[Correlation of the autopsy with the clinical diagnosis in common neoplasms in a general hospital].
The author correlated in a group of 1100 autopsies made in 1987-1989 the clinical and autoptic diagnosis of malignant neoplasms of the bronchi, lungs, stomach, large intestine and rectum, liver and extrahepatic biliary pathways, pancreas and kidneys. In the case of the stomach, large bowel, liver and pancreas the diagnosis moreover with the diagnosis of non-tumourous diseases of these organs. As compared with worldwide autoptic correlations, the diagnostic standard of carcinoma of the bronchi and lungs is roughly equal, in carcinoma of the liver it is better, in carcinoma of the extrahepatic biliary pathways and stomach it is worse. The diagnostic sensitivity of malignant tumours varies from 0.6 to 0.4 and thus in 40-60% of autoptic findings of the mentioned neoplasms an accurate clinical diagnosis was not established. The rate of diagnostic errors of the first type is, however, in this group of differing clinical and autoptic diagnoses lower than in diseases caused by infectious causal agents, the rate of errors of the second type is high. Comparison of the diagnosis of tumourous and non-tumourous diseases of the stomach, large bowel, pancreas and liver revealed roughly the same diagnostic standard with the exception of cirrhosis of the liver where it is lower.


The floating hip. Ipsilateral pelvic and femoral fractures.
A consecutive series is reported of 17 patients who underwent early surgical treatment for acetabular or unstable pelvic fractures associated with ipsilateral fractures of the femur. Treatment included external and internal fixation, and required careful consideration of the surgical approach and the positioning of the patient. The multiple injuries sustained by these patients required simultaneous procedures by several surgical teams. All the femoral fractures were internally fixed at the initial operation and eight patients had primary definitive treatment of all their other fractures as well. In nine patients the definitive treatment of their other fractures was delayed for an average of 11 days. There were no deaths, and no serious infections. The long-term morbidity resulted from the associated injuries and not from the pelvic or femoral fractures.


The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid.
A cryptococcal meningitis model in corticosteroid-treated rabbits was used to assess the requirement for the phosphoribosylaminoimidazole gene (ADE2) for virulence of Cryptococcus neoformans. A wild-type strain (H99), an ade2 auxotroph of H99 (M001), and a randomly selected prototrophic transformant of M001 (M001.1c) which had received the cloned ADE2 cDNA copy were inoculated intrathecally into immunosuppressed rabbits. While M001 was avirulent in the central nervous system model, virulence was completely restored to wild-type pathogenicity in the prototrophic transformant. This study identifies the pathogenic importance of an endogenous adenine pathway in this yeast and confirms that purine biosynthesis is a potential target for antifungal therapy. It also demonstrates that the virulence of C. neoformans can be molecularly changed and detected within a clinically relevant animal model.


Further careers of young British doctors.
After surveys in 1961 and 1966, further questionnaires were sent in 1969 to those who had responded in 1966. These showed that wastage due to emigration and unemployment of married women doctors was nearly 20%. Compared with 49% of all qualified for three to four years in 1966, 73% had definitely decided on their future career seven to eight years after qualifying in the 1969 survey, the choice tending to be for specialties less popular among more junior doctors. Responsibility for patient care seemed not to be related directly to seniority or to performance in medical school examinations.


Educating frontline health workers to support evidence-based management and treatment for chronic obstructive pulmonary disease patients: A literature review.
Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide, yet frontline workers lack the capacity and education required to provide evidence-based management and support for COPD patients. The aim of this review was to: (i) identify the respiratory education gaps within frontline health workers such as nurses, physicians, respiratory therapists, and other allied health professionals, in the initiation of integrated care coordination, and (ii) outline organizational strategies to initiate integrated care coordination towards comprehensive evidence-based management and treatment for COPD patients. A literature review representing articles published between 2011 and 2021 was conducted. The focus was examining the factors that are involved in educating frontline health workers to support evidence-based COPD management and identifying organizational strategies to provide this comprehensive care. The initial searches yielded 353 articles; 18 were retained for review. Thematic analysis revealed two prominent themes as contributing factors to the challenges and strategic solutions: (i) the perceived challenges of frontline health worker respiratory education and (ii) the current deficits within organizational strategies, collaboration, resources, and educational interventions. Providing respiratory education to frontline health workers is imperative to optimize evidence-based care, patient support, and improve outcomes. The solutions include recognizing and focusing on identified contextual barriers, implementing/disseminating strategic solutions, and engaging specialty trained COPD certified respiratory educators as facilitators of COPD primary care.


Family psychiatric screening instruments for epidemiologic studies: pilot testing and validation.
Family history, a risk factor for psychiatric disorders, is infrequently assessed in epidemiologic studies due to time and cost constraints. We designed a brief computer-scorable instrument, the Family History Screen for Epidemiologic Studies (FHE), which collects a pedigree and screens for 15 DSM-III diagnoses in an informant and in his family members. The FHE was administered to one informant in 77 families in which we had collected pedigrees, interviewed 77 informants and 239 relatives using the Lifetime Anxiety version of the schedule for Affective Disorders and Schizophrenia or the Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, and performed best-estimate diagnoses. We evaluated the accuracy with which the FHE predicted best-estimate diagnoses. For adults reporting on themselves, the FHE demonstrated high levels of sensitivity and specificity for depression (67.4, 75.0) and panic (92.5, 89.2), and low sensitivity and high specificity for substance abuse (33.3, 93.6). For informants reporting on adult relatives, sensitivity was low and specificity was high for depression (35.2, 84.9), panic (20.0, 91.7), and substance abuse (42.1, 93.4). For informants reporting on children, perhaps due to lower prevalence, sensitivity and specificity were poor. The FHE is a good screen for psychiatric disorders in adult informants, but it is not useful for family history. It may be useful in primary care medical settings as a screen for psychiatric history.


Multiple endocrine neoplasia type-I-like syndrome in two cats.
Multiple endocrine neoplasia (MEN) embodies a group of diseases in human patients and domestic animals that are characterized by hyperplasia or neoplasia, or both, of two or more endocrine tissues. The MEN-1 syndrome is associated with menin gene mutations that induce various combinations of parathyroid, pituitary, and pancreatic endocrine tumors in humans. Two male, Domestic Shorthair cats developed symmetric alopecia, insulin-resistant diabetes mellitus, and pituitary-dependent hyperadrenocorticism at 12 and 13 years of age. Examination of skin biopsy specimens revealed atrophic dermatosis associated with hyperadrenocorticism. In one cat, cutaneous lesions consistent with paraneoplastic alopecia associated with pancreatic adenocarcinoma also were evident. Multiple invasive pancreatic beta cell carcinomas, pituitary corticotroph adenomas, and thyroid C-cell and parathyroid chief cell hyperplasia were diagnosed on the basis of results of gross, histologic, and immunohistochemical findings in both cats. Pancreatic exocrine adenocarcinoma was diagnosed in both cats. One cat also had hepatocellular carcinoma. Exons 1-8 of the feline menin gene were sequenced and were found to bear 93% homology with the human gene sequence, and the corresponding amino acid sequences shared 98% homology. Purification of total RNA and amplification of cDNA from lesional tissues to document mutations in the feline menin gene sequence were unsuccessful. The combination of lesions observed was consistent with the diagnosis of MEN-1-like syndrome in both cats.


Persistent pain after cardiac surgery: an audit of high thoracic epidural and primary opioid analgesia therapies.
Persistent pain is an underreported morbidity after cardiac surgery. We sent pain surveys to all patients who underwent coronary artery bypass graft surgery from 1997 to 1999 from a single surgeon's experience. Two analgesia strategies were used: high thoracic epidural (HTEA) or IV and oral opiates (OPIOID) for 48-72 h after surgery. Persistent pain was defined as pain still present two or more months after surgery, and all questions referred to the time of survey only. From 356 questionnaires, 305 patients responded, and 61 of them refused consent, leaving 244 patients with complete surveys (HTEA, 150 patients [69%]; OPIOID, 94 patients [68%]). The incidence of persistent pain at any site was 29% and for sternotomy was 25%. The intensity of pain reported was mild, with only 7% reporting interference with daily living. Other common locations of persistent pain were the shoulders (17.4%), back (15.9%), and neck (5.8%). Twenty patients (8%) described symptoms suggestive of the internal mammary artery syndrome. A comparative audit of the HTEA and OPIOID groups showed no significant differences in the frequency or intensity of pain, although the time of survey from operation was longer in the OPIOID group. Mild persistent chest pain after sternotomy is common but infrequently interferes with daily life. Persistent wound pain after coronary artery bypass surgery is common, but it is usually is mild and infrequently interferes with daily living. An audit of two pain relief strategies (epidural analgesia or opiate analgesia) did not show any difference in the incidence of persistent pain.


[What place can the health executive hold in the internal contract process?].
The current context of cost control relative to health expenditures forces hospitals to wonder about their management style. Therefore, the question of the efficiency of the health system is raised. Would the formalization by contract bring the beginnings of an answer? This is what its growing development within numerous public health establishments leads one to suppose, thus signing an evolution towards some new "medical and administrative" governance. Through this article, I therefore suggest to you a questioning on the essence of the contractual method, its stakes, its limits and especially a projective approach on the consequences of this management method considering the "health executive" function. As the stake in this reflection is to highlight the fact that if the health executive has a place acknowledged in the internal formalization by contract, its competence will constitute an increase in value in the contractual process. Indeed, this questioning seems important to me and this, all the more as the ordinance dated May 2, 2005 including "various arrangements relative to the functioning of public health establishments and modifying the public health code", stipulates that public hospitals should resort to the method of internal formalization by contract in setting up centres of activity and this, at the latest, before December 31, 2006.


Endovascular abdominal aortic aneurysm repair by interventional cardiologists--a community-based experience.
Endovascular repair of abdominal aortic aneurysm (AAA) is a relatively recent technology. In comparison to the conventional open surgical treatment for AAA, endovascular AAA repair (EVAR) combines a less-invasive approach with lower morbidity and mortality. There have been few studies regarding the performance of this procedure in a community-based setting. We report our experience of EVAR performed primarily by interventional cardiologists in a community hospital. In our community hospital setting, between September 2005 and November 2007, we included all patients who underwent EVAR by interventional cardiologists, with available on-site vascular surgical support. Clinical and serial computed angiographic imaging outcomes were followed by a retrospective chart review. Data collection tools included demographic and clinical characteristics, anatomical aneurysm features, length of stay, peri- and postprocedural complications, and mortality. A total of 71 consecutive patients had EVAR attempted. The endovascular stent placement was successful in 67 (93%) patients. Thirty-day mortality in this study was 1 of 71 (1.4%). All four procedural failures and the single periprocedural mortality occurred in women. Mean follow-up was 12 months. There were a total of six mortalities and among these four were women (P ≤ 0.001); however, multivariate analysis revealed loss of significant difference in mortality (P = 0.16). Major complications following EVAR were noted in 10 of 71 (14%) patients. EVAR can be successfully performed by experienced interventional cardiologists with vascular surgical support in a community-based setting. In our experience, there is acceptable rate of complications and mortality in a carefully selected patient population.


Drug-induced exanthemata: a source of clinical and intellectual confusion.
Drug rashes are a common problem occurring in patients across the whole spectrum of medical specialties. They are a source of confusion not only to the wider medical community but even among dermatologists there is lack of clarity about how to describe, classify and approach them. Common patterns of drug rash, apart from the "classical" maculo-papular eruptions (MPE), include urticarial wheals and urticaria-like rashes which it is important to distinguish, because of differences in pathogenetic mechanisms, therapeutic response and prognostic significance. The purpose of this article is to try to offer some structure both from the point of view of clinical classification and also of underlying mechanisms.


The link between neighborhood poverty and health: context or composition?
Cross-sectional studies of neighborhood context and health are subject to upward bias due to unobserved heterogeneity and to downward bias due to overadjustment for potential mediators in the pathway between neighborhood context and health. In this study, the authors employed two strategies that addressed these two sources of bias. First, to mitigate overadjustment of mediators, they adjusted for baseline characteristics observed just prior to the measurement of neighborhood context, using a combined propensity score and regression strategy. Second, to mitigate underadjustment of unmeasured confounders, they employed a fixed-effects modeling strategy to account for unobserved non-time-varying heterogeneity. Analyses were based on a nationally representative sample of the nonimmigrant US population from the Panel Study of Income Dynamics (1980-1997) in which respondent-rated health was regressed on neighborhood poverty. The samples consisted of approximately 6,000 respondents for the propensity score/regression models and 45,000 person-years for the fixed-effects models. Both modeling strategies yielded significant estimates of neighborhood poverty and supported a causal link between neighborhood context and health.


Notes from the field: increase in gonorrhea cases in counties associated with American Indian Reservations -- Montana, January 2012-August 2014.
In May 2012, the Montana Department of Public Health and Human Services noted that 23 cases of gonorrhea were reported in Roosevelt County during October 2011-March 2012, compared with only three cases during January-September 2011. An analysis of surveillance data for Roosevelt County and the six other Montana counties most closely associated with American Indian (AI) reservations showed that, during 2000-2011, the annual incidence rates in the seven counties ranged from 9-43 cases per 100,000, compared with 4-19 cases per 100,000 for all the remaining 49 Montana counties, and 98-129 cases per 100,000 for the United States. Since May 2012, the rates have continued to increase in the seven counties. The 2012 and 2013 incidence rates in counties associated with AI reservations were 74 and 131 cases per 100,000, respectively, compared with four and 10 cases per 100,000 in the remaining counties, and 108 cases per 100,000 in the United States during 2012. This increase in gonorrhea incidence in counties associated with AI reservations began in 2012. During January 2012-August 2014, of the 553 gonorrhea cases reported in Montana, 315 (57%) had a race classification of AI/Alaska Native (AN). In comparison, 6.5% of Montana's population is classified as AI/AN. Cases were concentrated in few of Montana's 56 counties; 327 (59%) occurred among residents of seven counties associated with AI reservations that are the home of just 9.8% of Montana's population. Among all reported Montana cases, the median patient age was 24 years (range = 12-70 years), and 258 (47%) occurred among males. Gonorrhea incidence in Montana counties associated with AI reservations is now comparable to U.S. incidence rates.


The diagnostic reasoning involved in interpreting blood results.
Critical assessment of blood results is pivotal to a patient's management. Advanced practice involves autonomous consultation and diagnostic reasoning. The field of haematology is often an area that colleagues find daunting. But with a systematic review and analysis of results, differential diagnosis and plans for treatment or referral can be made. This is the second article in a two-part series. The first article in this two-part series examined history taking in patients with suspected haematological disease. This article will discuss common derangement in blood results and the significance relating to patient management, considering latest evidence and guidelines.


Protein 4.1R self-association: identification of the binding domain.
Erythroid protein 4.1 (4.1R) stabilizes the spectrin-actin network and anchors it to the plasma membrane. To contribute to the characterization of non-erythroid protein 4.1R, we used sedimentation, pull-down and co-immunoprecipitation assays to investigate the ability of protein 4.1R to establish inter-/intra-molecular associations. We demonstrated that the small 4.1R isoforms of 60 kDa (4.1R60), but not the larger isoforms of 80 and 135 kDa (4.1R80 and 4.1R135), were self-associated, and that a domain contained in all 4.1R isoforms, the core region, was responsible for 4.1R self-association. Results from denaturing-renaturing experiments, in which an initially non-self-associated 4.1R80 isoform became self-associated, suggested that an initially hidden core region was subsequently exposed. This hypothesis was supported by results from pull-down assays, which showed that the core region interacted with the N-terminal end of the FERM (4.1, ezrin, radixin, moesin) domain that is present in 4.1R80 and 4.1R135 isoforms but absent from 4.1R60 isoforms. Consistently, 4.1R80 isoforms bound neither to each other nor to 4.1R60 isoforms. We propose that 4.1R60 isoforms are constitutively self-associated, whereas 4.1R80 and 4.1R135 self-association is prevented by intramolecular interactions.


Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound?
Synovial inflammation is increasingly recognized as an important pathophysiologic process in osteoarthritis, but the stimuli and downstream pathways activated are not well defined. Innate immune system activation, best documented in responses to pathogens, likely plays a role in induction of inflammatory mediators and the specific cellular infiltrate seen in osteoarthritis. Thus, the Toll-like receptors (TLRs) and their signaling pathways are of particular interest. These innate pattern-recognition receptors are activated not only by pathogens but by endogenous 'danger signals'. In this report, we review evidence that certain extracellular matrix components of joint tissues (hyaluronan and fibronectin) may act as TLR stimuli, and summarize recent literature implicating TLR activation in osteoarthritis. Convincing evidence exists that hyaluronan/TLR interactions drive responses to tissue injury. Evidence of a similar role for fibronectin is growing. TLRs are expressed and functional in the joint, and many proteases and cytokines that promote cartilage catabolism are dependent on nuclear factor-kappaB, a TLR-activated transcription factor. Activation of TLR pathways seems likely in osteoarthritis and may play a central role in disease development and progression. A model of osteoarthritis as a chronic wound, in which the innate immune response is triggered by molecular signals of tissue damage, is presented as a framework for future study of inflammation in this prevalent joint disease.


A database of 9-mers from promoter regions of human protein-coding genes.
Discovery of lexical characteristics of specific sequence motifs in human genomic DNA can help with predicting and classifying regulatory cis elements according to the genes they control. In lexical models, some "words" may serve as downstream targets of signaling systems, whereas other "words" may specify sequences that selectively control the expression of a subset of genes to produce the various cell types and tissues. To discover lexical features of potential regulatory "words," we have created a database of 9-mers derived from the promoter regions of a subset of human protein-coding genes. This report describes the procedure for extracting information from that database through the web.


Real-time monitoring in vitro cellular cytotoxicity of silica nanotubes using electric cell-substrate impedance sensing (ECIS).
An electrical measurement known as Electric Cell-substrate Impedance Sensing (ECIS) has become increasingly applied to the study of cellular viability, proliferation and cytotoxicity with the advantages of label-free, non-invasion and real-time monitoring capability in comparison with other conventional methods (MTS, MTT). With this technique, cells are grown on the micro-sized gold electrodes where the micro-ampere alternative current is applied to measure the impedance changes due to the physiological changes caused by internal or external stimuli. In another field, Silica Nanotubes (SNTs) are a novel class of inorganic structures with promising potentials in bio-separation, drug delivery, imaging and other biomedical applications. In this study, by using ECIS-based self-fabricated cell chip, Cells were cultured on the working electrodes and separately exposure to the 0, 2 microm, 2 microm and 10 microm long at the varying concentrations of SNTs to evaluate the cellular responses such as viability, multiplication time and cytotoxicity. Final results were additionally compared with the MTS method as a reference to review the reliability


Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: a phase II randomised trial.
New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status >50%, no progression after 6 months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5mg daily until progression or a maximum of 6 months (arm B). The primary outcome measure was the probability of being progression-free at 6 months (PFS-6) from randomisation. Assuming P0 = 10%; P1 = 30%, α .10; β .10, the target accrual was 26 patients per arm. 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91 days (7-186). Main grade 3-4 toxicity was thrombocytopenia, neutropenia and hand-foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0-10.6%) and 22.2% (95% CI: 6.2-38.2%; P<0.01); 2 y overall survival was 7.1% (95% CI: 0-16.8%) and 22.9% (95% CI: 5.8-40.0%; P = 0.11), stable disease 21.4% and 51.9% (P = 0.02). This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2 y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population.


Delayed neuropathy in adult Peking ducks induced by some organophosphorus esters.
Trio-o-cresyl phosphate (TOCP), leptophos [O-methyl O-(4-bromo-2,5,-dichlorophenyl) phenylphosphonothioate] and cyanofenphos [O-ethyl O-(4-cyanophenyl) phenyl-phosphonothioate] were used to determine whether adult peking ducks would exhibit neurotoxicity after exposure to such chemicals. Clinical, histopathological, and specific biochemical tests were used to detect the neurologic dysfunctions that were induced by these neurotoxic agents. Ducks were orally treated with TOCP or leptophos at 100 or 10 mg/kg X d for 30 d, respectively. Another group of ducks received cyanofenphos at 4 mg/kg X d for 10 d. All the TOCP- and leptophos-treated ducks developed clinical signs of delayed neuropathy, as manifested by ataxia and paralysis. Two of the cyanofenphos-treated ducks died from cholinergic effect during the course of dosing. Surviving ducks of this group completely recovered from the cholinergic effect 2 or 3 d after finishing the dosing regimen. However, they developed signs of delayed neurotoxicity 10-17 d later. Surviving ducks of all groups were sacrificed for biochemical and/or histopathologic tests 1 d after the last treatment or when they became paralyzed. Histopathologic examinations indicated that degenerative lesions of axons consistent with the type occurring in delayed neurotoxicity were seen in all TOCP-, leptophos-, or cyanofenphos-treated ducks and were specially evident in sections of spinal cord. Biochemically, it was found that duck brain neurotoxic esterase (NTE) activity was inhibited in vivo to less than 15% of control levels as measured 24 h after the last treatment with TOCP, leptophos, or cyanofenphos. These results indicate that adult peking ducks could be used to screen organophosphorus compounds for delayed toxic neuropathy.


Invasive Aspergillosis in a Patient with Stage III (or 3a or 3b) Non-Small-Cell Lung Cancer Treated with Durvalumab.
Durvalumab is a therapeutic monoclonal antibody that blocks the checkpoint inhibitor, programmed death ligand 1 (PD-L1), resulting in T-cell activation and an antitumor response. Durvalumab is approved for patients with unresectable stage III non-small-cell lung cancer (NSCLC) which has not progressed following platinum-based chemoradiotherapy. A 63-year-old man presented to the emergency department with a 15-day history of increasing shortness of breath. Several months previously, he had been diagnosed with a poorly differentiated stage IIIB NSCLC. He had completed six cycles of chemotherapy with paclitaxel and carboplatin and four cycles of immunotherapy with durvalumab 13 days before his emergency hospital admission. Computed tomography (CT) imaging showed a large left-sided loculated hydropneumothorax suggestive of empyema, patchy opacification of the left lung, and a left upper lobe lung mass. Histology of the cell block from the pleural fluid and decorticated lung tissue showed hyphae suggestive of invasive Aspergillus fumigatus. Treatment with voriconazole resulted in clinical improvement. To our knowledge, this is the first reported case of pleural aspergillosis in a patient treated with durvalumab. However, the increasing use of immune checkpoint inhibitors in oncology requires increased awareness by clinicians of immune-related adverse events (irAEs) due to opportunistic infection.


Controlled-release system mediated by a retro Diels-Alder reaction induced by the photothermal effect of gold nanorods.
Controlled-release systems that respond to external stimuli have received great interest for use in medical treatments such as for drug delivery to specific sites. Gold nanorods have an absorption band at the near-infrared region and convert the absorbed light energy into heat, which is known as a "photothermal effect". Therefore, gold nanorods are expected to act not only as an on-demand thermal converter for photothermal therapy but also as a controller of a drug-release system capable of responding to the near-infrared light irradiation. In this study, to construct a controlled-release system that responds to near-infrared light irradiation, we modified gold nanorods with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the modified gold nanorods were irradiated by near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. As a result of the PEG release, the gold nanorods formed aggregates. This type of controlled-release system coupled with the aggregate formation of the gold nanorods triggered by near-infrared light could be expanded to applications of gold nanorods in medical fields such as drug and photothermal therapy.


Solid-Phase Synthesis of Cellulose Acetate Butyrate as Microsphere Wall Materials for Sustained Release of Emamectin Benzoate.
Emamectin benzoate (EB), a widely used pesticide, is prone to decomposition by ultraviolet light and suffers from the corresponding loss of efficacy. The timed release of EB based on microspheres is one of the effective methods to solve this issue. As a non-toxic cellulose ester, cellulose acetate butyrate (CAB) is regarded as one of the best wall-forming materials for microcapsules with a good controlled release performance. Herein, two methods-mechanical activation (MA) technology and a conventional liquid phase (LP) method-were employed to synthesize different CABs, namely CAB-MA and CAB-LP, respectively. The molecular structure, rheological property, and thermal stability of these CABs were investigated. The two CABs were used to prepare microspheres for the loading and release of EB via an o/w (oil-in-water) solvent evaporation method. Moreover, the performances such as drug loading, drug entrapment, and anti-photolysis of the drug for these microspheres were studied. The results showed that both CABs were available as wall materials for loading and releasing EB. Compared with CAB-LP, CAB-MA presented a lower molecular weight and a narrower molecular weight distribution. Moreover, the MA method endowed the CAB with more ester substituent groups and less crystalline structure in comparison to the LP method, which had benefits including pelletizing and drug loading.


Gas hydrate nucleation and cage formation at a water/methane interface.
Nucleation of gas hydrates remains a poorly understood phenomenon, despite its importance as a critical step in understanding the performance and mode of action of low dosage hydrate inhibitors. We present here a detailed analysis of the structural and mechanistic processes by which gas hydrates nucleate in a molecular dynamics simulation of dissolved methane at a methane/water interface. It was found that hydrate initially nucleates into a phase consistent with none of the common bulk crystal structures, but containing structural units of all of them. The process of water cage formation has been found to correlate strongly with the collective arrangement of methane molecules.


Therapeutic Approaches in Mitochondrial Dysfunction, Inflammation, and Autophagy in Uremic Cachexia: Role of Aerobic Exercise.
Chronic kidney disease (CKD) causes several systemic changes, including muscular homeostasis, and eventually results in muscle atrophy. CKD-induced muscle atrophy is highly prevalent, and exercise is well known to enhance muscle function in these cases, although the exact mechanism remains unclear. Here, we aim to assess whether the protective effect of aerobic exercise in 5/6 nephrectomized (CKD) mice is associated with mitochondrial dysfunction, autophagy, or inflammation. C57BL/6J mice were randomly allocated into 3 different experimental groups: Sham, CKD, and CKD+aerobic exercise (CKD+AE). Renal function was assessed via serum creatinine and urea levels, and histological PAS and Masson staining were performed. Muscle wasting was determined based on grip strength, cross-sectional area (CSA), and MyHC protein expression. We also measured mitochondrial dysfunction in mice by assessing mtDNA, ROS, ATP production, and mitochondrial configuration. Autophagy was determined via assessments for Atg7, LC3, and SQSTM1 on western blotting. Inflammation was identified via proinflammatory cytokines and NLRP3 inflammasome components using real-time PCR and western blotting. We found that CKD mice exhibited higher BUN and creatinine levels and more severe glomerulosclerosis in the glomeruli and renal tubulointerstitial fibrosis, relative to the Sham group; all these effects were relieved by aerobic exercise. Moreover, grip strength, CSA, and MyHC protein expression were improved after 8 weeks of aerobic exercise. Furthermore, aerobic exercise significantly decreased MDA levels, increased SOD2 activity and ATP production, and improved mitochondrial configuration, relative to the CKD group. In addition, aerobic exercise downregulated the overexpression of proinflammatory cytokines and NLRP3 inflammasome components and balanced the mitochondrial biogenesis and autophagy-lysosomal system. Thus, we observed that aerobic exercise may ameliorate CKD-induced muscle wasting by improving mitochondrial dysfunction, inflammation, and autophagy-lysosomal system in uremic cachexia.


CDC-42 and RHO-1 coordinate acto-myosin contractility and PAR protein localization during polarity establishment in C. elegans embryos.
In C. elegans one-cell embryos, polarity is conventionally defined along the anteroposterior axis by the segregation of partitioning-defective (PAR) proteins into anterior (PAR-3, PAR-6) and posterior (PAR-1, PAR-2) cortical domains. The establishment of PAR asymmetry is coupled with acto-myosin cytoskeleton rearrangements. The small GTPases RHO-1 and CDC-42 are key players in cytoskeletal remodeling and cell polarity in a number of different systems. We investigated the roles of these two GTPases and the RhoGEF ECT-2 in polarity establishment in C. elegans embryos. We show that CDC-42 is required to remove PAR-2 from the cortex at the end of meiosis and to localize PAR-6 to the cortex. By contrast, RHO-1 activity is required to facilitate the segregation of CDC-42 and PAR-6 to the anterior. Loss of RHO-1 activity causes defects in the early organization of the myosin cytoskeleton but does not inhibit segregation of myosin to the anterior. We therefore propose that RHO-1 couples the polarization of the acto-myosin cytoskeleton with the proper segregation of CDC-42, which, in turn, localizes PAR-6 to the anterior cortex.


Anthropomorphic or non-anthropomorphic? Effects of biological sex in observation of actions in a digital human model and a gantry robot model.
Robots are ever more relevant for everyday life, such as healthcare or rehabilitation, as well as for modern industrial environment. One important issue in this context is the way we perceive robots and their actions. From our previous study, evidence exists that sex can affect the way people perceive certain robot's actions. In our fMRI study, we analyzed brain activations of female and male participants, while they observed anthropomorphic and robotic movements performed by a human or a robot model. While lying in the scanner, participants rated the perceived level of anthropomorphic and robotic likeness of movements in the two models. The observation of the human model and the anthropomorphic movements similarly activated the biological motion coding areas in posterior temporal and parietal areas. The observation of the robot model activated predominantly areas of the ventral stream, whereas the observation of robotic movements activated predominantly the primary and higher order motor areas. To note, this later activation originated mainly from female participants, whereas male participants activated, in both robot model and robotic movements contrasts, areas in the posterior parietal cortex. Accordingly, the general contrast of sex suggests that men tend to use the ventro-dorsal stream most plausibly to rely on available previous knowledge to analyze the movements, whereas female participants use the dorso-dorsal and the ventral streams to analyze online the differences between the movement types and between the different models. The study is a first step toward the understanding of sex differences in the processing of anthropomorphic and robotic movements.


Nicotine evoked efferent transmitter release onto immature cochlear inner hair cells.
Olivocochlear neurons make temporary cholinergic synapses on inner hair cells of the rodent cochlea in the first 2 to 3 wk after birth. Repetitive stimulation of these efferent neurons causes facilitation of evoked release and increased spontaneous release that continues for seconds to minutes. Presynaptic nicotinic acetylcholine receptors (nAChRs) are known to modulate neurotransmitter release from brain neurons. The present study explores the hypothesis that presynaptic nAChRs help to increase spontaneous release from efferent terminals on cochlear hair cells. Direct application of nicotine (which does not activate the hair cells' α9α10-containing nAChRs) produces sustained efferent transmitter release, implicating presynaptic nAChRs in this response. The effect of nicotine was reduced by application of ryanodine that reduces release of calcium from intraterminal stores.NEW & NOTEWORTHY Sensory organs exhibit spontaneous activity before the onset of response to external stimuli. Such activity in the cochlea is subject to modulation by cholinergic efferent neurons that directly inhibit sensory hair cells (inner hair cells). Those efferent neurons are themselves subject to various modulatory mechanisms. One such mechanism is positive feedback by released acetylcholine onto presynaptic nicotinic acetylcholine receptors causing further release of acetylcholine.


Enhanced Th1 and Th17 responses and arthritis severity in mice with a deficiency of myeloid cell-specific interleukin-1 receptor antagonist.
The balance between interleukin-1 (IL-1) and its specific inhibitor, the IL-1 receptor antagonist (IL-1Ra), plays a major role in the development of arthritis. The purpose of this study was to investigate the role of IL-1Ra produced specifically by myeloid cells in the control of collagen-induced arthritis (CIA) by using myeloid cell-specific IL-1Ra-deficient mice (IL-1Ra(DeltaM)). IL-1Ra(DeltaM) mice were generated by using the loxP/Cre recombinase system. CIA was induced in IL-1Ra(DeltaM) mice and littermate control mice by a single immunization with bovine type II collagen (CII) in Freund's complete adjuvant. Arthritis severity was assessed by clinical and histologic scoring. Draining lymph node (DLN) cell responses were examined ex vivo, and ankle extracts were used in the quantification of cytokines and chemokines. Clinical and histopathologic evaluations revealed an early disease onset and a severe form of CIA in IL-1Ra(DeltaM) mice. This was characterized by increased production of interferon-gamma (IFNgamma) and IL-17 by CII-stimulated DLN cells. We also observed that the CII-specific CD4+ T cell response shifted in vivo, from a dominant Th1 response early in the course of the arthritis to the presence of both Th1 and Th17 cytokines later in the disease course. Interestingly, IL-1Ra levels were higher in the arthritic joints of IL-1Ra(DeltaM) mice as compared with the controls, indicating that nonmyeloid cells strongly contribute to the local production of IL-1Ra. However, this enhanced IL-1Ra production was not sufficient to limit joint inflammation and tissue damage. Our results suggest that myeloid cell-derived IL-1Ra plays a critical role in the control of the development and the severity of CIA by modulating Th1 and Th17 responses in lymphoid organs.


Single crowns in the resorbed posterior maxilla supported by either 11-mm implants combined with sinus floor elevation or 6-mm implants:A 5-year randomised controlled trial.
To assess the clinical performance of single crowns in the posterior maxilla supported by either 11-mm-long implants combined with maxillary sinus floor elevation surgery or 6-mm-long implants during a 5-year follow-up period. A total of 38 consecutive patients, missing a premolar or a molar in the posterior maxilla and residual bone height underneath the maxillary sinus between 6 to 8 mm, were included. Subjects were randomly allocated to receive one 11-mm-long implant in combination with maxillary sinus floor augmentation or to receive one 6-mm-long implant without any grafting. A total of 41 implants (21 implants in 20 patients in the 6-mm group, and 20 implants in 18 patients in the 11-mm group) were placed and subsequently restored after 3 months with custom-made titanium abutments and cemented zirconia-based porcelain crowns. Both groups were followed by clinical (implant survival, restoration survival, complications, pocket probing depth and presence of plaque, calculus, bleeding and peri-implant inflammation) and radiographic examinations up to 5 years. The patient satisfaction was scored before treatment, and 12 and 60 months after functional implant restoration. One patient (11-mm group) died before the 12-month evaluation and one patient (6-mm group) moved away. In addition, one patient in the 6-mm group lost one implant and no implants were lost in the 11-mm group. Two patients lost three restorations in the 6-mm group and no restorations were lost in the 11-mm group. From loading until the 60-month assessment, the mean marginal bone loss in the 6-mm group and the 11-mm group was 0.12 ± 0.36 mm and 0.14 ± 0.63 mm, respectively, without a significant difference (mean difference 0.02 mm; 95% CI -0.32 to 0.37; P = 0.884). Implant loss, restoration loss, screw loosening and porcelain chipping were defined as complications. Four patients in the 6-mm group and one patient in the 11-mm group had one or more complications, without a significant difference between the groups (95% CI 0.019 to 0.244; P = 0.198). The patient satisfaction was high in both groups (mean overall satisfaction in the 6-mm and the 11-mm groups was 9.4 ± 0.8 and 9.2 ± 0.8, respectively; mean difference 0.2; 95% CI -0.33 to 0.76; P = 0.434). Reconstructions performed using an 11-mm implant combined with maxillary sinus floor augmentation or a 6-mm implant in the resorbed posterior maxilla are equally successful in supporting a single restoration over 5 years.


Multi-sectoral urban growth in space and time: an empirical approach.
"This paper compares the distribution of growth of several economic sectors in an attempt to trace and analyse their spatiotemporal sequence of decentralization. The paper applies a polynomial regression model capable of dealing with detailed spatiotemporal series. The application of the model to the urban field of Philadelphia [Pennsylvania] shows population to be the farthest spread followed by manufacturing industries. Despite, or probably because of, their extensive spread, both sectors display low levels of growth." In addition to population and manufacturing, the patterns of growth in retail and wholesale trade, services, and the provision of financial, insurance, and real estate services are examined for the period 1960-1980. (summary in FRE, GER)


Antibodies to selected viral disease agents in wild boars from the Czech Republic.
Blood samples were collected from wild boar (Sus scrofa) shot during the hunting season from 1999 to 2005 in the Czech Republic. Sera were tested by enzyme-linked immunosorbent assay for the presence of antibodies against classical swine fever virus (CSFV), swine vesicular disease virus (SVDV), Aujeszky's disease virus (ADV), and bovine viral diarrhea virus (BVDV). Indirect fluorescence antibody test was used for detection of antibodies against porcine circovirus type 2 (PCV-2) and transmissible gastroenteritis virus (TGEV). Antibodies against ADV, BVDV, PCV-2, and TGEV were detected in 30% (101 of 338), 1% (2 of 352), 43% (57 of 134), and 1% (1 of 134) of wild boars, respectively. Sera of 6,471 and 362 tested wild boars were negative for the presence of antibodies against CSFV and SVDV, respectively. This is the first survey of TGEV antibodies in wild boars and the first serologic survey of viral diseases in wild boars in the Czech Republic. Wild boars in the Czech Republic may act as a potential reservoir of ADV and thus have a role in the epidemiology of this disease.


Heart rate variability monitoring for emotion and disorders of emotion.
Emotion is composed of cognitive processing, physiological response and behavioral reaction. Heart rate variability (HRV) refers to the fluctuations between consecutive heartbeat cycles, and is considered as a non-invasive method for evaluating cardiac autonomic function. HRV analysis plays an important role in emotional study and detection. In this paper, the physiological foundation of HRV is briefly described, and then the relevant literature relating to HRV-based emotion studies for the performance of HRV in different emotions, emotion recognition, the evaluation of emotional disorders, HRV biofeedback, as well as HRV-based emotion analysis and management enhanced by wearable devices, are reviewed. It is suggested that HRV is an effective tool for the measurement and regulation of emotional response, with a broad application prospect.


Acute hypoxia prolongs the apnea induced by right atrial injection of capsaicin.
Inspiratory central drive is augmented by acute hypoxia that leads to a hyperventilation, but it is inhibited by capsaicin (Cap)-induced stimulation of pulmonary C fibers (PCFs) that produces an expiratory apnea. We hypothesized that acute hypoxia should shorten or eliminate the Cap-induced apnea. The ventilatory responses to bolus injection of Cap (0.2-0.5 microg) into the right atrium before and during acute hypoxia (10% O(2) for approximately 1 min; Hypoxia+Cap) were compared in anesthetized and spontaneously breathing rats. We found that Cap injection during acute hypoxia produced an extremely long-lasting apnea (69.67 +/- 11.97 s) that was 16-fold longer than the apnea induced by Cap alone (expiratory duration = 4.37 +/- 0.53 s; P < 0.01). A similar prolonged apnea was also observed during hypoxia in anesthetized guinea pigs. Bilateral vagotomy abolished apneic responses to Cap both before and during hypoxia. Subsequent recording of single-fiber activity of PCFs (PCF(A)) showed that acute hypoxia did not significantly affect baseline PCF(A) but that it doubled PCF(A) responses to Cap via increasing both the firing rate (3.34 +/- 0.76 to 7.65 +/- 1.32 impulses/s; P < 0.05) and burst duration (1.12 +/- 0.18 to 2.32 +/- 0.31 s; P < 0.05). These results suggest that acute hypoxia augments PCF-mediated inspiratory inhibition and thereby leads to an extremely long-lasting apnea. This interaction is partially due to hypoxic sensitization of PCF response to Cap.


New Insights Into Cranial Synchondrosis Development: A Mini Review.
The synchondroses formed via endochondral ossification in the cranial base are an important growth center for the neurocranium. Abnormalities in the synchondroses affect cranial base elongation and the development of adjacent regions, including the craniofacial bones. In the central region of the cranial base, there are two synchondroses present-the intersphenoid synchondrosis and the spheno-occipital synchondrosis. These synchondroses consist of mirror image bipolar growth plates. The cross-talk of several signaling pathways, including the parathyroid hormone-like hormone (PTHLH)/parathyroid hormone-related protein (PTHrP), Indian hedgehog (Ihh), Wnt/β-catenin, and fibroblast growth factor (FGF) pathways, as well as regulation by cilium assembly and the transcription factors encoded by the RUNX2, SIX1, SIX2, SIX4, and TBX1 genes, play critical roles in synchondrosis development. Deletions or activation of these gene products in mice causes the abnormal ossification of cranial synchondrosis and skeletal elements. Gene disruption leads to both similar and markedly different abnormalities in the development of intersphenoid synchondrosis and spheno-occipital synchondrosis, as well as in the phenotypes of synchondroses and skeletal bones. This paper reviews the development of cranial synchondroses, along with its regulation by the signaling pathways and transcription factors, highlighting the differences between intersphenoid synchondrosis and spheno-occipital synchondrosis.


Functional Investigation of Meningeal Lymphatic System in Experimental Intracerebral Hemorrhage.
Promotion of hematoma resolution in a timely manner reduces intracerebral hemorrhage (ICH) brain injury induced by toxic blood components and subsequent neuroinflammation. The meningeal lymphatic system is responsible for clearance of macromolecules and pathogenic substances from the central nervous system; however, its role in intraparenchymal hematoma clearance and ICH outcomes is unknown. In the present study, we aimed to understand the contribution of the meningeal lymphatic system to ICH pathologies and to test whether pharmacological enhancement of meningeal lymphatic function promotes hematoma resolution and brain recovery after ICH. Immunofluorescence of whole-mount meninges was used to measure complexity and coverage level of meningeal lymphatic vasculature following ICH induction. Fluorescent microbeads and PKH-26-labeled erythrocytes were used to evaluate drainage function of the meningeal lymphatic system. Visudyne treatment, deep cervical lymph node ligation, and VEGF (vascular endothelial growth factor)-C injection were performed to manipulate meningeal lymphatic function. Neurobehavioral performance and hematoma volume were assayed by the cylinder test and histological measurements. Iron deposition, residual erythrocytes, neuronal loss, and astrogliosis were assessed by immunohistochemistry and antibody-based fluorescence staining. Meningeal lymphangiogenesis and enhanced lymphatic drainage occurred during the late phase of ICH. Ablation and blockage of meningeal lymphatic vessels impeded hematoma clearance, whereas pharmacological enhancement of their function reduced hematoma volume, improved behavioral performance, and reduced brain residual erythrocytes, iron deposition, neuronal loss, and astroglial activation. Early enhancement of meningeal lymphatic function is beneficial for ICH recovery. Targeting the meningeal lymphatic system is therefore a potential therapeutic approach for treating ICH.


Sequential adaptation in latent tuberculosis bacilli: observation by atomic force microscopy (AFM).
Mycobacterium tuberculosis (MTB) can persist within the human host for years without causing disease, in a syndrome known as latent tuberculosis. The mechanisms by which M. tuberculosis establishes a latent metabolic state is unknown, but it is hypothesized that reduced oxygen tension may trigger the bacillus to enter a state of latency. Therefore, we are studying anaerobic culture of M. tuberculosis (H37RV) as a model of latency. For the first time, the sequential adaptation of latent bacilli (every 90 days for 48 months) viewed under Atomic Force Microscopy (AFM). Two types of adaptation were observed and are described here. First, cells are undergoing temporary adaptation (from 1 to 18 months of latency) that includes; thickening of cell wall (20.5±1.8 nm versus 15.2±1.8 nm, P<0.05), formation of ovoid cells by "folding phenomena"(65-70%), size reduction (0.8±0.1 μm versus 2.5±0.5 μm), and budding type of cell division (20-25%).A second feature include changes that accompany development of specialized cells i.e., production of spore like cells (0.5±0.2 μm) and their progeny (filterable non -acid fast forms; 150 to 300 μm in size). Although, these cells were not real spore because they fail to form a heat resistant colony forming units, after incubation for 35-40 min at 65°C. The filterable non-acid fast forms of bacilli are metabolically active and increased their number by symmetrical type of cell-division. Therefore, survival strategies that developed by M. tuberculosis under oxygen limited condition are linked to its shape, size and conspicuous loss of acid fastness.


Mechanisms of hydroperoxide-induced broncho- and vasoconstriction in isolated and perfused rat lung.
The mechanisms of hydroperoxide-induced broncho- and vasoconstriction were investigated in the perfused and ventilated rat lung. Hydrogen peroxide (500 microM), tertiary butylhydroperoxide (500 microM) and arachidonic acid (100 microM) induced similar profiles of broncho- and vasoconstriction which could be prevented by the inhibitor of cyclooxygenase, diclofenac (100 microM) but not by nordihydroguaiaretic acid (5 and 25 microM), an inhibitor of lipoxygenase. The hydroperoxides also caused a time-dependent increase in the levels of thromboxane and prostacycline, products of cyclooxygenase. Furthermore, the thromboxane agonist, U44069 (100 pmoles), caused a very rapid broncho- and vasoconstriction that was preventable by the thromboxane antagonist L655.240 (1 microM). L655.240 also inhibited hydrogen peroxide-induced broncho- and vasoconstriction. The phospholipase A2 inhibitors, quinacrine (100 microM) and dibucaine (100 microM), did not prevent hydroperoxide-induced broncho- and vasoconstriction. The Ca2+ chelator, EGTA, prevented hydroperoxide and arachidonic acid-induced lung constriction, although it did not inhibit the release of thromboxane. The infusion of arachidonic acid and hydroperoxides resulted in edema in the lung which was prevented by prior administration of diclofenac, indomethacin or L655.240. These results indicate that hydroperoxide-induced broncho- and vasoconstriction and lung edema are mediated by thromboxane, a product of cyclooxygenase. The mechanism of hydroperoxide-induced release of arachidonic acid is not clear but does not seem to involve Ca2+ nor the activation of phospholipase A2.


Allergens of wild house dust mites: environmental Der p 1 and Der p 2 sequence polymorphisms.
Sequence diversity is a common feature of mite allergens. Previous studies, using predominantly commercial mite clones, have described several polymorphic residues for Der p 1 and Der p 2. This study aimed at determining the occurrence of sequence diversity in environmental mite isolates. Mites were isolated from houses in Perth and Sydney, Australia. Total RNA was extracted from 1 to 30 Perth mites, and cDNA was synthesized by reverse transcriptase PCR. Der p 1 and Der p 2 cDNAs were PCR amplified and sequenced. Genomic Der p 1 DNA was amplified from whole Sydney mites directly by PCR and then sequenced. Twelve Der p 1 and 9 Der p 2 cDNA clones and 3 Der p 1 genomic DNA were analyzed and showed a high frequency of amino acid polymorphisms. Der p 2 displayed a clear pattern of divergence toward 2 alleles that differed by 4 amino acids and had characteristic silent nucleotide changes. The pattern for Der p 1 was different and unusual, with almost no silent nucleotide substitutions but frequent sporadic missense changes. Proliferative responses of peripheral blood mononuclear cells to peptides containing polymorphic residues of Der p 1 were detected in 8 of 19 subjects, with stimulation being found only for either one of the variant forms of the peptides. However, the responses to variants of whole recombinant allergens were similar, as shown for 4 variants of Der p 2. Two clones for each of the allergens were identified as containing sequences that were largely representative of environmental isolates. A small-scale reverse transcriptase PCR used to produce cDNA from individual mites isolated from house dust will have wide application for studies on mite genetics and the production of recombinant mite allergens. Differences in T-cell responses to peptides representing variant epitopes were found, but responses to variants of whole recombinant allergens were similar. The GenBank and Swiss Prot database entries for Der p 1 (U11695) and Der p 2 (P49278) have been updated with the inclusion of the sequence polymorphisms described in this study.


Inhibition of nitrogen fixation in symbiotic Medicago truncatula upon Cd exposure is a local process involving leghaemoglobin.
Leguminous biological nitrogen fixation (BNF) is very sensitive to environmental fluctuations. It is still contentious how BNF is regulated under stress conditions. The local or systemic control of BNF and the role played by reactive oxygen species (ROS) in such regulation have still not been elucidated completely. Cadmium, which belongs to the so-called heavy metals, is one of the most toxic substances released into the environment. The mechanisms involved in Cd toxicity are still not completely understood but the overproduction of ROS is one of its characteristic symptoms. In this work, we used a split-root system approach to study nodule BNF and the antioxidant machinery's response to the application of a mild Cd treatment on one side of a nodulated Medicago truncatula root system. Cd induced the majority of nodule antioxidants without generating any oxidative damage. Cd treatment also provoked BNF inhibition exclusively in nodules directly exposed to Cd, without provoking any effect on plant shoot biomass or chlorophyll content. The overall data suggest that the decline in BNF was not due to a generalized breakdown of the plant but to control exerted through leghaemoglobin/oxygen availability, affecting nitrogenase function.


[The role of inflammatory reaction in Alzheimer's disease and neurodegenerative processes].
Recent studies state that specific inflammatory mechanisms contribute to neurodegeneration. The theory is based on laboratory evidence of local upregulation of inflammatory cytokines (ex. IL-1, IL-6), acute phase proteins (ex. alpha 1-antitrypsin), activation of the complement cascade and accumulation of microglia in damaged regions in AD. In addition epidemiologic studies suggest that anti-inflammatory treatment provides some protection from AD. The first trials with prednisone fail to show any positive influence in AD patients. The alternative therapies are now considered with nonsteroid anti-inflammatory drugs, colchicine, cyclophosphamide. The anti-inflammatory treatment gives hope for slowing progression of the disease and decline of AD incidence.


[Screening of H+ -ATPase deficient mutant of Lactobacillus delbrueckii subsp. bulgaricus].
We identified a neomycin-resistant mutant with reduced membrane-bound H+ -ATPase activity from L. delbrueckii subsp. bulgaricus originated from the traditional dairy product to develop a yoghurt starter culture with low post-acidification capacity. API 50 CH identification system and 16s rDNA sequence analysis were applied to identify the strain isolated from the indigenous yoghurt. Neomycin was used to screen spontaneous neomycin-resistant mutants. H+ -ATPase activity and metabolic dynamics were evaluated between the parent strain and mutants. One strain was identified as L. delbrueckii subsp. bulgaricus by API 50 CH identification system and 16s rDNA sequence analysis, coded as KLDS 1.9201. Two mutant strains were mutated from KLDS 1.9201 and coded as KLDS 1.9201-1, KLDS 1.9201-4. Compared with the parent strain,the H+ -ATPase activity of the mutants KLDS 1.9201-1 and KLDS 1.9201-4 decreased by 46% and 60% respectively. After cultured in MRS broth for 24 h, metabolic efficiency of the initial glucose for the parent strain was 65%, the mutants were 41% and 31%, the lactic acid concentration in the culture for the parent strain was 26 g/L, the mutants were 18 g/L and 15 g/L respectively. The cell density of the mutants was lower than that of the parent strain. The mutants of L. delbrueckii subsp. bulgaricus with reduced membrane-bound H+ -ATPase activity had low growth and acid production, which could be applied to develop yoghurt starter culture with lower post-acidification.


Palladium-catalyzed amination of allyl alcohols.
An efficient catalytic amination of aryl-substituted allylic alcohols has been developed. The complex [(η(3)-allyl)PdCl](2) modified by a bis phosphine ligand, L, has been used as catalyst in the reaction that afforded a wide range of allyl amines in good to excellent yield under mild conditions.


[Profile of patients submitted to amputation related to diabetes mellitus].
Retrospective study that aimed at describing the clinic and socio- demographical characteristics of 141 individuals which were interned in Teaching Hospital of Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil, who were submitted to amputations related to diabetes and compare the number of amputations considering the variables sex, age, co-morbidity, the type of treatment and then associated the number of amputations with the duration of internments and diagnosis. Data were collected from patient health records, totalizing 208 amputations. Major percentage of masculine individuals (58,9%), and a major occurrence of amputation among the elderly (70.2%); the cause: diabetic foot (35.7%); the most of patients (75.0%) went through internment at least twice; most frequent co-morbidity: arterial hypertension (74.0%); median in the number of amputations was two. It was not observed any significant difference between the variables of study.


Direct mapping of nanoscale compositional connectivity on intact cell membranes.
Lateral segregation of cell membranes is accepted as a primary mechanism for cells to regulate a diversity of cellular functions. In this context, lipid rafts have been conceptualized as organizing principle of biological membranes where underlying cholesterol-mediated selective connectivity must exist even at the resting state. However, such a level of nanoscale compositional connectivity has been challenging to prove. Here we used single-molecule near-field scanning optical microscopy to visualize the nanolandscape of raft ganglioside GM1 after tightening by its ligand cholera toxin (CTxB) on intact cell membranes. We show that CTxB tightening of GM1 is sufficient to initiate a minimal raft coalescence unit, resulting in the formation of cholesterol-dependent GM1 nanodomains < 120 nm in size. This particular arrangement appeared independent of cell type and GM1 expression level on the membrane. Simultaneous dual color high-resolution images revealed that GPI anchored and certain transmembrane proteins were recruited to regions proximal (< 150 nm) to CTxB-GM1 nanodomains without physical intermixing. Together with in silico experiments, our high-resolution data conclusively demonstrate the existence of raft-based interconnectivity at the nanoscale. Such a linked state on resting cell membranes constitutes thus an obligatory step toward the hierarchical evolution of large-scale raft coalescence upon cell activation.


Clinical Impacts of Juxtapapillary Duodenal Diverticulum Detected on Computed Tomography.
Diverticula are commonly observed in the duodenum. Duodenal Diverticulum (DD) usually does not give symptoms throughout life and is diagnosed by coincidence. However, it may present with different symptoms in patients. This study aims to evaluate the prevalence of DD and Juxtapapillary Duodenal Diverticulum (JDD) and its association with other possible pathologies and to determine its clinical impact by using Computed Tomography (CT). This retrospective observational study, which was taken consecutively between the years of 2013-2020, was evaluated in the Radiology Department. The total number of cases was 4850 (male-2440; female-2410). CT images were evaluated by two experienced radiologists at the workstation. DD and JDD prevalence and clinical findings in the hospital registry system were examined. The age of the patients included in the study ranged from 17 to 92 years (mean age 46.94±16.42). In patients with DD (female-130; male-101), mean age was 62.24 ± 12.69 (21-92). The prevalence of DD was 4.76% (n=231). The prevalence of JDD was 4.02% (n=195) and increased with age (p<0.01). The average diameter of the JDD was measured as 23.29±8.22 (9.5-55.3) mm. A significant positive correlation was found between age and DD diameter (p=0.039). DDs were found most commonly 84.42% (n=195) in the second segment of the duodenum as JDD. In patients with JDD, the mean diameter of choledochus and wirsung canal were 6.7 ± 2.4 (3-15.3) mm and 0.31 ± 0.1 (0.1-6.5) mm respectively. The choledochal diameter was correlated with the JDD size (p = 0.004). Cholelithiasis (n=56), choledocholithiasis (n=20), cholecystitis (n=52), diverticulitis (n=15), duodenitis (n=37), pancreatitis (n=5) and hiatal hernia (n=60) with JDD were observed. Periampullary carcinoma was detected in one patient. Our study shows that cholelithiasis, choledocholithiasis, cholecystitis, diverticulitis, duodenitis, pancreatitis may be associated with JDD. Therefore, in contrast-enhanced abdominal CT scans taken for various reasons, investigation of the presence and characteristics of JDD and detection of pathologies that may be associated with JDD are important for patients to benefit from early diagnosis and treatment opportunities and to take precautions against possible complications.


Displacing lateral meniscus masquerading as patella dislocation.
To alert the treating clinician to an uncommon knee meniscal condition that often masquerades as a more common patella condition. Retrospective chart review of a series of cases was undertaken. A series of 12 knees in 11 patients were referred to an orthopaedic surgeon with a diagnosis of recurrent lateral patella dislocation. Three knees had undergone patella realignment surgery with continuance of symptoms. Eight patients had prior magnetic resonance images read as no meniscal pathology and no acute patella/patella retinacular injury. All patients presented for a consult with a similar history. Under anaesthesia, all knees had a stable patella as judged by physical examination. At the time of surgery, six patients had a frank tear in the lateral meniscus, all of which were readily displaceable. Six knees showed a displaceable lateral meniscus with attenuation but not a visible frank tear. Ten menisci were treated with repair, and two knees underwent partial lateral meniscectomies. Patient follow-up of minimally 18 months revealed no further episodes of "knee-cap dislocation" or symptoms of catching and locking. The clinician treating a patient with a history of a knee locking in flexion should have a high index of suspicion for a lateral meniscus tear or an unstable hypermobile lateral meniscus, despite patient report of perceived patella movement. History of symptoms occurring in knee flexion and attention to patella physical examination should be key factors in this diagnostic conundrum. Retrospective chart review, Level IV.


Development of a Prototype Robotic System for Radiosurgery with Upper Hemispherical Workspace.
This paper introduces a specialized robotic system under development for radiosurgery using a small-sized linear accelerator. The robotic system is a 5-DOF manipulator that can be installed above a patient to make an upper hemispherical workspace centered in a target point. In order to determine the optimal lengths of the link, we consider the requirements for the workspace of a linear accelerator for radiosurgery. A more suitable kinematic structure than conventional industrial manipulators is proposed, and the kinematic analysis is also provided. A graphic simulator is implemented and used for dynamic analysis. Based on those results, a prototype manipulator and its control system are under development.


Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer.
To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks). Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05). This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.


Humoral response among patients with interstitial lung disease vaccinated with the BNT162b2 SARS-Cov-2 vaccine: a prospective cohort study.
Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy. We conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4-6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021. All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207-811] AU/ml vs. 820.75 [IQR, 459-1313] AU/ml; P < 0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P < 0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [IQR, 4.25-165] AU/ml vs. 970.1 [IQR, 505-1926] AU/ml; P < 0.001). IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4-6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.


Modification of the Red Beet Plasma Membrane H-ATPase by Diethylpyrocarbonate.
Incubation of the red beet (Beta vulgaris L.) plasma membrane H(+)-ATPase with micromolar concentrations of diethylpyrocarbonate (DEPC) resulted in inhibition of both ATP hydrolytic and proton pumping activity. Enzyme activity was restored when DEPC-modified protein was incubated with hydroxylamine, suggesting specific modification of histidine residues. Kinetic analyses of DEPC inhibition performed on both membrane-bound and solubilized enzyme preparations suggested the presence of at least one essential histidine moiety per active site. Inclusion of either ATP (substrate) or ADP (product and competitive inhibitor) in the modification medium reduced the amount of inhibition observed in the presence of DEPC. However, protection was not entirely effective in returning activity to noninhibited control values. These results suggest that the modified histidine does not reside directly in the ATP binding region of the enzyme, but is more likely involved in enzyme regulation through subtle conformational effects.


The cause and management of burning mouth condition.
This paper reviews the clinical presentation and many causes of burning mouth condition. A diagnostic approach and some management procedures that include eliminating all oral irritants, correcting predisposing systemic disease, and most important of all, allaying anxiety that induces parafunctional mouth habits. The term "burning mouth condition" (BMC) is considered more appropriate than the word "syndrome" for this common and troublesome complaint.


Diketopyrrolopyrrole-Based Photosensitizers Conjugated with Chemotherapeutic Agents for Multimodal Tumor Therapy.
For synergistic cancer therapy, it is highly desirable to devise a single multifunctional agent to combine photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy, which is soluble and excitable at low irradiation, as well as able to selectively target tumors and achieve high efficacy. Toward this ambition, here the chemotherapy drugs chlorambucil (Cb), and all trans retinoic acid (ATRA) are covalently conjugated onto a small dye molecule diketopyrrolopyrrole (DPP-Cb and DPP-ATRA). The soluble nanoparticles (NPs) of DPP-Cb and DPP-ATRA formed by reprecipitation can selectively accumulate in tumors, release chemotherapy drugs under acidic conditions, and exhibit efficient reactive oxygen species (ROS) generation and photothermal conversion under the irradiation of a low power xenon lamp (40 mW/cm2). We show in vitro and in vivo that both NPs can effectively kill cancer cells and suppress cancer growth at a low dose (0.4 mg/kg).


Default Priors for the Intercept Parameter in Logistic Regressions.
In logistic regression, separation occurs when a linear combination of predictors perfectly discriminates the binary outcome. Because finite-valued maximum likelihood parameter estimates do not exist under separation, Bayesian regressions with informative shrinkage of the regression coefficients offer a suitable alternative. Classical studies of separation imply that efficiency in estimating regression coefficients may also depend upon the choice of intercept prior, yet relatively little focus has been given on whether and how to shrink the intercept parameter. Alternative prior distributions for the intercept are proposed that downweight implausibly extreme regions of the parameter space, rendering regression estimates that are less sensitive to separation. Through simulation and the analysis of exemplar datasets, differences across priors stratified by established statistics measuring the degree of separation are quantified. Relative to diffuse priors, these proposed priors generally yield more efficient estimation of the regression coefficients themselves when the data are nearly separated. They are equally efficient in non-separated datasets, making them suitable for default use. Modest differences were observed with respect to out-of-sample discrimination. These numerical studies also highlight the interplay between priors for the intercept and the regression coefficients: findings are more sensitive to the choice of intercept prior when using a weakly informative prior on the regression coefficients than an informative shrinkage prior.


Herbicidal effects of extracts and residue incorporation of Datura metel against parthenium weed.
The present study was designed to evaluate the herbicidal activity of Datura metel against the noxious weed parthenium (Parthenium hysterophorus L.). In a laboratory bioassay, the effect of aqueous, methanol and n-hexane shoot and root extracts of 5, 10, 15 and 20% w/v (on a fresh weight basis) concentration of D. metel were tested against the germination and seedling growth of parthenium. Both aqueous and methanol extracts markedly suppressed the germination and seedling growth of parthenium. Generally, the effect of shoot extracts was more pronounced than the effect of root extracts. In foliar spray bioassay, aqueous and methanol shoot extracts of 10% w/v (on dry weight bases) concentrations were sprayed on one-week and two-week-old pot-grown parthenium seedlings. Two subsequent sprays were carried out at five day intervals each. Both the aqueous as well as the methanol extracts significantly suppressed shoot length as well as shoot and root biomass of one-week and two-week-old parthenium plants. In residue incorporation bioassay, crushed shoots of D. metel were incorporated in the soil at 1, 2, ... 5% w/w. Parthenium seeds were sown one week after residue incorporation and plants were harvested 40 days after sowing. Incorporation of 2-5% residues significantly reduced germination by 47-89%. Residues of 4 and 5% concentration significantly suppressed plant biomass by 90 and 97%, respectively. The present study concludes that root and shoots of D. metel contain herbicidal constituents for the management of parthenium weed.


Solubilization of a complex of tryptic fragments of Na,K-ATPase containing occluded Rb ions and bound ouabain.
The nonionic detergent C12E10 (polyoxyethylene 10-laurylether) has been used to solubilize a complex of tryptic fragments of Na, K-ATPase containing occluded Rb ions and bound ouabain. The aim was to define which fragments are required to maintain Rb occlusion. The experiments utilize "19 kDa membranes" consisting of a 19 kDa and several smaller tryptic fragments (8-11.7 kDa) of the alpha subunit, which include trans-membrane segments M7/M10 and the pairs M1/M2, M3/M4, and M5/M6 [Capasso, J. M., et al (1992) J. Biol. Chem. 267, 1150-1158]. The beta subunit is partially split into a 16 kDa fragment and a glycosylated approximately 50 kDa fragment. Cation occlusion and ouabain binding are intact. After preincubation of "19 kDa membranes" with Rb (5 mM) and then ouabain (10 mM), 90-100% of occluded Rb was solubilized by C12E10 at 0 degrees C. All fragments of the alpha and beta subunits, and also the gamma subunit, were cosolubilized by C12E10, and were observed to sediment together on a sucrose density gradient as a complex containing occluded Rb ions. The soluble complex consists of a monomer containing one copy of each fragment, as indicated by size-exclusion HPLC, as well as estimates of specific Rb occlusion (20.0 +/- 1.2 nmol/mg of protein). In the absence of Rb ions and ouabain, the complex was unstable. Whereas the 19 kDa fragment (M7-M10) and beta subunit remained associated, the smaller fragments, containing M5/M6 and M3/M4 and M1/M2, and the subunit dissociated. Observations on the thermal inactivation of Rb occlusion, and effect of pH and ionic strength, suggest that the soluble complex is stabilized by multiple interactions, both within the lipid bilayer and in hydrophilic domains (e.g., salt bridges).


[The effect of diazepam on the electroretinogram].
The effect of some drugs on electric potentials of the retina has been described in the literature. Data on the effect of drugs of the group of benzodiazepines on electric potentials of the retina in man have not come to our attention. In the present study diazepam was found to affect substantially the studied parameters of the electroretinogram. An inhibitory effect of diazepam on the electric response of the retina was established. The period of latency and that of culmination of the electroretinogram were found to be most intensively affect.


A rapid cleanup method for the isolation and concentration of pyrrolizidine alkaloids in comfrey root.
Preparations from comfrey (Symphytum officinale and S. x uplandicum) root and leaf contain varying levels of the hepatotoxic pyrrolizidine alkaloids (PAs). Reference compounds for comfrey are not commercially available, and there is currently no rapid extraction or analytical method capable of determining low levels in raw materials or as adulterants in commercially available extracts. A solid-phase extraction (SPE) method was developed using an Ergosil cleanup column that specifically binds the PAs. With this method, powdered comfrey root was extracted by sonication and shaking with basic chloroform. The extract was applied to the cleanup column under vacuum, washed with 2 mL acetone-chloroform (8 + 2, v/v) followed by 2 mL petroleum ether to remove excess chloroform. The column was dried under vacuum, and the PAs were eluted with 2 successive 1 mL aliquots methanol. Percent recoveries of the PAs following Ergosil SPE had an overall average of 96.8%, with RSD of 3.8% over a range of 1.0 to 25.0 g extracted in 100 mL. Average precision of the method (n = 3 over 4 extraction concentrations) gave an overall RSD of 6.0% for the 5 alkaloids, with a range of 0.8% (5 g in 100 mL) to 11.2% (25 g in 100 mL). Recovery optimization testing showed that 1.0 g comfrey root extracted in 100 mL yielded the greatest recovery (% dry weight) of the PAs, with an extraction efficiency and accuracy of 94.2%, and RSD of 1.7% (n = 9). The unique properties of the Ergosil cleanup column provide rapid sample cleanup, volume reduction, and concentration of PAs from comfrey extracts, and allow the eluant to be analyzed directly by traditional chromatographic methods.


Photodetectors Based on Micro-nano Structure Material.
Photodetectors converting optical signals into electrical signals have been widely utilized and have received more and more attention in scientific research and industrial fields including optical interconnection, optical communication, and environmental monitoring. Herein, we summarize the latest development of photodetectors with different micro-nano structures and different materials and the performance indicators of photodetectors. Several photodetectors, such as flexible, ultraviolet two-dimensional (2D) microscale, and dual-band photodetectors, are listed in this minireview. Meanwhile, the current bottleneck and future development prospects of the photodetector are discussed.


Cannabis-induced acute pancreatitis.
Acute pancreatitis is a common disease. Despite the frequent use of cannabis worldwide, only six reports have described cases of acute pancreatitis secondary to the use of tetrahydrocannabinoid (THC). Here we describe two cases of THC-induced pancreatitis. The first case occurred in a 38-year-old man with multiple admissions for THC-induced pancreatitis; the second case involved a 22-year-old man with no previous medical history. In both cases, other possible causes of acute pancreatitis were ruled out.


Comparison of a gel column blood typing method and a point-of-care cartridge for dog erythrocyte antigen 1.1.
Blood typing for the presence of Dog Erythrocyte Antigen (DEA) 1.1 is recommended in all donor and recipient dogs prior to transfusion of blood products. The objective of this study was to determine if a point-of-care DEA 1.1 blood typing cartridge could be used in place of the gel column typing method. Detection of DEA 1.1 was performed using a laboratory-based gel column method and a point-of-care cartridge. A convenience sample of 30 healthy blood donors, 13 dogs with immune-mediated hemolytic anemia (IMHA) (3 of which had concurrent immune-mediated thrombocytopenia [IMT]), and 44 dogs with other diseases was included in the study. Agreement was observed between the tests for normal dogs and dogs with nonimmune-mediated disease in 74/74 cases. Two dogs in the IMHA group had indeterminate gel column blood typing results; 1 dog in this group had a negative gel column test result but a positive cartridge test result. There was good agreement between the 2 methods for normal dogs and dogs with nonimmune-mediated disease. Blood typing methods in dogs with IMHA should be further investigated.


Real-Time Closed-Loop Detection Method of vSLAM Based on a Dynamic Siamese Network.
As visual simultaneous localization and mapping (vSLAM) is easy disturbed by the changes of camera viewpoint and scene appearance when building a globally consistent map, the robustness and real-time performance of key frame image selections cannot meet the requirements. To solve this problem, a real-time closed-loop detection method based on a dynamic Siamese networks is proposed in this paper. First, a dynamic Siamese network-based fast conversion learning model is constructed to handle the impact of external changes on key frame judgments, and an elementwise convergence strategy is adopted to ensure the accurate positioning of key frames in the closed-loop judgment process. Second, a joint training strategy is designed to ensure the model parameters can be learned offline in parallel from tagged video sequences, which can effectively improve the speed of closed-loop detection. Finally, the proposed method is applied experimentally to three typical closed-loop detection scenario datasets and the experimental results demonstrate the effectiveness and robustness of the proposed method under the interference of complex scenes.


Stepwise addition of CuNCS onto [Et(4)N][Tp*WS(3)]: design, syntheses, structures and third-order nonlinear optical properties.
Stepwise reactions of [Et(4)N][Tp*WS(3)] () (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) with 1-4 equiv. of CuNCS (and Et(4)NBr in the case of three equiv. of CuNCS) afforded the [1 + 1] to [1 + 4] addition products [Et(4)N][Tp*WS(mu-S)(2)(CuNCS)].0.5CH(2)Cl(2) (.0.5CH(2)Cl(2)), [Et(4)N][Tp*W(mu(3)-S)(mu-S)(2)(CuNCS)(2)].ClCH(2)CH(2)Cl (.ClCH(2)CH(2)Cl), [Et(4)N](2)[Tp*W(mu(3)-S)(3)(CuNCS)(3)(mu(3)-Br)].1.5aniline (.1.5aniline), and {[Et(4)N][Tp*W(mu(3)-S)(3)(Cu-mu-SCN)(3)(Cu-mu(3)-NCS)]}(n) (). Compounds were characterized by elemental analysis, IR spectra, UV-vis spectra, (1)H NMR, and single-crystal X-ray crystallography. The cluster anion of contains a [WS(2)Cu] core formed by addition of one CuNCS group onto the [Tp*WS(3)] species. The cluster anion of has a butterfly-shaped [WS(3)Cu(2)] core constructed by addition of two CuNCS groups onto the [Tp*WS(3)] species. The cluster dianion of consists of a cubane-like [Tp*WS(3)Cu(3)(mu(3)-Br)] core assembled by addition of three CuNCS groups onto the [Tp*WS(3)] species followed by filling a mu(3)-Br into the void of the incomplete cubane-like [Tp*WS(3)(CuNCS)(3)] fragment. has a 2D cluster-supported layer network in which each [Tp*WS(3)Cu(3)] core acting as a pyramidal 3-connecting node interconnects with the [Cu(NCS)(4)] units through thiocyanate bridges. In addition, the third-order nonlinear optical (NLO) performances of in DMF were also investigated by Z-scan techniques.


Serotonin transporter messenger RNA expression in neural crest-derived structures and sensory pathways of the developing rat embryo.
A growing body of evidence suggests that serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive serotonin transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate serotonin transporter messenger RNA expression during rat embryonic development. Serotonin transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, serotonin transporter messenger RNA was detected in neural crest cells, some of which respond to serotonin in vitro, and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were serotonin transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained serotonin transporter messenger RNA by late gestation. The expression of serotonin transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience 83, 1185-1201; Lebrand C. et al. (1996) Neuron 17, 823-835] to sensory nerves and target organs as shown in this study suggests that serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of serotonin transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a serotonin concentration gradient across epithelia, either from serotonin in the amniotic fluid or from neuronal enteric serotonin, as a developmental cue. Our results demonstrating serotonin transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the transporter most likely responsible for the previously identified accumulation of serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. 8, 265-276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development 102, 709-720; Shuey D. L. et al. (1992) Teratology 46, 367-378; Shuey D. L. et al. (1993) Anat. Embryol., Berlin 187, 75-85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. 77, 211-215; Yavarone M. S. et al. (1993) Teratology 47, 573-584] malformations. Serotonin transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of serotonin transporter messenger RNA in early development supports the hypothesis that serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. 16, 233-240], and that the morphogenetic actions of serotonin may be regulated by transport. The striking pattern of serotonin transporter messenger RNA throughout developing sensory pathways suggests that serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of serotonin transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of serotonin transporter messenger RNA during ontogeny suggests a previously unappreciated role of serotonin in diverse physiological systems during embryonic development.


Bcl-2 and Hsp27 act at different levels to suppress programmed cell death.
Apoptosis and necrosis, two morphologically distinct forms of cell death, can be induced by common stimuli depending on the doses and the cell type. This study compares the protective effect of oncoprotein Bcl-2 and of the small stress protein Hsp27 on these two types of cell death. We use rat embryo fibroblasts conditionally immortalized by the tsA58 mutant of SV40 large T antigen as parental cells to develop cell lines carrying inducible bcl-2 or hsp27 genes. Two apoptotic stimuli were used: shift to the restrictive temperature that induced p53-mediated apoptosis and treatment with low doses of hydrogen peroxide. Necrosis was induced by high doses of hydrogen peroxide. Although Bcl-2 and Hsp27 protect these cells from necrotic death, only Bcl-2 appears capable of preventing apoptotic death. Bcl-2 protection is not mediated by a negative effect on the induction of the p53 responsive genes bax or waf1 but it slows down at least two stages of apoptosis: decrease of mitochondrial membrane potential and subsequent morphological changes. In contrast, although Hsp27 has been recently shown to inhibit apoptosis induced by various stimuli, its overexpression has no effect on apoptosis in this cell system. It should be also noticed that the apoptotic stimuli (temperature shift or hydrogen peroxide treatment) induce Hsp27, but not Bcl-2 accumulation suggesting that, in parental cells, Hsp27 might already provide some protection. However, taken together these results suggest that Hsp27, as well as Bcl-2, acts at several levels to inhibit cell death, but that their protective functions only partially overlap.


Quantification of variability and uncertainty in air pollutant emission inventories: method and case study for utility NOx emissions.
The quality of stationary source emission factors is typically described using data quality ratings, which provide no quantification of the precision of the emission factor for an average source, nor of the variability from one source to another within a category. Variability refers to actual differences caused by differences in feedstock composition, design, maintenance, and operation. Uncertainty refers to lack of knowledge regarding the true emissions. A general methodology for the quantification of variability and uncertainty in emission factors, activity factors, and emission inventories (EIs) is described, featuring the use of bootstrap simulation and related techniques. The methodology is demonstrated via a case study for a selected example of NOx emissions from coal-fired power plants. A prototype software tool was developed to implement the methodology. The range of interunit variability in selected activity and emission factors was shown to be as much as a factor of 4, and the range of uncertainty in mean emissions is shown to depend on the interunit variability and sample size. The uncertainty in the total inventory of -16 to +19% was attributed primarily to one technology group, suggesting priorities for collecting data and improving the inventory. The implications for decision-making are discussed.


Flux balance analysis in the production of clavulanic acid by Streptomyces clavuligerus.
In this work, in silico flux balance analysis is used for predicting the metabolic behavior of Streptomyces clavuligerus during clavulanic acid production. To choose the best objective function for use in the analysis, three different optimization problems are evaluated inside the flux balance analysis formulation: (i) maximization of the specific growth rate, (ii) maximization of the ATP yield, and (iii) maximization of clavulanic acid production. Maximization of ATP yield showed the best predictions for the cellular behavior. Therefore, flux balance analysis using ATP as objective function was used for analyzing different scenarios of nutrient limitations toward establishing the effect of limiting the carbon, nitrogen, phosphorous, and oxygen sources on the growth and clavulanic acid production rates. Obtained results showed that ammonia and phosphate limitations are the ones most strongly affecting clavulanic acid biosynthesis. Furthermore, it was possible to identify the ornithine flux from the urea cycle and the α-ketoglutarate flux from the TCA cycle as the most determinant internal fluxes for promoting clavulanic acid production.


Birth outcome of 1886 pregnancies after exposure to phenoxymethylpenicillin in utero.
To examine the risk of congenital abnormalities, preterm birth and low birth weight after exposure to phenoxymethylpenicillin in utero. A population-based follow-up study in the County of North Jutland, Denmark. Birth outcome for 1886 women, who redeemed prescriptions for phenoxymethylpenicillin during pregnancy was compared with the outcome for 9263 women who did not redeem any prescription during pregnancy. The prevalence of congenital abnormalities in 654 users of phenoxymethylpenicillin with or without other drugs during the first trimester was 4.6% compared with 3.6% in the reference group, giving a prevalence odds ratio of 1.25 (95% CI: 0.84-1.86). The prevalence odds ratio was 1.35 (95% CI: 0.59-3.08) in 131 women who were exposed to phenoxymethylpenicillin only. Nine cardiovascular abnormalities were found, giving an adjusted prevalence odds ratio of 1.74 (95% CI: 0.83-3.65). The prevalence odds ratios of preterm birth and low birth weight were 0.83 (95% CI: 0.66-1.04) and 1.02 (95% CI: 0.71-1.47), respectively. We found no significantly increased risk of congenital abnormalities, including cardiovascular abnormalities, preterm birth, or low birth weight in women who purchased phenoxymethylpenicillin during pregnancy.