The development of a novel decision support system for regional land use planning for brownfield land.
Digital tools, particularly specialised decision support systems (DSSs), can be utilized to assist in the complex process of brownfield redevelopment. Existing brownfield DSSs typically focus on site-specific, late-stage applications, and socioeconomic factors are often overlooked. In this paper, we present a novel DSS aimed at providing support for early-stage, city region-scale brownfield land use planning and redevelopment. The proposed DSS is a prototype WebGIS application that enables land use planners and other brownfield regeneration professionals to examine a region and a set of sites during the initial planning phase for brownfield redevelopment. The DSS includes three bespoke modules comprising: (1) Land Use Potential (residential, commercial, and public open space), (2) risks posed by contamination and geotechnical hazards, (3) data pertinent to brownfield economic viability assessments. We outline a use case for this DSS, developed through comprehensive user-requirements gathering, and subsequently describe the techniques employed to construct the DSS modules and user interface. Finally, we present the results of user testing, wherein case-study stakeholders assessed the DSS. The feedback obtained during user testing aided in the identification of areas for improvement with regard to the functionality, usability, and effectiveness of the DSS in supporting decision-makers. The feedback was utilized to implement iterative improvements to the DSS and to plan future developments for the prototype DSS.


Insulin-requiring diabetes mellitus, hyperlipidemia, and anginal chest pains as prominent features of pheochromocytoma.
We report the case of a 60-year-old man with recent onset of poorly controlled diabetes mellitus, frequent anginal chest pains, paroxysmal hypertension, hyperlipidemia, and mild renal insufficiency. The patient was found to have pheochromocytoma of the left adrenal gland, resection of which resulted in total resolution of diabetes, hypertension, chest pain, hyperlipidemia and renal failure.


Cor triatriatum repair to eliminate suffering from paroxysmal atrial fibrillation.
Development of atrial fibrillation is one of the primary indicators of cor triatriatum in adults. Here we describe a case of a patient suffering cor triatriatum coexistent with frequent paroxysmal atrial fibrillation. Paroxysms of arrhythmia were not encountered after surgical correction. Resection of an anomalous membranous septum may have contributed to interrupting the development of ectopic beats, eliminating paroxysmal atrial fibrillation.


Genome-wide specificity of prime editors in plants.
Although prime editors (PEs) have the potential to facilitate precise genome editing in therapeutic, agricultural and research applications, their specificity has not been comprehensively evaluated. To provide a systematic assessment in plants, we first examined the mismatch tolerance of PEs in plant cells and found that the editing frequency was influenced by the number and location of mismatches in the primer binding site and spacer of the prime editing guide RNA (pegRNA). Assessing the activity of 12 pegRNAs at 179 predicted off-target sites, we detected only low frequencies of off-target edits (0.00~0.23%). Whole-genome sequencing of 29 PE-treated rice plants confirmed that PEs do not induce genome-wide pegRNA-independent off-target single-nucleotide variants or small insertions/deletions. We also show that ectopic expression of the Moloney murine leukemia virus reverse transcriptase as part of the PE does not change retrotransposon copy number or telomere structure or cause insertion of pegRNA or messenger RNA sequences into the genome.


Observation on the value of erythrocyte membrane fatty acids in the discrimination of hypothyroidism.
A computer-based 3-dimensional representation of two erythrocyte membrane saturated fatty acids (hexadecanoic acid, 16:0 and octadecanoic acid, 18:0), serum cholesterol and thyroid stimulating hormone (TSH) was performed in 26 hypothyroid patients and in 10 control subjects. The result indicates that a three-dimensional representation of grouped data discriminates normal people from individuals with hypothyroidism in a small population of highly selected cases.


Detection of Deformed wing virus, a honey bee viral pathogen, in bumble bees (Bombus terrestris and Bombus pascuorum) with wing deformities.
Honey bees (Apis mellifera) productively infected with Deformed wing virus (DWV) through Varroa destructor (V. destructor) during pupal stages develop into adults showing wing and other morphological deformities. Here, we report for the first time the occurrence of bumble bees (Bombus terrestris, Bombus pascuorum) exhibiting wing deformities resembling those seen in clinically DWV-infected honey bees. Using specific RT-PCR protocols for the detection of DWV followed by sequencing of the PCR products we could demonstrate that the bumble bees were indeed infected with DWV. Since such deformed bumble bees are not viable DWV infection may pose a serious threat to bumble bee populations.


Quality assurance in cervical screening of a high risk population: a study of 65,753 reviewed cases in Parana Screening Program, Brazil.
Epidemiological data from the Quality Assurance Unit (QAU) of the Cervical Cancer Screening Program of Paraná is discussed. Slides (65,753) reviewed by the QAU, from October 1997 to July 1999, were analyzed. Relations between agreement rate, diagnostic categories, and age groups were tested. The overall agreement rate was 97.04% (kappa +/- 95%, confidence interval = 0.888 +/- 0.003). Low-grade squamous intraepithelial lesion (LSIL) showed its peak prevalence in patients < or = 19 yr (8.3%). High-grade squamous intraepithelial lesion (HSIL) was more common in women between 40 and 49 yr (5.0%). Squamous-cell carcinoma (SCC) was almost exclusively seen in women > or = 40 yr. The lowest agreement rates were seen in adenocarcinoma (54.5%; kappa = 0.667) and LSIL cases (76.3%, kappa = 0.822), and in women < or = 19 yr (95.8%). It was concluded that constant monitoring to assess specific errors allows directed measures. The 10% rescreening model of quality assurance proved to be effective in a low resources setting with a positive overall financial impact.


Protein contributions to redox potentials of homologous rubredoxins: an energy minimization study.
The energetic contributions of the protein to the redox potential in an iron-sulfur protein are studied via energy minimization, comparing homologous rubredoxins from Clostridium pasteurianum, Desulfovibrio gigas, Desulfovibrio vulgaris, and Pyrococcus furiosus. The reduction reaction was divided into 1) the change in the redox site charge without allowing the protein to respond and 2) the relaxation of the protein in response to the new charge state, focusing on the latter. The energy minimizations predict structural relaxation near the redox site that agrees well with that in crystal structures of oxidized and reduced P. furiosus rubredoxin, but underpredicts it far from the redox site. However, the relaxation energies from the energy-minimized structures agree well with those from the crystal structures, because the polar groups near the redox site are the main determinants and the charged groups are all located at the surface and thus are screened dielectrically. Relaxation energies are necessary for good agreement with experimentally observed differences in reduction energies between C. pasteurianum and the other three rubredoxins. Overall, the relaxation energy is large (over 500 mV) from both the energy-minimized and the crystal structures. In addition, the range in the relaxation energy for the different rubredoxins is large (300 mV), because even though the structural perturbations of the polar groups are small, they are very near the redox site. Thus the relaxation energy is an important factor to consider in reduction energetics.


Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels.
Glutamate cysteine ligase (GCL), which synthesizes gamma-glutamyl-cysteine (gamma-GC), is the rate-limiting enzyme in GSH biosynthesis. gamma-GC may be produced by the catalytic subunit GCLC or by the holoenzyme (GCLholo), which comprises GCLC and the modifier subunit GCLM. The Gclm(-/-) knock-out mouse shows tissue levels of GSH that are between 9 and 40% of the Gclm(+/+) wild-type mouse. In the present study, we used recombinant GCLC and GCLM and Gclm(-/-) mice to examine the role of GCLM on gamma-GC synthesis by GCLholo. GCLM decreased the Km for ATP by approximately 6-fold and, similar to other species, decreased the Km for glutamate and increased the Ki for feedback inhibition by GSH. Furthermore, GCLM increased by 4.4-fold the Kcat for gamma-GC synthesis; this difference in catalytic efficiency of GCLholo versus GCLC allowed us to derive a mathematical relationship for gamma-GC production and to determine the relative levels of GCLholo and GCLC; in homogenates of brain, liver, and lung, the ratio of GCLC to GCLholo was 7.0, 2.0, and 3.5, respectively. In kidney, however, the relationship between GCLC and GCLholo was complicated. Kidney contains GCLholo, free GCLC, and free GCLM, and free GCLC in kidney cannot interact with GCLM. Taken together, we conclude that, in most tissues, GCLM is limiting, suggesting that an increase in GCLM alone would increase gamma-GC synthesis. On the other hand, our results from kidney suggest that gamma-GC synthesis may be controlled post-translationally.


The bovine milk microbiome - an evolving science.
Improved access to genome based, culture independent methods has generated great interest in defining the bovine milk microbiome. Several comprehensive reviews of this subject have recently been published and the purpose of this short review is to consolidate current understanding of the relevance and biological significance of this emerging topic. In contrast to mucosal organs that contain rich and well-characterized culturable and nonculturable microbial communities, milk obtained from the healthy bovine mammary gland usually contains few or no viable bacteria. The low bacterial biomass of milk has created methodological challenges that have resulted in considerable variability in results of studies that have used genomic methods to define the microbiota of milk obtained from healthy or diseased mammary glands. While genomes from several bacterial genera are routinely identified from samples of milk, teat skin and the teat canal, the viability, origin, and function of these organisms is uncertain as environmental factors have been shown to strongly influence the composition of these bacterial populations. Possible sources of microbial DNA include bacteria introduced from skin or the environment, bacteria trapped in teat canal keratin or bacteria engulfed by phagocytes. Researchers have not achieved consensus about key concepts such as the presence of a core commensal milk microbiome or dysbiosis as part of a causal pathway disrupting udder health. Understanding of the bovine milk microbiome has been greatly impeded by a lack of standardized methods used to collect, process, and assess bovine milk samples. Sample collection is a critical first step that will determine the validity of results. To minimize contamination with external sources of bacterial DNA, teat sanitation methods used for collection of milk samples that will be subjected to extraction and amplification of bacteria DNA should far exceed aseptic techniques used for collection of milk samples that will be submitted for microbiological culture. A number of laboratory issues have yet to be resolved. Contamination of low biomass samples with bacterial DNA from laboratory reagents is a well-known issue that has affected results of studies using bovine milk samples and results of sequencing of negative controls should always be reported. Replication of experiments has rarely been performed and consistency in results are lacking. While progress has been made, standardization of methods and replication using samples originating from differing farm conditions are critically needed to solidify knowledge of this emerging topic.


[Genetic effects in Drosophila caused by space flight factors in "Kosmos-573"].
It was proved in the experiments conducted on the space-ship "Cosmos 573" that the factors of the cosmic flight raised significantly the mutability in the D-32 wild type line of Drosophila melanogaster for two kinds of mutations: sex-linked recessive lethals and visible mutations in two X-chromosome's locuses: white and yellow.


Electrochemical Nitric Oxide Reduction on Metal Surfaces.
Electrocatalytic denitrification is a promising technology for removing NOx species (NO3- , NO2- and NO). For NOx electroreduction (NOx RR), there is a desire for understanding the catalytic parameters that control the product distribution. Here, we elucidate selectivity and activity of catalyst for NOx RR. At low potential we classify metals by the binding of *NO versus *H. Analogous to classifying CO2 reduction by *CO vs. *H, Cu is able to bind *NO while not binding *H giving rise to a selective NH3 formation. Besides being selective, Cu is active for the reaction found by an activity-volcano. For metals that does not bind NO the reaction stops at NO, similar to CO2 -to-CO. At potential above 0.3 V vs. RHE, we speculate a low barrier for N coupling with NO causing N2 O formation. The work provides a clear strategy for selectivity and aims to inspire future research on NOx RR.


N-(3,5-Dimethyl-phen-yl)succinamic acid.
In the title compound, C(12)H(15)NO(3), the N-H and C=O bonds are anti to each other. The C=O and O-H bonds of the acid group display an anti-periplanar orientation relative to each other. The crystal packing features a three-dimensional network of molecules held together by O-H⋯O and N-H⋯O hydrogen bonds.


recurrence following hepatectomy for metastatic colorectal cancer: development of a model that predicts patterns of recurrence and survival.
While several prognostic models have been developed to predict survival of patients who undergo hepatectomy for metastatic colorectal cancer (mCRC), few data exist to predict survival after recurrence. We sought to develop a model that predicts survival for patients who have developed recurrence following hepatectomy for mCRC. A retrospective analysis was performed on data from consecutive patients that underwent hepatectomy for mCRC. Clinicopathologic data, recurrence patterns, and outcomes were analyzed. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed. An integer-based model was created to predict the patterns of recurrence and survival after recurrence. This analysis included 280 patients with a median follow-up of 50.1 months. Of these, 53% underwent major hepatectomy and 87% had negative margins. Recurrent disease developed in 63% of patients. After hepatectomy, factors associated with short disease-free interval (DFI) and overall survival (OS) included CEA > 200 ng/ml (P < 0.0005), >1 metastasis (P < 0.0005), and a high Fong score (P < 0.0005). After recurrence, the pattern of recurrence was a strong predictor of OS (P < 0.0005). Independent predictors of the pattern of recurrence on multivariate analysis include CEA > 200 ng/ml, tumor size >5 cm, and >1 liver metastasis. A simple predictive scoring system was developed from the beta coefficients of this analysis that correlated with recurrence pattern (P < 0.0005). After hepatectomy, survival of patients with recurrent mCRC is strongly predicted by the patterns of recurrence, and the recurrence pattern can be predicted with a simple model. This can also be extended to create a scoring system that estimates expected survival.


Cytoplasmic activity in type I pulmonary epithelial cells induced by macroaggregated albumin.
After the intravenous injection of radioalbumin macroaggregate, large numbers of cytoplasmic inclusion bodies were observed in the lung tissue of rats. The inclusions were located mainly in the cytoplasm of type I alveolar lining cells, appeared 40 minutes after the injection, and lasted up to 2 days. These observations suggest that the type I alveolar lining cells participate in the clearing mechanism of the lung tissue, a function that thus far has not been attributed to this type of cell.


Enzyme electrophoretic polymorphism differentiates invasive from non-invasive Chlamydia psittaci ruminant isolates.
A group of 24 Chlamydia psittaci strains isolated from ruminants, belonging to serotype 1 and previously classified as invasive in a mouse model of virulence, was compared to a group of 10 non-invasive strains belonging to serotype 2 by using determination of glucose-6-phosphate and L-malate dehydrogenase zymotypes resulting of the infection of cells by these strains. The serotype 1 or invasive isolates represent a homogeneous group by sharing a unique zymotype which was not observed in the non-invasive strains. On the contrary, the serotype 2 or non-invasive isolates constitute a heterogeneous group in generating 2 different zymotypes. Zymotyping clearly distinguishes the ruminant strains from an avian C. psittaci and two C. trachomatis isolates studied for comparison. Our results suggest the usefulness of the studied molecular approach for chlamydiae typing. Furthermore, it can be used as marker of virulence within the C. psittaci strains isolated from ruminants.


Additional noradrenergic depletion aggravates forelimb akinesia and abnormal subthalamic nucleus activity in a rat model of Parkinson's disease.
This study aims to identify the contribution of additional noradrenergic depletion to forelimb akinesia and abnormal subthalamic nucleus (STN) firing activity in Parkinson's disease (PD). Forelimb akinesia behaviors were tested in awake rats with noradrenergic N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions, unilateral 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra pars compacta (SNc) and with combined 6-OHDA and DSP-4 lesions. STN extracellular single-unit and local field potential (LFP) activities were examined in the animals that were anesthetized with urethane. The adjusting steps and the contralateral touches of rats in the forelimb akinesia behavior tests were markedly inhibited by a further noradrenergic lesion with DSP-4 in 6-OHDA+DSP-4-lesioned group when compared with those of 6-OHDA-lesioned animals (P<0.05 for all comparisons). Meanwhile, the neuronal firing pattern of STN also changed significantly towards more bursty in 6-OHDA + DSP-4-lesioned group (P <0 .05). Compared with 6-OHDA-lesioned animals, an additional noradrenergic lesion increased the 0.3-2.5 Hz oscillatory activity and the spike power of STN neurons (P < 0.01 for both comparisons), and strengthened the synchronized oscillation between subthalamic neuronal firing and LFP activity in 6-OHDA + DSP-4-lesioned group (P < 0.01). The results provide evidence to support the correlation between noradrenergic depletion and the further exaggerated dysfunction of STN electrical activity in PD and suggest that an aberrant noradrenergic system might play a specific role in the motor deficits of PD.


[Isolation of Helicobacter pylori: necessity of control of transport conditions].
The aim of the study was the influence of transport conditions of antrum biopsies on the diagnostis of Helicobacter pylori infection by mean of bacteriological methods. We compare bacteriological to anatomopathological methods of Helicobacter pylori infection during two periods which differed by the transport conditions for antrum biopsies. During the first period (P1), 57 specimens were carried to the laboratory at room temperature and physiological serum immersion was inconstant. During the second period (P2), 56 specimens were all correctly immerged into 5 ml of physiological serum, in a 15 mm diameter tube which was vertically maintained in ice. Anatomopathological methods were considered as the reference method for the diagnostic of Helicobacter pylori infection. The sensibility of bacteriological culture was increased from 59% (P1) to 84% (P2) (p < 0.05) when specificity was unchanged. Furthermore sensibility of bacteriological direct examination was increased from 41% (P1) to 61% (P2). Complete biopsy immersion and ice transport of samples appear as necessary conditions for the optimal diagnostic of Helicobacter infections by mean of bacteriological methods.


Association between total-Tau and brain atrophy one year after first-ever stroke.
Although the most serious consequence of neuronal ischemia is acute neuronal death, mounting evidence suggests similarities between stroke and neurodegenerative disease. Brain atrophy visualized on structural MRI and pathological cerebrospinal fluid (CSF) concentrations of microtubule-associated protein tau (T-tau) and phosphorylated microtubule-associated protein tau indicate neurofibrillary degeneration. We aimed to explore the association between CSF T-tau and brain atrophy 1 year post-stroke. We included 210 patients with first-ever ischemic stroke or transitory ischemic attack without pre-existing cognitive impairment. After 12 months, subjects underwent MRI, and CSF biomarkers were assessed. Using SIENAX (part of FSL), ventricular CSF volume and total brain volume were estimated and normalized for subject head size. The association between T-tau as explanatory variable and ventricular and total brain volume as outcome variables were studied using linear regression. One hundred eighty-two patients completed the follow-up. Forty-four had a lumbar puncture. Of these, 31 had their MRI with identical scan parameters. Mean age was 70.2 years (SD 11.7). Ventricular volume on MRI was significantly associated with age, but not with gender. In the multiple regression model, there was a significant association between T-tau and both ventricular (beta 0.44, 95% CI 376.3, 394.9, p = 0.021) and global brain volume (beta -0.50, 95% CI -565.9, -78.3, p = 0.011). There was no significant association between CSF T-tau 1 year post-stroke and baseline volumes. T-tau measured 1 year post-stroke is associated with measures of brain atrophy. The findings indicate that acute stroke may enhance or trigger tau-linked neurodegeneration with loss of neurons. Clinicaltrials.gov NCT00506818 , July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.


Efficiency of active barriers attaching biofilm as sediment capping to eliminate the internal nitrogen in eutrophic lake and canal.
Three active barrier materials (zeolite, ceramicite and light porous media) were applied for preventing nitrogen (N) release from eutrophic lake sediments. Long term experiment of two different lake sediments were carried out and the effect of zeolite dose was evaluated. The results indicated that about 90%-100% of total N in overlying water was eliminated by using zeolite. While the N removal efficiency by ceramic was lower than that by zeolite, and light porous media present the lowest efficiency of 59%. Long term sediment incubation experiments indicated that two eutrophic sediments were both effective in preventing N release in spite of different release characteristics. Bio-zeolite capping technology was able to effectively inhibit the release of N from the sediment, and the zeolite dose was independently from N removal.


Multiple Alleles Encoding Atypical NLRs with Unique Central Tandem Repeats in Rice Confer Resistance to Xanthomonas oryzae pv. oryzae.
Plants have developed various mechanisms for avoiding pathogen invasion, including resistance (R) genes. Most R genes encode nucleotide-binding domain and leucine-rich repeat containing proteins (NLRs). Here, we report the isolation of three new bacterial blight R genes in rice, Xa1-2, Xa14, and Xa31(t), which were allelic to Xa1 and encoded atypical NLRs with unique central tandem repeats (CTRs). We also found that Xa31(t) was the same gene as Xa1-2. Although Xa1-2 and Xa14 conferred different resistance spectra, their performance could be attenuated by iTALEs, as has previously been reported for Xa1. XA1, XA1-2, XA14, and non-resistant RGAF differed mainly in the substructure of the leucine-rich repeat domain. They all contained unique CTRs and belonged to the CTR-NLRs, which existed only in Gramineae. We also found that interactions among these genes led to differing resistance performance. In conclusion, our results uncover a unique locus in rice consisting of at least three multiple alleles (Xa1, Xa1-2, and Xa14) that encode CTR-NLRs and confer resistance to Xanthomonas oryzae pv. oryzae (Xoo).


A CD14 gene polymorphism is associated with the IgE level for Dermatophagoides pteronyssinus.
CD14/-159 plays a role in sensitization to Dermatophagoides pteronyssinus in Japanese patients with allergic rhinitis. An association between a polymorphism in the 5'-flanking region of the CD14 gene and atopic phenotypes has been identified in a pediatric American population and an adult Dutch population. The aim of this study was to determine whether the CD14/-159 polymorphism is associated with specific IgE levels in allergic rhinitis patients in a Japanese population. The CD14/-159 genotypes of 81 unrelated patients with allergic rhinitis and 78 healthy subjects were determined and compared. The total IgE level and the specific IgE levels for three aeroallergens were determined. The IgE levels for each genotype were compared. The frequencies of CD14/-159 genotypes did not differ between the two groups. Among the allergic rhinitis patients, TT homozygotes had significantly fewer positive CAP-radioallergosorbent tests (CAP-RASTs) than CC homozygotes and CT heterozygotes, suggesting that the C allele is dominant. TT homozygotes also had significantly lower CAP-RAST scores for Dermatophagoides pteronyssinus, but not for Cryptomeria japonica or Dactylis glomerata, than CC homozygotes and CT heterozygotes. There was no significant association between total serum IgE levels and CD14/-159 genotypes in the allergic rhinitis patients.


ML-SA1 and SN-2 inhibit endocytosed viruses through regulating TRPML channel expression and activity.
Transient receptor potential mucolipin 2 and 3 (TRPML2 and TRPML3), as key channels in the endosomal-lysosomal system, are associated with many different cellular processes, including ion release, membrane trafficking and autophagy. In particular, they can also facilitate viral entry into host cells and enhance viral infection. We previously identified that two selective TRPML agonists, ML-SA1 and SN-2, that showed antiviral activities against dengue virus type 2 (DENV2) and Zika virus (ZIKV) in vitro, but their antiviral mechanisms are still elusive. Here, we reported that ML-SA1 could inhibit DENV2 replication by downregulating the expression of both TRPML2 and TRPML3, while the other TRPML activator, SN-2, suppressed DENV2 infection by reducing only TRPML3 expression. Consistently, the channel activities of both TRPML2 and TRPML3 were also found to be associated with the antiviral activity of ML-SA1 on DENV2 and ZIKV, but SN-2 relied only on TRPML3 channel activity. Further mechanistic experiments revealed that ML-SA1 and SN-2 decreased the expression of the late endosomal marker Rab7, dependent on TRPML2 and TRPML3, indicating that these two compounds likely inhibit viral infection by promoting vesicular trafficking from late endosomes to lysosomes and then accelerating lysosomal degradation of the virus. As expected, neither ML-SA1 nor SN-2 inhibited herpes simplex virus type I (HSV-1), whose entry is independent of the endolysosomal network. Together, our work reveals the antiviral mechanisms of ML-SA1 and SN-2 in targeting TRPML channels, possibly leading to the discovery of new drug candidates to inhibit endocytosed viruses.


Emergency Radical Gastrectomy with Pancreatico-duodenectomy for a Recent Onset Perforation of Locally Advanced Gastric Cancer with Pancreatic Head Involvement-Exceptional but a Definite Option.
Gastric cancer perforations are rare events with management options ranging from lavage and perforation closure, to resection. Usual aim is to perform a damage control procedure, and very few patients are suitable for a curative resection. We report the first case of emergency gastrectomy with pancreatico-duodenectomy performed in emergency for a perforated stomach cancer with pancreatic head invasion. The patient was a 32-year-old gentleman who presented with a perforated antro-pyloric cancer with infiltration of pancreatic head. Emergency radical gastrectomy with en-bloc pancreatico-duodenectomy was performed with due considerations to the patient and disease factors. He had an uneventful postoperative recovery and remains disease free at 18 months of follow-up after having received adjuvant chemotherapy. Curative resections should be selectively offered in advanced (T4b) gastric cancers in patients without multiple adverse factors. In an emergency situation with perforation peritonitis, if the magnitude of resection is deemed unlikely to add to significant morbidity of the surgery, taking multiple factors into consideration, an R0 resection can offer a large survival benefit in such settings.


Dysthymic disorder in the aged in the community.
The prevalence of dysthymic disorder and and its relationship to social and health variables were investigated in a Finnish population aged 60 years or over. The prevalence was lower in men (17.2 per 100) than in women (22.9 per 100). In the total population the occurrence was higher in the widowed (24.9 per 100) than in the married (18.3 per 100). In men, dysthymic disorder was more common in those with a lower educational level (22.6 per 100) than with a higher educational level (15.1 per 100), and more common in persons receiving long-term institutional care or home nursing or home help (28.7 per 100) than in persons living independently at home (14.6 per 100). The rate was not related to age, marital status or occupation. In women, the occurrence was not related to age, marital status, education, occupation or form of social and health care. The female rate was higher than the male in the older group (70 yrs. +), in married persons, in those with a higher educational level and in those living independently at home. Underdiagnosing was evident. The occurrence of dysthymic disorder was related to poor health and poor functional status and to the occurrence of social and health stressors. No differences were found in the occurrence of the related factors between persons with dysthymic disorder and persons with major depression. Our results support the conclusion that the majority of cases of dysthymic disorders in the elderly are affective illnesses and not personality disorders.


Human Periodontal Ligament Stem Cells Transplanted with Nanohydroxyapatite/Chitosan/Gelatin 3D Porous Scaffolds Promote Jaw Bone Regeneration in Swine.
Dental-tissue-derived stem cells have been used for tissue engineering owing to their ease of isolation and efficacy in in vitro and in vivo proliferation and differentiation. Nanohydroxyapatite/chitosan/gelatin (nHA/CG) three-dimensional porous scaffolds are promising for bone tissue engineering, especially jaw bone regeneration, because of their structural and functional similarity to natural bone. In our previous study, the efficiency of scaffolds with stem cell complexes in osteogenesis was confirmed in vivo in immunocompromised mice. However, studies on the bone regeneration efficiency of stem cell-seeded nHA/CG scaffolds using large animal jaw bone defect models have not been conducted. This study evaluated the bone regeneration potential of the nHA/CG scaffolds with transplanted human periodontal ligament stem cells (hPDLSCs) in critical-sized jaw bone defects in minipigs. The hPDLSCs isolated from periodontal ligaments of discarded teeth (postorthodontic purposes) were seeded onto the nHA/CG scaffolds. The scaffold was successfully synthesized according to our previous studies. Forty-eight critical-sized jaw bone defects were created in 12 minipigs. The defects were randomly assigned to one of three groups [scaffolds with seeded hPDLSCs (hPDLSCs/nHA/CG), only scaffold (nHA/CG), and a negative control group, ie, no cells and scaffolds implanted into defects] to investigate jaw bone regeneration. The bone regeneration capacities of the three groups were assessed for up to 12 weeks. The results showed that the hPDLSCs adhered well to the nHA/CG scaffold in vitro, and the cell-nHA/CG composites significantly increased new bone formation and generated large bones with normal architectures and vascularization in vivo compared to the nHA/CG and control groups. Immunohistochemistry staining showed that runt-related transcription factor 2 (Runx2) was highly expressed in the bone marrow formed in the hPDLSCs/nHA/CG group. This study provides strong evidence for future clinical applications of the nHA/CG scaffolds transplanted with hPDLSCs to regenerate the bone in large jaw bone defects.


Microbiome and Metabiotic Properties of Kefir Grains and Kefirs Based on Them.
The analysis of the literature on the microbiome composition and metabolic properties of kefir available at the RSCI and Web of Science was carried out. Kefir has been used by humans for centuries. It is a useful product of mixed lactic and alcoholic fermentation, produced using evolutionally established associative cultures, collected in an aggregated state termed kefir grains. General characterization of kefir grains from the territorial zones of different continents (Russia, Europe, Asia, and America) is provided. The methods for differentiation and identification of individual species are described, as well as their interactions within the community. The diversity of microbial composition of kefir grains depending on local cultivation conditions and storage processes is shown. The microorganisms present in kefir have a number of properties that determine their metabolism, interaction in the community, beneficial effects on human health and immune system, which is important for the prevention and control of bacterial and viral infections, especially during the COVID-19 pandemic.


Women's perceptions of PERSPECTIVE: a breast cancer risk stratification e-platform.
Breast cancer risk stratification categorizes a woman's potential risk of developing the disease as near-population, intermediate, or high. In accordance, screening and follow up for breast cancer can readily be tailored following risk assessment. Recent efforts have focussed on developing more accessible means to convey this information to women. This study sought to document the relevance of an informational e-platform developed for these purposes. To begin to assess a newly developed breast cancer risk stratification and decision support e-platform called PERSPECTIVE (PErsonalised Risk Stratification for Prevention and Early deteCTIon of breast cancer) among women who do not know their personal breast cancer risk (Phase 1). Changes (pre- and post- e-platform exposure) in knowledge of breast cancer risk and interest in undergoing genetic testing were assessed in addition to perceptions of platform usability and acceptability. Using a pre-post design, women (N = 156) of differing literacy and education levels, aged 30 to 60, with no previous breast cancer diagnosis were recruited from the general population and completed self-report e-questionnaires. Mean e-platform viewing time was 18.67 min (SD 0.65) with the most frequently visited pages being breast cancer-related risk factors and risk assessment. Post-exposure, participants reported significantly higher breast cancer-related knowledge (p < .001). Increases in knowledge relating to obesity, alcohol, breast density, menstruation, and the risk estimation process remained even when sociodemographic variables age and education were controlled. There were no significant changes in genetic testing interest post-exposure. Mean ratings for e-platform acceptability and usability were high: 26.19 out of 30 (SD 0.157) and 42.85 out of 50 (SD 0.267), respectively. An informative breast cancer risk stratification e-platform targeting healthy women in the general population can significantly increase knowledge as well as support decisions around breast cancer risk and assessment. Currently underway, Phase 2, called PERSPECTIVE, is seeking further content integration and broader implementation .


Do nanoparticles cause hormesis? Early physiological compensatory response in house crickets to a dietary admixture of GO, Ag, and GOAg composite.
This study aimed to identify the physiological responses of house cricket females following short-term exposure to relatively low dietary doses of graphene oxide (GO, 20 μg · g-1 food), silver (Ag, 400 μg · g-1 food) nanoparticles (NPs), or graphene oxide‑silver nanoparticle composite (GO-AgNPs, 20: 400 μg · g-1 food). Energy intake and distribution were measured on the third, sixth, and tenth day. A semi-quantitative API®ZYM assay of digestive enzyme fingerprints was performed on the third and tenth day of continuous treatment. Physicochemical properties of the NPs were obtained by combining SEM, EDX spectrometry, AFM, and DLS techniques. The obtained results showed decreased energy consumption, particularly assimilation as an early response to dietary NPs followed by compensatory changes in feeding activity leading to the same consumption and assimilation throughout the experimental period (10 days). The increased activities of digestive enzymes in NP-treated females compared to the control on the third day of the experiment suggest the onset of compensatory reactions of the day. Moreover, the insects treated with GO-AgNP composite retained more body water, suggesting increased uptake. The observed changes in the measured physiological parameters after exposure to NPs are discussed in light of hormesis.


Transport of L-ascorbic acid and dehydro-L-ascorbic acid across renal cortical basolateral membrane vesicles.
The uptake of L-ascorbic acid and dehydro-L-ascorbic acid into renal cortical basolateral membrane vesicles has been characterized. The uptake systems for both solutes demonstrate saturation kinetics. The presence of structural analogs of L-ascorbic acid and dehydro-L-ascorbic acid results in cis-inhibition and trans-stimulation. Uptake of each substrate is Na+-independent, proceeding to an endpoint of substrate equilibrium across the vesicular membrane. The transport mechanism(s) for L-ascorbic acid and dehydro-L-ascorbic acid appears to be facilitated diffusion.


The significance of group B streptococci in neonatal pneumonia.
Thirty-eight infants admitted to a neonatal intensive care unit because of pneumonia (14 patients) and pulmonary maladaption syndrome (PMA) (24 patients) were included in the study. Samples of potentially pathogenic, facultatively anaerobic bacteria were taken from the external ear, blood, throat, nasopharynx, umbilicus and gastric aspirates of the children, and from urethra and cervix of the mothers. Group B streptococci (GBS) and Escherichia coli were the only potentially pathogenic bacteria isolated from the infants. Out of 14 infants with pneumonia 11 (79%) harboured one of these bacteria, in contrast to 3 out of 24 (13%) with PMA (P less than 0.001). GBS was found in 8/14 infants with pneumonia and in 1/24 infants with PMA (P less than 0.001). The respective frequencies for Escherichia coli were 3/14 and 2/24 (not significant). The infant and/or the mother in 10/14 pneumonia cases harboured GBS, in contrast to 4/24 pairs in the PMA group (P less than 0.001). The levels of antibodies against GBS in sera of mothers to infants with pneumonia did not differ from the antibody levels in control sera (parturient GBS-carriers giving birth to healthy infants). The results gave evidence for an important manifestation of neonatal GBS-infection: pneumonia without septicemia. The incidence of the disease is estimated to be 1:25 parturient GBS-carriers. Finally, maternal fever, gestational age above 42 weeks, more severe respiratory difficulties and the occurrence of severe changes in fetal heart rate during the first stage of labour were found to be typical characteristics of pneumonia, as compared to PMA.


Measuring sexual and urinary outcomes in women after rectal cancer excision.
This study was designed to investigate sexual and urinary dysfunction in women who underwent rectal cancer excision, and the influence of tumor and treatment variables on long-term outcomes. Data were prospectively collected on 295 women who underwent rectal cancer excision at a tertiary referral colorectal center from 1998 to 2006. Sexual and urinary function was assessed preoperatively and at intervals up to five years after surgery. Functional outcomes were assessed by using univariate and multivariate regression analysis, chi-squared test for trend, or Kruskal-Wallis test. The mean age of the patients was 60.9 years. Anterior resection was performed in 222 patients (75.2 percent) and abdominoperineal resection in 73 patients (24.7 percent). Patients who underwent abdominoperineal resection were less sexually active (25 vs. 50 percent; P = 0.02) and had a lower frequency of intercourse than anterior resection patients at one year after surgery (anterior resection, 3 (0-5) (median interquartile range); abdominoperineal resection 0 (0-4); P = 0.029). The frequency of intercourse improved over time for abdominoperineal resection (4 months, 0 (0-0) median interquartile range; 5 years, 3 (0.25-4) median interquartile range; P = 0.028). Abdominoperineal resection was associated with increased dyspareunia (odds ratio, 5.75; 95 percent confidence interval (CI), 1.87-17.6; P = 0.002), urinary urgency (odds ratio, 8.52; 95 percent CI, 2.81-25.8; P < 0.001), incontinence (odds ratio, 2.41; 95 percent CI, 1.11-5.26; P = 0.026), poor stream (odds ratio, 5.64, 95 percent CI, 2.55-12.5; P <or= 0.001), and urinary retention (odds ratio, 11.7; 95 percent CI, 4.15-32.9; P < 0.001). Women who underwent radiotherapy had a 4.68-fold increase in dyspareunia (95 percent CI, 1.84-11.9; P = 0.001). Intra-abdominal sepsis was associated with decreased ability to achieve arousal (odds ratio, 0.085; 95 percent CI, 0.008-0.958; P = 0.046). Abdominoperineal resection, radiotherapy, intra-abdominal sepsis, and age 65 years or older are associated with significant impairments in female urinary and sexual outcomes after rectal cancer excision. Sexual and urinary outcomes should be considered when planning treatment for patients with rectal cancer.


Gaucher's disease. An unusual cause of intrathoracic extramedullary hematopoiesis.
A thoracic paravertebral mass in an asymptomatic woman with type 1 Gaucher's disease proved to be due to extramedullary hematopoiesis. This is, to our knowledge, the first case of intrathoracic extramedullary hematopoiesis reported with Gaucher's disease.


Enzyme-Activatable Near-Infrared Photosensitizer with High Enrichment in Tumor Cells Based on a Multi-effect Design.
Enzyme-activatable near-infrared (NIR) probes and photosensitizers (PSs) have emerged as promising tools for molecular imaging and photodynamic therapy (PDT). However, living organisms, especially animals, are highly dynamic systems; selective retention or even enrichment of these reagents after enzymatic activation at or near sites of interest remains a challenging task. Herein, we integrate the non-covalent and covalent retention approaches to introduce a novel "1-to-3" multi-effect strategy - one enzyme stimulus leads to three types of effects - for the design of enzyme-activatable NIR probe or PS. Using this strategy, we have constructed an alkaline phosphatase (ALP)-activatable NIR fluorogenic probe and a NIR PS, both of which proved to be selectively activated by ALP to switch on NIR fluorescence or photosensitizing ability. Additionally, these reagents resulted in significant enrichment (over 2000-fold) in ALP-overexpressed tumor cells, accompanied by massive depletion of intracellular thiols, the major antioxidants in cells. The investigation of this ALP-activatable NIR PS in in vivo PDT resulted in complete suppression of HeLa tumors and full recovery of all tested mice. Encouragingly, even a single PDT with this NIR PS was sufficient to completely suppress tumors in mice, demonstrating the high potential of this strategy in biomedical applications.


Intra- and extracellular measurements of frog neuromuscular transmission upon stretch of the muscle at different stimulus frequencies.
Flexible intracellular micro-electrodes were used to study the effect of changes in muscle length on the end-plate potential in the isolated m. cutaneus pectoris for different frequencies of stimulation (1/60-5Hz). A 20% step-wise increase in muscle length within the physiological range increases the end-plate potential immediately by about 50% (range 0-120%) at all frequencies tested. At stimulus frequencies lower than 1/5 Hz this increase is sustained during a period of 15 min stretch. At 1 Hz, however, the initial increase in the end-plate potential amplitude on the average declines within a few minutes to a steady-state value about 35% higher than the steady-state end-plate potential before stretch. At 5 Hz, the initial amplitude increase is followed by a decline of about 15 min duration and the final amplitude is not increased in comparison with the pre-stretch amplitude. The amplitude of the compound muscle action potential of the gastrocnemius muscle with intact circulation shows a similar time dependent increase upon stretch at different stimulus frequencies. It is concluded that stretch of a frog muscle gives both an immediate and a sustained increase in transmitter release from the nerve terminals during prolonged stimulation at frequencies up to about 5 Hz. This effect of stretch on transmitter release can improve in vivo neuromuscular impulse transmission.


QRS width does not reflect ventricular dyssynchrony in patients with heart failure.
The purpose of this study was to evaluate QRS width as an indication for cardiac resynchronization therapy. This study group consisted of 64 heart failure patients (51 men, age average 60.5 +/- 15.5 years) with a left ventricular ejection fraction (LVEF) of less than 35%. Patients were divided into two groups according to their QRS width; the wide QRS group (QRS width greater than or equal to 120 ms, 31 patients) and the narrow QRS group (QRS width less than 120 ms, 33 patients). The ventricular dyssynchrony (VD), i.e., the inter- and intraventricular dyssynchrony, of the two groups was compared. The correlation between QRS width and VD was evaluated in all patients. There were no significant differences between the wide and the narrow QRS groups concerning interventricular dyssynchrony [28.4 +/- 26.1 ms vs. 25.3 +/- 18.2 ms, not significant (NS)] or intraventricular dyssynchrony (99.0 +/- 43.8 ms vs. 109.0 +/- 56.6 ms, NS). Nor were there any differences in the LVEF (26.6 +/- 6.6% vs. 28.2 +/- 5.1%, NS), brain natriuretic peptide (BNP) (567.0 +/- 319.0 pg/ml vs. 390.0 +/- 375.8 pg/ml, NS), and New York Heart Association (NYHA) class (2.4 +/- 0.8 vs. 2.0 +/- 1.0, NS). QRS width did not correlate with interventricular (r = 0.026, NS) or intraventricular dyssynchrony (r = 0.052, NS). There were no differences in VD between the two groups based on differences in QRS width. There was also no correlation between QRS width and VD. It is suggested that QRS width is not an absolute indication for cardiac resynchronization therapy.


Characteristics of the deo operon: role in thymine utilization and sensitivity to deoxyribonucleosides.
Inability to grow on deoxyribonucleosides as the sole carbon source is characteristic of deo mutants of Escherichia coli. Growth of deoC mutants, which lack deoxyribose 5-phosphate aldolase, is reversibly inhibited by deoxyribonucleosides through inhibition of respiration. By contrast, deoB mutants are not sensitive to deoxyribonucleosides, and deoxyribose 5-phosphate aldolase and thymidine phosphorylase are present at normal levels but are not inducible by thymidine. Organisms with the genotype deoB(-)thy(-) or deoC(-)thy(-) are able to grow on low levels of thymine, whereas deoB(+)thy(-) or deoC(+)thy(-) strains require high levels of thymine for growth. The deoB and deoC mutations are transducible with and map on the counterclockwise side of the threonine marker. They are closely linked to deoA, a gene determining thymidine phosphorylase. Merodiploids heterozygous for either the deoB or deoC genes are resistant to deoxyribonucleosides and, in combination with the thy mutation, require high levels of thymine for growth. Cultures of thy(+)deoC(-) mutants are inhibited by thymidine until this compound has been completely degraded and excreted as deoxyribose and thymine, whereupon growth promptly resumes at a normal rate. The inhibition of respiration in deoC strains and the induction of thymidine phosphorylase and deoxyribose 5-phosphate aldolase in the wild-type organism are considered to result from the accumulation of deoxyribose 5-phosphate.


A pathway distinct from the mammalian unfolded protein response regulates expression of endoplasmic reticulum chaperones in non-stressed cells.
The stress-induced unfolded protein response (UPR) is the only signaling pathway known to regulate expression of genes encoding the resident endoplasmic reticulum (ER) molecular chaperones and folding enzymes, yet these genes are constitutively expressed in all cells. We have examined the expression of ER chaperones in several cell lines that are dependent on a variety of cytokines for growth and survival. When the various cell lines were deprived of essential growth factors, mRNA levels of the ER chaperones BiP and GRP94 decreased dramatically. Re-stimulation of ligand-deprived cells with the appropriate growth factor induced BiP and GRP94 as delayed-early response genes. Cytokine induction of BiP and GRP94 biosynthesis was not preceded by a burst of glycoprotein traffic through the ER nor accompanied by expression of the CHOP transcription factor. The glycosylation inhibitor tunicamycin potently induced expression of both ER chaperones and CHOP in ligand-deprived cells, demonstrating that the UPR pathway remains functionally intact in the absence of growth factor-mediated signaling. Therefore, basal expression of ER chaperones is dependent upon and regulated by a mitogenic pathway distinct from the stress-inducible UPR cascade and this probably controls expression of ER chaperones and folding enzymes needed to assist protein biogenesis in the ER of normal, non-stressed cells.


Intracellular H2S production is an autophagy-dependent adaptive response to DNA damage.
Hydrogen sulfide (H2S) is a gasotransmitter with broad physiological activities, including protecting cells against stress, but little is known about the regulation of cellular H2S homeostasis. We have performed a high-content small-molecule screen and identified genotoxic agents, including cancer chemotherapy drugs, as activators of intracellular H2S levels. DNA damage-induced H2S in vitro and in vivo. Mechanistically, DNA damage elevated autophagy and upregulated H2S-generating enzyme CGL; chemical or genetic disruption of autophagy or CGL impaired H2S induction. Importantly, exogenous H2S partially rescued autophagy-deficient cells from genotoxic stress. Furthermore, stressors that are not primarily genotoxic (growth factor depletion and mitochondrial uncoupler FCCP) increased intracellular H2S in an autophagy-dependent manner. Our findings highlight the role of autophagy in H2S production and suggest that H2S generation may be a common adaptive response to DNA damage and other stressors.


Factors influencing the choice of facility-based delivery in the ethnic minority villages of Lao PDR: a qualitative case study.
Facility-based delivery has been promoted to improve maternal and child health care in Lao PDR and a free delivery policy was introduced at designated health care facilities (HCF) in 2013. However, according to birth records of HCFs in the impoverished and remote district, only a few women utilized the HCFs despite good physical accessibility. The aim of this study was to analyze the factors influencing the choice of facility-based delivery in the impoverished and remote district after a free delivery policy was introduced. Qualitative case study was employed. Focus group discussions (FGDs) and in-depth interviews (IDIs) were conducted from August to October 2015. Five hamlets (or small village) located along the main road where only a few women delivered at HCFs were selected for the study based on birth records. The participants of the FGDs and IDIs were the village heads, village health volunteers, women who delivered at home or at a health facility within the past 2 years, their husbands, and mothers or mothers-in-law. Thematic analysis was used to analyze the data. A total of 12 FGDs and 27 IDIs were conducted, and the number of participants was 105. The factors influencing the choice of facility-based delivery were classified into nine categories and 19 subcategories. The categories were labeled, "perception of childbirth," "traditional health concept: sabaai (a condition of health, ease, and comfort)," "perception of health care facilities and staff," "previous pregnancy and childbirth experience," "mode of available transportation," "financial burden of childbirth at health care facility," "family and community context," "institutional context," and "government policy on delivery." Our study demonstrated that five major factors negatively influenced the choice of facility-based delivery: (1) perception of childbirth, (2) preference for sabaai, (3) financial burden, (4) family decision-making, and (5) institutional context. To promote facility-based delivery in the impoverished and remote district, three strategies are recommended: (1) promoting community-based health education involving women and strengthening community-based mutual support, (2) clarifying items essential for delivery at HCFs, and (3) making HCFs more comfortable in terms of "sabaai."


Therapeutic role of Glycyrrhiza Uralensis fisher on benign prostatic hyperplasia through 5 alpha reductase regulation and apoptosis.
Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources. In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis. To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells. In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity. These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.


Tumor necrosis factor-α upregulates polymeric immunoglobulin receptor expression by NF-κB signaling pathways in grass carp (Ctenopharyngodon idellus) liver cells.
The polymeric immunoglobulin receptor (pIgR) is essential for controlling polymeric immunoglobulin to defend species from invading pathogens. However, the modulation pathway of pIgR expression in teleosts remains unclear. In this paper, to define that the cytokine TNF-α impacted the expression of pIgR, the recombinant proteins of TNF-α of grass carp were first prepared after approving that natural pIgR was expressed in liver cells of grass carp (Ctenopharyngodon idellus) (L8824). L8824 cells were incubated with variable amounts of recombinant TNF-α at various times, the results revealed that pIgR expressions showed a significant dose-dependent elevation at the gene and proteins, and a similar alteration trend was detected for the pIgR protein (secretory component: SC) secreted by L8824 cells into the culture supernatant. Moreover, nuclear factor kappa-B (NF-κB) inhibitors PDTC was used to study whether TNF-α regulated pIgR expressions through the NF-κB signaling pathways. L8824 cells were treated with TNF-α, inhibitor PDTC, and TNF-α + PDTC mixtures, respectively, and the levels of pIgR genes and pIgR protein in cells and SC in the culture supernatant decreased in cells treated with PDTC contrasted to the control, and subjected to reduced expression of PDTC + TNF-α reduced expression contrasted to that treated just with TNF-α, demonstrating that suppression of NF-κB obstructed the ability of TNF-α to elevate pIgR gene and pIgR protein in cells and SC in the culture supernatant. These outcomes indicated that TNF-α raised pIgR gene expression, pIgR protein, and SC creation, and this pIgR expression induced by TNF-α was modulated by complicated pathways that included NF-κB signaling mechanism, confirming TNF-α as a pIgR expression modulator and enhancing a deeper insight of the regulatory pathway for pIgR expression in teleosts.


Visualization of myocardial infarction by post-mortem single-organ coronary computed tomography: a feasibility study.
Post-mortem imaging is increasingly used in forensic field in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. The aim of this study was to investigate the role of post-mortem multidetector coronary artery computed tomography in cases of sudden death in adults. We have enrolled 11 cases, all of whom were negative for macroscopic extra-cardiac lethal findings after standard autopsy procedure. Later, from the same individuals, isolated single-organ post-mortem computed tomography coronarography (PMCTA), using an iodinated non-ionic contrast medium, was achieved. After computed tomography examination, all the isolated hearths were carried to the forensic pathologist, and a conventional histology assessment was performed on them. In 7 out of 11 of cadavers, a final diagnosis of myocardial infarction was made after a complete autopsy and histology procedures. Isolated hearts underwent PMCTA scanning and was confirmed in 6/11 cases, with the autopsy findings showing the presence and the localization of occlusions or severe stenoses and the extension of the myocardial hypoxic area by the extravasation of contrast medium as well. Isolated single-organ PMCTA could be considered a valid and useful tool in addition to traditional autopsy investigation (macroscopic sections and histology) in identifying the cause of death by recognizing the presence and degree of coronary artery disease and myocardial infarction area visualization.


Subversion of Lipopolysaccharide Signaling in Gingival Keratinocytes via MCPIP-1 Degradation as a Novel Pathogenic Strategy of Inflammophilic Pathobionts.
Periodontal disease (PD) is an inflammatory disease of the supporting tissues of the teeth that develops in response to formation of a dysbiotic biofilm on the subgingival tooth surface. Although exacerbated inflammation leads to alveolar bone destruction and may cause tooth loss, the molecular basis of PD initiation and progression remains elusive. Control over the inflammatory reaction and return to homeostasis can be efficiently restored by negative regulators of Toll-like receptor (TLR) signaling pathways such as monocyte chemoattractant protein-induced protein 1 (MCPIP-1), which is constitutively expressed in gingival keratinocytes and prevents hyperresponsiveness in the gingiva. Here, we found that inflammophilic periodontal species influence the stability of MCPIP-1, leading to an aggravated response of the epithelium to proinflammatory stimulation. Among enzymes secreted by periodontal species, gingipains-cysteine proteases from Porphyromonas gingivalis-are considered major contributors to the pathogenic potential of bacteria, strongly influencing the components of the innate and adaptive immune system. Gingipain proteolytic activity leads to a rapid degradation of MCPIP-1, exacerbating the inflammatory response induced by endotoxin. Collectively, these results establish a novel mechanism of corruption of inflammatory signaling by periodontal pathogens, indicating new possibilities for treatment of this chronic disease. IMPORTANCE Periodontitis is a highly prevalent disease caused by accumulation of a bacterial biofilm. Periodontal pathogens use a number of virulence strategies that are under intensive study to find optimal therapeutic approaches against bone loss. In our work, we present a novel mechanism utilized by the key periodontal pathogen Porphyromonas gingivalis, based on the selective degradation of the negative regulator of inflammation, MCPIP-1. We found that the diminished levels of MCPIP-1 in gingival keratinocytes-cells at the forefront of the fight against bacteria-cause sensitization to endotoxins produced by other oral species. This results in an enhanced inflammatory response, which promotes the growth of inflammophilic pathobionts and damage of tooth-supporting tissues. Our observation is relevant to understanding the molecular basis of periodontitis and the development of new methods for treatment.


SWAP-70-deficient mast cells are impaired in development and IgE-mediated degranulation.
Cross-linking of the high-affinity IgE receptor (FcepsilonRI) on mast cell activates signaling pathways that trigger degranulation and the release of multiple pro-inflammatory mediators. Mature,immature and precursor mast cells are degranulation competent. We show here that the signaling protein SWAP-70 has a function in mast cell biology. While not found in many cell types, we find that apart from B cells, mast cells also express SWAP-70. In activated B cells, SWAP-70 shuttles between cytoplasm and nucleus, but in mast cells it is confined to the cytoplasm. SWAP-70(ko/ko) (double knockout) mice have reduced numbers of mature mast cells, and these are degranulation competent. However, although immature mast cells from SWAP-70(ko/ko) mice respond normally to SCF and IL-3 and have functional granules, their FcepsilonRI-mediated degranulation is inhibited. Thus, in mast cells SWAP-70 plays a role both in establishing the initial competence to degranulate and to develop into mature mast cells.


Coexistence mechanisms of Tamarix chinensis and Suaeda salsa in the Yellow River Delta, China.
To examine how two dominant species coexist within a tidal wetland in the Yellow River Delta, we studied the spatial distribution patterns and ecological relationships of Tamarix chinensis and Suaeda salsa. We also analyzed the relationship between these two plant species and soil chemical properties. Nine quadrats were established, and aerial photography was carried out in July 2018 in the study area to investigate plants and soil. Results showed that T. chinensis showed an aggregation distribution at scales of 0-10 m, 0-30 m, and 0-50 m from the sea to inland. Unlike T. chinensis, S. salsa showed an aggregation distribution at approximately 0-50 m in the study area, which meant the aggregation distributions of T. chinensis and S. salsa were found at different scales and S. salsa tended to aggregate distribution compared with T. chinensis. Meanwhile, T. chinensis and S. salsa had negative correlations far from the sea at a scale of 0-20 m and at the offshore area at a scale of 0-30 m. However, in the intermediate area, S. salsa and T. chinensis showed a positive correlation at a scale of 0-30 m. In general, the relationship between the two groups tends to be negatively correlated in a small range. Given that the tidal action decreased from the sea to inland, the driving factors of population aggregation gradually changed from tidal flooding to an interspecific relationship. The different characteristics of the different species may also have had an effect. And the aggregation of adult plant species had a beneficial impact on the establishment and growth of seedlings and plants. Furthermore, soil properties comprised complex actions including environmental conditions and ecological processes. The soil chemical properties such as soil salinity and nutrients were also influenced by the species' canopy.


Treatment of prosthetic valve infective endocarditis due to multi-resistant Gram-positive bacteria with linezolid.
Clinical experience with linezolid in the treatment of infective endocarditis either alone or in combination with other agents is limited. We describe our experience in the treatment of two patients with IE due to multi-resistant Gram-positive bacteria. One patient with MRSE and one with VRE endocarditis were treated with regimens containing linezolid. The killing kinetics of linezolid in combination with gentamicin or vancomycin against isolates of Staphylococcus epidermidis and Enterococcus faecalis were analysed in vitro. Clinical response and eradication of bacteraemia was achieved with linezolid therapy in both patients. Time-kill curve studies showed that linezolid was bacteriostatic against the MRSE and VRE isolates used. Combination with gentamicin or vancomycin did not produce synergy or antagonism but at best only marginal additive effect. Although bacteriostatic, linezolid provides an important therapeutic option in IE due to multi-resistant Gram-positive pathogens. It challenges the conventional wisdom that bactericidal synergy is required for the effective treatment of most cases of IE due to Gram-positive organisms.


Determinants of medicine use in a Swedish primary health care practice population.
Pharmaceuticals represent an increasing share of private and public health care expenditures. The aim of this study was to characterise users and to determine the pattern of uses of prescribed medicines and to identify determinants of medicine use in a multi-ethnic Swedish general practice population. The study was performed in 1055 of 1442 consecutive adult patients visiting the Jordbro Health Centre (JHC) in Stockholm, Sweden. In a regression analysis adjusted for the influence of confounders, subjects reporting 10-30 complaint symptoms, subjects with chronic disease and subjects that had a cost limitation card all reported a higher number of used medicines than subjects with a few (0-10) symptoms and those without chronic disease and a cost limitation card. In a Poisson's regression analysis, high age, female gender, not working, more than 10 symptoms, chronic disease and having a cost limitation card were related to use of prescribed medicines. All included variables predicted 19% of the explanation. Marital status, multi-symptomatology, chronic disease and having a cost limitation card were related to polypharmacy in a logistic regression analysis. A high number of complaint symptoms, chronic disease and having a cost limitation card were all significantly and independently related to use of medicines and polypharmacy.


The Off-Label Use of a Lumen-Apposing Metal Stent (LAMS) for a Benign Colon Anastomotic Stricture Causing Recurrent Bowel Obstruction in a Patient with Keloids.
Anastomotic strictures are a known complication of colorectal surgery. Despite a wide range of medical devices that have been deployed for this complication, outcomes remain challenging. Lumen-apposing metal stents (LAMSs) have recently emerged as a potentially superior therapeutic option. We herein report a patient with a past medical history of pT3, N0 adenocarcinoma of the colon with anastomotic stricture recurrence who underwent successful placement of an LAMS. We suggest that patients with a predisposition for keloid formation or fibrosis-prone anastomotic wound healing should be considered for LAMS deployment early in the treatment course.


Iterative joint classifier and domain adaptation for visual transfer learning.
Current available supervised classifiers cannot generalize across various domains due to distribution mismatch among them. Domain adaptation and transfer learning algorithms are proposed to tackle domain shift problem that originates from different data collection conditions. In this paper, we propose a transfer learning framework called iterative joint classifier and domain adaptation for visual transfer learning (ICDAV), which utilizes the balanced maximum mean discrepancy to better transfer knowledge across domains. Also, for learning a robust classifier against domain shift, a set of graph manifold regularizer and modified joint probability maximum mean discrepancy are simultaneously exploited to capture the domain structures and adapt the distribution of projected samples during the model learning process. Variety of experiments on several public datasets indicates that our approach achieves remarkable performance on visual domain adaptation and transfer learning tasks.


Hybrid Zn-β-Aminoporphyrin-Carbon Nanotubes: Pyrrolidine and Direct Covalent Linkage Recognition, and Multiple-Photo Response.
To unveil and shape the molecular connectivity in (metallo)porphyrin-carbon nanotube hybrids are of main relevance for the multiple medicinal, photoelectronic, catalytic, and photocatalytic applications of these materials. Multi-walled carbon nanotubes (MWCNTs) were modified through 1,3-dipolar cycloaddition reactions with azomethine ylides generated in situ and carrying pentafluorophenyl groups, followed by immobilization of the β-amino-tetraphenylporphyrinate Zn(II). The functionalities were confirmed via XPS and FTIR, whereas Raman spectroscopy showed disruptions on the graphitic carbon nanotube surface upon both steps. The functionalization extension, measured via TGA mass loss and corroborated via XPS, was 0.2 mmol·g-1. Photophysical studies attest to the presence of the different porphyrin-carbon nanotube connectivity in the nanohybrid. Significantly different emission spectra and fluorescence anisotropy of 0.15-0.3 were observed upon variation of excitation wavelength. Vis-NIR absorption and flash photolysis experiments showed energy/charge transfer in the photoactivated nanohybrid. Moreover, evidence was found for direct reaction of amino groups with a carbon nanotube surface in the presence of molecular dipoles such as the zwitterionic sarcosine amino acid.


Evidence for linkage to and association with type 1 diabetes at the 3q21 region in the Finnish population.
IDDM9-region on chromosome 3q has shown suggestive evidence for linkage to type 1 diabetes in some but not all genome scans. We analyzed 22 microsatellite markers in 121 Finnish type 1 diabetes multiplex families across the IDDM9-region. Two-point maximum LOD scores of 3.4 and 2.5 were detected with markers D3S1589 and D3S3606, respectively. Two markers were further tested for association using the transmission disequilibrium test in 384 Finnish type 1 diabetes simplex families. Marker AFM203wd10 showed association with type 1 diabetes (P = 0.0002 for allele R16). Association was present in families with children carrying the HphI-23 AA risk genotype at IDDM2 but not in families with children carrying protective AT or TT genotypes implying interaction between the two loci. Our data gives credence to earlier findings of linkage in this region and suggests a location for a polymorphism affecting type 1 diabetes susceptibility in the area surrounding AFM203wd10.


Construction and analysis of cDNA libraries from the antennae of male and female cotton bollworms Helicoverpa armigera (Hübner) and expression analysis of putative odorant-binding protein genes.
Two high-quality cDNA libraries were constructed from female and male antennae of the cotton bollworm Helicoverpa armigera (Hübner). The titers were approximately 2.0 × 10⁶ pfu/ml for females and 2.3 × 10⁶ pfu/ml for males, and this complies with the test requirement. From the libraries, 1750 male ESTs and 1640 female ESTs were sequenced and further analyzed. We identified 15 olfactory genes (12 are new), and 14 of them have the characteristic six conserved cysteine residues. With the exception of OBP9, all the genes were classified as classical OBP genes. By alignment and cluster analysis, the 14 classical OBPs were divided into pheromone binding protein (PBP) genes, odorant binding protein (OBP) genes, general odorant binding protein 1 (GOBP1) genes, general odorant binding protein 2 (GOBP2) genes and antennae binding protein (ABP) genes. Among these genes, we obtained three PBP genes (PBP1-PBP3) including two new PBP genes, one new ABP gene, nine new OBP genes (OBP1-OBP9), one known GOBP1 gene and one known GOBP2 gene. Furthermore, the expression patterns of these 14 classical OBP genes were investigated in various tissues by real-time quantitative polymerase chain reaction (qPCR). The results indicated that some OBP genes are expressed differently in different sexes and tissues, but most of them are highly expressed in antennae.


A comparison of Prx- and OxyR-based H2O2 probes expressed in S. cerevisiae.
Genetically encoded fluorescent H2O2 probes continue to advance the field of redox biology. Here, we compare the previously established peroxiredoxin-based H2O2 probe roGFP2-Tsa2ΔCR with the newly described OxyR-based H2O2 probe HyPer7, using yeast as the model system. Although not as sensitive as roGFP2-Tsa2ΔCR, HyPer7 is much improved relative to earlier HyPer versions, most notably by ratiometric pH stability. The most striking difference between the two probes is the dynamics of intracellular probe reduction. HyPer7 is rapidly reduced, predominantly by the thioredoxin system, whereas roGFP2-Tsa2ΔCR is reduced more slowly, predominantly by the glutathione system. We discuss the pros and cons of each probe and suggest that future side-by-side measurements with both probes may provide information on the relative activity of the two major cellular reducing systems.


Treatment of spent metalworking fluids.
Metalworking fluids (MWFs) are widely used for cooling and lubricating during the machining process. The worldwide annual usage is estimated to exceed 2 x 10(9)l and the waste could be more than ten times the usage, as the MWFs have to be diluted prior to use. For UK industry the disposal cost is estimated to be up to pound16 million per year. Used MWFs cause high levels of contamination and rancid odours due to the presence of complex chemicals, biocides, etc., so that their treatment and final disposal must be handled carefully. Conventionally this has been done by combined physical and chemical methods but, with tightened legislation, these routes are no longer acceptable. Now, biological treatment is being increasingly adopted as it seems to offer an alternative with the potential for significant cost saving. However, there are significant difficulties in operating bioreactors, such as maintenance of the stability of the microbial communities present in activated sludge plants (ASP). In order to resolve these problems, four major areas need to be considered: (1) the composition of the spent MWF and its inherent biodegradability, (2) the recalcitrant compounds existing in waste MWFs and their impact on microbes, (3) the nature of the microbial consortia and means of optimising it, e.g, temperature and the practical design of the bioreactor and (4) the requirements for nutrient supplements and optimal control conditions. The potential importance of understanding the microbial community has been studied by the use of molecular biological techniques such as polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), fatty acid methyl ester (FAME) and fluorescent in situ hybridization (FISH). The application of attached biofilm bioreactors and thermophilic aerobic technology (TAT) has also been studied. This review describes recent advances in each of these areas.


EEG correlates of hypnotic susceptibility based upon fast Fourier power spectral analysis.
The purpose of the present study was to determine if there were differences between high and low hypnotic susceptible subjects based upon fast Fourier power spectral analysis of the EEG recorded both before and during hypnotic tasks from frontal-temporal and occipital-parietal locations. Significant differences were obtained based upon EEG recording electrode location, EEG frequency within six different frequency domains, and hypnotic tasks. However, no main effect differences were obtained based upon hypnotic susceptibility. In contrast to some evoked potential studies in which a few differences have been obtained based on hypnotic susceptibility the lack of any EEG differences in this study even when positive and negative hallucination tasks were employed may have implications for the role of the neocortex in mediating hypnotic phenomena.


False positive cervicovaginal cytology. A follow-up study.
To determine what percentage of cervical cytologic diagnoses initially classified as false positives (based on a negative cervical biopsy within three months of the cervical cytologic smear) are recategorized as histologic false negatives when subsequent studies reveal abnormalities. A three-year review of 1,242 cervicovaginal biopsies with corresponding cytology in the preceding three months revealed 68 cases (5.5%) where the cytology was positive for a squamous intraepithelial lesion but the biopsy was within normal limits or showed benign cellular changes. Follow-up cytologic and/or histologic diagnoses were obtained for 53 of the 68 cases from the patients' hospital and physician office records. Of the 53 cases with follow-up, 24 (45%) were found to have a subsequent squamous intraepithelial lesion (indicating a sampling error at the time of the initial biopsy), and 9 showed atypical squamous cells of undetermined significance. In addition, 9 of the 20 patients (45%) who had negative follow-up studies had benign abnormalities on the initial, noncorrelating biopsy that may have contributed to the discrepancy. This study emphasized the importance of diligent follow-up of patients with noncorrelating studies since they represent a population at high risk for the subsequent detection of premalignant conditions.


Cefoxitin: a review of its antibacterial activity, pharmacological properties and therapeutic use.
Cefoxitin is a beta-lactam antibiotic derived from cephamycin C, a naturally occurring substance produced by Streptomyces lactamdurans. Its resistance to destruction by beta-lactamases results in a broad spectrum of antibacterial activity which includes anaerobic as well as Gram-positive and Gram-negative aerobic bacteria, including many resistant to cephalothin and other cephalosporins. Given by intravenous or intramuscular injection, cefoxitin is effective against a wide variety of infections caused by Gram-positive or Gram-negative aerobes as well as by anaerobic bacteria. It is generally well tolerated, thrombophlebitis, skin rash and some degree of discomfort after intramuscular injection, being the most commonly reported side effects. Cefoxitin has not been shown to cause adverse effects on renal function.


L-DOPA neurotoxicity is prevented by neuroprotective effects of erythropoietin.
The neurotoxicity of L-3,4-dihydroxyphenylalanine (L-DOPA), one of the most important drugs for the treatment of Parkinson's disease, still remains controversial, although much more data on L-DOPA neurotoxicity have been presented. Considering the well known neuroprotective effects of erythropoietin (EPO), the inhibitory effects of EPO on L-DOPA neurotoxicity need to be evaluated. Neuronally differentiated PC12 (nPC12) cells were treated with different concentrations of L-DOPA and/or EPO for 24h. Cell viability was evaluated using trypan blue, 4',6-diamidino-2-phenylindole (DAPI) and TUNEL staining, and cell counting. Free radicals and intracellular signaling protein levels were measured with 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. L-DOPA reduced nPC12 cell viability at higher concentrations, but combined treatment with EPO and L-DOPA significantly restored cell viability. Free radicals and hydroxyl radical levels increased by L-DOPA were decreased after combined treatment of L-DOPA and EPO. Levels of survival-related intracellular signaling proteins decreased in nPC12 cells treated with 200 μM L-DOPA but increased significantly in cells treated with 200μM L-DOPA and 5 μM EPO. However, cleaved caspase-3, a death-related protein, increased in nPC12 cells treated with 200 μM L-DOPA but decreased significantly in cells treated with 200 μM L-DOPA and 5 μM EPO. Pretreatment with LY294002, a phosphatidylinositol 3-kinase inhibitor, prior to combined treatment with EPO and L-DOPA almost completely blocked the protective effects of EPO. These results indicate that EPO can prevent L-DOPA neurotoxicity by activating the PI3K pathway as well as reducing oxidative stress.


Mitotic regulator SKAP forms a link between kinetochore core complex KMN and dynamic spindle microtubules.
Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent study shows that mitotic motor CENP-E cooperates with SKAP to orchestrate an accurate chromosome movement in mitosis. However, it remains elusive how kinetochore core microtubule binding activity KMN (KNL1-MIS12-NDC80) regulates microtubule plus-end dynamics. Here, we identify a novel interaction between MIS13 and SKAP that orchestrates accurate interaction between kinetochore and dynamic spindle microtubules. SKAP physically interacts with MIS13 and specifies kinetochore localization of SKAP. Suppression of MIS13 by small interfering RNA abrogates the kinetochore localization of SKAP. Total internal reflection fluorescence microscopic assays demonstrate that SKAP exhibits an EB1-dependent, microtubule plus-end loading and tracking in vitro. Importantly, SKAP is essential for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis. Based on those findings, we reason that SKAP constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division.


Cardiac Involvement in Systemic and Local Vasculitides: The Value of Noninvasive Multimodality Imaging.
Despite significant advances in managing systemic vasculitides, cardiovascular morbidity, and mortality are still of primary concern. Advances in noninvasive imaging have broadened our understanding of the clinical heterogeneity of cardiac involvement in vasculitides. Common cardiovascular complications in primary or secondary vasculitides are; coronary artery aneurysms, acute coronary syndromes, myocarditis, pericarditis, endocarditis, and valvular dysfunction. Echocardiography, cardiac magnetic resonance , positron emission tomography, and computed tomography angiography are essential in identifying cardiac involvement and guiding treatment. Here, we present our experiences of cardiac involvement in systemic vasculitides, covering most aspects of common cardiac complications based on a multi-modality approach to challenging (real-world) cases. As many cardiac manifestations are clinically silent, heart function should be systemically assessed by a multimodality imaging-based approach, including ECG, serial echocardiograms with strain imaging and 3D, and cardiac magnetic resonance to detect early signs of cardiac manifestations. This enables timely intervention and optimal medical treatment, which is essential for a better prognosis. There is a need for better and closer collaboration in clinical practice and research fields between cardiologists and rheumatologists.


Lumbosacral plexus block using a combination of ultrasound-guided lateral pre-iliac and parasacral approaches in cats.
To describe an ultrasound-guided lateral pre-iliac (LPI) and parasacral (PS) approach in feline cadavers (phase I) and compare the perioperative analgesic use and complications in cats administered LPI and PS blocks (group PNB) or epidural anesthesia (group EPI) for pelvic limb surgery (phase II). Experimental uncontrolled, anatomic and retrospective cohort study. A group of eight feline cadavers and 52 medical records. Bilateral LPI and PS approaches with 0.1 mL kg-1 of dye to stain the femoral and obturator nerves and the lumbosacral trunk, respectively, were performed on each cadaver. Nerve staining effect was evaluated upon dissections (phase I). Perioperative analgesics use, and complication rates were retrospectively compared between groups PNB and EPI (phase II). Continuous data were compared using the Mann-Whitney U test and the prevalence of events with Fisher's exact test. Differences were considered significant when p < 0.05. Dissections revealed that the LPI approach stained 94% and 75% of the femoral and obturator nerves, respectively. The PS approach stained 100% of the lumbosacral trunks. Cats enrolled in group PNB (n = 23) were administered lower doses of intraoperative opioids than those in group EPI (n = 25) (p = 0.006). Intraoperative rescue analgesia was required in 60% and 17.4% of cats enrolled in groups EPI and PNB, respectively (p = 0.003). Group PNB required more intraoperative anticholinergics than group EPI (p = 0.02). There were no differences in postoperative pain scores, analgesic use and complication rates. The ultrasound-guided LPI and PS approach stained the femoral/obturator nerves and the lumbosacral trunk, respectively, in feline cadavers. Furthermore, PNB was associated with lower intraoperative opioid use and similar postoperative pain and analgesic use compared with epidural anesthesia in a cohort of cats undergoing surgery of the pelvic limb.


Multi-criteria risk evaluation model for developing ventilator-associated pneumonia.
Ventilator-associated pneumonia is a hospital-acquired infection of the lungs occurring in mechanically ventilated patients. An active risk management approach can prevent the occurrence of the disease and promote positive organizational changes, subsequently decreasing mortality and hospitalization costs. Using scientific and clinical practice knowledge, a risk evaluation model was developed to identify patients more at risk of developing the disease. For this purpose, a Decision Expert qualitative multi-criteria decision method was used, in which alternatives are evaluated according to predetermined hierarchically arranged criteria. Characteristics of each evaluated alternative are described by the members of an interdisciplinary expert team and are represented by the values of the basic criteria. Values of hierarchically higher aggregated criteria are computed in an upwards fashion according to utility functions, which are defined as simple logical rules. This method is integrated into a software solution, DEXi. The approach is applicable to vastly diverse decision problems and has been successfully used before for health-related decision support. The designed model was tested using actual clinical data. Evaluations of alternatives that most distinctly demonstrated the functionality of the evaluation model were selected and are presented in the results. The evaluation model is intended to assist a holistic evaluation of the risk of developing ventilator-associated pneumonia, by considering patient-related risk factors and the use of preventive measures. The model incorporates nursing-specific data that have hitherto been poorly utilized in preventing ventilator-associated pneumonia and promotes the active engagement of nurses in confronting this interdisciplinary healthcare problem, which has gained more prominence with the onset of COVID-19 disease.


RBMX family proteins connect the fields of nuclear RNA processing, disease and sex chromosome biology.
RBMX is a ubiquitously expressed nuclear RNA binding protein that is encoded by a gene on the X chromosome. RBMX belongs to a small protein family with additional members encoded by paralogs on the mammalian Y chromosome and other chromosomes. These RNA binding proteins are important for normal development, and also implicated in cancer and viral infection. At the molecular level RBMX family proteins contribute to splicing control, transcription and genome integrity. Establishing what endogenous genes and pathways are controlled by RBMX and its paralogs will have important implications for understanding chromosome biology, DNA repair and mammalian development. Here we review what is known about this family of RNA binding proteins, and identify important current questions about their functions.


A case report on gangrene following simultaneous traumatic open metatarsophalangeal and interphalangeal dislocations of the left big toe.
Simultaneous metatarsophalangeal and interphalangeal dislocations of the big toe are rare injuries. Gangrene of the big toe following open dislocations was reported in a 20-year-old man.


Cardiovascular peripheric effects of a new tricyclic antidepressant, cianopramine (Ro 11-2465) in dogs.
In acute experiments in dogs anesthetized with pentobarbital, pressor responses produced by the i.v. injection of serotonin, noradrenaline and electric stimulation of the sympathetic nerves of the spleen, were registered before the i.v. injection of cianopramine (Ro 11-2465), a potent inhibitor of the uptake of serotonin into 5-HT neurones. Doses of 0.1 to 0.5 mg/kg of the antidepressant did not modify the blood pressure, while these produced a more intensive and prolonged pressor response during the i.v. injection of serotonin (p less than 0.05), noradrenaline (p less than 0.001) and stimulation of the splenic nerves (p less than 0.005). These effects resulted from the inhibition of the presynaptic reuptake of monoamines. The i.v. injection of 1-2 mg/kg of cianopramine produced significant hypotension (p less than 0.001) with baroreceptor and serotoninergic responses blockade. An induced strong hypertensive dose-dependent effect was observed after the i.v. administration of noradrenaline (+82%) and stimulation of splenic nerves (+80%). Cianopramine did not affect the hypotension produced by carbachol and histamine. The peripheric action of cianopramine showed a higher inhibitory effect on the presynaptic reuptake of noradrenaline than on serotonin.


Integrated oral care contributes positively to the course of treatment of oncopediatric patients.
The purpose of this study was to implement a model of permanent oral health care for oncopediatric patients and to observe its effects on severe oral mucositis and subsequent treatment interruptions. We performed a quasi-experimental study in the Pediatric Department of Napoleão Laureano Hospital, in the city of João Pessoa, Brazil. A integrated oral care was implemented by a dentistry team for prevention of comorbidities, such as infections, oral pain, oral function maintenance, oral mucositis, and interventions for lesions due to severe oral mucositis. The oral comorbidities were compared before and after the implementation. The duration of severe oral mucositis (SOM) before and after the interventions and the interruptions in treatment due to SOM were the main outcome measures. Permanent oral health care reduced the duration of SOM and reduced pediatric chemotherapy interruptions due to SOM by 81.8%.Conclusion: The permanent oral health care to offer to oncopediatric patients increased surveillance regarding oral comorbidities and reduced chemotherapy interruptions due to severe oral mucositis. This care plan could be adopted anywhere around the world. What is Known: • Several studies on oral care for pediatric oncology patients, especially regarding both prevention of and treatment for oral mucositis during antineoplastic therapy, have been published. What is New: • This study describes the benefits of permanent oral care with daily oral surveillance for pediatric patients, which reduced the duration of severe oral mucositis, increased surveillance and the efficiency in diagnostic for signs of oral mucositis, enabling early intervention, and decreased chemotherapy interruptions, contributing positively to the course of treatment.


An Organotypic Human Lymph Node Model Reveals the Importance of Fibroblastic Reticular Cells for Dendritic Cell Function.
Human lymph node (HuLN) models have emerged with invaluable potential for immunological research and therapeutic application given their fundamental role in human health and disease. While fibroblastic reticular cells (FRCs) are instrumental to HuLN functioning, their inclusion and recognition of importance for organotypic in vitro lymphoid models remain limited. Here, we established an in vitro three-dimensional (3D) model in a collagen-fibrin hydrogel with primary FRCs and a dendritic cell (DC) cell line (MUTZ-3 DC). To study and characterise the cellular interactions seen in this 3D FRC-DC organotypic model compared to the native HuLN; flow cytometry, immunohistochemistry, immunofluorescence and cytokine/chemokine analysis were performed. FRCs were pivotal for survival, proliferation and localisation of MUTZ-3 DCs. Additionally, we found that CD1a expression was absent on MUTZ-3 DCs that developed in the presence of FRCs during cytokine-induced MUTZ-3 DC differentiation, which was also seen with primary monocyte-derived DCs (moDCs). This phenotype resembled HuLN-resident DCs, which we detected in primary HuLNs, and these CD1a- MUTZ-3 DCs induced T cell proliferation within a mixed leukocyte reaction (MLR), indicating a functional DC status. FRCs expressed podoplanin (PDPN), CD90 (Thy-1), CD146 (MCAM) and Gremlin-1, thereby resembling the DC supporting stromal cell subset identified in HuLNs. This 3D FRC-DC organotypic model highlights the influence and importance of FRCs for DC functioning in a more realistic HuLN microenvironment. As such, this work provides a starting point for the development of an in vitro HuLN.


Patellofemoral ankylosis: case report and technical note.
It is our understanding that there is no consensual solution for the treatment of post-traumatic patellar ankylosis; therefore, the purpose of this work is to present two cases of patellofemoral retinacular interposition arthroplasty, and its corresponding technical note. CASE 1: Female, 24, patellar ankylosis secondary to supratranscondylar fracture, associated with comminuted diaphyseal tibia fracture. CASE 2: Female, 48, patellar ankylosis secondary to femoral diaphysis and lateral femoral condyle fracture. After going through a patellofemoral retinacular interposition release, both patients were satisfied with the results, presenting with significantly improved knee range of motion. Using our surgical technique, we were not able to restore normal function to our patients, but their improvement was certainly impressive relative to their initial clinical situation.


Giant adrenal pseudocyst presenting with gastric outlet obstruction and hypertension.
Adrenal pseudocysts are rare lesions that are usually nonfunctioning and asymptomatic. We describe a patient who presented with nonspecific upper abdominal pain, vomiting, and hypertension. Ultrasonography and computed tomography revealed a giant left adrenal cyst. Routine laboratory tests and endocrine function tests were all normal. The patient underwent surgery, and the cyst was completely removed. Histologic examination showed that the cystic wall consisted of fibrous tissue without an epithelial or endothelial lining, and a diagnosis of an adrenal pseudocyst was made. Symptoms of pyloric obstruction resolved after pseudocyst removal. His blood pressure normalized and he was normotensive and symptom free 6 years after surgery.


Questioning ZnO, Ag, and Ag/ZnO nanoparticles as antimicrobial agents for textiles: Do they guarantee total protection against bacteria and SARS-CoV-2?
Coronavirus Disease 2019 (COVID-19) occasioned global economic and health systems collapse. Also, it raised several concerns about using conventional cotton fabrics for manufacturing personal protective equipment without the antimicrobial capacity to inactivate viruses, such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its variants. Therefore, developing antimicrobial cotton fibers is crucial to avoid new global pandemics or the transmission of dangerous pathogens that remain on surfaces for long periods, especially in hospitals and medical clinics. Herein, we developed antimicrobial cotton fabrics with Ag, ZnO, and Ag/ZnO nanoparticles and evaluated their bactericidal activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), photocatalytic activity, and antiviral activity against Delta SARS-CoV-2. Although the antimicrobial fabrics are effective against these bacteria, they only reduce part of the SARS-CoV-2 virions during the first 15 min of direct contact via damage only to biological structures on the viral surface particle while the viral RNA remains intact.