High affinity of carozolol for beta-adrenoceptors coupled to the adenylyl cyclase in ventricular myocardium of kitten and Xenopus laevis.
Catecholamine-induced stimulation of adenylyl cyclase in ventricular membranes of kitten and Xenopus laevis was antagonized competitively by carazolol. Apparent equilibrium constants ranging between 100-170 pM were estimated for the beta-adrenoceptor-carazolol complex.


Pediatric urodynamics: baseline audit and effect on management.
To undertake a baseline audit of our pediatric urodynamic service, identifying areas for improvement, and to determine whether clinical management was affected by urodynamic results. All pediatric urodynamic studies during one calendar year were reviewed to determine the quality of reports that were issued and to assess any problems encountered. A postal questionnaire was sent to all referring doctors to determine whether the urodynamic report had influenced management. In all, 48 children attended for videocystometry, with successful tests in 39 (81%); 97% of written reports were judged to contain adequate information. In all, 33 postal questionnaires were returned (85%); in 30 (91%) the referring clinician felt that the urodynamic result had directly influenced management. The audit highlighted areas for improvement, which have been addressed. The response from the postal questionnaire showed that urodynamics directly influenced the management of children with complex urological and neurological abnormalities.


4-[18F]fluoroarylalkylethers via an improved synthesis of n.c.a. 4-[18F]fluorophenol.
This paper describes the improved synthesis of n.c.a. 4- 18F]fluorophenol for the preparation of 18F-labeled alkylarylethers. Nucleophilic fluorination of substituted benzophenone derivatives yielded n.c.a. 4- 18F]fluoro-4'-substituted benzophenones with 80- 90% RCY, which were converted to benzoic acid phenylesters by treatment with peracetic acid. Strong electron-withdrawing substituents like nitro, cyano and trifluoromethyl favor a fluorophenyl-to-oxygen migration resulting in the formation of corresponding benzoic acid fluorophenylesters. N.c.a. 18F]fluorophenol is almost quantitatively formed after hydrolysis and can easily be converted with alkylhalides into n.c.a. 18F]fluoroarylalkylethers.


The perceptions and experiences of medical students in a pediatric buddy program: a qualitative study.
Partnership programs between medical students and patients provide students with non-clinical experiences that enhance medical learning, especially with respect to humanistic care. We explored the perceptions and experiences of medical students in a pediatric oncology buddy program. Using a basic interpretive qualitative approach, we conducted interviews with 15 medical students at three time points: before meeting his/her buddy (pre-interview), four months into the partnership (4-month interview), and at the end of the partnership (post interview). We then conducted a thematic analysis of the interview data. All students in the program who met the study criteria (N = 15/16) participated. The medical students highlighted that: (a) providing support to buddies and their families is important; (b) providing care to children with serious illnesses is emotionally difficult; (c) developing deep connections with buddies and their families is rewarding; and (d) gaining empathy and personal fulfillment from buddies and their families is inevitable. This study provides an understanding of medical students' perceptions and experiences in a pediatric oncology, non-clinical buddy program. Tailored one-on-one partnerships between medical students and pediatric oncology patients play an important role in medical education and contributes to the teaching of humanistic care.


Relationships between diurnal changes in blood pressure and catecholamines among Filipino-American and European-American women.
Studies show that diurnal blood pressure (BP) sensitivity to epinephrine (EPI) in African-American women is significantly greater than that of European-American (EA) women. Few if any studies have examined diurnal catecholamine-BP relationships in women of other ethnic groups. The purpose of this study was to compare the effects of diurnal changes in EPI and norepinephrine (NE) on the diurnal changes in BP between Filipino-American (FA) and EA women. The subjects included 31 FA and 27 EA nurses and nurses aides and eight FA and 19 EA hotel workers from Hawaii who wore an ambulatory BP monitor and collected timed urine specimens (4 h at work, approx.4 h at home and approx. 8 h overnight) for assay of EPI and NE. Proportional changes in systolic and diastolic BP from sleep to work and sleep to home were examined using ANCOVA models including fixed effect-covariate interactions, with ethnicity as a fixed factor, and BMI and the appropriate proportional change in EPI or NE as covariates. The results show that there was no association between changes in EPI and BP, either overall or by ethnic group; however, overall changes in diastolic BP from sleep to work tended to be smaller among the FAs (P < 0.06). There was also an interactive effect of NE and ethnic group on diastolic BP such that among FAs, as diastolic BP increased, the corresponding NE change decreased (P < 0.039). The relationships between diurnal BP and catecholamine variations differ by ethnicity. Further research is needed to better understand the mechanisms behind the differences and to evaluate whether this vascular tonic relationship has been the focus of natural selective processes.


Evaluation of different biomass materials as feedstock for fermentable sugar production.
Saline crops and autoclaved municipal organic solid wastes were evaluated for their potential to be used as feedstock for fermentable sugar production through dilute acid pretreatment and enzymatic hydrolysis. The saline crops included two woods, athel (Tamarix aphylla L) and eucalyptus (Eucalyptus camaldulensis), and two grasses, Jose tall wheatgrass (Agropyron elongatum), and creeping wild rye (Leymus triticoides). Each of the biomass materials was first treated with dilute sulfuric acid under selected conditions (acid concentration =1.4% (w/w), temperature =165 degrees C, and time =8 min) and then treated with the enzymes (cellulases and beta-glucosidase). The chemical composition (cellulose, hemicellulose, and lignin contents) of each biomass material and the yield of total and different types of sugars after the acid and enzyme treatment were determined. The results showed that among the saline crops evaluated, the two grasses (creeping wild rye and Jose tall wheatgrass) had the highest glucose yield (87% of total cellulose hydrolyzed) and fastest reaction rate during the enzyme treatment. The autoclaved municipal organic solid wastes showed reasonable glucose yield (64%). Of the two wood species evaluated, Athel has higher glucose yield (60% conversion of cellulose) than eucalyptus (38% conversion of cellulose).


Bovine interferon alpha genes. Structure and expression.
The bovine genome contains a gene family of interferon-alpha s (bIFN-alpha) that consists of at least five distinct members. Four of the bIFN-alpha genes isolated show a high degree of homology (97% in the nucleotide sequence and 93% in amino acid sequence). The overall homology in amino acid sequence of bIFN-alpha to human, murine, and rat IFNs-alpha is approximately 60%. Yet there are amino acid clusters (positions 28-41 and 118-146) which are highly conserved throughout the mammalian evolution and in which the overall homology can be as high as 86%. Within the C terminus conserved cluster there is a sequence containing 9 amino acids completely conserved in 16 mammalian IFNs-alpha and of these, 7 are also shared with a similar domain in some bacterial toxins, implying a common functional role for these domains. One of the genes, IFN-alpha C, was expressed in Escherichia coli. The purified bacterial IFN (specific activity, 2 X 10(8) units/mg) exhibited antiviral activity on bovine cells but no detectable activity was demonstrated on human and simian cells.


Stability of a Stochastic Model of an SIR Epidemic with Vaccination.
We prove almost sure exponential stability for the disease-free equilibrium of a stochastic differential equations model of an SIR epidemic with vaccination. The model allows for vertical transmission. The stochastic perturbation is associated with the force of infection and is such that the total population size remains constant in time. We prove almost sure positivity of solutions. The main result concerns especially the smaller values of the diffusion parameter, and describes the stability in terms of an analogue [Formula: see text] of the basic reproduction number [Formula: see text] of the underlying deterministic model, with [Formula: see text]. We prove that the disease-free equilibrium is almost sure exponentially stable if [Formula: see text].


Specific and nonspecific immunisation against parasitic infections.
Parasitic diseases present major problems to man and his domesticated animals but do not respond easily to conventional vaccination procedures. Vaccines including attenuated stains, killed parasites, homogenates and soluble extracts all produce varying degrees of protection but controlled infections and immunisation with heterologous species or nonspecific antigens also induce protective immunity.


Correlation of background parenchymal enhancement on breast MRI with breast cancer.
To evaluate the prognostic value of background parenchymal enhancement (BPE) in breast magnetic resonance imaging (MRI) in women referred to radiological department as a high risk for breast cancer. A retrospective, cross-sectional study included 327 consecutive patients (mean age: 60 years, age range: 30-90 years) who underwent breast MRI and tissue biopsy between 2007 and 2016. All MRI images (T1, T2, and subtraction images) were evaluated visually. The relationship of BPE with patient age, fibroglandular tissue (FGT), Breast Imaging Reporting and Data System (BIRADS) categories, presence of breast cancer, and expression of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), oestrogen receptor (ER), and Ki67 were analysed. Furthermore, all variables were correlated with pre- and postmenopausal status. BPE of bilateral breast showed a weak correlation with FGT (right BPE: r=-0.14, p=0.004; left BPE: r=0.16, p=0.003), a weak negative correlation with patient age (right BPE: r=-0.14, p=0.007; left BPE: r=-0.15, p=0.006), and significant correlation with HER2 (right BPE, p=0.02), left BPE with HER2 was not significant. Among the correlations between BPE and BIRADS, only between right BPE and right BIRADS was significant (p=0.031). No clear evidence of an association between breast MRI BPE and breast cancer in premenopausal and postmenopausal status was observed, and no difference was found between the right and left breasts. The results of the present study showed no significant correlations between BPE and breast cancer. In addition, there was no significant difference between the right and left breast. Hence, BPE of MRI may not be a reliable biomarker of breast cancer development.


Influence of variations in preparation of dental amalgam on dimensional stability and porosities.
The susceptibility of amalgam to deviations in the preparation procedure produced an overall trend for both the setting dimensional stability and the number of porosities. The dimensional stability of ANA 2000 was the least affected by the deviations, while ANA 68 exhibited low susceptibility to the deviations when porosities are concerned. Lowered condensation pressure usually increased both the setting expansion and the number of porosities, and vice versa. Dispersalloy exhibited an increased number of porosities with both higher and lower condensation pressure. Except for ANA 2000, undertrituration caused increased expansion and porosities, while overtrituration resulted in increased contraction but minor effects on porosities. Lower mercury/alloy ratio increased the setting expansion and the number of porosities, while the response to a higher ratio was relatively small with the exception of a markedly increased setting expansion for ANA 68.


SIRT2 promotes the viability, invasion and metastasis of osteosarcoma cells by inhibiting the degradation of Snail.
Osteosarcomas (OS) are highly metastatic and usually lead to poor outcomes. Epithelial-mesenchymal transition (EMT) is reported to be a critical event in metastasis. SIRT2 exerts dual functions in many different tumors. However, the underlying molecular mechanisms of SIRT2 in osteosarcoma cell metastasis and the question of whether SIRT2 regulates EMT have not been fully explored. In this study, we confirmed that SIRT2 was highly-expressed in human osteosarcoma MG63 and Saos-2 cell lines. The viability, migration and invasion of osteosarcoma cells were inhibited by knockdown of SIRT2 and were enhanced by overexpression of SIRT2. Moreover, SIRT2 positively regulated EMT and upregulated the protein levels of the mesenchymal markers N-cadherin and Vimentin and the levels of MMP2 and MMP9. A xenograft mouse model showed that SIRT2 knockdown in osteosarcoma cells led to reduced tumor growth, decreased expression of mesenchymal markers and impaired lung and liver metastasis in vivo. Furthermore, we showed that SIRT2 interacted with and upregulated the protein level of the EMT-associated transcription factor Snail. SIRT2 inhibited Snail degradation via its deacetylase activity. Knockdown of Snail abrogated the promoting effects of SIRT2 on migration and invasion of osteosarcoma cells. In conclusion, SIRT2 plays a crucial role in osteosarcoma metastasis by inhibiting Snail degradation and may serve as a novel therapeutic target to manage osteosarcoma.


Factors Associated with Pre-Vaccination SARS-CoV-2 Infection Risk among Hospital Nurses Facing COVID-19 Outbreak.
The objective of this work was to evaluate the magnitude of COVID-19 spread and the related risk factors among hospital nurses employed in a COVID hospital in Rome, before the beginning of the vaccination programmes commenced in 2021. Participants periodically underwent (every 15-30 days) nasopharyngeal swab and/or blood sample for SARS-CoV-2 IgG examination. From 1 March 2020 to 31 December 2020, we found 162 cases of COVID-19 infection (n = 143 nasopharyngeal swab and n = 19 IgG-positive) in a total of 918 hospital nurses (17.6%). Most SARS-CoV-2-infected hospital nurses were night shift workers (NSWs), smokers, with higher BMI and lower mean age than that of individuals who tested negative. After adjusting for covariates, age (OR = 0.923, 95% C.I. 0.895-0.952), night shift work (OR = 2.056, 95% C.I. 1.320-2.300), smoking status (OR = 1.603, 95% C.I. 1.080-2.378) and working in high-risk settings (OR = 1.607, 95% C.I. 1.036-2.593) were significantly associated with SARS-CoV-2 hospital infection, whereas BMI was not significantly related. In conclusion, we found a high prevalence of SARS-CoV-2 infection among hospital nurses at a Rome COVID hospital in the pre-vaccination period. Smoking, young age, night shift work and high-risk hospital settings are relevant risk factors for hospital SARS-CoV-2 infection; therefore, a close health surveillance should be necessary among hospital nurses exposed to SARS-CoV-2.


Temperature gradients in female reproductive tissues.
Deep body temperature in mammals is generally but incorrectly regarded as uniform. Alterations of temperature in oviducts and preovulatory Graafian follicles may play a vital role in gamete maturation, fertilization and early embryonic development. At a molecular level, the conformation of regulatory proteins is susceptible to changes in temperature. Deviation from physiological temperature during IVF procedures could thereby exert a profound influence on patterns of gene expression as the embryonic genome unfolds during early cleavage stages and act to generate specific anomalies. Systematic studies are urgently required. The temperature of internal body organs in mammals such as rabbits and humans is widely regarded as uniform, but this is not correct. Temperatures in reproductive tissues such as ovaries and oviducts vary according to the stage of a menstrual or oestrous cycle. Such changes in temperature are thought to be critically involved in the maturation of eggs and spermatozoa and thus in events shortly before and after fertilization. Proteins in the cytoplasm and nuclei of eggs and very young embryos respond to small shifts in temperature by changing their three-dimensional shape. Conformational modifications in regulatory proteins in the nucleus would influence patterns of gene expression in developing embryos and may, when perturbed, alter the sexual phenotype of an individual. In the practical context of IVF, studies are needed of the influence of culturing gametes and embryos at different temperatures and ranges of temperature on the patterns of gene expression in preimplantation embryos.


Liquid-scintillation-based anticoincidence counting of Co-60 and Pb-210.
The method of liquid-scintillation-based 4pibeta-gamma anticoincidence counting was employed to assay the radioactivity concentration of acid solutions containing radionuclides (60)Co and (210)Pb (in equilibrium with its daughters). The limiting factors on the accuracy for such activity measurements and suggestions for minimizing such factors are reported.


Base-mediated cascade synthesis of indole diolefins: a route to spiro[cyclopentene-indole]thiones and thiepino[2,3-b]indoles.
Base-mediated cascade reactions of 3-hydroxymethyl-3-propenylindole-2-thiones afforded diolefins and involved deformylation, thioenolate alkylation and the thio-Claisen rearrangement. Subsequent ring-closing metathesis reactions of the diolefins furnished 3-spiro[cyclopentene-indole]-2-thiones or thiepino[2,3-b]indoles.


Treatment of malignant primary vasodepressive neurocardiogenic syncope with a rate responsive pacemaker driven by heart contractility.
In a 41-year-old man suffering from frequent syncope, the tilt test reproducibly induced a primary vasodepressive neurocardiogenic syncope. Pharmacotherapy either failed to prevent the syncope induced at the tilt test or was poorly tolerated. In the minutes preceding the syncope, a dramatic increase in heart contractility was sensed by a microaccelerometer located at the tip of a right ventricular pacing electrode. When the tilt test was repeated with the pacemaker programmed in the DDDR mode, high rate dual chamber pacing occurred during the tilt phase and prevented the syncope. Three months after implantation, the patient remains totally symptom free.


Brachial neuritis following infection with Epstein-Barr virus.
A 54-year-old woman developed stiffness across the shoulders and a mild headache during a motorcycle tour of the U.S.A. On return to the U.K. she complained of persisting exhaustion and painful muscles. Hospital admission was precipitated by her developing weakness in the right arm and paraesthesiae in the fingers. She was found to be suffering from infectious mononucleosis.


[Biopsy and cytology in the diagnosis and treatment of surgical diseases (author's transl)].
Surgical lesions of the gastrointestinal tract are usually of an ulcerous or polypoid nature. The macroscopic pathologic changes can be given a clinical diagnosis only after the histologic findings are known. Endoscopic biopsy meets this purpose. Furthermore, endoscopic snare biopsy can be a curative therapeutic procedure. Cytology should only be used as a method of second choice, for example when stenosis proximal to the lesion hinders biopsy.


Methods to study endocytic trafficking of the EGF receptor.
Endocytosis and postendocytic sorting of epidermal growth factor (EGF) receptor (EGFR) are the major regulators of EGFR signaling. EGFR endocytosis and ubiquitin-dependent lysosomal targeting are also considered to be the prototypic experimental system for studying the molecular mechanisms of stimulus-induced and constitutive endocytic trafficking. Therefore, elucidation of the mechanisms of EGFR endocytosis and its regulation of the signaling network is essential not only for better understanding of the EGFR biology but also for defining general regulatory principles in the endocytosis system. Comprehensive analysis of these mechanisms requires quantitative and physiologically relevant methodological approaches for measuring the rates of EGFR internalization, degradation, and recycling. Basic experimental protocols described in this chapter cover a combination of single-cell microscopy and biochemical methods that are used to follow EGF-induced endocytosis of EGFR in real time, measure the kinetic rate parameters of EGFR internalization and recycling, and analyze EGF-dependent ubiquitination and degradation of EGFR.


Combined Functional and Preservation Rhinoplasty.
Dorsal preservation rhinoplasty has aesthetic advantages over conventional hump takedown rhinoplasty. In dorsal preservation surgery, the nasal vault is treated en bloc. The internal nasal valve angle is not disrupted and there is no need for midvault reconstruction. Two techniques for management of the bony vault exist in dorsal preservation surgery: the let-down and the push-down techniques. There are a variety of techniques used for management of the septum in dorsal preservation. Available patient-reported outcomes of suggest positive results in nasal breathing. More robust data are needed to clarify the functional results of dorsal preservation and compare breathing outcomes.


Reactive nitrogen releases and nitrogen footprint during intensive vegetable production affected by partial human manure substitution.
Evaluating the sustainability of vegetable production is crucial to secure future food supply. A 2-year field study of four different vegetable crops was performed to investigate the effects of inorganic fertilizer and human manure at different ratios on vegetable yields, reactive gaseous nitrogen emissions (GNrEs), reactive nitrogen (Nr) footprint, and net ecosystem economic income (NEEI) by using life cycle analysis. Four fertilization strategies were studied, including CK (no fertilization); CF (inorganic fertilization); CHF1 (human manure /inorganic fertilizer, N ratio = 1:7); and CHF2 (human manure /inorganic fertilizer, N ratio = 1:3). Results showed that compared with CF treatment, both CHF1 and CHF2 treatments increased the N2O + NO emissions by 11.8% and 32.4% on average, while decreased the vegetable yields by 6.7% and 7.4%, respectively. Moreover, the addition of human manure increased the proportions of Nr footprint by 6.6% (CHF1) and 2.9% (CHF2) in comparison with CF treatment. However, although CHF2 treatment significantly increased the values of GNrEs and reactive gaseous nitrogen intensity (GNrI) by 8.4% and 12.5%, respectively, in relation to those in CF treatment, it still increased farmers' income by 16,404 CNY ha-1. These findings suggest that although human manure incorporation could not mitigate Nr releases, the appropriate ratio of inorganic fertilizer and human manure (CHF2) is able to improve net economic income (NEI) and NEEI during intensive vegetable production. Nevertheless, it should be further explored about the relationship between combinatorial treatment of inorganic fertilizer and human manure on Nr release mitigation in intensive vegetable production.


Core decompression combined with intralesional autologous bone marrow derived cell therapies for osteonecrosis of the femoral head in adults: A systematic review and meta-analysis.
Core decompression (CD) is beneficial in the early stage of osteonecrosis of the femoral head (ONFH). Adjunctive bone marrow derived cell therapies (BMDCT) have been advocated which potentially aid the regenerative process. This study was conducted to determine potential benefit of CD + BMDCT in ONFH, in terms of disease progression, conversion to arthroplasty (primary outcomes), and functional outcomes and complication rates (secondary outcomes). A systematic review of literature was performed on 3 databases. Studies reporting CD + BMDCT (intralesional instillation) in ONFH, with a minimum follow up of 1 year and reporting the pre-defined outcome measures were included in the review. Meta-analysis consisted of two different arms: a comparative arm, to compare CD + BMDCT to CD alone, and a non-comparative meta-analysis arm, to determine pooled rates of disease progression, conversion to arthroplasty and complication rates. A total of 18 studies were included in the systematic review. CD + BMDCT had lower rates of disease progression (OR 0.19 [95% CI, 0.09, 0.40]) and conversion to arthroplasty (OR 0.20 [95% CI, 0.11, 0.40]) as compared to CD alone. Functional score (MD = -7.07 [95% CI, -12.28, -1.86]) and visual analog scale also showed better improvement with the use of CD + BMAC (MD = -10.39 [95% CI, -12.87, -7.90]). Increasing age and post-collapse stage at presentation were noted to have an adverse effect on the outcomes. CD + BMDCT was found to decrease disease progression and conversion to arthroplasty, and was noted to have better functional outcome scores as compared to CD alone.


Epigenetic upregulation of hippocampal CXCL12 contributes to context spatial memory-associated morphine conditioning.
Conditioned place preference (CPP) is a learned behavior, in which animals learn to associate environmental contexts with rewarding effects. The formation of CPP is an integrated outcome of multiple learning processes. Although multiple anatomical substrates underlying this contextual learning have been proposed, it remains unknown whether a specific molecular signaling pathway within CA1 mediates context learning associated with morphine conditioning. Here, we showed that repeated context learning associated with morphine conditioning significantly increased CXCL12 levels in hippocampal CA1 neurons, and the inhibition of CXCL12 expression ameliorated the CPP behavior following context exposure with morphine conditioning. Additionally, repeated context exposure with morphine conditioning increased the phosphorylation of STAT3 and the acetylation of histone H4 in CXCL12-expressing neurons in CA1. Immunoprecipitation and chromatin immunoprecipitation assays demonstrated that repeated context exposure with morphine conditioning increased the binding of STAT3 to the CXCL12 gene promoter and the interaction between STAT3 and p300, which contributed to the enhanced transcription of CXCL12 by increasing the acetylation of histone H4 in the CXCL12 gene promoter. The inhibition of STAT3 by intrathecal injection of S3I-201 suppressed the acetylation of histone H4. These data demonstrated the epigenetic upregulation of CXCL12 following repeated context exposure with morphine conditioning, which potentially contributed to the spatial memory consolidation associated with conditioned place preference induced by morphine conditioning.


Differences in neuromuscular junctions of laryngeal and limb muscles in rats.
Laryngeal muscles are specialized for fine control of voice, speech, and swallowing, and may differ from limb muscles in many aspects. Because muscles and their controlling motor neurons communicate via neuromuscular junctions (NMJs), we hypothesized that NMJs in laryngeal muscles have specialized characteristics different from limb muscles. In vivo study. Single muscle fibers from 12 Sprague-Dawley rats (six male, six female) were used to analyze the postsynaptic side of NMJs from laryngeal thyroarytenoid (TA), cricothyroid (CT), posterior cricoarytenoid (PCA), limb soleus (SOL), and extensor digitorum longus (EDL) muscles. NMJs were labeled with rhodamine-conjugated α-bungarotoxin. With confocal microscopy, we counted cluster fragments and measured the NMJ area, both absolute and normalized (corrected by muscle fiber diameter), for at least 10 single fibers from each muscle of each animal. Differences between genders were also compared. Cluster fragments of postsynaptic NMJs were more numerous in PCA and TA compared to CT, SOL, and EDL muscles (P < .01) in both male and female rats. NMJ cluster fragments were more numerous in female than in male rats only in the TA muscle (P < .01). The absolute area covered by the NMJs showed SOL > EDL > PCA > CT > TA (P < .01); however, with normalization the SOL = EDL = PCA > CT = TA. Differences found in NMJ surface and organization between laryngeal and limb muscle fibers may relate to specialized laryngeal muscle functions. Differences in NMJs between male and female rats were found only in the TA muscle, suggesting an underlying mechanism for some gender-specific laryngeal disorders related to abnormal TA muscle activity.


Structural and functional analysis of endosomal compartments in epithelial cells.
Epithelial cells display segregated early endosomal compartments, termed apical sorting endosomes and basolateral sorting endosomes, that converge into a common late endosomal-lysosomal degradative compartment and common recycling endosomes (CREs). Unlike recycling endosomes of nonpolarized cells, CREs have the ability to sort apical and basolateral plasma membrane proteins into distinct apical and basolateral recycling routes, utilizing mechanisms similar to those employed by the trans Golgi network in the biosynthetic pathway. The apical recycling route includes an additional compartment, the apical recycling endosomes, consisting of multiple vesicles bundled around the basal body. Recent evidence indicates that, in addition to their role in internalizing ligands and recycling their receptors back to the cell surface, endosomal compartments act as intermediate stations in the biosynthetic routes to the plasma membrane. Here we review methods employed by our laboratory to study the endosomal compartments of epithelial cells and their multiple trafficking roles.


Transethmoid decompression of the optic nerve.
Delayed visual deterioration following trauma to the head can result from injury to the optic nerve or central visual pathways. Surgical decompression of the medial optic canal is indicated when central nervous system causes are ruled out and vision fails to improve on megadose intravenous steroids.


Association between exposure to urban waste and emotional and behavioral difficulties in schoolchildren.
To evaluate the association between living near waste recycling sites and emotional or behavioral difficulties in schoolchildren. A cross-sectional study with schoolchildren aged 6-13 years old from disadvantaged communities in a Brazilian city, divided between those who live less than 100m away from the central point of the recycling site and those that live more than 150m away from the site, as a control group and classified through georeferencing. The emotional and behavioral difficulties were investigated using the Strengths and Difficulties Questionnaire tool. Other variables were analyzed through logistic regression to determine their contribution to the outcomes. Children living near waste recycling sites had a higher prevalence of emotional and behavioral problems than children living farther away. In the logistic regression model, no other covariates had a significant impact on the results, except for attending preschool. As expected, the families of the exposed group had lower income and lower levels of schooling, thus being characterized as a highly vulnerable population. The association between living near waste recycling sites and lower test performance raises concerns about the impact of inappropriate waste management in urban centers on children's health.


Comparison of in vivo and in vitro readings when testing the accuracy of the Root ZX apex locator.
The purpose of the study was to compare the accuracy of the Root ZX electronic apex locator (J Morita Corp, Tokyo, Japan) between an in vivo and an in vitro model. The working length (WL) was determined electronically for 46 root canals of human teeth with a 15 K-file using both in vitro (n = 23) and in vivo (n = 23) models. The files were fixed at the WL. The apical 4 mm of each canal was trimmed to expose the file tip. The samples were observed under a scanning electron microscope, and the distance from the file tip to the point 0.5 mm coronal to the major foramen (the final WL) was measured. The data were analyzed using the Student t test, and significance was set at P ≤ .05. The statistical analysis revealed no significant differences between the in vivo group and in vitro group with respect to the accuracy of the Root ZX device in determining the final WL. The mean distance from the final WL to the file tip was 0.23 ± 0.39 mm for the in vivo group and 0.29 ± 0.32 mm for the in vitro group. In determining the final WL, the Root ZX was accurate 78.3% of the time to ±0.5 mm and 100% of the time to ±1 mm in the in vivo group, whereas it was accurate 74% of the time to ±0.5 mm and 100% of the time to ±1 mm in the in vitro group. No statistically significant differences were observed between the in vivo group and the in vitro group.


Emulating Target Trials With Real-World Data to Inform Health Technology Assessment: Findings and Lessons From an Application to Emergency Surgery.
International health technology assessment (HTA) agencies recommend that real-world data (RWD) are used in some circumstances to add to the evidence base about the effectiveness and cost-effectiveness of health interventions. The target trial framework applies the design principles of randomized-controlled trials to RWD and can help alleviate inevitable concerns about bias and design flaws with nonrandomized studies. This article aimed to tackle the lack of guidance and exemplar applications on how this methodology can be applied to RWD to inform HTA decision making. We use Hospital Episode Statistics data from England on emergency hospital admissions from 2010 to 2019 to evaluate the cost-effectiveness of emergency surgery for 2 acute gastrointestinal conditions. We draw on the case study to describe the main challenges in applying the target trial framework alongside RWD and provide recommendations for how these can be addressed in practice. The 4 main challenges when applying the target trial framework to RWD are (1) defining the study population, (2) defining the treatment strategies, (3) establishing time zero (baseline), and (4) adjusting for unmeasured confounding. The recommendations for how to address these challenges, mainly around the incorporation of expert judgment and use of appropriate methods for handling unmeasured confounding, are illustrated within the case study. The recommendations outlined in this study could help future studies seeking to inform HTA decision processes. These recommendations can complement checklists for economic evaluations and design tools for estimating treatment effectiveness in nonrandomized studies.


Reduced exercise capacity in patients with systemic sclerosis is associated with lower peak tissue oxygen extraction: a cardiovascular magnetic resonance-augmented cardiopulmonary exercise study.
Exercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. However, problems with skeletal muscle oxygen extraction have not been fully investigated. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. We performed CMR-CPET in 4 groups: systemic sclerosis (SSc); systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH); non-connective tissue disease pulmonary hypertension (NC-PAH); and healthy controls. We performed CMR-CPET in 60 subjects (15 in each group) using a supine ergometer following a ramped exercise protocol until exhaustion. Values for oxygen consumption, cardiac output and oxygen content gradient, as well as ventricular volumes, were obtained at rest and peak-exercise for all subjects. In addition, T1 and T2 maps were acquired at rest, and the most recent clinical measures (hemoglobin, lung function, 6-min walk, cardiac and catheterization) were collected. All patient groups had reduced peak oxygen consumption compared to healthy controls (p < 0.022). The SSc and SSc-PAH groups had reduced peak oxygen content gradient compared to healthy controls (p < 0.03). Conversely, the SSc-PAH and NC-PH patients had reduced peak cardiac output compared to healthy controls and SSc patients (p < 0.006). Higher hemoglobin was associated with higher peak oxygen content gradient (p = 0.025) and higher myocardial T1 was associated with lower peak stroke volume (p = 0.011). Reduced peak oxygen consumption in SSc patients is predominantly driven by reduced oxygen content gradient and in SSc-PAH patients this was amplified by reduced peak cardiac output. Trial registration The study is registered with ClinicalTrials.gov Protocol Registration and Results System (ClinicalTrials.gov ID: 100358).


Color preferences and gastrointestinal-tract retention times of microplastics by freshwater and marine fishes.
We examined ingestion and retention rates of microplastics (MPs) by two freshwater (Japanese medaka and zebrafish) and two marine fish species (Indian medaka and clown anemonefish) to determine their color preferences and gastrointestinal-tract retention times. In our ingestion experiments, clown anemonefish ingested the most MP particles, followed by zebrafish, and then Japanese and Indian medaka. Next, we investigated color preferences among five MP colors. Red, yellow, and green MP were ingested at higher rates than gray and blue MPs for all tested fish species. To test whether these differences truly reflect a recognition of and preference for certain colors based on color vision, we investigated the preferences of clown anemonefish for MP colors under light and dark conditions. Under dark conditions, ingestion of MP particles was reduced, and color preferences were not observed. Finally, we assessed gastrointestinal-tract retention times for all four fish species. Some individuals retained MP particles in their gastrointestinal tracts for over 24 h after ingestion. Our results show that fish rely on color vision to recognize and express preferences for certain MP colors. In addition, MP excretion times varied widely among individuals. Our results provide new insights into accidental MP ingestion by fishes.


Use of oral mucosal cell sheets for accelerated oral surgical wound healing.
We developed a highly efficient in vitro-engineered mucosa equivalent using completely autologous mucosa and blood and investigated its feasibility and efficacy for oral surgical wound healing. Small oral mucosa samples were obtained from surgical patients, and keratinocytes and fibroblasts were primarily grown in media without animal products for generating 3D cell sheets. Morphological characteristics of the cell sheets were comparable to those of human mucosa, although p63-positive cells were more numerous in cell sheets. In addition, cell sheets were flexible, expandable, and easy to handle or transfer. In further in vivo rat experiments with deep wounding of the buccal mucosa and soft tissues, controls had significantly thinner epithelium and thicker collagen densities than those with cell sheets. Autologous cell sheets can be engineered in vitro from oral keratinocytes, fibroblasts, and fibrin, and can be used clinically to accelerate healing of oral soft tissue defects.


Resection for pancreatic cancer metastases contributes to survival: A case report with sequential tumor genotype profiling during the long-term postoperative course.
Surgical management is not a standard treatment option for metastatic recurrence of pancreatic adenocarcinoma. However, the surgical management of a solitary metastasis is useful in selected cases. A 42-year-old woman was referred to our hospital on account of epigastric pain associated with a mass in the pancreatic body. The patient had a family history of branch duct-type intraductal papillary mucinous neoplasm of the pancreas. The patient was diagnosed with pancreatic ductal adenocarcinoma (PDA) complicated with pancreatitis due to pancreatic duct involvement. The patient underwent distal pancreatectomy, and pathological examination revealed a tubular adenocarcinoma. Solitary liver and lung metastatic tumors were found 6 and 43 months after the initial presentation, respectively, and sequential metastasectomies were performed. The patient survived until 8 years after her initial presentation. The genetic profiles of the resected specimens, primary PDA, and recurrent tumors in the liver and lung possessed identical KRAS mutations at codon 12, whereas there were no mutations in the main tumor suppressor genes, such as TP53, CDKN2A, and SMAD4. Multiplex polymerase chain reaction-based microsatellite instability assay demonstrated microsatellite stability. In our case, the patient with pancreatic adenocarcinoma survived for over 8 years following the resection of the primary tumor and resections of metachronous metastatic tumors. The outcome of PDA may be associated with the genetic profile that regulates its biological behavior. Operative management of solitary metastatic tumors may be a therapeutic options for selected patients with pancreatic cancer.


Impact of substrates for probe immobilization.
Protein chips are becoming a key technology in proteomic research and medical diagnostics. Surface chemistry for immobilization of proteins forms the basis for assay design and determines the properties of protein microarrays. Optimal substrates provide a homogeneous environment for probes, preventing loss of biological activity and unspecific adsorption. Numerous immobilization approaches, based on covalent binding, affinity, or adsorption, have been proposed thus far, and these represent the toolbox for choosing optimized strategies for each individual application.


Cadmium contents of vertically and horizontally deposited winter precipitation in Central Europe: Spatial distribution and long-term trends.
Cadmium (Cd) and its forms has recently been a focus of attention due to its toxic effects on human health and the environment. We evaluated the atmospheric deposition of Cd during three consecutive winter seasons (2009-2011) at 10 mountain-top locations in the Czech Republic along the borders with Poland, Germany, Austria and Slovakia. Cadmium concentrations of soluble and insoluble forms in both horizontal (rime) and vertical (snow) deposition were determined using sector-field ICP-MS. Across the sites, 94% of the total winter Cd deposition occurred in the soluble (environmentally available) Cd form. Mean concentrations of soluble Cd in rime were six times higher than in snow (398 vs. 66 ng L-1). Vertical deposition contributed as much as 41% to the total winter Cd input. Between-site variability in Cd deposition was large, ranging between 13 and 108 μg m-2 winter-1. Overall, Cd concentrations in winter deposition did not reach the drinking water limits and did not pose a direct threat for human health. Long-term trends (1996-2017) in winter Cd deposition were evaluated at six GEOMON sites (a monitoring network of small forested catchments). Since 1996, Cd input in winter atmospheric deposition decreased by 73-93%. Simultaneously, we found declines in between-site variability in winter Cd inputs. The highest recent winter Cd inputs were found at sites located in the northeast of the country. A north-south pollution gradient, which has frequently been mentioned in the literature, was not observed, with both northwestern sites and southern sites being among those with the lowest Cd pollution. Backward trajectories of the HYSPLIT model for fresh snow samples identified Poland and Germany as major transboundary Cd pollution sources for the Czech Republic.


Estimating the potential effects of COVID-19 pandemic on food commodity prices and nutrition security in Nepal.
The objective of the paper is to analyse changes in food commodity prices and estimate the potential effects of food price change on nutrition security in Nepal in the context of COVID-19 contagion control measures. It presents a comparative intra-country observational study design looking at events before and during the pandemic (after implementation of contagion control measures). The study design includes three districts, enabling comparison between diverse agro-ecological zones and geographical contexts. The methodology consists of primary data collection, modelling and quantitative analysis. The analysis is based on actual school meal food baskets which represent culturally and nutritionally optimised food baskets, developed by the local community and notional typical household food baskets. End May/early June 2020 is the 'Post-COVID-19' reference point, the same time period in 2019 i.e. June 2019 is the 'Pre-COVID-19' reference point. The study finds a substantial increase in food commodity prices across food groups and districts with marked inter-district variation. For school meal basket, all micronutrients show large average declines ranging from 9⋅5 % for zinc to 11 % for vitamin-A. For household food baskets on average, vitamin-A reduced 37 % followed by iron at 19 %, reduction in zinc is low due to the high zinc content in whole grain cereals. COVID-19 control measures are likely to have contributed to substantial price inflation over the reference period with potentially damaging effects on nutrition security in Nepal with serious implications for vulnerable populations.


Comparison of ultrasound speed in articular cartilage measured by different time-of-flight methods.
The purpose of this study was to investigate whether different time-of-flight (TOF) methods including amplitude-related methods, which determine tissue borders from the reflected wave itself, and the cross-correlation method, which requires reference signals to determine borders, influence speed of sound (SOS) values for articular cartilage. Left femoral condyle samples from a 6-month-old pig and a 3-year-old pig were used. Radiofrequency signals from the cartilage surface and cartilage-bone interface were acquired using the ultrasound transducer for nine points in each sample. TOF was calculated by three amplitude-related methods (peak amplitude, peak envelope, signal phase) and a cross-correlation method. Cartilage thickness was measured microscopically, and SOS was calculated at each point. Mean (± standard deviation) SOSs in cartilage from the 9-point measurement by the four TOF methods were 1488 ± 51, 1488 ± 48, 1487 ± 54, and 1466 ± 51 m/s (for peak amplitude, peak envelope, signal phase, and cross-correlation methods, respectively) for the 6-month-old pig, and 1709 ± 107, 1717 ± 104, 1713 ± 105, and 1695 ± 138 m/s, respectively, for the 3-year-old pig. Paired t testing identified no significant differences between the amplitude-related methods and the cross-correlation method, although SOS values yielded by the amplitude-related methods tended to be higher than those from the cross-correlation method. These results suggest that amplitude-related methods of TOF measurement and the cross-correlation method are equivalently applicable to articular cartilage SOS measurement when a wave is clearly reflected from cartilage. TOF methods should thus be considered in studies on SOS measurement.


[Controlled study on needle-pricking therapy combined with spinal massage for treatment of ankylosing spondylitis].
To observe the therapeutic effect of needle-pricking therapy combined with spinal massage on ankylosing spondylitis and to probe into the mechanism. Ninety-three cases who were definitely diagnosed as having ankylosing spondylitis at active stage were randomly divided into a medication group (n=46) and an observation group (n=47). The observation group were treated by needle-pricking the main points, Neck No. 2 nerve, Neck No. 5 nerve point, etc., combined with spinal rotation massage, and the medication group were treated with Azulfidine. Changes of cumulative score of arthralgia and arthroncus, function of joint, Keitel test, and ESR and CRP before and after treatment were observed. The effective rate and the markedly effective rate were 95.8%0 and 68.1% in the observation group and 78.3% and 23.9% in the medication group, respectively, the former being significantly better than the latter (P < 0.01). Needle-pricking therapy combined with spinal massage has a significant therapeutic effect with a steady and long-term effect for treatment of ankylosing spondylitis at active stage.


Spread of extended-spectrum beta-lactamase producing Escherichia coli isolates in Swedish broilers mediated by an incl plasmid carrying bla(CTX-M-1).
The already high and increasing occurrence of extended-spectrum beta-lactamases (ESBL) producing Escherichia coli in European broiler populations is of concern due to the fact that third and fourth generation cephalosporins are deemed critically important in human medicine. In Sweden 34% of the broilers carry ESBL/pAmpC producing E. coli in their gut, despite the absence of a known selection pressure such as antimicrobial usages. The aim of the current study was to characterise a selection of E. coli strains carrying the blaCTX-M-1, to determine if the spread was due to a specific clone. Ten isolates carrying blaCTX-M-1 from Swedish broilers belonged to eight different multi-locus sequence types with three isolates belonging to ST155. The ST155 isolates were identical as assessed by PFGE. The blaCTX-M-1 was in all isolates carried on a plasmid of replicon type incI, which also transferred resistance to tetracycline and sulfamethoxazole. The occurrence of ESBL-producing E. coli in the Swedish broilers is not due to the emergence of a single clone, but rather the spread of a specific incI plasmid carrying blaCTX-M-1.


Prorenin receptor mediates inflammation in renal ischemia.
We hypothesized that PRR contributes to renal inflammation in the 2-kidney, 1-clip (2K1C) renal ischaemia model. Male Sprague-Dawley rats were fed normal sodium diet. Blood pressure (BP) was obtained on days 0 and 28 after left renal artery clipping that reduced renal blood flow by 40%. Renal expression of TNF-α, COX-2, NF-κB, IL-1β, MCP-1 and collagen type I were assessed in sham and 2K1C rats with or without left renal administration of scramble or PRR shRNA. At baseline, there were no differences in BP. Compared to sham, MAP significantly increased in clipped animals (sham 102 ± 1.9 vs 2K1C 131.8 ± 3.09 mmHg, P < .05) and was not influenced by scramble or PRR shRNA treatment. Compared to sham and contra lateral (non-clipped) kidney, there was upregulation in mRNA and protein expression of PRR (99% and 45%, P < .01), TNF-α (72% and 50%, P < .05), COX-2 (72% and 39%, P < .05), p-NF-κB (92%, P < .05), MCP-1 (87%, P < .05) and immunostaining of collagen type I in the clipped kidney. These increases were not influenced by scramble shRNA. Compared to 2K1C and scramble shRNA, PRR shRNA treatment in the clipped kidney significantly reduced the expression of PRR (62% and 57%, P < .01), TNF-α (51% and 50%, P < .05), COX-2 (50% and 56%, P < .05), p-NF-κB by 68% (P < .05), MCP-1 by 73% (P < .05) and collagen type I respectively. Ang II was increased in both kidneys and did not change in response to scramble or PRR shRNA treatments. We conclude that PRR mediates renal inflammation in renal ischaemia independent of blood pressure and Ang II.


CT enterography vs. capsule endoscopy.
Small bowel imaging has been revolutionized by CT enterography and capsule endoscopy. We present an overview of both imaging modalities, discuss advantages and disadvantages of each, and compare findings in Crohn's disease, occult gastrointestinal bleeding, and small bowel tumors. Both methods complement each other often providing information that the other one cannot.


Validity evidence for the back beliefs questionnaire in the general population.
Despite common usage of the back beliefs questionnaire (BBQ) in a variety of studies, important validity evidence is missing. The objective of this study was to examine the validity of the BBQ in the general population. A population-based, cross-sectional study design was used. Adult residents in two Canadian provinces were randomly sampled. To examine structural validity, items from the BBQ were subjected to factor analysis. Construct validity was tested by examining two hypotheses: BBQ scores would be most pessimistic in those with a recent history of back pain and in those who utilized passive treatments for back pain. Multiple linear regression was used to analyse the two hypotheses. Complete data were available for 6171 subjects. The best structure for the BBQ was to use eight or nine of the 14 items for scoring, which is consistent with the structure reported by the BBQ developers. BBQ scores varied based on participants' history of low back pain (LBP) and depended on pain severity. Those with severe pain and a recent history of LBP had the most pessimistic BBQ scores. In addition, participants who utilized passive management behaviours such as bed rest and activity avoidance had more pessimistic BBQ scores compared with those that did not. This study provides strong validity evidence supporting the current structure and scoring of the BBQ. In addition, construct validity was evidenced by the behaviour of BBQ scores in a manner congruent with our hypotheses, further supporting use of the BBQ in the general population.


A comparative study of predicting the availability of power line communication nodes using machine learning.
Power Line Communication technology uses power cables to transmit data. Knowing whether a node is working in advance without testing saves time and resources, leading to the proposed model. The model has been trained on three dominant features, which are SNR (Signal to Noise Ratio), RSSI (Received Signal Strength Indicator), and CINR (Carrier to Interference plus Noise Ratio). The dataset consisted of 1000 readings, with 90% in the training set and 10% in the testing set. In addition, 50% of the dataset is for class 1, which indicates whether the node readings are optimum. The model is trained with multi-layer perception, K-Nearest Neighbors, Support Vector Machine with linear and non-linear kernels, Random Forest, and adaptive boosting (ADA) algorithms to compare between statistical, vector-based, regression, decision, and predictive algorithms. ADA boost has achieved the best accuracy, F-score, precision, and recall, which are 87%, 0.86613, 0.9, 0.8646, respectively.


The adverse effects of hydrogen cyanamide on human health: an evaluation of inquiries to the New Zealand National Poisons Centre.
Hydrogen cyanamide is used in New Zealand to induce bud break in kiwifruit vines. The aim of this investigation was to evaluate the calls received by the New Zealand National Poisons Centre (NZNPC) attributed to acute hydrogen cyanamide exposure, and to ascertain the clinical effects of such exposures. Call data from the NZNPC telephone collection databases regarding human hydrogen cyanamide exposures were analyzed retrospectively for the years 1990-2006. There were 68 human exposures, 69% were male and 22% female; 88% were adults and there were no suicide attempts. Common exposure routes were inhalation (56%) and skin contact (28%). The workplace accounted for 45% of calls. The predominant toxic effects were nausea and vomiting (29%), headache (22%), contact dermatitis (19%), and erythema (18%). Reported symptoms and signs were consistent with the expected effects of hydrogen cyanamide exposure. Other reports of similar exposures describe higher degrees of illnesses among workers using hydrogen cyanamide, which might have been because of lack of training, inadequate access to personal protective equipment, and the absence of engineering controls. Based on the calls received by the NZNPC, acute exposure to hydrogen cyanamide in the workplace or acute exposure to those living within the vicinity of its use may not pose a significant immediate threat to human health.


Vessel- and vasoconstrictor-dependent role of rho/rho-kinase in renal microvascular tone.
We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl and elevated renal arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In the condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only afferent (from 11.6 +/- 0.4 to 14.1 +/- 0.5 microm) but not efferent arterioles (from 11.6 +/- 0.2 to 12.6 +/- 0.7 microm) at 10(-5) mol/l. During renal vasoconstriction by Ang II, Y-27632 restored the afferent arteriolar constriction (141 +/- 10% reversal at 10(-5) mol/l), whereas the ability of Y-27632 to inhibit the Ang II-induced efferent arteriolar constriction was diminished (73 +/- 7% reversal). A similar action was observed with fasudil, another Rho-kinase inhibitor. Furthermore, Y-27632 impaired myogenic afferent arteriolar constriction, with 117 +/- 17% inhibition at 10(-5) mol/l. The inhibition by Y-27632 of the myogenic vasoconstriction was almost the same as that of the Ang II-induced tone of this vessel type. However, Y-27632 had a modest effect on KCl-induced vasoconstriction of afferent arterioles. In conclusion, the present study demonstrates a predominant role of Rho/Rho-kinase in mediating the basal and Ang II-induced tone of afferent, but not efferent, arterioles. Furthermore, the role of Rho/Rho-kinase in afferent arteriolar constriction differs, with a substantial contribution to Ang II-induced and myogenic constriction but a minimal role in depolarization-induced constriction. Since Ang II-induced, KCl-induced and myogenic constriction of afferent arterioles require calcium entry through voltage-dependent calcium channels, the interaction between Rho/Rho-kinase and the calcium entry pathway may determine the afferent arteriolar tone induced by these stimuli.


Effects of 1-stage revascularization and temporary external fixation combined with 2-stage Ilizarov technique in the treatment of bone defects in lower limb destruction injury: A case report.
To evaluate the clinical effects of 1-stage revascularization, vacuum sealing drainage covering the wound, temporary external fixation and 2-stage Ilizarov bone transport for the treatment limb destruction injury. Nine patients with limb destruction injury between September 2014 and June 2019 at our institute were evaluated retrospectively. The age of patient was 21 to 51 years with an average of 33 years. The injuries were caused by vehicle accidents in 4 patients, gunshot in 1 patient, and crushing injuries in 4 patients. All of them had vascular injury. The average length of bone defect was 9.5 (8.3-10) cm. Regular follow-up was performed on wound healing, bone transport time, bone healing time, external fixation index, and limb function. All patients underwent 1-stage revascularization and temporary external fixation during emergency surgery, and then gradual bone transport by Ilizarov fixator was performed until the broken fracture site was reunited. Nine patients were followed up for 12 to 48 months (average 30 months). Six patients were treated with autogenous cancellous bone graft for the second time, and 2 patients healed spontaneously. The mean wound healing time was 86 (73-90) days. The bone transport time was 97 (88.3-105.3) days, and the bone mineralization time was 164.5 (156.8-181.3) days, and the healing time of the docking sites was 6.8 (6.1-8.3) months. The external fixator time was 14.5 (12.5-17) months with the external fixation index was 1.5 (1.4-1.8) m/cm. At the last follow-up, according to the Association for the Study of the Method of Ilizarov functional scores, excellent functional outcomes were obtained in 5 patients, good in 1 patients, moderate in 2 patients. According to the Association for the Study of the Method of Ilizarov Radiological System, excellent functional outcomes were obtained in 6 cases and good in 2 cases. One-stage revascularization and temporary external fixation combined with 2-stage Ilizarov bone transport technique for the treatment of bone defects in limb destruction injury have satisfactory clinical effects and few complications, and can be applied under the condition of strict understanding of surgical indications.


Impact of Patient Navigation on Population-Based Breast Screening: a Systematic Review and Meta-analysis of Randomized Clinical Trials.
Unsatisfactory cancer screening results are often associated with poor prognosis. This study synthesized the literatures addressing the impact of patient navigation (PN) interventions on population-based breast cancer screening promotion to identify characteristics of the model for addressing breast cancer disparities. We searched Pubmed, Embase, Web of Science, and the Cochrane Central Registry from inception to 31 December 2020 for randomized controlled trials (PROSPERO: CRD42021246890). We double blindly abstracted data and assessed study quality. We assessed screening completion rates and diagnostic resolution using random-effects models between those receiving navigation and controls. Of 236 abstracts identified, 15 studies met inclusion criteria. Nine of the papers evaluated the impact of PN on breast screening, while the other six were on the resolution of abnormal screening results. Compared to the non-PN group, PN improved screening completion (OR: 2.0, 95% CI: 1.4-2.8]) and shortened the time to diagnosis (WMD: - 9.90 days, 95% CI: - 19.09 to - 0.71). Patient navigation improves breast cancer screening rates but does not improve resolution of abnormal tests.


Association between Electronic Cigarette Use and Asthma among High School Students in South Korea.
Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student's self-reported doctor diagnosis of asthma in the past 12 months. Prevalence rates of asthmatics in 'current EC users' (n = 2,513), 'former EC users' (n = 2,078), and 'never EC users' (n = 31,313), were 3.9% (n = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing 'current EC' users with 'never EC' users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89-2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the 'never CC' category, the unadjusted OR for asthma for 'current EC' users was 3.41 (95% CI: 1.79-6.49), and the adjusted OR was 2.74 (95% CI: 1.30-5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to 'never EC' users. When compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.


Moving upstream or muddying the waters? Incentives for managing for health.
The objective of this study was to identify factors influencing the capacity of NHS managers to 'manage for health'. Semi-structured interviews (32) were carried out over the telephone or face to face with national stakeholders (15) and NHS senior managers (17) from four Strategic Health Authorities (SHAs) and five Primary Care Trusts (PCTs) in England. Interviews were transcribed and a qualitative analysis carried out. The current system of targets and incentives prioritised access to acute services, public health skills were too thinly spread, baseline data were inadequate, decision-making for public health investment was fragmented and evidence for effective interventions was scanty. Health improvement targets should be plausible, longer term and locally owned, but key factors in creating a proactive public health organisation were a strong public health ethos, and effective management and leadership skills. Strengthening the NHS's role in managing for health was welcomed, but enthusiasm was tempered by concurrent NHS policy initiatives and incentives pulling in opposing directions. Key NHS policy initiatives have been developed in isolation from each other. While their combined effect remains unpredictable, they may serve to threaten the welcome shift towards managing for health improvement.


"Window shade" tympanoplasty for anterior marginal perforations.
Anterior marginal perforations of the tympanic membrane often present a reconstructive challenge to the otolaryngologist. Poor surgical outcomes are often due to inadequate exposure, a lack of residual tympanic membrane, impaired vascular supply, and delayed healing. This study reports on the success of the "window shade" technique, combining aspects of both the traditional underlay and overlay tympanoplasty techniques, for the management of anterior marginal tympanic membrane perforations. Retrospective review of patients undergoing window shade tympanoplasty from July 1, 1994, to July 1, 2003, at a tertiary care referral center. Only patients found to have anterior tympanic membrane perforations and who underwent a window shade tympanoplasty were included in the study. Tympanoplasty success rate was studied by examining postoperative complications of recurrent perforation, tympanic membrane lateralization, or anterior blunting. The authors identified 164 patients who underwent window shade tympanoplasty during the study period. The overall success rate for tympanic membrane repair was 94.5%. There were no cases of tympanic membrane lateralization or significant blunting. The average healing time was 4 weeks. The surgical technique is described in detail. The window shade tympanoplasty is an excellent surgical option for repair of anterior marginal perforations of the tympanic membrane.


Reversibility and exchangeability of intrastromal corneal ring segments.
To evaluate the effect of removal and/or exchange of intrastromal corneal ring segments (ICRS, Intacs); specifically the risk factors, degree of reversibility, and visual outcomes. Gimbel Eye Centres, Calgary, Edmonton, and Vancouver, Canada. Prospective cohort data were collected on 71 eyes that had ICRS placement by 3 surgeons at the Gimbel Eye Centres between August 1998 and July 1999. Data included patient symptoms, best spectacle-corrected visual acuity, uncorrected visual acuity (UCVA), manifest refraction, reason for removal or replacement, keratometry, corneal topography, and complications. Twenty-four eyes (33.8%) had exchange or removal procedures because of underresponse, 20 eyes; overresponse, 2 eyes; and induced astigmatism and shallow placement, 1 eye each. Secondary procedures were removal and replacement, removal with subsequent laser in situ keratomileusis, and segment repositioning. Two risk factors for secondary surgery were identified: high preoperative refractive astigmatism and postoperative spherical equivalent greater than +/-0.5 diopter (D). The 6 eyes that had ICRS removal stabilized to within +/-0.25 D of the original refractive error with no surgically induced astigmatism within 1 to 7 weeks (mean 4 weeks) and had a final UCVA of 20/20 or better. In the 15 eyes that had ICRS exchange procedures, the UCVA improved by at least 1 line and median UCVA improved from 20/40 to 20/20. Preliminary data from this study indicate that removal of segments resulted in reversal of the refractive effect.


Fatty acids revert the inhibition of respiration caused by the antidiabetic drug metformin to facilitate their mitochondrial β-oxidation.
While metformin has been widely used to treat type 2 diabetes for the last fifty years, its mode of action remains unclear. Hence, we investigated the short-term alterations in energy metabolism caused by metformin administration in 3T3-L1 adipocytes. We found that metformin inhibited mitochondrial respiration, although ATP levels remained constant as the decrease in mitochondrial production was compensated by an increase in glycolysis. While AMP/ATP ratios were unaffected by metformin, phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase augmented. The inhibition of respiration provoked a rapid and sustained increase in superoxide levels, despite the increase in UCP2 and superoxide dismutase activity. The inhibition of respiration was rapidly reversed by fatty acids and thus respiration was lower in treated cells in the presence of pyruvate and glucose while rates were identical to control cells when palmitate was the substrate. We conclude that metformin reversibly inhibits mitochondrial respiration, it rapidly activates AMPK without altering the energy charge, and it inhibits fatty acid synthesis. Mitochondrial β-oxidation is facilitated by reversing the inhibition of complex I and, presumably, by releasing the inhibition of carnitine palmitoyltransferase. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).


Solubility of solids in near-critical conditions: effect of a third component.
The effect of cosolvents on the solubility equilibria near the critical end-point of binary mixtures is analyzed. The problem has received recent attention for the particular case of ionic cosolvents (Mazo, R. M. J. Phys. Chem. B 2007, 111, 7288-7290), where a pronounced salting-out effect was predicted. Here we make a thermodynamic analysis to view the problem from a different perspective. Our conclusions are that, at the critical end-point, the Setchenov constant, which reflects the effect of cosolvents on solubility equilibria, diverges following the behavior of the osmotic susceptibility and that the sign of this divergence is encoded in the critical end-line of the ternary system.


[Metabolism of arsenic (Report 22). Effect of arsenic on the spontaneous motor activity, avoidance conditioning, extinction and swimming record in rats (author's transl)].
The experiments were conducted to determine the effect of arsenic on the pharmacological actions as seen in the behavior of Wistar albino rats. Nutrition during the suckling period has some apparently influence on the pharmacology behavior, we found no significant difference between the heavy (26 approximately 35g) and light (under 25g) groups. Also rats in group B1, were fed a diet which included As2O3 2 mg/kg, and rats in group B2 were fed a diet which included As2O3 15 mg/kg during the suckling period. There were no significant differences in spontaneous motor activity, avoidance conditioning and swimming record between the controls and group B1. However in group B2, the spontaneous motor activity increased as did the response on avoidance conditioning.


[Management of avoidable acute transfers from an intermediate care geriatric facility to acute hospitals: critical aspects of an intervention protocol].
The unplanned transfers (UT) from post-acute intermediate care facilities, are associated with adverse outcomes for patients, and a significant cost to the system. We present a practical protocol and the design of an intervention study aimed at reducing avoidable UT from a geriatric post-acute rehabilitation setting to acute care hospitals. A quasi-experimental non randomized study. The intervention consists in: 1) protocol for early detection of symptoms in order to conduct a pro-active management of decompensation; 2) an advanced care planning structured protocol for the acute decompensations. We will compare the intervention group with a parallel and a historical cohort for demographic, functional, cognitive, comorbidity and social variables. number of UT to acute care hospitals. This is a quasi-experimental study, focused on everyday care practice that intends to assess the impact of multi-disciplinary and multi-factorial intervention to reduce UT from a post-acute rehabilitation unit. We expect that the project results will be useful for future randomized and controlled studies.


Methodology for processing mastectomy and cryopreservation of breast cancer tissue in a resource- poor setting: A pilot study.
There is scarcity of breast cancer tissues derived from women of African origin available for patient - derived xenograft and organoid models. We aim to create a versatile protocol for processing mastectomy and cryopreservation of breast cancer tissue. An immediate collection of breast cancer tissue from mastectomy was bathed in 4 °C HBSS and immediately transferred to 4 °C RPMI1640 containing HEPES, 10% FBS, Streptomycin and Penicillin. Tissues were processed over ice yielding nine samples of cold ischemic time (20-45 min) stored at 3 min interval. Cut samples were transferred into cryovials containing 4 °C cryoprotectant agent (90% FBS +10% Me2SO) before snap -freezing in liquid Nitrogen vapour and final short-term storage in -80 °C Freezer. The histomorphology, tissue and molecular viability were assessed. The cold ischemic times had no detrimental effect to the nine samples despite being processed in a resource poor setting, hence providing a reproducible and reliable protocol.


Mitral regurgitation after percutaneous balloon mitral valvuloplasty in adults: evaluation by pulsed Doppler echocardiography.
Percutaneous balloon mitral valvuloplasty is a new technique used in the treatment of adult patients with mitral stenosis. To evaluate the occurrence and severity of mitral regurgitation after balloon valvuloplasty, 24 patients (20 women and 4 men, mean age 57 years) were studied using two-dimensional and Doppler echocardiography before and less than 24 h after this procedure. Mitral valve area increased after valvuloplasty in all patients, from 0.89 +/- 0.07 to 1.61 +/- 0.09 cm2 (p less than 0.001). Before valvuloplasty, 10 patients had no mitral regurgitation, 4 had 1+, 4 had 2+ and 6 had 3+ mitral regurgitation. After valvuloplasty, new mitral regurgitation occurred in six patients. Regurgitation grade did not change in 13 patients (54%), increased by one grade in 8 patients (33%) and by two grades in 3 patients (13%). Left atrial volume decreased in all except one patient from 100 +/- 12 to 83 +/- 12 cm3 (p less than 0.001). Neither age, sex, cardiac rhythm, initial mitral valve area, increase in mitral valve area, morphologic characteristics of the valvular and subvalvular apparatus, previous mitral commissurotomy nor effective balloon dilating area discriminated between those patients with and without an increase in mitral regurgitation after valvuloplasty. Thus, mitral balloon valvuloplasty is frequently associated with an increase in mitral regurgitation. However, in this series, no patient developed severe mitral regurgitation, and left atrial volume decreased in nearly all patients. An increase in mitral regurgitation could not be predicted from any features of the valve or subvalvular apparatus, clinical characteristics of the patients or technical aspects of the procedure.


Activation of bee venom phospholipase A2 by oleoyl imidazolide produces a thiol- and proteinase-resistant conformation.
Assay methods for bee venom phospholipase A2 are presented which respond to different aspects of enzymic behaviour and which allow basal activity, fatty acid activation and acyl-group activation to be distinguished. The stability of the enzyme to thiols and proteinases is dramatically increased by activation with the selective acylating agent, oleoyl imidazolide. These results support the model of activation by conformation change. Limited-fixation studies indicate that enzyme conformation is determined by interaction with the substrate. The oleoyl-enzyme is partially inactivated by trypsin, but its electrophoretic mobility is unchanged. This protective effect is highly selective and only one other component of the venom is protected against trypsin by oleoyl imidazolide. Combination of trypsin and thiol treatment produces a large fragment of the activated enzyme which could be used for structural studies of the activation site.


Interleukin-2: Old and New Approaches to Enhance Immune-Therapeutic Efficacy.
Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. Systemic delivery of IL-2 has shown clinical benefit in renal cell carcinoma and melanoma patients. However, its use has been limited by the numerous toxicities encountered with the systemic delivery. Intravenous IL-2 causes the well-known "capillary leak syndrome," or the leakage of fluid from the circulatory system to the interstitial space resulting in hypotension (low blood pressure), edema, and dyspnea that can lead to circulatory shock and eventually cardiopulmonary collapse and multiple organ failure. Due to the toxicities associated with systemic IL-2, an aerosolized delivery approach has been developed, which enables localized delivery and a higher local immune cell activation. Since proteins are absorbed via pulmonary lymphatics, after aerosol deposition in the lung, aerosol delivery provides a means to more specifically target IL-2 to the local immune system in the lungs with less systemic effects. Its benefits have extended to diseases other than cancer. Delivery of IL-2 via aerosol or as nebulized IL-2 liposomes has been previously shown to have less toxicity and higher efficacy against sarcoma lung metastases. Dogs with cancer provided a highly relevant means to determine biodistribution of aerosolized IL-2 and IL-2 liposomes. However, efficacy of single-agent IL-2 is limited. As in general, for most immune-therapies, its effect is more beneficial in the face of minimal residual disease. To overcome this limitation, combination therapies using aerosol IL-2 with adoptive transfer of T cells or NK cells have emerged.Using a human osteosarcoma (OS) mouse model, we have demonstrated the efficacy of single-agent aerosol IL-2 and combination therapy aerosol IL-2 and NK cells or aerosol IL-2 and interleukin 11 receptor alpha-directed chimeric antigen receptor-T cells (IL-11 receptor α CAR-T cells) against OS pulmonary metastases. Combination therapy resulted in a better therapeutic effect. A Phase-I trial of aerosol IL-2 was done in Europe and proved to be safe. Others and our preclinical studies provided the basis for the development of a Phase-I aerosol IL-2 trial in our institution to include younger patients with lung metastases. OS, our disease of interest, has a peak incidence in the adolescent and young adult years. Our goal is to complete this trial in the next 2 years.In this chapter, we summarize the different effects of IL-2 and cover the advantages of the aerosol delivery route for diseases of the lung with an emphasis on some of our most recent work using combination therapy aerosol IL-2 and NK cells for the treatment of OS lung metastases.


The K+-dependent phosphatase from human renal tissue: its properties and time dependent inhibition by ouabain.
The K+-dependent p-nitrophenyl phosphatase activity associated with human renal (Na+ + K+)-ATPase was examined for some of its kinetic properties. ATP inhibited the K+-dependent phosphatase and raised the Km for p-nitrophenylphosphate. Stimulation of the K+-dependent phosphatase by K+ was blocked by Na+ in a noncompetitive manner. Inhibition of the K+-dependent phosphatase by ouabain was dependent upon incubation time. The apparent Kï was 2.0 micron.


Osteoarthritis, osteoarthrosis, and idiopathic condylar resorption.
The term "osteoarthritis" has classically been defined as a low-inflammatory arthritic condition. The term "osteoarthrosis," a synonym for osteoarthritis in the medical orthopedic literature, has recently come to be identified in the dental/temporomandibular joint (TMJ) disorders literature with any noninflammatory arthritic condition that results in similar degenerative changes as in osteoarthritis. The term "idiopathic condylar resorption," also known as "progressive condylar resorption," is described as a dysfunctional remodeling of the TMJ manifested by morphologic change, decreased ramal height, progressive mandibular retrusion in the adult, or decreased mandibular growth in the juvenile. This article discusses the diagnosis and management of osteoarthritic TMJ disorders and idiopathic condylar resorption.


Computed tomographic detection of a swallowed denture.
A 89-year-old, nursing home female presented with a two-week history of drooling and a hard palpable mass in the region of the larynx. Initial fiberoptic laryngoscopy revealed a hard pinkish-white mass which was felt to represent a tumor. Computed tomography demonstrated swallowed, impacted, complete, mandibular denture. Radiologists should be aware of this problem, particularly in the elderly demented patient.


Sex differences in subsite incidence of large-bowel cancer.
A review of patients with large-bowel cancer at a major New Zealand hospital showed an excess of right-sided colonic tumors in females compared with males. These observations stimulated analysis of the National Cancer Registry registration data for large-bowel cancer for the whole of New Zealand in the years 1972 to 1975 (4678 patients). Rates for each site were calculated and age-standardized, using world population figures. The findings confirmed that females have a higher incidence of right-sided colonic cancer and males a higher incidence of rectal cancer and showed a significant trend in this direction from the ascending colon toward the rectum. The observed differences between males and females suggest differences in the etiology of the tumor and should be taken into account in assessing modalities and outcomes of treatment.


Limited MOMP, ATM, and their roles in carcinogenesis and cancer treatment.
Limited mitochondria outer membrane permeability (MOMP) is a novel biological process where mammalian cells initiate the intrinsic apoptosis pathway with increased mitochondrial permeability but survive. One of the major consequences of limited MOMP is apoptotic endonuclease-induced DNA double strand breaks. Recent studies indicate that these DNA double stand breaks and ensuing activation of DNA damage response factors such as ATM play important but previously underappreciated roles in carcinogenesis and tumor growth. Furthermore, novel non-canonical roles of DNA repair factors such as ATM in tumor growth and treatment are also emerging. In this review, we try to summarize recent findings on this newly revealed link between DNA double strand break repair and cell death pathways.


Renal cell carcinoma in a setting of chronic lithium toxicity.
Female, 72 FINAL DIAGNOSIS: Renal cell carcinoma Symptoms: - - Clinical Procedure: - Specialty: Oncology. Challenging differential diagnosis. Lithium salts are widely used in the treatment of affective disorders of the bipolar type. Lithium is a nephrotoxic substance which can cause both acute and chronic renal disease, including cyst formation. Cysts appear to predispose the kidney to renal cell carcinoma. A case of renal cell carcinoma in a background of acquired cystic disease due to chronic lithium toxicity is described. Kidneys with multiple cysts are at risk of renal cell carcinoma. Although it is difficult to determine if long term Lithium use renal cell carcinoma, patients leads to the development of on long-term lithium therapy should undergo regular renal function and imaging tests.


Subgroup analysis for the risk of cardiovascular disease with calcium supplements.
Calcium supplements have been reported to increase the risk of myocardial infarction (MI). We wished to determine whether the effects of calcium supplements on cardiovascular risk vary across different population groups. We modeled the effect of calcium (with or without vitamin D) on the time to incident cardiovascular events in pre-specified subgroups based on age, dietary calcium intake, body mass index, smoking history, history of hypertension, diabetes and prevalent cardiovascular disease, using interaction terms in Cox proportional hazards models in two randomized controlled trial data sets-our re-analysis of the Women's Health Initiative Calcium and Vitamin D study (WHI CaD), and our pooled patient-level meta-analysis of trials of calcium supplements with or without vitamin D. For women in WHI CaD not taking calcium supplements at randomization (n=16 718), we found no significant interactions between treatment allocation, the risk of MI, stroke or coronary revascularization, or any of the baseline variables. In the pooled patient-level data set of six trials of calcium with or without vitamin D (n=24 869), there were also no significant interactions between treatment allocation, risk of MI or stroke, and any of the baseline variables. We found no evidence that the increased cardiovascular risk from calcium supplements differs across varying patient subpopulations. These findings suggest that targeted prescription of calcium supplements to specific population subgroups, such as younger people and those with low dietary calcium intake, should not be endorsed.


Differential effects of ageing on distinct features of apomorphine stereotypy in the adult rat.
Locomotor features of stereotypy induced by 0.15 mg/kg of subcutaneous apomorphine increased over the age ranges of 2.5-8 and 8-10 months in the adult rat. Perioral features of stereotypy induced by 1 mg/kg of apomorphine, and spontaneous activity did not show age-dependent changes. Heterogeneous features of apomorphine stereotypy may have distinct physiological substrates that are differentially sensitive to parameters of maturation and ageing.


A new chronology for the Māori settlement of Aotearoa (NZ) and the potential role of climate change in demographic developments.
Understanding the role of climate change, resource availability, and population growth in human mobility remains critically important in anthropology. Researching linkages between climate and demographic changes during the short settlement history of Aotearoa (New Zealand) requires temporal precision equivalent to the period of a single generation. However, current modeling approaches frequently use small terrestrial radiocarbon datasets, a practice that obscures past Māori population patterns and their connection to changing climate. Our systematic analysis of terrestrial and marine 14C ages has enabled robust assessments of the largest dataset yet collated from island contexts. This analysis has been made possible by the recent development of a temporal marine correction for southern Pacific waters, and our findings show the shortcomings of previous models. We demonstrate that human settlement in the mid to late 13th century AD is unambiguous. We highlight initial (AD 1250 to 1275) settlement in the North Island. The South Island was reached a decade later (AD 1280 to 1295), where the hunting of giant flightless moa commenced (AD 1300 to 1415), and the population grew rapidly. Population growth leveled off around AD 1340 and declined between AD 1380 and 1420, synchronous with the onset of the Little Ice Age and moa loss as an essential food source. The population continued to grow in the more economically stable north, where conditions for horticulture were optimal. The enhanced precision of this research afforded by the robust analysis of marine dates opens up unique opportunities to investigate interconnectivity in Polynesia and inform the patterns seen in other island contexts.


Association Between Preoperative HbA1c Levels and Complications after Esophagectomy: Analysis of 15,801 Esophagectomies From the National Clinical Database in Japan.
To elucidate the association between preoperative hemoglobin A1c (HbAlc) levels and short-term outcomes after oncologic esophagectomy. Although diabetes mellitus is associated with an increased risk of postoperative morbidity in several types of surgery, the association of diabetes mellitus with short-term outcomes after esophagectomy has shown conflicting results. We analyzed 15,801 patients who underwent oncologic esophagectomy between 2015 and 2017 from the National Clinical Database. We evaluated the associations between preoperative HbA1c levels and short-term outcomes, using multivariable logistic regression and restricted cubic spline models. The cohort included 12,074, 1361, 1097, 909, and 360 patients with HbA1c levels of ≤5.9%, 6.0% to 6.4%, 6.5% to 6.9%, 7.0% to 7.9%, and ≥8.0%, respectively. There were value-dependent associations between HbA1c values and odds ratios for anastomotic leakage, surgical site infections, pneumonia, and composite outcomes. Compared with the HbA1c category of ≤5.9%, the categories of 7.0% to 7.9% and ≥8.0% were at higher risk for anastomotic leakage ( P < 0.001 and 0.031, respectively), the category of ≥8.0% was at higher risk for surgical site infections ( P = 0.001), the categories of 6.5% to 6.9% and 7.0% to 7.9% were at higher risk for pneumonia ( P = 0.016 and 0.002, respectively), and the categories of 7.0 to 7.9 and > 8.0% were at higher risk for composite outcomes (P < 0.001 and 0.001, respectively). Preoperative HbA1c levels are associated with the risk of postoperative complications after esophagectomy, and the threshold values differed among the outcomes. Preoperative HbA1c is useful in predicting the risk of postoperative complications.


Enhanced prostaglandin production in the ischemic-reperfused myocardium by captopril linked with its free radical scavenging action.
Captopril, an angiotensin converting enzyme inhibitor, has been shown to increase prostaglandin production by an as yet unknown mechanism, which this study was designed to explore. Isolated rat heart was perfused by the Langendorff technique for 15 minutes in the presence or absence of captopril. Ischemia was then induced for 60 minutes by terminating the coronary flow, followed by 60 minutes of reperfusion. Our results indicate that captopril stimulated prostaglandin and thromboxane production, but it inhibited malonaldehyde formation. Coronary flow and high energy phosphate compounds were increased, but lactate dehydrogenase and creatine kinase release decreased, demonstrating cardioprotective effects. Captopril also inhibited the production of hydroxyl radical in the heart during reperfusion, suggesting that stimulated prostaglandin production may be linked with the generation of free radicals via the eicosanoid system.


Natural killer activity of human blood lymphocytes.
Natural killer (NK) activity is an operational designation. It implies the in vitro cytotoxicities registered in short-term tests exerted by lymphocytes derived from donors with no known immunization history against the particular target. The strength of the effect exerted by unmanipulated blood lymphocytes shows an individual variation. Short-term in vitro treatment with interferon elevates the lytic potential of lymphocytes. Owing to the heterogeneity of the cytotoxic blood lymphocytes with regard of cell surface properties it is not possible to separate all active cells and inactive cells in clean populations. A considerable enrichment of active cells can be achieved if nylon wool non-adherent, large, granular Fc gamma receptor positive SRBC receptor negative--or low-avidity SRBC receptor positive--OKM1-reactive cells are separated. Negative cells are concentrated in the Fc receptor and OKM1-negative high-avidity SRBC receptor positive high cell density subset. The activity of lymphocytes in the former category is potentiated by interferon and the latter acquire the lytic function if PHA is added to the assay system. Freshly separated, non-cultured tumor cells are not or weakly sensitive to the effect of unmanipulated lymphocytes. However, when the lymphocytes are treated with interferon prior to the assay a lytic potential can be induced even against these in allogeneic effector target combinations. Cytotoxic cells which acquired the function after in vivo and/or in vitro immunization are designated as 'cytotoxic T-lymphocytes' (CTL), and were shown to act on the basis of antigen recognition. The expression of known T-markers on at least a fraction of the active cells and the recognition of alloantigens in NK systems suggest that the distinction between CTL and NK cells is not as sharp as initially suggested.


Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies.
The tolerability and pharmacokinetics of risedronate after a single oral administration and during multiple oral administrations were examined in healthy adult male volunteers. In the single dose study, the dose was increased gradually from 1 mg to 2.5, 5, 10, or 20 mg. Subsequently, risedronate was given by multiple administration, 5 mg per dosing, once daily, for 7 days. The observed adverse events, whose causality was possibly related or unknown, included headache, diarrhea, increased body temperature, increased CK-BB, and increased urinary Beta(2)-microglobulin excretion rate. However, none of these adverse events was clinically significant. The results thus showed that risedronate was well tolerated when delivered as a single administration of up to 20 mg or as a multiple administration of up to 5 mg/day. In the multiple dose study, changes in urinary deoxypyridinoline suggested the bone antiresorptive activity of risedronate. In the single dose study, AUC and C(max), after the administration of risedronate at 1, 2.5, 5, 10, and 20 mg, increased dose dependently, and the T(max), t(1/2), and urinary excretion rates were nearly constant. Therefore, the pharmacokinetic profile of risedronate was considered to show linearity in a dosage range of up to 20 mg. Furthermore, the results obtained in the multiple administration study indicated that the plasma concentrations of risedronate reached a steady state on day 4 of administration. The plasma concentrations of risedronate after the administration of 2.5 mg risedronate to the Japanese population were nearly comparable to the serum concentrations after the administration of 5 mg risedronate to the United Kingdom study population.


Isolation and identification of cDNA fragments and full-length cDNA differentially expressed in human glioblastoma cell line BT-325 versus all-trans retinoic acid induction .
To investigate the differentiation process of the human glioblastoma cells. Differential display reverse transcribed-PCR (DDRT-PCR) was used to isolate the genes differentially expressed in control and all-trans retinoic acid treated human glioblastoma cell line BT-325. Routine method of cDNA library screening was performed to clone full-length cDNA. Thirty-six RT-PCR reactions were performed and 64 differentially expressed fragments were recovered, amplified and cloned. Of them, 46 ESTs were sequenced and delivered into the GenBank. The homology comparison using BLAST algorithm revealed that 22ESTs are highly homologous with the known genes and many of them play important roles in the cell differentiation progress. A dot-blot hybridization was conducted to certify the differentiation expression. The result showed that 27 EST clones are expressed at different level in control and all-trans retinoic acid treated BT-325 cells. A full-length cDNA was cloned using the EST-HGBB098. DDRT-PCR was a simple and effective method to serially analyze the differentially expressed genes.


Gas exchange characteristics and nitrogen relations of two Mediterranean root hemiparasites:Bartsia trixago andParentucellia viscosa.
Plant height, light-saturated rates of photosynthesis (A max) and foliar nitrogen concentration (N 1) were measured forBartsia trixago under field conditions in Mallorca. All three variables were postively correlated, and were also positively related to the abundance of nitrogen-fixing legumes in the associated vegetation (putative host species).A max forB. trixago ranged from 7.7 to 18.8 μmol m-2 s-1; similar rates were measured for a second hemiparasiteParentucellia viscosa, and both species were within the range of rates measured for six putative hosts (10.6-19.2 μmol m-2 s-1). Fertilization of unattachedB. trixago plants with inorganic nitrogen (ammonium nitrate) elicited neither the growth nor the photosynthetic responses observed in plants considered to be parasitic on legumes and in receipt of an enriched organic nitrogen supply. Both hemiparasites had high diurnal leaf conductances (g s) (469-2291 mmol m-2 s-1) and were at the upper end of the range of those measured in putative hosts (409-879 mmol m-2 s-1). In contrast with the latter, high nocturnal rates ofg s were also recorded for the two hemiparasites (517-1862 mmol m-2 s-1). There was no clear relationship between eitherA max orN 1 and eitherg s, transpiration (E) or water use efficiency (A max/E) inB. trixago plants. The economics of water loss appear to be independent of both the supply of nitrogen from the host and autotrophic carbon fixation.


Usher's syndrome: electrophysiological tests of the visual and auditory systems.
The symptoms of Usher's syndrome - congenital hearing impairment and tapetoretinal dystrophy - are difficult to detect in young children. The electroretinogram (ERG), visual evoked potential (VEP), auditory nerve and brain-stem responses as well as the cochlear microphonic potentials were used to evaluate the defects of the visual and auditory systems in 20 patients, 3-45 years of age. This study demonstrates the usefulness, reliability and convenience of the electrophysiological tests for early diagnosis and functional evaluation of Usher's syndrome.