Chondroid syringoma. A case report.
Chondroid syringoma is a benign skin tumour characterized by several histological aspects similar to salivary gland adenomas. It generally affects the head and neck, mainly in the 6th and 7th decade of life. Its incidence in males is twice as high as in females. The neoplasm is usually an asymptomatic subcutaneous swelling that patients want removed for aesthetic reasons. Excision is the elective treatment. A few cases of malignant chondroid syringoma, however, have been reported. The neoplasm tends to produce metastases to both the regional and distant lymph nodes, causing the death of the patient. In these cases, radiation therapy follows the surgical excision. The authors report the case of a woman with chondroid syringoma located in the occipital region of the scalp. After a period of slow growth, the neoplasm suddenly increased in size. The patient asked for it to be removed out of concern for the concomitant hair loss.


Tattoo Infections, Personal Resistance, and Contagious Exposure through Tattooing.
Bacterial infection of tattoos remains a common complication. Pyogenic bacteria can cause infections shortly after the tattoo is made. Severity of infection varies from minor to major, ultimately with life-threatening septicemia. Viral infections may be introduced, i.e. HVB, HVC, and HIV. The risk of infection depends on the following triad: microbial pathogen and its aggressiveness, individual resistance of the tattooed, and inoculation and exposures by the tattoo needle and in the tattoo parlor. Some infectious risks can be controlled. Persons with weaknesses can refrain from tattooing. Tattoo parlors and tattooing can be hygienic and clean albeit not sterile; much has improved helped by hygiene guidelines of professional tattooists' organizations and through control instituted by local and national authorities. Tattoo inks remain a potential source of infection difficult to control in a low-priced competitive market operating over the Internet and across national borders. Ten percent of new inks are contaminated with bacteria pathogenic to humans, independent of a claim of 'sterility'. Known brands and established manufacturers are considered safer. Work is in progress aiming at common European standards for tattoo hygiene. Doctors have a role not only in treating tattoo infections but also in reporting cases to the competent authority in their country to support the monitoring of tattoo infections at any time, as an instrument for the authority to detect local outbreaks of tattoo infections early and prevent that new tattoo customers become infected. It is a potential risk of the future that new and very aggressive bacteria not seen in the past may unexpectedly show up in the tattoo scene.


Public attitudes towards human genetics research: endorsement, indifference or opposition (1)
Research in human genetics presents major ethical and moral issues as well as scientific and technological challenges. The potential contributions of genetics research to the alleviation of human suffering are virtually unlimited. It offers opportunities to help shift medicine from the biomedical model of "diagnosis and treatment" of disease to the ecological model of "prevention and early intervention" of disease. Genetics research promises to yield approaches to medical diagnosis and therapy that are truly "primary" technologies, rather than the "half-way" technologies that comprise much of the medicine practiced today. At a fundamental level, genetics research is a search for new knowledge. It is at this level that many of the ethical and moral issues arise. These issues are best addressed by an informed public willing to approach them honestly and dispassionately. Creation of an informed and objective public demands a productive and ongoing dialogue between science and society. Establishment of such a dialogue requires a major commitment of scientists, especially those engaged in genetics research.


[Protective and antioxidative effect of 2(3)tert-butyl-4-hydroxyanisole against cytotoxicity induced by doxorubicin in mice].
The protective and antioxidative effects of 2(3)tert-butyl-4-hydroxyanisole (BHA) against cardiotoxicity and hepatotoxicity induced by doxorubicin in mice were investigated. After pretreatment with different oral doses of BHA, doxorubicin 30 mg.kg-1 was given i.p. Serum GPT, GOT, LDH and CK were determined, and the mortality rate of animals was observed. Quinone reductase (QR), glutathione-S-transferases (GSTs) and glutathione reductase (GR) were determined on tissue cytosols with enzyme dynamic methods. Malondialdehyde (MDA) was measured by the method of thiobarbituric acid. Compared with the doxorubicin group, the serum GPT, GOT, LDH, CK and the mortality rate of mice were significantly decreased by BHA pretreatment, and BHA was shown to inhibit the increase of MDA induced by doxorubicin (P < 0.01 and P < 0.0001). Administration of BHA resulted in increased activities of QR, GSTs and GR in the myocardium and liver (P < 0.05 or P < 0.0001). These results suggest that BHA has protective effect against the toxicity induced by doxorubicin via the induction of QR, GSTs and GR activities and anti-lipid peroxidation.


Slug inhibition increases radiosensitivity of nasopharyngeal carcinoma cell line C666-1.
Slug is associated with the radioresistance of nasopharyngeal carcinoma (NPC) and the main current approach of treatment for NPC is radiotherapy. Hence, the aim of the current study was to determine the effect of Slug silencing on the radiosensitivity of NPC cells. Lentiviral-mediated transfection of Slug RNA interference (RNAi) in NPC cell line C666-1 was performed in vitro. Following Slug inhibition, its expression was detected using western blotting. A clonogenic survival assay and flow cytometry were then performed to evaluate the clonogenic cell survival, cell cycle distribution and apoptosis of C666-1 cells following irradiation. The results indicated that Slug RNAi decreased cell proliferation, and increased cell apoptosis and G0/G1 arrest. Thus, lentiviral-mediated transfection of Slug RNAi enhanced the radiosensitivity of the NPC cell line C666-1, and Slug may therefore be a potential target to improve radiotherapy in treatment of NPC and reduce the radioresistance of NPC.


Considerations for optimal management of patients with pulmonary arterial hypertension: a multi-stakeholder roundtable discussion.
A roundtable panel of national and regional managed care decision makers and providers met to discuss pulmonary arterial hypertension (PAH) and strategies for management. As a rare, complex disease with high economic costs and potentially devastating outcomes, PAH necessitates that managed care providers balance optimal care with efficient use of healthcare resources. PAH specialists are recognized by health plans as knowledgeable experts and integral partners in managing patients and resources. The diagnosis of PAH must be confirmed by a right heart catheterization. Available therapies are indicated almost exclusively for patients with PAH (riociguat is also indicated in chronic thromboembolic pulmonary hypertension) and target 1 of 3 pathways: endothelin receptor antagonists for the endothelin pathway; phosphodiesterase type-5 inhibitors and soluble guanylate cyclase stimulators for the nitric oxide pathway; and prostanoids as well as a prostacyclin receptor agonist for the prostacyclin pathway, with combination therapy becoming more common. Even in the modern treatment era, as shown in the REVEAL and French registries, PAH is often diagnosed years after symptoms first appear, which leads to a poor prognosis and increased burden on the healthcare system. Facilitating treatment of patients with PAH through centers of excellence, and coordinating care management between health plans and providers with evidence-based approaches can lead to both better results for patients and lower healthcare costs. When PAH experts have access to the right treatments for the right patients at the right time, they can work with insurers to improve the health of patients with PAH while helping to reduce the impact on the healthcare system.


Shape control of surface-stabilized disclination loops in nematic liquid crystals.
Recent studies on topological defects in conventional and active nematic liquid crystals have revealed their potential as sources of advanced functionality whereby the collective behavior of the constituent molecules or cells is controlled. On the other hand, the fact that they have high energies and are metastable makes their shape control a nontrivial issue. Here, we demonstrate stabilization of arbitrary-shaped closed disclination loops with 1/2 strength floating in the bulk by designing the twist angle distribution in a liquid crystal cell. Continuous variation of the twist angle from below to above |π/2| allows us to unambiguously position reverse twist disclinations at will. We also analyze the elastic free energy and uncover the relationship between the twist angle pattern and shrink rate of the surface-stabilized disclination loop.


Multimodal learning of noncoding variant effects using genome sequence and chromatin structure.
A growing amount of noncoding genetic variants, including single-nucleotide polymorphisms, are found to be associated with complex human traits and diseases. Their mechanistic interpretation is relatively limited and can use the help from computational prediction of their effects on epigenetic profiles. However, current models often focus on local, 1D genome sequence determinants and disregard global, 3D chromatin structure that critically affects epigenetic events. We find that noncoding variants of unexpected high similarity in epigenetic profiles, with regards to their relatively low similarity in local sequences, can be largely attributed to their proximity in chromatin structure. Accordingly, we have developed a multimodal deep learning scheme that incorporates both data of 1D genome sequence and 3D chromatin structure for predicting noncoding variant effects. Specifically, we have integrated convolutional and recurrent neural networks for sequence embedding and graph neural networks for structure embedding despite the resolution gap between the two types of data, while utilizing recent DNA language models. Numerical results show that our models outperform competing sequence-only models in predicting epigenetic profiles and their use of long-range interactions complement sequence-only models in extracting regulatory motifs. They prove to be excellent predictors for noncoding variant effects in gene expression and pathogenicity, whether in unsupervised "zero-shot" learning or supervised "few-shot" learning. Codes and data can be accessed at https://github.com/Shen-Lab/ncVarPred-1D3D and https://zenodo.org/record/7975777.


The effect of bystander cardiopulmonary resuscitation on the survival of out-of-hospital cardiac arrests: a systematic review and meta-analysis.
For many years, bystander cardiopulmonary resuscitation (BCPR) has been considered as a favorable factor to improve survival of out-of-hospital cardiac arrests (OHCAs). To examine the effect of BCPR on the survival of OHCAs and whether BCPR might also improve survival when the initial rhythm of OHCAs is limited, we performed a meta-analysis on published observational studies. We did a systematic review to identify all studies published up to March, 2018, in any language, that reported the relation between BCPR and the survival of OHCAs. Using standard forms, two authors independently identified studies for inclusion and extracted information. The outcome was survival. Meta-regression was done to ascertain weighted factors for the outcomes. Data were extracted from 19 studies involving 232,703 patients. Firstly, pooled odds ratio (OR) from 16 cohort studies showed that BCPR was associated with improved chance of survival of OHCAs compared with NO-BCPR (OR 1.95, 95% confidence interval [CI]: 1.66-2.30). Secondly, from 8 cohort studies of OHCAs whose initial rhythm is limited, the pooled OR was 2.10 (95% CI, 1.68-2.63) of 6 articles for shockable rhythm and 1.07 (95% CI, 0.37-3.13) of 2 articles for non-shockable rhythm. Meta-regression showed a relation between the survival of OHCAs and BCPR was influenced by area (p < 0.05). Based on currently available evidence, the findings of this meta-analysis suggest that BCPR increases the survival of OHCAs, and it also help OHCAs whose initial rhythm is shockable. That is to say BCPR is also helpful when emergency department response time is short. Therefore global priority should be given to increasing the incidence of BCPR by evidence-based best practice.


Qualifying to Use a Home Monitoring Device for Detection of Neovascular Age-Related Macular Degeneration.
Patients with intermediate age-related macular degeneration (AMD) using a home monitoring device have less loss of visual acuity, on average, at detection of choroidal neovascularization than do individuals using standard care monitoring techniques. Understanding the frequency with which patients are likely to initiate using a home monitoring device successfully is important in planning implementation of the device into practice. To determine the frequency with which patients with intermediate AMD qualify to use a home monitoring device and to establish a reliable baseline reference value with the device to monitor their AMD for progression to choroidal neovascularization. Between October 8, 2010, and May 20, 2011, a total of 131 eligible participants within a university-based retina practice with intermediate AMD in the study eye and visual acuity of 20/63 or better completed an in-clinic qualification test for the home device. Intermediate AMD was defined as multiple intermediate-sized drusen or at least 1 large druse. If both eyes were eligible, the eye with better visual acuity was selected as the study eye. If both eyes had the same visual acuity, the patient used the eye with subjectively better vision. Analysis was performed between August 1, 2011, and January 11, 2014. The proportion of patients with reliable qualification test results and a test score predictive of successful home use of a monitoring device for detecting neovascular AMD, and the proportion who established a baseline reference value at home. A total of 129 participants (98.5%; 95% CI, 96.4%-99.9%) had reliable qualification test results; 91 participants (69.5%; 95% CI, 61.6%-77.4%) who completed this test attained a score that suggested they would be able to successfully use the home device. Among the 91 participants who could initiate home testing, 83 did so, including 80 participants (87.9%; 95% CI, 81.2%-94.6%) who established a baseline value that could be used as a reference for future monitoring. Younger participants were more likely to qualify for home testing (mean [SD] age, 73.1 [8.4] vs 81.1 [7.1] years; P < .001). Visual acuity at study enrollment did not appear to be associated with successful qualification (mean visual acuity for those who did and did not qualify was 20/28 and 20/31, respectively; P = .10). These data suggest that the in-office qualification test is a useful screening tool to identify patients who may benefit from the home device. In any given retina practice, our data suggest an estimated 61.6% to 77.4% of patients with intermediate AMD should be able to produce reliable initial test results in the office test using the home monitoring device and pass a qualification test to initiate home monitoring. Subsequently, 81.2% to 94.6% of patients should be able to establish a home baseline reference value for future monitoring.


Cytotoxicity of synthetic barium hydroxyapatite.
Barium hydroxyapatite (Ba10(PO4)6(OH)2, Ba-HAp) was synthesized by a wet method using Ba(OH)2.8H2O and (NH4)2HPO4 as starting materials. The Ba-HAp obtained had a Ba/P atomic ratio of 1.76 and contained CO3 groups. The Ba-HAp was sintered at 1073 K for 12 hours. The sintered Ba-HAp had a three point bending strength of 29 MPa and Young's modulus of 27 GPa. Cytotoxicity of the sintered bodies and particles was tested using L-cells. The sintered Ba-HAp showed no cytotoxicity, and the cells were closely in contact with the surfaces of sintered Ba-HAp. Morphological observation of the cell around the Ba-HAp particles also showed no cytotoxicity. However, cell growth was inhibited by Ca adsorption on the Ba-HAp particles. These results suggested that the Ba-HAp had no cytotoxicity and can be applied as a bioactive X-ray opaque material.


Screening for hepatocellular carcinoma.
This article reviews methodological issues around screening for hepatocellular carcinoma, and discusses selection of the at-risk group, which screening test to use, and how frequently it should be applied. Screening of patients at risk for hepatocellular carcinoma should be undertaken using ultrasonography applied at six-month intervals. Patients at risk include all those with cirrhosis, and certain non-cirrhotic patients withchronic hepatitis B. In this population, screening has been shown to reduce disease-specific mortality. Although data do not exist for other populations, screening is nonetheless advised because small cancers can be cured with appreciable frequency.


Individual Differences in Adolescents' Civic Engagement: The Role of Civic Discussions with Parents and Environmental Sensitivity.
The main goal of the current study was to examine the direct and moderating effects of civic discussions with parents and environmental sensitivity using both the total score and its specific dimensions (i.e., Aesthetic Sensitivity, AES; Ease of Excitation, EOE; Low Sensitivity Threshold, LST) on youth civic engagement (attitudes and behaviours). The empirical analysis relied on a questionnaire-based survey conducted on a sample of 438 adolescents (30% males), aged between 14 and 18 years (M = 16.50, SD = 1.36). We used a structural equation model (SEM) with latent variables and the latent moderated structural equation (LMS) method to test our hypotheses. Our results showed that civic discussions with parents were positively and significantly associated with general environmental sensitivity and with AES and predicted both civic attitudes and civic behaviours; EOE was negatively and significantly related to civic behaviours; AES was positively and significantly related to civic attitudes; and LST was not significantly related to either civic attitudes or behaviours. Contrary to our expectations, environmental sensitivity did not moderate the relationship between civic discussions with parents and civic engagement. Our study further highlights the relevance that parents have in shaping their children's civic engagement and makes a novel contribution regarding how differences in perceiving and processing environmental stimuli can affect beliefs and behaviours toward community issues among young individuals.


"A renewed sense of purpose": mothers' and fathers' experience of having a child following a recent stillbirth.
Most research has focused on mothers' experiences of perinatal loss itself or on the subsequent pregnancy, whereas little attention has been paid to both parents' experiences of having a child following late perinatal loss and the experience of parenting this child. The current study therefore explored mothers' and fathers' experiences of becoming a parent to a child born after a recent stillbirth, covering the period of the second pregnancy and up to two years after the birth of the next baby. In depth interviews were conducted with 7 couples (14 participants). Couples were eligible if they previously had a stillbirth (after 24 weeks of gestation) and subsequently had another child (their first live baby) who was now under the age of 2 years. Couples who had more than one child after experiencing a stillbirth and those who were not fluent in English were excluded. Qualitative analysis of the interview data was conducted using Interpretive Phenomenological Analysis. Five superordinate themes emerged from the data: Living with uncertainty; Coping with uncertainty; Relationship with the next child; The continuing grief process; Identity as a parent. Overall, fathers' experiences were similar to those of mothers', including high levels of anxiety and guilt during the subsequent pregnancy and after the child was born. Coping strategies to address these were identified. Differences between mothers and fathers regarding the grief process during the subsequent pregnancy and after their second child was born were identified. Despite difficulties with bonding during pregnancy and at the time when the baby was born, parents' perceptions of their relationship with their subsequent child were positive. Findings highlight the importance of tailoring support systems not only according to mothers' but also to fathers' needs. Parents', and particularly fathers', reported lack of opportunities for grieving as well as the high level of anxiety of both parents about their baby's wellbeing during pregnancy and after birth implies a need for structured support. Difficulties experienced in bonding with the subsequent child during pregnancy and once the child is born need to be normalised.


[Molecular phylogenetic analysis of Diacyclops and Acanthocyclops (Copepoda: Cyclopoida) from Lake Baikal].
Lake Baikal is inhabited by a relatively large number of cyclopid species, many of which are endemics. Two genera, Diacyclops Kiefer, 1927 and Acanthocyclops Kiefer, 1927, are the most specious in the lake. Taxonomic discrimination of the majority of representatives of these genera is difficult owing to their high morphological similarities and poor standard description. In this study, a molecular phylogenetic analysis of Lake Baikal members of the Diacyclops/Acanthocyclops group is performed on the basis of mitochondrial cytochrome c oxidase subunit I (COI) gene. It is shown that a fragment of COI 1000 bp long is sufficient for intragenus discrimination of the cyclopids of Lake Baikal. The issues of Diacyclops/Acanthocyclops taxonomy are reflected in the obtained molecular data. Two distinct phylogenetic groups of Diacyclops genus with uncertain taxonomic status are revealed.


Hand-assisted laparoscopic nephroureterectomy for upper urinary-tract transitional-cell carcinoma.
Hand-assisted laparoscopic nephroureterectomy with laparoscopic, cystoscopic, or open management of the distal ureter and bladder cuff allow anyone from the novice to the advanced laparoscopic surgeon to perform en-bloc resection of the kidney, ureter, and bladder cuff without compromising oncologic principles. Patients receive significant benefits in the form of less pain, shorter hospital stay, and rapid convalescence. As more urologic surgeons develop skills with this procedure, a more critical analysis of early and long-term results will be possible. As operative times decrease, hand-assisted laparoscopic nephroureterectomy may become the procedure of choice for upper-tract transitional-cell carcinoma. The techniques and early results are described.


Influence of cementation variables on fatigue of simulated two-unit cantilever resin-bonded fixed partial dentures.
To determine the influence of various combinations of surface pretreatment and luting cement on flexural fatigue limits of two-unit CoCr cantilever resin-bonded fixed partial dentures. Cyclic fatigue tests were performed at 1 Hz on an ACTA fatigue tester. The staircase test method was used on CoCr beams, simulating cantilever resin-bonded fixed partial dentures, using flat ground bovine teeth as substrate. Two series of tests have been executed: (1) 10(4) cycles, and (2) 10(5) cycles. Prior to cementation, the CoCr beams were subjected to either sandblasting or Rocatec or Silicoater treatments. Three commercially available resin luting cements were used. Fatigue tests were performed 72 hours after cementation and storage in 37 degrees C tap water. Each possible combination of cement and pretreatment (n = 20) was tested. One cement, UniFix, showed hardly any debondings with any of the three surface pretreatments. The other two cements, RelyX ARC and Panavia, both showed significantly better performance with Rocatec than when pretreated with sandblasting or Silicoater.


H2O2 dynamics in the malaria parasite Plasmodium falciparum.
Hydrogen peroxide is an important antimicrobial agent but is also crucially involved in redox signaling and pathogen-host cell interactions. As a basis for systematically investigating intracellular H2O2 dynamics and regulation in living malaria parasites, we established the genetically encoded fluorescent H2O2 sensors roGFP2-Orp1 and HyPer-3 in Plasmodium falciparum. Both ratiometric redox probes as well as the pH control SypHer were expressed in the cytosol of blood-stage parasites. Both redox sensors showed reproducible sensitivity towards H2O2 in the lower micromolar range in vitro and in the parasites. Due to the pH sensitivity of HyPer-3, we used parasites expressing roGFP2-Orp1 for evaluation of short-, medium-, and long-term effects of antimalarial drugs on H2O2 levels and detoxification in Plasmodium. None of the quinolines or artemisinins tested had detectable direct effects on the H2O2 homeostasis at pharmacologically relevant concentrations. However, pre-treatment of the cells with antimalarial drugs or heat shock led to a higher tolerance towards exogenous H2O2. The systematic evaluation and comparison of the two genetically encoded cytosolic H2O2 probes in malaria parasites provides a basis for studying parasite-host cell interactions or drug effects with spatio-temporal resolution while preserving cell integrity.


Diffuse fluorodeoxyglucose-positron uptake in the bone marrow of a patient with granulocyte colony-stimulating factor-producing pleomorphic carcinoma of the lung: A case report.
The current study presents the case of a 66-year-old male presenting with fever and chest pain. Chest enhanced computed tomography scanning revealed a mass shadow in the right upper lobe with chest wall invasion. 18-Fluorodeoxyglucose-positron emission tomography (FDG-PET) identified the localized uptake of the mass lesion in the right upper lobe, in addition to diffuse uptake by the bone marrow. The laboratory data on admission revealed marked leukocytosis and an elevated C-reactive protein level (CRP). Serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin 6 were increased. Based on a clinical diagnosis of non-small cell lung cancer (c-T3N0M0 stage IIB), the patient underwent right upper lobectomy with chest wall resection. The histological examination showed a pulmonary pleomorphic carcinoma. Immunohistochemical analysis of the resected tumor tissues revealed positive staining for G-CSF. The patient's high-grade fever, leukocytosis, and elevated CRP level rapidly subsided following the resection. This confirmed that the tumor was a G-CSF-producing pulmonary pleomorphic carcinoma. Five months after the resection, the diffuse FDG uptake in the bone marrow was absent, even with the presence of a small pulmonary metastasis and marginal serum G-CSF elevation. Diffuse FDG uptake in bone marrow induced by G-CSF producing pleomorphic carcinoma must be taken into consideration, in order for it not to be misinterpreted as diffuse bone marrow metastases or hematologic malignancy.


Wideband tympanometry in ears with superior canal dehiscence before and after surgical correction.
Wideband tympanometry (WBT) has been shown to be sensitive to mechanical changes in the ear. This study investigated the effect of surgical correction of superior canal dehiscence (SCD) on WBT (i.e. absorbance and middle ear resonance frequency) compared to those on common surgical outcomes such as symptom resolution, vestibular evoked myogenic potentials (VEMP), and hearing thresholds. Seven patients (eight ears with SCD) who underwent surgical correction of SCD underwent WBT in addition to pure-tone audiometry and VEMP assessment. Postoperatively, all ears showed normalised/decreased absorbance at low frequencies and slightly enhanced absorbance in the middle frequency range (7/8 ears). The middle ear resonance frequency, which was initially lower than normal in most patients, increased in 6/8 operated ears, and decreased in two ears with no/partial symptom relief. In comparison, complete symptom control was observed in 6/8 operated ears, VEMP amplitudes reduced or normalised in all ears, and hearing thresholds remained stable or improved in 6/8 ears and worsened in two ears. Surgery seems to change the response to WBT in patients with SCD. The results of WBT may represent mechanical changes induced by SCD, and should be considered when evaluating surgical outcomes.


On the origin of the large electron correlation contribution to the hyperpolarizabilities of some diacetylene rare gas compounds.
A comprehensive study of the linear and nonlinear molecular optical properties of HRgC(4)H, where Rg = Ar,Kr,Xe, has been performed. Dynamical electron correlation effects were computed by employing the coupled cluster methodology. A large electron correlation contribution to the nonlinear properties of HArC(4)H has been revealed. This contribution decreases by increasing the atomic number of the inserted rare gas atom. In order to interpret the origin of this noteworthy property, the complete active space self-consistent field method was employed. We have performed a systematic study of the linear and nonlinear electric properties by modifying the active space. The calculations have shown the significant contribution of the doubly excited sigma(*2) configuration and a negligible contribution of pi(*2). A quite remarkable discrepancy between numerically and analytically evaluated hyperpolarizabilities has also been observed for HArC(4)H. This was attributed to the contribution of near degenerate states.


Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney.
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Here, we identify a cDNA encoding a novel mucin protein, shown previously to be up-regulated in IgAN patients, from a human kidney cDNA library. This protein contains a mucin tandem repeat of 19 amino acids consisting of many threonine, serine, and proline residues and likely to be extensively O-glycosylated; thus, this gene was classified in the mucin family and named MUC20. The human MUC20 gene contains at least four exons and is localized close to MUC4 on chromosome 3q29. We found variations in repeat numbers in the mucin tandem domain, suggesting polymorphism of this region. Northern blot and reverse transcription-PCR analyses revealed that human MUC20 mRNA was expressed most highly in kidney and moderately in placenta, colon, lung, prostate, and liver. Immunohistochemical analysis of human kidney revealed that MUC20 protein was localized in the proximal tubules. Immunoblotting analysis of MUC20 proteins produced in Madin-Darby canine kidney and HEK293 cells indicated the localization of MUC20 protein in a membrane fraction and extensive posttranslational modification. Immunoelectron microscopy of MUC20-producing Madin-Darby canine kidney cells demonstrated that MUC20 protein was localized on the plasma membrane. Expression of MUC20 mRNA in a human kidney cell line was up-regulated by tumor necrosis factor-alpha, phorbol 12-myristate 13-acetate, or lipopolysaccharide. Two species of MUC20 mRNA (hMUC20-L and hMUC20-S), resulting from alternative transcription, were identified in human tissue, whereas only one variant was observed in mouse tissues. Mouse MUC20 mRNA was expressed in the epithelial cells of proximal tubules, and the expression increased dramatically with the progression of lupus nephritis in the kidney of MRL/MpJ-lpr/lpr mice. Moreover, the expression of mouse MUC20 was augmented in renal tissues acutely injured by cisplatin or unilateral ureteral obstruction. These characteristics suggest that the production of MUC20 is correlated with development and progression of IgAN and other renal injuries.


[Mortality and morbidity worldwide, now and tomorrow: what is known?].
The knowledge of the global distribution of death, diseases and risk factors is important to make clear to the general public and to governments that health inequalities are incredibly high, at the dawn of this 21(st) century, and to help fight these. More than 20% of the 56 millions of deaths in 2001 were of children less than 5 years old. There are at least 1 million deaths per year from malaria. Diarrhoea kill more than 1.5 million, and measles more than half a million. The large majority of deaths by infectious diseases occur in underdeveloped countries. Moreover, chronic diseases kill an increasing number in underdeveloped countries, because populations are aging, because expansive health care which is needed to prevent and control these diseases is unavailable, and because the inhabitants are increasingly exposed to risk factors. In particular, smoking is increasing dramatically in underdeveloped countries as a result of the aggressive marketing of tobacco companies, the delay in implementing antismoking regulations, and because the public perception of the risk of smoking is still low. More than 4 million deaths per year are presently attributed to smoking, and reports forecast a death toll of 10 million in 2030. The WHO, Harvard University and the World Bank are at the origin of comprehensive data analyses on the "global burden of diseases" which help to identify health priorities. Unfortunately, global data are still scarce and of low quality, particularly in those underdeveloped countries where they would be most useful. Precise knowledge of the variations of mortality, morbidity and exposure to risk factors would be essential to monitor the improvements, or failures of health care progress. The optimal interpretation of the available data requires expertise in demography, epidemiology, statistics, and computer sciences, which are rarely found in this area. Thus, improvements in the collection of data and in the research effort in this field are necessary.


Differential organization of a LINE-1 family in Indian pygmy field mice.
Southern blot hybridization analysis of genomic DNAs digested with restriction endonuclease EcoR I and Ava II from Mus musculus domesticus, Mus booduga and Mus terricolor with a cloned repetitive DNA fragment of Mus booduga as a probe showed difference in restriction pattern of this DNA in these three species. Further Southern analysis of the BamH I digested genomic DNAs from these species hybridized with cloned DNA fragment as a probe and sequencing of the cloned DNA revealed that this 252 bp cloned DNA fragment is a part of BamHI repeat element of genus Mus and is 87% homologous to the contiguous portion of the Mus musculus domesticus LINE-1 element. The species specific fragment pattern generated by different restriction endonucleases using this DNA as a probe revealed difference in the organization of LINE-1 repetitive element in the three species of genus Mus.


Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study.
In the current post-pandemic era, recipients of an allogeneic hematopoietic stem cell transplant (HCT) deserve special attention. In these vulnerable patients, vaccine effectiveness is reduced by post-transplant immune-suppressive therapy; consequently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is often associated with elevated morbidity and mortality. Characterizing SARS-CoV-2 adaptive immunity transfer from immune donors to HCT recipients in the context of immunosuppression will help identify optimal timing and vaccination strategies that can provide adequate protection to HCT recipients against infection with evolving SARS-CoV-2 variants. We performed a prospective observational study (NCT04666025 at ClinicalTrials.gov) to longitudinally monitor the transfer of SARS-CoV-2-specific antiviral immunity from HCT donors, who were either vaccinated or had a history of COVID-19, to their recipients via T-cell replete graft. Levels, function, and quality of SARS-CoV-2-specific immune responses were longitudinally analyzed up to 6 months post-HCT in 14 matched unrelated donor/recipients and four haploidentical donor/recipient pairs. A markedly skewed donor-derived SARS-CoV-2 CD4 T-cell response was measurable in 15 (83%) recipients. It showed a polarized Th1 functional profile, with the prevalence of central memory phenotype subsets. SARS-CoV-2-specific IFN-γ was detectable throughout the observation period, including early post-transplant (day +30). Functionally experienced SARS-CoV-2 Th1-type T cells promptly expanded in two recipients at the time of post-HCT vaccination and in two others who were infected and survived post-transplant COVID-19 infection. Our data suggest that donor-derived SARS-CoV-2 T-cell responses are functional in immunosuppressed recipients and may play a critical role in post-HCT vaccine response and protection from the fatal disease. clinicaltrials.gov, identifier NCT04666025.


Addressing rainfall data selection uncertainty using connections between rainfall and streamflow.
Studies of the hydroclimate at regional scales rely on spatial rainfall data products, derived from remotely-sensed (RS) and in-situ (IS, rain gauge) observations. Because regional rainfall cannot be directly measured, spatial data products are biased. These biases pose a source of uncertainty in environmental analyses, attributable to the choices made by data-users in selecting a representation of rainfall. We use the rainforest-savanna transition region in Brazil to show differences in the statistics describing rainfall across nine RS and interpolated-IS daily rainfall datasets covering the period of 1998-2013. These differences propagate into estimates of temporal trends in monthly rainfall and descriptive hydroclimate indices. Rainfall trends from different datasets are inconsistent at river basin scales, and the magnitude of index differences is comparable to the estimated bias in global climate model projections. To address this uncertainty, we evaluate the correspondence of different rainfall datasets with streamflow from 89 river basins. We demonstrate that direct empirical comparisons between rainfall and streamflow provide a method for evaluating rainfall dataset performance across multiple areal (basin) units. These results highlight the need for users of rainfall datasets to quantify this "data selection uncertainty" problem, and either justify data use choices, or report the uncertainty in derived results.


Bilateral extraordinary huge, multi-compartmental tuberculous abscesses: a case report.
To illustrate computerized tomography (CT) and magnetic resonance imaging (MRI) findings of tuberculous spondylitis with extensive abscess collections. A review of one patient with tuberculous spondylitis and extensive paraspinal, subligamentous, retroperitoneal, and subcutaneous abscesses including pertinent history, important physical examination, CT and MR imaging findings was performed. This case demonstrates multiple patterns of tuberculous abscess formation secondary to spinal tuberculosis; included are paraspinal, subligamentous, retroperitoneal, and subcutaneous locations. The extension of the abscess should be kept in mind when treating a patient with tuberculous spondylitis. MR imaging is a modality of choice to illustrate full extension of the disease process, which is necessary for therapeutic decision making and planning.


The impact of embryo transfer on implantation--a review.
Embryo transfer has received little clinical attention and has been, until recently, the most inefficient step in in-vitro fertilization (IVF). In this article, the authors review the literature and their personal experience regarding the process of intrauterine transfer of embryos, which remains the object of much discussion. Factors which appear to influence implantation rates are: contamination of the catheter tip with cervical bacteria, stimulation of uterine contractions during the procedure, the type of catheter, ultrasound guidance during the transfer, and the position of the embryos in the uterine cavity. Easy and atraumatic transfer is essential for successful implantation and the embryos need to be placed in the middle of the cavity, away from the fundus. Knowing, beforehand, the position and length of the uterus can provide better results and may reduce the rate of ectopic pregnancies. Evidence from randomized studies has supported this claim. Despite the number of available studies controlling certain variables, most authors, even using the same catheter, ultrasound guidance and/or a trial transfer use different protocols or similar instruments in different ways. Standardization of the transcervical intrauterine transfer of embryos in a large randomized study is needed before definitive conclusions can be drawn. The goal of improved implantation and pregnancy rates deserve these efforts.


Contemporary medical therapy for polycystic ovary syndrome.
Polycystic ovary syndrome is a multi-system endocrinopathy with long-term metabolic and cardiovascular health consequences. Patients typically present due to symptoms of irregular menstruation, hair growth, or infertility; however, recent management options are aimed at further treating underlying glucose-insulin abnormalities as well as androgen excess for proactive control of symptoms. By a 2003 international consensus conference, diagnosis is made by two out of three criteria: chronic oligoovulation or anovulation after excluding secondary causes, clinical or biochemical evidence of hyperandrogenism (but not necessarily hirsutism due to inter-patient variability in hair follicle sensitivity), and radiological evidence of polycystic ovaries. Traditional medical treatment options include oral contraceptive pills, cyclic progestins, ovulation induction, and anti-androgenic medications (aldosterone antagonist, 5alpha-reductase antagonist, and follicle ornithine decarboxylase inhibitor). Recent pharmacotherapies include insulin-sensitizing medications metformin and two thiazolidinediones (rosiglitazone/Avandia and pioglitazone/Actos), a CYP19 aromatase inhibitor (letrozole/Femara), and statins to potentially lower testosterone levels.


Comparison of two methods to compute the absorbed dose to water for photon beams.
Cross-validation was performed between an in-house dose-to-water (D(water)) calculation method used at Virginia Commonwealth University and the VMC++ D(water) calculation during particle transport. The effect of Monte Carlo statistical precision was observed. The results of the two calculations on homogeneous phantoms with densities varying from 0.3 g cm(-3) to 2.95 g cm(-3) were compared. Depth and field size dependence were tested. D(water) calculations were compared in a bone-lung-bone phantom to observe how the calculations differed in steep density gradients. The methods were compared for five prostate and five head-and-neck (H/N) patient cases as well. In all phantom tests, the differences between the two D(water) calculations were less than 1%. The largest differences in patient cases was a prostate case in which 1% of the voxels with doses greater than 50% of the maximum dose had a systematic difference corresponding to 1.16% of the maximum dose. All differences were clinically insignificant.


Effect of desogestrel on blood-lipid in relation to its biological activities.
Desogestrel (DG), a 19-nor progestin, is widely used in replacement therapy as a contraceptive steroidal hormone. Considering the importance of its partition coefficient parameter (log P = 5.68), a significant contributor to its action mechanism, interactions of the drug with blood-lipids had been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation to explain its pharmacodynamic behavior. From the present investigation, it was observed that lipid loss after incubation of whole blood with DG (80 ng/ml, effective contraceptive concentration in blood) for varying periods of time was accompanied with significant changes in fatty acid composition, which may be ascribed to binding affinity of DG with lipid constituents in blood that may have a role in the mediation of its therapeutic effect. Lipid peroxidation induction potential of DG has been quantitatively measured in the context of its toxicity. The results reveal that DG caused significant extent of lipid peroxidation. Ascorbic acid, an antioxidant, at equivalent human dose of 250 mg could significantly reduce DG-induced lipid peroxidation.


Intimal CD31-Positive Relative Surfaces Are Associated with Systemic Inflammatory Markers and Maturation of Arteriovenous Fistula in Dialysis Patients.
Arteriovenous fistula dysfunction is a widely disputed subject in the scientific literature on end-stage kidney disease (ESKD). The main cause of mortality and morbidity in these patients is the non-maturation or dysfunction of the arteriovenous fistula. Despite the many complications, the native arteriovenous fistula remains the gold standard in the treatment of these patients requiring renal replacement. This study aims to discuss the predictive role of some systemic inflammatory biomarkers (NLR, PLR, SII, IL-6), intimal hyperplasia, and neoangiogenesis (characterized by intimal-media CD31-positive relative surface) in arteriovenous fistula maturation failure. The present study was designed as an observational, analytical, and prospective study which included patients diagnosed with ESKD with indications of radio-cephalic arteriovenous fistula (RCAVF). Demographic data, comorbidities, preoperative laboratory data and histological/digital morphometry analysis results were processed. The patients included were divided into two groups based on their AVF maturation status at 8 weeks: "Maturation" (Group 1) and "Failed Maturation" (Group 2). There was no difference in the demographic data. In terms of comorbidities, the second group had a greater incidence of heart failure (p = 0.03), diabetes (p = 0.04), peripheral artery disease (p = 0.002), and obesity (p = 0.01). Additionally, regarding the laboratory findings, these patients had higher levels of serum uric acid (p = 0.0005), phosphates (p < 0.0001), and creatinine (p = 0.02), as well as lower levels of total calcium (p = 0.0002), monocytes (p = 0.008), and lymphocytes (p < 0.0001). Moreover, all inflammatory markers (p = 0.001; p < 0.0001; p = 0.006, and p = 0.03) and Ca-P product (p < 0.0001) had higher baseline values in Group 2. Upon immunohistochemical analysis, regarding the density of neoformed vessels, there was a higher incidence of CD31-positive surfaces (p = 0.006) and CD31-positive relative surfaces (p = 0.001); the NLR (r = 0.323; p = 0.03), PLR (r = 0.381; p = 0.04), SII (r = 0.376; p = 0.03), and IL-6 (r = 0.611; p < 0.001) are all significantly correlated with vascular density, as evidenced by CD31. Heart failure, peripheral artery disease, obesity, and diabetes, as well as the systemic inflammatory markers (NLR, PLR, SII, IL-6), intimal hyperplasia, and CD31-positive relative surfaces are predictors of arteriovenous fistula maturation failures.


Heritable genetic variation via mutation-selection balance: Lerch's zeta meets the abdominal bristle.
Most quantitative traits in most populations exhibit heritable genetic variation. Lande proposed that high levels of heritable variation may be maintained by mutation in the face of stabilizing selection. Several analyses have appeared of two distinct models with n additive polygenic loci subject to mutation and stabilizing selection. Each is reviewed and a new analysis and model are presented. Lande and Fleming analyzed extensions of a model originally treated by Kimura which assumes a continuum of possible allelic effects at each locus. Latter and Bulmer analyzed a model with diallelic loci. The published analyses of these models lead to qualitatively different predictions concerning the dependence of the equilibrium genetic variance on the underlying biological parameters. A new asymptotic analysis of the Kimura model shows that the different predictions are not consequences of the number of alleles assumed but rather are attributable to assumptions concerning the relative magnitudes of per locus mutation rates, the phenotypic effects of mutation, and the intensity of selection. This conclusion is reinforced by analysis of a model with triallelic loci. None of the approximate analyses presented are mathematically rigorous. To quantify their accuracy and display the domains of validity for alternative approximations, numerically determined equilibria are presented. In addition, empirical estimates of mutation rates and selection intensity are reviewed, revealing weaknesses in both the data and its connection to the models. Although the mathematical results and underlying biological requirements of my analyses are quite different from those of Lande , the results do not refute his hypothesis that considerable additive genetic variance may be maintained by mutation-selection balance. However, I argue that the validity of this hypothesis can only be determined with additional data and mathematics.


CT Evaluation of Squamous Cell Carcinoma of the Nasopharynx.
Squamous cell carcinoma is the most common type of neoplasia which affects the mucosa of the upper aero-digestive tract. Nasopharyngeal carcinoma is a unique disease with clinical behavior, epidemiology, and histopathology that is different from that of squamous cell carcinomas of the head and neck. For malignant tumors such as SCC, rapid growth may occur even though there are no previous clinical signs. Enlargement of a cervical lymph node, as the first presenting feature of neoplasia, is not uncommon, particularly with certain "silent" site, such as nasopharynx. Therefore, clinical examination must be complemented by radiological examination for the assessment of size, thickness and depth of the tumor, the degree of bone tissue invasion, and to detect the presence of enlarged lymph nodes. A total of 16 cases of patients were studied using CT, all diagnosed and operated with squamous cancer with localization in the nasopharynx.


Does primary biliary cirrhosis in men differ from primary biliary cirrhosis in women?
Primary biliary cirrhosis is infrequently diagnosed in men, so that the clinical, biochemical and histopathological spectrum of this disease in men has not been evaluated. Therefore, we studied 30 men who had a histological diagnosis of primary biliary cirrhosis and had positive tests for antimitochondrial antibodies. Five patients had no hepatobiliary symptoms, and two of these patients had neither biochemical nor histological evidence of cholestasis. These 30 male patients' findings were compared with the findings in 30 age-matched women who also had primary biliary cirrhosis and antimitochondrial antibodies. Six of these patients were asymptomatic. Clinical findings and symptomatic status, in addition to biochemical and histopathological features, were generally similar in both male and female patients. The possible significance of higher serum alkaline phosphatase activities and lower frequency of occurrence of piecemeal necrosis in men with primary biliary cirrhosis, as compared with women, requires further study.


[Recto-sigmoid cancer and polyps in children. Comments apropos of 2 cases of atypical juvenile polyps].
The writers present a report of 2 observations of colo-rectal carcinoma, on a 19 month old infant with a mixed juvenile and adenomatous polyp situated at the recto-sigmoid junction and treated successfully by segmental colectomy, and on a 10 years old girl presenting a large colloid rectal carcinoma which occurred 6 years after resection of an atypical rectal juvenile polyp. After recalling the rarity and the gravity of colo-rectal carcinoma in childhood, the authors underline the importance of histological investigations in the juvenile polyposis which is usually benign; the possibility of histological aspects on separate polyps and sometimes on the same polyp explains the degeneration of some multiple juvenile polyps (several cases in the literature), or isolated polyp (first case described).


Plasma-soluble urokinase-type plasminogen activator receptor levels are associated with clinical and pathological activities in lupus nephritis: a large cohort study from China.
In this study, we detected plasma urokinase plasminogen activator (uPA) and soluble urokinase-type plasminogen activator receptor (uPAR) levels in Chinese lupus nephritis patients from a large cohort. The associations between plasma uPA and soluble uPAR and clinico-pathological characteristics were further analyzed. The levels of plasma uPA and soluble uPAR were detected by ELISA in 202 patients with active lupus nephritis, 17 systemic lupus erythematosus (SLE) patients without renal involvement and 21 normal controls. There were no significant differences in the levels of the average plasma uPA among the lupus nephritis group, non-renal SLE group and normal control group (p = 0.129). The plasma-soluble uPAR level in the lupus nephritis group was significantly higher than that in the non-renal involvement SLE group (p = 0.004) and that in normal controls (p < 0.001). The plasma uPAR levels were positively associated with SLEDAI scores (r = 0.215, p = 0.007). In renal pathological data, there was significant difference of plasma-soluble uPAR levels among various pathological classes, which was the highest in the class IV group (p = 0.012). The level of plasma-soluble uPAR was found to be a risk factor for long-term renal outcomes in lupus nephritis by univariate survival analysis (p = 0.013, HR = 6.326, 95% CI: 1.466-27.298). Our study showed that the significantly increased plasma levels of soluble uPAR could be found in active lupus nephritis, and they were associated with some clinico-pathological features. Its involvement in the pathogenesis of lupus nephritis warrants further study.


Triterpenoid saponins from Scabiosa stellata collected in North-eastern Algeria.
Eight undescribed triterpenoid saponins, scabiostellatosides A-H, together with three known compounds were isolated from the whole plant of Scabiosa stellata L. Their structures were established by spectroscopic analyses (1D, 2D-NMR and HRESIMS) and chemical methods. Scabiostellatosides A-H were evaluated for their cytotoxicity against human fibrosarcoma cell line (HT1080). Scabiostellatoside F, a heptasaccharide derivative of oleanolic acid, exhibited moderate cytotoxicity against HT1080 cell line with IC50 value of 12.0 μM.


First report of 'Candidatus Phytoplasma palmae' (16SrIV-A subgroup) associated with palm Lethal Yellowing disease on Cocos nucifera and Pritchardia sp. in Guadeloupe, French West Indies.
Lethal Yellowing (LY) disease causes major damage to palms in Central America and the Caribbean. It has been reported as far south as Antigua (Myrie et al., 2014). LY affects over forty palm species, seriously impacts the coconut industry and alters the landscapes on islands with a tourist-based economy. In March 2021, the presence of LY disease was regularly monitored in Guadeloupe. Two palm species (Cocos nucifera and Pritchardia sp.) died on a private property in Saint-Anne, Grande Terre. Yellowing of lower fronds and necrosis of inflorescences were reported on some neighboring palms. One symptomatic Cocos nucifera (GP21-007) and four symptomatic Pritchardia sp. (GP21-005, GP21-006, GP21-008 and GP21-009) were sampled by stem drilling. Samples from four asymptomatic coconut trees (GP21-001 to GP21-004) were collected in the locality of Deshaies. DNA was extracted from the nine sawdust samples following a cetyltrimethylammonium bromide (CTAB) modified protocol (Doyle and Doyle, 1990). A quantitative polymerase chain reaction (PCR), following the protocol described by Christensen et al. (2004), was performed on DNA to diagnose the presence of phytoplasmas. An exponential amplification was observed for all DNA extracts from symptomatic palm samples (threshold number of PCR cycles (Ct) ranged from 18.50 to 23.58). DNA from asymptomatic samples yielded negative results (undetermined Ct). To identify the phytoplasma associated with LY, DNA samples were subjected to PCR, based on the 16SrRNA gene, plus internal transcribed spacers (ITS) using P1-1T (Pilet et al., 2021)/P7 (Schneider et al., 1995) primers, and secA gene using the primer pair secAFor1/secARev1 (Hodgetts et al. 2008). Amplicons of 1.8 kb covering the 16S ribosomal operon and 830 bp for the secA gene were produced using DNA from symptomatic trees. All amplicons were double strand sequenced (Genewiz, UK). The corresponding sequences were deposited in GenBank and subjected to BLASTn on NCBI. Sequences of the ribosomal operon gene (accession no. ON521114 to ON521118) were identical for the five positive samples. Sequencing revealed two distinct ribosomal operons with heterozygous peaks on the DNA chromatogram. The first aMino ambiguity (M = Adenine or Cytosine) was observed in the 16Sr RNA gene. The second was observed in the first intergenic transcript spacer. The 16S rDNA sequence (M = Cytosine) presented 100% identity with accession no. HQ613874 and 99.93% with accession no. U18747, the reference sequence for 'Candidatus Phytoplasma palmae'. The virtual RFLP pattern derived from the 16S rDNA F2nR2 fragment and identified using iPhyclassifier (Zhao et al. 2009) was identical to the reference pattern for the 16SrIV-A subgroup. A unique sequence was obtained for the partial secA gene (OP136139 to OP136143), sharing 100% identity with EU267187 for the palm LY phytoplasma preprotein translocase subunit (secA) gene. This is the first report of 'Ca. Phytoplasma palmae' (subgroup 16SrIV-A) associated with palm LY disease on Cocos nucifera and Pritchardia sp. in Guadeloupe. Measures to eradicate LY were implemented as soon as its presence was confirmed in Guadeloupe. LY phytoplasmas continue to spread in the Caribbean and are approaching South America, where the known vector, Haplaxius crudus, has already been reported (Silva et al., 2019). This poses a major threat to the coconut economy and the diversity of palm trees.


Importance of lead aVL in the diagnosis of inferior wall myocardial infarction: A case report.
Ischaemic heart disorders are among the leading causes of mortality worldwide. There has been a growing occurrence of heart disease among young adults. Thus, acute myocardial infarction (MI) should be considered in all patients with central chest pain. Herein, we report the case of a young, fit, active smoker with underlying dyslipidaemia presenting with acute MI, characterised by dynamic changes in lead aVL wherein T wave flattening progressed to inversion, suggestive of early reciprocal changes. Soon after, electrocardiogram (ECG) revealed ST elevation in leads III and aVF, indicative of acute inferior wall MI. Subsequently, coronary angiogram showed right coronary artery occlusion. This case report highlights the importance of serial ECGs in patients who present with chest pain and have a high clinical suspicion for acute MI with normal or inconclusive ECG findings. Measurement of highly sensitive serum troponin based on a 1- or 3-h protocol is important in diagnosing acute MI but not ST-elevation MI. An early sign of inferior wall MI may be a new T wave inversion in lead aVL.


CHLORORESPIRATORY REDUCTION 9 is a Novel Factor Required for Formation of Subcomplex A of the Chloroplast NADH Dehydrogenase-Like Complex.
In vascular plants, the chloroplast NADH dehydrogenase-like (NDH) complex, a homolog of respiratory NADH:quinone oxidoreductase (Complex I), mediates plastoquinone reduction using ferredoxin as an electron donor in cyclic electron transport around PSI in the thylakoid membrane. In angiosperms, chloroplast NDH is composed of five subcomplexes and forms a supercomplex with PSI. The modular assembly of stroma-protruded subcomplex A, which corresponds to the Q module of Complex I, was recently reported. However, the factors involved in the specific assembly steps have not been completely identified. Here, we isolated an Arabidopsis mutant, chlororespiratory reduction 9 (crr9), defective in NDH activity. The CRR9 gene encodes a novel stromal protein without any known functional domains or motifs. CRR9 is highly conserved in cyanobacteria and land plants but not in green algae, which do not have chloroplast NDH. Blue native-PAGE and immunoblot analyses of thylakoid proteins indicated that formation of subcomplex A was impaired in crr9 CRR9 was specifically required for the accumulation of NdhK, a subcomplex A subunit, in NDH assembly intermediates in the stroma. Furthermore, two-dimensional clear native/SDS-PAGE analysis of the stroma fraction indicated that incorporation of NdhM into NDH assembly intermediate complex 400 was impaired in crr9 These results suggest that CRR9 is a novel factor required for the formation of NDH subcomplex A.


Stable and Temporary Enzyme Complexes and Metabolons Involved in Energy and Redox Metabolism.
Significance: Alongside well-characterized permanent multimeric enzymes and multienzyme complexes, relatively unstable transient enzyme-enzyme assemblies, including metabolons, provide an important mechanism for the regulation of energy and redox metabolism. Critical Issues: Despite the fact that enzyme-enzyme assemblies have been proposed for many decades and experimentally analyzed for at least 40 years, there are very few pathways for which unequivocal evidence for the presence of metabolite channeling, the most frequently evoked reason for their formation, has been provided. Further, in contrast to the stronger, permanent interactions for which a deep understanding of the subunit interface exists, the mechanism(s) underlying transient enzyme-enzyme interactions remain poorly studied. Recent Advances: The widespread adoption of proteomic and cell biological approaches to characterize protein-protein interaction is defining an ever-increasing number of enzyme-enzyme assemblies as well as enzyme-protein interactions that likely identify factors which stabilize such complexes. Moreover, the use of microfluidic technologies provided compelling support of a role for substrate-specific chemotaxis in complex assemblies. Future Directions: Embracing current and developing technologies should render the delineation of metabolons from other enzyme-enzyme complexes more facile. In parallel, attempts to confirm that the findings reported in microfluidic systems are, indeed, representative of the cellular situation will be critical to understanding the physiological circumstances requiring and evoking dynamic changes in the levels of the various transient enzyme-enzyme assemblies of the cell. Antioxid. Redox Signal. 35, 788-807.


TCMNER and PubMed: A Novel Chinese Character-Level-Based Model and a Dataset for TCM Named Entity Recognition.
Intelligent traditional Chinese medicine (TCM) has become a popular research field by means of prospering of deep learning technology. Important achievements have been made in such representative tasks as automatic diagnosis of TCM syndromes and diseases and generation of TCM herbal prescriptions. However, one unavoidable issue that still hinders its progress is the lack of labeled samples, i.e., the TCM medical records. As an efficient tool, the named entity recognition (NER) models trained on various TCM resources can effectively alleviate this problem and continuously increase the labeled TCM samples. In this work, on the basis of in-depth analysis, we argue that the performance of the TCM named entity recognition model can be better by using the character-level representation and tagging and propose a novel word-character integrated self-attention module. With the help of TCM doctors and experts, we define 5 classes of TCM named entities and construct a comprehensive NER dataset containing the standard content of the publications and the clinical medical records. The experimental results on this dataset demonstrate the effectiveness of the proposed module.


Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.
Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.


Renal allograft rejection: protection of renal epithelium from natural killer cells by cytokine-induced up-regulation of class I major histocompatibility antigens.
The potential of natural killer (NK) cells to contribute to renal allograft rejection was modelled by mixing NK cells with cultured renal epithelial cells. It was found that the renal cells were readily lysed by cytokine-activated NK cells. Renal cells which were previously stimulated by culture with either interferon-gamma (IFN-gamma) or supernatant from mixed leucocyte cultures (MLC) were relatively resistant to such lysis; stimulation with tumour necrosis factor-alpha (TNF-alpha) had no effect. None of these cytokine preparations had any effect on the lysis of renal cells by either specific cytotoxic T lymphocytes or the antibody-dependent cell-mediated cytotoxic mechanism. The expression of class I major histocompatibility complex (MHC) antigens was up-regulated by stimulation of renal cells with either IFN-gamma or MLC supernatant; treatment with TNF-alpha had no effect on the expression of these antigens. Protection from NK cell-mediated lysis appeared to correlate with the expression of class I MHC antigens by the renal cells. Artificial removal of these MHC antigens by treatment with citric acid significantly increased the susceptibility of cytokine-stimulated renal cells to lysis by activated NK cells. This increase was not caused by enhanced binding of NK cells to acid-treated renal cell targets. These results suggest that high levels of class I MHC antigen expression block NK cell triggering after engagement with renal epithelial cells. It is concluded that cytokines present within the renal microenvironment during rejection protect graft cells from lysis by NK cells by causing local upregulation of the expression of class I MHC molecules.


A worldwide experience of the management of battery failures and chronic device retrieval of the Nanostim leadless pacemaker.
The Nanostim leadless pacemaker (LP) met the primary endpoints in an investigational device exemption trial, and was shown to be fully retrievable percutaneously. In October 2016, St Jude Medical issued a worldwide alert of a battery malfunction that caused lost pacing output and LP communication. To report the battery failure mechanism and incidence and the worldwide patient management, including device retrieval experiences. The affected LP battery is a custom lithium-carbon monofluoride cell. These were returned after failure and underwent analysis assessing electronics and battery performance. Data were collected in ongoing clinical studies when LPs were abandoned or retrieved. Of 1423 LPs implanted worldwide, there were 34 battery failures, occurring at 2.9 ± 0.4 years with no instances of associated patient injury. Analysis of returned batteries revealed an increase in battery resistance caused by insufficient electrolyte availability at the cathode/anode interface. A total of 66 of 73 retrieval attempts were successful (90.4%; implant duration range: 0.2-4.0 years). The LP docking button was inaccessible in 6 patients, and the docking button detached from the LP during retrieval in 1 patient. There was 1 case of arteriovenous fistula and another case of the LP docking button migrating into the pulmonary artery. There were also 115 non-LP retrieval patients after the advisory who received an additional pacemaker, with no adverse device-to-device interactions reported. As with standard pacers, LPs can have critical battery failures. Chronic retrieval of LPs is safe and efficacious.


Amide proton transfer-weighted magnetic resonance imaging for the differentiation of parotid gland tumors.
To assess the usefulness of amide proton transfer-weighted (APTw) imaging in the differentiation of parotid gland tumors. Patients with parotid gland tumors who underwent APTw imaging were retrospectively enrolled and divided into groups according to pathology. Two radiologists evaluated the APTw image quality independently, and APTw images with quality score ≥3 were enrolled. The maximum and average values of APTw imaging for tumor lesions (APTmax and APTmean) were measured. The differences in APTmax and APTmean were compared between malignant tumors (MTs) and benign tumors (BTs), as well as between MTs and pleomorphic adenomas (PAs) and between MTs and Warthin tumors (WTs). Independent-samples t-test, Kruskal-Wallis H test, and receiver operating characteristic (ROC) curve analyses were used for statistical analysis. Seventy-three patients were included for image quality evaluation. In this study, 32/73 and 29/73 parotid tumors were scored as 4 and 3, respectively. After excluding lesions with quality score ≤2 (12/73), the APTmean and APTmax of MTs were 4.15% ± 1.33% and 7.43% ± 1.61%, higher than those of BTs 2.74% ± 1.04% and 5.25% ± 1.54%, respectively (p < 0.05). The areas under the ROC curve (AUCs) of the APTmean and APTmax for differentiation between MTs and BTs were 0.819 and 0.821, respectively. MTs indicated significantly higher APTmean and APTmax values than those of PAs (p < 0.05) and WTs (p < 0.05). The AUCs of the APTmean and APTmax for differentiation between MTs and PAs were 0.830 and 0.815 and between MTs and WTs were 0.847 and 0.920, respectively. Most APTw images for parotid tumors had acceptable image quality for APTw value evaluation. Both APTmax and APTmean can be used to differentiate MTs from BTs and to differentiate MTs from subtype parotid gland tumors.


[Phlebography in chronic venous insufficiency of the lower extremities. Technic and value of different tests].
Remainder of the various phlebographic procedures in chronic venous insufficiency of the lower extremities: peripheral phlebography, popliteal phlebography, femoral phlebography, varicography. The techniques and the informations they provide are presented for each one of these examinations.


Accumulation of particulate matter, heavy metals, and polycyclic aromatic hydrocarbons on the leaves of Tilia cordata Mill. in five Polish cities with different levels of air pollution.
Urbanized areas are struggling with the problem of air pollution and as the number of people living in cities is increasing, the situation is likely to deteriorate. One of the most harmful pollutants is particulate matter (PM). Increased levels of PM in the atmosphere are likely to have a negative impact on human health. Phytoremediation technology could be a solution. It involves plants acting as bio-filters by accumulating particles on, and in the leaves, thus removing the particles from the atmosphere. This study investigates the accumulation of PM including heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs), on the foliage of small-leaved lime (Tilia cordata Mill.) in five Polish cities. There were significantly different PM amounts found in the trees between the cities which related to the different quantities of PM in the atmosphere at these cities. Significant differences were found between cities for the amounts of the different particulate size fractions, and the HMs and PAHs in leaves. Strong winds reduced the amount of PM on leaves, especially the smallest fractions, but no relationship with precipitation was found. The results suggest that T. cordata improves the air quality in cities and can be used as an effective bioindicator for PM air pollution.


The primitive streak, the caudal eminence and related structures in staged human embryos.
The caudal region of the trunk was reassessed in 52 serially sectioned human embryos of stages 8-23, 42 of which were controlled by precise graphic reconstructions. The following observations, new for the human, are presented. (1) The neurenteric canal is an important landmark because rostral to it the neural plate of stages 8, 9, and the main part of the notochord develop, whereas caudal to it the neural plate of stages 10-12 and the caudal portion of the notochord are formed. All somites at stages 9-11 and probably also at stage 12 arise rostral to the site of the neurenteric canal. (2) A 'chordoneural hinge' can be detected in stages 10 and 11, where the caudal part of the neural plate gives off cells that probably participate in the production of mesenchyme. (3) When apparent disappearance of the epiblast is used as a criterion, then the primitive streak seems to end during stage 9. (4) The caudal eminence, derived from the primitive streak and covered by ectoderm, forms at stage 10 caudal to the site of the former neurenteric canal and persists as a terminal cap to at least stage 14, although formation of mesenchyme continues in stages 15 to 17 or 18. (5) As the region rostral to the site of the neurenteric canal grows because of the development of somites, the caudal eminence is shifted caudally. (6) The caudal eminence is most active developmentally during stage 13, when most of the required (ca 6 out of 9) pairs of somites appear. (7) The eminence produces the caudal part of the notochord and, after closure of the caudal neuropore, all caudal structures, but it does not produce even a temporary 'tail' in the human. (8) A temporal overlap results between primary and secondary development in the caudal part of the notochord. (9) Primary development begins very early with the formation of the inner cell mass at stage 3, and includes the development of the somites rostral to the neurenteric canal, whereas secondary development, with the exception of the notochord caudally, commences at stage 12. (10) Primary neurulation lasts from stage 8 to stage 12, secondary from stage 12 to stages 17 or 18. (11) Secondary development and secondary neurulation are characterized morphologically by direct formation of structures (notochord, postcloacal gut, neural cord/neural tube) from mesenchyme.


Disease associations of excessive daytime sleepiness in multiple sclerosis: A prospective study.
Excessive daytime sleepiness (EDS) in multiple sclerosis (MS) can be a significant source of disability. Despite this, its prevalence as a patient-reported outcome in this condition has not been well established, and its causes are not well understood. We prospectively assessed EDS as part of an observational study for patients referred for diagnostic neuro-ophthalmological testing. EDS was evaluated by the Epworth Sleepiness Scale (ESS), and visual data were also collected as part of a research protocol. Analysis with patient data was performed following the exclusion of patients with known primary sleep disorders. A total of 69 patients with MS were included in the analysis. The mean ESS was 6.5 with a SD of 4.3. ESS ≥ 10 was present in 23% of the cohort even in the presence of minimal mean neurological disability (Patient Determined Disease Steps (PDDS) = 1.5). The ESS score was not associated with age, sex, disease-related disability, retinal nerve fiber layer (RNFL), or optic neuritis (ON), but displayed an association with visual dysfunction. There is an increased prevalence of EDS in MS. The increased values of the ESS are not explained by other sleep disorders, suggesting separate mechanisms. Further study of the underlying mechanisms is warranted.


Bovine tuberculosis disturbs parasite functional trait composition in African buffalo.
Novel parasites can have wide-ranging impacts, not only on host populations, but also on the resident parasite community. Historically, impacts of novel parasites have been assessed by examining pairwise interactions between parasite species. However, parasite communities are complex networks of interacting species. Here we used multivariate taxonomic and trait-based approaches to determine how parasite community composition changed when African buffalo (Syncerus caffer) acquired an emerging disease, bovine tuberculosis (BTB). Both taxonomic and functional parasite richness increased significantly in animals that acquired BTB than in those that did not. Thus, the presence of BTB seems to catalyze extraordinary shifts in community composition. There were no differences in overall parasite taxonomic composition between infected and uninfected individuals, however. The trait-based analysis revealed an increase in direct-transmitted, quickly replicating parasites following BTB infection. This study demonstrates that trait-based approaches provide insight into parasite community dynamics in the context of emerging infections.


Association of coping strategies with mortality and health-related quality of life in hemodialysis patients: The Japan Dialysis Outcomes and Practice Patterns Study.
Hemodialysis patients are exposed to disease- and treatment-related stresses, and use various coping strategies to deal with these stresses. Although some studies have reported the association of coping strategies with mortality or health-related quality of life (QOL) in some populations, the effect of coping strategies on clinical outcomes in hemodialysis patients remains unclear. We investigated the association in a longitudinal design among Japanese hemodialysis patients. We examined Japanese hemodialysis patients who participated in the Dialysis Outcomes and Practice Patterns Study (DOPPS) IV, which was conducted between 2009 and 2012. The exposure variable was stress coping strategy, as assessed using subscales in Coping Strategies Inventory Short Form: problem-focused engagement, problem-focused disengagement, emotion-focused engagement, and emotion-focused disengagement. Hazard ratios were estimated using Cox proportional hazard model for all-cause mortality and mean differences for change in health-related QOL in 1 year were estimated using a regression model. Among 1,354 patients, only problem-focused engagement was significantly associated with longer survival; other subscales were not associated with all-cause mortality after adjustment for potential confounding factors. In terms of health-related QOL, the subscale of problem-focused engagement was also associated with improvement in physical functioning and mental health among 1,045 patients. Emotion-focused disengagement was associated with deterioration in mental health, but not with change in physical functioning. The other subscales were not associated with change in physical functioning or mental health. Among hemodialysis patients, "problem-focused engagement" coping strategies were associated with longer survival and also with improvement in physical functioning and mental health. To achieve greater longevity and improve QOL in hemodialysis patients under ongoing stresses, problem-focused engagement should be encouraged.


Low-grade slightly elevated and polypoid colorectal adenomas display differential β-catenin-TCF/LEF activity, c-Myc, and cyclin D1 expression.
To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas. Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. Five commonly mutated genes (APC, BRAF, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index (AI) and Ki-67 labeling index (KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. Western blots, luciferase assays for β-catenin-T-cell factor protein/β-catenin-lymphoid enhancer factor (β-catenin-TCF/LEF)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines. Slightly elevated lesions showed a significantly lower APC mutational frequency and a significantly higher KRAS mutational frequency (both P < 0.05). Slightly elevated lesions showed a significantly lower AI (P < 0.05). β-catenin and β-catenin-TCF/LEF-driven transcriptional activity was significantly upregulated in slightly elevated lesions (both P < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated (both P < 0.05). β-catenin-TCF/LEF-driven transcriptional activity was negatively correlated with c-Myc (ρ = -0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-xL upregulation (both P < 0.05) along with significant decreases in caspase-9 and caspase-3 activity (both P < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-xL (ρ = -0.74 and -0.78, respectively). The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.


Fracture Risk After Bariatric Surgery: Roux-en-Y Gastric Bypass Versus Adjustable Gastric Banding.
The long-term consequences of bariatric surgery on fracture risk are unclear but are likely to vary by procedure type. In physiologic studies, Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) have differential effects on rates of bone loss. Therefore, our objective was to compare fracture risk in obese adults after RYGB and AGB procedures. Using claims data from a US commercial health plan, we analyzed rates of nonvertebral fractures within a propensity score-matched cohort (n = 15,032) of morbidly obese adults who received either RYGB or AGB surgery between 2005 and 2013. A total of 281 nonvertebral fractures occurred during a mean follow-up time of 2.3 ± 1.9 years. RYGB patients had an increased risk of nonvertebral fracture (hazard ratio [HR] = 1.43, 95% confidence interval [CI] 1.13-1.81) compared with AGB patients. In fracture site-specific analyses, RYGB patients had increased risk of fracture at the hip (HR = 1.54, 95% CI 1.03-2.30) and wrist (HR = 1.45, 95% CI 1.01-2.07). Nonvertebral fracture risk associated with RYGB manifested >2 years after surgery and increased in subsequent years, with the highest risk in the fifth year after surgery (HR = 3.91, 95% CI 1.58-9.64). In summary, RYGB is associated with a 43% increased risk of nonvertebral fracture compared with AGB, with risk increasing >2 years after surgery. Fracture risk should be considered in risk/benefit discussions of bariatric surgery, particularly among patients with high baseline risk of osteoporosis who are deciding between RYGB and AGB procedures. © 2017 American Society for Bone and Mineral Research.


Pipeline for large-scale microdroplet bisulfite PCR-based sequencing allows the tracking of hepitype evolution in tumors.
Cytosine methylation provides an epigenetic level of cellular plasticity that is important for development, differentiation and cancerogenesis. We adopted microdroplet PCR to bisulfite treated target DNA in combination with second generation sequencing to simultaneously assess DNA sequence and methylation. We show measurement of methylation status in a wide range of target sequences (total 34 kb) with an average coverage of 95% (median 100%) and good correlation to the opposite strand (rho = 0.96) and to pyrosequencing (rho = 0.87). Data from lymphoma and colorectal cancer samples for SNRPN (imprinted gene), FGF6 (demethylated in the cancer samples) and HS3ST2 (methylated in the cancer samples) serve as a proof of principle showing the integration of SNP data and phased DNA-methylation information into "hepitypes" and thus the analysis of DNA methylation phylogeny in the somatic evolution of cancer.


Global analysis of differentially expressed genes in androgen-independent prostate cancer.
Progression to androgen independent (AI) is the main cause of death in prostate cancer, and the mechanism is still unclear. By reviewing the expression profiles of 26 prostate cancer samples in a holistic view, we found a group of genes differentially expressed in AI compared with androgen-dependent groups (P-value<0.01, t-test). Focusing on apoptosis, proliferation, hormone and angiogenesis, we found a group of genes such as thioredoxin domain containing 5 , tumor necrosis factor receptor superfamily, member 10a , ribosomal protein S19 and Janus kinase 2 upregulated in AI prostate cancer, could play important roles in the transition from AD to AI and could be biomarkers of prognosis.


Neoadjuvant chemoradiation versus perioperative chemotherapy followed by surgery in resectable adenocarcinomas of the esophagogastric junction: A retrospective single center analysis.
The current study presents a retrospective comparison, performed at a single academic center, of preoperative chemoradiation (CRT) and perioperative chemotherapy (CT) in addition to surgery in locally advanced but resectable adenocarcinoma of the esophagogastric junction (AEG). A total of 29 consecutive patients with locally advanced AEGs were retrospectively analyzed. Treatment consisted of preoperative CRT (mean dose, 45.0 Gy) plus two cycles of CT with cisplatin and 5-FU or perioperative CT with epirubicin, cisplatin and capecitabine (three cycles preoperatively and postoperatively). Within four to six weeks following preoperative treatment, surgical therapy was performed. Median overall survival was 21.0 months in the perioperative CT group versus 41.7 months in the CRT group [P=0.36; hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.58-3.84]. Three-year survival rates were 55 and 38%, respectively, in favor of the CRT group, and progression-free survival was 20.0 months in the CT group compared with 24.1 months in the CRT group (P=0.71; HR, 1.19; 95% CI, 0.46-3.05). The total number of major surgical complications was almost equal in the two groups. Margin-free resections were achieved in all patients of the CRT group, but only 76.9% of the CT group (P=0.05). In addition, significantly higher R0 resection rates and an increased number of pathological complete remissions were demonstrated in the CRT group compared with those of the CT group. These results appear to indicate a trend for improved progression-free and overall survival for the CRT group. As postoperative morbidity and mortality rates were similar in the two groups, the results support the use of CRT for patients with advanced AEG tumors.


Early developability screen of therapeutic antibody candidates using Taylor dispersion analysis and UV area imaging detection.
Therapeutic antibodies represent one of the fastest growing segments in the pharmaceutical market. They are used in a broad range of disease fields, such as autoimmune diseases, cancer, inflammation and infectious diseases. The growth of the segment has necessitated development of new analytical platforms for faster and better antibody selection and characterization. Early quality control and risk assessment of biophysical parameters help prevent failure in later stages of antibody development, and thus can reduce costs and save time. Critical parameters such as aggregation, conformational stability, colloidal stability and hydrophilicity, are measured during the early phase of antibody generation and guide the selection process of the best lead candidates in terms of technical developability. We report on the use of a novel instrument (ActiPix/Viscosizer) for measuring both the hydrodynamic radius and the absolute viscosity of antibodies based on Taylor dispersion analysis and UV area imaging. The looped microcapillary-based method combines low sample consumption, fast throughput and high precision compared to other conventional methods. From a random panel of 130 antibodies in the early selection process, we identified some with large hydrodynamic radius outside the normal distribution and others with non-Gaussian Taylor dispersion profiles. The antibodies with such abnormal properties were confirmed later in the selection process to show poor developability profiles. Moreover, combining these results with those of the viscosity measurements at high antibody concentrations allows screening, with limited amounts of materials, candidates with potential issues in pre-formulation development.


Blood sampling technique for measurement of plasma arginine vasopressin concentration in conscious and unrestrained rats.
A new technique for collecting blood from conscious and unrestrained rats is reported. Plasma arginine vasopressin (AVP) concentration has been known to be influenced by various procedures used for blood collection (e.g., manual contact and anesthesia). In the study reported here, the improvement of the routine jugular vein cannula method was undertaken by extending the connection tubing to allow use of a swivel mechanism. Plasma AVP, glucose, and corticosterone concentrations in virgin rats were measured in blood samples collected by use of the new method and of two generally accepted methods (decapitation and routine jugular vein cannula methods). All values of the three parameters obtained were the lowest when the new method was used, suggesting that this new swivel method induced the least stress in the rats.


Giant enhancement of acoustic and fluorescence emission from an off-axis reflective femtosecond laser filamentation system.
Femtosecond laser filamentation propagating tens of meters to several kilometers with high intensity in the atmosphere has been demonstrated as a powerful tool for remote sensing. In contrast to the refractive systems, the reflective optical systems possess a variety of advantages including broad bandwidth, large aperture, light weight and low energy loss. However, astigmatic aberration is inevitably introduced by off-axis reflective mirrors. It can greatly affect the filament quality, which is critical for exciting and detecting the fluorescence of target molecules. Here we elaborately design a free-form phase plate to correct the astigmatism in off-axis reflective optical systems. It is demonstrated that the free-form surface exhibits excellent performance, significantly reducing the astigmatic difference from 44 cm to 4 cm and increasing the maximum acoustic intensity by a factor of 53. In addition, extremely strong nitrogen fluorescence spectra have been detected. These results indicate that the free-form phase plate can effectively compensate for astigmatic aberration in off-axis reflective system, providing a guiding significance for the optimal control of filamentation and remote sensing.


Focus groups: examining a community-based group intervention for depressed Puerto Rican women.
Puerto Ricans manifest high rates of depression but avoid seeking treatment. The purpose of this pilot was to learn directly from Puerto Rican women how culturally appropriate they would consider a proposed community-based intervention for treating depression. Interactive activities were reviewed by two focus groups of women (N = 16), all working in community-based health programs. All activities (e.g., writing, role playing, and music) except individual drawing were deemed appropriate. Categories that emerged were family/community values, mainland/non-mainland cultural variances, communication style, religion, education/occupational variances, health beliefs, Puerto Rican traditions/customs, emotions, and coping skills. Categories provided guidance for refining a community-based intervention for treating depression in Puerto Rican women.


Core values and evaluation processes associated with academic tenure.
This study replicated the 1989 national study by the Carnegie Foundation for the Advancement of Teaching in which the relative importance of teaching, scholarship, and service in tenure decisions was examined. The deans of the National League for Nursing accredited programs (N= 187) and deans of Allied Health programs belonging to the Association of Schools of Allied Health Professions (N=75) were surveyed to identify the core values and evaluation processes used in granting tenure. Most deans who participated stated it is difficult to achieve tenure in the absence of publication in refereed journals. The number of journal publications, reputation of the journal, presentation at scientific conferences, and published reviews of the scholars' books are considered critical in granting tenure. Furthermore, advising students, service in the department and university, and course evaluation by students were considered critical to granting tenure. Overall, the opinions of the nursing and allied health deans on the core values and the evaluation processes used in tenure decisions were similar, but divergent from those of the "health sciences" faculty members in the Carnegie Foundation study. These findings suggest a shift in the criteria used in tenure decisions today.


Chemically modified tetracyclines selectively inhibit IL-6 expression in osteoblasts by decreasing mRNA stability.
In bone biology, interleukin (IL)-6 is an autocrine/paracrine cytokine which can induce osteoclasts formation and activation to help mediate inflammatory bone destruction. Previous studies have shown that tetracycline and its derivatives have potentially beneficial therapeutic effects in the prevention and treatment of metabolic bone diseases by modulating osteoblast and osteoclast activities. Our previous studies indicated that non-antimicrobial chemically modified tetracyclines (CMTs) can dose-dependently inhibit IL-1 beta-induced IL-6 secretion in osteoblastic cells. In the present study, we explored the molecular mechanisms underlying the ability of doxycycline analogs CMT-8 and its non-chelating pyrazole derivative, CMT-5 to affect IL-6 gene expression in murine osteoblasts. Steady-state IL-6 mRNA was decreased with CMT-8 (ca. 50%) but not by CMT-5 when stimulated by IL-1 beta. CMT-8 regulation of IL-1 beta-induced IL-6 gene expression was further explored. CMT-8 did not affect IL-6 promoter activity in reporter gene assays. However, the IL-6 mRNA stability was decreased in the presence of CMT-8. These effects require de novo protein synthesis as they were inhibited by cycloheximide. Western blot analysis indicated that CMT-8 did not affect p38 mitogen-activated protein kinase, c-jun NH(2)-terminal kinases, or extracellular signal-regulated kinases (1 and 2) phosphorylation in response to IL-1 beta. These data suggest that CMT-8 can modulate inhibit IL-1 beta-induced IL-6 expression in MC3T3-E1 cells at the post-transcriptional level affecting IL-6 mRNA stability. These observations may offer a novel molecular basis for this treatment of metabolic bone diseases that are mediated by IL-6.


[Clinical features and course of Kawasaki disease in central Tunisia: a study about 14 cases collected over a period of three years (2000-2002)].
To analyze the clinical features and course of Kawasaki disease in central Tunisia. We studied retrospectively 14 cases of children with Kawasaki disease collected in tunisian center during three years (2000-2002). The study is about 11 boys and 3 girls (sex - ratio: 3.6/1) aged from 6 months to 8 years (mean age : 4 years). Twelve patients had at least 5 diagnostic criteria of the illness, the two others had an incomplete form. We noted cardiac complications in seven patients treated belatedly, beyond 10 days of progression, because of atypical clinical presentations. All patients had all a middle caliber coronary aneurysm that was complicated by a thrombus in three cases, associated with pericarditis and minimal mitral insufficiency in a case and with a cardiac rhythm disturbance (block of branch) in another case. Besides the cardiac complications, several other visceral manifestation could be noted: joint symptoms in five cases, GI tract symptomes in three cases, neuro-meningeal in two cases and urinary trad symptomes in two other cases. Specific treatment (aspirin with antiinflammatory dose and intravenous immune globulin (IVIG)) has been instituted in all patients. The course was favorable for 12 patients with fast regression of clinical manifestation and progressive normalisation of biologic values. Two patients did not respond to the initial IVIG treatment, and had to recense received an additional course of IGIV but without clinical nor biological improvement. These two patients were treated with corticosteroids. Cardiac lesions disappeared completely in all patients even for those with thrombosis and in patients with IVIG-resistant Kawasaki disease. Only one patient had kept neurologic sequellae: aphasia, bevavioral problemes and partial epilepsy. Kawasaki disease is not rare in our region. Incomplete or atypical presentations are frequent and are a source of diagnostic delay. Coronary aneurysm due to the delay of treatment often regresses even in patients with IVIG-resistant Kawasaki disease.


A Morphometric Study of the Foramen of Diaphragma Sellae and Delineation of Its Relation to Optic Neural Pathways through Computer Aided Superimposition.
The diaphragma sellae (DS) is a fold of dura that forms a partial roof over the pituitary gland. The foramen of the diaphragma sellae (FDS) is thereby a pathway for suprasellar extension of pituitary tumors. The purpose of this study was to describe the anatomical dimensions of the DS and FDS and to understand the relationship of FDS with the overlying optic chiasma. The study was conducted in 100 autopsy cases. Measurements were taken using vernier calipers. Photographs, taken before and after removal of optic pathway, were superimposed using image processing software. The results showed that the mean A-P dimension of DS was 1.17 ± 0.48 cm; the lateral dimension of DS was 1.58 ± 0.60 cm. The mean A-P dimension of FDS was 0.66 ± 0.42 cm; the lateral dimension of FDS was 0.82 cm ± 0.54 cm. The shapes of FDS were irregular (40%), transversely oval (29%), circular (13%), sagittally oval (11%), or trapezoid with posterior dimension more than the anterior one (6%) or anterior dimension more than the posterior one (1%). The margins of FDS were either well defined (31%) or ill defined (69%). The positional relation of FDS to optic chiasma was also found out.