Study of pollutant distribution in the Guaxindiba Estuarine System--SE Brazil.
The Guaxindiba Estuarine System is located in the northeast portion of Guanabara Bay. Despite the location inside an environmental protection zone, the main affluent of the river runs through the extremely urbanized area of the cities of Niterói and São Gonçalo. In order to understand the contamination levels of the estuary, 35 surface sediment samples were collected along the river and estuarine area and analyzed for the presence of heavy metals, PAHs, organochlorated pesticides, polychlorinated biphenyl and other contaminants. The analyzed data revealed a greatly affected environment with respect to most of these substances. The results suggested propitious deposits of contaminants, with high concentrations of organic matter and fine sediment. The levels of heavy metal in the entire estuarine system were high compared with the local background. The total mean concentrations of As, Cd, Pb, Cu, Zn, Hg, Cr and Ni in the surface sediments were: 3.74; 0.03; 19.3; 15.0; 99.0; n.d.; 29.0; and 22.0mg/kg, respectively, confirming, in certain cases, the high capacity of the environment to concentrate pollution.


Salt losing obstructive uropathy with paradoxically low urinary sodium concentration: salt entrapment in an obstructed ectopic ureterocele.
A 6-month-old hyponatremic female with failure to thrive had low urinary sodium concentration. Renal sonography revealed a duplex left collecting system with obstruction of the upper moiety as a blind-ended ectopic ureterocele extending to the bladder base. The echogenicity of the urine within the upper pole system was greater than the bladder contents. We believed that low urinary sodium concentration represented a false negative test and the salt loss by the obstructed left kidney was entrapped in the upper pole collecting system. Prior to ureterocele repair, intraoperative bladder and ureterocele aspirates revealed discordant sodium concentration supporting the sonographic conclusion.


Simple vs. Complex Carbohydrate Dietary Patterns and the Global Overweight and Obesity Pandemic.
Nowadays, obesity and being overweight are among the major global health concerns. Many, diet-related diseases impose high tangible and intangible costs, and threaten the sustainability of health-care systems worldwide. In this study, we model, at the macroeconomic level, the impact of energy intake from different types of carbohydrates on the population's BMI (body mass index). We proceed in three steps. First, we develop a framework to analyse both the consumption choices between simple and complex carbohydrates and the effects of these choices on people health conditions. Second, we collect figures for 185 countries (over the period 2012-2014) regarding the shares of simple (sugar and sweetener) and complex (cereal) carbohydrates in each country's total dietary energy supply. Third, we use regression techniques to: (1) estimate the impact of these shares on the country's prevalence of obesity and being overweight; (2) compute for each country an indicator of dietary pattern based on the ratio between simple and complex carbohydrates, weighted by their estimated effects on the prevalence of obesity and being overweight; and (3) measure the elasticity of the prevalence of obesity and being overweight with respect to changes in both carbohydrate dietary pattern and income per capita. We find that unhealthy eating habits and the associated prevalence of excessive body fat accumulation tend to behave as a 'normal good' in low, medium- and high-HDI (Human Development Index) countries, but as an 'inferior good' in very high-HDI countries.


On physical analysis of topological indices via curve fitting for natural polymer of cellulose network.
Plant materials are processed in a variety of ways to produce biologically active compounds. Cellulose (natural polymer) has the ability to deliver physiologically active compounds to organ targets that have been extracted by CO 2 . Researchers have recently become interested in polymers that can transport biologically active compounds into human bodies. For appropriately selecting bearers of biologically active chemicals, knowledge of the thermodynamic properties of cellulose is required. In QSPR/QSAR modelling, which provides the theoretical and optimum foundation for costly experimental drug discovery, molecular descriptors are extremely important. In this article, we investigated a natural polymer of cellulose network which has interesting pharmacological applications, outstanding characteristics, and a novel molecular structure. We plan to look into and compute a variety of closed-form formulas of various K-Banhatti indices along with their respective K-Banhatti entropies and the heat of formation. The numerical and graphical characterization of computed results was combined with curve fitting between calculated thermodynamic properties and topological indices. This presentation will provide a complete description of potentially important thermodynamic features that could be useful in modifying the structure of natural polymer of cellulose network CN y x .


Reactivity of the [Au(C^N^C)Cl] complex in the presence of H2O and N-, S- and Se-containing nucleophiles: a DFT study.
Gold complexes are promising compounds used in cancer chemotherapy. Besides their steric features, which enable biomolecule interactions, the redox instability and the high affinity of gold with cellular nucleophiles influence the biological action in these complexes. Both features were herein theoretically investigated for the [Au(C^N^C)Cl] probe complex (C^N^C = 2,6-diphenylpyridine) using H2O, CH3SH/CH3S-, CH3Se- and meim-4-H (4-methylimidazole) as biomimetic nucleophiles. Based on the results, the lowest energy reaction path followed two consecutive steps: (1) chloride-exchange ([Formula: see text] = 4.14 × 107 M-1 s-1) and (2) reduction of the resulting Au(III) metabolite to the corresponding Au(I) analog with chelate ring-opening ([Formula: see text] =+0.15 V-data based on the reaction with CH3Se-). These findings bring new insights about the mechanism of the Au(III) complex/biomolecule interaction in the cell, which is responsible for triggering biological responses.


Phylogenetic and diversity analyses revealed that leek yellow stripe virus population consists of three types: S, L, and N.
Phylogenetic and evolutionary analyses were performed on the P1 and CP genes of global isolates to clarify the phylogrouping of leek yellow stripe virus (LYSV, genus Potyvirus), a pathogen affecting Allium spp. worldwide, into different types based on genetic variation and host species. The constructed phylogenetic trees divided the isolates into three major groups: S, L, and N. Low nucleotide (nt) and amino acid (aa) percent identities among the three groups were observed on full ORF (75.4-99.0 and 79.1-99.0), P1 (59.1-98.3 and 36.8-98.3), and CP (76.6-100 and 75.7-100) coding regions. The dN/dS values of P1 and CP confirmed that both genes are under strong negative (purifying) selection pressure. Neutrality tests on Eastern Asian isolates suggested that the ancestors of current LYSV isolates evolved with garlic while they were in Asia before spreading to other world regions through garlic propagative materials. Genetic differentiation and gene flow analysis showed extremely frequent gene flow from S group to L and N groups, and these phylogroups differentiated from each other over time. Host differences, inconsistent serological test results, substantial nt and aa variation, and phylogenetic and diversity analyses in this study supported previous reports that LYSV can be separated into three major evolutionary lineages: S, L, and N types.


Investigation of genes involved in nisin production in Enterococcus spp. strains isolated from raw goat milk.
Different strains of Lactococcus lactis are capable of producing the bacteriocin nisin. However, genetic transfer mechanisms allow the natural occurrence of genes involved in nisin production in members of other bacterial genera, such as Enterococcus spp. In a previous study, nisA was identified in eight enterococci capable of producing antimicrobial substances. The aim of this study was to verify the presence of genes involved in nisin production in Enterococcus spp. strains, as well as nisin expression. The nisA genes from eight Enterococcus spp. strains were sequenced and the translated amino acid sequences were compared to nisin amino-acid sequences previously described in databases. Although containing nisin structural and maturation related genes, the enterococci strains tested in the present study did not present the immunity related genes (nisFEG and nisI). The translated sequences of nisA showed some point mutations, identical to those presented by Lactococcus strains isolated from goat milk. All enterococci were inhibited by nisin, indicating the absence of immunity and thus that nisin cannot be expressed. This study demonstrated for the first time the natural occurrence of nisin structural genes in Enterococcus strains and highlights the importance of providing evidence of a link between the presence of bacteriocin genes and their expression.


A microcomputer approach to storage of qualitative patient data using key words.
A microcomputer program is presented which stores and retrieves qualitative patient information, such as diagnosis and physical findings. Users can design and enter a key word list and modify it as needed. Using those key words, up to 5000 patient entries can be made on a single floppy disk. Application of the program to CT scan study results is discussed.


Surface anesthetic effect and topical tolerance of one dose 0.25% bupranolol in eye-healthy people.
In a randomised, prospective, parallel, double-masked study we examine the surface anesthetic effect of Bupranolol 0.25% in an oily solution. Bupranolol 0.25% decreases the corneal sensitivity to 23 mg/S, with the maximum between the 6th and 15th minute after application.


Abnormal preoperative digital brachial index is associated with lower 2-year arteriovenous fistula access patency.
The aim of the present study was to assess whether a single measurement of the digital brachial index (DBI; systolic finger pressure/systemic pressure ratio), reflecting the arm's circulation, was associated with access patency in patients with severe chronic kidney disease scheduled for arteriovenous fistula (AVF) creation. A bilateral DBI was obtained using digital plethysmography just before construction of the patient's first AVF from January 2009 to December 2017 at one center. A DBI of 80% to 99% was considered normal, and a DBI of <80% (low) or DBI of ≥100% (high) were considered abnormal. DBI values ipsilateral to the AVF were used for analysis. The primary and secondary access patency rates were calculated using reported standards and compared using standard statistical techniques. Data sets of 163 patients were obtained (69 women; age, 71 ± 12 years). The median follow-up was 40 weeks (range, 0-104 weeks; follow-up index, 99% ± 1%). Patients with abnormal preoperative DBI values had lower 2-year primary patency rates (low DBI, 25% ± 11%; high DBI, 28% ± 6%; normal DBI, 49% ± 8%; P = .018). After correction for age, sex, hypertension, diabetes mellitus, cardiovascular disease, smoking status, and a history of ipsilateral central venous catheter use, an adjusted model demonstrated that abnormal DBI values conferred an increased risk of primary patency failure (low DBI [<80%]: hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.13-4.48; high DBI [≥100%]: HR, 1.74; 95% CI, 1.06-2.85; P < .030 for both). Patients with a low preoperative DBI had also had diminished secondary patency (HR, 2.86; 95% CI, 1.08-7.59; P = .035). In contrast, the diameters of the outflow veins did not determine access patency. Patients with abnormal DBI values before AVF construction for hemodialysis had lower 2-year access patency rates compared with patients with a normal DBI. Plethysmographic finger measurements might have a role in the preoperative counseling of patients with severe chronic kidney disease requiring an AVF.


Bladder neuropathy in lumbar disc disease.
Disturbances of bladder, function often occur in cases of sciatica due to intervertebral disc lesions, although other clinical signs of sacral root compression are absent. In 32 patients, operated upon because of lumbar disc diseases without cauda equina syndrome, micturition symptoms were registered, and bladder function was investigated. Intravesical pressure/volume relations (water cystometry) and simultaneous intravesical pressure/urinary flow relations (urodynamic examination) were recorded preoperatively together with anal sphincter surface EMG. In almost half of the patients cystometry revealed bladder hyposensibility (late first sensation), and a quarter voided mainly by straining (detrusor paresis). These findings were unrelated to the neurosurgical pathology. Pronounced micturition symptoms or abnormal preoperative urodynamic examinations indicated evaluation two months after lumbar disc operation. Two-thirds tended towards recovery, one third remained unchanged.


Policy Update: Immigration Status No Longer Affected by Use of Public Health Benefits.
A Trump-era rule that penalized immigration and citizenship applicants has been rescinded.


Studying the interaction of alpha-gal carbohydrate antigen and proteins by quartz-crystal microbalance.
The interaction of alpha-galacosyl antigen and its binding protein (anti-Gal antibody) has been studied by quartz crystal microbalance through a SAM immobilization technique which overcomes the nonspecific interactions and molecule trapping for current piezoelectric biosensors.


Expression of nitrogen fixation genes in foreign hosts. Assembly of nitrogenase Fe protein in Escherichia coli and in yeast.
In Klebsiella pneumoniae, the nifH gene encodes the Fe protein (Kp2) polypeptide that is assembled into a homodimer responsible for the reduction of nitrogenase. Escherichia coli or the yeast Saccharomyces cerevisiae, transformed with the K. pneumoniae nifH gene in suitable expression vectors, synthesize the Fe protein polypeptide. This study examines the assembly of the nifH gene product into its characteristic dimeric structure in E. coli and in yeast. Immunoblotting methods, as well as 55Fe2- labeling of K. pneumoniae were employed to detect native nitrogenase components in cell lysates. E. coli and yeast transformants contained a protein similar to native Kp2 in its immunoreactivity, apparent molecular weight, and lability in the presence of oxygen or MgATP. While in E. coli the co-introduction of nifH and nifM resulted in enhanced levels of the nifH product, it appears that the nifH gene product alone is sufficient for the assembly of an Fe protein-like structure in foreign prokaryotic and eukaryotic hosts.


Could a careful clinical examination distinguish physiologic phimosis from balanitis xerotica obliterans in children?
The diagnosis of balanitis xerotica obliterans (BXO) in children may be challenging, since clinical examination only could lead to an underestimation of its incidence. The aim of this retrospective and single-centre study is to assess the diagnostic performance of clinical examination, together with clinical history, in identifying BXO. Ninety-seven children underwent circumcision for phimosis from 2015 to 2019. Histology was routinely performed. Cohen's kappa coefficient, sensitivity, specificity, predictive values, likelihood ratios and accuracy of macroscopic appearance of the foreskin, steroid administration and past medical history were estimated. Forty-eight patients (50%) were affected by BXO; 31 of them (69%) presented with suggestive clinical signs. A strictured or whitish urethral meatus was detected during surgery in nine cases (19%); this was associated to allergic or immune diseases (p = 0.046). Foreskin appearance alone mildly correlated with histology (k = 0.494; p < 0.001) and it showed a diagnostic accuracy of 75%. The specificity and positive predictive value of abnormal macroscopic findings at examination, together with a positive clinical history for other allergic or immune diseases, and/or for balanitis, were 100% and the positive likelihood ratio was greater than 10. Conversely, sensitivity decreased to 4.5% (95% CI 0-11%).Conclusion: Foreskin appearance together with clinical history could predict BXO with certainty. However, since the absence of a positive medical history could not exclude the diagnosis, foreskin histology is still highly recommended. What is Known: • Occurrence of balanitis xerotica obliterans may be underestimated in children and it could lead to long-term complications. • The diagnostic accuracy of clinical examination is controversial. What is New: • Clinical signs together with patients' medical history present high specificity and positive predictive values but low sensitivity. • When suggestive clinical aspects are present, patient should be referred to surgery avoiding prolonged conservative treatment; and preputial histology is highly recommended.


[The mechanism and techniques of vaccination].
From the discovery of the first vaccines to the development of the latest ones, such as the one against Covid-19, research has improved the service rendered against infectious diseases by diversifying vaccination techniques to evolve responses to aggression by microorganisms.


Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes.
Monocyte chemotactic protein-1 (MCP-1)-directed transendothelial migration of monocytes plays a key role in the development of inflammatory diseases. Infiltration of tissues by monocytes requires degradation of extracellular matrices, a process that involves matrix metalloproteinases. We studied the effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and matrix metalloproteinase expression of a human acute monocytic leukemia cell line (THP-1). PPARgamma ligands attenuated MCP-1-induced migration, with 50% inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for rosiglitazone. PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14-eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN 4204 (IC(50): 3.6 nM) also blocked monocyte migration. Troglitazone, rosiglitazone, or AGN 4204 inhibited phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 expression. PPARalpha activators WY-14643 and 5,8,11,14-eicosatetraynoic acid, however, had no inhibitory effect. AGN 4204 increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) expression, whereas all PPAR ligands showed no effect. All PPAR and RXRalpha ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier. This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed monocyte migration, mediated, at least in part, through their effects on matrix metalloproteinase-9 or TIMP-1 production, or chemotaxis.


[Melanoma-associated macrophages-from molecular signals to therapeutic application].
Macrophages are an important component of the innate immune system. They are abbreviated as Mφ, MΦ, or MP. The name is derived from Greek: large eaters, μακρóς (makrós) = large, φαγεῖν (phagein) = to eat, because they engulf and digest pathogens. Tumor-associated macrophages (TAMs) are associated with drug resistance in cancers, including melanoma, and targeting them may improve cancer treatment. The purpose of this article is to examine the role of TAMs in cancer, particularly in melanoma. The relationship between TAM and treatment resistance and their potential application in the treatment of melanoma are discussed. A literature search in PubMed and Google Scholar databases for TAM and melanoma was performed. Clinical trials were searched via clinicaltrials.gov and graphical representations were created using BioRender. In melanoma, macrophages are among the most abundant immune cells in the tumor microenvironment (TME). TAMs are associated with poor prognosis and resistance. They are involved in tumorigenesis and metastasis development. M2 is the predominant type of TAM and the M2 markers CD163 and CD204 are unfavorable prognostic biomarkers. Therapeutic approaches aim to decrease their recruitment, modulate their function, or reprogram them. Treatment using chimeric antigen receptor (CAR)-M cells and nanoparticles are currently being investigated. Drugs being tested for melanoma include signal transducer and activator of transcription 3 (STAT3) inhibitors, macrophage colony-stimulating factor (M-CSF) antagonists, interferons (IFN), talimogene laherparepvec (TVEC), histone deacetylase (HDAC) inhibitors, indoleamine 2,3-dioxygenase (IDO) inhibitors, colony-stimulating factor 1 receptor (CSF-1R) antagonists, CD40 agonists, arginase 1 (ARG-1) inhibitors, and phosphoinositide 3‑kinase γ (PI3K-γ) inhibitors. TAMs participate in developing resistance to current melanoma therapies. Treatment directed against them may help reduce the development of resistance and improve survival.


External validation of existing nomograms predicting lymph node metastases in cystectomized patients.
Karakiewicz et al. and Green et al. created pre-cystectomy nomograms to predict lymph node involvement. The aim of the study was to externally validate these two nomograms in intermediate-volume institutions in Europe. Data from a Serbian single-centre cystectomy series comprising 183 patients with bladder cancer were used for the validation of two US nomograms, which were originally based on data from 726 and 201 patients, respectively. A multivariate regression model assessed the value of the clinical parameters integrated in the two nomograms. The expected predictive accuracy, calibration and clinical utility according to the nomograms were calculated. Comparison of our dataset with the previously published data shows differences in nearly all underlying risk variables. Overall, 109 (59.6 %) patients had lymph node metastases. The analysis demonstrated that hydronephrosis and status of lymph nodes on computed tomography have independent prognostic value. The performance of the nomograms deteriorated from the development set, and the predictive accuracies for the two models showed moderate discriminatory ability (61.2-69.1 %). In the decision curve analysis, only the Green et al. model predicting lymph node positivity provided net benefit. The Green et al. nomogram seems applicable to patients from Europe, despite varying risk factors in the validation dataset. Acceptance of such a tool into daily clinical management may lead to more appropriate decision-making. Nevertheless, further improvement and implementation of novel statistical models with enhanced predictive accuracy is needed.


Recent advances in the genetics and immunology of Stevens-Johnson syndrome and toxic epidermal necrosis.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are rare but life-threatening severe cutaneous adverse reactions (SCARs), which are majorly (65-75%) induced by a variety of drugs. SJS/TEN could be recognized as SCARs or drug immune reactions, if the reactions are elicited by drugs. The recent studies suggested that SJS/TEN is a specific immune reaction initiated by the cytotoxic T lymphocytes (CTLs) via human leukocyte antigens (HLAs)-restricted pathway. The patho-mechanism involving HLA-restricted presentation of a drug or its metabolites for T-cell activation is supported by the findings of strong genetic associations with HLA alleles (e.g. HLA-B*15:02 and carbamazepine-SJS/TEN, and HLA-B*58:01 and allopurinol-SJS/TEN). However, the genetic associations of SJS/TEN or drug induced cutaneous immune reactions are complex, which are drug specific and ethnicity specific. The genetic polymorphisms and diversity of HLA alleles may provide different binding affinities for drug antigens to launch the activation of specific CTLs responses, further leading to the unique clinical manifestations in SJS/TEN. Fas-FasL and perforin/granzyme B have been advocated mediating the epidermal necrosis in SJS/TEN. Our recent study showed that granulysin, a cytotoxic protein produced by CTLs or natural killer (NK) cells, is the key mediator for disseminated keratinocyte death in SJS/TEN. From the point of view of a physician, the profounder understanding of the genetic predisposition and patho-mechanism we discover, the better strategies for prevention, clinical management, and therapeutic methods of SJS/TEN we can develop in the near future.


Long-term prognosis of vaccine-induced contact allergy to aluminium: Third patch-test with additional test preparations.
A high incidence of local itching subcutaneous nodules and aluminium allergy was observed in clinical trials of a new aluminium adsorbed pertussis vaccine in Gothenburg, Sweden, in the 1990s. A total of 495 children with itching nodules were patch tested with aluminium chloride hexahydrate 2% and an empty Finn Chamber®, 377 (76%) with positive reactions. When 241 of them were re-tested some years later 186 (3 out of 4) had unexpectedly lost their patch test reactivity. To investigate the long-term prognosis of vaccine-induced contact allergy to aluminium by a third patch test about 20 years after Patch test I. Twenty individuals with positive and 11 with negative results in Patch test II were tested a third time with the same sensitisers as in in the first two tests. Three additional aluminium preparations were also tested. A total 15 out of 20 persons with positive results in the second test had lost their patch test reactivity. Two of 11 with negative tests had turned positive again. The addition of the preparations gave no conclusive results. Contact allergy to aluminium caused by vaccination with aluminium-adsorbed vaccines in childhood seems to fade away with time as measured by loss of patch test reactivity.


A Radiomics-Based Model for Potentially More Accurate Identification of Subtypes of Breast Cancer Brain Metastases.
Breast cancer brain metastases (BCBM) may involve subtypes that differ from the primary breast cancer lesion. This study aimed to develop a radiomics-based model that utilizes preoperative brain MRI for multiclass classification of BCBM subtypes and to investigate whether the model offers better prediction accuracy than the assumption that primary lesions and their BCBMs would be of the same subtype (non-conversion model) in an external validation set. The training and external validation sets each comprised 51 cases (102 cases total). Four machine learning classifiers combined with three feature selection methods were trained on radiomic features and primary lesion subtypes for prediction of the following four subtypes: 1) hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, 2) HR+/HER2+, 3) HR-/HER2+, and 4) triple-negative. After training, the performance of the radiomics-based model was compared to that of the non-conversion model in an external validation set using accuracy and F1-macro scores. The rate of discrepant subtypes between primary lesions and their respective BCBMs were 25.5% (n=13 of 51) in the training set and 23.5% (n=12 of 51) in the external validation set. In the external validation set, the accuracy and F1-macro score of the radiomics-based model were significantly higher than those of the non-conversion model (0.902 vs. 0.765, p=0.004; 0.861 vs. 0.699, p=0.002). Our radiomics-based model represents an incremental advance in the classification of BCBM subtypes, thereby facilitating a more appropriate personalized therapy.


Utilization of corn steep liquor for biosynthesis of pullulan, an important exopolysaccharide.
Five different agricultural wastes viz. rice bran oil cake, soya bean oil cake, cotton seed oil cake, mustard seed oil cake and corn steep liquor (CSL) were evaluated for their use as nutrient along with 15% (w/v) glucose as carbon source for biosynthesis of pullulan using Aureobasidium pullulans RBF 4A3. Among the selected agricultural wastes, CSL was found to be the best and supported production of 77.92gL(-1) pullulan under un-optimized conditions. Single point optimization technique resulted in increase in 18% pullulan (88.59gL(-1)) production. The process was successfully validated in a 7-L fermenter and a process economic analysis has suggested that use of CSL as nutrient may result in 3-fold reduction of cost of raw materials for pullulan production as compared to a process where conventional nitrogen sources were used. These observations may be helpful in development of a cost effective process for pullulan production.


H-2 linked immune response to murine experimental Schistosoma mansoni infections.
Mice of two congenic inbred strains C3H/Sn (H-2k) and C3H.B10 (H-2b) were infected with 100 Schistosoma mansoni cercariae. After the infection, the following parameters for the immunological response were studied: worm burden, mortality, antibody titre, spleen index, eosinophilia, delayed type of hypersensitivity and in vitro response to three S. mansoni antigen preparations. No difference in the worm burden and in the in vitro response to the antigen preparations of adult worm antigen, soluble egg antigens and the egg antigen MSA1, was found. The C3H.B10 mice showed a significantly higher mortality, antibody titre and delayed type of hypersensitivity while the C3H/Sn mice showed asignificantly higher spleen index and eosinophilia. This indicates that the H-2 region influences the course of an acute S. mansoni infection, whereas the susceptibility to the infection seems not to be influenced, as is shown by the worm burden.


The NASS lumbar spine outcome assessment instrument: Large sample assessment and sub-scale identification.
Accurately assessing patient-reported pain and functional ability is essential to measuring quality of care. Evaluating the instruments used in assessing quality of care is often overlooked. The North American Spine Society Lumbar Spine Outcome Assessment (NASS-LS) instrument measures patient-reported pain and function in a combined scale. We evaluated the original instrument and assessed separate pain and function subscales based on a set of the items in the original instrument. Data were collected from seven spine clinics in the United States participating in the Spinal Surgery Consortium for Outcomes Research Project. Consenting patients were enrolled in the project and asked to complete the NASS instrument when arriving for a surgical consult. Data from 811 lumbar spine patients were used. Analyses were conducted on the original instrument to determine its internal consistency and to determine the structural existence of any underlying scales. Internal consistency of the original and new scales were assessed with Cronbach's coefficient alpha. The original scale was found to be a useful measure of pain and functional ability. Important subscales of pain and functional ability were also identified allowing us to report more meaningful results. The original instrument is useful for assessing low-back pain and function as a combined concept. The separate pain and function scales may prove useful assessing varying outcome levels and/or different decisions about subsequent follow-up care.


Reaction of various human normal and leukemic cells and cells of different cell lines with rabbit antisera prepared against membrane fraction of B and T cell lines.
Serological analysis of human membrane antigens have been performed using rabbit xenosera against membrane fraction obtained from different cells (B cell lines: RAJI, RAMOS, DAUDI, UHKT-2: T cell line: MOLT-3, as well as normal pooled lymphocytes). The direct cytotoxicity testing demonstrated that xenogeneic rabbit B lymphoid antisera mediated a significant reaction in the complement-dependent cytotoxicity assay against an antigenic determinant on normal peripheral blood B lymphocytes but not against T lymphocytes and granulocytes. Moreover, these xenoantisera react with antigenic specificities present on the CLL leukocytes, on some AML myeloblasts, on the hairy cells, on majority of ALL and CML blasts, but not on eosinophilic leukocytes and on T lymphocytes from peripheral blood of patients with CLL, ALL, AML, and CML in remission. These xenoantisera react with antigenic specificities present on the cells of cultured lymphoid cell lines of B type, but not on cells of T cell lines.


Role of pokeweed mitogen spleen conditioned medium in regulating haematopoiesis in long-term human marrow cultures.
The modulatory effect of pokeweed mitogen spleen conditioned medium (PWM-SCM) on the growth of myeloid progenitors (CFU-C) and on the composition of the stromal layer in human bone marrow long-term cultures was studied. In the presence of PWM-SCM there was enhanced CFU-C growth in the adherent layer throughout 6 weeks of incubation, with 2-fold, 2-fold and 3.4-fold increases during wk 2, 4 and 6 respectively (p less than 0.05). In the non-adherent layer of control cultures, however, there was a rapid decline in haematopoiesis which could not be offset by PWM-SCM. The differentiation pattern of CFU-C (entailing monocyte - macrophage progenitors CFU-M, granulocytic progenitors CFU-G or monocyte - granulocyte progenitors CFU-GM) was not altered by PWM-SCM. Fewer lipid-containing cells developed in the adherent layer of cultures treated with PWM-SCM than in control cultures, but the distribution pattern of monocytes - macrophages or granulocytes was not affected. These results suggest that in long-term cultures of human marrow cells there may be extensive haematopoiesis in the presence of PWM-SCM. Whether this is a direct effect on progenitor cells of stimulating factors, or rather of accessory cells in the adherent layer, remains to be clarified.


[Chemical-induced polycyst with renal tumor and expression of 8-OHdG in kidney tissue].
To induce the rat model of polycyst with renal tumor and investigate the expression of 8-OHdG in the kidney tissues. The rat model of polycyst with renal tumor, similar to human acquired cystic disease of the kidney (ACDK), was induced by oral administration of 2-amino-4, 5-diphenylthiazole (DPT) and N-nitrosomorpholine (NNM). Immunohistochemical method (LSAB) was used to assay the expression of 8-hydroxydeoxyguanosine (8-OHdG) in the rat kidney tissue. Three of 10 rats in the NNM group had renal solid adenomatous lesions. Bilateral polycysts were observed in all 9 rats of the DPT/NNM group. Seven of the 9 rats had cystic multistage renal tumor. In the DPT/NNM group, 4 rats had cystic adenomatous lesions, but none in the other groups showed this lesion. In the model, adenomatous lesions derived from polycysts in the rats were closely consistent to human ACDK in morphology. The significant expression of 8-OHdG was found on renal tubular cell, cystic epithelial cell, stromal cell and tumor cell in all rats of the NNM and DPT/NNM group. A rat model of polycysts with renal tumor, similar to human ACDK, induced by DPT and NNM provides evidences for further study on pathogenic mechanism in human ACDK with renal cell carcinoma. The expression of 8-OHdG, a DNA damage marker, in the renal tissues of rat model might help to explain the mechanism of cysticogenesis and carcinogenesis in human ACDK.


Did the Highly Pathogenic Avian Influenza A(H7N9) Viruses Emerged in China Raise Increased Threat to Public Health?
The low pathogenic avian influenza A(H7N9) viruses (LPAI) were first identified in 2013 and have continued to infect humans since then. It was reported in February 2017 that the LPAI H7N9 virus has evolved into highly pathogenic avian influenza (HPAI) viruses, potentially increasing the risk for human and poultry. We in this study overviewed the emergence, epidemiology, and biological characterizations of the HPAI H7N9 viruses for the risk assessment.


A longitudinal study of the impact of parental discipline on wellbeing among primary school students in China: The roles of school attachment and growth mindset.
Various parental disciplinary strategies may have different impacts on children's wellbeing. Protective factors, such as school attachment and a growth mindset, may mitigate the influence of harsh discipline on a child's wellbeing. Based on the strengths-based trauma-informed positive education model, the current study investigated the impacts of three types of parental discipline (corporal punishment, psychological aggression, and nonviolent discipline) on primary school students' wellbeing and examined the moderating roles of school attachment and a growth mindset (both disjunctive and conjunctive moderating effects) in the relationship between parental discipline and student wellbeing. A sample of 854 primary school students (M = 9.40) from eight schools in Hong Kong, China, completed the questionnaire survey at two time points (Time 1 and Time 2), one year apart. Hierarchical regression analysis was applied for data analysis. Parental psychological aggression at Time 1 (T1) was significantly and negatively related to student wellbeing at Time 2 (T2). Parental nonviolent discipline students' school attachment and growth mindset at T1 were significantly and positively correlated with student wellbeing at T2, when controlling for the students' initial wellbeing and important confounding demographic variables. School attachment moderated the association between parental psychological aggression and student wellbeing. Parental psychological aggression has negative impacts while nonviolent discipline has positive impacts on primary school students' wellbeing. Students who are more attached to school and have a growth mindset show higher levels of wellbeing. The study provides further evidence of the role of school attachment in moderating the effect of parental psychological aggression on children's wellbeing in the trauma-informed positive education model.


Goat Milk Consumption Ameliorates Abnormalities in Glucose Metabolism and Enhances Hepatic and Skeletal Muscle AMP-Activated Protein Kinase Activation in Rats Fed with High-Fat Diets.
Diabetes endangers health and causes serious economic impediment. The aim of this study is to identify the effects of goat milk consumption on glucose metabolism of rats with high-fat (HF) diet. Sixty male Sprague Dawley rats are divided into five groups and fed with different diets for 24 weeks: goat-milk-based HF diet (GHF group; goat milk powder+HF diet), cow-milk-based HF diet (CHF group; cow milk powder+HF diet), HF diet, HF diet plus acarbose (HF+A group; acarbose+HF diet), and chow diet (CD group). Fasting glucose in GHF-fed rats are lower than HF-fed rats on weeks 16 and 20. GHF-fed rats display improved insulin sensitivity in oral glucose and insulin tolerance tests. Compared with HF-fed rats, glycated hemoglobin and triglycerides in GHF-fed rats are lower and high-density lipoprotein level is higher. AMP-activated protein kinase activation (AMPK) in the liver and skeletal muscle is higher in GHF rats than HF rats. Phosphoenolpyruvate carboxykinase and glucose 6-phosphatase protein levels in the liver are lower and hexokinase 2 protein level in the skeletal muscle is higher in GHF rats compared with HF rats. Goat milk consumption can ameliorate abnormalities in glucose metabolism, and AMPK pathway in the liver and skeletal muscle plays an important role in the process.


Carbon nanotube salts. Arylation of single-wall carbon nanotubes.
[reaction: see text] Carbon nanotube salts prepared by treating single-wall carbon nanotubes (SWNTs) with lithium in liquid ammonia react readily with aryl iodides to give SWNTs functionalized by aryl groups.


Capsaicin desensitization and stimulus-induced recovery on facial compared to lingual skin.
It was recently demonstrated that capsaicin desensitization of the tongue can be temporarily reversed during bouts of recurrent or constant stimulation. The present study investigated whether this "stimulus-induced recovery" (SIR) also occurs on skin other than the oral mucosa. Twenty-two subjects received capsaicin treatments on the cheek and on the tongue tip at concentrations (330 and 33 microM) that produced approximately equal sensory irritation on the two sites. Desensitization and SIR occurred on both test sites, although the longer time course of irritation on the face changed the magnitude and form of SIR. There were large individual differences in the extent of desensitization and recovery, and the two phenomena were not correlated across sites, i.e., the capacity for SIR on the tongue was not a good predictor of an individual's capacity for SIR on the face. The results are discussed in terms of possible sources of regional and individual differences, and the implications they may have for the efficacy of topical analgesics that contain capsaicin.


Gene silencing in mammalian cells by PCR-based short hairpin RNA.
RNA interference (RNAi) provides a powerful tool to silence genes in a sequence-specific manner in a variety of systems. However, not all sequences are effective in the RNAi-mediated gene silencing. In this study, we developed a polymerase chain reaction (PCR)-based RNAi strategy for a quick screening of small interfering RNA (siRNA) efficiency. This method utilized a two-step PCR to generate a chimeric DNA template containing the U6 promoter or cytomegalovirus promoter and short hairpin DNA. We demonstrated that the transfection of the PCR products into mammalian cells resulted in specific depressions of exogenous (luciferase, green fluorescent protein and beta-galactosidase) and endogenous (annexin II) gene expressions. This PCR strategy provides a rapid, easy and cheap approach for testing candidates siRNA sequences and is an attractive alternative to subcloning.


Neurological and electroencephalographic changes in newborns treated with prostaglandins E1 and E2.
Six newborns with obstructive right heart lesions were examined neurologically and electroencephalographically during treatment with prostaglandin (PG) E1 or E2 given to maintain patency of the ductus arteriosus and to increase pulmonary blood flow. PG was administered intravenously or intraarterially in the aortic isthmus proximal to the ductus arteriosus. Besides a rise in arterial oxygen saturation, all patients had some sign of central nervous system involvement. The electroencephalogram showed minor changes suggestive of sedation. In addition, three patients in whom PG was given intravenously presented various combinations of neurological abnormalities ("myoclonic jerks", apnoeic spells, hiccup) of subcortical origin. Side-effects subsided after stopping the treatment and posed no problem in the management of the patients. These findings confirm the usefulness and safety of the PG therapy and indicate that the intraaortic route of administration is preferable.


Fusobacterial infections in children.
Fusobacteria are members of the oral and gastrointestinal flora and are important potential pathogens in children. They are increasingly recognized as a cause of infections in children. These include infections of the head and neck (Lemierre syndrome, acute and chronic mastoiditis, chronic otitis and sinusitis, tonsillitis, peritonsillar and retropharyngeal abscesses, postanginal cervical lymphadenitis, periodontitis), brain, lungs, abdomen, pelvis, bones, joints, and blood. This review describes the clinical spectrum of fusobacterial infection in children and their management.


Health information needs regarding diabetes mellitus in China: an internet-based analysis.
Today,. most people use the Internet to seek online health-related information from general public health-related websites and discussion groups. However, there are no Internet-based analyses of health information needs pertaining to diabetes in China until now. With the development of artificial intelligence,we can analyzed these online health-related information and provide references for health providers to improve their health service. We have done a study of statistically analyzing the questions about diabetes collected from 39 health website, the number of which is 151,589. We have divided these questions into 9 categories using a convolutional neural network. The diabetes problems of consumer are presented as follows, diagnosis: 34.95%, treatment: 25.17%, lifestyle: 21.09%, complication: 8.00%, maternity-related:5.00%, prognosis: 2.59%, health provider choosing: 1.40%, prevention: 1.23%, others: 0.58%, The elderly are more concerned about the treatment and complications of diabetes, while the young are more concerned about the maternity-related and prognosis of diabetes. The diabetes drugs most frequently mentioned by consumers are insulin, metformin and Xiaoke pills, The most concerned complication is caidiovascular disease and diabetic eye disease. Diabetes health education should focus on how to prevent diabetes and the contents of health education should be different for differernt age groups;on diabetes treatment, the use of insulin and oral hypoglycemic drugs education should be strengthened.


Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphorylation by PKC but is due to the loss of E258.
To stimulate renal water reabsorption, vasopressin induces phosphorylation of Aquaporin-2 (AQP2) water channels at S256 and their redistribution from vesicles to the apical membrane, whereas vasopressin removal results in AQP2 ubiquitination at K270 and its internalization to multivesicular bodies (MVB). AQP2-E258K causes dominant nephrogenic diabetes insipidus (NDI), but its subcellular location is unclear, and the molecular reason for its involvement in dominant NDI is unknown. To unravel these, AQP2-E258K was studied in transfected polarized Madin-Darby canine kidney (MDCK) cells. In MDCK cells, AQP2-E258K mainly localized to MVB/lysosomes (Lys). Upon coexpression, wild-type (wt) AQP2 and AQP2-E258K formed multimers, which also localized to MVB/Lys, independent of forskolin stimulation. Orthophosphate labeling revealed that forskolin increased phosphorylation of wt-AQP2 and AQP2-E258K but not AQP2-S256A, indicating that the E258K mutation does not interfere with the AQP2 phosphorylation at S256. In contrast to wt-AQP2 but consistent with the introduced protein kinase C (PKC) consensus site, AQP2-E258K was phosphorylated by phorbol esters. Besides the 29-kDa band, however, an additional band of about 35 kDa was observed for AQP2-E258K only, which represented AQP2-E258K uniquely monoubiquitinated at K228 only. Analysis of several mutants interfering with AQP2-E258K phosphorylation, and/or ubiquitination, however, revealed that the MVB/lysosomal sorting of AQP2-E258K occurred independent of its monoubiquitination or phosphorylation by PKC. Instead, our data reveal that the loss of the E258 in AQP2-E258K is fundamental to its missorting to MVB/Lys and indicate that this amino acid has an important role in the proper structure formation of the C-terminal tail of AQP2.


Bioaccumulation of toxic metals (Cr, Cd, Pb and Cu) by seeds of Euryale ferox Salisb. (Makhana) W.
The level of toxic metals Cr, Cd, Pb and Cu was determined in seeds, water and sediments collected from nine closed waterbodies of Darbhanga, north Bihar, used for cultivation of the edible aquatic macrophyte Euryaleferox Salisb. during harvesting season of the crop for two successive years (1996 and 1997). Seeds bioconcentrated appreciable amount of these toxic metals in the order Pb > Cr > Cu > Cd. The increased load of metal pollution due to domestic and municipal discharges threatened the habitats of the plant. The toxic metal contents in seeds were found positively correlated with the ambient concentration of metals in water and sediments. The importance of these findings has been discussed for national water resource economy of the country and human health perspectives.


Aging and the COVID-19 pandemic: The inter-related roles of biology, physical wellbeing, social norms and global health systems.
The coronavirus disease 2019 (COVID-19) pandemic has had a devastating and disproportionate impact on the elderly population. As the virus has swept through the world, already vulnerable elderly populations worldwide have faced a far greater burden of deaths and severe disease, crippling isolation, widespread societal stigma, and wide-ranging practical difficulties in maintaining access to basic health care and social services - all of which have had significant detrimental effects on their mental and physical wellbeing. In this paper, we present an overview of aging and COVID-19 from the interrelated perspectives of underlying biological mechanisms, physical manifestations, societal aspects, and health services related to the excess risk observed among the elderly population. We conclude that to tackle future pandemics in an efficient manner, it is essential to reform national health systems and response strategies from an age perspective. As the global population continues to age, elderly-focused health services should be integrated into the global health systems and global strategies, especially in low- and middle-income countries with historically underfunded public health infrastructure and insufficient gerontological care.


WITHDRAWN: One of COVID-19's many costs: Malta's expenditure in consumables and non-consumables, a population-based study.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Antifungal efficacy of sanitizers and electrolyzed waters against toxigenic Aspergillus.
The presence of mycotoxin-producing fungi in food production environments is a cause of concern since they can contaminate food products, synthesizing toxic compounds in later steps. To avoid this, an effective hygiene and sanitation process of the environment and equipment should be adopted, using sanitizing agents with adequate antifungal efficacy. This work evaluated the effectiveness of different chemical sanitizers: benzalkonium chloride (0.3%, 1.2%, 2%), biguanide (2%, 3.5%, 5%), iodine (0.2%, 0.6%, 1%), peracetic acid (0.3%, 0.6%, 1%), sodium hypochlorite (0.5%, 0.75%, 1%), besides a new non-polluting technology, the electrolyzed water, both the acid in the chlorine concentrations of 60, 85 and 121 ppm and the respective basic electrolyzed water formed against strains of toxigenic Aspergillus flavus, Aspergillus nomius, Aspergillus parasiticus, Aspergillus carbonarius, Aspergillus niger, Aspergillus ochraceus and Aspergillus westerdijkiae through the methodology recommended by the European Committee for Standardization. Benzalkonium chloride and iodine were the most effective sanitizers to eliminate Aspergillus from the Flavi and Nigri section. Peracetic acid showed the best elimination of the growth of Aspergillus from Circumdati section. Sodium hypochlorite, biguanide, and electrolyzed water agents were the least effective, reducing less than 3 log from initial control, not being the most suitable agents for the control of toxigenic fungi in food industries.


Assessing Food Access, Exercise, and Dietary History among Older African American Parishioners During the COVID-19 Pandemic (C-FED Study): Design, Opportunities, Challenges, and Lessons Learned.
Unhealthy diets and inadequate exercise are associated with chronic health conditions and excess mortality. Older African Americans do not meet dietary and exercise guidelines, and this may have worsened during the COVID-19 pandemic due to individual and environmental factors, including food insecurity. Studies evaluating these dynamics are essential for developing interventions. This narrative details a study protocol and data collection experiences during the pandemic. Participants > 55 years African American old completed detailed food frequency, exercise, and food access questionnaires between October 2020 and July 2021. Observations of the study administrators (authors of this manuscript) for the duration of the study are presented. Details on the study design and reflections on the opportunities, challenges, and lessons learned are summarized. Future manuscripts will report data analysis of study findings. A total of 123 older African American adults participated in the study, and 118 (70% female) completed all three questionnaires. More than 50% of the participants had at least two primary chronic conditions. About 85% were fully vaccinated against COVID-19. Applying community-based participatory approaches, leveraging partnerships, and exercising flexibility approaches were pivotal to successfully implementing the study protocol. Despite challenges related to the COVID-19 pandemic, detailed data on older African American adults' diet and exercise habits were obtained. Our study design and experiences will benefit future researchers. More importantly, results from our study will inform interventions and policies aimed at minimizing consequences associated with poor diet and exercise habits during the pandemic among this vulnerable population.


Toxoplasma gondii infection in Blanford's fox (Vulpes cana).
Fatal toxoplasmosis was diagnosed in a Blanford's fox (Vulpes cana) from the United Arab Emirates. Toxoplasma gondii-like tachyzoites were found associated with necrosis in intestine, spleen, liver, kidneys, lungs, skeletal muscle, brain and heart. Protozoal tachyzoites reacted positively with T. gondii-specific polyclonal antibodies. Antibodies to T. gondii were detected in 10 of 12 V. cana assayed by the latex agglutination or the modified direct agglutination test.


Quantum battles in attoscience: tunnelling.
What is the nature of tunnelling? This yet unanswered question is as pertinent today as it was at the dawn of quantum mechanics. This article presents a cross section of current perspectives on the interpretation, computational modelling, and numerical investigation of tunnelling processes in attosecond physics as debated in the Quantum Battles in Attoscience virtual workshop 2020.


Effects of preoptic injections of gastrin, cholecystokinin, secretin, vasoactive intestinal peptide and PHI on the secretion of luteinizing hormone and prolactin in ovariectomized estrogen-primed rats.
The effects of intracerebral injections of brain-gut peptides in the preoptic region on the secretion of luteinizing hormone (LH) and prolactin (PRL) were examined in ovariectomized, estrogen-primed rats. Gastrin or cholecystokinin-octapeptide injection in the preoptic region induced a moderate increase of circadian rise of LH secretion in some animals but no appreciable change in PRL secretion. Secretin injection was strikingly effective in increasing circadian rise of LH and PRL secretion. Vasoactive intestinal peptide injection completely abolished the occurrence of circadian rise of LH secretion whereas PHI injection facilitated LH secretion undergoing the circadian rhythm. The results suggest that those peptides act as neurotransmitters or neuromodulators in the preoptic region and are implicated in the regulation of LH and PRL secretion.


A microfluidic protease activity assay based on the detection of fluorescence polarization.
This article describes a fluorescence polarization (FP)-based protease assay on a microfluidic device that is compatible with fast and reproducible analyses of protease activities. The optical systems were arranged for simultaneously measuring fluorescence intensities of vertical and horizontal polarization planes, and the binding of tetramethylrhodamine (TMR) labeled-biotin with streptavidin was utilized for optimizing FP detection in continuously flowing solutions within 74-microm wide, 12-microm deep microchannels of a glass chip. In developing off-chip FP-based assays for proteinase K, trypsin, papain and elastase, TMR conjugated-casein protein (TMR-alpha-casein) was employed as a universal substrate. After optimization of the hydrodynamic flow control to allow complete mixing of TMR-alpha-casein and short proteolysis time as possible, and of buffer composition to minimize protein sticking problems, the developed assay was transferred to the microfluidic chip by monitoring FP changes of TMR-alpha-casein in the main microchannel. The results indicate that the proposed device would serve as an integrated microfluidic platform with automated injection of reacting species, diffusion-controlled mixing, reaction and detection for protease activities without the need to separate the products.


Meningitis: is a major cause of disability amongst Papua New Guinea children?
This article is intended to focus on the need for the use of rehabilitation services, for children with meningitis in Papua New Guinea, which is one of largest developing country in The Pacific with diverse culture and landscape. Meningitis is the fifth leading disease that results in disability in the country. The first line of treatment is usually antibiotics, administration of vaccination is also recommended. Currently community based rehabilitation workers and Physiotherapist offer the rehabilitation services. There is a need for the other rehabilitation professionals and appropriate education to the CBR workers, caregivers for providing effective Rehabilitation. Articles related to meningitis were recruited through various electronic database such as Ovid SP, MEDLINE, CINHAL, Google Scholar and HINARI and EBSCOhost for full text. The search includes journal articles, editorials, research reports, systematic reviews and books. The neurological sequelae resulting from meningitis are increasing. There is a need for Hib vaccination to reduce the rate of mortality. Physiotherapists are new professionals that emerged since 2006 and are assisting in reducing the motor and neurological disability. A multidisciplinary approach is required to manage the child with meningitis. Adequate knowledge, resources and assistance about the condition among the health professionals, carers and teachers would enable the children to achieve the quality of life.


[Dysfibrinogenemia. A new case: dysfibrinogenemia Giessen III (author's transl)].
A new case of dysfibrinogenemia is reported which shows no signs of a haermorrhagic diathesis (dysfibrinogenemia Giessen III). The abnormal fibrinogen was detected by only slight but characteristic alterations of some parameter of the coagulation analysis (prolonged clotting times after addition of thrombin, Reptilase and thrombin coagulase; low fibrinogen concentration determined by methods based on clot formation in comparison to the immunological fibrinogen determination; delayed fibrin polymerization). In addition, clinical features and diagnosis of dysfibrinogenemia are described in general.


Bombyx mori nucleopolyhedrovirus F-like protein Bm14 is a cofactor for GP64-Mediated efficient infection via forming a complex on the envelope of budded virus.
Our previous study showed that Bombyx mori nucleopolyhedrovirus F-like protein Bm14 is involved in infectious BV production and its deletion reduces the production rate. However, the peculiar relationship between Bm14 and GP64, two major BV envelope proteins, is still unknown. Here, we demonstrated the predominant distribution of Bm14 in BVs rather than in ODVs. Further experiments revealed that the absence of Bm14 moderately reduced trafficking of GP64 to the plasma membrane and impaired GP64-mediated fusion activity. Coimmunoprecipitation analysis demonstrated the associations of Bm14 with GP64, and confocal microscopy also displayed their colocalization throughout nonviral or viral infection. More interestingly, an approximately 270-kDa complex containing Bm14 and GP64 was detected in the cytoplasm using BN-PAGE and Western blotting. The disruption of Bm14 resulted in a subcomplex of ~190 kDa. Collectively, Bm14 functions as a cofactor of GP64 via forming a complex on the surface of BVs, thus affecting the efficient infection.


Sarcomas of fat and bone: a case report.
Osteosarcomas are the most common primary malignant bone tumors and are classified by the WHO into several intramedullary and surface subtypes. One of these is the rare parosteal osteosarcoma. Liposarcomas are the second most common soft tissue sarcoma and are classified into several types ranging from intermediate to high grade tumors. In one of our recent patients we found an unusual combination of a parosteal osteosarcoma and a large fatty component, which fluorescence-in-situ-hybridization revealed as liposarcoma. Radiologists, pathologists, and surgeons should consider the possibility of bone and soft tissue malignancies consisting of different components, as this may be of paramount importance for oncologically complete resection.


Putting in harm to cure: Drug related adverse events do not affect outcome of patients receiving treatment for multidrug-resistant Tuberculosis. Experience from a tertiary hospital in Italy.
Treatment of multi-drug resistant Tuberculosis (MDR-TB) is challenging because it mostly relies on drugs with lower efficacy and greater toxicity than those used for drug-susceptible TB. Aim of the study was to describe the frequency and type of adverse drug reactions in a cohort of MDR-TB patients and their potential impact on treatment outcome. We conducted a retrospective study in a cohort of MDR-TB patients enrolled at a tertiary referral hospital in Italy from January 2008 to December 2016. The records of patients were reviewed for epidemiological, clinical, microbiological and adverse drug reactions data. Seventy-four MDR-TB patients (mean age 32 years, 58.1% males, 2 XDR, 12 pre-XDR TB) were extracted from the Institute data base and included in the retrospective study cohort in the evaluation period (January 2008-December 2016). Median length of treatment duration was 20 months (IQR 14-24). Treatment outcome was successful in 57 patients (77%; 51 cured, 6 treatment completed); one patient died and one failed (2.7% overall); 15 patients were lost to follow-up (20.3%). Sixty-six (89.2%) presented adverse drug reactions during the whole treatment period. Total number of adverse drug reactions registered was 409. Three hundred forty-six (84.6%) were classified as adverse events (AEs) and 63 (15.4%) were serious AEs (SAEs). One third of the total adverse drug reactions (134/409; 32.8%) was of gastrointestinal origin, followed by 47/409 (11.5%) ototoxic drug reactions, thirty-five (8.6%) regarded central nervous system and 33 (8.1%) affected the liver. All 63 SAEs required treatment suspension with 61 SAEs out of 63 (96.8%) occurring during the first six months of treatment. Factors associated with unsuccessful treatment outcome were smoking (p = 0.039), alcohol abuse (p = 0.005) and homeless condition (p = 0.044). Neither the number of antitubercular drugs used in different combinations nor the number of AEs showed significant impact on outcome. Patients who completed the treatment experienced a greater number of AEs and SAEs (p < 0.001) if compared to lost to follow-up patients. Our data demonstrate that, despite the high frequency of adverse drug reactions and long term therapy, the clinical management of MDR-TB patients in a referral center could reach successful treatment according to WHO target, by implementing active and systematic clinical and laboratory assessment to detect, report and manage suspected and confirmed adverse drug reactions.


A rare case and review of pulmonary ossification.
Pulmonary ossification (PO) is a rare metastatic disease characterized by the formation of diffuse heterotopic bone units in the lung parenchyma. Herein, we describe a 45-year-old Filipino male with dendriform pulmonary ossification in combination with gastroesophageal reflux disease and chronic dust exposure, a notably unique association. Radiographic imaging and pathology findings are examined with discussion of various pulmonary disease entities from current literature. Further recognition of PO will facilitate appropriate treatment and better outcomes for patients diagnosed with this enigmatic condition.


Prevalence of 22q11.2 deletions in 311 Dutch patients with schizophrenia.
The objectives of this study were 1) to examine whether the prevalence of 22q11.2 deletion syndrome (22q11DS) in schizophrenia patients with the Deficit syndrome is higher than the reported approximately 2% for the population of schizophrenia patients as a whole, and 2) to estimate the overall prevalence of 22q11DS among schizophrenia patients by combining all available studies. Our sample, enriched for patients with the Deficit syndrome, had 88% power to detect an estimated prevalence of 5% of 22q11.2 deletions. No 22q11.2 deletions were detected in 311 schizophrenia patients, 146 of whom met criteria for the Deficit syndrome. Our literature research revealed that in eight studies sixteen deletions were identified in 2133 patients with schizophrenia. This corresponds to a prevalence of 0.75% (95%CI: 0.5%-1.2%). The prevalence of 22q11.2DS in schizophrenia patients with the Deficit syndrome is not higher than in the population of schizophrenia patients as a whole. The prevalence of 22q11.2DS in schizophrenia patients is lower than the frequently reported prevalence of 2% or more.


Polycyclic aromatic hydrocarbons in soil of the backfilled region in the Wuda coal fire area, Inner Mongolia, China.
The Wuda coal fire area in Inner Mongolia, China, has existed for 50 years and been controlled by digging and backfilling for many years. However, few studies have focused on its impact on the local environmental and ecological systems due to emission of organic contaminants from the backfilled region. In the study, topsoil samples were collected at a 0-5 cm depth from the backfilled region of the Wuda coal fire area, which has existed for five years. The samples were analyzed for 16 priority control contaminants, namely polycyclic aromatic hydrocarbons (PAHs), with a standard operation procedure and high-performance liquid chromatograph (HPLC). The results showed that the total mass contentration of 16 PAHs (∑16PAHs) ranged from 279 to 8258 μg kg-1, with an average value of 2853 ± 2948 µg kg-1, which exceeded the stipulated limit for heavily contaminated soil (1000 μg kg-1). Among the 16 PAHs, 2- and 3-ring compounds accounted for more than half of ∑16PAHs. Furthermore, the results show that the main contaminants were the naphthalene (Nap), phenanthrene (Phe), pyrene (Pyr), chrysene (Chr), and benzo[b]fluoranthene (BbF) in this area (24.8%, 51.1%, 3.9%, 4.5%, and 5.7% of ∑16PAHs, respectively). The diagnostic ratio of FLA/(FLA + PYR) exceeded 0.4 and IcdP/(IcdP + BghiP) was less than 0.5, indicating gentle smoldering or spontaneous combustion of coal fire, which differs from traditional coal burning. The environmental health risk or specifically the cancer risk (CR), calculated using the surface soil of the backfilled region, was 2.84 × 10-6 for adults and 1.01 × 10-6 for children, thus indicating potential cancer risks. Therefore, PAHs pollution in the surface soil of the backfilled region in the studied coal fire area is an issue that deserves urgent attention.


Construction and application of high-quality genome-scale metabolic model of Zymomonas mobilis to guide rational design of microbial cell factories.
High-quality genome-scale metabolic models (GEMs) could play critical roles on rational design of microbial cell factories in the classical Design-Build-Test-Learn cycle of synthetic biology studies. Despite of the constant establishment and update of GEMs for model microorganisms such as Escherichia coli and Saccharomyces cerevisiae, high-quality GEMs for non-model industrial microorganisms are still scarce. Zymomonas mobilis subsp. mobilis ZM4 is a non-model ethanologenic microorganism with many excellent industrial characteristics that has been developing as microbial cell factories for biochemical production. Although five GEMs of Z. mobilis have been constructed, these models are either generating ATP incorrectly, or lacking information of plasmid genes, or not providing standard format file. In this study, a high-quality GEM iZM516 of Z. mobilis ZM4 was constructed. The information from the improved genome annotation, literature, datasets of Biolog Phenotype Microarray studies, and recently updated Gene-Protein-Reaction information was combined for the curation of iZM516. Finally, 516 genes, 1389 reactions, 1437 metabolites, and 3 cell compartments are included in iZM516, which also had the highest MEMOTE score of 91% among all published GEMs of Z. mobilis. Cell growth was then predicted by iZM516, which had 79.4% agreement with the experimental results of the substrate utilization. In addition, the potential endogenous succinate synthesis pathway of Z. mobilis ZM4 was proposed through simulation and analysis using iZM516. Furthermore, metabolic engineering strategies to produce succinate and 1,4-butanediol (1,4-BDO) were designed and then simulated under anaerobic condition using iZM516. The results indicated that 1.68 mol/mol succinate and 1.07 mol/mol 1,4-BDO can be achieved through combinational metabolic engineering strategies, which was comparable to that of the model species E. coli. Our study thus not only established a high-quality GEM iZM516 to help understand and design microbial cell factories for economic biochemical production using Z. mobilis as the chassis, but also provided guidance on building accurate GEMs for other non-model industrial microorganisms.


Predicting overall and major postoperative morbidity in gastric cancer patients.
Postoperative complications after gastric cancer resection vary in different series and they might have a significant impact in long-term outcomes. Our aim was to build a prediction rule on gastric cancer patients' overall and major morbidity risks. This retrospective study included 1223 patients from a single center who were resected between 1992 and 2016. Overall and major morbidity predictors were identified through multiple logistic regression. Models' performances were assessed through discrimination, calibration, and cross-validation, and nomograms were constructed. The mean age was 61.3-year old and the male gender was more frequent (60%). The most common comorbidities were hypertension (HTN), diabetes, and chronic obstructive pulmonary disease (COPD). A D2-distal gastrectomy was the most frequent procedure and 87% of all lesions were located in the middle or distal third. Age, COPD, coronary heart disease, chronic liver disease, pancreatic resection, and operative time were independent predictors of overall and major morbidity. The extent of resection and splenectomy was associated with overall events and HTN with major ones. Both models were very effective in predicting events among patients at higher risk. The overall and major morbidity models and nomograms included clinical- and surgical-related data that were very effective in predicting events, especially for high-risk patients.


Emergent layer stacking arrangements in c-axis confined MoTe2.
The layer stacking order in 2D materials strongly affects functional properties and holds promise for next-generation electronic devices. In bulk, octahedral MoTe2 possesses two stacking arrangements, the ferroelectric Weyl semimetal Td phase and the higher-order topological insulator 1T' phase. However, in thin flakes of MoTe2, it is unclear if the layer stacking follows the Td, 1T', or an alternative stacking sequence. Here, we use atomic-resolution scanning transmission electron microscopy to directly visualize the MoTe2 layer stacking. In thin flakes, we observe highly disordered stacking, with nanoscale 1T' and Td domains, as well as alternative stacking arrangements not found in the bulk. We attribute these findings to intrinsic confinement effects on the MoTe2 stacking-dependent free energy. Our results are important for the understanding of exotic physics displayed in MoTe2 flakes. More broadly, this work suggests c-axis confinement as a method to influence layer stacking in other 2D materials.


Brain hemodynamic effects of doxapram in preterm infants.
Doxapram is a respiratory stimulant widely used for the treatment of idiopathic apnea of prematurity, although it has been demonstrated that it can induce a transient decrease of cerebral blood flow and that isolated mental delay in infants weighing <1,250 g is associated with the total dosage and duration of doxapram therapy. To evaluate the effects of doxapram on cerebral hemodynamics in preterm infants using cerebral Doppler ultrasonography and near-infrared spectroscopy. Preterm infants who required treatment with doxapram for apnea of prematurity unresponsive to caffeine were treated with doxapram at an hourly dose of 0.5 mg x kg(-1).h(-1), followed by 1.5 and 2.5 mg x kg(-1).h(-1). 20 preterm infants were studied. Doxapram induced a significant decrease of oxygenated hemoglobin (O(2)Hb) and cerebral intravascular oxygenation (HbD = O(2)Hb - HHb) and an increase of HHb and CtOx concentrations, while cerebral blood volume and cerebral blood flow velocity did not change. Doxapram infusion induces the increase of cerebral oxygen consumption and requirement and the contemporary decrease of oxygen delivery probably mediated by a decrease of cerebral blood flow. Caution must be recommended in prescribing this drug for apnea of prematurity.


How is spatial transcriptomics influencing cancer research and diagnostics?
[Formula: see text] Spatial transcriptomics has continued to rise in popularity since it was developed in 2016; but how is it being utilized in tumor biology and diagnostics research?


High-throughput sequencing of microbial diversity in implant-associated infection.
Few molecular studies have shown that the number of bacterial species in implant-associated infection may have been underestimated. To determine the actual microbial diversity in implant-associated infection, a high-throughput sequencing method was adopted to sequence the DNAs extracted from the tissues of infected and uninfected patients. Principal component analysis (PCA) and β diversity showed an obvious divergence of infected and uninfected groups, and that the overgrowth of Proteobacteria (80.87%), Firmicutes (13.41%) in the positive deep infection group (P.d, via biopsy) and Proteobacteria (91.68%) in the positive surface infection group (P.s, via swabs) might be the causative factors in implant-associated infection. Moreover, Venn results indicated that a mean of 330 common operational taxonomic units (OTUs) was obtained in all groups, of which 113, 109, 45, 20, 13 and 12 OTUs belonging to Proteobacteria, Actinobacteria, Acidobacteria, Planctomycetes, Gemmatimonadetes and Chloroflexi were identified. In conclusion, many traditional "pathogenic bacteria" were identified as the common bacteria in operation sites, and the disruption of their complex interaction caused infection; therefore, further work is need to illustrate the aetiology of implant-associated infection using in-depth systems-level analyses.


Influence of photo-initiators in the preparation of methacrylate monoliths into poly(ethylene-co-tetrafluoroethylene) tubing for microbore HPLC.
In this study, poly(butyl methacrylate-co-ethyleneglycol dimethacrylate) polymeric monoliths were in situ developed within 0.75 mm i.d. poly(ethylene-co-tetrafluoroethylene) (ETFE) tubing by UV polymerization via three different free-radical initiators (α,α'-azobisisobutyronitrile (AIBN), 2,2-dimethoxy-2-phenylacetophenone (DMPA) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMPP). The influence of the nature of each photo-initiator and irradiation time on the morphological features of the polymer was investigated by scanning electron microscopy, and the chromatographic properties of the resulting microbore columns were evaluated using alkyl benzenes as test substances. The beds photo-initiated with MTMPP gave the best performance (minimum plate heights of 38 μm for alkyl benzenes) and exhibited a satisfactory reproducibility in the chromatographic parameters (RSD < 11%). These monolithic columns were also successfully applied to the separation of phenylurea herbicides, proteins and a tryptic digest of β-casein.


Investigation of structural and physicochemical properties of microcapsules obtained from protein-polysaccharide conjugate via the Maillard reaction containing Satureja khuzestanica essential oil.
In this study, some common proteins including, whey protein isolate (WPI), soy protein isolate (SPI), and gelatin (G) conjugated with maltodextrin (MD) via Maillard reaction and were then used to encapsulate Satureja khuzestanica essential oil (SKEO). The higher glycation degree was obtained at a pH of 9 and 3 h of heating at 60 °C for SPI and WPI, and 90 °C for G. The results of FTIR and intrinsic fluorescence test showed the possibility of covalent binding formation between proteins and maltodextrin. The encapsulation efficiencies were obtained about 83.84 %, 88.95 %, and 89.27 % for MD-SPI, MD-G, and MD-WPI, respectively. Moreover, the Maillard reaction-based microcapsules had higher antioxidant activity than the physical mixture of protein-polysaccharide. The addition of SKEO to microcapsules improved antimicrobial activity. The results of this study demonstrated that MD-WPI and MD-G, as encapsulating materials, can be used to enhance the physiochemical properties of microcapsules loaded with SKEO.


Real time kinetic analysis of the interaction between immunoglobulin G and histidine using quartz crystal microbalance biosensor in solution.
Quartz crystal microbalance (QCM) biosensor integrated in a flow injection analysis (FIA) system was used for the investigation of the specific interaction between immunoglobin G (IgG) and histidine. The histidine was immobilized on the gold electrodes of the piezoelectric crystal using appropriate procedures based on self-assembling of the dithiothreitol (DTT). The specific interaction of the immobilized ligand with IgG in solution was followed as a change in the resonant frequency of the modified crystal and studied in real time without any additional labels. With the mass sensitive biosensor system, the differences in affinity of three different species of IgG: human IgG, goat IgG and mouse IgG were easily distinguished and their respective kinetic rate constants (kass and kdiss) and equilibrium association constants (KA) were determined from the curves of frequency versus time. For the interactions, KA were 2.92 x 10(4), 3.23 x 10(4) and 4.08 x 10(4) M(-1) for human IgG, goat IgG and mouse IgG, respectively.


Experimental neodymium:YAG laser damage to acrylic, poly(methyl methacrylate), and silicone intraocular lens materials.
To compare neodymium:YAG (Nd:YAG) laser effects on acrylic, silicone, and poly(methyl methacrylate) (PMMA) intraocular lens (IOL) polymers. Ten Nd:YAG laser exposures were produced in each of 6 implantation-quality acrylic (Alcon MA60BM), silicone (Staar AQ1016), and PMMA (Alcon MC60BM) IOLs under identical conditions. Each polymer type was irradiated at 6 power settings (0.3, 0.5, 1.0, 1.5, 2.0, and 3.0 mJ) and at 2 focal points (midpoint of lens optic and on the posterior surface to which a cellophane membrane was affixed). The linear extent of the damage was measured using light microscopy. Specimens exposed to 1.0 mJ were processed for scanning electron microscopy. The damage threshold (> or = 5 microns depth) was 0.3 mJ for silicone and 1.0 mJ for acrylic and PMMA IOLs. At the clinically relevant power levels, 1.0 to 2.0 mJ, the depth of damage in the acrylic polymer was 11.9 to 30.5 times less than the depth in the silicone polymer. Similarly, the depth of damage in the PMMA polymer was 5.4 to 52.6 times less than the depth in the silicone polymer. The morphologic pattern of damage in the silicone IOL showed a deep, irregularly configured trough with meandering tendrils. Acrylic IOL damage morphology consisted of an ameboid-shaped entry site without radiating fractures and mild posterior penetration. Poly(methyl methacrylate) IOL damage consisted of a shallow focal trough with radiating fractures. The silicone IOL polymer had the lowest threshold for laser-induced damage and greater linear extension of damage than the PMMA and acrylic IOL polymers. Poly(methyl methacrylate) and silicone polymers exhibited collateral damage or ejected particulates adjacent to the entry site, whereas the acrylic polymer showed a discrete locus of damage.


Occurrence of free D-aspartate and aspartate racemase in the blood shell Scapharca broughtonii.
Substantial concentrations of D-aspartate were found in several tissues of Scapharca broughtonii together with approximately equal concentrations of L-aspartate. The foot and mantle extracts also contained an aspartate racemase activity. The formation of L-aspartate from the D-enantiomer by the foot extract was apparently slower than the reverse reaction, and this unbalance seemed to be due to the presence of an enzyme activity which rapidly converted L-aspartate to L-alanine. The possible role of D-aspartate in the anaerobiosis was discussed.


Ovarian recurrence after radical trachelectomy for adenocarcinoma of the cervix.
Radical trachelectomy is an effective fertility-sparing treatment for women with early-stage cervical cancer. We describe the first reported ovarian recurrence after radical trachelectomy for stage IB1 adenocarcinoma cervical cancer.


Uncertainty-dependent activity within the ventral striatum predicts task-related changes in response strategy.
Recent neuroimaging work has demonstrated that the ventral striatum (VS) encodes confidence in perceptual decisions. However, it remains unclear whether perceptual uncertainty can signal the need to adapt behavior (such as by responding more cautiously) and whether such behavioral changes are related to uncertainty-dependent activity within the VS. Changes in response strategy have previously been observed following errors and are associated with both medial frontal cortex (MFC) and VS, two components of the performance-monitoring network. If uncertainty can elicit changes in response strategy (slowing), then one might hypothesize that these changes rely on the performance-monitoring network. In the present study, we investigated the link between perceptual uncertainty and task-related behavioral adaptations (response slowing and accuracy increases), as well as how such behavioral changes relate to uncertainty-dependent activity within MFC and VS. Our participants performed a two-choice perceptual decision-making task in which perceptual uncertainty was reported on each trial while behavioral and event-related functional magnetic resonance imaging data were collected. Analysis of the behavioral data revealed that uncertain (but correct) responses led to slowing on subsequent trials, a phenomenon that was positively correlated with increased accuracy. Critically, post-uncertainty slowing was negatively correlated with the VS activity elicited by uncertain responses. In agreement with previous reports, increases in MFC activation were observed for uncertain responses, although MFC activity was not correlated with post-uncertainty slowing. These results suggest that perceptual uncertainty can serve as a signal to adapt one's response strategy and that such behavioral changes are closely tied to the VS, a key node in the performance-monitoring network.


Move to list monkey as endangered spurs dispute.
U.S. group challenges decision to reclassify macaque widely used in biomedical research.


Swimming Impacts on Pancreatic Inflammatory Cytokines, miR-146a and NF-кB Expression Levels in Type-2 Diabetic Rats.
Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and type-2 diabetes Objective: This study aimed to evaluate the effect of swimming exercise on pancreatic expression levels of inflammatory cytokines, miR-146a and NF-кB in type-2 diabetic male rats. Twenty- eight male Wistar rats were divided into four groups: control (Con), exercise, diabetes and diabetic exercise (n = 7). Diabetes induction performed by the combination of high-fat diet (HFD, 4 weeks) and streptozotocin (35 mg/kg. ip). After induction of diabetes, the rats swam in the exercise groups for 12 weeks. Then, blood and tissue samples were collected. Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group. Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group.


Extraction of Cu, Fe, Mn, and Ni from Margarine Samples Using Extraction Induced by Emulsion Breaking Procedure Prior to Graphite Furnace Atomic Absorption Spectrometry and Comparison of Results to Provisional Tolerable Daily Intake Values.
The emulsion induced by emulsion breaking (EIEB) procedure was previously reported for the extraction of copper, iron, manganese, and nickel from liquid oil samples such as vegetable oil. To optimize the EIEB procedure for determination of copper, iron, manganese, and nickel in solid oil (margarine) samples by Graphite Furnace Atomic Absorption Spectrometry (GFAAS). The extraction procedure uses a surfactant in nitric acid to form an emulsion followed by heating to break the emulsion. Optimization included variation of the test portion size, the type and concentration of the surfactant, the concentration of nitric acid in the aqueous solution, the emulsion agitation time, heating temperature, and the time required to break the emulsion. Mean element concentrations of 11 margarine samples were in the following ranges: Cu 0.031-0.131 µg/g, Fe 5.7-24.9 µg/g, Mn 0.542-1.11 µg/g, and Ni 0.108-0.134 µg/g. Under the optimized extraction conditions, the detection limits (µg/kg) were 4.8, 13, 1.5, and 23 for Cu, Fe, Mn, and Ni, respectively. The accuracy of the extraction procedure was determined by comparison to commonly used microwave digestion procedure. The EIEB results were not statistically different from the microwave digestion results when analyzed by GFAAS as determined by the statistical tests. The EIEB procedure was shown to be equivalent to the commonly used microwave digestion procedure for extraction of analytes from margarine samples. The optimized EIEB extraction procedure is simple, rapid, low cost, and environmentally friendly. It has improved detection limits and allows calibration with aqueous standards.


TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study.
To evaluate which girls with Turner syndrome (TS) could benefit from fertility preservation by ovarian tissue cryopreservation on the basis of karyotype, puberty status, and hormonal data. Prospective intervention study; participants were included between 2018 and 2020. Tertiary hospital in the Netherlands. In total, 106 girls with TS aged between 2 and 18 years were included. Girls with minor X chromosome deletions, Y chromosomal content, active infections, or contraindications for surgery were excluded. A laparoscopic unilateral ovariectomy was performed to obtain ovarian cortical tissue for cryopreservation. One tissue fragment per participant was used to determine the number of follicles per ovary by serial sectioning and staining. Chromosome analysis was performed on lymphocytes and buccal cells. A blood sample was taken before the ovariectomy for hormonal analysis. The presence of follicles in ovarian cortex tissue from girls with TS in relation to karyotype, puberty status, and hormonal data. A unilateral ovariectomy was performed on 93 girls with TS. Complications after surgery occurred in 5 girls, including luxation of psychological symptoms in 2 girls. In 13 (14%) girls, a 46,XX cell line was found in buccal cells that was absent in lymphocytes. Follicles were observed in 30 (32%) of the 93 girls and were found mainly in girls with a 46,XX cell line in lymphocytes or buccal cells (Phi coefficient = 0.55). Spontaneous onset of puberty (Phi coefficient = 0.59), antimüllerian hormone (AMH; point-biserial correlation [r] = 0.82), inhibin B (r = 0.67), and follicle-stimulating hormone (r = -0.46) levels were also correlated strongly with the presence of follicles. Furthermore, AMH levels had a significant correlation with the number of follicles per ovary (r = 0.66). Favorable predictive markers for the presence of follicles included either a 46,XX cell line, spontaneous onset of puberty, or a combination of measurable AMH and normal follicle-stimulating hormone levels. Karyotyping of two peripheral cell lines in girls with TS is recommended to reveal hidden mosaicisms. Ovarian tissue cryopreservation should be offered with caution in a research setting to those with a sufficient ovarian reserve, considering the significant loss of follicles after ovarian tissue cryopreservation and autotransplantation. Physicians should pay attention to the mental health of the girls during the whole process. Trial registration number: NCT03381300- Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome - Full Text View - ClinicalTrials.gov. Registered on: December 21, 2017. First patient recruited on January 1, 2018.


Functional significance of serine 13 in the active site of glutathione S-transferase F3 from Oryza sativa.
Plant glutathione S-transferase (GST, EC 184.108.40.206) is an enzyme that detoxifies various electrophilic compounds including herbicides and organic pollutants by catalyzing the formation of conjugates with reduced glutathione (GSH). Although the structure and function of the GST subunits in rice, an important food in Asia, are not well understood, they are crucial for herbicide development. To investigate the role of active site residues in rice Phi-class GSTF3 (OsGSTF3), evolutionarily conserved serine residues were replaced with alanine using site-directed mutagenesis to obtain the mutants S13A, S38A, S69A, and S169A. These four mutants were expressed in Escherichia coli and purified to electrophoretic homogeneity using immobilized GSH affinity chromatography. Mutation of Ser13 to Ala resulted in substantial reductions in specific activities and kcat/Km values for the GSH-[1-chloro-2,4-dinitrobenzene (CDNB)] conjugation reaction. In contrast, mutations of Ser38, Ser69, and Ser169 to Ala had little effect on the activities and kinetic parameters. Additionally, the mutation of Ser13 to Ala significantly affected the KmGSH and I50 values of S-hexylglutathione and S-(2,4-dinitrophenyl)glutathione, which compete with GSH and the product of GSH-CDNB conjugation, respectively. A pH-log (kcat/KmCDNB) plot was used to estimate the pKa value of GSH in the enzyme-GSH complex of the wild-type enzyme, which was approximately 6.9. However, the pKa value of GSH in the enzyme-GSH complex of the S13A mutant was approximately 8.7, which was about 1.8 pK units higher than that of the wild-type enzyme. OsGSTF3 was also crystallized for crystallographic study, and the structure analyses revealed that Ser13 is located in the active site and that its side chain is in close proximity to the thiol group of glutathione bound in the enzyme. Based on these substitution effects on kinetic parameters, the dependence of kinetic parameters on the pH and 3-dimensional structure, it was suggested that Ser13 in rice OsGSTF3 is the residue responsible for catalytic activity by lowering the pKa of GSH in the enzyme-GSH complex and enhancing the nucleophilicity of the GSH thiol in the active site.


[Virological surveillance on hemorrhagic fever with renal syndrome in Hunan province in 2006].
To understand the rate of viral carrying status among rodents as well as genotypes and distribution of Hantaviruses (HV) isolated in Hunan province. With DFA, the HV antigen in lung tissues of rodents was detected. The total viral RNA was extracted from the lung tissues of the HV infected rats and amplified with reverse transcrition-polymerase chain reaction (RT-PCR), using the HV genotype specific primers. The amplified genes were then sequenced and subjected to genotyping and homologic analysis. The average density of rodents was 3.15% and the virus carrying rate among rodents was 1.31%. Data from genotype analysis showed that the HV isolated from seven lung specimens taken from Rattus norvgicus, Apodemus agraius, Mus musculus, Rattus flavipectus among indoor rodents in Shaodong and Liuyang belonged to HV type II (SEOV), and one isolated from Apodemus agraius in Shaungfen belonged to HV type I (HTNV) among outdoor rodents. Six strains were sequenced successfully and the homology between six srains was 88.3%-100%. The homology of HN1, HN2, HN4, HN6 came from Liuyang and the HN7 and HN8 from Shaodong were both 100% while the homology between L99 and the strains from Liuyang and Shaodong were 94.4% and 88.3% respectively. HV type II (SEOV) and the HV type I (HTNV) were all existed in Hunan province while SEOV was the main genotype.


Growth control in the ontogenetic and regenerating zebrafish fin.
The growth and regeneration of the zebrafish fin provide yet another opportunity to exploit genetics to study important vertebrate problems. Mutants have been identified in zebrafish that affect the development of the embryonic fin, disrupt the normal growth relationship of fin and body, or disrupt the regeneration of the fin. Analysis of a regeneration mutation suggests that the developmental checkpoints that ensure developmental integrity in normal growth are absent in the early stages of regeneration. These stages correspond to the only time in fish developmental when differentiated bone cells divide.


Urothelium-Specific Expression of Mutationally Activated Pik3ca Initiates Early Lesions of Noninvasive Bladder Cancer.
Although approximately 70% of bladder cancers are noninvasive and have high recurrence rates, early-stage disease is understudied. The lack of models to validate the contribution of molecular drivers of bladder tumorigenesis is a significant issue. Although mutations in PIK3CA are frequent in human bladder cancer, an in vivo model for understanding their contribution to bladder tumorigenesis is unavailable. Therefore, a Upk2-Cre/Pik3caH1047R mouse model expressing one or two R26-Pik3caH1047R alleles in a urothelium-specific manner was generated. Pik3caH1047R functionality was confirmed by quantifying Akt phosphorylation, and mice were characterized by assessing urothelial thickness, nuclear atypia, and expression of luminal and basal markers at 6 and 12 months of age. While at 6 months, Pik3caH1047R mice developed increased urothelial thickness and nuclear atypia, progressive disease was not observed at 12 months. Immunohistochemistry showed urothelium maintained luminal differentiation characterized by high forkhead box A1 (Foxa1) and peroxisome proliferator-activated receptor γ expression. Surprisingly, Pik3caH1047R mice subjected to low-dose carcinogen exposure [N-butyl-N-(4-hydroxybutyl)nitrosamine] exhibited no significant differences after exposure relative to mice without exposure. Furthermore, single-sample gene set enrichment analysis of invasive human tumors showed those with mutant PIK3CA did not exhibit significantly increased phosphatidylinositol 3-kinase/AKT pathway activity compared with wild-type PIK3CA tumors. Overall, these data suggest that Pik3caH1047R can elicit early tumorigenic changes in the urothelium, but progression to invasion may require additional genetic alterations.


Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models.
To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.