A planetary gear reducer backlash identification based on servo motor current signal and optimized fisher discriminant analysis.
Planetary gear reducer is widely used in industrial automation, and its performance highly affects the equipment reliability. The backlash and stiffness may cause the performance decline of planetary, hence the vibration, temperature, current and other signals are applied in planetary condition monitoring. The purpose of this paper is to develop a practical and effective method based on motor current signal analysis (MCSA) to identify backlash faults of planetary gear reducers. The sensitivity weight ratio (SWR) is proposed to optimize the introduced fisher discriminant analysis (FDA) algorithm, which is used to extract and screen the current signal characteristics of the servo motor. The motor is connected to the reducer, so the changes in the operating conditions of the planetary gears can be observed in the motor current. Compared with the traditional detection method of equipment health status, the Hall current sensor is a non-invasive method with lower cost and easy installation. Besides, the support vector machine (SVM) classifier and some published methods are utilized to classify the backlash of the planetary gear. Finally, experimental tests were carried out under different backlashes and loads to verify the effectiveness of the method.


Characterization of long-term outcomes for pediatric patients with epithelioid hemangioma.
Epithelioid hemangioma (EH) is a rare benign vascular tumor that occurs in soft tissues and bone and presents between the third and sixth decades of life. Little is known about the clinical course and outcomes of pediatric EH. We report 11 patients diagnosed with EH at a median age of 14.4 years. One patient treated with interferon and one with sirolimus exhibited partial response for >2 years. Although a benign neoplasm, EH is difficult to manage without standard protocols and portends considerable morbidity. Our findings suggest medical management, particularly sirolimus, may benefit these patients; however, long-term follow-up is needed.


Nemorubicin.
Nemorubicin is a 3'-deamino-3'[2-(S)-methoxy-4-morpholinyl]derivative of doxorubicin. This derivative has been synthesized in the early 1990s by the Farmitalia CarloErba Research Center in Italy. The idea was to develop doxorubicin analogues able to circumvent the emergenceof chemoresistance, in particular the multi-drug resistance. The drug was reported to be active in vitroagainst both murine and human tumor cells resistant to doxorubicin. Similar results were obtained whenthe drug was administered in vivo to mice bearing multi-drug resistant tumors. The compound retained thesame activity also in alkylating agents and topoisomerase II resistant tumors and showed an increased potencyrelative to the parent drug doxorubicin. It is metabolized via P450 CYP3A enzyme to an extremely cytotoxicderivative. Both nemorubicin and its metabolite have a mechanism of action different from that ofdoxorubicin, with a key role played by the nucleotide excision repair system. The drug is activelytested in clinics as a single agent or in combination with cisplatin.


Therapeutic alliance in family therapy and clinical outcomes among adolescents at risk for mood disorders.
Family-focused therapy (FFT) is associated with longer intervals between mood episodes and reductions in suicidal ideation among adolescents at risk for bipolar disorders. However, the mediating processes underlying the efficacy of FFT are not well understood. In an open trial of an 18-week FFT program, we explored the association between the therapeutic alliance of adolescents/parents with their therapists and the symptomatic outcomes of adolescents over 18 weeks. Participants were enrolled in a treatment development trial of FFT supplemented with a mobile app. We used the System for Observing Family Therapeutic Alliances (SOFTA) to rate alliance between adolescents, parents, and therapists using videotaped FFT sessions from the beginning and end of treatment. Pearson correlations were computed between SOFTA alliance ratings and changes in Children's Depression Rating Scale, Revised (CDRS-R) scores over 18 weeks of treatment. SOFTA ratings were obtained from sessions conducted with 17 adolescents (mean age 14.9+/-2.0 years; 41.2% female) and 22 parents. CDRS-R ratings were obtained from 16 adolescents at baseline and 18 weeks. Parents had significantly higher levels of engagement and emotional connection with therapists than their offspring. Adolescents' therapeutic engagement scores were significantly correlated with reductions in CDRS scores over 18 weeks (r(14) = -0.58, p = 0.018; N = 16). We could not draw conclusions about the causal relationship between therapeutic alliance and improvement in depression. Among high-risk adolescents undergoing FFT, therapeutic alliance is associated with clinical improvement over 4 months. Strategies to enhance adolescent engagement may strengthen the long-term effects of family interventions.


Forgotten topological index of chemical structure in drugs.
A massive of early drug tests implies that there exist strong inner relationships between the bio-medical and pharmacology characteristics of drugs and their molecular structures. The forgotten topological index was defined to be used in the analysis of drug molecular structures, which is quite helpful for pharmaceutical and medical scientists to grasp the biological and chemical characteristics of new drugs. Such tricks are popularly employed in developing countries where enough money is lacked to afford the relevant chemical reagents and equipment. In our article, by means of drug molecular structure analysis and edge dividing technology, we present the forgotten topological index of several widely used chemical structures which often appear in drug molecular graphs.


Can storytelling of women's lived experience enhance empathy in medical students? A pilot intervention study.
This pilot study aimed to investigate the acceptability and efficacy of a patient storytelling intervention (live and recorded) on empathy levels of medical students. Medical students participated in a storytelling intervention that had three components: listening to live or recorded stories from women with abnormal uterine bleeding, reflective writing, and a debriefing session. Empathy scores of students pre- and post-intervention were measured using the Jefferson Scale of Empathy-student version (JSE-S). Students also completed a feedback survey. Descriptive and inferential statistics were used to analyse quantitative data and content analysis was used for text comments. Both live and recorded storytelling interventions had positive effects on student's empathy scores post intervention. Overall, students were satisfied with the intervention and reported that it improved their understanding of life experiences of women. Suggestions were made for an in-person storytelling session and interactive discussion after listening to each story. A storytelling intervention has the potential to improve medical students' empathy and understanding of lived experience of women with health conditions. This could be valuable when student-patient interactions are limited in healthcare settings, or to enable stories of small numbers of patient volunteers to reach students.


Pediatric anemia in rural Ghana: a cross-sectional study of prevalence and risk factors.
To assess anemia prevalence and identify associated parameters in children <3 years of age in a rural area of Ghana. Univariate and multivariate logistic regression of cross-sectional survey results from 861 children aged <3 years attending routine immunization services in Berekum district. Anemia prevalence was 73.1%; most were either mildly (31.2%) or moderately (38.7%) affected. Risk factors for anemia (hemoglobin < 11.0 g/dl) in multivariate analysis were malaria parasitemia and male sex; these factors and younger age were associated with anemia severity. A partial defect in glucose-6-phosphate dehydrogenase was associated with decreased severity. Height-for-age, but not weight-for-age, was associated with anemia and its severity. Malaria parasitemia was strongly associated with anemia and its severity, suggesting that malaria control may be the most effective way to reduce the burden of anemia in rural Ghanaian children.


Dynamic magnetic resonance imaging of vocal cord closure during deglutition.
Vocal cord closure is instrumental in airway protection during deglutition. Conventional imaging of vocal cord closure and reopening during deglutition requires invasive and nonphysiological methods. The aim of this study was to characterize the biomechanical properties of normal vocal cord adduction/abduction during deglutition using echoplanar magnetic resonance imaging, a technique that has the capability of imaging soft-tissue motion with real-time temporal resolution. The movements of laryngeal and vocal cord structures during swallowing were determined in 11 normal volunteers by single slice and axially reformatted multislice coronal echoplanar images. During swallowing, the larynx ascended to peak elevation, maintained peak elevation for a discrete interval, and descended to its resting position. Vocal cord adduction occurred with a symmetric tent-like configuration at the midpoint of maximal laryngeal elevation, whereas vocal cord abduction occurred at the midpoint of laryngeal descent. Spatial analysis of vocal cord configuration during adduction determined that the vocal cords attained an initial parallel configuration during ascent, followed by closure at peak laryngeal elevation. These results show that the vocal cords adduct and abduct synchronously with laryngeal ascent and descent, respectively, during deglutition. Echoplanar magnetic resonance imaging constitutes a novel tool used to assess clinical abnormalities of deglutitive laryngeal function.


Green tea infusion improves cyclophosphamide-induced damage on male mice reproductive system.
Green tea presents catechins as its major components and it has a potential antioxidant activity. Cyclophosmamide (CP) is an antineoplastic and immunosuppressive agent, known to reduce fertility. In the present study, we evaluated the effect of green tea infusion on cyclophosphamide-induced damage in male mice reproductive system. Mice received green tea infusion (250 mg/kg) or vehicle by gavage for 14 days. Saline or CP were injected intraperitoneally at a single dose (100 mg/kg) at the 14th day. Animals were euthanized 24 h after CP administration and testes and epididymis were removed for biochemical analysis and sperm evaluation. Catechins concentration in green tea infusion was evaluated by HPLC. CP increased lipid peroxidation, DNA damage and superoxide dismutase activity whereas sperm concentration, glutathione peroxidase (GPx), glutathione S-transferase (GST) and 17β-hydroxysteroid (17β-HSD) dehydrogenase activities were reduced in both tissues tested. Catalase activity and protein carbonyl levels were changed only in testes, after CP administration. Green tea pre-treatment reduced significantly lipid peroxidation, protein carbonylation, DNA damage and restored GPx and GST activity in testes. In epididymis, therapy significantly increased sperm concentration and restored GPx and 17β-HSD activity. Green tea improves CP-induced damage on reproductive system, probably due to their high catechins content.


[Autoxidation rate increase of linoleic acid in the presence of tocopherol in aqueous medium ; study of the transformation of tocopherol].
Linoleic acid in aqueous emulsion is spontaneously autoxidized and product hydroperoxides. In vitro the autoxidation of the cis-9, cis-12, octadecadienoic acid with DL-alpha-tocopherol, both emulsified in water, shows an important increase of the hydroperoxides. During this time the tocopherol quickly disappears.


English goalkeepers are not responsible for England's poor performance in penalty shootouts in the past.
Scrutinizing public opinion is one of the central goals of science as the divergence between public opinion and scientific evidence can have negative consequences. The present study aims to further investigate the alleged English 'penalty curse' and determine if it can be linked to the prevalent stereotype of the 'English goalkeeper problem'. We analyzed a large sample of 2379 penalty kicks that 629 different goalkeepers faced in World Cups and European Championships, as well as in the Champions and Europa League by comparing the goalkeeper success rates of different nations by fitting a generalized linear model (binomial regression) to the data. However, the results do not reveal meaningful differences between the success rates (on average 22.23%). Consequently, we conclude that English goalkeepers are not responsible for England's poor performance in penalties in the past as they perform as well as goalkeepers from other nations and, in turn, provide a counterargument to the widespread stereotype that 'England has a goalkeeper problem'.


Eye lens protection for radiological personnel.
Various radiodiagnostic procedures expose the eye lens of the diagnostic technician to radiations. With the aid of lead glasses with an attenuation of radiation equivalent to 0.25 mm of lead, the dose can be reduced by 90%.


Early stages of interactions of cell-penetrating peptide penetratin with a DPPC bilayer.
Cell-penetrating-peptides (CPPs) can deliver themselves together with a macromolecular cargo into cells and, hence, have promising applications in drug delivery. The detailed physical mechanisms that underlie and determine their cellular uptake remain unknown. We used molecular dynamics (MD) simulations to study the interaction of a well-known CPP, namely penetratin, with a zwitterionic di-palmitoyl-phosphatidyl-choline (DPPC) bilayer. Our study shows that the arginine and lysine residues play a crucial role in peptide-membrane binding through charge-pair and hydrogen bond interactions. We also characterize peptide conformation and show that it remains helical near the N-terminus but can fold into a variety of other conformations in the residues close to the C-terminus. The response of membrane to the peptide is also investigated.


[Primary treatment for localized prostate cancer: evaluation of patients' quality of life].
Radical prostatectomy (RP) and percutaneous radiotherapy (RT) are viable options for the primary treatment of localized prostate cancer (PC). Given the comparable efficacy of both modalities quality of life (QOL) has been suggested as an additional decision criterion. In recent years several validated instruments have been introduced to assess QOL. Most of them allow for patient-based rating of QOL. Herein, we aim to compare QOL after RP and RT in our own cohort of patients in Tübingen using validated questionnaires. In total, 165 patients who had been treated for PC in Tübingen were enrolled. Of those 100 men had RP and 65 had RT. The validated QOL questionnaires EORTC QLQ-C30 and EORTC QLQ-PR 25 were used for assessment. Statistical analyses focused on analyses of variance. Concordant to previous studies it could be shown that RP mainly creates voiding problems most importantly urinary incontinence but also erectile dysfunction. After RT, patients mainly complained about disturbed bowel function including diarrhea and proctitis as well as about urgency and frequency. RP patients had better PF2 Scale values than RT patients (p= 0.00357143). On DI scales RT patients yielded significantly poorer values than the RP group (p= 0.003333). Our data comply well with those from other international centers. QOL is an important yet underestimated variable in oncological research. Our investigations underline the importance of an interdisciplinary approach for the successful management of PC.


Lipopolysaccharide preconditioning prevents acceleration of kindling epileptogenesis induced by traumatic brain injury.
10-20% of symptomatic epilepsies are post-traumatic. We examined effect of LPS preconditioning on epileptogenesis after controlled cortical impact (CCI). LPS (0.01, 0.1 and 0.5 mg/kg) was injected i.p. to rats 5 days before induction of CCI to parieto-temporal cortex. Kindling started 24h after CCI by i.p. injection of 30 mg/kg of pentylenetetrazole every other day until manifestation of 3 consecutive generalized seizures. CCI injury accelerated the rate of kindled seizures acquisition. LPS (0.1 and 0.5 mg/kg) prevented the acceleration of kindling. LPS preconditioning significantly decreased IL-1β and TNF-α over-expression and the number of damaged neurons in the hippocampus of traumatic rats.


Congenital radial head dislocation.
Fifty patients with 77 congenitally dislocated radial heads were reviewed to assess the diagnostic features, functional limitations, symptomatology, and results of treatment. Twenty-three patients had associated anomalies of the affected upper extremity, and 35 had anomalies in other parts of the body. In six patients no other anomaly was found, all six had bilateral involvement. No patient had congenital radial head dislocation as a unilateral isolated anomaly, and therefore we doubt its existence. Functional limitation with congenital radial head dislocation is minimal and pain is uncommon. Radial head excision relieves pain and improves appearance: however, it does not increase motion.


A multivariate analysis of health law education in American medical schools.
With the growing impact of legal regulation of clinical practice, students of medicine and other clinical specialties need to know how these developing legal concepts apply to their future practices.


Paragangliomas of the Head and Neck: An Overview from Diagnosis to Genetics.
Paragangliomas (PGL) develop from the parasympathetic system in the head and neck (HN) and arise primarily in four distinct areas: Carotid body, vagal, middle ear, and larynx. Globally, the diagnosis and morphologic features are the same regardless of anatomic site, however the incidence, frequency of genetic alterations/syndromes and differential diagnosis vary. It is now recognized that nearly 40% of all HN PGLs are hereditary, including a significant subset without a known family history. Now pathologists are central to the evaluation for diagnosis and further management of patients with HNPGLs. Specifically, SDHB immunohistochemical evaluation is an excellent screening tool to detect tumors with alterations in the SDH family of genes that represent the majority of hereditary cases in HNPGL. Similarly, SDHB immunohistochemical analysis allows for screening of PGL syndrome associated tumors (gastrointestinal stromal tumor (GIST), renal cell carcinoma (RCC), and pituitary adenomas) that have now been linked by their overlapping gene alterations. Awareness of the spectrum of these syndromes, and their associated tumors, positions the pathologist to augment patient care and surveillance.


Does Sex, Race, and the Size of a Kidney Transplant Candidate's Social Network Affect the Number of Living Donor Requests? A Multicenter Social Network Analysis of Patients on the Kidney Transplant Waitlist.
A kidney transplant candidate's social network serves as a pool of potential living donors. Sex and racial differences in network size, network strength, and living donor requests may contribute to disparities in living donor kidney transplantation. In this multicenter cross-sectional study, we performed an egocentric network analysis via a telephone survey of 132 waitlisted candidates (53% female and 69% Black) to identify demographic and network factors associated with requesting living kidney donations. Female participants made requests to more network members than male participants: incidence rate ratio (IRR) 1.95, 95% confidence interval (CI) [1.24-3.06], P < 0.01. Black participants tended to make more requests than whites (IRR 1.65, 95% CI [0.99-2.73], P = 0.05). The number of requests increased with the size of the network (IRR 1.09, 95% CI [1.02-1.16], P = 0.01); however, network size did not differ by sex or race. Network members who provided greater instrumental support to the candidates were most likely to receive a request: odds ratio 1.39, 95% CI [1.08-1.78], P = 0.01. Transplant candidates' networks vary in size and in the number of requests made to the members. Previously observed racial and sex disparities in living donor kidney transplantation do not appear to be related to network size or to living donation requests, but rather to the network members themselves. Future living donor interventions should focus on the network members and be tailored to their relationship with the candidate.


Geniposide ameliorates acute kidney injury via enhancing the phagocytic ability of macrophages towards neutrophil extracellular traps.
Acute kidney injury (AKI) is a clinically serious disorder associated with high mortality rates and an increased risk of progression to end-stage renal disease. As an essential supportive treatment for patients with respiratory failure, mechanical ventilation not only save many critically ill patients, but also affect glomerular filtration function by changing renal hemodynamics, neurohumoral and positive end-expiratory pressure, eventually leading to AKI. AMP-activated protein kinase (AMPK), a crucial energy homeostasis regulator, could enhance macrophage phagocytic ability and inhibit inflammation, but whether it can engulf neutrophil extracellular traps (NETs) and alleviate mechanical ventilation-associated AKI is still unclear. In this study, we found that geniposide significantly ameliorated histopathological damage, reduced serum Cre and BUN levels. Besides, geniposide can also induce AMPK activation and enhance macrophage phagocytic ability toward NETs. Moreover, geniposide can markedly reduce the levels of high mobility group box 1 (HMGB1), and these effects were dependent on AMPK-PI3K/Akt signaling. Altogether, these results indicated that geniposide promoted macrophage efferocytosis by inducing AMPK-PI3K/Akt signaling activation, clearing NETs and ameliorating AKI.


Intravenous administration of Gd-DTPA prior to DWI does not affect the apparent diffusion constant.
MRI measurements of water diffusion and blood perfusion are increasingly used for the evaluation of organ functionality and tissue viability (e.g., in tumors). While diffusion-weighted imaging is performed without contrast agents, measurement of blood perfusion is normally performed based on the administration of paramagnetic substances such as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Simultaneous measurements of these two parameters are often preferred. However, it may be argued that Gd-DTPA causes constriction of small blood vessels or alters hemodynamic parameters such as blood viscosity, thereby corrupting subsequent measurements of the apparent diffusion constant (ADC). The objective of the current study was to investigate the possible changes in the ADC in tumors following intravenous administration of 0.2 and 0.4 mmol/kg of Gd-DTPA in mice. The study was conducted with C3H mouse mammary carcinomas inoculated in the right foot of the animal subjects. The results were compared with findings in a sham group, demonstrating that Gd-DTPA had no significant impact on the ADC as measured in a 7-T animal system.


Megabase inversions in the human genome as physiological events.
The genes of the immunoglobulin kappa light chains are assembled during B-cell differentiation by somatic recombination of one of the V kappa (variable) gene segments and the J kappa-C kappa (joining-constant) gene region. This seems to occur by deletion of the DNa between V kappa and J kappa-C kappa if they are arranged in germ-line DNA in the same transcriptional polarity or by inversion of a fragment containing the V kappa gene if the polarities are opposite. We have cloned 75 V kappa genes and pseudogenes of the human kappa locus and linked them in large contigs. There seem to be no more than 85 such genes, less than 50 of these being potentially functional. Thirty-eight of the cloned genes have the same transcriptional polarity as J kappa-C kappa and are part of the so-called J kappa proximal cluster; 35 genes in a distal cluster (the result of a duplication event in evolution) have a polarity that was suggested to be opposite to the one of J kappa-C kappa. We now show that the V kappa genes of the proximal cluster rearrange by a deletion mechanism whereas the others join J kappa-C kappa by inversion of megabase-sized DNA fragments.


Webtag: a new web tool providing tags/anchors for RT-PCR experiments with prokaryotes.
Webtag is a tool providing oligonucleotide sequences (usually called tags or anchors) that are absent from a specified genome. These tags/anchors can be appended to gene specific primers for reverse transcriptase polymerase chain reaction experiments, circumventing genomic DNA contamination. The use of a relational database, in conjunction with a series of scripts written in PHP and Perl, allows the user to rapidly obtain tags that are: 1) suitable for a specific organism, and 2) compatible with other oligonucleotides to be used in the experimental procedures. This new web tool allows scientists to easily and rapidly obtain suitable tags for RT-PCR experiments, and is available at http://www.egs.uu.se/software/webtag/.


The in vitro activity of sulphones alone and in combination with ampicillin or amoxicillin against Legionella pneumophila and other Legionella spp. including beta-lactamase studies.
Penicillinate sulphone beta-lactamase inhibitors, sulbactam, and BL-P2013, were very effective alone and in combination with ampicillin-like penicillins against 34 strains of Legionellae. The minimum concentrations inhibiting 50% of tested isolates (MIC50) results were as follows: sulbactam, BL-P2013, and amoxicillin = 2.0 micrograms/ml; ampicillin = 1.0 microgram/ml; erythromycin = 0.5 microgram/ml; and rifampin = 0.03 microgram/ml. Synergy was commonly observed when the sulphones were combined with ampicillin or amoxicillin, generally reducing the drug minimum inhibitory concentrations (MICs) fourfold to eightfold (synergy rates 85-91%). BL-P2013 was a slightly more active inhibitor of Legionella spp. beta-lactamase than dicloxacillin or sulbactam.


Effect of metformin on exercise capacity: A meta-analysis.
To evaluate the effect of metformin on various parameters of exercise capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate (HR), exercise test duration, respiratory exchange ratio (RER), rating of perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)]. Studies reporting change in VO2 or VO2peak after metformin administration were included. Subgroup analyses were performed as applicable. Mean difference with 95% CIs were pooled using random-effects model [RevMan (v5.3)]. There were no changes in VO2 and VO2peak in the overall population [VO2: n = 388, mean difference: -0.12 ml/kg/min, 95% CI: -0.74, 0.51, p = 0.71 (i2 = 0%, p = 0.99); VO2peak: n = 345, mean difference: 0.41 ml/kg/min, 95% CI: -0.51, 1.33, p = 0.38 (i2 = 0%, p = 0.89)], healthy volunteers and patients (type 2 diabetes mellitus, insulin resistance, impaired glucose tolerance/impaired fasting glucose and metabolic syndrome). For patients with insulin resistance, there was a decrease in VO2peak, but not VO2. In the overall population, there was a significant decrease in HR and RER, a significant increase in RPE, and no changes in exercise test duration and VAT. In addition, there was an increased VAT in the healthy volunteers. In the overall population, metformin did not affect VO2, VO2peak, exercise test duration and VAT, although it significantly decreased HR, RER and increased RPE.


LCST-type liquid-liquid phase separation behaviour of poly(ethylene oxide) derivatives in an ionic liquid.
We present a new series of polymer-ionic liquid solutions exhibiting LCST-type liquid-liquid phase separation behaviour, and reveal their phase behaviour and intermolecular interactions based on phase diagrams and NMR analysis.


The prevalence of GB virus C/hepatitis G virus RNA among healthy and HCV-infected Catalan children.
GB virus C (GBV-C) is a blood-borne flavivirus. The prevalence of GBV-C viremia among healthy adults is 0.5% to 4% and, to date, no disease has been definitely associated with GBV-C infection. We conducted a cross-sectional study to evaluate GBV-C viremia prevalence in a group of 327 healthy children with normal alanine amino transferase (ALT) levels (Group A) and elevated ALT levels (Group B) of unknown origin, and among 38 pediatric patients with mother-to-child-transmitted hepatitis C virus (HCV) infection (Group C). No statistically significant differences were observed between prevalences in Groups A and B (2.2% vs 6.7%, p = 0.06). None of the children in Groups A or B who tested positive for GBV-C RNA showed any clinical symptoms. The prevalence of GBV-C viremia in Group A was lower than for patients in Group C (2.2% vs 13.2%, p = 0.007); no differences were observed in HCV infection characteristics between those patients who were co-infected with GBV-C and those who were not. In conclusion, while GBV-C viremia is more frequent among HCV-infected pediatric patients, it is neither associated with liver disease nor has any influence on HCV-related chronic hepatitis.


Retracted: Meta-Analysis of Knee Joint Function Recovery after Anterior Cruciate Ligament Reconstruction by Accelerated Rehabilitation Surgery.
[This retracts the article DOI: 10.1155/2022/5085143.].


Identification of two alfalfa early nodulin genes with homology to members of the pea Enod12 gene family.
In a search for plant genes expressed during early symbiotic interactions between Medicago sativa and Rhizobium meliloti, we have isolated and characterized two alfalfa genes which have strong sequence similarity to members of the Enod12 gene family of Pisum sativum. The M. sativa genes, MsEnod12A and B, encode putative protein products of 8066 Da and 12849 Da, respectively, each with a signal sequence at the N-terminus followed by a repetitive proline-rich region. Based on their expression during the initial period of nodule development, MsEnod12A and B are alfalfa early nodulin genes.


Compliance and persistence with osteoporosis therapies.
The US Food and Drug Administration has approved a diverse group of effective osteoporosis therapies. However, these therapies obviously only work when patients with osteoporosis take them. Data from retrospective observational databases have shown poor compliance and persistence with all osteoporosis drugs, particularly oral bisphosphonate therapy. Patients on weekly therapies are more compliant and persistent than those on daily dosing. Data have also shown decreased fracture risk, decreased health care utilization, and lower costs in compliant and persistent patients.


Serum Urate Levels of Hemodialyzed Renal Patients Revisited.
The need of maintaining serum urate (SU)-lowering agents in hemodialysis (HD) patients is an understudied area that requires a review, as it is a common practice. The aims were to assess the SU reduction achieved under HD and to analyze the kinetics of SU in a week of intermittent HD. The serum urate levels were determined before and after HD sessions in 96 consecutive patients with end-stage renal disease, and the average SU reduction was assessed. Variables related to HD were analyzed whether they were associated with SU reductions of 80% greater. In addition, a kinetics study was performed on 10 selected patients with hyperuricemia (SU before HD >6.8 mg/dL) throughout intermittent HD sessions in a 1-week period. The mean ± SD age of the patients was 66.5 ± 13.8 years, and 62 of them were male (64.6%). The mean ± SD time on HD replacement was 7.1 ± 7.2 years, and 16 (16.4%) continued with urate-lowering agents. The mean SU reduction immediately after HD was 80.2% (95% confidence interval, 78.4-82.0); 51 patients (56.7%) showed SU reduction of 80% or greater. In the SU kinetics study, SU levels significantly reduced all over the period and persisted below hyperuricemia threshold (p = 0.015). Noteworthy, 6 patients (60%) were hyperuricemic before session 1, but only 1 (10%) before session 2 and none before session 3. Under HD replacement therapy, the SU levels effectively reduced and persisted below saturation point, suggesting that the SU-lowering therapy would be unnecessary for patients on HD, but necessary in selected cases. The definition of hyperuricemia under HD needs to be revised.


Management of ruptured aneurysms combined with coexisting aneurysms.
In patients suffering from subarachnoid haemorrhage (SAH) and presenting with multiple intracranial aneurysms (MIA) two questions have to be decided on: 1st when is the ideal moment to eliminate the ruptured aneurysm and 2nd when to treat the coexisting aneurysms. In our series we retrospectively analysed 124 SAH-patients presenting with a total of 323 aneurysms. In 57 patients the ruptured aneurysm and all coexisting aneurysms were clipped during the first operation, whereas in 9 patients only some of the coexisting aneurysms (group-A; age in median 55 years) were clipped besides the ruptured one. In 55 patients (group-B; age in median 55 years) the first operation was restricted to clipping the ruptured aneurysm, dealing with the coexisting aneurysm subsequently. Immediately after admission 3 patients passed away. One of the 64 patients waiting (average 60 days, median 14 days) for the subsequent clipping of the not yet secured aneurysms suffered a SAH. Six to 12 months after the initial SAH, 78% of the cases in both groups reached a Glasgow Outcome Score of 4 or 5. Even if in patients with coexisting unruptured intracranial aneurysms the elimination of each and every aneurysm is recommended, the advantages of an unstaged procedure versus the additional strain caused by the prolongation of the procedure, e.g. approach over the midline, 2 or more craniotomies, and the risk of additional ischemic damage to the brain, caused by increased manipulation of cerebral arteries and brain tissue, have to be carefully considered. This is of special importance in dealing with patients in higher Hunt and Hess grades.


Tenascin-C is upregulated in the skin lesions of patients with atopic dermatitis.
Tenascin-C is a large, hexameric extracellular matrix glycoprotein that is expressed during embryogenesis, carcinogenesis and wound healing. In normal adult human skin the expression level of tenascin-C is low, but levels are elevated in skin tumors and rise significantly in the dermal compartment during wound healing. Although the expression of tenascin-C could be upregulated by inflammatory cytokines, the role of tenascin-C in atopic dermatitis (AD) is still unclear. To identify genes that plays a role in AD. We screened for differentially expressed genes in lesional and non-lesional skin of AD patients using DNA microarray. Then we monitored with quantitative PCR the expression of the novel disease related genes in human keratinocytes or pinnae from NC/Nga mice. We found that tenascin-C gene expression was expressed at higher levels in lesional skin compared to non-lesional skin of the patients, whereas it was not upregulated in the skin of psoriatic patients or healthy controls. In human cultured keratinocytes, tenascin-C was markedly upregulated by IL-4 and IL-13, and moderately upregulated by IFN-gamma. Tenascin-C expression was also upregulated in the AD-like skin lesions induced in NC/Nga mice ears by intradermal injection of mite antigen, and this upregulation was inhibited by prednisolone. These results suggest that upregulation of the tenascin-C expression is specific to AD lesions, and that tenascin-C may therefore play a critical role in regulating the underlining inflammatory processes, which are involved in the pathology of AD.


Susceptibilities of Pseudomonas species to tetracycline, minocycline, gentamicin, and tobramycin.
Members of the genus Pseudomonas are widely implicated in human disease. Although most isolates are P. aeruginosa, there have been serious outbreaks of infection with other members of the genus. The susceptibility patterns of 5) Pseudomonas isolates are reported. It was notable that of the four antibiotics tested, uniform susceptibility was observed with minocycline.


Light-associated nitrogen distribution profile in flowering canopies of sunflower (Helianthus annuus L.) altered during grain growth.
In vegetative canopies of many species, the vertical gradient of lamina nitrogen concentration (NW) parallels the profile of light distribution in such a way that the actual nitrogen partitioning approaches the optimum pattern for canopy photosynthesis. This paper evaluates the hypothesis that a strong sink for nitrogen, viz. growing grain, affects the pattern of lamina nitrogen distribution usually described for vegetative canopies. The light and NW profiles of sunflower (Helianthus annuus L.) crops were characterised from anthesis to physiological maturity. The factorial combination of two plant populations (2.4 and 4.8 plants m-2) and two levels of nitrogen supply (0 and 5 g N m-2) were the sources of variation for NW and light profiles. Before the onset of nitrogen accumulation in grain, the pattern of NW was similar to that described for other species and it was related to the distribution of light in the canopy. Important changes in the profile of NW occurred during grain filling that were unrelated to the light regime. Nitrogen was mobilised from leaves in all positions in the canopy and the rate of NW change was greater in leaves closer to the grain, which were also the leaves where nitrogen was more concentrated. It is concluded that the physiological mechanisms involved in determining the distribution of leaf nitrogen in vegetative canopies do not apply to sunflower during grain filling.


Chylothorax as a manifestation of rheumatic mitral stenosis: its postoperative management with a diet of medium-chain triglycerides.
Chylothorax occurred as a manifestation of severe congestive heart failure resulting from rheumatic mitral stenosis. Following replacement of the mitral valve, chylothorax recurred and was treated by thoracocentesis initially and then resolved during six months of therapy with a diet of medium-chain triglycerides. Ultimately, the patient resumed a regular diet with no further accumulation of pleural fluid.


Haemagglutinating activity of modeccin.
Modeccin, the toxin of Adenia digitata, agglutinates erythrocytes from several mammalian species. The haemagglutinating activity is enhanced by neuraminidase and is inhibited by galactose and by galactose-containing sugars.


Effect of D-penicillamine treatment on brain metabolism in Wilson's disease: a case study.
Sequential measurements of brain glucose metabolism were carried out in a patient with Wilson's disease, before and after successful treatment with D-penicillamine. They demonstrate an evolution of regional metabolism consistent with clinical improvement. The first study showed marked hypometabolism in the putamen on both sides. The second analysis showed bilateral improvement, with predominant residual deficits in the right putamen, while clinical symptoms of striatal dysfunction persisted on the left side. This observation suggests that positron emission tomography is able to follow the neurological evolution in cases of Wilson's disease.


Post direct acting anti-viral agents associated primary hepatic Castleman's disease: A case report.
Castleman's disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. Here we present a case of primary hepatic CD associated with hepatocellular carcinoma (HCC). Sixty-two years old, male received direct-acting antiviral agents (DAAs) for HCV infection. Follow up revealed sustained virologic response; however, three hepatic focal lesions were accidently discovered. Triphasic CT confirmed the HCC nature of two masses while the other mass remained undiagnosed. Surgical intervention was the treatment of choice, and pathological examination showed a fairly circumscribed mass formed of angiolymphoid hyperplasia displayed atrophic germinal center, expanded mantle zone, and variable hyalinization. The radiological evaluation of lymph nodes was unremarkable. The patient is 40 months alive after resection, with no further management advised. The immune-modulatory effect of DAAs may induce hepatic CD development in a cirrhotic patient, necessitating further studies. A new radiologic finding was observed in the present case in the form of vessels traversing through the lesion with no attenuation or occlusion. Pathology remains the gold standard in the diagnosis of CD.


Effect of renal formic acid excretion on urinary calcium and ammonia concentrations.
Intragastrically given formic acid (300 mg/kg) caused high urinary formate concentrations in rabbits with continuously decreasing urinary pH up to 30 h after the dose despite the fact that the bulk of the formate in urine was excreted within 15 h. Urinary formic acid inversely correlated to urinary ammonia in 23 workers occupationally exposed to methanol or formic acid so that the delayed urinary acidification could have been caused by the effects of formate on renal ammonia genesis. The urinary excretion of calcium was linearly correlated to the formic acid excretion by the same subjects. The latter effect may have been caused by interferences with the tubular reabsorption mechanisms for the calcium ion.


Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), infection has been deemed as a global pandemic by the World Health Organisation. While diffuse alveolar damage (DAD) is recognised to be the primary manifestation of COVID-19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. This topic is of great interest, due to growing concerns regarding the potential long-term complications in prolonged survivors. Here we report a detailed histopathological study of 30 autopsy cases with COVID-19 virus infection, based on minimally invasive autopsies performed between February and March, 2020. The mean age was 69 years, with 20 (67%) males and 10 (33%) females and frequent (70.0%) underlying comorbidities. The duration of illness ranged from 16 to 82 (median = 42) days. Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organising (25%) and/or fibrosing (43%) patterns. Patients with fibrosing DAD were one decade younger (P = 0.034) and they had a longer duration of illness (P = 0.033), hospitalisation (P = 0.037) and mechanical ventilation (P = 0.014) compared to those with acute DAD. Patients with organising DAD had a longer duration of illness (P = 0.032) and hospitalisation (P = 0.023) compared to those with acute DAD. COVID-19 pneumonia patients who develop DAD can progress to the fibrosing pattern. While we observed fibrosing DAD in fatal cases, whether or not surviving patients are at risk for developing pulmonary fibrosis and the frequency of this complication will require further clinical and radiological follow-up studies.


Cognitive impairment and antiretroviral treatment in a Peruvian population of patients with human immunodeficiency virus.
HIV-associated cognitive impairment occurs even in the early stages of infection. Short-term memory, psychomotor speed, attention, and executive functioning are the main capacities affected. Controversy exists regarding whether highly active antiretroviral therapy (HAART) is helpful in combating this process. The objective of the present study is to determine the association between cognitive impairment and HAART in HIV-infected patients from Hospital Regional de Huacho. Prospective study of HIV patients meeting criteria to start HAART. Twenty-one HIV-positive patients were recruited between April and July 2011. Researchers administered a standardised neuropsychological test battery before and 4 weeks after onset of HAART. Psychomotor speed, executive function, short term memory (visual and verbal), attention, and visuospatial performance were evaluated. Nineteen patients completed the study (14 males and 5 females). In the pre-HAART evaluation, most patients scored below average on the executive function and psychomotor speed subtests. Psychomotor speed and immediate visual memory improved significantly after four months of treatment with HAART. Some degree of cognitive decline may present even in the early and asymptomatic stages of HIV infection. The benefits of antiretroviral treatment for cognitive performance can be detected after only a few weeks of follow-up.


Visualizing Clonal Evolution in Cancer.
Rapid and inexpensive single-cell sequencing is driving new visualizations of cancer instability and evolution. Krzywinski discusses how to present clone evolution plots in order to visualize temporal, phylogenetic, and spatial aspects of a tumor in a single static image.


Neuroendocrine adenoma of middle ear with new bone formation and review of literature.
Neuroendocrine adenoma of the middle ear has been described in literature as middle ear adenoma with neuroendocrine differentiation or carcinoid tumor. While there have been several case reports describing imaging features of carcinoid tumors of the ear and middle ear adenomas, in our literature review, we have not found a single case where bone formation is described as a prominent radiological feature. We report a first documented case of middle ear carcinoid tumor with new bone formation demonstrated on CT imaging and performed a review literature regarding the tumor. A differential diagnosis of neuroendocrine adenoma of the middle ear should be considered when there is prominent bone formation with a soft tissue mass in the middle ear on CT imaging.


Biliary drainage combined with simultaneous 125I seed strand brachytherapy for the treatment of hilar cholangiocarcinoma.
To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9-4.7) months and 2.8 (95% CI 2.5-3.1) months and 13.5 (95% CI 10.7-16.3) months and 8.8 (95% CI 7.8-9.8) months, respectively, with significant differences (P < 0.05). PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS.


The impact of crisis and COVID-19 on Syrian children growth, health awareness and nutritional practices. a cross-sectional study.
Despite the great steadfastness that Syria has achieved in the face of more than a decade of stifling crisis followed by the global COVID-19 pandemic, the heavy impacts of these long rough years are certain and crucial on the health and nutrition levels, specially on vulnerable groups like women and children. Moreover, the lack of research and data on health and nutritional status of children within Syria makes it very difficult to draw conclusions and act effectively. The purpose of the current study was to evaluate growth development and give an insight about the public health awareness and nutritional practices among Syrian primary schools children. A cross-sectional study was conducted among private and public primary schools' students aged 6 to 9 years old in Homs governorate in January to April 2021, anthropometric measures were taken and data assessment of socioeconomic background, nutritional practices, and health awareness was achieved by conducting two surveys answered by parents and students. We defined the total prevalence of obesity (11.8%), underweight (5.6%) and stunting (13.8%), with a significant increased in underweight and stunting prevalence ,(9%, 21.6%) respectively, among public schools' students compared to private schools' students. Differences in nutritional practices and health awareness were recorded between public and private schools' students under socioeconomic impact. This study contributes to evaluate the burden of crisis and COVID-19 pandemic on Syrian children growth and health practices in Syria. Improving health awareness and nutritional support among Syrian families to help children meet their growth needs is recommended. Moreover, additional research should be conducted to evaluate micro-nutrients deficiencies and provide appropriate medical support effectively.


In vitro plaque-forming cell responses induced by Streptococcus pneumoniae in humans.
When peripheral blood lymphocytes (PBL) were stimulated in vitro with the rough form of type 2 Streptococcus pneumoniae R36a, the resulting plaque-forming cells (PFC) did not produce antibodies directed against phosphorylcholine, a major antigenic determinant of the cell wall C-polysaccharide. Instead, R36a stimulated polyclonal PFC in PBL and splenic lymphocytes. We compared the polyclonal responses stimulated by R36a with those induced by two well-characterized polyclonal activators (PA), Staphylococcus aureus Cowan I and pokeweed mitogen (PWM). We found that R36a was a poor mitogen for PBL, whereas the other two PA were potent mitogens; that the predominant isotype produced in response to all three PA was IgM; that adherent cells strongly inhibited the polyclonal PFC response to both R36a and Staph. aureus but not PWM; and that T cells were necessary for induction of polyclonal antibody-secreting cells by all three stimuli.


Mapping dreams in a computational space: A phrase-level model for analyzing Fight/Flight and other typical situations in dream reports.
This article demonstrates that an automated system of linguistic analysis can be developed - the Oneirograph - to analyze large collections of dreams and computationally map their contents in terms of typical situations involving an interplay of characters, activities, and settings. Focusing the analysis first on the twin situations of fighting and fleeing, the results provide densely detailed empirical evidence of the underlying semantic structures of typical dreams. The results also indicate that the Oneirograph analytic system can be applied to other typical dream situations as well (e.g., flying, falling), each of which can be computationally mapped in terms of a distinctive constellation of characters, activities, and settings.


Bacillus cereus in a whey process.
A cheese dairy and its whey manufacturing line were examined for Bacillus cereus. Colonies typical of B. cereus were detected in 120 (17%) samples out of 720 analysed. Only 3% of the sampled raw milk contained B. cereus ( > or = 10 cfu ml(-1)) whereas in evaporated whey concentrate B. cereus was present in 76% of the samples. Nitrate reductase negative and weakly casein hydrolysis isolates were rare in raw milk and the early parts of the process but these defective biotypes became increasingly frequent towards the end of the whey process. The composition of whole cell fatty acids of B. cereus isolates originating from the whey part of the process was different from that of the type strain and of the isolates originating from the raw materials of cheese making. The B. cereus strains in concentrated whey were 100% similar to the type strain in 16S rDNA sequence (500 bp) although they were not or only poorly recognized as B. cereus by a commercial whole cell fatty acid library. All of B. cereus isolates in raw milk were sensitive to one or more of the B. cereus group phages (n = 17) whereas 43% of the isolates from the whey process were sensitive to none. None of the 23 strains originating from the whey processing lines grew at < or = 8 degrees C. although strains with minimum growth temperatures of 5.3 degrees C and 7.0 degrees C were present in the raw materials. Our results indicate that the B. cereus population of the warm ( > 30 degrees C) parts of the cheese dairy process was separate from that of cold (2 degrees C to 4 degrees C) part of the process.


Exposure of chronic obstructive pulmonary disease patients to particulate matter: relationships between personal and ambient air concentrations.
Mot time-series studies of particulate air pollution and acute health outcomes assess exposure of the study population using fixed-site outdoor measurements. To address the issue of exposure misclassification, we evaluate the relationship between ambient particle concentrations and personal exposures of a population expected to be at risk of particle health effects. Sampling was conducted within the Vancouver metropolitan area during April-September 1998. Sixteen subjects (non-smoking, ages 54-86) with physician-diagnosed chronic obstructive pulmonary disease (COPD) wore personal PM2.5 monitors for seven 24-hr periods, randomly spaced approximately 1.5 weeks apart. Time-activity logs and dwelling characteristics data were also obtained for each subject. Daily 24-hr ambient PM10 and PM2.5 concentrations were measured at five fixed sites spaced throughout the study region. SO4(2-), which is found almost exclusively in the fine particle fraction and which does not have major indoor sources, was measured in all PM2.5 samples as an indicator of accumulation mode particulate matter of ambient origin. The mean personal and ambient PM2.5 concentrations were 18 micrograms/m3 and 11 micrograms/m3, respectively. In analyses relating personal and ambient measurements, ambient concentrations were expressed either as an average of the values obtained from five ambient monitoring sites for each day of personal sampling, or as the concentration obtained at the ambient site closest to each subject's home. The mean personal to ambient concentration ratio of all samples was 1.75 (range = 0.24 to 10.60) for PM2.5, and 0.75 (range = 0.09 to 1.42) for SO4(2-). Regression analyses were conducted for each subject separately and on pooled data. The median correlation (Pearson's r) between personal and average ambient PM2.5 concentrations was 0.48 (range = -0.68 to 0.83). Using SO4(2-) as the exposure metric, the median r between personal and average ambient concentrations was 0.96 (range = 0.66 to 1.0). Use of the closest ambient site did not improve the median correlation of the group for either PM2.5 or SO4(2-). All pooled analyses resulted in lower correlation coefficients than the median correlation coefficient of individual regressions. Personal SO4(2-) was more highly correlated with all ambient measures than PM2.5. Inclusion of time-activity and dwelling characteristics data did not result in a useful predictive regression model for PM2.5 personal exposure, but improved the model fit from simply regressing against ambient concentration (R2 = 0.27). The model for SO4(2-) was predictive (R2 = 0.82), as personal exposures were largely explained by ambient levels. These results indicate a relatively low correlation between personal exposure and ambient PM2.5 that is not improved by assigning exposure to the closest ambient monitor. The correlation between personal exposure and ambient concentration is high, however, when using SO4(2-), an indicator of accumulation mode particulate matter of ambient origin.


In-house television news: focus on employees boosts morale.
A medical center is using a monthly videotaped television news program to effectively inform its departments and personnel about one another, to provide them with special recognition, and to help nurture their esprit de corps. For these reasons, staff participation, especially by nonsupervisory personnel, both in producing and in appearing on the program is emphasized.


Wolf-pack (Canis lupus) hunting strategies emerge from simple rules in computational simulations.
We have produced computational simulations of multi-agent systems in which wolf agents chase prey agents. We show that two simple decentralized rules controlling the movement of each wolf are enough to reproduce the main features of the wolf-pack hunting behavior: tracking the prey, carrying out the pursuit, and encircling the prey until it stops moving. The rules are (1) move towards the prey until a minimum safe distance to the prey is reached, and (2) when close enough to the prey, move away from the other wolves that are close to the safe distance to the prey. The hunting agents are autonomous, interchangeable and indistinguishable; the only information each agent needs is the position of the other agents. Our results suggest that wolf-pack hunting is an emergent collective behavior which does not necessarily rely on the presence of effective communication between the individuals participating in the hunt, and that no hierarchy is needed in the group to achieve the task properly.


Ureteral stenosis following iliac artery stenting.
Ureteral complications after open aortoiliac reconstruction for aneurysmal and occlusive disease have been reported previously. However, ureteral complications from endovascular interventions for iliac artery disease are relatively rare. We describe a case of left ureteral stenosis resulting in hydroureteronephrosis after multiple endovascular interventions involving the left common and external iliac arteries. The intraoperative findings during robotic ureterolysis revealed significant peri-iliac fibrosis and scarring in the area of the iliac stents. This case illustrates that, although uncommon, ureteral stenosis may occur after iliac stenting owing to peristent fibrosis.


Spironolactone inhibits apoptosis in rat mesangial cells under hyperglycaemic conditions via the Wnt signalling pathway.
Mesangial cells (MCs) play a crucial role in maintaining structure and function of glomerular tufts, providing structural support for capillary loops and modulating glomerular filtration by their contractility. MCs apoptosis occurs in experimental diabetic nephropathy, and this correlates with worsening albuminuria. Accumulating evidence suggests that mineralocorticoid receptor (MR) blockade effectively reduces proteinuria in diabetic nephropathy; however, it is rarely known whether spironolactone (SPI), a nonspecific MR antagonist, inhibits apoptosis in MCs under hyperglycaemic conditions. The objectives of this study are to determine the relationship between SPI and apoptosis, and investigate the cell signalling pathway by which SPI inhibits apoptosis. Rat MCs were treated with 30 mM D-glucose and 10(-8), 10(-7) or 10(-6) M aldosterone (ALD) for 24 h. In some experiments, MCs were pretreated with 10(-7) M SPI or 10 mM LiCl for 1 h. Apoptosis was evaluated by cell nucleus staining and flow cytometric analyses, and caspase-3 activity was assayed. Gene and protein expression were quantified using quantitative real-time PCR and Western blotting, respectively. SPI directly inhibited high glucose and ALD-induced MCs apoptosis in a caspase-dependent manner. Importantly, SPI inhibited MCs apoptosis via the Wnt signalling pathway. SPI promoted activation of the Wnt signalling pathway in MCs, leading to upregulation of Wnt4 and Wnt5a mRNA expression, decreased GSK-3β protein expression and increased β-catenin protein expression. As a conclusion, this study suggests that SPI may inhibit apoptosis in MCs during hyperglycaemic conditions via the Wnt signalling pathway. Blockade of the ALD system may represent a novel therapeutic strategy to prevent MCs injury under hyperglycaemic conditions.


One-site versus 2-site phacotrabeculectomy: a randomized study.
To compare 1-site and 2-site combined phacoemulsification with foldable intraocular lens (IOL) implantation and trabeculectomy. El-Maghraby Eye Hospital, Jeddah, Saudi Arabia. Seventy-six eyes with coexisting cataract and glaucoma were randomly assigned to have a mitomycin-C trabeculectomy in a superior quadrant combined with phacoemulsification and foldable IOL implantation through the same incision (1-site group) or a separate, temporal, clear corneal incision (2-site group). Postoperative evaluation included visual acuity, intraocular pressure (IOP), bleb assessment, and number of antiglaucoma medications. Follow-up ranged from 12 to 18 months. Mean preoperative IOP was 28.1 mm Hg +/- 7.1 (SD) in the 2-site group and 26.2 +/- 6.5 mm Hg in the 1-site group. At 6 months postoperatively, mean IOP was 16.9 +/- 4.3 and 16.8 +/- 3.8 mm Hg, respectively (P = .9) and at 12 months, 17.6 +/- 3.3 and 19.1 +/- 3.1 mm Hg, respectively (P = .044). Twenty-three of 39 eyes (59%) in the 2-site group and 14 of 37 (38%) in the 1-site group had clinically apparent filtering blebs at 12 months (P = .065). Postoperative astigmatic change and complications were comparable. Mitomycin-C trabeculectomy superiorly combined with separate temporal clear corneal phacoemulsification provided 1 year IOP control comparable to that with single-incision (1-site) combined cataract and glaucoma surgery.


Citrinin in fruit juices.
Despite the wide distribution of citrinin-producingPenicillium spp. there are only rare reports about the occurence of this mycotoxin in foodstuffs. Particularly, the discrepancy between the common detection of the applerotting fungusP expansum and the complete lack of data about the occurrence of citrinin in apple-based foods is noteworthy. Based on an indirect enzyme immunoassay (EIA) a study was performed aiming at the sensitive detection of citrinin in apple and other fruit juices. The direct analysis of diluted apple juices by the EIA failed due to pronounced sample matrix effects. Though these problems could be resolved by the extraction of artificially contaminated apple juice with dichloromethane, a poor recovery rate (20-30%) for citrinin was observed. Astonishingly, similar results (mean recovery of 29.9%) were received when doted apple juices were directly purified on immunoaffinity columns despite the minimal sample treatment associated with this method. For the detection of citrinin in tomatoe juices samples were purified with a liquid-liquid partition step. Again, the mean recovery rate was very low (32.0%). Analyzing 55 fruit and vegetable juices purchased in local retail stores only traces of citrinin (maximum 0.2 μg/L) could be detected in the samples.


Quality of life after extended pelvic exenterations.
The aim of the study was to compare health-related quality of life (QoL) and oncological outcome between gynaecological cancer patients undergoing pelvic exenteration (PE) and extended pelvic exenteration (EPE). EPEs were defined as extensive procedures including, in addition to standard PE extent, the resection of internal, external, or common iliac vessels; pelvic side-wall muscles; large pelvic nerves (sciatic or femoral); and/or pelvic bones. Data from 74 patients who underwent PE (42) or EPE (32) between 2004 and 2019 at a single tertiary gynae-oncology centre in Prague were analysed. QoL assessment was performed using EORTC QLQ-C30, EORTC CX-24, and QOLPEX questionnaires specifically developed for patients after (E)PE. No significant differences in survival were observed between the groups (P > 0.999), with median overall and disease-specific survival in the whole cohort of 45 and 49 months, respectively. Thirty-one survivors participated in the QoL surveys (20 PE, 11 EPE). No significant differences were observed in global health status (P = 0.951) or in any of the functional scales. The groups were not differing in therapy satisfaction (P = 0.502), and both expressed similar, high willingness to undergo treatment again if they were to decide again (P = 0.317). EPEs had post-treatment QoL and oncological outcome comparable to traditional PE. These procedures offer a potentially curative treatment option for patients with persistent or recurrent pelvic tumour invading into pelvic wall structures without further compromise of patients´ QoL.


Application of the Huisgen cycloaddition and 'click' reaction toward various 1,2,3-triazoles as HIV non-nucleoside reverse transcriptase inhibitors.
The development of novel anti-HIV agents remains an important medicinal chemistry challenge given that no cure for the disease is imminent, and the continued use of current NNRTIs inevitably leads to problems associated with resistance. Inspired by the pyrazole-containing NNRTI lersivirine (LSV), we embarked upon a study to establish whether 1,2,3-triazole heterocycles could be used as a new scaffold for the creation of novel NNRTIs. An especially attractive feature of triazoles used for this purpose is the versatility in accessing variously functionalised systems using either the thermally regulated Huisgen cycloaddition, or the related 'click' reaction. Employing three alternative forms of these reactions, we were able to synthesise a range of triazole compounds and evaluate their efficacy in a phenotypic HIV assay. To our astonishment, even compounds closely mimicking LSV were only moderately effective against HIV.


An easy prepared dual-channel chemosensor for selective and instant detection of fluoride based on double Schiff-base.
A colorimetric and fluorescent dual-channel fluoride chemosensor N,N'-bis (4-diethylaminosalicylidene) hydrazine (sensor S) bearing two imine groups has been designed and synthesized. This structurally simple probe displays rapid response and high selectivity for fluoride over other common anions (Cl(-), Br(-), I(-), AcO(-), H2PO4(-), HSO4(-), ClO4(-), CN(-) and SCN(-)) in a highly polar aqueous DMSO solution. Mechanism studies suggested that the sensor firstly combined with F(-) through hydrogen bonds and then experienced the deprotonation process at higher concentrations of F(-) anion to the two Ar-OH groups. The detection limit was 5.78×10(-7)M of F(-), which points to the high detection sensitivity. Test strips based on sensor S were fabricated, which could act as a convenient and efficient F(-) test kit to detect F(-) for "in-the-field" measurement.


Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant.
The purpose of the study was to investigate the impact of the lung allocation score (LAS) on mortality among highly urgent (HU) and urgent (U) lung transplant (LTx) candidates in Eurotransplant (ET) and to identify useful additional parameters (LASplus). All adult LTx candidates for whom a first request for HU or U status was made in 2008 in ET were included (N = 317). Patients were followed until LTx, death on the waiting list (WL), delisting, or closure date (i.e., January 10, 2010). The relationship between the LAS/LASplus and waiting list, post-transplant, and overall mortality was assessed with a multivariate regression model. The LAS and LASplus were decomposed into their basic waitlist and post-transplant components. Waiting list mortality rate was 22% and 1-year post-transplant mortality rate was 34%. The waitlist component of the LASplus was significantly associated with waiting list mortality (hazard ratio [HR] 1.91, p = 0.021), whereas the LAS was not (p = 0.063). The post-transplant components of both scores were significantly associated with 1-year post-transplant mortality (LAS: HR 2.69, p = 0.005; LASplus: HR 2.55, p = 0.004). Both scores strongly predicted overall mortality (LAS: HR 1.65, p = 0.008; LASplus: HR 1.72, p = 0.005). LAS accurately predicts overall mortality in critically ill transplant candidates and should therefore be considered as the basis for a new lung allocation policy in ET. An adjustment of the original LAS may be indicated to accurately predict waiting list mortality.


The association of cytokine gene polymorphisms with tuberculosis susceptibility in several regional populations.
By collecting the data of all relevant articles, the goal of this study was to better understand the relationship between the IL-6/IL-18 polymorphism and susceptibility to tuberculosis in several regional populations. Pubmed, Embase, WOS and CNKI were used to find relevant literature. The findings of separate research were merged using Review Manager. A total of 25 studies were included in this study. IL-6 rs1800795 (dominant. comparison: p-value < 0.0001, OR 1.43, 95 % CI 1.23-1.67; recessive comparison: p-value < 0.0001, OR 0.48, 95 % CI 0.35-0.65; allele comparison: p-value < 0.0001, OR 1.43, 95 % CI 1.27-1.62), IL-18 rs1946518 (dominant comparison: p-value = 0.01, OR 1.19, 95 % CI 1.04-1.35; recessive comparison: p-value = 0.01, OR 0.82, 95 % CI 0.71-0.96; allele comparison: p-value = 0.002, OR 1.14, 95 % CI 1.05-1.24), IL-18 rs187238 (dominant comparison: p-value = 0.0002, OR 1.35, 95 % CI 1.15-1.58; allele comparison: p-value < 0.0001, OR 1.31, 95 % CI 1.14-1.50). All gene polymorphisms were shown to be substantially linked to tuberculosis in the general population. Positive findings of rs187238 and rs1800795 polymorphisms were primarily driven by several regional populations, according to subgroup analyses. This meta-analysis found that the the IL-6 rs1800795and IL-18 rs187238 polymorphisms may have a role in TB susceptibility.


Diagnostic accuracy of fiberendoscopy in the detection of upper intestinal malignancy. A follow-up analysis.
The accuracy of fiberendoscopy with directed biopsy in the detection of upper intestinal malignancies has been evaluated by studying the operative or postmortem findings or the clinical follow-up data after at least 1 year and, for relevant lesions, after 2 or 3 years. Of 1005 patients examined, a satisfactory follow-up was obtained in 990. There turned out to be no false-positive diagnoses of malignancy in the 167 patients diagnosed fiberendoscopically to harbor an upper intestinal malignancy, and only two false-negative diagnoses in the fiberendoscopically benign group. Seven of the 135 adenocarcinomas of the stomach turned out to be early gastric cancers. The two missed malignancies were interpreted initially as benign gastric ulcers. The over-all endoscopic-bioptic accuracy rate calculated for all patients amounts to 99.8%. Such a high accuracy rate can only be reached provided high numbers of biopsies are taken, and particularly at least 10 of gastric ulcers and of suspicious lesions. Endoscopy by itself is not sufficiently reliable in determining the nature of the lesion. Indeed an incorrect endoscopic interpretation was made in 7.3% of the ulcerous lesions, and in 8.2% of them no firm conclusion could be reached.


Recovery period of sinonasal quality of life and its associated factors after endoscopic endonasal approach for anterior skull base tumors.
Although endoscopic endonasal approach (EEA) for skull base tumors showed a good prognosis in sinonasal quality of life (QOL), what factors have influence on QOL is still in question. Aim/Objectives: To investigate the recovery of sinonasal QOL after EEA for anterior skull base tumors and find its prognostic factors. The study enrolled 250 patients undergoing EEA for anterior skull base tumors over 3 years. Sinonasal QOL was evaluated via sinonasal outcome test (SNOT-22) during 6 months. Age, gender, previous surgery, surgical extent, tumor pathology, combined surgical procedures, and surgical complications were analyzed. There were 101 male and 149 female with average 48.6 ± 16.1 years old. SNOT-22 increased from baseline (median 17.0; Q1-Q3 8.25-30.0) to postoperative 1 and 3 months (27.0; 15.0-36.0; p < .001 and 20.5; 11.0-32.0; p = .021, respectively) and it returned to the baseline within 6 months. Reconstruction with calcium hydroxyapatite and postoperative mucosal edema had a negative impact on the recovery (p = .016 and .010, respectively), after adjustment for the baseline scores and postoperative months. Sinonasal QOL was recovered within 6 months. Avoidance of calcium hydroxyapatite could prevent delayed recovery. Surgeons should carefully manipulate nasal mucosa to minimize postoperative mucosal edema.


Renal cell carcinoma extending into inferior vena cava.
Of 18 patients with renal cell carcinoma extending into the inferior vena cava 16 underwent radical nephrectomy with either venacavotomy and tumor thrombectomy or vena cava resection. Of 8 patients with no evidence of metastasis at the time of surgery 4 (50 per cent) are free of cancer for a mean duration of 93 months. Of 8 patients with known preoperative metastasis 7 died with cancer after a mean survival of 12 months. Operative mortality was 6.2 per cent and morbidity was minimal.


Dental caries status of preschool children in Hong Kong.
To describe the dental caries status of preschool children in Hong Kong and factors which affect their caries status. 658 preschool children aged 4 to 6 years from six randomly selected kindergartens in Hong Kong were surveyed in December 1997. A questionnaire to investigate possible explanatory variables for caries status was completed by their parents. Dental caries was diagnosed according to the criteria recommended by the World Health Organization (1997). Caries experience as measured by the mean number of decayed, missing and filled primary teeth (dmft) of the 4-, 5-, and 6-year-old children were found to be 0.9, 1.8, and 3.3 respectively. Overall, 61% of the children had a zero dmft score. Children born in Mainland China had a higher mean dmft score (4.6) than those born in Hong Kong (1.4). Statistically significant correlations were found between the children's dental caries status and their oral health practices as well as their socio-economic background. Parents' education level, dental knowledge and attitudes were also associated with the children's dental caries experience. In general, the caries status of Hong Kong Chinese preschool children was similar to that of children in industrialised countries and was better than that of children in the nearby areas. However, special dental programmes should be made available to children from lower socio-economic classes and new immigrants from Mainland China because they are the high risk groups for caries in Hong Kong.


Effects of long-term detraining on muscle performance in young soccer players.
Long-term detraining consists of a physiological partial or total reduction of the adaptations induced by training caused by a suspension period of the training itself longer than 4 weeks. The aim of this study was to analyze a group of young soccer players by assessing the effects of long-term detraining on neuromuscular performance. A study sample of 35 young soccer players of subelite level (age: 14.5±0.5 years) was recruited. The subjects were tested 7 days before the interruption of training for the summer break (T0), and at the end of the 7-week detraining period (T1). No statistically significant differences were found for BMI (P=0.283) and percentage of fat mass (P=0.273) between T0 and T1. PUSH UP (P=0.016; ES [effect size]=0.2) and SIT UP (P=0.001; ES=1.2) test values show statistically significant increase, those of CHIN UP (P=0.05; ES=-0.2), instead, a statistically significant worsening. Statistically significant but moderate differences on speed running test 30 meters (P=0.001; ES=0.3) are observed as well as trivial differences on 50 meters (P=0.001; ES=0.2), while differences on 10, 15 and 20 meters are irrelevant. As for the jump tests, values show a slight worsening (P=0.135; ES=0.2) in Squat Jump and Counter Movement Jump (P=0.153; ES=0.2) without statistical significance. A 7-week-long detraining period does not seem to produce any appreciable changes on neuromuscular performance of the lower limb (trained muscle) in young soccer players. As regards the analyzed age group, coaches should not focus their attention on neuromuscular efficiency maintenance exercises in the off-season period.


Radiation-induced osteosarcoma of the chest wall after treatment for unresectable thymoma.
Secondary osteosarcoma is a rare complication of radiation therapy for a primary tumor. Here we report a unique presentation of radiation-induced osteosarcoma of the chest wall after radiation treatment for thymoma. This patient underwent multiple imaging studies, including magnetic resonance imaging and computed tomography with cinematic rendering. Diagnosis of osteosarcoma was confirmed through imaging features and histology. Several surgical procedures were performed to evaluate and attempt resection of the tumor, but ultimately the tumor location and involvement prevented adequate resection and chemotherapy was initiated. This case highlights the importance of identifying clear cumulative dose thresholds for radiation therapy and rare complications of radiotherapy.


Preparation and performance of alginate/basil seed mucilage biocomposite for removal of eriochrome black T dye from aqueous solution.
Mucilage extracted from Basil seeds were captured in calcium alginate biobeads. The beads were tested as eco-friendly adsorbents to eriochrome black T dye from aqueous solution. The synthesized biocomposite was characterized by FESEM, EDX, TGA, and FTIR techniques. Batch and continuous experiments were performed for dye adsorption studies using the synthesized biocomposite. The effect of contact time, pH, initial concentration of dye, and amount of adsorbent on dye adsorption capacity, and also kinetics, isotherm, thermodynamics, regeneration, and swelling investigations were performed. The results showed that the adsorption of eriochrome black T follows the pseudo-second-order batch kinetic model, Yoon-Nelson and Thomas dynamic models, and Freundlich isotherm model. The thermodynamic results showed that the dye adsorption process with the synthetic adsorbent is an exothermic spontaneous process.


Release of biologically active kinin peptides, Met-Lys-bradykinin and Leu-Met-Lys-bradykinin from human kininogens by two major secreted aspartic proteases of Candida parapsilosis.
In terms of infection incidence, the yeast Candida parapsilosis is the second after Candida albicans as causative agent of candidiases in humans. The major virulence factors of C. parapsilosis are secreted aspartic proteases (SAPPs) which help the pathogen to disseminate, acquire nutrients and dysregulate the mechanisms of innate immunity of the host. In the current work we characterized the action of two major extracellular proteases of C. parapsilosis, SAPP1 and SAPP2, on human kininogens, proteinaceous precursors of vasoactive and proinflammatory bradykinin-related peptides, collectively called the kinins. The kininogens, preferably the form with lower molecular mass, were effectively cleaved by SAPPs, with the release of two uncommon kinins, Met-Lys-bradykinin and Leu-Met-Lys-bradykinin. While optimal at acidic pH (4-5), the kinin release yield was only 2-3-fold lower at neutral pH. These peptides were able to interact with cellular kinin receptors of B2 subtype and to stimulate the human endothelial cells HMEC-1 to increased secretion of proinflammatory interleukins (ILs), IL-1β and IL-6. The analysis of the stability of SAPP-generated kinins in plasma suggested that they are biologically equivalent to bradykinin, the best agonist of B2 receptor subtype and can be quickly converted to des-Arg(9)-bradykinin, the agonist of inflammation-inducible B1 receptors.


A hand-held, power-free microfluidic device for monodisperse droplet generation.
Here we develop a microfluidic device to generate monodispersion sub-nanoliter size droplets. Our system reaches steady state within 3 s after the flow starts and generates 100,000 droplets in 28 s with high size consistency (CV < 8%). This low cost device is composed with a microfluidic chip, 2 tubings, a collection vial, a syringe and a station; and is in the size of an iPad Mini (4" × 6" × 3/4"). In this system, all incoming reagents share the same pressure drop across the fluidic passage to generator droplets. A single source negative pressure is applied to the fluids to create the flow by a vacuum at the exit end of the device. The vacuum is generated on-site by pulling the plunger of a syringe. The position of the plunger before and after pulling determines the degree of vacuum. A fixture is used to hold the plunger after it is pulled to maintain its vacuum. Although this system loses vacuum gradually as the liquid filling in, it maintains a flow rates with the changes less than 10% and droplet sizes changes less than 2% during the course of generating 150,000 droplets. The pressure drop across the chip, the flow rates of all reagents, the droplet size and generation frequency are predictable, programmable, and reproducible. This device is designed for generating droplets for single cell genome profiling application but can be also used for digital PCR or other droplet-based applications.


HSV-IgA serum antibodies in cervical intraepithelial neoplasia and invasive cancer patients, and in their spouses: a case control study.
Class-specific IgG and IgA antibodies to HSV were assayed in women with CIN (76), invasive cancer (52) (histological diagnosis) and age-matched controls (119), employing HSV-2-infected HEp-2 cells as antigen during IFA assay. We observed an elevated geometric mean titre (GMT) of serum antibody (IgG five-to eight-fold and IgA four-to five-fold) for the entire spectrum of cervical lesions, as compared to controls. The odds of finding HSV-IgA antibodies were highest with CIN III (OR = 22.0), followed by invasive carcinoma, and CIN I & II (OR = 9.5 and 5.2), respectively. Furthermore, the investigations with respect to married couples (husbands and wives) who volunteered to participate in this study (33 cases and 47 control group) also indicated relatively high antibody titres and increased frequency of HSV sero positivity amongst husbands of cases as compared to their wives, as well as the control group males and females. The contribution of HSV infection in women and/or their husbands to the risk of developing abnormal cervical lesions was analysed after adjusting for the same in respective counterparts. It was observed that the risk was increased 14-fold with HSV-IgA positivity of women, and that HSV-IgA positivity of husbands (male partners) further increased the risk 16-fold. This preliminary observation shows the importance of serum HSV-IgA antibodies as a risk indicator in cervical precancer and cancer lesions in women without a history of recent genital herpes lesions. The serum HSV-IgA may also be taken as an indicator of "high risk" males.


Hematologic problems in pregnancy V. Obstetric transfusion therapy.
A study of 37,186 admissions, from 1970 through 1974, to a large southern charity hospital obstetrics service revealed a striking 63 per cent reduction in number of patients receiving blood transfusions. Analysis showed no change in patient population, bleeding disorders, toxemia, incidence of obstetric hemorrhage, serious febrile morbidity, or incidence of antepartum anemia. In the study period cesarean section rate increased 77 per cent and anemia at delivery markedly decreased. Transfusions associated with spontaneous abortion decreased by 70 per cent, and after the third study year no patient undergoing legal abortion received blood. The study demonstrated improvement in specific hematinic therapy of antepartum anemia and avoidance of transfusion therapy in the presence of uncharacterized antepartum or puerperal anemia. Despite the remarkable decrease in blood transfusions, obstetric outcome (including perinatal mortality rate, maternal mortality rate, and serious febrile morbidity) did not suffer but, indeed, improved.


Toxicity of fumonisin B1 administered intraperitoneally to male Sprague-Dawley rats.
The toxicity of purified fumonisin B1 (FB1) administered ip was examined in male Sprague-Dawley rats. FB1 was injected at 7.5 or 10 mg/kg body weight/day for 4 consecutive days. This resulted in significant reductions in body weight, food consumption and faeces production. Polyuria without a compensatory increase in water consumption was observed in treated rats. Erythrocytosis, elevated haematocrits and haemoglobin levels were attributed to dehydration. Nephrotoxicity in treated rats was evident by clinical changes including elevated blood urea nitrogen and by subtle changes in kidney morphology. Histopathology and serum biochemistry also indicated that the liver was an important target organ in FB1-treated rats. A small increase in liver glutathione concentration was also evident in rats receiving 10 mg FB1/kg body weight. Effects on the immune system included reduced thymus weight, disseminated thymic necrosis and consistently elevated serum immunoglobulin M levels. Circulating phagocytic cell numbers were elevated in treated rats, probably owning to tissue damage associated with ip dosing. The liver and kidneys appear to be target organs of FB1 in Sprague-Dawley rats.


Causal relationship between Gut Microbiota and Obstructive sleep apnea.
Although observational studies have identified relations between gut microbiota and obstructive sleep apnea (OSA), their causal links remain elusive. Hence, we aimed to investigate this causal relation using the Mendelian randomization (MR) approach. Summary-level gut microbiota data were acquired using the maximum available genome-wide association study (GWAS) from the MiBioGen consortium while obtaining summary-level OSA data using publicly available GWAS from the FinnGen Consortium. A two-sample MR analysis was used for assessing gut microbiota and OSA causal effect, using the inverse variance-weighted (IVW) approach as the primary analysis method. The results were further examined for pleiotropy and heterogeneity. Moreover, the reverse MR analysis did not find a causal relationship. Four gut microbiota were found to have nominally significant association to OSA according to the IVW method. Among them, the family Peptostreptococcaceae (OR = 1.171, 95% CI: 1.027-1.334) and genus Coprococcus3 (OR = 1.163, 95% CI: 1.007-1.343), these two florae that may increase the risk of OSA. Family Acidaminococcaceae (OR = 0.843, 95% CI: 0.729-0.975) and genus Blautia (OR = 0.830, 95% CI: 0.708-0.972) may have an ameliorative effect on OSA. No evidence of pleiotropy or heterogeneity was found. MR analysis indicated that a causal relation is existed between specific gut microbiota and OSA at the genetic prediction level, offering innovative perspectives into the mechanisms underlying gut microbiota-mediated OSA development.


Clinical and pathological characteristics of IgG4-related sclerosing sialadenitis.
A new concept of IgG4-related sclerosing sialadenitis characterized by high serum IgG4 levels and tissue infiltration of IgG4-expressing plasmacytes has recently been proposed. To determine appropriate serum levels of IgG4 for monitoring disease activity, a total of 36 serum samples and eight tissue samples from patients with IgG4-related sclerosing sialadenitis were studied. A retrospective clinical study at Yamagata University School of Medicine. The patient group consisted of six males and four females with an average age of 60 years (range, 47-74 years). Serum levels of IgG4 and the density of IgG4-positive plasmacytes in affected tissues were studied. All patients had elevated serum IgG4 levels (>135 mg/dL), and IgG4-positive plasmacytes (IgG4+ plasma cells/IgG+ plasma cells >50%) were observed in the involved salivary glands. Six patients with IgG4-related sclerosing sialadenitis with high IgG4/IgG ratios and prominent infiltration of IgG4-positive plasmacytes in the involved salivary glands had systemic complications, including pancreatitis, retroperitoneal fibrosis, and/or inflammatory pseudotumor of the lung after swelling of the salivary glands. All six of these patients were successfully treated with systemic corticosteroids. In the six patients with systemic complications, treatment with systemic corticosteroids reduced the salivary gland enlargement and lowered serum IgG4 concentrations. These results suggest that IgG4 plays an important role in the pathogenesis of IgG4-related sclerosing sialadenitis, and that IgG4 levels and IgG4/IgG ratios may be used as additional indicators of disease activity and as biomarkers for potential life-threatening complications.


Mutagenicity studies by co-cultivation of bronchoalveolar cells and blood lymphocytes with V79 Chinese hamster cells.
Human bronchoalveolar cells, consisting of approximately 85% pulmonary alveolar macrophages (PAMs), and peripheral blood lymphocytes isolated from healthy volunteers were investigated for their ability to metabolize 7,8-diol of benzo[a]pyrene (B(a)P). The mutagenicity of reactive metabolites was analyzed by employing a co-cultivation system using V79 Chinese hamster cells for the detection of mutations. The metabolic activity of the human cells was compared to PAMs isolated from rabbits. The number of PAMs obtained by bronchoalveolar lavage of smokers was found to be significantly elevated compared with nonsmokers. However, the mean number of induced mutations of the 7,8-diol mediated by PAMs during co-cultivation did not differ significantly between smokers and nonsmokers. The aryl hydrocarbon hydroxylase (AHH) activity of human lymphocytes has been studied by others, but to the best of our knowledge this is the first demonstration that human blood lymphocytes could be successfully used in a co-cultivation assay for the characterization of xenobiotic metabolism in terms of mutations, as illustrated by the linear increase of induced mutations in the V79 cells. Rabbit PAMs were less efficient in mediating mutations as compared to both smokers' and nonsmokers' PAMs or lymphocytes. This can probably be explained by less efficient bioactivation of 7,8-diol in rabbit PAMs, which is supported by the fact that the rabbit PAMs metabolized B(a)P in a different way as compared to human PAMs as revealed by HPLC analysis of ethyl acetate extractable metabolites of 3H-B(a)P. No qualitative or quantitative difference in the patterns of B(a)P metabolism by PAMs isolated from smokers and nonsmokers could be established. In conclusion, human PAMs were found to be more efficient in terms of cell-mediated mutagenicity than human lymphocytes, which are more efficient than rabbit PAMs. The present results differ from previous reports concerning the xenobiotic metabolizing capacity of these cells assessed by other methods. This illustrates the usefulness of the co-cultivation assay, because it measures not only the bioactivating capacity of isolated mammalian cells, but also their detoxifying capacity, the transfer of mutagens to other cells and the ability of their metabolites to cause mutations.


[Juvenile idiopathic epiretinal membrane].
Idiopathic epiretinal membrane (iERM) is very rare in adolescent patients. The pathogenesis remains unclear although the role of hyalocytes is of major importance. The clinical features in young patients are different from those in older patients. We describe a case of iERM in a 15-year-old girl who presented with metamorphopsia of the right eye. This case report presents the basis for the decision for surgical treatment as well as the clinical features at follow-up examination 9 months after surgery.


Hydrophilic polymers--biocompatibility testing in vitro.
Biocompatibility is one of the main prerequisites for safe use of medical devices. Estimation of cytotoxicity is a part of the initial evaluation laid down in ISO standards on biological evaluation of medical devices. Hydrophilic polymers (based on 2-hydroxyethyl methacrylate HEMA) doped by addition of selected additives with antioxidant and/or free radical scavenging potential (vitamin C and hindered amine stabilizer N-(2,2,6,6-tetramethylpiperidin-4-yl)methacrylamide) were tested in different in vitro systems (3T3 Balb/c cell culture and a 3D human skin model) for biocompatibility and suitability for use as wound dressings. The results of the 3T3 NRU cytotoxicity test using both the direct and indirect contact approaches and a 3D skin model modified irritation test (EpiDerm) confirmed high biocompatibility and good skin tolerance of both the basic polymers and those enriched with specific additives up to a balanced level. HEMA polymer showed a beneficial effect against cytotoxicity of an irritant (sodium dodecyl sulfate). The in vitro biocompatibility test results were confirmed by human local skin tolerance testing.


Thymic epithelial neoplasms with rhabdomyomatous component: a clinicopathological and immunohistochemical study of 7 cases.
Seven primary thymic epithelial neoplasms, 3 thymomas and 4 thymic carcinomas, with rhabdomyomatous component are herein described. The patients are 2 women and 5 men between the ages of 42 and 62 years (average, 52 years). Clinically, the patients presented with nonspecific symptoms of cough, chest pain, and dyspnea. None of the patients had history of myasthenia gravis or of previous malignancy. Diagnostic imaging revealed the presence of an anterior mediastinal mass in all the patients. Surgical resection was accomplished in all the cases. The 3 thymoma cases were encapsulated tumors: histologically, 2 were lymphocyte rich (World Health Organization type B1), and 1 was an atypical thymoma (World Health Organization type B3). All the thymic carcinomas were ill-defined tumor masses with infiltrative borders and histologically were high-grade carcinomas. In each tumor, in different proportion, there were easily identifiable areas with rhabdomyomatous component characterized by larger cells with eosinophilic cytoplasm and eccentrically placed nuclei. Immunohistochemical stains in all cases showed clearly demarcated presence of the epithelial component (keratin positive/desmin and myoglobin negative) and the rhabdomyomatous component (desmin and myoglobin positive/keratin negative). The 3 patients with thymoma are alive and without recurrence 3 and 5 years after surgical resection, whereas 3 patients with carcinoma died between 2 and 3 years after surgical resection. One patient with thymic carcinoma was lost to follow-up. The current cases highlight the ubiquitous distribution of myoid cells in different types of thymic epithelial neoplasms.


Enhancement of in vitro antibody responses by human serum proteins cleaved by trypsin.
Tryptic cleavage of human serum proteins remarkably enhanced in vitro plaque-forming cell (PFC) responses of mouse spleen cells primed with sheep erythrocytes (SE). Moreover, trypsin cleaved proteins could mimic the activity of T-cells in immune responses of SE-primed B cells. Eluted with 6 M guanidine-HCl on a Sepharose 6B-CL Column, the activity was found in the fraction corresponding to the molecular weight greater than 100,000. The results suggest that tryptic cleavage of human serum proteins produced a factor(s) that resembled the T-cell augmentation of B-cell immune responses.


Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity.
The adenosine A2A receptor (A2AR) is the major cellular adenosine receptor commonly associated with immunosuppression. Here, we investigated whether A2AR activation holds the potential for impacting the severity of experimental autoimmune myasthenia gravis (EAMG) induced following immunization of Lewis rats with the acetylcholine receptor (AChR) R97-116 peptide. This report demonstrates reduced A2AR expression by both T cells and B cells residing in spleen and lymph nodes following EAMG induction. A2AR stimulation inhibited anti-AChR antibody production and proliferation of AChR-specific lymphocytes in vitro. Inhibition was blocked with the A2AR antagonists or protein kinase A inhibitor. We also determined that the development of EAMG was accompanied by a T-helper cell imbalance that could be restored following A2AR stimulation that resulted in increased Treg cell levels and a reduction in Th1-, Th2-, and Th17-cell subtypes. An EAMG-preventive treatment regimen was established that consisted of (2-(p-(2-carbonylethyl)phenylethylamino)-5-N-ethylcarboxamidoadenosine) (CGS21680; A2AR agonist) administration 1 day prior to EAMG induction. Administration of CGS21680 29 days post EAMG induction (therapeutic treatment) also ameliorated disease severity. We conclude that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of myasthenia gravis or other T-cell- and B-cell-mediated autoimmune diseases.


Atrial fibrillation in trauma patients requiring intensive care.
To evaluate the incidence and risk factors of atrial fibrillation (AF) in trauma patients. Prospective observational study in a surgical intensive care unit (ICU). All trauma patients admitted in the surgical ICU except those who had AF at admission. AF occurred in 16/293 patients (5.5%). AF patients were older, had a higher number of regions traumatized, and received more fluid therapy, transfusion products, and catecholamines. They more frequently experienced systemic inflammatory response syndrome, sepsis, shock, and acute renal failure and had higher scores of severity (Simplified Acute Physiology Score, SAPS II; Injury Severity Score). ICU length of stay and resources use were also increased. ICU and hospital mortality rates were twice higher in AF patients whereas standardized mortality ratio (observed/expected mortality by SAPS II) was similar in the two groups. We found five independent risk factors of developing AF: catecholamine use (OR = 5.7, 95% CI 1.7-19.1), SAPS II of 30 or higher (OR = 11.6, 95% CI 1.3-103.0), three or more regions traumatized (OR = 6.2, 95% CI 1.8-21.4), age 40 years or higher (OR = 6.3, CI 1.4-28.7), and systemic inflammatory response syndrome (OR = 4.4, 95% CI 1.2-16.1). In addition to age and catecholamine use, inflammation and severity of injury may be involved in the development of AF in trauma patients. Our results suggest that AF could rather be a marker of a higher severity of illness without major effect on mortality.