Evaluation of the Use of Caffeine Citrate Maintenance Doses >5 mg/kg/day in Preterm Neonates for Apnea of Prematurity.
Caffeine citrate doses >5 mg/kg/day are frequently used for apnea of prematurity. The primary objective was identification of patients maintained on 5 mg/kg/day (Group 1). Secondary objectives included identification of patients requiring dose increases: 7.5 mg/kg every 24 hours (Group 2), 10 mg/kg every 24 hours (Group 3), and 5 mg/kg every 12 hours (Group 4); comparison of demographics and clinical characteristics; and identification of patients requiring dose adjustments owing to caffeine-associated tachycardia. Retrospective study of neonates born between 23 to <31 weeks' gestation, receiving caffeine between January 1, 2015, and July 31, 2019. Patients receiving caffeine <1 week, initial maintenance dose >5 mg/kg/day, or with congenital abnormalities were excluded. Descriptive and inferential statistics were performed, with a p < 0.05. Overall, 281 patients were included, with 99 (35.2%) in Group 1; 56 (19.9%) in Group 2; 47 (16.7%) in Group 3; and 79 (28.1%) in Group 4. Significant differences in gestational age were noted, with Group 3 and 4 patients being more premature than Groups 1 and 2 (p < 0.001). Dose increases occurred at a median postnatal age and postmenstrual age of 13.0 days and 31.4 weeks in Group 2; 17.0 days and 30.3 weeks in Group 3; and 16.0 days and 30.1 weeks in Group 4. Significant differences were noted for development of tachycardia requiring dose adjustment, with Groups 3 and 4 having the highest percentage (p < 0.001). Two-thirds received caffeine citrate doses >5 mg/kg/day, with 44% receiving 10 mg/kg/day. Further exploration is necessary to determine the optimal PNA or PMA for dose adjustments.


Danon disease: intrafamilial phenotypic variability related to a novel LAMP-2 mutation.
Danon disease is an X-linked lysosomal disorder, characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation. We report a family with a novel mutation, in which the mother and her three sons were affected with various clinical presentations. A massive hypertrophy of the left ventricle was the predominant feature in the three male patients, with different degrees of severity of cardiac symptoms, from isolated palpitations to cardiac failure and sudden death. Muscle pain and weakness were also variable, but constantly associated with increased plasma CK levels. Finally, the male patients had variable degree of a mental retardation. The mother had an attenuated phenotype, limited to a mild hypertrophic cardiomyopathy with premature ventricular contractions diagnosed during her 40's. Microscopy examination of skeletal muscle biopsy, performed in the youngest patient, demonstrated atrophic myofibers with intracytoplasmic vacuoles suggesting lysosomal glycogen storage disease. Immunohistochemistry analyses in muscle specimen showed no detectable Lysosomal-Associated Membrane Protein-2 (LAMP-2), in keeping with the diagnosis of Danon disease. However, a very low expression of a shortened LAMP-2 protein could be evidenced by Western-blot in the patient's fibroblasts. Molecular investigations identified a novel splicing mutation (IVS6 + 1delG) in the LAMP-2 gene. This case report highlights the intrafamilial variability of Danon disease phenotype. In this case, morphological examination of muscle biopsy, showing lysosomal storage myopathy, and immunohistochemistry analyses can provide key elements for orienting etiologic investigations.


Testicular and epididymal plasmacytoma: a report of 7 cases, including three that were the initial manifestation of plasma cell myeloma.
We report the cases of six men, 40 to 89 years of age, with testicular (6 cases) or epididymal (1 case) plasmacytoma. Patients presented with a mass in five cases. One tumor was found during evaluation of progressive myeloma. In the final case, the testicular lesion was identified when the patient presented with pathologic fractures. Gross inspection revealed discrete or, less often, ill-defined lesions. Microscopic examination disclosed masses of atypical plasma cells, including binucleated and multinucleated cells and, occasionally, anaplastic cells that obliterated the underlying parenchyma or invaded between seminiferous or epididymal tubules. Immunohistochemical stains on paraffin sections in five cases showed tumor cell expression of monotypic cytoplasmic immunoglobulin. The cells were positive for the leukocyte common antigen (CD45) in three of five cases. All four cases tested were negative for B (CD20) and T (CD3) cell specific antigens and for CD30 and placental alkaline phosphatase. Expression of CD43, CD45RO, and epithelial membrane antigen was found in three, two, and one of four cases respectively. All the patients also had plasma cell neoplasia distant from the testis, identified before (3 cases), concurrent with (3 cases) or after (1 case) the testicular or epididymal plasmacytoma. In one patient a plasmacytoma developed in the contralateral testis three years later; he was alive with plasma cell myeloma 51 months after diagnosis. Another had a plasmacytoma in the contralateral epididymis 8 years later; he also had a nasal cavity plasmacytoma and multiple subcutaneous plasmacytomas, and was alive and well after 26 years. One additional patient was alive with myeloma 6 months later, and four final patients died between 2 months and 3 years after orchiectomy. Three of the four consultation cases in this series were submitted with diagnoses of spermatocytic seminoma, anaplastic seminoma and lymphoma. The diagnosis of plasmacytoma should be borne in mind when examining testicular or paratesticular tumors with a diffuse pattern without glandular differentiation, particularly in men 40 years of age or older.


Workplace Aggression and Burnout in Nursing-The Moderating Role of Follow-Up Counseling.
The aim of this study is to obtain a better understanding of the association between the frequency of nurses' exposure to workplace aggression from patients and their levels of burnout. In particular, we seek to shed light on the role of the availability of follow-up counseling in organizations after critical incidents in mitigating the adverse relationships between physical and verbal aggression and nurses' burnout. A total of 582 nurses reported how frequently they had experienced physical and verbal aggression from patients in the last 12 months and whether they had the opportunity to receive follow-up counseling in their organization. In addition, nurses rated the extent to which they experienced each of the three dimensions of burnout (i.e., emotional exhaustion, depersonalization, and personal accomplishment). The results showed that both physical and verbal aggression were substantially related to the burnout dimensions. Furthermore, we found that the availability of follow-up counseling in organizations attenuated the relationships between physical aggression and all three burnout dimensions. While we found that the availability of follow-up counseling moderated the relationship between verbal aggression depersonalization, the moderating effects were not significant for emotional exhaustion and personal accomplishment. The findings indicate that the availability of follow-up counseling might help minimize the adverse impact of exposure to aggression from patients on nurses' mental health.


Antibodies against nuclear poly(A) polymerases in rheumatic autoimmune diseases.
Sera from 53 patients, 26 with systemic lupus erythematosus (SLE), 8 with rheumatoid arthritis (RA), 9 with Sjogren's syndrome (SS), and 10 with scleroderma (Scl), were screened for the presence of antibodies against liver-type poly(A) polymerase and tumor-type poly(A) polymerase. Sixty percent of the patients with the above four autoimmune diseases have antibodies directed against liver poly(A) polymerase, whereas sera from 74% of the patients contained anti-hepatoma poly(A) polymerase antibodies. About 25% of the patients produced antibodies exclusively against the tumor poly(A) polymerase. IgG containing anti-liver or anti-tumor poly(A) polymerase antibodies inhibited the activity of the respective enzyme. IgG containing antibodies against liver and tumor enzymes inhibited the activity of both enzymes, whereas IgG from sera that did not react with poly(A) polymerase had no effect on either enzyme. These data demonstrated the specificity of these autoantibodies and confirmed the results of the radioimmunoassay.


Biomechanical Changes After Thoracic Endovascular Aortic Repair in Type B Dissection: A Systematic Review.
Thoracic endovascular aortic repair (TEVAR) has evolved into an established treatment option for type B aortic dissection (TBAD) since it was first introduced 2 decades ago. Morbidity and mortality have decreased due to the minimally invasive character of TEVAR, with adequate stabilization of the dissection, restoration of true lumen perfusion, and subsequent positive aortic remodeling. However, several studies have reported severe setbacks of this technique. Indeed, little is known about the biomechanical behavior of implanted thoracic stent-grafts and the impact on the vascular system. This study sought to systematically review the performance and behavior of implanted thoracic stent-grafts and related biomechanical aortic changes in TBAD patients in order to update current knowledge and future perspectives.


Rituximab therapy for primary Sjögren's syndrome: an open-label clinical trial and mechanistic analysis.
To study the safety and clinical efficacy of rituximab therapy for primary Sjögren's syndrome, as well as to investigate its mechanisms. Patients with primary Sjögren's syndrome were enrolled in an open-label trial, were given rituximab (1 gm) infusions on days 1 and 15, and were monitored through week 52. The primary end point was safety, with secondary end points evaluating clinical and biologic efficacy. Blood was obtained for enumeration of lymphocyte subsets, measurement of serum autoantibody and BAFF levels, and analysis of gene expression. Twelve female patients with primary Sjögren's syndrome were administered rituximab. They had a median age of 51 years (range 34-69 years) and a median disease duration of 8.0 years (range 2-18 years). We observed no unexpected toxicities from the rituximab therapy. Modest improvements were observed at week 26 in patient-reported symptoms of fatigue and oral dryness, with no significant improvement in the objective measures of lacrimal and salivary gland function. The recovery of blood B cells following the nadir from rituximab therapy was characterized by a predominance of transitional B cells and a lack of memory B cells. While blood B cell depletion was associated with an increase in serum BAFF levels, no significant changes were observed in the levels of serum anti-Ro/SSA, anti-La/SSB, and anti-type 3 muscarinic acetylcholine receptor autoantibodies or in the blood interferon signature. In patients with primary Sjögren's syndrome, a single treatment course of rituximab was not associated with any unexpected toxicities and led to only modest clinical benefits despite effective depletion of blood B cells.


Effect of therapeutic intensification followed by HIV DNA prime and rAd5 boost vaccination on HIV-specific immunity and HIV reservoir (EraMune 02): a multicentre randomised clinical trial.
Achievement of a cure for HIV infection might need reactivation of latent virus and improvement of HIV-specific immunity. As an initial step, in this trial we assessed the effect of antiretroviral therapy intensification and immune modulation with a DNA prime and recombinant adenovirus 5 (rAd5) boost vaccine. In this multicentre, randomised, open-label, non-comparative, phase 2 clinical trial, we enrolled eligible adults 18-70 years of age with chronic HIV-1 infection on suppressive antiretroviral therapy with current CD4 count of at least 350 cells per μL and HIV DNA between 10 and 1000 copies per 10(6) peripheral blood mononuclear cells. After an 8 week lead-in of antiretroviral intensification therapy (standard dose raltegravir and dose-adjusted maraviroc based on baseline antiretroviral therapy), patients were randomly assigned (1:1) to receive antiretroviral therapy intensification alone or intensification plus injections of HIV DNA prime vaccine (4 mg VRC-HIVDNA016-00-VP) at weeks 8, 12, and 16, followed by HIV rAd5 boost vaccine (10(10) particle units of VRC-HIVADV014-00-VP) at week 32. Randomisation was computer generated in permuted blocks of six and was stratified by study site. The primary endpoint was a 0·5 log10 or greater decrease in HIV DNA in peripheral blood mononuclear cells at week 56. This study is registered with ClinicalTrials.gov, number NCT00976404. Between Nov 29, 2010, and Oct 28, 2011, we enrolled 28 eligible patients from three academic HIV clinics in the USA. After the 8 week lead-in of antiretroviral intensification therapy, 14 patients were randomly assigned to continue antiretroviral therapy intensification alone and 14 to intensification plus vaccine. Enrolled participants had median CD4 count of 636 cells per μL, median HIV DNA 170 copies per 10(6) peripheral blood mononuclear cells, and duration of antiretroviral therapy of 13 years. The median amount of HIV DNA did not change significantly between baseline and week 56 in the antiretroviral therapy intensification plus vaccine group. One participant in the antiretroviral therapy intensification alone group reached the primary endpoint, with 0·55 log10 decrease in HIV DNA in peripheral blood mononuclear cells. Both treatments were well tolerated. No severe or systemic reactions to vaccination occurred, and five serious adverse events were recorded during the study, most of which resolved spontaneously or were judged unrelated to study treatments. Antiretroviral therapy intensification followed by DNA prime and rAd5 boost vaccine did not significantly increase HIV expression or reduce the latent HIV reservoir. A multifaceted approach that includes stronger activators of HIV expression and novel immune modulators will probably be needed to reduce the latent HIV reservoir and allow for long-term control in patients off antiretroviral therapy. Objectif Recherche Vaccin SIDA (ORVACS).


[An electroencephalographic study of disorders of amino-acid metabolism during the first days of life (author's transl)].
The authors have attempted a systematic E.E.G. study in 32 neonates suffering from disorders of amino-acid metabolism, during the first days of life. These consisted of cases with ketosis (13 cases of leucinosis, 5 methylmalonic acidaemia, isovaleric acidaemia and 3 with hyperlactacidaemia) and cases without ketosis (6 cases of hyperglycinaemia and 3 with congenital hyperammonaemia). A study of the E.E.G. showed some characteristic features, the most typical of which were: -a periodic tracing with large sharps complexes intermingled with less active periods occurring in every case of hyperglycinaemia without ketosis, in 2 cases of leucinosis and 2 cases of methylmalonic acidaemia. This record indicates a poor prognosis. -a less stereotyped periodic tracing with variable evolution. -distinctive figures characterised by rapid Rolandic rhythms always found in cases of leucinosis compared with sharp spindles (between the 10th and 30th day). It is concluded that the E.E.G. patterns are not in close correlation with the anatomical lesions.


Highly Efficient Near-Infrared Delayed Fluorescence Organic Light Emitting Diodes Using a Phenanthrene-Based Charge-Transfer Compound.
Significant efforts have been made to develop high-efficiency organic light-emitting diodes (OLEDs) employing thermally activated delayed fluorescence (TADF) emitters with blue, green, yellow, and orange-red colors. However, efficient TADF materials with colors ranging from red, to deep-red, to near-infrared (NIR) have been rarely reported owing to the difficulty in molecular design. Herein, we report the first NIR TADF molecule TPA-DCPP (TPA=triphenylamine; DCPP=2,3-dicyanopyrazino phenanthrene) which has a small singlet-triplet splitting (ΔEST ) of 0.13 eV. Its nondoped OLED device exhibits a maximum external quantum efficiency (EQE) of 2.1 % with a Commission International de L'Éclairage (CIE) coordinate of (0.70, 0.29). Moreover, an extremely high EQE of nearly 10 % with an emission band at λ=668 nm has been achieved in the doped device, which is comparable to the most-efficient deep-red/NIR phosphorescent OLEDs with similar electroluminescent spectra.


[Early attachement relationships and epigenetic customization].
Recently, new findings in epigenetic science switched the focus from the observation of physiological intragenomic dynamics to the idea of an environmental co-construction of phenotypic expression. In psichodynamic field, objectual relations and attachement theoreticians emphasized the interpersonal dimension of individual development, focusing the attention on the relational matrix of self organization. The construction of stable affective-behavioral traits throughout different parenting styles has actually found a coincidence in ethological studies, which have explored the epigenetic processes underlying the relationship between caregiving and HPA stress responsiveness. An adequate parenting style seems to support affective regulation throughout psychobiological hidden moderators, which would tend to rebalance the physiological systems homeostasis; an unconfident attachment style would promote, on the other hand, the allostatic load rise. Sites of longlife epigenetic susceptibility have also been identified in humans; although associated with risk of maladaptive developing in adverse environmental conditions, they seem to confer protection under favorable conditions. This persisting possibility of reorganization of stable traits throughout lifetime, which seems to be activated by a relevant environmental input, grant to significant relationships, and to therapeutical one as well, an implicit reconditioning potential which could result into the configuration of new stable affective-behavioral styles.


MicroRNA-504 modulates osteosarcoma cell chemoresistance to cisplatin by targeting p53.
Chemoresistance implicates the therapeutic value of cisplatin and remains a primary obstacle to its clinical use. MicroRNAs (miRs) negatively modulate the expression of their target genes and are associated with the occurrence and progression of various types of tumor. The abnormal expression of miR-504 has been reported in certain types of human tumor and has been associated with tumor prognosis. However, the association between miR-504 and cisplatin in human osteosarcoma remains unclear. The present study therefore aimed to assess the in vitro effects and possible mechanism of miR-504 in cell proliferation, apoptosis and cisplatin resistance in MG63 osteosarcoma cells. The results demonstrated that miR-504 was overexpressed in osteosarcoma tissues and cells. This overexpression also induced cell proliferation, as determined by MTT and EdU staining assays. Furthermore, miR-504 suppressed cisplatin-induced apoptosis, which was demonstrated via MTT, cell morphology analysis and flow cytometry. Cisplatin-induced G1 arrest was also suppressed, which was determined by flow cytometry. The potential target genes of miR-504 were predicted using bioinformatics. p53 was confirmed to be a direct target of miR-504 using a luciferase reporter assay and western blot analysis revealed that miR-504 negatively regulated p53 expression at a molecular level. These results indicate that miR-504 contributes to cisplatin resistance in MG63 osteosarcoma cells by suppressing p53. miR-504 may therefore be a potential biomarker for cisplatin resistance in patients with osteosarcoma.


Protein intake regulates the vasodilatory function of the kidney and NMDA receptor expression.
Glycine infusion in normal rats causes an increase in renal plasma flow and glomerular filtration rate (GFR). Although the renal response to glycine infusion is well characterized, the mechanism initiating this vasodilation is unknown. We recently observed functionally active N-methyl-d-aspartate (NMDA) receptors in the kidney, located primarily in tubular structures. The mechanisms regulating activity of the NMDA receptor within the kidney are also unknown, as is its normal day-to-day functional role. Therefore, we hypothesize that dietary protein may impact the functional response to glycine infusion in both untreated rats and rats pretreated with angiotensin-converting enzyme (ACE) inhibitor and, furthermore, that renal NMDA receptors may be involved in the glycine response. Surprisingly, 2 wk of low-protein diet (8% protein vs. 21% protein in control diet) totally inhibited the glycine-induced vasodilation and GFR response. Associated with the absence of renal vasodilation, a significant reduction in proximal tubular reabsorption was observed during glycine infusion in low-protein-diet rats. In contrast to the disease models previously studied in our laboratory, administration of ACE inhibitors did not restore the glycine response in rats treated with low-protein diet. Western blots of normal- and low-protein-diet kidneys demonstrate that the newly described renal NMDA receptor is downregulated in rats fed a low-protein diet. Low-protein feeding results in loss of glycine-induced vasodilation and GFR responses associated with decreased renal NMDA receptor expression. Kidney NMDA receptor expression is conditioned by protein intake, and this receptor may play an important role in the kidney vasodilatory response to glycine infusion and protein feeding in rats.


Risk Factors for Alzheimer's Disease: An Epidemiological Study.
Dementia becomes a major public health challenge in both the Czech Republic and worldwide. The most common form of dementia is Alzheimer's disease (AD). We conducted two successive epidemiological projects in 2012-2015 and 2016-2019. Their aim was to study the effect of selected potential genetic, vascular and psychosocial risk factors on the development of AD by comparing their frequencies in AD patients and controls. Epidemiological case-control studies were conducted. In total, data from 2106 participants (1096 cases, 1010 controls) were analyzed. Three times more females than males suffered from AD. The highest proportion of cases were those with primary education, unlike controls. There were statistically significantly more manual workers among cases than among controls. Of selected vascular risk factors, coronary heart disease was found to be statistically significantly more frequent in cases than in controls. The onset of hypertension and diabetes mellitus was earlier in controls than in cases. As for hobbies and interests, there were statistically significant differences in physical activity, reading and solving crosswords between the groups, with these activities being more common in controls. The prevalence of chronic neurodegenerative diseases, in particular AD, is currently increasing. Given the aging of the population, these conditions may be expected to rise in prevalence. Potential risk of AD needs to be studied, analyzed and confirmed; a detailed knowledge of the risks of AD and early detection of the pathology may therefore be very beneficial for prevention and early treatment of this condition.


Three-Dimensional Printed Fish Graders: A Tool to Rapidly and Reliably Size Select Zebrafish.
Research into adult zebrafish often requires fish to be of a specific size. Currently, fish must be individually measured to achieve this goal. Here, we design and utilize fish graders to quickly sort fish by width. We characterize graders individually for the length of fish they discriminate between and we also analyze graders in pairs to define the range of lengths for a retained population of fish. We note that a 1 mm increase of fish width increases fish length by 6.2-7.2 mm. We provide the schematics to print a series of eight retention widths, and note that graders of any desired retention width can easily be printed by slightly modifying our design files.


Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations.
The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background. A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients. Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively. This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis.


Curved adjustable fiberoptic laser for endoscopic cholesteatoma surgery.
To determine whether endoscopic cholesteatoma removal can be performed efficiently and safely using a curved fiberoptic-based laser. Angled instruments are required in endoscopic ear surgery to access recesses of the middle ear without extra drilling. Lasers are effective at ablating visible and microscopic cholesteatoma matrix and removing granulation tissue. Retrospective case review from 2006 to 2013. Single tertiary care center. Patients who underwent cholesteatoma surgery with otoendoscopy. Residual cholesteatoma that could not be reached by conventional microinstruments was identified using an endoscope. This residual cholesteatoma was ablated in a contactless manner using a fiberoptic-based curved laser carrier with an argon laser. The laser tip through the carrier probe has a 45-degree curve, and the length of the tip is adjustable, allowing it to be used in recesses or around corners, such as in the sinus tympani, around the stapes suprastructure, in the oval window, or in the Eustachian tube orifice. Presence or absence of residual cholesteatoma after laser ablation and complications. In 7 cases, the fiberoptic curved laser was used to ablate cholesteatoma completely with no injury to surrounding structures and with no evidence of recidivism with a mean follow-up period of 19 months. There were no cases of sensorineural hearing loss or perilymphatic fistula. The curved laser probe allows for precise removal of cholesteatoma endoscopically.


Trade-offs between immune investment and sexual signaling in male mallards.
Allocation trade-offs between the immune system and sexual traits are central to current sexual selection hypotheses but remain contentious. Such trade-offs could be brought about by the dual action of testosterone that stimulates sexual signals but also suppresses immune functions and/or by competition for carotenoids that can be deposited in ornaments or used as antioxidants in support of immune functions. We investigated the trade-off between investment in immunity and maintenance of testosterone, carotenoids, and sexually selected, carotenoid-based bill color in male mallards. Following a nonpathogenic immune challenge, facultative immune investment resulted in a syndrome of changes in allocation. Plasma carotenoids disappeared from circulation proportional to antibody production. In addition, the reflectance spectrum of the bill was affected; greater antibody production was associated with an increase in relative UV reflectance. Although changes in bill reflectance and plasma carotenoids were related, the relationship appeared more complex than direct competition with immunity. Finally, maintenance of testosterone was affected by immune investment: testosterone levels declined substantially when males produced more antibodies. Because males with high testosterone are preferred by females, the decline in testosterone, in addition to carotenoid depletion and effects on bill reflectance, could constitute a significant cost of immune investment.


Global caries experience in children and its relationship with government expenditures on education and health, sugar consumption, and years of schooling: An ecological study.
To evaluate the influence of gross domestic product (GDP), government expenditures on education and health (% of GDP), per capita sugar consumption, and years of schooling on caries experience (DMFT) in 12-year-old children globally. The study analyzed global data of GDP, sugar consumption, years of schooling, expenditure on education and health, and DMFT from 69 countries. Information about DMFT and sugar consumption was retrieved from the World Health Organization while data of other study variables were available from the United Nations Development Program. Data were compared among low, middle, and high-income countries. Sugar consumption (p = 0.005) and years of schooling increased progressively from low-income to high-income countries (p < 0.001). The greater percentage of GDP was spent on health (6.55 ± 2.94) than on education (3.48 ± 2.60). Upper-middle-income countries had the highest mean DMFT score (2.23 ± 1.23) and per capita sugar consumption (33.28 ± 14.06). High-income countries spent 4.33% of their GDP on education followed by low-income countries (3.92%) (p = 0.037). Similar trends were observed with regards to the percentage of GDP spent on health (p = 0.003). Univariate analysis showed a significant negative correlation between the percentage of GDP spent on education (r = -0.252, p = 0.037) and DMFT. Significant correlation remained in multivariate analysis; the percentage of GDP spent on education and DMFT in children (B = -0.128, p = 0.028). Low, middle, and high-income countries demonstrated significant inequalities regarding caries experience, sugar consumption, and share of GDP spent on health and education. Increasing the share of GDP on education may reduce caries burden in children globally.


Expression of distinct splice variants of the stem cell marker prominin-1 (CD133) in glial cells.
Prominin-1 (CD133) is a cholesterol-interacting pentaspan membrane glycoprotein specifically associated with plasma membrane protrusions. Prominin-1 is expressed by various stem and progenitor cells, notably neuroepithelial progenitors found in the developing embryonic brain. Here, we further investigated its expression in the murine brain. Biochemical analyses of brain membranes at early stages of development revealed the expression of two distinct splice variants of prominin-1, s1 and s3, which have different cytoplasmic C-terminal domains. The relative abundance of the s3 variant increased toward adulthood, whereas the opposite was observed for the s1 variant. Our combined in situ hybridization and immunohistochemistry revealed the expression of prominin-1 in a subpopulation of Olig-2-positive oligodendroglial cells present within white matter tracts of postnatal and adult brain. Furthermore, immunohistological and biochemical characterization suggested strongly that the s3 variant is a novel component of myelin. Consistent with this, the expression of prominin-1.s3 was significantly reduced in the brain of myelin-deficient mice. Finally, oligodendrocytes expressed selectively the s3 variant whereas GFAP-positive astrocytes expressed the s1 variant in primary glial cell cultures derived from embryonic brains. Collectively, our data demonstrate a complex expression pattern of prominin-1 molecules in developing adult brain. Given that prominin-1 is thought to act as an organizer of plasma membrane protrusions, they further suggest that a specific prominin-1 splice variant might play a role in morphogenesis and/or maintenance of the myelin sheath.


[Clinical case of dirofiariosis in the practice of otorhinolaryngologist].
The article presents the clinical case of a young woman with the dirofilariosis of the nose slope on the right side. This disease is quite rare, and therefore there is a difficulty in setting the correct one. This case is a professional interest both for young doctors and for experienced specialists. Specialists,will be able, if necessary, to correctly diagnose and effectively treat this disease analyzing the given clinical example.


[Survey of possible aerosol transmission of a COVID-19 epidemic caused by 2019-nCoV Delta variant].
Objective: To investigate the epidemiological characteristics and the transmission chain of a family clustering of COVID-19 cases caused by severe acute respiratory 2019-nCoV Delta variant in Changping district of Beijing. Methods: Epidemiological investigation was conducted and big data were used to reveal the exposure history of the cases. Close contacts were screened according to the investigation results, and human and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: On November 1, 2021, a total of 5 COVID-19 cases caused by 2019-nCoV Delta variant were reported in a family detected through active screening. The infection source was a person in the same designated isolation hotel where the first case of the family cluster was isolated from 22 to 27, October. The first case was possibly infected through aerosol particles in the ventilation duct system of the isolation hotel. After the isolation discharge on October 27, and the first case caused secondary infections of four family members while living together from October 27 to November 1, 2021. Conclusion: 2019-nCoV Delta variant is prone to cause family cluster, and close attention needs to be paid to virus transmission through ventilation duct system in isolation hotels.


Effects of protein intake on rate of growth, protein deposition, and carcass traits of heavy Iberian pigs.
A feeding, digestibility, and balance trial was performed to determine the effect of the incorporation of increasing amounts of soybean protein concentrate (SPC) to a basal acorn diet at a fixed energy intake on the rate of growth, protein deposition (PD), and carcass traits of heavy Iberian (IB) pigs. Sixteen purebred IB barrows (103.9 ± 0.9 kg initial BW) were used. The pigs were individually confined and allocated to 4 groups of 4 pigs each. Whole acorns were provided with slight restriction to minimize acorn kernel (AK) remains. Water was freely available. The incorporation of SPC raised the available CP from 49.1 g/kg DM (1.91 g total Lys/kg DM) in AK up to 135 g/kg DM (7.24 g total Lys/kg DM). After 72 d of trial, the pigs achieved 134.4 ± 1.3 kg BW and were then slaughtered. Average daily BW gain increased with increasing dietary CP (linear, P < 0.001; quadratic, P < 0.01), with a plateau at dietary CP concentrations (provided by AK and SPC) beyond 72.2 and 100 g/kg DM, respectively, for which an ADG of 449 g was achieved. There was a linear and quadratic effect of dietary CP and Lys level on the apparent digestibility of CP (linear, P < 0.001; quadratic, P < 0.05) and on the efficiencies of utilization of total N (retained N/N intake; linear, P < 0.001; quadratic, P < 0.001) and N apparently absorbed (retained N/apparent digestible N; linear, P < 0.05; quadratic, P = 0.067). Protein deposition ranged between −4.59 g/d in pigs not provided with SPC to 61.4 g/d in pigs fed the greatest level of SPC inclusion. The lowest daily intake of total Lys resulting in maximum PD (69.5 g/d) at the fixed level of energy intake observed (2.36 × ME maintenance requirements) was 21.0 g. Hot carcass and cold carcass weights, but not carcass yield, increased when feeding the daily ration containing 100 g SPC and leveled off thereafter (linear, P < 0.01; quadratic, P < 0.01). An average increase of 8.3% and 8.7% was obtained, respectively. The provision of SPC had no effect on back fat thickness. Primal cuts, but not yield (except for loin), increased (sirloin: linear, P < 0.05; loin: linear, P < 0.001; quadratic, P < 0.05; ham: linear, P < 0.05) or showed a tendency to increase (butt lean: linear, P = 0.068; quadratic, P = 0.077; ribs: quadratic, P = 0.067; shoulder: quadratic, P = 0.064) with the provision of dietary protein. No effect of the level of incorporation of SPC to the diet was observed on CP, total fat, total ash, and energy contents or on relative fatty acid profile of loin and sirloin.


Sarcoidosis as the initial manifestation of Takayasu's arteritis.
Takayasu's arteritis is a chronic inflammatory arteriopathy of unknown cause. The pulseless phase of Takayasu's arteritis is preceded by a period of "prepulseless disease" when the patients suffer from systematic symptoms without obvious evidence of obstruction of larger arteries. Herein we report a unique case of Takayasu's arteritis presenting as sarcoidosis manifested by restrictive lung disease, hilar adenopathy and non-caseating granulomas of the skin. We are aware of only one report in which non-caseating skin granulomas were evident at the prepulseless phase of Takayasu's arteritis. However, in our patient the clinical picture was typical of sarcoidosis. Increased awareness of this possibility will lead to more frequent skin biopsies in patients with Takayasu's arteritis and nodular skin lesions, which may increase the number of reported cases with this combination.


[The effect of borneol on level of HA and 5-HT in rat's hypothalamus].
To observe the effect of borneol on level of HA and 5-HT in rat's hypothalamus. The levels of HA and 5-HT in rat's hypothalamus were determined before and after p.o. with different amount of borneol by high performance liquid chromatography with electrochemical detection (HPLC-ECD), and the borneol's effect on the levels of HA and 5-HT was also studied. The level of HA in rat's hypothalamus after different dose of borneol were higher than before administration. The level of HA in 20 min group after middle dose increased significantly comparing with before administration (P < 0.01), the others of group after middle dose, the 45 min group after high dose, the 20 and 45 min after low dose were also increased significantly than before administration (P < 0.05). After different dose of borneol, the level of 5-HT in rat's hypothalamus changed as follows: the level of 5-HT after high dose were higher than before administraton (P <0.05 or P < 0.01 ); the level of 5-HT after 5, 20 and 45 min of middle and low dose incrased significantly (P <0.05 or P < 0.01). Borneol could increase the levels of HA and 5-HT in rat's hypothalamus.


RNA-binding protein Hfq downregulates locus of enterocyte effacement-encoded regulators independent of small regulatory RNA in enterohemorrhagic Escherichia coli.
Enterohemorrhagic Escherichia coli (EHEC) causes severe human diseases worldwide. The type 3 secretion system and effector proteins are essential for EHEC infection, and are encoded by the locus of enterocyte effacement (LEE). RNA-binding protein Hfq is essential for small regulatory RNA (sRNA)-mediated regulation at a posttranscriptional level and full virulence of many pathogenic bacteria. Although two early studies indicated that Hfq represses LEE expression by posttranscriptionally controlling the expression of genes grlRA and/or ler, both of which encode LEE regulators mediating a positive regulatory loop, the detailed molecular mechanism and biological significance remain unclear. Herein, we show that LEE overexpression was caused by defective RNA-binding activity of the Hfq distal face, which posttranscriptionally represses grlA and ler expression. In vitro analyses revealed that the Hfq distal face directly binds near the translational initiation site of grlA and ler mRNAs, and inhibits their translation. Taken together, we conclude that Hfq inhibits grlA and ler translation by binding their mRNAs through the distal face in an sRNA-independent manner. Additionally, we show that Hfq-mediated repression of LEE is critical for normal EHEC growth because all suppressor mutations that restored the growth defect in the hfq mutant abolished hfq deletion-induced overexpression of LEE.


MCM3: A Novel Proliferation Marker in Oral Squamous Cell Carcinoma.
The present study sought to evaluate and compare the immunoexpression of proteins minichromosome maintenance (MCM) 3 and Ki-67 in oral squamous cell carcinoma (OSCC) to assess the potential of these proteins as markers of cellular proliferation. Twenty-eight cases of OSCC, 9 of tumor-free resection margins (TM), and 4 of non-neoplastic oral mucosa (NNM) were subjected to immunohistochemistry to detect the expression of proteins MCM3 and Ki-67. All OSCCs demonstrated positivity for both proteins. In these tumors, greater MCM3 immunoreactivity was observed in comparison with Ki-67, whereas TMs and NNMs exhibited greater Ki-67 expression compared with MCM3. The immunoexpression of Ki-67 seemed to be influenced by the inflammatory process, particularly in TM and NNM. Our findings indicate that although both MCM3 and Ki-67 represent reliable markers of cellular proliferation in OSCC, as MCM3 expression does not appear to be influenced by external factors, this protein may emerge as a novel marker of cellular proliferation in these types of tumors.


Experience with vocal cord injection.
For 14 years investigators accredited by the FDA have been injecting a Teflon - glycerin mixture into lateral-lying, paralyzed vocal cords. This paper represents a summary of the work of this author, including successes, failures, and complications; it is the largest reported series, plus that of accredited investigators. The method described is exceptionally useful; it has restored voices, laughter, the ability to strain, and has prevented aspiration. A new surgical technique involving the injection of sterile glycerin into comparable vocal cords in acute new situation is also described. This is done by direct or indirect laryngoscopy, and has been used to eliminate some tracheotomy surgery by virtue of the immediately improved cough effectiveness.


The role of intergenerational discrepancy of cultural orientation in drug use among Latina adolescents.
The role of intergenerational discrepancy for cultural orientation was examined in the etiology of drug use among Latina adolescents and in the context of family support. Intergenerational discrepancy occurs when a family member of one generation differs from a family member of another generation in cultural identity factors; this is usually manifested in conflict between a first generation child and the immigrant generation parent. It was hypothesized that the Latina adolescents experiencing intergenerational discrepancy might use drugs more frequently than Latina adolescents who were not; and that family support would be an important moderator of the relationship. A sample of 295 ninth and tenth grade Latina students (approximately 80% Mexican-American) from four Los Angeles area schools were surveyed as part of a larger study. In this secondary analysis, a 2 (family support ) x 2 (discrepancy) ANOVA revealed that intergenerational discrepancy was associated with more drug use in certain cases, and that family support did not moderate this relationship. Results partially validate and extend a theoretical model presented by Szapocznik and Kurtines (1980), and indicate a need to focus on cultural variables when intervening in drug use/misuse among Latina adolescents.


Vitamin K Status in Women of Childbearing Years Before or After Bariatric Surgery.
Vitamin K adequacy has not been widely studied before or after bariatric surgery. Reports of babies born with intracranial bleeds to women after bariatric surgery make this an important vitamin to study in women of childbearing years. The aim of this study was to assess the functional vitamin K status in 2 groups of women of childbearing age, 1 group seeking bariatric surgery and 1 group post Roux-en-Y gastric bypass (RYGB). In a cross-sectional design, 40 women [19 presurgical and 21 post-RYGB (6-18 mo following surgery)], aged 18-40 y, completed the study. Participants provided a 3-d food intake record and a list of dietary supplements routinely taken. Participants then underwent a commercially available test to measure des-γ-carboxyprothrombin (DCP) concentration as a measure of functional vitamin K status. Independent-samples t tests (P < 0.05) indicated that there was no significant difference [Sig (2-tailed) 0.821] between the DCP concentrations of the presurgical group and those of the post-RYGB group (mean ± SD DCP: 0.3 ± 0.1 and 0.4 ± 0.2 ng/mL, respectively). Vitamin K intake from food (248 ± 227 and 210 ± 239 μg) and supplements (13 ± 31 and 750 ± 271 μg) showed no linear correlation to DCP (presurgical group: 0.25 and -0.15, respectively; post-RYGB group: 0.13 and 0.05, respectively). Vitamin K intakes for both groups were above the current Institute of Medicine's recommended 90 μg/d for women. Bivariate correlation was conducted on other independent variables with only current BMI for the post-RYGB group having a moderate negative correlation to DCP (-0.54, P < 0.05). No correlation with statistical significance was found between other variables and DCP. Although the American Society for Metabolic and Bariatric Surgery recommends DCP as a test to determine vitamin K adequacy, no published studies in pre- or post-RYGB patients have been performed with the current commercially available test, which is not FDA approved as a vitamin K biomarker. Previous studies reporting vitamin K inadequacies based on DCP utilized a different assay than the one currently available. Due to the importance of ensuring adequate maternal concentrations of vitamin K after bariatric surgery in order to prevent intracranial bleeding in babies, more research is needed to determine suitable vitamin K measures.


A fadD mutant of Sinorhizobium meliloti shows multicellular swarming migration and is impaired in nodulation efficiency on alfalfa roots.
Swarming is a form of bacterial translocation that involves cell differentiation and is characterized by a rapid and co-ordinated population migration across solid surfaces. We have isolated a Tn5 mutant of Sinorhizobium meliloti GR4 showing conditional swarming. Swarm cells from the mutant strain QS77 induced on semi-solid minimal medium in response to different signals are hyperflagellated and about twice as long as wild-type cells. Genetic and physiological characterization of the mutant strain indicates that QS77 is altered in a gene encoding a homologue of the FadD protein (long-chain fatty acyl-CoA ligase) of several microorganisms. Interestingly and similar to a less virulent Xanthomonas campestris fadD(rpfB) mutant, QS77 is impaired in establishing an association with its host plant. In trans expression of multicopy fadD restored growth on oleate, control of motility and the symbiotic phenotype of QS77, as well as acyl-CoA synthetase activity of an Escherichia coli fadD mutant. The S. meliloti QS77 strain shows a reduction in nod gene expression as well as a differential regulation of motility genes in response to environmental conditions. These data suggest that, in S. meliloti, fatty acid derivatives may act as intracellular signals controlling motility and symbiotic performance through gene expression.


Aeromonas hydrophila-induced alterations in cytosolic calcium activate pro-apoptotic cPKC-MEK1/2-TNFα axis in infected headkidney macrophages of Clarias gariepinus.
Alterations in intracellular-calcium (Ca2+)i homeostasis is critical to Aeromonas hydrophila-induced headkidney macrophages (HKM) apoptosis of Clarias gariepinus, though the implications are poorly understood. Here, we describe the role of intermediate molecules of Ca2+-signaling pathway that are involved in HKM apoptosis. We observed phosphoinositide-3-kinase/phospholipase C is critical for (Ca2+)i release in infected HKM. Heightened protein kinase-C (PKC) activity and phosphorylation of MEK1/2-ERK1/2 was noted which declined in presence of 2-APB, Go6976 and PD98059, inhibitors to IP3-receptor, conventional PKC isoforms (cPKC) and MEK1/2 respectively implicating Ca2+/cPKC/MEK-ERK1/2 axis imperative in A. hydrophila-induced HKM apoptosis. Significant tumor necrosis factor-α (TNFα) production and its subsequent reduction in presence of MEK-ERK1/2 inhibitor U0126 suggested TNFα production downstream to cPKC-mediated signaling via MEK1/2-ERK1/2 pathway. RNAi and inhibitor studies established the role of TNFα in inducing caspase-8-mediated apoptosis of infected HKM. We conclude, alterations in A. hydrophila-induced (Ca2+)i alterations activate cPKC-MEK1/2-ERK1/2-TNFα signaling cascade triggering HKM apoptosis.


The density distributions of the counterions and the coions confined in two similarly charged plates.
By using the field-theoretic method, we established a unified systematic formulation of a model of counterions and coions confined in two similarly charged plates, and calculated the density distributions of counterions and coions with various coupling parameters by the two methods: Poisson-Boltzmann (PB) approach and the strong coupling (SC) theory, respectively. We also performed Monte Carlo simulations, and obtained the density distributions of counterions and coions with several different coupling parameters. Comparing our theoretical results with those from Monte Carlo simulation, we find that the PB approach is valid when the coupling parameter Xi is smaller than 1, but, as Xi > or = 1, the results by the PB approach deviate from the corresponding Monte Carlo simulation data, and the deviation gets larger with the coupling parameter increasing. This shows that the PB approach is completely invalid when the coupling parameter is equal to 1 or larger than 1. For the latter case, the development trend of the distribution curve calculated by SC theory agrees with that from Monte Carlo simulation as the coupling parameter increases. This demonstrates that the SC theory can give a qualitative available explanation on the density distribution of the counterions in the system in which the coupling parameters are strictly confined.


In-fiber temperature sensor based on green up-conversion luminescence in an Er3+-Yb3+co-doped tellurite glass microsphere.
A novel, to the best of our knowledge, in-fiber temperature sensor based on green up-conversion (UC) luminescence in an Er3+-Yb3+ co-doped tellurite glass microsphere is described. The tellurite glass microsphere is located firmly inside a suspended tri-core hollow-fiber (STCHF) structure. The pump light launched via a single-mode fiber (SMF) is passed through a section of multimode fiber, which is fusion spliced between the SMF and the STCHF into the cores suspended inside the hollow fiber and coupled into the microsphere. Green and red UC emissions of the Er3+ ions are observed using 980 nm pump excitation. The temperature-sensing capability of the tellurite glass microsphere is based on the thermally coupled effect between the upper energy levels responsible for green emissions at 528 nm and 549 nm. The resulting fluorescence intensity ratio, depending on the surrounding temperature range from 303 K to 383 K, is experimentally determined, and a maximum sensitivity of 5.47×10-3 K-1 is demonstrated. This novel in-fiber microsphere-resonator-based device is highly integrated and has the additional advantages of ease of fabrication, compact structure, and low fabrication cost and therefore has great application potential in integrated optical sources including lasers.


Elevated brain 5-hydroxytryptophol levels in experimental portal-systemic encephalopathy.
Brain tissue levels of the two serotonin metabolites 5-hydroxytryptophol and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured in porta-caval shunted rats, an in vivo model of portal-systemic encephalopathy. An intraperitoneal challenge of L-tryptophan (280 mg/kg body weight) to sham-operated rats was also instituted to increase the brain serotonin metabolism in these rats. The results revealed significant increases in 5-hydroxytryptophol (by 31% and 5-HIAA (by 87%) brain levels in porta-caval shunted rats as compared to sham-operated controls. The brain 5-hydroxytryptophol-to-5-HIAA ratio was lower in the porta-caval shunted rats. The 5-hydroxytryptophol levels in sham rats after the L-tryptophan challenge were intermediate between the porta-caval shunted and sham rats but not statistically significant for either group. These results suggest that increased brain 5-hydroxytryptophol levels might be associated with the pathogenesis of portal-systemic encephalopathy. Further, the elevated brain 5-hydroxytryptophol levels in experimental portal-systemic encephalopathy are probably a result of the increased brain serotonin metabolism prevailing in this condition rather than changes in the brain redox potential.


[Steroid and non-steroidal anti-inflammatory drug therapy of vasculitis].
Before corticosteroids were used in the treatment of the systemic necrotizing vasculitides of the polyarteritis nodosa, the disease almost always progressed with variable degree of fulminance leading to death. The use of corticosteroids improves the 5-year survival. The most dramatic break-through in the therapeutic approach to the vasculitides has been clinical experience with cyclophosphamides in treating Wegener's granulomatosis. With this therapeutic regimen, Wegener's granulomatosis can now be considered a curable disease, if treated early and appropriately with therapeutic regimen. These therapeutic strategy can be extended to that of polyarteritis nodosa group of vasculitides. Now, it is clear that cyclophosphamide, either alone or in combination with pre-existing corticosteroid therapy, can effect a dramatic response if instituted early in the course of the disease process. With the advent of deeper insight as to immuno-pathogenesis and pathophysiologic mechanism, the striking therapeutic success can be expected in near future.


A glibenclamide sensitive potassium conductance in terminal arterioles isolated from guinea pig heart.
The aim was to isolate terminal arterioles from guinea pig heart, to describe their basic electrical properties, and to obtain evidence for the presence of KATP channels in microvascular coronary smooth muscle cells. Terminal arterioles of 20-50 microns diameter were obtained by enzymatic digestion of isolated perfused hearts. The isolated arterioles were viable for up to 8 h and constricted upon application of high potassium solution. Whole cell clamp experiments on smooth muscle cells of these arterioles were performed at room temperature. The resting potential of coronary smooth muscle cells in terminal arterioles showed a bimodal distribution with one peak at -23(SD 8) mV and the other peak at -61(4) mV. Application of glibenclamide (50 microM) to the latter group of arterioles produced a depolarisation to -37(8) mV; application of cromakalim (1 microM) produced a hyperpolarisation to -71(1) mV. The current changes associated with voltage steps and slow voltage ramps in the range -120 to +40 mV indicated that the smooth muscle cells in the arterioles were coupled electrically. The steady state current-voltage relation was sigmoid with a flat region in the range -50 to -30 mV. In the presence of 2-50 microM glibenclamide the slope resistance at potentials negative to -50 mV and positive to -30 mV was markedly increased. In the presence of 1 microM cromakalim the slope resistance was decreased and the current-voltage relation at negative potentials became nearly linear. The crossover point of the current-voltage relations measured under control conditions and in the presence of glibenclamide was near the calculated potassium equilibrium potential. Glibenclamide closes and cromakalim opens potassium channels in smooth muscle cells of coronary arterioles. The voltage dependence of the steady state current changes suggests that the current activated by cromakalim is not carried by the same channels as the current inhibited by glibenclamide. The glibenclamide sensitive channels make a significant contribution to the membrane potential of isolated arterioles.


Antitumour activity and plasma kinetics of bleomycin by continuous and intermittent administration.
We have studied the cytotoxicity of bleomycin (4--10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units(LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62 +/- 0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u.kg/day had a terminal-phase plasma t1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.


Room-Temperature Dynamics of Vanishing Copper Nanoparticles Supported on Silica.
In heterogeneous catalysis, a nanoparticle (NP) system has immediate chemical surroundings with which its interaction needs to be considered, as nanoparticles are typically loaded onto certain supports. Beyond what is known about these interactions, dynamic atomic interactions between the nanoparticle and support could result from the increased energetics at the nanoscale. Here, we show that the dynamic response of atoms in copper nanoparticles to the underlying silica support at room temperature and ambient atmosphere results in the complete disappearance of supported nanoparticles over the course of only a few weeks. A quantitative study of copper nanoparticles at various size regimes (6-17 nm) revealed the significance of size-dependent nanoparticle energetics to the interaction with the support. Extended X-ray absorption fine structure is used to show that copper atoms could readily diffuse into the support to be locally surrounded by oxygen and silicon with structurally disordered outer coordination shells. Increased energetic states at the nanoscale and the energetically favorable configuration of individual copper atoms within silica, identified through EXAFS, are suggested as the cause of nanoparticle disappearance. This unexpected observation opens up new questions as to how nanoparticles interact with surrounding environments that could fundamentally change our conventional view of supported nanoparticle systems.


Clip reconstruction and sling wrapping of a fusiform aneurysm: technical note.
To describe an alternative method of clip reconstruction and wrapping of fusiform aneurysms that provides structural support for the reconstructed parent artery or residual aneurysm. A 57-year-old woman with an unruptured distal middle cerebral artery fusiform aneurysm underwent surgical treatment via a pterional craniotomy. A right-angled titanium clip was used to obliterate the aneurysm and to clip reconstruct the parent vessel, which was composed of a single inflow and outflow vessel. After the aneurysm was decompressed with a fine-gauge needle, the remnant/parent artery was wrapped with a thin layer of muslin gauze followed by circumferential application of the Gore-tex (W.L. Gore and Associates, Inc., Flagstaff, AZ) sling. Finally, a second right-angled aneurysm clip was applied to the free ends of the sling immediately adjacent to the parent vessel while the sling was cinched against the parent vessel. This maneuver allowed the Gore-tex material to buttress the reconstructed vessel circumferentially. Clip reconstruction with a Gore-tex sling preserves the parent vessel and simultaneously buttresses the reconstructed vessel wall with radial forces provided by the Gore-tex material. This method is a novel alternative to conventional methods for the treatment of fusiform aneurysms.


Liposome encapsulation and EDTA formulation of dsRNA targeting essential genes increase oral RNAi-caused mortality in the Neotropical stink bug Euschistus heros.
The Neotropical stink bug Euschistus heros is a major pest in soybean fields. Development of highly species-specific pesticides based on RNA interference (RNAi) could provide a new sustainable and environmentally friendly control strategy. Here, the potential of RNAi as a pest control tool against E. heros was assessed. First, target gene selection using a microinjection approach was performed. Seven of the 15 candidate genes tested exhibited > 95% mortality after hemolymph injection of 27.5 ng dsRNA. Subsequently, dsRNA was administered orally using different formulations: naked dsRNA, liposome-encapsulated-dsRNA and dsRNA formulated with EDTA. Liposome-encapsulated dsRNA targeting vATPase A and muscle actin led to significant mortality after 14 days (45% and 42%, respectively), whereas EDTA-formulated dsRNA did so for only one of the target genes. Ex vivo analysis of the dsRNA stability in collected saliva indicated a strong dsRNA-degrading capacity by E. heros saliva, which could explain the need for dsRNA formulations. The results demonstrate that continuous ingestion of dsRNA with EDTA or liposome-encapsulated dsRNA can prevent dsRNA from being degraded enzymatically and suggest great potential for using these formulations in dsRNA delivery to use RNAi as a functional genomics tool or for pest management of stink bugs. © 2018 Society of Chemical Industry.


Serratia marcescens bacteremia at a medical center in southern Taiwan: high prevalence of cefotaxime resistance.
Antimicrobial resistance of isolates and risk factors for mortality were retrospectively investigated in 71 adult patients with Serratia marcescens bacteremia. During the 4-year study period, 78 clinically significant episodes of S. marcescens bacteremia occurred in 71 patients. The mean age of the patients was 65 years (range, 25-86 years) with a male predominance (45 patients, 63%). Most of the bacteremic episodes were nosocomial (78%), and 34% were polymicrobial. The overall mortality rate within 2 weeks after the onset of bacteremia was 41%. The presence of malignancy and critical illness at initial presentation were independent risk factors for mortality. By disk susceptibility test, 72 isolates were resistant to cefotaxime (92%) but susceptible to ceftazidime (99%). All isolates were susceptible to meropenem. Among the 47 patients with monomicrobial S. marcescens bacteremia, the mortality rate within 5 days of onset in patients receiving appropriate empirical antimicrobial therapy was lower than that in patients receiving inappropriate therapy although this difference was not significant (14% vs 28%, p = 0.27). Among the patients with cefotaxime-resistant but ceftazidime-susceptible S. marcescens bacteremia treated with ceftazidime, 6 of 7 patients (86%) survived for more than 2 weeks, suggesting the potential effectiveness of ceftazidime in the treatment of cefotaxime-resistant Serratia infections. Further clinical studies are required to delineate the clinical role of ceftazidime therapy for infections caused by S. marcescens with this resistant phenotype.


Crosstalk in transition: the translocation of Akt.
Akt/PKB is an important crosstalk node at the junction between a number of major signalling pathways in the mammalian cell. As a significant nutrient sensor, Akt plays a central role in many cellular processes, including cell growth, cell survival and glucose metabolism. The dysregulation of Akt signalling is implicated in the development of many diseases, from diabetes to cancer. The translocation of Akt from cytosol to plasma membrane is a crucial step in Akt activation. Akt is initially synthesized on the endoplasmic reticulum, but translocates to the plasma membrane (PM) in response to insulin stimulation, where it may be activated. The Akt is then recycled to the cytoplasm. The activated Akt may propagate signals to downstream substrates both at the PM and in the cytosol, hence understanding the translocation dynamics is an important step in dissecting the signalling system. At the present time, however, knowledge concerning the translocation of either activated and unactivated Akt is scant. Here we present a simple, deterministic, three-compartment ordinary differential equation model of Akt translocation in vitro. This model can reproduce the salient features of Akt translocation in a manner consistent with the experimental data. Furthermore, we demonstrate that this system is equivalent to a damped harmonic oscillator, and analyse the steady state and transient behaviour of the model over the entire parameter space.


Trace detection of explosive particulates with a phosphole oxide.
Phosphole oxides exert the ability to detect explosives, especially nitroaromatic explosives such as 2,4,6-trinitrotoluene (TNT), by fluorescence quenching. In the image sensing of explosives sprayed with phosphole oxide, fluorescence quenching permits the visual determination of the lower detection limits of the nitroaromatic explosives in the nanogram level.


A Rare Clinical Entity: Staphylococcus-Related Glomerulonephritis.
Staphylococcus aureus is a rare cause of postinfectious glomerulonephritis, and Staphylococcus-related glomerulonephritis primarily occurs in middle-aged or elderly patients. Patients with Staphylococcus-related glomerulonephritis also present with hematuria, proteinuria of varying degrees, rising serum creatinine levels, and/or edema. The severity of renal insufficiency is proportional to the degree of proliferation and crescent formation. Here, we present a diabetic patient admitted with a history of 1 week of left elbow pain. Laboratory results revealed that erythrocyte sedimentation rate was 110 mm/hour, serum creatinine level was 1 mg/dL, C-reactive protein level was 150 mg/L, and magnetic resonance imaging showed signal changes in favor of osteomyelitis at the olecranon level, with diffuse edematous appearance in the elbow skin tissue and increased intra-articular effusion. After diagnosis of osteomyelitis, ampicillin/sulbactam and teicoplanin were administered. After day 7 of admission, the patient developed acute kidney injury requiring hemodialysis under antibiotic treatment. Kidney biopsy was performed to determine the underlying cause, which showed Staphylococcus-related glomerulonephritis. Recovery of renal functions was observed after antibiotic and supportive treatment.


SmartFluo: A Method and Affordable Adapter to Measure Chlorophyll a Fluorescence with Smartphones.
In order to increase the monitoring capabilities of inland and coastal waters, there is a need for new, affordable, sensitive and mobile instruments that could be operated semi-automatically in the field. This paper presents a prototype device to measure chlorophyll a fluorescence: the SmartFluo. The device is a combination of a smartphone offering an intuitive operation interface and an adapter implying a cuvette holder, as well as a suitable illumination source. SmartFluo is based on stimulated fluorescence of water constituents such as chlorophyll a. The red band of the digital smartphone camera is sensitive enough to detect quantitatively the characteristic red fluorescence emission. The adapter contains a light source, a strong light emitting diode and additional filters to enhance the signal-to-noise ratio and to suppress the impact of scattering. A novel algorithm utilizing the red band of the camera is provided. Laboratory experiments of the SmartFluo show a linear correlation (R 2 = 0.98) to the chlorophyll a concentrations measured by reference instruments, such as a high-performance benchtop laboratory fluorometer (LS 55, PerkinElmer).


Lead poisoning among pregnant women in New York City: risk factors and screening practices.
This article presents information on pregnant women with incident blood lead levels (BLLs) of 20 microg per deciliter or greater as reported to the New York City Department of Health between September 1996 and June 1999 (n = 33). Almost half of the women were diagnosed during their third trimester of pregnancy, often at their first prenatal visit. The median BLLs at incidence and at last report among women who were retested were 25 and 15 gamma/dL, respectively, a 40% decline. The median incident BLL among newborns (n = 25) was 12 microg/dL. The BLLs were inversely associated with maternal age and length of time in the United States and directly associated with gestational age and pica behavior. Cases were more than twice as likely to be foreign-born women than all women who gave birth in New York City. Prenatal care facilities employing a policy of universal blood lead testing of all pregnant women at the time of their first visit reported disproportionate numbers of cases, accounting for 77% of cases yet only 11% of all births citywide. The findings suggest that (1) the promulgation of recent rules and guidelines for lead risk assessment and screening among pregnant women appears to have been effective in identifying cases that might not have otherwise come to light; (2) case management and environmental interventions were initiated promptly; (3) cases experienced, on average, significant BLL reductions over time; and (4) there is a need for additional public health interventions for pregnant women in urban, multicultural centers. While the data suggest that universal screening may increase case finding among high-risk, immigrant populations, further studies and surveillance are needed to determine systematically the most effective approach.


Human epidermal growth factor receptor residue covalently cross-linked to epidermal growth factor.
An epidermal growth factor (EGF) receptor monoclonal antibody (mAb), mAb LA22, was used to analyze the covalent coupling of human EGF receptors to mouse EGF by the amine-reactive cross-linking agent disuccinimidyl suberate. A soluble Mr 105,000 truncated form of the receptor secreted by A-431 epidermoid carcinoma cells and consisting of the ligand-binding extracellular domain was cross-linked to 125I-labeled EGF. Digestion of this complex with an endoproteinase that specifically cleaves at the COOH side of glutamyl residue released a single radiolabeled glycosylated fragment of Mr 18,000 that reacted with mAb LA22. As the epitope for mAb LA22 resided between Ala-351 and Asp-364 of the mature receptor, this result localized the cross-linked receptor residue(s) to the 47-amino acid interval from Phe-321 to Glu-367. The receptor residue(s) involved in the covalent coupling of rat 125I-labeled transforming growth factor alpha was similarly localized to this region of the receptor. This receptor interval, which included two glycosylated asparaginyl residues at positions 328 and 337, contained but three amino acid residues that were potentially reactive with disuccinimidyl suberate: Lys-332, Lys-333, and Lys-336. Characterization of mAb LA22-reactive 125I-EGF-labeled receptor fragments generated by an endoproteinase specific for the COOH side of lysyl residue placed the NH2 termini of the two smallest fragments between the glycosylated residues Asn-328 and Asn-337. These results indicated that disuccinimidyl suberate cross-linked the NH2 group of EGF residue Asn-1 to the human EGF receptor residue Lys-336. Our results further suggest that EGF and transforming growth factor alpha, two members of the EGF family of peptide growth factors, interact with closely apposed or identical features of the receptor.


Latitudinal cline of chronotype.
The rotation of the Earth around its own axis and around the sun determines the characteristics of the light/dark cycle, the most stable and ancient 24 h temporal cue for all organisms. Due to the tilt in the earth's axis in relation to the plane of the earth's orbit around the sun, sunlight reaches the Earth differentially depending on the latitude. The timing of circadian rhythms varies among individuals of a given population and biological and environmental factors underlie this variability. In the present study, we tested the hypothesis that latitude is associated to the regulation of circadian rhythm in humans. We have studied chronotype profiles across latitudinal cline from around 0° to 32° South in Brazil in a sample of 12,884 volunteers living in the same time zone. The analysis of the results revealed that humans are sensitive to the different sunlight signals tied to differences in latitude, resulting in a morning to evening latitudinal cline of chronotypes towards higher latitudes.


Design of pusher-plate-type left ventricular assist device based on mechanical analyses.
A permanently implantable left ventricular assist device (LVAD) pump of the pusher-plate type was designed based on mechanical analyses. A series of three different segmented polyether polyurethanes was utilized for the diaphragm, cannulae, and their blood-contacting surfaces, considering each material's characteristics. The span and thickness of the pump diaphragm were determined so as to minimize the stress developed by the bending and blood pressure forces. The inflow and outflow cannulae were designed using fundamental equations that describe the operation of a piston-type reciprocating pump. The pump diameter was determined considering the required flow for the average Japanese person. In vitro and in vivo experiments showed good pump performance, which satisfied the design specifications. No failure was observed in the designed diaphragm. The Hall effect sensor incorporated in the pump was very useful in monitoring the cardiac output of the pump.


[Reduction of influenza-like infections by a phytoextract-vitamin-combination: a randomized, double-blind, placebo-controlled study].
Recurrent infections are signs of a weakened immune system, and can be traced to a lack of vitamins and minerals. The objective of this study was to investigate the effect of a nutriological combination of vitamins, trace elements and phytochemicals on the incidence and duration of influenza-like infections. Healthy subjects at risk of increased infection exposure took part in a randomized, double-blind, placebo controlled study, each involving a supplementation period of 12 weeks. The occurrence and severity of influenza-like infections and resort to study medication was documented by diary entries. SF-36 questionnaires to measure the health-related quality of life were completed at the start and end of the study. At final examination compliance was examined with respect to returned study medication, diaries and a questionnaire administered to evaluate the effect, safety, and tolerability of the test substance. Of 100 randomized participants, 80 (38 test treatment and 42 placebo) completed the study according to the protocol. In the test treatment group there were 60 influenza-like infections (1.6 infections/12 weeks), significantly fewer (p = 0.0003) compared with the placebo group with 113 episodes (2.7 infections/12 weeks). Further, the average number of days that the infection lasted was shorter in the test treatment group at 10.0 +/- 6.7 days, which was significantly shorter (p = 0.0003) than the placebo group at 28.5 +/- 13.6 days. The influenza-like symptom score and the mean duration of sick leave did not differ statistically between groups. Participants in the test treatment group assessed the global effectiveness of the test substance significantly better (p < 0.0001) than the participants of the placebo group. At the beginning of the study there was no difference between groups with respect to SF-36 results. However, at the completion of the study 6 of the 8 scales of SF-36 in the test treatment group were significantly better compared with the placebo group. In summary, consumption of the complex nutriological test preparation was associated with a significant reduction in the incidence of influenza-like infections, as well as their duration, and it was associated with significantly improved vitality, social functioning, and psychological well-being.


Imaging the Bonds of Dehalogenated Benzene Radicals on Cu(111) and Au(111).
Dissociative adsorption of doubly substituted benzene molecules leads to formation of benzyne radicals. In this study, co-adsorbed hydrogen molecules are used in scanning tunneling hydrogen microscopy to enhance the contrast of the meta- and the para-isomers of these radicals on Cu(111) and Au(111). Up to three hydrogen molecules are attached to one radical. One hydrogen molecule reveals the orientation of the carbon ring and its adsorption site, allowing discrimination between the two radicals. Two hydrogen molecules reflect the bond picture of the carbon skeleton and reveals that adsorption on Cu(111) distorts the meta- isomer differently from its gas-phase distortion. Three hydrogen molecules allow us to determine the bond picture of a minor species.


GC-MS Metabolomics Reveals Distinct Profiles of Low- and High-Grade Bladder Cancer Cultured Cells.
Previous studies have shown that metabolomics can be a useful tool to better understand the mechanisms of carcinogenesis; however, alterations in biochemical pathways that lead to bladder cancer (BC) development have hitherto not been fully investigated. In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to unveil the metabolic alterations between low-grade and high-grade BC cultured cell lines. Multivariable analysis revealed a panel of metabolites responsible for the separation between the two tumorigenic cell lines. Significantly lower levels of fatty acids, including myristic, palmitic, and palmitoleic acids, were found in high-grade versus low-grade BC cells. Furthermore, significantly altered levels of some amino acids were observed between low- and high-grade BC, namely glycine, leucine, methionine, valine, and aspartic acid. This study successfully demonstrated the potential of metabolomic analysis to discriminate BC cells according to tumor aggressiveness. Moreover, these findings suggest that bladder tumorigenic cell lines of different grades disclose distinct metabolic profiles, mainly affecting fatty acid biosynthesis and amino acid metabolism to compensate for higher energetic needs.


Rural and urban physicians' perceptions regarding the role and practice of the nurse practitioner, physician assistant, and certified nurse midwife.
There is a dearth of literature citing the differences in rural and urban physicians' perceptions of the role and practice of nurse practitioners, physician assistants, and certified nurse midwives (nonphysician providers). The purpose of this study was to investigate and compare differences, if any, between rural and urban primary care physicians' perceptions of the role and practice of nonphysician providers. Despite a 15.55% response rate using a mail-out survey in South Carolina, data from 681 rural and urban primary care physicians indicated that they perceived that nonphysician providers possess the necessary skills and knowledge to provide primary care to patients, are an asset to a physician's practice, free the physician's time to handle more critically ill patients, and increase revenue for the practice, but increase the risk of patient care mistakes and a physician's time in administrative duties. Urban physicians' mean scores were higher for perceiving that nonphysician providers are able to see as many patients in a given day as a physician but experience impediments in the delivery of patient care. Results will be used to clarify physicians' perceptions regarding the role and practice of nonphysician providers to reduce impediments to patient care access.


The effect of exogenous adenosine triphosphate on potassium movements in HeLa cells.
The effect of exogenous adenosine triphosphate (ATP) on the potassium movements of cultured HeLa cells has been studied. The results obtained were consistent with the hypothesis that, in these cells, externally applied ATP activates a tightly coupled potassium-potassium (K-K) exchange mechanism. The response to ATP was characterized by a transient, 20-fold increase in both the potassium influx and potassium efflux. The tight coupling of the K-K exchange mechanism was confirmed by the results of several different types of experiment, all of which demonstrated the consistent matching of the ATP-stimulated fluxes. Two different strains of HeLa cells gave quantitatively different responses under similar experimental conditions. The reason for this difference was investigated and evidence was obtained which was consistent with the view that the membrane potential also influenced the HeLa cell K-K exchange mechanism.


Laparoscopic sigmoidectomy in moderate and severe diverticulitis: analysis of short-term outcomes in a continuous series of 121 patients.
The role of laparoscopic surgery has been shown to be safe, feasible, and equivalent to open surgery for moderate diverticulitis, but its role in severe disease is still being elucidated. The aim of this study was to compare short-term outcomes in patients who underwent laparoscopic sigmoidectomy for moderate and severe diverticulitis. All patients who had elective laparoscopic sigmoidectomy for diverticulitis between April 2003 and September 2011 at the University Hospital of Luxembourg were selected from a retrospective database. The patients were divided in two groups: moderate acute diverticulitis (MAD) included patients with an episode of left-lower-quadrant pain, elevated inflammatory markers, and radiologic evidence of diverticulitis, and severe acute diverticulitis (SAD) included patients with diverticula associated with abscess, phlegmon, perforation, fistula, obstruction, bleeding, or stricture. A total of 121 patients (81 MAD and 40 SAD) underwent elective laparoscopic sigmoidectomy with primary anastomosis. There were no significant differences between the two groups with respect to demographic characteristics, except for sex ratio. In this series the overall morbidity rate at 30 postoperative days (POD) was 12.4 %, with no significant differences between MAD and SAD (16.0 vs. 5 %, respectively; P = 0.083). No significant differences were found with respect to mean length of hospital stay (6.7 vs. 7.7 days; P = 0.399) as well. The overall conversion rate to open surgery was 2.5 % (3 patients), with no difference between the two groups. Conversion to laparotomy was associated with an increased morbidity rate (11.0 % for full laparoscopy vs. 66.6 % for conversion; P = 0.040) and a longer length of stay (6.8 vs. 16.7 days; P = 0.008). There were no deaths within 30 POD. Elective laparoscopic sigmoidectomy is safe and feasible for patients with moderate and severe acute diverticulitis and the outcomes are equivalent.


Arabidopsis GT34 family contains five xyloglucan α-1,6-xylosyltransferases.
The Arabidopsis genome includes seven family 34 glycosyltransferase (GT34) encoding genes. XXT1 and XXT2 have previously been shown to encode XyG α-1,6-xylosyltransferases, while knockout mutants of a third, XXT5, exhibit decreased XyG content, suggesting a similar activity. Here, we extend the study to the rest of the Arabidopsis GT34 genes in terms of biochemical activity and their roles in XyG biosynthesis. The enzyme activity of XXTs was investigated using recombinant protein expressed in E. coli. XyG analysis of single and double T-DNA insertion knockouts, together with overexpression of GT34s in selected mutant lines, provided detailed function of each gene. We reveal the activity of the third member of the GT34 gene family (XXT4) that exhibits xylosyltransferase activity. Double mutants for either xxt2 or xxt5 had a large impact on XyG content, structure and size distribution. Overexpression of the remaining member, XXT3, was able to restore XyG epitopes in xxt2, xxt5 and xxt2 xxt5 double knockouts, suggesting that it also encodes a protein with XXT activity. Our work demonstrates that five of the seven Arabidopsis GT34 genes encode XXT enzymes.


Deficient expression of antibodies specific for bacterial DNA by patients with systemic lupus erythematosus.
Antibodies to DNA occur commonly in the sera of normal human subjects and bind to nonconserved sites exclusive to DNA from certain bacterial species. These antibodies are primarily IgG2 and differ from anti-DNA antibodies in systemic lupus erythematosus (SLE) sera, which are primarily IgG1 and bind conserved sites on all DNA. To investigate the immune response to bacterial DNA in SLE, antibodies to single-stranded DNA from Micrococcus lysodeikticus (MC) were measured in normal human subjects and in SLE sera by enzyme-linked immunosorbent assay either directly or following absorption by cellulose bearing calf thymus (CT) DNA; isotype-specific reagents were used to assess the IgG2 response. In these assays, SLE sera had a marked deficiency in antibodies specific for MC single-stranded DNA as demonstrated by the reduction of antibody levels by CT DNA cellulose absorption. Furthermore, IgG2 anti-DNA in SLE sera were cross-reactive with MC and CT single-stranded DNA, whereas IgG2 anti-DNA in normal human subjects' sera were specific for the bacterial DNA antigen. Together, these findings indicate that SLE patients have a marked deficiency in the production of antibodies specific for bacterial DNA antigen. This deficiency could predispose to anti-DNA autoantibody production and result from tolerance defects that distort the array of specificities in the B-cell repertoire.


Decreases in heart rate variability are associated with postoperative complications in hip fracture patients.
To explore relevant associations between deviations in linear and nonlinear heart rate variability (HRV) scores, and short-term morbidity and mortality in patients undergoing hip-surgery after a fracture. 165 patients with hip fractures being admitted for surgery at two hospitals were included in a prospective cohort study. A short-term ECG was recorded within 24 hours of arrival. 15 patients had to be excluded due to insufficient quality of the ECG recordings. 150 patients were included in the final analysis. Linear parameters were calculated in time domain: standard deviation of NN intervals (SDNN), root mean square of successive differences (rMSSD); and frequency domain: Total Power (TP), High Frequency Power (HF), Low Frequency Power (LF), Very Low Frequency Power (VLF), and the ratio of LF/HF. Postoperative outcome was evaluated at the time of discharge. This included occurrence of pneumonia, overall infection rate, stroke, myocardial infarction, and all-cause mortality. Patients experiencing complications had significantly lower rMSSD (p = 0.04), and TP (p = 0.03) preoperatively. Postoperative infections were predicted by decreased VLF preoperatively (p = 0.04). There was a significant association between pneumonia and LF/HF<1 (p = 0.03). The likelihood ratio to develop pneumonia when LF/HF < 1 was 6,1. HRV seems to reflect the general frailty of the patient with hip fracture and might be used to identify patients in need of increased surveillance or prophylactic treatment.


[Dopamine receptor signaling regulates human osteoclastogenesis].
Although the central nervous system and the neurotransmitters are known to control not only the immune system but also the homeostasis of bone mass, their pathological relevance to bone disorders remains unclear. Osteoclasts in the synovium of rheumatoid arthritis (RA) play an important role in bone destruction. It is known that increased sympathetic nervous activity increases both differentiation and function of osteoclasts, which leads to bone loss. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. We previously reported that dopamine plays an important role in IL-6-IL-17 axis and subsequent joint destruction in RA. The major source of dopamine in the synovial tissue of RA was dendritic cells (DCs) that stored and secreted dopamine. Dopamine released by DCs bounded to D1-like dopamine receptors on T cells and induced activation of cAMP and differentiation to Th17 cells via IL-6 production We here overview the interplay among the immune system, bone metabolism and neurologic system shedding light upon dopaminergic signals upon osteoclastogenesis.


Meeting physical activity recommendations: self-regulatory efficacy characterizes differential adherence during arthritis flares.
Using social-cognitive theory, we examined whether adults who experienced an arthritis flare and met/did not meet the disease-specific public health recommended dose for physical activity differed in their self-regulatory efficacy beliefs, overall pain, and flare-related factors. Adults with arthritis (N = 56; M(age) = 49.41 ± 11.56 years) participated in this prospective study. Multivariate analysis of variance comparing groups who met or did not meet the recommended dose (n(met) = 24, ≥ 150 minutes/week vs. n(not met) = 32, < 150 min/week) on efficacy, overall pain, and flare-related factors was significant (p < .01; η(partial)² = .28). People meeting the dose had significantly greater self-regulatory efficacy to overcome arthritis barriers (M(met dose) = 7.33 ± 1.95 vs. M(did not meet dose) = 5.74 ± 2.08, η(partial)² = .14) and to schedule/plan (M(met dose) = 7.27 ± 1.80 vs. M(did not meet dose) = 5.72 ± 1.90, η(partial)² = .15). Overall pain and flare-related factors did not differ (ps > .05). During flares, individuals with greater self-regulatory efficacy to manage disease barriers and plan their physical activity were more adherent to disease-specific public health activity recommendations. This study was the first to demonstrate differences in social cognitions that characterize adherence to recommended activity among people challenged by arthritis flares. Findings support the theoretical position that self-regulatory efficacy is related to better adherence in the face of challenging disease-related circumstances. The importance of studying individual characteristics of people who succeed in being active despite such obstacles is stressed.


'Baby Doe' rulings-review and comment.
The recent controversy over the "Baby Doe" regulations issued by the Department of Health and Human Services represents the culmination of a dilemma that has faced the medical and legal professions for more than a decade. Although they have not been upheld by the courts, the regulations express the position that withholding treatment from defective newborns may constitute discrimination on the basis of handicap and advocate mechanisms for the reporting of such practices. Legislation regarding this issue is pending at both the national and state levels. The rulings have been disputed by many medical and professional groups, which are working to provide acceptable alternatives.


Conditional removal of the canonical TGF-β1 signaling delays condylar cartilage degeneration induced by a partial discectomy in mice.
Recent emerging data indicate that the increase in the expression and activity of the transforming growth factor beta 1 (Tgf-β1) signaling may have detrimental effect to mature articular cartilage of knee joints. However, there is no information about whether or not this is the case in condylar cartilages. The objective of this study is to investigate the protein expression and activity of Tgf-β1 signaling in degenerative condylar cartilages. We also investigate biological effects of the conditional deletion of transforming growth factor receptor type II (Tgfbr2) in condylar cartilage of adult mice after a partial discectomy. Two mouse models of osteoarthritis (OA) were used to examine protein expressions of Tgf-β1 and p-Smad2/3 in condylar cartilages at early degenerative stages. In addition, cartilage specific Tgfbr2-deficient adult mice were subjected to a partial discectomy. The morphological condition of condylar cartilages was evaluated in mice at 4 and 12 weeks after the surgery. We found that protein levels of Tgf-β1 and p-Smad2/3 were increased in the degenerative condylar cartilage of the mouse models. The conditional removal of Tgfbr2 in mature condylar cartilage significantly delayed the progressive progression of the cartilage degeneration induced by a partial discectomy. We conclude that the increase in the expression and activity of Tgf-β1 signaling may have detrimental effect to mature condylar cartilages. Therefore, inhibition of Tgf-β1 signaling may be able to protect condylar cartilages from being degraded in mature temporomandibular joints.


Glue versus suture fixation of mesh during open repair of inguinal hernias: a systematic review and meta-analysis.
Glue fixation of mesh has been explored for some time as a strategy for reducing postoperative chronic groin pain. Previous studies have come to different conclusions about the superiority of one method over another. We conducted a meta-analysis of randomized control trials comparing the performance of glue versus suture fixation of mesh in open inguinal hernioplasty. Studies published up to November 2012 were searched using PubMed, EMBASE, MEDLINE, Cochrane Library, and the international standard randomised controlled trials number (ISRCTN) register. Mean differences (MDs) were derived from secondary continuous outcomes and pooled risk ratios (RRs) for categoric outcomes. Meta-analysis was conducted utilizing the random-effects and fixed-effects models as appropriate. Ten randomized controlled studies were selected, with a total of 1,623 patients. Glue fixation for open inguinal hernioplasty reduced chronic groin pain (RR 0.46, 95 % confidence interval (CI) 0.22-0.97), hematoma (RR 0.56, 95 % CI 0.34-0.90), acute postoperative pain (MD -7.92, 95 % CI, -13.17 to -2.66), and time taken to return to normal activities (MD -1.39, 95 % CI, -2.58 to -0.21). There was no evidence of an increase in adverse outcomes including recurrence with glue fixation (RR 0.83, 95 % CI 0.30-2.35). Glue fixation of mesh for open inguinal hernioplasty is superior in many outcomes including the reduction of chronic groin pain. Glue fixation was not associated with an increased risk of hernia recurrence.


Stabilization of Escherichia coli isopropylmalate dehydrogenase by single amino acid substitution.
To determine the key position for the unusual stability of isopropylmalate dehydrogenase from extreme thermophiles (Thermus thermophilus and T. aquaticus), sequence comparisons were carried out. As a result, a motif which is characteristic to the thermophilic dehydrogenases was found between two highly conserved stretches. The sequence motif was introduced into a mesophilic (Escherichia coli) isopropylmalate dehydrogenase, one by one. Contrary to our expectation, introduction of the whole motif led the mesophilic enzyme to be more unstable whereas substitution of only one amino acid residue in the motif thermostabilized the enzyme. From the 3D structure of the enzyme, a mechanism for the thermostabilization is speculated.


A Novel Clinical and Stress Cardiac Magnetic Resonance (C-CMR-10) Score to Predict Long-Term All-Cause Mortality in Patients with Known or Suspected Chronic Coronary Syndrome.
Vasodilator stress cardiac magnetic resonance (stressCMR) has shown robust diagnostic and prognostic value in patients with known or suspected chronic coronary syndrome (CCS). However, it is unknown whether integration of stressCMR with clinical variables in a simple clinical-imaging score can straightforwardly predict all-cause mortality in this population. We included 6187 patients in a large registry that underwent stressCMR for known or suspected CCS. Several clinical and stressCMR variables were collected, such as left ventricular ejection fraction (LVEF) and ischemic burden (number of segments with stress-induced perfusion defects (PD)). During a median follow-up of 5.56 years, we registered 682 (11%) all-cause deaths. The only independent predictors of all-cause mortality in multivariable analysis were age, male sex, diabetes mellitus (DM), LVEF and ischemic burden. Based on the weight of the chi-square increase at each step of the multivariable analysis, we created a simple clinical-stressCMR (C-CMR-10) score that included these variables (age ≥ 65 years = 3 points, LVEF ≤ 50% = 3 points, DM = 2 points, male sex = 1 point, and ischemic burden > 5 segments = 1 point). This 0 to 10 points C-CMR-10 score showed good performance to predict all-cause annualized mortality rate ranging from 0.29%/year (score = 0) to >4.6%/year (score ≥ 7). The goodness of the model and of the C-CMR-10 score was separately confirmed in 2 internal cohorts (n > 3000 each). We conclude that a novel and simple clinical-stressCMR score, which includes clinical and stressCMR variables, can provide robust prediction of the risk of long-term all-cause mortality in a population of patients with known or suspected CCS.


Three-dimensional in vivo planum temporale reconstruction.
We describe a new multistep technique for three-dimensional reconstruction and analysis of the in vivo planum temporale (PT) based on the manipulation of magnetic resonance raw data obtained with a special protocol. Measurements of left and right plana confirm previous neuroanatomical descriptions of a larger left planum temporale. This method can be easily adopted, allowing anatomically valid PT measurements.