[Treatment of bone infections with gentamicin-containing acrylic cement beads. Prognostic value of the study of the suction drainage fluid].
Treatment of bone infections with gentamicin-PMMA beads is an adjunct to conventional surgery. Early failures occurred in a number of cases, due to technical problems, such as incomplete debridement, residual alloplastic material, or gentamicin-resistant pathogens. To evaluate short term results of the method, clinical and bacteriological pre-therapy data were compared with results obtained two and six weeks after surgery, in 25 patients. Gentamicin concentrations, gentamicin levels/MBC for gentamicin, and bactericidal activity in secretions collected from suction drainage were not correlated with outcome. Cultures from the drains were the best parameters: cultures remained positive throughout follow-up in patient with poor clinical results.


A State-Level Examination of School Nurses' Perceptions of Condom Availability Accompanied by Sex Education.
School nurses are often sources of health-care support for teens with sexually transmitted infections (STIs) and unintended pregnancies. However, providing prevention (e.g., condoms) and teaching technical skills (e.g., condom use) needed to reduce high-risk sexual behavior may require a change in perceptions and policies. This study used a cross-sectional study design to assess nurses' perceptions of condom availability accompanied by sex education programs among high school nurses (n = 87) in Kansas. Results showed that school nurses in this study supported condom availability, were comfortable providing condoms, and felt condom availability was within the scope of their job but were less likely to provide condoms because of external barriers. Common barriers include administration, parents, cost, community support, and policies. School nurses, by virtue of their access to the majority of Kansas' adolescents, have the potential to provide sex education and tools such as condoms, so young people can prevent STIs and unintended pregnancies.


[Cardiac and extracardiac complications in Kawasaki disease].
In terms of frequency and prognosis, discussions of the complications of Kawasaki disease have focused on coronary artery aneurysms and stenosis. However, as revealed by autopsy findings, medium and small muscular arteries in various organs could be injured in patients with Kawasaki disease, leading to the development of a variety of complications. Accurate diagnosis of Kawasaki disease can be especially difficult when incomplete Kawasaki disease is accompanied by rare complications involving the central nervous system, digestive system, and other systems in the body, which leads to delay in treatment and subsequent development of coronary artery aneurysms and delayed improvement of the existing complications. Doctors who treat Kawasaki disease should be familiar with the rare but important complications of Kawasaki disease.


Development of a tightly regulated U6 promoter for shRNA expression.
Short hairpin RNAs (shRNAs) have been used to achieve stable target knockdown in a variety of biological systems. Here, we report the development of a tightly regulated tetracycline-responsive human U6 promoter for shRNA expression. By engineering two copies of the tet operators flanking the TATA box of the human U6 promoter, we created a U6 promoter derivative (2O2) that exhibited much lower basal transcriptional activity compared with recently reported inducible pol III dependent promoters. As a consequence of its tighter regulation, the 2O2 system greatly improved the success rate in making inducible knockdown cell lines.


Serum Preadipocyte Factor 1 Levels Are Not Associated with Bone Mineral Density among Healthy Postmenopausal Korean Women.
Multipotent mesenchymal stem cells can differentiate into adipocytes or osteoblasts through closely regulated lineage-control processes. However, adipocyte precursor cells release preadipocyte factor 1 (Pref-1), which inhibits the differentiation of mesenchymal stem cells into mature adipocytes and osteoblasts. Previous studies have also reported an inverse association between Pref-1 levels and bone mineral density (BMD) among patients with anorexia nervosa. In this retrospective study, we examined the correlations between Pref-1 levels and BMD among 124 healthy postmenopausal women (>50 years old). The patients had provided information regarding their clinical characteristics, and underwent blood testing and serum Pref-1 testing. The subjects' mean age was 59.9±7.1 years and the median time since menopause onset was 9.1 years. A history of osteoporotic fracture was identified in 23 subjects (19%). Serum Pref-1 levels were not significantly correlated with BMD values at the lumbar spine (R²=0.038, P=0.109), femur neck (R²=0.017, P=0.869), and total hip (R²=0.041, P=0.09), and multivariate analyses with adjustment for age and body mass index also did not detect any significant correlations. Subgroup analyses according to a history of fracture also did not detect significant associations between Pref-1 levels and BMD values. In our study population, it does not appear that serum Pref-1 levels are significantly associated with BMD values and osteoporosis.


Decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection.
Thoracic aortic aneurysmal diseases are characterized by degeneration of elastin within the aortic wall. Although proteinases, such as matrix metalloproteinase, appear to contribute to elastin degradation, little is known about the role of elastic fiber assembly in such diseases. Fibulin-5 is an extracellular protein that is expressed in the vascular basement membrane and regulates elastic fiber assembly by microfibril machinery. In this study, we examined whether thoracic aortic dissection (TAD) is associated with abnormal fibulin-5 expression. Intraoperative aortic samples were obtained from 21 patients with proximal aortic dissection. Control aortic tissue was obtained from 11 organ donors, heart transplant recipients, and patients undergoing coronary artery bypass. An in vitro culture of vascular smooth muscle cells was obtained from 2 TAD patients and 1 control subject. To evaluate elastin expression, we stained tissue sections with Verhoeff-Van Gieson stain. Fibulin-5 messenger RNA (mRNA) expression was determined by quantitative real-time reverse-transcriptase-polymerase chain reaction. Aortic fibulin-5 mRNA and elastin content were decreased in TAD patients, compared with controls (P=.001 and P=.02, respectively). Decreased fibulin-5 expression strongly correlated with decreased amounts and fragmentation of elastin in aortic samples from patients with TAD (r=0.83, P < .0001 and F=20.7, P < .0001 respectively). The fibulin-5 mRNA in aortic vascular smooth muscle cells collected from TAD demonstrated a 38% decrease in expression, compared with the control. Patients with proximal aortic dissection exhibited significantly decreased expression of aortic fibulin-5. Decreased fibulin-5 may contribute to the pathogenesis of aortic dissection by impairing elastic fiber assembly.


Epidemiology of infertility: social problems of the infertile couples.
Infertility is of public health importance in Nigeria and many other developing nations because of its high prevalence and especially due to its serious social implications. A review of the epidemiology of infertility in Nigeria and other parts of Sub-Saharan Africa is presented and socio-cultural issues including the social impact on couples are discussed. The major cause of infertility in Africa is infection--STDs, post-abortal and puerperal sepsis. Beliefs about causes, and failure of orthodox methods of treatment have led many couples to seek solution from traditional doctors and faith healers without success. Infertility causes marital disharmony, which often leads to divorce. Women are often blamed for the infertility and men engage in polygyny in an attempt to have children. The couple can also suffer stress from the management of the infertility. Adoption is not popular and assisted reproduction has medico-legal implications. Preventive measures are suggested, including counselling at every stage of the management.


A research synthesis on successful educational practices and student outcomes for physical education in schools.
Although successful educational practices (SEPs) in higher education institutions have well-established student outcomes, the vast majority do not meet physical education standards in schools. Despite the promising nature of policy initiatives supporting schools, there is scant evidence of how these SEPs affect student outcomes. This review aimed to determine the status of the literature and the type of evidence regarding school SEPs. Several studies have demonstrated that these SEPs contribute directly or indirectly to improving student outcomes. Three objectives were examined and synthesized in our review of SEP research findings. The first goal is to identify different types of impacts on students in schools. The second goal is to provide educators, principals, and policymakers with a unified and comprehensive framework. Lastly, we provide suggestions for future SEP research. The review identified 45 studies that met our inclusion criteria. Our reviewed studies documented impacts on the individual level. It encompasses both students' instrumental abilities and their sense of self-esteem and motivation. Secondly, improving interpersonal relationships, reducing conflict, and increasing group cohesion are important components at the group level. Finally, there are factors at the community level, including absenteeism reduction, parental involvement, and changes in attitudes toward school. Current research supports the effectiveness of successful school practices. It stresses the importance of implementing policies to maximize student outcomes. Finally, the review concludes by discussing findings implications and future research directions.


Discovery of Potent and Selective MRCK Inhibitors with Therapeutic Effect on Skin Cancer.
The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here, we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphologic changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent antiproliferative effects with greatest activity in hematologic cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy.Significance: The development of selective small-molecule inhibitors of the Cdc42-binding MRCK kinases reveals their essential roles in cancer cell viability, migration, and invasive character. Cancer Res; 78(8); 2096-114. ©2018 AACR.


Transancestral mapping and genetic load in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.


Analysis of CO2 bands near 2600 cm-1.
The collision-broadened linewidths and band intensities of three overlapping CO(2) bands near 2600 cm(-1) have been determined from spectra obtained with a Fourier transform spectrometer. These spectra have SNRs in excess of 500 and a spectral resolution of approximately 0.06 cm(-1). Calculated spectra were matched to the observed spectra by nonlinear least squares regression over 100-cm(-1) intervals. More than forty parameters were estimated simultaneously, and the mean differences between the spectra were about one and a half times the mean noise in the experimental spectra.


Effect of Melissa officinalis supplementation on growth performance and meat quality characteristics in organically produced broilers.
1. A trial was conducted to study the effect of Melissa officinalis supplementation on organic broiler performance and meat chemical, microbiological, sensory and nutritional quality. 2. Male and female day-old Ross 308 chicks were fed on a standard commercial diet containing 0, 2.5, 5 or 10 g/kg feed ground M. officinalis for 84 d before slaughter. 3. Weight gain and feed conversion ratio were significantly improved in the broilers receiving either 5 or 10 mg M. officinalis/kg feed. 4. Inclusion of M. officinalis did not affect muscle chemical and fatty acid composition. 5. On the basis of microbiological and sensory experimental data and subsequent extension of meat shelf life, M. officinalis did not reduce the microbial populations of the meat, but was effective in limiting lipid oxidation.


'A good fit?' Bringing the sociology of footwear to the clinical encounter in podiatry services: a narrative review.
This narrative review explores the ways in which drawing on theories and methods used in sociological work on footwear and identity can contribute to healthcare research with podiatrists and their patients, highlighting recent research in this field, implications for practice and potential areas for future development.Traditionally, research within Podiatry Services has tended to adopt a quantitative, positivist focus, developing separately from a growing body of sociological work exploring the importance of shoes in constructing identity and self-image. Bringing qualitative research drawing on sociological theory and methods to the clinical encounter has real potential to increase our understanding of patient values, motivations and - crucially - any barriers to adopting 'healthier' footwear that they may encounter. Such work can help practitioners to understand why patients may resist making changes to their footwear practices, and help us to devise new ways for practitioners to explore and ultimately break down individual barriers to change (including their own preconceptions as practitioners). This, in turn, may lead to long-term, sustainable changes to footwear practices and improvements in foot health for those with complex health conditions and the wider population. A recognition of the complex links between shoes and identity is opening up space for discussion of patient resistance to footwear changes, and paving the way for future research in this field beyond the temporary 'moment' of the clinical encounter.


Eosinophilic meningitis triggered by implanted Gliadel wafers: case report.
Although carmustine (Gliadel) wafers improve local tumor control and extend the overall survival in patients with malignant glioma, adverse effects have been documented. The authors report the first case of eosinophilic meningitis triggered by the placement of Gliadel wafers. A 61-year-old man with a history of alimentary allergy and glioblastoma in the right frontal lobe underwent resection followed by the implantation of Gliadel wafers. Three weeks later he suffered the sudden onset of headache, vomiting, and progressive consciousness disturbance. Computed tomography revealed enlargement of the ventricular system and subdural space on the side of the tumor. His CSF leukocyte count increased up to 3990 cells/mm3; 95% of the cells were eosinophilic granulocytes (EGs), suggesting eosinophilic meningitis. Laboratory examination showed the patient to have various elevated allergy indicators. The administration of corticosteroids failed to improve his condition. Despite the insertion of a lumbar drain his symptoms failed to improve. He underwent a second surgical intervention to remove the Gliadel wafers. Histologically, EGs had assembled around the wafers. Eosinophilic infiltrate was present in the brain parenchyma around small vessels. After ventriculoperitoneal shunting his course was favorable. A drug lymphocyte stimulation test against the Gliadel wafers failed to demonstrate a positive reaction; polifeprosan, the wafer matrix without 1,3-bis(2-chloroethyl)-1-nitrosourea, yielded a positive reaction. These findings strongly suggest that although extremely rare, polifeprosan (the wafer matrix) can elicit an allergic reaction. When eosinophilic meningitis is suspected after the implantation of Gliadel wafers, their immediate removal should be considered.


Wireless vitals-Proof of concept for wireless patient monitoring in an emergency department setting.
Vital sign assessment is a common task in emergency medicine, but resources for continuous monitoring are restricted, data is often recorded manually, and entangled wires cause frustration. Therefore, we designed a small, wireless photoplethysmographic device capable of continuously assessing pulse, respiratory frequency and oxygen saturation on the sternum and tested the performance and feasibility in an emergency department setting. Fifty (56.3 ± 20.2 years), consenting emergency patients (29 male) were recruited. Heart rate, respiratory rate and oxygen saturation were recorded simultaneously using the device and standard monitoring equipment. Data was compared using Bland-Altman plotting (heart rate, respiratory rate) and mean difference (oxygen saturation). The bias for heart- and respiratory rate was 0.4 (limits of agreements -11.3, 12.2 and -6.1, 7.0). Mean difference for oxygen saturation was -0.21 ± 2.35%. This may be the first wireless device to use photoplethysmography on the sternum for vital sign assessment. We noted good agreement with standard monitors, but lack of standardization in data processing between monitoring systems may limit the generalizability of these findings. Although further improvements are needed, the feasibility of this approach provides proof of concept for a new paradigm of large scale, wireless patient monitoring.


Invisible and unequal: Unincorporated community status as a structural determinant of health.
Despite increasing awareness of the importance of political determinants of health, place-based research has not interrogated one of the most common political statuses: the impact of living in a community without municipal incorporation. In 2010 an estimated 37% of the U.S. population lived in an unincorporated area; despite their ubiquity, unincorporated communities are largely absent from the public health literature. Residents of unincorporated areas typically do not have their own local (e.g., city or municipal) government. This lack of representation leads to political exclusion and diminished access to resources, especially for low-income communities of color, Furthermore, by not disaggregating health data to unincorporated communities, residents are subsumed into county or census tract data that may not be reflective of their community's composition or context. Without jurisdictional distinction in research, there is no accountability for the manufacturing of health inequities in unincorporated communities . In the absence of empirical research on unincorporated communities, this paper uses the Commission on Social Determinants of Health (CSDH) Framework of the World Health Organization to argue that lack of municipal status is a structural determinant of health responsible for social conditions which generate cumulative health risks for residents. This includes using existing evidence on social conditions typical of unincorporated communities to describe patterns of residential segregation, neighborhood disadvantage, and environmental hazards that may increase residents' exposure to unhealthy environments in unincorporated communities. Finally, we provide an agenda for future public health research that can begin to address this health and racial equity gap for low-income unincorporated communities of color who have, until now, been absent in health equity discourse.


Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine-needle aspiration.
The management of thyroid nodules with indeterminate cytology is challenging. Recently, molecular testing on fine-needle aspirates (FNAs) has been advocated to determine whether clinical follow-up or surgery is warranted for patients. Three different testing platforms were performed on aspirates from our institution (Afirma Thyroid FNA Analysis, RosettaGX Reveal, and Interpace ThyGenX/ThyraMIR). This study compares their diagnostic efficacy. We conducted a retrospective analysis of indeterminate thyroid FNAs with correlating molecular testing over 4 years (2015-2018). The aspirates included diagnoses of follicular lesion of undetermined significance, follicular neoplasm, or suspicious for malignancy (SM). Based on cases that underwent surgical resection (Afirma, n = 37; Rosetta, n = 19; Interpace, n = 14), we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for risk of malignancy and neoplasia. The three tests performed similarly when predicting risk of malignancy. They showed high sensitivity (80-100%) and NPV (90-100%) but lower specificity (10-64%) and PPV (21-44%). When assessing their value to predict neoplasia, each test had a high PPV (76-89%) but low NPV (20-33%). The sensitivity for neoplasm was intermediate to high (50-93%), and the specificity remained extremely variable (11-67%). Overall, these molecular platforms performed similarly, displaying high NPV but low to intermediate PPV for malignancy and low NPV but high PPV for neoplasm. The risk of neoplasm is a good index for surgery, and we argue that many of the neoplasms are low-risk tumors. We endorse conservative treatment with lobectomy for cases that are indeterminate at FNA but suspicious by molecular testing.


Endothelin in human autoimmune diseases with renal involvement.
Endothelin (ET)-1 is a potent renal vasoconstrictor with pro-inflammatory, profibrotic and mitogenic potential. Animal studies support a pathogenetic contribution of ET-1 and its cognate receptors in several renal manifestations of autoimmune disorders. However, data in humans are limited. The present minireview thus summarizes the observations available in humans. Similar to animal models, ET-1 is overexpressed in glomerular and tubulointerstitial lesions, which is reflected by an increased urinary excretion of ET-1. Since antagonizing the ET system has beneficial effects in experimental models, this approach may be translated to the human kidney, thus counteracting vasoconstriction, inflammation and extracellular matrix deposition during the course of human autoimmune disease.


[The surgical treatment of pelvic thrombosis during pregnancy (author's transl)].
Pelvic venous thrombosis during pregnancy is a rare event. The treatment discussed in the literature consists mostly of recommendations for therapeutic fibrinolysis. The surgical alternative is the retrograde operative thrombectomy with concommitant Caesarean Section. Two cases were successfully treated by this method at 33 and 39 weeks gestation. The cases are reported. The operative technique is described. The advantages and disadvantages of this treatment are discussed.


Health status among urban residents living in proximity to petroleum coke storage: a first examination.
We conducted an in-person survey in neighborhoods in south Chicago to examine whether residence near outdoor petroleum coke storage piles was associated with poorer health status and illness symptoms. A total of 223 adults (≥18) completed the surveys in English or Spanish, including 136 from a neighborhood exposed to the petroleum coke and 87 from a nearby comparison neighborhood. Exposure was defined based on prevailing winds and distance. We conducted a propensity score regression analysis, and found that residents in the exposed neighborhood were significantly more likely to report poor self-rated health, more unhealthy physical and mental health days, more illness symptoms including in particular respiratory and neurological symptoms, and worse perceived environmental conditions. The survey is limited by the small sample and the self-report nature of the data, but provides initial quantitative evidence that residence near outdoor petroleum coke storage piles may pose a public health risk.


Possible relationship between the gut leaky syndrome and musculoskeletal injuries: the important role of gut microbiota as indirect modulator.
This article aims to examine the evidence on the relationship between gut microbiota (GM), leaky gut syndrome and musculoskeletal injuries. Musculoskeletal injuries can significantly impair athletic performance, overall health, and quality of life. Emerging evidence suggests that the state of the gut microbiota and the functional intestinal permeability may contribute to injury recovery. Since 2007, a growing field of research has supported the idea that GM exerts an essential role maintaining intestinal homeostasis and organic and systemic health. Leaky gut syndrome is an acquired condition where the intestinal permeability is impaired, and different bacteria and/or toxins enter in the bloodstream, thereby promoting systemic endotoxemia and chronic low-grade inflammation. This systemic condition could indirectly contribute to increased local musculoskeletal inflammation and chronificate injuries and pain, thereby reducing recovery-time and limiting sport performance. Different strategies, including a healthy diet and the intake of pre/probiotics, may contribute to improving and/or restoring gut health, thereby modulating both systemically as local inflammation and pain. Here, we sought to identify critical factors and potential strategies that could positively improve gut microbiota and intestinal health, and reduce the risk of musculoskeletal injuries and its recovery-time and pain. In conclusion, recent evidences indicate that improving gut health has indirect consequences on the musculoskeletal tissue homeostasis and recovery through the direct modulation of systemic inflammation, the immune response and the nociceptive pain.


The urge to merge: linking vital statistics records and Medicaid claims.
This paper describes a procedure used to link Medicaid claims data to California vital statistics records for very low birthweight infants. The linkage involved about 53,000 infants born from 1980 to 1987 and 1.46 million claims for delivery/birth-related hospital admissions during the same period. Because the two data files did not share a unique identifier, record linkage required combining evidence across several linking variables: delivery hospital, delivery/birth date or hospitalization period, names, mother's age, and zip code. To combine the various pieces of evidence, we used record linkage theory to compute scores that measure the likelihood of a match, i.e., that two records correspond to the same delivery. These scores appropriately weight the various pieces of evidence for or against a match. Implementation required dealing with large amounts of missing data in one of the files, errors and variations in reported names, and the need to minimize the number of incorrect links. The approach applies to a wide range of linkage problems. The ability to combine existing datasets to form new datasets containing analysis variables from each facilitates analyses that would otherwise be impossible, or prohibitively expensive.


Identifying Nutrition Risk in a Charitable Pharmacy Population.
While prior research has shown that food insecurity and malnutrition worsen health outcomes and increase health care costs, nutrition risk is rarely assessed in the community setting. Tools exist to screen for food insecurity and malnutrition individually, but none screen for both. This study aimed to implement a dual-purpose screening tool to identify nutrition risk in a community setting, to characterize nutrition risk in a charitable pharmacy population, and to identify patients who screen positive for nutrition risk and connect them to community nutrition resources. Of the 221 patients screened during their initial and annual qualification interview at the Charitable Pharmacy of Central Ohio, 140 (63%) screened positive for nutrition risk. There were 84 (38%) patients positive for food insecurity, 14 (6%) positive for malnutrition risk, and 42 (19%) positive for both. Patients at nutrition risk were referred to nutrition resources, including food pantries, home-delivered meals, and SNAP.


[Informational function of heart].
The facts, testifying that electric, magnetic and hydrodynamic impulses generated by heart can be information carriers in human organism, are represented in the article. The conclusion about presence in the heart a modulation mechanism transforming cardiac impulses to signals according to filling information, and about presence structural elements accepting these signals, made by the author. Informational analysis technology based on transformation of space-time electric cardiac dynamics to pattern is proposed. First experience of the use of this technology for internal organs diseases diagnostics is obtained. A new computer diagnostic system for preliminary diagnostics of latent or preclinical diseases has been developed.


Single Drop Whole Blood Diagnostics: Portable Biomedical Sensor for Cardiac Troponin I Detection.
Detection of disease biomarkers from whole blood is very important in disease prevention and management. However, new generation assays like point-of-care or mobile diagnostics face a myriad of challenges in detecting proteins from whole blood. In this research, we have designed, fabricated, and characterized a portable biomedical sensor for the detection of cardiac troponin I (cTnI) directly from whole blood, without sample pretreatments. The sensing methodology is based on an extended gate electrical double layer (EDL) gated field effect transistor (FET) biosensor that can offer very high sensitivity, a wide dynamic range, and high selectivity to target analyte. The sensing methodology is not impeded by electrostatic screening and can be applied to all types of FET sensors. A portable biomedical system is designed to carry out the diagnostic assay in a very simple and rapid manner, that allows the user to screen for target protein from a single drop of blood, in 5 min. This biomedical sensor can be used in hospitals and homes alike, for early detection of cTnI which is a clinical marker for acute myocardial infarction. This sensing methodology could potentially revolutionize the modern health care industry.


[Study of T cell-directed gene transfer for a patient with ADA deficiency].
We have been undertaking the gene therapy for a 6 year-old boy with ADA deficiency and performed 11 cycles of the infusion of the peripheral T cells transduced with retroviral vector LASN since August 8th 1995. The percentage of the peripheral blood lymphocytes carrying the transduced ADA gene has remained stable at 10% to 20% since the 4th infusion. ADA enzyme activity in his circulating T cells increased to levels comparable to 1/3 of a heterozygous carrier individual and was associated with increased T lymphocytes counts and improvement in both humoral and cellular immune function. The results obtained in this clinical study support the usefulness of T lymphocyte-directed gene transfer in the treatment of ADA deficiency.


Regulation of the ring finger E3 ligase Siah2 by p38 MAPK.
The RING finger ubiquitin ligase Siah2 controls the stability of various substrates involved in stress and hypoxia responses, including the PHD3, which controls the stability of HIF-1alpha. In the present study we determined the role of Siah2 phosphorylation in the regulation of its activity toward PHD3. We show that Siah2 is subject to phosphorylation by p38 MAPK, which increases Siah2-mediated degradation of PHD3. Consistent with these findings, MKK3/MKK6 double-deficient cells, which cannot activate p38 kinases, exhibit impaired Siah2-dependent degradation of PHD3. Phosphopeptide mapping identified T24 and S29 as the primary phospho-acceptor sites. Phospho-mutant forms of Siah2 (S29A or T24A/S29A) exhibit impaired degradation of PHD3, particularly after hypoxia. Conversely, a phospho-mimic form of Siah2 (T24E/S29D) exhibits stronger degradation of PHD3, compared with wild type Siah2. Whereas phospho-mutant Siah2 exhibits weaker association with PHD3, phospho-mimic Siah2 associates as well as wild type and is localized within the perinuclear region, suggesting that phosphorylation of Siah2 affects its subcellular localization and, consequently, the degree of its association with PHD3. In all, our findings reveal the phosphorylation of Siah2 by p38 and the implications of such phosphorylation for Siah2 activity toward PHD3.


[Postcoital interception].
It constitutes a descriptive, retrospective study whose aim is to come to know the number and traits of the patients demanding post-coital interception at the Severo Ochoa Hospital in Leganés. We consider the patient's age and place of origin as well as the precise day of the week in which the consultation takes place. Likewise, we take account of the number of women that reiterated their demands during this period. We compare the resultant information with the voluntary interruptions of pregnancy carried out at this hospital in order to approach an assessment of the method's effectiveness. We pose the question of whether the post-coital interception is really a gynaecological emergency or, rather, it could be administered as part of the Primary Health Care services and, even, as other studies suggest, without medical prescription.


Imipenem-cilastatin in the treatment of hospital infections.
Imipenem was tested on 65 gram-negative bacterial strains consecutively isolated in patients affected by hospital infection and used as empiric therapy in 52 patients presenting a hospital infection suspected of gram-negative origin. More than 96% of the tested strains resulted sensitive to imipenem. This antibiotic showed a good clinical result in more than 80% of the cases when used as therapy. Therefore imipenem could be considered the drug of first choice in patients with a severe prognosis and a nosocomial infection suspected to be due to a gram-negative microorganism.


Nonbacterial Thrombotic Endocarditis of Bioprosthetic Aortic Valve Presenting as Cardioembolic Stroke in a Patient without Predisposing Systemic Disease.
Nonbacterial thrombotic endocarditis (NBTE) describes a cluster of noninfectious heart valve lesions and is histologically characterised by the presence of sterile platelet and fibrin-rich aggregates. Risk factors include hypercoagulable states such as active malignancy, autoimmune disorders, and prothrombotic haematological conditions. NBTE involving bioprosthetic heart valves is exceedingly rare. We present a case of a 73-year-old man with a bioprosthetic aortic valve and no NBTE risk factors who developed right-sided homonymous hemianopia during an admission for decompensated congestive cardiac failure. After detailed clinical work-up including brain MRI, the man was diagnosed with acute ischemic cardioembolic stroke involving the left posterior cerebral artery territory. He subsequently underwent successful bioprosthetic aortic valve replacement with histologic examination of the explant supporting diagnosis of NBTE. Evidence of new neurological deficit or disturbance in patients with prosthetic heart valves should prompt investigation for cardioembolic stroke. Whilst rare, NBTE should be considered as a differential diagnosis for cardioembolic stroke, even in patients without predisposing systemic disease.


Two tropical seagrass species show differing indicators of resistance to a marine heatwave.
Marine heatwaves (MHWs) are a growing threat to marine species globally, including economically and ecologically important foundation species, such as seagrasses. Seagrasses in tropical regions may already be near their thermal maxima, and, therefore, particularly susceptible to increases in temperature, such as from MHWs. Here, we conducted a 10-day MHW experiment (control +4°C) to determine the effects of such events on the two tropical seagrasses Halophila beccarii and Halophila ovalis. We found that both species were largely resistant to the MHW, however, there were differences between the species' responses. For H. beccarii, the surface area of existing leaves was smaller under MHW conditions, yet a substantial increase in the number of new leaves under the MHW indicated its tolerance to-or even increased performance under-the MHW. While there was no direct effect of the MHW on H. ovalis, this species saw less epiphyte biomass and percentage cover on its leaves under the MHW. While a lower epiphyte cover can potentially increase the health and ecophysiological performance of the seagrass, the change of epiphytes can lead to bottom-up trophic implications via the influence on mesograzer feeding. Together, the results of this study demonstrate the species-specific responses of seagrasses of the same genus to a warming event. With the current global decline of seagrasses, our results are encouraging for these important habitat formers as we show that anomalous warming events may not necessarily lead to ecosystem collapse.


Target Specific Inhibition of Protein Tyrosine Kinase in Conjunction With Cancer and SARS-COV-2 by Olive Nutraceuticals.
The fact that viruses cause human cancer dates back to the early 1980s. By reprogramming cellular signaling pathways, viruses encoded protein that can regulate altered control of cell cycle events. Viruses can interact with a superfamily of membrane bound protein, receptor tyrosine kinase to modulate their activity in order to increase virus entrance into cells and promotion of viral replication within the host. Therefore, our study aimed at screening of inhibitors of tyrosine kinase using natural compounds from olive. Protein tyrosine kinase (PTK) is an important factor for cancer progression and can be linked to coronavirus. It is evident that over expression of Protein tyrosine kinase (PTK) enhance viral endocytosis and proliferation and the use of tyrosine kinase inhibitors reduced the period of infection period. Functional network studies were carried out using two major PTKs viz. Anaplastic lymphoma kinase (ALK) and B-lymphocytic kinase (BTK). They are associated with coronavirus in regulation of cell signaling proteins for cellular processes. We virtually screened for 161 library of natural compounds from olive found overexpressed in ALK and BTK in metastatic as well as virus host cells. We have employed both ligand and target-based approach for drug designing by high throughput screening using Multilinear regression model based QSAR and docking. The QSAR based virtual screening of 161 olive nutraceutical compounds has successfully identified certain new hit; Wedelosin, in which, the descriptor rsa (ratio of molecular surface area to the solvent accessible surface area) plays crucial role in deciding Wedelosin's inhibitory potency. The best-docked olive nutraceuticals further investigated for the stability and effectivity of the BTK and ALK during in 150 ns molecular dynamics and simulation. Post simulation analysis and binding energy estimation in MMGBSA further revealed the intensive potential of the olive nutraceuticals in PTK inhibition. This study is therefore expected to widen the use of nutraceuticals from olive in cancer as well as SARS-CoV2 alternative therapy.


A new method for the production of experimental diabetes in rabbits.
Oral administration of 250 mg hydrochlorothiazide/kg, with previous i.v. injection of 4 i.u. soluble insulin or s.c. injection of protamine-zinc insulin, has been found to produce stable hyperglycaemia in rabbits irrespective of sex. It is thought that insulin helps the selective action of hydrochlorothiazide on the beta cells by removing the protective glucose barrier. Although stimulation of glucagon or some extra-pancreatic mechanism at the initial stage could not be altogether ruled out, the central action of the drug is supported by the finding that the hydrochlorothiazide-induced hyperglycaemia was lowered by the sulphonylurea derivative, chlorpropamide.


An interesting two-phase solvent system and its use in preparative isolation of aconitines from aconite roots by counter-current chromatography.
Two-phase solvent system plays crucial role in successful separation of organic compounds using counter-current chromatography (CCC). An interesting two-phase solvent system, composed of chloroform/ethyl acetate/methanol/water, is reported here, in which both phases contain sufficient organic solvents to balance their dissolving capacities. Adjusting the solvent system to get satisfactory partition coefficients (K values) for target compounds becomes relatively simple. This solvent system succeeded in sample preparation of aconitine (8.07 mg, 93.69%), hypaconitine (7.74 mg, 93.17%), mesaconitine (1.95 mg, 94.52%) from raw aconite roots (102.24 mg, crude extract), benzoylmesaconine (34.79 mg, 98.67%) from processed aconite roots (400.01 mg, crude extract), and yunaconitine (253.59 mg, 98.65%) from a crude extract of Aconitum forrestii (326.69 mg, crude extract).


Tumor growth inhibition by simultaneously blocking epidermal growth factor receptor and cyclooxygenase-2 in a xenograft model.
Our previous study revealed that simultaneously targeting epidermal growth factor receptor (EGFR) tyrosine kinase and cyclooxygenase-2 (COX-2) additively or synergistically inhibited growth of squamous cell carcinoma of the head and neck (SCCHN) in vitro. However, an in vivo efficacy of this combined treatment in SCCHN has not been studied. Nude mice were pretreated with control (1% Tween 80), ZD1839 (50 mg/kg) alone, celecoxib (50 mg/kg) alone, or a combination of ZD1839 and celecoxib at the same dosages for 7 days before injection of a human SCCHN cell line Tu212. The animals were continuously treated with the agents 5 days a week for about 11 weeks. Tumor growth in the combined treatment was significantly inhibited compared with the control (P < 0.001), ZD1839 (P = 0.005), or celecoxib (P < 0.001). At the same time, a dramatic delay of tumor progression was observed in the combined treatment compared with all other three groups. Molecular analysis showed that the combined treatment significantly decreased prostaglandin E metabolite production. The cooperative effect of these two agents in combination was also associated with down-regulation of phosphorylated EGFR, phosphorylated extracellular signal-regulated kinase, and phosphorylated signal transducers and activators of transcription 3 levels and reduction of vascular endothelial growth factor and Ki-67 expression. Specifically, gene silencing of both EGFR and COX-2 by small interfering RNA further confirmed the cooperative antitumor effect. The current results strongly suggest that a cooperative effect of the combined treatment on tumor progression is mediated through blocking both EGFR- and COX-2-related pathways. This combination regimen may provide a promising strategy for cancer therapy and chemoprevention in SCCHN.


Ambipolar surface conduction in ternary topological insulator Bi₂(Te₁-xSex)₃ nanoribbons.
We report the composition- and gate voltage-induced tuning of transport properties in chemically synthesized Bi2(Te1-xSex)3 nanoribbons. It is found that increasing Se concentration effectively suppresses the bulk carrier transport and induces semiconducting behavior in the temperature-dependent resistance of Bi2(Te1-xSex)3 nanoribbons when x is greater than ∼10%. In Bi2(Te1-xSex)3 nanoribbons with x ≈ 20%, gate voltage enables ambipolar modulation of resistance (or conductance) in samples with thicknesses around or larger than 100 nm, indicating significantly enhanced contribution in transport from the gapless surface states.


Safety analysis of endoscopic haemostasis using a high-frequency live tissue electric welding device - EKVZ300 PATONMED.
The method of a bipolar high-frequency welding (HFEW) of soft living tissues of animals and humans has been used in various areas of surgery. However, it has not been utilized in endoscopic gastrointestinal procedures yet. HFEW has strong potential to be used in gastrointestinal endoscopic procedures due to the competitive cost of generator devices and due to its proven ability to coagulate vessels of wide diameter as compared to standard electrocautery devices. To investigate the effectiveness of the endoscopic haemostasis using HFEW generator device - 300 PATONMED - in a porcine model of arterial gastrointestinal bleeding. A porcine model of arterial gastrointestinal bleeding was created. A 300 PATONMED set to the "welding" regime and a flexible 7 Fr bipolar coagulation probe with two electrodes on the tip fashioned spirally attached to convey energy were tested. Once bleeding from the artery had been initiated, the bipolar probe was applied to coagulate the bleeding site. Animals were observed for clinical evidence of recurrent bleeding and subsequently were euthanised for histological examination. A total of 10 experiments were successfully completed. An optimal haemostatic effect was achieved with durations of cautery of five to eight seconds in all animals. Continuous observation after haemostasis revealed no evidence of re-bleeding. No systemic side-effects of the technique were observed. Histological examination has shown that the peripheral thermal injury area that surrounded the coagulation zone did not spread beyond the mucosal layer in depth and 2 mm in width. This animal study provided evidence for the safety of an HFEW in the treatment of gastrointestinal bleeding. The advantages of this technology are smokeless operative area, no tissue overheating, minimal necrosis and damage to surrounding gastric tissue, and the fact that the area of HFEW is confined to the area of the electrodes.


Induction of cell death by tospoviral protein NSs and the motif critical for cell death does not control RNA silencing suppression activity.
Groundnut bud necrosis virus induces necrotic symptoms in different hosts. Previous studies showed reactive oxygen species-mediated programmed cell death (PCD) resulted in necrotic symptoms. Transgenic expression of viral protein NSs mimics viral symptoms. Here, we showed a role for NSs in influencing oxidative burst in the cell, by analyzing H2O2 accumulation, activities of antioxidant enzymes and expression levels of vacuolar processing enzymes, H2O2-responsive microRNA 319a.2 plus its possible target metacaspase-8. The role of NSs in PCD, was shown using two NSs mutants: one in the Trp/GH3 motif (a homologue of pro-apototic domain) (NSsS189R) and the other in a non-Trp/GH3 motif (NSsL172R). Tobacco rattle virus (TRV) expressing NSsS189R enhanced the PCD response, but not TRV-NSsL172R, while RNA silencing suppression activity was lost in TRV-NSsL172R, but not in TRV-NSsS189R. Therefore, we propose dual roles of NSs in RNA silencing suppression and induction of cell death, controlled by different motifs.


Cure of a direct carotid cavernous fistula by endovascular stent deployment.
A 53-year-old woman underwent surgical thrombendarterectomy for treatment of artherosclerotic stenoses of her left internal carotid artery (ICA). A Fogarty catheter was used during this operation. The postoperative course was complicated by the development of a sixth cranial nerve palsy, protrusio, chemosis and ciliar injection of both eyes. Digital subtraction angiography showed a direct fistula between the cavernous segment of the left ICA and the cavernous sinus, with early and retrograde opacification of both superior ophthalmic veins. Endovascular occlusion of the fistula was achieved with preservation of the ICA by stent deployment over the rupture site of the ICA, as two detachable balloons could not obliterate the fistula while preserving the ICA patent. Follow-up angiography 7 months after the endovascular treatment confirmed persisting occlusion of the fistula with a patent ICA. Highly flexible porous coronary stents can easily be introduced into tortuous vessels, including the distal ICA. The haemodynamic effects achieved by stent deployment together with two balloons detached in the cavernous sinus may be sufficient to interrupt a direct carotid cavernous fistula.


LRRK2 Knockout Confers Resistance in HEK-293 Cells to Rotenone-Induced Oxidative Stress, Mitochondrial Damage, and Apoptosis.
Leucine-rich repeat kinase 2 (LRRK2) has been linked to dopaminergic neuronal vulnerability to oxidative stress (OS), mitochondrial impairment, and increased cell death in idiopathic and familial Parkinson's disease (PD). However, how exactly this kinase participates in the OS-mitochondria-apoptosis connection is still unknown. We used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 LRRK2 knockout (KO) in the human embryonic kidney cell line 293 (HEK-293) to evaluate the cellular response to the mitochondrial inhibitor complex I rotenone (ROT), a well-known OS and cell death inducer. We report successful knockout of the LRRK2 gene in HEK-293 cells using CRISPR editing (ICE, approximately 60%) and flow cytometry (81%) analyses. We found that HEK-293 LRRK2 WT cells exposed to rotenone (ROT, 50 μM) resulted in a significant increase in intracellular reactive oxygen species (ROS, +7400%); oxidized DJ-1-Cys106-SO3 (+52%); phosphorylation of LRRK2 (+70%) and c-JUN (+171%); enhanced expression of tumor protein (TP53, +2000%), p53 upregulated modulator of apoptosis (PUMA, +1950%), and Parkin (PRKN, +22%); activation of caspase 3 (CASP3, +8000%), DNA fragmentation (+35%) and decreased mitochondrial membrane potential (ΔΨm, -58%) and PTEN induced putative kinase 1 (PINK1, -49%) when compared to untreated cells. The translocation of the cytoplasmic fission protein dynamin-related Protein 1 (DRP1) to mitochondria was also observed by colocalization with translocase of the outer membrane 20 (TOM20). Outstandingly, HEK-293 LRRK2 KO cells treated with ROT showed unaltered OS and apoptosis markers. We conclude that loss of LRRK2 causes HEK-293 to be resistant to ROT-induced OS, mitochondrial damage, and apoptosis in vitro. Our data support the hypothesis that LRRK2 acts as a proapoptotic kinase by regulating mitochondrial proteins (e.g., PRKN, PINK1, DRP1, and PUMA), transcription factors (e.g., c-JUN and TP53), and CASP3 in cells under stress conditions. Taken together, these observations suggest that LRRK2 is an important kinase in the pathogenesis of PD.


Covalent Patterning of Graphene for Controllable Functionalization from Microscale to Nanoscale: A Mini-Review.
Covalent patterning of graphene opens many application possibilities in the field of photonics, electronics, sensors, and catalysis due to order-dependent optical properties, band structure engineering, and processibility and reactivity improvement. Owing to the low reactivity of the graphene basal plane, harsh reagents (e.g., radicals) used for covalent functionalization normally result in poor spatial control, which largely compromises the intrinsic properties of graphene. Therefore, precisely spatial control on covalent patterning of graphene is of great importance. Herein, we summarize recent advances for covalent patterning of graphene from the microscale to nanoscale resolution using different techniques such as laser or electrochemical writing, template-directed growth, and tip-induced nanoshaving.


Bioinformatics analysis of prognostic value and immune cell infiltration of SERPINA1 gene in cutaneous melanoma.
Cutaneous melanoma (CM) has a poor overall prognosis. Immune checkpoint inhibitor (ICI) therapy effectively improves overall survival in individuals with advanced melanoma, but only some patients benefit. Serpin Family A Member 1 (SERPINA1), a type of proteinase inhibitor that is used for many targets, is abnormally expressed and plays a vital role in multiple cancers. However, little is known about the clinical significance of SERPINA1 in CM. The Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) datasets were used to compare SERPINA1 expression levels. The association between SERPINA1 and other clinical factors were examined with R software, and receiver operating characteristic (ROC) curves for identification was developed. The Tumor IMmune Estimation Resource (TIMER) was used to examine the invasion of immune cells, markers for immune cells, and immunological checkpoints. The predictive value of SERPINA1 DNA methylation levels for every CpG was analyzed with the MethSurv web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the roles of genes that interacted with SERPINA1. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict SERPINA1's response to ICIs. SERPINA1 was substantially expressed in CM. Overexpression of SERPINA1 was significantly associated with CM severity. The outcome for individuals with elevated SERPINA1 expression was good (HR =0.54, P<0.001). Using SERPINA1 expression levels, tumors and normal tissues could be reliably differentiated [area under the curve (AUC) =0.889]. Positive associations were found between SERPINA1 in CM and the infiltration of immune cells and immunological checkpoints [programmed cell death-1 (PD-1) and CTLA-4]. The efficacy of immune checkpoint blockade (ICB) in patients with a low expression of SERPINA1 was good. The GO pathway enrichment analysis showed that activation of neutrophil granulocytes participated in enrichment in the immune response pathway. Patients with low SERPINA1 expression had low TIDE scores. SERPINA1 is involved not only in the development and progression of CM but also in the immunological control of CM. Thus, SERPINA1 may serve as a possible biomarker for CM diagnosis, as well as its therapeutic target.


Uncommon Cases of Venous Thromboembolism.
There is a growing incidence of new cases of venous thromboembolismworldwide.Some of these patients do have a predisposition to the development of thrombosis, some of them do however have various risk factors associated with this event, but few of them have unrecognized etiology. This paper aimsto describe different scenarios of venous thromboembolism.


Clinical and molecular findings in a Moroccan family with Jervell and Lange-Nielsen syndrome: a case report.
Jervell and Lange-Nielsen syndrome (Online Mendelian Inheritance in Man 220400) is a rare autosomal recessive cardioauditory ion channel disorder that affects 1/200,000 to 1/1,000,000 children. It is characterized by congenital profound bilateral sensorineural hearing loss, a long QT interval, ventricular tachyarrhythmias, and episodes of torsade de pointes on an electrocardiogram. Cardiac symptoms arise mostly in early childhood and consist of syncopal episodes during periods of stress, exercise, or fright and are associated with a high risk of sudden cardiac death. Jervell and Lange-Nielsen syndrome is caused by homozygous or compound heterozygous mutations in KCNQ1 on 11p15.5 or KCNE1 on 1q22.1-q22.2. We report the case of a 10-year-old Moroccan boy with congenital hearing loss and severely prolonged QT interval who presented with multiple episodes of syncope. His parents are first-degree cousins. We performed Sanger sequencing and identified a homozygous variant in KCNQ1 (c.1343dupC, p.Glu449Argfs*14). The identification of the genetic substrate in this patient confirmed the clinical diagnosis of Jervell and Lange-Nielsen syndrome and allowed us to provide him with appropriate management and genetic counseling to his family. In addition, this finding contributes to our understanding of genetic disease in the Moroccan population.


Telemedicine in the perioperative experience.
Telemedicine, the remote diagnosis and treatment of patients by means of technology, provides an alternative means for patients to gain access to health care services. Telemedicine is a general term that includes the use of various communication technologies, including telephone, email, or videoconferencing. Telemedicine has the potential to reduce inefficiencies in the delivery of healthcare, diminish patient travel and wait times, and increase access to specialists for patients in rural settings. We review the use of telemedicine in the perioperative phase of care for pediatric surgical patients, their caregivers, and surgical providers, including pre-operative assessments, and post-operative follow-up. We also discuss physician billing compliance with remote telemedicine consultation and explore the barriers to adoption among the caregivers of pediatric surgery patients.


MiR-19b/20a/92a regulates the self-renewal and proliferation of gastric cancer stem cells.
Human gastric cancers contain a population of gastric cancer stem cells (GCSCs) that can undergo self-renewal and multipotent differentiation. GCSCs can be enriched with EpCAM+/CD44+ gastric cancer cells. However, the underlying mechanisms controlling the balance of GCSC self-renewal and differentiation remain to be explored. Because miRNAs can regulate cancer cell fates, we compared miRNA expression in tumorspheric cancer cells enriched with GCSCs and more differentiated cells. We found that the miR-17-92 cluster members miR-19b, miR-20a and miR-92a were gradually reduced during the differentiation of GCSCs. Therefore, we speculated that miR-17-92 members might regulate the self-renewal ability of GCSCs. By downregulating miR-19b, miR-20a and miR-92a in EpCAM+/CD44+ GCSCs, or overexpressing them in EpCAM-/CD44- non-GCSC populations, we found that miR-19b, miR-20a and miR-92a could sustain the self-renewal function of GCSCs. Furthermore, we found that miR-19b, miR-20a and miR-92a could also promote the proliferation of gastric cancer cells. miR-17-92 targeted the E2F1 and HIPK1 proteins, which suppressed Wnt-β-catenin signaling. A real-time PCR analysis of miR-19b, miR-20a and miR-92a expression in 97 gastric cancer specimens suggested that miR-92a could be used as an independent prognostic factor in gastric cancer. This study showed that several members of the miR-17-92 cluster, miR-19b, miR-20a and miR-92a, might play important roles in the development of gastric cancer stem cells and that miR-92a has the potential to be used as a predictive prognostic marker in gastric cancer.


Prediction of medium-term outcome in cluster B personality disorder following residential and outpatient psychosocial treatment.
There is a paucity of research concerning the identification of individual characteristics predictive of outcome in the treatment of personality disorders (PDs). In this study, we carried out a predictor analysis of a sample of 73 hospitalized patients with a primary diagnosis of cluster B PD admitted to two different psychosocial programs for PD: (a) long-term inpatient treatment, and (b) a step-down program. Younger age, higher Global Assessment Scale intake scores, longer length of treatment, absence of self-mutilation and avoidant PDs were a significant predictor of outcome at 24-month follow-up. Self-harming patients allocated to the step-down program had higher rates of improvement compared with patients allocated to the long-term inpatient model. The findings may carry potential clinical implications concerning patient selection and treatment delivery for inpatient and outpatient psychosocial programs for cluster B PD. Limitations include a relatively low sample size for a regression analysis, and a larger sample of cluster B patients may be needed to ensure greater reliability of results.


Endoscopic holmium laser excision of intravesical tension-free vaginal tape and polypropylene suture after anti-incontinence procedures.
We report on our technique of endoscopic excision of intravesical tension-free vaginal tape procedure and polypropylene sutures using the holmium laser following various anti-incontinence procedures. Three patients who previously underwent the tension-free vaginal tape, Burch colposuspension and Stamey vesicopexy, respectively, presented with a range of symptoms including hematuria, recurrent urinary tract infection, frequency, urgency and urinary incontinence. Patients were evaluated with history and examination, and all 3 were found to have nonabsorbable intravesical material. There was obvious encrustation over the eroded polypropylene material within the bladder. A 365 microm tip firing holmium laser fiber was inserted through the working channel of the flexible cystoscope. The tape and sutures were successfully excised using a holmium laser output of 1.0 J per pulse at a rate of 10 Hz. Mean operative time was 15 minutes. Holmium laser excision of intravesical polypropylene tape or suture is a minimally invasive solution to the problem of intravesical perforation or erosion following anti-incontinence procedures.


TUMOUR CELLS IN THE CIRCULATING BLOOD OF PATIENTS WITH CARCINOMA OF THE BREAST AND OF THE GASTROINTESTINAL TRACT.
In view of the differences in the frequency of tumour cells in various reported series and the difficulty in reconciling the presence of these cells with survival, three groups of patients were studied in the following manner. In one group of 20 patients with breast cancer, multiple 20-ml. blood samples were studied. In another group of 18 patients, a single 100-ml. sample was used. Using this technique, tumour cells were found in 82.5% of patients in Group 1 and in 89% in Group 2. Similarly, in 44 patients with cancer of the gastrointestinal tract, tumour cells were identified in 70% of the patients, using the multiple-sampling technique. It seems therefore that if a sufficient volume of blood is studied, tumour cells are present in every patient with cancer of the breast and gastrointestinal tract. The presence of tumour cells in the peripheral blood does not mean that hematogenous metastases will invariably develop, and the presence of these cells is only one of many factors responsible for the development of such metastases.


Novel inhibitor discovery against aromatase through virtual screening and molecular dynamic simulation: a computational approach in drug design.
Inhibition of aromatase (CYTP450) as a key enzyme in the estrogen biosynthesis could result in regression of estrogen-dependent tumors and even preventing the promotion of breast cancer. Although today potent steroid and non-steroid inhibitors of aromatase are available, isoflavanone derivatives as natural compounds with least side effects have been described as the candidate for a new generation of aromatase inhibitors. 2a as an isoflavanone derivative is the most potent inhibitor of aromatase, synthesized by Bonfield et al. (2012[7]). In our computational study, the mentioned compound was used as the template for virtual screening. Between 286 selected compounds with 70 % of structural similarity to 2a, 150 of them showed lower docking energy in comparison with 2a. Compound 2a_1 with 11.2 kcal/mol had the lowest docking energy. Interaction of 2a_1 with aromatase was further investigated and compared with 2a and androstenedione (ASD) as a natural substrate of aromatase, through 20 ns of molecular dynamic simulation. Analysis of trajectories showed, while ASD interacts with aromatase through hydrogen bonds and 2a just interacts via hydrophobic forces, 2a_1 not only accommodates in the hydrophobic active site of aromatase in a suitable manner but it also makes a stable coordination with iron atom of aromatase heme group via OB.


Airway mucosal thickening and bronchial hyperresponsiveness induced by inhaled beta 2-agonist in mice.
Patients with chronic persistent asthma require frequent use of inhaled beta(2)-agonist, which may result in aggravation of asthma symptoms. Our recent in vitro study has shown that beta(2)-agonist stimulates the growth of human airway epithelial cell lines. To determine whether beta(2)-agonist likewise affects airway epithelial cell proliferation in vivo and, if so, what the mechanism of action is, we examined the effect of salbutamol on the morphology of murine airways. Seventy-two BALB/c mice were administered aerosolized salbutamol using "flow-through" nose-only inhalation chambers at daily doses of 0.2 to 20 microg for up to 6 weeks. Morphology of tracheal mucosa, labeling of epithelial cells with 5-bromo-2'-deoxyuridine (BrdU), and bronchial responsiveness were assessed. Exposure to salbutamol increased the thickness of tracheal epithelial layer and the number of BrdU-positive epithelial cells in a dose- and time-dependent manner: the values in mice receiving 20 microg salbutamol for 6 weeks were 247% and 642%, respectively, of those in control animals receiving saline solution alone. These effects were inhibited by the mitogen-activated protein (MAP) kinase kinase inhibitors PD98059 and U0126. Salbutamol also caused a decrease in the provocative concentration of methacholine to achieve 400% of baseline enhanced pause. Combined treatment with inhaled budesonide attenuated salbutamol-induced airway morphologic changes and bronchial hyperresponsiveness. beta(2)-agonist stimulates proliferation of airway epithelial cells and produces airway wall thickening in vivo via MAP kinase-dependent pathway, and these effects are prevented by inhaled corticosteroid.


Histopathological types of breast cancer in Nigerian women: a 12-year review (1993-2004).
To determine the commonest histological types of breast cancer in Nigerian women in Edo State and the mean age at diagnosis, we reviewed the histological slides of breast cancer received in the pathology department of University of Benin Teaching Hospital over a twelve-year period (January 1993-December 2004). The clinical data was obtained from the original request form and case notes where necessary. The mean age of the patients was 45.7 (SD= 13.4, SEM = 0.7). Invasive ductal carcinoma (not otherwise specified) constituted the majority of breast cancer accounting for 75.5% while papillary carcinoma was the least common (2.7%). Ductal carcinoma in situ accounted for 6.6%. Breast cancer occur more on the left (53.3%) than the right (45.7%). Bilateral breast cancer was found in only 0.8% of the cases. The frequency of invasive breast cancer is still very high among Nigerian women. Late presentation possibly due to ignorance, alternative medicine and fear of surgery may account for this high prevalence.


ECG signal compression based on Dc equalization and complexity sorting.
In this brief, we present new preprocessing techniques for electrocardiogram signals, namely, dc equalization and complexity sorting, which when applied can improve current 2-D compression algorithms. The experimental results with signals from the Massachusetts Institute of Technology - Beth Israel Hospital (MIT-BIH) database outperform the ones from many state-of-the-art schemes described in the literature.


Application of the Povarov Reaction in Biaryls under Iron Catalysis for the General Synthesis of Dibenzo[a,c]Acridines.
A modified Povarov reaction involving 2'-alkynylbiaryl-2-carbaldehydes and aryl amines with tandem oxidation was performed using catalytic FeCl3. The outcome was an efficient general synthesis of dibenzo[a,c]acridines with moderate to high yields. This method offers simplicity in the preparation of substrates, diverse substrate scope, and high atom economy. The generality of the protocol was verified by synthesizing a tribenzo[a,c,h]acridine derivative. Photophysical properties of the synthesized compounds were also studied. The compounds absorb UV light typically in the range 230-330 nm and emit in the visible range of 400-420 nm.


Bromocriptine does not alter growth hormone (GH) responsiveness to GH-releasing hormone in acromegaly.
GHRH (100 micrograms) and TRH (200 micrograms) were administered to 24 active acromegalic patients before and during chronic bromocriptine (Br) treatment (Br, 10-15 mg/day for 3-5 months) to evaluate the possible effects of the dopamine agonist on GH release induced by these releasing hormones. Mean daily plasma GH levels were reduced by Br treatment from 34 +/- 40 (SD) to 16 +/- 19 ng/ml (P less than 0.01). No significant changes were found when comparing the GH response to GHRH as mean area under the response curve (nanograms per min/ml above the basal) (pretreatment, 5453 +/- 7843; during Br, 7017 +/- 12763 ng/ml . min), and as mean individual peak GH values (pretreatment, 130 +/- 148; during Br, 126 +/- 187 ng/ml) before and during treatment. The percentage GH increase (pretreatment, 340 +/- 354; during Br, 617 +/- 539%) was however significantly higher during Br. Br treatment significantly reduced the GH response to TRH in terms of mean of individual peak levels (from 136 +/- 134 to 60 +/- 52 ng/ml; P less than 0.01) and area under the response curve (from 3142 +/- 3998 to 1331 +/- 1646 ng/min . ml; P less than 0.01). However, the percentage GH increase was not significantly different (pretreatment, 486 +/- 729; during Br, 1059 +/- 1862%). When the patients were divided into Br responders, i.e. mean daily GH reduction during Br of at least 50% below baseline, and nonresponders, the initial response to GHRH was significantly higher in the latter group, but was unaffected by Br treatment in either group. On the contrary, the response to TRH, statistically significant initially only in the Br responder group, was reduced by Br treatment. We suggest that cells sensitive to Br and TRH but not to GHRH (lactotroph-like) and cells sensitive to GHRH but not to Br (pure somatotrophs) may coexist in GH-secreting adenomas.


Successful treatment of infectious endocarditis associated glomerulonephritis mimicking c3 glomerulonephritis in a case with no previous cardiac disease.
We report a 42-year-old man with subacute infectious endocarditis (IE) with septic pulmonary embolism, presenting rapidly progressive glomerulonephritis and positive proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA). He had no previous history of heart disease. Renal histology revealed diffuse endocapillary proliferative glomerulonephritis with complement 3- (C3-) dominant staining and subendothelial electron dense deposit, mimicking C3 glomerulonephritis. Successful treatment of IE with valve plastic surgery gradually ameliorated hypocomplementemia and renal failure; thus C3 glomerulonephritis-like lesion in this case was classified as postinfectious glomerulonephritis. IE associated glomerulonephritis is relatively rare, especially in cases with no previous history of valvular disease of the heart like our case. This case also reemphasizes the broad differential diagnosis of renal involvement in IE.


Terbutaline pharmacokinetics in cows: preliminary data.
The objective of this study was to determine the serum pharmacokinetics of terbutaline in healthy cows. In the initial experiment, terbutaline was administered once as an intravenous (i.v.) bolus to 6 near-term pregnant beef cows within 24 h after parturition at a low but therapeutically relevant dose, 5 microg/kg. A 2nd experiment was conducted in the same cows with a higher dose, 0.5 mg/kg, but an otherwise similar experimental design. The serum concentration of terbutaline was determined by means of high-performance liquid chromatography with fluorescence detection in both experiments. After i.v. administration of 0.5 mg/kg, the mean peak serum concentration, residence time, and half-life were 708.22 (standard deviation 509.6) ng/mL, 6.75 (3.6) min, and 6.93 (2.4) min, respectively. The results indicate that terbutaline is rapidly eliminated from the bloodstream after i.v. administration in cattle, falling below the assay's limit of detection 30 min after administration.


Dual time point fluorodeoxyglucose positron emission tomography/computed tomography in differentiation between malignant and benign lesions in cancer patients. Does it always work?
Assess the added value of dual time point F-18-fluorodeoxyglucose positron emission tomography/computed tomography (DTP F-18-FDG-PET/CT) in the differentiation of malignant from a benign lesion in cancer patients. Totally, 140 F-18-FDG PET/CT scans of 60 cancer patients who underwent DTP protocol (early whole body PET/CT [E] at 60 min [range, 45-76 min] and delayed limited PET/CT [D] on areas of interest at 120 min [range, 108-153 min] after the tracer injection) were retrospectively reviewed. Visual and semi-quantitative analysis was performed on both early and delayed images. All findings were confirmed by histopathology and/or at least 3 months follow-up (F-18-FDG PET/CT, CT, or magnetic resonance imaging). The result was considered true positive (TP) if delayed standardized uptake value (SUV) of suspicious lesions increased and confirmed to be malignant, false positive (FP) if delayed SUV increased and confirmed to be benign, true negative (TN) if delayed SUV unchanged or decreased and confirmed to be benign, and false negative (FN) if delayed SUV unchanged or decreased and confirmed to be malignant. A total of 164 suspicious lesions were detected (20 presacral lesions, 18 lung nodules, 18 Hodgkin's disease (HD) lesions, 16 rectal lesions, 16 head and neck (H and N) lesions, 14 hepatic lesions, 14 non-Hodgkin's lymphoma (NHL) lesions, 12 mediastinal lymph nodes (LNs), 10 focal gastric uptake, 10 soft tissue lesions, 8 breast lesions, 4 peritoneal nodule, and 4 others). Sixty-four lesions were pathologically confirmed, and 100 lesions were confirmed based on 3-6 months follow-up. There were 62 TP lesions, 44 FP, 58 TN and no FN results. The overall sensitivity was 100% of DTP F-18-FDG PET/CT in detecting suspicious lesions. The specificity was 57% in differentiating malignant from benign lesions, and the accuracy was 73%. Positive predictive value was 59%, negative predictive value (NPV) 100%. All hepatic lesions were TP. Accuracy in metastatic hepatic lesions HD, presacral soft tissue, lung nodules, H, and N cancer, breast cancer, NHL and mediastinal LN was100%, 88.8%, 80%, 78%, 75%, 75%, 71%, and 33.3%, respectively. DTP F-18-FDG-PET/CT protocol does not always work in differentiation between benign and malignant lesions. However; it has high NPV, and promising results was noted in hepatic lesions, lymphoma, and recurrent rectal cancer.


[Prenatal investigations for Down's syndrome: medical-technical considerations and dilemmas arising from current screening methods].
Prenatal investigations can be divided into specific diagnostic investigations i.e. chorionic villus sampling, amniocentesis and selective ultrasonography for the detection of fetal abnormality, and screening tests which estimate the chances of the condition being present. These include routine ultrasonography and tests based on biochemical and echoscopic markers. Amniocentesis is the most reliable test to detect chromosomal anomalies, but is associated with a low risk of miscarriage and the results are known only relatively late in pregnancy. Implementing the prenatal screening tests will enable the better identification of those women with an increased risk of chromosomal anomalies, and consequently to fewer invasive diagnostic procedures. The choice whether to have prenatal screening should always be made by the parents after they have been told of the advantages and disadvantages of these investigations.


The use of the category of vulnerability has been multiplied in moral philosophy social sciences and bioethics. Being vulnerable can refer rhetorically to all mortal agents, but also to those lacking agency which makes of it a very ambiguous notion. The notion of vulnerability is part of everyday language and is mostly perceived as a determination which limits our aspirations to autonomy. Why has it become a notion a bioethical principle or concept per se? Historically, anthropology of the vulnerable subject is needed and can be found in the work of Nussbaum and Honneth which could be used in bioethical discourse. The link between care theory and capability of recognition theories developed by Sen and Nussbaum, enrich the picture. Vulnerability we will argue does not have to be from an anthropological point of view, exposition to dependence and exploitation.


Amplifying the red-emission of upconverting nanoparticles for biocompatible clinically used prodrug-induced photodynamic therapy.
A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal β-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP-PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics.


Fluorescent Nanowire Ring Illumination for Wide-Field Far-Field Subdiffraction Imaging.
Here we demonstrate an active method which pioneers in utilizing a combination of a spatial frequency shift and a Stokes frequency shift to enable wide-field far-field subdiffraction imaging. A fluorescent nanowire ring acts as a localized source and is combined with a film waveguide to produce omnidirectional illuminating evanescent waves. Benefitting from the high wave vector of illumination, the high spatial frequencies of an object can be shifted to the passband of a conventional imaging system, contributing subwavelength spatial information to the far-field image. A structure featuring 70-nm-wide slots spaced 70 nm apart has been resolved at a wavelength of 520 nm with a 0.85 numerical aperture standard objective based on this method. The versatility of this approach has been demonstrated by imaging integrated chips, Blu-ray DVDs, biological cells, and various subwavelength 2D patterns, with a viewing area of up to 1000 μm^{2}, which is one order of magnitude larger than the previous far-field and full-field nanoscopy methods. This new resolving technique is label-free, is conveniently integrated with conventional microscopes, and can potentially become an important tool in cellular biology, the on-chip industry, as well as other fields requiring wide-field nanoscale visualization.


Evaluation in mammalian oocytes of gene transcripts linked to epigenetic reprogramming.
The mature mammalian metaphase II (MII) oocyte has a unique ability to reprogram sperm chromatin and support early embryonic development. This feature even extends to the epigenetic reprogramming of a terminally differentiated cell nucleus as observed in connection with somatic cell nuclear transfer. Epigenetic nuclear reprogramming is highly linked to chromatin structure and includes covalent modifications of DNA and core histone proteins as well as reorganization of higher-order chromatin structure. A group of conserved enzymes mediating DNA methylation, methyl-CpG-binding protein (MeCP), histone acetylation and methylation, and chromatin remodeling are extensively involved in epigenetic reprogramming in mammalian cells. Using the oligonucleotide microarray technique, the present study compared the expression levels of 86 genes associated with epigenetic reprogramming in murine in vivo matured MII oocytes with that of germinal vesicle oocytes. Correlation between biological replicates was high. A total of 57 genes with potential reprogramming effect were detected. In MII oocytes, four genes were significant up-regulated, whereas 18 were down-regulated and 35 unchanged. The significantly regulated genes were validated by real-time quantitative RT-PCR. For example, MII oocytes showed a significant down-regulation of oocyte-specific maintenance DNA methyltransferase, Dnmt1o, and up-regulation of MeCP transcript, methyl-CpG binding domain protein 2. Furthermore, histone acetyltransferases were proportionally overrepresented when compared with histone deacetylases. These data elucidate for the first time some of the mechanisms that the oocyte may employ to reprogram a foreign genome either in form of a spermatozoa or a somatic nucleus and may thus be of importance for advancing the fields of stem cell research and regenerative medicine.


Cooperative melting in caged dimers of rigid small molecule-DNA hybrids.
Rigid small-molecule DNA hybrids (rSMDHs) have been synthesized with three DNA strands attached to a rigid tris(phenylacetylene) core. When combined under dilute conditions, complementary rSMDHs form cage dimers that melt at >10 degrees C higher and much sharper than either unmodified DNA duplexes or rSMDH aggregates formed at higher concentrations. With a 2.97 average number of cooperative duplexes, these caged dimers constitute the first example of cooperative melting in well-defined DNA-small-molecule structures, demonstrating the important roles that local geometry and ion concentration play in the hybridization/dehybridization of DNA-based materials.


Case report: concurrent herpesviral and presumptive iridoviral infection associated with disease in cultured shortnose sturgeon, Acipenser brevirostrum (L.), from the Atlantic coast of Canada.
Approximately 8 weeks after a chlorine insult associated with the city water supply, shortnose sturgeon, Acipenser brevirostrum (L.), from one group presented with small (3-4 mm) irregular foci of cutaneous pallor that involved the dorsocranial integument with progressive ulceration of the nascent lesions. Various bacterial organisms were isolated from the cutaneous lesions, but not from the internal viscera. Histologically, the nuclei of the intralesional and perilesional epidermal cells often exhibited margination of the chromatin that resulted in a homogenous, pale, amphophilic, tinctorial quality of the nucleoplasm consistent with a herpesvirus infection. In addition, rare lamellar epithelial cells were prominently enlarged due to an abundant, dense, basophilic cytoplasm characteristic of an iridovirus infection. Inoculation of cutaneous lesion and kidney, spleen, liver sample pools from affected shortnose sturgeon onto white sturgeon spleen (WSS-2) cell line induced cytopathic effect characterized by syncytia formation. Ultrastructural analysis of infected WSS-2 cells revealed viral particles with a characteristic herpesvirus morphology. Intranuclear hexagonal capsids had a diameter of 95-108 nm, and enveloped particles present in the cytoplasm of infected cells had a diameter of 176-196 nm. This is the first report of a herpesvirus and a possible iridovirus-like infection in shortnose sturgeon.


A novel topoisomerase 2a inhibitor, cryptotanshinone, suppresses the growth of PC3 cells without apparent cytotoxicity.
DNA topoisomerase 2, which is ubiquitously expressed in eukaryotic cells, is an essential nuclear enzyme that promotes cell survival by regulating DNA topology and chromatid separation. This enzyme has been validated as a target for anticancer agent screening. It can be poisoned by common chemotherapeutics, such as etoposide and doxorubicin, which leads to the accumulation of cytotoxic enzyme-linked DNA double-stranded breaks. However, recent studies have suggested that the topoisomerase 2a isozyme is predominantly responsible for the carcinogenic side effects associated with etoposide and doxorubicin chemotherapy. Thus, we need to find a promising topoisomerase 2-targeting anticancer agent that avoids these carcinogenic side effects. Recent studies have found that cryptotanshinone has obvious anticancer activities against diverse cancer cells. Here, we demonstrate that cryptotanshinone markedly decreases the steady-state mRNA level of topoisomerase 2a, thereby decreasing the protein and activity levels of this enzyme. Moreover, cryptotanshinone exhibited dramatic in vitro and in vivo antitumor activity with low toxicity to normal tissues. Collectively, our findings support the development of cryptotanshinone as a promising candidate for treating cancer by targeting topoisomerase 2a.


Cobalt diselenide nanobelts grafted on carbon fiber felt: an efficient and robust 3D cathode for hydrogen production.
Design and fabrication of low-cost, highly efficient and robust three-dimensional (3D) hierarchical structure materials for electrochemical reduction of water to make molecular hydrogen is of paramount importance for real water splitting applications. Herein, a 3D hydrogen evolution cathode constructed by in situ growing of cobalt diselenide nanobelts on the surface of commercial carbon fiber felt shows exceptionally high catalytic activity with 141 mV overpotential to afford a current density of 10 mA cm-2, and a high exchange current density of 5.9 × 10-2 mA cm-2. Remarkably, it also exhibits excellent catalytic stability, and could be used for more than 30 000 potential cycles with no decrease in the current density in 0.5 M H2SO4. This easily prepared 3D material with excellent electrocatalytic performance is promising as a realistic hydrogen evolution electrode.


On the dissociation and association of Escherichia coli ribosomes.
The dissociation and association behaviour of 70-S ribosomes of Escherichia coli has been studied. It has been shown that the dissociation-association reaction can be both a real dynamic equilibrium and a non-equilibrium reaction, dependent upon the ionic conditions of the solvent. At relatively high ionic strength (I = 0.15 M or more) the dissociation-association reaction is an equilibrium reaction, whereas at lower ionic strength (I = 0.1 M or less) there is no dynamic equilibrium between 70-S ribosomes and its subunits. In the latter case a hysteresis in the dissociation-association reaction is observed. Whether there is a dynamic equilibrium or not can be demonstrated by a single centrifugation experiment, using the analytical ultracentrifuge.


The institutional turn in professional ethics.
The traditional ideal in which professionals alone or in small groups serve their patients and clients in accord with a public-spirited goal is giving way to practice in which professionals serve in organizations that value mainly their expertise and expect them to act in accord with the organization's goals. The study of professional ethics has not kept pace with this trend and, as a result, has neglected the institutional aspects of ethical problems. I focus attention on these aspects by considering a case that raises 2 problems that are particularly relevant in the context in which professionals now practice: the problem of representation (whom does the professional act for) and the problem of authority (who has the right to make the policy for the institution).


Assessment of Anteroposterior Subpedicular Approach and Oblique Scotty Dog Subpedicular Approach for Selective Nerve Root Block.
The technique used to administer a selective nerve root block (SNRB) varies depending on individual expertise. Both the anteroposterior (AP) subpedicular approach and oblique Scotty dog subpedicular approach are widely practiced. However, the literature does not provide a clear consensus regarding which approach is more suitable. Hence, we decided to analyse the procedural parameters and clinical outcomes following SNRBs using these two approaches. Patients diagnosed with a single lumbar herniated intervertebral disc (HIVD) refractory to conservative management but not willing for immediate surgery were selected for a prospective nonrandomized comparative study. An SNRB was administered as a therapeutic alternative using the AP subpedicular approach in one group (n = 25; mean age, 45 ± 5.4 years) and the oblique Scotty dog subpedicular approach in the other group (n = 22; mean age, 43.8 ± 4.7 years). Results were compared in terms of the duration of the procedure, the number of C-arm exposures, accuracy, pain relief, functional outcome and the duration of relief. Our results suggest that the oblique Scotty dog subpedicular approach took a significantly longer duration (p = 0.02) and a greater number of C-arm exposures (p = 0.001). But, its accuracy of needle placement was 95.5% compared to only 72% using the AP subpedicular approach (p = 0.03). There was no significant difference in terms of clinical outcomes between these approaches. The AP subpedicular approach was simple and facile, but the oblique Scotty dog subpedicular approach was more accurate. However, a brief window period of pain relief was achieved irrespective of the approaching technique used.


Quasiparticle energy spectra of alkali-metal clusters: all-electron first-principles calculations.
A good approximation to the one-electron self-energy operator in the calculation of quasiparticle energy spectra including the first ionization potential (IP) and electron affinity (EA) is to expand it as a simple product of a one-particle Green's function G and a dynamically screened Coulomb interaction W, namely, GW approximation. We developed a spin-polarized version of the all-electron GW approach and applied it to the first-principles calculation of quasiparticle energy spectra of alkali-metal clusters (Na(n) and K(n), n=1-8). Our all-electron mixed basis approach, in which wave functions are expressed as a linear combination of numerical atomic orbitals and plane waves, enables us to compare the absolute values of the singly (or highest) occupied molecular orbital and the lowest unoccupied molecular orbital levels with available experimental IPs and EAs. The agreements with the corresponding experimental values are fairly good. Comparing with the non-spin-polarized results of Na(2n) and K(2n) (n=1-4), we discuss the effect of spin polarization as well as the cluster size dependence of IPs or EAs.


Asymmetric Total Synthesis of Illisimonin A.
The discovery of illisimonin A in 2017 extended the structural repertoire of the Illicium sesquiterpenoids─a class of natural products known for their high oxidation levels and neurotrophic properties─with a new carbon backbone combining the strained trans-pentalene and norbornane substructures. We report an asymmetric total synthesis of (-)-illisimonin A that traces its tricyclic carbon framework back to a spirocyclic precursor, generated by a tandem-Nazarov/ene cyclization. As crucial link between the spirocyclic key intermediate and illisimonin A, a novel approach for the synthesis of tricyclo[5.2.1.01,5]decanes via radical cyclization was explored. This approach was applied in a two-stage strategy consisting of Ti(III)-mediated cyclization and semipinacol rearrangement to access the natural product's carbon backbone. These key steps were combined with carefully orchestrated C-H oxidations to establish the dense oxidation pattern.


Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study.
Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin. This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg(-1) day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls. A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study. The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment.


Optimal control for micro-algae on a raceway model.
We apply numerical optimal control methods to an existing algae growth model with the aim to determine the best performance of the model under known conditions using a variety of decision variables. We transform the system of differential algebraic equations in the existing model to a system of ordinary differential equations which introduces dynamics for average light intensity and chlorophyll. In addition, we allow for variable nitrogen concentration of the inflow as well as variable initial nitrogen concentration of the raceway. Our main focus is on optimizing of the production of lipids. We calculate both open and closed loop optimal controllers and test their robustness. Finally, we also consider raceway depth as a decision variable. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:107-119, 2018.


[Dual x-ray absorptiometry in the diagnosis of osteoporosis].
The author presents a review providing information on contemporary modern radiological possibilities as regards the diagnosis of osteoporosis at the First Orthopaedic Clinic in Bratislava. At present this department possesses a densitometer LUNAR DPX-L. This apparatus assesses the bone density on the basis of double X-ray absorption. The software available at present makes it possible to assess the bone density of the lumbar spine in the anterio-posterior and lateral projection, as well as the proximal femur and whole body. The mean time required for assessment is 4 mins. 24 secs. to 16 mins. 30 secs. The mean radiation load of the patient is 1.5 mrem, the maximal load 3.5 mrem. The apparatus compares the assessed density values with mean values of the healthy population, it evaluates automatically statistical values of the Z and T score. These results are presented either as a coloured graph or as values of bone mineral density and bone mineral content. The author explains in more detail the principle of modern densitometry and its development during the past three decades.


Engineering of mesostructured silicas by pseudomorphism.
Pseudomorphic transformation is introduced as an effective and versatile method to independently optimize the morphology of the grains and the structural properties of mesostructured silicas. In this account a short overview is given of the preparation of MCM-41 and MCM-48 mesophases as non-aggregated and homogeneously distributed particles with sizes ranging from 5 to 800 microm.


Patterns of Neurological Recovery After Anterior Decompression With Fusion and Posterior Decompression With Laminoplasty for the Treatment of Multilevel Cervical Spondylotic Myelopathy.
The pattern of neurological recovery in the overall modified Japanese Orthopedic Association scores, upper limb function score, and lower limb function score after surgical decompression for patients suffering from multilevel cervical spondylotic myelopathy (CSM) were analyzed in this independent retrospective study. The primary objective of this retrospective study was to compare the upper and lower limb function changes after anterior decompression with fusion versus posterior decompression with laminoplasty for patients suffering from multilevel CSM. An additional objective was to describe the neural recovery speed. Few comparative studies have been conducted to evaluate the outcome of anterior versus posterior surgery in multilevel CSM. However, these assessments tend to be of a more global perspective, looking at a composite score for upper limb, lower limb, and bladder function. No reports have separately analyzed the upper and lower limb function changes after anterior and posterior decompression for multilevel CSM. A total of 132 patients were classified into anterior and posterior decompression groups based on the different surgical approach they underwent. The pattern of neurological recovery in the overall modified Japanese Orthopedic Association scores, upper limb function score, and lower limb function score after surgical decompression were documented and analyzed. There was no significant difference in the overall neurological recovery between anterior and posterior decompression groups. But in terms of the upper or lower limb function changes after operation, it appeared that the upper limbs recovered better with anterior decompression. The surgical approach did not significantly alter lower extremity recovery potential. In addition, most of the neurological recovery occurred in the first 9 months after surgical decompression. We recommend a individualized approach when it is difficult to determine an anterior or posterior surgery for multilevel CSM. Rehabilitation training should be carried out as early as possible.