Effects of A23187 and CaCl(2) on tri-n-butyltin-induced cell death in rat thymocytes.
As tri-n-butyltin (TBT), one of the environmental pollutants, is accumulated in wild animals, concern regarding the toxicity of TBT in both wildlife and human is increasing. TBT has been reported to increase intracellular Ca(2+) concentration in several types of cells. In order to examine how Ca(2+) is involved in TBT-induced cell death, the effect of TBT on rat thymocytes has been compared with that of A23187, a calcium ionophore, under various concentrations of external Ca(2+) using a flow cytometer and fluorescent probes. Although both TBT and A23187 were toxic to cells under normal Ca(2+) condition, under external Ca(2+)-free condition the cytotoxic action of TBT was potentiated without changing the threshold concentration while that of A23187 was completely abolished. A23187 attenuated the TBT-induced descent in cell viability under normal Ca(2+) concentration despite intracellular Ca(2+) concentration was increased. As external Ca(2+) concentration increased, the TBT-induced increase in number of dead cells gradually decreased whereas the number of cells in an early stage of apoptosis increased. Results suggest that Ca(2+) has contradictory actions on the process of TBT-induced cell death in rat thymocytes.


Racial Disparities in Surgical Outcomes Among Women with Endometrial Cancer.
Endometrial cancer (EC) is the most common gynecological cancer among women in the United States. Despite well-documented racial/ethnic disparities in EC incidence and mortality rates, limited data exist regarding disparities in hysterectomy surgical outcomes. We evaluated associations of race/ethnicity with postoperative complications, serious adverse events (SAEs), and length of hospital stay among women undergoing EC-related hysterectomy. Using National Surgical Quality Improvement Program (NSQIP) data, we identified women (≥18 years) undergoing hysterectomy to treat EC between 2014 and 2020. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of race/ethnicity (white, black, and Latina) with postoperative complications and SAEs. We used Poisson regression with robust standard errors to calculate incidence rate ratios (IRRs) and 95% CIs for the association of race/ethnicity with length of hospital stay. Of 22,778 women undergoing EC-related hysterectomy, 3.1% developed postoperative complications. Black (adjusted OR: 1.62; 95% CI 1.05-2.48) and Latina women (adjusted OR: 1.79; 95% CI 1.04-3.09) had higher postoperative complication risks than white women. The overall SAE incidence was 5.0%. Black women (adjusted OR: 1.55, 95% CI 1.13-2.15) had higher SAE risks than white women. Length of hospital stay was significantly longer for black women than white women (IRR: 1.18; 95% CI 1.07-1.30). We observed racial/ethnic disparities in EC-related hysterectomy surgical outcomes in a large, diverse sample of U.S. women between 2014 and 2020. Studies to elucidate the underlying mechanisms of these racial disparities, with a focus on social context remain necessary.


Possible mechanism of nitric oxide production from N(G)-hydroxy-L-arginine or hydroxylamine by superoxide ion.
It has been speculated the N(G)-hydroxy-L-arginine (OH-L-Arg), which is an intermediate in NO production from L-arginine, may be converted to NO by superoxide ion. However, there is still no direct evidence for this conversion. In the present study this was investigated using superoxide ion generated either in acellular or cellular systems. It was found that OH-L-Arg and hydroxylamine were converted to nitrite and nitrate apparently via NO by superoxide ion in aqueous solution. Arginine remained unaffected. These changes were observed during reaction of chemical substances as well as in a biological system (zymosan-activated macrophages in culture). Superoxide dismutase prevented this transformation. OH-L-Arg was also spontaneously hydrolysed to hydroxylamine and L-citrulline, however this occurred at pH > 9 only. Activated microsomes (containing different isoforms of cytochrome P450) were unable to replace NO-synthase in its ability to produce OH-L-Arg from L-arginine. These data support the hypothesis that a pathway alterative to the well-known synthesis of NO by NO-synthase via OH-L-Arg exists. This pathway may involve the production of OH-L-Arg by NO-synthase and decomposition of OH-L-Arg to NO by the action of superoxide ion. Alternatively, hydrolysis of OH-L-Arg to hydroxylamine may occur followed by its oxidation to NO, again by superoxide ion.


The role of Notch signaling in adult neurogenesis.
Neurogenesis occurs throughout adulthood in the mammalian brain. Newly born neurons are incorporated into the functional networks of both the olfactory bulb and the hippocampal dentate gyrus, and there is growing evidence that adult neurogenesis is important for various brain functions. Continuous neurogenesis is achieved by the coordinated proliferation and differentiation of adult neural stem cells. In this review, we discuss the recent findings concerning the roles of Notch signaling in adult neural stem cells.


Influence of liposomes rich in unsaturated or saturated fatty acids on the growth of human xenotransplanted mammary carcinomas and on the levels of heart type fatty acid binding protein.
A panel of 4 human mammary carcinomas passaged in nude mice were subjected to intraperitoneal application of cholesterol-free liposomes enriched with linoleic (unsaturated fatty acid) or stearic acid (saturated fatty acid). The liposomes were examined with regard to their influence on the tumor growth and level of heart type fatty acid binding protein (FABP). Liposomes with different fatty acid composition influenced the growth of mammary carcinomas 3366, BO, 4000 and 4151 in distinct ways. Liposomes with a high content of stearic acid significantly inhibited the growth of mammary carcinomas 3366 and BO, whereas mammary carcinomas 4000 and 4151 were not affected. The growth of mammary carcinoma 3366 was moderately increased after supplementation of liposomes rich in linoleic acid, the tumor BO was significantly inhibited and the growth of MaCa 4000 and 4151 was unchanged. Liposome treatment led to a significant increase in heart type FABP in mammary carcinomas 3366 and BO regardless of whether the animals were treated with liposomes rich in stearic or linoleic acid. Such significant changes of FABP level could not be observed in mammary carcinomas 4000 or 4151. We suggest that the lipid-mediated growth modulation seems to be dependent on an increase of heart type FABPs in these tumor models.


Probing the viscoelastic response of glassy polymer films using atomic force microscopy.
The mechanical properties of glassy films and glass surfaces have been studied using an atomic force microscope (AFM) through various imaging modes and measuring methods. In this paper, we discuss the viscoelastic response of a glassy surface probed using an AFM. We analyzed the force-distance curves measured on a glassy film or a glassy surface at temperatures near the glass transition temperature, Tg, using a Burgers model. We found that the material's characteristics of reversible anelastic response and viscous creep can be extracted from a force-distance curve. Anelastic response shifts the repulsive force-distance curve while viscous creep strongly affects the slope of the repulsive force-distance curve. When coupled with capillary force, due to the condensation of a thin layer of liquid film at the tip-surface joint, the anelasticity and viscous creep can alter the curve significantly in the attractive region.


Fractionating stem cells secretome for Parkinson's disease modeling: Is it the whole better than the sum of its parts?
Human mesenchymal stem cells (hMSCs) secretome has been have been at the forefront of a new wave of possible therapeutic strategies for central nervous system neurodegenerative disorders, as Parkinson's disease (PD). While within its protein fraction, several promising proteins were already identified with therapeutic properties on PD, the potential of hMSCs-secretome vesicular fraction remains to be elucidated. Such highlighting is important, since hMSCs secretome-derived vesicles can act as biological nanoparticles with beneficial effects in different pathological contexts. Therefore, in this work, we have isolated hMSCs secretome vesicular fraction, and assessed their impact on neuronal survival, and differentiation on human neural progenitors' cells (hNPCs), and in a 6-hydroxydopamine (6-OHDA) rat model of PD when compared to hMSCs secretome (as a whole) and its protein derived fraction. From the results, we have found hMSCs vesicular fraction as polydispersity source of vesicles, which when applied in vitro was able to induce hNPCs differentiation at the same levels as the whole secretome, while the protein separated fraction was not able to induce such effect. In the context of PD, although distinct effects were observed, hMSCs secretome and its derived fractions displayed a positive impact on animals' motor and histological performance, thereby indicating that hMSCs secretome and its different fractions may impact different mechanisms and pathways. Overall, we concluded that the use of the secretome collected from hMSCs and its different fractions might be active modulators of different neuroregeneration mechanisms, which could open new therapeutical opportunities for their future use as a treatment for PD.


Effect of Mycobacterium avium subsp. paratuberculosis (MAP) infection on the diagnostic accuracy for Mycobacterium bovis (M. bovis) infection under field conditions in cattle belonging to low M. bovis prevalence herds.
Currently, the Chilean authority has implemented a National Eradication Program for bovine tuberculosis (bTB), aimed at controlling and eradicating the disease in Chile. The area under study has a low within-herd prevalence, has a relatively low number of infected herds, and is one of the major milk and beef producing areas in the country. However, so far, no attempts at eradicating the disease have been successful. It has been suggested that the diagnostic tests used were either not sensitive or specific enough. In addition, previous studies have shown that a great number of herds are infected with Mycobacterium avium subsp. paratuberculosis (MAP). The present study estimates the effect of MAP infection under field conditions, on the diagnostic sensitivity and specificity of routine tests in live animals for Mycobacterium bovis infection diagnosis in cattle. In general, the estimations of test accuracy observed an increase in the sensitivity and specificity on MAP-infected animals for tuberculin test but observed a decrease in the sensitivity of gamma interferon tests for MAP-infected cattle. These results are different from those of previous studies considering the role of MAP infection as an interfering infection. More research is needed in order to understand the complex interactions of the different mycobacteria that can be found infecting production cattle.


The Depression Intensity Scale Circles (DISCs): a first evaluation of a simple assessment tool for depression in the context of brain injury.
To assess the validity, responsiveness, and test-retest reliability of DISCs (Depression Intensity Scale Circles) as a simple screening tool for depression in patients with cognitive or communicative deficits following acquired brain injury. Cohort analysis of consecutive patients entered into an integrated care pathway for screening and management of depression in the context of rehabilitation. Regional neurological rehabilitation service in the UK. 114 patients with complex disabilities caused by acquired brain injury (mean (SD) age, 42.8 (14.5) years). DISCs (a graphic rating scale depicting six circles with increasing proportion of dark shading), Numbered Graphic Rating Scale (NGRS), Yale single question ("Do you often feel sad or depressed"), Beck Depression Inventory-II (BDI-II), DSM-IV criteria for depression. At initial assessment the DISCs correlated with total BDI-II scores (Spearman rho = 0.66, p < 0.001), NGRS (rho = 0.87, p<0.001), and DSM-IV (rho = 0.59, p<0.001). A DISCs score > or =2 identified depression (major or minor) according to DSM-IV criteria with 60% sensitivity, 87% specificity, 75% positive predictive value, and 77% negative predictive value. Test-retest reliability after 24 hours (n = 66) showed "excellent" level of agreement (weighted kappa = 0.84). In 45 patients who received intervention for depression, the DISCs showed a significant change in response to treatment (Wilcoxon; p<0.001). DISCs had acceptable convergent validity, reliability, and responsiveness as a simple graded tool for screening and assessment of depression in patients with complex disabilities following acquired brain injury. It warrants further investigation in patients with more profound language and cognitive deficits for which it is primarily intended.


Multi-parametric MRI without artificial erection for preoperative assessment of primary penile carcinoma: A pilot study on the correlation between imaging and histopathological findings.
We aimed to evaluate the diagnostic potential of non-erectile multi-parametric magnetic resonance imaging (mpMRI) for preoperative assessment of primary penile squamous cell carcinoma (SCC). Twenty-five patients who underwent surgery for penile SCC were included. Preoperative mpMRI without artificial erection was performed in all patients. The preoperative MRI protocol consisted of high-resolution morphological and functional sequences (diffusion-weighted imaging and dynamic contrast-enhanced MRI perfusion) covering the penis and lower pelvis. T and N staging, according to the 8th edition of the Union for International Cancer Control TNM classification, as well as the largest diameter and thickness/infiltration depth of the primary lesions were determined in all patients. Imaging data were retrospectively collected and compared with the final histopathology reports. Very good agreement was observed between MRI and histopathology for the involvement of corpus spongiosum (p = 0.002) and good agreement was observed for the involvement of penile urethra and tunica albuginea/corpus cavernosum (p < 0.001 and p = 0.007, respectively). Good agreement was observed between MRI and histopathology for overall T staging and weaker, but still good agreement was observed for N staging (p < 0.001 and p = 0.002, respectively). A strong and significant correlation was observed between MRI and histopathology for the largest diameter and thickness/infiltration depth of the primary lesions (p < 0.001). Good concordance was observed between MRI and histopathological findings. Our initial findings indicate that non-erectile mpMRI is useful in preoperative assessment of primary penile SCC.


Multifunctional hierarchical nanohybrids perform triple antitumor theranostics in a cascaded manner for effective tumor treatment.
Gene therapy based on transfection of RNAs/DNAs offers tremendous promise for tumor treatment. However, the relatively weak therapeutic efficiency of current genetic nanohybrids in vivo has limited the application of this strategy. Herein, we fabricated multifunctional core-shell-corona nanohybrids by combining cascaded theranostics for enhanced gene therapy. The nanohybrids consist of polydopamine-modified Fe3O4 nanoparticles as core, anti-miRNA-21 oligonucleotides (anti-miRNA) strands as shell, and doxorubicin (DOX)-conjugated DNA-8pb (DOX-DNA-8bp) as corona. The polydopamine/Fe3O4 core not only serves as an active agent for local photothermal therapy under NIR irradiation, but it also provides magnetic targeting to tumor tissue for accurate treatment, which could enhance the therapeutic effect and reduce the undesired side effects to healthy tissues. The DOX-DNA-8bp corona was grafted on the anti-miRNA shell through base pairing, which could be replaced by overexpressed miRNA-21 in tumor cells due to the strong interaction between miRNA-21 and anti-miRNA, resulting in tumor-specific gene therapy through tumorigenic miRNA-21 consumption and tumor selective chemotherapy through miRNA-21-triggered DOX-DNA-8bp release in tumor cells. Moreover, the intelligent controlled release system can gradually stop the release of DOX to prevent side effects caused by drug overdose, once sufficient damage of tumor cells has occurred, due to the downregulation of miRNA-21. The results of both in vitro and in vivo analyses showed that the nanohybrids combining cascaded chemo-photo-gene therapy could effectively inhibit tumor growth, promote the survival of tumor-bearing mice, and show no visible adverse effects on these mice, resulting in a promising nanoplatform for tumor treatment. STATEMENT OF SIGNIFICANCE: Gene therapy based on transfection of RNAs/DNAs offers tremendous promise for cancer treatment. However, the relatively weak therapeutic efficiency of current genetic nanovectors in vivo that results in insufficient tumor targeting and easy decomposition/elimination of RNAs/DNAs during therapy has limited its application. Although some approaches have combined photothermal agents or antitumor drugs with RNA/DNA nanocarriers to achieve better treatment, the spatiotemporal differences in photothermal therapy, chemotherapy, and gene therapy using current nanohybrids may hinder their synergistic effect. In the present study, we fabricated multifunctional core-shell-corona nanohybrids (Fe3O4@PDA@anti-miRNA/DNA) to simultaneously perform on-demand photothermal therapy, miR-21-triggered chemotherapy, and miR-21-dependent gene therapy at the same location, which can achieve an efficient synergistic effect for precise and effective tumor treatment.


Anti-EGFR (cetuximab) combined with irinotecan for treatment of elderly patients with metastatic colorectal cancer (mCRC).
This study was conducted to test the efficacy and toxicity of cetuximab and irinotecan as a biweekly regimen in treatment of elderly patients with metastatic colorectal cancer (mCRC). Forty-nine elderly patients (≥65 years) with mCRC who progressed after at least one previous line of treatment were enrolled into this study from May 2008 to January 2011. All recruited patients received cetuximab 500 mg/m(2) and irinotecan 180 mg/m(2) every 2 weeks. Thirty-seven patients (76 %) were men, and 76 % of patients had colonic cancer in origin. Median age was 69 years. Median overall survival time was 7 months, and median progression-free survival was 4 months. Grade 3-4 skin rash occurred in 20 % of patients, grade 3-4 diarrhea in 18 % of patients, and neutropenia in 28 % of patients. Cetuximab combined with irinotecan when administered biweekly is safe and effective for treatment of pretreated elderly patients with mCRC.


Pediatric burns in University Clinical Center of Kosovo from 2005-2010.
The objective of this study was to determine the incidence and cause of burns in children of our population. This was a retrospective study that included 399 patients with burns, younger than 15 years old who were admitted to the Department of Plastic Surgery, University Clinical Center of Kosovo, between 1 January 2005 and 31 December 2010. The patients were categorized into the following three age groups: infants and toddlers (0-2 years), early childhood (3-6 years), and late childhood (7-15 years). Arithmetic median and standard deviation were calculated from statistical parameters for gender and age; the differences between the three age groups were measured with one-way analysis of variance (ANOVA). A p value of <0.05 was considered statistically significant. During the study period 2005-2010, in our population, burns in children were predominant in boys with 257 cases or 64.4%, while 142 patients were girls or 35.5% The difference between the three age groups related to the causes of burns was statistically significant: p<0.000 for electrical burns and p<0.002 for burns caused by pyrotechnic devices. A high rate of childhood burns in Kosovo induces hospital admissions and prolonged hospital stays.


Cryptic developmental events determine medulloblastoma radiosensitivity and cellular heterogeneity without altering transcriptomic profile.
It is unclear why medulloblastoma patients receiving similar treatments experience different outcomes. Transcriptomic profiling identified subgroups with different prognoses, but in each subgroup, individuals remain at risk of incurable recurrence. To investigate why similar-appearing tumors produce variable outcomes, we analyzed medulloblastomas triggered in transgenic mice by a common driver mutation expressed at different points in brain development. We genetically engineered mice to express oncogenic SmoM2, starting in multipotent glio-neuronal stem cells, or committed neural progenitors. Both groups developed medulloblastomas with similar transcriptomic profiles. We compared medulloblastoma progression, radiosensitivity, and cellular heterogeneity, determined by single-cell transcriptomic analysis (scRNA-seq). Stem cell-triggered medulloblastomas progressed faster, contained more OLIG2-expressing stem-like cells, and consistently showed radioresistance. In contrast, progenitor-triggered MBs progressed slower, down-regulated stem-like cells and were curable with radiation. Progenitor-triggered medulloblastomas also contained more diverse stromal populations, with more Ccr2+ macrophages and fewer Igf1+ microglia, indicating that developmental events affected the subsequent tumor microenvironment. Reduced mTORC1 activity in M-Smo tumors suggests that differential Igf1 contributed to differences in phenotype. Developmental events in tumorigenesis that were obscure in transcriptomic profiles thus remained cryptic determinants of tumor composition and outcome. Precise understanding of medulloblastoma pathogenesis and prognosis requires supplementing transcriptomic/methylomic studies with analyses that resolve cellular heterogeneity.


Derivation and Internal Validation of a Prediction Model for Pediatric Hand Fracture Triage.
Pediatric hand fractures are common, and most can be managed by a period of immobilization. However, it remains challenging to identify those more complex fractures requiring the expertise of a hand surgeon to ensure a good outcome. The purpose of this study was to develop a prediction model for identification of complex pediatric hand fractures requiring care by a hand surgeon. A 2-year retrospective cohort study of consecutively referred pediatric (<18 years) hand fracture patients was used to derive and internally validate a prediction model for identification of complex fractures requiring the expertise of a hand surgeon. These complex fractures were defined as those that required surgery, closed reduction, or four or more appointments with a hand surgeon. The model, derived by multivariable logistic regression analysis, was internally validated using bootstrapping and then translated into a risk index. Of 1170 fractures, 416 (35.6%) met criteria for a complex fracture. Multivariable regression analysis identified six significant predictors of complex fracture: open fracture, rotational deformity, angulation, condylar involvement, dislocation or subluxation, and displacement. Internal validation demonstrated good performance of the model (C-statistic = 0.88, calibration curve p = 0.935). A threshold of ≥1 point (ie, any one of the predictors) resulted in a simple, easy-to-use tool with 96.4% sensitivity and 45.5% specificity. A high-performing and clinically useful decision support tool was developed for emergency and urgent care physicians providing initial assessment for children with hand fractures. This tool will provide the basis for development of a clinical care pathway for pediatric hand fractures.


Retrospective study of the influence of hypothyroidism on liver function before radioiodine therapy in China: a comparison analysis based on patients with differentiated thyroid cancer.
The aim of the present study is to investigate the risk factors for hepatic dysfunction before radioiodine therapy in patients with differentiated thyroid cancer (DTC). 996 patients (314 men, 682 women; age of 45.07±12.98 years) with postoperative DTC were recruited and divided into two groups including patients with and without hepatic dysfunction. The changes in baseline data and traced liver function levels, together with other metabolic profiles, were compared between the two groups. Overall, 31.6% of patients had hepatic dysfunction. Higher aspartate aminotransferase and/or alanine aminotransferase was the most common abnormality (the prevalence rate was 47.5%). The percentages of mild and moderate hepatic dysfunction were 80.0% and 20.0%, respectively. Univariate analyses demonstrated that the most prominent risk factors for hepatic dysfunction (OR=0.324-3.171, p<0.01) were male sex with levothyroxine discontinuation and free triiodothyronine <2.01 pmol/L, free thyroxine (FT4) <4.78 pmol/L, thyroid-stimulating hormone >78.195 µIU/mL, total cholesterol >5.17 mmol/L, triglycerides (TG) >1.71 mmol/L and more than 21 days of thyroid hormone withdrawal. Multivariate analyses demonstrated that for men, FT4 <3.80 pmol/L and TG ≥1.28 mmol/L were the most prominent risk factors. Patients with minor hepatic dysfunction and ortholiposis are more likely to recover to normal liver function. Patients with moderate hepatic dysfunction should be treated with hepatoprotective drugs. For men, FT4 and TG levels tended to be associated with hepatic dysfunction, and the prognosis of hepatic dysfunction was closely related to the TG level.


Studies of the nature of herpesvirus-induced tumour-associated antigens induced by herpes simplex virus type 1 and further analysis of their relationship with squamous-cell carcinomas of the head and neck region.
The differences seen in levels of antibody response to HSV-TAA between non-laryngeal and laryngeal cancers in cured and untreated patient populations were due to the use of filtered sera. In previous and present studies using unfiltered sera, these differences were not noted. Of unfiltered sera from patients with squamous-cell carcinomas of the head and neck, 89% (49 out of 55) were positive for CF reactivity to HSV-TAA, and 44% of these unfiltered sera had titres of 1:4 or greater to 44 microng of antigen. The upper band of the antigen appears to be present in early provirus formation and is highly unstable whereas the lower band does not seem to be part of the assembly process.


Lung Transplantation for End-Stage Respiratory Failure After Severe COVID-19: A Report of 2 Cases.
We report 2 cases of bilateral lung transplantation for nonresolving coronavirus disease 2019 associated respiratory failure. In the first patient, the severe acute respiratory syndrome coronavirus 2 infection caused acute respiratory distress syndrome requiring prolonged extracorporeal membrane oxygenation support; in the second patient, coronavirus disease 2019 resulted in irreversible pulmonary fibrosis requiring only ventilatory support. The 2 cases represent the 2 ends of the spectrum showing significant differences in preoperative and postoperative courses.


Getting the most from the sleeve: the importance of post-operative follow-up.
Bariatric approach to obesity provides substantial weight loss and comorbidity resolution. Our unique service includes pre- and postoperative visits to the Health and Nutrition Clinic headed by a specialist in gastroenterology and nutrition. We compared patients attending regular clinic routine with those who were lost to follow-up with regard to anthropometry, comorbidity, quality of life, and food tolerance and determined who benefited most from the operation. A retrospective review was performed on patients 30 months after undergoing sleeve gastrectomy. Body mass index was used to report weight loss. Bariatric Analysis and Reporting Outcome System (BAROS) and Food Tolerance Score were (FTS) completed by all patients at the 30-month follow-up visit and compared between two groups (group I-30 months of active postoperative follow-up; group II-without). A total of 119 patients participated in the study. For groups I and II, the mean percentage of excess BMI loss at 30 months was 82.08 ± 9.83 and 74.88 ± 8.75, respectively, with better comorbidity improvement in group I. BAROS scores were 7.62 ± 0.72 and 6.92 ± 0.92. FTS was 24.30 ± 2.09 and 22.55 ± 2.27, respectively. From our experience, getting the most from the sleeve is attributed to two main factors: surgery and nutrition. Surgery results in optimal restriction and improved satiety, whereas nutrition relies on a professional medical team providing constant, ongoing patient support throughout all the bariatric process stages. These teams of surgeons and gastroenterologists specializing in nutrition, working side by side, each in their area of specialty, are the main pillars leading to the success of the sleeve.


Bariatric barosensor: a new paired structure in the paravetebral region of the iliac crest.
A new anatomical entity, which we have decided to name bariatric borosensor, is described. It represents a paired structure under the skin, supero-lateral to the posterior superior iliac spine, overlying the iliac crest at the level of the fourth lumbar vertebra. Each of the paired structure is about the size of an enlarged lymph node; 0.5-2.0 cm in the largest diameter, spherical or ovoid in shape and firm in consistency. They are easily palpated clinically and can be demonstrated objectively by ultrasound examination. A hypothesis is put forth, conjecturing that this new structure may have relevance to the problem of obesity in modern, civilised western societies.


Maternal position, labor, and comfort.
The purpose of this study was to determine if women who assumed upright positions during the phase of maximum slope would have a shorter phase of maximum slope in their labor and experience more comfort than women who assumed recumbent positions. Forty laboring women were randomly assigned to either an upright or recumbent position group. Subjects assumed the positions of their assigned group during the phase of maximum slope in their labor (cervical dilatation from 4 cm to 9 cm). Every hour during the phase of maximum slope, each subject was examined vaginally to determine her cervical dilatation and assessed for her level of comfort using the Maternal Comfort Assessment Tool. Women in the upright position group had a significantly shorter phase of maximum slope in labor, but did not significantly differ in comfort level from women in the recumbent group. Newborn Apgar scores were not significantly different between the two groups. Nurses need to be aware that the upright labor positions have the distinct advantages of facilitating efficient uterine contractions and reducing the duration of the phase of maximum slope in labor, with no increase in the discomfort experienced or adverse effect on newborn well-being.


A new X-linked mental retardation syndrome.
There are now more than 70 X-linked mental retardation syndromes associated with physical findings documented in McKusick's "Mendelian Inheritance in Man". We describe a boy and his maternal uncle who appear to have a previously unreported X-linked mental retardation syndrome, consisting of moderate mental retardation, coarse facial features, epilepsy and slowly progressive joint contractures.


Care of acute myocardial infarction by noninvasive and invasive cardiologists: procedure use, cost and outcome.
This study sought to determine how noninvasive and invasive cardiologists may differ in the hospital care of patients with acute myocardial infarction. Scant information exists regarding the effect of noninvasive and invasive cardiology subspecialization on invasive cardiac procedural use, cost and outcome in the care of patients with acute myocardial infarction. This study analyzed a prospective cohort of 292 patients admitted to an urban tertiary care hospital from the emergency room under the care of noninvasive or invasive cardiologists. Clinical characteristics; hospital course, including management, utilization of diagnostic coronary angiography and percutaneous transluminal coronary angioplasty; direct hospital costs; length of hospital stay; and post-hospital discharge follow-up data were collected by a prospective data base instrument. Despite similar clinical characteristics, extent and severity of coronary artery disease and utilization of diagnostic coronary angiography in the two groups of patients, those under the care of an invasive cardiologist were significantly more likely to undergo coronary angioplasty than those under the care of a noninvasive cardiologist. The direct hospital costs and length of stay of the noninvasive and invasive group patients who underwent coronary angioplasty were similar, although overall the direct hospital costs and length of stay were higher for the invasive than for the noninvasive group patients. Noninvasive and invasive cardiologists differ in their rate of utilization of coronary angioplasty in similar patients with acute myocardial infarction.


1-Thioglycerol: inhibitor of glycerol kinase activity in vitro and in situ.
The infantile form of glycerol kinase (GK) deficiency (McKusick No. 30703) (1) is characterized by adrenal cortical insufficiency, adrenal hypoplasia and developmental delay. The underlying biochemical mechanism(s) responsible for the observed clinical presentations are undetermined. Pursuant to our examination of the molecular pathogenesis of this enzyme deficiency, we have endeavored to develop a model for this disorder. 1-thioglycerol (1-TG) was investigated as a potential GK inhibitor in adrenal gland, an organ consistently affected, and in cultured fibroblasts, available from affected individuals. In 105,000 g bovine adrenal supernatant the Ki for 1-TG was 1.9 mM. In human fibroblast 105,000 g supernatant, the Ki for 1-TG was 3.4 mM. In both tissues the inhibition was purely competitive with respect to glycerol. Using incorporation of [14C(U)]-glycerol into protein as an index of GK activity in situ in human skin fibroblasts, GK deficient fibroblasts incorporate less than 10% of that observed in normal fibroblasts. Addition of 1-TG to normal fibroblasts resulted in inhibited incorporation rates. The specificity of these effects in situ was examined. Our findings indicate that 1-TG may be a suitable inhibitor of GK activity for the development of a model for glycerol kinase deficiency.


Comparative study of computed tomography and ventriculography with water-soluble contrast media.
From material of over 10,000 CTs a comparative study of computed tomography and ventriculography with contrast media was carried out. We examined 18 patients with suspected expansive lesions localized in the 3rd ventricle, aqueduct of Sylvius, and 4th ventricle. We have found that CT is the method of choice in these cases and that ventriculography should be reserved for those cases which have clear clinical indications.


24S-hydroxycholesterol and cholesterol-24S-hydroxylase (CYP46A1) in the retina: from cholesterol homeostasis to pathophysiology of glaucoma.
Free cholesterol is the predominant form of cholesterol in the neural retina. The vertebrate neural retina exhibits its own capacity to synthesize cholesterol and meets its demand also by taking it from the circulation. Defects in cholesterol synthesis and trafficking in the neural retina has detrimental consequences on its structure and function, highlighting the crucial importance of maintaining cholesterol homeostasis in the retina. Our purpose was to give a review on the functioning of the retina, the role of cholesterol and cholesterol metabolism therein, with special emphasis on cholesterol-24S-hydroxylase (CYP46A1). Similar to the brain, the retina expresses cholesterol-24S-hydroxylase (CYP46A1) and is enriched in its metabolic product, 24S-hydroxycholesterol. We recently published that one single nucleotide polymorphism in CYP46A1 gene, designated as rs754203, was a risk factor for glaucoma. Glaucoma is the second leading cause of blindness worldwide, affecting more than 60 million people. Glaucoma is characterized by the loss of retinal ganglion cells, which show high CYP46A1 expression. These data suggest the potential involvement of CYP46A1 and 24S-hydroxycholesterol in the pathophysiology of glaucoma.


The homeostatic and circadian sleep recovery responses after total sleep deprivation in mice.
Many studies on sleep deprivation effects lack data regarding the recovery period. We investigated the 2-day homeostatic and circadian sleep recovery response to 24 h of total sleep deprivation (TSD) induced by brief rotation of an activity wheel. Eight mice were implanted with telemetry transmitters (DSI F40-EET) that recorded simultaneously their electroencephalography (EEG), locomotor activity and temperature during 24 h of baseline (BSL), TSD and 2 days of recovery (D1 and D2). In a second experiment, two groups of five non-implanted mice underwent TSD or ad libitum sleep, after which they were killed, adrenal glands were weighed and blood was collected for analysis of corticosterone concentration. During TSD mice were awake at least 97% of the time, with a consecutive sleep rebound during D1 that persisted during D2. This was characterized by increases of non-rapid eye movement (NREM) sleep (44.2 ± 6.9% for D1 and 43.0 ± 7.7% for D2 versus 33.8 ± 9.2% for BSL) and the relative delta band power (179.2 ± 34.4% for D1 and 81.9 ± 11.2% for D2). Greater NREM and REM sleep amounts were observed during the 'light' periods. Temperature and locomotor activity characteristics were unchanged during D1 and D2 versus BSL. In non-implanted mice, corticosterone levels as well as adrenal gland and overall body weights did not differ between TSD and ad libitum sleep groups. In conclusion, 24 h of TSD in an activity wheel without stress responses influence homeostatic sleep regulation with no effect on the circadian regulation over at least 2 days of recovery in mice.


The Monostrut Björk-Shiley heart valve.
To avoid the possibility of a fracture of the welded two-armed outflow strut of the Björk-Shiley heart valve, since 1982 it has been machined from one piece of Haynes 25 in the form of a monostrut valve without welds. Of the first 864 patients with a monostrut Björk-Shiley valve implanted, 268 have now been followed up to 3 years. The clinical findings, as well as absence of hemolysis, excellent hemodynamics even with a narrow aortic root as demonstrated by transseptal cardiac catheterization and excellent functional improvement are reported. No valve thrombosis in patients receiving anticoagulant therapy was observed with valves in either the aortic or the mitral position and there was no case of mechanical failure.


Anisotropic Contraction of a Polyaromatic Capsule and Its Cavity-Induced Compression Effect.
Anisotropic contraction of a spherical polyaromatic capsule was demonstrated through simple meta-to-ortho modification of the bent polyaromatic ligands. The resultant capsule, composed of two metal ions and four ortho-substituted ligands, possesses a spheroidal cavity (1.1 nm × 1.5 nm × 1.5 nm) fully encircled by a polyaromatic framework. One large planar or bowl-shaped molecule (e.g., porphine or sumanene) is quantitatively bound by the capsule, in which the cavity-induced compression effect causes the acceleration of the bowl-to-bowl inversion of sumanene. Temperature-dependent 1H NMR analysis revealed that the activation energy of the inversion decreases greatly (ΔG⧧ = -2.8 kcal mol-1 at 318 K) upon encapsulation, whereas the opposite effect was observed in the spherical cavity of the previous polyaromatic capsule.


A comparative study reveals the higher resolution of RAPD over ARDRA for analyzing diversity of Nostoc strains.
Nostoc is a diverse genus of filamentous cyanobacteria with tremendous potential for agricultural and industrial applications. Morphometric methods and routine 16S rDNA-based identification undermines the genetic diversity and impedes strain-level differentiation. A comparative study to deduce the discriminatory power of random amplified polymorphic DNA (RAPD) and amplified ribosomal DNA restriction analysis (ARDRA) for analyzing the genetic diversity of 20 Nostoc strains of diverse geographical origin was carried out. The RAPD primer used in the study generated 100% polymorphic profile. HIP TG primer produced the highest number of bands and fragments. Five primers, viz. OPA 08, OPA 11, HIP GC, OPAH 02 and OPF 05 could produce unique bands for 11 strains. Cluster analysis using the RAPD profile showed 12.5-25% similarity among the strains. Following in silico restriction analysis, two restriction enzymes, viz. HaeIII and HinfI were selected for ARDRA. However, clustering based on the restriction pattern showed 22.5-100% similarity. Results of the present study clearly indicate higher resolution of RAPD which can be reliably used for strain-level differentiation of Nostoc strains.


Differential diagnosis of solitary pulmonary nodules based on 99mTc-EDDA/HYNIC-TOC scintigraphy: the effect of tumour size on the optimal method of image assessment.
The aim of the study was to determine an optimal method for the evaluation of scintigrams obtained with (99m)Tc-EDDA/HYNIC-TOC for the purpose of differential diagnosis of solitary pulmonary nodules (SPNs) and to assess the diagnostic value of the method. Eighty-five patients (48 males and 37 females, mean age 57 years, range 34-78 years) were enrolled in the study. Patients underwent (99m)Tc-EDDA/HYNIC-TOC scintigraphy for the purpose of differential diagnosis of SPNs (size between 1 and 4 cm). Images of all patients were evaluated visually in a prospective manner. Positive scintigraphic results were found in 37 out of 40 (93%) patients with malignant SPNs including 34 out of 35 (97%) patients with primary lung carcinoma. Two remaining false negative cases turned out to be metastatic lesions of malignant melanoma and leiomyosarcoma. Among 45 benign tumours, negative results were obtained in 31 cases (69%) and positive results in 14. The accuracy of the method was 80%. Analysis of the results of the visual assessment of scintigrams revealed a significantly higher frequency of false positive results among larger nodules (diameter at least 1.4 cm). Uptake of the tracer in those nodules was therefore assessed semi-quantitatively (using the tumour-to-background ratio), in expectation of an improvement in the low specificity of the visual method. The semi-quantitative assessment reduced the total number of false positive results in a subgroup of larger nodules from 13 to six, while preserving the high sensitivity of the method. The combination of visual analysis (for lesions smaller than 1.4 cm in diameter) and semi-quantitative assessment (for larger lesions) provided a high sensitivity of the method and significantly improved its specificity (84%) and accuracy (88%) in comparison with visual analysis (p<0.05).


Prevalence and predictors of chronic postsurgical pain after colorectal surgery: A prospective study.
The aim was to investigate the incidence, characteristics and the potential predictors of chronic postsurgical pain (CPSP) after colorectal surgery. Patients who underwent colorectal surgery at our institution from July 2014 to December 2016 were prospectively enrolled in this study. Perioperative potential demographic, clinical and psychological predictors for CPSP were collected. The follow-up visits were conducted through telephone interviews at 3 and 6 months postoperatively. The interview questionnaire comprised items regarding pain intensity, frequency, site, analgesic administration and impact on activities of daily living. A total of 624 patients completed the 6-month follow-up and were included in the analysis. CPSP was reported by 32.1% of these patients at 3 months and 21.8% at 6 months after colorectal surgery. The pain interfered with several activities of daily living in a considerable proportion of CPSP cases. At 3 months, the identified predictors of CPSP were young age, preoperative abdominal pain and pain elsewhere, preoperative anxiety and depression, longer duration of surgery, and high pain intensity on movement within 24 h after surgery. Predictors of CPSP at 6 months were young age, preoperative abdominal pain, preoperative anxiety, longer duration of surgery, and high pain intensity on movement within 24 h after surgery. Chronic pain after colorectal surgery is a common complication associated with young age, preoperative abdominal pain and pain elsewhere, preoperative anxiety and depression, longer duration of surgery, and high pain intensity on movement within 24 h after surgery.


2,4-Bis(4-fluoro-phen-yl)-2,3-dihydro-1H-1,5-benzodiazepine.
In the title compound, C(21)H(16)F(2)N(2), the seven-membered 1,4-diazepine ring of the benzodiazepine ring system adopts a distorted-boat conformation. The benzene ring of this system makes dihedral angles of 18.6 (2) and 78.8 (2)° with those of two fluoro-phenyl substituents. In the crystal, inversion dimers linked by two weak C-H⋯F hydrogen bonds generate R(2) (2)(20) ring motifs. There are also weak N-H⋯π and C-H⋯π inter-actions.


Investigations into a vascular etiology for low-tension glaucoma.
Increased intraocular pressure is accepted as a primary etiologic factor for the atrophy of the optic nerve head and visual field defects of high-tension glaucoma. Other factors must be present to explain these findings in low-tension glaucoma. One of the current theories is that low-tension glaucoma is the result of decreased optic nerve perfusion on the basis of vascular disease or other factors such as altered blood viscosity. This study compared the non-invasive vascular profiles, coagulation tests, and rheological profiles of 46 consecutive cases of low-tension glaucoma with 69 similarly unselected cases of high-tension glaucoma and 47 age-matched controls. Despite the multifactorial approach and the use of previously validated objective tests, no significant group differences were detected with any of the above investigations. If vascular disease is important in the etiology of low-tension glaucoma, then it must be localized or vasospastic since this study does not support the concept of a generalized vascular etiology, either of an atheromatous or hyperviscous nature, for the genesis of low-tension glaucoma.


Total skin high-dose-rate electron therapy dosimetry using TG-51.
An approach to dosimetry for total skin electron therapy (TSET) is discussed using the currently accepted TG-51 high-energy calibration protocol. The methodology incorporates water phantom data for absolute calibration and plastic phantom data for efficient reference dosimetry. The scheme is simplified to include the high-dose-rate mode conversion and provides support for its use, as it becomes more available on newer linear accelerators. Using a 6-field, modified Stanford technique, one may follow the process for accurate determination of absorbed dose.


Dual functional rhodium oxide nanocorals enabled sensor for both non-enzymatic glucose and solid-state pH sensing.
Both pH-sensitive and glucose-responsive rhodium oxide nanocorals (Rh2O3 NCs) were synthesized through electrospinning followed by high-temperature calcination. The as-prepared Rh2O3 NCs were systematically characterized using various advanced techniques including scanning electron microscopy, X-ray powder diffraction and Raman spectroscopy, and then employed as a dual functional nanomaterial to fabricate a dual sensor for both non-enzymatic glucose sensing and solid-state pH monitoring. The sensing performance of the Rh2O3 NCs based dual sensor toward pH and glucose was evaluated using open circuit potential, cyclic voltammetry and amperometric techniques, respectively. The results show that the as-prepared Rh2O3 NCs not only maintain accurate and reversible pH sensitivity of Rh2O3, but also demonstrate a good electrocatalytic activity toward glucose oxidation in alkaline medium with a sensitivity of 11.46 μA mM-1 cm-2, a limit of detection of 3.1 μM (S/N = 3), and a reasonable selectivity against various interferents in non-enzymatic glucose detection. Its accuracy in determining glucose in human serum samples was further demonstrated. These features indicate that the as-prepared Rh2O3 NCs hold great promise as a dual-functional sensing material in the development of a high-performance sensor forManjakkal both solid-state pH and non-enzymatic glucose sensing.


Surgeons' stress from surgery and night duty: a multi-institutional study.
To examine the stress experienced by surgeons in response to surgery and night duty. Analyses were done by subjective questionnaires and an objective urine analysis. One university hospital and 15 community/public hospitals in Kitakyushu City, Japan. Sixty-six Japanese surgeons. Scores on the NASA Task Load Index and Stress Arousal Checklist and urine biopyrin levels. The Task Load Index score significantly increased in association with the duration of surgery and the amount of surgical blood loss. Urine biopyrin levels significantly increased with the duration of surgery. Night duty significantly decreased sleep time and significantly increased urine biopyrin levels. Stress Arousal Checklist Arousal Scale scores significantly decreased the morning after night duty and the evening after the end of the following day shift. Surgery was associated with stress on surgeons and night duty influenced the arousal of the surgeons during the day shift following night duty.


Renal failure in haemorrhagic shock in dogs: salutary effects of the calcium entry blocker felodipine.
The efficacy of felodipine, a dihydropyridine calcium entry blocker to restore renal function was investigated in Wiggers model of haemorrhagic shock. Mongrel dogs were anaesthetized with sodium pentobarbital and subjected to haemorrhagic shock by allowing the animals to bleed into a reservoir. After maintaining the hypotensive state (mean blood pressure 40-45 mm Hg) for a period of 150 min, the blood was reinfused and the recovery of the various parameters were monitored for an additional 120 min. These studies were conducted in three different groups of dogs: (A) Solvent control, (B) Felodipine 0.01 mumol/kg i.v., administered 10 min prior to reinfusion of the blood, and (C) Felodipine 0.01 mumol/kg i.v., administered prior to haemorrhage. In all the three groups arterial blood pressure returned to similar basal levels following reinfusion. Felodipine administration prior to haemorrhage or before reinfusion (Group B and C) resulted in a 80-95% recovery in the renal blood flow, 60-65% in the glomerular filtration rate, 150-300% in the urine volume and 80-100% in the urinary sodium and potassium excretions. In the vehicle-treated control group, despite a 45% recovery in the renal blood flow, renal function was not restored following reinfusion. The observations made in these studies suggest that felodipine, an arteriolar dilator which also possesses natriuretic properties, could be clinically useful in the treatment of renal failure in haemorrhagic shock. Prevention of cellular calcium overload during ischaemia and reperfusion by this dihydropyridine derivative, may account for its ability to preserve vascular as well as tubular function.


Bioinspired polysaccharide hybrid hydrogel promoted recruitment and chondrogenic differentiation of bone marrow mesenchymal stem cells.
Cartilage regeneration by biomimetic cartilage matrix with synchronously recruited stem cells was one of ideal strategies. Inspired by catechol for proteins adhesion, dopamine modified polysaccharide hybrid hydrogel (HD-C) was prepared by integrating collagen I (Col I) and hyaluronic acid derivatives (HA-DN) with sulfhydryl modified polysaccharide hybrid hydrogel (HS-C) as control. Because of double-crosslinking architecture, HD-C hydrogel was endowed with a more compact pore structure, higher mechanical properties and water retention ability in comparison with those of HS-C hydrogel. Meanwhile, it significantly promoted the proliferation and spread of rabbit bone marrow stem cells (rBMSCs), and accelerated cartilaginous matrix secretion. RT-PCR results also verified higher related gene expression of chondrogenesis (Sox 9, Agg and Col II). Moreover, HD-C hydrogel could enhance the enrichment and migration of rBMSCs in vitro by potential functional protein adsorption mechanisms, and this phenomenon was further confirmed by more rBMSCs migration in short-term joint implantation experiments in vivo.


Reduction of saliva immunoglobulin levels by swim training.
Saliva immunoglobulin A (IgA) and cortisol levels were measured in 21 male members of a major midwestern swim team. Saliva samples were collected before and after training sessions four times during the fall season; the training intensity was light, moderate, heavy and during the taper period before a major competitive meet. Saliva IgA levels were decreased after each training session, reaching statistical significance with the moderate training intensity. Over the 3-month training period the pre-session and post-session IgA levels both decreased significantly during the heavy and taper training intensities later in the fall season. Cortisol levels were significantly elevated only after the heavy-intensity training session. The Profile of Mood States (POMS) was used to assess the swimmers' overall mood on each test day. No significant correlations were found between the global POMS score and IgA or cortisol. Also, cortisol and IgA were not significantly correlated except after the light training session. Results from this study indicate that acute bouts of exercise can reduce salivary IgA levels and that chronic exercise of high intensity can reduce the resting levels of IgA. These changes may render the athletes more vulnerable to respiratory infections after exercise and even at rest during the later stages of the competitive season.


Cooperative ATP binding by cloned lamin C.
Cloned human lamin C was expressed in and purified from bacteria and used in ATP binding assays. Scatchard analysis revealed strong positive cooperative and noncooperative binding, with estimated apparent dissociation constants of 3 X 10(-6) and 2 X 10(-5) M, respectively. The binding is strongly pH dependent. ATP binding by lamins A/C (presumably as intermediate filaments) may provide a substantial storage depot for ATP at the peripheral lamina for use by a number of ATP-requiring nuclear scaffold enzymes.


RNA-targeted therapeutics in cardiovascular disease: the time is now.
Ribonucleic acid (RNA)-targeted therapeutics, including antisense oligonucleotide technologies as well as small interfering RNAs (siRNAs), represent a new class of medications that may overcome several of the disadvantages of small molecule drugs or monoclonal antibodies. Specifically, upstream targeting at the messenger RNA (mRNA) level renders any disease-related protein a potential target, even those pathways previously deemed 'undruggable'. Additional advantages include the comparably simple and cost-effective way of manufacturing and the long dosing intervals. A few agents are already approved and a wide array of cardiovascular drugs is in development, aimed at hypercholesterolaemia, hypertension, myocardial storage diseases, and the coagulation system. Here, we provide an update on the current status of RNA-targeted therapeutics in the cardiovascular arena.


Hematogenous metastases of carcinoma to dorsal root ganglia.
Hematogenous metastases of carcinoma to dorsal root ganglia was found in 2 of approximately 500 consecutive autopsies in which a lumbar dorsal root ganglion was routinely examined microscopically. The primary tumors were poorly differentiated colonic adenocarcinoma and oat cell carcinoma of the lung, both with widespread hematogenous metastases which spared the central nervous system. No symptoms were detected clinically. In the same series of patients the sural nerve as well as the lumbar plexus were histologically sampled but no examples of distant endoneurial metastases were found. The vascular endothelium of dorsal root ganglia is fenestrated and, presumably as a consequence, provides no blood-ganglion barrier. This microvascular difference may account for the susceptibility of the ganglia to metastases when compared to nerve trunks which posses unfenestrated endothelium and blood-nerve barrier.


Current Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome in Children.
We highlight the new clinical entity multisystem inflammatory syndrome in children (MIS-C), the progress in understanding its immunopathogenesis, and compare and contrast the clinical and immunologic features of MIS-C with Kawasaki disease (KD). Studies show immune dysregulation in MIS-C including T lymphocyte depletion and activation, T cell receptor Vbeta skewing, elevated plasmablast frequencies, increased markers of vascular pathology, and decreased numbers and functional profiles of antigen-presenting cells. MIS-C is a late manifestation of infection with SARS-CoV-2 associated with marked immune activation and many potential mechanisms of immunopathogenesis. MIS-C and KD have clinical similarities but are distinct. Myocardial dysfunction with or without mild coronary artery dilation can occur in MIS-C but generally corrects within weeks. In contrast, the coronary arteries are the primary target in KD, and coronary artery sequelae can be lifelong. Supportive care and anti-inflammatory therapy appear to hasten improvement in children with MIS-C, and there is hope that vaccines will prevent its development.


A new joystick technique for unsuccessful closed reduction of supracondylar humeral fractures: minimum trauma.
The purpose of this study was to compare operation duration, radiological and functional results of the open reduction with either posterior or lateral approach and closed reduction with joystick method in unsuccessful closed reduction of displaced (Gartland type III) supracondylar humeral fractures. Between February 2010 and August 2011, 37 patients who were not obtained satisfactory reduction with classic closed reduction attempts for three times in operating room were included in this study. Patients were treated with three different surgical methods. Group I have 13 patients who had joystick and lateral K-wire-assisted closed reduction, group II have 12 patients who had open reduction by lateral approach, and group III have 12 patients who had open reduction by posterior approach. In final follow-up, AP and lateral radiographs of both elbows were taken and bilateral Baumann angles, lateral humerocapitellar angles, carrying angles, and elbow range of motion were measured. These angles and operation times compared between the groups. The functional and cosmetic outcome of surgery was evaluated by criteria of Flynn et al. There was no statistical significance difference between Baumann angles, lateral humerocapitellar angles, and carrying angles of fractured and uninjured sides in between three groups (respectively, p = 0.761, p = 0.354, p = 0.750). In group I, operation duration is shorter than the other groups. Functional scoring showed that in group I and group II, all patients have satisfactory results; however, in group III, three patients (25%) had poor results. In the perspective of cosmetic results, all three groups have satisfactory results. When classical closed reduction fail, lateral joystick and K-wire-assisted reduction is a useful way to make and maintain the reduction. Functional and radiological results are as good as lateral and posterior open approaches. Short operation time is an advantage. This method reduces the risk of complications due to repeated closed reduction and open reduction in unsuccessful closed reduction in pediatric supracondylar humeral fractures. Level III.


Unearthing the secrets of ERFVIIs: new insights into hypoxia signaling.
Group VII ethylene-responsive factor (ERFVII) transcription factors are crucial for the adaption of plants to conditions that limit oxygen availability. A recent study by Zubrycka et al. reveals new aspects of ERFVII stabilization through the PLANT CYSTEINE OXIDASE (PCO)-N degron pathway and non-autonomous regulation in response to different endogenous and exogenous cues.


Early primary abdominal pregnancy: Diagnosis and management. A case report.
Abdominal pregnancy is a rare type of ectopic pregnancies associated with a high mortality rate. Symptoms are not specific and usually resemble the other types of ectopic pregnancies. Medical management is used in cases where a potentially lethal hemorrhage can be anticipated. Nowadays, laparoscopic surgery has become the most common choice especially in cases diagnosed during the first trimester. A 35-year-old woman consulted for a pelvic pain and menstruation delay. She had a stable hemodynamic status and hypogastric tenderness during deep abdominal palpation. The βHCG rate was at 16041 IU/l. Pelvic ultrasonography revealed a gestational sac next to the right adnexa of 1.2 cm. Laparoscopic exploration was performed finding normal fallopian tubes and ovaries with a 2 cm mass on the vesical peritoneum. Resection of ectopic pregnancy was successfully performed and patient was discharged the next day with no postoperative complications. To date, there is no therapeutic protocol that has been established and there are no predictive criteria of success concerning medical management for ectopic pregnancy. Surgery is the most common choice in the therapeutic management of ectopic abdominal pregnancy. Laparotomy was preferred to the laparoscopic surgery because of the high risk of perioperative hemorrhage which can be uncontrollable from the implantation site. Nowadays, laparoscopic surgery should be the first measure if the abdominal pregnancy is diagnosed at an early stage (< 12 weeks) or if the implantation site allows a non-hemorrhagic surgical excision. Laparoscopic management of abdominal pregnancies is an encouraging choice to laparotomy.


MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.
Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.


Molar pregnancy presenting in the emergency department.
A 27-year-old female grava1 para 0 presented to the emergency department with complaints of intractable nausea and vomiting associated with fatigue and shortness of breath for the past 2 weeks with concerns for pregnancy. Physical exam was benign. Labs were significant for a β-hcg level of 348,260 mIU/mL. Ultrasonography showed a 12.4 pelvic mass possibly arriving from the anterior uterus concerning for fibroid. US also showed an anechoic focus suggestive of a gestational sac measuring 2.09 cm. The presentation was concerning for hyperemesis gravidarum due to molar pregnancy.


The determinants of thermal comfort in cool water.
Water-based activities may result in the loss of thermal comfort (TC). We hypothesized that in cooling water, the hands and feet would be responsible. Supine immersions were conducted in up to five clothing conditions (exposing various regions), as well as investigations to determine if a "reference" skin temperature (Tsk) distribution in thermoneutral air would help interpret our findings. After 10 min in 34.5 °C water, the temperature was decreased to 19.5 °C over 20 min; eight resting or exercising volunteers reported when they no longer felt comfortable and which region was responsible. TC, rectal temperature, and Tsk were measured. Rather than the extremities, the lower back and chest caused the loss of overall TC. At this point, mean (SD) chest Tsk was 3.3 (1.7) °C lower than the reference temperature (P = 0.005), and 3.8 (1.5) °C lower for the back (P = 0.002). Finger Tsk was 3.1 (2.7) °C higher than the reference temperature (P = 0.037). In cool and cooling water, hands and feet, already adapted to colder air temperatures, will not cause discomfort. Contrarily, more discomfort may arise from the chest and lower back, as these regions cool by more than normal. Thus, Tsk distribution in thermoneutral air may help understand variations in TC responses across the body.


Targeting novel folds for structural genomics.
The ultimate goal of structural genomics is to obtain the structure of each protein coded by each gene within a genome to determine gene function. Because of cost and time limitations, it remains impractical to solve the structure for every gene product experimentally. Up to a point, reasonably accurate three-dimensional structures can be deduced for proteins with homologous sequences by using comparative modeling. Beyond this, fold recognition or threading methods can be used for proteins showing little homology to any known fold, although this is relatively time-consuming and limited by the library of template folds currently available. Therefore, it is appropriate to develop methods that can increase our knowledge base, expanding our fold libraries by earmarking potentially "novel" folds for experimental structure determination. How can we sift through proteomic data rapidly and yet reliably identify novel folds as targets for structural genomics? We have analyzed a number of simple methods that discriminate between "novel" and "known" folds. We propose that simple alignments of secondary structure elements using predicted secondary structure could potentially be a more selective method than both a simple fold recognition method (GenTHREADER) and standard sequence alignment at finding novel folds when sequences show no detectable homology to proteins with known structures.


Intraoperative echocardiography to detect and prevent tricuspid valve regurgitation after heart transplantation.
Tricuspid valve regurgitation (TVR) is frequently observed following orthotopic heart transplantation. The etiology of this phenomenon remains unclear. In a prospective study, we tried to identify pre-, intra- and postoperative factors possibly related to the occurrence of TVR in 15 patients (14 male, 1 female). Epicardial echocardiography was used during the transplant procedure and transthoracic echocardiography was performed at weekly intervals thereafter, TVR was graded semiquantitatively (grade 0-4). If TVR grade greater than 1 was detected after discontinuation of cardiopulmonary bypass, pericardial reduction plasty was performed (group R). If no or mild TVR (less than grade 1) was present, simple closure of the pericardium was carried out (control group). In group R the mean grade of TVR was 1.6 +/- 0.3 (SEM) before and 0.6 +/- 0.07 after pericardial closure (p less than 0.05). Following moderate elevation during the first 5 weeks, the degree of TVR reached levels slightly above the initial levels after 8 weeks. In the control group, a moderate increase of TVR developed during the first 8 weeks after surgery and remained at a significantly higher level than in group R (p less than 0.05). No preoperative risk factors for TVR, such as underlying disease or hemodynamic status of the recipients, was identified. Estimation of differences in heart volume between recipient and donor organs, by contrast, showed a significant discrepancy in group R but not in the controls. We therefore conclude that TVR in recipients of orthotopic heart transplants may be due to a size mismatch of donor heart and recipient pericardial cavity, resulting in distortion of the tricuspid valve ring.(ABSTRACT TRUNCATED AT 250 WORDS)


Incidence of Glaucoma-Related Adverse Events in the First 5 Years After Pediatric Lensectomy.
Glaucoma can develop following cataract removal in children. To assess the cumulative incidence of glaucoma-related adverse events (defined as glaucoma or glaucoma suspect) and factors associated with risk of these adverse events in the first 5 years after lensectomy prior to 13 years of age. This cohort study used longitudinal registry data collected at enrollment and annually for 5 years from 45 institutional and 16 community sites. Participants were children aged 12 years or younger with at least 1 office visit after lensectomy from June 2012 to July 2015. Data were analyzed from February through December 2022. Usual clinical care after lensectomy. The main outcomes were cumulative incidence of glaucoma-related adverse events and baseline factors associated with risk of these adverse events. The study included 810 children (1049 eyes); 443 eyes of 321 children (55% female; mean [SD] age, 0.89 [1.97] years) were aphakic after lensectomy, and 606 eyes of 489 children (53% male; mean [SD] age, 5.65 [3.32] years) were pseudophakic. The 5-year cumulative incidence of glaucoma-related adverse events was 29% (95% CI, 25%-34%) in 443 eyes with aphakia and 7% (95% CI, 5%-9%) in 606 eyes with pseudophakia; 7% (95% CI, 5%-10%) of aphakic eyes and 3% (95% CI, 2%-5%) of pseudophakic eyes were diagnosed as glaucoma suspect. Among aphakic eyes, a higher risk for glaucoma-related adverse events was associated with 4 of 8 factors, including age less than 3 months (vs ≥3 months: adjusted hazard ratio [aHR], 2.88; 99% CI, 1.57-5.23), abnormal anterior segment (vs normal: aHR, 2.88; 99% CI, 1.56-5.30), intraoperative complications at time of lensectomy (vs none; aHR, 2.25; 99% CI, 1.04-4.87), and bilaterality (vs unilaterality: aHR, 1.88; 99% CI, 1.02-3.48). Neither of the 2 factors evaluated for pseudophakic eyes, laterality and anterior vitrectomy, were associated with risk of glaucoma-related adverse events. In this cohort study, glaucoma-related adverse events were common after cataract surgery in children; age less than 3 months at surgery was associated with elevated risk of the adverse events in aphakic eyes. Children with pseudophakia, who were older at surgery, less frequently developed a glaucoma-related adverse event within 5 years of lensectomy. The findings suggest that ongoing monitoring for the development of glaucoma is needed after lensectomy at any age.


LSD and 5-HTP: tolerance and cross-tolerance relationships.
Tolerance and cross-tolerance relationships between lysergic acid diethylamide (LSD) and 5-hydroxytryptophan (5-HTP) were studied in rats trained on an operant task. The results demonstrated that behavioral tolerance to both compounds occur in the rat and that asymmetrical cross-tolerance relationships exist; that is, animals tolerant to 5-HTP were cross-tolerant to LSD, but animals tolerant to LSD were not cross-tolerant to 5-HTP.


NeuRiPP: Neural network identification of RiPP precursor peptides.
Significant progress has been made in the past few years on the computational identification of biosynthetic gene clusters (BGCs) that encode ribosomally synthesized and post-translationally modified peptides (RiPPs). This is done by identifying both RiPP tailoring enzymes (RTEs) and RiPP precursor peptides (PPs). However, identification of PPs, particularly for novel RiPP classes remains challenging. To address this, machine learning has been used to accurately identify PP sequences. Current machine learning tools have limitations, since they are specific to the RiPPclass they are trained for and are context-dependent, requiring information about the surrounding genetic environment of the putative PP sequences. NeuRiPP overcomes these limitations. It does this by leveraging the rich data set of high-confidence putative PP sequences from existing programs, along with experimentally verified PPs from RiPP databases. NeuRiPP uses neural network archictectures that are suitable for peptide classification with weights trained on PP datasets. It is able to identify known PP sequences, and sequences that are likely PPs. When tested on existing RiPP BGC datasets, NeuRiPP was able to identify PP sequences in significantly more putative RiPP clusters than current tools while maintaining the same HMM hit accuracy. Finally, NeuRiPP was able to successfully identify PP sequences from novel RiPP classes that were recently characterized experimentally, highlighting its utility in complementing existing bioinformatics tools.


Left ventricular function in children and adults after renal transplantation in childhood.
Renal transplantation improves left ventricular (LV) function, but cardiovascular mortality remains elevated. The aim of this cross-sectional study was to determine whether subclinical abnormalities of LV longitudinal function also persist in patients who underwent renal transplant in childhood. Conventional and speckle tracking echocardiography was performed in 68 renal transplant recipients (34 children and 34 adults, median 9.8 years (range 2.0-28.4 years) after first transplantation and 68 age- and sex-matched healthy controls. Mean age at first transplantation was 8.8 ± 4.8 years. Forty-three percent had a pre-emptive transplant. Of the remaining, 70% received haemodialysis and 30% peritoneal dialysis on average for 6.9 months. Thirty-one percent of paediatric and 35% of adult patients had hypertension. LV mass index was increased in adult patients (92 ± 24 vs 75 ± 11 g/m(2), P< 0.01). LV diastolic function and exercise capacity were impaired in both paediatric and adult patients. LV longitudinal peak systolic strain and strain rate were comparable in patients and controls. In multivariate analysis, systolic blood pressure and LV diastolic relaxation were the main covariates of LV peak systolic strain and strain rate (all P < 0.01). Patients who underwent renal transplantation in childhood have abnormal LV diastolic function and impaired exercise capacity, despite preserved LV longitudinal systolic deformation.


Lentinan as a natural stabilizer with bioactivities for preparation of drug-drug nanosuspensions.
Lentinan is a natural β-glucan with various bioactivities and is combined with chemotherapy drugs for cancer treatment. Regorafenib is an oral multi-kinase inhibitor approved by FDA for treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors. Regorafenib has poor water solubility and multiple toxicities. We report drug-drug nanosuspensions of regorafenib and lentinan. Results of dynamic light scattering and scanning electron microscopy showed that the mean particle size of the regorafenib-lentinan nanosuspensions was approximately 200 nm and was uniformly distributed. Transmission electron microscopy findings indicated that lentinan stabilized the nanosuspensions by steric manner. Hydrogen bonds and hydrophobic interactions were found between regorafenib and lentinan by molecular dynamics simulation. The results of cytotoxicity assay and pharmacokinetics study in rats showed that the regorafenib-lentinan nanosuspensions reduced the toxicity and enhanced the in vitro anticancer activity and oral bioavailability of regorafenib. Lentinan as a natural stabilizer has the potential using for drug nanosuspensions. Drug-drug nanosuspensions are a new form of combination therapies that can reduce the number of drugs taken by patients and improve their compliance.


Epidemiological investigation and antimicrobial susceptibility analysis of Ureaplasma and Mycoplasma hominis in a teaching hospital in Shenyang, China.
The aim of this study was to estimate the prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis in a comprehensive teaching hospital Shenyang, China over the past 4 years. A total of 1448 individuals with urogenital symptoms underwent mycoplasma testing between April 2016 and March 2020. Detection, identification and antimicrobial susceptibility testing were carried out using Mycoplasma ID/AST kits. The total infection rate of genital mycoplasmas was 37.5% (543/1448 cases) with an observed increase over the past 4 years. The positive rates of all three detected infections, as well as overall infection rate, were significantly higher in females than in males (P < 0.05). A higher positive rate of infection was observed in females aged 25-29 (60.5%), and in the 15-19 years age group (57.7%). The changes observed among all age groups of females were statistically significantly different (P < 0.001). The positive rates of U. urealyticum and M. hominis co-infection among the four seasons during which the survey was carried out were also observed to be statistically different (P = 0.01). More than 70% of U. urealyticum isolates were found to be resistant to ciprofloxacin, and more than 80% of M. hominis isolates were resistant to erythromycin, roxithromycin, azithromycin and clarithromycin. Josamycin, doxycycline and minocycline were most effective against U. urealyticum and M. hominis. Results of this study found increasing rates of U. urealyticum and M. hominis infection over the past 4 years, particularly among younger age groups. U. urealyticum/Mycoplasma hominis screening among younger age cohorts are therefore strongly recommend to preventing the spread of pathogens. Monitoring antimicrobial resistance is important for preventing transmission of resistant strains of infection and for the management of antibiotics.


Electroencephalographic effects of nicotine chewing gum in humans.
The electroencephalographic (EEG) and subjective effects of nicotine chewing gum (0, 2 and 4 mg) were compared in three tobacco deprived (12 hr) heavy smokers. EEG responses were recorded from F7, F8, T5, and T6 positions before and after the subjects chewed nicotine gum (chew rate = 1 per 2 sec) for 10 min and subsequently analyzed by a computer-based data acquisition and analysis system. Analysis of the chewed gum indicated that the subjects extracted approximately 50 percent of the available nicotine. The nicotine gum increased EEG frequencies in the alpha (7.25-14 Hz) and beta (14.25-25 Hz) bands and decreased theta (4-7) Hz) power. The EEG effects were most evident in the resting subject; the effects of the gum were similar but weaker when the EEG was aroused by a mental arithmetic task. Nicotine gum had EEG stimulant effects like those of inhaled tobacco smoke which were most apparent in the relaxed subject. In spite of this similarity, the subjects did not identify the effects of the gum as being identical to those of cigarettes.


Efficacy of Dexon microsutures in rat major abdominal vessel anastomosis. I: Application to heterotopic heart transplant.
A total of 52 syngeneic heterotopic heart transplants were performed using 9-0 Dexon microsutures to see if these anastomoses could be tolerable when challenged by the burden of transplanted heart and lung. Eighteen long-term surviving transplants were verified by reliable ECG, Doppler tracings, and direct palpation of the heart grafts. Animals sacrificed at monthly intervals beginning 3 to 6 months posttransplantation were free of thrombus, lung abscesses, and separation at the anastomoses. Even though foreign body reaction was still present up to 5 months posttransplantation, no actual sutures were present after 3 months. From these observations, Dexon microsuture is acceptable in organ transplantation procedures.


A de novo frameshift FGFR1 mutation extending the protein in an individual with multiple epiphyseal dysplasia and hypogonadotropic hypogonadism without anosmia.
Multiple epiphyseal dysplasia (MED) is a genetically and clinically heterogeneous disease with both dominant and recessive inheritance. Eight different genes are known to cause the disease but in 15% of cases of MED, no mutation is found. Fibroblast growth factor receptor 1 (FGFR1) is a crucial regulator of bone formation and when mutated, can cause diseases with skeletal manifestations; nevertheless, MED has not been described in individuals with FGFR1 mutations. In this report, we describe a proband with MED and congenital normosmic hypogonadotropic hypogonadism (HH). DNA analysis showed a de novo frameshift variant in FGFR1 likely explaining the HH (p.Arg852Thrfs*165). No other mutation was found after a large gene sequencing panel, exome sequencing and an array CGH, except for a variant of unknown significance in FBN1 (rs755375255), but there were no features of a disease associated with FBN1 mutations and this variant is found a few times in population databases. We thus discuss the possibility that MED might be a new skeletal feature associated with FGFR1 mutations.


Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study.
In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is integral to cholesterol metabolism, have also been observed. PCSK9 was also reported to be associated with insulin secretion and diabetes mellitus (DM). Therefore, we aimed to examine the clinical significance of PCSK9 antibodies (PCSK9-Abs) levels. We measured blood PCSK9-Abs and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with DM (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. The primary endpoint of this study was to examine whether PCSK9-Abs can be a prognostic marker for overall mortality among the patients with diabetes. The secondary endpoint was to examine the relationship between PCSK9-Abs and clinical parameters. Although both PCSK9-Abs and PCSK9 protein levels were significantly higher in the DM group than in the HD group (p < 0.008), PCSK9-Abs and PCSK9 protein levels showed no correlation in either group. Mortality was significantly associated with higher PCSK9-Ab levels, but unrelated to PCSK9 protein levels. After investigating for potential confounding factors, higher PCSK9-Ab levels were still associated with increased mortality among the patients with DM. PCSK9-Abs may be a novel prognostic marker for overall mortality in patients with diabetes, and further studies are warranted to verify its usefulness.


Evaluation of acridine orange, LysoTracker Red, and quinacrine as fluorescent probes for long-term tracking of acidic vesicles.
Acidic vesicles can be imaged and tracked in live cells after staining with several low molecular weight fluorescent probes, or with fluorescently labeled proteins. Three fluorescent dyes, acridine orange, LysoTracker Red DND-99, and quinacrine, were evaluated as acidic vesicle tracers for confocal fluorescence imaging and quantitative analysis. The stability of fluorescent signals, achievable image contrast, and phototoxicity were taken into consideration. The three tested tracers exhibit different advantages and pose different problems in imaging experiments. Acridine orange makes it possible to distinguish acidic vesicles with different internal pH but is fairly phototoxic and can cause spectacular bursts of the dye-loaded vesicles. LysoTracker Red is less phototoxic but its rapid photobleaching limits the range of useful applications considerably. We demonstrate that quinacrine is most suitable for long-term imaging when a high number of frames is required. This capacity made it possible to trace acidic vesicles for several hours, during a process of drug-induced apoptosis. An ability to record the behavior of acidic vesicles over such long periods opens a possibility to study processes like autophagy or long-term effects of drugs on endocytosis and exocytosis.


High pressure, temperature and time-dependent effects on enzymatic and microbial properties of fresh sugarcane juice.
Efficacy of variable high pressure, temperature and time on the browning causing enzymes and microbial activities, which are major spoilage factors during preservation of sugarcane juice, was studied. The juice was processed at 200-600 MPa pressure for 2-8 min at 40 and 60 °C and their effect on polyphenol oxidase and peroxidase as well as microbiological quality in terms of total plate count, yeast and molds and total coliforms was studied. Application of high pressures were found to cause significant decrease in enzymatic and microbial activities. The effects were found to be significantly more pronounced at 60 °C as compared to 40 °C. Process time also caused significant (p < 0.05) negative effect on microbial and enzyme activities. The sugarcane juice treated at 600 MPa for 6 min at 60 °C was found sufficient to inactivate the microbial counts completely. Whereas, enzymes were found to be completely inactivated in the samples processed at 600 MPa for 8 min at 60 °C. A pressure of 600 MPa at 60 °C for 8 min could be applied during commercial preservation of sugarcane juice for getting complete inactivation of browning causing enzymes and spoilage causing microorganisms.


On the role of the Agulhas system in ocean circulation and climate.
The Atlantic Ocean receives warm, saline water from the Indo-Pacific Ocean through Agulhas leakage around the southern tip of Africa. Recent findings suggest that Agulhas leakage is a crucial component of the climate system and that ongoing increases in leakage under anthropogenic warming could strengthen the Atlantic overturning circulation at a time when warming and accelerated meltwater input in the North Atlantic is predicted to weaken it. Yet in comparison with processes in the North Atlantic, the overall Agulhas system is largely overlooked as a potential climate trigger or feedback mechanism. Detailed modelling experiments--backed by palaeoceanographic and sustained modern observations--are required to establish firmly the role of the Agulhas system in a warming climate.


Lack of association between dietary alcohol and HDL-cholesterol concentrations in obese women.
The relationships of alcohol intake and corpulence to HDL-cholesterol were studied in 653 women taking medical advice about body weight. The body mass index (BMI) was positively correlated with triglyceride and negatively with HDL-cholesterol. The relation between BMI and HDL-cholesterol was discontinuous. Total cholesterol, triglycerides and diastolic blood pressure were increased for alcohol intakes greater than 10 g/d regardless of body weight. Alcohol intake was associated with higher concentrations of HDL-cholesterol (P = 0.006) in non obese (BMI = 25.2 +/- 1.5 kg/m2) subjects, but not in mildly (27.3 less than or equal to BMI less than 32.3) or massively (BMI greater than or equal to 32.3) obese subjects. The fact that HDL concentrations were not associated with alcohol intake in obese patients suggests that (1) alcohol acts on the HDL pool through one of the pathways which are perturbed in obesity, possibly lipolysis, (2) obesity is one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol, (3) myocardial infarction might not be inversely correlated with alcohol intake in the obese as it is in the non-obese population.


High-dose cisplatin in disseminated melanoma: a comparison of two schedules.
A total of 38 patients with metastatic melanoma received monthly chemotherapy with cisplatin at a dose of 200 mg/m2, per cycle; 14 received 20 mg/m2 cisplatin i.v. on days 1-5 and 24 were given 100 mg/m2 i.v. on days 1 and 8. Objective responses were seen in 2/14 treated on days 1-5 and in 5 of 22 evaluable subjects receiving cisplatin on days 1 and 8, for an overall response rate of 22%. The median survival of all patients was 6 months, with no significant difference observed between the two schedules. Severe neurotoxicity and myelosuppression were more common in patients treated on days 1-5. Two patients treated in this manner were bedridden due to neurotoxicity and four developed grade 4 leukopenia after the first cycle of chemotherapy. Only one patient treated with the divided-dose schedule became leukopenic during the first cycle, and none of the patients were debilitated by neurotoxicity. Thrombocytopenia was statistically more severe. Nausea and vomiting, fatigue, ototoxicity, and paresthesia were seen with equal frequency. Very high doses of cisplatin can be delivered with acceptable toxicity using a divided-dose schedule. As the response rate on this schedule appeared to be comparable with that achieved on the more toxic consecutive 5-day schedule, the former deserves to be tested in diseases known to show a dose response to cisplatin. However, in melanoma, administration of 200 mg/m2 per course did not appear to be associated with a markedly improved response rate, compared with cisplatin alone at "standard" doses.


In vitro evaluation of the effects of different treatment procedures on dentine tubules.
The objective of this preliminary study was to evaluate the occluding effect of topical gaseous ozone application and Er:YAG laser on human dentine tubules by scanning electron microscopic (SEM) analysis. Twenty-four dentine specimens were divided into three groups. Group I, including specimens treated only with citric acid, served as the control. Group II was treated with Er:YAG (30 Hz 60 mJ, 10 sec), and Group III received only topical gaseous ozone application (10 sec at level 2). Diameters and the number of open dentinal tubules per 100 μm(2) were counted from SEM photomigrophraphs at ×2000 magnification. In terms of diameters and numbers of open dentinal tubules per 100 μm(2), both treatment modalities presented significant occlusion. The mean values of the diameters and the number of open dentinal tubules per 100 μm(2) were observed in Group I, Group II, and Group III, in decreasing order. Significant differences were found among the groups in favor of the topical gaseous ozone applied group. The dentine tubules in both treatment groups were occluded, however more marked occlusion were seen in ozone treated group.


SIROF stabilized PEDOT/PSS allows biocompatible and reversible direct current stimulation capable of driving electrotaxis in cells.
Electrotaxis is a naturally occurring phenomenon in which ionic gradients dictate the directed migration of cells involved in different biological processes such as wound healing, embryonic development, or cancer metastasis. To investigate these processes, direct current (DC) has been used to generate electric fields capable of eliciting an electrotactic response in cells. However, the need for metallic electrodes to deliver said currents has hindered electrotaxis research and the application of DC stimulation as medical therapy. This study aimed to investigate the capability of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) on sputtered iridium oxide film (SIROF) electrodes to generate stable direct currents. The electrochemical properties of PEDOT/PSS allow ions to be released and reabsorbed depending on the polarity of the current flow. SIROF stabilized PEDOT/PSS electrodes demonstrated exceptional stability in voltage and current controlled DC stimulation for periods of up to 12 hours. These electrodes were capable of directing cell migration of the rat prostate cancer cell line MAT-LyLu in a microfluidic chamber without the need for chemical buffers. This material combination shows excellent promise for accelerating electrotaxis research and facilitating the translation of DC stimulation to medical applications thanks to its biocompatibility, ionic charge injection mechanisms, and recharging capabilities in a biological environment.


Congenital airway anomalies.
Congenital airway anomalies (CAA) include a variety of conditions that cause respiratory distress in neonates and infants. These malformations occur at various anatomic levels and manifest in a wide spectrum of airway symptoms, with presentation significantly influenced by the level at which obstruction occurs as well as by the severity of obstruction. The prevalence of congenital airway malformations has been estimated to range between 0.2 and 1 in 10,000 live births. The most frequent CAA are laryngomalacia, bilateral vocal cord paralysis, subglottic stenosis, laryngeal webs, subglottic hemangioma, tracheomalacia, congenital tracheal stenosis, laryngotracheal cleft, and tracheal agenesis.


Demographic and prosocial intrapersonal characteristics of biobank participants and refusers: the findings of a survey in the Netherlands.
Research in genetics relies heavily on voluntary contributions of personal data. We aimed to acquire insights into the differences between participants and refusers of participation in a Dutch population-based biobank. Accordingly, we assessed the demographic and prosocial intrapersonal characteristics of respondents who participated (n = 2615) or refused to participate (n = 404) in the Lifelines biobank and databank. Our results indicated that health-related values critically influence participation decisions. The participation threshold for Lifelines was determined by an absence of health-related values and of trust in government. Therefore, considering these factors in communication and recruitment strategies could enhance participation in biomedical research. No indications were found of a stronger general prosociality of participants or their trust in researchers beyond the context of biobanking. This emphasizes the contextual understanding of the decision of participation in biobanking. Our findings may contribute to improving recruitment strategies by incorporating relevant values and/or highlighting prosocial benefits. Moreover, they foreground the need to address trust issues in collaborations between data repositories and commercial companies. Future research should explore how prosocial intrapersonal characteristics drive participation and withdrawal decisions and relate to contextual attributes.


Ileal-ileal intussusception: an unusual complication following enterocystoplasty.
Postoperative ileal-ileal intussusception is an unusual and uncommonly cited complication of bladder augmentation. The preoperative diagnosis is difficult due to the vague clinical findings. We report a case of ileal-ileal intussusception that occurred following gastrocystoplasty in a child. Computed tomography accurately diagnosed the condition preoperatively, and led to early exploratory laparotomy and successful reduction.


Hemicrania Continua Subsequent to Vertebral Artery Dissection: A Case Report.
We herein report the case of a 45-year-old woman who developed a continuous hemicranial headache subsequent to vertebral artery dissection (VAD). After remission of VAD, the patient repeatedly experienced right forehead and temporal region throbbing headache, accompanied by nausea, ocular hyperemia and lacrimation of the right eye, nasal congestion, and rhinorrhea. Magnetic resonance angiography did not reveal the recurrence of dissection. Daily use of indomethacin (190.8 mg/day) showed an excellent effect on the headache, suggesting that the patient had developed hemicrania continua subsequent to VAD.


Steroid exposure, acute coronary syndrome, and inflammatory bowel disease: insights into the inflammatory milieu.
Steroids are anti-inflammatory agents commonly used to treat inflammatory bowel disease. Inflammation plays a critical role in the pathophysiology of both inflammatory bowel disease and acute coronary syndrome. We examined the relationship between steroid use in patients with inflammatory bowel disease and acute coronary syndrome. In 177 patients with inflammatory bowel disease (mean age 67 years, 75% male, 44% Crohn's disease, 56% ulcerative colitis), we performed a 1:2 case-control study matched for age, sex, and inflammatory bowel disease type, and compared 59 patients with inflammatory bowel disease with acute coronary syndrome to 118 patients with inflammatory bowel disease without acute coronary syndrome. Steroid use was defined as current or prior exposure. Acute coronary syndrome was defined as myocardial infarction or unstable angina, confirmed by cardiac biomarkers and coronary angiography. In patients with inflammatory bowel disease, 34% with acute coronary syndrome had exposure to steroids, vs 58% without acute coronary syndrome (P < .01). Steroid exposure reduced the adjusted odds of acute coronary syndrome by 82% (odds ratio [OR] 0.39; 95% confidence interval [CI], 0.20-0.74; adjusted OR 0.18; 95% CI, 0.06-0.51) in patients with inflammatory bowel disease, 77% in Crohn's disease (OR 0.36; 95% CI, 0.14-0.92; adjusted OR 0.23; 95% CI, 0.06-0.98), and 78% in ulcerative colitis (OR 0.41; 95% CI, 0.16-1.04; adjusted OR 0.22; 95% CI, 0.06-0.90). There was no association between other inflammatory bowel disease medications and acute coronary syndrome. In patients with inflammatory bowel disease, steroid use significantly reduces the odds of acute coronary syndrome. These findings provide further mechanistic insight into the inflammatory processes involved in inflammatory bowel disease and acute coronary syndrome.