Pretransplant C-reactive protein-to-albumin ratio predicts mortality in kidney transplant recipients: a retrospective cohort study.
The C-reactive protein (CRP)-to-albumin ratio (CAR) is a more effective prognostic indicator than CRP or albumin alone in various diseases. This study aimed to evaluate the predictive value of the CAR for mortality in kidney transplant recipients (KTRs). A total of 924 patients who underwent their first kidney transplantation at Kyungpook National University Hospital during 2006-2020 were enrolled and classified into quartile (Q) groups according to their pretransplant CAR values. A Cox regression analysis was conducted to analyze the hazard ratios (HRs) of mortality. Fifty-nine patients died during the posttransplant period (mean, 85.2±44.2 months). All-cause mortality (Q1, 3.0%; Q2, 4.8%; Q3, 7.8%; Q4, 10.0%; P for trend <0.001) and infection-related mortality increased linearly with an increase in CAR (P for trend=0.004). The Q3 and Q4 had higher risks of all-cause mortality than Q1 after adjusting for confounding factors (Q3 adjusted HR [aHR] 2.49, 95% confidence interval [CI] 1.04-5.99, P=0.041; Q4 aHR 3.09, 95% CI 1.31-7.27, P=0.010). Q4 was also independently associated with infection-related mortality (aHR 5.83, 95% CI 1.27-26.8, P=0.023). The area under the curve of the CAR for all-cause and infection-related mortality was higher than that of CRP or albumin alone. There was no association between CAR and death-censored graft failure or acute rejection. A higher pretransplant CAR increases the risk of posttransplant mortality, particularly infection-related, in KTRs. Pretransplant CAR can be an effective and easily accessible predictor of posttransplant mortality.


In silico study of HASDI (high-affinity selective DNA intercalator) as a new agent capable of highly selective recognition of the DNA sequence.
Cancer as an acquired genetic disease is based on changes both in the genome itself and in transcription processes. Accordingly, it is at the DNA level that it makes sense to search for and design agents capable of effective and selective anticancer action. In this study, we used an iterative approach based on a molecular dynamics simulation to design a highly selective DNA-intercalating agent called HASDI. To confirm its selective affinity to DNA, we conducted two simulation experiments: HASDI in a complex with a DNA fragment of the EBNA1 gene (it targets 16 nucleotide pairs of this gene) and HASDI in a complex with a random DNA fragment of the KCNH2 gene. The molecular dynamics simulation was carried out in the GROMACS 2019 package. The binding energy was calculated by gmx_MMPBSA 1.5.2. The further analysis was performed using the built-in utilities of GROMACS, gmx_MMPBSA and also XMGRACE and Pymol 1.8. As a result, we determined that the EBNA1-50nt/HASDI complex was stable throughout the whole simulation trajectory. HASDI, due to the presence of a linker modified depending on a specific pair of nitrogenous bases, formed an average of 32 hydrogen bonds with a sequence of 16 nucleotide pairs. Phenazine rings were stably intercalated every 2 base pairs. The root-mean-square deviation of HASDI in such a complex fluctuated around the value of 6.5 Å and had no tendency to increase. The calculated value of the binding free energy was - 235.3 ± 7.77 kcal/mol. The KCNH2-50nt/HASDI complex, as an example of the intercalation of the designed structure into a random part of the human genome, maintained the stability of its position at a level comparable to the EBNA1-50nt/HASDI complex. The phenazine rings were constantly intercalated in their original positions, and the root-mean-square deviation fluctuated around one value, although it had a tendency to chaotic changes. At the same time, this complex was characterized by 17-19 hydrogen bonds, on average, and the binding free energy was - 193.47 ± 14.09 kcal/mol. Moreover, the DNA duplex had local single-nucleotide melting in the region of the 4th linker. According to a significant decrease in the number of hydrogen bonds, a decrease in energy gain, as well as a decrease in the stability of the DNA duplex characteristic of the KCNH2-50nt/HASDI complex compared to the target EBNA1-50nt/HASDI complex, the molecule we designed can be considered a potentially selective DNA polyintercalating agent capable of relatively accurate recognition of 16 base pairs.


Optimization of the operation of packed bed bioreactor to improve the sulfate and metal removal from acid mine drainage.
The present study discusses the potentiality of using anaerobic Packed Bed Bioreactor (PBR) for the treatment of acid mine drainage (AMD). The multiple process parameters such as pH, hydraulic retention time (HRT), concentration of marine waste extract (MWE), total organic carbon (TOC) and sulfate were optimized together using Taguchi design. The order of influence of the parameters towards biological sulfate reduction was found to be pH > MWE > sulfate > HRT > TOC. At optimized conditions (pH - 7, 20% (v/v) MWE, 1500 mg/L sulfate, 48 h HRT and 2300 mg/L TOC), 98.3% and 95% sulfate at a rate of 769.7 mg/L/d. and 732.1 mg/L/d. was removed from the AMD collected from coal and metal mine, respectively. Efficiency of metal removal (Fe, Cu, Zn, Mg and Ni) was in the range of 94-98%. The levels of contaminants in the treated effluent were below the minimum permissible limits of industrial discharge as proposed by Bureau of Indian Standards (IS 2490:1981). The present study establishes the optimized conditions for PBR operation to completely remove sulfate and metal removal from AMD at high rate. The study also creates the future scope to develop an efficient treatment process for sulfate and metal-rich mine wastewater in a large scale.


Quantitative ultrasound measurements at the calcaneus in natural and surgically induced menopause.
The aim of the study was to assess skeletal status in natural and surgically induced menopausal women regarding the presence of previous osteoporotic fracture. Ninety-three females after bilateral oophorectomy in mean age of 56.8+/-8.3y. (48 without and 45 with fracture, groups 1 and 2, respectively) and 285 females with natural menopause in mean age of 56.4+/-7.0y (176 without and 109 with fracture, groups 3 and 4, respectively) were studied. Mean age, age of menopause, years since menopause (YSM), duration of fertile period (durFER) and body size did not differ between women after surgical and natural menopause and between non-fractured and fractured groups. No additional factors known to influence bone metabolism (either diseases or medications) or osteoporosis treatment were noted in the subjects studied. Skeletal status was evaluated by quantitative ultrasound (QUS) of the calcaneum using the Achilles system (Lunar, USA). Calcaneal QUS results were significantly higher: in women after natural than surgical menopause (p<0.05), in non-fractured females after natural menopause than in non-fractured females after surgical menopause (p<0.001) and in women after natural menopause without fracture compared with those with fracture (p<0.000001). The same comparisons between fractured groups and between women after surgical menopause with and without fracture revealed no significant differences. QUS parameters were regressed in a stepwise, multiple regression analysis on age, YSM, durFER, weight and height for all groups. In group 1, YSM had a negative influence and durFER was a protective factor; in group 2, age and durFER were a negative factors and YSM had no influence; in group 3, age and YSM were a negative factors (no role of durFER) and in group 4, only YSM had a negative influence, and durFER was a protective factor. Surgical menopause seems to be a risk factor for osteoporotic fracture because of low ultrasound values.


Histamine relaxation of aortic rings from diabetic rats.
The effect of histamine-induced relaxation on thoracic aortic rings from rats 5, 12, 24 and 52 weeks following streptozotocin-induced diabetes was determined. Preliminary studies confirmed the dependence of histamine-induced relaxation and the independence of nitroglycerin-relaxation (GTN) on the presence of endothelium (EDRF). Diabetes was confirmed by blood glucose levels exceeding 300 mg/dl. Rings with endothelium were depolarized several times with 50 mM KCL and then contracted with phenylephrine (10(-6)). Dose-response curves were plotted from data obtained following exposure to histamine (10(-7)-10(-3)) and GTN (10(-9)-10(-7)) and compared to responses from age-matched untreated controls, diabetic and diabetic rats treated with insulin (2 U/day). The relaxation produced by histamine on phenylephrine pre-contracted rings was similar in all three groups from 5-week age matched rats. However, histamine-induced relaxation from untreated diabetic rats was significantly depressed at 12, 24 and 52 weeks (p less than 0.001). Conversely there was no difference in the relaxation elicited by GTN on rings obtained from the three groups at any age. Pretreatment with diphenhydramine (5 x 10(-7)) on aortic rings from 12 and 52-week age matched rats resulted in qualitatively similar histamine dose-response curves that were displaced about two orders of magnitude to the right, indicative of H1 receptor competitive antagonism. These results demonstrate that the duration of diabetes alters the responsiveness of rat thoracic aortic rings to histamine but not to GTN and suggests that the responses elicited by certain agonists on target tissues may be significantly altered depending on the duration of diabetes.


Growth dynamics of meningiomas in patients with multiple sclerosis treated with interferon: report of two cases.
Although multiple sclerosis (MS) is a common disease of the central nervous system, the association of intraparenchymal tumour has been rarely reported and the potential relationship between intracranial meningioma and MS has not been seriously analysed. This report addresses the association of multiple sclerosis and intracranial meningioma and discusses the effect of interferon treatment on tumour progression. We report two cases with multiple sclerosis, who developed meningioma four and twenty years after the diagnosis of MS was made. Neither patient had a history of meningioma initially and both were being treated interferon when the meningioma was progressed. Histological examination of two cases revealed meningothelial meningioma. The first patient's KI67 level was 2.5% and was positive for the progesterone and estrogen receptor. Chromosomal analysis showed some abnormalities. In the second case, mild atypical change by presence of nuclear enlargement and rare mitotic figures were noted and PCNA, KI67 levels were less than 2%. We reported the association of multiple sclerosis and intracranial meningioma and observed the progression of the meningiomas during interferon treatment. Although, we cannot exclude the coincidence between the two diseases we discussed suspicious relationship between the interferon treatment and the tumour progression.


Discovery of the DIGIRR gene from teleost fish: a novel Toll-IL-1 receptor family member serving as a negative regulator of IL-1 signaling.
Toll-IL-1R (TIR) family members play crucial roles in a variety of defense, inflammatory, injury, and stress responses. Although they have been widely investigated in mammals, little is known about TIRs in ancient vertebrates. In this study, we report a novel double Ig IL-1R related molecule (DIGIRR) from three model fish (Tetraodon nigroviridis, Gasterosteus aculeatus, and Takifugu rubripes), adding a previously unknown homolog to the TIR family. This DIGIRR molecule contains two Ig-like domains in the extracellular region, one Arg-Tyr-mutated TIR domain in the intracellular region, and a unique subcellular distribution within the Golgi apparatus. These characteristics distinguish DIGIRR from other known family members. In vitro injection of DIGIRR into zebrafish embryos dramatically inhibited LPS-induced and IL-1β-induced NF-κB activation. Moreover, in vivo knockdown of DIGIRR by small interfering RNA significantly promoted the expression of IL-1β-stimulated proinflammatory cytokines (IL-6 and IL-1β) in DIGIRR-silenced liver and kidney tissues and in leukocytes. These results strongly suggest that DIGIRR is an important negative regulator of LPS-mediated and IL-1β-mediated signaling pathways and inflammatory responses. The Arg-Tyr-mutated site disrupted the signal transduction ability of DIGIRR TIR. Evolutionally, we propose a hypothesis that DIGIRR and single Ig IL-1R related molecule (SIGIRR) might originate from a common ancient IL-1R-like molecule that lost one (in DIGIRR) or two (in SIGIRR) extracellular Ig-like domains and intracellular Ser and Arg-Tyr amino acids. DIGIRR might be an evolutionary "transitional molecule" between IL-1R and SIGIRR, representing a shift from a potent receptor to a negative regulator. These results help define the evolutionary history of TIR family members and their associated signaling pathways and mechanisms.


Ovarian cytology. An application of cytology in an attempt at the early detection of ovarian carcinoma.
The possibility of detecting pre-clinical ovarian carcinoma by ovarian cytology taken at the time of laparotomy has been studied in 472 patients. Malignant cells have been recovered from ovarian carcinomas but never from macroscopically normal ovaries. It is suggested that this simple, inexpensive technique of sampling cells from the ovarian surface should be continued to be practised on all occasions at which ovaries present such as at laparotomy or at laparoscopy, as with further experience this technique may prove to be of help in the early diagnosis of ovarian carcinoma.


The use of fish-derived cell lines for investigation of environmental contaminants.
This unit describes protocols for growing salmonid cell lines and using them in in vitro toxicology studies. Cell viability of cultures is assessed with three indicator dyes: alamar blue for metabolic activity, CFDA-AM for membrane integrity, and neutral red for lysosomal activity. These protocols are essential tools for investigating environmental toxicity at the cellular level.


Eicosapentaenoic acid/arachidonic acid ratio in Japanese junior high school students.
This epidemiological study investigated the eicosapentaenoic acid/arachidonic acid ratio (EAR) and docosahexaenoic acid/ arachidonic acid ratio (DAR) in ninth-graders in Japan. A total of 175 ninth-grade children from Tsunan Town (115 boys and 60 girls) were enrolled in the study between 2015 and 2017. All participants were assessed during annual health checkups to determine their EAR and DAR. All data were compared between boys and girls using the Mann-Whitney test. Spearman's rank correlation coefficient was used to describe the strengths of correlations between the EAR, DAR, and relevant parameters. The median (minimum, maximum) EAR and DAR of all participants were 0.13 (0.05, 0.46) and 0.47 (0.25, 0.84), respectively. There was no significant difference in the EAR between boys and girls at 0.12 (0.05, 0.46) and 0.13 (0.06, 0.27) (P = 0.375), respectively. The DAR was not significantly different (P = 0.125). There was a significant positive correlation between EAR and triglyceride, body mass index, and homeostasis model assessment but a significantly negative correlation with HbA1c (r = -0.209, P = 0.006). In contrast, there was no significant correlation between DAR and any parameters. This is the first epidemiological study investigating the EAR using a population-based cohort of Japanese adolescents. The EAR in boys/girls in Japan is 0.12 (0.05, 0.46)/0.13 (0.06, 0.27). The study results suggest that children with a healthy diet may generally have a lower average blood glucose level.


Naringenin inhibits seed germination and seedling root growth through a salicylic acid-independent mechanism in Arabidopsis thaliana.
Flavonoids fulfill an enormous range of biological functions in plants. In seeds, these compounds play several roles; for instance proanthocyanidins protect them from moisture, pathogen attacks, mechanical stress, UV radiation, etc., and flavonols have been suggested to protect the embryo from oxidative stress. The present study aimed at determining the role of flavonoids in Arabidopsis thaliana (L.) seed germination, and the involvement of salicylic acid (SA) and auxin (indole-3-acetic acid), two phytohormones with the same biosynthetic origin as flavonoids, the shikimate pathway, in such a putative role. We show that naringenin, a flavanone, strongly inhibits the germination of A. thaliana seeds in a dose-dependent and SA-independent manner. Altered auxin levels do not affect seed germination in Arabidopsis, but impaired auxin transport does, although to a minor extent. Naringenin and N-1-naphthylphthalamic acid (NPA) impair auxin transport through the same mechanisms, so the inhibition of germination by naringenin might involve impaired auxin transport among other mechanisms. From the present study it is concluded that naringenin inhibits the germination of Arabidopsis seeds in a dose-dependent and SA-independent manner, and the results also suggest that such effects are exerted, at least to some extent, through impaired auxin transport, although additional mechanisms seem to operate as well.


Current possibilities of cervical precancerous lesions screening in Slovakia: prevalence of high risk human papillomavirus in patients with cytological diagnoses of atypical squamous cells of unknown significance.
It has been confirmed, that there is a causal relationship between persistent infection of high risk human papillomavirus (HR-HPV) and the development of cervical cancer. In population of women older than 30 years HPV infection becomes a significant etiological factor of precancerous lesion of the cervix, but HPV infection may spontaneously regress in the majority of the cases. The analysed study group consisted of 397 samples with cytological diagnosis of atypical squamous cells of unknown significance (ASCUS). All cases underwent HPV DNA testing using the Hybrid Capture 2 (HC2) assay. We analysed prevalence of HR-HPV and a viral load expressed as relative light units/cut off ratio (RLU/CO) in different age groups with cytological diagnoses of ASCUS. The prevalence of HR-HPV with cytological diagnoses of ASCUS was detected in 44 %. The prevalence of HR-HPV between patients aged 17-29 and between patients aged 30-40 was 55 % and 48 % respectively and we detected significant reduction of prevalence (28 %) in patients older than 41 years. Based on the results of presented study we assumed that age the 40 and over is crucial for the development of serious precancerous lesions in Slovakia, thus this age group is the most suitable for HPV triage of ASCUS. As a refinement of that type of ASCUS triage we recommend to add to the algorithm quantitative measurement of viral load in the specimens in the form of RLU/CO ratio (Fig. 3, Ref. 27).


Identifying environmental risk factors for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the recover program.
Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the association between "exposome"-the totality of environmental exposures and the risk of PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified environmental risk factors for 23 PASC symptoms and conditions from nearly 200 exposome factors. The three domains of exposome include natural environment, built environment, and social environment. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each exposome factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) exposome characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), particulate matter (PM2.5) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, blood, circulatory, endocrine, and other organ systems. Specific environmental risk factors for each PASC condition and symptom were different across the New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular exposome characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection.


Estimation of allele frequencies in polyploids under certain patterns of inheritance.
Allele frequencies have long been studied by biologists interested in evolution and speciation. More recently, with the application of molecular markers in human DNA profiling we have also seen the need for reliable population allele frequency estimates for making probabilistic inferences. There is now interest in applying the same DNA profiling technology to identification of plant varieties. HortResearch maintains a large germplasm of horticultural plant species. It is becoming evident that accurate identification of these accessions through DNA fingerprinting is essential for effective utilisation and maintenance of this germplasm. Microsatellites are the markers of choice for this fingerprinting. However, such markers do not reveal the dosage of alleles in a polyploid. Polyploidy is common amongst horticultural plants. Estimating allele frequencies in a polyploid population is, therefore, complicated because of some marker genotypes being phenotypically indistinguishable. For example, in a tetraploid, with four alleles at a locus showing polysomic inheritance, although 35 genotypes are possible, these will fall into only 15 marker phenotypic classes. Furthermore 'null' individuals are rarely detected in polyploids. Furthermore, some polyploids can be cryptic exhibiting disomy, instead of the polysomic inheritance. We will discuss the implications of these factors and present an EM-type algorithm for estimating allele frequencies of a polyploid population under certain patterns of inheritance. The method will be demonstrated on simulated data. We also discuss the nature of some of the additional problems that may be encountered with estimating allele frequencies in polyploids for which other solutions still need to be developed.


Malreduction of syndesmosis--are we considering the anatomical variation?
Previous studies have demonstrated the need for accurate reduction of ankle syndesmosis. Measurement of syndesmosis is difficult on plain radiographs. A computed tomography (CT) scan allows better visualisation of the transverse relationship between the fibula and incisura fibularis. The difference ('G' a term we coined for ease of description) between the fibula and the anterior and posterior facets of the incisura fibularis was compared between normal and injured ankles following syndesmotic fixation in 19 patients. The mean diastasis (MD) was also calculated, representing the average measurement between the fibula and the anterior and posterior incisura. When compared with the normal side, eight out of 19 (42%) cases were found to have a residual diastasis even after fixation across the syndesmosis. However, if a standard value of G (2mm) was used for the injured leg only, all of the 19 cases would have abnormal values of 'G' following reduction. Our study has clearly demonstrated the need for individualising the assessment method to guide surgeons and radiologists prior to revision surgery. A standard value of 'G' of 2mm as the normal limit cannot be applied universally, as apparent from the data presented in this study.


Sulfur deposition changed the community structure of soil nematodes by affecting omnivores-predators.
Nematodes generally occupy multiple trophic levels in detrital food webs, which play a vital role in energy flow, material conversion and nematodes community structure stability in the underground ecosystem. Sulfur (S) is one of the important soil nutrients, and it plays an important role in the nutrient cycle of grassland ecosystem. However, the impacts of S on soil fauna and subsurface detrital food webs in grassland ecosystems were rarely studied. Accordingly, to investigate the effects of sulfur deposition on soil nematodes and detrital food webs, we conducted a S addition experiment with distinct intensities from 0 to 50 g S m-2 yr-1 (S 0, S 1, S 2, S 5, S 10, S 15, S 20, and S 50) to simulated sulfur deposition in a meadow steppe of northern China. We documented a significant effect of S addition on the diversity and richness of nematodes, and the species richness of soil nematodes was high in the study site. But S addition had no significant effect on the total abundance and dominant species of nematodes (Cervidellus and Aphelenchus). Results of correlation analysis and structural equation modeling consistently indicated that omnivores-predators were significantly affected by sulfur addition. A significant increase in the Structural Index (which indicates food web structure) suggested increased top-down forces and changed community structure, although bacterivores, fungivores, plant parasites did not significantly. The present results suggest that sulfur deposition would change the composition of nematode community, affect the stability of nematode community structure, and increase the disturbance to the underground ecosystem. The study provides that the detailed information of the response of nematode to S deposition can be used to analyze the process of global change affecting the underground ecosystem.


Small renal masses managed with active surveillance: predictors of tumor growth rate after long-term follow-up.
The purpose of the study was to evaluate the relationships between the patients' clinical characteristics and the growth pattern of SRMs, and to investigate the predictive factors of tumor growth rates in patients initially managed with AS. We retrospectively reviewed data from our prospectively collected database of 70 patients diagnosed with 72 SRMs between 1996 and 2013. Clinical and demographic data, and linear and volumetric growth rates were recorded for each patient. A Pearson correlation test was used to evaluate initial tumor size and linear or volumetric growth rate. Logistic regression models were used to evaluate the predictive factors affecting tumor growth kinetics. The mean age was 76 ± 6.8 years, and 47 (67.1%) of patients were male. The mean (± SD) and the median (interquartile range [IQR]) tumor size at presentation were 2.1 ± 1.3 and 2.7 (1.8-3.7) cm, respectively. The mean (± SD) and the median (IQR) linear growth rate were 0.5 ± 0.3 and 0.6 (0.4-1.5) cm per year, respectively. Patients treated with delayed surgery experienced a significantly greater mean linear growth rate (1.4 vs. 0.3 cm per year) than those observed in the AS group (P < .001). Male sex (HR, 1.70; P = .04) and symptomatic presentation (HR, 1.85; P = .02) were found to be significant predictors of tumor growth rates during AS. Conversely, age, Charlson Comorbidity Index, and initial tumor size failed to predict growth kinetics. Male sex and symptomatic presentation are associated with faster growth rates in patients managed with AS after long-term follow-up.


Intranasal effects in chemically sensitive volunteers: an experimental exposure study.
During inhalational exposure to irritants stimulation of the trigeminal nerve endings in the nasal mucosa or other biochemical mechanisms might initiate inflammatory processes. Increased sensitivity of this physiological system in response to chemical stimulation is postulated in subjects reporting chemical intolerance. In the present study 12 subjects reporting chemical sensitivity and 12 controls were exposed to different concentrations of the industrial solvents ethyl benzene and methyl ethyl ketone (MEK). Concentrations of various inflammatory biomarkers, namely eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin 1β (IL-lβ), substance P (SP), and neurokinin A (NKA) were measured in nasal secretion after exposures. Before, during, and after the exposures subjects rated the severity of nasal irritations. The biomarker concentrations and reported irritations were not affected by the exposures. Regardless of substance and concentration sensitive subjects reported more nasal irritations. In conclusion, the investigated substances might possess weaker potency to elicit intranasal irritative effects than postulated.


Physicochemical design rules for the formulation of novel salt particles with optimised saltiness.
Novel sodium reduction strategies are urgently required by the food industry. We hypothesised that redesigning salt crystals (size, density, hydrophobicity and flow properties) will offer a new route to increase saltiness and therefore reduce sodium. Eight salts were compared with different physicochemical properties, the resultant particles were characterised and adhesion to product, loss in-pack, rate of dissolution and ultimately saltiness perception were evaluated. Principle findings included that particle adhesion was driven by particle size (r = -0.85, p = 0.008), bulk density (r = -0.80, p = 0.017) and flow properties (r = 0.77, p = 0.015); loss in-pack was associated with particle size and hydrophobicity of the salt particle while dissolution and/or saltiness perception was also driven by particle size and hydrophobicity of the salt particle. The findings offer a new set of design rules for future ingredient design for the food and flavour industries.


Retention of inhaled perfluoroisobutene in the rat.
Perfluoroisobutene (PFIB) is produced by the pyrolysis, and as a by-product during the manufacture, of polytetrafluoroethylene. When inhaled it produces a fulminating and sometimes fatal pulmonary oedema similar to that of phosgene after a latent period of 6-8 h. As part of a study to determine the retained dose and the factors that control the amount retained, this study has investigated the retention in rats of inhaled PFIB at concentrations of 10, 50 and 250 micrograms l-1 in a flow-through system combining head-only exposure and plethysmography. Uptake of PFIB was measured by gas chromatography during elevated and reduced inspired volume and respiratory rate induced by exposure to increased CO2 and injection of pentobarbitone, respectively. The percentage of PFIB retained in the upper airways and lungs was found to be 27.5, 28.1 and 23.7% of the amount inspired at the three concentrations tested. The rate of uptake (nmol min-1 kg-1) of PFIB was a power law of the amount inhaled, an n-fold increase in minute volume producing an nb-fold increase in uptake, where b varied between 0.4 and 0.85. Thus, doubling the inhaled dose produces a 1.3-1.8-fold increase in uptake with a corresponding decrease in percentage retained. The relative contribution of respiratory rate and tidal volume upon PFIB retention could not be defined.


Protective action of L-carnitine on cardiac mitochondrial function and structure against fatty acid stress.
Cardiovascular risks are frequently accompanied by high serum fatty acid levels. Although recent studies have shown that fatty acids affect mitochondrial function and induce cell apoptosis, L-carnitine is essential for the uptake of fatty acids by mitochondria, and may attenuate the mitochondrial dysfunction and apoptosis of cardiocytes. This study aimed to elucidate the activity of L-carnitine in the prevention on fatty acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats. Palmitoyl-CoA-induced mitochondrial respiration that was observed with L-carnitine was inhibited with oligomycin. The palmitoyl-CoA-induced mitochondrial membrane depolarization and swelling were greatly inhibited by the presence of L-carnitine. In ultrastructural observations, terminally swollen and ruptured mitochondria with little or no distinguishable cristae structures were induced by treatment with palmitoyl-CoA. However, the severe morphological damage in cardiac mitochondria was dramatically inhibited by pretreatment with L-carnitine. Treatment with L-carnitine also attenuated 4-hydroxy-L-phenylglycine- and rotenone-induced mitochondrial swelling even when the L-carnitine could not protect against the decrease in oxygen consumption associated with these inhibitors. Furthermore, L-carnitine completely inhibited palmitoyl-CoA-induced cytochrome c release. We concluded that L-carnitine is essential for cardiac mitochondria to attenuate the membrane permeability transition, and to maintain the ultrastructure and membrane stabilization, in the presence of high fatty acid β-oxidation. Consequently, the cells may be protected against apoptosis by L-carnitine through inhibition of the fatty acid-induced cytochrome c release.


Dietary fish oil normalize dyslipidemia and glucose intolerance with unchanged insulin levels in rats fed a high sucrose diet.
The aim of this study was to investigate the relationship between the lipid-lowering effects of fish oils and concomitant consequences on glucose tolerance and insulin sensitivity in an experimental animal model of hypertriglyceridemia induced by high sucrose intake. To achieve this goal, male Wistar rats were fed a semi-synthetic sucrose rich diet (SRD) (w/w: 62.3% sucrose, 8% corn oil, 17% protein) for 90 days. At the time, a well established and permanent hypertriglyceridemia accompanied by glucose intolerance was present. After that, one half of the animals continued on the SRD up to 120 days. The other half received an SRD in which the source of fat was substituted by cod liver oil (w/w 7% CLO plus 1% corn oil) from day 90 to 120 (SRD+CLO). Control rats were fed a semi-synthetic diet (CD) (w/w: 62.5% corn starch, 8% corn oil, 17% protein) throughout the 120 days experimental period. Results obtained after the experimental period show that the hypertriglyceridemia and glucose intolerance ensuing long term feeding normal rats with a sucrose-rich diet could be completely reversed mediating no change in circulating insulin levels by shifting the source of fat in the diet from corn oil to cod liver oil. These findings suggest that manipulation of dietary fats may play a role in the management of the lipid disorders associated with glucose intolerance and insulin resistance.


Manufacturing a Bone Marrow-On-A-Chip Using Maskless Photolithography.
The bone marrow (BM) is a complex microenvironment in which hematopoietic stem and progenitor cells (HSPCs) interact with multiple cell types that regulate their quiescence, growth, and differentiation. These cells constitute local niches where HSPCs are confined and subjected to specific set of physical and biochemical cues. Endothelial cells forming the walls of blood capillaries have been shown to establish a vascular niche, whereas osteoblasts lying along the bone matrix organize the endosteal niche with distinct and specific impact on HSPC fate. The observation of the interaction of HSPCs with niche cells, and the investigation of its impact on HSPCs behavior in vivo is hindered by the opacity of the bone matrix. Therefore, various experimental strategies have been devised to reconstitute in vitro the interaction of HSPCs with distinct sets of BM-derived cells. In this chapter, we present a method to manufacture a pseudo BM-on-a-chip with separated compartments mimicking the vascular and the endosteal niches. Such a configuration with connected but distant compartments allowed the investigation of the specific contribution of each niche to the regulation of HSPC behavior. We describe the microfabrication of the chip with a maskless photolithography method that allows the iterative improvement of the geometric design of the chip in order to optimize the adaptation of the multicellular architecture to the specific aim of the study. We also describe the loading and culture of the various cell types in each compartment.


Balance between community assembly processes mediates species coexistence in agricultural soil microbiomes across eastern China.
Revealing the linkages between community assembly and species coexistence, which is crucial for the understanding of ecosystem diversity and functioning, is a fundamental but rarely investigated subject in microbial ecology. Here we examined archaeal, bacterial, and fungal community assembly in adjacent pairs of maize (water-unsaturated) and rice (water-saturated) fields across different habitats and regions throughout Eastern China. The high-throughput sequencing dataset was analyzed by variation partitioning, null model, and neutral community model analyses. We demonstrated that microbial community assembly was governed more by species sorting than by dispersal limitation in maize fields, and to a lesser extent in rice fields. The relative importance of species sorting in maize soils was greater at low latitudes than at high latitudes, while rice soils exhibited an opposite trend. Microbial co-occurrence associations tended to be higher when communities were primarily driven by dispersal limitation relative to species sorting. There were greater community dissimilarities between maize and rice soils in low-latitude regions, which was consistent with the higher proportion of negative edges in the correlation networks. The results indicate that a balance between species sorting and dispersal limitation mediates species coexistence in soil microbiomes. This study enhances our understanding of contemporary coexistence theory in microbial ecosystems.


Use of intravoxel incoherent motion imaging to monitor a rat kidney chronic allograft damage model.
Chronic allograft damage (CAD) is the leading cause of long-term graft dysfunction. A noninvasive method that can diagnose CAD early and monitor its development is needed. Kidneys from Fisher rats were transplanted into Lewis rats to establish a CAD model (n = 20). The control group underwent syngeneic kidney transplantation (n = 20). The serum creatinine of the rats was monitored. At 4, 12, and 20 weeks after modeling, a magnetic resonance imaging (MRI) examination was performed. The apparent diffusion coefficient (ADC), pseudo diffusion coefficient (D*), true diffusion coefficient (D) and perfusion fraction (f) of the two groups were analyzed. Chronic allograft damage index (CADI) scoring was used to evaluate the transplanted kidney specimens. Immunohistochemistry was used to detect the expression of fibrosis markers in the transplanted kidney tissues and to analyze their correlations with all MRI parameters. The transplanted kidneys in the experimental group developed CAD changes before the appearance of elevated creatinine. The MRI parameters in the experimental group [ADC (1.460 ± 0.109 VS 2.095 ± 0.319, P < 0.001), D (1.435 ± 0.102 VS 1.969 ± 0.305, P < 0.001), and f (26.532 ± 2.136 VS 32.255 ± 4.013, P < 0.001)] decreased, and D* (20.950 ± 2.273 VS 21.415 ± 1.598, P = 0.131) was not significantly different from those in the control group. ADC, D and f were negatively correlated with the CADI and the α-SMA and vimentin expression levels. Intravoxel incoherent motion (IVIM) imaging could detect CAD earlier than creatinine and reflect the degree of fibrosis in grafts quantitatively.


Simultaneous determination of dysprosium and iron in urine by capillary zone electrophoresis coupled to cloud point extraction.
Automated preconcentration strategies are needed when analyzing metals in real samples by capillary electrophoresis (CE) with UV detection. The on-line incorporation of cloud point extraction (CPE) to flow injection analysis (FIA) associated with CE for simultaneously determining dysprosium and iron at ppb levels in urine is presented and evaluated for the first time. The preconcentration step is mediated by micelles of the non-ionic surfactant polyethyleneglycol-mono-p-nonylphenylether (PONPE 7.5) with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol. The micellar system containing the complex was loaded into the FIA manifold at a flow rate of 8 mlmin(-1), and the surfactant rich-phase was retained in a microcolumn packed with cotton, at pH 9.2. The surfactant-rich phase was eluted with 50 microl acetonitrile directly into the CE sample vial, allowing to reach an enrichment factor of 200-fold for a 10 ml sample urine. The type and composition of the background electrolytes (BGE) were investigated with respect to separation selectivity, reproducibility and stability. A BGE of 20mM sodium tetraborate buffer containing 13% acetonitrile, pH 9.0 was found to be optimal for the separation of metal chelates. Detection was performed at 585 nm. An enhancement factor of 200 was obtained for the preconcentration of 10 ml of sample solution. The detection limits for the preconcentration of 10 ml of urine were 0.20 microgl(-1) for Dy, and. 0.48 microgl(-1) for Fe. The calibration graphs using the preconcentration system were linear with a correlation coefficient of 0.9989 (Dy) and 0.9976 (Fe) at levels near the detection limits up to at least 500 microgl(-1). The method was successfully applied to the determination of dysprosium and iron in urine for monitoring the elimination of dysprosium-based pharmaceuticals.


Detection of cytomegalovirus infection during clinical trials of glycoprotein B vaccine.
Preabsorption of sera with cytomegalovirus (CMV) glycoprotein B (gB) prior to testing for CMV IgG antibody was evaluated for detection of CMV infection during CMV gB vaccine clinical trials. Although, 98.2% of 109 CMV gB vaccine recipients were seropositive with a standard assay, preabsorption of sera with gB reduced their CMV antibody to extremely low levels compared with subjects with CMV infection. One subject who acquired CMV during a vaccine trial was easily identified by gB-absorbed CMV IgG results. The gB-absorbed CMV IgG antibody assay is a promising approach for screening CMV gB vaccine trial participants for CMV infection.


Aluminum-free low-modulus Ti-C composites that exhibit reduced image artifacts during MRI.
Feasibility studies were performed to determine the suitability of a novel synthesis technique for fabricating multifunctional composite materials for orthopedic implants. By blending paramagnetic Ti powder with diamagnetic graphite and consolidating the resulting mixtures, Ti-C composites that cannot be feasibly obtained via conventional alloying techniques or ingot metallurgy were synthesized. The synthesized composite material exhibited extremely low magnetic susceptibility (χ=67.6×10(-6)), and, as a result, exhibited fewer artifacts during magnetic resonance imaging. The strength of the composite material (σ=770MPa) was such that it could support external loads to which the human body is subjected, but its Young's modulus was low (E=81.9 GPa) such that it could mitigate the stress-shielding effect. The material was also free from toxic elements such as Al and V and, thus, can be considered less harmful.


Influence of neuroglial transport on the action of gamma-aminobutyric acid on mammalian ganglion cells.
1 The effect of inhibiting the transport of gamma-aminobutyric acid (GABA) by neuroglial cells on the depolarizing action of exogenous amino acids on isolated superior cervical ganglia of the rat was studied. 1 Transport (measured by uptake of [3H]-GABA) was inhibited by (a) reducing external [na+] from 143 to 2mM and (b) administering alternative carrier-sbustrates, 3-amino-n-butyric acid (beta-amino-butyric acid, BABA) and (+/-)-nipecotic acid at a concentration of 1 mM. 3 All three procedures enhanced the depolarization produced by low concentrations of GABA (less than or equal to 10 muM) but did not alter the maximum response, nor the response to 3-aminopropanesulphonic acid (a gabamimetic with low affinity for the neuroglial carrier). 4 It is concluded that the neuroglial uptake process can limit the action of exogenous GABA upon neurones, by reducing the interstitial GABA concentration.


Effects of low central venous pressure during preanhepatic phase on blood loss and liver and renal function in liver transplantation.
Although the low central venous pressure (LCVP) technique is used to decrease blood loss during liver resection, its efficacy and safety during transplant procedures are still debatable. Our study aimed to assess the effects of this technique and its clinical safety for recipients undergoing liver transplantation. Eighty-six adult patients were randomly divided into a LCVP group and a control group. In the LCVP group, CVP was maintained below 5 mmHg or 40% lower than baseline during the preanhepatic phase by limiting infusion volume, manipulating the patient's posture, and administration of somatostatin and nitroglycerine. Recipients in the control group received standard care. Hemodynamics, blood loss, liver function, and renal function of the two groups were compared perioperatively. A lower CVP was maintained in the LCVP group during the preanhepatic phase, resulting in a significant decrease in blood loss (1922 +/- 1429 vs. 3111 +/- 1833 ml, P < 0.05) and transfusion volume (1200 +/- 800 vs. 2400 +/- 1200 ml, P < 0.05) intraoperatively. Compared with the control group, the LCVP group had a significantly lower mean arterial pressure at 2 h after the start of the operation (74 +/- 11 vs. 84 +/- 14 mmHg, P < 0.05), a lower lactate value at the end of the operation (5.9 +/- 3.0 vs. 7.2 +/- 3.0 mmol/l, P < 0.05), and a better preservation of liver function after the declamping of the portal vein. There were no significant differences in perioperative renal function and postoperative complications between the groups. The LCVP technique during the preanhepatic phase reduced intraoperative blood loss, protected liver function, and had no detrimental effects on renal function in LT.


Climate of conspiracy: A meta-analysis of the consequences of belief in conspiracy theories about climate change.
Despite widespread scientific consensus on climate change, conspiracy theories about its causes and consequences are flourishing. In response, psychological research has started to investigate the consequences of espousing conspiracy beliefs about climate change. Although some scholars maintain that the evidence for a causal link between belief in conspiracy theories and behavior remains elusive, others have argued that climate change conspiracy theories undermine pro-climate action. To shed further light on this question across a range of outcome measures, we present a meta-analysis of 22 independent samples (Nparticipants = 20,765). Overall, we find clear evidence that climate conspiracy beliefs have moderate-to-large negative correlations with not only acceptance of (climate) science, trust, and pro-environmental concern, but also with behavioural intentions and policy support. Most of these effects were not moderated by design (experimental vs. correlational), political ideology, or prior conspiracy beliefs. However, we note publication bias and in several cases sufficient experimental data were lacking. Implications for addressing conspiracy theories about climate change are discussed.


Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin-ceramide pathway in human macrophages.
Exposure of human blood monocytes derived macrophages to modified (oxidized or acetylated) LDL induced a approximately 40% elevation (60 pmol/10(6) cells) of the endogenous level of the sphingolipid ceramide. A rise of both neutral and acidic SMase activity was found after treatment with oxidized LDL (250 and 80%), while addition of acLDL stimulated only the neutral enzyme (280%). Sphingo(phospho)lipids from LDL were transferred to the cell membrane and distributed into intracellular compartments as observed with acLDL containing BODIPY-FL-C5-SM. Quantitation of ceramide after the addition of [3H-N-acetyl]- or BODIPY-FL-C5-SM-labeled modified LDL (27 microg/ml) to the cell culture medium indicated that approximately 210 pmol CA/10(6) cells was generated from exogenous (ox/acLDL) SM. These results demonstrate a stimulation of the sphingomyelin-ceramide pathway by modified LDL utilizing primarily exogenous (LDL-derived) substrate and suggest that the effects of modified LDL are at least partially due to an increased level of the messenger ceramide.


Bone stress for a mini-implant close to the roots of adjacent teeth--3D finite element analysis.
This study aimed to evaluate stress in the bone when an orthodontic mini-implant is close to the roots of adjacent teeth using finite element models (FEMs), and to investigate the causes of the high implant failure rate in the mandible. Four FEMs were used: the implant touches nothing; the implant touches the surface of the periodontal membrane; part of the screw thread is embedded in the periodontal membrane; and the implant touches the root. The effect of cortical bone thickness was evaluated using values of 1, 2 and 3 mm. Maximum stress value and stress distribution on the bone elements was determined. Maximum stress on the bone increased when the mini-implant was close to the root. When the implant touched the root, stress increased to 140 MPa or more, and bone resorption could be predicted. Stress was higher for a cortical bone thickness of 2 mm than for other thicknesses. Cortical bone 2 mm thick had a higher risk for bone resorption. A mandible with an average cortical bone thickness of 2 mm may have a higher risk for implant loosening than a maxilla with the same degree of root proximity, which may be related to the lower success rate in the mandible.


Allele distribution of 15 STR loci used for human identity purposes in the Greek Cypriot population of the island of Cyprus.
Allele frequencies for 15 STRs (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, THO1, Penta E, D16S539, CSF1PO, Penta D and TPOX) in the PowerPlex-16 System (Promega Corporation) were derived from a sample of 1475 unrelated Greek Cypriot individuals from the island of Cyprus.


Herpes-Simplex-Virus 1 pneumonia in the immunocompromised host: high-resolution CT patterns in correlation to outcome and follow-up.
To identify the high-resolution CT (HRCT) patterns of Herpes-Simplex-Virus 1 (HSV) pneumonia in immunocompromised patients and correlate findings to outcome and radiographic follow-up until death or complete resolution of findings. HRCT data-sets and plain radiographic follow-ups were reviewed in 25 immunocompromised patients with confirmation of new onset HSV-1 pneumonia. Pattern and distribution of abnormalities was assessed by two chest radiologists and findings evaluated regarding outcome and dynamics. The most frequent CT abnormalities included ground-glass attenuation (n=18; 72%) in a bilateral, symmetric and random distribution, air-space consolidations (n=13; 52%) in a bilateral, asymmetric and peribronchial allocation and interlobular septal thickening (n=6; 24%). When classified by leading HRCT pattern, patients subdivided into distinct groups with either dominant ground-glass attenuation or air-space consolidation. Six patients died after a median 8 days of diagnosis; the median interval until complete radiographic remission of pathology was 20 days. Pre-dominance of air-space consolidations was associated with significant delay of improvement (p=0.023); however, patient outcome was comparable in both subgroups (p=0.9). Diagnosis of HSV pneumonia is challenging and requires familiarity with two distinct HRCT patterns: predominance of ground-glass opacities or air-space consolidations. Whilst the two forms are not linked to patient outcome they demonstrate a variable dynamic at follow-up.


A novel human anti-BAFF neutralizing monoclonal antibody derived from in vitro immunization.
B-cell activating factor (BAFF) plays a key role in the normal regulation of B cell development and immune response. Its abnormal expression level is accompanied by the occurrence of various autoimmune diseases. Therefore, BAFF is an effective target for the treatment of such diseases. Here, we report a new anti-BAFF monoclonal antibody. Based on improved in vitro immunization method, we used a recombinant BAFF containing unnatural amino acid p-nitro-phenylalanine (pNO2Phe) as an antigen to trigger immune response in vitro. The plasma cells were sorted by flow cytometry (FACS), and the antibody library was constructed based on the sorted plasma cells. The high affinity antigen-binding fragments were panned by phage display technology, and finally the anti-BAFF human IgG was obtained. The antibody demonstrated its ability to neutralize BAFF effectively both in vitro and in vivo. We propose that this novel full-length human anti-BAFF monoclonal antibody is a promising therapeutic candidate for the treatment of autoimmune diseases.


Open government data: A systematic literature review of empirical research.
Open government data (OGD) holds great potential for firms and the digital economy as a whole and has attracted increasing interest in research and practice in recent years. Governments and organizations worldwide are struggling in exploiting the full potential of OGD and require a comprehensive understanding of this phenomenon. Although scientific debates in OGD research are intense and heterogeneous, the field lacks theoretical integration of OGD topics and their systematic consideration in the context of the digital economy. In addition, OGD has been widely neglected by information systems (IS) research, which promises great potential for advancing our knowledge of the OGD concept and its role in the digital economy. To fill in this gap, this study conducts a systematic literature review of 169 empirical OGD studies. In doing so, we develop a theoretical review framework of Antecedents, Decisions, Outcomes (ADO) to unify and grasp the accumulating isolated evidence on OGD in context of the digital economy and provide a theory-informed research agenda to tap the potential of IS research for OGD. Our findings reveal six related key topic clusters of OGD research and substantial gaps, opening up prospective research avenues and particularly outlining how IS research can inform and advance OGD research. The online version contains supplementary material available at 10.1007/s12525-022-00582-8.


Associative learning deficits increase symptoms of anxiety in humans.
Unpredictability has been postulated to be fundamental to anxiety and mood disorders. The origin of this unpredictability remains obscure. Because classical conditioning promotes predictability, this study investigated whether failure to learn conditioned stimulus (CS)-unconditioned stimulus (US) relationship during fear conditioning increased anxiety and avoidance. Healthy subjects participated in two similar differential fear conditioning sessions separated by 1 week (n = 72) or a month (n = 61) in which one of two conditioned stimuli was associated with a shock/US. Following initial acquisition, subjects' awareness of CS-US relationship was assessed. Conditioned responses (CR) to the CS and to the experimental context were examined using the startle reflex and the skin conductance. Avoidance was operationally defined as failure to return for the second session. Only aware subjects showed differential CR. In the unaware subjects, the deficit in differential conditioning was associated with increased signs of anxiety during the first and second sessions. In addition, there was greater avoidance in the unaware subjects. Deficits in explicit cue fear conditioning can enhance anxiety. These findings are consistent with theories that associate anxiety and mood disorders with perceived unpredictability. Contextual conditioning models may be relevant to study chronic forms of anxiety.


[Long-term prognosis in patients with rheumatoid arthritis depending on baseline variability of cardiac rhythm].
The study of outcomes of rheumatoid arthritis (RA) depending on cardiac rhythm variability (CRV). A total of 78 patients with RA of I--III degree of activity aged 38-83 years (mean age 60.3 +/- 10.8 years) were examined using 24-h AP and ECG monitoring. Follow-up was 2-4 years. A clear correlation was seen between RA activity and CRV. In patients with high activity of RA, CRV decline reflect severity of inflammation. In low RA activity, low CRV may point to the presence of IHD. Low CRV in RA activity of degree I-II may indicate high risk of sudden cardiac death and acute myocardial infarction within 2-4 years.


SSH-EPI diffusion-weighted MR imaging of the spine with low b values: is it useful in differentiating malignant metastatic tumor infiltration from benign fracture edema?
Conventional MR sequences are sometimes not helpful in differentiating benign from pathologic fractures. Our aim was to evaluate the usefulness of single-shot echo-planar imaging sequences (diffusion-weighted imaging (DWI)/SSH-EPI) with low b value in differentiating malignant metastatic tumor infiltration of vertebral bone marrow from benign vertebral fracture edema. A total of 47 patients, 20 with benign fractures and 27 with tumor infiltration, were included in this prospective study. Diffusion-weighted MR images were obtained by single-shot echo-planar imaging technique with diffusion gradient (b = 300 s/mm2; TR/TE, 1,400/100), using a 1.5 T MR scanner. T1- and T2-weighted images and short inversion time inversion-recovery images were available for all 64 lesions. The lesions on DWI/SSH-EPI were categorized as having hypo-, iso-, or hyperintense signal intensity relative to normal vertebrae by two experienced radiologists. We evaluated signal intensity patterns on DWI/SSH-EPI in 64 lesions, which showed low signal intensity on T1-weighted images in both benign fractures and metastasis. With the exception of sclerotic metastases in two patients, malignant metastatic tumor infiltration was hyperintense with respect to normal bone marrow on diffusion-weighted images; all but four benign vertebral fractures were isointense with respect to normal bone marrow. Single-shot echo-planar imaging sequences (DWI/SSH-EPI) with low b value provided excellent distinction between metastatic tumor infiltration and benign vertebral fracture edema. Hyperintense signal intensity on DWI/SSH-EPI was highly specific for the diagnosis of metastatic tumor infiltration of the spine.


[Necrotizing fasciitis of the neck: diagnosis by computer tomography].
Necrotizing fasciitis is a rare but serious infection of subcutaneous tissue and deep fascia with resulting skin gangrene and septicaemia. Compute tomography (CT) seems to play a role in completing the clinical suspicion, especially in those case in which the disease does not manifest itself with subcutaneous crepitus or emphysema. Condition's causation reminded unknown and the microbial culture showed members of Streptococcus milleri genus.


Surface electric field manipulation of the adsorption kinetics and biocatalytic properties of cytochrome c on a 3D macroporous Au electrode.
Upon adsorbing on a solid-state substrate, water-soluble proteins are prone to denaturation and deterioration of their functions due to the conformation change. The surface electric field of a conductive substrate is one of the important factors that influence the character of adsorbed proteins. In this work, a 3D macroporous gold electrode has been prepared and served as the working electrode to study the influence of surface electric field on the adsorption kinetics and conformation of the adsorbed cytochrome c (cyt-c) with the help of electrochemical, in situ electrochemical IR spectroscopic, atomic force microscopic, and contact angle measurements. The external electric field creates excess surface charge which can manipulate the adsorption rate of proteins on the substrate by the enhanced electrostatic interactions between the electrode and protein patches by coupling with complementary charges. The amount of immobilized cyt-c with electrochemical activity on the 3D macroporous gold electrode showed a minimum at potential of zero charge (PZC) and it increased with increasing net excess surface charge. Higher electric field could influence the conformation and the corresponding properties such as direct electrochemistry, bioactivity, and surface character of the adsorbed cyt-c molecules. However, high external electric field leads to damage of the protein secondary structure. This study provides fundamentals for the fabrication of biomolecular devices, biosensors, and biofuel cells through electrostatic interactions. [figure: see text] Two cases are illustrated for the protein immobilized on electrode surfaces: a retention of protein structure under moderate excess surface charge, b denaturation and conformation change of proteins adsorbed at high excess surface charge, e.g., due to the higher external electric field.


The Effectiveness of Prophylactic Modified Neck Dissection for Reducing the Development of Lymph Node Recurrence of Papillary Thyroid Carcinoma.
The most frequent recurrence site of papillary thyroid carcinoma (PTC) is the cervical lymph nodes. The introduction of an electric linear probe for use with ultrasonography in 1996 improved preoperative lateral neck evaluations. Before 2006, however, our hospital routinely performed prophylactic modified neck dissection (p-MND) for N0 or N1a PTCs >1 cm to prevent node recurrence. In 2006, we changed our policy and the indications for p-MND to PTCs >3 cm and/or with significant extrathyroid extension. Here, we retrospectively compared lymph node recurrence-free survival between PTCs with/without p-MND. We examined the cases of N0 or N1 and M0 PTC patients who underwent initial surgery in 1992-2012. To compare lymph node recurrence-free survival between patients who did/did not undergo p-MND, we divided these patients into three groups (excluding those whose surgery was in 2006): the 2045 patients whose surgery was performed in 1992-1996 (Group 1), the 2989 with surgery between 1997 (post-introduction of ultrasound electric linear probes) and 2005 (Group 2), and the 5332 operated on in 2007-2012 (Group 3). The p-MND performance rate of Group 3 (9%) was much lower than that of Group 1 (80%), but the lymph node recurrence-free survival of the former was significantly better, probably due to differences in clinical features and neck evaluations by ultrasound between the two groups. Our analysis of the patients aged <75 years with 1.1-4-cm PTCs in Groups 2 and 3 showed that p-MND did not improve lymph node recurrence-free survival. p-MND did significantly improve lymph node recurrence-free survival for the extrathyroid extension-positive 3.1-4-cm PTCs, but not for the other subsets. Abolishing routine p-MND for PTCs in 2006 did not decrease lymph node recurrence-free survival, probably due to improved ultrasound preoperative neck evaluations and clinical feature changes. Selective p-MND for high-risk cases improved lymph node recurrence-free survival.


Sexual function following sphincteroplasty for women with third- and fourth-degree perineal tears.
Our goal was to evaluate sexual function following anal sphincteroplasty in women with third and fourth degree perineal tears secondary to birth trauma Our study was performed using a retrospective cohort design in a group of women (n = 32) who had experienced either third-degree or fourth-degree perineal tears during labor and then elected to undergo sphincteroplasty for fecal incontinence. We surveyed our patients with a questionnaire that was developed by the Obstetrics and Gynecology Epidemiology Center at Harvard Medica School and was previously used to survey women with obstetric injuries. Self-reported presphincteroplasty and post sphincteroplasty degree of physical sensation, sexual satisfaction, and likelihood of achieving orgasm were measured Also measured were libido, partner satisfaction, and presence of emotional or physical inability to engage in sexual behavior. Our results reaffirmed the findings of the Obstetrics and Gynecology Epidemiology Center's study that sexual function is compromised in women with third and fourth-degree perineal tears. For our patients with this degree of perineal tearing who underwent sphincteroplasty after primary repair, our survey showed consistent improvement in several parameters of sexual function. After sphincteroplasty, physical sensation was higher/much higher in 40 percent, sexual satisfaction was better/much better in 33.3 percent, and 28.6 percent of the patients were more/much more likely to reach orgasm. Libido was improved in 37.5 percent of the study population, and 20 percent reported increased partner satisfaction. Before surgery, 23.5 percent of patients were physically and 31.2 percent emotionally unable to participate in sexual activity because of fear of incontinence or intimacy; after surgery only 6.3 percent were physically unable and 0 percent were emotionally unable to engage in sexual activity. The response rate for our study was 18/32 (56 percent). Anal sphincteroplasty for the treatment of incontinence in women with third- and fourth-degree perineal tears improves physical and emotional sexual well-being and function.


Diagnosis of multiple sclerosis in times of MOG and AQP4 autoantibody testing - A monocentric study.
Myelin oligodendrocyte glycoprotein-IgG-associated encephalomyelitis (MOG-EM) and neuromyelitis optica spectrum disorders are challenging differential diagnoses of multiple sclerosis (MS). Hence, there is uncertainty, whether to test all MS patients for corresponding antibodies. Our objective was to provide a systematic study on the frequency of MOG and Aquaporin-4 (AQP4) autoantibodies in MS patients to evaluate a possible risk of misclassification. Retrospective study in MS patients (including an unselected cohort of patients diagnosed with MS, a cohort of patients with PPMS and a healthy control group) for seroprevalence of MOG and AQP4 autoantibodies by cell-based assay. None of 241 patients with relapsing-remitting, 19 with secondary progressive and 82 with primary progressive MS revealed MOG or AQP4 autoantibodies. General testing of MOG and AQP4 autoantibodies in MS patients seems not necessary, but should be limited to selected cases only.


T-lymphocyte development and models of thymopoietic reconstitution.
T-cell development occurs in the thymus and involves a complex stepwise differentiation process from hematopoietic progenitor cell through to the emergence of positively selected, non-self reactive naïve T cells, which emigrate from the organ into the blood stream. This process takes place in the three-dimensional context of a delicate latticework of thymic stromal cells, including epithelial-derived cells and dendritic cells that assist in the development of the mature T cell. The details of the steps in T-cell development are now more comprehensively understood and furthermore in vitro systems are in development to reiterate this process in vitro. The clinical impact of this work is clearly the understanding of immune reconstitution in immune compromised patients (e.g., those with HIV/AIDS or post transplantation) and the development of novel techniques for regenerating the spectrum of T-cell function in these individuals.


The 13 item Family Support Scale: Reliability and validity of the Greek translation in a sample of Greek health care professionals.
The Julkunen Family Support Scale aims to record the sense of support that a subject receives from the members of his family. The object of the present study was to investigate the reliability and to assess the validity of the Greek translation of the Julkunen Family Support Scale in Greek health care professionals in a public general hospital. In order to determine the indicator of validity of content we addressed nine expert professionals and one sociologist, asking them to evaluate how much relevant to the sense of familial support are the items of the questionnaire. Additionally, to assess reliability we used a sample of health care professionals. There was agreement among experts for the validity of content. Cronbach's alpha for the total items was 0.820, pointing to high validity. Only replacing item four could increase the scale's validity, but without significant differences. The scale, in its Greek version, appears to be a brief and reliable tool that can be used for inpatients, in clinics as well as in epidemiologic studies of received family support.


Profiling protein expression in Klebsiella pneumoniae with a carbohydrate-based covalent probe.
We report the application of a covalent probe based on a d-glucosamine scaffold for the profiling of the bacterial pathogen Klebsiella pneumoniae. Incubation of K. pneumoniae lysates with the probe followed by electrophoretic separation and in-gel fluorescence detection allowed the generation of strain-specific signatures and the differentiation of a carbapenem-resistant strain. The labelling profile of the probe was independent of its anomeric configuration and included several low-abundance proteins not readily detectable by conventional protein staining. Initial target identification experiments by mass spectrometry suggest that target proteins include several carbohydrate-recognising proteins, which indicates that the sugar scaffold may have a role for target recognition.


Metabolomics reveals the phytotoxicity mechanisms of foliar spinach exposed to bulk and nano sizes of PbCO3.
PbCO3 is an ancient raw material for Pb minerals and continues to pose potential risks to the environment and human health through mining and industrial processes. However, the specific effects of unintentional PbCO3 discharge on edible plants remain poorly understood. This study unravels how foliar application of PbCO3 induces phytotoxicity by potentially influencing leaf morphology, photosynthetic pigments, oxidative stress, and metabolic pathways related to energy regulation, cell damage, and antioxidant defense in Spinacia oleracea L. Additionally, it quantifies the resultant human health risks. Plants were foliarly exposed to PbCO3 nanoparticles (NPs) and bulk products (BPs), as well as Pb2+ at 0, 5, 10, 25, 50, and 100 mg·L-1 concentrations once a day for three weeks. The presence and localization of PbCO3 NPs inside the plant cells were confirmed by TEM-EDS analysis. The maximum accumulation of total Pb was recorded in the root (2947.77 mg·kg-1 DW for ion exposure), followed by the shoot (942.50 mg·kg-1 DW for NPs exposure). The results revealed that PbCO3 and Pb2+ exposure had size- and dose-dependent inhibitory effects on spinach length, biomass, and photosynthesis attributes, inducing impacts on the antioxidase activity of CAT, membrane permeability, and nutrient elements absorption and translocation. Pb2+ exhibited pronounced toxicity in morphology and chlorophyll; PbCO3 BP exposure accumulated the most lipid peroxidation products of MDA and H2O2; and PbCO3 NPs triggered the largest cell membrane damage. Furthermore, PbCO3 NPs at 10 and 100 mg·L-1 induced dose-dependent metabolic reprogramming in spinach leaves, disturbing the metabolic mechanisms related to amino acids, antioxidant defense, oxidative phosphorylation, fatty acid cycle, and the respiratory chain. The spinach showed a non-carcinogenic health risk hierarchy: Pb2+ > PbCO3 NPs > PbCO3 BPs, with children more vulnerable than adults. These findings enhance our understanding of PbCO3 particle effects on food security, emphasizing the need for further research to minimize their impact on human dietary health.


Studies on the respiratory enzymes of the adrenal gland. I. The medulla.
In contrast to the thoroughness with which the respiratory enzymes of such tissues as heart muscle and liver have been studied, information concerning these enzymes in the adrenal gland is scant. Such information as is available suggests that an unusual pattern for the cytochromes exists in this tissue. Cohen and Elvehjem (2) commented on the "peculiar cytochrome spectrum"of the adrenal medulla of the cow. They concluded that a very strong cytochrome c component was present, and that cytochrome a and 6 were absent. Huszák (3) noted that the adrenal cortex possessed a nearly normal cytochrome pattern. In the medulla he could observe no cytochrome a or c bands, but reported a strong band in the region of 559 rnp which he attributed to cytochrome 5. Since Huszák could demonstrate no cytochrome oxidase activity in the medulla, he felt that oxidation of substrates proceeded by way of a peroxidative mechanism. Tsou (4), on the other hand, was able to demonstrate cytochrome oxidase activity in the medulla, but little if any cytochrome c. He observed the presence of a strong band at 561 millimicron which was referred to as cytochrome b. In view of these divergent conclusions and in the light of newer methods and knowledge, it seemed worth-while to reinvestigate some of the oxidative pathways in the adrenal gland. The present study deals with the adrenal medulla, and an accompanying paper deals with the cortex (5). It will be shown here that the adrenal medulla contains the regular mitochondrial cytochrome system. In addition, this tissue contains a hemochromogen which is apparently microsomal in origin and is abundantly present in the epinephrine-containing granules. The presence in the medulla of the enzymes succinate dehydrogenase,reduced di- and triphosphopyridine nucleotide-cytochrome c reductase,and transhydrogenase is also demonstrated.


Effects of presenting risk information in different formats to cardiologists. A Latin American survey.
Previous publications demonstrated that the presentation of treatment benefits in terms of relative risk reduction (RRR) rather than in terms of absolute risk reduction (ARR) or number of patients to treat (NNT) might favor the perception of outcome effectiveness. The objective was to perform a cognitive evaluation to assess how the manner in which risks and benefits of screening methods and treatments are presented can affect medical care decision-taking in a sample of cardiologists. Four-hundred and six Latin American cardiologists answered a questionnaire reporting the results of clinical trials presented as RRR, ARR or NNT, associated or not to biased graphs. Cardiologists' decision-taking was different when comparing treatment benefits presented as RRR (62.2%) vs. ARR (40.4%) (p=0.000000), and as RRR vs. NNT (44.4%) (p=0.000000). However, their decision-taking was similar when information was presented as NNT or ARR (p=0.073). The inclusion of biased graphs was misinterpreted as an actual data difference (RRR: 61.6% vs. ARR: 14.0%, p=0.000000). This study demonstrated that Latin American cardiologists could misinterpret statistical data when information of clinical trials is presented in terms of RRR. We emphasize the need to enhance cardiologists' training in quantitative techniques, to improve medical care decision-making.


Is nipple sparing mastectomy associated with increased complications, readmission and length of stay compared to skin sparing mastectomy?
We sought to determine rates of complications, reoperation, and length of stay (LOS) between nipple-sparing (NSM) and skin-sparing (SSM) mastectomy patients, hypothesizing that rates would be higher in the former. Patients undergoing NSM or SSM at our institution between January 1, 2010 and December 31, 2017 were compared. 217 patients underwent NSM; 581 underwent SSM. NSM patients were more likely to be younger, with private insurance, lower BMI, lighter breasts, have bilateral mastectomy, with implant-based reconstruction, for BRCA, and/or lower stage disease and were less likely to have diabetes, axillary dissection, and/or neoadjuvant therapy. Controlling for these factors, NSM patients had a higher complication rate than SSM patients (OR: 1.822; 95% CI: 1.163-2.853, p = 0.009). Length of stay and reoperation rates were not significantly different between the two groups. NSM and SSM patients have similar reoperation rates and LOS; however, complication rate is higher in NSM patients.


Computer assisted tomography in neuropsychological research: a simple procedure for lesion mapping.
A simple procedure for mapping the brain lesions observed on the CT scan sections onto a standard diagram of the cerebral hemisphere is described in detail, and its utility for neuropsychological research is briefly discussed.


Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death.
Quantum dots (QDs) are luminescent nanoparticles with unique optical properties that have been exploited for single-cell and whole-animal imaging. When coated with proteins or biocompatible polymers, QDs are not deleterious to cells and organisms. However, when QDs are retained in cells or accumulated in the body for a long period of time, their coatings may be degraded, yielding "naked" QDs. Here, we show that "naked" QDs induce damage to the plasma membrane, mitochondrion, and nucleus, leading to cell death. Reactive oxygen species (ROS) are important players in mediating QD-induced cellular damage. QD-induced cytotoxicity can be reduced or even eliminated without covalent binding of protective agents to the QD surface. Results from these studies suggest the critical role of several subcellular compartments in QD-induced cytotoxicity and point toward multiple molecular targets in nonclassical apoptosis.


Imatinib-induced hepatotoxicity via oxidative stress and activation of NLRP3 inflammasome: an in vitro and in vivo study.
Imatinib (IM), a milestone drug used in the field of molecular targeted therapy, has been reported to cause serious adverse liver effects, including liver failure and even death. Immune-mediated injury and mitochondrial dysfunction are involved in drug-induced liver injury. However, the mechanism of IM-induced hepatotoxicity remains unclear and warrants further study. In our study, Sprague Dawley rats were administered IM by gavage with 50 mg/kg body weight (BW) once daily for 10 days. Drug-induced liver injury accompanied by inflammatory infiltration was observed in rats following IM exposure, and the expression of NOD-like receptor protein 3 (NLRP3) inflammasome-related proteins was significantly increased compared with that of the control. HepG2 cells were exposed to 0-100 μM IM for 24 h. The results showed that IM decreased cell viability in a dose-dependent manner. Moreover, IM induced a state of obvious oxidative stress and activation of nuclear factor kappa B (NF-κB) in cells, which resulted in the activation of NLRP3 inflammasomes, including caspase 1 cleavage and IL-1β release. These results were significantly reduced after the use of the antioxidants N-acetyl-l-cysteine or the NF-κB inhibitor pyrrolidine di-thio-carbamate. Furthermore, NLRP3 knockdown significantly reduced the release of inflammatory cytokines and improved cell viability. In summary, our data demonstrated that oxidative stress and NLRP3 inflammasome activation are involved in the process of IM-induced hepatotoxicity. The results of this study provide a reference for the prevention and treatment of IM-induced hepatotoxicity.


Nanomedicine and nanoparticle-based delivery systems in plastic and reconstructive surgery.
Nanotechnology and nanomedicine are rising novel fields in plastic and reconstructive surgery (PRS). The use of nanomaterials often goes with regenerative medicine. Due to their nanoscale, these materials stimulate repair at the cellular and molecular levels. Nanomaterials may be placed as components of nanocomposite polymers allowing enhancement of overall biochemical and biomechanical properties with improved scaffold properties, cellular attachment, and tissue regeneration. They may also be formulated as nanoparticle-based delivery systems for controlled release of signal factors or antimicrobials, for example. However, more studies on nanoparticle-based delivery systems still need to be done in this field. Nanomaterials are also used as frameworks for nerves, tendons, and other soft tissues. In this mini-review, we focus on nanoparticle-based delivery systems and nanoparticles targeting cells for response and regeneration in PRS. Specifically, we investigate their roles in various tissue regeneration, skin and wound healing, and infection control. Cell surface-targeted, controlled-release, and inorganic nanoparticle formulations with inherent biological properties have enabled enhanced wound healing, tumor visualization/imaging, tissue viability, and decreased infection, and graft/transplantation rejection through immunosuppression. Nanomedicine is also now being applied with electronics, theranostics, and advanced bioengineering technologies. Overall, it is a promising field that can improve patient clinical outcomes in PRS.


Psychosocial rehabilitation of cancer patients after curative therapy.
The concept of rehabilitation of cancer patients is based on the relatively recent awareness of the strong interrelations existing between physical, psychological and social aspects of human life. Cancer potentially disrupts all of these primary components of quality of life. The aim of rehabilitation is to promote global physical and psychosocial adjustment by acting at all modifiable levels, namely strengthening individual coping resources through psychotherapy, improving quantity and quality of familial and social support, and restoring optimal physical functioning.


Polychlorinated dioxins and dibenzofurans (PCDD/F), polybrominated dioxins and dibenzofurans (PBDD/F), polychlorinated biphenyls (PCB), polybrominated diphenyl ethers (PBDE), and per- and polyfluoroalkyl substances (PFAS) in German breast milk samples (LUPE 8).
Most organic pollutants (POP) are persistent in the environment, accumulate in fatty tissues, and so a transfer through the food chain is probably, thereby causing various health effects. We quantified PCDD/F, PBDD/F, PCB, PBDE, perfluorinated substances, and ADONA in breast milk samples collected in two German federal states and breast milk and blood samples from subjects additionally exposed to PFOA. The median (95th percentile) concentrations were 2.43 (6.58) pgWHO2005TEQ/g l.w. for PCDD/F, 2.45 (4.82) pgWHO2005TEQ/g l.w. for dioxin-like PCB (dl-PCB), and 0.62 (2.69) pgWHO2005TEQ/g l.w. for PBDD/F. The relative contributions of the median values of PCDD/F, dl-PCB, and PBDD/F to the total-TEQ were approximately 41%, 42%, and 11%, respectively. Nondioxin-like PCB (ndl-PCB) concentrations were clearly dominated by the higher chlorinated PCB congeners, with medians of 23.2 ng/g l.w. for PCB 153, 13.9 ng/g l.w. for PCB 138, and 13.0 ng/g l.w. for PCB 180. The sum of the 3 congeners (PCB 138, 153, and 180) were multiplied with 1.64 (total PCB) and showed a median of 82.16 ng/g l.w. and a 95th percentile of 173.3 ng/g l.w. Only PFOA and PFOS could be quantified in 29% and 17% of in total 180 samples with 95th percentiles of 53 ng/l and 33 ng/l, respectively. Milk samples (n = 13) from subjects living on PFOA contaminated sites showed higher levels between 33 and 854 ng/l PFOA (mean: 199 ng/l), whilst PFOS could be quantified only in three samples. The sum of 17 PBDE congeners showed medians (95th percentile) of 1737 pg/g l.w. (22,806 pg/g l.w.), with the highest medians of 422 pg/g l.w. for BDE 209 and 378 pg/g l.w. for BDE 153. Overall, our study confirms the declining contamination level in breast milk during the last decade, but points out the need to further reduce the environmental contamination with persistent substances and subsequently the exposure in childhood.


Advantages of the use of deciduous teeth, hair, and blood analysis for lead and cadmium bio-monitoring in children. A study of 6-year-old children from Krakow (Poland).
The population of about 300 6-year-old preschool children was studied for lead (Pb) and cadmium (Cd) in deciduous teeth, scalp hair, and capillary blood. Zinc (Zn) content in hair was also measured due to its possible interferences with the elements studied. The Pb and Cd contents were measured by graphite furnace atomic absorption spectrometry with Zeeman background correction, and Zn, by flame method. Metal levels found were comparable to those in European countries. Positive correlations between Pb and Cd in the same and different tissues were widespread (r=0.23-0.68). A positive correlation was found between Pb in teeth and blood (r=0.65, p<0.001). Pb blood threshold 100 μg L(-1) referred to 2.6 μg g(-1) Pb in teeth. Predictability of this Pb teeth limit was 14% vs. 5% for Pb blood. Strong negative correlation was found between hair Pb and Zn (r=-0.68, p<0.001). Enhanced Cd and Zn levels in hair were associated with the household drinking water hardness. The associations with some other environmental and behavioral factors were also presented and discussed. The results proved the advantage of analysis of primary teeth for Pb exposure screening of preschool children.


Associations between feeding practices and maternal and child weight among mothers who do and do not correctly identify their child's weight status.
This study aimed to explore factors associated with accuracy of maternal weight perception and determine if maternal feeding practices are associated with weight status. Overweight/obese mothers reported demographics and perception of their child's weight and completed a modified preschooler feeding questionnaire. Mother's and child's height and weight were measured. Logistic regression was used to explore associations between demographic factors and accuracy. Correlations between the preschooler feeding questionnaire scales and mom's body mass index (BMI) and child's BMI-percentile were explored for the total sample and accurate and underestimating moms. Among mothers whose child was overweight or obese, only 20% of mothers correctly identified the child as overweight. Forty percent of moms were underestimaters. There was a positive correlation between concern the child was overweight/overeating and the child's BMI-percentile among underestimating moms; in the total sample (r = 0.32, p < .001) and accurate moms (r = 0.52, p < .001). In underestimaters only, there was a negative relationship between child BMI-percentile and pressure to eat (r = -0.30, p < .001) and concern about child underweight (r = -0.47, p < .001). This study identified different associations between child weight and mother's feeding practices in mothers accurately and inaccurately perceiving her child's weight. Intervention studies should explore targeting education on feeding practices based on these perceptions.


Areal and laminar distribution of gangliosides in the fetal human neopallium at 28 weeks of gestation.
Correlative histological, histochemical and biochemical investigations on laminar compartments from four different areas of fetal human neopallium at 28 weeks of gestation revealed discrete distribution of gangliosides in the cerebral wall. Highest level of total ganglioside concentration was found in the layers of cortical anlage (cortical plate and "subplate layer") which are concomittantly characterized by highest activity of acetylcholinesterase (AChE) and which are known to be involved in intensive synaptogenesis at this stage of cortical development. In three of four areas the proportion of GD1a - ganglioside from total ganglioside amount tended to increase and that of GT1b to decrease from inside (ventricle) to outside (cortical anlage) throughout the cerebral wall.


Identification of the causative gene of a transparent phenotype of juvenile red sea bream Pagrus major.
Deformities in cultured fish species may be genetic, and identifying causative genes is essential to expand production and maintain farmed animal welfare. We previously reported a genetic deformity in juvenile red sea bream, designated a transparent phenotype. To identify its causative gene, we conducted genome-wide linkage analysis and identified two single nucleotide polymorphisms (SNP) located on LG23 directly linked to the transparent phenotype. The scaffold on which the two SNPs were located contained two candidate genes, duox and duoxa, which are related to thyroid hormone synthesis. Four missense mutations were found in duox and one in duoxa, with that in duoxa showing perfect association with the transparent phenotype. The mutation of duoxa was suggested to affect the transmembrane structure and thyroid-related traits, including an enlarged thyroid gland and immature erythrocytes, and lower thyroxine (T4) concentrations were observed in the transparent phenotype. The transparent phenotype was rescued by T4 immersion. Loss-of-function of duoxa by CRISPR-Cas9 induced the transparent phenotype in zebrafish. Evidence suggests that the transparent phenotype of juvenile red sea bream is caused by the missense mutation of duoxa and that this mutation disrupts thyroid hormone synthesis. The newly identified missense mutation will contribute to effective selective breeding of red sea bream to purge the causative gene of the undesirable phenotype and improve seed production of red sea bream as well as provide basic information of the mechanisms of thyroid hormones and its related diseases in fish and humans.


Comparison of plasma exchange procedures using three apheresis systems.
A new protocol for the Amicus separator (Fresenius Kabi) enables the device to perform plasma exchange (PE). The aim of the study was to compare retrospectively the plasma removal efficiency (PRE) of the Amicus, the Optia (TerumoBCT), and the Spectra (TerumoBCT) when performing PEs. We retrospectively reviewed patients who received at least one PE with the Amicus and at least one PE with the Optia, the Spectra, or both. We collected data regarding PRE, volume of anticoagulant and calcium-magnesium (Ca-Mg) solution infused, and changes in laboratory data from patients' blood sampled immediately before starting and immediately after finishing each PE procedure: complete blood count, coagulation, acid-base equilibrium, and biochemistry variables. We also collected severe adverse events (AEs). We performed 18, 44, and 14 PEs with the Amicus, Optia, and Spectra, respectively. We observed significant differences among the Amicus, Optia, and Spectra regarding PRE (79.8 ± 8.2, 82.9 ± 5.8, and 70.4 ± 8.2%; p < 0.001), volume of anticoagulant infused (542 ± 196, 687 ± 120, and 647 ± 111 mL; p = 0.002), volume of Ca-Mg solution infused (81 ± 28, 56 ± 16, and 63 ± 15 mL; p < 0.001), absolute change of ionic Ca (-0.04 ± 0.13, -0.05 ± 0.12, and -0.19 ± 0.16 mmol/L; p = 0.002), and absolute change of Na (1.18 ± 1.97, 1.02 ± 1.93, and 3.71 ± 1.98 mEq/L; p < 0.001). We observed no significant differences in other analytic variables and we observed no severe AEs. The Amicus device could effectively perform PE procedures. In terms of PRE, the Amicus and Optia were similar, but both devices were superior to the Spectra. The Amicus used a lower volume of anticoagulant when compared with the Optia.


Effective sleep apnoea treatment improves cardiac function in patients with chronic heart failure.
Sleep disordered breathing (SDB) is highly prevalent in patients with chronic heart failure (CHF) and is associated with adverse effects on cardiac geometry and function. Continuous positive airway pressure (CPAP) has been proved an effective treatment modality for obstructive sleep apnoea (OSA), whereas adaptive servoventilation (ASV) is more effective in patients with central sleep apnoea (CSA). The impact of selection of therapy and effective apnoea alleviation on cardiac performance and reverse left ventricular remodelling (r-LVR) has not yet been evaluated. Eighty five patients with stable CHF were screened for SDB and underwent polysomnography and treatment according to the type of SDB. Clinical evaluation and a comprehensive echocardiographic study was performed before initiation of therapy and after six months of effective treatment (ventilator use >5h/day with AHI <5 events/h). Seventeen compliant patients under effective treatment were included in the analysis (8 OSA under Autoset CPAP and 9 CSA under ASV). In both groups, a significant improvement in all measured, conventional and TDI LV systolic indexes was recorded, including LVEF (32% ± 6% vs. 27% ± 6%, p<0.001). A decrease in LV end-systolic volume (189 ± 94 ml vs. 211 ± 88 ml, p=0.015, difference >10%) was indicative of r-LVR. Furthermore, RV systolic parameters were also increased (TAPSE, p<0.001; systolic TDI wave from lateral tricuspid annular aspect, p=0.001), whereas right heart dimensions and areas were diminished, indicating better pulmonary haemodynamics. Moreover, a significant improvement in patients' clinical status, as evaluated by New York Heart Association Class was also documented at the end of six months follow-up. Effective alleviation of SDB in CHF patients is associated with significant improvements in LV and RV systolic function and r-LVR. Longitudinal studies are needed to evaluate effects on morbidity and mortality.


Systemic lupus erythematosus in patients with chronic renal failure.
The clinical courses of 36 patients with systemic lupus erythematosus (SLE) in whom chronic renal failure developed and who required dialysis for more than three months were studied. At the time dialysis was initiated, 14 of 36 patients (38.9 percent) had clinically active SLE, but only three of 24 (12.5 percent) had activity in subsequent years while receiving dialysis therapy. In the majority of patients, however, renal disease progressed to end-stage despite clinical quiescence of SLE. During the follow-up period (mean +/- SD, 36 +/- 39.8 months), eight patients died--six from infections and two from cardiac disease. Actuarial survival rates at one, two, and five years after dialysis treatment were 91.1, 78.8, and 68.9 percent, respectively. This study suggests that the progression of renal disease to end-stage in patients with SLE may be mediated by nonimmunologic mechanisms as well as SLE-related immunologic insults. In most of these patients undergoing long-term dialysis, SLE remains clinically inactive despite persistent serologic abnormalities. Survival of the patients undergoing dialysis is comparable with that of the general dialysis population.


Are deficits in executive sub-processes simply reflecting more general cognitive decline in schizophrenia?
Schizophrenia is associated with both global and specific cognitive deficits. We sought to investigate whether deficits in executive subcomponents differed in their relationship to global cognitive impairments. 95 patients were classified according to pre-morbid and current general cognitive ability as having either (a) intact pre-morbid and current general cognitive ability; (b) intact pre-morbid but deteriorated current ability, and (c) deteriorated both pre-morbid and current cognitive ability. All patients completed measures of verbal and spatial working memory, sustained selective attention, attentional set sifting, and inhibitory control. Deficits on both measures of working memory were associated with general cognitive ability. None of the attentional control deficits observed were associated with general ability. Further, spatial working memory deficits were also associated with more severe negative symptoms. These results provide further evidence of the discreet nature of attentional deficits in schizophrenia. By contrast, this study suggests that working memory deficits may to some extent index more general cognitive decline. Awareness of such overlap is important for schizophrenia genetics studies where working memory measures has been used to index supposedly discreet aspects of cognitive dysfunction.


Diet approach before and after bariatric surgery.
Bariatric surgery (BS) is today the most effective therapy for inducing long-term weight loss and for reducing comorbidity burden and mortality in patients with severe obesity. On the other hand, BS may be associated to new clinical problems, complications and side effects, in particular in the nutritional domain. Therefore, the nutritional management of the bariatric patients requires specific nutritional skills. In this paper, a brief overview of the nutritional management of the bariatric patients will be provided from pre-operative to post-operative phase. Patients with severe obesity often display micronutrient deficiencies when compared to normal weight controls. Therefore, nutritional status should be checked in every patient and correction of deficiencies attempted before surgery. At present, evidences from randomized and retrospective studies do not support the hypothesis that pre-operative weight loss could improve weight loss after BS surgery, and the insurance-mandated policy of a preoperative weight loss as a pre-requisite for admission to surgery is not supported by medical evidence. On the contrary, some studies suggest that a modest weight loss of 5-10% in the immediate preoperative period could facilitate surgery and reduce the risk of complications. Very low calories diet (VLCD) and very low calories ketogenic diets (VLCKD) are the most frequently used methods for the induction of a pre-operative weight loss today. After surgery, nutritional counselling is recommended in order to facilitate the adaptation of the eating habits to the new gastro-intestinal physiology. Nutritional deficits may arise according to the type of bariatric procedure and they should be prevented, diagnosed and eventually treated. Finally, specific nutritional problems, like dumping syndrome and reactive hypoglycaemia, can occur and should be managed largely by nutritional manipulation. In conclusion, the nutritional management of the bariatric patients requires specific nutritional skills and the intervention of experienced nutritionists and dieticians.