Body temperature rhythms, cold tolerance, and fever in young and old rats of both genders.
The circadian rhythm of body temperature (CTR) of male and female rats living at 23 degrees C, as well as their body temperature response to a yeast injection or to a 2-h exposure to 0 degree C, was investigated by telemetry. Young rats had a clear CTR with a mean nocturnal peak of 38.0 +/- 0.1 degree C and diurnal trough of 36.2 +/- 0.1 degree C. Older rats, starting at about 18 months of age, tended to have poor (that is, lower amplitude) rhythms. Mean daily body temperature was 37.1 +/- 0.2 degree C at all ages. After exposure to the cold, the body temperature of young rats, old rats with a strong CTR, and old rats with a poor CTR changed in the ranges of -0.3 to +1.5 degree C, -3.1 to +0.7 degree C, and -5.2 to +0.4 degree C, respectively. This indicates that old animals, especially but not exclusively those with poor CTRs, are less resistant to cold stress. On the other hand, the capacity to develop a fever in response to a yeast injection was equivalent in the three groups of animals, although females had a smaller response than males. It is concluded that the process of aging does not have a generalized debilitating effect on temperature regulation in rats. Rather, aging seems to affect individual components of the thermoregulatory system differentially.


Simultaneous enantiomeric determinations of acid and ester imidazolinone herbicides in a soil sample by two-dimensional direct chiral liquid chromatography.
A two-dimensional HPLC method for the simultaneous direct chiral enantiomeric determination of acid and ester IMI herbicides has been described. Difficulties arising from differences in polarity were overcome. Firstly, the imazaphyr, imazethapyr and imazamethabenz methyl herbicides were separated in a C18 achiral column. Then, their respective enantiomers were separated using a protein chiral AGP(TM) column; a heart-cut mode was used. Mobile phases of the two systems were compatibilized, after optimizing by factorial design using multiple response analysis. The proposed method has been validated by recovery studies from an enriched soil sample. Important enantiomer parameters such as enantioresolution higher than 1.12, enantiomeric ratio (ER) close to 1 and enantiomeric fraction (EF) around 0.5 were obtained for standards, confirming that herbicides are present as racemates.


Defining the contractile prostanoid component in hyperosmolar-induced bronchoconstriction in human small airways.
Exercise-induced bronchoconstriction (EIB) is thought to be triggered by increased osmolarity at the airway epithelium. The aim of this study was to define the contractile prostanoid component of EIB, using an ex vivo model where intact segments of bronchi (inner diameter 0.5-2 mm) isolated from human lung tissue and subjected to mannitol. Exposure of bronchial segments to hyperosmolar mannitol evoked a contraction (64.3 ± 3.5 %) which could be prevented either by elimination of mast cells (15.8 ± 4.3 %) or a combination of cysteinyl leukotriene (cysLT1), histamine (H1) and thromboxane (TP) receptor antagonists (11.2 ± 2.3 %). Likewise, when antagonism of TP receptor was exchanged for inhibition of either cyclooxygenase-1 (8 ± 2.5 %), hematopoietic prostaglandin (PG)D synthase (20.7 ± 5.6 %), TXA synthase (14.8 ± 4.9 %), or the combination of the latter two (12.2 ± 4.6 %), the mannitol-induced contraction was prevented, suggesting that the TP-mediated component is induced by PGD2 and TXA2 generated by COX-1 and their respective synthases.


Periventricular rather than deep white matter hyperintensities mediate effects of hypertension on cognitive performance in the population-based 1000BRAINS study.
White matter hyperintensities (WMH) of presumed vascular origin are frequent in cerebral MRI of older people. They represent a sign of small vessel disease, are promoted by arterial hypertension, and relate to cognitive deficits. The interdependence of blood pressure and its treatment, WMH, and cognitive performance has not systematically been studied in population-based studies. Consequently, we analysed the interdependence of SBP, DBP, and antihypertensive medications, as well as BP/treatment category, with WMH and cognitive performance in 560 participants of the population-based 1000BRAINS study. BP, its treatment, and BP/treatment category were moderately associated with cognitive performance (e.g. unadjusted β = -0.10, 95%CI = -0.19 to -0.02 for the association of SBP (per standard deviation of 17.2 mmHg) with global cognition (per standard deviation of 0.5 z score)]. The harmful effect of BP on cognition was strongly mediated by periventricular hyperintensities (PVH), which were significantly associated with both SBP [ β = 0.24, 95% CI = 0.14-0.34 (per 1-point-increase in Fazekas score)] and global cognition ( β = -0.22, 95%CI = -0.32 to -0.13). Thus, PVH mediated as much as 52% of the effects of SBP on cognitive performance. Mediation was less strong for deep white matter hyperintensities (DWMH, 16%), which showed less association with SBP ( β = 0.14, 95% CI = 0.05-0.24) and global cognition ( β = -0.12, 95%CI = -0.21 to -0.03). Regarding different cognitive domains, PVH most strongly mediated effects of SBP on nonverbal memory (94%) and executive function (81%). Our results indicate that PVH may predispose to cognitive impairment associated with hypertension, especially in the domains of nonverbal memory and executive function.


[Behavior of the impedance of the middle ear and of the stapedius reflex under static conditions of barometric depression].
The authors present the preliminary results of a range of their aero-space medicine studies, carried out in hypobaric chamber, in simulated flight and at different atmospheric pressures, to asses the tubal function in normal hearing people. The tympanometric determination through a Z072 Madsen inpendenzometer in static and dynamic conditions of barometric depression gave a clear and exact indications about the impedence variation capacity of the middle ear in similated flight, giving homogenous data which allow the use of this method in flying recruitment aptitude test routine.


[Frontotemporal dementias].
Frontotemporal dementias (FTD) account for only 5-7% of all dementia aetiologies. However, FTD is one common form of dementia in the presenile period with a symptom onset between an age of 45 and 65 years. FTD are clinically classified into a group of rare genetic variants, the behavioural variant, primary progressive aphasias and a variant including motor neuron symptoms (FTD-MNS). In recent years the pathobiological characteristics of some FTD variants was clarified, demonstrating a pathological accumulation of TAR-DNA binding protein 43 (TDP-43) as a common pathological substrate. The revised diagnostic criteria of the behavioural variant of the FTD require at least three of six clinically discriminating features (disinhibition, apathy, loss of sympathy, perseverative behaviours, hyperorality and dysexecutive neuropsychological profile). The primary progressive aphasias are classified in a nonfluent/agrammatic variant, a logopenic variant and a semantic variant according to clinical and imaging features. Movement disorders and more precisely a Parkinsonian syndrome can be part of the FTD spectrum. Some clinical features overlap the clinical diagnosis of a progressive supranuclear paralysis and the corticobasal ganglionic degeneration. A causal therapy does not exist and medical treatment is directed at the patient's key symptoms. Different agents such as serotonin reuptake inhibitors, tricyclic antidepressants, atypical neuroleptics, carbamazepine, valproate, lamotrigine and when indicated also acetylcholinesterase inhibitors are potentially helpful. All together, theses medical treatments have a low level of evidence. Non-pharmacological therapies such as physiotherapy, occupational therapy, speech therapy and disease-specific education of the patient and their relatives are important to ensure a safe residential environment and daily routine.


Comprehensive assessment of impaired peripheral and coronary artery endothelial functions in smokers using brachial artery ultrasound and oxygen-15-labeled water PET.
Comprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers. Eight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055). Smokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries.


Ultra-High-Field Targeted Imaging of Focal Cortical Dysplasia: The Intracortical Black Line Sign in Type IIb.
Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight correlations between neuropathology and ultra-high-field imaging. Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality. We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (n = 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (n = 1/4) and in all those with focal cortical dysplasia IIb (n = 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (n = 4/5), while its incomplete removal yielded unsatisfactory results (n = 1/5). The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures.


Multimarker RT-PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients.
The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT-PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT-PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT-PCR. We conclude that a multimarker RT-PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation.


Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma.
The majority of patients with hepatocellular carcinoma will develop either unresectable or metastatic disease and, therefore, are candidates for systemic chemotherapy. Only a few chemotherapeutic agents have shown documented activity in the treatment of advanced hepatocellular carcinoma and there is clearly a need for the evaluation of new active drugs. Therefore, we performed a phase I trial with a weekly schedule of paclitaxel in patients with advanced hepatocellular carcinoma. 16 patients with documented progression of unresectable hepatocellular carcinoma were included. After premedication, paclitaxel was given as a 1 h infusion on days 1, 8, 15, 22, 29 and 36 representing one treatment cycle. The cycle was repeated every 50 days. The starting dose was 70 mg/m2 and the doses were escalated in steps of 10 mg/m2/week. A minimum of 3 patients were treated at each dose level. All treatment was given on an out-patient basis. Dose-limiting toxicity was reached at a dose of 100 mg/m2/week with 2 of 6 patients treated at that dose level having WHO grade 4 neutropenia. Other toxic side-effects were only mild. 1 partial response and 9 cases with disease stabilisation were observed in 16 patients with initially progressive disease. We, therefore, conclude that the recommended dose for a further phase II trial in patients with hepatocellular carcinoma is 90 mg/m2/week. These data indicate that paclitaxel given at this dose and schedule might have activity in hepatocellular carcinoma and further investigation in phase II trials is warranted.


Olfactory thresholds for nicotine and menthol in smokers (abstinent and nonabstinent) and nonsmokers.
Nonsmokers and smokers were compared for olfactory sensitivity to two odors associated with cigarettes: nicotine and menthol. Smokers were tested twice--while nonabstinent, and after 16-20 h of smoking abstinence. Smokers showed a higher olfactory threshold for nicotine than did nonsmokers, but the same threshold for menthol. Furthermore, when the smokers were abstinent, they showed a lower olfactory threshold for nicotine than when they were nonabstinent, but again, the same threshold for menthol. These results suggest a nicotine specific olfactory deficit in smokers that is reduced during abstinence.


Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing.
To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which women's health can be improved.


Preimplantation genetic diagnosis for early-onset torsion dystonia.
Early-onset primary torsion dystonia (DYT1) is the most severe and common form of hereditary movement disorders, characterized by sustained twisting contractures that begin in childhood, which is caused in majority of cases by a 3-bp deletion of the DYT1 gene on chromosome 9q34 at the heterozygote state. As there is no effective treatment of this disease, preimplantation genetic diagnosis (PGD) may be a useful option for at-risk couples to establish an DYT1 mutation-free pregnancy. PGD was performed for two obligate carriers of the DYT1 3-bp deletion, using blastomere testing to preselect the mutation-free embryos, based on mutation analysis with simultaneous testing of the three closely linked markers, D9S62, D9S63 and ASS. Of 19 tested blastomeres in three cycles, 17 had conclusive information about the mutation and linked markers, of which eight were predicted to be free of 3-bp deletion. Six of these embryos were transferred back to patients, two in each cycle, yielding singleton DYT1 3-bp deletion-free clinical pregnancies in two. One of these pregnancies was terminated due to severe anencephaly and the other resulted in birth of a mutation-free child. This is the first PGD for primary torsion dystonia, providing an alternative for those at-risk couples who cannot accept prenatal diagnosis and termination of pregnancy as an option for avoiding early onset torsion dystonia.


Conjugates of tacrine and 1,2,4-thiadiazole derivatives as new potential multifunctional agents for Alzheimer's disease treatment: Synthesis, quantum-chemical characterization, molecular docking, and biological evaluation.
We synthesized conjugates of tacrine with 1,2,4-thiadiazole derivatives linked by two different spacers, pentylaminopropene (compounds 4) and pentylaminopropane (compounds 5), as potential drugs for the treatment of Alzheimer's disease (AD). The conjugates effectively inhibited cholinesterases with a predominant effect on butyrylcholinesterase (BChE). They were also effective at displacing propidium from the peripheral anionic site (PAS) of acetylcholinesterase (AChE), suggesting that they could block AChE-induced β-amyloid aggregation. In addition, the compounds exhibited high radical-scavenging capacity. Conjugates 5 had higher anti-BChE activity and greater anti-aggregant potential as well relatively lower potency against carboxylesterase than compounds 4. Quantum-mechanical (QM) characterization agreed with NMR data to identify the most stable forms of conjugates for docking studies, which showed that the compounds bind to both CAS and PAS of AChE consistent with mixed reversible inhibition. Conjugates 4 were more potent radical scavengers, in agreement with HOMO localization in the enamine-thiadiazole system. Computational studies showed that all of the conjugates were expected to have good intestinal absorption, whereas conjugates 4 and 5 were predicted to have medium and high blood-brain barrier permeability, respectively. All conjugates were predicted to have medium cardiac toxicity risks. Overall, the results indicated that the conjugates are promising candidates for further development and optimization as multifunctional therapeutic agents for the treatment of AD.


Double strand binding-single strand incision mechanism for human flap endonuclease: implications for the superfamily.
Detailed structural, mutational, and biochemical analyses of human FEN1/DNA complexes have revealed the mechanism for recognition of 5' flaps formed during lagging strand replication and DNA repair. FEN1 processes 5' flaps through a previously unknown, but structurally elegant double-stranded (ds) recognition/single stranded (ss) incision mechanism that both selects for 5' flaps and selects against ss DNA or RNA, intact dsDNA, and 3' flaps. Two major DNA binding interfaces, including a K(+) bridge between the DNA and the H2TH motif, are spaced one helical turn apart and together select for substrates with dsDNA. A conserved helical gateway and a helical cap protects the two-metal active site and selects for ss flaps with free termini. Structures of substrate and product reveal an unusual step between binding substrate and incision that involves a double base unpairing with incision occurring in the resulting unpaired DNA or RNA. Ordering of the active site requires a disorder-to-order transition induced by binding of an unpaired 3' flap, which ensures that the product is ligatable. Comparison with FEN superfamily members, including XPG, EXO1, and GEN1, identifies superfamily motifs such as the helical gateway that select for ss-dsDNA junctions and provides key biological insights into nuclease specificity and regulation.


Management of advanced colorectal cancer: state of the art.
Colorectal cancer (CRC) caused over 500 000 deaths worldwide in 2002. Recent advances in the treatment of advanced disease include the incorporation of two new cytotoxic agents, irinotecan and oxaliplatin, into first-line regimens. The concept of planned sequential therapy involving three active agents during the course of a patient's treatment is evolving. Coupled with the integrated use of targeted monoclonal antibodies, we can now expect overall survival rates for advanced disease to exceed 20 months. This review considers current treatments and suggests where future progress may occur.


Artificial Intelligence Based Body Sensor Network Framework-Narrative Review: Proposing an End-to-End Framework using Wearable Sensors, Real-Time Location Systems and Artificial Intelligence/Machine Learning Algorithms for Data Collection, Data Mining and Knowledge Discovery in Sports and Healthcare.
With the rising amount of data in the sports and health sectors, a plethora of applications using big data mining have become possible. Multiple frameworks have been proposed to mine, store, preprocess, and analyze physiological vitals data using artificial intelligence and machine learning algorithms. Comparatively, less research has been done to collect potentially high volume, high-quality 'big data' in an organized, time-synchronized, and holistic manner to solve similar problems in multiple fields. Although a large number of data collection devices exist in the form of sensors. They are either highly specialized, univariate and fragmented in nature or exist in a lab setting. The current study aims to propose artificial intelligence-based body sensor network framework (AIBSNF), a framework for strategic use of body sensor networks (BSN), which combines with real-time location system (RTLS) and wearable biosensors to collect multivariate, low noise, and high-fidelity data. This facilitates gathering of time-synchronized location and physiological vitals data, which allows artificial intelligence and machine learning (AI/ML)-based time series analysis. The study gives a brief overview of wearable sensor technology, RTLS, and provides use cases of AI/ML algorithms in the field of sensor fusion. The study also elaborates sample scenarios using a specific sensor network consisting of pressure sensors (insoles), accelerometers, gyroscopes, ECG, EMG, and RTLS position detectors for particular applications in the field of health care and sports. The AIBSNF may provide a solid blueprint for conducting research and development, forming a smooth end-to-end pipeline from data collection using BSN, RTLS and final stage analytics based on AI/ML algorithms.


Serum ferritin as a risk factor for type 2 diabetes mellitus, regulated by liver transferrin receptor 2.
The aim of this study was to evaluate the effect of TFR2 on iron storage in type 2 diabetes. A cross-sectional study was conducted among 1938 participants from the Jiangchuan Community of Shanghai. A total of 784 participants with T2DM and 1154 normal participants (non-T2DM) were enrolled in this study. Serum ferritin, fasting blood glucose, postprandial blood glucose, and HbA1C (glycated hemoglobin A1c) levels were determined. Eighteen Wistar male rats were randomly assigned into three groups (n = 6/group): rats in a high-fat diet streptozotocin (HFD+STZ) group were fed with HFD for 4 weeks and intraperitoneally injected with streptozotocin (STZ); rats in a control group were fed with a standard diet for 4 weeks and intraperitoneally injected with buffer; rats in an STZ group were fed with a standard diet for 4 weeks and intraperitoneally injected with streptozotocin. Glucose tolerance test was performed at the end of the study. Blood samples and liver tissues were assessed for liver TFR2, blood glucose, serum ferritin, and iron levels. The mean serum ferritin level of T2DM participants was significantly higher than that of the control group (227 (140-352) vs 203.5 (130.5-312) ng/mL, P < 0.05). Serum ferritin level was an independent risk factor for T2DM (high ferritin group vs low ferritin group, 1.304 (1.03-1.651), P < 0.05). Diabetic rats showed reduced liver TFR2 levels, with increased serum ferritin levels. T2DM participants exhibited iron disorder with elevated serum ferritin levels. Elevated serum ferritin levels in diabetic rats were accompanied by reduced liver TFR2 levels.


Recycling phosphogypsum in road construction materials and associated environmental considerations: A review.
Phosphogypsum (PG) is a major hazardous by-product of the phosphate industry. The whole world is facing the challenge of increasing stockpiles of PG, which significantly affect safety and the environment. Recycling this material may be an environmentally friendly and safe solution to this challenge. In this paper, we searched the Web of Science database for 2369 articles from 1975 to 2022 using "phosphogypsum" as the keyword. Using the VOSviewer as the literature visualisation tool, density visualisation was performed with keywords as the analysis units, and it was found that the researchers focused mainly on PG applications in construction and radionuclides. Over the years, different routes to PG valorisation have been developed in the agricultural, construction, environmental and energy sectors, and these topics are described in this review. As infrastructure projects, highway engineering is characterised by a large land area and high resource consumption. Therefore, applying PG to road materials can significantly increase the reuse and consumption of PG and reduce PG stockpiles. We hope that PG can be used for road construction on a large scale in the future. This paper focuses on the latest developments in PG as road materials. The most serious difficulty in using PG as road materials at present is that it contains radionuclides and heavy metal impurities, which can be purified by pretreatment methods. However, how to scale it up requires continuous research.


Sclerosing mediastinitis with occlusion of pulmonary veins. Manifestations and management.
A case of mediastinal fibrosis with occlusion of the right inferior and middle lobe pulmonary veins is described. The patient had severe hemoptysis, and the diagnosis was established with thoracotomy. Review of the literature emphasizes the lethal nature of this syndrome if untreated. Resection of the involved bronchopulmonary tissue, when feasible, offers good palliation, although the long-term prognosis is unpredictable.


Treatment of livestock with systemic insecticides for control of Anopheles arabiensis in western Kenya.
Despite the implementation of vector control strategies, including insecticide-treated bed nets (ITN) and indoor residual spraying (IRS) in western Kenya, this area still experiences high level of malaria transmission. Novel vector control tools are required which target such vector species, such as Anopheles arabiensis, that feed outdoors and have minimal contact with ITNs and IRS. To address this need, ivermectin, eprinomectin, and fipronil were evaluated in Zebu cattle under semi-field conditions to evaluate the potential of these compounds to reduce the survival of blood feeding An. arabiensis. Over the course of four experiments, lactating cattle received doses of oral ivermectin at 0.1 or 0.2 mg/kg, oral eprinomectin at 0.2 or 0.5 mg/kg, topical eprinomectin at 0.5, 0.75, or 1.5 mg/kg, or oral fipronil at 0.25, 0.5, 1.0, or 1.5 mg/kg. On days 1, 3, 5, 7, 14, and 21 days post-treatment, cattle were exposed to An. arabiensis, and mosquito mortality post-blood feeding was monitored. For the analysis of survival data, the Kaplan-Meier estimator and Mantel-Haenszel test was used to contrast the treatment and control survival functions. All three compounds significantly reduced the survival time of An. arabiensis. Twenty-one days post-treatment, mortality of mosquitoes fed on cattle dosed orally with 0.2 or 0.5 mg/kg eprinomectin, topically with eprinomectin at 0.5 mg/kg, or orally with either 1.0 or 1.5 mg/kg fipronil was still significantly higher than control mortality. These data demonstrate the effectiveness of three insecticidal compounds administered systemically to cattle for controlling the cattle-feeding mosquito An. arabiensis. Eprinomectin and fipronil provided the longest-lasting control. Such endectocidal treatments in cattle are a promising new strategy for control of residual, outdoor malaria transmission and could effectively augment current interventions which target more endophilic vector species.


The R2R3MYB transcription factors MaMYBF and MaMYB1 regulate flavonoid biosynthesis in grape hyacinth.
R2R3 MYBs play vital roles in the regulation of flavonoid biosynthesis. However, the regulatory network of R2R3 MYBs in flavonoid biosynthesis is not fully understood in grape hyacinth (Muscari spp.). Here, we identified two R2R3 MYBs, MaMYBF and MaMYB1, as potential regulators of flavonol and anthocyanin biosynthesis, respectively. MaMYBF and MaMYB1 expression was elevated during flower development and was light-induced, and the expression patterns were related to those of the flavonoid structural genes MaFLS and MaDFR, respectively. The BiFC assay verified that MaMYB1 interacts with MabHLH1, but MaMYBF does not. A dual luciferase assay revealed that MaMYBF alone strongly activated pMaFLS, and its activation was attenuated at reduced doses of MaMYBF in the presence of MabHLH1, MaMybA, and MaMYB1. MaDFR transcription mediated by MaMybA and MabHLH1 was inhibited by MaMYB1. Moreover, overexpression of MaMYBF and MaMYB1 in tobacco reduced flower pigmentation and repressed the expression of flavonoid pathway key structural genes. Therefore, MaMYBF regulates the flavonol pathway independently of cofactors. Whereas MaMYB1 regulates anthocyanin biosynthesis by binding to MabHLH1 and disrupting the MaMybA-bHLH complex in grape hyacinth. Our results offer new insights into the intricate regulatory network of flavonoids in grape hyacinth involving the regulation of both flavonol and anthocyanin.


Properties improvement of paper mill sludge-based granular activated carbon fillers for fluidized-bed bioreactor by bentonite (Na) added and acid washing.
Properties improvement of paper mill sludge (PMS) based granular activated carbon fillers for fluidized-bed bioreactor (FBBR) was investigated in this study. Bentonite (Na) powders were blended in the dewatered paper mill sludge powders to strengthen the abrasion resistance strength of the fillers. Different acid washing treatments were studied to produce FBBR fillers with optimum performance. The results indicated that granulation was easy and the abrasion resistance strength of the fillers increased by 15% with 8 wt% of bentonite (Na) added. Acid washing treatment prior to activation had a better effect on the removal of Fe than post-activation acid washing treatment. HCl was the most appropriate acid during the acid washing treatment. The optimum acid washing treatment was carried out prior to activation with 2M HCl soaking for 6h. After acid washing treatment, the fillers with grain density of 1170 kg/m(3), specific surface area of 176 m(2)/g were obtained.


Ibuprofen modifies cognitive disease progression in an Alzheimer's mouse model.
Prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of developing Alzheimer's disease (AD) and delay disease onset. Negative results of clinical AD trials were rationalised by the discovery that certain NSAIDs reduce amyloid-beta( 1-42) (A beta(1- 42)) peptide production, the proposed central culprit in AD pathophysiology and main constituent of amyloid plaques, whereas other compounds do not affect A beta levels. Latter observations motivated further in-vitro and in-vivo research regarding the applicability of NSAIDs in treating and/or preventing AD. We used the age-dependent cognitive decline in the APP23 transgenic mouse model for AD to evaluate disease-modifying efficacy of chronic ibuprofen treatment at the cognitive level. At age 6 weeks, heterozygous APP23 mice and control littermates were subcutaneously implanted with osmotic pumps delivering saline or ibuprofen (50 mg/kg daily). After 2 months of treatment, a 3-week washout period prevented bias from potential symptomatic effects before cognitive evaluation commenced. Ibuprofen-treated APP23 mice performed significantly better than their sham-treated counterparts and almost attained the same level of performance as control animals on a complex visual-spatial learning task. This study clearly reports disease-modifying efficacy of ibuprofen at the cognitive level in transgenic mice modelling AD.


An in vitro study on the maturation of conventional glass ionomer cements and their interface to dentin.
The objective of the study was to investigate the influence of long-term storage (up to 1 year) and coating on the variation of micro-mechanical properties of four conventional restorative glass ionomer cements (GICs) within 3.5 mm deep class I cavities. Four commercially available GICs (Riva Self Cure (SDI), ChemFil Rock (Dentsply), Fuji IX Fast and Fuji IX GP Extra/Equia (GC)) were applied to 100 teeth. In each tooth, two similar 3.5 mm deep class I cavities were prepared and filled with the GICs, with and without resin coating. The samples were stored in artificial saliva at 37 °C for 1 week, 1 month, 3 months, 6 months and 1 year. The variation in mechanical properties (indentation modulus (E) and Vickers hardness (HV)) were determined in 100 μm steps starting from the filling surface, through the intermediate layer in between dentine and GIC, and ending 100 μm in dentin. HV and E were strongly influenced by the material (P<0.05, partial eta-squared ηP(2) = 0.31 and 0.23) but less by aging duration (P<0.05, ηP(2) = 0.02 and 0.12) and resin coating (P<0.05, ηP(2) = 0.02 and 0.03). The depth of measurement (0-2 mm) has no influence on HV (P = 0.789). HV shows a gentle increase over the 1 year storage period (P = 0.002). A ∼300 μm GIC zone at the areas close to dentin with weaker properties as those measured in dentin or GIC was identified in all fillings, irrespective of the presence of coating, and at all storage periods. The thickness of this zone is more strongly influenced by storage (P<0.05, ηP(2) = 0.081) than by material type (P<0.05, ηP(2) = 0.056), while coating showed no influence (P = 0.869). Filler morphology and dimension were similar to upper parts of the GIC filling; however, the amount of low cations was higher. We concluded that the development of an intermediate layer in between dentine and GIC with lower mechanical properties might be responsible for the bond quality of GIC to dentine. Moreover, class I GIC restorations are unlikely to feature constant mechanical properties throughout the cavity, regardless of conditions such as aging and coating.


Plasma nitrate values in patients with obsessive-compulsive disorder.
Recently there has been increasing evidence that free oxygen species may play an important role in the pathophysiology of various neuropsychiatric disorders. The present study was performed to assess the changes in plasma nitric oxide (NO) levels in patients with obsessive-compulsive disorder (OCD) compared to age- and sex-matched normal controls. Twenty-three patients with OCD and 23 healthy volunteers were included in the study. NO values were determined in the plasma of normal healthy controls and the OCD patients. Plasma nitrate levels in OCD patients were significantly higher than those in controls and were significantly and positively correlated with Yale-Brown Obsession Compulsion Scale scores but not related to age or to the duration of illness. These findings indicated a possible role of increased NO may be relevant to the pathophysiology of OCD.


Characteristics of hospital-based Munchausen Syndrome by Proxy in Japan.
This article explores characteristics of Munchausen Syndrome by Proxy (MSBP) in Japan, a country which provides an egalitarian, low cost, and easy-access health care system. We sent a questionnaire survey to 11 leading doctors in the child abuse field in Japan, each located in different hospital-based sites. Child abuse doctors answered questions regarding the characteristics of MSBP cases for whom they had helped care. Twenty-one MSBP cases (20 families) were reported. Characteristics of the victims included: no differences based on sex, 4.6 years of age on average when MSBP was confirmed, and an average of 1.9 years duration of MSBP abuse. Biological mothers were at least one of the perpetrators in 95% of cases. Among the 12 cases (57%) who remained with their families, 2 victims died. Only 5% of perpetrators had a medical background or relatives who engaged in healthcare work. There are similar features of MSBP cases between Japan and other English-speaking countries, such as the UK or the US. However, perpetrators of MSBP in Japan did not have a medical background. Easier access to hospital resources in Japan may give greater opportunities for perpetrators to obtain medical knowledge from doctors or nurses. The findings suggest that perpetrators of MSBP should not be assumed to possess a medical background in a country which provides universal medical care such as Japan. A contributory factor of MSBP may be the high frequency of medical consultations and equal level of accessibility of medical resources for Japanese citizens. Social welfare services that need to decide on custody for MSBP victims should recognize the relatively high risk of life-threatening danger in their family of origin. Further collaboration between hospital staff including pediatricians, nurses, medical social workers and staff at the social welfare services is needed to protect children from MSBP.


Socioeconomic status over the life-course and adult bone mineral density: the Midlife in the U.S. Study.
Adult bone mass depends on acquisition in childhood and decline in adulthood, and may be influenced by socioeconomic conditions over the entire life course. We examined associations of bone mineral density (BMD) in adulthood with life course socioeconomic status in 729 participants in the Midlife in the United States Biomarker Project, adjusting for age, menopausal transition stage, race, gender, body weight, smoking, physical activity in several life stages, and research site. Primary predictors were a) childhood socioeconomic advantage score (including parental education, self-rated financial status relative to others, not being on welfare), b) adult education level (no college vs. some college vs. college graduate), and c) adult current financial advantage score (including family-adjusted poverty to income ratio, self-assessed current financial situation, having enough money to meet needs, ease in paying bills). Mean age was 56.9 (range 34-85) years. After adjustment for covariates, childhood socioeconomic advantage and adult education level were positively associated with lumbar spine BMD: 0.27 standard deviations (SD) higher at 90th compared to 10th percentile of childhood advantage score (P=0.009), and 0.24 SD higher in college graduates compared to participants without college education (P=0.01). Adult current financial advantage was not associated with lumbar spine BMD. None of the three socioeconomic indicators was significantly associated with femoral neck BMD. Childhood socioeconomic advantage and adult education level were associated with higher adult lumbar spine BMD. Current financial advantage was not associated with BMD. Childhood socioeconomic factors may influence acquisition of lumbar BMD.


Preventing surgical complications: A survey on surgeons' perception of intra-articular malleolar screw misplacement in a cadaveric study.
Intra-articular hardware penetration can occur during osteosynthesis of ankle fractures, jeopardizing patients' outcomes. The intraoperative recognition of misplaced screws may be difficult due to the challenge of adequate interpretation of specific radiographic views. The present study was designed to investigate the diagnostic accuracy of standardized radiographic ankle views to determine the accuracy of diagnosis for intra-articular hardware placement of medial malleolar screws in a cadaveric model. Nine preserved human cadaveric lower extremity specimens were used. Under direct visualization, two 4.0 mm cancellous screws were inserted into the medial malleolus. Each specimen was analyzed radiographically using antero-posterior (AP) and mortise views. The X-rays were randomly uploaded on a CD-ROM and included in a survey submitted to ten selected orthopaedic surgeons. The "Standards for Reporting of Diagnostic Accuracy" (STARD) questionnaire was used to determine the surgeons' perception of accuracy of screw placement in the medial malleolus. The selection of items was based on evidence whenever possible, therefore the "inconclusive" category was added. Inter and intraobserver variations were analyzed by kappa statistics to measure the amount of agreement. There was a poor level of agreement (kappa 0.4) both in the AP and in the mortise view among all the examiners. Associating the two x-rays, the agreement remained poor (kappa 0.4). In the cases in which there was a diagnosis of articular penetration, there was a poor agreement related to which of the screws was intra-articular. The number of "inconclusive" responses was low and constant, without a statistically significant difference between the subspecialists The routine intraoperative radiographic imaging of the ankle is difficult to interpret and unreliable for detection of intra-articular hardware penetration. We therefore recommend to reposition medial malleolar screws intraoperatively if there is any doubt regarding inadequate screw placement.


Body Habitus Considerations During Right Heart Catheterization.
Obese and overweight body habitus are common among patients undergoing right heart catheterization for suspected pulmonary hypertension, but previous studies have described only patients with severe obesity. This study examined the effect of body habitus on intracardiac pressures, thermodilution cardiac output (TDCO), indirect Fick (iFick) cardiac output (CO), and pulmonary vascular resistance (PVR) in subjects with normal cardiopulmonary hemodynamics. A retrospective analysis was conducted on healthy volunteers and patients referred for right heart catheterization for dyspnea of unknown origin with normal hemodynamics. Of the 65 subjects (53 ± 14 years; 51% female), 31% were normal weight, 49% were overweight, and 20% had obesity, as defined by a body mass index of 30-39.9 kg/m2. Mixed venous oxygen saturations and intracardiac pressures were compared across body mass index categories. Agreement between iFick CO calculated by 3 formulae, and TDCO and PVR was examined. No differences in intracardiac pressures were observed, but mixed venous oxygen saturations were lower in the obese group. iFick CO underestimated TDCO, particularly with the LaFarge formula, with a systematic difference of 0.33 L/min for every 1 L/min increase in CO. This difference was largest in the obese group-on average by 23% ± 10%, translating to an overestimation of PVR by 34% ± 16% on average. In individuals without severe obesity, intracardiac pressures are not different, but mixed venous oxygen saturations are lower. Obesity confounds estimations of CO and PVR by iFick methods, which could result in inappropriate hemodynamic classification. These data can inform best practices in hemodynamic assessment of populations with obesity.


The unique metabolism of SAR11 aquatic bacteria.
The deeply branching clade of abundant, globally distributed aquatic α-Proteobacteria known as "SAR11", are adapted to nutrient-poor environments such as the surface waters of the open ocean. Unknown prior to 1990, uncultured until 2002, members of the SAR11 clade can now be cultured in artificial, defined media to densities three orders of magnitude higher than in unamended natural media. Cultivation in natural and defined media has confirmed genomic and metagenomic predictions such as an inability to reduce sulfate to sulfide, a requirement for pyruvate, an ability to oxidize a wide variety of methylated and one-carbon compounds for energy, and an unusual form of conditional glycine auxotrophy. Here we describe the metabolism of the SAR11 type strain Candidatus "Pelagibacter ubique" str. HTCC1062, as revealed by genome-assisted studies of laboratory cultures. We also describe the discovery of SAR11 and field studies that have been done on natural populations.


Accuracy of currently available neonatal respiratory function monitors for neonatal resuscitation.
This study aimed to test the accuracy in volume measurements of three available respiratory function monitors (RFMs) for neonatal resuscitation and the effect of changing gas conditions. The Florian, New Life Box Neo-RSD (NLB Neo-RSD) and NICO RFM were tested on accuracy with volumes of 10 and 20 mL and on changes in volume measurements under changing gas conditions (oxygen level 21-100 % and from cold dry air (24 ± 2 °C) to heated humidified air (37 °C). Volume differences >10 % were considered clinically relevant. We found that the mean (SD) volume difference was clinically acceptable for all devices (10, 20 mL): Florian (+8.4 (1.2)%, +8.4 (0.5)%); NLB Neo-RSD (+5.8 (1.1)%, +4.3 (1.4)%); and NICO (-8.2 (0.9)%, -8.7 (0.8)%). Changing from cold dry to heated humidified air increased the volume difference using the Florian (cold dry air, heated humidified air (+5.2 (1.2)%, +12.2 (0.9)%) but not NLB Neo-RSD (+2.0(1.6)%, +3.4(2.8)%) and NICO (-2.3 % (0.8), +0.1 (0.6)%). Similarly, when using heated humidified air, increasing oxygen enlarged increased the volume difference using the Florian (oxygen 21 %, 100 %: +12.2(1.0)%, +19.8(1.1)%), but not NLB Neo-RSD (+0.2(1.9)%, +1.1(2.8)%) and NICO (-5.6(0.9)%, -3.7(0.9)%). Clinically relevant changes occurred when changing both gas conditions (Florian +25.7(1.7)%; NLB Neo-RSD +3.8(2.4)%; NICO -5.7(1.4)%). The available RFMs demonstrated clinically acceptable deviations in volume measurements, except for the Florian when changing gas conditions. •Respiratory function monitors (RFMs) are increasingly used for volume measurements during respiratory support of infants at birth. •During respiratory support at birth, gas conditions can change quickly, which can influence the volume measurements. What is new: •The available RFMs have clinically acceptable deviations when measuring the accuracy of volume measurements. •The RFM using a hot wire anemometer demonstrated clinically relevant deviations in volume measurements when changing the gas conditions. These deviations have to be taken into account when interpreting the volumes directly at birth.


Physiopathology of transient ventricular occlusion during balloon valvuloplasty for pulmonic or aortic stenosis.
Hemodynamic observations were made at different cardiac levels during transient balloon occlusion at the time of aortic or pulmonary valvuloplasty in 37 patients (mean age 8 +/- 9 years); 22 had pulmonary stenosis and 15 had aortic stenosis (6 valvular and 9 discrete subvalvular types). Eighty-two tentative dilatations were performed in patients with pulmonary stenosis and 61 in patients with aortic stenosis. The hemodynamics of the right and left heart were monitored during inflation-deflation time. From selected tracings mean beat-to-beat pressures curves were constructed during occlusion-recovery time. The cycle length (RR interval) did not change significantly during occlusion, except for patients with pulmonary occlusion and patent foramen ovale, where a significant increase in cycle length (p less than 0.01) was observed during recovery time. The mean maximal increase in ventricular pressure reached 95% of basal values for the right ventricle and 58% for the left ventricle. The hypertension was retrogradely transmitted to all cardiac chambers. Angiographic observations during occlusion suggest that the atrioventricular valves and the foramen ovale, when patent, become escape orifices during occlusion, for adapting and relieving intracavitary pressures. The ventricle seems to adapt to sudden occlusion by generating hypertensive and hypokinetic contractions, with atrioventricular regurgitation.


Post Parotidectomy Quality of Life in Patients with Benign Parotid Neoplasm: A Prospective Study.
Parotid tumours are not uncommon. The management is surgical for benign and malignant parotid neoplasm. Due to the location of parotid gland and its intricate relationship with facial nerve, cosmetic and functional outcomes after parotid surgery are extremely important. Objectives of the study were to analyse facial nerve functions with emphasis on the quality of life of patients undergoing surgery for parotid neoplasm. A prospective study was conducted on patients presented with parotid neoplasm and undergone parotid surgery. Patient with malignant neoplasm were excluded. 30 patients with benign parotid neoplasm in final histopathology were included in the study. Post operative assessment of facial nerve was done using postparotidectomy facial nerve grading system. Symptom-specific QOL was assessed with the parotidectomy outcome inventory-8. Aesthetic outcome was evaluated with an ordinal scale. Posterior belly of digastric muscle and tragal pointer were the commonest landmark used for facial nerve identification. Temporary facial nerve dysfunction was present in six (20%) patients with marginal mandibular branch most commonly involved. 96% of the female patients and 91% of the male patients rated the cosmetic result as good or very good. A statistically significant difference is noted between superficial parotidectomy and total Parotidectomy for cosmetic outcome and sensory impairment. We noted that changed appearance due to resection of the parotid gland and scar and sensory impairment in the area affect the quality of life of patients and such affect are more after total conservative parotidectomy.


Technetium-99m-labeled doxorubicin as an imaging probe for murine breast tumor (4T1 cell line) identification.
Early diagnosis of malignant tumors is essential to successfully plan a radical and curative approach. In this study we describe the direct radiolabeling of doxorubicin (DOX) at physiological pH to identify murine breast tumor (4T1 cells)-bearing BALB/c mice. Technetium-99m (99mTc) DOX was prepared by adding 99mTc-pertechnetate to a PBS (pH 7.4) solution containing DOX in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of 99mTc-DOX was determined by measuring blood radioactivity in healthy animals. Scintigraphic images and biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 8 h after injection. The 99mTc-DOX complex showed high radiochemical purity (99.27 ± 0.34%) and in-vitro stability until 8 h. Tc-DOX levels in blood declined in a biphasic manner, with an α half-life of 4.5 min and a β half-life of 277.2 min. High uptake was achieved in kidneys, liver, and spleen, because of the drug elimination routes. Moreover, tumor uptake was higher than that of control tissue, resulting in high tumor-to-muscle ratios. DOX was successfully labeled with 99mTc-pertechnetate and showed high stability. Biodistribution and scintigraphic studies indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. These results suggested the feasibility of 99mTc-DOX as a functional agent in tumor diagnosis.


Contrasting Pattern of Chronic Inflammatory Bowel Disease in Primary and Autoimmune Sclerosing Cholangitis.
Primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (AISC) are related, but distinct chronic liver diseases. PSC is associated with a high prevalence of ulcerative colitis while the intestinal inflammation associated with AISC is less well characterised. To assess and contrast aspects of intestinal inflammation in patients with AISC and PSC and compare the clinical features with those of patients with ulcerative colitis and Crohn's disease. 23 and 22 patients with AISC and PSC, respectively, underwent review of colonoscopy and biopsy findings, capsule enteroscopy and assessment of clinical and inflammatory (faecal calprotectin) disease activity, which was compared with that of patients with ulcerative colitis and Crohn's disease (n = 55 each). Five and 6 patients with AISC and PSC, respectively, had normal colonoscopy and faecal calprotectin levels of 34.4 ± 8.3 and 39.7 ± 8.4 μg/g, respectively (normal < 50 μg/g), whereas 18 and 16, respectively, had identical variably severe, right sided colitis with frequent rectal sparing, consistent with ulcerative colitis. Mean (± SD) faecal calprotectin levels did not differ significantly (p > 0.05) between patients with intestinal inflammation in AISC (588 ± 549 μg/g), PSC (421 ± 351 μg/g), ulcerative colitis (501 ± 656 μg/g) or Crohn's disease (476 ± 571 μg/g). Capsule enteroscopy showed that 7 of 18 (39%) (p < 0.03) of those with AISC had small bowel mucosal breaks whereas no patient with PSC had these findings. Collectively these findings lend support to the suggestion that the chronic inflammatory bowel disease associated with PSC and in particular AISC may represent a distinct nosologic entity different from classic ulcerative colitis and Crohn's disease.


Isocitrate dehydrogenase of Bacillus cereus is involved in biofilm formation.
Isocitrate dehydrogenase (IDH), a key enzyme in the TCA cycle, participates in the formation of biofilms in Staphylococcus aureus, but it remains to be clarified whether it is involved in the formation of Bacillus cereus biofilms. In this study, we scanned the genome of B. cereus 0-9 and found a gene encoding isocitrate dehydrogenase (FRY47_22620) named icdH. The IcdH protein was expressed and purified. The enzyme activity assay showed that the protein had IDH activity dependent on NADP+, indicating that this gene encoded an IDH. The ΔicdH mutant and its complemented strains were obtained by a homologous recombination strategy, and crystal violet data and CLSM were measured. The results showed that the biofilm yield of the mutant ΔicdH decreased, and the biofilm morphology also changed, while the growth of ΔicdH was not affected. The extracellular pH and citric acid content results showed that the ΔicdH mutant exhibited citric acid accumulation and acidification of the extracellular matrix. In addition, the addition of excess Fe3+ restored the biofilm formation of the ΔicdH mutant. It is speculated that IDH in B. cereus may regulate biofilm formation by modulating intracellular redox homeostasis. In addition, we found that the icdH deletion of B. cereus 0-9 could result in a reduced sporulation rate, which was significantly different from sporulation in B. subtilis caused by interruption of the stage I sporulation process due to icdH loss. All the above results provide us with new insights for further research on IDH.


The surgical management of esophageal stricture in children. A century of progress.
Early in this century all procedures performed on the esophagus were accomplished through its lumen. Ingestion of caustics was common and resulted in dense strictures for which complicated and ingenious methods of dilation were advised. Because obstructions usually recurred, by-pass operations were devised with conduits of skin or segments of the gastrointestinal tract. Now, in contrast, when burns occur, intensive steroid therapy usually prevents all but localized areas of stricture. These areas, if short, can be treated with hydrostatic balloon dilation under fluoroscopic control. If longer or resistant to dilation, these strictures can be managed by incision and insertion of a colic patch with excellent long-term results. To a previous series of children who have had esophageal patch with a vascularized segment of colon, now added is an experience with a free segment of small intestine with vascular anastomosis to an artery and vein in the neck and another case of a free patch of pericardium to the esophageal stricture.


Enhanced pyruvate production in Candida glabrata by overexpressing the CgAMD1 gene to improve acid tolerance.
To enhance acid tolerance of Candida glabrata for pyruvate production by engineering AMP metabolism. The physiological function of AMP deaminase in AMP metabolism from C. glabrata was investigated by deleting or overexpresseing the corresponding gene, CgAMD1. At pH 4, CgAMD1 overexpression resulted in 59 and 51% increases in biomass and cell viability compared to those of wild type strain, respectively. In addition, the intracellular ATP level of strain Cgamd1Δ/CgAMD1 was down-regulated by 22%, which led to a 94% increase in pyruvate production. Further, various strengths of CgAMD1 expression cassettes were designed, thus resulting in a 59% increase in pyruvate production at pH 4. Strain Cgamd1Δ/CgAMD1 (H) was grown in a 30 l batch bioreactor at pH 4, and pyruvate reached 46.1 g/l. CgAMD1 overexpression plays an active role in improving acid tolerance and pyruvate fermentation performance of C. glabrata at pH 4.


Analysis of diagnostic characteristics and clinical related factors of 70 patients with atelectasis by painless bronchoscopy.
To analyze the diagnostic characteristics and clinical related factors of patients with atelectasis by painless electronic bronchoscopy. A retrospective analysis was performed on 70 patients with atelectasis admitted to Xuancheng People's Hospital from April 2019 to June 2021. The clinical data of the patients and the diagnosis characteristics under painless electronic bronchoscope were analyzed, and the clinical related factors were investigated. Seventy patients with atelectasis underwent pathological examination and bacteriological examination after painless electronic bronchoscopy, including 16 cases (22.86%) of inflammation, 11 cases (15.71%) of tuberculosis, 36 cases (51.43%) of tumor, one case (1.43%) of inflammatory polyp, one case (1.43%) of congenital dysplasia, two cases (2.86%) of foreign body inhalation, and three cases (4.29%) of other symptoms. Male patients with atelectasis showed most cauliflower-like tumors and mucosal swelling under electronic bronchoscopy (P<0.05), while female patients showed scar occlusion/stenosis at most (P<0.05). Middle-aged and elderly patients under electronic bronchoscopy showed most cauliflower-like tumors, scar stenosis/occlusion and mucosal swelling cavity, while young patients mainly showed necrosis and purulent secretions. Heavy smokers were most likely to have cauliflower-like tumors, while non-smokers were predominantly with scar stenosis/occlusion. Painless electronic bronchoscopy is of great value in the clinical diagnosis of patients with atelectasis, and it is likely to further clarify the etiology of atelectasis. Age, sex, and quantity of smoking may be clinical factors associated with atelectasis.


Evidence that gonadotropin-releasing hormone II is not a physiological regulator of gonadotropin secretion in mammals.
Gonadotropin-releasing hormone (GnRH)-II stimulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion when administered at high doses in mammals, and this effect has been assumed to be mediated through the GnRH-II receptor expressed on gonadotropes. This study used two selective GnRH-I receptor antagonists to test the alternative hypothesis that GnRH-II acts through the GnRH-I receptor to elicit gonadotropin secretion. The antagonist, antide, was used to characterize the receptor-relay because it was a pure antagonist in vitro based on inositol phosphate responses in COS-7 cells transfected with either mammalian GnRH-I and GnRH-II receptors and, in vivo, potently antagonized the gonadotropin-releasing effect of a single injection of 250 ng GnRH-I in our sexually inactive sheep model. In a series of studies in sheep, antide (i). blocked the acute LH response to a single injection of GnRH-II (20 microg antide: 10 microg GnRH-II); (ii). blocked both the acute, pulsatile LH response and the FSH priming response to 2-hourly injections of GnRH-II over 36 h (100 microg antide/8 h: 4 microg GnRH-II/2 h); and (iii). chronically blocked both the pulsatile LH response and the marked FSH priming response to 4-hourly injections of GnRH-II over 10 days (75 microg antide/8 h: 4 microg GnRH-II/4 h). In two final experiments, the GnRH-I antagonist 135-18, shown previously to agonize the mammalian GnRH-II receptor, blocked the gonadotropin-releasing effects of GnRH-I (250 ng) but failed to elicit an LH response when given alone, and simultaneous administration of GnRH-II (250 ng) failed to alter the LH-releasing effect of GnRH-I (50-500 ng). These data thus support our hypothesis. Based on additional literature, it is unlikely that the GnRH-II decapeptide is a native regulator of the gonadotrope in mammals.


The definition and classification of disasters.
The universe, we are told, began with a big bang, and ever since, nature has provided a series of unexpected bangs and calamities of one type or another. Since the advent of the industrial revolution, man has been more or less controlling larger and larger amounts of energy. World population has rocketed. The interaction of crowded humanity and escalating energy has added a series of man-made disasters to the continuing natural calamities.


[SARS, avian influenza, and human metapneumovirus infection].
Beginning in the 1950s respiratory viruses have been gradually discovered by isolation in cell cultures The last were the coronaviruses in the 1960s. No new respiratory viruses were discovered until 2001 when human metapneumovirus was found in respiratory specimens from children with bronchiolitis. A year later, in November 2002, severe acute respiratory syndrome (SARS) suddenly appeared as atypical pneumonia. A novel virus belonging to the Coronaviridae family was found to be a cause of this infection. In 2004, a second coronavirus was discovered (CoV-NL63) and in 2005 a third new coronavirus was described (CoV-HKU1). In addition, several subtypes of the influenza A virus, previously known to infect only poultry and wild birds, were recently found to have been directly transmitted to humans. Respiratory infection has been a considerable problem for humans for centuries. Now, in the 21st century, with new associated viruses continuously emerging, it remains an important field for work.


Active Solidarity and Its Discontents.
Traditional welfare states were based on passive solidarity. Able bodied, healthy minded citizens paid taxes and social premiums, usually according to a progressive taxation logic following the ability to pay principle. Elderly, fragile, weak, unhealthy and disabled citizens were taken care of in institutions, usually in quiet parts of the country (hills, woods, sea side). During the nineteen eighties and nineties of the twentieth century, ideas changed. Professionals, patients and policy makers felt that it would be better for the weak and fragile to live in mainstream society, rather than be taken care of in institutions outside society. This might be cheaper too. Hence policy measures were taken to accomplish deinstitutionalization. This article discusses the implications of deinstitutionalization for distributive justice. It is argued that the weakest among the weak and fragile stand to lose from this operation. For able bodied citizens deinstitutionalization entails a move from passive to active solidarity. Rather than just pay taxes they have to actively care for and help the needy themselves. The move from passive to active solidarity tends to take advantage of benevolent citizens and burden the socioeconomically disadvantaged. This may be a reason to reconsider the policy move toward deinstitutionalization.


Testicular torsion: usefulness of contrast-enhanced power Doppler sonography.
A 13-year-old-boy with suspected left testicular torsion was referred to our institute. During preparation, a significant decrease of signals on the left testis was found, however, slight blood flow was detected by the ultrasound examination enhanced by Levovist. As a result of the examination we left the testis intact, although the color of the testicular parenchyma remained black. One year after the surgery, an ultrasound examination was done again and good vascurality was observed.


Adult bone marrow-derived stem cells in muscle connective tissue and satellite cell niches.
Skeletal muscle includes satellite cells, which reside beneath the muscle fiber basal lamina and mainly represent committed myogenic precursor cells, and multipotent stem cells of unknown origin that are present in muscle connective tissue, express the stem cell markers Sca-1 and CD34, and can differentiate into different cell types. We tracked bone marrow (BM)-derived stem cells in both muscle connective tissue and satellite cell niches of irradiated mice transplanted with green fluorescent protein (GFP)-expressing BM cells. An increasing number of GFP+ mononucleated cells, located both inside and outside of the muscle fiber basal lamina, were observed 1, 3, and 6 months after transplantation. Sublaminal cells expressed unambiguous satellite cell markers (M-cadherin, Pax7, NCAM) and fused into scattered GFP+ muscle fibers. In muscle connective tissue there were GFP+ cells located close to blood vessels that expressed the ScaI or CD34 stem-cell antigens. The rate of settlement of extra- and intralaminal compartments by BM-derived cells was compatible with the view that extralaminal cells constitute a reservoir of satellite cells. We conclude that both muscle satellite cells and stem cell marker-expressing cells located in muscle connective tissue can derive from BM in adulthood.


Synergistic interaction between trifluorothymidine and docetaxel is sequence dependent.
Docetaxel is a microtubule inhibitor that has actions in the S and G(2)-M phase of the cell cycle. The pyrimidine trifluorothymidine (TFT) induces DNA damage and an arrest in the G(2)-M phase. TFT, as part of TAS-102, has been clinically evaluated as an oral chemotherapeutic agent in colon and gastric cancer. The aim of the present study was to determine the optimal administration sequence of TFT and docetaxel and to investigate the underlying mechanism of cytotoxicity. Drug interactions were examined by sulforhodamine B assays and subsequent combination index analyses, and for long-term effects the clonogenic assay was used. A preincubation with docetaxel was synergistic in sulforhodamine B (combination index 0.6-0.8) and clonogenic assays, and was accompanied by a time-dependent cell death induction (17-36%), the occurrence of polynucleation (22%), and mitotic spindle inhibition as determined by flow cytometry and immunostaining. Interestingly, administration of TFT followed by the combination displayed strong antagonistic activity, and was accompanied by less polynucleation and cell death induction than the synergistic combinations. Western blotting showed that the G(2)-M-phase arrest (25-50%) was accompanied by phosphorylation of Chk2 and dephosphorylation of cdc25c in the synergistic combinations. Together, this indicates that synergistic activity requires docetaxel to initiate mitotic failure prior to the activation of TFT damage signaling, whereas antagonism is a result of TFT cell cycle-arrested cells being less susceptible to docetaxel. Caspase 3 activation was low after docetaxel, suggestive of caspase-independent mechanisms of cell death. Taken together, our models indicate that combination treatment with docetaxel and TFT displays strong synergy when docetaxel is given first, thus providing clues for possible clinical studies.


Absence of long-term potentiation in the subcortically deafferented dentate gyrus.
All subcortical afferents to the dorsal hippocampus, running in the fimbria-fornix and supracallosal path, were removed by aspiration. Three to 5 months later the rats were implanted with chronic recording electrodes in the dentate gyrus and CA1 region, and stimulating electrodes in the angular bundle. In non-lesioned rats, high-frequency trains delivered to the angular bundle gave rise to a sustained increase of the evoked population spike in the dentate gyrus. In lesioned animals, high-frequency stimulation resulted in only short-lasting changes, and by 15 min after the conditioning trains the amplitude of both the population spike and field postsynaptic potentials returned to baseline. In lesioned rats large amplitude interictal spikes (less than 40 ms, 3-8 mV) occurred spontaneously. These findings suggest that either (1) coactivation of entorhinal and subcortical inputs is essential for the induction of long-lasting plastic changes in the dentate gyrus, or (2) the long-term potentiation mechanism is saturated by the chronically occurring interictal discharges in the subcortically denervated dentate gyrus.


MHC Class I Immunopeptidome: Past, Present, and Future.
In the 35 years since the revelation that short peptides bound to major histocompatibility complex class I and II molecules are the secret of the major histocompatibility complex-restricted nature of T-cell recognition, there has been enormous progress in characterizing the immunopeptidome, the repertoire of peptide presented for immunosurveillance. Here, the major milestones in the journey are marked, the contribution of proteasome-mediated splicing to the immunopeptidome is discussed, and exciting recent findings relating the immunopeptidome to the translatome revealed by ribosome profiling (RiboSeq) is detailed. Finally, what is needed for continued progress is opined about, which includes the infusion of talented young scientists into the antigen-processing field, currently undergoing a renaissance; thanks in part to the astounding success of T-cell-based cancer immunotherapy.


Knowledge of Turkish mothers with children in the 0-13 age group about cancer symptoms.
There have been few studies in Turkey on the incidence of childhood cancers. A mother's knowledge about signs and symptoms of cancer is important for early diagnosis, effective treatment, and improvement of life expectancy. This study was conducted with a group of mothers of children, aged 0-13, at a Family Health Center (FHC) in Turkey's Eastern Black Sea Region, to analyze their knowledge about cancer symptoms in childhood. The study group of this descriptive/cross-sectional research comprised 2,061 mothers, ages 19-49, at an FHC in the Eastern Black Sea Region in February 1, 2011 - June 1, 2011. Before the study, permission was obtained from the local ethics board and the institutions concerned. A value of p<0.05 was accepted as statistically significant. Of the mothers, 34.9% were between the ages of 40-47, 40.5% had three children, 73.8% had no experience with children with cancer, 45.9% said they learned about cancer on television, 39.7% stated that the primary reason for childhood cancer was the mother's smoking during pregnancy, 68.8% said that early diagnosis would save a child, and 98% wanted to learn about childhood cancer. It was determined that the mothers' knowledge of cancer was deficient.


Is the human chorionic gonadotropin secreted by ectopic trophoblast different from that in normal intrauterine pregnancies?
To determine whether different isoforms of hCG are secreted by trophoblast tissue from ectopic pregnancy (EP). Retrospective study of surgically confirmed EPs compared with normal pregnancies. Teaching hospital in South Africa. One hundred patients with EPs and 120 patients with normal pregnancies. Isoforms of hCG were measured by specific immunoassays, lectin binding, and examination of disappearance rates of hCG after surgical clearance of EP. There were no obvious differences between the two types of pregnancy apart from a lower binding of beta-subunit immunoactivity to ricin 120. No clinically useful diagnostic measures to distinguish hCG from normal and EPs were found. No obvious differences were found in the isoforms of hCG between the two types of pregnancy using these methods.


Influence of puffing conditions on the carbonyl composition of e-cigarette aerosols.
Owing to their harmful effects on human health, the presence of carbonyl compounds in e-cigarette aerosols raises concerns. To date, the reported concentration levels in e-vapors vary greatly between studies and several factors that markedly influence carbonyl emission during vaping have been highlighted including the heating temperature, the power supply, the device architecture, the filling level of the tank and the main e-liquid constituents. This study investigated the impact of puffing regimen parameters on the carbonyl composition of e-cigarette aerosols with the aim of: (1) better estimating the variability of carbonyl emissions depending on puffing conditions; (2) highlighting puffing profiles that increase the exposure to carbonyls; and (3) estimating to what extent puffing topography could be implied in the variability of carbonyl concentrations reported in the current literature. E-vapors from a single e-liquid were generated from two e-cigarette models with a smoking machine. A total of 7 different puffing regimens were used to individually study the influence of the puff volume, duration and frequency. Carbonyls were collected by DNPH cartridges and analysed by HPLC-UV. E-liquid consumption and e-vapor temperature were also monitored. E-vapor concentrations of formaldehyde, acetaldehyde, acetone, acrolein, propionaldehyde and methylglyoxal were affected, sometimes differently, by the modification of the puffing regimen, as well as by the e-cigarette model. For example, formaldehyde concentration ranged from 20 to 255 ng/puff depending on the puffing conditions. The results of principal component analyses, applied to the concentration data sets for the 6 carbonyls, suggest that the studied parameters interact and highlight some "carbonyl-emitting" combinations of concern (e-cigarette model/puffing regimen). However, the highest concentrations measured in the present study remain far lower than those observed in conventional cigarette mainstream smoke. This study confirms that the chosen puffing regimen contributes a part of the observed variability in the carbonyl levels reported in the scientific literature, hampering comparisons between studies and making interpretation difficult. Thus, harmonized and realistic protocols for the assessment of e-cigarette toxicity by physicochemical or experimental approaches are clearly needed.


Effect of ingestion of cow's milk protein hydrolysate formulas on alpha-casein-specific immunoglobulin E and G1 antibody responses in naïve and sensitized mice.
Cow's milk protein hydrolysate formulas are widely used for genetically predisposed atopic infants. Whether hydrolysate formulas can induce oral tolerance to alpha-casein was studied for the first time in naive and sensitized mice. Using immunoblotting, residual antigenicity to alpha-casein was examined for in animals fed hydrolysate formulas. Naïve mice fed hydrolysate formulas for 1 to 4 weeks were later sensitized with alpha-casein. Another group of mice sensitized first with alpha-casein were then fed hydrolysate formulas continually for 12 weeks. Oral tolerance measured by immunoglobulin (Ig)E and IgG1 antibody responses to alpha-casein was induced in naïve mice fed NAN for 1 week or NAN-HA for 4 weeks. IgE responses to alpha-casein were suppressed in mice fed NAN-HA for 1 week or Neoangelac FL for 4 weeks. In contrast, mice fed Alfare, Pepti-Junior, or Pregestimil for 1 to 4 weeks did not develop tolerance to alpha-casein. Antibody responses to alpha-casein were not significantly suppressed in sensitized mice fed NAN or hydrolysate formulas for 12 weeks. Primary IgE responses to alpha-casein are readily suppressed in naïve mice first fed cow's milk formula or partially hydrolyzed formula for 1 week. Conversely, ongoing IgE, IgG1, and IgG antibody responses to alpha-casein are poorly suppressed in previously sensitized mice even after prolonged feeding of cow's milk formula or hydrolysate formulas.


Combined analysis of pri-miR-34b/c rs4938723 and TP53 Arg72Pro with cervical cancer risk.
miR-34 family members can form a p53-miR-34 positive feedback loop and induce apoptosis, DNA repair, angiogenesis, and cell cycle arrest. We conducted a case-control study to examine whether two polymorphisms (i.e., rs4938723 in the promoter of pri-miR-34b/c and TP53 Arg72Pro) were linked to the carcinogenesis of cervical cancer among Chinese Han women. Genotypes of the two polymorphisms in 328 cervical cancer patients and 568 control subjects were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. We found a significantly increased cervical cancer risk in the pri-miR-34b/c rs4938723 under dominant and overdominant model (CT/CC vs. TT: adjusted OR = 1.34, 95 % CI = 1.01-1.77; CT vs. TT/CC: adjusted OR = 1.37, 95 % CI = 1.05-1.80, respectively). Increased cervical cancer risks were also found in the TP53 Arg72Pro under a heterozygous comparison and overdominant model (CG vs. GG: adjusted OR = 1.44, 95 % CI = 1.06-1.95; CG vs. GG/CC: adjusted OR = 1.47, 95 % CI = 1.12-1.94, respectively). Stratification analysis showed that patients carrying the pri-miR-34b/c rs4938723 CT genotype had a significantly increased risk for developing poorly differential status and clinical stage I. Moreover, increased cancer risks were observed for the TP53 Arg72Pro polymorphism in patients with poorly differential status, clinical stage II, and without lymph node metastasis. Combined analysis revealed that the genotypes of rs4938723 CT/CC and TP53 Arg72Pro CG/CC had an increased cervical cancer risk (OR = 2.21, 95 % CI = 1.38-3.53). These findings suggest that the pri-miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may contribute to the genesis of cervical cancer.


Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study.
14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.


Effect of perioperative blood pressure variability on cerebral hyperperfusion syndrome after carotid artery stenting: A retrospective study.
To investigate the effect of perioperative blood pressure variability on cerebral hyperperfusion syndrome after carotid artery stenting. A retrospective analysis was conducted of data collected from 418 patients who underwent carotid artery stenting in Guangxi Zhuang Autonomous Region People's Hospital in China. The blood pressure data were collected during operation (after balloon dilation, before stent release, after stent release) and within 3 days after the operation. The blood pressure variability was evaluated by measuring the mean, maximum, minimum, max-min, standard deviation (SD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The correlation between blood pressure variability and cerebral hyperperfusion syndrome was analysed. Blood pressure data from 418 patients were analysed. Twenty patients (4.8%) developed cerebral hyperperfusion syndrome. The parameters of blood pressure variability were divided into four groups according to quartile. After adjusting for age, symptomatic carotid stenosis, unilateral carotid stenosis, bilateral carotid stenosis, collateral circulation, diabetes mellitus and chronic kidney disease, multivariate analysis showed that SBPMax, SBPMin, SBPMax-Min, SBPCV, DBPSD, DBPMax, DBPMin, DBPMax-Min and DBPCV were associated with the occurrence of cerebral hyperperfusion syndrome (P < 0.05), respectively. This study suggests that blood pressure variability during the perioperative period may increase the risk of cerebral hyperperfusion syndrome.


Barriers and attitudes towards cervical cancer screening in primary healthcare in Poland - doctors' perspective.
Healthcare systems have adopted different strategies to reduce the burden of cervical cancer. In Poland, a population-based screening program was implemented in 2006, leading to a downward trend in cervical cancer burden. However, screening rates are still low in relation to other EU member states. In Poland, Pap smears are mainly performed by gynecologists rather than Primary Health Care (PHC) physicians. Little is known about the experiences and attitudes of the latter regarding cervical cancer screening in a PHC setting. A cross-sectional questionnaire-based survey was carried out among 43 PHC physicians from the Malopolska region in Poland. Barriers and attitudes towards cytology in a PHC setting were evaluated. Approximately 35% of surveyed physicians reported having experience in performing cytology. Almost 75% of PHC physicians lacked the necessary equipment in their office to perform the screening. None of the studied physicians performed Pap smears in their office at the time. The reasons included: shortage of competence (78.57%) and time (69.05%), the perception of Pap smears as a task for gynecologists (69.05%), the lack of financial incentives (61.90%), and the belief that their patients would be unwilling to undergo the test in their PHC physician's office (33.33%). More than three quarters (76.74%) declared they would be ready to perform Pap smears if the tests were additionally paid. No significant associations between PHC physicians' characteristics and their willingness to perform cytology screening were found. The primary barrier to perform Pap smears by PHC physicians does not lie in their personal reluctance but in the organization of the healthcare system. Provision of required training and proper funding allocation can likely improve the screening rate of cervical cancer in Poland.


The influence of a male's dominance status on female choice in Syrian hamsters.
This study evaluated the importance of dominance status on mate selection in Syrian hamsters. In one experiment, sexually receptive females were allowed to choose between tethered males which differed in status. The choice was consistently in favor of the dominant male. The female spent more time in lordosis in the presence of the dominant male. The dominant also obtained a significantly greater number of intromissions. A second experiment investigated whether prior familiarization was essential to permit a female to express mating preferences in a situation where she was free to interact with three males. Again, the dominants were most often preferred and obtained greater sexual access to the female. Prior familiarization or extensive contact with the males was not necessary to support the female's selection of the dominant as a mating partner. The choice occurred quickly, generally within 5 min after contacting the males. Although females did mate with the subordinates, this typically occurred late in the tests. The significance of these data with respect to mate choice and probable paternity effects are discussed.


Associations Between Practice Characteristics and Demonstration of Stage 1 Meaningful Use for the Electronic Health Record Incentive Program.
The Medicare and Medicaid meaningful use (MU) incentive programs promote adoption and "meaningful use" of certified electronic health records among hospitals and eligible providers in outpatient settings, with a goal of improving the quality of patient care. Despite the potential importance of MU for providers and patients, little is currently known about the practice characteristics that facilitate providers' demonstration of MU. This study examined whether selected practice characteristics were associated with providers' meeting Stage 1 MU objectives at the end of 1 year in a single large North Carolina integrated delivery system. Our retrospective database analysis included all 702 eligible providers from 54 ambulatory care practices on the main campus of the University of North Carolina Health Care System. We assessed associations between providers' ability to meet Stage 1 MU objectives as of December 2012 and the following practice characteristics: practice specialty, size, and mix of Medicare- and Medicaid-eligible providers. The following practice characteristics were associated with providers' ability to meet MU objectives: primary care practices as compared to specialty practices (odds ratio [OR] = 2.49; 95% CI, 1.11-5.62), small practices as compared to medium-sized practices (OR = 0.29; 95% CI, 0.09-0.89), and the presence of only Medicare-eligible providers in the practice as compared to the presence of only Medicaid-eligible providers (OR = 6.48; 95% Cl, 1.08-38.97). Because our sample was drawn from a single integrated delivery system, results may not be generalizable to all ambulatory practice settings. This study suggests that larger practices, primary care practices, and practices comprised of Medicare-eligible providers may be better able to meet MU objectives. Further research is needed to evaluate strategies that account for practice characteristics and other contextual factors in the MU implementation process.


Design, Synthesis, and Biological Evaluation of 4-Phenoxyquinoline Derivatives Containing Benzo[d]thiazole-2-yl Urea as c-Met Kinase Inhibitors.
A series of novel 4-phenoxyquinoline derivatives containing the benzo[d]thiazole-2-yl urea moiety were synthesized and evaluated for their cytotoxicity against the HT-29, MKN-45, and H460 cell lines. The structures of the target compounds were confirmed by (1) H NMR and MS spectra. Most of them showed moderate to excellent potency against the three tested cell lines. Especially, compound 23 was identified a promising agent (c-Met IC50 = 17.6 nM), showing the most potent anticancer activities with IC50 values of 0.18, 0.06, and 0.01 µM against the HT-29, MKN-45, and H460 cell lines, respectively. The docking results of 23 with the c-Met kinase model 3LQ8 showed a specific binding mode between the ligand and the target protein.


Predictors of deep-vein thrombosis in subarachnoid hemorrhage: a retrospective analysis.
Subarachnoid hemorrhage is a severe subtype of hemorrhagic stroke, and deep-vein thrombosis is a frequent complication detected in these patients. In addition to other well-established risk factors, the early activation of coagulation systems present in patients with subarachnoid hemorrhage could potentially play a role in the incidence of deep-vein thrombosis. This study aims to identify possible predictors for deep-vein thrombosis related to subarachnoid hemorrhage. We conducted a retrospective cohort study on patients with a diagnosis of subarachnoid hemorrhage who presented to our institution between 1 January 2014 and 1 August 2018. We reviewed electronic medical records and analyzed several parameters such as Fisher scale, World Federation of Neurosurgical Surgeons scale, aneurysm site, surgical or endovascular treatment, decompressive craniectomy, vasospasm, infection (meningitis and pneumonia), presence of motor deficit, length of stay in the ICU, length of hospital stay, number of days under ventilator support, d-dimer at hospitalization, and the time to thromboprophylaxis (days). The univariate analysis showed that intraparenchymal cerebral hemorrhage, d-dimer at hospitalization, the time to thromboprophylaxis, motor deficit, and aneurysm located at the internal carotid artery were statistically significant factors. Intraparenchymal cerebral hemorrhage (OR 2,78 95%CI 1.07-7.12), motor deficit (OR 3.46; 95%CI 1.37-9.31), and d-dimer at hospitalization (OR 1.002 95% CI 1.001-1.003) were demonstrated as independent risk factors for deep-vein thrombosis. Length of hospital stay was also found to be significantly longer in patients who developed deep-vein thrombosis (p value 0.018). Elevated d-dimer level at the time of hospitalization, motor deficit, and the presence of an intraparenchymal hemorrhage are independent risk factors for deep-vein thrombosis. Patients with DVT also had a significantly longer hospital stay. Even though further studies are needed, patients with elevated d-dimer at hospitalization and intraparenchymal cerebral hemorrhage may benefit from a more aggressive screening strategy for deep-vein thrombosis.


Impact of perinatal prebiotic consumption on gestating mice and their offspring: a preliminary report.
To assess the impact of prebiotic supplementation during gestation and fetal and early neonatal life, gestating BALB/cj dam mice were fed either a control or a prebiotic (galacto-oligosaccharides-inulin, 9:1 ratio)-enriched diet throughout pregnancy and lactation, and allowed to nurse their pups until weaning. At the time of weaning, male offspring mice were separated from their mothers, weaned to the same solid diet as their dam and their growth was monitored until killed 48 d after weaning. Prebiotic treatment affected neither the body-weight gain nor the food intake of pregnant mice. In contrast, at the time of weaning, pups that had been nursed by prebiotic-fed dams had a higher body weight (11.0 (se 1.2) g) than pups born from control dams (9.8 (se 0.9) g). At 48 d after weaning, significantly higher values were observed for colon length and muscle mass in the offspring of prebiotic-fed dams (1.2 (se 0.1) cm/cm and 5.7 (se 1.8) mg/g, respectively), compared with control offspring (1.1 (se 0.1) cm/cm and 2.9 (se 0.9) mg/g, respectively), without any difference in spleen and stomach weight, or serum leptin concentration. The present preliminary study suggests that altering the fibre content of the maternal diet during both pregnancy and lactation enhances offspring growth, through an effect on intestinal and muscle mass rather than fat mass accretion.


Multistep adsorption of anionic dyes on silica/chitosan hybrid. 1. Comparative kinetic data from liquid- and solid-phase models.
In this work, a hybrid silica/chitosan was synthesized and characterized by nitrogen elemental analysis and thermal analysis (TG, DTG, DTA, and DSC) and BET surface area. The hybrid was used in adsorption studies of two anionic dyes from aqueous solutions. A rise of temperature accelerates mass transfer of dyes into the hybrid. However, the maximum adsorption capacities reach similar values from 25 to 55 degrees C. The kinetic data were first evaluated in relation to the decrease of the time-related residual concentration of the dyes in solution, where the second-order model has presented the best fitting. The solid-phase interaction of dye data presents a rough fitting to the traditional first-order Lagergren kinetic model. However, a modified Avrami kinetic equation was successfully fitted to the kinetic quantities, where from five to seven kinetic regions were found. A pore-diffusion model has also demonstrated that the diffusion is the rate-controlling interaction mechanism. However, the experimental-calculated comparative values are the best way to evaluate a specific aqueous- or solid-phase kinetic model.


Minimally invasive perventricular device closure of doubly committed sub-arterial ventricular septal defects: single center long-term follow-up results.
To evaluate the long-term safety and efficacy of using perventricular device closure in treating selected patient with doubly committed sub-arterial ventricular septal defect (VSD) METHODS: During July 2007 and April 2011, 86 patients with doubly committed subarterial VSD who met the inclusion criteria were enrolled in this study. Perventricular closure was attempted using a unique design eccentric device under the guidance of transesophageal echocardiography. Complications such as residual shunt, arrhythmia, valve regurgitation were all recorded in postoperative period and during follow-up. Multiple logistic regression analysis was performed to study risk factors for procedure failure and complications. Perventricular device closure was successfully done in 75 patients (87.2 %) with mean age 7.0 ± 7.0 years old, VSD size 4.8 ± 1.5 mm and device size 6.7 ± 1.7 mm. Complete closure rate was achieved in 94.7 % at discharge and 96 % during follow-up. No severe complications such as device embolism, significant arrhythmia, left ventricular outflow tract obstruction as well as obvious valve regurgitation were noted during follow-up (Mean 4.5 ± 1.5 years). Procedure induced trivial-mild grade aortic valve regurgitation (AR) was noted in 16 (21.3 %) patients at discharge while 8 of them resolved during follow-up. Multivariable analysis revealed that procedure-induced AR was associated device diameter to patients' weight (OR=12.3 95 % CI 1.5- 99.2). Perventricular device closure was failed in 11 patients, preoperative aortic valve prolapse was the major risk factor for failure of the procedure (OR=65 95 % CI 7.5- 564.1). Perventricular closure of doubly committed subarterial VSDs appears to be a safe and effective minimally invasive treatment option in selected patients with good long-term outcomes. Unique Identifier: ChiCTR-TNC-00000203 .


Envelopes: presidential address.
The fabric of medical care has been altered during the past 2 decades. Initially this alteration was furtive but it rapidly escalated, producing change that will be irrevocable. Physicians, dedicated to caring for their patients, frequently were found struggling in the wake of the changes in the health care system. In most situations they found themselves swept aside from crucial decision making because of timidity, practice obligations, and absence of knowledge related to "medical business." With about 600 managed care operations in the United States, physicians can no longer afford to sit in the stands and just watch the play on the field. Participation is crucial and must be accompanied by additional learning, such as masters degrees in business administration or MBAs. This will allow the new players to read the playbook of business medicine. Although on-the-job training is possible, it usually has a slow learning curve as a result of diluting the new assignment with practice obligations. Despite these formidable challenges, physicians must enter the local, state, and national arenas and participate. Despite change and reaction to change, physicians have an irrevocable trust that cannot be withdrawn or overlooked. It has been earned and pervades every facet of our professional careers. The physician has an uncompromising duty and privilege to care for his or her patient in the highest and most ethical manner, a duty that will remain forever. This will never change!


Lipid peroxidation in platelets from patients with Spielmeyer-Vogt-Batten syndrome.
Platelet lipid peroxidation was studied in normal controls, subjects with epilepsy and patients with the Spielmeyer-Vogt-Batten syndrome. The results showed wide intra- and inter-individual variation, particulary in the latter group. The mean value in Spielmeyer-Vogt-Batten syndrome was not significantly higher than the mean values for the other two groups.


Correlation investigation between a single nucleotide polymorphism in ADAMTS14 (rs4747096) and osteoarthritis: a meta-analysis.
Current evidence of the association between a single nucleotide polymorphism (SNP) in ADAMTS14 (rs4747096) and osteoarthritis (OA) is controversial. This study aimed to determine whether the ADAMTS14 SNP is closely related to OA risk. An electronic search of for the association between the rs4747096 polymorphisms and OA was performed using four online databases (updated on September 10, 2022). The association between susceptibility to OA and rs4747096 polymorphism was evaluated in four genetic models: the allele (mutation [A] vs. wild type [G]), additive (AA vs. GG and AG vs. GG), recessive (AA vs. AG + GG), and dominant (AA + AG vs. GG). This meta-analysis was performed in the R software, and effects were assessed using odds ratios (ORs) and 95% confidence intervals (CI). Four studies (707 cases in the case group and 859 cases in the control group) were included. The results of the meta-analysis showed that, except in the recessive genetic model, there was a significant correlation between OA risk and the rs4747096 polymorphism using the allele (OR [95% CI] = 1.48 [1.26-1.73], P < 0.001), additive (AG vs. GG, OR [95% CI] = 2.56 [1.79-3.65], P < 0.001; AA vs. GG, OR [95% CI] = 2.81 [1.98-3.98], P < 0.001), and dominant (OR [95% CI)] = 1.72 [1.34-2.2], P < 0.001) genetic models. The ADAMTS14 rs4747096 polymorphism is associated with susceptibility to OA.