Case report: a successful treatment with immune checkpoint inhibitors was associated with severe dermatologic toxicities in a patient with double primary malignancies.
Dermatological toxicities are well-recognized immune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) use. Corticosteroids are considered the first-line therapy for grade 3 or grade 4 skin irAEs, but long-term usage of corticosteroids may abolish the effect of ICIs. Multiple antitumor therapies might be an influencing factor in an increased incidence of skin irAEs. The safety and prognostic value in resuming ICIs after irAEs has been inconsistently reported, especially the severe skin irAE. We report a case of a 75-year-old man with non-small cell lung cancer (NSCLC) and prostate cancer with a Stevens-Johnson syndrome (SJS)-like eruption. The severe rash might have been induced by resuming pembrolizumab was successfully treated with a combination of corticosteroids, gamma globulin, and immunosuppressants. Early detection of dermatologic toxicity is crucial, especially for patients receiving multiple antitumor treatments. We should treat ICI resumption seriously after skin irAE.


Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging.
This study used diffusion tensor imaging to examine fractional anisotropy in the anterior cingulum and posterior cingulum bundles in patients with schizophrenia. Twenty-one male patients and 20 healthy comparison men were studied. Reduced fractional anisotropy was seen for both sides of the anterior cingulum in the schizophrenia patients, who also exhibited less left-greater-than-right asymmetry in the anterior cingulum than was seen in the comparison subjects. The findings suggest structural disconnections in the anterior cingulum in patients with schizophrenia.


Condition Factor and Length-Weight Relationship of Scardinius erythrophthalmus (Linnaeus, 1758) in Anzali Lagoon.
Background and Objective: Studies on fish biology are essential for the sustainable management and conservation of fish biodiversity. This study observed the length-weight relationships and condition factors of common rudd fish, which give us some information about the ecological and nutritional conditions of fish. This information is crucial to fishery management. Materials and Methods: The length-weight relationship (LWR) and condition factors (K) of 270 Scardinius erythrophthalmus caught in Anzali Lagoon from April to August, 2015. Results: The total length and body weight of S. erythrophthalmus ranged from 94-179 mm and 11.98-98.5 g, respectively. A strong positive relationship was observed between length and weight (r = 0.96). There were no significant differences in the condition factors of males and females (p>0.05). The lowest K value was observed in April (K = 1.5±0.04) and the highest in July (K = 2.25±0.34). The sex ratio of 1.0 male: 1.15 female was observed, with no significant difference between males and females (p>0.05). Conclusion: In this study, the regression coefficient (b) in males and females was 3.35 and 3.29, respectively, more than 3.0, which means they have positive allometry growth in both sexes.


Mother-to-infant emotional involvement at birth.
To study mother-to-infant emotional involvement at birth, namely factors (socio-demographics, previous life events, type of delivery, pain at childbirth, support from partner, infant characteristics, early experiences with the newborn, and mother's mood) that interfere with the mother's positive, negative and not clear emotions toward the newborn. The Bonding Scale (an extended Portuguese version of the 'New Mother-to-Infant Bonding Scale') and the Edinburgh Postnatal Depression Scale were administrated during the first after delivery days to 315 mothers recruited at Júlio Dinis Maternity Hospital (MJD, Porto, Portugal). A worse emotional involvement with the newborn was observed when the mother was unemployed, unmarried, had less than grade 9, previous obstetrical/psychological problems or was depressed, as well as when the infant was female, had neonatal problems or was admitted in the intensive care unit. Lower total bonding results were significantly predicted when the mother was depressed and had a lower educational level; being depressed, unemployed and single predicted more negative emotions toward the infant as well. No significant differences in the mother-to-infant emotional involvement were obtained for events related to childbirth, such as type of delivery, pain and partner support, or early experiences with the newborn; these events do not predict mother's bonding results either. The study results support the need for screening and supporting depressed, unemployed and single mothers, in order to prevent bonding difficulties with the newborn at birth.


Age does not influence taxol dose intensity in recurrent carcinoma of the ovary.
In the treatment of advanced-stage ovarian cancer, it is common practice to treat elderly patients in a less aggressive fashion than young patients. This approach is based on the notion that age is associated with poor patient tolerance to aggressive chemotherapy. Relatively little data exist to support this contention. The most exciting new chemotherapy agent to be developed in the last 10 years is taxol, a diterpeniod derivative of the Northwestern yew Taxus brevifolia. The ability to administer dose-intensive taxol to adult patients with recurrent ovarian cancer was assessed retrospectively, and the question was asked whether the administered dose intensity of taxol was unfavorably influenced by age. Forty-eight patients with recurrent ovarian carcinoma received taxol at an initial dose of 250 mg/m2 every 3 weeks. Age in this cohort ranged from 26 to 74 years, with a median of 55. Twenty-nine percent (14 of 48) of the patients treated were 61 years of age or greater. Criteria for administration of taxol included a creatinine clearance of > 45 ml/minute, minimal abnormalities in liver function tests, good performance status, and the absence of substantial comorbid disease. Elderly patients in this cohort (age > 60 years) did not differ from younger patients with respect to administered dose intensity, number of cycles of therapy administered, or the occurrence of serious or mild toxicities.


Benefits of carotid patching: a randomized study.
Advocates of carotid artery patching claim a reduced incidence of recurrent stenosis after endarterectomy. A prospective study was undertaken to determine its value with random selection between primary closure and saphenous vein patching. A consecutive series of 129 carotid endarterectomies was evaluated by duplex scanning at 3, 6, and 12 months after operation. Intravenous digital subtraction angiography (DSA) was performed in the first postoperative days for control of the surgical technique and after 1 year to serve as a reference for the duplex scanning. Sixty-two patients were selected to have primary closure and 67 were chosen for the patching technique. Both groups were identical with regard to risk factors (mean age 63 years, 74% were men, 57% had hypertension, 41% had coronary disease, 37% had peripheral arterial disease, and 9% had diabetes mellitus), side of operation (55% left), symptoms (18% were asymptomatic), and postoperative DSA (81% were normal, 17% had residual lesions, and 2% had occlusions). A complete 1-year follow-up was obtained in 105 cases (81%); duplex scanning showed recurrent stenosis of more than 50% in 12 cases (11%). This was significantly higher after primary closure (10 of 48 patients = 21%) compared with patch closure (2 of 57 = 3.5%; p = 0.006) and also in women (6 of 25 = 24%) compared with men (6 of 80 = 7.5%; p = 0.03). Recurrent stenosis was present in 6 of 11 women with primary closure (55%), 4 of 37 men with primary closure (11%), 2 of 43 men with patching (5%), and none of 14 women with patch closure (0%).(ABSTRACT TRUNCATED AT 250 WORDS)


Immobilized pH gradient focusing of alkaline proteins: analysis of the isoform composition of purified human non-secretory ribonucleases from kidney, liver and spleen.
Previous studies on the isoform composition of human ribonucleases (RNAases) have resulted in confusing and inconsistent results, presumably due to methodological problems in electrofocusing of alkaline proteins. In the present study, immobilized pH gradient (IPG) carrier ampholyte (CA) isoelectric focusing (IEF) and conventional CA-IEF have been evaluated for the analysis of the isoforms of human non-secretory RNAases purified from kidney, liver and spleen. CA-IEF proved unsuitable since the alkaline RNAase isoforms migrated into the cathode. IPG-CA-IEF, however, resolved the RNAase isoforms and marker proteins in the basic region of the gel matrix. The three RNAases had comparable isoform profiles, each with two protein bands with approximate pI values of 10.3 and 10.4. Western blotting showed that the two protein bands of each RNAase were immunoreactive (with polyclonal antibodies that recognize RNAase), indicating that the protein bands are RNAase isoforms. The present results provide reliable pI data on human RNAase isoforms and suggest that IPG-CA-IEF should be a suitable technique for analysing the isoforms of other alkaline proteins.


Molecular characterization of the lgals1 gene in large scale loach Paramisgurnus dabryanus.
Galectins constitute a group of lectins with binding specificity for β-galactoside sugars. Galectin-1 is a prototype galectin and the multifunctionality of mammalian galectin-1s is well-known, but only a few of fish galectin-1s have been identified. In this study, we obtained the full-length cDNA and genomic sequence of the galectin-1 gene (designated as Pdlgals1) from large scale loach (Paramisgurnus dabryanus), performed phylogenetic analysis, and characterized the expression pattern and the transcriptional activity of its 5' flanking region. The Pdlgals1 gene contains 4 exons that encode a peptide of 132 amino acids with all the galectin signature motifs. Phylogenetic analysis and sequence alignment indicated that Pdlgals1 is a homologue of human LGALS1. RT-PCR and whole-mount in situ hybridization revealed that Pdlgals1 is mainly expressed in the skin, muscle, intestine and cavum oropharyngeum. Transcriptional activity assays demonstrated that the basal promoter of Pdlgals1 is located in a region from -500bp to its transcriptional start site. Potential binding sites for transcription factors including C/EBP, AP-1, GATA, Oct-1, δEF1, NF-κB, c-Myb, SP-1, AP-2, AML-1α, and AP-4 were identified in the basal promoter, suggesting that these factors are associated with the regulation of Pdlgals1. These results provided clues for further investigation of galectin-1 functions in loaches.


Simulation analysis of optimized brachytherapy for uterine cervical cancer: Can we select the best brachytherapy modality depending on tumor size?
To choose the optimal brachytherapeutic modality for uterine cervical cancer, we performed simulation analysis. For each high-risk clinical target volume (HR CTV), we compared four modalities [classical conventional intracavitary brachytherapy (ConvICBT), Image-guided ICBT (IGICBT), intracavitary/interstitial brachytherapy (ICISBT), and interstitial brachytherapy (ISBT) with perineal approach] using dose-volume histograms using eight sizes of HR CTV (2 × 2 × 2 cm to 7 × 4 × 4 cm) and organs at risk model. In ConvICBT, the doses covered 90% of the HR CTV [D90(HR CTV)] decreased from 197% prescribed dose (PD) for the HR CTV size (2 × 2 × 2 cm) to 73% PD for 5 × 4 × 4 cm, whereas the other three modalities could achieve 100% PD for all HR CTV sizes. The minimum doses received by the maximally irradiated 2-cm(3) volumes for organs at risks of IGICBT demonstrated lower values than those of ConvICBT for the HR CTV size of 4 × 3 × 3 cm or smaller. ICISBT demonstrated lower values than those of IGICBT for 4 × 3 × 3 cm or larger. ISBT demonstrated lowest values for 5 × 4 × 4 cm or larger. HR CTV size of 4 × 3 × 3 cm seems to be a threshold volume in this simulation analysis, and IGICBT is a better choice for smaller HR CTV than the threshold volume. On larger HR CTV, ICISBT or ISBT is the better choice.


A descriptive analysis of scoring patterns on clinically relevant questionnaires in 26 adults with diagnosed muscle dysmorphia.
Few studies have recruited adults with a formal diagnosis of muscle dysmorphia (MD), a psychological illness defined by preoccupation that one lacks muscularity and/or leanness, combined with significant functional impairment. This study presented descriptive statistics for a range of clinically relevant questionnaires in one of the largest samples of adults with confirmed diagnoses of MD. We recruited 29 adults who met diagnostic criteria for MD as determined by semi-structured diagnostic interviews and administered a battery of questionnaires assessing MD symptomology, compulsive exercise, and disordered eating. Descriptive statistics were calculated for both total and subscale scores for each questionnaire. Raincloud plots are included to show the distribution of total scores. Of the 29 participants, 26 completed all questionnaires. Mean scores were high across all questionnaires and broadly consistent with results in past studies that also recruited a clinical MD sample. Most participants scored above proposed clinical cut-off scores for questionnaires assessing compulsive exercise and disordered eating. This study adds to the small body of published questionnaire data in clinical MD samples. We stress that questionnaire scores should not be used alone to infer the presence of MD, but could be considered as a useful adjunct to a comprehensive clinical interview.


Special Rhodococcus sp. CR-53 esterase Est4 contains a GGG(A)X-oxyanion hole conferring activity for the kinetic resolution of tertiary alcohols.
Rhodococci are highly adaptable bacteria, capable to degrade or transform a large number of organic compounds, including recalcitrant or toxic products. However, little information is available on the lipases of the genus Rhodococcus, except for LipR, the first lipase isolated and described from strain Rhodococcus CR-53. Taking into consideration the interest raised by the enzymes produced by actinomycetes, a search for new putative lipases was performed in strain Rhodococcus CR-53. We describe here the isolation, cloning, and characterization of intracellular esterase Est4, a mesophilic enzyme showing preference for short-chain-length acyl groups, without interfacial activation. Est4 displays moderate thermal and pH stability and low tolerance to most tested ions, being inhibited by detergents like sodium dodecyl sulfate and Triton X-100®. Nevertheless, the enzyme shows good long-term stability when stored at 4-20 °C and neutral pH. Amino acid sequence analysis of Est4 revealed a protein of 313 amino acids without a signal peptide, bearing most of the conserved blocks that define bacterial lipase family IV, thus being assigned to this family. Detection of a GGG(A)X oxyanion hole in the enzyme motivated the evaluation of Est4 ability to convert tertiary alcohol esters. The newly discovered esterase Est4 from Rhodococcus CR-53 successfully hydrolyzed the tertiary alcohol esters linalyl acetate, terpinyl acetate, and 1,1,1-trifluoro-2-phenylbut-3-yn-2-yl acetate.


Prevalence and incidence of systemic lupus erythematosus in Tucumán, Argentina.
The aim of this study was to determine the prevalence and incidence of Systemic Lupus Erythematosus (SLE) in Tucumán, Argentina. The study included inpatient and outpatient charts from four public hospitals and private practice rheumatology clinics, all of them members of the Tucumán Rheumatology Society. Patients older than 16 years with diagnosis of SLE between January 2005 and December 2012 were included. Prevalence and annual incidence were calculated as the number of cases per 100.000 inhabitants during the period 2005 to 2012. Three hundred fifty-three patients were identified. The mean age at diagnosis was 30.5 ± 11.7 years, 93.5% women, 83% mestizos. Prevalence was 24.3 cases/100.000 inhabitants (CI 95% 22.6-28.8) and age-adjusted (≥16 years) of 34.9 cases/100.000 inhabitants (CI 95% 32.8-41.1). The annual incidence in 2005 was 1.8 cases/100.000 inhabitants (95% CI 1-2.9) and 2012 of 4.2 cases/100.000 inhabitants (95% CI 2.9-5.8). Mortality was 9.1%, with infections being the most frequent cause (14/32). The prevalence of SLE in the province of Tucumán was 34.9 cases/100.000 inhabitants.


Delayed reversal of impaired vasodilation in congestive heart failure after heart transplantation.
The effects of changes in central cardiovascular function on peripheral vasodilation were investigated. Strain gauge plethysmography was used to measure the maximal blood flow response following release of forearm arterial occlusion and the peak reactive hyperemic blood flow response (ml/min.100 ml) before and twice after orthotopic heart transplantation in 10 subjects with severe congestive heart failure. The 2 posttransplantation studies were done before hospital discharge (mean 18 days after transplantation) and again after discharge (mean 114 days after transplantation). Transplantation led to a significant but delayed increase in maximal vasodilation (reactive hyperemic blood flow: pretransplant 21 +/- 3; predischarge 25 +/- 2; postdischarge 43 +/- 5) and a concurrent significant reduction in minimal forearm resistance. Although the improvement in peripheral vasodilator function may be linked to improvement in cardiac function, this linkage is not direct, nor is it immediate. If the normalization of maximal metabolic blood flow is related to resumption of normal physical activity postdischarge, then much of the basic abnormality in vasodilator capacity in congestive heart failure may be related to physical deconditioning.


A clinico-pathological conference on constrictive pericarditis secondary to rheumatoid arthritis: a case report with expert commentary and review of the literature.
Constrictive pericarditis is the commonest cardiac complication of rheumatoid arthritis (RA). Two percent of patients with RA develop significant clinical symptoms of pericarditis, which may not correlate with joint disease duration or severity. Symptoms are often vague and non-specific, which frequently delays the diagnosis and subsequent management. Surgical excision of the pericardium is the only definitive treatment option. We present the case of a 60 year-old lady with RA who presented with symptoms due to pericardial constriction and underwent radical pericardectomy.


Erythropoietin promotes MCF-7 breast cancer cell migration by an ERK/mitogen-activated protein kinase-dependent pathway and is primarily responsible for the increase in migration observed in hypoxia.
Recent studies indicate that cancer cells express erythropoietin receptor (EpoR). In this study, we have shown that erythropoietin (Epo) activates the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), and promotes migration in MCF-7 breast cancer cells. Epo-stimulated MCF-7 cell migration was blocked by the MEK inhibitor PD098059 and by dominant negative MEK-1, indicating an essential role for ERK. When MCF-7 cells were exposed to hypoxia (1.0% O(2)) for 3 h, the Epo mRNA level increased 2.4 +/- 0.5-fold, the basal level of ERK activation increased, and cell migration increased 2.0 +/- 0.1-fold. Soluble EpoR and Epo-neutralizing antibody significantly inhibited hypoxia-induced MCF-7 cell migration, suggesting a major role for autocrine EpoR cell signaling. MCF-7 cell migration under hypoxic conditions was also inhibited by PD098059. These experiments identify a novel pathway by which exogenously administered Epo, and Epo that is produced locally by cancer cells under hypoxic conditions, may stimulate cancer cell migration.


Knowledge, Attitudes, and Practices Regarding Brucellosis Among the General Population in Qassim Region, Saudi Arabia: A Cross-Sectional Study.
Background Brucellosis is an endemic infection in the Middle East. The World Health Organization has identified the illness as one of the most prevalent "neglected zoonotic diseases." Public perceptions regarding brucellosis infection vary across different regions. Thus, this study aimed to assess the knowledge, attitudes, and practices concerning brucellosis among the general population in the Qassim region of Saudi Arabia. Methods A descriptive, cross-sectional study was conducted in the Qassim region of Saudi Arabia between March 2023 and May 2023. We distributed an online questionnaire through social media platforms and received a total of 1,244 responses from different governorates in the Qassim region. Results The level of awareness of brucellosis was moderate. Out of the 1,244 participants, 706 (56.8%) were aware of the disease. Among the participants who were aware of the disease, their knowledge of brucellosis was assessed. The majority of these respondents demonstrated a good level of knowledge (70.5%). Regarding attitudes and practices toward brucellosis, no significant association was found between the participants' level of knowledge and their attitudes. Conclusion Awareness levels about brucellosis in the Qassim region vary depending on age group, area of residency, and other factors. The younger age group and certain governorates in the Qassim region showed low levels of awareness. Moreover, participants with good knowledge about the disease obtained their information from healthcare practitioners. The significant difference in our findings between Qassim's governorates demonstrates the need for more targeted awareness campaigns in areas with lower levels of awareness.


Regulation of growth of an interleukin 2 (IL-2)-dependent murine T-cell clone (HT-2) in a defined serum-free medium.
In this study, we demonstrate that an IL-2-dependent T-cell clone (HT-2) can be grown in a serum-free medium (HB101) with defined additives at rates comparable to those which can be obtained in serum-containing medium. Further, we show that cells cultured in the serum-free medium in the absence of IL-2 arrest growth in the G1 portion of the cell cycle, and that these arrested cells can be stimulated to reenter the cell cycle upon the addition of IL-2 to the culture medium. Growth of these cells in the absence of serum requires the presence of IL-2 as well as other hormones and growth factors and 2-mercaptoethanol. HT-2 cells have been grown continuously in the serum-free medium for periods of up to 1 month.


A Review of the Status of Brain Structure Research in Transsexualism.
The present review focuses on the brain structure of male-to-female (MtF) and female-to-male (FtM) homosexual transsexuals before and after cross-sex hormone treatment as shown by in vivo neuroimaging techniques. Cortical thickness and diffusion tensor imaging studies suggest that the brain of MtFs presents complex mixtures of masculine, feminine, and demasculinized regions, while FtMs show feminine, masculine, and defeminized regions. Consequently, the specific brain phenotypes proposed for MtFs and FtMs differ from those of both heterosexual males and females. These phenotypes have theoretical implications for brain intersexuality, asymmetry, and body perception in transsexuals as well as for Blanchard's hypothesis on sexual orientation in homosexual MtFs. Falling within the aegis of the neurohormonal theory of sex differences, we hypothesize that cortical differences between homosexual MtFs and FtMs and male and female controls are due to differently timed cortical thinning in different regions for each group. Cross-sex hormone studies have reported marked effects of the treatment on MtF and FtM brains. Their results are used to discuss the early postmortem histological studies of the MtF brain.


Differential susceptibility effects: the interaction of negative emotionality and sibling relationship quality on childhood internalizing problems and social skills.
Whereas socialization influences in early childhood have been linked to children's emerging internalizing problems and prosocial behavior, relatively few studies have examined how NE might moderate such associations in both advantageous and maladaptive ways. Furthermore, more research is needed to evaluate the impact of sibling relationships as an influential socialization influence on these child outcomes. In the current study we examined how NE might differentially moderate the associations between quality of relationships with siblings and both internalizing problems and social skills at school entry. NE moderated the effects of positive and destructive sibling relationship quality on child internalizing problems. Specifically, for boys high on NE, more positive sibling relationship quality predicted fewer internalizing problems, but more destructive sibling conflict predicted more internalizing problems. NE also moderated the effects of destructive sibling conflict on child social skills. For boys high on NE, destructive sibling conflict predicted fewer social skills. Boys high on NE appear to show greater susceptibility to the effects of sibling socialization on child outcomes, relative to boys low on NE. The implications of these interactions are discussed with respect to differential susceptibility theory.


Detection of diatoms in blood by a combination of membrane filtering and chemical digestion.
An improved method for detecting diatom in blood is reported. Blood of cadavers was obtained by cardiac puncture at inquest or from the left atrium directly at autopsy. The blood was hemolyzed by sodium dodecyl sulfate (SDS) and filtered through membrane filter (47 mm in diameter and 5 microns in pore size). When the blood was putrefied, two or three pieces of membranes filters were needed because of choking membrane pore. The membrane filters were digested with fuming nitric acid and diluted with distilled water. The diluted solution was filtered through membrane filter (25 mm in diameter) again. After drying the membrane filter was immersed in oil. Diatoms on the membrane filter were clearly observed microscopically.


Charting the process of change: a primer on survival analysis.
Survival analysis is a powerful and useful technique for understanding qualitative change. This article provides a practical, nontechnical introduction to the use of survival analysis for social scientists. Important issues in using survival analysis are discussed, including research design, data preparation and management, and data analysis. Attendance data from a self-help organization are used to illustrate common survival analysis tasks such as describing the overall survival and hazard functions, examining covariate effects, and modeling the form of the hazard function over time. An appendix that discusses the strengths and weaknesses of current survival analysis computer programs is included.


Site-selectivity of protonation in gaseous toluene.
The favoured protonation sites leading to isomeric toluenium ions have been assayed, envisaging the mildest possible route for proton transfer to naked toluene.


Renal cystic disease of infancy: results of histochemical studies. A report of the Southwest Pediatric Nephrology Study Group.
Histochemical techniques utilizing Tetragonolobus lotus (proximal tubules), Arachis hypogaea (distal nephron, i.e., distal convoluted tubules and collecting ducts), and antibodies against Tamm-Horsfall protein (thick ascending limbs of Henle) were used to determine the site of origin of renal cysts in five children with autosomal recessive polycystic kidney disease (ARPKD) and three patients with glomerulocystic disease (GCD) presenting in the 1st year of life. The findings support a distal nephron origin for the cysts in the children who had ARPKD, whereas the majority of cysts in the children with GCD were confirmed as having a glomerular origin. Tamm-Horsfall protein was identified in the cysts of both ARPKD and GCD; this finding suggests free communication between some of the cysts with the thick ascending limb of Henle. An unexpected finding was the frequent presence of cysts surrounded by muscle fibers. We suggest that these cysts are of collecting duct origin.


Association of Operative Day of the Week with the Length of Stay and Total Hospitalization Costs in Patients with Partial Mastectomy: A Nationwide Database Study in Japan.
Length of stay (LOS) is a major concern while optimizing medical resources and costs. Hence, factors influencing LOS should be investigated. In Japan, breast cancer surgery generally involves several days of hospitalization for observation, despite few complications. We hypothesized that the day of surgery (weekday; Monday-Friday) affects LOS. Using a Japanese nationwide database, we retrospectively identified 146,610 patients who underwent partial mastectomy for stage 0-III breast cancer from July 2010 to March 2017. We conducted multivariable linear and logistic regression analyses adjusting for background characteristics (such as comorbidities and hospital characteristics) with a generalized estimating equation for within-hospital clustering to compare postoperative and total LOS, total hospitalization costs, and postoperative complications between the groups for whom the surgery was performed on different days of the week. In total, whereas the median postoperative LOS was 4 days (interquartile range, 3-6 days), the median total LOS was 6 days (5-8 days). The median total hospitalization cost was 6,189 US dollars (5,609-6,668 US dollars), and postoperative complications occurred in 3.3% of cases. Despite no significant difference in postoperative complications, Monday-Wednesday surgeries showed significantly shorter postoperative LOS than Friday surgeries (-0.11 days [95% confidence interval, -0.14 to -0.07] on Monday with reference to Friday). Nevertheless, Monday surgeries showed significantly increased total LOS (0.69 days [0.64-0.74]) and hospitalization costs (93 US dollars [71-116]) in comparison with Friday surgeries. The operative day of the week was associated with increased LOS and cost, with no difference in postoperative complications after partial mastectomy. Surgeries on Monday involved longer preoperative hospital stays and higher total hospitalization costs than those on other weekdays.


Calcium-binding sites as determined by electron microscope X-ray microanalysis in the electrocytes of the electric organ of Torpedo marmorata.
Application of the Oschman and Wall technique to slices of non-stimulated electric organs of Torpedo marmorata reveals electron-dense deposits along the uninnervated and innervated membranes and in mitochondria of the electrocytes as well as in synaptic vesicles of the nerve terminals. As identified by X-ray microprobe analysis, the area containing these deposits reveal higher concentrations of calcium than the other probed regions in which they are lacking. The deposits generally occur in the form of rounded corpuscles, of about 10--20 nm in diameter in the plasma membranes to 30 nm in synaptic vesicles. In mitochondria, they can reach 100 nm or more. These results are briefly discussed with regard to previous data concerning calcium involvement in cholinergic transmission and its possible role in ionic regulation of the electrocyte.


Lateral distribution of cholesterol in dioleoylphosphatidylcholine lipid bilayers: cholesterol-phospholipid interactions at high cholesterol limit.
Lateral organization of cholesterol in dioleoyl-phosphatidylcholine (DOPC) lipid bilayers at high cholesterol concentration (>45 mol%) was investigated using steady-state fluorescence anisotropy and fluorescent resonance energy transfer techniques. The recently devised Low Temperature Trap method was used to prepare compositionally uniform cholesterol/DOPC liposomes to avoid the problem of lipid demixing. The fluorescence anisotropy of diphenylhexatrience chain-labeled phosphatidylcholine (DPH-PC) in these liposomes exhibited local maxima at cholesterol mol fractions of 0.50 and 0.57, and a sharp drop at 0.67. For the liposomes labeled with both dehydroergosterol and DPH-PC, the fluorescent resonance energy transfer efficiency from dehydroergosterol to DPH-PC displayed a steep jump at cholesterol mol fraction of 0.5, and dips at 0.57 and 0.68. These results indicate the presence of highly ordered cholesterol regular distribution domains at those observed critical compositions. The observed critical mol fraction at 0.67 agreed favorably with the solubility limit of cholesterol in DOPC bilayers as independently measured by light scattering and optical microscopy. The regular distribution at 0.57 was previously predicted from a Monte Carlo simulation based on the Umbrella model. The results strongly support the hypothesis that the primary requirement for cholesterol-phospholipid mixing is that the polar phospholipid headgroups need to cover the nonpolar body of cholesterol to avoid the exposure of cholesterol to water.


Cytology: screening or diagnostic tool?
Previously used only as a screening tool, cytology now emerges as a powerful diagnostic technique, especially since the advent of the fine needle aspiration (FNA) biopsy. This article highlights the use of ancillary techniques, primarily electron microscopy (EM), and immunohistochemistry (IHC). When coupled with routine cytological examination such as FNA and body cavity fluid cytology, EM and IHC can refine the diagnosis and make it more precise. The authors discuss how to solve common diagnostic dilemmas by the use of cytology along with IHC and EM. The following common diagnostic problems are addressed: mesothelioma versus adenocarcinoma, neuroendocrine neoplasms and their mimickers, melanoma versus carcinoma versus sarcoma, hepatocellular carcinoma versus adenocarcinoma and adenocarcinomas of unknown primary.


Glycolipids isolated from Aplysia kurodai can activate cyclic adenosine 3',5'-monophosphate-dependent protein kinase from rat brain.
Cyclic AMP (cAMP)-dependent protein kinase (cAMP-kinase) partially purified from the membrane fractions of rat brains was stimulated by novel phosphonoglycosphingolipids (glycolipids) derived from the skin and nerve fibers of Aplysia kurodai. Among various glycolipids tested, a major glycolipid from the skin, 3-O-MeGal beta 1-->3GalNAc alpha 1-->3[6'-O-(2-aminoethylphosphonyl)Gal alpha 1-->2](2-aminoethylphosphonyl-->6)Glc beta 1-->4Glc beta 1-->1ceramide (SGL-II), was most potent, giving half-maximal activation at 32.2 microM. Activation of cAMP-kinase was maximal with 250 microM SGL-II using kemptide as substrate. The effect of SGL-II was additive on kinase activity at submaximal concentrations of cAMP. The kinase activity activated with SGL-II was inhibited by the addition of protein kinase inhibitor peptide, a specific peptide inhibitor for cAMP-kinase. Its inhibitory pattern was similar to that for the catalytic subunit. Of the various substrates tested, the glycolipid-stimulated cAMP-kinase could phosphorylate microtubule-associated protein 2, synapsin I, and myelin basic protein but not histone H1 and casein. The regulatory subunit strongly inhibited the activity of purified catalytic subunit of cAMP-kinase. This inhibition was reversed by addition of SGL-II, as observed for cAMP. SGL-II was capable of partially dissociating cAMP-kinase, which was observed by gel filtration column chromatography. However, the binding activity of cAMP to the holoenzyme was not inhibited with SGL-II. These results demonstrate that the glycolipids can directly activate cAMP-kinase in a manner similar, but not identical, to that of cAMP.


Evidence for tetrameric structure of mammalian hypoxanthine phosphoribosyltransferase.
A fast electrophoretic variant of hypoxanthine phosphoribosyltransferase (HPRT) has been detected in Mus musculus bactrianus, a mouse subspecies from Middle Asia (USSR). The electrophoretic HPRT pattern yielded by hybrids between the somatic cell of LMTK- (deficient in thymidine kinase) and the splenocytes of a male of M. m. bactrianus was five-banded. The pattern obtained from the germ cells of the ovaries from 14.5-day-old embryos from laboratory CBA mice X M. m. bactrianus crosses was also composed of five bands. The hybrids between the somatic cells of human fibroblasts X LMTK- cells gave a three-banded electrophoretic HPRT pattern because the asymmetrical heteropolymeric isozymes are probably unstable. Taken together, all the evidence is in favor of a tetrameric structure of mammalian HPRT.


[The analysis of climatic and biological parameters for the pest spread risk modelling of the wood nematode species Bursaphelenchus spp. and Devibursaphelenchus teratospicularis (Rhabditida: Aphelenchoidea)].
Based on the forest woody species wilt areassurvey in Nizhniy Novgorod region in August 2014, the possible factors of the pest spread risk modelling were analysed on six species of the genus Bursaphelenchus and Devibursaphelenchus teratospicularis using six parameters: plant host species, beetle vector species, average temperatures in July and January, annual precipitation. It was concluded that these parameters in the evaluated wilt spots correspond to climatic and biological data of the already published woody plants wilt records in Europe and Asia caused by the same nematode pest species. It was speculated that the annual precipitation of 600 mm and average July temperature of 25 degrees C or higher, are the critical combination that may be used to develop the predicative risk modelling in the forests' and parks' wilt monitoring.


The minimally invasive open pyeloplasty.
The dismembered pyeloplasty is the operation of choice for ureteropelvic junction obstruction (UPJO). Recently, with the advent of improved minimally invasive techniques and equipment, laparoscopic dismembered pyeloplasty has gained popularity. We present our experience with a minimally invasive open pyeloplasty. A retrospective review of the last 5 years of consecutive open pyeloplasties was performed with regard to age, surgical operative time, length of hospital stay, need for postoperative narcotics and surgical success. Seventy-four patients had a dismembered pyeloplasty using an open flank incision: 34 patients (<1 year), 13 (1-5 years), 7 (5-10 years) and 20 (>10 years). Mean surgical time for patients according to age was: <1 year, 109.4+/-36.4 min; 1-5 years, 105.5+/-37.4 min; 5-10 years, 131.1+/-76.4 min; >10 years, 134+/-37.8 min. Mean incision sizes for the respective groups were 2.01+/-0.50 cm, 1.93+/-0.73 cm, 2.71+/-1.55 cm and 3.5+/-1.58 cm. The last 20 patients under 1 year of age had incisions of 1-1.5 cm. The majority of incisions were via a posterior subcostal muscle splitting approach. All patients received postoperative ketorolac and acetaminophen. Supplemental narcotics were not required in any patient less than 10 years old. All patients were discharged in <23 h. Radiologic and/or symptomatic improvement was seen in 70/74 (95%) patients after surgery. The minimally invasive approach to open pyeloplasty is a safe and effective treatment choice for UPJO. In small children our technique can be easily performed through a small incision without excessive postoperative pain allowing for early discharge. Our results with a refined open surgical technique challenge the current trend in the literature that laparoscopic pyeloplasty techniques are superior with regard to cosmesis, length of stay and postoperative narcotic use.


Photoluminescence of Mn2+ in the Borosulfate Zn[B2 (SO4 )4 ] : Mn2+ -A Tool to Detect Weak Coordination Behavior of Ligands.
The impact of the surrounding ligand field is successfully exploited in the case of Eu2+ to tune the emission characteristics of inorganic photoactive materials with potential application in, e.g., phosphor-converted white light-emitting diodes (pc-wLEDs). However, the photoluminescence of Mn2+ related to intraconfigurational 3d5 -3d5 transitions is also strongly dependent on local ligand field effects and has been underestimated in this regard so far. In this work, we want to revive the idea how to electronically tune the emission color of a transition metal ion in inorganic hosts by unusual electronic effects in the metal-ligand bond. The concept is explicitly demonstrated for the weakly coordinating layer-like borosulfate ligand in the Mn2+ -containing solid solutions Zn1-x Mnx [B2 (SO4 )4 ] (x = 0, 0.03, 0.04, 0.05, 0.10). Zn[B2 (SO4 )4 ]:Mn2+ shows orange narrow-band luminescence at 590 nm, which is an unusually short wavelength for octahedrally coordinated Mn2+ and indicates an uncommonly weak ligand field. On the other hand, the analysis of the interelectronic Racah repulsion parameters reveals ionic Mn-O bonds with values close to the Racah parameters of the free Mn2+ ion. Overall, this strategy demonstrates that electronic control of the metal-ligand bond can be a tool to make Mn2+ a potent alternative emitter to Eu2+ for inorganic phosphors.


The skeletal effects of colony-stimulating factor-1 in toothless (osteopetrotic) rats: persistent metaphyseal sclerosis and the failure to restore subepiphyseal osteoclasts.
Toothless (tl), one of four osteopetrotic mutations in the rat, is characterized by few osteoclasts, undetectable bone resorption, and failure of correction by bone marrow transplantation. We recently reported that CSF-1 treatment improves these skeletal problems but that metaphyseal sclerosis persists. In the present study we demonstrate that optimal reduction of the skeletal sclerosis in tl rats following CSF-1 treatment has lower and upper dosage thresholds and that skeletal sclerosis returns after CSF-1 withdrawal. Osteoclasts increase significantly in tl rats after CSF-1 treatment, but compared to untreated normal littermates, histochemical staining for characteristic enzymes and osteoclast number is reduced and no osteoclasts appear in the subepiphyseal areas of long bones. These data are interpreted to mean that there are dosage limits to the beneficial skeletal effects of CSF-1, that persistent sclerosis is related to the failure to restore subepiphyseal osteoclasts, that osteoclast or progenitor populations may be deficient or differ in their responses to CSF-1, and that the defect in tl rats is not merely lack of a circulating, biologically active form of CSF-1.


Spanish validation of the Detachment and Compartmentalization Inventory (DCI) in a community and clinical sample. A new instrument for measuring dissociation.
Dissociative symptoms are a type of phenomenon which is present in a wide variety of psychopathological disorders. It is therefore necessary to develop scales that measure this type of experience for therapy and research. Starting out from the bipartite model of dissociation, this study intended to adapt and validate the Detachment and Compartmentalization Inventory (DCI) in Spanish. For this, 308 participants (268 from the community population and 40 with psychiatric pathology) completed the DCI, the Dissociative Experiences Scale (DES-II), the Somatoform Dissociation Questionnaire (SDQ20) and the Mindfulness Attention Awareness Scale (MAAS). The results showed that the Spanish version has a two-factor structure similar to the original version and was invariant across participants. The reliability of DCI scores was adequate and acquired evidence of validity related to other instruments. It is concluded that the DCI is a valid scale for detecting detachment and compartmentalization dissociative experiences, both in the clinic and research.


Content analysis of the impact of COVID-19 on weight and shape control behaviors and social media content of U.S. adolescents and young adults.
The current study examines impacts of the COVID-19 pandemic on weight/shape control behaviors among adolescents and young adults in the U.S., and perceived changes to related social media content. A sample of youth (14-24 years) from MyVoice, a national text-message-based cohort, provided open-ended responses to questions on changes in eating and exercise habits due to concern about weight/shape, and social media content related to weight/shape, during the pandemic. Responses were collected using a secure online platform and analyzed using content analysis. Among respondents (n = 939/1153, response rate = 81%), 40.0% adopted behaviors for the purpose of weight/shape control during the pandemic. Nearly half (49.2%) reported seeing posts about weight/shape on social media during the pandemic. Findings from this study indicate that weight/shape concerns among adolescents and young adults in the U.S. may have increased due to the COVID-19 pandemic, with social media content as a potentially contributing factor.


Optimal method for measuring tumor extent in needle biopsy specimens to identify small-volume prostate cancer.
To compare various methods for measuring tumor extent in prostate biopsy specimens to identify small-volume prostate cancer. A total of 100 radical prostatectomy specimens were retrospectively analyzed. Receiver operating characteristic analysis was used to compare the abilities of prostate-specific antigen density, and four measures of tumor extent in prostate biopsy specimens - positive core number, greatest percentage of cancer in a single core, greatest length of cancer in cores and total length of cancer in cores - to identify small volume prostate cancer. Four definitions of insignificant cancer volume were used in this analysis: index and total tumor volume <0.5 mL, index tumor volume <1.3 mL and total tumor volume <2.5 mL. Multivariate analysis was also used to evaluate variables for predicting small-volume prostate cancer. Total length of cancer in cores had the highest areas under the curve of all the measures defining small-volume prostate cancer: index tumor volume <0.5 mL (0.855), total tumor volume <0.5 mL (0.877), index tumor volume <1.3 mL (0.784) and total tumor volume <2.5 mL (0.818). On multivariate analysis total length of cancer in cores was an independent predictive factor for prostate cancers with index tumor volume <0.5 mL (P < 0.001), <1.3 mL (P < 0.001) and total tumor volume <0.5 mL (P < 0.001), respectively. Our data suggest that total length of cancer in cores is the optimal measure of tumor extent in prostate biopsy specimens for identifying small-volume prostate cancer.


More Attacks and Analgesic Use in Old Age: Self-Reported Headache Across the Lifespan in a German Sample.
Background: Reliable population-based data on the prevalence and characteristics of primary headache across the lifespan are essential. However, robust data are lacking. Methods: We utilized questionnaire data from a random general population sample in Germany, that comprised 2,478 participants aged ≥14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. Results: The 6-month prevalence of self-reported headache in the total sample amounted to 39.0% (known diagnosis of migraine 7.2%; tension-type headache 12.4%; another diagnosis or unknown diagnosis 23.4%). Age-specific prevalence rates were 37.9% (14-34 years), 44.6% (35-54 years), 38.5% (55-74 years), and 26.9% (≥75 years). Compared to age group 14-34, participants aged 35-54 were more (OR = 1.29, 95%-CI 1.05-1.60, p = 0.018) and those aged ≥75 were less (OR = 0.55, 95%-CI 0.40-0.76, p < 0.001) likely to have any headache. Of the participants with headache, 79.5% reported headache on <4 days per month, 15.6% on 4-14 days per month and 4.9% on >14 days per month. The frequency of headache did not differ significantly between age groups in men [ χ ( 3 , N = 384 ) 2 = 1.45, p > 0.05], but in women [ χ ( 3 , N = 651 ) 2 = 21.57, p < 0.001]: women aged ≥75 years were over-represented in the group reporting 4-14 headache days per month. The analgesic use (days per month) differed significantly between age groups among participants with headache on <4 days per month and on >14 days per month: 1.8 (14-34 years), 2.5 (35-54 years), 3.2 (55-74 years), and 3.4 (≥75 years), respectively 7.9 (14-34 years), 11.4 (35-54 years), 18.4 (55-74 years), and 22.8 (≥75 years). Conclusions: In general, the prevalence of headache decreases with age. However, older women suffer from more frequent attacks and older participants take analgesics on more days per month than younger participants. This might put them at risk of medication overuse which may lead to medication overuse headache. More research is needed to understand these specifics in headache frequency and treatment behavior in older people.


Myocardial dysfunction after out-of-hospital cardiac arrest: predictors and prognostic implications.
We aim to determine the incidence of early myocardial dysfunction after out-of-hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54-15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival.


Bioremediation of polycyclic aromatic hydrocarbon-contaminated saline-alkaline soils of the former Lake Texcoco.
Polycyclic aromatic hydrocarbons (PAHs) such as phenanthrene, anthracene and Benzo[a]pyrene (BaP) are toxic for the environment. Removing these components from soil is difficult as they are resistant to degradation and more so in soils with high pH and large salt concentrations as in soil of the former lake Texcoco, but stimulating soil micro-organisms growth by adding nutrients might accelerate soil restoration. Soil of Texcoco and an agricultural Acolman soil, which served as a control, were spiked with phenanthrene, anthracene and BaP, added with or without biosolid or inorganic fertilizer (N, P), and dynamics of PAHs, N and P were monitored in a 112-day incubation. Concentrations of phenanthrene did not change significantly in sterilized Acolman soil, but decreased 2-times in unsterilized soil and >25-times in soil amended with biosolid and NP. The concentration of phenanthrene in unsterilized soil of Texcoco was 1.3-times lower compared to the sterilized soil, 1.7-times in soil amended with NP and 2.9-times in soil amended with biosolid. In unsterilized Acolman soil, degradation of BaP was faster in soil amended with biosolid than in unamended soil and soil amended with NP. In unsterilized soil of Texcoco, degradation of BaP was similar in soil amended with biosolid and NP but faster than in the unamended soil. It was found that application of biosolid and NP increased degradation of phenanthrene, anthracene and BaP, but to a different degree in alkaline-saline soil of Texcoco compared to an agricultural Acolman soil.


Risk Stratification of Thyroid Nodules: From Ultrasound Features to TIRADS.
Thyroid nodules are common in iodine deficient areas, in females, and in patients undergoing neck irradiation. High-resolution ultrasonography (US) is important for detecting and evaluating thyroid nodules. US is used to determine the size and features of thyroid nodules, as well as the presence of neck lymph node metastasis. It also facilitates guided fine-needle aspiration (US-FNA). The most consistent US malignancy features of thyroid nodules are spiculated margins, microcalcifications, a taller-than-wide shape, and marked hypoechogenicity. Increased nodular vascularization is not identified as a predictor of malignancy. Thyroid elastosonography (USE) is also used to characterize thyroid nodules. In fact, a low elasticity of nodules at USE has been related to a higher risk of malignancy. According to their US features, thyroid nodules can be stratified into three categories: low-, intermediate-, and high-risk nodules. US-FNA is suggested for intermediate and high-risk nodules.


Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats.
Research indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1-10mg/kg, subcutaneously [s.c.]; n=8/dose), LY255582 (LY; 0.03-1mg/kg, s.c.; n=8/dose), or vehicle were injected 30min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors.


Endocapsular ring approach to the subluxed cataractous lens.
The surgical management of the cataract associated with extensive zonular dialysis presents a challenge for the anterior segment surgeon. In 1993, a poly(methyl methacrylate) endocapsular ring was introduced to stabilize the capsular bag. We describe the use of this endocapsular ring in phacoemulsification and intraocular lens (IOL) implantation in the capsular bag in four patients with extensive traumatic or congenital zonular dialysis. The endocapsular ring allows expansion and stabilization of the capsular bag to facilitate cortical aspiration and uncomplicated IOL implantation. With follow-up of 4 to 10 months, all IOLs have remained well centered and the patients have had excellent vision free of complications.


Absence of the derived allele at the DYS199 locus in 3 NE Chinese populations.
The allelic states of DYS199 locus were studied by allele-specific PCR. We found that all of the 107 samples chosen from three populations of northeast China had DYS199 C alleles. The result excluded the possibility that this mutation first identified in native American populations came from the three populations of northeast China.


SCFD1 expression quantitative trait loci in amyotrophic lateral sclerosis are differentially expressed.
Evidence indicates that common variants found in genome-wide association studies increase risk of disease through gene regulation via expression Quantitative Trait Loci. Using multiple genome-wide methods, we examined if Single Nucleotide Polymorphisms increase risk of Amyotrophic Lateral Sclerosis through expression Quantitative Trait Loci, and whether expression Quantitative Trait Loci expression is consistent across people who had Amyotrophic Lateral Sclerosis and those who did not. In combining public expression Quantitative Trait Loci data with Amyotrophic Lateral Sclerosis genome-wide association studies, we used Summary-data-based Mendelian Randomization to confirm that SCFD1 was the only gene that was genome-wide significant in mediating Amyotrophic Lateral Sclerosis risk via expression Quantitative Trait Loci (Summary-data-based Mendelian Randomization beta = 0.20, standard error = 0.04, P-value = 4.29 × 10-6). Using post-mortem motor cortex, we tested whether expression Quantitative Trait Loci showed significant differences in expression between Amyotrophic Lateral Sclerosis (n = 76) and controls (n = 25), genome-wide. Of 20 757 genes analysed, the two most significant expression Quantitative Trait Loci to show differential in expression between Amyotrophic Lateral Sclerosis and controls involve two known Amyotrophic Lateral Sclerosis genes (SCFD1 and VCP). Cis-acting SCFD1 expression Quantitative Trait Loci downstream of the gene showed significant differences in expression between Amyotrophic Lateral Sclerosis and controls (top expression Quantitative Trait Loci beta = 0.34, standard error = 0.063, P-value = 4.54 × 10-7). These SCFD1 expression Quantitative Trait Loci also significantly modified Amyotrophic Lateral Sclerosis survival (number of samples = 4265, hazard ratio = 1.11, 95% confidence interval = 1.05-1.17, P-value = 2.06 × 10-4) and act as an Amyotrophic Lateral Sclerosis trans-expression Quantitative Trait Loci hotspot for a wider network of genes enriched for SCFD1 function and Amyotrophic Lateral Sclerosis pathways. Using gene-set analyses, we found the genes that correlate with this trans-expression Quantitative Trait Loci hotspot significantly increase risk of Amyotrophic Lateral Sclerosis (beta = 0.247, standard deviation = 0.017, P = 0.001) and schizophrenia (beta = 0.263, standard deviation = 0.008, P-value = 1.18 × 10-5), a disease that genetically correlates with Amyotrophic Lateral Sclerosis. In summary, SCFD1 expression Quantitative Trait Loci are a major factor in Amyotrophic Lateral Sclerosis, not only influencing disease risk but are differentially expressed in post-mortem Amyotrophic Lateral Sclerosis. SCFD1 expression Quantitative Trait Loci show distinct expression profiles in Amyotrophic Lateral Sclerosis that correlate with a wider network of genes that also confer risk of the disease and modify the disease's duration.


Surgery in three-channeled aortic dissection. A 31-patient review.
Three-channeled aortic dissection with 2 adjacent false lumens present is rare. The 31 patients whose dissections we treated surgically accounted for 7.3% of the 426 patients with aortic dissection treated surgically between 1978 and May 1999. The 17 men and 14 women ranged in age from 24 to 77 years (mean: 45 +/- 12 years). Marfan syndrome was present in 18. Pain was observed at different times in 20. computed tomography scanning and magnetic resonance image proved useful in preoperative diagnosis. The morphology of the 1st and 2nd false lumens was Stanford type A + B in 13, type B + B in 15, type A + A in 2, and localized abdominal dissection in 1. Descending aortic replacement was done in 18 patients, thoracoabdominal aortic replacement in 7, ascending aortic replacement in 3, and others in 3. Five patients died in hospital and later during follow-up for 1-181 months (mean, 57 +/- 55 months). Pain recurring in patients with aortic dissection should alert the physician to the possibility of 3-channeled dissection and the necessity of surgery. The incidence of such dissection is high in patients with Marfan syndrome.


The B7x Immune Checkpoint Pathway: From Discovery to Clinical Trial.
B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a broad spectrum of human cancers, where it suppresses antitumor immunity. Further, B7x and PD-L1 tend to have mutually exclusive expression in cancer cells. Therapeutics targeting B7x are effective in animal models of cancers and autoimmune disorders, and early-phase clinical trials are underway to determine the efficacy and safety of targeting B7x in human diseases. It took 15 years moving from the discovery of B7x to clinical trials. Further studies will be necessary to identify its receptors, reveal its physiological functions in organs, and combine therapies targeting B7x with other treatments.


[Evolution of Host-Beneficial Traits in Nitrogen-Fixing Bacteria: Modeling and Construction of Systems for Interspecies Altruism].
The literature and our own data on N2-fixing bacteria forming symbioses with plants and providing convenient models to study the evolution of interspecies (microsymbionts --> hosts) altruism are considered in the review. It is presented as a deeply reorganized intraspecies altruism implemented in the clonal population of rhizobia (bacteroids --> undifferentiated bacteria) under the control of kin selection induced by plant hosts. The analysis of this model suggests that it is possible to engineer practically valuable rhizobial strains in which high N2-fixing activity is combined with decreased survival outside of plants.


Presidential address at the European Society for Medical Oncology, Nice, 30 November 1986.
Medical oncology is now accepted in Europe as a branch both of internal medicine and of clinical oncology. In this article the present situation of this discipline is analysed with reference to the plateau in the results achieved in chemosensitive tumours and to the small effect of chemotherapy in tumours considered to be "big killers". Although new avenues in tumour biology do not necessarily mean therapeutic success in the near future, at present basic discoveries are being developed for clinical therapy faster than before. Besides biological response modifiers, the development of new drugs should receive constant attention from medical oncologists. This attitude has persisted despite an awareness that the political community has had little interest in the allocation of funds for the development of new anticancer agents. Clinical trials have recently been subjected to some criticism. But unless large multicentre trials are continued with better quality control and organization it will not be possible to provide adequate resources for the many and various new drugs and biological response modifiers expected to enter the field in the next few years. The active involvement of medical oncologists in controlled clinical trials should then continue. Finally, the task and achievements of the scientific society, which allows close contacts among European medical oncologists, are briefly underlined.


Design of a website on nutrition and physical activity for adolescents: results from formative research.
Teens do not meet guidelines for healthy eating and physical activity. The Internet may be an effective method for delivering programs that help them adopt healthy behaviors. To collect information to design content and structure for a teen-friendly website promoting healthy eating and physical activity behaviors. Qualitative research, encompassing both focus group and interview techniques, were used to design the website. Participants were 12-17 year olds in Houston, Texas, and West Lafayette, Indiana. A total of 133 participants took part in 26 focus groups while 15 participated in one-on-one interviews to provide guidance for the development of teen-friendly content and structure for an online behavior change program promoting healthy eating and physical activity to 12-17 year olds. The youth made suggestions to overcome common barriers to healthy eating and physical activity. Their feedback was used to develop "Teen Choice: Food & Fitness," a 12-week online behavior change program, populated by 4 cartoon character role models. It is critical that members of the target audience be included in formative research to develop behavior change programs that are relevant, appealing, and address their needs and interests.


Corneal stability after discontinued soft contact lens wear.
To determine the time needed to reach corneal stability after discontinued daily wear of soft contact lenses and to identify corneal topographic and pachymetric changes during this period. We prospectively studied the eyes of 21 consecutive soft contact lens wearers evaluated for keratorefractive surgery. Each eye was examined once immediately after lens removal, 3 and 7 days later, and weekly thereafter. At each visit, manifest refraction, keratometry, corneal topography (EyeSys Corneal Analysis system, EyeSys Laboratories, Houston, TX) and pachymetry were performed. Incidence of associated corneal warpage and changes in corneal curvature and thickness during corneal stability time were determined. Of the 42 eyes examined, 26 corneas showed no significant change after the initial evaluation (stable group). The minimum stability time was 3 days in the remaining 16 eyes (unstable group), 7 of which had significant evidence of abnormal topography. Statistical analysis showed no significant differences between two groups regarding age, sex, duration of contact lens wear, and refractive and topographic measures. The mean central corneal thickness on the final visit was significantly different between two groups (P<0.05). Contact lens induced corneal warpage may occur in a considerable proportion of soft contact lens wearers. A 2-week contact lens free period seems to be adequate for the cornea to stabilize; however, one cannot predict the minimum time needed for each individual patient. Repeating examinations to document corneal stability before refractive surgery may be a safer alternative.


Innate immunity and the etiology of late-onset Alzheimer's disease.
Neuropathological studies supported by experimental animal studies show that the constituents of the innate immunity are intimately involved in the early steps of the pathological cascade of Alzheimer's disease (AD). To show the evidence that constituents of the innate immunity contribute to the etiology of late-onset AD. Evaluation of the relationship between the constituents of the innate immunity and genetic risk factors for late-onset AD. Complement activation and activated microglia are early neuropathogical events in AD brains. Genome-wide association studies have demonstrated gene loci that are linked to the complement system. The production capacity for inflammatory cytokines is under genetic control and the offspring with a parental history of late-onset AD have a higher production capacity for inflammatory cytokines. Epidemiological and genetic data suggest that the innate immunity is involved in the etiology of late-onset AD.


Fully digital workflow for the design and manufacture of prostheses for maxillectomy defects.
A fully digital workflow for the design and manufacture of prostheses for maxillectomy defects was described. Three-dimensional images from spiral computed tomography and intraoral scanning were used to generate a three-dimensional digital cast of a maxillectomy defect. The obturator prosthesis was then designed on the digital cast by combining dental computer-aided design and reverse engineering software programs. The prosthesis was subsequently milled from polyetheretherketone or three-dimensional-printed from polylactic acid.


Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis.
Colonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission. Single-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES≤1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC. A total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n=34, r=0.83, p<0.001). The median FC levels in the subgroup with endoscopic activity (MES 2-3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES≤1) (1000μg/g, IQR 575-1800μg/g vs. 100μg/g, IQR 80-223μg/g, p<0.001). At a cut-off of 298.5μg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93-1, p<0.001) to predict endoscopic activity. FC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.


Fibrinogen binding on human platelets. Influence of different heparins and of pentosane polysulfate.
Unfractionated heparin increased the binding of fibrinogen on ADP-treated platelets. The results varied according to both, the platelets of the donor and the kind of heparin preparation used. Beef lung heparin was more active than porcine intestinal mucosa heparin (p less than 0.02). A fraction of low molecular weight low sulfated heparin, did not significantly increase the binding of fibrinogen, except in one case for which the binding of fibrinogen to platelets was largely increased by standard heparin. On the contrary, pentosane polysulfate, a sulfated polysaccharide (of low molecular weight) significantly increased the binding of fibrinogen (p less than 0.01).


Liking of anthocyanin-rich juices by children and adolescents.
There is evidence that a diet rich in plant foods is protective against cardiovascular disease and cancer, partly attributable to secondary plant metabolites such as anthocyanins, a colourful group of flavonoids. As at present children and adolescents do not consume the recommended amounts of fruits and vegetables, one possible way of increasing intake, and particularly intake of anthocyanins, may be an anthocyanin-rich juice, since fruit juice is popular with young Germans. We produced eight different fruit products (six juices, two smoothies), and conducted hedonic tests with participants from the DONALD Study. Paired comparisons showed that most subjects preferred apple to apple-bilberry juice, but grape vs. grape-bilberry juice was liked equally frequently. Rated on a hedonic scale the grape-bilberry mixture was preferred to apple-bilberry, both as juice and as smoothie. With regard to viscosity, juices were preferred to smoothies, both as grape-bilberry and as apple-bilberry. Internal Preference Mapping revealed however consumer subgroups with different preferences, raising the question which product should be promoted in order to reach a large target group. The product richest in anthocyanins, grape-bilberry juice, was accepted very well and may therefore be suitable for promotion to children, although the high sugar content of this juice must be taken into account.


Capillary versus Serum b-hydroxybutyrate in Pediatric Diabetic Ketoacidosis.
To find the strength of agreement between point-of-care and serum b-hydroxybutyrate. 236 paired samples (capillary b-hydroxybutyrate by a point of care device and serum b-hydroxybutyrate by colorimetric enzymatic estimation) samples were collected from 26 children aged <13 years admitted with diabetic ketoacidosis. Inborn errors of metabolism and septic shock were excluded. Capillary b-hydroxybutyrate showed excellent agreement with serum â-hydroxybutyrate with mean (SD) bias of 0.027 (0.78); 95% limit of agreement -1.51, 1.56 and intraclass correlation 96.1% (95%CI 95%-97%, P<0.001). An increase in the bias noted for value above 5 mmol/L (P<0.001) (serum measurements were higher than capillary point-of-care measure-ments). Capillary â-hydroxybutyrate correlated significantly with blood pH, anion gap,bicarbonate and carbon dioxide levels on blood gas analysis (P<0.05). Capillary b-hydroxybutyrate estimation is a valid method for monitoring of ketonemia in pediatric diabetic ketoacidosis.


Automatic selection of macromolecules from electron micrographs by component labelling and symbolic processing.
A new solution to the problem of extracting images of individual biological macromolecules from electron micrographs is described. There are three distinct steps in the process. The initial stage of low-level image processing consists of noise suppression and edge detection. An intermediate stage of component labelling and feature computation bridges the gap between the iconic (low-level) processing and the final phase of symbolic (high-level) processing. Simple symbolic objects (bounding boxes) are derived from the edges, and are easily represented and manipulated in the decision-making process. The efficacy of the algorithm is demonstrated using electron micrographs of ribosomes and ribosomal subunits. The hierarchical nature of the analysis embodies a reduction in the amount of data and a change in its nature. Initially, thousands of pixels of continuous gray levels must be dealt with. After component labelling, there are fewer than a hundred bounding boxes whose manipulation can easily be defined and articulated by an expert. The software package that has been written can thus serve as a basis for applying artificial intelligence methodologies to analysis of electron micrographs.


Iodination significantly influences the binding of human transferrin to the transferrin receptor.
The human transferrin receptor (TfR) and its ligand, the serum iron carrier transferrin, serve as a model system for endocytic receptors. Although the complete structure of the receptor's ectodomain and a partial structure of the ligand have been published, conflicting results still exist about the magnitude of equilibrium binding constants, possibly due to different labeling techniques. In the present study, we determined the equilibrium binding constant of purified human TfR and transferrin. The results were compared to those obtained with either iodinated TfR or transferrin. Using an enzyme-linked assay for receptor-ligand interactions based on the published direct calibration ELISA technique, we determined an equilibrium constant of Kd=0.22 nM for the binding of unmodified human Tf to surface-immobilized human TfR. In a reciprocal experiment using soluble receptor and surface-bound transferrin, a similar constant of Kd=0.23 nM was measured. In contrast, covalent labeling of either TfR or transferrin with 125I reduced the affinity 3-5-fold to Kd=0.66 nM and Kd=1.01 nM, respectively. The decrease in affinity upon iodination of transferrin is contrasted by an only 1.9-fold decrease in the association rate constant, suggesting that the iodination affects rather the dissociation than the association kinetics. These results indicate that precautions should be taken when interpreting equilibrium and rate constants determined with covalently labeled components.


A new imaging method for assessment of aortic dissection using four-dimensional phase contrast magnetic resonance imaging.
Medical management of type B aortic dissection can result in progressive dilation of the false lumen and poor long-term outcome. Recent studies using models of aortic dissection have suggested flow characteristics, such as stroke volume, velocity, and helicity, are related to aortic expansion. The aim of this study was to assess whether four-dimensional phase-contrast magnetic resonance imaging (4D PC-MRI) can accurately visualize and quantify flow characteristics in patients with aortic dissection and whether these features are related to the rate of aortic expansion. Twelve consecutive patients with medically treated type B thoracic aortic dissection underwent a three-dimensional (3D) MRI anatomy scan using a blood pool contrast agent. Two-dimensional phase contrast MRI data (2D PC-MRI) were acquired in the ascending and descending aorta and 4D PC-MRI data were acquired in the entire thoracic aorta. The 2D PC-MRI measurements were used to assess the quality of the 4D PC-MRI velocity data. Stroke volume, velocity, and the direction of flow were calculated using 4D PC-MRI and related to the rate of aortic expansion measured on contrast-enhanced computed tomography. Comparison of 2D PC-MRI and 4D PC-MRI measurements showed good correlation (Pearson R(2) = 0.98; 95% confidence interval [CI], 0.9818-0.9953; P < .0001) and no proportional bias (bias = 1.0 mL; standard deviation, 4.6). The median aortic growth rate was 6.1 mm/y (interquartile range [IQR], 1.1-15.1 mm/y), and this correlated well with the growth rate of the false lumen (Spearman ρ = 0.62; 95% CI, 0.06-0.89; P = .0347). False lumen thrombosis (FLT) was seen in 7 of 12 patients and was not associated with reduced aortic expansion rate (FLT present: 11.4 mm/y; IQR, 3.6-21.4) vs FLT absent: 9.9 mm/y; IQR, 3.4-24.2; Mann-Whitney P = .8763). False lumen stroke volume and velocity were associated with more rapid aortic expansion (ρ = 0.80 [95% CI, 0.39-0.94; P = .0029] and ρ = 0.59 [95% CI, 0.09-0.87; P = .0480] respectively). The position of the dominant entry tear was associated with rapid expansion, which tended to be higher with distal vs proximal entry tears (distal, 21.4 mm/y [IQR, 11.4-48.9] vs proximal, 5.5 mm/y [IQR, 3.4-16.6]; Mann-Whitney P = .096). Helical flow was seen in the false lumen in 8 of 12 patients and was related to the rate of aortic expansion (ρ = 0.83, P = .0154). 4D PC-MRI can be accurately applied to visualize and quantify flow characteristics in patients with aortic dissection. Stroke volume, velocity, distal dominant entry tears, and helical flow are related to the rate of aortic expansion. This study demonstrates the potential of this new imaging method. A larger prospective study is now required to measure flow characteristics and determine their predictive value for risk stratification of patients with aortic dissection.


A rare case of leptomeningeal carcinomatosis in a patient with uveal melanoma: case report and review of literature.
Uveal melanoma is a rare subtype of melanoma, accounting for only 3-5% of all melanoma cases in the USA. Although fewer than 4% of uveal melanoma patients present with metastasis at diagnosis, approximately half will develop metastasis, more than 90% of which disseminate to the liver. Infrequently, a number of malignancies can lead to leptomeningeal metastases, a devastating and terminal complication. In this case report, we present an exceedingly rare case of a patient with uveal melanoma who developed leptomeningeal carcinomatosis as the sole site of metastasis. After conventional methods to diagnose leptomeningeal carcinomatosis fell short, a diagnosis was confirmed on the basis of identification and genomic analysis of melanoma circulating tumor cells in the cerebrospinal fluid.


Ulnar neuropathy at the elbow: results of medial epicondylectomy.
Retrospective analysis of 48 medial epicondylectomy procedures in 46 patients demonstrated that symptomatic and objective improvement was usual. Most patients experienced improvement of symptoms (98%) and moving two-point discrimination (87%), and many demonstrated improved motor strength (54%). By use of the McGowan scheme for grading ulnar neuropathy, 92% of the patients with grade I neuropathy had a return to normal function. Subdividing patients with grade II neuropathy into grade IIA and IIB on the basis of the extent of motor compromise was useful in predicting postoperative outcome. Forty-five percent of the patients with grade IIA neuropathy had a return to normal ulnar nerve function and only 11% (one patient) in the IIB group had a full recovery. In the group with grade III neuropathy, one patient had improvement to grade II level and the other five remained grade III. No patient in this study demonstrated deterioration of his McGown grade. Medial epicondylectomy is a safe and predictable procedure for the treatment of symptomatic cubital tunnel syndrome.


Multivesicular liposomes for oral delivery of recombinant human epidermal growth factor.
The purpose of the present study was to prepare multivesicular liposomes with a high drug loading capacity and to investigate its potential applicability in the oral delivery of a peptide, human epidermal growth factor (rhEGF). The multivesicular liposomes containing rhEGF was prepared by a two-step water-in-oil-in-water double emulsification process. The loading efficiency was increased as rhEGF concentration increased from 1 to 5 mg/mL, reaching approximately 60 % at 5 mg/mL. Approximately 47% and 35% of rhEGF was released from the multivesicular liposomes within 6 h in simulated intra-gastric fluid (pH 1.2) and intra-intestinal fluid (pH 7.4), respectively. rhEGF-loaded multivesicular liposomes markedly suppressed the enzymatic degradation of the peptide in an incubation with the Caco-2 cell homogenate. However, the transport of rhEGF from the multivesicular liposomes to the basolateral side of Caco-2 cells was two times lower than that of the rhEGF in aqueous solution. The gastric ulcer healing effect of rhEGF-loaded multivesicular liposomes was significantly enhanced compared with that of rhEGF in aqueous solution; the healing effect of the liposomes was comparable to that of the cimetidine in rats. Collectively, these results indicate that rhEGF-loaded multivesicular liposomes may be used as a new strategy for the development of an oral delivery system in the treatment of peptic ulcer diseases.


Fast-Responding Bio-Based Shape Memory Thermoplastic Polyurethanes.
Novel fast response shape-memory polyurethanes were prepared from bio-based polyols, diphenyl methane diisocyanate and butane diol for the first time. The bio-based polyester polyols were synthesized from 9-hydroxynonanoic acid, a product obtained by ozonolysis of fatty acids extracted from soy oil and castor oil. The morphology of polyurethanes was investigated by synchrotron ultra-small angle X-ray scattering, which revealed the inter-domain spacing between the hard and soft phases, the degree of phase separation, and the level of intermixing between the hard and soft phases. We also conducted thorough investigations of the thermal, mechanical, and dielectric properties of the polyurethanes, and found that high crystallization rate of the soft segment gives these polyurethanes unique properties suitable for shape-memory applications, such as adjustable transition temperatures, high degree of elastic elongations, and good mechanical strength. These materials are also potentially biodegradable and biocompatible, therefore suitable for biomedical and environmental applications.


Cross-cultural adaptation and translation of the Constant Murley Score into Arabic.
Shoulder pain is a major disorder of the musculoskeletal system. To the best of our knowledge, there is no documentation of an Arabic version of the shoulder disability and pain measurements. Constant Murley Score (CMS) is one of the standard questionnaires for clinical practice and research. The aim of this research centred around the evaluation of the Arabic Constant Murley Score and subsequently assessing the reliability and validity in comparison to disabilities of the arm, shoulder, and hand (DASH). Hundred and twenty five patients took part in this research. We did the internal consistency tests with Cronbach's alpha. Intra-correlation coefficient, convergent validity, convergent construct validity, responsiveness, and floor and ceiling effects were also calculated. Principal component analysis showed that the variance was 63.31% with a factor range of 0.42-0.85, which fulfils the uni-dimensionality criterion. Also, the Arabic CMS correlated negatively with the DASH score (-0.82, p < 0.001). The Arabic version of CMS was consistent with Cronbach's alpha of 0.74. With Inter Class Correlation Coefficient (ICC) = 0.83 it also showed a very good test-retest reliability. Ours is the first translation and cross-cultural adaptation of the CMS into Arabic. Important evidences of validity were tested such as uni-dimensionality, convergent validity, and internal consistency. Results demonstrate an acceptable Cronbach's alpha of 0.74, ICC = 0.830 indicating excellent reliability and a strong correlation of the Arabic CMS with the DASH score (r = -0.820). Overall, the Arabic version of CMS is a good and reliable diagnostic tool for patients experiencing shoulder pain.


An Unusual Complication of the Ventricular Septal Defect Closure by Device: Late Right Aortic Cusp Perforation.
Aortic regurgitation (AR) is a rare complication of transcatheter closure of perimembranous ventricular septal defects (pmVSD). It results from iatrogenic pinching of the aortic valve by the VSD occluder or perforation by the catheter. It is usually detected during control echocardiography (ECHO). The current study reports the first case of a late AR, which resulted from late right coronary cusp perforation by the VSD occluder. The current manuscript discusses the possible causes of late cusp erosion due to occluder, advantages of early operation in such cases, and an alternative treatment method where the occluder removal is not possible at the operation.


Impact of donor benign intimal thickening on cardiac allograft vasculopathy.
Epicardial cardiac allograft vasculopathy (CAV) is commonly described as a homogeneous smooth muscle cell (SMC)-rich inward intimal lesion with the SMC oriented circumferentially around the vessel. Recent findings have called this description into question. In this study we aimed to clarify the clinical presentation of epicardial CAV. Autopsied samples of the 3 major coronaries were analyzed from patients fitting cardiac donor criteria (n = 10) and patients who had undergone cardiac transplantation (n = 34). Histology and immunohistochemistry were performed to identify cellular components of CAV, and image analysis was used to measure the various vascular compartments. Of the 34 cases examined, 28 of the epicardial intimal lesions contained 2 clearly definable layers overlying the media. The layer most adjacent to the media was SMC-rich, with the SMC oriented longitudinally along the vessel length and containing few macrophages, both characteristics of donor-derived benign intimal thickening (BIT). Transplants harvested at 1, 4 or 10 days post-transplant confirmed retention of BIT after transplantation. Image analysis of later transplants supported a hypothesis of carry-over BIT in CAV. The more lumenal CAV layer more closely resembled naturally occurring atherosclerosis. We propose that retention of the SMC-rich BIT layer after transplantation accounts, to a large extent, for the donor-derived, SMC-rich nature of human CAV, and that perturbation of the BIT provides the inflammatory foundation for the development of an accelerated atherosclerosis in the epicardial coronaries of transplant patients. This expanding accelerated atherosclerosis along with the underlying BIT demonstrates the characteristics ascribed to CAV.


Research progress in mitochondrial gene editing technology.
Mitochondrial DNA (mtDNA) mutations result in a variety of genetic diseases. As an emerging therapeutic method, mtDNA editing technology recognizes targets more based on the protein and less on the nucleic acid. Although the protein recognition type mtDNA editing technology represented by zinc finger nuclease technology, transcription activator like effector nuclease technology and base editing technology has made some progress, the disadvantages of complex recognition sequence design hinder further popularization. Gene editing based on nucleic acid recognition by the CRISPR system shows superiority due to the simple structure, easy design and modification. However, the lack of effective means to deliver nucleic acids into mitochondria limits application in the field of mtDNA editing. With the advances in the study of endogenous and exogenous import pathways and the deepening understanding of DNA repair mechanisms, growing evidence shows the feasibility of nucleic acid delivery and the broad application prospects of nucleic acid recognition type mtDNA editing technology. Based on the classification of recognition elements, this article summarizes the current principles and development of mitochondrial gene editing technology, and discusses its application prospects.


CXCR4 transfection of cord blood mesenchymal stromal cells with the use of cationic liposome enhances their migration toward stromal cell-derived factor-1.
The interaction between stromal cell-derived factor (SDF)-1 and its receptor CXCR4 is one of the mechanisms by which mesenchymal stromal cells (MSCs) are recruited to sites of injury. SDF-1 is upregulated in damaged tissues, but because the surface expression of CXCR4 on cultured MSCs is low, we investigated whether the delivery of CXCR4 into MSCs with the use of the cationic liposomal reagent IBAfect would increase their migration toward SDF-1. We examined (i) the effect of MSC confluency, passage number, duration of transfection and amount of IBAfect and plasmid on transfection efficiency as determined by flow cytometric analysis of CXCR4 and (ii) whether IBAfect-mediated CXCR4 transfection affected the viability, proliferation and differentiation of MSCs as well as their response toward an SDF-1 gradient in a trans-Matrigel migration assay. We found that transfection efficiency of up to 40% was achieved after 24-h transfection of 50% confluent MSCs (at passage 4) with an IBAfect:plasmid ratio of 3.6 μL:0.6 μg, and CXCR4 transcript expression in transfected MSCs was 10(5)-fold higher than in non-transfected cells. Transfected MSCs retained their ability to differentiate to osteocytes and chondrocytes but had lower proliferation. Importantly, overexpression of surface CXCR4 with the use of IBAfect significantly increased (>3-fold) the number of cells migrating toward an SDF-1 gradient relative to cells migrating to media alone, compared with non-transfected cells (1.3-fold). Our results suggest that IBAfect-mediated delivery of CXCR4 into MSCs is a highly efficient technique that may be useful for enhancing the recruitment of systemically infused MSCs for tissue repair.


[Breast cancer: News tools in imaging].
Breast cancer imaging is always improving for the last 20 years in spite of digitalization and computer development. News tools in mammography (Digital Breast Tomosynthesis, Contrast enhanced mammography), sonography (elastography, Automated echography), MRI (Diffusion, abbreviated MRI) and Nuclear medicine has the great potential to be the future of breats imaging. But true revolution will be to use the huge volume of "hidden" imaging data, by Intelligence Artificial process or Biological progress (in genomics, proteiomics) to purpose to our patient a personalized imaging.


Enhanced protein profiling arrays for quantitative measurement of protein expression in multiple samples.
Simultaneous measurement of molecules from many samples is particularly useful for screening of certain molecules from different samples, for targeting verification of results obtained from protein and cDNA arrays, and for molecular epidemiology-based investigations. Described herein is a sensitive and quantitative approach, referred to as enhanced protein profiling arrays, that measures molecular expression levels from numerous samples. Enhanced protein profiling arrays can easily be constructed from tissue lysates, cell lysates, conditioned media, and body fluids, along with standard proteins and appropriate controls onto antibody-coated surfaces of solid supports. Coupled with many common detection techniques, the expression levels of certain molecules can be determined quantitatively. An account of the successful development and application of this enhanced protein profiling array technology is presented.


Large-scale network functional interactions during distraction and reappraisal in remitted bipolar and unipolar patients.
The human brain is organized into large-scale networks that dynamically interact with each other. Extensive evidence has shown characteristic changes in certain large-scale networks during transitions from internally directed to externally directed attention. The aim of the present study was to compare these context-dependent network interactions during emotion regulation and to examine potential alterations in remitted unipolar and bipolar disorder patients. We employed a multi-region generalized psychophysiological interactions analysis to quantify connectivity changes during distraction vs reappraisal pair-wise across 90 regions placed throughout the four networks of interest (default-mode, frontoparietal, salience, and dorsal attention networks). Using network contingency analysis and permutation testing, we estimated the likelihood that the number of significant condition-dependent connectivity changes in every pair of networks exceeds the number expected by chance. We first examined the pattern of functional connectivity in 42 healthy subjects (sample I) and then compared these connectivity patterns across healthy individuals (n=23) and remitted bipolar (n=21) and unipolar disorder patients (n=21) in an independent sample II. In sample I, distraction compared to reappraisal was characterized by reduced connectivity within the default-mode network and between the default-mode and two cognitive control networks and increased connectivity among the cognitive control networks. In sample II, both patient groups exhibited abnormally increased default-mode intra- and inter-network connectivity during distraction compared to reappraisal. The present study highlights the role of large-scale network interactions in emotion regulation and provides preliminary evidence of default-mode inter- and intra-network connectivity impairments in remitted bipolar and unipolar patients during emotion regulation.


Drug interaction between carbapenems and extended-release divalproex sodium in a patient with schizoaffective disorder.
Clinicians prescribing divalproex sodium (DVX) are well aware of its potential to cause a drug-drug interaction. One specific interaction occurs between the carbapenem antibiotics and DVX resulting in decreased valproic acid (VPA) levels immediately following the initiation of this antibiotic class. We describe a case of a 46 year-old Caucasian male who had an undetectable VPA level following treatment with carbapenems. On admission the patient's VPA level was 115 μg/ml; however, a routine VPA level on day 19 of his hospitalization returned a value of 16 μg/ml. At this point, he had received a total of 15 days of carbapenem antibiotics for treatment of lower leg cellulitis. His DVX dose was increased to a maximum of 6g daily, twice his home dose, but it did not produce a therapeutic VPA concentration. The patient was lost to follow-up before an outpatient VPA level was drawn. Our case report is the first to document this drug-drug interaction in a patient diagnosed with schizoaffective disorder, bipolar type.


[Elution of urinary proteins preserved on nitrocellulose membrane with heating].
The preservation of urinary proteins on a membrane plays a vital role in biomarker research, and the efficient elution of proteins preserved on nitrocellulose membrane (NC membrane) determines the application of this method. During the heating elution procedure, we raised the temperature to reduce the intense vortexing time, and kept gentle rotating while precipitation to prevent nitrocellulose reformation. We also used SDS-PAGE and LC-MS/MS to analyze the urinary proteins prepared by heating elution procedure, intense vortexing elution procedure and acetone precipitation method. There was no degradation of proteins prepared by heating elution procedure. Compared with proteins prepared by heating elution method and acetone precipitation method, the overlapping rates of the proteins was almost the same (92.6% versus 96.8%) and the ratios of CV values (< 20%) of the proteins were both high (85.2% and 94.4%). The heating elution procedure achieved good technical reproducibility, and was much simpler and more efficient than the previous one. It can facilitate the application of the preservation of urinary proteins on membrane.