Descriptive epidemiology of vulvar and vaginal cancers in Vaud, Switzerland, 1974-1994.
To analyse trends in incidence, survival and risk of second neoplasms following vaginal and vulvar cancers using data collected by the Swiss Cancer Registry of Vaud over the 21-year period 1974-1994. Subjects were 257 vulvo-vaginal cancers. Of these, 69 were vaginal, 153 vulvar cancers, and 35 non-specified lower genital tract neoplasms; 94 in situ neoplasms were also registered (85 for the vulva). Invasive vaginal cancer incidence decreased from 0.8 in 1974-1984 to 0.4/100,000 women in 1985-1994, while invasive vulvar cancer incidence remained approximately stable around 1.2/100,000 (world standard); incidence of in situ vulvar cancer increased from 0.8 to 1.3/100,000, the rise being larger in younger women. Significant excesses for second primary neoplasms were observed for pro-pharyngeal and lung cancer, and for non-melanomatous skin neoplasms, as well as for invasive vulvar cancers following in situ cancers. This population-based dataset confirms that the incidence of in situ vulvar (but not invasive vulvar or vaginal cancer) has been increasing over the last 20 years. The excess second primary neoplasms supports the hypotheses that human papillomavirus and cigarette smoking are related to vulvo-vaginal neoplasms.


Relevance of vascular PGI2 synthase to vascular prostacyclin production in Dahl rats susceptible to salt-induced hypertension.
To assess the roles of prostacyclin (PGI2) synthase in vascular PGI2 generation, the enzymatic activity was examined in the mesenteric artery of Dahl S rats in the prehypertensive or hypertensive stage. Elevation of blood pressure in Dahl S rats was accompanied by an increase of vascular PGI2 synthase activity. The enzymatic activity was positively correlated to the blood pressure value. Similarly, impaired vascular capacity to generate PGI2, which was observed in prehypertensive Dahl S rats, was restored to the control level of Dahl R rats with the elevation of blood pressure. These data indicate that vascular PGI2 synthase activity is increased with blood pressure elevation, thereby contributing to the restoration of vascular capacity to generate PGI2 in Dahl S rats.


Site-selective time-resolved laser fluorescence spectroscopy of Eu3+ in calcite.
Three samples of calcite homogeneously doped with Eu(3+) were synthesized in a mixed-flow reactor. By means of selective excitation of the 5D0-->7F0 transition at low temperatures (T<20 K), three different Eu(3+) species (species A, B, and C, respectively) could be discriminated. For each one, the emission spectrum and lifetime were obtained after selective excitation of the single species. On the basis of these data, species C could be identified as Eu(3+) incorporated into the calcite lattice on the (nearly) octahedral Ca(2+) site. Species B was also identified as Eu(3+) incorporated into the calcite lattice, but the ligand field shows a much weaker symmetry. Species A, however, is not incorporated into the crystal's bulk, having 1-2 H(2)O ligands left in its first coordination sphere and showing very little symmetry, and is considered as Eu(3+) adsorbed onto the calcite surface. The emission spectra of species C for Eu:calcite grown in the presence of Na(+) were found to differ from those of Eu:calcite synthesized in the presence of K(+). The latter revealed a strong distortion in site symmetry, which was not observed in the samples grown in Na(+) solutions. This finding provides spectroscopic evidence in favor of an incorporation mechanism based on the charge-balanced coupled substitution of Na(+)+Eu(3+)<-->2Ca(2+).


Baroreflex control of muscle sympathetic nerve activity is attenuated in the elderly.
To determine whether the baroreflex control of sympathetic nerve activity is attenuated in the elderly, muscle sympathetic nerve activity (MSNA) from the tibial nerve was monitored using microneurography, and heart rate and blood pressure were recorded during the depressor (phase II) or pressor (phase IV) period to Valsalva's maneuver in 10 younger subjects and 7 aged subjects. The baroreflex slope for heart rate showed attenuation in the aged subjects during the pressor phase but not during the depressor phase, the baroreflex slope for MSNA was also attenuated in the aged subjects during the pressor and tended to be attenuated during the depressor phases. These data suggest impaired baroreflex function for both heart rate and sympathetic nerve activity in the elderly.


Classification of DNA damages on segmented comet assay images using convolutional neural network.
Identification and quantification of DNA damage is a very significant subject in biomedical research area which still needs more robust and effective methods. One of the cheapest, easy to use and most successful method for DNA damage analyses is comet assay. In this study, performance of Convolutional Neural Network was examined on quantification of DNA damage using comet assay images and was compared to other methods in the literature. 796 single comet grayscale images with 170 x 170 resolution labeled by an expert and classified into 4 classes each having approximately 200 samples as G0 (healthy), G1 (poorly defective), G2 (defective) and G3 (very defective) were utilized. 120 samples were used as test dataset and the rest were used in data augmentation process to achieve better performance with training of Convolutional Neural Network. The augmented data having a total of 9995 images belonging to four classes were used as network training data set. The proposed model, which was not dependent to pre-processing parameters of image processing for DNA damage classification, was able to classify comet images into 4 classes with an overall accuracy rate of 96.1%. This paper primarily focuses on features and usage of Convolutional Neural Network as a novel method to classify comet objects on segmented comet assay images.


Factors affecting family planning literacy among women of childbearing age in the rural Lake zone, Tanzania.
Low uptake of various recommended modern family planning methods is associated with inadequate family planning literacy among potential beneficiaries of the methods. As such, understanding factors affecting family planning literacy is key to addressing this problem. This study, therefore, explored factors affecting family planning literacy among women of childbearing age in the rural Lake Zone of Tanzania. The study utilized an exploratory descriptive qualitative research approach using focus group discussions to collect data. A total of eight focus group discussion sessions were held to solicit information from childbearing age women involved in the study. Thematic analysis was used to analyze the data collected from the study participants. Several factors were found to negatively affect the family planning literacy of women of childbearing age in the communities under review. These factors were low levels of education, religious affiliation, and low family income. Other factors that were also found to negatively affect women's family planning literacy include fertility preference, negative perceptions of family planning, preference of unproven family planning methods, limited access to reliable sources of family planning information, household responsibilities, and poor male partner support on family planning matters. This study has identified a multitude of factors affecting the family planning literacy of women of childbearing age. These factors can limit the women's capacity to make informed decisions on the utilization of modern family planning methods. Thus, addressing these factors is pivotal in increasing the women's overall uptake of various recommended family planning methods and enhancing their reproductive health outcomes.


Transfer of pathological α-synuclein from neurons to astrocytes via exosomes causes inflammatory responses after METH exposure.
Methamphetamine (METH) is a highly addictive psychostimulant drug whose abuse can cause many health complications. Our previous studies have shown that METH exposure increases α-synuclein (α-syn) expression. Recently, it was shown that α-syn could be transferred from neurons to astrocytes via exosomes. However, the specific role of astrocytes in α-syn pathology involved in METH neurotoxicity remains unclear. The objective of this study was to determine whether exosomes derived from METH-treated neurons contain pathological α-syn and test the hypothesis that exosomes can transfer pathological α-syn from neurons to astrocytes. To this end, using animal and cell line coculture models, we show that exosomes isolated from METH-treated SH-SY5Y cells contained pathological α-syn. Furthermore, the addition of METH exosomes to the medium of primary cultured astrocytes induced α-syn aggregation and inflammatory responses in astrocytes. Then, we evaluated changes in nuclear receptor related 1 protein (Nurr1) expression and the levels of inflammatory cytokines in primary cultured astrocytes exposed to METH or α-syn. We found that METH or α-syn exposure decreased Nurr1 expression and increased proinflammatory cytokine expression in astrocytes. Our results indicate that α-syn can be transferred from neuronal cells to astrocytes through exosomes. When internalized α-syn accumulated in astrocytes, the cells produced inflammatory responses. Nurr1 may play a crucial role in this process and could be a therapeutic target for inflammatory damage caused by METH.


Impact of public health interventions in controlling the spread of SARS: modelling of intervention scenarios.
A variety of intervention measures exist to prevent and control diseases with pandemic potential like SARS or pandemic influenza. They differ in their approach and effectiveness in reducing the number of cases getting infected. The effects of different intervention measures were investigated by a mathematical modelling approach, with comparisons based on the effective reproduction number (R(e)). The analysis showed that early case detection followed by strict isolation could control a SARS outbreak. Tracing close contacts of cases and contacts of exposed health care workers additionally reduces the R(e). Tracing casual contacts and measures aiming to decrease social interaction were less effective in reducing the number of SARS cases. The study emphasizes the importance of early identification and isolation of SARS cases to reduce the number of people getting infected. However, doing so transfers cases to health care facilities, making infection control measures in hospitals essential to avoid nosocomial spread. The modelling approach applied in this study is useful for analysing interactions of different intervention measures for reducing the R(e) of SARS.


Cardiovascular effects of anesthesia and operation.
Anesthesia and surgery have a wide range of effects on the cardiovascular system. Even in healthy patients having minor operations, anesthetic agents can cause significant cardiac depression and hemodynamic instability. Virtually all anesthetic agents have intrinsic myocardial depressant properties, although some may mask this with sympathetic stimulation. The vasodilatory effects of the volatile agents can result in serious hypotension when combined with this negative inotropy. In the patient with pre-existing cardiac disease, these cardiovascular anesthetic effects become much more serious. These patients will not tolerate wide swings of hemodynamic variables, and the cardiodepressant effects of anesthetics are more pronounced in them. The stress of anesthesia and surgery frequently unmasks previously undiagnosed heart disease. Surgery itself provides many insults to the cardiovascular system, and these may be additive with the effects of anesthesia. These include loss of blood and other volume shifts, release of various substances into the circulation, hypothermia, sudden changes in cardiac preload and afterload, myocardial ischemia, and effects of drugs or blood products given for surgical reasons. The signs and symptoms of these surgical stresses to the cardiovascular system are often masked by anesthesia.


Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons.
Parkinson's disease is characterized by a severe loss of dopaminergic neurons resulting in a range of motor deficits. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain with corresponding Parkinsonian symptoms. Several animal species have also shown sensitivity to MPTP, including primates, mice, goldfish, and, most recently, zebrafish. This study demonstrates that the effect of MPTP on dopaminergic neurons in zebrafish larvae is mediated by the same pathways that have been demonstrated in mammalian species. MPTP-induced neurodegeneration was prevented by co-incubation with either the monoamine oxidase-B (MAO-B) inhibitor l-deprenyl or the dopamine transporter (DAT) inhibitor nomifensine. Furthermore, targeted inactivation of the DAT gene by antisense morpholinos also protected neurons from MPTP damage. Thus, the mechanism for MPTP-induced dopaminergic neuron toxicity in mammals is conserved in zebrafish larvae. Effects on swimming behavior and touch response that result from MPTP damage are partially ameliorated by both l-deprenyl and DAT knockdown.


Combination of intracellular cryoprotectants preserves the structure and the cells proliferative capacity potential of adult collared peccary testicular tissue subjected to solid surface vitrification.
The objective was to evaluate different permeating cryoprotectants to vitrify testicular tissue biopsies from adult collared peccaries. Five pairs of testicles were dissected into fragments (9 mm³) that were allocated to non-vitrified (control) and vitrified groups using a solid-surface method following exposure to different cryoprotectants (3.0 M dimethyl sulfoxide (DMSO), 3.0 M ethylene glycol (EG) or 1.5 M DMSO + 1.5 M EG). After warming, samples were evaluated for histomorphology, ultrastructure, viability, and proliferative capacity potential. The appropriate conservation of the ultrastructural organization of the seminiferous tubule in terms of lumen presence and cell junctions was only observed at the use of DMSO/EG combination. Regardless of the cryoprotectant, the vitrification effectively preserved cell nuclear visualization and condensation similarly as observed at the non-vitrified group. Moreover, DMSO/EG combination provided a better preservation of basal membranes of seminiferous tubules than DMSO (P < 0.05). The occurrence of cell swelling was more evident in the use of DMSO than EG (P < 0.05), but both isolate cryoprotectants were similar to the DMSO/EG combination. Only the DMSO/EG combination maintained the proliferative capacity potential for spermatogonia (3.69 NORs/cell) and Sertoli cell (3.19 NORs/cell) similar to controls (3.46 and 3.31 NORS/cell, respectively). Moreover, ~40% cell viability was found after vitrification independent of cryoprotectant. In conclusion, DMSO/EG in combination is better than DMSO or EG alone for SSV of testicular tissue biopsies from adult collared peccaries.


Prevalence of malnutrition in systemic sclerosis patients assessed by different diagnostic tools.
Gastrointestinal complaints of scleroderma (SS) patients are risk factors for impaired nutritional status, so insightful assessment is necessary. The aim was comparison of malnutrition rates in SS patients using different tools. Nutritional status was assessed using 7-SGA and SNAQ in 56 patients (47F, 9M) with SS. Anthropometric measurements and analysis of body composition were done. Serum levels of CRP, albumin, and hemoglobin were determined. Retrospectively, in 2018, diagnosis of malnutrition was verified using ESPEN 2015 and GLIM 2018 criteria. Gastrointestinal complaints were present in 76.8% of respondents. BMI < 18.5 was found in only 5.4% subjects. However, the percentage of patients with impaired nutritional status was higher and varied, depending on the tools used: 16.1% in SNAQ, 17.9% according to ESPEN 2015, 23.2% in 7-SGA, and as high as 62.5% when GLIM criteria were used. A significant part of patients with SS is malnourished. Screening for malnutrition should be focused on the percentage of unintentional weight loss, presence of gastrointestinal symptoms, and analysis of body composition. The choice of diagnostic tool appropriate for patients with SS will enable starting on-time nutritional intervention.Key Points:• Gastrointestinal involvement causes a significant proportion of patients to be malnourished.• It is important to look for early signs of malnutrition in patients with SS.• Assessment of nutritional status by adequate tools enables starting on-time nutritional intervention and improving prognosis in SS patients.


Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease.
CLN2 disease is a fatal, childhood autosomal recessive disorder caused by mutations in ceroid lipofuscinosis type 2 (CLN2) gene, encoding tripeptidyl peptidase 1 (TPP-1). Loss of TPP-1 activity leads to accumulation of storage material in lysosomes and resultant neuronal cell death with neurodegeneration. Genotype/phenotype comparisons suggest that the phenotype should be ameliorated with increase of TPP-1 levels to 5-10% of normal with wide central nervous system (CNS) distribution. Our previous clinical study showed that intraparenchymal (IPC) administration of AAVrh.10hCLN2, an adeno-associated vector serotype rh.10 encoding human CLN2, slowed, but did not stop disease progression, suggesting that this may be insufficient to distribute the therapy throughout the CNS (Sondhi 2020). In this study, we assessed whether the less invasive intracisternal delivery route would be safe and provide a wider distribution of TPP-1. A study was conducted in nonhuman primates (NHPs) with intracisternal delivery to cerebrospinal fluid (CSF) of AAVrh.10hCLN2 (5 × 1013 genome copies) or phosphate buffered saline (PBS). No abnormal behavior was noted. CNS magnetic resonance imaging and clinical chemistry data were all unremarkable. Histopathology of major organs had no abnormal finding attributable to the intervention or the vector, except that in one out of two animals treated with AAVrh.10hCLN2, dorsal root ganglia showed mild-to-moderate mononuclear cell infiltrates and neuronal degeneration. In contrast to our previous NHP study (Sondhi 2012) with IPC administration where TPP-1 activity was >2 × above controls in 30% of treated brains, in the two intracisternal treated NHPs, the TPP-1 activity was >2 × above controls in 50% and 41% of treated brains, and 52% and 84% of brain had >1,000 vector genomes/μg DNA, compared to 0% in the two PBS NHP. CSF TPP1 levels in treated animals were 43-62% of normal human levels. Collectively, these data indicate that AAVrh.10hCLN2 delivered by intracisternal route is safe and widely distributes TPP-1 in brain and CSF at levels that are potentially therapeutic. Clinical Trial Registration: NCT02893826, NCT04669535, NCT04273269, NCT03580083, NCT04408625, NCT04127578, and NCT04792944.


Influence of protein transduction domains on target-specific chimeric proteins.
Direct targeting to the cytoplasm and nucleus using protein transduction domains (PTD) has been described to be efficient but non-cell-type-specific, and only has clinical relevance when the molecule is active exclusively in the diseased cell. The use of PTDs is an attractive mechanism to improve drug delivery. In this work, we designed recombinant proteins that contain epidermal growth factor as ligand to render uptake target cell-specific. We evaluated the potential of several PTDs to induce the cytosolic uptake of the catalytic domain of diphtheria toxin by measuring cytotoxicity. Although PTD-dependent membrane transfer is very low, the proteins exhibited concentration-dependent cytotoxic activity. Higher binding at 4 degrees C compared to 37 degrees C suggests that uptake by the PTDs MTS and TLM occurs via an endocytic pathway. Non-specific binding is predominantly a function of the PTD and greatly increases by substitution of a non-polar glycine with a negatively charged glutamate in the PTD HA2.


Incidence of VTE and Bleeding Among Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.
Individual studies have reported widely variable rates for VTE and bleeding among hospitalized patients with coronavirus disease 2019 (COVID-19). What is the incidence of VTE and bleeding among hospitalized patients with COVID-19? In this systematic review and meta-analysis, 15 standard sources and COVID-19-specific sources were searched between January 1, 2020, and July 31, 2020, with no restriction according to language. Incidence estimates were pooled by using random effects meta-analyses. Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using the Begg and Egger tests. The pooled incidence was 17.0% (95% CI, 13.4-20.9) for VTE, 12.1% (95% CI, 8.4-16.4) for DVT, 7.1% (95% CI, 5.3-9.1) for pulmonary embolism (PE), 7.8% (95% CI, 2.6-15.3) for bleeding, and 3.9% (95% CI, 1.2-7.9) for major bleeding. In subgroup meta-analyses, the incidence of VTE was higher when assessed according to screening (33.1% vs 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs 7.1% in the ward), in prospective studies (25.5% vs 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs. The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%). Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT, and subsegmental PE, in critically ill patients and in prospective studies. Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants and nature of data collection. Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes. PROSPERO; No.: CRD42020198864; URL: https://www.crd.york.ac.uk/prospero/.


Chitosan-modified biochar: Preparation, modifications, mechanisms and applications.
The chitosan-modified biochar composite, as a carbohydrate polymer, has received increasing attention and becomes a research hotspot. It is a promising impurity adsorption material, which has potential application value in the agricultural environment fields such as soil improvement and sewage purification. The composite can combine the advantages of biochar with chitosan, and the resulting composite usually exhibits a great improvement in its surface functional groups, adsorption sites, stability, and adsorption properties. In addition, compared to other adsorbents, the composite truly achieves the concept of "waste control by waste". In this paper, the preparation method, composite classification, adsorption mechanism, and models of biochar modified by chitosan are introduced, meanwhile, we also review and summarize their effects on the decontamination of wastewater and soil. In addition to common heavy metal ions, we also review the adsorption and removal of some other organic/inorganic pollutants, including (1) drug residues; (2) dyes; (3) phosphates; (4) radionuclides; (5) perfluorochemicals, etc. Moreover, challenges and prospects for the composite are presented and further studies are called for the chitosan-biochar composite. We believe that the composite will lead to further achievements in the field of environmental remediation.


Predictors of 15-year survival among Australian women with diabetes from age 76-81.
To assess the impact of diabetes on the survival of older women, adjusted for other all-cause mortality predictors. Data were used from the 1921-26 cohort of the Australian Longitudinal Study on Women's Health, when the women were aged 76-81 years at baseline, with linkage to the National Death Index. Survival curves were plotted to compare the survival of women with no diabetes, incident diabetes and prevalent diabetes over 15 years. Cox proportional hazards models were used to examine the association between diabetes and all-cause mortality risks. A total of 972 (11.7%) of 8296 eligible women reported either incident, 522 (6.3%) or prevalent, 450 (5.4%) diabetes. The median survival times were 10.1, 11.4 and 12.7 years among women with prevalent, incident and no diabetes, respectively. The risks of death were 30% [HR: 1.30 (95% CI: 1.16-1.45)] and 73% [HR: 1.73 (CI: 1.57-1.92)] higher for women with incident and prevalent diabetes compared to women without diabetes. These associations were sustained after controlling for demographics, body mass index, smoking status, comorbidities and health care use. This study revealed that diabetes is associated with reduced survival probabilities for older women with minimal moderation after adjustment for other predictors. Our findings suggest that diabetes management guidelines for older women need to integrate factors such as comorbidities, smoking and being underweight to reduce the risk of mortality.


Body stiffness is a mechanical property that facilitates contact-mediated mate recognition in Caenorhabditis elegans.
Physical contact is prevalent in the animal kingdom to recognize suitable mates by decoding information about sex, species, and maturity. Although chemical cues for mate recognition have been extensively studied, the role of mechanical cues remains elusive. Here, we show that C. elegans males recognize conspecific and reproductive mates through short-range cues, and that the attractiveness of potential mates depends on the sex and developmental stages of the hypodermis. We find that a particular group of cuticular collagens is required for mate attractiveness. These collagens maintain body stiffness to sustain mate attractiveness but do not affect the surface properties that evoke the initial step of mate recognition, suggesting that males utilize multiple sensory mechanisms to recognize suitable mates. Manipulations of body stiffness via physical interventions, chemical treatments, and 3D-printed bionic worms indicate that body stiffness is a mechanical property for mate recognition and increases mating efficiency. Our study thus extends the repertoire of sensory cues of mate recognition in C. elegans and provides a paradigm to study the important roles of mechanosensory cues in social behaviors.


Two-sample Mendelian randomization study does not reveal a significant relationship between cytomegalovirus (CMV) infection and autism spectrum disorder.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting ~ 2% of children worldwide and is characterized by repetitive, stereotypical behaviours and impaired expressive communication. Cytomegalovirus (CMV) is considered a risk factor for ASD; however, published studies are usually limited by covering too few events and have different conclusions, indicating that the relationship between CMV infection and ASD remains elusive. To investigate the association between CMV infection and ASD, we conducted this 2-sample Mendelian randomization (MR) study using genome-wide association studies (GWAS) summary data from FinnGen and the IEU Open GWAS project. Our results showed no significant relationship between all 3 CMV infections (unspecified cytomegaloviral diseases, anti-CMV IgG levels, and maternal CMV) and ASD. Our results indicate that CMV infection does not significantly increase ASD risk. These results show that the relationship between CMV infection and ASD remains elusive and needs to be further clarified.


Can Acetaminophen Pretreatment Decrease the Pain Associated With Closed Nasal Bone Reduction? A Triple-Blind Randomized Clinical Trial.
Nasal bone fracture is a common maxillofacial injury, which is usually managed under local anesthesia because it is fast and effective but painful. We designed this study to see if pre-emptive analgesia with acetaminophen can reduce the pain associated with nasal bone reduction under local anesthesia. This was a triple-blind, randomized clinical trial. Our sample was patients with nose fracture (eligible for closed reduction) who presented to our nasal fracture clinic and they were divided into 2 arms. Medication was randomly delivered via packages, and the surgeon, patients, and data analyzer were all blind to the intervention. Demographic data along with the visual analog scale pain scores (1 to 10 score from least to most severe pain) during local anesthesia, during reduction, and 24 hours after reduction were recorded, then analyzed using χ2, nonparametric Mann-Whitney test, and correlation analysis. One hundred participants were divided into 2 arms (placebo or acetaminophen 500-mg tablet 45 minutes before reduction). The patients were mostly men (74%), and the most common mechanism was involvement in a fight (30%). Pain scores, as well as surgeon satisfaction analysis, returned no statistical difference between the 2 groups. Correlation analysis was performed, and the only factor for pain severity during reduction was the number of tries needed. Acetaminophen pretreatment did not add analgesia any more than that of placebo. Its use before reduction of nasal bone fracture is not justified.


The protective effect of PK11195 on D-galactose-induced amnestic mild cognitive impairment in rats.
This study aimed to investigate the preventive effect of translocator protein 18kDa (TSPO) ligand PK11195 on amnestic mild cognitive impairment (aMCI), as well as its influence on astrocytes, in order to identify effective ways to prevent aMCI. Male SD rats were randomly divided into control group (n=10), aMCI group (n=10), PK11195 group (n=10), PK11195 + D-gal group (n=10). The preventive effect of PK11195 on aMCI in rats was evaluated. The cognitive function of rats in four different treatment groups was determined using the Morris water maze (MWM), as well as whole-brain pathology and immunofluorescence of rat brain tissue. The results of the MWM behavioral test showed that rats pre-treated with PK11195 had improved escape latency and a higher number of platform crossings compared with the aMCI model rats. PK11195 was also shown to prevent the D-galactose (D-gal)-induced senescence of pyramidal cells in the hippocampal CA1 region and to inhibit the apoptosis of astrocytes. At the same time, compared with the aMCI model rats, the TSPO in the brain tissue of rats pretreated with PK11195 had a lower distribution density. Our results prove that PK11195 can effectively prevent D-gal-induced decline of learning and memory function as well as inhibit abnormal changes of related cells.


Shape-restricted estimation and spatial clustering of COVID-19 infection rate curves.
The study of regional COVID-19 daily reported cases is used to understand pattern of spread and disease progression over time. These data are challenging to model due to noise that is present, which arises from failures in reporting, false positive tests, etc., and the spatial dependence between regions. In this work, we extend a recently developed Bayesian modeling framework for inference of functional data to jointly estimate and cluster daily reported cases data from US states, while accounting for spatial dependence between US states. Shape-restriction allows us to directly infer the number of extrema of a smooth infection rate curve that underlies noisy data. Other parameters in the model account for the relative timing of extrema, and the magnitude and severity of infection rates. We incorporate mobility behavior of each US state's population into an informative prior model to account for the spatial dependence between US states. Our model corroborates past work that shows that different US states have indeed experienced COVID-19 differently, but that there are regional patterns within the US. The modeling results can be used to assess severity of infection in individual US states and trends of neighboring US states to aid pandemic planning. Retrospectively, this model can be used to see which factors (governmental, behavioral, etc.) are associated with the varying shapes of infection rate curves, which is left as future work.


CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia.
Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival. CD36 was dispensable for lipid uptake but fostered blast migration through its binding with thrombospondin-1. CD36-expressing blasts, which were largely enriched after chemotherapy, exhibited a senescent-like phenotype while maintaining their migratory ability. In xenograft mouse models, CD36 inhibition reduced metastasis of blasts and prolonged survival of chemotherapy-treated mice. These results pave the way for the development of CD36 as an independent marker of poor prognosis in AML patients and a promising actionable target to improve the outcome of patients. CD36 promotes blast migration and extramedullary disease in acute myeloid leukemia and represents a critical target that can be exploited for clinical prognosis and patient treatment.


NDM-5-producing carbapenem-resistant Klebsiella pneumoniae of sequence type 789 emerged as a threat for neonates: a multicentre, genome-based study.
Klebsiella pneumoniae is a major human pathogen. Carbapenems are the main agents of choice to treat severe K. pneumoniae infections, but carbapenem-resistant K. pneumoniae (CRKP) have emerged as a major global problem. Novel high-risk CRKP lineages are continuously emerging, but those associated with neonatal infections are under-researched. In this study, we identified a common CRKP lineage carrying the blaNDM-5 carbapenemase-encoding gene belonging to sequence type 789 (ST789) based on analysis of the genome sequences of 28 isolates, including 27 clinical isolates from neonates and 1 isolate from a sink recovered in 2019 from multiple hospitals in Chengdu, southwest China. Isolates of this lineage caused various infections (pneumonia, bloodstream infection and urinary tract infection) in neonates and had circulated in and been transmitted between neonatal intensive care units of multiple local hospitals for several years. Its emergence was likely due to clonal expansion after acquiring a blaNDM-5-carrying self-transmissible IncX3 plasmid. Genome clock analysis dated the emergence of this lineage to December 2016 (95% confidence interval, January 2015 to December 2017). The above findings highlight that CRKP lineages in neonates and adults may differ. This ST789 blaNDM-5-carrying CRKP lineage represents a new, emerging threat for neonates and warrants rigorous monitoring.


Commitment to quality of the Spanish scientific societies.
This article summarises the objectives, methodology and initial conclusions of the project "Commitment to Quality of the Spanish Scientific Societies", coordinated by the Ministry of Health, Social Services and Equality, the Spanish Society of Internal Medicine and the Aragon Institute of Health Sciences, in which 48 scientific societies participate. This project's objectives are to decrease the use of unnecessary medical interventions, which are those that have shown no efficacy, have little or questionable effectiveness or are not cost-effective; decrease variability in clinical practice; promote the commitment among physicians and patients to properly use healthcare resources; and to promote clinical safety. The document includes 135 final recommendations for what not to do, prepared by 30 Spanish scientific societies.


Cardioprotective effect of dexrazoxane during treatment with doxorubicin: a study using low-dose dobutamine stress echocardiography.
To assess the late cardioprotective effect of dexrazoxane associated with doxorubicin during treatment of osteosarcoma by means of low-dose dobutamine stress echocardiography (LDDSE) in non-relapsed asymptomatic children and teenagers. The study population included 58 patients with osteosarcoma divided in three groups, with equivalent age range, gender proportion and body surface area. Group I (21 patients, 14 males, 15 +/- 4 years) was analyzed before chemotherapy and considered the control group; Group II (19 patients, 11 males, 19.7 +/- 4 years) was treated with 348.4 +/- 18 mg/m2 of doxorubicin only and Group III (18 patients, 14 male, 16.8 +/- 5 years) treated with 396.5 +/- 55 mg/m2 of doxorubicin with dexrazoxane in the ratio 10:1. The patients were submitted to LDDSE (maximal dose 5 microg/kg/min). No major side effects were observed. Heart rate, blood pressure, left ventricular diameters, end systolic wall stress (ESWS), and other diastolic and systolic function indexes were assessed at rest conditions and during LDDSE and compared between the three groups. Group III received a doxorubicin dose significantly greater than Group II (P = 0.001). During LDDSE there were no significant changes in the diastolic function indexes in any of the groups, but there was a significant increase of systolic indexes and a decrease of ESWS in Group III compared to group II. There was no significant difference of any systolic functional parameters between Group I and III. Considering the ejection fraction (EF) at rest or at LDDSE, 13 patients (69.4%) in Group II and 5 patients (27.7%) in Group III were considered to have systolic dysfunction. (P = 0.02). Myocardial response to LDDSE in patients treated with doxorubicin and dexrazoxane was similar to patients without chemotherapy and better than those treated with doxorubicin only, suggesting less cardiotoxicity.


Psychological aspects of weekend headache sufferers in comparison with migraine patients.
Sometimes the relaxation after stress may trigger a migraine attack. This is the principle that underlies that particular variant of migraine called "weekend headache". We hypothesize the presence in weekend headache prone subjects of a particular psychological background, different from that of common migraine sufferers. In order to detect possible differences supporting our hypothesis, we studied 104 new outpatients: 46 patients suffering from headache only on weekends (23 males and 23 females) and 58 matched common migraineurs (26 males and 32 females) with no weekend predilection. The psychological assessment was performed using the following psychometric tools: MMPI, BDI, STAIX1-X2. A clinical assessment of each patient was also carried out. Significant differences were found after statistically analyzing the test results. Most of the MMPI scales were found to be more elevated in both male and female weekend headache sufferers. From a clinical point of view, the weekend headache attacks proved to be similar to those of common migraine, but with a significantly higher incidence of concomitant symptoms. Our study confirms the important role that psychological factors play in the pathogenesis and clinical development of migraine and leads us to conclude that a psychic tension component is associated with the vascular one in weekend headache.


Effectiveness of furosemide in attenuating exercise-induced pulmonary haemorrhage in horses when administered at 4- and 24-h prior to high-speed training.
Due to the high prevalence of EIPH in racehorses and its potential impact on the horse's health, furosemide administration is permitted up to 4-h prior to post time in most North American racing jurisdictions. Anecdotal reports suggest that administration of furosemide 24-h prior to strenuous exercise may be equally effective in decreasing the severity of EIPH. To 1) compare the efficacy of furosemide in reducing the presence and severity of EIPH when administered 4- or 24-h prior to strenuous exercise 2) characterise electrolyte and blood parameters following administration of furosemide at 4- and 24-h prior to exercise. 3-way crossover. Fifteen Thoroughbred racehorses received 5 mL of 0.9% NaCl or 250 mg of furosemide either 4- or 24-h prior to a 5-furlong simulated race. Blood samples were collected prior to and post-run for determination of furosemide, lactate, haemoglobin and electrolyte concentrations. One-hour post-race, an endoscopic exam and bronchoalveolar lavage (BAL) were performed. Horses were assigned an EIPH score based on predetermined criteria and the number of red blood cells in BAL fluid was determined. Endoscopic EIPH scores were lower in the 4-h vs. the 24-h (P = 0.03) furosemide groups. RBC counts in BAL fluid were lower in the 4-h furosemide vs. saline treatment groups (P = 0.01) but no difference was noted between the saline and 24-h furosemide groups (P = 0.3), nor between the 4- and 24-h groups (P = 0.5). Small sample size and large range of running times for the 5-furlong work. While none of the treatments prevented EIPH, endoscopic scores and RBC counts in BAL fluid support the efficacy of furosemide in reducing the severity of EIPH. Endoscopic scores were lower in the 4-h furosemide group compared with 24-h administration. Red blood cell counts were lower in the 4-h furosemide group compared with saline treatment.


Ethanol modulates evoked dopamine release in mouse nucleus accumbens: dependence on social stress and dose.
Ethanol may modulate the activity of presynaptic terminals to increase extracellular dopamine release in the nucleus accumbens though conflicting results have been published. It has been suggested that the stress of social defeat might be a factor influencing the effects of ethanol. We investigated the effects of ethanol on the evoked dopamine overflow in the nucleus accumbens in anaesthetised mice by in vivo voltammetry. Dominant animals, subordinates which had been defeated following eight intruder-resident encounters, and subordinate nondefeated mice were used. The overflow was evoked by electrical stimulation of the median forebrain bundle (100 pulses) at low (20 Hz) and high (50 Hz) frequencies of stimulation. Ethanol at 0.1 and 2 g/kg had no effects on evoked dopamine overflow in aggressive and nondefeated mice. Ethanol increased dopamine release at 0.1 g/kg and decreased release at 2 g/kg following high frequency stimulation in defeated mice. These data suggest that the stress of social defeat may have sensitised the machinery involved in dopamine release to ethanol, a process that may increase the reinforcing properties of this compound.


Adoption and feeding of fieldfare nestlings and fledglings by European blackbird.
Interspecific adoption is an intriguing topic in behavioral and evolutionary ecology. As it is a rare phenomenon, seldom documented in the literature, reports of interspecific adoption based on solid data are particularly valuable. A long-term and extensive monitoring programme involving a local population of European blackbirds (Turdus merula, hereafter blackbird) has yielded, among other things, observations of alloparental behavior exhibited by blackbirds toward fieldfare (Turdus pilaris) nestlings (a single nest, the first-ever record) and fledglings (12 cases in all). We discuss the observations in the context of the available literature.


[Liver cirrhosis in Cotonou, Republic of Benin: clinical aspects and factors related to death].
Infection by hepatitis B virus is the main cause of liver cirrhosis in Africa. The purpose of this retrospective study was to evaluate clinical and epidemiological features as well as factors related to death in cirrhosis patients admitted to the National University Hospital in Cotonou, Benin. The files of patients admitted from January 1 to December 31, 2004 were reviewed. Out of the 230 useable files reviewed, a total of 52 involved patients were admitted for liver cirrhosis. The male/female sex ratio was 2.25 and mean age was 49 years. The proportion of unemployed and salaried patients was 42.3% and 28.8% respectively. Hepatitis B and alcohol consumption were the main etiological factors: 53.3% and 23.2% respectively. The main reasons for hospitalization were asthenia in 73% of cases, abdominal pain in 57%, and digestive bleeding in 21%. The revealing manifestations were ascitis (75%), jaundice (71.7%), and hepatocellular carcinoma (42.3%). Higher risk for in-hospital death (42.3%) was correlated with male gender, salaried employment, and presentation with jaundice, ascitis, or hepatocellular carcinoma. The risk of death during hospitalization was higher for patients who were of male gender, working as salaried employees and admitted for the first time with jaundice, ascitis, or hepatocellular carcinoma. A program for mass vaccination of children against hepatitis B virus is needed to prevent cirrhosis and hepatocellular carcinoma. A campaign against alcohol abuse could reduce cirrhosis due to alcohol consumption.


The sperm ultrastructure of the click beetles (Elateridae) and related groups (Buprestidae and Lampyridae).
In the present study, we describe the sperm morphology of 11 species of Elateriformia (9 elaterids, 1 lampyrid and 1 buprestid) using transmission electron microscopy. All species exhibited sperm that is not usually observed in insects in general. The most highlighted features are the displacement of the nucleus running parallel to the flagellar components, hitherto observed only in coccinellid and carabid beetles, and the presence of thin and dense structures along the nucleus, probably derived from the centriole adjunct, a feature that is so far exclusive to these insects. The other structures are a typical axoneme for insects with 9 + 9 + 2 microtubules, in a position diametrically opposite relative to the nucleus, two slender, symmetrical mitochondrial derivatives and a pair of discrete accessory bodies. This arrangement provides a bilaterally symmetrical flagellum, which favourably influences sperm hydrodynamics, as will be discussed. The occurrence of this unusual structural arrangement in the sperm of species from superfamilies that are phylogenetically as distant as Elateroidea and Buprestoidea support the monophyly of the infraorder Elateriformia, as proposed by some previous molecular studies.


Circulating antioxidant profile of pregnant women with asthma.
One of the most prevalent complications of pregnancy is asthma which is associated with an increased incidence of intrauterine growth restriction. The mechanisms that affect fetal development in pregnancies complicated by asthma are not clearly defined. Antioxidants are particularly important during pregnancy due to their protective role against a state of high oxidative stress as gestation progresses. The current study was designed to characterise the circulating profile of tocopherols and carotenoids in pregnant women with asthma to determine whether asthma severity and dietary intake were associated with an altered antioxidant profile. Maternal dietary intake and plasma and erythrocyte concentrations of tocopherols and carotenoids were examined in women with (n = 84) and without asthma (n = 47) at 18, 30 and 36 weeks gestation. Tocopherol and carotenoid levels were related to fetal and birth outcomes. Pregnant women with moderate/severe asthma were found to have increased plasma concentrations of total carotenoids (P < 0.05), lutein (P < 0.05 and α-tocopherol (P < 0.02) late in gestation compared to those women with mild asthma and healthy pregnant controls. Moderate/severe asthmatics had higher erythrocyte α-tocopherol quinone levels early in gestation relative to the controls (P < 0.02) but this marker of oxidative stress decreased as gestation progressed. Tocopherols and carotenoids were positively associated with birth weight centile (P < 0.05). These findings suggest that the maternal system adjusts antioxidant pathways in response to the presence of a high oxidative load induced by asthma during pregnancy in an attempt to ensure continued fetal growth in an adverse environment.


[Lichen planopilaris. Successful treatment with tacrolimus].
Lichen planopilaris (LPP) is an inflammatory condition of unknown etiology that affects pilosebaceous units, mainly of the scalp, and results in scaring alopecia. A 51-year-old male presented with a pruritic eruption on the cheek consisting of atrophic macules and erythematous folliculocentric papules. Biopsy revealed a perifollicular lymphocytic infiltrate and vacuolar degeneration of the dermoepidermal junction consistent with LPP. Many treatment modalities have been utilized, with varying degrees of success. Our patient responded poorly to topical steroids. After nine months of topical tacrolimus therapy, his lesions resolved entirely. The treatment of our patient demonstrates tacrolimus as a novel topical therapeutic option for patients with LPP.


Gene therapy for inherited immunodeficiencies.
Extensive research into gene therapy technologies has produced few clinically relevant results. Advances in the understanding of the genetics of inherited immunologic diseases, gene transfer methodologies, and stem cell manipulation have all contributed to successes in treating X-linked severe combined immunodeficiency and adenosine deaminase deficiency. This review examines the progress and the problems that have arisen, and discusses the improvement and future of gene therapy for primary immunodeficiencies.


Osmolytes and mechanisms involved in regulatory volume decrease under conditions of sudden or gradual osmolarity decrease.
A decrease in external osmolarity results in cell swelling and the immediate activation of a mechanism to restore cell volume, known as regulatory volume decrease (RVD). When exposed to a gradual osmolarity decrease (GODE), some cells do not swell. This reflects the operation of an active regulatory process known as isovolumetric regulation (IVR). The mechanisms underlying IVR appear similar to those activated during RVD, namely the extrusion of K+, Cl-, amino acids, and other organic molecules. A previous study has documented IVR in cerebellar granule neurons, parallel to an early efflux of taurine and Cl-, whereas K+ efflux is delayed. In this work we briefly review the importance of amino acids in the mechanisms of cell volume control in the brain, with emphasis on IVR. We also present experiments showing the response to GODE in cerebellar astrocytes. The currents activated during GODE, recorded in the whole-cell configuration of the patch clamp technique, indicate the early activation of an anion current, followed by a more delayed cation current. A correlation between the time course of amino acid efflux during GODE and the occurrence or not of IVR in various cell types, suggest the importance of these osmolytes in the volume regulatory process in this model.


Case report: Birth achieved after effective ovarian stimulation combined with dexamethasone in a patient with resistant ovary syndrome.
Resistant ovary syndrome (ROS) is a rare endocrine disorder and there have been few reports of live births by affected patients. As gonadotropin resistance leads immature oocytes, some researchers reported few live births with in vitro maturation (IVM) of oocytes, but IVM is not always successful in ROS patients. Here, we report an original case of ROS, associated with Ig-FSHR in the serum, who achieved a live birth following ovarian stimulation combined with dexamethasone treatment. The 30-year-old woman presented with secondary amenorrhea and infertility. Her serum FSH levels were found to be higher than normal, but in discordance with a normal anti-Müllerian hormone (AMH) level and antral follicle count. Genetic investigation found no mutations potentially affecting FSHR. With reference of previous ROS studies, the patient's serum was analyzed for antibodies directed against FSHR and dot blot analysis showed strong reactivity with FSHR. Then, dexamethasone was proposed to the patient, and she successfully became pregnant, finally delivering a healthy girl by caesarean section. To our best knowledge, this is the first report of the successful treatment of ROS using ovarian stimulation combined with dexamethasone. In some cases of ROS, high doses of exogenous gonadotropins in combination with immunosuppressive therapy could be an effective approach.


Are emotion and motivation localized in the limbic system and nucleus accumbens?
Groups of control rats without surgery or groups of rats prepared with surgical lesions of the septal nuclei, amygdala, cingulate cortex, accumbens nucleus, section of the fornix, or sham surgical operations, were tested in a simple autonomic conditioning situation (conditioned defecation). Control rats and rats with lesions of the accumbens nucleus were also tested in a straight alley maze under varying conditions of water deprivation. In general, the lesions had little effect except that amygdaloid damage impaired acquisition of conditioned defecation. The theory that 'emotion' and 'motivation' can be localized in the 'limbic system' and nucleus accumbens is discussed critically.


Detection of melanomas by digital imaging of spectrally resolved ultraviolet light-induced autofluorescence of human skin.
Digital images of autofluorescence excited with 366 nm Hg line were recorded in a narrow 475 nm band for 408 pigmented lesions of the skin (90 melanomas, 205 common melanocytic and dysplastic naevi, 113 lesions of different kinds) and analysed photometrically with respect to spatial distribution of intensity to differentiate between melanomas and other melanocytic lesions. Earlier reports describing patterns of intensity distributions characteristic for melanomas have not been confirmed in this study. However, our evaluations showed that an algorithm based on ratios of maximum intensity recorded outside the lesions and minimum intensity found within them, allows melanomas to be detected with a sensitivity of 82.5%, a specificity of 78.6% and a positive predictive value of 58.9% (melanomas versus common and dysplastic naevi) or 76.7% (melanomas versus other pigmented lesions). The method is now being tested in a multicentre study involving three groups in three different cities in Poland.


Isolation of clinically significant microorganisms from prosthetic joint tissue using BacT/ALERT paediatric blood culture bottles compared with solid culture media and enrichment broth.
The diagnosis of prosthetic joint infections and isolation of causative microorganisms has been found to be challenging in microbiology laboratories due to low sensitivity of microbiological culture. The aim of this study was to compare the use of conventional culture methods with the use of both enrichment broth and BacT/ALERT paediatric blood culture bottles, for the diagnosis of prosthetic joint infections. A total of 121 specimens from 44 patients were processed using three methods of microbiological culture: solid media, enrichment broth and paediatric bottles. The paediatric bottle method had a significantly lower (p<0.0001) time to detection than the standard solid media method, and was significantly more sensitive than solid media when used independently (93.33%, CI 83.27-98.09, vs 60.00%, CI 45.43-73.33). The combination use of solid media with paediatric bottles was found to be superior to the conventional solid media method and combination use with enrichment broth.


Molecular mechanisms of anti-cancer bioactivities of seaweed polysaccharides.
Seaweed is a traditional Chinese medicine homologous to food, in which polysaccharides are responsible for anti-cancer by enhancing immunity, inducing cancer cell apoptosis, inhibiting cancer cell invasion and metastasis or directly scavenging oxidative free radicals that induce cancer cell changes. Among them, regulating immunity and promoting cancer cell apoptosis are intensively studied due to the important role in preventing cancer. Here we reviewed seaweed in the apoptosis-inducing signaling pathways including PI3K/AKT, ROS and JNK and discussed challenges in studying seaweed.


Development and screening of contrast agents for in vivo imaging of Parkinson's disease.
The goal was to identify molecular imaging probes that would enter the brain, selectively bind to Parkinson's disease (PD) pathology, and be detectable with one or more imaging modalities. A library of organic compounds was screened for the ability to bind hallmark pathology in human Parkinson's and Alzheimer's disease tissue, alpha-synuclein oligomers and inclusions in two cell culture models, and alpha-synuclein aggregates in cortical neurons of a transgenic mouse model. Finally, compounds were tested for blood-brain barrier permeability using intravital microscopy. Several lead compounds were identified that bound the human PD pathology, and some showed selectivity over Alzheimer's pathology. The cell culture models and transgenic mouse models that exhibit alpha-synuclein aggregation did not prove predictive for ligand binding. The compounds had favorable physicochemical properties, and several were brain permeable. Future experiments will focus on more extensive evaluation of the lead compounds as PET ligands for clinical imaging of PD pathology.


Extended follow-up of palatal implants for OSA treatment.
Evaluate long-term safety and outcomes of palatal implants for patients with mild to moderate obstructive sleep apnea (OSA). Continuation of a prospective case series of patients with palatal implants. Polysomnography, daytime sleepiness, and snoring intensity were measured at baseline, 90 days, and extended follow-up. Twenty-two (42%) patients from the previous study were followed for a median of 435.5 days. Thirteen were classified as responders, based on their 90-day evaluation. 76.9% of initial responders maintained improvements in apnea-hypopnea index (AHI), daytime sleepiness, and snoring at extended follow-up. Nine patients were initial nonresponders for AHI and daytime sleepiness and remained unchanged at extended follow-up. However, snoring for these nine patients initially improved, and the improvement continued through extended follow-up. Initial response or nonresponse to palatal implants remains stable over an extended period. The generalizability of these results is unknown because of significant loss to follow-up. Study results report safety and beneficial long-term outcomes of palatal implants for mild to moderate OSA treatment in selected patients.


On the performance of random-coefficient pattern-mixture models for non-ignorable drop-out.
Random-coefficient pattern-mixture models (RCPMMs) have been proposed for longitudinal data when drop-out is thought to be non-ignorable. An RCPMM is a random-effects model with summaries of drop-out time included among the regressors. The basis of every RCPMM is extrapolation. We review RCPMMs, describe various extrapolation strategies, and show how analyses may be simplified through multiple imputation. Using simulated and real data, we show that alternative RCPMMs that fit equally well may lead to very different estimates for parameters of interest. We also show that minor model misspecification can introduce biases that are quite large relative to standard errors, even in fairly small samples. For many scientific applications, where the form of the population model and nature of the drop-out are unknown, interval estimates from any single RCPMM may suffer from undercoverage because uncertainty about model specification is not taken into account.


Paper aging and degradation monitoring by the non-destructive two-dimensional micro-Raman mapping.
The aim of this research is the identification of main and common physical-chemical parameters which induce paper degradation. A simple protocol to monitor the quality and molecular structure of ancient papers under natural degradation processes was proposed. Two-dimensional micro-Raman mapping were carried out. Then, point to point, the changes of both the cellulose Raman signature and fluorescence signal intensity were analysed. Modern papers were artificially aged to simulate the natural degradation and a comparison with the trend found for the ancient paper was presented and discussed. Cellulose degradation involves different mechanisms such as dehydration, cleaving of cellulose-glycosidic bonds and glucopyranose rings oxidation, that induce a reduction in the polymerization degree. As shown by the changes of Raman and fluorescence signals and NMR relaxation times, the rate of each processes depends on the initial amount of glycosidic bonds in the cellulose amorphous and crystalline regions, respectively. All these informations are useful both to define procedures to restore old documents and also to preserve the quality of modern papers for a long-term time.


Celastrol relieves myocardial infarction-induced cardiac fibrosis by inhibiting NLRP3 inflammasomes in rats.
Myocardial infarction (MI) triggers a strong inflammatory response mediating by NLRP3 inflammasome which is associated with cardiac fibrosis. The key players in this response are Interleukin (IL)-1 and IL-18, which are regulated by NLRP3 inflammasomes. Celastrol, a traditional Chinese medicine with strong anti-inflammatory activity, has recently reported as a cardioprotective agent. However, the mechanisms by which celastrol is cardioprotective in MI remain elusive. We hypothesized that Celastrol could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in rats, improve poor heart remodeling, and preserve heart function. Myocardial infarction (MI) was caused by ligating the left anterior descending of male SD rats. Celastrol (1 mg/kg) or saline was administered every other day for 4 weeks. Heart function and fibrosis were assessed. Inflammatory and fibrotic markers in the myocardia were evaluated with immunohistochemistry, western blot, and ELISA. Molecular docking was employed to predict Celastrol's binding to NLRP3 protein. The effects of Celastrol on the expression of NLRP3 inflammasome and myocardial fibrosis genes were then examined in vitro. Celastrol maintained the left ventricular fractional shortening (FS) and ejection fraction (EF). Fibrosis was significantly reduced in animals treated with 1 mg/kg Celastrol (15.17 ± 1.82%) relative to controls (29.88 ± 4.28%). Celastrol also significantly reduced the NLRP3, IL-18, and IL-1β levels, together with macrophage and neutrophil infiltration in the myocardium. Molecular docking predicted that NLRP3 would bind tightly to Celastrol [Docking energy: -8.9 (kcal/mol)]. In vitro experiments showed reduced NLRP3 inflammasome and myocardial fibrosis-associated proteins expression in neonatal rat cardiac fibroblasts treated with Celastrol. In post-MI rats, Celastrol, a naturally occurring active ingredient, was able to reduce myocardial fibrosis and improve cardiac function, according to our study. These effects may result from inhibiting the NLRP3 inflammasome and attenuating the early inflammatory storm after MI, suggesting that Celastrol may be useful in treating acute MI.


Modulation of proteoglycan metabolism by hydrocortisone and by growth factors in rhabdomyosarcoma cell lines of different metastatic potentials.
Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials, grown in the presence or in the absence of hydrocortisone and of growth factor (EDF and EDGF) were investigated comparatively. The newly formed [35S]sulphate and [3H]glucosamine-labelled glycosaminoglycans were analysed in the extra-, peri- and intra-cellular compartments of the following cell lines: the strongly metastatic and colonizing 9-4/0 parental line, the very weakly metastatic and weakly colonizing subline 8 and the very weakly metastatic but colonizing subline 13a2. The cell surface of the weakly metastatic 8 and 13a2 lines was richer at least 5 and 2 times respectively in sulphated glycosaminoglycan label than the surface of the strongly metastatic 9-4/0 parental line. Hydrocortisone provoked an approximately four-fold increase in the label of the sulphated cell surface glycosaminoglycans of the 9-4/0 line. The pattern of the labelled cell surface glycosaminoglycans of these cells become similar to that of cells from the very weakly invading subline 8. Hydrocortisone induced only minor changes in the distribution of the glycosaminoglycans in the 8 and 13a2 lines, and at the same time, their proliferation rate and differentiation state was only slightly affected by this drug. Conversely to hydrocortisone, EGF increases the proliferation of the 9-4/0 line and also increases the label in sulphated cell surface glycosaminoglycans. This increase is about 50 per cent of that obtained by hydrocortisone. Thus, the accumulation of the glycosaminoglycan label on the cell surface is not directly related to the cell growth in the case of these cells. The results suggest that sulphated cell surface glycosaminoglycans, especially chondroitin sulphate, are involved in the inhibition of metastasis formation of the rhabdomyosarcoma cell lines studied.


Association between symptomatic profile and remission following antidepressant treatment in unipolar major depression.
To evaluate, in patients affected by an acute major depressive episode, what predictive value certain baseline psychopathological characteristics have with regard to expected therapeutic remission following biological antidepressant treatment (pharmacological/electroconvulsive; non-psychological). Six predefined psychopathological characteristics in acute major depressive episode were evaluated using a logistic regression model through a protocolised antidepressant treatment to assess their predictive value with regard to expected remission rate. The final study sample consisted of 129 subjects affected by an acute major depressive episode. From the baseline evaluation of the anguish/restlessness, reduced emotional reactivity, reduced attention, reduced motor response, feeling of worthlessness, and mood characteristics items, it was possible to correctly classify 88.1% of the sample as remitter/non-remitter with sensitivity of 0.77 and specificity of 0.96. Addition of the 17-item HRSD baseline variable to the regression model increased the capacity for correct classification of the baseline sample by only 0.09%. Protocolised antidepressant treatment was used. The results of this study may not be generalisable to pharmacological treatments not included in this protocol. The results of this study suggest that certain baseline psychopathological characteristics (and perhaps other clinical variables too) of the acute major depressive episode may be of great use in establishing patient subgroups according to expected clinical remission to the administration of biological antidepressant treatment. This could have considerable consequences for individualised therapeutic decision-making and for future researches (clinical trials included).


Somatic growth and renal function after unilateral nephrectomy for Wilms' tumor.
Solitary kidneys in renal donors and patients who have undergone unilateral nephrectomy for malignant disease have been reported to undergo hyperfiltration injury. This study was undertaken to evaluate the somatic growth and development of followed-up patient after Wilms' tumor to evaluate their renal function and identify any evidence of injury in the remaining kidney. The growth and development of all the children was found to be normal, as was DTPA clearance. Microalbuminuria in 24-h urinary collections was detected in 84% of the patients, indicating evidence of hyperfiltration injury. This study highlights the need for close monitoring of the renal function of long-term follow-up patients after Wilms' tumor in addition to the routine monitoring for tumor recurrence.


Induction of neutral proteinase and prostanoid production in bovine nasal chondrocytes by interleukin-1 and tumor necrosis factor alpha: modulation of these cellular responses by interleukin-6 and platelet-derived growth factor.
We have previously reported that recombinant human interleukin-1 (IL-1) stimulates matrix erosion in bovine nasal cartilage explants (R. J. Smith et al., Inflammation 13, 367-382, 1989). This action of IL-1 is believed to be caused by matrix-degrading neutral proteinases produced by activated chrondrocytes. Accordingly, we investigated the effects of recombinant human interleukin-1 alpha (IL-1 alpha), recombinant human interleukin-1 beta (IL-1 beta), and recombinant human tumor necrosis factor alpha (TNF alpha) on bovine nasal chondrocyte (BNC) responsiveness. IL-1 alpha and IL-1 beta stimulated a time (0-72 hr) and concentration-dependent (0.01-10 ng/ml) production of collagenase, gelatinase, caseinase, and prostaglandin E2 (PGE2) in BNC monolayer cultures. Neutral proteinase and PGE2 production by BNC was also induced by TNF alpha (0.2-200 ng/ml) in a time-dependent (0-72 hr) manner. Recombinant human interleukin-6 (IL-6) caused a concentration-dependent (6-200 ng/ml) potentiation of IL-1-stimulated neutral proteinase and PGE2 production by BNC. However, recombinant human platelet-derived growth factor homodimer BB suppressed BNC responsiveness to IL-1. A recombinant human IL-1 receptor antagonist protein inhibited BNC activation by IL-1 but not TNF alpha.


CO2 laser microfabrication of an integrated polymer microfluidic manifold for the determination of phosphorus.
A simple colorimetric technique is implemented in a polymer microfluidic manifold. The simple chemistry aids an uncomplicated microchannel design, which is fabricated by CO(2) laser ablation. Issues such as bonding of multiple layers, alignment of micro-fabricated structures and integration of optical components are addressed. A demonstration of a stopped flow regime in the microfluidic manifold is also presented.


Human brain monoamine oxidase: solubilization and kinetics of inhibition by octylglucoside.
Complete solubilization of both the A and B forms of human brain monoamine oxidase (MAO) occurred when crude mitochondria were incubated in the presence of 50 mM octylglucoside (OG). Upon removal of this nonionic detergent by dialysis, approximately 100% of the starting activity was present in the dialysate. The effects of solubilization were examined by comparison of several properties of the membrane-bound and OG-treated oxidases. The percentage inhibition of phenylethylamine (PEA) and the 5-hydroxytryptamine (5-HT) deamination by deprenyl and clorgyline were identical. The Km values obtained for the deamination of PEA, a B-selective substrate, 5-HT, an A-selective substrate, and tyramine (TYR), a nonselective substrate, were also comparable. OG was found to inhibit type A (I50 = 8.1 mM) and B (I50 = 4.7 mM) MAO activities at concentrations at least 10-fold below those used to solubilize the oxidases. Kinetic studies revealed that OG was an apparent competitive inhibitor of PEA deamination whereas OG produced a mixed-type pattern of inhibition when 5-HT was the variable substrate. Inhibition of TYR deamination by either the A or B form of MAO produced a mixed pattern of inhibition. The findings herein suggest that solubilization of the A and B forms of MAO by OG does not significantly alter the substrate and inhibitor specificity of the oxidases following removal of detergent. However, in the presence of concentrations of OG 50 times less than the critical micellar concentration of this detergent, marked inhibition of deamination by both forms of human brain MAO is observed. Accordingly, the usefulness of OG is limited to situations where the detergent is completely removed before quantitation of MAO activity.


Pre-B cells in agammaglobulinemia: evidence for disease heterogeneity among affected boys.
Six immunodeficient boys were found to have agammaglobulinemia and lack circulating B cells. These patients could be divided into two groups based on bone marrow findings and clinical course. In one group, pre-B cells and lymphocytes were present at normal frequencies and in normal absolute numbers. Recurrent serious infections were documented in the first few months of life in these patients, and this consequently led to early diagnosis. In the second group, pre-B cells were virtually undetectable. Patients in this group did not present with recurrent infections until the second year and were thus diagnosed later than were those in the first group. Childhood agammaglobulinemia with deficiency of both pre-B and B lymphocytes appears to be a different disease from X-linked infantile agammaglobulinemia. This disease may involve an arrest of B-lineage cell development at an earlier stage than that responsible for X-linked agammaglobulinemia.


Late follow-up of genital and ophthalmologic chronic graft-vs-host disease in females after allogeneic stem cell transplantation.
Genital chronic graft-vs-host disease (cGvHD) is a common late effect after allogeneic stem cell transplantation. In a previous cross-sectional study, prevalence, signs and symptoms of genital and extra-genital cGvHD were accounted for in a cohort of 42 women. Classifications of cGvHD were performed as per the National Institutes of Health (NIH) 2005 criteria. In this follow-up study on surviving women, the aim was to assess genital and extra-genital cGvHD status after long period of time. Our hypothesis was that signs and symptoms of cGvHD alleviate over time. All surviving women (n = 38) were re-examined by an ophthalmologist, a gynecologist and a hematologist. Signs and symptoms were classified according to the NIH 2014 criteria. Clinical scorings of affected organs were combined for estimating global score of cGvHD. To make possible comparisons between the two studies, data from the original study were re-classified as per the NIH 2014 criteria, and the four dead women were excluded. The same questionnaires were completed. Cervical smear, human papilloma virus test and vulvar photo-documentation were performed. Median time after original study was 8.4 (5.8-12) years and after transplant 14.5 (10-19.3) years. The prevalence of genital cGvHD was similar in the original (50%) and follow-up (58%) studies (p = 0.646) as well as extra-genital cGvHD. Systemic corticosteroid treatment of cGvHD was ongoing in 34% and 29%, respectively (p = 0.805). Ocular cGvHD was found in 24 of 37 examined women (65%) in the follow-up study. Genital cGvHD had disappeared in three women and developed in two women 5-12 and 9-17 years, respectively, after transplantation. The severity of global cGvHD changed over time in 14 women, but was the same on group level (p = 0.345). Atrophic mucous membranes as in estrogen deficiency were seen in 66%. Three women had human papilloma virus genotypes associated with the risk of developing cervical cancer. Chronic GvHD did not alleviate over time. Allotransplanted women require early and continuous life-long contact with a gynecologist and an ophthalmologist for the detection of cGvHD. Specific attention should be given to the need for local estrogen and the risk of genital epithelial malignancies.


Accurate quantification of modified cyclic peptides without the need for authentic standards.
There is a growing interest in the use of cyclic peptides as therapeutics, but their efficient production is often the bottleneck in taking them forward in the development pipeline. We have recently developed a method to synthesise azole-containing cyclic peptides using enzymes derived from different cyanobactin biosynthetic pathways. Accurate quantification is crucial for calculation of the reaction yield and for the downstream biological testing of the products. In this study, we demonstrate the development and validation of two methods to accurately quantify these compounds in the reaction mixture and after purification. The first method involves the use of a HPLC coupled in parallel to an ESMS and an ICPMS, hence correlating the calculated sulfur content to the amount of cyclic peptide. The second method is an NMR ERETIC method for quantifying the solution concentration of cyclic peptides. These methods make the quantification of new compounds much easier as there is no need for the use of authentic standards when they are not available.


Thymidine enhancement of methotrexate and 5-fluorouracil toxicity in cultured human colon carcinoma.
Cultures of human colon carcinoma, HCT-8, were treated with millimolar concentrations of thymidine by different schedules designed to cytokinetically and biochemically modulate methotrexate (MTX) and 5-fluorouracil (FUra) toxicity. Thymidine (dThd)-synchronized HCT-8 cells monitored by flow cytofluorometry showed increased sensitivity to MTX and synergistic cytotoxicity to the combination MTX-FUra. FUra toxicity in synchronized cells showed no significant phase specificity overall, but a pattern of relative G2/M resistance was correlated with decreased intracellular FUra accumulation, incorporation into RNA, and formation of FdUMP. In asynchronous cultures dThd reduced MTX toxicity when given within the first 12 h of a 24-h MTX exposure, and also appeared to reduce the MTX-induced synergistic enhancement of FUra toxicity. When dThd was administered with FUra alone in asynchronous cultures, progressive, and synergistic enhancement of FUra toxicity was observed only after 6 h dThd pretreatment. Unlike MTX-FUra synergy, this schedule-dependent synergism between dThd and FUra did not correlate with intracellular FUra accumulation or specific incorporation into total cellular RNA. These results suggest that less well studied mechanisms of dThd modulation, other than enhanced deoxynucleotide formation or total RNA incorporation, may biochemically enhance FUra toxicity in HCT-8 cells.


Effects of buffered and plain acetylsalicylic acid formulations with and without ascorbic acid on gastric mucosa in healthy subjects.
The most frequently reported adverse events associated with acetylsalicylic acid intake are minor gastrointestinal complaints. Galenic modifications, such as buffered formulations with or without ascorbic acid, may improve the benefit-risk ratio by decreasing the local mucosal side-effects of acetylsalicylic acid. To assess endoscopically-proven gastrointestinal lesions and the amount of gastric microbleeding of four different buffered and plain acetylsalicylic acid formulations, one containing paracetamol. A randomized, four-fold cross-over study was performed in 17 healthy subjects who underwent serial oesophago-gastro-duodenoscopy before and after each course of 4-day dosing. Gastric aspirates were collected for the determination of haemoglobin concentrations to detect microbleeding. Buffered acetylsalicylic acid plus ascorbic acid yielded the lowest Lanza score, the lowest increase in the number of mucosal petechiae and the lowest increase in the amount of gastric microbleeding. Subjects receiving acetylsalicylic acid plus paracetamol plus caffeine showed the highest Lanza score of all treatments, and a considerably greater sum of petechiae in the oesophagus, stomach and duodenum compared with those receiving buffered acetylsalicylic acid plus ascorbic acid. The trial confirms that buffering of acetylsalicylic acid improves local gastric tolerability. Acetylsalicylic acid in combination with ascorbic acid shows significantly fewer gastric lesions and the lowest increase in gastric microbleeding compared with the other tested formulations.


Integration between bacterial consortium and magnetite (Fe3O4) nanoparticles for the treatment of oily industrial wastewater.
The study aimed to investigate the efficiency of exogenous bacterial consortium (Enterobacter cloacae and Pseudomonas otitidis) decorated (immobilized) with Fe3O4 Nanoparticles for the treatment of petroleum hydrocarbon-contaminated wastewater. Glycine coated magnetite Nanoparticles (Fe3O4 NPs) were prepared using reverse co-precipitation method and were characterized using X-ray diffraction, transmission and scanning electron microscopy and vibrating sample magnetometer. They were used to decorate exogenous bacterial consortium (Enterobacter cloacae and Pseudomonas otitidis) at 3 different Fe3O4/bacteria ratios (1:1, 1:3 and 3:1 w/w). Bioremediation of oil contaminated wastewater collected from one of the petroleum distribution companies, Alexandria was conducted for 168 h using Fe3O4/bacterial association at the best ratio (3:1) and compared with non-decorated consortium and the indigenous bacteria in the control. Analysis indicated crystalline structure of Fe3O4 NPs with spherical particles (size: 15-20 nm) and superparamagnetic properties. Glycine modified-Fe3O4 exhibited high ability to immobilize bacteria which acquired its magnetic properties. The highest coating efficiency (92%) was achieved at 3:1 Fe3O4/bacteria ratio after 1 h. This ratio positively affected bacterial growth reaching the highest growth rate (5.07 fold higher than the control) after 4 h. The highest removal efficiencies of the total suspended solids (TSS), chemical oxygen demands (COD), oil and grease (O&G) and total petroleum hydrocarbons (TPH) recording 96, 65.4, 83.9 and 85% reaching residual concentrations of 9.5, 598, 99 and 60 mg/l respectively were achieved after 4 h by the Fe3O4-bacteria assembly. Compared with the maximum permissible limits of the tested parameters, TSS residue was highly compiled with its limit (50 mg/l), while COD, O&G and TPH were 7.5, 9.9, and 120-folds higher than their limits (100, 15 and 0.5 mg/l respectively). To the best of our knowledge it is first time to use integrated Enterobacter cloacae and Pseudomonas otitidis consortium decorated with Fe3O4 NPs for the treatment of petroleum hydrocarbon-contaminated wastewater. The proposed system proved to be a very efficient, economical and applicable for the removal of the included contaminants in very short running time which increases its biotechnological added value.


Perivascular brown adipocytes-derived kynurenic acid relaxes blood vessel via endothelium PI3K-Akt-eNOS pathway.
Several metabolites from the kynurenine pathway of tryptophan metabolism play a critical role in vascular function and vascular wall remodeling. This study aimed to test whether metabolite kynurenic acid (KYNA) from the kynurenine pathway relaxes blood vessels. We employed histological staining, in vitro cell culture, Western blotting, real-time PCR, and nitric oxide detection to validate kynurenine aminotransferase (KAT) localization in the vasculature as well as KYNA action on endothelial cells. We also detected vascular reactivity by organ chamber and monitored blood pressure by telemetry to investigate the regulation effect of KYNA on vascular tone. The results presented that perivascular adipose tissue (PVAT) from mice thoracic aorta had robust staining of anti-KAT1 and KYNA than PVAT from the abdominal aorta and mesenteric artery, which is consistent with the expression profile of brown adipocyte marker uncoupling protein 1. KYNA, metabolized from kynurenine by KAT, relaxed pre-contracted both aortic ring and mesenteric artery. In addition, KYNA derived from KAT in PVAT participates in the cross-talk between PVAT and vessel by mediating PVAT inhibition on agonist-induced thoracic aorta contraction. Furthermore, intraperitoneal injection of KYNA in mice reduced blood pressure. The vessel relaxation effect of KYNA was through the endothelium-dependent PI3K-Akt-eNOS pathway. Finally, the high-fat diet decreased KAT1 expression in perithoracic aortic fat and led to KYNA reduction in blood. Our research identified KYNA generated by KAT as a novel perivascular brown adipocyte-derived vascular relaxation factor and suggests that KYNA reduction is a critical event in vascular dysfunction under obese condition.


Orbital expansion in plagiocephaly.
In moderate to severe plagiocephaly, the transverse diameter of the orbit on the affected side is consistently decreased. In these cases, the supraorbital rim has been expanded by the required amount and bone grafted. This makes for greater orbital symmetry and ease in obtaining the correct supraorbital convexity. Ten patients have been handled in this way with satisfactory postoperative results.


[Serological passage of bacteria of the genus Providencia isolated from patients with wound, urological and intestinal infections].
A total of 395 Providencia strains isolated from patients and the environment were studied. Their differentiation by O and H antigens revealed that these strains belonged to 36 serological groups and contained 26 varieties of the flagellar antigen. In accordance with the combinations of O and H antigens, 59 serological variants were found among the Providencia strains. 33 new, formerly unknown serovars and 2 flagellar antigens were added to the existing antigenic and diagnostic scheme of Providencia. Most of the strains isolated from patients with surgical complications and burns were found to belong to P. stuartii, serovars O44: H4 and O4: H4, and from patients with acute intestinal diseases, to P. alcalifaciens, serovars O2: H26 and O50: H33.


DNA methylation mediates differentiation in thermal responses of Pacific oyster (Crassostrea gigas) derived from different tidal levels.
Epigenetic mechanisms such as DNA methylation have the potential to affect organism acclimatization and adaptation to environmental changes by influencing their phenotypic plasticity; however, little is known about the role of methylation in the adaptive phenotypic divergence of marine invertebrates. Therefore, in this study, a typical intertidal species, the Pacific oyster (Crassostrea gigas), was selected to investigate the epigenetic mechanism of phenotypic plasticity in marine invertebrates. Intertidal and subtidal oysters subjected to one-generation common garden experiments and exhibited phenotypic divergence were used. The methylation landscape of both groups of oysters was investigated under temperate and high temperature. The two tidal oysters exhibited divergent methylation patterns, regardless of the temperature, which was mainly original environment-induced. Intertidal samples exhibited significant hypomethylation and more plasticity of methylation in response to heat shock, while subtidal samples showed hypermethylation and less plasticity. Combined with RNA-seq data, a positive relationship between methylation and expression in gene bodies was detected on a genome-wide scale. In addition, approximately 11% and 7% of differentially expressed genes showed significant methylation variation under high temperatures in intertidal and subtidal samples, respectively. Genes related to apoptosis and organism development may be regulated by methylation in response to high temperature in intertidal oysters, whereas oxidation-reduction and ion homeostasis-related genes were involved in subtidal oysters. The results also suggest that DNA methylation mediates phenotypic divergence in oysters adapting to different environments. This study provides new insight into the epigenetic mechanisms underlying phenotypic plasticity in adaptation to rapid climate change in marine organisms.


Simple azo-based salicylaldimine as colorimetric and fluorescent probe for detecting anions in semi-aqueous medium.
A series of novel, highly sensitive, and selective azo-based anion sensors 1-3 have been designed and synthesized from the condensation reaction between 4-amino azo benzene and three different aldehydes. The structure of the sensors 1-3 were confirmed by IR, HRMS, (1)H NMR, and (13)C NMR spectroscopic methods. Colorimetric naked-eye analysis revealed the anion detection by receptors 2 and 3 as color changes from yellow to pink and yellow to orange, respectively. Anion sensing ability of all receptors was further investigated by (1) H NMR titration, UV-vis experiment, and fluorescence titration. UV-vis measurements highly indicate the selective recognition of fluoride and acetate ions in 9:1 dimethyl sulfoxide-H2O (v/v) for receptors 2 and 3. Binding constant value showed among all receptors, receptor 3 has strong affinity toward F(-) and AcO(-) in semi-aqueous medium, which is due to the presence of chromogenic signaling unit in it. The F(-) ion detection property of receptor 2 in organic medium was also extended in the real sample like toothpaste.


Acute pancreatitis and non-Hodgkin's lymphoma.
We report two patients presenting with acute pancreatitis, the aetiology of which was subsequently proven to be non-Hodgkin's lymphoma. Histological confirmation of tumour-associated pancreatitis is essential so that appropriate therapy can be planned.


Late sodium current inhibition as a new cardioprotective approach.
There is increasing evidence that the late sodium current of the sodium channel in myocytes plays a critical role in the pathophysiology of myocardial ischemia and thus is a potential therapeutic target in patients with ischemic heart disease. Ranolazine, an inhibitor of the late sodium current, reduces the frequency and severity of anginal attacks and ST-segment depression in humans, and unlike other antianginal drugs, ranolazine does not alter heart rate or blood pressure. In experimental animal models, ranolazine has been shown to reduce myocardial infarct size and to improve left ventricular function after acute ischemia and chronic heart failure. This article reviews published data describing the role of late sodium current and its inhibition by ranolazine in clinical and experimental studies of myocardial ischemia.


Combined effect of freeze chilling and MAP on quality parameters of raw chicken fillets.
The effect of short-term frozen storage prior to thawing on the quality of freeze-chilled chicken fillets was investigated, as was the effect of modified atmosphere packaging (MAP). Four process treatments were used: (1) fresh chicken chilled at 4 degrees C without previous freezing, (2) freeze-chilled for 7 days and thawed at 4 degrees C, (3) chilled at 4 degrees C packaged under MAP (70% N(2)-30%CO(2)), and (4) packaged under MAP, freeze-chilled for 7 days and thawed at 4 degrees C. Microbiological, chemical and sensory analyses were conducted on samples for a period up to 15 days. Freeze-chilled fillets gave a lower total viable count (TVC) at a given sampling day than chilled fillets. MAP, as expected, delayed microbial growth. The Pseudomonads were the dominant microbial species in fillets under aerobic conditions. MAP reduced the populations of Pseudomonads by 2-4 log cfu/g. Lactic acid bacteria (LAB) and Enterobacteriaceae increased progressively for all treatments throughout storage. Yeasts and molds were inhibited by MAP and by freeze chilling. Total volatile basic nitrogen (TVB-N) values increased rapidly for the chilled fillets but remained significantly lower for the freeze-chilled and the MA-packaged samples. MAP and especially freeze chilling enhanced drip loss. MAP did not affect redness or yellowness of product while freeze chilling decreased product redness. Lightness was not affected by either MAP or freeze chilling. Based on taste, which proved to be the most sensitive sensory attribute, shelf life of product ranged from 6 to 7 days for all treatments leading to the conclusion that freeze chilling is a suitable technology for fresh chicken fillets enabling their distribution as a frozen product and upon subsequent thawing at their final destination, their retail display as chilled products. MAP in combination with freeze chilling had a negligible effect on product quality.


Incremental costs of scaling up kangaroo mother care: Results from implementation research in Ethiopia and India.
To estimate incremental costs of an implementation model for scaling up Kangaroo Mother Care (KMC) for neonates with birthweight <2000 g. Seven sites across Ethiopia and India collected data for 2018-19 to calculate incremental recurrent costs (of health worker time, supplies, and operations) and start-up costs for KMC scale up. The costs were estimated per live newborn <2000 g eligible for KMC identified in the study population. Scaling up KMC in study districts required average incremental costs of US$59 (95% CI US$ 52-67) in Ethiopia and US$72 (95% CI US$ 41-103) in India per eligible newborn in the population. Most of these costs were recurrent; the annualised start-up costs per eligible newborn ranged from 12%-25% of total costs in Ethiopia and 9%-16% in India. The major cost driver was human resources, followed by initial and recurrent training, supplies, and communications costs. Incremental infrastructure costs were only 2%-6% of total costs in both countries. Most of the costs were for activities at the KMC implementing facility, accounting for 79%-88% of the total costs in Ethiopia and 89%-93% of those in India. The costs for successful scale up of KMC seem affordable but must be included in programme budgets.


Computed tomography of retroperitoneal castleman disease (plasma cell type) with sonographic and angiographic correlation.
The CT and sonographic appearances of a case of retroperitoneal Castleman disease of the plasma cell type are reported along with angiographic correlation. In this case CT demonstrated a minimally calcified homogeneously enhancing retroperitoneal mass. Sonography showed the mass to be hypoechoic with good through transmission. The lesion was hypervascular with prominent early venous drainage on inferior mesenteric arteriography.


Bilateral laparoscopic adrenalectomy: retroperitoneal and transperitoneal approaches.
To report our experience with bilateral laparoscopic adrenalectomy using either the retroperitoneal or the transperitoneal approach. Between June 1998 and October 2000, 6 consecutive patients with bilateral adrenal disease (Cushing syndrome in 4, pheochromocytoma in 1, and solitary adrenal metastases in 1) underwent bilateral laparoscopic adrenalectomy by way of the retroperitoneal or transperitoneal approach. Bilateral adrenalectomy was performed either synchronously (4 patients) or in a staged manner (2 patients). All laparoscopic procedures were performed successfully. For the bilateral synchronous cases (n = 4) and metachronous cases (n = 4), the median surgical time was 278 and 195 minutes, blood loss was 175 and 125 mL, resumption of oral intake and ambulation required less than 1 day for both groups, and postoperative narcotic requirement comprised 14 and 10 mg morphine sulfate equivalent, respectively. For the synchronous and metachronous cases, the hospital stay was 1.5 and less than 1 day and convalescence was 3 and 2.5 weeks, respectively. An intraoperative surgical complication (adrenal vein bleeding) occurred in 1 case, but did not require open conversion. No postoperative complications or rehospitalization occurred. The retroperitoneal approach was used in 3 of the 4 bilateral synchronous and 3 of the 4 bilateral metachronous cases. In both synchronous and metachronous cases, the actual surgical time, blood loss, time to oral intake and ambulation, postoperative analgesia use, hospital stay, and convalescence of the transperitoneal approach were well within the range of those of the retroperitoneal approach. Retroperitoneal and transperitoneal bilateral laparoscopic adrenalectomy is feasible, safe, and results in minimal postoperative morbidity.


Lower extremity general muscle moment patterns in healthy individuals during recumbent cycling.
The purpose of this study was to compare lower extremity generalized muscle moments across two workloads during recumbent bicycling in younger and older healthy adults. The study design was a comparative investigation of cycling patterns. Biomechanical data regarding muscle activation, kinematic, and kinetic patterns have been presented for upright cycling, but only a few studies have evaluated biomechanical patterns during the alternative configuration of recumbent cycling. Twenty-four healthy adults, classified by age into two different groups, under 35 and over 50 years of age, rode a recumbent bicycle at a constant cadence (60-65 rpm) and at two different resistances (0.5 and 1.0 kg m) while kinematic and kinetic data were recorded. General muscle moments were calculated using joint kinematic and kinetic data via inverse dynamic equations. The ankle general muscle moment remained plantar flexor throughout the pedaling cycle; the knee general muscle moment remained flexor throughout the cycle, except during the power phase of the higher workload where an extensor general muscle moment was observed; and the hip general muscle moment was extensor with a transient flexor general muscle moment period during the recovery phase. Increased workload led to increases in ankle plantar flexor and knee extensor general muscle moment magnitudes, but no changes at the hip. Age had no effect on general muscle moment magnitudes or patterns. Configurational differences between the upright and recumbent bicycle do not affect patterns, but the total output requirements do affect the magnitudes of the general muscle moments. Based on previous studies, the recumbent bicycle appears to be a safe rehabilitation tool for post-cerebrovascular accident and cardiorespiratory patients, but in order to more properly and efficiently use the recumbent bicycle as a rehabilitation tool, normative biomechanical data are necessary. The current study is the first such investigation to report normative data of lower extremity general muscle moment patterns during recumbent cycling. Effects of age and workload were also demonstrated.