Modeling Tube Clearance and Bounding the Effect of Friction in Concentric Tube Robot Kinematics.
The shape of a concentric tube robot depends not only on the relative rotations and translations of its constituent tubes, but also on the history of relative tube displacements. Existing mechanics-based models neglect all history-dependent phenomena with the result that when calibrated on experimental data collected over a robot's workspace, the maximum tip position error can exceed 8 mm for a 200-mm-long robot. In this paper, we develop a model that computes the bounding kinematic solutions in which Coulomb friction is acting either to maximize or minimize the relative twisting between each pair of contacting tubes. The path histories associated with these limiting cases correspond to first performing all tube translations and then performing relative tube rotations of sufficient angle so that the maximum Coulomb friction force is obtained along the interface of each contacting tube pair. The robot tip configurations produced by these path histories are shown experimentally to bound position error with respect to the estimated frictionless model compared to path histories comprised of translation or mixed translation and rotation. Intertube friction forces and torques are computed as proportional to the intertube contact forces. To compute these contact forces, the standard zero-clearance assumption that constrains the concentrically combined tubes to possess the same centerline is relaxed. The effects of clearance and friction are explored through numerical and physical experiments and it is shown that friction can explain much of the prediction error observed in existing models. This model is not intended for real-time control, but rather for path planning-to provide error bounds and to inform how the ordering of tube rotations and translations can be used to reduce the effect of friction.


Modern sialography for screening of salivary gland obstruction.
To revisit and reintroduce sialography as an important tool for the assessment and diagnosis of salivary gland obstruction. A sample of 30 consecutive patients undergoing sialography was selected. Parotid sialography was performed in 22 patients (12 females and 10 males). The patients undergoing parotid sialography presented with bilateral or unilateral enlargement or swelling. Submandibular sialography was performed in 8 patients (all males) who had presented with swelling and pain in the affected gland. Parotid sialography revealed 6 cases of sialolithiasis without significant duct narrowing, 3 of narrowing and strictures of Stensen's duct without a sialolith, 3 glands with gland sialectasis, 1 parotid gland with intraglandular cyst-like duct degeneration, 1 of a parotid mass displacing Stensen's duct, and 1 gross dilation of duct. The findings of 7 parotid gland sialograms were normal. Submandibular gland sialography revealed the presence of sialolithiasis (single and multiple) in 4 patients, narrowing of the duct in 2, and normal findings in 2. Sialography is a simple technique and an important tool for the assessment of salivary gland obstruction in patients presenting with sialadenitis.


Trends of congestive heart failure epidemiology: contrast with clinical trial results.
Congestive heart failure (CHF) is an important and growing public health problem and the cause of substantial morbidity and mortality. Its increasing incidence and prevalence may be in part explained by the progressive aging of the world population. The improvement in coronary artery disease and hypertension treatment allows the individuals to lie longer and develop CHF. Indeed, the most common etiology of CHF is coronary artery disease, the leading cause of cardiovascular morbidity and mortality worldwide, and the second cause of CHF is hypertension which is still markedly increasing in developing countries. Estimates of prevalence of CHF are 0.4 to 2% of the general population. The number of hospital admissions for CHF has also been steadily increasing. Half of the patients carrying a diagnosis of CHF will die within 4 years and patients with severe CHF will die within 1 year. At present, there is no evidence that the prognosis of heart failure in the community has changed despite the advances in therapy over the past decades, such as the demonstration that angiotensin-converting enzyme inhibitors and other vasodilators improve the clinical signs and symptoms of patients with CHF, reduce mortality and slow the progression of myocardial dysfunction. Nevertheless, the overall mortality from this condition remains very high. It is possible that the results of the trials have not yet been evidenced in the majority of patients with CHF because the ideal conditions, treatment and follow-up in the trials are not yet widely achieved in the population.


Effects of oral administration of heparan sulphate in the rat remnant kidney model.
Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 +/- 22 vs. 80 +/- 54 mg/24 h, p < 0.01), lower urea plasma levels (75 +/- 34 vs. 134 +/- 105 mg/dl, p < 0.01) and higher creatinine clearance (66 +/- 15 vs. 47 +/- 21 ml/min. 10(2), p < 0.05) than control rats. Remnant kidney weight (2.3 +/- 1.1 vs. 1.3 +/- 0.2 g, p < 0.01) and heart weight (1.3 +/- 0.2 vs. 1.1 +/- 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 +/- 19 vs. 115 +/- 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.


[Radiographic visualization of pleural space under negative pleural pressure].
Although many imaging modalities have developed in the area of pulmonary medicine, information about the condition of pleural surface is limited. In this study, we carried out contrast pleurography under negative pleural pressure in dogs and humans to evaluate the condition of the pleural space including adhesion between the two pleural layers, incomplete fissure and features of the pleural surface. After insertion of a flower-type catheter into the pleural space under ultrasonic guidance, contrast material (60% Meglumine iotalamate, Conray 60, 0.5-1.0 ml/kg) was injected into the pleural space through the catheter. In dogs with intact pleura, contrast material distributed to the pulmonary surface, including interlobar spaces, rapidly. In dogs with pleural adhesion which was induced artificially with talc, affected areas were visualized as defects of contrast material. In humans, this contrast pleurography provided information about pleural adhesion, pulmonary lobulation, extent of cancer to neighbouring lobes, irregular pleural surface due to bullae formation and pleural indentation by cancerous lesion. There was no serious complication in dogs and human studies. This contrast pleurography is unique because it is possible to evaluate the pleural space physiologically under negative pressure condition. It may be concluded that this method of pleurography is useful for the clinical evaluation of the condition of the pleura in various lung diseases.


Exploring patient perceptions of movement through the stages of change model within a diabetes tele-care intervention.
Achieving strict control of diabetes is challenging for many patients and most need regularly to depend on ongoing support from health care professionals. One approach that might successfully provide this in a cost-effective and acceptable way is the delivery of advice and support over the telephone (tele-care). To date the process and effects of tele-care have however rarely been studied. This article explores the potential of one behavioural model, the trans-theoretical stages of change model (TTM), to understand and theorize about behaviour change for this chronic disease. Case study data are drawn from a wider randomized controlled trial (RCT) set up to assess the effectiveness of a pro-active call centre-based stepped treatment support to people with type 2 diabetes. The case study demonstrates the relevance and importance of the TTM model in this area. Different experiential and behavioural processes were of particular significance and held different meanings for the various change groups.


Neurological complications following adult lung transplantation.
The full spectrum of neurologic complications and their impact on survival in lung recipients has not been reported. A retrospective cohort review of the Mayo Clinic Lung Transplant Registry (1988-2008) was performed to determine the range of neurologic complications in a cohort of adult lung recipients. Cox regression models were used to assess risk factors for neurological complications and death posttransplant. One hundred and twenty lung transplant recipients (53% women, median age at transplantation 53 years, range 21-73, median survival 4.8 years) were identified, of whom 95 had a neurological complication posttransplantation (median time to complication 0.8 years). Neurological complications were severe in 46 patients (requiring hospitalization or urgent care and evaluation) and were most often perioperative stroke or encephalopathy. Age predicted neurological complications of any type, whereas lung allocation score, bilateral lung transplantation, sex, underlying lung disease, elevated hemoglobin A1C, renal insufficiency and smoking history did not. Neurological complications of any severity (HR 4.3, 95% CI 2.2-8.6, p < 0.001) and high severity (HR 7.2, 95% CI 3.5-14.6, p < 0.001) were associated with increased risk of death. Neurological complications are common after lung transplantation, affecting 92% of recipients within 10 years. Severe neurologic complications are also common, affecting 53% of recipients within 10 years.


Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers.
Chronic fatigue syndrome (CFS) is defined according to subjective symptoms only, and several conflicting case definition exist. Previous research has discovered certain biological alterations. The aim of the present study was to explore possible subgroups based on biological markers within a widely defined cohort of adolescent CFS patients and investigate to what extent eventual subgroups are associated with other variables. The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) has previously performed detailed investigation of immunological, autonomic, neuroendocrine, cognitive and sensory processing functions in an adolescent group of CFS patients recruited according to wide diagnostic criteria. In the present study, hierarchical cluster analyses (Ward's method) were performed using representative variables from all these domains. Associations between clusters and constitutional factors (including candidate genetic markers), diagnostic criteria, subjective symptoms and prognosis were explored by standard statistical methods. A total of 116 patients (26.7% males, mean age 15.4 years) were included. The final cluster analyses revealed six clusters labelled pain tolerant & good cognitions, restored HPA dynamics, orthostatic intolerance, low-grade inflammation, pain intolerant & poor cognitions, and high vagal (parasympathetic) activity, respectively. There was substantial overlap between clusters. The pain intolerant & poor cognitions-cluster was associated with low functional abilities and quality of life, and adherence to the Canada 2003 diagnostic criteria for CFS. No other statistically significant cluster associations were discovered. Within a widely defined cohort of adolescent CFS patients, clusters could be delineated, but no distinct subgroups could be identified. Associations between clusters and constitutional factors, subjective symptoms and prognosis were scarce. These results question the clinical usefulness of searching for CFS subgroups, as well as the validity of the most "narrow" CFS diagnostic criteria. Clinical Trials NCT01040429.


[Bone and Men's Health. The role of androgens in bone metabolism].
Testosterone is the major gonadal sex steroid produced by the testis and act as strong androgen. The adrenal glands produce the weaker androgens dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. These gonadal and adrenal androgens collectively affect skeletal homeostasis in both men and women. Because of the high prevalence of osteoporosis in women, investigators have been concerned especially in estrogen to resolve the mechanisms of bone metabolism. Estrogens play greater role in maintenance of skeletal health than testosterone, the current evidence suggests that androgens also have direct beneficial effects on bone metabolism. Androgens have anti-osteoporotic effect via direct interaction with androgen receptors, as well as effects mediated by estrogen receptors after aromatization to estradiol.


Bis(4-fluoro-benz-yl-κC)bis-(3-methyl-sulfanyl-1,2,4-thia-diazole-5-thiol-ato-κN,S)tin(IV).
The mononuclear title molecule, [Sn(C(7)H(6)F)(2)(C(3)H(3)N(2)S(3))(2)], has 2 symmetry. The Sn(IV) atom, located on a twofold rotation axis, is in a skew trapezoidal-bipyramidal geometry, with the basal plane defined by two S,N-chelating 3-methyl-sulfanyl-1,2,4-thia-diazole-5-thiol-ate ligands. The apical positions are occupied by the C atoms of two 4-fluoro-benzyl groups.


General and cardiac toxicity of doxorubicin-loaded gelatin nanoparticles.
General and cardiac toxicity of doxorubicin loaded gelatin nanoparticles cross-linked by glutaraldheyde were investigated in healthy rats. The rats were treated with free doxorubicin (DXR), unloaded nanoparticles (UNp), physical mixture of doxorubicin and unloaded nanoparticles (DRX/UNp), and DXR-loaded nanoparticles (DXR-Np). Each group of animals received the same dose of DXR (3 mg/kg) via i.p. once a week. Both electrocardiogram (ECG) parameters and body weight were measured 24 h before each administration. Rats treated with UNp behaved as controls. DXR/UNp provoked the same toxic effects as free DXR. On the contrary, DXR-Np resulted more toxic since significant variations of both the body weight and the ECG parameters were observed during the first week of treatment. In addition, the rats treated with DXR-Np died between the 3rd and the 5th day after the 2nd administration. These results demonstrate that, in these experimental conditions, the couplage of DXR to nanoparticles enhanced the cardiotoxicity of the drug. Since DXR was linked to the protein matrix of nanoparticles via glutaraldehyde, the high toxicity of DXR-loaded nanoparticles could be due to the covalent binding of the drug to the carrier.


Histochemical Evidence for the Occurrence of Oligomycin-sensitive Plasmalemma ATPase in Corn Roots.
A cytochemical study has been made on the localization of ATPase activity in corn (Zea mays L.) roots. Light microscopy shows washing for 4 hours to increase the general ATPase activity in the peripheral layers of the root cortex; oligomycin and N,N-dicyclohexylcarbodiimide inhibit this activity, oligomycin being more effective. Ultrastructural studies of ATPase location show oligomycin treatment to inhibit both mitochondrial and plasmalemma ATPase, but only in the epidermis and outer cortex. Studies with lipid-soluble dyes indicate that oligomycin might not penetrate very deeply into root tissue in the time span of these experiments. It is suggested that the strong inhibition of ion absorption by oligomycin without a corresponding decline in ATP content is probably due to inhibition of ion absorption in the peripheral cell layers, thus limiting the supply of ion for symplastic transport to the uninhibited tissues.


Calculation of energy expenditure in women using the MET system.
Interpretation of physical activity as energy expenditure requires adjustment for body size. This is usually accomplished by means of the MET system, which assumes a basal metabolic rate (BMR) of 4.184 kJ.kg(-1).h(-1) and, when the standard calculation is used, that the energy costs of different activities are proportional to BMR. These relationships may be altered by increases in percent total body fat (% TBF), and this paper examines relationships between % TBF and total energy expenditure (TEE) obtained using the standard and a proposed calculation. Published data regarding body composition, physical activity (heart rate recording), and BMR in 11 American women (before and after weight gain) and in 15 Swedish women (before and during pregnancy) were used to calculate TEE. Reference estimates of TEE were obtained using doubly labeled water. In Swedish women, reference TEE minus standard TEE (MJ.24 h(-1)) was 1.37 +/- 1.29 (P < 0.01) before and 1.03 +/- 1.13 (P < 0.05) during pregnancy. For proposed TEE these differences were 0.43 +/- 1.63 (P > 0.05) and 0.31 +/- 1.28 (P > 0.05) (MJ.24 h(-1)), respectively. In American women before and after weight gain, reference TEE minus standard TEE (MJ.24 h(-1)) were 0.38 +/- 1.79 (P > 0.05) and 1.39 +/- 2.36 (P > 0.05), respectively, whereas the corresponding differences for proposed TEE (MJ.24 h(-1)) were -0.52 +/- 2.20 (P > 0.05) and 0.21 +/- 2.36 (P > 0.05), respectively. In Swedish women before pregnancy and American women after weight gain (N = 26, BMI = 18-39), significant (P < 0.001) relationships were found for standard TEE/proposed TEE (y) versus % TBF, (x, r = -0.65) and versus BMI (x, r = -0.70). : In individuals with a TBF content typical for contemporary Western women, standard TEE is lower than proposed TEE. This bias increases as the TBF content of subjects increases. The results indicate that proposed TEE is more accurate than standard TEE, but this requires confirmation.


Molecular characterization of a novel big defensin from clam Venerupis philippinarum.
Antimicrobial peptides (AMPs) are important mediators of the primary defense mechanism against microbial invasion. In the present study, a big defensin was identified from Venerupis philippinarum haemocytes (denoted as VpBD) by RACE and EST approaches. The VpBD cDNA contained an open reading frame (ORF) of 285 bp encoding a polypeptide of 94 amino acids. The deduce amino acid sequence of VpBD shared the common features of big defensin including disulfide array organization and helix structure, indicating that VpBD should be a new member of the big defensin family. The mRNA transcript of VpBD was up-regulated significantly during the first 24 hr after Vibrio anguillarum challenge, which was 7.4-fold increase compared to that of the control group. Then the expression decreased gradually from 24 hr to 96 hr, and the lowest expression level was detected at 96 hr post-infection, which was still 3.9-fold higher than that of control. The mature peptide of VpBD was recombined in Escherichia coli and purified for minimum inhibitory concentration (MIC) determination. The rVpBD displayed broad-spectrum inhibitory activity towards all tested bacteria with the highest activity against Staphyloccocus aureus and Pseudomonas putida. These results indicated that VpBD was involved in the host immune response against bacterial infection and might contribute to the clearance of invading bacteria.


Chemical, microbial, color, oxidative and sensory properties of clean-label pastırma produced with raspberry water extracts as a novel ingredient.
In recent years, plant extracts are used as colorant and antioxidant in meat products. Therefore, the effects of cemen pastes produced using different concentrations (0%, 3%, 4% and 5%) of raspberry water extract (RWE) on pastırma were investigated. RWE was tested to improve the color quality of pastırma and decrease lipid and pigment oxidation during production and storage at 4 °C for 150 days. Increasing RWE concentration in cemen paste reduced pH, TBARS (P < 0.05) and lactic acid bacteria counts (P < 0.01) of pastırma, while redness values (P < 0.05) increased compared to control sample without extract. The use of RWE contributed to improve sensory attributes of pastırma, and the groups with 4% and 5% RWE had the highest sensory scores. Also, the color and oxidative stabilities of the pastırma containing RWE were maintained better than control during storage period (P < 0.01). The overall results suggested that use of 4.0% or 5.0% RWE as a new additive in cemen paste can be considered an antioxidant and colorant for pastırma processing to prevent color and lipid oxidation.


Cultural assessment in home healthcare.
As the nurse becomes adept at performing cultural assessments and culturally competent care, it will become clear that "although it is critical to conduct a cultural assessment with culturally and ethnically diverse groups, it is also important to realize that every client needs a cultural assessment. Every client has values, beliefs, and practices that must be considered when a clinician renders healthcare services. Therefore, cultural assessments are not limited to specific ethnic groups, but rather should be conducted on each individual" (Campinha-Bacote, 1995, p.148). Nurses who have been identified as good transcultural nurses have been found to be empathetic, caring, open, and flexible. They have a positive attitude toward cultural differences and have a genuine interest in learning from the client about the client's culture (Emerson, 1995). Talabere (1996) states that openness, appreciation of another's perspective, holistic communication, genuine interest, and a nonjudgmental attitude are central to cultural sensitivity. When a culturally sensitive nurse develops mutually agreeable goals with a patient from another culture, a kind of cultural synergy occurs, resulting in care that is "meaningful, satisfying and beneficial to clients" (Leininger, 1988, p.155).


Prevalence of Internet Addiction and its Correlates Among Regular Undergraduate Medicine and Health Science Students at Ambo University. Cross-Sectional Study.
Internet addiction (IA) is causing academic failure, decreased concentration ability, and a negative affective state. In Ethiopia, studies conducted on IA were limited; therefore, this study aimed to assess its prevalence and risk factors among medicine and health science (MHS) students of Ambo University. This study was a cross-sectional study and included MHS students of Ambo University from July 15 to August 15, 2021. Data were collected using a self-administered questionnaire after receiving informed consent from study participants. The results were analyzed using the statistical software for social sciences version 24. Bivariate and multivariate logistic regressions were performed to explore the relationship between IA and dependent variables. Of the 253 participants who participated in the study, 201 (79%) were found to have an IA. Having one's own computer, Internet access at home and an email account were 2 times more risky to develop IA compared to their counterparts with AOR = 2.615 (95% CI = 1.118-5.956) with a P value of .022, AOR = 2.154 (95% CI = 1.054-4.405) with a P value of .35 and (=2.154 (95% CI = 1.054-4.405 with a P value of .035 respectively. Additionally, those who use the Internet for news were 2.5 times more likely to develop IA compared to those who do not (AOR = 2.551 (95% CI = 1.225-5.349) with a P-value of .013). The use of the Internet for scientific research and education reduces IA by 0.7 times (AOR = 0.323 (95% CI = 0.120-0.868) with a P value of .025). The prevalence of IA was found to be high in this study. Therefore, strategies are needed to minimize the prevalence of this problem.


Metabolic effects of thia fatty acids.
Thia substituted fatty acids are saturated fatty acids which are modified by insertion of a sulfur atom at specific positions in the carbon backbone. During the last few years pleiotropic effects of the 3-thia fatty acid tetradecylthioacetic acid have been revealed. The biological responses to tetradecylthioacetic acid include mitochondrial proliferation, increased catabolism of fatty acids, antiadiposity, improvement in insulin sensitivity, antioxidant properties, reduced proliferation and induction of apoptosis in rapidly proliferating cells, cell differentiation and antiinflammatory action. These biological responses indicate that tetradecylthioacetic acid changes the plasma profile from atherogenic to cardioprotective. As a pan-peroxisome proliferator-activated receptor ligand, tetradecylthioacetic acid regulates the adipose tissue mass and the expression of lipid metabolizing enzymes, particularly those involved in catabolic pathways. In contrast, circumstantial evidences suggest that peroxisome proliferator-activated receptor-independent metabolic pathways may be of importance for the antioxidant, antiproliferative and antiinflammatory action of tetradecylthioacetic acid.


Pyrazinamide Resistance Assays and Two-Month Sputum Culture Status in Patients with Multidrug-Resistant Tuberculosis.
Phenotypic drug susceptibility testing is the current "gold standard" for detecting Mycobacterium tuberculosis susceptibility to antituberculous drugs. Pyrazinamide is one antituberculous drug for which the correlation between in vitro resistance and clinical outcomes remains unclear. Here we performed latent class analysis (LCA) to develop a consensus gold standard definition of pyrazinamide resistance using three paired standard pyrazinamide resistance assays. We then compared this consensus measure to the 2-month culture results for patients with multidrug-resistant tuberculosis (MDR-TB) who were treated for 2 months with first-line antituberculous drugs before their resistance results were known. Among 121 patients with MDR-TB, 60 (49.6%) were resistant to pyrazinamide by the Wayne method (L. G. Wayne, Am Rev Respir Dis 109:147-151, 1974), 71 (58.7%) were resistant by the Bactec MGIT 960 method, and 68 (56.2%) were resistant by pncA sequencing. LCA grouped isolates with positive results by at least two assays into a category which we considered the "consensus gold standard" for pyrazinamide resistance. The sensitivity and specificity for this consensus gold standard were 82.4% and 92.5%, respectively, for the Wayne method; 95.6% and 88.7%, respectively, for the Bactec MGIT 960 method; and 92.6% and 90.6%, respectively, for pncA sequencing. After we adjusted for other factors associated with poor outcomes, including age, sex, alcohol use, and baseline ethambutol resistance, patients whose isolates were resistant by the LCA-derived consensus gold standard were more likely to be culture positive at 2 months with an odds ratio of 1.95 (95% confidence interval, 0.74 to 5.11), but this result was not statistically significant. These findings underscore the need for improved diagnostics for routine use in programmatic settings.


[Clinical management of the most important cancers in older patients].
The clinical management of cancer in senior adult patients is based on the results of clinical trials which were performed in adults, generally younger adult patients. It is therefore difficult to assess the feasibility of such treatments, mainly chemotherapy, in older patients. The evaluation of health status is an important step in the decision making of cancer treatment in senior adults. In non Hodgkin lymphomas, the standard treatment remains chemotherapy with Rituximab. Specific protocols and treatment adaptation have been proposed in very old seniors. Surgery is a very efficient treatment in breast cancer, colorectal cancer and sometimes in non small cell lung cancer. Radiotherapy is important in the curative management of prostate cancer and in the multidisciplinary treatment of breast, colorectal and lung cancers. Chemotherapy is generally feasible in senior adults. However, Cisplatin is often too much toxic. Chemotherapy has a palliative impact in the treatment of metastatic prostate and breast cancers. It would be discussed in some high-risk groups of patients with breast and colorectal cancers. New targeted drugs are active in breast, colorectal cancers and in non Hodgkin lymphomas. Indications of treatment tailored on health status evaluation are discussed in the manuscript.


[A study on health examination services under the Health Service Law for the Aged--multiple logistic regression analysis of service methods and the service-acceptance rate].
A survey on health services provided in accordance with the Health Service Law for the Aged was conducted in 3,278 cities, wards, towns, and villages throughout Japan in May 1985. Responses were returned from 2,645 districts and data on beneficiaries of these health services in 2,625 districts became available. Because the exact number of people constituting the subjects of health services could not be obtained, the service-acceptance rate was calculated by the number of people utilizing the services divided by the those in the population who were at least 40 years old. The service-acceptance rate was affected by both the size of the population of the local community and the methods of implementation of health services. Therefore, the mutual effects of population size and service methods were corrected by logistic regression analysis to find the relationship between methods of implementing health services and the response rate of the public in accepting the services. The service-acceptance rate was divided into two categories: one less than 30% and the other 30% and over. Odds ratios were calculated for an acceptance ratio of 30% and over. The results were summarized as follows: 1. In the jurisdictions where the local organizations cooperated in notifying citizens about the results of their general health examination, in comparison with the areas where there was no cooperation, the odds ratio was found to be 2.40. A similar comparison was made between the communities with local cooperation for notification of a general health examination and those communities without it. The odds ratio for the former was found to be 1.66.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinicopathologic and Immunohistochemical Characteristics of Solitary Fibrous Tumor and Its Mimics: A Single-Center Experience.
Solitary fibrous tumor (SFT) is a fibroblastic tumor that has been originally reported as a pleural tumor but now has been defined as a tumor that can be seen everywhere in the human body. Histopathologically, many of the fibroblastic tumors can mimic SFT, and immunohistochemistry is necessary for differential diagnosis. Several markers have been used, and recently, STAT6 has been introduced as a diagnostic marker. No research study has been reported from Iran. In this report, we are trying to introduce our experience about the clinicopathologic findings of 35 cases of SFT during the last 10 years from our center with an emphasis on the diagnostic role of STAT6 in this tumor. During the last 10 years, we confirmed the diagnosis of 35 cases of SFT in the pathology archives of Shiraz University of Medical Sciences. These 35 cases were considered as cases. All the clinicopathologic findings were also extracted from the clinical charts of the patients. To evaluate the diagnostic role of STAT6, another 35 cases of spindle cell tumors were also extracted from the pathology archives as mimickers of SFT. STAT6 was stained in all of the 70 cases and controls. Our experience showed that SFT is more common in middle-aged men with a wide age range, although it is very rare in children. It can be present in every location with a wide size range from less than 1 cm to more than 15 cm. The presence of abnormal staghorn vessels is one of the main diagnostic histopathologic characteristics. STAT6 showed a sensitivity and specificity of 91% and 86% in the diagnosis of SFT. Other markers such as CD99, CD34, and BCL2 have also been considered useful in the differential diagnosis of this tumor, although the diagnostic accuracy seems to be lower than STAT6. High mitosis, presence of necrosis, and atypia are important criteria for predicting malignant and aggressive behavior in SFT. Among 35 cases in our study, 17% showed malignant behavior as recurrent or metastatic tumors. Solitary fibrous tumor is a common soft tissue tumor that can be seen everywhere and needs careful histopathologic and immunohistochemical evaluation for the correct diagnosis and prediction of aggressive or benign behavior.


Anticoagulant rodenticide intoxication in east China: a three-year analysis.
The study was designed to analyze the incidence and pattern of anticoagulant rodenticide intoxication in east China and to discuss strategies of diagnosis based on laboratory analysis experience. A total of 117 patients with anticoagulant rodenticide poisoning confirmed by toxicological analysis in east China were included in this study from 2011 to 2013. The mean concentration of anticoagulant rodenticide, age, and gender of these patients, as well as the mode and type of poisoning, were discussed. The age ranged from less than 1 to 80 years with the feeble preponderance of males (M = 53.0%, F = 47.0%). The 0-9 age group covered the largest ratio of these anticoagulant rodenticide poisoning patients. Accidental or voluntary ingestion seems to be the most common cause of intoxication, with still the poisoning cause being unknown for a large number of positive analyses. Bromadiolone was the most commonly observed anticoagulant rodenticide found in the biological samples, followed by brodifacoum. The concentrations of bromadiolone and brodifacoum that were detected in the first collected whole blood from each patient ranged from 1 to 878 ng/mL (mean 97.9 ng/mL) and from 0.5 to 1566 ng/mL (mean 225.1 ng/mL), respectively. The data analysis shows a high incidence of anticoagulant rodenticide poisoning without awareness of the poisoned subjects, clearly emphasizing the need for toxicological analysis in patients with vitamin K-dependent coagulation disorder and restriction on availability of anticoagulant rodenticide.


[Eosinophilic cystitis. A survey].
The purpose of this study was to evaluate the incidence, diagnostic criteria and treatment of eosinophilic cystitis in the period 1989-94 in Denmark. A questionnaire was sent to all Danish surgical, urological and pathological-anatomical departments. Fifty-six patients were diagnosed as having eosinophilic cystitis at the surgical departments and 135 patients were diagnosed at the pathological-anatomical departments. The treatment was most often instillation of steroids in the bladder or oral antihistamine. Success of treatment was generally acceptable. The questionnaire confirmed that eosinophilic cystitis is a rare disease. We recommend the pathological-anatomical departments to use certain diagnostic criteria for eosinophilic cystitis. The treatment is symptomatic. A diagnostic number from the Danish Health Board is needed.


Whole body barometric plethysmography: a screening method to investigate airway reactivity and acute lung injuries in freely moving pigs.
The aim of this work was to investigate whether the Penh index, measured using whole body barometric plethysmography, can be used as a screening parameter to evaluate the airway reactivity and the intensity of the pulmonary response to endotoxins. Penh was firstly recorded in non-sedated freely moving piglets exposed (1) to a nebulized acetylcholine (Ach) pre-treated or not with clenbuterol, or (2) to endotoxin challenge. To measure Penh simultaneously with total pulmonary resistance (R(L)), dynamic compliance (C(dyn)) and intrapleural pressure changes (Max Delta Ppl), an oesophageal balloon catheter technique was used and the piglets were anaesthetised. The recordings were performed during (1) an intravenous metacholine (Mch) challenge and (2) in endotoxin-exposed animals. In freely moving animals, Ach induced a significant dose-dependent increase in Penh, which was significantly blocked by clenbuterol. Endotoxin instillation also resulted in a significant rise in Penh while the corresponding response measured under anaesthesia was significantly and positively correlated with R(L) and Max Delta Ppl. Similar results were obtained during Mch challenge but the Penh was negatively correlated with C(dyn). We conclude that Penh could be used in freely moving piglets as a screening index for airway reactivity and pulmonary functional changes in cholinergic and endotoxin challenges.


Duplicated tramadol use in chronic low back pain: A nationwide cross-sectional study.
Tramadol is a weak opioid that is commonly used for chronic low back pain (LBP). Despite its effectiveness, duplicated use of tramadol, which may indicate abuse or dependence, may exacerbate potential adverse reactions. This population-based, cross-sectional study aimed to investigate the prevalence of duplication of tramadol and its associated factors among patients with LBP. From a Korean nationwide claims database, non-hospitalized patients aged 40-99 years with LBP without malignancy were prescribed tramadol during 2014-2016. Duplication of tramadol was defined as overlapping of prescription days. Among them, we defined "extensive duplication (ED)" when days of tramadol duplication cover 10% or more of the days prescribed tramadol. Patient and healthcare utilization factors associated with ED were examined using a logistic regression model. The study population was 6 417 503 patients. Of these, 13.7% were ED users. The age- and sex-standardized prevalence of using tramadol twice or more a year was 14.06 per 100 people in 2014, 13.74 per 100 people in 2015 and 13.52 per 100 people in 2016. ED occurred more in those in the group aged 70-79 years (OR 1.12, 95% CI 1.11-1.13) than 40-49 years and in those with comorbidities, such as drug abuse (OR 2.99, 95% CI 2.05-4.36) or depression (OR 1.75, 95% CI 1.72-1.77). Based on the results of this study, a proper management system is needed to avoid tramadol duplication among older people and patients with drug abuse or depression.


Dietary fat and risk of type 2 diabetes.
Nutrition recommendations emphasize that not only dietary fat quantity but also fat quality plays a role in the prevention of type 2 diabetes (T2D). The aim of this review is to summarize the evidence for dietary fat and risk of T2D, to highlight recent findings and point out future research directions. Total fat intake was not associated with risk of T2D, whereas the findings on fatty acids (FAs) and risk of T2D were controversial. Recent findings suggested that FAs from the same classes (e.g. omega-6 FAs) but different sources might be differently associated with the risk of T2D, with indication for an association with lower risk of T2D for plant-based and higher risk/no association for animal-based FAs. In addition, differences between populations from different geographic areas might exist, but no interaction effects for fat intake and genetic predisposition were observed regarding T2D risk. The simultaneous investigation of different fats and dietary patterns can provide important and meaningful insights into these associations. The evidence for the association between dietary fat intake and risk of T2D is not conclusive yet. To strengthen the evidence, the complexity of the different associations of dietary fats should be considered in well conducted future studies.


Development and use of miRNA-derived SSR markers for the study of genetic diversity, population structure, and characterization of genotypes for breeding heat tolerant wheat varieties.
Heat stress is an important abiotic factor that limits wheat production globally, including south-east Asia. The importance of micro (mi) RNAs in gene expression under various biotic and abiotic stresses is well documented. Molecular markers, specifically simple sequence repeats (SSRs), play an important role in the wheat improvement breeding programs. Given the role of miRNAs in heat stress-induced transcriptional regulation and acclimatization, the development of miRNA-derived SSRs would prove useful in studying the allelic diversity at the heat-responsive miRNA-genes in wheat. In the present study, efforts have been made to identify SSRs from 96 wheat heat-responsive miRNA-genes and their characterization using a panel of wheat genotypes with contrasting reactions (tolerance/susceptible) to heat stress. A set of 13 miRNA-derived SSR markers were successfully developed as an outcome. These miRNA-SSRs are located on 11 different common wheat chromosomes (2A, 3A, 3B, 3D, 4D, 5A, 5B, 5D, 6A, 6D, and 7A). Among 13 miRNA-SSRs, seven were polymorphic on a set of 37 selected wheat genotypes. Within these polymorphic SSRs, three makers, namely HT-169j, HT-160a, and HT-160b, were found promising as they could discriminate heat-tolerant and heat-susceptible genotypes. This is the first report of miRNA-SSR development in wheat and their deployment in genetic diversity and population structure studies and characterization of trait-specific germplasm. The study suggests that this new class of molecular makers has great potential in the marker-assisted breeding (MAB) programs targeted at improving heat tolerance and other adaptability or developmental traits in wheat and other crops.


Rapid detection of hypervariable regions by the polymerase chain reaction technique.
The polymerase chain reaction (PCR) technique has provided a substantial improvement for the detection and analysis of known genetic polymorphisms. Here, we describe the application of this method for the detection of variable number of tandem repeat (VNTR) sequences. With the use of unique oligonucleotide primers, flanking the repeat sequence, and the thermostable Taq DNA polymerase, the hypervariable regions 3' of the Ha-ras gene, 3' of the apolipoprotein B gene, and 5' to the joining segments of the heavy-chain immunoglobulin gene could be amplified. Alleles up to 2,000 bp could be visualized directly on ethidium bromide-stained agarose gels. Larger alleles were seen only after traditional Southern blot analysis with an internal probe. The value of this new approach for the detection of VNTRs is illustrated in a case of paternity dispute.


Multiplex PCR-based reverse line blot hybridization assay to identify 23 Streptococcus pneumoniae polysaccharide vaccine serotypes.
We developed a multiplex PCR-based reverse line blot assay to identify 23 pneumococcal serotypes represented in the polysaccharide vaccine, using 334 well-characterized isolates, representing all 90 serotypes, and 268 "unknowns." The assay identified all target serotypes, but 11, which cross-react with 1 to 4 nonvaccine serotypes, could be distinguished using serotype-specific antisera.


Development of a New Route for Separating and Purifying 4-Ethyl-2-methoxyphenol Based on the Reaction Mechanism between the Chemical and Calcium Ion.
Based on the characteristic that Ca2+ can react with 4-ethyl-2-methoxyphenol (EMP) to form a complexation with a phenol-calcium ratio of 4:1, a new extraction and purification method of EMP is developed for the first time in this work. At an optimum purification condition, 99.60% purity of EMP can be obtained through a reaction and decomposition operation. By combining a variety of characterizations, which consist of in situ Fourier transform infrared spectrometer (FTIR), nuclear magnetic resonance (NMR), inductively coupled plasma optical emission spectrometer (ICP-OES), gas chromatography-mass spectrometry (GC-MS)/flame ionization detector (FID), elemental analysis, and thermogravimetric analysis, the reaction mechanism of the coordination process is studied. It is demonstrated that there are three stages of the coordination reaction between Ca2+ and EMP. A neutralization reaction occurs in the first stage, while the second stage is a mixing reaction stage including neutralization and coordination reaction. When the reaction proceeds to the third stage, another coordination reaction occurs. Furthermore, phenol and ethanol are added as impurities in EMP. EMP with a purity of more than 99.50% can be obtained using this purification method. It confirms that this efficient method can achieve a good purification effect even for EMP solutions with complicated components.


Predicting success on the certification examinations of the American Board of Anesthesiology.
Currently, residency programs lack objective predictors for passing the sequenced American Board of Anesthesiology (ABA) certification examinations on the first attempt. Our hypothesis was that performance on the ABA/American Society of Anesthesiologists In-Training Examination (ITE) and other variables can predict combined success on the ABA Part 1 and Part 2 examinations. The authors studied 2,458 subjects who took the ITE immediately after completing the first year of clinical anesthesia training and took the ABA Part 1 examination for primary certification immediately after completing residency training 2 yr later. ITE scores and other variables were used to predict which residents would complete the certification process (passing the ABA Part 1 and Part 2 examinations) in the shortest possible time after graduation. ITE scores alone accounted for most of the explained variation in the desired outcome of certification in the shortest possible time. In addition, almost half of the observed variation and most of the explained variance in ABA Part 1 scores was accounted for by ITE scores. A combined model using ITE scores, residency program accreditation cycle length, country of medical school, and gender best predicted which residents would complete the certification examinations in the shortest possible time. The principal implication of this study is that higher ABA/ American Society of Anesthesiologists ITE scores taken at the end of the first clinical anesthesia year serve as a significant and moderately strong predictor of high performance on the ABA Part 1 (written) examination, and a significant predictor of success in completing both the Part 1 and Part 2 examinations within the calendar year after the year of graduation from residency. Future studies may identify other predictors, and it would be helpful to identify factors that predict clinical performance as well.


The efficiency of the sets and the cuscore techniques under biased baseline rates.
Statistical techniques used for surveillance of disease incidence rates are generally based on the assumption of known baseline rate of the disease monitored, whereas actually it is an estimate obtained from a large sample. As a result, the time interval until true or false alarm is shorter or longer than assumed. In this study, we evaluate the performance of the sets and of the cuscore techniques when the estimate of the baseline rate is biased. We evaluate the effect of an underestimated baseline rate with respect to frequency of false alarms and to that of an over estimated rate with respect to the delay until elicitation of a true alarm. We evaluate the effects of 5 per cent and 10 per cent bias in the estimated baseline rate for specified conditions associated with sparse data. The results show that the effect of plus or minus 5 per cent bias in the estimate are moderate and those of 10 per cent are substantial. In general, the effect of an overestimated baseline rate is greater on the sets technique than it is on the cuscore technique and the effect of an underestimated rate is greater on the cuscore technique than it is on the sets technique. However, the differences between the two techniques are small on both perspectives. The two methods differ also with respect to the expected time until true alarm when the specified baseline rate is unbiased. The sets technique is the more efficient in detecting a two-fold increased rate when the number of diagnoses expected annually (E(X)) is less than 1.62, and the cuscore is the more efficient technique when E(X) > 1.62. We use the term 'turning point' to define the regions in which the sets technique and the cuscore techniques are preferred. With an estimated baseline rate that is 5 per cent higher than the actual rate, the turning point falls from 1.62 to 1.45 when the rate is twice the baseline rate, and from 5.75 to 4.34 when the rate is triple the baseline rate.


Relative contribution to speech intelligibility of different envelope modulation rates within the speech dynamic range.
The contribution of envelope cues at different rates to intelligibility in a competing-speech task was measured as a function of the short-term envelope level. The target and background mixture was processed using tone vocoders. Envelope signals for each vocoder channel were simultaneously extracted with two low-pass filters, the cutoff frequency of one filter (L) being two octaves below that of the other (H). The envelope from the H filter was used at the peaks and that from the L filter at valleys, or vice versa. This was achieved by cross-fading between the two envelope signals based on a "switching threshold" that was parametrically varied relative to the long-term RMS level of the channel signal. When the cutoff frequencies of the H and L filters were 50 and 12.5 Hz, changes in speech intelligibility occurred mainly when the switching threshold was between -18 and +10 dB. The range was slightly narrower when the cutoff frequencies of the H and L filters were 200 and 50 Hz. Intensity-importance functions for higher-rate envelope modulations suggested that levels ranging from 20 dB below to about 10 dB above the channel RMS level were important, with maximum importance for levels around -5 dB.


Advances in the understanding of diabetes mellitus.
The American Diabetic Association held its 64th Scientific Sessions on June 4-8, 2004, in Orlando, Florida, USA. The meeting was devoted to developments in different areas of diabetes mellitus research: epidemiology; understanding of diabetic microvascular and macrovascular complications; various modes of treatment including complementary and alternative medicine; new targets in the treatment of the disease, including islet cell transplantation; and the approach to the concept of good quality of care.


Nitric oxide modulates expression of matrix metalloproteinase-9 in rat mesangial cells.
Nitric oxide modulates expression of matrix metalloproteinase-9 in rat mesangial cells. High-output levels of nitric oxide (NO) are produced by rat mesangial cells (MCs) in response to proinflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) by the inducible isoform of NO synthase (iNOS). We tested modulatory effects of NO on the expression and activities of matrix metalloproteinases-9 and -2 (MMP-9 and MMP-2), respectively. Temporal and spatial expression of these MMPs and their specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), seems to be critical in the extensive extracellular matrix (ECM) remodeling that accompanies sclerotic processes of the mesangium. Methods and Results. Using the NO donors S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) and DETA-NONOate, we found strong inhibitory effects of NO mainly on the IL-1beta-induced MMP-9 mRNA levels. NO on its own had only weak effects on the expression of MMP-9 and MMP-2. The addition of the NOS inhibitor NG-monomethyl L-arginine (L-NMMA) dose dependently increased steady-state mRNA levels of cytokine-induced MMP-9, suggesting that endogenously produced NO exerts tonic inhibition of MMP-9 expression. MMP-9 activity in conditioned media from MCs costimulated with IL-1beta and NO donor contained less gelatinolytic activity than media of cells treated with IL-1beta alone. Exogenously added NO did not alter gelatinolytic activity of MMP-9 in cell-free zymographs. The expression levels of TIMP-1 were affected by NO similarly to the expression of MMP-9. We conclude that NO modulates cytokine-mediated expression of MMP-9 and TIMP-1 in rat MCs in culture. Our results provide evidence that NO-mediated attenuation of MMP-9 gelatinolytic activity is primarily due to a reduced expression of MMP-9 mRNA, and not the result of direct inhibition of enzymatic activity.


A novel missense mutation of the XBP1 gene in diffuse large B-cell lymphoma.
The differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, B lymphocyte-induced maturation protein 1 (BLIMP1) and X-box-binding protein 1 (XBP1). XBP1 is a positively acting transcription factor in the CREB/ATF family that is expressed at a high level in plasma cells, and Xbp1-deficient mice were devoid of plasma cells, demonstrating that XBP1 is crucial for plasmacytic differentiation. XBP1 acts downstream of BLIMP1 and regulates a variety of genes encoding endoplasmic reticulum-associated proteins. We have previously reported mutations in the PRDM1 gene (previously BLIMP1) in 2 of 15 cases of B-cell lymphoma. Here, we describe a novel mutation in the XBP1 gene in 1 of 5 cases of B-cell lymphoma. A single-base substitution was found in exon 1 (227G>A) of the XBP1 gene in a patient with diffuse large B-cell lymphoma, resulting in a somatic missense mutation (R76K). To date, no mutations in the XBP1 gene in B-cell lymphoma have been reported. Taken together with previous reports, the present results suggest that two key transcription factors for the plasmacytic differentiation, XBP1 and BLIMP1, are involved in the pathogenesis in diffuse large B-cell lymphoma.


Dutch pharmacogenetics working group guideline for the gene-drug interaction of ABCG2, HLA-B and Allopurinol, and MTHFR, folic acid and methotrexate.
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the gene-drug interaction of ABCG2 with allopurinol, HLA-B with allopurinol, MTHFR with folic acid, and MTHFR with methotrexate, relevant for the treatment of gout, cancer, and rheumatoid arthritis. A systematic review was performed based on which pharmacotherapeutic recommendations were developed. Allopurinol is less effective in patients with the ABCG2 p.(Gln141Lys) variant. In HLA-B*58:01 carriers, the risk of severe cutaneous adverse events associated with allopurinol is strongly increased. The DPWG recommends using a higher allopurinol dose in patients with the ABCG2 p.(Gln141Lys) variant. For HLA-B*58:01 positive patients the DPWG recommends choosing an alternative (for instance febuxostat). The DPWG indicates that another option would be to precede treatment with allopurinol tolerance induction. Genotyping of ABCG2 in patients starting on allopurinol was judged to be 'potentially beneficial' for drug effectiveness, meaning genotyping can be considered on an individual patient basis. Genotyping for HLA-B*58:01 in patients starting on allopurinol was judged to be 'beneficial' for drug safety, meaning it is advised to consider genotyping the patient before (or directly after) drug therapy has been initiated. For MTHFR-folic acid there is evidence for a gene-drug interaction, but there is insufficient evidence for a clinical effect that makes therapy adjustment useful. Finally, for MTHFR-methotrexate there is insufficient evidence for a gene-drug interaction.


Antioxidant enzyme peroxiredoxin 5 is upregulated in degenerative human tendon.
Peroxiredoxin 5 (PRDX5) is a novel thioredoxin peroxidase recently identified in a variety of human cells and tissues, which is considered to play an important role in oxidative stress protection mechanisms. However, little is known about its expression in tendon degeneration, a common and disabling condition that primarily affects older people, in which oxidative stress may be implicated. The present study demonstrated that normal human tendon expresses PRDX5 and its expression is significantly increased in degenerative tendon. In addition, we have localized PRDX5 to fibroblasts in normal tendon and to both fibroblasts and endothelial cells in degenerate tendon. The differential expression of PRDX5 in normal and degenerate tendon shows that a thioredoxin peroxidase with antioxidant properties is upregulated under pathophysiological conditions and suggests that oxidative stress may be involved in the pathogenesis of tendon degeneration. PRDX5 may play a protective role against oxidative stress during this pathophysiological process.


Fibromuscular dysplasia of the superior mesenteric artery--case report and review of the literature.
Fibromuscular dysplasia is a multifactorial arteriopathy most commonly affecting the renal and carotid arteries. In this report we present a case of visceral artery involvement, causing occlusion of the superior mesenteric artery and celiac trunk and resulting in visceral ischemia. Treatment consisted of superior mesenteric artery reimplantation. Visceral artery FMD can present as occlusive or aneurysmal disease and treatment depends on patient characteristics and symptoms.


Iron-mediated reduction rates and pathways of halogenated methanes with nanoscale Pd/Fe: analysis of linear free energy relationship.
The influence of halogen substitution in chlorinated methanes and brominated methanes on their abiotic reductive dehalogenation with nanoscale Pd/Fe bimetallic particles was investigated in this study. The 0.2% and 1.0% Pd/Fe particles, with particle sizes of less than 100nm, were synthesized in the laboratory. Reduction of the halogenated methanes with the Pd/Fe particles followed pseudo-first-order kinetics. The Pd/Fe bimetallic particles demonstrated at least an order of magnitude higher in reactivity compared to the unpalladized Fe particles of similar particle size. Comparing the 0.2% Pd/Fe and the 1.0% Pd/Fe particles, the latter exhibited higher reduction rates of various halogenated methanes. On the other hand, the reduction rates of chlorinated methanes were consistently lower than those of their brominated counterparts. The compounds with higher number of halogen substitutions were more readily reduced than the lightly halogenated ones. Coupled hydrogenolysis-elimination processes were the important mechanism for complete dehalogenation of the chlorinated and brominated methanes. From the kinetic examination of their transformation rates and mechanistic insight into the associated pathways, an attempt to analyze linear free energy relationship between the observed kinetics and the associated thermodynamic constants was performed. The observed reaction rate constants were analyzed for their correlations with one-electron potential (E(1)), two-electron potential (E(2)), bond dissociation energy (BDE) and the lowest unoccupied molecular orbital (LUMO) energy (E(LUMO)). LUMO energy appeared to be the best descriptor for the kinetic prediction, while E(1) and E(2) might be more suitable for mechanistic analysis.


Pleiotropic effects of YC-1 selectively inhibit pathological retinal neovascularization and promote physiological revascularization in a mouse model of oxygen-induced retinopathy.
Vascular endothelial growth factor (VEGF) and inducible nitric-oxide synthase (iNOS) have been implicated in ischemia-induced retinal neovascularization. Retinal ischemia has been shown to induce VEGF and iNOS expression. It has been postulated that one of the crucial consequences of iNOS expression in the ischemic retina is the inhibition of angiogenesis. Furthermore, iNOS was shown to be overexpressed in Müller cells from patients with diabetic retinopathy. YC-1, a small molecule inhibitor of hypoxia-inducible factor (HIF)-1 alpha, has been shown to inhibit iNOS expression in various tissue models. Our aim was to assess the pleiotropic effects of YC-1 in an oxygen-induced retinopathy (OIR) mouse model and evaluate its therapeutic potential in HIF-1- and iNOS-mediated retinal pathologies. Dual-injections of YC-1 into the neovascular retinas decreased the total retinopathy score, inhibited vaso-obliteration and pathologic tuft formation, and concomitantly promoted physiological retinal revascularization, compared with dimethyl sulfoxide (DMSO)-treated group. Furthermore, YC-1-treated retinas exhibited a marked increase in immunoreactivities for CD31 and von Willebrand factor and displayed significant inhibition in HIF-1alpha protein expression. Furthermore, YC-1 down-regulated VEGF, erythropoietin, endothelin-1, matrix metalloproteinase-9, and iNOS message and protein levels. When hypoxic Müller and neuoroglial cells were treated with YC-1, iNOS mRNA and protein levels were reduced in a dose-dependent fashion. We demonstrate that YC-1 inhibits pathological retinal neovascularization by exhibiting antineovascular activities, which impaired ischemia-induced expression of HIF-1 and its downstream angiogenic molecules. Furthermore, YC-1 enhanced physiological revascularization of the retinal vascular plexuses via the inhibition of iNOS mRNA and protein expressions. The pleiotropic effects of YC-1 allude to its possible use as a promising therapeutic iNOS inhibitor candidate for the treatment of retinal neovascularization.


[Case of radial nerve injury induced by withdrawing a catheter from the cephalic vein].
There are many reports of neuropathic pain describing nerve injuries sustained by sticking or penetrating nerves by metal needles on venipuncture. However, there was no previous report of neuropathic pain caused by withdrawing a catheter from the vein as in this case. Neuropathic pain in this case was quickly cured by intravenous ketamine hydrochloride and stellate ganglion block. The neuropathic pain occurred when a medical student withdrew a catheter from the cephalic vein during clinical training. Clinical training of medical students is very important for medical education, but we must also recognize that this training involves many risks not only for patients but also for the students.


[Comparative study of bovine adrenodoxin and renorenodoxin].
The ferredoxin from bovine renal mitochondria (renoredoxin) has been obtained in a highly purified state. The A415/A280 ratio of the purified renoredoxin is 0.84. The absorption spectrum of renoredoxin was shown to be identical to that of bovine adrenodoxin. Two forms of renoredoxin (Mr 14200 and 13300) were detected by using polyacrylamide gel electrophoresis. These forms exhibit a very similar immunologic cross-reactivity with polyclonal antibodies to adrenodoxin. The N-terminal amino acid sequence of renal ferredoxin was shown to be identical to that of adrenodoxin; the C-terminal sequences of both ferredoxins undergo a similar post-translational proteolytic modification. The amino acid composition of ferredoxins are also very close. Renal ferredoxin can be replaced by adrenodoxin in reconstituted systems from bovine adrenal cortex mitochondria which catalyze the side chain cleavage of cholesterol to pregnenolone and the 11 beta-hydroxylation of deoxycorticosterone to corticosterone.


Endothelin and collecting duct sodium and water transport.
The renal collecting duct (CD) produces and binds more endothelin (ET)-1 than any other region of the kidney. ET-1 has the potential to act as an autocrine regulator of CD function since ET-1 is secreted abluminally and ET receptors are located primarily on the basolateral side of the CD cell. A large number of in vitro studies have supported this notion of an autocrine function for ET-1, demonstrating that the peptide, largely through activation of the ET(B) receptor, inhibits both sodium (Na) and water reabsorption in the CD. The physiologic relevance of these findings has been confirmed in vivo wherein mice with CD-specific knockout of ET-1 are hypertensive on a normal Na diet and develop worsened hypertension associated with Na retention when placed on a high-Na diet. Similarly, CDET-1-deficient mice demonstrate enhanced responsiveness to vasopressin and an impaired ability to excrete an acute water load. CD-specific knockout of both ET(A) and ET(B) receptors together causes a similar hypertensive and Na-retaining phenotype. The mechanisms by which ET-1 exerts its effects on CD Na and water reabsorption are being increasingly understood. ET-1 inhibits epithelial Na channel (ENaC) activity through src- and mitogen-activated protein kinase-dependent pathways; channel number is also reduced by a β1Pix-dependent mechanism. In addition, nitric oxide is an important modulator of ET-1 actions on the ENaC, although the mechanism by which this occurs remains to be determined. ET-1 reduces CD water reabsorption by inhibition of vasopressin-stimulated adenylyl cyclase activity through G(i) and protein kinase C-dependent pathways, leading to a reduction in cellular cAMP levels. Taken together, these findings indicate that the CD ET system is an important physiologic regulator of systemic blood pressure and volume homeostasis.


S-100 immunoreactive cells in non-nervous duck tissues.
S-100 protein was detected in endocrine cells of the islet of Langerhans, hypophysis, ultimobranchial body, proventriculus, gizzard and intestine, and epithelial cells of the interlobular bile duct, gall bladder, renal tubules and epididymal and urinary ducts except for the nerve elements in the duck. Sertoli cells and oocytes were also S-100-protein immuno-reactive. The types of S-100-protein-positive cells detected in the duck differ from those of mammalian species.


Quantification of ATP-producing and consuming processes in quiescent pig spleen lymphocytes.
ATP production in quiescent pig spleen lymphocytes was estimated on the basis of their coupled respiration. ATP-consuming processes were assessed from the effects of inhibitors of protein synthesis, proteolysis, RNA synthesis, Na+ K(+)-ATPase and Ca(2+)-ATPase on respiration. About 95% of the total ATP consumption could be assigned to specific processes. More than 50% of the ATP produced appear to be consumed by the cation transport ATPases.


AG488 as a therapy against gliomas.
High-grade gliomas such as glioblastomas (GBM) present a deadly prognosis following diagnosis and very few effective treatment options. Here, we investigate if the small molecule AG488 can be an effective therapy against GBM with both anti-angiogenic as well as an anti-microtubule inhibiting modalities, using a human G55 glioma xenograft model in nude mice. From in vitro studies, we report that AG488 incubation reduced cell viability in G55 and HMEC-1 cells more so than TMZ treatment, and AG488 treatment also decreased cell viability in normal astrocytes, but not as much as for G55 cells (p<0.0001). In vivo investigations indicated that AG488 therapy helped reduce tumor volumes (p<0.0001), prolong survival (p<0.01), increase tumor perfusion (p<0.01), and decrease microvessel density (MVD) (p<0.05), compared to untreated mice or mice treated with non-specific IgG, in the G55 xenograft model. Additionally, AG488 did not induce apoptosis in normal mouse brain tissue. Animal survival and tumor volume changes for AG488 were comparable to TMZ or anti-VEGF therapies, however AG488 was found to be more effective in decreasing tumor-related vascularity (perfusion and MVD). AG488 is a potential novel therapy against high-grade gliomas.


[Advanced dermatofibrosarcoma protuberans treated with imatinib mesylate].
To evaluate the efficacy, side effects and toxicity of imatinib mesylate in the treatment of patients with locally advanced and/or metastatic dermatofibrosarcoma protuberans (DFSP). Twenty-four cases of advanced DFSP diagnosed by pathology and treated in our hospital from Nov. 2004 to Oct. 2009 were included in this study. The patients were treated with imatinib mesylate (dosage: 400 mg, po, qd) and carefully observed for treatment efficacy, side effects and survival time. There were 2 patients taking the drug as second line therapy, and other 22 patients as third or more than third line therapy. The 24 patients were evaluable for the efficacy. There were 8 patients (33.3%) with CR, 10 pts (41.7%) PR, 2 patients (8.3%) SD, and 4 patients (16.7%) PD. The disease control rate (DCR = CR+PR+SD) was 83.3%. The median response time in 18 cases with CR and PR was 5.6 months. The median survival time in 20 cases with disease control was 30 months, however, that in nonresponse (PD) cases was only 10 months. Side reactions related to imatinib mesylate included nausea and vomiting (20.8%), neutropenia (12.5%), and edema (8.3%). Our results are consistent with previous reports in the literature. Imatinib is a safe and effective moleucular target drug used for Chinese. Only mild adverse reactions occur in the treated patients. It is worth using imatinib in the treatment of advanced DFSP patients.


Multiparameter flow cytometry analysis of leukocyte markers for diagnosis in preterm neonatal sepsis.
Neonatal sepsis is an important public health concern worldwide due to its immediate lethality and long-term morbidity rates, Clinical evaluation and laboratory analyses are indispensable for diagnosis of neonatal sepsis. However, assessing multiple biomarkers in neonates is difficult due to limited blood availability. The aim is to investigate if the neonatal sepsis in preterm could be identified by multiparameter analysis with flow cytometry. The expression of activation-related molecules was evaluated by flow cytometry in newborn with or without risk factors for sepsis. Our analysis revealed that several markers could be useful for sepsis diagnosis, such as CD45RA, CD45RO, or CD71 on T cells; HLA-DR on NKT or classic monocytes, and TREM-1 on non-classic monocytes or neutrophils. However, ROC analysis shows that the expression of CD45RO on T lymphocytes is the only useful biomarker for diagnosis of neonatal late-onset sepsis. Also, decision tree analyses showed that CD45RO plus CD27 could help differentiate the preterm septic neonates from those with risk factors. Our study shows a complementary and practical strategy for biomarker assessment in neonatal sepsis.


The transmission and evolution of experimental microcultures in groups of young children.
A new experimental microculture approach was developed to investigate the creation and transmission of differing traditions in small communities of young children. Four playgroups, with a total of 88 children, participated. In each of 2 playgroups, a single child was shown how to use 1 of 2 alternative methods of tool use, "lift" or "poke," to extract a reward from an artificial "foraging" device (the "panpipes") used in earlier diffusion experiments with chimpanzees. Each of these proficient models then participated in his or her playgroup during free play for 5 days, with the panpipes available to all. Compared with a condition in which no model was witnessed, where only 18% of children successfully gained rewards and the lift technique never appeared, 66% of children in the open diffusion conditions (83% of those who attempted the task) were successful. Each of the 2 different seeded approaches initially spread strongly in their respective groups. These seeded differences eroded over time as modifications were spontaneously invented, but social learning played a dominant role throughout, with a majority of children adopting the technique they witnessed most commonly, whether initially seeded or resulting from other children's innovations. A majority of children thus fell into 1 of several categories of "follower," relying primarily on social learning, with a minority displaying 1 of several other categories of innovation. One of the techniques was modified into a distinctively different form that was then socially transmitted further, allowing us to document the microevolution of small-scale traditions in this cultural microcosm.


Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/.NO through a radical reaction.
A labile inorganic free radical, nitric oxide (.NO), is produced by nitric oxide synthase from the substrate L-arginine in various cells and tissues. It acts as an endothelium-derived relaxing factor (EDRF) or as a neurotransmitter in vivo. We investigated the reactivity of stable radical compounds, imidazolineoxyl N-oxides such as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), carboxy-PTIO, and carboxymethoxy-PTIO against .NO/EDRF in both chemical and biological systems. By using electron spin resonance (ESR) spectroscopy, imidazolineoxyl N-oxides were found to react with .NO in a stoichiometric manner (PTIO/.NO = 1.0) in a neutral solution (sodium phosphate buffer, pH 7.4) with rate constants of approximately 10(4) M-1 s-1, resulting in the generation of NO2-/NO3- and imidazolineoxyls such as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl (PTI), carboxy-PTI, or carboxymethoxy-PTI. Furthermore, the effects of imidazolineoxyl N-oxides on acetylcholine- or ATP-induced relaxation of the smooth muscle of rabbit aorta were tested. The vasorelaxations were inhibited by all three imidazolineoxyl N-oxides markedly. The inhibitory effects of carboxy-PTIO was almost 2-fold stronger than those of .NO synthesis inhibitors, N omega-nitro-L-arginine and N omega-monomethyl-L-arginine. Generation of EDRF/.NO was identified by reacting the PTIO in aortic strips and quantitating the reaction product with ESR spectroscopy. Thus, it was clarified that imidazolineoxyl N-oxide antagonize EDRF/.NO via a unique radical-radical reaction with .NO.


Prognostic role of tumor necrosis in patients undergoing curative resection for gastric gastrointestinal stromal tumor: a multicenter analysis of 740 cases in China.
Tumor necrosis is associated with poor clinical outcomes in many malignancies. We aimed to determine whether tumor necrosis was an independent predictor of outcomes in gastric gastrointestinal stromal tumors (GISTs). We retrospectively analyzed data from 740 patients undergoing curative resection for gastric GIST at four centers between 2001 and 2015. Disease-free survival (DFS) was estimated with the Kaplan-Meier method, and associations with prognosis were assessed with Cox regression models. Tumor necrosis was present in 122 cases (16.5%). The prevalence of tumor necrosis increased with higher risk-stratification, including 0.7%, 7.4%, 17.3%, and 39.3% for very low-, low-, intermediate- and high-risk tumors, respectively (P < 0.001). Tumor necrosis was associated with aggressive tumor biology, such as larger tumor size, higher mitotic index, tumor rupture, and presence of nuclear atypia (all P < 0.05). Multivariate analysis revealed that tumor necrosis was an independent predictor of unfavorable DFS (HR: 2.641; 95% CI: 1.359-5.131; P = 0.004). When stratified by the modified National Institutes of Health (NIH) classification, tumor necrosis still independently predicted DFS in high-risk patients (P = 0.001) but not in non-high-risk patients (P = 0.349). The 5-year DFS rate in high-risk patients with and without tumor necrosis was 56.5% and 82.9%, respectively (P = 0.004). Notably, the prognostic significance of tumor necrosis was maintained when the patients were stratified by age, sex, tumor location, tumor size, and mitotic index (All P < 0.05). Tumor necrosis is a useful predictor of outcomes in gastric GIST, especially in high-risk patients. Based on these results, we recommend that the current NIH classification should be further improved and expanded to include tumor necrosis as a valuable prognostic indicator.


Entry of US medical school graduates into family practice residencies: 1992-1993 and three-year summary.
This is the 12th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each medical school's graduates entering family practice residency programs. Approximately 10.8% of the 15,466 graduates of LCME-accredited US medical schools between July 1991 and June 1992 were first-year residents in family practice in October 1992. This compares to 10.3% the previous year. This is the first increase since 1989. Medical school graduates from publicly funded medical schools were more than twice as likely to be first-year residents in family practice in October 1992 than were residents from privately funded schools, 13.8% compared to 6.4%. The Mountain region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1992 at 18.3%; the Middle Atlantic and New England regions continued with the lowest percentages, 5.6% and 7.8%, respectively. Approximately one in two medical school graduates entering a family practice residency program as a first-year resident in October 1992 entered a program in the same state as that of his or her medical school of graduation. The percentages for each medical school have varied substantially from year to year since the AAFP has reported this information. The average percentage for each medical school for the last three years is reported. In addition, the number and percentage of graduates from colleges of osteopathic medicine who entered ACGME-accredited family practice residency programs are reported.


Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii.
In a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an "urgent threat." Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii's expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii's response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.


[A case of relapsing sarcoidosis with pleurisy 14 years after spontaneous remission].
An 83-year-old woman was referred to our hospital with dyspnea on exertion and right pleural effusion. At the age of 69, she had been given a clinical diagnosis of sarcoidosis due to uveitis, bilateral hilar lymphadenopathy, bilateral multiple nodular shadows on chest images, and serum angiotensin-converting enzyme (SACE) level elevation. Remission was spontaneous. The pleural effusion was exudative lymphocyte-rich. On thoracoscopy, the macroscopic appearance of the parietal pleura was telangiectasia without nodular lesions and the pleural biopsy specimens revealed non-caseating epitheloid cell granulomas whose cultures were negative for acid-fast bacilli and fungi. A tuberculin skin test and QFT-2G were negative, thus we diagnosed sarcoidsis pleurisy.


Biochemical heterogeneity and phosphorylation of coatomer subunits.
The coat protomer complex I (COPI) family of coat proteins are involved in the assembly of membrane-associated coats thought to mediate vesicular transport between the endoplasmic reticulum and the Golgi complex, between adjacent Golgi cisternae, and possibly in the endocytic pathway. We investigated whether this heterogeneity in the sites of COPI action might be reflected in biochemical heterogeneity of one or more COPI subunits. A simplified method was devised to purify the cytosolic COPI precursor complex, coatomer, from rat liver cytosol. The individual subunits were analyzed by high resolution two dimensional gel electrophoresis and mass spectroscopic analysis of tryptic peptides. Considerable charge heterogeneity was observed, particularly for the beta-COP and delta-COP subunits. The multiple species detected, however, did not appear to reflect the presence of distinct translation products but rather a significant degree of protein phosphorylation. The observed pI of beta-COP was sensitive to alkaline phosphatase digestion. Moreover, isolation of coatomer from metabolically labeled tissue culture cells demonstrated directly that both beta-COP and delta-COP, but no other coatomer subunits, were serine-phosphorylated. COPI phosphorylation may regulate coatomer assembly, membrane recruitment, or the specificity of coatomer-organelle interaction.


New frontiers in cardiac devices.
This article provides an overview of current cardiac device management, complications, and future areas for development. The last 70 years have seen huge advances in the field of implantable cardiac devices, from diagnostic tools to electrical therapies for bradycardia, ventricular arrhythmia and cardiac resynchronisation. While out-of-hours specialist cardiology cover and regional arrhythmia pathways are increasingly established, they are not universal, and the management of arrhythmia remains an important facet of clinical medicine for the general physician. This article discusses core recommendations from international guidelines with respect to heart rhythm diagnostics, pacing for bradycardia, cardiac resynchronisation and implantable cardioverter defibrillators, along with common complications. Finally, future innovations such as the diagnostic potential of portable technologies, antibiotic envelopes for cardiac devices and the increasing use of leadless pacemakers are described.


Social determinants of tuberculosis in Europe: a prospective ecological study.
Tuberculosis (TB) is considered to be a disease of poverty, since its incidence is exacerbated by socioeconomic factors, inconsistent or partial treatment practices, and immigration from endemic countries. A prospective country level study, using a comprehensive dataset of TB incidence and prevalence taken from countries within the World Health Organization (WHO) European region, was conducted. We employed quintile regression to investigate the prospective association between baseline (measured in 2000) and a nation's wealth, level of egalitarianism, migration rate, health-related lifestyle and social capital with TB incidence and prevalence over a 10-yr period (2000-2009). We found that ∼50% of TB variation is accounted for by a nation's wealth and level of egalitarianism. We observed a negative prospective association between logged gross domestic product and TB rates, and a positive prospective association between income inequality and TB. National income levels per capita and income inequality are important predictors for TB incidence and prevalence in the WHO European region. They account for 50% of country-level variation, indicating the importance of a combined absolute and relative socioeconomic disadvantage in the development of TB. These findings also provide a tool for forecasting potential fluctuations in the level of TB epidemics in the WHO European region, with respect to socioeconomic changes.


Oxygen, oxidants, and antioxidants in wound healing: an emerging paradigm.
Disrupted vasculature and high energy-demand by regenerating tissue results in wound hypoxia. Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of hyperbaric oxygen in promoting wound healing is sketchy, however. Topical oxygen therapy involves local administration of pure oxygen. The advantages of topical oxygen therapy include low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this modality of wound care is of outstanding interest, it clearly lacks the support of mechanism-oriented studies. The search for mechanisms by which oxygen supports wound healing has now taken another step. Respiratory burst-derived oxidants support healing. Oxidants serve as cellular messengers to promote healing. Although this information is of outstanding significance to the practice of oxygen therapy, it remains largely unexplored. The search for "natural remedies" has drawn attention to herbals. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are likely to be of outstanding significance in wound healing.


Availability of Tracer Drugs and Implementation of Their Logistic Management Information System in Public Health Facilities of Dessie, North-East Ethiopia.
Tracer drugs are the representative of essential medicines and satisfy the priority healthcare needs of the population. Managing tracer drugs through logistics management information systems is a strategy to enhance their smooth flow for continuous provision of quality health service. This study assessed the availability of tracer drugs and implementation of their logistic management information system in public health facilities of Dessie, North-East Ethiopia. Cross-sectional study was conducted from September 15-30, 2017, in all public health facilities of Dessie. The data were collected by reviewing tracer drugs logistic formats and conducting physical inventory. Key informant interview was employed to all pharmacy heads and store managers. Data analysis was done using statistical package for social science version 20 and Microsoft Excel 2010. Twelve tracer drugs were managed by health facilities. The overall mean availability, mean duration, and average frequency of stock out of tracer drugs (last 6 months) were 74.7%, 48.8 days, and 1.43, respectively. In eight health facilities, logistic records were available, but all health facilities did not use stock cards. Also, 3 out of 9 used the health commodity management information system. On average, 77.8% of the tracer drugs had bin cards, of which, 86% were updated. The discrepancy between physical count and stock keeping records was ranged from 0% to 100%. The causes of stock out were inadequate supply, lack of recording forms, and their inconsistent use. The availability of tracer drugs was less than the recommended percent, and inadequate supply, poor availability and use of recording forms were the reasons for stock out. Thus, health facility managers and pharmacy heads should work in harmony to ensure uninterrupted supply and implement a logistic management information system.


Efficient heterologous expression of cytochrome P450 enzymes in microorganisms for the biosynthesis of natural products.
Natural products, a chemically and structurally diverse class of molecules, possess a wide spectrum of biological activities, have been used therapeutically for millennia, and have provided many lead compounds for the development of synthetic drugs. Cytochrome P450 enzymes (P450s, CYP) are widespread in nature and are involved in the biosynthesis of many natural products. P450s are heme-containing enzymes that use molecular oxygen and the hydride donor NAD(P)H (coupled via enzymic redox partners) to catalyze the insertion of oxygen into C-H bonds in a regio- and stereo-selective manner, effecting hydroxylation and several other reactions. With the rapid development of systems biology, numerous novel P450s have been identified for the biosynthesis of natural products, but there are still several challenges to the efficient heterologous expression of active P450s. This review covers recent developments in P450 research and development, including the properties and functions of P450s, discovery and mining of novel P450s, modification and screening of P450 mutants, improved heterologous expression of P450s in microbial hosts, efficient whole-cell transformation with P450s, and current applications of P450s for the biosynthesis of natural products. This resource provides a solid foundation for the application of highly active and stable P450s in microbial cell factories to biosynthesize natural products.


The Effect of Fat Distribution on the Inflammatory Response of Multiple Trauma Patients-A Retrospective Study.
Objectives In recent years; increasing evidence pointed out the clinical importance of adipose tissue (AT) distribution in various patient populations. In particular, visceral adipose tissue (VAT), when compared to subcutaneous adipose tissue (SAT), was found to play a pivotal role in the development of inflammatory reaction. The aim of the present study was to examine whether body fat distribution has an impact on the development of systemic inflammatory response syndrome (SIRS) in patients with polytrauma. Methods In our retrospective study; we filtered our institution records of the German Trauma Registry (Trauma Register DGU) from November 2018 to April 2021 and included 132 adult polytrauma patients with injury severity score (ISS) >16. Subsequently; we measured the visceral and subcutaneous adipose tissue area based on whole-body CT scan and calculated the ratio of VAT to SAT (VSr). Thereafter, the patient population was evenly divided into three groups; respectively VSr value less than 0.4 for the first group (low ratio), 0.4-0.84 for the second group (intermediate ratio), and greater than 0.84 for the third group (high ratio). Considering the other influencing factors; the groups were further divided into subgroups in the respective analysis according to gender (male/female), BMI (<25 or ≥25), and ISS (<26 or ≥26). Result VSr was an independent factor from body mass index (BMI) (r2 = 0.003; p = 0.553). VSr in male patients was significantly higher (p < 0.001). Patients with low VSr had higher ISS scores (p = 0.028). Polytrauma patients with higher VSr tended to have lower SIRS scores and significant differences of SIRS score were found on multiple days during the whole hospitalization period. In the low VAT/SAT group, male patients, and patients with BMI greater than 25, both exhibited higher SIRS scores during hospital stay (day 16: p = 0.01; day 22: p = 0.048 and p = 0.011; respectively). During hospitalization, patients with higher ISS score (≥26) in the low VSr group was found to have higher SIRS score (day 16; p = 0.007). Over the hospital stay; serum markers of CRP; CK; and leukocyte in patients with low VSr were higher than those in patients in the intermediate and high VSr groups; with significant difference discovered on multiple days (day 16: 0.014; day 22: p = 0.048). Conclusion Lower VSr is associated with increased inflammatory response and worse clinical outcome in patients with polytrauma. Furthermore; VSr is an independent factor providing additional information to BMI.


Is Hughes-Stovin syndrome Behçet's disease?
Hughes-Stovin syndrome (HSS) is a rare clinical disorder, which has been described as the presence of pulmonary artery aneurysm in the setting of systemic thrombosis. The term "Incomplete Behçet's Disease" has also been used to describe this syndrome due to the clinical and histopathological similarities between Behçet's disease and HSS. Indeed, pulmonary involvement can be indistinguishable between these two conditions of unknown pathophysiology. We describe an HSS patient who presented with a recurrent pulmonary artery aneurysm, review the clinical and pathological manifestations of HSS, discuss its similarities to Behçet's disease, and finally make the argument that HSS is in fact Behçet's disease.


Development of a Fragment-Based Screening Assay for the Focal Adhesion Targeting Domain Using SPR and NMR.
The Focal Adhesion Targeting (FAT) domain of Focal Adhesion Kinase (FAK) is a promising drug target since FAK is overexpressed in many malignancies and promotes cancer cell metastasis. The FAT domain serves as a scaffolding protein, and its interaction with the protein paxillin localizes FAK to focal adhesions. Various studies have highlighted the importance of FAT-paxillin binding in tumor growth, cell invasion, and metastasis. Targeting this interaction through high-throughput screening (HTS) provides a challenge due to the large and complex binding interface. In this report, we describe a novel approach to targeting FAT through fragment-based drug discovery (FBDD). We developed two fragment-based screening assays-a primary SPR assay and a secondary heteronuclear single quantum coherence nuclear magnetic resonance (HSQC-NMR) assay. For SPR, we designed an AviTag construct, optimized SPR buffer conditions, and created mutant controls. For NMR, resonance backbone assignments of the human FAT domain were obtained for the HSQC assay. A 189-compound fragment library from Enamine was screened through our primary SPR assay to demonstrate the feasibility of a FAT-FBDD pipeline, with 19 initial hit compounds. A final total of 11 validated hits were identified after secondary screening on NMR. This screening pipeline is the first FBDD screen of the FAT domain reported and represents a valid method for further drug discovery efforts on this difficult target.


[Methodology for superiority versus equivalence and non-inferior clinical studies. A practical review].
Physicians should always remember that a negative result in a superiority trial never would prove that the therapies under research are equivalent; more often, there may be a risk of type 2 (false negative) error. Equivalence and not inferiority studies demand high standards to provide reliable results. Physicians should take into account above all that the equivalence margins tend to be too large to be clinically significant and that the claim of equivalence can be misleading if a study has not been conducted at a sufficiently high level. In addition, physicians must be a bit skeptical of judgments that do not include the basic requirements of information, including the definition and justification of the equivalence margin, the calculation of the size of the sample bearing in mind this margin, the presentation of both analysis (intention-to-treat and by protocol), and provide confidence intervals for the results. Equivalence and inferiority studies are not indicated in certain areas. If one follows the required strict adherence to the specific methodology, such studies can provide new and important knowledge.


Shoulder Pain, Function, and Ultrasound-Determined Structure in Elite Wheelchair-Using Para Athletes: An Observational Study.
This study aimed to determine the relationship between shoulder pain, physical examination, and tissue pathology in manual wheelchair users competing in elite sport. Eighty elite para athletes who used a manual wheelchair for daily mobility were recruited from international track (n = 40), field (n = 19), and powerlifting (n = 21) competitions. Athletes were surveyed regarding shoulder pain history and symptoms (Wheelchair User's Shoulder Pain Index (WUSPI)), whereas independent blind observers measured signs (Physical Examination of the Shoulder Scale (PESS)) and tissue pathology (Ultrasound Shoulder Pathology Rating Scale (USPRS)). Relationships between measures for the total cohort and for subgroups defined by sporting discipline were calculated. A large proportion of athletes reported a history of upper limb pain (39% dominant and 35% nondominant). For the total cohort, WUSPI score was 22.3 ± 26.9, PESS score was 7.4 ± 6.7, and USPRS score was 5.2 ± 4.0. There were no USPRS score differences between athlete subgroups; however, track athletes had lower WUSPI and PESS scores, especially compared with field athletes. The first principal component explained most of the variance in the WUSPI and PESS, which were strongly correlated (r = 0.71), and the second orthogonal component explained the USPRS, which did not correlate with either the PESS (r = 0.21) or WUSPI (r = 0.20). Subgroup analysis showed that track athletes had lower symptom scores for a given physical examination score. Elite para athletes who use manual wheelchairs for daily mobility have a high prevalence of shoulder symptoms, positive signs on physical examination, and ultrasound-determined tissue pathology. Ultrasound-determined tissue pathology does not correlate with symptoms or signs. This information can help to guide clinicians in managing shoulder problems in this athlete population at high risk of injury.