comprehensive model conceptualizing biosocial factors involved in ED in autistic people. Linehan's biosocial model (1993) is one of the leading etiological models of ED in borderline personality disorder (BPD). It conceptualizes ED as emerging from transactions between a pre-existing emotional vulnerability in the child and an invalidating developmental environment. Beyond its clinical relevance, Linehan's model has gathered empirical evidence supporting its pertinence in BPD and in other psychiatric disorders. Although ASC and BPD are two distinct diagnoses, because they may share ED, Linehan's biosocial model might be useful for understanding the development of ED in ASC. Hence, this article aims to provide an application and extension of Linehan's model to conceptualize ED in ASC. To do so, we conducted a narrative review of the literature on ED and its underlying factors in ASC from a developmental perspective. To investigate the pertinence of the biosocial model applied to ED in autistic people, we were interested on data on (i) ED and its behavioral correlates in ASC, in relation to the biosocial model, (ii) the potential biological and psychosocial correlates of ED in ASC and (iii) the overlapping difficulties in ASC and BPD. Finally, to assess the pertinence of the model, we applied it to the case of an autistic woman presenting with ED and suicidal behaviors. Our review and application to the case of an autistic woman suggest that ED in ASC encompasses factors related to both biological and psychosocial risk factors as conceptualized in the BPD framework, although in both domains ASC-specific factors might be involved.


Effect of low serum concentrations (0%-2.5%) on growth, production, and shear sensitivity of hybridoma cells.
In a stirred culture of hybridoma cells, the effects of serum reduction from 2.5% to 0% on growth and monoclonal antibody production have been investigated. The shear sensitivity of cells from the same culture has been tested in a bubble column. Serum reduction does not greatly affect viable-cell concentrations, but cell specific monoclonal-antibody production rate shows a decreasing trend. A gradual increase in sensitivity for sparging, which is nor the result of a long-term biological effect, has been measured in a bubble column at decreasing fetal calf serum concentrations. Finally, the hypothetical killing-volume model describing the death rate of insect cells in bubble columns has now been completely validated for the pertinent hybridoma-cell line.


Mechanocombinatorially Screening Sensitivity of Stretchable Strain Sensors.
Stretchable strain sensors have aroused great interest for their application in human activity recognition, health monitoring, and soft robotics. For various scenarios involving the application of different strain ranges, specific sensitivities need to be developed, due to a trade-off between sensor sensitivity and stretchability. Traditional stretchable strain sensors are developed based on conductive sensing materials and still lack the function of customizable sensitivity. A novel strategy of mechanocombinatorics is proposed to screen the sensor sensitivity based on mechanically heterogeneous substrates. Strain redistribution over substrates is optimized by mechanics and structure parameters, which gives rise to customizable sensitivity. As a proof of concept, a local illumination method is used to fabricate heterogeneous substrates with customizable mechanics and structure parameters. A library of mechanocombinatorial strain sensors is created for extracting the specific sensitivity. Thus, not only is an effective strategy for screening of sensor sensitivity demonstrated, but a contribution to the mechanocombinatorial strategy for personalized stretchable electronics is also made.


Ureteral cannulation as a complication of urethral catheterization.
Urinary catheterization is a common procedure, particularly among patients with neurogenic bladder secondary to spinal cord injury. Urethral catheterization is associated with the well-recognized complications of catheter-associated urinary tract infections and limited genitourinary trauma. Unintentional ureteral cannulation represents a rare complication of urethral catheterization and has been previously described in only eight cases within the literature. We describe two cases of aberrant ureteral cannulation involving two patients with quadriplegia. These cases along with prior reports identify the spastic, insensate bladder and altered pelvic sensorium found in upper motor neuron syndromes as major risk factors for ureteral cannulation with a urinary catheter.


Short Stature and Distinct Growth Characteristics in Angelman Syndrome.
Objectives - Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition and motor skills accompanied by unique behaviors, distinct facial features and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history and endocrine abnormalities. Methods - Data was collected from patients' medical files in AS national clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak-height velocity, and final-height. Results - The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual , produced 280 data points. Final-height-SDS was significantly lower compared to general population (-1.23±1.26, p<0.001), and in deletion group vs. non-deletion (-1.67±1.3 vs. -0.65±0.96, p=0.03). Final-height-SDS was significantly lower compared to height-SDS in preschool period (-1.32 vs -0.47, p=0.007). Patient's final-height-SDS was significantly lower than the parents' (∆final-height-SDS=0.94±0.99, p=0.002). IGF1-SDS was significantly decreased compared to general population (-0.55±1.61, p=0.04), with lower values among deletion group (-0.70±1.44, p=0.01) Conclusions - AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.


DGAT1-Dependent Lipid Droplet Biogenesis Protects Mitochondrial Function during Starvation-Induced Autophagy.
Lipid droplets (LDs) provide an "on-demand" source of fatty acids (FAs) that can be mobilized in response to fluctuations in nutrient abundance. Surprisingly, the amount of LDs increases during prolonged periods of nutrient deprivation. Why cells store FAs in LDs during an energy crisis is unknown. Our data demonstrate that mTORC1-regulated autophagy is necessary and sufficient for starvation-induced LD biogenesis. The ER-resident diacylglycerol acyltransferase 1 (DGAT1) selectively channels autophagy-liberated FAs into new, clustered LDs that are in close proximity to mitochondria and are lipolytically degraded. However, LDs are not required for FA delivery to mitochondria but instead function to prevent acylcarnitine accumulation and lipotoxic dysregulation of mitochondria. Our data support a model in which LDs provide a lipid buffering system that sequesters FAs released during the autophagic degradation of membranous organelles, reducing lipotoxicity. These findings reveal an unrecognized aspect of the cellular adaptive response to starvation, mediated by LDs.


Household-based ceramic water filters for the prevention of diarrhea: a randomized, controlled trial of a pilot program in Colombia.
Household water treatment is increasingly recognized as an effective means of reducing the burden of diarrheal disease among low-income populations without access to safe water. Oxfam GB undertook a pilot project to explore the use of household-based ceramic water filters in three remote communities in Colombia. In a randomized, controlled trial over a period of six months, the filters were associated with a 75.3% reduction in arithmetic mean thermotolerant coliforms (TTCs) (P < 0.0001). A total of 47.7% and 24.2% of the samples from the intervention group had no detectible TTCs/100 mL or conformed to World Health Organization limits for low risk (1-10 TTCs/100 mL), respectively, compared with 0.9% and 7.3% for control group samples. Overall, prevalence of diarrhea was 60% less among households using filters than among control households (odds ratio = 0.40, 95% confidence interval = 0.25, 0.63, P < 0.0001). However, the microbiologic performance and protective effect of the filters was not uniform throughout the study communities, suggesting the need to consider the circumstances of the particular setting before implementing this intervention.


Sequence Variation Associated with SLC12A5 Gene Expression Is Linked to Brain Structure and Function in Healthy Adults.
A single-nucleotide polymorphism in the promoter region of the Matrix Metalloproteinase-9 (MMP9) gene, rs3918242, has been shown to affect MMP9 expression in macrophages and was associated with schizophrenia by two independent groups. However, rs3918242's effects on MMP9 expression were not replicable in cell lines or brain tissue. Additionally, publically available data indicate that rs3918242 genotype is related not to MMP9 expression, but rather to expression of SLC12A5, a nearby gene coding for a K+/Cl- cotransporter, whose expression has also been related to schizophrenia. Here, we studied brain structure and function in healthy participants stratified by rs3918242 genotype using structural MRI (N = 298), functional MRI during an N-back working memory task (N = 554), and magnetoencephalography (MEG) during the same task (N = 190). We found rs3918242 was associated with gray matter volume (GMV) in the insula and dorsolateral prefrontal cortex bilaterally, closely replicated in discovery and replication samples; and with inferior parietal lobule (IPL) GMV when the samples were meta-analytically combined. Additionally, using both fMRI and MEG, rs3918242 was associated with right IPL working memory-related activation, replicated in two cohorts and across imaging modalities. These convergent results provide further impetus for examinations of the relationship of SLC12A5 with brain structure and function in neuropsychiatric disease.


Driving CO2 to a Quasi-Condensed Phase at the Interface between a Nanoparticle Surface and a Metal-Organic Framework at 1 bar and 298 K.
We demonstrate a molecular-level observation of driving CO2 molecules into a quasi-condensed phase on the solid surface of metal nanoparticles (NP) under ambient conditions of 1 bar and 298 K. This is achieved via a CO2 accumulation in the interface between a metal-organic framework (MOF) and a metal NP surface formed by coating NPs with a MOF. Using real-time surface-enhanced Raman scattering spectroscopy, a >18-fold enhancement of surface coverage of CO2 is observed at the interface. The high surface concentration leads CO2 molecules to be in close proximity with the probe molecules on the metal surface (4-methylbenzenethiol), and transforms CO2 molecules into a bent conformation without the formation of chemical bonds. Such linear-to-bent transition of CO2 is unprecedented at ambient conditions in the absence of chemical bond formation, and is commonly observed only in pressurized systems (>105 bar). The molecular-level observation of a quasi-condensed phase induced by MOF coating could impact the future design of hybrid materials in diverse applications, including catalytic CO2 conversion and ambient solid-gas operation.


Spontaneous rupture of both flexor tendons in a single digit.
The rare event of simultaneous, spontaneous rupture of both flexor tendons in the mid-segment of one finger is described and discussed in relation to previous reports of tendon rupture in the hand.


Additive interaction of intrathecal ginsenosides and neostigmine in the rat formalin test.
The authors evaluated the effect of intrathecal mixture of ginsenosides with neostigmine on formalin-induced nociception and made further clear the role of the spinal muscarinic (M) receptors on the activity of ginsenosides. A catheter was located in the intrathecal space of male Sprague-Dawley rats. Pain was evoked by injection of formalin solution (5%, 50 µl) to the hindpaw. Isobolographic analysis was done to characterize drug interaction between ginsenosides and neostigmine. The antagonism of ginsenosides-mediated antinociception was determined with M1 receptor antagonist (pirenzepine), M2 receptor antagonist (methoctramine), M3 receptor antagonist (4-DAMP), M4 receptor antagonist (tropicamide). The expression of muscarinic receptor subtypes was examined with RT-PCR. Intrathecal ginsenosides and neostigmine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed an additive interaction between ginsenosides and neostigmine in both phases. Intrathecal pirenzepine, methoctramine, 4-DAMP, and tropicamide reversed the antinociception of ginsenosides in both phases. M1-M4 receptors mRNA detected in spinal cord of naïve rats and the injection of formalin decreased the expression of M1 receptor mRNA, but it had no effect on the expression of other three muscarinic receptors mRNA. Intrathecal ginsenosides little affected the expression of all of muscarinic receptors mRNA in formalin-injected rats. Intrathecal ginsenosides additively interacted with neostigmine in the formalin test. Furthermore, M1-M4 receptors exist in the spinal cord, all of which contribute to the antinocieption of intrathecal ginsenosides.


Lysine-heparin interactions in antithrombin. Properties of K125M and K290M,K294M,K297M variants.
Lysine residues in two different regions of antithrombin have been proposed to be involved in heparin binding and heparin-mediated acceleration of proteinase inhibition. Lysine 125 has been implicated as an essential heparin binding residue from chemical modification studies [Peterson, C. B., Noyes, C. M., Pecon, J. M., Church, F. C., & Blackburn, M. N. (1987) J. Biol. Chem. 262, 8061-8065] whereas lysines 290, 294, and 297 have been proposed from model building studies to constitute the heparin binding site [Villanueva, G. B. (1984) J. Biol. Chem. 259, 2531-2536]. To evaluate both of these proposals, we have prepared two variant human antithrombins, K125M and K290M,K294M,K297M, in which these lysines have been changed by site-directed mutagenesis to methionines. The K290M,K294M,K297M variant had properties very similar to those of wild-type recombinant antithrombin in affinity for heparin, and in rates of inhibition of thrombin and factor Xa. In contrast, K125M antithrombin had reduced affinity for both heparin pentasaccharide and full-length heparin, corresponding to delta delta Gs of 3.1 and 2.0 kcal mol-1, respectively. However, this variant was still able to inhibit both thrombin and factor Xa. Whereas the rate of thrombin inhibition was similar to that of wild-type antithrombin, the rate of factor Xa inhibition was enhanced between 2- and 3-fold, suggesting a role for lysine 125 in the allosteric coupling between the heparin binding site and the reactive center region. At saturation with either heparin pentasaccharide or full-length high-affinity heparin, the rates of inhibition of both proteinases were similar to those of wild-type antithrombin for both the K125M and K290M,K294M,K297M variants.(ABSTRACT TRUNCATED AT 250 WORDS)


Estimating soil degradation in montane grasslands of North-eastern Italian Alps (Italy).
Grasslands cover a large portion of the terrestrial ecosystems, and are vital for biodiversity conservation, environmental protection and livestock husbandry. However, grasslands are degraded due to unreasonable management worldwide, i.e., soil erosion indirectly due to the damage of overgrazing on vegetation coverage and soil texture. An in-depth investigation is necessary to quantify soil erosion in alpine pastures, in order to manage grasslands more sustainably. In this work, we collected freely available satellite images and carried out intensive field surveys for the whole Autonomous Province of Trento (Northeastern Italian Alps) in 2016. The area (and volume) of soil erosions were then estimated and shown in maps. The average of the depths of soil erosion measured in field was used as a reference for estimating soil erosion of the entire study area. High-resolution DEMs difference in soil surface conditions was also computed in two representative areas between pre- and post-degradation to estimate the volume and the average depth of eroded soils. The degradation of soil in the study areas has been estimated in 144063 m2 and an estimated volume of 33610 ± 1800 m3. Results indicate that our procedure can serve as a low-cost approach for a rapid estimation of soil erosion in mountain areas. Mapping soil erosion can improve the sustainability of grazing management system and reduce the risk of pastureland degradation at large spatial scales.


Absorption spectral properties of purified halorhodopsin.
Halorhodopsin in the membrane fragments of Halobacterium halobium Y1 showed an absorption band at 576 nm, the intensity of which decreased on irradiation with red light at 0 degrees C (Ogurusu, T., Maeda, A., Sasaki, N., & Yoshizawa, T. (1981) J. Biochem. 90, 1267-1273). Using this photobleachable property as the basis for an assay of halorhodopsin, we purified halorhodopsin by octyl-Sepharose column chromatography after extracting it from the membrane with Triton X-100. In NaDodSO4-polyacrylamide gel electrophoresis, hR appeared as a major band with an apparent molecular weight of 22,000, but the preparation still showed several other faint bands. The purified halorhodopsin showed a main absorption band at 576 nm and a small band at around 415 nm in 1 M NaCl. The photoreactions of the purified halorhodopsin at 0 degrees C and at -75 degrees C were similar to those of halorhodopsin in membrane fragments. Irradiation of the purified halorhodopsin with red light at 0 degrees C resulted in a decrease of absorbance at around 576 nm with a concomitant increase of absorbance at around 410 nm. A hypsochromic photoproduct was obtained on irradiation with 650 nm light at -75 degrees C. The dependency of the absorption spectrum of halorhodopsin on the concentration of chloride indicates that halorhodopsin has a single chloride binding site, occupation of which is responsible for modifying the spectrum.


[Expectant therapy versus curettage for retained products of conception after second trimester termination of pregnancy: analysis of outcomes and complications].
To evaluate the prognosis and complications of expectant therapy and curettage for retained product of conception (RPOC) after second trimester termination of pregnancy (TOP). A total of 270 patients with RPOC following second trimester TOP in Nanfang Hospital between January, 2014 and December, 2015 were included in this study. The duration of vaginal bleeding time and menstruation recovery interval were compared between patients receiving expectant therapy and curettage for RPOC, and binary logistic regression was used to assess the risk factors for complications in bivariate and multivariate analyses. The duration of vaginal bleeding time was significantly longer in expectant therapy group than in curettage group (P=0.005), while the menstruation recovery interval did not differ significantly between the two groups. The incidence of vaginal bleeding time for over 42 days was significantly higher in curettage group than in expectant therapy group (P=0.040), and the incidence of a menstruation recovery interval beyond 60 days was comparable between them. The incidence of complications was significantly higher in curettage group than in expectant therapy group either with adjustment of age, gravidity, parity, history of uterine surgery status, gestational age, type of indications, regimens for TOP and induction-abortion interval (OR=18.26 [95% CI: 3.57-93.42], P<0.001) or without adjustment (OR=10.60, [95% CI: 2.36-47.66], P=0.002). Expectant therapy and curettage for RPOC after second trimester TOP have comparable prognosis, but curettage is associated with a significantly higher rate of complications.


g-force induced giant efficiency of nanoparticles internalization into living cells.
Nanotechnology plays an increasingly important role in the biomedical arena. Iron oxide nanoparticles (IONPs)-labelled cells is one of the most promising approaches for a fast and reliable evaluation of grafted cells in both preclinical studies and clinical trials. Current procedures to label living cells with IONPs are based on direct incubation or physical approaches based on magnetic or electrical fields, which always display very low cellular uptake efficiencies. Here we show that centrifugation-mediated internalization (CMI) promotes a high uptake of IONPs in glioblastoma tumour cells, just in a few minutes, and via clathrin-independent endocytosis pathway. CMI results in controllable cellular uptake efficiencies at least three orders of magnitude larger than current procedures. Similar trends are found in human mesenchymal stem cells, thereby demonstrating the general feasibility of the methodology, which is easily transferable to any laboratory with great potential for the development of improved biomedical applications.


Cytochemical hybridization with fluorochrome-labeled RNA. II. Applications.
The cytochemical detection of specific DNA sequences by hybridization with fluorochrome-labeled RNA and detection of the hybrids by fluorescence microscopy is described. RNAs complementary to the DNA of the kinetoplasts of Crithidia luciliae (an insect trypanosome) or to adenovirus-5 (Ad-5) DNA were labeled with the hydrazine derivative of tetramethylrhodamine isothiocyanate (TRITC). The specificity of the reactions between the complementary RNAs labeled both with 3H and tetramethylrhodamine was studied by cross-hybridization experiments using a model system in which the DNAs were bound to Sepharose beads. The extent of the reaction was measured by scintillation counting of the bead suspensions and quantitative fluorescence microscopy of individual Sepharose beads. The ability of the rhodamine-labeled cRNAs to hybridize and the absence of interference of the fluorochrome label with the specificity of the hybridization reaction was thus demonstrated. After cytochemical hybridization on microscopic preparations of C. luciliae cells the rhodamine-labeled kinetoplast cRNA stains only the kinetoplasts. No fluorescence was observed in the nuclei. After cytochemical hybridization of rhodamine-labeled Ad-5 cRNA with virus infected KB cells a distinct staining pattern in the nuclei was observed. No fluorescence was seen in uninfected cells, or after hybridization with heterologous rhodamine-labeled RNA. The possibilities and limitations of cytochemical hybridization with rhodamine-labeled RNA are discussed.


Clustering of slowly adapting type II mechanoreceptors in human peripheral nerve and skin.
The intrafascicular organization of human peripheral nerves was studied with percutaneous microneurography in the median, radial and peroneal nerves with one-surface or two-surface thin diameter concentric needle electrodes. Data from 33 recording sites containing 47 slowly adapting type II (SAII) units were analysed. At many sites two, sometimes even three, neighbouring SAII units were recorded from the explored nerve fascicle and they had adjacent or even overlapping cutaneous receptive fields. Among pairs of SAII units found at the same site, one unit often had ongoing discharge, whereas the other was silent under resting conditions. The neighbouring SAII units were optimally activated by stretching the skin in different directions. Stretching the same skin area in different directions produced different unit recruitment. Clustered SAII units were often found in sites where Pacinian afferents and skin sympathetic activity were also recorded. No significant difference was observed in the degree of grouping of SAII units either between recordings obtained with one-surface versus two-surface electrodes or between glabrous and hairy skin. The data do not support the notion that myelinated fibres are randomly organized in peripheral nerve fascicles. Instead, the findings suggest that SAII units tend to be clustered in human peripheral nerves. Furthermore, the response of groups of SAII units to skin stretch suggests that they play a role in proprioception. Dual channel recordings with two-surface concentric needle electrodes may provide a novel approach to study fibre organization in human peripheral nerves and the behaviour of groups of nerve fibres.


Determination of serotonin in nuts and nut containing products by liquid chromatography tandem mass spectrometry.
An ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for the determination of serotonin in raw and roasted nuts (almond, Brazil nut, cashew, chestnut, coconut, hazelnut, Macadamia nut, pecan, peanut, pine nut, pistachio and walnut) as well as nut products (nut containing snack bars, chocolate and spreads) for the first time. Water extraction without prior defatting was performed to leach serotonin from complex matrices of nuts. Mean recoveries ranged from 64.2 ± 9.6 to 94.7 ± 20.1%. Limit of detection and limit of quantification were between 0.4 and 2.3 and 1.0-7.4 ng/g, respectively. Repeatability and reproducibility values were below 2%. Serotonin content of nuts ranged from 0.05 ± 0.01 (pine nut) to 155 ± 57.0 µg/g (walnut) in raw nuts while it was between 0.03 ± 0.00 (Macadamia nut) and 15.3 ± 1.27 µg/g (pecan) in roasted nuts. Serotonin in nut products was found to range from 0.09 ± 0.00 to 8.99 ± 0.92 µg/g, depending on the nuts they contain.


Quantification of fibrosis in the lungs of rats using a morphometric method.
The Wagner grading system is a qualitative histopathologic method designed to describe the severity of nonmalignant respiratory disease (NMRD) as it pertains to the pathology induced by fibrous particulates in humans and later in rats. However, once the method had been used in several rodent fiber studies it was found that it did not adequately differentiate the magnitude of early fibrosis. This article describes a modification of the Wagner scoring system that incorporates a semiquantitative yet simple approach to assuage this problem.


Massive development of amebas in the large intestine. Fedor Aleksandrovich Lesh (Lösch).
Fedor Aleksandrovich Lesh (Lösch) 1840-1903. Although Lösch was a distinguished Russian physician, little has been written about him in English. A graduate of the Medico-chirurgical Academy in St. Petersburg (1863), he defended a doctoral thesis on pulmonary embolism and infarction in 1866, and became an assistant professor of medicine in 1871. From 1872 to 1885 he was a lecturer on diagnosis at the Women's Medical College and a consultant to the Nikolayev Military Hospital. In 1885 he became Professor of Diagnostic Medicine at Kiev University where he remained until his retirement in 1897. In 1870, Lösch found Balantidium coli in the stools of two patients and made a detailed study of the clinical aspects of balantidiasis. In the same year he described in detail Giardia lamblia and Blastocystis hominis. Altogether, he published some 20 papers on the diagnostic and clinical aspects of various diseases, with special emphasis on the microscopic aspects of coprology. It was in 1875 (exactly 100 years ago) that Lösch, in this monumental paper, reported the clinical aspects of recurrent intestinal amebiasis, identified and described its cause, Entamoeba histolytica, and produced the disease in an experimental animal. This work on amebiasis was completed while he was assistant professor at St. Petersburg, on the wards of Prof. E. Eichwald. Clinicians will cherish the description of the patient's symptoms; protozoologists must be delighted by the description of the parasite and its motility; experimentalists will be nervous about his luck in infecting one of three dogs; and iconoclasts must derive satisfaction from Lösch's caution in not automatically assigning a direct causal relationship between the presence of the parasite and the disease.


[Effect on image data resampling in evaluation of the basic imaging properties for a digital radiographic system based on a flat panel detector].
We investigated the effect on image data resampling in an evaluation of the basic imaging properties for a digital radiographic system based on a flat panel detector (FPD). One of the latest digital radiographic systems was used in this study. This system was based on a direct-conversion FPD of amorphous selenium. The basic imaging properties of the system were evaluated by measuring characteristic curve, presampled modulation transfer function (MTF), and Wiener spectrum (WS) using DICOM image with a matrix size of 2048 x 2048. The evaluations were performed under two conditions because matrix size automatically changes according to the selection of imaging size. One of the conditions was a different matrix size between image data acquired on the FPD and the output image (DICOM image for which resampling was performed). The other condition was that these matrices be the same size (DICOM image with no resampling performed). Resampling did not affect the characteristic curves. However, MTF and the WS obtained from the resampled data were different from those of the one not resampled, which is considered to be the "inherent" basic imaging properties, and this phenomenon was remarkable, especially in terms of the MTFs. Our study indicates that the effect on resampling should not be disregarded in evaluating the basic imaging properties of digital radiographic systems. Therefore, it is mandatory to use DICOM images for which no resampling was performed in order to evaluate the inherent basic imaging properties for digital radiographic systems.


Analysis of Endogenous Semicarbazide during the Whole Growth Cycle of Litopenaeus vannamei and Its Possible Biosynthetic Pathway.
This research aims to analyze the biosynthetic pathway of endogenous semicarbazide (SEM) in shrimps using Litopenaeus vannamei as the model target. To achieve this objective, the content of SEM in L. vannamei throughout the whole growth cycle was monitored under the strict control of external environmental interference. Experimental results showed that SEM was found in the shrimp shell at all stages, with its content decreasing first and then increasing, and no SEM was detected in the shrimp muscle of each growth stage. This indicated that endogenous SEM in L. vannamei was derived from the shrimp shell. At the same time, the content of amino acids in the shrimp shell and the corresponding substances involved in the urea cycle in the entire growth cycle of shrimp were monitored. The correlation analysis between them and the changes in the SEM content in shrimp showed that arginine had the largest correlation coefficient (0.952) with the changes in the SEM content. The main substances of the urea cycle may be related to the production of SEM. In combination with the water environmental test of high ammonia nitrogen, it was presumed that the formation of endogenous SEM was related to the amidine group of arginine and amide structure of citrulline and urea. Arginine, citrulline, and urea in the urea cycle of L. vannamei eventually produced SEM via an oxaziridine intermediate under the action of hydrogen peroxide and ammonia, and a standardized reaction test was conducted to verify the hypothesis and, thus, provided a new idea for future endogenous SEM research.


Maintaining Cross-Border Cargo Movements Between Jordan and Saudi Arabia During the COVID-19 Pandemic.
One of Jordan's essential border crossings, the Al-Omari border crossing, is 1 of 3 land crossings between Jordan and Saudi Arabia and is located 160 km west of the capital city of Amman. Given its economic importance and essential role in the functioning of food supply networks across the region, Jordan undertook evidence-driven actions to keep the border crossing safely open during the initial phase of the COVID-19 pandemic. Cross-border coordination and collaboration, specifically with international contact tracing and case management, have been critical elements of Jordan's response. While several bottlenecks and delays led to documented clusters of infections among truck drivers, this case study illustrates the use of evidence to mitigate disease exposure and spread. Plans to manage public health threats need to consider sustainable strengthened surveillance and laboratory capacities coupled with efficient cross-border communication and coordination plans implemented across multiple sectors engaged in cross-country health.


Novel cephalosporins for the treatment of MRSA infections.
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are among the most difficult to treat, Efforts toward the development of cephalosporin antimicrobial agents with activity against MRSA have been ongoing for the last decade. In spite of advancement of several potential drugs into clinical trials no such drugs are available for anti-MRSA therapy yet. The recent emergence of MRSA strains resistant to vancomycin, which is the treatment of choice for MRSA infection, has made the clinical need for new effective drugs even more pressing. In the present review structure-activity relationships are discussed with an emphasis on anti-MRSA activity, pharmacokinetics and efficacy in animal models. Clinical trial status of promising drug candidates is also provided where available.


Interaction between Brassica yellows virus silencing suppressor P0 and plant SKP1 facilitates stability of P0 in vivo against degradation by proteasome and autophagy pathways.
P0 protein of some polerovirus members can target ARGONAUTE1 (AGO1) to suppress RNA silencing. Although P0 harbors an F-box-like motif reported to be essential for interaction with S phase kinase-associated protein 1 (SKP1) and RNA silencing suppression, it is the autophagy pathway that was shown to contribute to AGO1 degradation. Therefore, the role of P0-SKP1 interaction in silencing suppression remains unclear. We conducted global mutagenesis and comparative functional analysis of P0 encoded by Brassica yellows virus (BrYV) (P0Br ). We found that several residues within P0Br are required for local and systemic silencing suppression activities. Remarkably, the F-box-like motif mutant of P0Br , which failed to interact with SKP1, is destabilized in vivo. Both the 26S proteasome system and autophagy pathway play a role in destabilization of the mutant protein. Furthermore, silencing of a Nicotiana benthamiana SKP1 ortholog leads to the destabilization of P0Br . Genetic analyses indicated that the P0Br -SKP1 interaction is not directly required for silencing suppression activity of P0Br , but it facilitates stability of P0Br to ensure efficient RNA silencing suppression. Consistent with these findings, efficient systemic infection of BrYV requires P0Br . Our results reveal a novel strategy used by BrYV for facilitating viral suppressors of RNA silencing stability against degradation by plant cells.


Inflammatory cytokines in heart failure: mediators and markers.
Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis of chronic heart failure (HF) contributing to cardiac remodeling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as tumor necrosis factor (TNF)α, interleukin (IL)-1β and IL-6 in HF patients in plasma and circulating leukocytes, as well as in the failing myocardium itself. There is strong evidence that these mediators are involved in processes leading to cardiac remodeling such as hypertrophy, fibrosis and apoptosis. Some of these cytokines can also give useful prognostic information as reliable biomarkers in this disorder. In general, immunomodulating treatments have, with a few exceptions, been neutral or even harmful. However, the negative results of anti-TNF studies, for instance, do not necessarily argue against the 'cytokine hypothesis'. These studies just underscore the challenges in developing treatment modalities that can modulate the cytokine network in HF patients and result in beneficial net effects. Future studies should identify the crucial actors and their mechanisms of action in the immunopathogenesis of chronic HF and, in particular, clarify the balance between adaptive and maladaptive effects of these molecules. Such studies are a prerequisite for the development of new treatment strategies that target inflammatory and immunopathogenic mechanisms in HF. In this review article, these issues are thoroughly discussed, and we also argue for the possibility of future therapeutic targets such as mediators in innate immunity, chemokines and mediators in matrix remodeling.


[Unresectable stage 4-cancer of the esophagus well responded to combined chemoradiotherapy--a case report].
We experienced a long-term survived case with unresectable Stage 4 esophageal carcinoma well responded to chemoradiotherapy of combination of cisplatin (C), vindesine (V) and peplomycin (P) with radiotherapy (R). The patient was a male, aged 53, and diagnosed to have carcinoma, 8 cm in length, located at the IuCe region of the esophagus and right subclavicular lymph node metastasis on admission. He received radiotherapy at total dose of 60 Gy for the primary and metastatic lesions, and also 2 cycle CVP chemotherapy concomitantly. The mass of the primary lesion endoscopically changed to a flat area with small erosion while the right subclavicular metastatic node disappeared and was not found on CT after the end of the treatment. Objective response of this case was determined to the partial response since carcinoma cells were still found at the flat lesion. After discharge, 9 cycles of CVP therapy were further given in 3-year periods. At present, the patient is alive well although a part of the primary esophageal lesion is proved to have malignancy on biopsy.


Information needs and information sources of individuals living with spinal cord injury.
Access to health information is important for the well-being of people living in the community after spinal cord injury (SCI). In order to design appropriate information interventions, it is critical first to understand the information sources typically used. The goal of this study therefore is to identify the information-seeking practices of this group. A sample of 207 individuals living in the community following traumatic spinal cord injury were surveyed regarding their ongoing information needs and practices for seeking information. The results reveal that respondents have unmet information needs, despite the fact that they typically access information through a variety of channels. SCI specialists are the most commonly used source, although they are viewed as relatively inaccessible. By contrast, the Internet (used by a relatively high proportion of respondents) is viewed as comparatively accessible, although there are some concerns about the quality of information found there. These survey results point to the need for an information source that is accessible and delivers high quality information. Although respondents use a variety of information sources, none meets this ideal profile. Information professionals should consider this gap in the design of information interventions.


Intermacrocyclic Interaction Triggers Facile One-Pot Synthesis of a Chlorin-Porphyrin Heterodimer.
This work reports a highly facile one-pot synthesis of a new series of fully π-conjugated unsymmetric chlorin-porphyrin heterodimers with quantitative yields by utilizing intermacrocyclic interactions. One-electron oxidations of dicopper(II) and dipalladium(II) porphyrin dimers using mild oxidants such as iodine at room temperature resulted in the formation of a strongly interacting cofacial mixed-valent π-cation radical dimers. The radical, being highly reactive, drives spontaneous and rapid transformation involving a new N=C bond formation, 1,2-ethyl migration, and the generation of a new indolizinium ring that bridges between the two macrocycles. X-ray structural characterization of the heterodimers reveals that the two macrocycles are nearly coplanar and thereby extends the π-conjugation from one end to the other. DFT calculations that reproduce the experimental results are also reported.


iCCM data quality: an approach to assessing iCCM reporting systems and data quality in 5 African countries.
Ensuring the quality of health service data is critical for data-driven decision-making. Data quality assessments (DQAs) are used to determine if data are of sufficient quality to support their intended use. However, guidance on how to conduct DQAs specifically for community-based interventions, such as integrated community case management (iCCM) programs, is limited. As part of the World Health Organization's (WHO) Rapid Access Expansion (RAcE) Programme, ICF conducted DQAs in a unique effort to characterize the quality of community health worker-generated data and to use DQA findings to strengthen reporting systems and decision-making. We present our experience implementing assessments using standardized DQA tools in the six RAcE project sites in the Democratic Republic of Congo, Malawi, Mozambique, Niger, and Nigeria. We describe the process used to create the RAcE DQA tools, adapt the tools to country contexts, and develop the iCCM DQA Toolkit, which enables countries to carry out regular and rapid DQAs. We provide examples of how we used results to generate recommendations. The DQA tools were customized for each RAcE project to assess the iCCM data reporting system, trace iCCM indicators through this system, and to ensure that DQAs were efficient and generated useful recommendations. This experience led to creation of an iCCM DQA Toolkit comprised of simplified versions of RAcE DQA tools and a guidance document. It includes system assessment questions that elicit actionable responses and a simplified data tracing tool focused on one treatment indicator for each iCCM focus illness: diarrhea, malaria, and pneumonia. The toolkit is intended for use at the national or sub-national level for periodic data quality checks. The iCCM DQA Toolkit was designed to be easily tailored to different data reporting system structures because iCCM data reporting tools and data flow vary substantially. The toolkit enables countries to identify points in the reporting system where data quality is compromised and areas of the reporting system that require strengthening, so that countries can make informed adjustments that improve data quality, strengthen reporting systems, and inform decision-making.


Use of Cone-Beam Computed Tomography in the Diagnosis and Treatment of an Unusual Canine Abnormality.
Diagnosis and treatment planning are important for successful endodontic treatment. We report a 24-year old male who presented to the Government Dental College in Kozhikode, Kerala, India, in 2015 with pain in his right upper canine. A digital periapical radiograph indicated the presence of a supernumerary tooth superimposing the root of the canine. However, cone-beam computed tomography (CBCT) confirmed that the supernumerary tooth was an illusion and that the canine root had a sharp invagination involving the labial and pulpal dentin surfaces, with evidence of periapical bone destruction. A blunt resection was performed at the level of the invagination and the resected end was filled with a dentin substitute. At a one-year follow-up, the patient was asymptomatic and the periapical region appeared to be healing well. This report highlights the importance of CBCT in visualising abnormal canine morphology, thus allowing appropriate endodontic treatment.


Intracellular FITC-derivatization with PEG.
In order to investigate the amino acids (AAs) in plant cells, we explore an avenue for intracellular derivatization with FITC. In this method, FITC was used to mark AAs in living protoplasts derived from embryogenic calli of common wheat (Triticum aestivum L. c.v. Jinan 177) mediated by PEG. After FITC-derivatization, the AAs in the lysate were determined by CE. The result reveals that this PEG method can be used to transfer FITC into plant cells efficiently, which provides a good method for AA analysis in plant cells.


The Evaluation of Fibrin-Related Markers for Diagnosing or Predicting Acute or Subclinical Venous Thromboembolism in Patients Undergoing Major Orthopedic Surgery.
The cutoff values of fibrin-related markers (FRMs) diagnosing or predicting the occurrence of a venous thromboembolism (VTE) were evaluated. Fibrin-related markers such as fibrin monomer complex (FMC), D-dimer, and fibrinogen and fibrin degradation products (FDPs) before surgery were measured in 326 patients undergoing orthopedic surgery to diagnose subclinical VTE or predict postoperative VTE. Although the FMC, D-dimer, and FDP levels were all useful for the diagnosis of acute VTE, the FDP level was not useful for diagnosing subclinical VTE or predicting postoperative VTE. The results of several D-dimer assays closely correlated with other D-dimer assays. There were various cutoff ranges for diagnosing or predicting VTE. Some D-dimer assays were useful for diagnosing low levels of D-dimer and others were useful for diagnosing moderate to high D-dimer levels. Increased D-dimer levels were useful for diagnosing acute (cutoff values: 2.0-5.9 μg/mL) or about 10% of subclinical VTE (cutoff values: 3.4-5.3 μg/mL), for predicting about 10% of postoperative VTE (cutoff values: 3.4-5.3 μg/mL), and for excluding VTE. Although increased D-dimer levels were useful for diagnosing subclinical VTE and predicting the risk of VTE, there were various cutoff values for the diagnosis or prediction of VTE.


Paracrystalline sheets reaggregated from solubilized exosporium of Bacillus cereus.
Fragments of exosporium, isolated from dormant spores of Bacillus cereus, were disintegrated by treatment with sodium dodecyl sulfate (SDS) or with phenol and acetic acid. After centrifugation of each preparation, proteins in the supernatant fractions were resolved by disc gel electrophoresis into either two or eight bands, respectively. The SDS-solubilized fraction contained spheroidal particles 11 to 44 nm in diameter. When centrifuged until clear, this fraction after dialysis still gave rise to crystal-like sheets which had the same lattice symmetry and major chemical components (protein, lipid, and carbohydrate) as fragments of the native exosporium.


Development and validation of a predictive nomogram for the risk of recurrence in patients with cystitis glandularis.
Most patients with cystitis glandularis (CG) suffer from recurrence after primary treatment. Therefore, we performed this multicenter study to clarify the recurrent risk factors and constructed a predictive nomogram for the risk of recurrence. Also, we try to investigate the correlation between CG and bladder cancer. Consecutive patients with pathologically confirmed CG were divided into training and validation sets. Clinicopathological characters were collected from electronic medical records. Uni- and multivariate logistic regression analyses were used to identify independent risk factors of CG recurrence in the training set. The predictive nomogram was developed by incorporating these independent factors and histological subtype. The performance of the nomogram was assessed and validated with respects to its calibration, discrimination, and clinical usefulness. The risk of developing subsequent bladder cancer was analyzed from the follow-up data. Ultimately, 278 eligible patients were included and were allocated to a training set (n=190) and a validation set (n=88). Of them, 165 (59.35%) patients experienced CG recurrence, and none showed evidence of subsequent bladder carcinoma during a median (IQR) follow-up time of 27 months (14-57 months). Results of multivariate analysis showed that urinary infections, long-term indwelling catheter usage, urinary calculus, squamous metaplasia, and atypical hyperplasia were independent risk factors of CG recurrence. The C-index (95% CI) of the nomogram was 0.76 (0.69-0.83) in the training set and 0.72 (0.61-0.83) in the validation set. A decision curve analysis (DCA) demonstrated that this predictive nomogram was clinically useful. We developed and validated a nomogram to predict the individualized risk of CG recurrence. Also, we demonstrated that neither intestinal nor typical CG increased the consequent risk of bladder cancer during the follow-up period.


Maximum entropy approach to H-theory: Statistical mechanics of hierarchical systems.
A formalism, called H-theory, is applied to the problem of statistical equilibrium of a hierarchical complex system with multiple time and length scales. In this approach, the system is formally treated as being composed of a small subsystem-representing the region where the measurements are made-in contact with a set of "nested heat reservoirs" corresponding to the hierarchical structure of the system, where the temperatures of the reservoirs are allowed to fluctuate owing to the complex interactions between degrees of freedom at different scales. The probability distribution function (pdf) of the temperature of the reservoir at a given scale, conditioned on the temperature of the reservoir at the next largest scale in the hierarchy, is determined from a maximum entropy principle subject to appropriate constraints that describe the thermal equilibrium properties of the system. The marginal temperature distribution of the innermost reservoir is obtained by integrating over the conditional distributions of all larger scales, and the resulting pdf is written in analytical form in terms of certain special transcendental functions, known as the Fox H functions. The distribution of states of the small subsystem is then computed by averaging the quasiequilibrium Boltzmann distribution over the temperature of the innermost reservoir. This distribution can also be written in terms of H functions. The general family of distributions reported here recovers, as particular cases, the stationary distributions recently obtained by Macêdo et al. [Phys. Rev. E 95, 032315 (2017)10.1103/PhysRevE.95.032315] from a stochastic dynamical approach to the problem.


Dopamine Reverses Lung Function Deterioration After Cardiopulmonary Bypass Without Affecting Gas Exchange.
To investigate the effects of dopamine on the adverse pulmonary changes after cardiopulmonary bypass. A prospective, nonrandomized clinical investigation. A university hospital. One hundred fifty-seven patients who underwent elective cardiac surgery that required cardiopulmonary bypass. Fifty-two patients were administered intravenous infusion of dopamine (3 µg/kg/min) for five minutes after weaning from cardiopulmonary bypass; no intervention was applied in the other 105 patients. Measurements were performed under general anesthesia and mechanical ventilation before cardiopulmonary bypass, after cardiopulmonary bypass, and after the intervention. In each protocol stage, forced oscillatory lung impedance was measured to assess airway and tissue mechanical changes. Mainstream capnography was performed to assess ventilation- and/or perfusion-matching by calculating the normalized phase-3 slopes of the time and volumetric capnograms and the physiologic deadspace. Arterial and central venous blood samples were analyzed to characterize lung oxygenation and intrapulmonary shunt. After cardiopulmonary bypass, dopamineinduced marked improvements in airway resistance and tissue damping, with relatively small decreases in lung tissue elastance. These changes were associated with decreases in the normalized phase-3 slopes of the time and volumetric capnograms. The inotrope had no effect on physiologic deadspace, intrapulmonary shunt, or lung oxygenation. Dopamine reversed the complex detrimental lung mechanical changes induced by cardiopulmonary bypass and alleviated ventilation heterogeneities without affecting the physiologic deadspace or intrapulmonary shunt. Therefore, dopamine has a potential benefit on the gas exchange abnormalities after weaning from cardiopulmonary bypass.