A radiologist looks at AIDS: imaging evaluation based on symptom complexes.
Many other symptom complexes could be discussed that affect virtually every organ system of patients with AIDS or ARC. While important and interesting, these are less likely to come to the attention of the radiologist for assistance in diagnosis and management. The scope of this review has also precluded discussion of infection control, although an effective plan for handling AIDS patients in a radiology department is absolutely vital. My hope is that this review will serve as a reasonable introduction or summary of the current role of the radiologist in dealing with AIDS. Obviously, new developments are coming at an extraordinary pace, and all radiologists must avail themselves of the most current sources of information.


What is the quality of surgery-related information on the internet? Lessons learned from a standardized evaluation of 10 common operations.
Although there is high-quality information on the Internet, it is difficult for patients to identify high-quality Web sites from those with inaccurate or misleading information. Our goal was to determine specific characteristics of Web search results that yield high-quality information and can be discerned easily by patients. A validated rating system was used to evaluate surgical Web sites for appropriateness and adequacy. Web sites were identified using three search term types (technical, descriptive, and layperson) for 10 common surgical procedures. The top three sponsored (paid) and unsponsored (unpaid) Web site matches were identified. The search and analysis were repeated 1 month later. One hundred forty-five Web sites were retrieved: 90 unsponsored and 55 sponsored. Unsponsored sites had higher mean composite scores than sponsored Web sites (50.6% versus 25%, p < 0.0001). Searches using layperson terms had lower mean composite scores compared with those using technical terms (36.9% versus 47.5%, p < 0.02). Professional Web sites had the highest mean composite scores (66.3%); legal Web sites had the lowest (6.3%). On regression analysis, unsponsored Web sites were associated with higher composite scores (p < 0.0001); number 1 match results (p < 0.02) and using layperson search terms (p < 0.052) were associated with lower mean composite scores. Repeat search results demonstrated no significant differences, except number 3 match results were no longer significant. To optimize patients' Web searches, surgeons should recommend unsponsored sites; suggest professional society sites, if available; and provide technical search terms. But information on some topics, such as risks of not undergoing surgery, remains poor and requires discussion between the surgeon and patient.


Spontaneous symmetry breaking in self-organizing neural fields.
We extend the theory of self-organizing neural fields in order to analyze the joint emergence of topography and feature selectivity in primary visual cortex through spontaneous symmetry breaking. We first show how a binocular one-dimensional topographic map can undergo a pattern forming instability that breaks the underlying symmetry between left and right eyes. This leads to the spatial segregation of eye specific activity bumps consistent with the emergence of ocular dominance columns. We then show how a 2-dimensional isotropic topographic map can undergo a pattern forming instability that breaks the underlying rotation symmetry. This leads to the formation of elongated activity bumps consistent with the emergence of orientation preference columns. A particularly interesting property of the latter symmetry breaking mechanism is that the linear equations describing the growth of the orientation columns exhibits a rotational shift-twist symmetry, in which there is a coupling between orientation and topography. Such coupling has been found in experimentally generated orientation preference maps.


Cancer incidence among a cohort of smokeless tobacco users (United States).
Smokeless tobacco (ST) use remains a prevalent form of tobacco use among certain US populations. The purpose of this paper is to clarify its role in cancer development. Using data from a prospective cohort of the US population, we categorized 6,779 subjects 45-75 years of age as ST users or non-ST users. Subjects were further stratified by cigarette smoking status in order to differentiate 'exclusive' ST users (n=414) from never tobacco users (n=2,979). In this cohort, exclusive ST use was not associated with increased incidence of all cancer in males (hazard ratio=0.8, 95% CI: 0.4, 1.6) or females (HR=1.2, 95% CI: 0.7-2.1) or oral cancer (standardized incidence ratio=30, 95% CI: 3, 95). No synergistic effect was observed between ST and cigarette smoking among male combined users (females were not analyzed for combined use) for the major cancers. In contrast to the well-known deleterious effects of cigarette smoking, ST use did not substantially increase the risk for cancer incidence above that of non-tobacco users, particularly among males. Although the use of tobacco in any form is to be discouraged, our data suggests that cancer risks are much lower from ST use than from cigarette smoking.


[Breast metastases from lung cancers with the EGFR mutation].
The breast is a rare site for metastases from lung cancers. Their occurrence in patients with adenocarcinoma which has the EGFR mutation is exceptional. In this context, it is sometimes difficult to differentiate a second primary breast cancer from a breast metastasis. We report the cases of two patients who developed breast metastases from lung adenocarcinoma that was TTF1 positive with a deletion of exon 19 of the EGFR gene. A non-smoking woman of Asian origin, presented with a solitary breast metastasis 29 months after being established on first-line chemotherapy. The second case was a Caucasian patient who was an active smoker presented with tumor progression with multiple metastases including involvement of both breasts 10 months after the start of treatment with a tyrosine kinase inhibitor. In both, tumor cells from the breast showed positive immunostaining for TTF1 and genotyping detected the presence of the deletion of exon 19 of the EGFR gene. In patients with lung adenocarcinoma and EGFR mutation, immunohistochemical examination, including TTF1 and genotyping of synchronous breast tumour, is needed to confirm its metastatic nature and to guide treatment.


Does healing of esophagitis improve esophageal motor function?
This study investigates whether healing of erosive esophagitis leads to an improvement of esophageal motor abnormalities. Manometric studies were performed in 18 patients with erosive esophagitis before and after healing of the mucosal lesions and in 15 healthy controls. Nine patients were treated with a Nissen fundoplication and nine with H2-receptor antagonists. After healing, patients were followed for a mean duration of 3.0 +/- 0.4 years. Compared to controls, patients had significantly lower contraction amplitudes and lower esophageal sphincter pressures (P less than 0.01), while the duration and velocity of esophageal contractions was similar in both groups. Lower esophageal sphincter pressure increased after surgical treatment, while no such changes were observed in medically treated patients. In both groups amplitude, duration, and velocity of esophageal contractions were not affected by healing of esophagitis. On extended follow-up, all surgically treated patients remained asymptomatic while eight of nine medically treated patients developed a symptomatic relapse which was accompanied by erosive esophagitis in six of them. The lack of improvement in esophageal motor function after healing of esophagitis may contribute to the frequent occurrence of relapse in medically treated patients.


Exosome-functionalized magnesium-organic framework-based scaffolds with osteogenic, angiogenic and anti-inflammatory properties for accelerated bone regeneration.
Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effective therapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promising strategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study, motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized an exosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of the benefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhance osteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated the beneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bone marrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells (HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells, stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and accelerated bone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed that PLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, we provide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesis property.


Telemedicine for multiple sclerosis patients: assessment using Health Value Compass.
Telemedicine carries the potential of improving accessibility to health services, especially for disabled people. To assess the health-related outcomes of short-term implementation of telemedicine (telemed) for MS patients. A prospective study of 40 MS patients divided into a control group and a telemed group was conducted, in two stages: A. Six months' follow-up for measurement of baseline health-related variables; B. Implementation stage, adding home telecare to the telemed group. A Health Value Compass was applied to assess the outcomes of home telecare implementation. Clinical status, cost data, patients' self-assessment of Health Related Quality of Life (HRQoL) and satisfaction with telecare were studied. Patients in the telemed group demonstrated improved clinical outcome measured by symptoms severity. There was a decrease of at least 35% in the medical costs for 67% of the telemed group patients. Satisfaction with telecare was high and most patients would recommend this service to others. The present pilot study, applying Health Value Compass-based analysis, suggests that telecare is a powerful tool for monitoring MS patients at home, carries the potential to improve health care while reducing costs, and should be considered for implementation as part of the management of chronic neurological diseases.


MultisHRP-DNA-coated CMWNTs as signal labels for an ultrasensitive hepatitis C virus core antigen electrochemical immunosensor.
An ultrasensitive and selective electrochemical immunosensor was developed for the detection of hepatitis C virus (HCV) core antigen. The immunosensor consists of graphitized mesoporous carbon-methylene blue (GMCs-MB) nanocomposite as an electrode modified material and a horseradish peroxidase-DNA-coated carboxyl multi-wall carbon nanotubes (CMWNTs) as a secondary antibody layer. After modification of the electrode with GMCs-MB nanocomposite, Au nanoparticles were electrodeposited on to the electrode to immobilize the captured antibodies. The bridging probe and secondary antibodies linked to the CMWNTs, and DNA concatamers were obtained by hybridization of the biotin-tagged signal and auxiliary probes. Finally, streptavidin-horseradish peroxidases (HRP) were labeled on the secondary antibody layer via biotin-streptavidin system. The reduction current of MB were generated in the presence of hydrogen peroxide and monitored by square wave voltammetry. Under optimum conditions, the amperometric signal increased linearly with the core antigen concentration (0.25pgmL(-1) to 300pgmL(-1)). The immunosensor exhibites the detection limit as low as 0.01pgmL(-1) and it has a high selectivity. The new protocol showed acceptable stability and reproducibility, as well as favorable recovery for HCV core antigen in human serum. The proposed immunosensor has great potential for clinical applications.


Lipoblastoma/lipoblastomatosis: a clinicopathologic study of 16 cases in Taiwan.
Lipoblastoma/lipoblastomatosis is an uncommon benign lipomatous tumor affecting mainly infants and children. It presents as a painless mass located frequently in upper and lower extremities. The present study was conducted to characterize the clinicopathologic features of lipoblastoma/lipoblastomatosis in a Chinese population. A retrospective survey of 16 cases of pathologically confirmed lipoblastoma/lipoblastomatosis from 1988 to 2002 was performed. The available clinical information and histological sections were reviewed. The study involved 10 males and 6 females ranging in age from 5 to 49 months (median, 11.5 months). The patients presented with mass involving neck (n = 5), inguina (n = 3), feet (n = 2), arm (n = 1), leg (n = 1), thorax (n = 1), mesentery (n = 1), buttock (n = 1), and presacral region (n = 1). The lesions were removed surgically. Histologically, the majority (11/16) of primary tumors were of diffuse type. Follow-up ranging from 5 to 125 months was available in 13 patients. Four patients experienced a recurrence of tumors in the neck (n = 2) and lower extremities (n = 2) 11-84 months after operation. The most common site of involvement of lipoblastoma/lipoblastomatosis in our series was the neck. A follow-up period of more than 3 years is recommended for patients with this condition.


Impact of lens densitometry on phacoemulsification parameters and usage of ultrasound energy in femtosecond laser-assisted lens surgery.
The aim of this study was to find the correlation between lens densitometry measurements using Pentacam Scheimpflug imaging system with equivalent average ultrasound power and cumulative dissipated energy (CDE) in femtosecond laser-assisted lens surgery (FLALS). One hundred and twenty-four eyes were analyzed retrospectively, of which 109 had undergone cataract surgery and 15 had received refractive lens exchange with FLALS. Using the Pentacam Nucleus Staging (PNS) lens densitometry program, preoperative mean lens density and cataract grading score were evaluated. Average ultrasound power and CDE were recorded during surgery and correlated with the PNS grading and average lens density value. Exclusion criteria included small pupil size, previous ocular surgeries, tumors, optic atrophy, corneal scarring, intraoperative capsular rupture, and zonular dehiscence. Preoperative average lens density compared with CDE showed a weak significant positive linear correlation (p < 0.0001). CDE increased as lens density increased. This was also noticed when CDE and ultrasound time were compared with the PNS grading, demonstrating a significant moderate correlation (p < 0.0001). With increasing average lens density, the equivalent average ultrasound power showed a positive correlation (p < 0.0001). A weak positive correlation between estimated fluid use and PNS was also observed (p < 0.0001). Forty-one cases that did not require ultrasound energy during phacoemulsification had a PNS score between 0 and 1. The Centurion Phacoemulsification machine has been shown to correlate positively with the Pentacam Scheimpflug System offering an objective and repeatable measure of lens density and cataract grading. This can aid in intraoperative phacodynamics and help reduce phacoemulsification complications, such as corneal endothelial injury.


Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study.
This study compared measured physical performance, health-related quality of life (HRQOL), and social role attainment between extremity sarcoma survivors and controls, and evaluated associations between disease and treatment exposures, health conditions, and performance measures. Survivors of extremity sarcoma from the St. Jude Lifetime cohort and controls frequency matched by age-, sex-, and race completed physical performance testing and questionnaires. Survivors with Z-scores on outcome measures ≤ -2.0 SD (compared to controls) were categorized with severe impairment/limitation. Among 206 survivors (52.4 % male median age 36 years (range 19-65)), 37 % had low relative lean mass, 9.7 % had an ejection fraction <50 %, 51.5 % had diffusion capacity for carbon monoxide <75 %, 27.7 % had sensory and 25.2 % motor neuropathy, and 78.2 % had musculoskeletal complications. Severe impairments/limitations were present among ≥25 % of survivors on fitness, balance, and physical HRQOL measures, and among ≥15 % on strength and activity of daily living measures. Lower extremity tumor location (OR 8.23, 95 % CI 2.54-26.67, P value 0.0004) and amputation (OR 8.07, 95 % CI 3.06-21.27, P value <0.0001) were associated with poor fitness. Poor fitness was associated with increased odds of scoring <40 on the SF-36 physical component summary (OR 4.83, 95 % CI 1.95-11.99, P value 0.001) and role-physical subscale (OR 3.34, 95 % CI 1.33-8.43, P value 0.01). Survivors and controls had similar rates of marriage, independent living, employment, and college attendance. Extremity sarcoma survivors experience high rates of physical impairment and report lower than expected physical HRQOL. However, they are as likely as peers to be married, live independently, be employed, and attend college. Follow-up for extremity sarcoma survivors should include assessment of need for further orthopedic care and rehabilitation to address cardiopulmonary and musculoskeletal health.


Long-term mental health outcome of returning migrant children and adolescents.
We examined how remigration influences the prevalence of psychiatric symptoms among children and adolescents in the long term. We investigated depressive and behavioral symptoms in 320 Finnish children and adolescents who moved back from Sweden while of school-age during the years 1984-1985 and in a series of controls. The data were gathered in two phases, with questionnaires sent to the parents, children and teachers in 1986, and with further questionnaires sent to the parents and children in 1992. Depression was measured by means of the Children's Depression Inventory (CDI) (8) and behavioral symptoms with the Children's Behavioral Questionnaire, filled in by the teachers (14) in the first phase and by the parents (15) in the second. We compared prevalence of these psychiatric symptoms between the migrants and controls in groups divided by age and sex in the two phases and examined how depressiveness or behavioral disturbance shortly after migration served to predict later psychiatric symptoms. The following findings emerged: The boys who moved before puberty had more psychiatric symptoms than their controls in both phases, while the best-adapted group consisted of the girls who moved before puberty. Those migrant children who moved during puberty had more psychiatric symptoms than their controls only in the second phase. The depressive features and behavioral disturbances observed among the migrants during the first phase did not lead to disturbances in the second phase, whereas an association was found between psychiatric disturbances among the native controls in the first and second phases.


Citrus limon peroxidase-assisted biocatalytic approach for biodegradation of reactive 1847 colfax blue P3R and 621 colfax blue R dyes.
One of the big environmental problems in today's world is dye-contaminated toxic waste. Peroxidase is known as highly efficient for the degradation of various pollutants, including dyes. Environmental contamination caused by the discharge of dyes into water bodies is an onerous challenge that poses both human and ecological hazards. In the current studies, biocatalysts used for enzyme decolorization (1847 Colafx Blue P3R and 621 Colafx Blue) are regarded as an eco-friendly method utilizing commonly available low-cost material lemon peels (Citrus limon peroxidase). Peroxidase was extracted in a phosphate buffer of pH 7.0 and partially purified by 20-80% ammonium sulfate precipitation technique from Citrus limon peels. The soluble enzyme was characterized in terms of kinetic and thermodynamic parameters. The values of Km and Vmax (23.16 and 204.08 μmol/ml/min) were determined, respectively. The enzyme showed maximum activity at pH 5.0 and a temperature of 55 °C. Citrus limon efficiently degraded 1847 Colafx Blue P3R and 621 Colafx Blue R dyes with maximum degradation of 83 and 99%, respectively, with an initial dye concentration of 200 ppm at pH 4 and 35 °C temperature within 5-10 min of incubation time. The effect of the redox mediator on the degradation process was examined. Results showed that the peroxidase HOBT system efficiently enhanced the degradation of dyes from water. Hence, Citrus limon peroxidase is an efficient biocatalyst for the treatment of effluents.


CircATP2B4 promotes hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells via the miR-223/ATR axis.
Circular RNAs (circRNAs) function as important modulators in the progression of pulmonary arterial hypertension (PAH). Here, we aimed to discover the role and working mechanism of circATP2B4 in hypoxia-induced proliferation and migration of PASMCs. The proliferation, migration and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing assay and flow cytometry. The expression of circATP2B4, ATPase plasma membrane Ca2+ transporting 4 (ATP2B4), microRNA-223 (miR-223) and ATR serine/threonine kinase (ATR) was quantified by quantitative real time polymerase chain reaction (qRT-PCR). Circular RNA Interactome and microT-CDS were used to search the targets of circATP2B4 and miR-223, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to validate the above predictions. Western blot assay was performed to detect the protein expression of ATR. Hypoxia treatment promoted the proliferation and migration and impeded the apoptosis of PASMCs. A significant increase of circATP2B4 expression was observed in the serum of PAH patients and hypoxia-induced PASMCs compared with healthy volunteers and PASMCs under normoxia condition. MiR-223 is a target of circATP2B4, and the effects of circATP2B4 silencing on PASMCs were overturned by the transfection of anti-miR-223. ATR is a functional target of miR-223, and miR-223 inhibited the proliferation and migration while accelerated the apoptosis of PASMCs through targeting and down-regulating ATR. CircATP2B4 could up-regulate the level of ATR through sponging miR-223 in PSAMCs. CircATP2B4 potentiated hypoxia-induced proliferation and migration of PASMCs through the miR-223/ATR axis. Restoration of the level of miR-223 might be an effective therapeutic method for the treatment of PAH.


Effect of high power low frequency ultrasound processing on the stability of lycopene.
The stability of lycopene was evaluated after application of high power low frequency ultrasound. The study was carried out on a solution containing pure lycopene to evaluate the direct effect of ultrasound on lycopene and on tomato purée to evaluate the direct and indirect effects of ultrasound application within a food matrix. Power densities ranging from 55 to 5000 W/L and temperatures ranging from 23°C (ambient) to 60°C were evaluated. The experiments on pure lycopene showed that the application of ultrasound did not have any direct effect over lycopene. However, the retention of lycopene in tomato puree has decreased indicating an indirect effect on lycopene stability caused by high concentration of hydrogen peroxide and the activation of peroxidase enzymes leading to the reduction of ascorbic acid and its regenerative action towards lycopene.


Kawasaki disease: ubiquitin-specific protease 5 promotes endothelial inflammation via TNFα-mediated signaling.
This study aimed to explore the functions of ubiquitin-specific protease 5 (USP5) in the endothelial inflammation of Kawasaki disease (KD). USP5 expression levels in HCAECs were examined after stimulation with TNFα or KD sera. The inflammatory cytokine expression level and nuclear factor κB (NF-κB) signaling activation proteins were also investigated in HCAECs by using USP5 overexpression/knockdown lentivirus as well as its small molecule inhibitor vialinin A. USP5 expression level is upregulated in HCAECs after stimulation with KD sera. Similarly, the USP5 expression level is also increased in a time- and dose-dependent manner upon TNFα stimulation in HCAECs. Moreover, USP5 sustains proinflammatory cytokine production and NF-κB signaling activation, whereas USP5 knockdown causes the proinflammatory cytokine levels to decrease and suppress NF-κB signaling activation. Notably, the USP5 inhibitor vialinin A can suppress the expression of inflammatory genes induced by TNFα and IL-1β in HCAECs. Our study identified USP5 as a positive regulator of TNFα production and its downstream signaling activation during the inflammatory responses in HCAECs, and demonstrated that its inhibitor vialinin A might serve as a candidate drug for KD therapy to prevent the excessive production of proinflammatory cytokines. USP5 is upregulated in human coronary artery endothelial cells (HCAECs) whether incubated with acute KD sera or TNFα in vitro. USP5 promotes proinflammatory cytokine expression by sustaining NF-κB signaling activation in HCAECs. The USP5 inhibitor vialinin A can suppress the expression levels of proinflammatory cytokines in HCAEC, thus providing a novel mechanism and intervention strategy in KD therapy.


Use of high frequency ultrasonography in dermatology departments in Spain.
High Frequency Ultrasonography (HFUS) is a rapid, reliable, and effective diagnostic technique that has become progressively employed within the past years among dermatologists. To describe the use of HFUS among dermatology departments in Spain. An observational, cross-sectional descriptive study was conducted in 23 dermatology departments at Spanish public hospitals. Study data was collected during 10 working days. Fifty dermatologists from 11 Spanish regions participated in the study; 659 HFUS procedures were undertaken in 633 patients. HFUS indications were benign tumors (41%), malignant tumors (28%), inflammatory diseases (18%), skin appendage conditions (10%), and cosmetic conditions (1%). HFUS was performed for assessing the clinical differential diagnosis (58% of cases), surgical planning (17%), follow-up (17%), and other reasons (7%). Among the diagnostic group, the scan confirmed clinical diagnosis in 82% of cases and helped to change the clinical diagnosis in 17% cases (10% of total scans). HFUS procedure duration was less than 5 minutes (45%), between 5 and 10 minutes (32%), and more than 10 minutes (21%). Mean patient satisfaction score (range 0 to 5) was 4.8. The use of HFUS in usual practice is increasing, especially among younger dermatologists. This procedure is effective both for confirming and changing diagnosis, as well as for therapy decision making and follow-up. It is also worth remarking that a very high degree of patient satisfaction was recorded. The descriptive results reported in this study support the use of ultrasonography techniques and further reinforce their use in Dermatology.


A requirement for ARF6 during the completion of cytokinesis.
During cancer development, coordinated changes in cell motility and cell cycle progression are required for the gradual transformation of normal cells into cancer cells. Previous studies have shown that ARF6 is a critical regulator of epithelial cell integrity and motility via its role in membrane movement and actin-based cytoskeletal remodeling. Recently, we have found that ARF6 also plays a role during cell division. It localizes to the cleavage furrow and midbody of cells during mitosis, and its activity is regulated during cytokinesis. Here, we investigate the requirement for ARF6 during mitosis and find that depletion of ARF6 using RNA interference disrupts the completion of cytokinesis. This finding demonstrates that ARF6 is essential during the final stages of cytokinesis. In addition, we have identified Ku70, a DNA-binding protein that is required for DNA damage repair, as a new ARF6-interacting protein and found that it is part of a complex with ARF6, especially during mitosis. These results clarify the importance of ARF6 activity during cytokinesis and begin to reveal other molecules that may contribute to the function of ARF6.


Prognostic performance of lymphocyte-to-monocyte ratio in diffuse large B-cell lymphoma: an updated meta-analysis of eleven reports.
The findings on the prognostic value of lymphocyte-to-monocyte ratio (LMR) in diffuse large B-cell lymphoma (DLBCL) are inconsistent. This meta-analysis was conducted to more precisely evaluate the prognostic significance of LMR in DLBCL. This analysis combined eleven studies with 4,578 patients aiming to assess the association of LMR with overall survival (OS) and progression-free survival (PFS) in DLBCL. Data from studies directly reporting a hazard ratio (HR) with 95% corresponding confidence interval (CI) in multivariate analysis were pooled to estimate the effect. Our results suggested that patients with decreased LMR had shorter OS (HR =1.79, 95% CI =1.54-2.08, P<0.001) and PFS (HR =2.21, 95% CI =1.80-2.72, P<0.001) in DLBCL. Stratified analyses indicated that each confounder showed consistent prognostic value in DLBCL. There was no significant heterogeneity for PFS (P H=0.192) and OS (P H=0.212) among the enrolled studies. This meta-analysis indicated that decreased LMR might be a marker in the prediction of poor prognosis for patients with DLBCL.


Morphological and biomechanical analyses of the human healthy and glaucomatous aqueous outflow pathway: Imaging-to-modeling.
Intraocular pressure (IOP) is maintained via a dynamic balance between the production of aqueous humor and its drainage through the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of the conventional outflow pathway. Primary open angle glaucoma (POAG) is often associated with IOP elevation that occurs due to an abnormally high outflow resistance across the outflow pathway. Outflow tissues are viscoelastic and actively interact with aqueous humor dynamics through a two-way fluid-structure interaction coupling. While glaucoma affects the morphology and stiffness of the outflow tissues, their biomechanics and hydrodynamics in glaucoma eyes remain largely unknown. This research aims to develop an image-to-model method allowing the biomechanics and hydrodynamics of the conventional aqueous outflow pathway to be studied. We used a combination of X-ray computed tomography and scanning electron microscopy to reconstruct high-fidelity, eye-specific, 3D microstructural finite element models of the healthy and glaucoma outflow tissues in cellularized and decellularized conditions. The viscoelastic TM/JCT/SC complex finite element models with embedded viscoelastic beam elements were subjected to a physiological IOP load boundary; the stresses/strains and the flow state were calculated using fluid-structure interaction and computational fluid dynamics. Based on the resultant hydrodynamics parameters across the outflow pathway, the primary site of outflow resistance in healthy eyes was in the JCT and immediate vicinity of the SC inner wall, while the majority of the outflow resistance in the glaucoma eyes occurred in the TM. The TM and JCT in the glaucoma eyes showed 1.32-fold and 1.13-fold larger beam thickness and smaller trabecular space size (2.24-fold and 1.50-fold) compared to the healthy eyes. Characterizing the accurate morphology of the outflow tissues may significantly contribute to constructing more accurate, robust, and reliable models, that can eventually help to better understand the dynamic IOP regulation, hydrodynamics of the aqueous humor, and outflow resistance dynamic in the human eyes. This model demonstrates proof of concept for determining changes to outflow resistance in healthy and glaucomatous tissues and thus may be utilized in larger cohorts of donor tissues where disease specificity, race, age, and gender of the eye donors may be accounted for.


Gastric and Caecal Amoebiasis in a Red Kangaroo (Macropus rufus) with Disseminated Toxoplasmosis.
A 1-year-old male red kangaroo (Macropus rufus) with an acute clinical history of lethargy, depression and increased respiratory rate was presented for necropsy examination. Gross lesions in the digestive tract were a distended stomach with watery content and multifocal raised ulcers covered by fibrinous pseudomembranes in the forestomach and caecum. On histopathology, there was necrotizing and ulcerative gastritis and typhlitis with intralesional amoebic trophozoites and Toxoplasma gondii zoites. Lesions due to T. gondii infection were observed in multiple organs and diagnosis was confirmed by fluorescent antibody test and immunohistochemistry. Both toxoplasmosis and gastric amoebiasis are diseases described in macropods. In this case report, we describe concurrent disease caused by both protozoa in a red kangaroo. Lesions of amoebiasis were also observed in the caecum. Both toxoplasmosis and amoebiasis should be considered as differential diagnoses of ulcerative lesions in the gastrointestinal tract in macropods during necropsy examination. Amoebiasis should be suspected especially when ulcerative lesions are observed in the forestomach.


Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells.
Pseudolaric acid B (PAB), a natural diterpene acid present in the traditional Chinese medicinal herb Tu-Jin-Pi, exerted anticancer effects on various cancer cells. However, the effect of PAB on DU145 cells, an in vitro model of hormone-refractory prostate cancer (HRPC), has not been reported previously. In the study, PAB significantly suppressed proliferation of DU145 cells in a dose-dependent manner without obvious cytotoxicity. IC(50) values of 0.89 ± 0.18 and 0.76 ± 0.15 μM at 48h was determined by Cell counting kit (CCK-8) assay and clone formation assay, respectively. PAB also induced DU145 cells apoptosis as confirmed by typical morphological changes and Annexin V-FITC staining. Furthermore, we demonstrated that PAB caused a concentration-dependent elevation of reactive oxygen species (ROS) level in DU145 cells, and N-acetyl-l-cysteine (NAC, a well-known ROS scavenger) could block PAB-induced ROS generation and apoptosis. Western blotting and/or caspase activity data indicated that PAB downregulated anti-apoptotic Bcl-2 protein and activated caspase-9 and caspase-3, which were largely rescued by NAC or MG-132 (proteasome inhibitor). Taken together, these findings provide the first evidence that PAB may inhibit growth of HRPC DU145 cells and induce apoptosis through ROS generation and Bcl-2 degradation via the activation of the ubiquitin-proteasome pathway.


Small molecule-inducible gene regulatory systems in mammalian cells: progress and design principles.
Small molecule-inducible gene circuits are some of the most important tools in biology because they provide a convenient way to exert precise regulation of biological systems. These systems typically are designed to govern gene activation, repression, or disruption at multiple levels, such as through genome modification, transcription, translation, or post-translational regulation of protein activity. Due to their importance, many new systems have been created in the past few years to address different needs or afford orthogonality. They can be broadly characterized based on the inducer used, the mode of regulation, and the effector protein enabling the regulation. Furthermore, each synthetic circuit has varying performance metrics and design considerations. Here, we provide a concise comparison of recently developed tools and recommend standardized metrics for evaluating their performance and potential as biological interrogators or therapeutics.


The prevalence of osteoarthrosis in cases of advanced internal derangement of the temporomandibular joint: a clinical, surgical and histological study.
The articular disk has a central role in the pathology of internal derangement of the Temporomandibular Joint (TMJ). What is less clear is the role of osteoarthrosis in the development of internal derangement. The aim of this study is to determine the prevalence of osteoarthrosis in cases of advanced and recalcitrant TMJ internal derangement that were treated by diskectomy. This study involved 22 joints in 18 patients who underwent surgery for the treatment of advanced and recalcitrant internal derangement of the TMJ. All patients included in the study failed to respond to at least 6 months of pre-operative conservative treatment and the clinical diagnoses of advanced TMJ internal derangement were confirmed on pre-operative MRI's. Tissue specimens were obtained from all 22 joints for histopathology. The specimens included articular disks that were excised from all 22 joints which were found to have severely displaced and deformed disks that were judged to be irreparable at the time of surgery. Also included were eight tissue samples from the mandibular condyles that were judged to be diseased on pre-operative tomograms and at the time of surgery. All samples were prepared in serial sections in the standard way and examined under light microscopy by two experienced Oral Pathologists. There were 22 specimens of articular disk examined together with 8 specimens from the mandibular condyle. All 22 joints (100%) showed histological evidence of disk pathology and eight of the 22 joints (34.4%) were found to have condylar pathology. The most common disk pathology was hyalinization indicative of disk degeneration (12/22). The most common condylar pathology found was articular surface degeneration indicative of osteoarthrosis (8/22). The clinical and radiological diagnoses of advanced TMJ internal derangement correlated with histological findings of degeneration and inflammation of the articular disk in all 22 specimens. The 8 specimens obtained from the condylar head showed histological features consistent with osteoarthrosis. This study showed that osteoarthrosis and internal derangement were found to co-exist in the same joint in about one-third of cases. The fact that osteoarthrosis was not found in all cases suggests that perhaps the widely held view that subclinical osteoarthrosis may lead to pathologic tissue responses in the form of internal derangement will need to be re-examined.


Results of chromosome analysis of rabies virus infected human diploid cells (WI-38).
Fixed rabies virus strains did not induce mitotic or chromosome abnormalities in infected WI-38 cultures. Infected cells were shown to undergo mitosis thus indicating an endosymbiotic type of infection.


Feature-preserving adaptive mesh generation for molecular shape modeling and simulation.
We describe a chain of algorithms for molecular surface and volumetric mesh generation. We take as inputs the centers and radii of all atoms of a molecule and the toolchain outputs both triangular and tetrahedral meshes that can be used for molecular shape modeling and simulation. Experiments on a number of molecules are demonstrated, showing that our methods possess several desirable properties: feature-preservation, local adaptivity, high quality, and smoothness (for surface meshes). We also demonstrate an example of molecular simulation using the finite element method and the meshes generated by our method. The approaches presented and their implementations are also applicable to other types of inputs such as 3D scalar volumes and triangular surface meshes with low quality, and hence can be used for generation/improvement of meshes in a broad range of applications.


Specifying conformational heterogeneity of multi-domain proteins at atomic resolution.
The conformational landscape of multi-domain proteins is inherently linked to their specific functions. This also holds for polyubiquitin chains that are assembled by two or more ubiquitin domains connected by a flexible linker thus showing a large interdomain mobility. However, molecular recognition and signal transduction are associated with particular conformational substates that are populated in solution. Here, we apply high-resolution NMR spectroscopy in combination with dual-scale MD simulations to explore the conformational space of K6-, K29-, and K33-linked diubiquitin molecules. The conformational ensembles are evaluated utilizing a paramagnetic cosolute reporting on solvent exposure plus a set of complementary NMR parameters. This approach unravels a conformational heterogeneity of diubiquitins and explains the diversity of structural models that have been determined for K6-, K29-, and K33-linked diubiquitins in free and ligand-bound states so far. We propose a general application of the approach developed here to demystify multi-domain proteins occurring in nature.


Invasive Giant Cell Tumor of the Lateral Skull Base: A Systematic Review, Meta-Analysis, and Case Illustration.
The current literature regarding cranial giant cell tumor (GCT) management includes scattered case reports and small case series. We present a comprehensive literature review and meta-analysis on this subject, along with a case report describing our management of a patient with temporal GCT. A systematic literature review of all reports on GCTs of the skull was performed, followed by a meta-analysis examining the effect of radiation and degree of resection on tumor recurrence. Fifty-nine abstracts published between 1945 and 2015, reporting 110 cases of GCT, were reviewed. After exclusions were applied, 31 reports, covering 67 patients, were selected for meta-analysis. Average patient age was 33.7 years, and the male:female ratio was roughly 1:1. Tumor locations were temporal in 37 patients, sphenoid in 20 patients, occipital in 6 patients, frontal in 2 patients, and the temporomandibular joint in 2 patients. Treatments were surgery plus radiation in 25 patients, surgery alone in 41 patients, and radiation alone in 1 patient. In the 66 patients who underwent surgery, the degree of resection was gross total resection (GTR) in 34 patients, subtotal resection (STR) in 31 patients, and not recorded in 1 patient. The mean follow-up time was 36 months. Recurrence occurred in 8.8% of patients in the GTR group and in 32.3% of those in the STR group (odds ratio, 0.203; 95% confidence interval, 0.033-0.937; P = 0.018). The odds ratio for STR alone compared with STR plus radiation was 14.01 (P = 0.0038). GCTs of the skull commonly affect young adults, with an equal sex distribution, and are most often centered in temporal bone. GTR is associated with the lowest recurrence rate and should be the goal of treatment. If GTR cannot be achieved, the combination of STR and radiation results in a similar recurrence rate. With the advent of denosumab, there is now a role for chemotherapy in the treatment of GCTs.


The parameters to estimate postoperative severe complications classified through Clavien-Dindo after upper abdominal surgery in patients with primary and recurrent ovarian cancer.
The more surgical effort and performing extensive upper abdominal surgery (UAS) are often required to accomplish the highest rates of optimally cytoreduction in patients with ovarian cancer. Nonetheless, the rate of complications increases with extensive surgery. We have studied the upper abdominal surgery complications by Clavien-Dindo Classification (CDC) and analyzed parameters affecting post-operative severe complications classified through Clavien-Dindo. A retrospective cohort of patients diagnosed with epithelial ovarian cancer from January 1st 2009 to April 30th 2016 was evaluated. Patients who underwent at least one UAS procedure with or without optimal cytoreduction for epithelial ovarian cancer (stage IIIC-IV or recurrent) were included. Postoperative complications were recorded according to the Clavien-Dindo Classification. In total, 58 patients were included. There were 120 UAS procedures performed on the 58 patients. Diaphragm peritonectomy was the most performed surgery (50%, 29/58), and then the other UAS procedures were liver surgery (39.7%, 23/58), cholecystectomy (24.1%, 14/58), splenic surgery (24.1%, 14/58), full-thickness diaphragm resection (22.4%, 13/58), pancreatic surgery (19%, 11/58), resection of tumor from porta hepatis (17.2%, 10/58), celiac lymph node excision (8.6%, 5/58), partial gastrectomy (1.7%, 1/58), respectively. Thirteen patients (22.4%) had post-operative grade 3-5 complications according to CDC within 30 days after surgery. This current study demonstrated that the addition of extensive upper abdominal surgery procedures were not associated with increased postoperative severe complications in patients with recurrent or advanced ovarian cancer. These procedures are safe and feasible for patients in need and also can be performed with acceptable mortality and morbidity.


Wound healing in the early chick embryo studied by scanning electron microscopy.
A simple incision was made in the early chich embryo (stages 3-5) are pellucida endoderm and its subsequent healing studied by scanning electron microscopy (SEM). Initially the wounded edges of the endoderm layer curl towards the ectoderm creating a gaping slit. The endoderm cells adjacent to the slit from large mounds probably in response to a loss of substrate and the trauma of the incision. Healing begins as the endoderm cells direct processes across the underlying cell layers and the two cut edges move towards one another. Many intervening mesoderm cells have cup-shaped processes. As the two endoderm edges meet in the corners of the wound, the wound outline changes to an oval shape. After 2 hours the wound outline is changed to a slit with the cut edges contracting in one or two areas. The cup-shaped mesoderm processes remain in the slit until the wound is healed primarily by endoderm cell movement.


X-STR decaplex study on the population of Czech Republic.
Sample containing 234 unrelated males and 197 unrelated females from Czech Republic was genotyped using an X-STR decaplex system in the following loci: DXS6789, DXS6809, DXS7132, DXS7133, DXS7423, DXS8378, DXS9898, DXS9902, GATA172D05, and GATA31E08. The linkage disequilibrium was observed between DXS6789 and DXS6809. The combined power of discrimination was 0.9999999998 (females) and 0.999998 (males). The mean exclusion chance was 0.999995 (trios) and 0.9998 (duos). This work presents the first population data for X-STR decaplex in Central Europe.


A systematic review of robotic breast surgery versus open surgery.
Robotic-assisted breast surgery (RABS) is controversial. We systematically reviewed the evidence about RABS, comparing it to open conventional breast surgery (CBS). Following prospective registration (osf.io/97ewt), a search was performed in January 2023, without time or language restrictions, through bibliographic databases (PubMed, Web of Science, EMBASE, Scopus, Trip database and CDSR) and grey literature. Quality was assessed in duplicate using Qualsyst criteria (score range 0.0-1.0); reviewer agreement was 98%. The 16 selected studies (total patients: 334,804) had overall high quality (mean score 0.82; range 0.68-0.91). Nine of 16 (56.3%) were cohort studies, 2/16 (12.5%) RCTs, and 5/16 (31.3%) case-control studies. Taking p < 0.05 as the significance threshold, RABS versus CBS was better in aesthetic results and patient satisfaction (10/11 studies; 90%), was surgically costly (4/4 studies; 100%), time-consuming (9/13 studies; 69%), and less painful in the first 6-24 h (2/2 studies; 100%) and without statistically significant differences in complication rates (10/12 studies; 83%) or short-term oncological outcomes (10/10 studies; 100%). Surgical time could be dramatically reduced by training surgical teams, reaching no significant differences between approaches (p = 0.120). RABS was shown to be feasible and safe. The advantages of RABS and long-term outcomes need further research.


A novel percutaneous transhepatic treatment of a benign bile duct stricture - a pilot study.
To assess the effectiveness and outcome of repeated percutaneous transhepatic balloon dilatation combined with targeted intramucosal corticosteroid injection in patients with benign biliary stricture. This single-center pilot study, conducted between February 2014 and June 2016, involved five patients with benign biliary stricture (4 men and 1 woman, mean age 58.2 years). The study included only patients in whom previous surgical or/and non-surgical treatments failed or could not be performed due to patients' medical history and local status. We successfully developed an alternative treatment for patients with benign biliary stricture and performed it without side effects. There were no major complications, and the only one minor complication was cholangitis. In the median follow-up period of 30.24 months (range 14.5 to 44.6 months), no re-occlusion was detected. The disease-free survival, calculated after excluding the first patient (who died of heart attack), was 34.175 months. Percutaneous transhepatic corticosteroid injection combined with balloon dilatation could provide an alternative method for the treatment of benign biliary strictures that is effective in the long term and results in positive outcomes.


Variation in prescribing for the prevention of postoperative nausea, vomiting, and pain following abdominal surgery: A retrospective study.
Adequate postoperative analgesia and prevention of post-op nausea and vomiting (PONV) are core components of modern day anaesthesia and peri-operative care. As well as contributing to overall morbidity, postoperative pain and PONV are frequently cited as one of the most unpleasant and distressing aspects of surgery for patients. Variation in healthcare delivery is known to exist but has often been poorly described. A first step to understanding the consequences of variation is to describe the extent of variation. We aimed to assess variation in pharmacological strategies to prevent postoperative pain, nausea and vomiting in patients undergoing elective major abdominal surgery at a tertiary hospital in Perth, Western Australia, over a three-month period. Retrospective cross-sectional study. We observed considerable variation in prescribing of postoperative analgesia and PONV prophylaxis and suggest that despite adequate evidence based guidelines, they are often overlooked in practice. Measurement of the consequences of variation requires randomised clinical trials that evaluate differences in outcome and cost, associated with the strategies that exist within the spectrum of variation.


Saccadic search performance: the effect of element spacing.
In a saccadic search task, we investigated whether spacing between elements affects search performance. Since it has been suggested in the literature that element spacing can affect the eye movement strategy in several ways, its effects on search time per element are hard to predict. In the first experiment, we varied the element spacing (3.4 degrees -7.1 degrees distance between elements) and target-distracter similarity. As expected, search time per element increased with target-distracter similarity. Decreasing element spacing decreased the search time per element. However, this effect was surprisingly small in comparison to the effect of varying target-distracter similarity. In a second experiment, we elaborated on this finding and decreased element spacing even further (between 0.8 degrees and 3.2 degrees). Here, we did not find an effect on search time per element for element spacings from 3.2 degrees to spacings as small as 1.5 degrees . It was only at distances smaller than 1.5 degrees that search time per element increased with decreasing element spacing. In order to explain the remarkable finding that search time per element was not affected for such a wide range of element spacings, we propose that irrespective of the spacing crowding kept the number of elements processed per fixation more or less constant.


Clinical presentations and outcomes of pancreaticobiliary maljunction in different pediatric age groups.
Pancreaticobiliary maljunction (PBM) is a congenital defect, with risk of developing various pancreaticobiliary and hepatic complications. The presentations of PBM in children and adults are believed to be different, but studies on PBM children of different age groups are limited. This study was to evaluate clinicopathologic characteristics and outcomes in PBM children of different ages. A total of 166 pediatric patients with PBM were reviewed retrospectively. Clinicopathological, imaging, laboratory, surgical, and follow-up data were collected and analyzed. The patients were divided into three age groups, namely, group A (< 1 year, n = 31), group B (1-3 years, n = 63), and group C (> 3 years, n = 72). The major clinical manifestation was jaundice in group A and abdominal pain and vomiting in groups B and C. Acute pancreatitis was more often seen in group C than group A. The length of common channel was significantly longer in group C than group A, while the maximum diameter of common bile duct in group C was smaller than that in group A. Cholangitis and cholecystitis were more commonly performed in groups B and C, while hepatic fibrosis in group A. Whether preoperatively or postoperatively, group C was more likely to have elevated serum amylase, while groups A and B were more likely to present with abnormal liver function indicators, including the increase of aspartate transaminase, alanine transaminase, and gamma-glutamyl transpeptidase. Presentation of PBM varies among different pediatric age groups, thus suggesting that targeted management should be carried out according to these differences.


Effective purification of recombinant peptide ligands for GPCR research.
Peptide purification from natural sources and chemical synthesis is cumbersome with various shortcomings such as low yield, high cost of production, error prone, and restricted by nature of amino acids. Though recombinant DNA technology had overcome all these setbacks for larger proteins, it is still a challenge to produce peptides that are salt free and without impurities. Our approach discussed in this chapter deals with easy and effective purification of peptides of varying sizes (up to 10kDa), expressed as fusion proteins in bacterial system. This includes cleavage of fusion affinity tag by "PreScission protease" in volatile buffer followed by selective acetonitrile precipitation of high-molecular-weight tag in order to purify peptides in solution. This method can be used to purify peptides in large scale for various biochemical and physiological studies.


A double-blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis: a multicentre trial.
Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K(+)-ATPase. To compare pantoprazole 40 mg with omeprazole 20 mg as once daily dosing in the treatment of reflux oesophagitis (grades II and III). This double-blind, randomized, multicentre study included 286 patients. Patients were reendoscoped after 4 weeks, and continued to receive a further 4 weeks of treatment if they were not healed at this time. After 4 weeks of treatment, complete healing occurred in 126/170 (74%) patients in the pantoprazole group and in 67/86 (78%) patients in the omeprazole group (per-protocol analysis). At 8 weeks, the corresponding healing rates were 153/170 (90%) and 81/86 (94%). The differences between the treatment groups were not significant (P = 0.57 and 0.34). Improvement in the principal symptoms of reflux oesophagitis was also very similar between the treatment groups, with 59% and 69% at 2 weeks, and 83% and 86% at 4 weeks, respectively, being free from any individual symptom. Both treatments were well tolerated. This study has shown pantoprazole and omeprazole to be similarly effective and well tolerated in the treatment of mild to moderate reflux oesophagitis.


Unexpected response of a pulmonary blastoma on radiotherapy: a case report and review of the literature.
Pulmonary blastoma (PB) is a rare malignant tumor of the lung. Treatment is primarily surgical, although, combination chemotherapy has been reported to result in objective responses in inoperable tumors or after incomplete resections. To our knowledge, this is the first report of a very radiosensitive PB, which showed major tumor reduction after several fractions of radiotherapy without further tumor regression after additional chemotherapy with cisplatin and etoposide. The literature on the treatment of PB is reviewed.


Plasma amino acid response to single test meals in humans. VI. Determination of available lysine.
The plasma amino acid response to single test meals in young adults was used to determine the amount of physiologically available lysine in heat-treated milk samples. The plasma amino acid responses were evaluated as PAA ratios according to a modified calculation procedure based on the method proposed by Longenecker and Hause. The amount of available lysine was determined by two separate series of single-meal tests. In the first, a relationship was established between the plasma amino acid response (PAA ratio) and the dietary level of lysine (given as synthetic amino acid mixtures). This relationship could be described by linear regression (r = 0.90). This regression line was then used to quantitatively evaluate the lysine PAA ratios obtained from single test meals with heat-treated milk samples. The heat-treatment of the milk samples caused a marked reduction of the amount of physiologically available lysine. The quantitative estimates obtained by the present plasma amino acid technique were in good agreement with determinations of available lysine in the same milk samples based on rat bioassay and chemical analysis.


A brush-border-bound peptidase and amino acid transport.
Aminopeptidase when in its integral form interacts with lecithin to form a stable lipoprotein complex. The reconstituted system is a single-bilayer vesicle about 30 nm in diameter. The hydrophobic part of the amphipathic hydrolase is incorporated in the lecithin bilayer with the portion carrying enzymic activity oriented towards the external aqueous phase. This part can be detached by proteases.


Diverse biological and engineering strategies towards organ regeneration.
Organ regeneration is an important, fascinating, and old topic while much remains unknown in spite of extensive investigations for decades. From March 25th to 27th, 2021, the Third Chinese Symposium on Organ Regeneration took place in the beautiful ocean city of Zhoushan, Zhejiang, China. This biennial conference attracted ~ 300 academic attendees: students, postdoctoral fellows, and principal investigators, in addition to few industrial investigators. The mixed live and virtual talks covered the broad field of organ regeneration from different animal organisms to human organoids, and concluded with some impressive advances on inflammatory signaling, regenerative signaling mechanisms, new technologies, and applications for organ regeneration.


Cognitive bias in line-up identifications: the impact of administrator knowledge.
Prior knowledge of the likely or expected outcome of a forensic investigation has been shown to produce biases in the results obtained, reducing objectivity. The wide prevalence of such cognitive biases in many judgments has long been recognised by social psychologists, but its importance is only now gaining appreciation within forensic science communities. It is therefore timely to draw attention to the power of cognitive biases found in a study of the influence of administrator expectations on photographic identifications. Data are presented to show that when a line-up administrator knows the identity and position of a target within a line-up choice, in which the 'witness' is ignorant of the actual target, that target is more than twice as likely to be selected compared with when the administrator is kept 'blind'. These findings, taken together with related studies, support the recommendation that all forensic analyses are made 'double-blind'-a method that has proven to be effective in reducing such effects within the social sciences.


Unilateral morning glory optic disc anomaly in a case with Down syndrome.
This case is unique because it is the first reported case of Down syndrome with morning glory optic disc anomaly in literature. A 15-year-old girl with features of Down syndrome presented to the Clinic of Ophthalmology for a regular ophthalmologic examination. Her best corrected visual acuity was 20/50 in the right eye and 20/20 in the left eye. The fundus examination revealed findings compatible with unilateral morning glory optic disc anomaly in the right eye. The patient underwent a complete ophthalmologic and systemic evaluation to explore possible associated findings. This case report emphasizes the importance of ophthalmic screening-examinations in Down children to rule out any vision relevant pathology.


Acute physical exercise in humans enhances reconsolidation of emotional memories.
Increasing evidence suggests that when a memory is reactivated through retrieval, it becomes temporarily vulnerable to environmental or pharmacological manipulation, which can consequently update or strengthen the memory. Physical exercise has been shown to modulate the maintenance of fear memories in animals following memory reactivation. This study investigated the effect of intense exercise in modulating the reconsolidation of trauma memories. Fifty-four undergraduate students watched a trauma film depicting the aftermath of a highway car crash. Two days later, participants engaged in either (a) 20-25min of incremental cycling following a memory reactivation induction (Reactivation/Exercise), (b) 20-25min of mild cycling (Reactivation/No Exercise) following memory reactivation, or (c) 20-25min of incremental cycling but no memory reactivation (No Reactivation/Exercise). Saliva samples were collected to index salivary amylase and cortisol at baseline and post activity. Participants completed memory questionnaires relating to declarative and intrusive memory recall two days after memory reactivation. Reactivation/Exercise participants recalled more central details of the trauma film relative to other participants. Increased cortisol predicted better total memory recall in the Reactivation/Exercise, but not in the other conditions. These findings suggest that intense exercise during the period of memory reactivation enhances subsequent trauma memory, and provides human evidence consistent with recent findings of exercise-induced fear reconsolidation in animals.


ACC and IPL networks in the perception of the faces of parents during selective tasks.
The perception of the faces of parents is different from that of other faces. Mother's face perception is associated with childbearing and parenting and has specific cognitive processing properties. Yet, the underlying mechanism remains unknown. We investigated the neural network that is involved in the perception of parent's face based upon parental face selective tasks that were completed by 23 normal adults. Resting state functional magnetic resonance imaging (fMRI) and a task block design with fixation cross sign control fMRI were used. The faces activated the right inferior frontal gyrus, the left and right middle frontal gyri, and the left and right inferior parietal lobule. In addition, the parental faces task resulted in more activation than the control tasks in the left and right anterior cingulate, left middle (superior) temporal gyrus, right and left inferior frontal gyrus. The anterior cingulate cortex (ACC) and the inferior parietal lobe (IPL) are central nodes of the brain network, while the parental face perception network includes the anterior cingulate cortex and superior temporal gyrus (ACC-STG)/parahippocampal network as well as the inferior frontal and inferior parietal lobule (IFG-IPL) network. The network of father's face perception involves the left inferior parietal lobule and left middle frontal gyrus/right middle frontal gyrus/right inferior frontal gyrus, while mother's face perception involves the right inferior parietal lobe and frontal network (MFG.L/IFG.R). The experiments showed that the ACC-STG/parahippocampal network and IFG-IPL network are neural networks used in parental face perception, and the ACC and IPL are central nodes in the network. The neural pathway of parental face perception is similar to the perception of a stranger's face, as both include the STG, but is different in that the perception of the stranger's face involves a connected STG and IPL as a specific neural pathway.


Radiographic Outcomes Following ACDF With Hyperlordotic Implants to Achieve Cervical Anterior Column Realignment.
Degenerative disc disease and progressive sagittal malalignment can both contribute to degenerative cervical myelopathy and radiculopathy. For patients with symptoms refractory to conservative management, anterior cervical discectomy and fusion (ACDF) is a thoroughly vetted intervention shown to improve pain and disability measures. Hyperlordotic implants can also help restore cervical sagittal balance through anterior column realignment (ACR). A consecutive bi-institutional series of patients who underwent ACDF with hyperlordotic polyetheretherketone (PEEK) implants between 2014 and 2016 was reviewed. All included patients underwent ACDF between C3 and C7 inclusive of a hyperlordotic PEEK cervical implant (>10° lordosis), and had ≥12 months of radiographic follow-up. Lateral radiographs were analyzed to compare pre- and postoperative cervical parameters. Forty-six patients were included (mean age, 58.0 years; male, 35%). Mean body mass index was 28.3 kg/m2, and mean radiographic follow-up 14.4 months. Overall, cervical lordosis increased from -7.8° preoperatively to -14.8° postoperatively and to -15.7° at last follow-up (P < 0.001). Additionally, the mean segmental lordosis of ACR levels treated increased from -0.2° preoperatively to -4.8° postoperatively (P < 0.001), but no significant change was observed at last follow-up. Lastly, improvement in segmental lordosis was seen at both postoperative time points at the C3-C4 (P = 0.002 and P = 0.005, respectively), C4-C5 (P < 0.001 and P < 0.001, respectively), and C5-C6 levels (P < 0.001 and P < 0.001, respectively). Our study demonstrates that hyperlordotic PEEK implants used for ACR effectively contribute to restoration of cervical lordosis in patients undergoing ACDF, potentially reducing the need for additional posterior surgery.


Lipoprotein subfractions in patients with sarcopenia and their relevance to skeletal muscle mass and function.
Loss of skeletal muscle mass is a characteristic of aging. Growing evidence suggests the role of fatty acids and their derived lipid intermediates in the regulation of skeletal muscle and function. However, the exact association between lipoprotein subfractions and sarcopenia in elderly individuals remains unclear. In this study, we aimed to investigate the levels of lipoprotein subfractions in sarcopenia patients and their relationship with skeletal muscle mass and function. A total of 84 elderly Chinese subjects aged ≥65 years who did not have diseases that obviously affected lipid metabolism were included. Concentrations of lipoprotein subfractions, including total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), HDL2, HDL3, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), VLDL3, LDL-particle (LDL-P), lipoprotein(a) and remnant-like particle cholesterol (RLP-C), were determined by vertical auto profile. Triglyceride (TG) was measured by an enzymatic colorimetric assay. The skeletal muscle index (SMI) was assessed by bioelectrical impedance analysis. Handgrip strength was measured using a hand-held dynamometer. The levels of TC, TG, LDL-C, LDL-P, IDL, VLDL, VLDL3, RLP-C and C-reactive protein were significantly higher in sarcopenia patients than in controls (p < 0.05). Pearson Product-Moment Correlation Coefficient analysis showed that the TC, TG, LDL-C, IDL, VLDL, VLDL3, and RLP-C levels were negatively associated with the SMI; The TG, IDL, VLDL, VLDL3, and RLP-C were negatively correlated with handgrip strength. In multivariate stepwise regression analysis, the VLDL and RLP-C levels were significantly correlated with the SMI. The sensitivity and specificity of the combined measurement of VLDL and RLP-C in predicting sarcopenia were 69.8% and 92.5% (AUC: 0.831; 95% CI:(0.739, 0.924); p < 0.05). The occurrence of sarcopenia is associated with disorders of lipid metabolism, particularly VLDL and RLP-C.


Accuracy and validity of IK4 handheld video keratometer measurements in children.
The infant keratometer (IK4) is a custom handheld instrument that was designed specifically to allow measurement of corneal astigmatism in infants as young as 6 months of age. In this study, accuracy of IK4 measurements with the use of standard toric surfaces was within 0.25 D. Validity measurements obtained in 860 children aged 3-7 years demonstrated slightly greater astigmatism measurements in the IK4 than in the Retinomax K+. Measurement success was 98% when the IK4 was used. The IK4 may prove to be clinically useful for screening children as young as 3 years of age at high risk for corneal astigmatism.


Evidence of an incerto-hypothalamic dopamine neurone system in the rat.
With the recently introduced glyoxylic acid histochemical fluorescence method, a previously unknown catecholamine-containing fibre system has been revealed in the zona incerta, hypothalamus and the caudal septum. These fibres, designated the incerto-hypothalamic system, have a characteristic, very delicate, finely varicose appearance, and they have a weak fluorescence, indicating an unusually low intra-neuronal amine content. On the basis of their distribution a caudal and a rostral part can be discriminated: the caudal part extends from the area of the dopamine-containing cell bodies in the caudal thalamus, the posterior hypothalamic area and the medial zona incerta (the A11 and A13 cell groups) into the dorsal part of the dorso-medial nucleus and the dorsal and anterior hypothalamic areas; the rostral part extends from the area of the rostral periventricular dopaminergic cell system (the A14 cell group) into the medial preoptic area and the periventricular and suprachiasmatic preoptic nuclei. The system probably extends also into the most caudal portion of the lateral septal nucleus. From a series of lesions and in vitro uptake studies, evidence has been obtained that the incerto-hypothalamic fibres are the projections of short, intradiencephalic dopaminergic neurones whose cell bodies are located in the A11, A13 and A14 cell groups. The projection areas of these neurones signify an involvement of the system in the control of secretion of pituitary hormones.


Catching the circadian rhythm of intervertebral disc and association with clinical outcomes by twice-a-day magnetic resonance imaging.
We conducted a prospective magnetic resonance imaging(MRI) surveillance program of the whole spine twice a day to aim at investigating the diurnal prevalence of MRI parameters of intervertebral discs and their associations with relevant symptoms. Sixty-four young volunteers underwent MRI of the whole spine twice on the same day (in the morning and evening). Sagittal T2-weighted MRIs of the whole spine were compared and analyzed. Two independent observers assessed the images for the disc height, anterior-posterior distance, and T2 values. Subject demographics and clinical findings were assessed by standardized questionnaires. There was a statistically significant diurnal disc height change in all the disc level groups. Except four lumbar levels, there was no statistically significant diurnal disc AP distance change seen in other levels. There were statistically significant diurnal T2 value changes in all intervertebral discs except T3/4 levels. The multivariate linear regression analysis showed a positive linear trend association between BMI and the diurnal variations of T1/2 T2 value, T12/L1, L1/2, L2/3, L3/4,L4/5 and L5/S1 disc heights (p < 0.05) . Smoking and passive smoking affected cervical levels of T2 value changes. Interestingly, a reverse trend was observed in all disc changes in the case of more than ten years shift work history. Smoking and passive smoking are associated with cervical disc T2 value diurnal changes and BMI is associated with lumbar disc height changes. Long time disruption of circadian clock may cause reverse changes of discs, however not in short or medium-time shift workers.


Mechanical Thrombectomy in Basilar Artery Occlusion: Clinical Outcomes Related to Posterior Circulation Collateral Score.
Basilar artery occlusion (BAO) is associated with a high risk of disability and mortality. The objective of this study was to investigate prognostic factors in patients with acute basilar artery occlusion treated with mechanical thrombectomy, focusing on collateral status and recanalization time from symptom onset. Eligible patients from January 2012 to October 2019 who underwent endovascular treatment due to acute BAO were reviewed. The baseline posterior circulation collateral status was assessed with the basilar artery on computed tomography angiography score and posterior circulation collateral score. Good outcomes were defined as a modified Rankin Scale score of ≤2 at 3 months and successful recanalization as Thrombolysis in Cerebral Infarction grades 2b, 3. The associations between baseline and clinical parameters and favorable outcomes were evaluated with logistic regression. Our sample included a total of 81 eligible patients (49 males, mean age 70.3 years) with a median baseline and discharge National Institutes of Health Stroke Scale score of 12. Patients with good outcomes showed a lower baseline National Institutes of Health Stroke Scale score, a greater proportion of distal BAO, and a higher basilar artery on computed tomography angiography and posterior circulation collateral score (P<0.001). According to subgroup analysis of patients within and over 6 or 12 hours, the time from symptom onset to recanalization was not correlated with good outcomes. Multivariable logistic analysis showed baseline National Institutes of Health Stroke Scale <15 (odds ratio, 8.49 [95% CI, 2.01-35.82]; P=0.004), posterior circulation collateral score ≥6 (odds ratio, 3.79 [95% CI, 1.05-13.66]; P=0.042), and distal BAO (odds ratio, 3.67 [95% CI, 1.10-12.26]; P=0.035) were independent predictors of good outcomes. This study suggested that good collateral circulation and distal BAO are independent predictors of clinical outcome after endovascular treatment in patients with acute BAO. In particular, patients with good initial collateral status and distal BAO may consider endovascular treatment even if the treatment is started beyond the standard time limits.


Glycaemic impact of treatment intensification in patients with type 2 diabetes uncontrolled with oral antidiabetes drugs or basal insulin.
To investigate the impact of treatment intensification (TI) on glycaemic outcomes in patients with type 2 diabetes with glycated haemoglobin A1c (A1C) ≥7% after ≥6 months of treatment with 2 oral antidiabetes drugs (OADs) or basal insulin (BI). Data were extracted from the Optum administrative claims database from 1 January 2009 to 31 August 2015. Patients with TI ≤6 months after the first A1C ≥7% (index date) were compared with patients with no TI (NTI). TI included addition of OAD, GLP-1 receptor agonist or premixed insulin in OAD and BI cohorts, addition of BI and/or bolus insulin in the OAD cohort and addition of bolus insulin or increasing BI dose in the BI cohort. Change from the index A1C value and hypoglycaemia events was compared at 12 months after TI after adjusting for confounders. A total of 3990/28 123 (14.2%) and 10 425/16 140 (65%) of eligible adults in the OAD and BI cohorts, respectively, underwent TI. These patients showed greater adjusted A1C change vs NTI patients (OAD cohort: -0.59% vs -0.25%; BI cohort: -0.30% vs -0.16%; P < .001 for both comparisons), but with higher hypoglycaemia rates (OAD cohort: odds ratio [OR] 1.68; P < .001; BI cohort: OR: 1.23; P = .004) at follow-up. Clinical inertia appears to be a significant issue in this population. Although associated with more frequent hypoglycaemia, these results demonstrate that timely TI improves A1C levels, highlighting the need for new and improved agents to effectively manage glycaemia while reducing hypoglycaemia risk.


Nicotinamide drives T cell activation in the mammary tumor microenvironment.
Nicotinamide (NAM, a variant of vitamin B3) has recently been shown to accelerate the activation of human CD4+ and CD8+ T cells exposed to repeated CD3/CD28 agonism in vitro. Here, we demonstrate that T cells infiltrating mouse mammary carcinomas that are therapeutically controlled by NAM also express multiple markers of late-stage activation. Taken together, these findings lend additional support to the notion that the antineoplastic effects of NAM involve at least some degree of restored cancer immunosurveillance.


Malaria epidemiology and stratification of incidence in the malaria elimination setting in Harari Region, Eastern Ethiopia.
Ethiopia has shown notable progress in reducing the burden of malaria over the past two decades. Because of this progress, the country has shifted efforts from control to elimination of malaria. This study was conducted to analyse the malaria epidemiology and stratification of incidence in the malaria elimination setting in eastern Ethiopia. A retrospective study was conducted to analyse the epidemiology of malaria by reviewing the district health office data from 2013 to 2019 in Harari Region. In addition, three years of sub-district level malaria data were used to stratify the malaria transmission intensity. Malaria interventions (Long-lasting insecticidal nets [LLIN] and indoor residual spraying [IRS]) employed were reviewed to analyse the intervention coverage at the Regional level. Descriptive statistics were used to show the malaria transmission in terms of years, season and species of the malaria parasite. Incidence rate per 1000 population and death rate per 1 000 000 population at risk were computed using the total population of each year. In the Harari Region, malaria incidence showed a more pronounced declining trend from 2017 to 2019. Plasmodium falciparum, P. vivax and mixed infections accounted for 69.2%, 30.6% and 0.2% of the cases, respectively. There was an increment in malaria intervention coverage and improved malaria diagnosis. In the year 2019 the coverage of LLIN and IRS in the Region were 93.4% and 85.1% respectively. The annual malaria incidence rate dropped from 42.9 cases per 1000 population in 2013 to 6.7 cases per 1000 population in 2019. Malaria-related deaths decreased from 4.7 deaths per 1 000 000 people annually in 2013 to zero, and there have been no deaths reported since 2015. The malaria risk appears to be heterogeneous and varies between districts. A higher number of malaria cases were recorded in Erer and Jenella districts, which constitute 62% of the cases in the Region. According to the sub-district level malaria stratification, there was shrinkage in the malaria transmission map and about 70% of the sub-districts have achieved elimination targets. In the Harari Region, malaria morbidity and mortality have been significantly declined. Thus, if this achievement is sustained and scaling-up of the existing malaria prevention and control strategies by focusing on those populations living in the higher malaria transmission districts and sub-districts, planning of malaria elimination from the study area might be feasible.


Self-supervised representation learning from 12-lead ECG data.
Clinical 12-lead electrocardiography (ECG) is one of the most widely encountered kinds of biosignals. Despite the increased availability of public ECG datasets, label scarcity remains a central challenge in the field. Self-supervised learning represents a promising way to alleviate this issue. This would allow to train more powerful models given the same amount of labeled data and to incorporate or improve predictions about rare diseases, for which training datasets are inherently limited. In this work, we put forward the first comprehensive assessment of self-supervised representation learning from clinical 12-lead ECG data. To this end, we adapt state-of-the-art self-supervised methods based on instance discrimination and latent forecasting to the ECG domain. In a first step, we learn contrastive representations and evaluate their quality based on linear evaluation performance on a recently established, comprehensive, clinical ECG classification task. In a second step, we analyze the impact of self-supervised pretraining on finetuned ECG classifiers as compared to purely supervised performance. For the best-performing method, an adaptation of contrastive predictive coding, we find a linear evaluation performance only 0.5% below supervised performance. For the finetuned models, we find improvements in downstream performance of roughly 1% compared to supervised performance, label efficiency, as well as robustness against physiological noise. This work clearly establishes the feasibility of extracting discriminative representations from ECG data via self-supervised learning and the numerous advantages when finetuning such representations on downstream tasks as compared to purely supervised training. As first comprehensive assessment of its kind in the ECG domain carried out exclusively on publicly available datasets, we hope to establish a first step towards reproducible progress in the rapidly evolving field of representation learning for biosignals.


Spontaneous ischemic neuropathy of the sciatic nerve due to arterial occlusion - a rare cause of acute neuropathy not to be missed, a report of two cases.
Ischemic neuropathy of the sciatic nerve without preceding vascular surgical procedures is a rare condition and may be due to arterial occlusion in one limb. We present two cases with acute onset of pain and sensory symptoms such as pins and needles and numbness in the foot with no or mild motor symptoms. In the neurological work-up, electrophysiological signs of axonal neuropathy of both peroneal and tibial nerves were demonstrated and T2 hyperintensity was seen in the distal sciatic nerves on MR neurography as well as signs indicating arterial thrombosis in the corresponding vessels. Recanalization was obtained in both patients angiographically with significant improvement in one patient. Spontaneous arterial occlusion of major or peripheral arteries is a rare but important cause of acute onset of single or multiple axonal mononeuropathies of one extremity. Recognition of this infrequent cause is essential since it requires immediate and specific therapeutic options.


Polygenic risk scores and risk stratification in deep vein thrombosis.
Deep vein thrombosis (DVT) is a complex disease, where 60 % of risk is due to genetic factors, such as the Factor V Leiden (FVL) variant. DVT is either asymptomatic or manifests with unspecific symptoms and, if left untreated, DVT leads to severe complications. The impact is dramatic and currently, there is still a research gap in DVT prevention. We characterized the genetic contribution and stratified individuals based on genetic makeup to evaluate if it favorably impacts risk prediction. In the UK Biobank (UKB), we performed gene-based association tests using exome sequencing data, as well as a genome-wide association study. We also constructed polygenic risk scores (PRS) in a subset of the cohort (Number of cases = 8231; Number of controls = 276,360) and calculated the impact on the prediction capacity of the PRS in a non-overlapping part of the cohort (Number of cases = 4342; Number of controls = 142,822). We generated additional PRSs that excluded the known causative variants. We discovered and replicated a novel common variant (rs11604583) near the region where are located the TRIM51 and LRRC55 genes and identified a novel rare variant (rs187725533) located near the CREB3L1 gene, associated with 2.5-fold higher risk of DVT. In one of the PRS models constructed, the top decile of risk is associated with 3.4-fold increased risk, an effect that is 2.3-fold when excluding FVL carriers. In the top PRS decile, the cumulative risk of DVT at the age of 80 years is 10 % for FVL carriers, contraposed to 5 % for non-carriers. The population attributable fractions of having a high polygenic risk on the rate of DVT was estimated to be around 20 % in our cohort. Individuals with a high polygenic risk of DVT, and not only carriers of well-studied variants such as FVL, may benefit from prevention strategies.


Increased risk of hyperthyroidism among patients hospitalized with bipolar disorder.
Hyperthyroidism has been associated with affective disorder in many cross-sectional studies, but longitudinal studies in this connection are scarce. We assessed whether hospitalization with depressive disorder or bipolar disorder was a risk factor for development of hyperthyroidism. We conducted a historical cohort study using the Danish register data. The observational period was 1977--99. Three study cohorts were identified: all patients with a first hospital admission with resulting index discharge diagnoses of depression, bipolar disorder, or osteoarthritis. The risks of subsequently being readmitted with a resulting discharge diagnosis of hyperthyroidism were estimated in survival analyses. A study sample of 133,570 patients discharged with an index diagnosis was identified. Exactly 610 patients were later readmitted following diagnoses of hyperthyroidism. Patients with depressive disorder did not have an increased risk of hyperthyroidism, whereas patients with bipolar disorder had an increased of risk on the margin of statistical significance, when compared to patients with osteoarthritis. Patients with bipolar disorder had a significantly increased risk of hyperthyroidism when compared to patients with depression. The results apply only to hospitalized patients. Diagnoses are not validated for research purposes. Patients hospitalized with bipolar disorder tend to be at greater risk of readmission with hyperthyroidism than suitable control patients.


Developmental treatment with the dopamine D2/3 agonist quinpirole selectively impairs spatial learning in the Morris water maze.
Developmental exposure to the dopamine D2/3 receptor agonist quinpirole is reported to induce D2 priming, impair Morris water maze performance, reduce acoustic startle prepulse inhibition (PPI), and alter locomotor activity. We treated rats from postnatal days 1-21 with the dose reported to induce these effects, 1.0 mg/kg/day, and two higher doses, 2.0 and 4.0 mg/kg/day, or saline. Offspring were tested in the Morris water maze, PPI, exploratory locomotor activity, activity after quinpirole and (+)-methamphetamine challenge, elevated zero maze, light-dark box, marble burying, straight channel swimming, and Cincinnati water maze. In the Morris water maze, all quinpirole groups had longer latencies on test days 3-5 of acquisition, but no effects on reversal or shifted-reduced platform trials. The quinpirole 4.0 mg/kg group had significantly reduced mean search distances on probe trials when combined across the 3 phases of testing but not separately. The male 4.0 mg/kg quinpirole group showed a greater increase in methamphetamine-stimulated activity during the first 10 min after drug challenge but not in the remainder of the 2 h test. No quinpirole effects were found for light-dark box, marble burying, exploratory locomotor activity, straight channel, Cincinnati water maze, or locomotor activity after quinpirole challenge. No effects were found on most measures in the elevated zero maze however the quinpirole 4.0 mg/kg females had longer latencies to enter an open quadrant. The results partially support prior Morris maze deficits induced by developmental quinpirole treatment but little evidence of dopamine D2/3 priming was found using locomotor activity with quinpirole or methamphetamine challenge or acoustic startle/PPI. The limited comparability to published data using developmental quinpirole exposure may be attributable to differences in experimental procedures or may be the result of quinpirole having limited effects. The data suggest that caution is warranted concerning the developmental efficacy of quinpirole.


Use of pleura, azygos vein, pericardium, and muscle flaps in tracheobronchial surgery.
Desmoplastic reactions secondary to adjuvant chemotherapy and radiation in stage IIIA lung cancer, plus advances in complex tracheobronchial surgery, have rejuvenated an interest for augmenting bronchial stump coverage and suture line reinforcement. We present the techniques and applications of harvesting pleural, azygos vein, pericardial flaps, and fat pad grafts, and intrathoracic transposition of chest wall muscle flaps.


Formulation of medium for tick cell culture.
We examined the effectiveness of bovine cholesterol concentrate in reducing the high level (10-20%) of fetal bovine serum (FBS) necessary to promote tick cell growth in vitro. Tick cell lines isolated from embryos of Anocentor nitens (ANE 58), Boophilus microplus (BME 26), and Rhipicephalus appendiculatus (RAE 25) were used. They were incubated in L-15 (BME 26) or L-15B (ANE 58 and RAE 25) supplemented with 10% tryptose phosphate broth (TPB), 5% (ANE 58 and BME 26) or 3% FBS, 10-90 microns/ml cholesterol. A concentration of 10 micrograms/ml cholesterol stimulated the growth rate of all three lines but more than 30 micrograms/ml depressed growth in ANE 58 and RAE 25 cells, while multiplication of BME 26 cells was enhanced by all cholesterol concentrations tested. All three lines could be continuously grown in 5% FBS, provided that 10 micrograms/ml cholesterol was included. Nutrients added to L-15 in the formulation of L-15B were tested singly or in combination for their ability to support tick cell growth in medium supplemented only with 5% FBS and 10 microns/ml cholesterol. In L-15 alone, RAE 25 cells did not multiply. Adding glucose (Glc), glutamic acid (Glu), or alpha-ketoglutaric acid (alpha K) had little or no effect, and the same was true for combinations of Glc plus alpha K, aspartic acid (Asp) plus proline (Pro) and glutamine (Gln), and minerals plus vitamins (MV). When Asp, Gln, Pro, and alpha K were combined with Glc and/or MV and added to L-15, there was appreciable growth stimulation, but best results were obtained when Glu was also included. In this medium, i.e., L-15B with 5% FBS and 10 mu/ml cholesterol, lines BME 26 and RAE 25 could be continuously subcultured.


Perioperative risk factors for postpartum pulmonary embolism in Taiwanese Cesarean section women.
To explore the perioperative risk factors for predicting postpartum pulmonary embolism (PE) in Taiwanese women with Cesarean section (CS) delivery. Data from Taiwan Longitudinal Health Insurance Database were analyzed. All CS women (2002-2007) in Taiwan, according to Diagnosis-Related Group codes, were included. Women having postpartum PE were identified by the diagnosis codes of PE from the medical records within 40 days after CS. Risk factors were analyzed using multivariate logistic regression. A total of 285,043 women who received CS between 2002 and 2007 were analyzed. Among them, 44 women were diagnosed as having postpartum PE. The overall incidence of postpartum PE was 0.154 per 1000 CS women. Analysis revealed that the perioperative risk factors for predicting postpartum PE in CS women included chronic heart disease (adjusted odds ratio [OR] = 89.92, 95% confidence intervals [CI] = 41.34-195.60, P < 0.001), systemic lupus erythematosus (adjusted OR = 45.05, 95% CI = 7.56-268.40, P < 0.001), postpartum hemorrhage (adjusted OR = 3.20, 95% CI = 1.10-9.31, P = 0.033), postpartum blood transfusion (adjusted OR = 8.92, 95% CI = 4.17-19.09, P < 0.001) and postpartum infection (adjusted OR = 7.13, 95% CI = 2.93-17.38, P < 0.001). Of note, anesthetic mode was not a risk factor for predicting postpartum PE in CS women, as women receiving general anesthesia for CS delivery were not associated with an increased risk of developing postpartum PE comparing to those who received neuraxial anesthesia (adjusted OR = 1.28, 95% CI = 0.52-3.14, P = 0.591). Chronic heart disease, systemic lupus erythematosus, postpartum hemorrhage, postpartum blood transfusion and postpartum infection, but not anesthetic mode, were strong perioperative risk factors for predicting postpartum PE in Taiwanese CS women.


Prolonged sedation with propofol in ICU patients: recovery and blood concentration changes during periodic interruptions in infusion.
Propofol (mean dose 2.85 mg kg-1 h-1) was administered for 4 days by continuous i.v. infusion for sedation in 14 agitated and restless ICU patients. This provided rapid control of the level of sedation. When the infusion was discontinued, adequate recovery with response to commands was obtained in most patients by 10 min. Recovery times and the decrease in blood propofol concentration were similar after 24, 48, 72 and 96 h of infusion. Cumulative effects, tachyphylaxis, or other untoward effects were not observed.


The complex genetic and psychosocial influences on polysubstance misuse.
Polysubstance misuse is a costly and complex behavioral phenotype that is concurrent with internalizing and externalizing disorders. Research on genetic and psychosocial influences suggests that a life course framework composed of a transactional etiology sheds light on the complex nature of polysubstance misuse. Further, given the extensive comorbidity with mental illness and behavioral dysregulation, viewing polysubstance misuse as asymmetrical in the population is helpful for guiding broad decision-making around prevention and policy.


The morphology of Saccharomyces cerevisiae colonies is affected by cell adhesion and the budding pattern.
Formation of organized colony morphology is clearly a result of organized, coordinated behavior of cells within a colony, which reflects changes in the cell environment, nutrient availability, inter- and intracolony signaling and others. Under standard conditions, colony morphology is specific to the particular yeast strain, which indicates that reproducibility of the structure appears to be a hallmark of programmed development. Our data indicate that markedly structured morphology of colonies formed by some haploid and diploid Saccharomyces cerevisiae strains is linked to formation of clusters of incompletely separated yeast cells organized into larger aggregates. A prerequisite to aggregate formation appears to be a monopolar budding pattern and the presence of an extracellular matrix and adhesins connecting individual clusters within aggregates. In contrast, less structured colonies of other strains are composed of non-aggregated cells exhibiting different modes of budding (axial/polar/random) in different colony areas. The budding pattern appears to be influenced more by the environment (the presence of surrounding cells, nutrient gradients, etc.) than by strain ploidy. Disruption of the BUD2 gene results in uniform random budding of cells and it partially influences colony morphology.


Molecular cloning and characterization of rat trp homologues from brain.
Identification of trp (transient receptor potential) gene from Drosophila photoreceptor and subsequent molecular cloning of the human cDNA homologues suggest its participation in capacitative calcium entry (CCE) or so called store-operated Ca2+ channel (SOC). We identified five different trp-related amplifications of reverse-transcription-polymerase chain reaction (RT-PCR) from rat brain; these corresponded to mouse trp homologues, mtrp1,3,4,5,6 and were distributed in various tissues with multiple expression levels. Two cDNAs, homologous to Drosophila trp from rat brain, designated rtrp3 and rtrp6, were isolated and characterized. By RT-PCR analysis, mRNAs of rtrp3 and rtrp6 were found to be expressed differently in brain and other tissues. In situ hybridization analysis revealed that rtrp6 mRNA was preferentially expressed in hippocampal dentate gyrus and cortical layers II and III. Expression of rat TRP3 and TRP6 in COS cells revealed an increase in CCE, as compared to that in the mock-transfected COS cells of the control. Isolation of cDNAs of rat trp gene family provides a useful model for studying mechanism of CCE.


Epidemiology of suicidal behaviors among junior and senior high school adolescents: Exploring the interactions between bullying victimization, substance use, and physical inactivity.
Suicide is a pandemic among global youths and adolescents. Still, there is insufficient evidence to show whether the interactions between bullying victimization, physical inactivity, substance use, and mental health illness aggravate suicidal behaviors among high school students. Based on the Global School-Based Student Health Survey, we analyzed the individual and interaction impacts of bullying victimization, physical inactivity, substance use, and suicidal behaviors among 3,632 adolescents. The 12-month prevalence of suicidal thoughts and plans among senior high school students was over fifty percent. Junior high school students had higher rates of suicide attempts and bullying victimization than senior high school students. Multivariate results indicate that bullying victimization, substance use, and physical inactivity were significantly associated with suicidal thoughts, plans, and attempts among high school students. The interaction of physical inactivity and alcohol was significantly associated with suicidal thoughts in junior high school. In contrast, the interaction of bullying and alcohol was associated with suicidal plans among senior high school adolescents. We hope the findings from this study will generate interventions toward reducing the suicide epidemic in Ghana.