A low-molecular-weight protein from rat liver that resembles ligandin in its binding properties.
A protein of S20,W 1.6S and mol.wt. 14000, which binds covalently a metabolite of the aminoazodye carcinogen NN-dimethyl-4-amino-3'-methylazobenzene, was isolated from rat liver cytosol from both carcinogen-treated and normal rats. The protein binds non-covalently palmitoyl-CoA, fatty acids, bilirubin, sex steroids and their sulphates, bile acids and salts, bromosulphophthalein, diethylstilboestrol and 20-methylcholanthrene with a wide range of affinities. The protein is isolated as three components with isoelectric points of 5.0, 5.9 and 7.6 by a method involving isoelectric focusing. All three components have closely similar amino acid analyses, tryptic-peptide 'maps' and u.v. spectra. Each single component redistributes into all three on further electrophoresis. However, the three forms differ in their binding characteristics, the form of pI 7.6 having much the highest affinity for compounds bound non-covalently. The protein was identified immunologically in rat liver, small intestine, adipose tissue, skeletal muscle, myocardium and testis. The protein was compared with other hepatic binding-protein preparations of similar molecular weight.


Induction of a dwarf phenotype with IBH1 may enable increased production of plant-made pharmaceuticals in plant factory conditions.
Year-round production in a contained, environmentally controlled 'plant factory' may provide a cost-effective method to produce pharmaceuticals and other high-value products. However, cost-effective production may require substantial modification of the host plant phenotype; for example, using dwarf plants can enable the growth of more plants in a given volume by allowing more plants per shelf and enabling more shelves to be stacked vertically. We show here that the expression of the chimeric repressor for Arabidopsis AtIBH1 (P35S:AtIBH1SRDX) in transgenic tobacco plants (Nicotiana tabacum) induces a dwarf phenotype, with reduced cell size. We estimate that, in a given volume of cultivation space, we can grow five times more AtIBH1SRDX plants than wild-type plants. Although, the AtIBH1SRDX plants also showed reduced biomass compared with wild-type plants, they produced about four times more biomass per unit of cultivation volume. To test whether the dwarf phenotype affects the production of recombinant proteins, we expressed the genes for anti-hepatitis B virus antibodies (anti-HBs) in tobacco plants and found that the production of anti-HBs per unit fresh weight did not significantly differ between wild-type and AtIBH1SRDX plants. These data indicate that P35S:AtIBH1SRDX plants produced about fourfold more antibody per unit of cultivation volume, compared with wild type. Our results indicate that AtIBH1SRDX provides a useful tool for the modification of plant phenotype for cost-effective production of high-value products by stably transformed plants in plant factory conditions.


Quantitative analysis of tissue deformation dynamics reveals three characteristic growth modes and globally aligned anisotropic tissue deformation during chick limb development.
Tissue-level characterization of deformation dynamics is crucial for understanding organ morphogenetic mechanisms, especially the interhierarchical links among molecular activities, cellular behaviors and tissue/organ morphogenetic processes. Limb development is a well-studied topic in vertebrate organogenesis. Nevertheless, there is still little understanding of tissue-level deformation relative to molecular and cellular dynamics. This is mainly because live recording of detailed cell behaviors in whole tissues is technically difficult. To overcome this limitation, by applying a recently developed Bayesian approach, we here constructed tissue deformation maps for chick limb development with high precision, based on snapshot lineage tracing using dye injection. The precision of the constructed maps was validated with a clear statistical criterion. From the geometrical analysis of the map, we identified three characteristic tissue growth modes in the limb and showed that they are consistent with local growth factor activity and cell cycle length. In particular, we report that SHH signaling activity changes dynamically with developmental stage and strongly correlates with the dynamic shift in the tissue growth mode. We also found anisotropic tissue deformation along the proximal-distal axis. Morphogenetic simulation and experimental studies suggested that this directional tissue elongation, and not local growth, has the greatest impact on limb shaping. This result was supported by the novel finding that anisotropic tissue elongation along the proximal-distal axis occurs independently of cell proliferation. Our study marks a pivotal point for multi-scale system understanding in vertebrate development.


Big data, big contributions: outcomes research in thoracic surgery.
In recent years, analysis of registry data has defined clinically significant practice patterns and treatment strategies that optimize cancer care for thoracic surgery patients. These higher-order outcome studies rely on large patient cohorts that minimize the risk of selection bias and allow for a powered analysis that is not achievable with single- or multi-institutional data. This review uses recent study examples to highlight important contributions to our knowledge of thoracic surgery and describes how outcomes research using large data can address high impact clinical questions.


Patterns, mechanisms, and functions of translation regulation in mammalian spermatogenic cells.
Translational regulation is a fundamental aspect of the atypical patterns of gene expression in mammalian meiotic and haploid spermatogenic cells. Every mRNA is at least partially translationally repressed in meiotic and haploid spermatogenic cells, but the extent of repression of individual mRNA species is regulated individually and varies greatly. Many mRNA species, such as protamine mRNAs, are stored in translationally repressed free-mRNPs in early haploid cells and translated actively in late haploid cells. However, translation does not regulate developmental expression of all mRNAs. Some mRNAs appear to be partially repressed for the entire period that the mRNA is expressed in meiotic and haploid cells, while other mRNAs, some of which are expressed at high levels, are almost totally inactivated in free-mRNPs and/or generate little or no protein. This distinctive phenomenon can be explained by the hypothesis that translational repression is used to prevent the potentionally deleterious effects of overproduction of proteins encoded by overexpressed mRNAs. Translational regulation also appears to be frequently altered by the widespread usage of alternative transcription start sites in spermatogenic cells. Many ubiquitously expressed genes generate novel transcripts in somatic spermatogenic cells containing elements, uORFs and secondary structure that are inhibitory to mRNA translation, while the ribosomal proten L32 mRNA lacks a repressive element that is present in somatic cells. Very little is known about the mechanisms that regulate mRNA translation in spermatogenic cells, largely because few labs have utilized in vivo genetic approaches, although there have been important insights into the repression and activation of protamine 1 mRNA, and the role of Y-box proteins and poly(A) lengthening in mRNA-specific translational activation mediated by the cytoplasmic poly(A) element binding protein and a testis-specific isoform of poly(A) polymerase. A very large literature by evolutionary biologists suggests that the atypical patterns of gene expression in spermatogenic cells are the consequence of the powerful and unusual selective pressures on male reproductive success.


Salty solutions near a charged modulated interface.
Charged monolayers at a liquid-vapor interface may be found in a crystalline state, resulting in a surface density of charge that displays periodic modulations. In this paper we discuss how these modulations affect different thermodynamical and mechanical properties (compared with the equivalent uniform charge density) of a system consisting of the charged monolayer and a bulk solution including a finite concentration of counter-ions and co-ions. It is shown that very accurate results for low and moderate salt concentrations are possible within an expansion in the Fourier modes of the modulations, the Weak Amplitude Perturbation (WAP), if the finite size of the ions are included as a Stern layer. We conclude by discussing the implications and the relevance of these results for both theoretical studies and experiments.


Merkel cell carcinoma arising in the head and neck: optimizing therapy.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine dermal neoplasm. Because of the limited number of cases described in the literature (approximately 600 to date), statistically significant data regarding treatment are difficult to obtain. The majority of MCC cases affect the head and neck and are thought to be caused by the actinic damage associated with sun exposure. This study evaluates cases of head and neck MCC at Naval Medical Center San Diego (NMCSD) and compares the treatment regimens and outcomes from multiple institutions. This study is a retrospective outcomes analysis of all cases of head and neck MCC seen at NMCSD, between January 1, 1988 and June 30, 1998. The records of the NMCSD Tumor Registry were searched for patients with that diagnosis, and supplemental information was retrieved from the Radiation Oncology and Head & Neck Surgery Clinic charts. Eight of nine patients in this study were treated with either wide-local excision or Mohs microsurgery. The surgical margins were free of disease in all eight patients. One patient presented with distant metastatic disease, and two others were subsequently found to have nodal involvement. Subsequent therapy varied among the patients. Survey of the available literature revealed inconsistency in terms of which treatment regimens are optimal. Tumor resections are recommended by most groups to include a 2-cm to 3-cm tumor-free margin around the primary lesion when possible, but this is often difficult to achieve in the head and neck. Data, which do not reach statistical significance, suggest improved outcomes with tumor-free margins. Treatment of the regional draining lymph nodes is also recommended in most series. Prophylactic lymph node dissection or radiation therapy to the nodal chain may decrease local recurrence but does not consistently affect overall survival. Adjuvant chemotherapy is advocated by most groups in the treatment of metastatic disease because MCC is pathologically similar to small-cell lung carcinoma. However, no chemotherapy protocol has been shown to improve survival. Head and neck MCC is a rare and aggressive dermal tumor of neuroendocrine origin that requires multimodality therapy, including surgery, radiation therapy, and possibly adjuvant chemotherapy. Multiinstitutional studies are crucial to obtain sufficiently large populations to investigate and optimize therapy in this disease.


Electrophysiological properties of macrophages.
Electrophysiological studies indicate that the macrophage can display at least two different K conductances, a Ca-mediated K conductance and an inward rectifying K conductance, as well as an electrogenic Na+-K+ pump. Spontaneous hyperpolarizations associated with a Ca-mediated K permeability have been noted in all types of macrophages studied. Similar membrane hyperpolarizations can be elicited by a variety of stimuli that presumably increase intracellular calcium. These include mechanical and electrical stimulation as well as exposure to endotoxin-activated serum, chemotactic peptides, and the Ca ionophore A23187. Recent patch clamp studies on macrophages demonstrated channel activity that probably corresponds to currents through the inward rectifying K conductance previously described with current clamp techniques. With the advent of the patch clamp, this and other conductances can be effectively examined by using both whole-cell voltage clamp and patch recordings in a variety of different macrophages, including small freshly isolated cells.


Lateral lumbar interbody fusion after reduction using the percutaneous pedicle screw system in the lateral position for Meyerding grade II spondylolisthesis: a preliminary report of a new lumbar reconstruction strategy.
Utilization of a cage with a large footprint in lateral lumbar interbody fusion (LLIF) for the treatment of spondylolisthesis leads to a high fusion rate and neurological improvement owing to the indirect decompression effect and excellent alignment correction. However, if an interbody space is too narrow for insertion of an LLIF cage for cases of spondylolisthesis of Meyerding grade II or higher, LLIF cannot be used. Therefore, we developed a novel strategy, LLIF after reduction by the percutaneous pedicle screw (PPS) insertion system in the lateral position (LIFARL), for surgeons to perform accurate and safe LLIF with PPS in patients with such pathology. This study aimed to introduce the new surgical strategy and to present preliminary clinical and radiological results of patients with spondylolisthesis of Meyerding grade II. Six consecutive patients (four men and two women; mean age, 72.7 years-old; mean follow-up period, 15.3 months) with L4 spondylolisthesis of Meyerding grade II were included. Regarding the surgical procedure, first, PPSs were inserted into the L4 and L5 vertebrae fluoroscopically, and both rods were placed in the lateral position. The L5 set screws were fixed tightly, and the L4 side of the rod was floated. Second, the L4 vertebra was reduced by fastening the L4 set screws so that they expanded the anteroposterior width of the interbody space. At that time, the L4 set screws were not fully tightened to the rods to prevent the endplate injury. Finally, the LLIF procedure was started. After inserting the cage, a compression force was added to the PPSs, and the L4 set screws were completely fastened. The mean operative time was 183 min, and the mean blood loss was 90.8 mL. All cages were positioned properly. Visual analog scale score and Oswestry disability index improved postoperatively. Bone union was observed using computed tomography 12 months after surgery. For cases with difficulty in LLIF cage insertion for Meyerding grade II spondylolisthesis due to the narrow anteroposterior width of interbody space, LIFARL is an option to achieve LLIF combined with posterior PPS accurately and safely. UMIN-Clinical Trials Registry, UMIN000040268, Registered 29 April 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000045938.


BioCatalogue: a universal catalogue of web services for the life sciences.
The use of Web Services to enable programmatic access to on-line bioinformatics is becoming increasingly important in the Life Sciences. However, their number, distribution and the variable quality of their documentation can make their discovery and subsequent use difficult. A Web Services registry with information on available services will help to bring together service providers and their users. The BioCatalogue (http://www.biocatalogue.org/) provides a common interface for registering, browsing and annotating Web Services to the Life Science community. Services in the BioCatalogue can be described and searched in multiple ways based upon their technical types, bioinformatics categories, user tags, service providers or data inputs and outputs. They are also subject to constant monitoring, allowing the identification of service problems and changes and the filtering-out of unavailable or unreliable resources. The system is accessible via a human-readable 'Web 2.0'-style interface and a programmatic Web Service interface. The BioCatalogue follows a community approach in which all services can be registered, browsed and incrementally documented with annotations by any member of the scientific community.


Trimethoprim-sulfamethoxazole and hypouricemia.
Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX). Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1. Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005). Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.


Theory of the optical spectra of the bacteriochlorophyll a antenna protein trimer from Prosthecochloris aestuarii.
A reasonable theoretical fit to the experimental low-temperature absorption and CD spectra of the BChl a-protein from Prosthecochloris aestuarii has been obtained for the unaggregated protein trimer based on standard assumptions regarding QY transition moment directions. The fits depend to some extent upon varying the site wavelengths of the individual BChls not just in one subunit but in the entire trimer, a procedure not tried before. Features in both spectra, but especially in CD, at wavelengths longer than ≈810 nm are very strongly influenced by the intersubunit interactions of BChls 7 (in the Fenna-Matthews numbering). Unlike earlier theoretical models, which also gave reasonable fits but were based on unorthodox or incorrect assumptions, this exciton model gives every indication of being refineable by improved choices of site wavelengths and exciton-transition lineshapes. Calculated exciton-transition wavelengths and line widths are compared with values deduced from recent laser hole-burning experiments (Johnson and Small 1991). As in the case of the absorption and CD spectra, agreement is best for the long-wavelength half of the QY region.


Pacman and hangman metal tetraazamacrocycles.
Metal complexes of derivatized 2,12-dimethyl-3,7,11,17-tetraazabicyclo[11.3.1]heptadeca-1(17),2,11,13,15-pentane (bapa) ligands were prepared from 4-substituted diacetylpyridine derivatives by templated condensation with 3,3'-diaminodipropylamine in the presence of a metal halide or nitrate. The diacetylpyridine derivatives with Pacman and Hangman scaffolds are delivered from borylation of the 4-postion of diacetylpyridine and subsequent Suzuki coupling with the appropriate Hangman or Pacman backbone. Electrochemical examination of the parent [Co(bapa)](2+) scaffold reveals it to be a catalyst for the hydrogen evolution reaction (HER) in acetonitrile. Similar studies of the Hangman complex appear to be obscured by trace amounts of residual palladium remaining from the Suzuki coupling reaction to provide a cautionary note for the use of such cross-coupling methodologies in the preparation of HER catalysts.


The Value of Survival Gains in Pancreatic Cancer from Novel Treatment Regimens.
Metastatic pancreatic cancer (mPC) is associated with low survival, with less than 10% of patients surviving 5 years. Recent therapies improve survival outcomes where few alternative therapies exist, but few economic analyses measure the value of survival gains attributable to new therapies. To estimate the value of survival gains in advanced or mPC attributable to the introduction of novel treatment regimens. Multivariate Cox proportional hazards models were used to estimate real-world survival gains associated with the introduction of gemcitabine (GEM) for patients diagnosed with stage IV or unstaged mPC in the Surveillance, Epidemiology, and End Results Program cancer registries. Then, evidence from clinical trials was used to evaluate the survival gains associated with nab-paclitaxel + gemcitabine (nP +GEM) and FOLFIRINOX (FFX) relative to GEM. The survival estimates and clinical trial evidence were used to calibrate an economic model and assess the cumulative value of survival gains in mPC to patients. Costs of treatment were calculated based on published cost-effectiveness studies. We estimated that the introduction of GEM in 1996 was associated with a hazard ratio of 0.920 (P < 0.05) and an increase in median survival from 3.1 to 4.5 months. Results suggested that the value of survival gains attributable to GEM equaled about $71,000 per patient, while the value attributable to nP + GEM was an additional $56,700. Estimates for the value of survival gains per patient, net of total incremental lifetime treatment costs (drugs, adverse events, and other costs), were $50,294 for GEM and an additional $31,900 for nP + GEM. Clinical trials and cost-effectiveness studies reported an overall survival gain from FFX that was larger than, but statistically similar to, nP + GEM and had greater risk of adverse events and total incremental costs. We estimated that the total value of survival gains to mPC patients, net of total costs, associated with GEM was up to $47.6 billion, and the additional values attributable to nP+GEM and FFX were up to $39.0 billion and $26.3 billion, respectively. Historically, mPC patients have faced high disease burden and had few treatment options. Treatments introduced since 1996 have led to improved survival, with varying costs associated with treatment and adverse events. Accounting for total incremental costs, the majority of the value of survival gains from GEM and nP+GEM was retained by mPC patients, highlighting the value of innovation in settings where survival is low and few alternative therapies exist. Support for this research was provided by Celgene. Precision Health Economics was compensated by Celgene for work on this study. MacEwan is an employee of, and Yin is a consultant to, Precision Health Economics. Kaura and Khan are employees of Celgene. Study concept and design were contributed primarily by Yin and MacEwan, along with Kaura and Khan. MacEwan collected the data, and data interpretation was performed primarily by MacEwan and Yin, along with Kaura and Khan. The manuscript was written and revised by MacEwan, Yin, Kaura, and Khan.


Spatial and temporal patterns in the microbial diversity of a meromictic soda lake in Washington State.
The microbial community diversity and composition of meromictic Soap Lake were studied using culture-dependent and culture-independent approaches. The water column and sediments were sampled monthly for a year. Denaturing gradient gel electrophoresis of bacterial and archaeal 16S rRNA genes showed an increase in diversity with depth for both groups. Late-summer samples harbored the highest prokaryotic diversity, and the bacteria exhibited less seasonal variability than the archaea. Most-probable-number assays targeting anaerobic microbial guilds were performed to compare summer and fall samples. In both seasons, the anoxic samples appeared to be dominated by lactate-oxidizing sulfate-reducing prokaryotes. High numbers of lactate- and acetate-oxidizing iron-reducing bacteria, as well as fermentative microorganisms, were also found, whereas the numbers of methanogens were low or methanogens were undetectable. The bacterial community composition of summer and fall samples was also assessed by constructing 16S rRNA gene clone libraries. A total of 508 sequences represented an estimated >1,100 unique operational taxonomic units, most of which were from the monimolimnion, and the summer samples were more diverse than the fall samples (Chao1 = 530 and Chao1 = 295, respectively). For both seasons, the mixolimnion sequences were dominated by Gammaproteobacteria, and the chemocline and monimolimnion libraries were dominated by members of the low-G+C-content group, followed by the Cytophaga-Flexibacter-Bacteroides (CFB) group; the mixolimnion sediments contained sequences related to uncultured members of the Chloroflexi and the CFB group. Community overlap and phylogenetic analyses, however, not only demonstrated that there was a high degree of spatial turnover but also suggested that there was a degree of temporal variability due to differences in the members and structures of the communities.


Effects of material properties and object orientation on precision grip kinematics.
Successfully picking up and handling objects requires taking into account their physical properties (e.g., material) and position relative to the body. Such features are often inferred by sight, but it remains unclear to what extent observers vary their actions depending on the perceived properties. To investigate this, we asked participants to grasp, lift and carry cylinders to a goal location with a precision grip. The cylinders were made of four different materials (Styrofoam, wood, brass and an additional brass cylinder covered with Vaseline) and were presented at six different orientations with respect to the participant (0°, 30°, 60°, 90°, 120°, 150°). Analysis of their grasping kinematics revealed differences in timing and spatial modulation at all stages of the movement that depended on both material and orientation. Object orientation affected the spatial configuration of index finger and thumb during the grasp, but also the timing of handling and transport duration. Material affected the choice of local grasp points and the duration of the movement from the first visual input until release of the object. We find that conditions that make grasping more difficult (orientation with the base pointing toward the participant, high weight and low surface friction) lead to longer durations of individual movement segments and a more careful placement of the fingers on the object.


Amputation characteristics vary by branch of service.
This study examines the amputees from the Army and Marine Corps, the two military branches that have sustained the majority of combat-related amputations. All U.S. service members who sustained major extremity amputations from October 2001 through July 2011 were analyzed. Amputation levels, demographics, and mounted or dismounted status at injury were examined. There were 835 Army and 344 Marine amputees; 52.9% of all Marine amputees occurred during 2010 and 2011. Over 50% of Marine and 44% of Army amputees sustaining an amputation during 2010 and 2011 sustained multiple amputations. Dismounted service members had significantly (p < .0001) higher Injury Severity Scores and were significantly more likely to sustain double (p = .0082) and triple (p < .0001) amputations than mounted personnel. Marine amputees were significantly (p < .0001) more likely to be dismounted than Army amputees. The number of multiple amputees increased substantially in 2010 and 2011. Marine amputees, particularly dismounted, are at an increased risk of sustaining multiple amputations.


Bifunctional mannoside-glucosinolate glycoconjugates as enzymatically triggered isothiocyanates and FimH ligands.
Glucosinolates are sulfur-containing secondary metabolites found in plants of the Brassicale order. They are precursors of isothiocyanate species, resulting from C-S hydrolysis catalysed by the thioglucohydrolase myrosinase. We describe the synthesis of bifunctional glucosinolate-mannoside glycoconjugates combining both the structural features of a substrate of myrosinase and a ligand of the lectin FimH. We show that these glycoconjugates serve as enzyme substrates and that myrosinase can indeed hydrolyze the glucosinolate moiety with affinities (KM, Vmax) comparable to the natural substrates glucomoringin and sinigrin. This enzymatic hydrolysis of the thioglycosidic bond led to the efficient formation of an isothiocyanate which was assessed by the formation of the corresponding dithiocarbamate derivatives. Finally, we show that our synthetic bifunctional glycoconjugates also serve as FimH ligands where the glucosinolate moiety does not hamper the interaction with the lectin. Our findings set the stage for an original bioconjugation tool, allowing for myrosinase-triggered specific labelling of lectins using glucosinolate glycoconjugates as non-toxic, water soluble isothiocyanate precursors.


Association of Diabetes Mellitus in Pregnancy and Perinatal Depression.
Diabetes is frequently linked with depression, and both conditions are common complications during pregnancy. However, research findings exploring the relationship between diabetes mellitus in pregnancy (DMP) and perinatal depression (PND) have been inconsistent. Thus, this study seeks to examine the association between DMP and PND in a prospective population-based cohort. Women aged 18 to 48 years ( n = 4459) were identified from the Biology, Affect, Stress, Imaging and Cognition study. The diagnosis of DMP was based on International Classification of Diseases code O24 from medical records and was classified as pregestational, gestational, or unspecified diabetes. PND was assessed using psychometric instruments, clinical interviews, and/or register data and categorized into antepartum or postpartum depression. Multivariable logistic regressions were used to study the associations of DMP with antepartum and postpartum depression. The association between DMP and continuous depression scores, antepartum and postpartum, was investigated with multivariable linear regressions. Of 4459 pregnancies, 949 women had antepartum depression (21.2%) and 1123 had postpartum depression (25%). DMP had a prevalence of 1.2%. Women with DMP had twofold higher odds for postpartum depression compared with women without DMP. Although no association was observed between DMP and antepartum depression, DMP was associated with higher antepartum depression scores. Our study shows an association between DMP and PND, which might be considered a risk factor when screening for high-risk groups.


Analysis of discordant PET and CT findings in 18F-FDG PET-CT scans in the management of oncology patients.
Discordant findings are often noted between PET-CT and CT images of 18F-FDG PET-CT scans and cause ambiguity in image interpretation. This study aimed at determining the significance of these findings in the management of oncology patients. Discordant findings are often noted between PET-CT and CT images of 18F-FDG PET-CT scans and cause ambiguity in image interpretation. This study aimed at determining the significance of these findings in the management of oncology patients. This was an observational, descriptive study. Hence, retrospective analysis of all discordant findings in oncology patients undergoing a PETCT imaging between Jan 2013 and Jan 2016 was done. Those patients who had a follow-up period of minimum 1 year in either of the following forms - repeat PETCT imaging, other radiological imaging, clinical, or histopathological evidence were included. From all the discordant lesions, the sensitivity, specificity, positive predictive, negative predictive value, and accuracy of both PET-CT and CT modalities were determined. Of 348 discordant lesions, 16.7% was noted in soft tissues, 25% in viscera, 28.7% in lungs, 14.1% in lymph nodes, and 15.5% in bones. At the end of follow-up, 15.2% lesions were PET true positive, 57.5% PET true negative, 10.1% CT true positive lesions, 13.8% CT true negative, and 3.4% were inconclusive. 18F-FDG PET-CT is superior to CT imaging and should be considered as the first-line imaging modality in oncology patients.


Deletion of the min operon results in increased thermosensitivity of an ftsZ84 mutant and abnormal FtsZ ring assembly, placement, and disassembly.
To investigate the interaction between FtsZ and the Min system during cell division of Escherichia coli, we examined the effects of combining a well-known thermosensitive mutation of ftsZ, ftsZ84, with DeltaminCDE, a deletion of the entire min locus. Because the Min system is thought to down-regulate Z-ring assembly, the prediction was that removing minCDE might at least partially suppress the thermosensitivity of ftsZ84, which can form colonies below 42 degrees C but not at or above 42 degrees C. Contrary to expectations, the double mutant was significantly more thermosensitive than the ftsZ84 single mutant. When shifted to the new lower nonpermissive temperature, the double mutant formed long filaments mostly devoid of Z rings, suggesting a likely cause of the increased thermosensitivity. Interestingly, even at 22 degrees C, many Z rings were missing in the double mutant, and the rings that were present were predominantly at the cell poles. Of these, a large number were present only at one pole. These cells exhibited a higher than expected incidence of polar divisions, with a bias toward the newest pole. Moreover, some cells exhibited dramatically elongated septa that stained for FtsZ, suggesting that the double mutant is defective in Z-ring disassembly, and providing a possible mechanism for the polar bias. Thermoresistant suppressors of the double mutant arose that had modestly increased levels of FtsZ84. These cells also exhibited elongated septa and, in addition, produced a high frequency of branched cells. A thermoresistant suppressor of the ftsZ84 single mutant also synthesized more FtsZ84 and produced branched cells. The evidence from this study indicates that removing the Min system exposes and exacerbates the inherent defects of the FtsZ84 protein, resulting in clear septation phenotypes even at low growth temperatures. Increasing levels of FtsZ84 can suppress some, but not all, of these phenotypes.


Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome.
Substance use disorders are associated with disruptions in sleep and circadian rhythms that persist during abstinence and may contribute to relapse risk. Repeated use of substances such as psychostimulants and opioids may lead to significant alterations in molecular rhythms in the nucleus accumbens (NAc), a brain region central to reward and motivation. Previous studies have identified rhythm alterations in the transcriptome of the NAc and other brain regions following the administration of psychostimulants or opioids. However, little is known about the impact of substance use on the diurnal rhythms of the proteome in the NAc. We used liquid chromatography coupled to tandem mass spectrometry-based quantitative proteomics, along with a data-independent acquisition analysis pipeline, to investigate the effects of cocaine or morphine administration on diurnal rhythms of proteome in the mouse NAc. Overall, our data reveal cocaine and morphine differentially alter diurnal rhythms of the proteome in the NAc, with largely independent differentially expressed proteins dependent on time-of-day. Pathways enriched from cocaine altered protein rhythms were primarily associated with glucocorticoid signaling and metabolism, whereas morphine was associated with neuroinflammation. Collectively, these findings are the first to characterize the diurnal regulation of the NAc proteome and demonstrate a novel relationship between the phase-dependent regulation of protein expression and the differential effects of cocaine and morphine on the NAc proteome. The proteomics data in this study are available via ProteomeXchange with identifier PXD042043.


Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin.
In this study the effect of crocin, a carotenoid isolated from saffron, on malathion (an organophosphate insecticide) induced depressive- like behavior in subacute exposure was investigated. Moreover the molecular mechanism of malathion induced depressive- like behavior and its decreasing effect on the level of brain derived neurotrophic factor (BDNF) in rat hippocampus and cerebral cortex were evaluated. Male Wistar rats were exposed to malathion (50 mg/kg/day, IP) alone or in combination with crocin (10, 20 and 40 mg/kg/day, IP), imipramine (20 mg/kg/day, IP) and vitamin E (200 mg/kg, three times a week, IP) respectively for 14 days. The forced swimming test (FST) was performed on days 1(st), 7(th) and 14(st). The level of malondealdehyde (MDA) and reduced glutathione (GSH) were measured in cerebral cortex and hippocampus of rats. The protein level of BDNF was evaluated using Western blot analysis. Malathion (50 mg/kg, IP) increased immobility time in the FST, without affecting total locomotor activity in open-field test. Malathion increased the malondealdehyde (MDA) and decreased the glutathione (GSH), whereas these effects were reversed by crocin and vitamin E. Malathion decreased plasma acetylcholinesterase activity, however this effect was not reversed by crocin or vitamin E. Malathion reduced the protein level of BDNF in rat hippocampus. Imipramine and crocin prevented the decreasing effect of malathion on BDNF. These results showed that crocin attenuates some neurochemical and behavioral effects induced by malathion. This neuroprotective effect of crocin may be in part due to its effect on BDNF.


Role of deoxycytidine kinase in the inhibitory activity of 5-substituted 2'-deoxycytidines and cytosine arabinosides on tumor cell growth.
A number of 5-substituted derivatives of dCyd and 1-beta-D-arabinofuranosylcytosine (araC) have been evaluated for their inhibitory effects on the growth of three murine leukemia cell lines (L1210/0, L1210/BdUrd, and L1210/araC). The L1210/BdUrd and L1210/araC cell lines were selected from the parental L1210/0 cell line by their ability to grow at high concentrations of 5-bromo-2'-deoxyuridine and araC, respectively; the L1210/BdUrd cell line was deficient in dThd kinase activity, whereas the L1210/araC cell was deficient in dCyd kinase activity. The most effective inhibitors of L1210/0 cell proliferation were 5-fluoro-dCyd, araC, and 5-fluoro-araC. Their 50% inhibitory dose fell within the 0.001-0.015 micrograms/ml range. The 5-substituted araC analogues were much less inhibitory for L1210/araC cells but equally inhibitory for L1210/BdUrd as for the parental L1210/0 cell line. The role of dCyd kinase in the antitumor activity of the dCyd and araC analogues was further assessed by kinetic studies with dCyd kinase extracted from L1210/0 cells. All dCyd and araC analogues caused a competitive inhibition of dCyd kinase, the most potent inhibitor being 5-fluoro-dCyd (Ki/Km value 0.24). The Km of dCyd kinase from L1210/0 cells for dCyd was 23.1 microM as compared with 50 microM for araC. These values were increased to 53 and 182 microM, respectively, for the dCyd kinase isolated from L1210/araC cells.


Gall Wasp Transcriptomes Unravel Potential Effectors Involved in Molecular Dialogues With Oak and Rose.
To gain insight into wasp factors that might be involved in the initial induction of galls on woody plants, we performed high throughput (454) transcriptome analysis of ovaries and venom glands of two cynipid gall wasps, Biorhiza pallida and Diplolepis rosae, inducing galls on oak and rose, respectively. De novo assembled and annotated contigs were compared to sequences from phylogenetically related parasitoid wasps. The relative expression levels of contigs were estimated to identify the most expressed gene sequences in each tissue. We identify for the first time a set of maternally expressed gall wasp proteins potentially involved in the interaction with the plant. Some genes highly expressed in venom glands and ovaries may act to suppress early plant defense signaling. We also identify gall wasp cellulases that could be involved in observed local lysis of plant tissue following oviposition, and which may have been acquired from bacteria by horizontal gene transfer. We find no evidence of virus-related gene expression, in contrast to many non-cynipid parasitoid wasps. By exploring gall wasp effectors, this study is a first step toward understanding the molecular mechanisms underlying cynipid gall induction in woody plants, and the recent sequencing of oak and rose genomes will enable study of plant responses to these factors.


Acquired increase in leucocyte binding by intestinal microvascular endothelium in inflammatory bowel disease.
Endothelial cells that line microvascular blood vessels have an important role in inflammation through their ability to bind and recruit circulating leucocytes. Endothelial cells from the intestines of patients with chronically inflamed Crohn's disease and ulcerative colitis--the two forms of inflammatory bowel disease--display an increased leucocyte-binding capacity in vitro. We investigated whether this enhanced leucocyte binding is a primary or an acquired defect. We cultured human intestinal microvascular endothelial cells (HIMEC) from the uninvolved intestine and chronically inflamed bowel of three patients with inflammatory bowel disease (two Crohn's disease, one ulcerative colitis). We assessed HIMEC binding to polymorphonuclear leucocytes and U937 cells by means of an adhesion assay. After activation with interleukin-1beta or lipopolysaccharide, HIMEC from the chronically inflamed tissue in all three patients with inflammatory bowel disease bound twice as many polymorphonuclear leucocytes and U937 cells as endothelial cells from uninvolved tissue. Enhanced leucocyte binding by HIMEC from chronically inflamed tissue in patients with inflammatory bowel disease is an acquired defect since it is not found in the uninvolved intestinal segments from the same individuals. Because interaction between endothelial cells and leucocytes is a key regulatory step in the inflammatory process, this enhanced binding may contribute to the pathophysiology of chronic intestinal inflammation.


Characterization of an ampicillin-resistant Haemophilus influenzae type B.
A 28-year-old female in Denver was found in early 1974 to have frontal sinusitis, osteomyelitis, and bacteremia due to Haemophilus influenzae, type B. The minimal inhibitory concentration of ampicillin for this organism was 100 mug/ml and the minimal bactericidal concentration was >100 mug/ml. It was inhibited by chloramphenicol at 0.4 mug/ml. Further studies demonstrated that ampicillin and methicillin were synergistic against this organism. It was shown to produce a diffusible beta-lactamase. Transferase of resistance from this organism to a susceptible Haemophilus parainfluenzae and a reciprocal transfer were accomplished. A test for transformation was negative as was a test for reversal of resistance by ethylenediaminetetraacetic acid.


Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells.
Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or 'alveolospheres' with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology.


Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure.
Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation.


Investigate the Odontogenic Differentiation and Dentin-Pulp Tissue Regeneration Potential of Neural Crest Cells.
Stem cell-based developmental engineering has been considered as a promising strategy for tissue/organ regeneration. Tooth is formed by sequential reciprocal interactions between epithelium derived from surface ectoderm and mesenchymal cells derived from cranial neural crest. The neural crest cell is an appealing cell source for tooth development and regeneration research. In this study, we investigated the odontogenic differentiation and dentin-pulp complex regeneration potential of neural crest cells. Our results showed that neural crest cells (O9-1 mouse cranial neural crest cell line) can sequentially differentiate into dentin matrix acidic phosphoprotein 1 (DMP-1)-positive odontoblasts within a developing tooth germ in vitro. Moreover, O9-1 cells and induced pluripotent stem cell (iPSC)-derived neural crest-like cells (iNCLCs) can form well-organized vascularized dentin-pulp complex when transplanted in vivo with tooth scaffold. Furthermore, both O9-1 cells and iNCLCs can be differentiated into odontoblast-like cells, positive staining with odontogenic-related markers DMP-1 and dentin sialophosphoprotein (DSPP), under odontogenic induction with the administration of bone morphogenetic protein 4 (BMP-4). These results demonstrated that neural crest cells, especially the unlimited iNCLCs, are a promising cell source for tooth development and dental tissue/tooth organ regeneration studies.


A Long-Term Energy-Rich Diet Increases Prefrontal BDNF in Sprague-Dawley Rats.
Findings of the effect of high-fat feeding including "Cafeteria Diets" (CAF) on brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and prefrontal cortex (PFC) in rodents are conflicting. CAF is a non-standardized, highly palatable energy-rich diet composed by everyday food items for human consumption and is known to induce metabolic syndrome and obesity in rats. However, the highly palatable nature of CAF may counteract a negative effect of chronic stress on anticipatory behavior and synaptic plasticity in the hippocampus, hence represent a confounding factor (e.g., when evaluating functional effects on the brain). This study investigated the effects of a chronic, restricted access to CAF on BDNF, monoamine neurotransmitters, and redox imbalance in HIP and PFC in male rats. Our results show that CAF induced BDNF and its receptor TrkB in PFC compared to the controls (p < 0.0005). No differences in monoamine neurotransmitters were detected in either PFC or HIP. CAF increased dehydroascorbic acid and decreased malondialdehyde in PFC (p < 0.05), suggesting an early redox imbalance insufficient to induce lipid peroxidation. This study supports that a chronic CAF on a restricted schedule increases BDNF levels in the PFC of rats, highlighting that this may be a suboptimal feeding regime when investigating the effects of diet-induced obesity in the brain and emphasizing this as a point of attention when comparing the findings.


Watershed identification of polygonal patterns in noisy SAR images.
This paper describes a new approach to pattern recognition in synthetic aperture radar (SAR) images. A visual analysis of the images provided by NASA's Magellan mission to Venus has revealed a number of zones showing polygonal-shaped faults on the surface of the planet. The goal of the paper is to provide a method to automate the identification of such zones. The high level of noise in SAR images and its multiplicative nature make automated image analysis difficult and conventional edge detectors, like those based on gradient images, inefficient. We present a scheme based on an improved watershed algorithm and a two-scale analysis. The method extracts potential edges in the SAR image, analyzes the patterns obtained, and decides whether or not the image contains a "polygon area". This scheme can also be applied to other SAR or visual images, for instance in observation of Mars and Jupiter's satellite Europa.


A Person-Centered Perspective on Physical Activity-Related Barriers Perceived by Male Fluctuators 50 Plus: A Cross-Sectional Study.
Men aged 50 or older (50 plus) represent a hard-to-reach target group for health-enhancing physical activity (PA) interventions. However, a considerable percentage of men 50 plus do not entirely fail to achieve the PA milestones set by the World Health Organization (WHO) guidelines. They show fluctuating PA behavior, influenced by various barriers hindering or preventing regular PA participation. As "one-size-fits-all" behavioral change interventions are only partially effective in specific subgroups, it is essential to tailor PA promotion measures to the particular needs of male fluctuators 50 plus. The standardized questionnaire included validated instruments measuring participants' current stage of behavioral change, their perceived barriers to PA, questions on selected psychosocial correlates of PA, and sociodemographic variables. Out of 1,013 participants, 133 men (13.1%) classified themselves as fluctuators. Using a person-centered approach, we formed groups with similar intra-individual relevant barrier profiles using hierarchical cluster analysis (Ward method) followed by k-means clustering. We identified four clusters. Cluster 1 (n = 31) involves men predominantly perceiving physical constraints. Cluster 2 (n = 33) represents men lacking self-motivation and struggling with their weaker selves. Men in Cluster 3 (n = 51) primarily indicate professional and private obligations that prevent them from being physically active. Finally, men in Cluster 4 (n = 18) miss appropriate sports courses that meet their individual needs. Our findings support identifying individually tailored strategies designed to promote regular PA in male fluctuators 50 plus. Further research is required to determine the effectiveness of this approach in improving adherence to PA guidelines and corresponding health-enhancing effects for men 50 plus.


Bulk growth of ninhydrin single crystals by solvent evaporation method and its characterization for SHG and THG applications.
Ninhydrin is a well-known compound generally used in amino acid synthesis and also for detecting the latent fingerprints on porous surfaces. Single crystals can be grown by dissolving the compound in double distilled water at ambient temperature, and can be used as a potential material for second and third harmonic generation applications. The grown specimen was subjected to different characterization techniques in order to find out its suitability for device fabrication. Its lattice dimensions have been confirmed by X-ray powder diffraction and its crystalline quality has been assessed by high resolution X-ray diffraction and X-ray topography methods. The presence of functional groups was identified from HETCOR analysis and confirmed the absence of impurities during crystallization. Its optical properties have been examined by photoluminescence and birefringence analyses. Its thermal parameters such as thermal diffusivity, thermal conductivity and specific capacity have been carried out by following photopyroelectric method. Third order nonlinear optical measurements have been carried out using Z-scan technique and its nonlinear optical absorption coefficient has been determined.


The immune self, hygiene and performative virtue in general public narratives on antibiotics and antimicrobial resistance.
This paper employs an assemblage lens to generate analyses of general public narratives on antimicrobial resistance (AMR). Global efforts to reduce AMR include communications aiming to promote general public awareness, provide knowledge, encourage careful antibiotics use, and discourage demands for them. These efforts are somewhat compromised by the assumptions they make of individual lack of knowledge and motivation and the manner in which the AMR problem is framed in isolation from the biological, social and economic structures that produce it. Conceptualising AMR as an effect of antimicrobial assemblages of which publics are but one part, we analysed interviews with the general public on the lived experience of infections, antibiotic treatments and AMR. Far from science and policy discourse on AMR, these narratives showed antibiotics to be partly solutions to the social and biomedical challenges of infection, framed by self-defensive immunity and hygiene, the affective benefits of 'immune boosting', and the imperative to sustain the moral standing of the healthy citizen. Failing public awareness and action on AMR can be attributed to public health messages that overlook the social, affective and moral dimensions of infection care and separate AMR from its socio-economic drivers.


Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model.
Social withdrawal is the first sign and key component of the negative symptoms of schizophrenia. The efficacy of risperidone, an atypical antipsychotic, on the symptom is practically limited by dose-dependent side effects in clinical trials, therefore there is the need for adjuvant treatments. In the present study, we aimed to investigate the synergistic effect and mechanism of risperidone and galantamine, which is a nicotinic acetylcholine receptor (nAChR)-allosteric modulator and a modest cholinesterase inhibitor, on phencyclidine (PCP)-treated mouse model of social withdrawal. At non-effective doses by themselves, co-administration of galantamine (0.05mg/kg) and risperidone (0.05mg/kg) showed synergistic effects on PCP-induced impairments of social interaction and dopamine release in the medial prefrontal cortex (mPFC). The behavioral synergistic effect was abolished by the administration of a dopamine-D(1) receptor antagonist, SCH 23390 (0.02mg/kg, systemic; or 0.02microg/0.5microL/mouse, intra-mPFC), and a nAChR antagonist, mecamylamine (3mg/kg), but not a muscarinic receptor antagonist, scopolamine (0.1mg/kg). Mecamylamine (3mg/kg) also abolished the synergistic effect on dopamine release in the mPFC. We conclude that galantamine may have synergistic effect with risperidone on the negative symptom of social withdrawal in schizophrenia, which is mediated by dopamine-D(1) receptors in the mPFC through nAChR activation-increased dopamine release.


Current status of oncothermia therapy for lung cancer.
Lung cancer is one of the most common malignant tumors, and it has the highest death rate. Oncothermia is a feasible and successful treatment for lung cancer. Results show a remarkable survival benefit for patients, with a good quality of life. The treatment has no, or in some cases mild, side-effects and could decrease the adverse effects of the complementary treatment. Applying oncothermia together with other treatment methods could increase the effects and result in better performance. A comparison of studies demonstrates a good correspondence in the data, which strengthens the reliability of the studies, and clearly shows the feasibility of the application of oncothermia to treating all kinds of pulmonary malignancies including non-small-cell and small-cell primary tumors, and all of the metastatic diseases of the pulmonary system.


[Sonography in prehepatic portal vein occlusion].
In a retrospective analysis, the sonographic findings of 125 patients with prehepatic portal hypertension (of these 76 with condition after varix bleeding) were evaluated. The main cause were portal venous thromboses after umbilical venous catheter; 98% of these patients had a case history of hemorrhages. Of 113 cases with portal vein thrombosis, 54% had a cavernomatous transformation of the portal vein, 87% of them had a varix hemorrhage. In 12 patients with isolated lienal vein stenosis, no hemorrhage had occurred so far. All portal vein thromboses were correctly diagnosed by sonography. Besides the detection of thromboses, only in 5% of all cases no sonographically identifiable collaterals of the portal system were present; such collateral vessels could be imaged in 94% of the patients with endoscopic detection of varices. Sonography can be used as a screening method in suspicion of portal hypertension of prehepatic origin.


Plant diversity and community composition in managed humid coastal dune slacks in NW England.
Humid coastal dune slacks are an endangered habitat in Northwestern Europe. In the UK, dune slacks are currently classified as being in 'unfavourable' condition, with projected decrease in England of up to 30% by 2036. Studies in mainland Europe suggest that regional factors (e.g. slack area, age, and isolation) are more important than local factors (e.g. soil, pH, soil nutrient and water status) in driving successional vegetation processes in coastal slacks. However, this has never been tested for the UK, where approximately 14% of European slacks occur. We used previously established survey protocols to test whether regional factors are more important than local factors in UK coastal slacks, along the Sefton Coast in NW England. We found that slack area and slack age were more important than local factors in driving plant community composition and species richness. We also showed that higher levels of management, such as active grazing and invasive shrub and tree removal, are effective in increasing soil moisture levels in slacks. Our results suggest that similar successional processes are likely to be important in slacks in the NW of England, compared to mainland Europe.


Determination of Changes in Crystal Violet and Phenoxyethanol (Dating Ink).
Ink dating is a significant problem in terms of forensic science. Ballpoint pens are generally used as writing tools on the documents. Aging is determination of the changes in dyes and solvents in the composition of ink over time by analytical methods. The evaporation of the solvents from the paper surface is faster than the decomposition process of the dyes. In this study, in 2017, we were asked by the court to determine whether the texts on the suspicious pages of an agenda dated 1996 were written within 2 years or earlier. Phenoxyethanol and dyes were examined in the composition of all suspected ink samples. The results show the determination of both the decomposition process of the dyes and the evaporation process of phenoxyethanol in the aging of the document entries written by ballpoint pen.


A novel in vivo receptor occupancy methodology for the glucocorticoid receptor: toward an improved understanding of lung pharmacokinetic/pharmacodynamic relationships.
Investigation of pharmacokinetic/pharmacodynamic (PK/PD) relationships for inhaled drugs is challenging because of the limited possibilities of measuring tissue exposure and target engagement in the lung. The aim of this study was to develop a methodology for measuring receptor occupancy in vivo in the rat for the glucocorticoid receptor (GR) to allow more informative inhalation PK/PD studies. From AstraZeneca's chemical library of GR binders, compound 1 [N-(2-amino-2-oxo-ethyl)-3-[5-[(1R,2S)-2-(2,2-difluoropropanoylamino)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propoxy]indazol-1-yl]-N-methyl-benzamide] was identified to have properties that are useful as a tracer for GR in vitro. When given at an appropriate dose (30 nmol/kg) to rats, compound 1 functioned as a tracer in the lung and spleen in vivo using liquid chromatography-tandem mass spectrometry bioanalysis. The methodology was successfully used to show the dose-receptor occupancy relationship measured at 1.5 hours after intravenous administration of fluticasone propionate (20, 150, and 750 nmol/kg) as well as to characterize the time profile for receptor occupancy after a dose of 90 nmol/kg i.v. The dose giving 50% occupancy was estimated as 47 nmol/kg. The methodology is novel in terms of measuring occupancy strictly in vivo and by using an unlabeled tracer. This feature confers key advantages, including occupancy estimation not being influenced by drug particle dissolution or binding/dissociation taking place postmortem. In addition, the tracer may be labeled for use in positron emission tomography imaging, thus enabling occupancy estimation in humans as a translatable biomarker of target engagement.


Speech and magnetic resonance imaging results following autologous fat transplantation to the velopharynx in patients with velopharyngeal insufficiency.
To measure velopharyngeal closure with magnetic resonance imaging (MRI) and to evaluate speech when treating velopharyngeal insufficiency (VPI) with autologous fat transplantation to the velopharynx. Nine patients were recruited. Six patients had undergone cleft palate repair and subsequently developed VPI. Three were noncleft patients of which one had developed VPI after nasopharyngeal cancer treatment; another patient had developed VPI after combined adenotonsillectomy, and a third patient had VPI of unknown etiology. Preoperative and 1-year postoperative MRIs were obtained during vocal rest and during phonation. Data measured were the velopharyngeal distance in the sagittal plane and the velopharyngeal gap area in the axial plane. Preoperative and 1-year postoperative audio recordings were blinded for scoring independently by three senior speech therapists. When comparing preoperative and 1-year postoperative MRI during phonation we found a significant reduction of the median velopharyngeal distance from 4 to 0 mm (p = .011), and a significant reduction of the median velopharyngeal gap area from 42 to 34 mm(2) (p = .038). Nasal turbulence improved significantly (p = .011). Hypernasality/hyponasality and audible nasal emission did not change significantly. Autologous fat transplantation to the velopharynx resulted in a significant reduction of the velopharyngeal distance and the velopharyngeal gap area during phonation, as measured by MRI. This was in accordance with a significant improvement in nasal turbulence. However, hypernasality and audible nasal emission did not change significantly and could not be correlated to the MRI findings.


Multiline Transmit Beamforming Combined With Adaptive Apodization.
Increased frame rate is of high importance to cardiac diagnostic imaging as it enables examination of fast events during the cardiac cycle and improved quantitative analysis, such as speckle tracking. Multiline transmission (MLT) is one of the methods proposed for this purpose. In contrast to the single-line transmission (SLT), where one focused beam is sent in each direction, MLT beams are simultaneously transmitted and focused in several ( ) directions improving the frame rate accordingly. The simultaneous transmission is known to cause crosstalk artifacts due to the interference between the main lobes and the sidelobes of the transmitted and received beams. Usually, the artifacts are attenuated using a Tukey window apodization, but the lateral resolution is degraded. Several other methods, such as minimum variance beamforming and filtered delay multiply and sum beamforming were proposed to deal with these artifacts. The assumption examined in this paper is that a receive apodization can be chosen adaptively from a number of apodization windows in order to provide better artifact rejection and to increase the spatial resolution. The entire study was performed on an experimental MLT data set including wire and tissue mimicking phantoms, as well as in vivo cardiac data. The results demonstrate that application of a predefined apodization bank outperforms Tukey windowing alone, in terms of both resolution and receive crosstalk artifact rejections. Moreover, the achieved spatial resolution is superior to the nonapodized SLT, as measured from wire phantoms. The proposed method can also be combined with wider transmit beams, suitable for multiline acquisition.


Risk factors of epidural hematoma in patients undergoing spinal surgery: a meta-analysis of 29 cohort studies.
The authors conducted this meta-analysis to identify risk factors for spinal epidural haematoma (SEH) among patients following spinal surgery. The authors systematically searched Pub: Med, Embase, and the Cochrane Library for articles that reported risk factors associated with the development of SEH in patients undergoing spinal surgery from inception to 2 July 2022. The pooled odds ratio (OR) was estimated using a random-effects model for each investigated factor. The evidence of observational studies was classified as high quality (Class I), moderate quality (Class II or III) and low quality (Class IV) based on sample size, Egger's P value and between-study heterogeneity. In addition, subgroup analyses stratified by study baseline characteristics and leave-one-out sensitivity analyses were performed to explore the potential sources of heterogeneity and the stability of the results. Of 21 791 articles screened, 29 unique cohort studies comprising 150 252 patients were included in the data synthesis. Studies with high-quality evidence showed that older patients (≥60 years) (OR, 1.35; 95% CI, 1.03-1.77) were at higher risk for SEH. Studies with moderate-quality evidence suggested that patients with a BMI greater than or equal to 25 kg/m² (OR, 1.39; 95% CI, 1.10-1.76), hypertension (OR, 1.67; 95% CI, 1.28-2.17), and diabetes (OR, 1.25; 95% CI, 1.01-1.55) and those undergoing revision surgery (OR, 1.92; 95% CI, 1.15-3.25) and multilevel procedures (OR, 5.20; 95% CI, 2.89-9.37) were at higher risk for SEH. Meta-analysis revealed no association between tobacco use, operative time, anticoagulant use or American Society of Anesthesiologists (ASA) classification and SEH. Obvious risk factors for SEH include four patient-related risk factors, including older age, obesity, hypertension and diabetes, and two surgery-related risk factors, including revision surgery and multilevel procedures. These findings, however, must be interpreted with caution because most of these risk factors had small effect sizes. Nonetheless, they may help clinicians identify high-risk patients to improve prognosis.


The Satisfaction Level of Undergraduate Medical and Nursing Students Regarding Distant Preclinical and Clinical Teaching Amidst COVID-19 Across India.
The COVID-19 pandemic has disrupted the educational system and led to a drastic shift of professional undergraduate teaching for medical and nursing students into online mode. This was a cross-sectional, observational questionnaire-based study to assess the satisfaction level of the students. The questionnaire had 25 items of which 23 were questions with responses on the Likert scale and two items on views and suggestions were open-ended. The online questionnaire was shared through various messaging/mailing platforms. Overall satisfaction was assessed, and a satisfaction index was calculated for each item. Data are presented in frequencies and percentages, and SPSS was used to analyze the data. A total of 1068 students participated in the study. The majority were from the age group 21-23 years (54%) and there was almost the same number of participants from both genders. The majority of the students were medical undergraduates (n=919), were in their second year (n=669), belonged to a government institution (n=897) and used a mobile phone for their online classes (n = 871). The majority of the students were dissatisfied (42%) with no significant difference between medical and nursing students (p = 0.192). First-year students were significantly dissatisfied compared with other senior students (p = 0.005). The maximum satisfaction index (78.23%) was observed with faculties being supportive and responsive in resolving the queries and the minimum (46.39%) was observed with issues related to communication and discussion with peer students. There were 662 responses as views which mostly contained negative comments regarding interaction and focus, practical learning, teaching content, and technological/infrastructural flaws. There was major dissatisfaction regarding the practical and clinical learning. Online learning is essential at current times but is not an effective alternative for medical and nursing education. Face-to-face classes and practical sessions along with online learning can be a viable option.


Cross-sectional survey study of primary care clinics on evidence-based colorectal cancer screening intervention use.
The purpose of this study was to examine differences between urban and rural primary care clinics in the use of colorectal cancer (CRC) screening methods and evidence-based interventions to promote CRC screening. This was a cross-sectional survey of primary care clinics in Nebraska. Surveys in paper form were sent out and followed up with telephone interviews to nonrespondents. Of the 375 facilities, 263 (70.1%) responded to the survey. Over 30% of urban clinics indicated that 80% or more of their patients were meeting the CRC guidelines compared to 18.3% of rural clinics (P = .03). Rural clinics were more likely than urban clinics to prefer the use of colonoscopy alone or in combination with stool tests (P = .02). The most common interventions for CRC screening included one-on-one patient education and use of computer-based pop-ups to remind providers. In conclusion, we found some important differences between rural and urban primary care clinics in the implementation of CRC screening. Given that there is evidence for differences in preference for CRC screening methods (colonoscopy vs stool-based tests) between rural and urban community members, it is important to assess the effectiveness of different types of CRC screening interventions by comparing rural and urban primary care clinic patient populations.


Cholinergic Behavior State-Dependent Mechanisms of Neocortical Gain Control: a Neurocomputational Study.
The embodied mammalian brain evolved to adapt to an only partially known and knowable world. The adaptive labeling of the world is critically dependent on the neocortex which in turn is modulated by a range of subcortical systems such as the thalamus, ventral striatum, and the amygdala. A particular case in point is the learning paradigm of classical conditioning where acquired representations of states of the world such as sounds and visual features are associated with predefined discrete behavioral responses such as eye blinks and freezing. Learning progresses in a very specific order, where the animal first identifies the features of the task that are predictive of a motivational state and then forms the association of the current sensory state with a particular action and shapes this action to the specific contingency. This adaptive feature selection has both attentional and memory components, i.e., a behaviorally relevant state must be detected while its representation must be stabilized to allow its interfacing to output systems. Here, we present a computational model of the neocortical systems that underlie this feature detection process and its state-dependent modulation mediated by the amygdala and its downstream target the nucleus basalis of Meynert. In particular, we analyze the role of different populations of inhibitory interneurons in the regulation of cortical activity and their state-dependent gating of sensory signals. In our model, we show that the neuromodulator acetylcholine (ACh), which is in turn under control of the amygdala, plays a distinct role in the dynamics of each population and their associated gating function serving the detection of novel sensory features not captured in the state of the network, facilitating the adjustment of cortical sensory representations and regulating the switching between modes of attention and learning.


Reorganization of Active Surveillance of Acute Flaccid Paralysis (AFP) in Emilia-Romagna, Italy: a two-step Public Health intervention.
The International Health Regulations Emergency Committee declared in 2014 that poliovirus circulation is a public health emergency of international concern. In 2017 and 2018 Italy was classified at intermediate risk of poliovirus reintroduction based on suboptimal poliovirus surveillance. Acute flaccid paralysis active surveillance is the gold standard in the polio eradication process. The aims of this study were to investigate the causes of reduced acute flaccid paralysis case reporting in Emilia-Romagna in the last few years (step 1) and to study a public health intervention to restore an adequate level of acute flaccid paralysis surveillance in that region (step 2). In the first step a context analysis was performed by analysing the 2015-2017 Hospital Discharge Registers in Emilia-Romagna with the ICD-9-CM differential diagnosis codes for acute flaccid paralysis. Data from context analysis was then used to plan a new regional collaborative network of acute flaccid paralysis active surveillance. The active surveillance network was, at the end of the study, composed by 49 doctors from both hospital administrations and clinical wards from 4 University Hospitals and 7 Local Health Authorities throughout the Region. In 15 months, 7 acute flaccid paralysis cases have been reported; 85,7% received a full clinical and virological investigation and 83,3% completed the 60 day's follow-up. The mean response to each e-mail was 48,5% (SD 7,5%). In 2019, the Emilia-Romagna's active surveillance system reached the sensitivity, completeness of case investigation and follow-up required to achieve the minimum levels for certification standard surveillance.


Effects of home environment on respiratory symptoms and lung function in a general population sample in north Italy.
Effects of indoor pollution exposure were evaluated in a general population sample (n = 3,289) living in the Po River Delta area. Prevalence rates of chronic cough in men and dyspnoea in women were significantly higher in association with the use of bottled gas (propane) for cooking instead of natural gas (methane). Chronic cough and phlegm in men and dyspnoea in women were significantly associated with the use of a stove for heating. When combining type of heating and fuel used, in men a trend toward higher prevalence rates of chronic cough and phlegm was shown in those with stove or fan heating (regardless of the fuel); in women the trend reached statistical significance for dyspnoea. The relationship between stove (regardless of fuel) and decrease in forced expirograms was statistically significant only in women. In multiple logistic models, accounting for independent effects of age, smoking, pack-years, parents' smoking, socio-economic status, body mass index, significantly increased odds ratios were found in males for the associations of: bottled gas for cooking with cough (1.66) and dyspnoea (1.81); stove for heating with cough (1.44) and phlegm (1.39); stove fuelled by natural gas and fan or stove fuelled other than by natural gas with cough (1.54 and 1.66). In females, significantly increased odds ratios were found only for dyspnoea when associated with bottled gas for cooking (1.45), stove for heating (1.46), stove fuelled by natural gas (1.58), stove or fan fuelled other than by natural gas (1.73).(ABSTRACT TRUNCATED AT 250 WORDS)


Brazilian National Network of Alternative Methods (RENAMA) 10th Anniversary: Meeting of the Associated Laboratories, May 2022.
The Brazilian National Network of Alternative Methods (RENAMA), which is linked to the Ministry of Science, Technology and Innovation, is currently comprised of 51 laboratories from CROs, academia, industry and government. RENAMA's aim is to develop and validate new approach methodologies (NAMs), as well as train researchers and disseminate information on their use - thus reducing Brazilian, and consequently Latin American, dependence on external technology. Moreover, it promotes the adoption of NAMs by educators and trained researchers, as well as the implementation of good laboratory practice (GLP) and the use of certified products. The RENAMA network started its activities in 2012, and was originally comprised of three central laboratories - the National Institute of Metrology, Quality and Technology (INMETRO); the National Institute of Quality Control in Health (INCQS); and the National Brazilian Biosciences Laboratory (LNBio) - and ten associated laboratories. In 2022, RENAMA celebrated its 10th anniversary, a milestone commemorated by the organisation of a meeting attended by different stakeholders, including the RENAMA-associated laboratories, academia, non-governmental organisations and industry. Ninety-six participants attended the meeting, held on 26 May 2022 in Balneário Camboriú, SC, Brazil, as part of the programme of the XXIII Brazilian Congress of Toxicology 2022. Significant moments of the RENAMA were remembered, and new goals and discussion themes were established. The lectures highlighted recent innovations in the toxicological sciences that have translated into the assessment of consumer product safety through the use of human-relevant NAMs instead of the use of existing animal-based approaches. The challenges and opportunities in accepting such practices for regulatory purposes were also presented and discussed.


Lunar eclipse: infrared images and an anomaly of possible internal origin.
Infrared images of the lunar eclipse of 13 April 1968 were obtained and compared with infrared images of the 19 December 1964 eclipse. A similarity of apparent strength and distribution of most thermal anomalies on the maria is evident from inspection of these images, indicating that these features are not ephemeral. One new linear thermal anomaly was discovered, which is thermally enhanced during the lunar afternoon. Its close relation to a lunar crustal fracture line and other features of probable internal origin suggests that this anomaly may be of internal origin.


[Pathomorphosis of infectious diseases in children].
The general and therapeutically conditioned pathomorphosis was expressed in a significantly reduced number of autopsies predominantly due to reduced incidence of infectious diseases in children. Histological features of reactions in various organs in antibiotic therapy are examined. The necessity of continuous study of the clinical features and time course of infectious diseases in children is emphasized because the evolution of these processes continues.


Induction of tyrosine hydroxylase by cyclic AMP and glucocorticoids in a rat pheochromocytoma cell line: effect of the inducing agents alone or in combination on the enzyme levels and rate of synthesis of tyrosine hydroxylase.
The enzymatic activity of tyrosine hydroxylase (EC 22.214.171.124) increases in rat pheochromocytoma PC18 cells exposed to either elevated levels of cyclic AMP or glucocorticoids. The cyclic AMP-mediated increase in activity is elicited by cyclic AMP analogs or by compounds which activate adenylate cyclase or inhibit phosphodiesterase. The glucocorticoid-mediated increase is elicited only by glucocorticoid steroid hormones; nonglucocorticoid steroid hormones have no effect on tyrosine hydroxylase. In PC18 cells exposed simultaneously to both cyclic AMP-elevating agents and glucocorticoids, the increase in tyrosine hydroxylase activity is greater than that observed in cells treated with optimal concentrations of either inducing agent alone. Immunochemical titration experiments demonstrate that the increases in tyrosine hydroxylase activity observed in cells treated with the cyclic AMP analog, 8-bromocyclic AMP, and/or the synthetic glucocorticoid, dexamethasone, are due to increases in enzyme protein. Time course studies show that in cells treated with either 8-bromocyclic AMP or dexamethasone, the enzyme level increases slowly to a level 5-7-fold greater than that observed in untreated cells after 4 days of treatment. In cells treated with both of these inducing agents simultaneously, the enzyme level increases to a level 10-12-fold greater than that observed in control cells after 4 days of treatment. This additive increase in activity in cells treated with both inducing agents is observed at all time points. The rates of synthesis and degradation of tyrosine hydroxylase have also been measured in PC18 cells, using an antiserum to tyrosine hydroxylase to rapidly isolate radiolabeled enzyme from cells that have been incubated in the presence of [3H]leucine. The apparent half-life of tyrosine hydroxylase in the PC18 cells is approximately 30 hr. In PC18 cells incubated in the presence of radiolabeled leucine for 60 min, 0.2-0.3% of the total soluble protein synthesized is identified as tyrosine hydroxylase. In cells treated with either 8-bromocyclic AMP or dexamethasone for 24 hr, there is a 6-8-fold increase in the rate of synthesis of the enzyme. In cells treated with both inducing agents simultaneously, there is a 10-12-fold increase in the rate of synthesis; thus, the additive increase in enzyme level observed in cells treated with both inducing agents is paralleled by an additive increase in the rate of synthesis of the enzyme in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)


Antigenic diversity in the human malaria parasite Plasmodium falciparum.
Monoclonal antibodies against blood forms of Plasmodium falciparum were used to demonstrate considerable antigenic diversity in this species. Different isolates were distinguished by their ability to react with certain antibodies, and most of the antibodies reacted specifically with merozoites, schizonts, or both. The distribution of different antigenic types appeared not to be related to geographic origin. Serological typing with monoclonal antibodies extends the range of methods for identification of different strains of this malaria parasite.


Placental transfer of albendazole sulphoxide enantiomers in sheep.
Albendazole sulphoxide (ABZSO) is an anthelmintic drug used in veterinary practice. Its molecule has a chiral centre in the sulphur atom and racemic formulations are always used. The kinetics of the ABZSO enantiomers in the last third of pregnancy in ewes, and the placental transfer to the fetus, were studied after a single-dose oral administration (7.5 mg/kg) of a racemic formulation. In mothers, the area under the plasma concentration-time curve (AUC) and C(max) values of (+)-ABZSO (42.4+/-10.5 microg/mL and 1.9+/-0.4 microg/mL, respectively) were higher than those of (-)-ABZSO (15.3+/-5.1 microg/mL and 1.0+/-0.3 microg/mL). The MRT values were 17.0+/-1.6 h for (+)-ABZSO and 13.1+/-1.8 h for (-)-ABZSO. Similar kinetic parameters were obtained in the fetus for both enantiomers, but the fetal concentrations were lower compared with values for the dam. The AUC ratio between (-)-ABZSO/(+)-ABZSO in the dam was 0.36 and in the fetuses 0.64, indicating a higher impairment for the (+)-enantiomer in its placental transfer to the fetus.


BLNK mediates Syk-dependent Btk activation.
Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling, and its activity is regulated by Lyn and Syk. Although the molecular mechanism of Lyn-dependent Btk activation has been investigated, that of Syk-dependent Btk activation has remained unidentified. We have demonstrated that BLNK mediates Syk-dependent Btk activation. In a reconstitution cell system, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement of Btk activity. This phosphorylation depends on the interaction of Btk and BLNK by means of the Btk-Src homology 2 domain. The existence of such an activation mechanism is supported by the observation that the BCR-induced Btk phosphorylation and activation are significantly reduced in BLNK-deficient B cells as well as in Syk-deficient B cells. Although previous observations have identified the function of BLNK as the linker that integrates the action of Btk and Syk into downstream effectors such as phospholipase Cgamma2, our present study indicates another function of BLNK that connects the activity of Syk to that of Btk.


Prospective clinical study on the efficacy of bacterial removal with mechanical debridement in and around chronic leg ulcers assessed with fluorescence imaging.
Bacterial colonisation in wounds delays healing, mandating regular bacterial removal through cleaning and debridement. Real-time monitoring of the efficacy of mechanical debridement has recently become possible through fluorescence imaging. Red fluorescence, endogenously produced during bacterial metabolism, indicates regions contaminated with live bacteria (>104 CFU/g). In this prospective study, conventional and fluorescence photos were taken of 25 venous leg ulcers before and after mechanical debridement, without use of antiseptics. Images were digitally segmented into wound bed and the periwound regions (up to 1.5 cm outside bed) and pixel intensity of red fluorescence evaluated to compute bacterial area. Pre-debridement, bacterial fluorescence comprised 10.4% of wound beds and larger percentages of the periwound area (~25%). Average bacterial reduction observed in the wound bed after a single mechanical debridement was 99.4% (p<0.001), yet periwound bacterial reduction was only 64.3%. On average, across bed and periwound, a single mechanical debridement left behind 29% of bacterial fluorescence positive tissue regions. Our results show the substantial effect that safe, inexpensive, mechanical debridement can have on bacterial load of venous ulcers without antiseptic use. Fluorescence imaging can localise bacterial colonised areas and showed persistent periwound bacteria post-debridement. Fluorescence-targeted debridement can be used quickly and easily in daily practice.


Parallel selection on thermal physiology facilitates repeated adaptation of city lizards to urban heat islands.
Only recently have we begun to understand the ecological and evolutionary effects of urbanization on species, with studies revealing drastic impacts on community composition, gene flow, behaviour, morphology and physiology. However, our understanding of how adaptive evolution allows species to persist, and even thrive, in urban landscapes is still nascent. Here, we examine phenotypic, genomic and regulatory impacts of urbanization on a widespread lizard, the Puerto Rican crested anole (Anolis cristatellus). We find that urban lizards endure higher environmental temperatures and display greater heat tolerance than their forest counterparts. A single non-synonymous polymorphism within a protein synthesis gene (RARS) is associated with heat tolerance plasticity within urban heat islands and displays parallel signatures of selection in cities. Additionally, we identify groups of differentially expressed genes between habitats showing elevated genetic divergence in multiple urban-forest comparisons. These genes display evidence of adaptive regulatory evolution within cities and disproportionately cluster within regulatory modules associated with heat tolerance. This study provides evidence of temperature-mediated selection in urban heat islands with repeatable impacts on physiological evolution at multiple levels of biological hierarchy.


Knowledge, Attitudes, and Practices Toward COVID-19 Among Rural Residents of Hebei Province: A Cross-Sectional Survey.
Coronavirus disease (COVID-19) has spread worldwide due to high infectivity. The social sexual environment in rural areas of China and the weak basic medical facilities may affect the treatment and transmission of the disease. The aim of this study was to understand the knowledge, attitudes, and practices (KAP) related to COVID-19 among residents in rural areas experiencing the epidemic and the factors, to provide a basis for further epidemic prevention and control. The COVID-19 KAP of rural residents in Hebei Province was collected by the snowball sampling method. The COVID-19 KAP questionnaire was distributed on social platforms such as WeChat and QQ through a network questionnaire. The overall level of COVID-19 KAP in rural residents was good, but in terms of knowledge, the correct rate of isolation was 73.2%, the correct rates of 2 disinfection items were 72.3% and 77.4%, and the correct rate of hand-washing was 70.7%; 54.5% residents felt panic; 81.0% disinfected household items; and 84.9% washed their hands correctly. Residents still needed to strengthen these aspects. A binary logistic analysis showed that age, education, and participation in training were factors affecting the level of COVID-19 KAP. This study found that rural residents had good levels of COVID-19 KAP, but there were gaps in specific issues that warrant attention. We advocate training on COVID-19 for rural residents.


Monitoring abscopal responses to radiation in mice.
Focal radiation therapy has the potential to generate systemic tumor-targeting immune responses so potent as to eradicate anatomically distant, non-irradiated malignant lesions, a phenomenon commonly referred to as "the abscopal response." In cancer patients, bona fide abscopal responses are rare, although the recent introduction of immune checkpoint blockers into the clinical practice has significantly increased their incidence. In rodents, abscopal responses can be conveniently modeled by establishing two, slightly asynchronous and anatomically distant subcutaneous tumors in syngeneic immunocompetent hosts, provided that the therapeutic partners of radiation potentially included in the regimen of choice do not mediate systemic anticancer effects per se. Here, we describe such method to monitor abscopal responses based on mammary carcinoma TSA cells implanted in syngeneic immunocompetent BALB/c mice. With minor variations, the same technique can be conveniently applied to a variety of transplantable mouse tumors.


Plastic litter pollution along sandy beaches in the Caribbean and Pacific coast of Colombia.
Plastic pollution is a global problem that poses a threat to coastal and marine ecosystems and human livelihoods and requires effective solutions adaptable to local conditions. In Colombia, the knowledge about marine plastic pollution is still limited and the development of effective strategies for managing marine and coastal environments is crucial. Therefore, plastic pollution was assessed on 43 Colombian sandy beaches on the Caribbean and Pacific coasts. Amounts of macroplastic ranged from 35 ± 15 to 81 ± 23 items 100 m-1, being product's packaging the most common. Microplastic densities ranged from 3 to 1387 items m-2. The highest microplastic concentrations were found on the beaches from Caribbean cities and in rural areas of Pacific municipalities. Fragments and polyethylene were the most commonly observed shape and polymer categories, respectively. Tourism and poor waste management practices are the primary plastic sources on the studied beaches. Plastic litter on Colombian beaches are a problem that requires prevention, mitigation, and control actions to help conserve this ecosystem.


Increase in G(i alpha) protein accompanies progression of post-infarction remodeling in hypertensive cardiomyopathy.
Hypertensive cardiac hypertrophy and myocardial infarction (MI) are clinically relevant risk factors for heart failure. There is no specific information addressing signaling alterations in the sequence of hypertrophy and post-MI remodeling. To investigate alterations in beta-adrenergic receptor G-protein signaling in ventricular remodeling with pre-existing hypertrophy, MI was induced by coronary artery ligation in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Ten weeks after the induction of MI, the progression of left ventricular dysfunction and increases in plasma atrial natriuretic peptide (ANP) and cardiac ANP mRNA were more pronounced in SHR than WKY. In addition, the impaired contractile response to beta-adrenergic stimulation was observed in the noninfarcted papillary muscle isolated from SHR. Immunochemical G(s alpha) protein and beta-adrenoceptor density were not significantly altered by MI in both strains. However, immunochemical G(i alpha) was increased (1.5-fold) in the noninfarcted left ventricle of the SHR in which infarction had been induced when compared with that in SHR that underwent sham operation. This increase was observed especially in rats with a high plasma ANP level. Furthermore, there was a positive correlation between G(i alpha) and the extent of post-MI remodeling in WKY. A similar correlation between G(i alpha) and the extent of hypertensive hypertrophy was observed in SHR. In conclusion, the vulnerability of hypertrophied hearts to ischemic damage is greater than that of normotensive hearts. An increase in G(i alpha) could be one mechanism involved in the transition from cardiac hypertrophy to cardiac failure when chronic pressure overload and loss of contractile mass from ischemic heart disease coexist.


Tracheal intubation by novice staff: the direct vision laryngoscope or the lighted stylet (Trachlight)?
To compare the ease of use of the direct vision laryngoscope and the lighted stylet (Trachlight) by novice staff. Ten novice medical officers (MOs) performed orotracheal intubations using either the conventional direct vision laryngoscope (DL) or a lighted stylet device (Trachlight). They performed their DL intubations during the first phase of the study, followed by the Trachlight intubations in the subsequent phase. 51 of 54 (94%) of the DL intubation attempts were successful compared with 36 of 54 (67%) of the Trachlight intubations (p<0.001). The mean (SEM) time for intubation was 44 (7) seconds in the DL group and 66 (13) seconds in the Trachlight group (p=0.004). In addition 45 of 54 (83%) of the DL intubations were successful at the first attempt versus 15 of 54 (28%) in the Trachlight group (p<0.001). The results show that the use of the conventional direct vision laryngoscope in novices is associated with significantly shorter mean intubation times and higher success rates on the first attempt compared with the Trachlight.


Metabolism of inorganic arsenic in children with chronic high arsenic exposure in northern Argentina.
This study concerns the metabolism of inorganic arsenic (As) in children in three villages in northern Argentina: San Antonio de los Cobres and Taco Pozo, each with about 200 microg As/l in the drinking water, and Rosario de Lerma, with 0.65 microg As/l. Findings show that the concentrations of As in the blood and urine of the children in the two As-rich villages were on average 9 and 380 microg/l, respectively, the highest ever recorded for children. The concentrations were about 10 and 30 times higher for blood and urine, respectively, than in Rosario de Lerma. Total As in urine was only slightly higher than the sum of metabolites of inorganic As (U-Asmet), i.e., inorganic As, methylarsonic acid (MMA), and dimethylarsinic acid (DMA); this shows that inorganic As was the main form of As ingested. In contrast to previous studies on urinary metabolites of inorganic As in various population groups, the children and women in the present study excreted very little MMA. Thus, there seems to be a polymorphism for the enzymes (methyltransferases) involved in the methylation of As. Interestingly, the children had a significantly higher percentage of inorganic As in urine than the women, about 50% versus 32%. Also, the percentage of inorganic As in the children is considerably higher than in previous studies on children (about 13% in the two studies available) and adults (about 15-25%) in other population groups. This may indicate that children are more sensitive to As-induced toxicity than adults, as the methylated metabolites bind less to tissue constituents than inorganic As. In the children, the percentage inorganic arsenic in urine decreased, and the percentage of DMA increased with increasing U-Asmet, indicating an induction of As methylation with increasing exposure.