Comprehensive evaluation of Loblolly fruit by high performance liquid chromatography four wavelength fusion fingerprint combined with gas chromatography fingerprinting and antioxidant activity analysis.
Loblolly fruit (LBF) is mainly used as raw material for beverage, but there are few researches on its quality evaluation or control. The aim of this study was to develop comprehensive evaluation methods for the quality control of Loblolly fruit. firstly, double wavelength coefficient ratio spectrum was used to identify the purity of chromatographic fingerprint peak. It is very important to identify the purity of fingerprint peaks because only the quantitative determination of pure chromatographic peaks is meaningful for its efficient quality control. Then, multi-wavelength fusion fingerprint was established to avoid one-sidedness of a single wavelength for further evaluation by systematically quantified fingerprint method (SQFM). According to the outcome of Pm, 25 batches of LBF were classified into two classifications by hierarchical cluster analysis, which was consistent with the SQFM evaluation results. Two active components, gallic acid (GAC) and ethyl gallate (EGA) in LBF, were quantitatively determined by quantitative analysis of multi-components by single marker (QAMS). In addition, the fingerprint efficacy relationship was established using an off-line antioxidant system and partial least-squares model to explore the connection between chemical components and antioxidant activities. Finally, the evaluation results of high-performance liquid chromatography and gas chromatography were integrated by the mean algorithm, which could reduce the error caused by single method. The results showed that the proposed strategy could provide a method for quality evaluation of LBF and even other traditional Chinese medicines (TCMs).


Potential cytotoxic and mutagenic effect of Pinus wallichiana, Daphne oleiodes and Bidens chinensis.
The Pinus wallichiana, Daphne oleiodes and Bidens chinensis have a long history of being used traditionally for treatment of various types of disorders. Most of the uses have been without any scientific evidence and toxicological assessment. We evaluated the mutagenic and cytotoxic capabilities of various parts of P. wallichiana, D. oleoides and B. chinensis. Ames Salmonella mutagenicity assay determined the mutagenicity activity against TA 98 and TA 100 bacterial strains of Salmonella typhimurium without metabolic activator S9 system. The number of mutant colonies in negative control was considered as limit to determine the mutagenicity effects of every extract. Brine shrimps lethality bioassay was used to determine the cytotoxic capabilities of the selected plants. The P. wallichiana, D. oleiodes and B. chinensis did not showed any mutagenic activity both for frameshift mutation (TA98) and base-pair substitution (TA100) without S9 mixture. The crude methanolic extract of P. wallichiana stem showed moderate cytotoxicity (53.33%) at 1000 μg/ml with LD50 value 599.634. The D. oleoides fruit showed a toxicity of 60% at 1000 μg/ml with LD50 value 367.730. The B. chinensis (whole plant) showed lethality of 63.3% at 1000 μg/ml, with LD50 204.833. The absence of any mutagenic activity of crude extract of the tested plants in both bacteria strains, TA 98 and TA 100 without the S9 mix confirms the safety of these plants to the consumers.


Immunization with a DNA chimeric molecule encoding a hemagglutinin peptide and a scFv CD21-specific antibody fragment induces long-lasting IgM and CTL responses to influenza virus.
Killed viral vaccines are known to induce primarily antibody responses. By contrast DNA vaccination using naked DNA encoding viral antigens induces both humoral and cellular immune responses. Various approaches have been used to construct DNA vaccines with build-in adjuvanticity. We hypothesized that sequences encoding a common epitope of influenza A virus hemagglutinin jointed to sequences encoding a single-chain variable fragment (scFv) antibody fragment to a costimulatory B cell surface receptor would result in the in vivo expression of a chimeric viral peptide with increased immunogenicity. Such a hybrid DNA molecule was constructed by us, encoding a T and B cell epitope-containing influenza hemagglutinin peptide and a scFv antibody fragment binding to mouse complement receptors I and II (CR1 and CR2). A single immunization with a plasmid containing the described construct induced a strong anti-influenza cytotoxic response lasting for more than six months and a weak antibody response.


Impact of infiltrative growth on the outcome of patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma.
Infiltrative growth, frequently observed in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS), is often associated with a positive surgical margin as well as a local failure. The purpose of our study was to determine whether the radiographic growth patterns were associated with the outcomes of patients with UPS and MFS. We reviewed 89 patients diagnosed with UPS or MFS and underwent initial surgery at our institute between 1994 and 2011. Growth patterns were assessed radiographically on preoperative MRI. Clinicopathological factors were collected and uni- and multivariate analyses were performed for survival. Infiltrative growth was observed in 21 patients (24%), which correlated with superficial tumors and positive surgical margin. Infiltrative growth correlated with poor disease-specific and distant failure-free survivals relative to non-infiltrative growth. Multivariate analysis confirmed that these factors remained as significant factors. Patients with non-infiltrative tumors resected inadequately exhibited slightly more favorable local control with postoperative radiotherapy, although no clinical benefit was seen for those with infiltrative tumors. Infiltrative growth was an adverse prognostic factor for not only local control, but also disease-specific and metastasis-free survival in patients with UPS and MFS. Radiotherapy could not salvage inadequately resected infiltrative tumors.


[Fibroepithelial polyp of the ureter in a child. A case report].
Fibroepithelial polyp of the ureter is benign tumor of mesodermal origin that rarely occurs in children. The most common presenting symptoms are hematuria and flank pain by obstruction of the urinary tract. The etiology of this tumor is not clear. It occurs more frequently in boys and often arises in the proximal ureter and the ureteropelvic junction. The preoperative diagnosis is difficult. We present the case of a 10-year-old boy who had recurrent episodes in the left flank owing to polyps of the lumbar ureter of which the fibroepithelial nature was confirmed by the pathological examination of the surgical specimen. We discuss the clinical presentations, imaging, histological features and treatment options of this unusual tumor through a review of the literature.


The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 preadipocytes.
Obesogens are chemicals that predispose exposed individuals to weight gain and obesity by increasing the number of fat cells, storage of fats into existing cells, altering metabolic rates, or disturbing the regulation of appetite and satiety. Tributyltin exposure causes differentiation of multipotent stromal stem cells (MSCs) into adipocytes; prenatal TBT exposure leads to epigenetic changes in the stem cell compartment that favor the production of adipocytes at the expense of bone, in vivo. While it is known that TBT acts through peroxisome proliferator activated receptor gamma to induce adipogenesis in MSCs, the data in 3T3-L1 preadipocytes are controversial. Here we show that TBT can activate the RXR-PPARγ heterodimer even in the presence of the PPARγ antagonist GW9662. We found that GW9662 has a 10-fold shorter half-life in cell culture than do PPARγ activators such as rosiglitazone (ROSI), accounting for previous observations that GW9662 did not inhibit TBT-mediated adipogenesis. When the culture conditions are adjusted to compensate for the short half-life of GW9662, we found that TBT induces adipogenesis, triglyceride storage and the expression of adipogenic marker genes in 3T3-L1 cells in a PPARγ-dependent manner. Our results are broadly applicable to the study of obesogen action and indicate that ligand stability is an important consideration in the design and interpretation of adipogenesis assays.


The effect of 2-mercaptoethanol on IgM and IgG antibody activity.
The effect of reduction by 2-mercaptoethanol (2-ME) on antibody activity was studied in antisera with high and low IgG concentrations. Sera obtained from B10.LP nu/nu mice during a primary response against a rat PVG/c skin graft contained only 2-ME sensitive antibodies. However, when analyzed on sucrose gradients, IgG as well as IgM antibody activity was present. After raising the low serum IgG concentration (0.3-0.7 mg/ml) of these sera by addition of normal mouse serum (5.1 mg IgG/ml), 2-ME resistant antibodies became detectable. Hyperimmune C57BL6 anti PVG/c lymphocyte serum with a high IgG concentration (20.2 mg/ml) and antibody activity predominantly located in the IgG class was not affected by 2-ME treatment. These data show that IgG antibodies, although less susceptible to reduction than IgM antibodies, are not resistant to this treatment. At high IgG concentrations the proportion of inactivated IgG with specific antibody activity will be negligible but at low IgG concentrations the use of this method leads to serious underestimation of IgG antibody activity.


mTOR pathway candidate genes and obesity interaction on breast cancer risk in black women from the Women's Circle of Health Study.
Obesity is known to stimulate the mammalian target of rapamycin (mTOR) signaling pathway and both obesity and the mTOR signaling pathway are implicated in breast carcinogenesis. We investigated potential gene-environment interactions between mTOR pathway genes and obesity in relation to breast cancer risk among Black women. The study included 1,655 Black women (821 incident breast cancer cases and 834 controls) from the Women's Circle of Health Study (WCHS). Obesity measures including body mass index (BMI); central obesity i.e., waist circumference (WC) and waist/hip ratio (WHR); and body fat distribution (fat mass, fat mass index and percent body fat) were obtained by trained research staff. We examined the associations of 43 candidate single-nucleotide polymorphisms (SNPs) in 20 mTOR pathway genes with breast cancer risk using multivariable logistic regression. We next examined interactions between these SNPs and measures of obesity using Wald test with 2-way interaction term. The variant allele of BRAF (rs114729114 C > T) was associated with an increase in overall breast cancer risk [odds ratio (OR) = 1.81, 95% confidence interval (CI) 1.10-2.99, for each copy of the T allele] and the risk of estrogen receptor (ER)-defined subtypes (ER+ tumors: OR = 1.83, 95% CI 1.04,3.29, for each copy of the T allele; ER- tumors OR = 2.14, 95% CI 1.03,4.45, for each copy of the T allele). Genetic variants in AKT, AKT1, PGF, PRKAG2, RAPTOR, TSC2 showed suggestive associations with overall breast cancer risk and the risk of, ER+ and ER- tumors (range of p-values = 0.040-0.097). We also found interactions of several of the SNPs with BMI, WHR, WC, fat mass, fat mass index and percent body fat in relation to breast cancer risk. These associations and interactions, however, became nonsignificant after correction for multiple testing (FDR-adjusted p-value > 0.05). We found associations between mTOR genetic variants and breast cancer risk as well as gene and body fatness interactions in relation to breast cancer risk. However, these associations and interactions became nonsignificant after correction for multiple testing. Future studies with larger sample sizes are required to confirm and validate these findings.


Cross-resistance phenotypes of fluconazole-resistant Candida species: results with 655 clinical isolates with different methods.
Candida species test results with two broth macrodilution antifungal susceptibility methods were compared using 655 clinical isolates, and the frequency of fluconazole resistance and phenotypes of azole cross resistance are detailed. A method with an 80% inhibition endpoint (as compared to clear tube endpoint) suggested greater fluconazole susceptibility to C. albicans but had a less pronounced effect on C. glabrata, and seemed to have a negligible influence on results with C. parapsilosis and C. tropicalis. The latter were grouped as susceptible and resistant (based on achievable blood levels), respectively, by both methods. Cross resistance was method dependent and more pronounced with itraconazole than ketoconazole. In vivo correlations are needed to validate the groupings proposed by any in vitro method.


Labilibaculum antarcticum sp. nov., a novel facultative anaerobic, psychrotorelant bacterium isolated from marine sediment of Antarctica.
A novel facultative anaerobic and facultative psychrophilic bacterium, designated SPP2T, was isolated from an Antarctic marine sediment. Cells of the isolate were observed to be long rods (0.5 × 5-10 μm), Gram-stain negative and to have gliding motility. For growth, the optimum NaCl concentration was found to be 2-3% and the optimum temperature to be 18-22 °C. Strain SPP2T cannot use sulfate and nitrate as electron acceptors in the presence of lactate. The G+C content of the genomic DNA was determined to be 36.0 mol%.. The major cellular fatty acids were identified as anteiso-C15:0 and iso-C15:0. MK-7 was found to be the predominant respiratory quinone. Phylogenetic analysis based on the 16S rRNA gene revealed that the novel strain belongs to the family Marinifilaceae and to be closely related to Labilibaculum manganireducens 59.10-2MT with 16S rRNA gene sequence identity of 98%. The OrthoANI and dDDH values between the genome sequences of strain SPP2T and its close relative were 84% and 27.3%, which are lower than the threshold values for species delineation. On the basis of phylogenetic and phenotypic characterisation, Labilibaculum antarcticum sp. nov. is proposed with the type strain SPP2T (= NBRC 111151T = CECT 9460T).


Immunologic findings in Peyronie's disease: a controlled study.
Recent literature suggests the hypothesis of an immune etiology of Peyronie's disease. In this controlled study, the immune response pattern of the disease is investigated. Sixty-six patients with Peyronie's disease and 20 age-matched controls were studied. In all patients, skin test (multitest), in vitro lymphocyte transformation test (LTT), serum immunoglobulin (Ig) A, G, and M, anti-DNA, antinuclear and anti-smooth muscle cell antibodies, C3 and C4 complement fractions, antistreptolysin, and C-reactive protein titers were evaluated. A fair percentage (75.8%) of the patients with Peyronie's disease exhibited at least one abnormal immunologic test, in comparison to only 10% among controls (chi-square = 27.8, df = 1; P < 0.0001). Alterations of cell-mediated immunity (multitest, LTT) were observed in 48.5% of patients, alterations of humoral immunity (Ig) in 31.8%, and alterations of markers of autoimmune disorders (autoantibodies, complement activation) in 37.9% of the cases. Our results support the hypothesis that there is some involvement of the immune system in the pathogenesis of Peyronie's disease, although the available data still appear to be insufficient to formulate a definite pathogenetic hypothesis.


High pressure induced changes on sarcoplasmic protein fraction and quality indicators.
The combined effect of pressure and mild temperature treatments on bovine sarcoplasmic proteins and quality parameters was assessed. M. longissimus dorsi samples were pressurised in a range of 200-600 MPa and 10-30 degrees C. High Pressure Processing (HPP) induced a reduction of protein solubility (p<0.001) compared to non-treated controls (NT), more pronounced above 200 MPa. HPP at pressures higher than 200 MPa induced a strong modification (p<0.001) of meat colour and a reduction of water holding capacity (WHC). SDS-PAGE analysis demonstrated that HPP significantly modified the composition of the sarcoplasmic protein fraction. The pressurisation temperature mainly affected protein solubility and colour; a smaller effect was observed on protein profiles. Significant correlations (p<0.001) between sarcoplasmic protein solubility and both expressible moisture (r=-0.78) and colour parameters (r=-0.81 to -0.91) suggest that pressure induced denaturation of sarcoplasmic proteins could influence to some extent WHC and colour modifications of beef. Changes in protein band intensities were also significantly correlated with protein solubility, meat lightness and expressible moisture. These results describe the changes induced by HPP on sarcoplasmic proteins and confirm a relationship between modification of the sarcoplasmic protein fraction and alteration of meat quality characteristics.


Novel regioselectivity: three-component cascade synthesis of unsymmetrical 1,4- and 1,2-dihydropyridines.
The three-component sequential reaction of alpha,beta-unsaturated aldehydes, amines, and enaminones proceeded smoothly to give 1,3,4-trisubstituted 1,4-dihydropyridines in aqueous DMF. Moreover, the unexpected regioselective formation of 1,2-dihydropyridines has been observed for the first time in such an approach. On the basis of a systematic study, the novel regioselectivity could be assigned both to steric and electronic effects originating from the amine partner.


Phosphatidylserine decarboxylase.
Phosphatidylserine decarboxylase (PSD) is an important enzyme in the synthesis of phosphatidylethanolamine in both prokaryotes and eukaryotes. The cloned bacterial gene encodes an integral membrane protein that is first made as a proenzyme, and subsequently proteolyzed to an alpha subunit, containing a pyruvoyl prosthetic group, and a beta subunit. Two types of decarboxylases are found in yeast, PSD1 and PSD2, that localize to the inner mitochondrial membrane and the Golgi/vacuole membrane, respectively. The mammalian enzyme is also found in the inner mitochondrial membrane. The yeast genes and mammalian cDNA have been cloned and sequenced. The yeast genes contain 5' sequences associated with regulation of expression by inositol and choline. The yeast PSD1 and the mammalian PSD both contain an LGST amino acid motif that identifies the site of proteolysis and pyruvoyl prosthetic group attachment in the bacterial enzyme. The yeast PSD1 and mammalian PSD also have mitochondrial targeting and inner membrane sorting sequences. Processing intermediates have been defined in the mammalian enzyme that correspond to the sequential removal of the mitochondrial targeting and inner membrane sorting sequence, followed by formation of the alpha and beta subunits. In contrast, the PSD2 enzyme contains a putative Golgi localization/retention sequence and a C2 homology domain, in addition to predicted alpha and beta subunits. The transport requirements for substrate access to the PSD enzymes have provided important information about lipid trafficking, and the availability of yeast mutants is likely to provide important new genetic selections in the future.


Pens versus syringes to deliver insulin among elderly patients with type 2 diabetes: a randomized controlled clinical trial.
Diabetes mellitus (DM) is a prevalent disease among elderly population. As the disease progresses, insulin may become necessary. The use of pens application seems to be more practical. However, the influence of this method on glycemic control needs to be defined in elderly people. Randomized clinical trial comparing pens and syringes for insulin application among patients with type 2 DM over 60 years old and Glycated Hemoglobin > 8.5% at baseline. The follow-up was 24 weeks, with monthly medical visits to adjust the treatment. All patients received insulin NPH and, if necessary, insulin Regular. We assessed glycemic control, adherence to treatment, hypoglycemia occurrence, need for adjustment in treatment and impact on quality of life, RESULTS: We included 121 patients with mean age of 65.75 years. Sixty-one were randomized for pen group (PG) and 60 patients for syringe group (SG). At baseline, mean HbA1c was 10.34 ± 1.66% and 9.90 ± 1.25% (p = 0.103) in PG and SG respectively. Mean HbA1c was 8.39 ± 1.28% in PG and 8.85 ± 1.74% in SG (p = 0.101) at 24 weeks. However, there was a more significant reduction in PG (- 1.94 ± 1.93% in PG and - 1.04 ± 1.46% in SG, p < 0.05) during follow-up. We found no difference in treatment adherence rates, hypoglycemia, greater need for insulin doses or oral medication, and progression to basal-bolus insulin scheme. We also found no difference in the impact of the disease on quality of life between groups. Although we did not find any difference in the impact on quality of life, frequency of hypoglycemia or adherence, the PG showed a reduction in HbA1c higher in 24 weeks of follow-up. NCT02517242.


Hyperuricemia as a clue for central diabetes insipidus (lack of V1 effect) in the differential diagnosis of polydipsia.
In the differential diagnosis of patients with polyuria-polydipsia one must distinguish usually between primary polydipsia (PP) and central diabetes insipidus (CDI). The first situation is a state of volume expansion and the second of volume contraction. We evaluate whether serum uric acid determination could help to differentiate between the two conditions. We analyzed the score of 13 consecutive patients with CDI, 7 patients with PP, and 7 patients with nephrogenic diabetes insipidus (NDI). Serum uric acid concentration was available during normonatremia without treatment with 1-desamino-8-D-arginine vasopressin (dDAVP), during mild dehydration and during treatment with dDAVP. In 8 of these patients plasma renin activity (PRA), urate, urea and creatinine clearances were also available. These data were also obtained in the patients with NDI. In 1 patient with CDI, we studied the effect on urate clearance of dDAVP, which stimulates exclusively the V2 receptors, and of triglycyl-lysine-vasopressin (TGLV), a potent V1-receptor agonist. Normonatremic polydypsic patients with CDI presented an increase in uric acid concentration (7.1 +/- 2.2 mg/dL), whereas in the PP group the value was decreased (3 +/- 0.75 mg/dL; P <0.001). All the normonatremic PP presented a serum uric acid concentration lower than 5 mg/dL, whereas all the normonatremic CDI patients, exept 1, presented a value higher than 5 mg/dL. In both groups blood urea concentration was decreased as a consequence of high renal clearances. The hyperuricemia of CDI was related to low uric acid clearances. Patients with hypernatremia and NDI presented a lower increase in serum uric acid concentration than those with similar levels of hypernatremia and CDI (NDI: 5.7 +/- 0.8 mg/dL and CDI: 7.9 +/- 2.3 mg/dL; P <0.05) and the NDI patients presented an urate clearance corrected for creatinine clearance which was significantly higher than in CDI (9% +/- 3% and 4% +/- 1.1%; P <0.01). When the patients with CDI were treated with dDAVP and normalyzed their PRA (0.9 +/- 0.4 ng/mL/h) we observed still mild hyperuricemia compared to controls (5.5 +/- 1.4 mg/dL and 4.3 +/- 0.9 mg/dL; P <0.01) and a low fractional excretion of filtered uric acid (6.5% +/- 1.7% compared to 8.2% +/- 2% in controls; P <0.05). Acute administration of dDAVP, stimulating the V2 receptors, in one patient with CDI, had no effect on urate clerance, while TGLV, which stimulates the V1 receptor, increased urate clearance. The presence of an serum uric acid concentration higher than 5 mg/dL in polyuric polydipsic patients is highly suggestive of CDI. Even when these patients are treated with dDAVP many of them remain hyperuricemic, and this seems to be the consequence of a lack of V1 receptor stimulation.


Metallothionein dependent-detoxification of heavy metals in the agricultural field soil of industrial area: Earthworm as field experimental model system.
Earthworms are known to reclaim soil contamination and maintain soil health. In the present study, the concentration of DTPA extractable heavy metals, Cd, Cu, Cr, Pb, and Zn in vermicasts and tissues of the earthworms (anecic: Lampito mauritii; epigeic: Drawida sulcata) collected from the soils of four different industrial sites, Site-I (Sago industry), Site-II (Chemplast industry), Site-III (Dairy industry) and Site-IV (Dye industry) have been studied. The heavy metals in industrial soils recorded were 0.01-326.42 mg kg-1 with higher Cu, Cr, and Zn contents while the vermicasts showed lower heavy metal loads with improved physicochemical properties and elevated humic substances. The higher humic substances dramatically decreased the heavy metals in the soil. The bioaccumulation factors of heavy metals (mg kg-1) are in the order: Zn (54.50) > Cu (17.43) > Cr (4.54) > Pb (2.24) > Cd (2.12). The greatest amount of metallothionein protein (nmol g-1) was recorded in earthworms from Site-IV (386.76) followed by Site-III (322.14), Site-II (245.82), and Site-I (232.21). Drawida sulcata can produce a considerable amount of metallothionein protein than Lampito mauritii as the metallothionein production is dependent upon the presence of pollutants. The molecular docking analysis indicates a binding score of 980 for Cd, Cr and Cu, and 372 for Zn. Pb may bind with a non-metallothionein protein of earthworms and bio-accumulated in the internal chloragogenous tissues. Metallothionein neutralizes the metal toxicity and controls the ingestion of essential elements.


Hyponatraemia and intracellular water in sepsis: an experimental comparison of the effect of fluid replacement with either 0.9% saline or 5% dextrose.
Hyponatraemia associated with sepsis is known to have an increased morbidity and mortality. The cause of this phenomenon is unknown, but may be related to dilution of the extracellular space with retained exogenous fluid. Fluid and ion redistribution across the cell membrane of striated muscle was investigated in an animal sepsis model and compared with sham controls. The objective was to study the effect of different volumes of fluid replacement with either 0.9% saline or 5% dextrose. Significant shifts of sodium, chloride, and water occurred into the cell in all septic animals but not in controls. This trend was exacerbated by the use of dextrose for intravenous replacement even when the estimated normal fluid requirements had not been exceeded. Hyponatraemia and plasma hypoosmolality were induced only in septic animals, which received 100% of their fluid requirements as dextrose. These animals at the same time had significantly reduced extracellular and increased intracellular volumes compared with controls and the septic animals that received saline replacement. It is concluded that the hyponatraemia and plasma hypoosmolality that occurs in these animals is caused by a combination of intracellular shift of sodium and water, and dilution of the extracellular space, probably on the basis of physiological antidiuretic hormone (ADH) secretion. Dextrose (and by implication 4% dextrose/0.18% saline) is inappropriate, potentially dangerous, and should be avoided in these circumstances.


The effect of Escherichia coli endotoxin and culture filtrate on the dry bovine mammary gland.
The mammary glands of eight non-lactating dairy cows were infused with either endotoxin or the sterile culture filtrate in which Escherichia coli had been grown (CCF). Animals were necropsied at intervals up to 24 h after infusion. Only mild inflammation of the teat and lactiferous sinuses occurred after 4 h, subsiding gradually to 24 h. After mixing dry cow secretion with either endotoxin or CCF, an intense inflammatory response was produced on inoculation of quarters of a lactating cow; CCF also produced necrosis of the epithelium. Thus, dry gland secretions do not inhibit the effect of filtrate or endotoxin. It was concluded that the refractory nature of the gland to these toxins in the non-lactating animal is due to the changes which occur in the ductular epithelium during involution.


Change of the protein p53 electrochemical signal according to its structural form - quick and sensitive distinguishing of native, denatured, and aggregated form of the "guardian of the genome".
Presence of mutated and/or structurally modified (e.g., denatured, aggregated) protein p53 form is associated with several disorders such as Alzheimer's disease, Parkinson's disease, prion diseases, and many types of tumours. The aim of this work was to distinguish native, denatured and aggregated form of full-length p53 by flow injection analysis coupled with electrochemical detector (FIA-ED). Firstly FIA-ED method used for protein native form determination was optimized (detection limit 45.8 amol per 5 mul injection; 3 x S/N). In addition the technique was applied to identify p53 structural forms (denatured and aggregated). It was found out that denatured form provides about three times higher electrochemical response (protein structure unfolding, approach of more electroactive centers - aminoacid residues - towards electrode surface) in comparison with native form. On the other hand, aggregated form offers lower response (steric eclipse of electroactive protein parts) when compared with the signal of native form. The obtained data show that we are not only able to sensitively determine native, denatured, and aggregated structural forms of p53 protein but also to distinguish them.


Risk of Severe COVID-19 and Protective Effectiveness of Vaccination Among Solid Organ Transplant Recipients.
Solid organ transplant recipients (SOTRs) are at higher risk for severe infection. However, the risk for severe COVID-19 and vaccine effectiveness among SOTRs remain unclear. This retrospective study used a nationwide health care claims database and COVID-19 registry from the Republic of Korea (2020 to 2022). Adult SOTRs diagnosed with COVID-19 were matched with up to 4 non-SOTR COVID-19 patients by propensity score. Severe COVID-19 was defined as treatment with high-flow nasal cannulae, mechanical ventilation, or extracorporeal membrane oxygenation. Among 6783 SOTRs with COVID-19, severe COVID-19 was reported with the highest rate in lung transplant recipients (13.16%), followed by the heart (6.30%), kidney (3.90%), and liver (2.40%). SOTRs had a higher risk of severe COVID-19 compared to non-SOTRs, and lung transplant recipients showed the highest risk (adjusted odds ratio, 18.14; 95% confidence interval [CI], 8.53-38.58). Vaccine effectiveness against severe disease among SOTRs was 47% (95% CI, 18%-65%), 64% (95% CI, 49%-75%), and 64% (95% CI, 29%-81%) for 2, 3, and 4 doses, respectively. SOTRs are at significantly higher risk for severe COVID-19 compared to non-SOTRs. Vaccination is effective in preventing the progression to severe COVID-19. Efforts should be made to improve vaccine uptake among SOTRs, while additional protective measures should be developed.


Anti-inflammatory response after infusion of p55 soluble tumor necrosis factor receptor fusion protein for severe sepsis.
To investigate the effects of Lenercept , a recombinant soluble TNF receptor p55 fused to an immunoglobulin heavy chain IgG1, on the balance of pro- and anti-inflammatory mediators in sepsis. Post hoc analysis of a subgroup of patients enrolled in a multicenter phase III, prospective, double-blind, placebo-controlled, randomized study of Lenercept in severe sepsis. Surgical and medical intensive care units, and postoperative recovery room of a tertiary care teaching hospital. A total of 57 patients were enrolled in the multicenter study in our center. Septic patients were randomly assigned to receive either Lenercept 0.125 mg/kg or placebo. The patients were followed for up to 28 days after randomization. Circulating levels of TNF-alpha, IL-6, TNFsR75 and IL-1Ra were measured before and after treatment. The two groups were comparable with regard to age, gender and diagnosis distribution. The total level of TNF-alpha increased significantly in treated patients, compared to patients receiving placebo. The levels of the other inflammatory mediators did not differ between the two groups Lenercept -treated patients experienced a protracted TNF-alpha half-life, leading to higher total TNF-alpha levels throughout the study. However, the treatment had no effects on anti-inflammatory mediators. Therefore, peripheral inflammatory processes might not have been significantly modified by the treatment. This might account for the lack of efficacy this treatment in septic patients


Model for end-stage liver disease: impact of the new deceased donor liver allocation policy in São Paulo, Brazil.
Since 1997, organ transplantation in Brazil has been regulated by a federal law, which was created to guarantee equal access to treatment on a national scale. Centralized deceased donor organ procurement and sharing are controlled by the Health Department of each state of the nation, following a regional allocation policy. In São Paulo, time on the waiting list was the main criterion adopted to allocate deceased donor livers up to July 15, 2006. After that, model for end-stage liver disease/pediatric end-stage liver disease (MELD/PELD) scores were the main criteria. The aim of this study was to investigate the impact of the new criteria on patient survival rates using 895 consecutive liver recipients. The 1-year patient survival rates were compared between recipients transplanted based on the waiting time policy and based on MELD/PELD scores showing similar results (69.79% vs 66.69%; P = NS). Regarding liver allocation based on MELD/PELD scores, worse survival outcomes were observed among recipients transplanted with higher MELD scores. Also, under the new criteria, a high frequency of hepatocellular carcinoma and pediatric recipients underwent transplantation.


Impact of the Lysine-urethane Adhesive TissuGlu® on Postoperative Complications and Interventions After Drain-free Mastectomy.
The influence of a polyurethane-based tissue adhesive (TissuGlu®) on common complications following breast surgery was investigated. Within a Randomized-Controlled-Trial 70 women (n=35 TissuGlu®, n=35 drain) underwent a mastectomy with or without sentinel lymph node excision (SLNE), followed by a 90-day postoperative follow-up. Postoperative interventions: Non-inferiority of the application of TissuGlu® was seen. Pain-Level/ Hospitalization: A statistically significant pain reduction from day four onwards (p<0.001) and a shorter hospitalization period (p<0.001) was observed. In contrast, the TissuGlu® group showed increased mean puncture incidence (p=0.013), and increased puncture volume (p=0.021). Application of the polyurethane-based tissue adhesive TissuGlu® after mastectomy, with or without SLNE, showed potential for improvement of the clinical outcome. In contrast, high intervention rates and increased puncture volume, caused by recurring seromas following application of the surgical adhesive TissuGlu®, have a negative impact on the patient-specific convalescence.


New type of linker useful for cloning experiments.
A new class of linker oligodeoxynucleotide sequences is described which allows the original sequence of a foreign DNA to be restored after cloning. In the standard linker approach the terminal base pairs of the linker-sequences are irreversibly attached to the cloned DNA, thus altering the genetic information. The use of the new type of linker is demonstrated by the transformation of the unique Pvu II site in pBR322 into Bam HI site using the ISO ('in-site-out') linker d(GATCCGGATC). Possible further applications of these linker sequences are described.


Dyspnea during daily activities in chronic spinal cord injury.
To assess factors associated with breathlessness in chronic spinal cord injury (SCI) during daily activities. Cross-sectional survey. Veterans Affairs SCI service and the community. Four hundred forty-one participants 1 or more years post-SCI, and without acute illness, were recruited between 1994 and 2003 and were categorized according to their ability to walk unassisted, walk with an aid, or to move about by either hand-propelled wheelchair or motorized wheelchair (MWC). Assessment of injury extent, respiratory symptoms, cigarette smoking, comorbid medical conditions, and spirometry. Breathlessness during talking, eating, or dressing. Breathlessness was more common in MWC users (20/85 users, 24%) than in nonusers (20/356, 6%). The main activity associated with breathlessness in 15 MWC users was talking (18%). In MWC users, the risk of breathlessness was related to lifetime cigarette smoking (odds ratio [OR]=1.02; 95% confidence interval [CI], 1.00-1.03 per pack year), and reports of chronic cough (OR=7.8; 95% CI, 2.0-32.7), and wheeze (OR=3.5; 95% CI, 1.04-13.6). SCI level, percentage of predicted forced vital capacity and forced expiratory volume in 1 second, and maximal inspiratory pressures were not related to breathlessness. Breathlessness during selected daily activities (most commonly talking) was greatest in SCI participants who were most impaired with regard to mobility and was associated with reports of coughing, wheezing, and cigarette smoking.


Immediacy concept application in the teaching of courses in environmental health.
Immediacy, a communication behaviour, is defined and its application in the teaching of environmental health courses is illustrated. The practical experience gained from engaging in this teaching behaviour includes enhancement of student-professor relationships, affective learning and increased sensory stimulation, etc. The dynamics of this concept are exemplified in this article.


Molecular analysis and rescue of a vitelline membrane mutant in Drosophila.
The eggshell in Drosophila is produced by ovarian follicle cells during the later stages of oogenesis. Eggshell formation involves the ordered synthesis and assembly of several protein components. Genes encoding the most abundant eggshell proteins have been identified by molecular cloning studies. Morphological examination of eggs produced by females carrying female sterile mutations on the X and third chromosomes have revealed additional loci involved in chorion formation. In this study we screened a collection of female sterile mutants carrying EMS-induced mutations on the second chromosome for eggshell mutants. A class of six mutants with potential vitelline membrane defects was identified on the basis of the response of mutant eggs to hypochlorite solutions. Biochemical analysis showed that one mutant, fs(2)QJ42, failed to produce a major vitelline membrane protein, sV23. The mutation was mapped cytogenetically to 26A, a region previously implicated in vitelline membrane formation by molecular cloning studies. Northern blot analysis using a cloned copy of the sV23 gene as probe showed a 10- to 15-fold reduction of sV23 RNA levels in the mutant. sV23 synthesis and fertility were restored when a normal copy of the sV23 gene was introduced into the mutant via germ line transformation. Transposons carrying the sV23 gene with as little as 147 bp of 5' flanking DNA were capable of restoring fertility and sV23 protein to wild type levels.


Distribution of hepatitis B virus genotypes in the general population of Myanmar via nationwide study.
Hepatitis B virus (HBV) infections are a severe health concern worldwide. HBV is a DNA virus with a rapid rate of mutation. Based on heterogeneity of the nucleotide sequence, the HBV strains are divided into nine genotypes, each with a characteristic geographical distribution. Identifying and tracking alterations of HBV genotypes is important in epidemiological and transmission studies, and contributes to predicting the risk for development of severe liver disease and response to antiviral treatment. The present study was undertaken to detect HBV genotypes and sub-genotypes in the general population of different states and regions in Myanmar. In 2015, a total of 5547 adults of the general population, residing in seven states, seven regions and the Nay Pyi Taw Union Territory, were screened for Hepatitis B Surface antigen (HBsAg) by the immunochromatographic test (ICT). Of the 353 HBsAg positive samples, the HBVDNA was identified using polymerase chain reactions (PCR) targeting the DNA sequences encoding the Pre-S region. A total of 153 PCR positive samples were subsequently subjected to genotyping by partial genome sequencing in both directions. The resulting sequences were then edited, aligned, and compared with reference sequences using the National Centre for Biotechnology Information (NCBI) web-based genotyping tool. Three HBV genotypes (HBV genotype B, genotype C and genotype D) were detected in Myanmar, of which genotype HBV genotype C (66.7%) was the most prevalent, followed by HBV genotype D (32%) and HBV genotype B (1.3%). Sub-genotyping revealed a total of 7 variants within the B, C and D genotypes: 2 (B4 and B5) in HBV genotype B, 3 (C1, C5 and C7) in HBV genotype C, and 2 (D3 and D6) in HBV genotype D. HBV genotype C, sub-genotype C1 was predominantly distributed in all states and regions of Myanmar. This study is the first report on the nationwide distribution of HBV genotypes and sub-genotypes in Myanmar. We believe our findings will enable huge support for the hepatitis disease surveillance program, since HBV infection is one of the National Priority Diseases in Myanmar.


False-positive IgM serology in coccidioidomycosis.
The clinical observation has been made that there might be an unacceptable number of false-positive enzyme immunoassay (EIA) test results for IgM among persons suspected of having coccidioidomycosis. Patients with a positive result for IgM by EIA are thought to have a diagnosis of acute coccidioidomycosis. However, this study found that 82% of patients with an IgM-positive and IgG-negative EIA result did not have coccidioidomycosis.


Causes of variation in serum IgE levels in normal populations.
Serum IgE was measured in 326 individuals 5 years of age and older who were members of families of both black and white populations. IgE levels were higher in blacks than in whites and much higher in children than in adults. No marked change with age was detected in children 5 to 15 years of age, but IgE levels decreased rapidly with increasing age after 15. Secretors of ABH substances had higher IgE levels than nonsecretors, but sex, blood group systems ABO, MN, and Rh had no effect on IgE levels. Levels varied widely from person to person and showed almost continuous frequency distributions. Comparisons among relatives revealed that, in the populations under study, from 40% to 50% of the total variation was accounted for by genetic variation. The basis of variation in IgE levels appears to be polygenic, that is, in addition to environmental factors many genes may contribute to the end product. Levels of IgE appeared to be independent of those of the other 4 classes of immunoglobulins.


Doppler indices in the umbilical arteries: influence of vessel curvature induced by bladder filling.
Doppler indices are widely used to assess normal versus pathologic haemodynamics. In obstetrics, the assessment of abnormal values in some critical compartments, such as the umbilical arteries (UA), may be crucial in the clinical management of growth-restricted foetuses. It was recently proposed that the UA should be sampled in their perivesical portion (PVC), i.e., where they surround the foetal urinary bladder. However, measurements at this site could be biased by the degree of curvature of the vessel due to bladder filling. We investigated this possibility in vivo and in vitro, i.e., measurements on rubber tubes at different radii of curvature R(c). There was significant dependence of the Doppler indices A/B and PI on the vessel curvature and insonation angle; in fact, we recorded errors of about 25% when R(c) was 10 times larger than the radius of the vessel and about 100% when R(c) was five times larger than the radius of the vessel. Therefore, measurements of the UA at the PVC site should only be performed when the foetal bladder is empty.


Creating good veterinary workplaces: how mentoring can offer a helping hand.
Regular mentoring should be part of the core values of a good veterinary workplace, but what benefits can it bring to individuals and practices as a whole? These benefits, and more, will be explored by Donna Kennedy, who will be one of two speakers in a careers session at BVA Live.


[AIDS Study Group/Spanish AIDS Consensus Plan Document on sexually transmitted infections in HIV-infected patients].
Sexually transmitted infections (STI) are a major public health problem. Considering their high morbidity and potential short and long term after effects, physicians must have enough knowledge on the management of these infections for a correct prevention, diagnosis and treatment. HIV infection is associated with STI, not only because they share route of transmission, but also because they lead to an increased risk of HIV transmission. In this article, we summarise the updated clinical practice guidelines, for the evaluation, management and prevention of STI in HIV-infected patients, from a panel of experts in HIV, dermatologists, proctologic surgeons, and microbiologists on behalf of the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan (PNS).


Reciprocal Associations between Electronic Media Use and Behavioral Difficulties in Preschoolers.
The use of electronic media has increased substantially and is already observable in young children. The present study explored associations of preschoolers' use of electronic media with age, gender, and socio-economic status, investigated time trends, and examined reciprocal longitudinal relations between children's use of electronic media and their behavioral difficulties. The study participants included 527 German two- to six-year-old children whose parents had provided information on their use of electronic media and their behavioral difficulties at two time points, with approximately 12 months between baseline and follow-up. The analyses revealed that older vs. younger children, as well as children from families with a lower vs. higher socio-economic status, were more often reported to use electronic media. Furthermore, the usage of mobile phones increased significantly between 2011 and 2016. Most interestingly, baseline usage of computer/Internet predicted more emotional and conduct problems at follow-up, and baseline usage of mobile phones was associated with more conduct problems and hyperactivity or inattention at follow-up. Peer relationship problems at baseline, on the other hand, increased the likelihood of using computer/Internet and mobile phones at follow-up. The findings indicate that preschoolers' use of electronic media, especially newer media such as computer/Internet and mobile phones, and their behavioral difficulties are mutually related over time.


The Adjunct of Electric Neurostimulation to Rehabilitation Approaches in Upper Limb Stroke Rehabilitation: A Systematic Review With Network Meta-Analysis of Randomized Controlled Trials.
This review analyzed the current evidence and the potential for the application of electric neurostimulation such as transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS) in upper limb stroke rehabilitation. We performed a systematic review of randomized controlled trials (RCTs) using network meta-analysis (NMA), searching the following data bases: PubMed, Web of Science, Cochrane, and Google Scholar, using specific keywords, from January 2010 to April 2021, and assessing the effects of "tDCS" or "VNS" combined with other therapies on upper limb motor function and activities of daily living (ADL) after stroke. We included 38 RCTs with 1261 participants. Pairwise NMA showed transcutaneous VNS (tVNS) and anodal tDCS were effective in improving upper limb motor function (tVNS: mean difference [MD]: 5.50; 95% CI [0.67-11.67]; p < 0.05; anodal tDCS: MD: 5.23; 95% CI [2.45-8.01]; p < 0.05). tVNS and tDCS (anodal and cathodal) were also effective in improving ADL performance after stroke (tVNS: standard MD [SMD]: 0.96; 95% CI [0.15-2.06]; p < 0.05; anodal tDCS: SMD: 3.78; 95% CI [0.0-7.56]; p < 0.05; cathodal tDCS: SMD: 5.38; 95% CI [0.22-10.54]; p < 0.05). Surface under the cumulative ranking curve analysis revealed that tVNS is the best ranked treatment in improving upper limb motor function and performance in ADL after stroke. There was no difference in safety between VNS and its control interventions, measured by reported adverse events (VNS: risk ratio = 1.02 [95% CI = 0.48-2.17; I2 = 0; p = 0.96]). Moderate- to high-quality evidence suggests that tVNS and anodal tDCS were effective in improving upper limb motor function in both acute/subacute and chronic stroke. In addition to tVNS and anodal tDCS, cathodal tDCS is also effective in improving ADL performance after stroke.


De novo biosynthesis of 2'-fucosyllactose in engineered Pichia pastoris.
Pichia pastoris is well known for its ability to produce short and low-immunogenic humanized glycosyl chains onto recombinant glycoproteins, it was thus speculated to be applicable to synthesize oligosaccharides. In this study, generally recognized as safe (GRAS) microorganism Pichia pastoris GS115 was tested for its potential to be used as a new synthetic chassis to produce the most abundant human milk oligosaccharide 2'-fucosyllactose (2'-FL). To enable the de novo synthesis of 2'-FL, lactose transporter lac12, two enzymes of gmd, gmer, and fucosyltransferases futC were integrated into the genome of P. pastoris, under the control of constitutive PGAP promoter. The resulting recombinant yeasts yielded up to 0.276 g/L through culture optimization in a 5 L bioreactor. To our knowledge, this is the first report of 2'-FL production in engineered Pichia pastoris. This work is a good starting point to produce 2'-FL using Pichia pastoris as a viable chassis.


MARML: Motif-Aware Deep Representation Learning in Multilayer Networks.
The rapid increase in high-throughput, complex, and heterogeneous data has led to the adoption of network-structured models and analyses for interpretation. However, these data are inherently complex and challenging to understand, prompting researchers to turn to graph embedding methods to facilitate analysis. While general network embedding techniques have shown promise in improving downstream prediction and classification tasks, real-world data are complicated due to cross-domain interactions between different types of entities. Multilayered networks have been successful in integrating biological data to represent biological systems' hierarchy, but embedding nodes based on different types of interactions remains an unsolved problem. To address this challenge, we propose the Motif-aware deep representation learning in multilayer (MARML) networks for learning network representations. Our method considers recurring motif patterns, topological information, and attributive information from other sources as node features. We validated the MARML method using various multilayer network datasets. In addition, by incorporating motif information, MARML considers higher order connections across different hierarchies. The learned features exhibited excellent accuracy in tasks related to link prediction and link differentiation, enabling us to distinguish between existing and disconnected triplets. Through the integration of both intrinsic node attributes and topological network structures, we enhance our understanding of complex biological systems.


Genotoxicity and apoptosis in Drosophila melanogaster exposed to benzene, toluene and xylene: attenuation by quercetin and curcumin.
Monocyclic aromatic hydrocarbons (MAHs) such as benzene, toluene and xylene are being extensively used for various industrial and household purposes. Exposure to these hydrocarbons, occupationally or non-occupationally, is harmful to organisms including human. Several studies tested for toxicity of benzene, toluene and xylene, and interestingly, only a few studies looked into the attenuation. We used Drosophila model to test the genotoxic and apoptotic potential of these compounds and subsequently evaluated the efficiency of two phytochemicals, namely, quercetin and curcumin in attenuating test chemical induced toxicity. We exposed third instar larvae of wild type Drosophila melanogaster (Oregon R+) to 1.0-100.0 mM benzene, toluene or xylene, individually, for 12, 24 and 48 h and examined their apoptotic and genotoxic potential. We observed significantly (P<0.001) increased apoptotic markers and genotoxicity in a concentration- and time-dependent manner in organisms exposed to benzene, toluene or xylene. We also observed significantly (P<0.001) increased cytochrome P450 activity in larvae exposed to test chemicals and this was significantly reduced in the presence of 3',4'-dimethoxyflavone, a known Aryl hydrocarbon receptor (AhR) blocker. Interestingly, we observed a significant reduction in cytochrome P450 activity, GST levels, oxidative stress parameters, genotoxic and apoptotic endpoints when organisms were exposed simultaneously to test chemical along with quercetin or curcumin. The study further suggests the suitability of D. melanogaster as an alternate animal model for toxicological studies involving benzene, toluene and xylene and its potential in studying the protective role(s) of phytochemicals.


Fractional excretion of K, Na and Cl following furosemide infusion in healthy, young and very old people.
Furosemide test is a simple and useful test of renal physiology used to evaluate the capability of the collecting ducts to secrete potassium under the effect of serum aldosterone. Its behaviour pattern has been established in children and young adults but not described in very old healthy people, which we explored in this study. Twenty-six healthy volunteers on a standard Western diet (50 mmol of K/day) were studied: 20 of them were young (between 17 and 40 years old) and the rest were very old (between 75 and 85 years old). They suffered from no diseases and were not on any medication. Before, during the test and 180 min after a single dose of intravenous furosemide (1 mg/kg), urine and blood samples were obtained for creatinine and electrolytes levels. From these data we calculated fractional excretion (FE) of electrolytes; serum aldosterone was measured pre and post furosemide infusion. Statistical analysis was performed by applying Student's t-test. There was no significant difference regarding pre-furosemide (basal) FE of potassium between the very old and young group. Post-furosemide average FE of potassium was significantly lower in the very old group (27.4 +/- 2%) compared with the young group (35.4 +/- 9%) (P = 0.04). Even though there was no significant difference in post-furosemide peak FE of potassium value, it was reached later in the very old (120 min) compared with the young (30 min). Serum aldosterone levels were significantly higher post furosemide in both groups: 18.3 +/- 12.2 ng/dl (pre) versus 32.5 +/- 18.6 ng/dl (post) in the young (P = 0.007) and 69.8 +/- 13.7 ng/dl (pre) versus 113.3 +/- 54.8 ng/dl (post) in the very old (P = 0.04). Furthermore, all serum aldosterone values (pre and post furosemide) were significantly higher in very old people compared with young people (P < 0.001). Basal fractional excretion of sodium and chloride were slightly higher in the very old group compared with the young group (P = 0.05). Average post-furosemide FE of sodium and chloride were slightly and significantly lower in the very old (P = 0.05 and P = 0.03), respectively. However, there was no significant difference in peak post-furosemide FE of sodium and chloride values, which were reached later in the very old (120 min) compared with the young (30 min). Furosemide test showed a significantly lower average post-furosemide FE of potassium value, delayed post-furosemide peak FE of Na, K and Cl and a hormonal pattern of aldosterone resistance in very old people.


Association of depression symptoms and sleep quality with state-trait anxiety in medical university students in Anhui Province, China: a mediation analysis.
The prevalence of depression symptoms among medical students is particularly high, and it has increased during the COVID-19 epidemic. Sleep quality and state-trait anxiety are risk factors for depression, but no study has yet investigated the mediating role of state-trait anxiety in the relationship between poor sleep quality and depression symptoms in medical students. This study aims to investigate the relationship among depression symptoms, sleep quality and state-trait anxiety in medical university students in Anhui Province. This was a cross-sectional survey of 1227 students' online questionnaires collected from four medical universities in Anhui Province using a convenience sampling method. We measured respondents' sleep quality, state-trait anxiety, and depression symptoms using three scales: the Pittsburgh Sleep Quality Index (PSQI), the State-Trait Anxiety Inventory (STAI) and the Self-rating Depression Scale (SDS). We analysed the mediating role of STAI scores on the association between PSQI scores and SDS scores through the Sobel-Goodman Mediation Test while controlling for covariates. P < 0.05 was considered statistically significant. A total of 74.33% (912) and 41.40% (518) of the respondents reported suffering from poor sleep quality and depression symptoms. Sleep quality, state-trait anxiety, and depression symptoms were positively associated with each other (β = 0.381 ~ 0.775, P < 0.001). State-trait anxiety partially mediated the association between sleep quality and depression symptoms (Sobel test Z = 15.090, P < 0.001), and this mediating variable accounted for 83.79% of the association when adjusting for potential confounders. Subgroup analysis further revealed that STAI scores partially mediated the association between PSQI scores and SDS scores in females and rural students and fully mediated the association between PSQI scores and SDS scores in males and urban students. This study found that sleep quality and state-trait anxiety have a significant predictive effect on depression symptoms. State-trait anxiety mediated the relationship between sleep quality and depression symptoms, with a more complex mechanism observed among rural and female medical students. Multiple pathways of intervention should be adopted, such as encouraging students to self-adjust, providing professional psychological intervention and timely monitoring, enriching extracurricular activities, and making changes in policies regarding long shifts and working hours.


Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system.
A specific form of cytochrome P450, P450 IIE1, active in ethanol oxidation, is known to be induced about 10-fold in rat liver following ethanol treatment. This isozyme of P450 participates effectively in the metabolic activation of precarcinogens, such as N-dimethylnitrosamines, and of solvents such as carbon tetrachloride and benzene. In the present investigation, two different polyclonal antisera against P450 IIE1 were used in order to map the regional distribution of this P450 form in the rat central nervous system. The presence of P450 IIE1 in various brain regions was confirmed by Western blot analysis. The P450 IIE1-immunoreactivity was heterogeneously distributed between brain areas. Neuronal cell bodies and glial cells of presumed astroglial as well as oligodendroglial identity contained immunoreactivity. All fiber tracts harbored P450 IIE1-immunoreactive glial cells as did the ependymal lining of the ventricular wall as well as small and large vessels throughout the brain. P450 IIE1-immunoreactive glial cells were present in all areas of the neocortex, in the olfactory bulb, in the piriform cortex and in several different thalamic nuclei. In the cerebellum, P450 IIE-immunoreactivity was found in all cell layers and was exclusively localized to glial cells and their processes. Staining of blood vessels was prominent in the white matter where P450 IIE1-immunoreactive glial cells were seen to have end-feet on the vessels. A subgroup of pyramidal cells of the frontal cortex showed strong P450 IIE1-immunoreactivity, as did a component of the olfactory nerve which innervates the accessory bulb. In the hippocampal region, the pyramidal cells of all subfields were P450 IIE1-immunoreactive. Some polymorphic cells of the hilus and subfield CA stained intensely with the P450 IIE1 antibodies. A high density of P450 IIE1-immunoreactivity was detected throughout the striatal complex. The immunoreactivity was localized to neuronal cell bodies as well as the neurophil. Fibers of the nigrostriatal system were strongly P450 IIE1-immunoreactive. Mechanical lesions of this pathway showed an accumulation of P450 IIE1-immunoreactivity proximal to the lesion relative to the striatum and a depletion in the reticular part of the substantia nigra, suggesting that the antigen may be transported from the striatum to the substantia nigra. In the brain stem a high density of P450 IIE-immunoreactive neurons was detected in the substantia nigra, the pontine nucleus, lateral superior olive and the nucleus of the trigeminal nerve and facial nucleus. A great number of large- to medium-sized immunoreactive neurons were situated in the central gray and in the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)


Relative morbidity of abdominal myomectomy for very large uterine fibroids in a developing country hospital.
Data on comparative outcomes of abdominal myomectomy for varying uterine sizes that could guide informed decision by women and clinicians in resource-constrained settings are scarce. To evaluate safety of abdominal myomectomy and compare perioperative morbidities for women with very large uterine size (≥20 weeks) with that of women with smaller uterine size (<20 weeks) in a developing country hospital. Retrospective and comparative chart review of 224 women with uterine sizes between 12 and 36 weeks who had abdominal myomectomy performed at a Nigerian university hospital. Primary outcome measure was overall perioperative morbidity, with the following secondary outcomes: hemorrhage, febrile morbidity, unintended major surgical procedures, life-threatening events, and rehospitalization (according to validated criteria). Other variables included operating time, estimated blood loss, wound complications and postoperative hospital stay. Overall morbidity occurred in 31.7% of women with hemorrhage (20.5%) and febrile morbidity (16.1%) being leading contributors. Unintended procedures (0.9%) and life-threatening events (1.8%) were rare and no death was recorded. Forty women (17.9%) had blood loss ≥ 1 l and 11.6% received homologous blood transfusion. Overall morbidity and all secondary morbidity outcomes (according to predefined criteria) were comparable between women with very large uterine size and those with smaller uteri. However, the mean blood loss was significantly more and the procedure and average hospital stay were significantly longer in women with very large uterine size. Abdominal myomectomy in this setting is associated with significant but acceptable perioperative morbidity. Increased uterine size does not significantly affect clinically important morbidities and women with very large uterine size should not be denied this procedure for safety concerns.


Long-Term Outcomes of Left Main Coronary Artery Disease Treated With Drug-Eluting Stents vs Coronary Artery Bypass Grafting: A Meta-Analysis and Systematic Review.
Currently, DES is a reasonable treatment option for LMCA disease but CABG continues to be first-line treatment. Multiple randomized clinical trials (RCTs) have compared outcomes between these two treatment modalities. Recently, these trials published their long-term results with conflicting findings. We conducted a systematic review and meta-analysis of RCTs that compared DES vs CABG in patients with LMCA disease. We only included trials with follow up duration of at least 5 years. The primary outcome was all-cause mortality. Secondary outcomes included risk of cardiac death, myocardial infarction (MI), stroke and repeat revascularization. We included a total of 4 RCTs. The median-weighted follow up period was 6.5 years. There was no significant difference between DES and CABG in all-cause mortality (Risk ratio (RR) 1.10; 95% confidence interval (CI) 0.92 to 1.31; p = 0.28), risk of cardiac death (RR of 1.08, 95% CI 0.84 to 1.38; p = 0.56), total MI (RR of 1.22, 95% CI 0.96 to 1.56; p = 0.11), and stroke (RR of 0.85, 95% CI 0.46 to 1.57; p = 0.60). The risk of repeat revascularization (RR of 1.75, 95% CI 1.50 to 2.03; p < 0.00001), and non-periprocedural MI (RR of 2.13, 95% CI 1.53 to 2.97; p < 0.00001) were significantly higher in the DES arm. DES has similar long-term outcomes compared to CABG in terms of all-cause mortality, cardiac death, total MI and stroke; but was associated with a higher risk of repeat revascularization, and non-periprocedural MI.


Evaluation of the prognostic role of co-morbidities on disease outcome in renal cell carcinoma patients.
Co-morbidities may induce local and systemic tumor progression of renal cell carcinoma (RCC); however, the prognostic impact of co-morbidities has not yet been well characterized. RCC patients (n = 2206) surgically treated at three academic institutions in the US and Europe were included in the analysis. Presence of diabetes mellitus, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, and hypothyroidism were investigated for their association with clinicopathological features and cancer-specific survival. Hypertension was associated with less advanced T stages (p = 0.025), a lower risk of lymph-node (p = 0.026) and distant metastases (p = 0.001), and improved cancer specific survival in univariable analysis (HR 0.81 95% CI 0.69-0.96, p = 0.013). However, hypertension was not an independent prognostic factor after adjustment for TNM stages, grading, and ECOG performance status (HR 0.95, 95% CI 0.80-1.12; p = 0.530). A correlation between the use of concomitant anti-hypertensive medications and improved survival outcome was not identified. All other investigated co-morbidities did not show significant associations with clinicopathological features or cancer-specific survival. Although the investigated co-morbidities are capable or inducing pathophysiological changes that are predisposing factors for tumor progression, none is an independent prognostic factor in patients with RCC.


Retraction.
Retraction: 'Beta-elemene increases chemosensitivity to 5-fluorouracil through downregulating microRNA-191 expression in colorectal carcinoma cells', by Zongbing Guo, Zhenzhen Liu. Haifeng Yue, Jingyuan Wang, J Cell Biochem. 2018; 7032-7039: The above article, published online on 8 May 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcb.26914), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.


Current experience with renal transplantation across the ABO barrier.
Solid organ transplantation has traditionally been governed by the rules of blood group compatibility. Thus, it has been demonstrated that crossing the ABO blood group barrier generally results in hyperacute rejection. However, the A2 subtype of the blood group A is a weaker antigen. Under certain circumstances, organs from donors with blood group A2 can be transplanted across the ABO blood group barrier into recipients of O or B blood type. Since 1986, 33 patients including 24 blood group O and 9 blood group B patients received A2 (30) or A2B (3) donor kidneys. Both cadaver donor (31) and living-related grafts (2) have been undertaken. The mean follow-up since transplantation for the 21 patients with functioning grafts is 36 months, with a 67.2% current graft survival. Immunosuppression for these transplants consisted of azathioprine, prednisone, and cyclosporine, often in combination with prophylactic OKT3 or antilymphocyte globulin as protocol dictated. Special immunosuppressive protocols such as splenectomy or plasmapheresis were not used. The serum of the potential recipient was analyzed for immunoglobulin G (IgG) and immunoglobulin M (IgM) forms of antibody against A1 and A2 red blood cells. There is a strong correlation between a low (less than or equal to 1:8) anti-A1 IgG titer and both early and long-term graft function. Recipients with an IgG titer greater than 1:8 in the pretransplant serum had a much higher incidence of early graft failure. We no longer recommend transplantation of A2 kidneys into O or B recipients with a pretransplant titer of greater than 1:8 but found that recipients with low titers have graft function rates essentially equal to those of ABO-compatible patients. Patients with blood group B have, over time, lower anti-A IgG titers than do blood group O patients. In addition, the graft survival among blood group B patients is 89% compared with 58% among group O recipients. This may be due to the generally low titers found in blood group B recipients. Since instituting a policy in 1988 of not transplanting the kidney when the anti-A IgG titer is greater than 1:8, the survival in O patients is 88%. We recommend the screening of all organ donors with blood group A for the A2 subgroup and believe that transplantation can be safely and successfully performed in certain patients with blood group O or B.(ABSTRACT TRUNCATED AT 400 WORDS)


Spectroscopic studies on the conformational transitions of a bovine growth hormone releasing factor analog.
The secondary structure of the bovine growth hormone releasing factor analog, [Ile2, Ser8.28, Ala15, Leu27, Hse30] bGRF(1-30)-NH-Ethyl, acetate salt (U-90699F) was studied in solution by Fourier transform infrared and Raman spectroscopies. Spectroscopic studies revealed that concentrated aqueous solutions of U-90699F (100 mg ml-1) undergo a secondary structure transition from disordered coil/alpha-helix to intermolecular beta-sheet. Disordered coil and alpha-helical structure were grouped together in the infrared and Raman studies since the amide I vibrations are close in frequency and overlap in assignments was possible. Before the conformational transition, the facile exchange of the peptide's amide hydrogens for deuterium indicated that the majority of amide hydrogens were readily accessible to solvent. The kinetics of the conformational transition coincided with an increase in solution viscosity and turbidity. An initiation phase preceded the conformational transition during which only minor spectral changes were observed by infrared spectroscopy. The initiation phase and reaction kinetics were consistent with a highly cooperative nucleation ultimately leading to a network of intermolecular beta-sheet structure and gel formation. Increased temperature accelerated the conformational transition. The conformational transition was thermally irreversible but the beta-sheet structure of aggregated or gelled peptide could be disrupted by dilution and agitation.


Genome-wide scan for myopia in the Old Order Amish.
To identify myopia susceptibility genes influencing common myopia in 34 Old Order Amish families, a genetically well-defined founder population. A prospective study of families with myopia consisting of a minimum of two individuals affected with myopia. Extended families consisting of at least two siblings affected with myopia were ascertained. A genome-wide linkage scan using 387 markers was conducted by the Center for Inherited Disease Research (CIDR). Linkage analyses were conducted with parametric (autosomal dominant, fixed penetrance model) and nonparametric methods. Model-free linkage analysis was also performed maximizing over penetrance and over dominance (that is, fitting a wide range of both dominant and recessive models). Under the fixed penetrance model, the maximum two-point heterogeneity LOD score (HLOD) was 1.59 at D20S451 and the maximum multipoint HLOD was 1.92 at D6S1021. The nonparametric maximum multipoint (NPL) at D3S2427 had a P-value of .0005. Under the model-free analysis, multipoint heterogeneity LOD scores of 2.03 were observed on both chromosomes 8 (under a recessive model between D8S1130 and D8S1106) and X (under a recessive model between DXS6800 and DXS6789). Reanalyses of chromosomes 3, 6, 8, 20, and X using the best penetrance models resulted in maximum multipoint HLODs of 1.84 at D3S3053; 1.84 at D3S2427; 2.04 at D8S1130; and 2.34 at DXS6800. The locus on chromosome 8p23 independently confirms a report by Hammond and associates mapping a myopia quantitative trait loci (QTL) to this region.


ATP-binding cassette transporter A1 gene polymorphisms and serum lipid levels in young Greek nurses.
The ATP-binding cassette transporter A1 (ABCA1) is essential protein involved in lipid metabolism. The present study was undertaken to detect the possible association of polymorphisms in the ABCA1 gene [rs2230806 (R219K) and rs2230808 (R1587K)] and lipid profile in Greek young nurses. The study population consisted of 308 unrelated nurses who were genotyped and the ABCA1 polymorphisms were detected. Additionally, lipid profile [total cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) A] was evaluated. There was no difference in the genotypic and allelic frequencies of the R219K polymorphism according to lipid profile. The R1587K genotypes differed significantly according to TC, LDL-C and TGs concentration (p = 0.023, p = 0.014 and p = 0.047, respectively). Particularly, significant difference in TC, LDL-C and TGs concentration was detected between RK and RR genotypes (p = 0.006, p = 0.004, p = 0.014, respectively). Women with RK genotype compared to RR genotype had higher concentration of TGs (134.25 mg/dl vs 108.89 mg/dl, p = 0.014, respectively), total cholesterol (207.41 mg/dl vs 187.69 mg/dl, p = 0.006, respectively), and LDL-C (110.6 mg/dl vs 96.9 mg/dl, p = 0.004, respectively). These findings suggest that the R1587K polymorphism of ABCA1 gene was associated with lipid profile of Greek nurses. Women with RK genotype had higher TGs, total and LDL-C concentration compared to RR genotype. These observations may be significant in assessing the risk of CAD since a 1% change in LDL-C is associated with a 1% change of cardiovascular events. Also, TGs concentration were documented to play a significant role in women. However, this needs to be confirmed by larger studies.


Studies of bivalent copper ion binding to poly C.
Ultraviolet differential spectra of single-stranded poly C, taken in the presence of Cu2+ ions, are studied at various ionic strengths and temperatures. Coordinational and conformational components of these spectra are obtained. The Cu2+ ion coordination site on the polynucleotide bases is found to be N(3) and possibly O(2). The direction of the poly C absorption band shift due to ion binding and conformational transitions is established. At low ionic strengths of the solution Cu2+ ions cause the helical parts of poly C to melt. At high ones the formation of double-stranded parts was observed in addition to the above effect. The calculated concentration dependences of ion-poly C bases association constants show that binding is cooperative at any ionic strength.


DNA methylation mediated RSPO2 to promote follicular development in mammals.
In female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of -758/-749 and -563/-553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of -758/-749 and -563/-553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.


Astragaloside IV alleviates PM2.5-induced lung injury in rats by modulating TLR4/MyD88/NF-κB signalling pathway.
Astragaloside IV (AS IV) is antioxidant and anti-inflammatory product, which is extracted from the Chinese herb Astragalus membranaceus. It is widely used in a variety of inflammatory diseases. The research was to explored the protective effects of AS IV against lung injury induced by particulate matter 2.5 (PM2.5) in vivo. Thirty-five male Sprague-Dawley rats were randomly divided into five groups (n=7 per group). (1) Normal saline group (NS), (2) AS IV group (AS) (100 mg/kg), (3) PM2.5 group (PM2.5), (4) PM2.5 + AS IV group (ASL) (50 mg/kg), and (5) PM2.5 + AS IVgroup (ASH) (100 mg/kg). Rats were pre-treated with AS IV intraperitoneally (50 and 100 mg/kg/day) for three days. Then, PM2.5 (7.5 mg/kg) was given by intratracheal instillation to induce lung injury. Six hours after PM2.5 stimulation, the rats were euthanized. Bronchoalveolar lavage fluid (BALF) was collected for assay of cytokines. Lung tissue was collected for oxidative stress, histology, immunohistochemistry, transmission electron microscope, and western blot analyses. AS IV alleviated PM2.5-induced lung injury by decreasing lung dry-wet ratio, reducing the level of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) in BALF, and reduced oxidative stress response in lung tissue. Western blot results revealed that AS-IV regulated the expression of TLR4/MyD88/NF-κB pathway proteins in lung tissues. AS IV mitigated PM2.5 induced lung injury by regulating the activity of TLR4/MyD88/NF-κB signalling pathway, reducing inflammatory and oxidative stress responses.


Which morphological scoring system is relevant in human embryo development?
In the past several scoring systems were proposed for early human development aiming to assist in the identification of the best embryos. Scoring criteria are usually assessed at static developmental time points by microscopy. For almost every scoring system controversial results on its benefit can be found in the literature. With the introduction of time-lapse imaging static assessment of developmental parameters needs to be revised. The objective of this study was to critical review the strategy of static assessment by using an embryo monitoring system to study time-dependent variations of scoring criteria. Human oocytes were subjected to intracytoplasmic sperm injection and subsequently incubated in an embryo monitoring device. Images from individual oocytes were captured at given time intervals allowing a time-lapse analysis of early embryo development. Scoring of pronuclear morphology, early cleavage and embryo morphology up to day 3 of development was performed at standard time points and compared to the morphological fate present in time intervals prior and after standard assessment. Pronuclear morphology showed a high variability within very short time intervals. First cleavage can be observed at very early time points questioning the criterion "early cleavage". Embryo morphology can change within short time intervals and thus may be misleading if assessment is done at a static time point. Scoring of early embryo development has limitations if based on static observation only. Time-lapse imaging will lead to revised scoring systems emphasizing the need for a new look on embryological parameters.


Reproductive number of the COVID-19 epidemic in Switzerland with a focus on the Cantons of Basel-Stadt and Basel-Landschaft.
The reproductive number in Switzerland was between 1.5 and 2 during the first third of March, and has consistently decreased to around 1. After the announcement of the latest strict measure on 20 March 2020, namely that gatherings of more than five people in public spaces are prohibited, the reproductive number dropped significantly below 1; the authors of this study estimate the reproductive number to be between 0.6 and 0.8 in the first third of April.


Effector and regulatory T cells derived from the same T cell clone differ in MHC class II-peptide multimer binding.
MHC class II-peptide multimers are a valuable tool for antigen-specific detection of CD4(+) T cells. However, it has been proposed that T cells in a hypo-responsive state can have diminished binding of such multimers. In the present study, we investigated this phenomenon at the clonal level. We found that anergic CD4(+) T cells had a reduced capacity to bind MHC class II-peptide multimers compared to their non-anergic counterparts. Increasing the incubation temperature, time, or MHC-peptide valency could not equalize multimer binding by anergic and non-anergic T cells. Neither anergic T cells nor non-anergic T cells internalized the MHC class II-peptide dimers efficiently, and in both cases the dimers bound to the plasma membrane at locations containing a low amount of raft-associated lipids. Disruption of lipid rafts, however, led to decreased dimer binding by non-anergic T cells and to a lesser extent by anergic T cells. Finally, we show that the depth of the anergic state of the T cell, which determines its ability to regulate other T cell responses, correlates with the reduced dimer binding. We here demonstrate for the first time differential MHC class II-peptide multimer binding by regulatory (anergic) and effector T cells with identical TCR.


AI-driven deep and handcrafted features selection approach for Covid-19 and chest related diseases identification.
To identify various pneumonia types, a gap of 15% value is being created every five years. To fill this gap, accurate detection of chest disease is required in the healthcare department to avoid any serious issues in the future. Testing the affected lungs to detect a Coronavirus 2019 (COVID-19) using the same imaging modalities may detect some other chest diseases. This wrong diagnosis strongly needs a multidisciplinary approach to the right diagnosis of chest-related diseases. Only a few works till now are targeting pathological x-ray images. Many studies target only a single chest disease that is not enough to automate chest disease detection. Only a few studies regarding the observation of the COVID-19, but more cases are those where it can be misclassified as detecting techniques not providing any generic solution for all types of chest diseases. However, the existing studies can only detect if the person has COVID-19 or not. The proposed work significantly contributes to detecting COVID-19 and other chest diseases by providing useful analysis of chest-related diseases. One of our testing approaches achieves 90.22% accuracy for 15 types of chest disease with 100% correct classification of COVID-19. Though it analyzes the perfect detection as the accuracy level is high enough, but it would be an excellent decision to consider the proposed study until doctors can visually inspect the input images used by models that lead to its detection.


Intraoperative care of elderly patients with COVID-19 undergoing double lung transplantation: Two case reports.
Lung transplantation is considered an effective method for treating patients with end-stage coronavirus disease 2019 (COVID-19). The nurses play a pivotal role in lung transplantation for COVID-19 patients. Two elderly patients were admitted to the emergency department due to cough, and the nucleic acid test was positive. The patients were preliminarily diagnosed with COVID-19. The chest computed tomography scan revealed massive lung consolidation, and the patients did not improve after treatment with antiviral drugs, glucocorticoids, antibiotics, and other drugs. Under the support of pure oxygen in extracorporeal membrane oxygenation, the patients' oxygen levels were still poor, indicating that they were in the terminal stage of viral pneumonia. The patients underwent double-lung transplantation and received intraoperative care. The extracorporeal membrane oxygenation device was removed within a week of the surgical procedure, and the respiratory circulation of the patients were stabilized. High-quality care for COVID-19 patients undergoing lung transplantation ensures patient safety during operation while protecting the safety of the medical staff.


Intraoperative Detection of Surgical Gauze Using Deep Convolutional Neural Network.
During laparoscopic surgery, surgical gauze is usually inserted into the body cavity to help achieve hemostasis. Retention of surgical gauze in the body cavity may necessitate reoperation and increase surgical risk. Using deep learning technology, this study aimed to propose a neural network model for gauze detection from the surgical video to record the presence of the gauze. The model was trained by the training group using YOLO (You Only Look Once)v5x6, then applied to the testing group. Positive predicted value (PPV), sensitivity, and mean average precision (mAP) were calculated. Furthermore, a timeline of gauze presence in the video was drawn by the model as well as human annotation to evaluate the accuracy. After the model was well-trained, the PPV, sensitivity, and mAP in the testing group were 0.920, 0.828, and 0.881, respectively. The inference time was 11.3 ms per image. The average accuracy of the model adding a marking and filtering process was 0.899. In conclusion, surgical gauze can be successfully detected using deep learning in the surgical video. Our model provided a fast detection of surgical gauze, allowing further real-time gauze tracing in laparoscopic surgery that may help surgeons recall the location of the missing gauze.


Blood eosinophils associate with reduced lung function growth in adolescent asthmatics.
Some children with asthma have low lung growth, putting them at increased risk for COPD later in life. However, it is currently not clear who will experience this adverse growth pattern. We therefore investigated the predictive role of blood eosinophils as a type 2 inflammation marker in lung growth, focusing on the presence and severity of asthma. We investigated blood eosinophils and lung function growth (percentage of predicted values) using linear mixed models in children and adolescents from two longitudinal cohorts. One cohort was hospital-based and consisted of asthmatic children at their first outpatient clinic visit after referral by the general practitioner (n = 133, mean age 9.8), while the second was a general population-based birth cohort (PIAMA, asthma n = 52 and non-asthma n = 433, mean age 8.1). The hospital-based cohort had not been treated with inhaled corticosteroids (ICS) before referral. Subjects in the hospital-based asthma cohort had more severe asthma compared with the asthmatic subjects in the population-based cohort, defined by lower lung function levels and a higher prevalence of bronchial hyper-responsiveness. In the asthma cohort, higher blood eosinophil numbers were associated with less growth in FEV1 (estimated change in lung function per 1 unit increase in ln blood eosinophils (B): -0.66%/year (95% confidence interval (CI): -1.11 to -0.20, p < .01)) and FVC (B: -0.40%/year (95% CI: -0.75 to -0.05), p = .025)) during follow-up in adolescence (min 7, max 17 years). These associations were not observed in the general population-based birth cohort, regardless of asthma status during follow-up (age 8-16). Blood eosinophil counts in children with asthma not treated with ICS at referral were predictive of lower growth in FEV1 and FVC during follow-up in adolescence. Our findings indicate that this association is dependent on the degree of asthma severity. Future studies should address whether anti-eosinophilic treatments preserve lung function growth in children with asthma.


Update on allergies in pregnancy, lactation, and early childhood.
The factors responsible for the induction of allergic disease at an early age have not been completely identified. Therefore a major research focus is their identification to elaborate recommendations for prevention of sensitization in high-risk or atopic children. This review analyzes known or suspected reasons for sensitization in pregnant women and infants from both clinical and experimental animal studies. Recent studies and meta-analyses could not confirm the protective effect of an allergen-poor diet on the part of the mother during pregnancy and lactation. Likewise, the type of bottle feeding or the introduction of solid food into the child's diet might not significantly influence the development of atopy, allergy, or asthma in the child's life. Disappointingly, the few preventive measures remaining to reduce the risk of allergic sensitization and atopic diseases in mother and child are the avoidance of smoking and alcohol consumption during pregnancy and lactation and the avoidance of the impairment of gastric function. Further studies are urgently needed to address the influence of certain foods and nutrients, as well as environmental factors, for prevention of allergic diseases in the low- or high-risk infant.


Bilateral arachnoid cyst-associated subdural fluid collections in an infant following TBI.
arachnoid cyst-associated subdural fluid collections have been documented in children and adults following traumatic brain injury (TBI). However, this phenomenon has not been previously demonstrated in infants less than 12 months of age. We present a case of an infant with bilateral arachnoid cyst-associated subdural fluid collections identified after TBI. a 9-month-old female infant with profound macrocephaly presented to medical care with altered mental status following a witnessed fall down steps while unsecured in a stroller. Neuroimaging revealed bilateral subdural fluid collections, in addition to a hyperdense subdural hematoma, that raised concern for abusive head trauma (AHT) among the pediatric inpatient team and the hospital's Suspected Child Abuse and Neglect (SCAN) Team was consulted. After excluding occult abusive injuries as well as testing for underlying medical conditions, the infant's bilateral subdural fluid collections were attributed to rupture of a pre-existing left middle cranial fossa arachnoid cyst with evidence of prior macrocephaly. In infants and toddlers, the identification of subdural fluid collections on neuroimaging warrants inclusion of AHT in the differential diagnosis. However, in infants with a history of congenital macrocephaly, and an otherwise negative AHT workup, an accidental mechanism for the formation of subdural collections should be considered, especially when co-occurring with an arachnoid cyst.


Structure-dependent induction of CYP2B1/2 by 3-methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats.
The effects of eleven 3-methylsulfonyl (3-MeSO(2))-metabolites of polychlorinated biphenyl (PCB) congeners (which were reported to remain in Swedish mother's milk and Japanese Yusho patient's tissues) and their two structurally similar 3-MeSO(2)-PCBs on the hepatic drug-metabolizing enzyme activities were compared with those of phenobarbital (PB) and 3-methylcholanthrene (3-MC).The induction profile of the drug-metabolizing enzymes, CYP2B1 and CYP2B2 in the hepatic microsomes of rats treated with nine 3-MeSO(2) derivatives, namely 3-MeSO(2)-2,4',5-trichlorobiphenyl, 3-MeSO(2)-2,2',4',5-tetrachlorobiphenyl (3-MeSO(2)-2,2',4',5-tetraCB), 3-MeSO(2)-2,2',5,5'-tetraCB, 3-MeSO(2)-2,3',4',5-tetraCB, 3-MeSO(2)-2,2',3',4',5-pentachlorobiphenyl (3-MeSO(2)-2,2',3',4',5-pentaCB), 3-MeSO(2)-2,2',4',5,5'-pentaCB, 3-MeSO(2)-2,2',3',4',5,5'-hexachlorobiphenyl (3-MeSO(2)-2,2',3',4',5,5'-hexaCB), 3-MeSO(2)-2,2',3',4',5,6-hexaCB and 3-MeSO(2)-2,2',4',5,5',6-hexaCB, was similar to that of rats treated with PB, but was different from that of rats treated with 3-MC. These findings indicate that 3-MeSO(2) metabolites derived from nine PCBs are PB-type inducers of microsomal drug-metabolizing enzymes. The relative inducing potencies of 3-MeSO(2) derivatives on the hepatic drug-metabolizing enzyme activities differed with the extent of chlorination and the positions of chlorine substituent on the phenyl rings. The results of present study show that the structure-CYP2B1/2 induction relationship exists for the 3-MeSO(2) derivatives studied. The inducing abilities of 3-MeSO(2)-2,2',4',5-tetraCB and 3-MeSO(2)-2,2',4',5,5'-pentaCB (2 μmol/kg) on the content of cytochrome P450 were higher than those of 2,3',4,4',5-pentaCB (mono-ortho-substituted PCB) (80 μmol/kg), 3,3',4,4'-tetraCB (coplanar PCB) (80 μmol/kg) and 3,3',4,4',5-pentaCB (coplanar PCB) (0.5 μmol/kg). The inducing effects of the administration of 3-MeSO(2)-2,2',4',5-tetraCB and 3-MeSO(2)-2,2',4',5,5'-pentaCB at 2 μmol/kg on the contents of total cytochrome P450, CYP2B1 and CYP2B2 corresponded to those of PB at 431 μmol/kg twice at a 24 h interval. It is noticeable that 3-MeSO(2)-2,2',4',5-tetraCB and 3-MeSO(2)-2,2',4',5,5'-pentaCB have highly potent PB-type inducing activity on drug-metabolizing enzyme systems.


The rates of evolution in some ribosomal components.
The rate of nucleotide substitution (k(nuc)) of 5s RNA was estimated to be (1.8 +/- 0.5) x 10(-10) per site per year by comparing the nucleotide sequences of human and Xenopus 5s RNA and using the geological time elapsed since the separation of mammals and amphibians. Similarly, k(nuc) of 5.8s rRNA was calculated to be 0.93 10(-1u) per site per year from the sequences of rat hepatoma cells and Saccbaromyces cerevisiae. For the comparison of these data with the amino acid substitution rate of known proteins, the k(nuc) values of 5s rRNA and 5.8s rRNA were converted to the rate of amino acid substitution (k(aa')). The k(aa') values in pauling units were 0.4 and 2 0.3, respectively. The average k(aa) of ribosomal proteins was also estimated to be 0.2 0.3 pauling from the N-terminal amino acid sequences of seventeen 30s ribosomal proteins of Bacillus stearothermopbilus and Eschericbia coli. Thus, the evolutionary rates of these ribosomal components studied here are similar to each other; they considerably slower than that of the known cellular proteins. Most, if not all, of the replacements in ribosomal proteins occurred between amino acids of a chemically similar nature.


The association between mental health and shift work: Findings from the Atlantic PATH study.
We evaluated the relationship between mental health and shift work in the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. In a matched study with 12,413 participants, including 4155 shift workers and 8258 non-shift workers, we utilized general linear models and logistic regression models to assess the differences in depression, anxiety, and self-rated health. Shift workers reported higher levels of each of the mental health-related domains compared to non-shift workers. There was a significant increased risk of depression (OR = 1.13, 95% CI, 1.00-1.27) and poor self-rated health (OR = 1.13, 95% CI, 1.14-1.55) among shift workers compared to non-shift workers. Shift workers were more likely to have increased rates of depression and poor self-rated health, as well as depressive and anxiety symptom scores compared to non-shift workers. As a result, shift workers may be at increased risk of comorbidity, poor quality of life, missed work, and early retirement.


MicroRNA qPCR normalization in Nile tilapia (Oreochromis niloticus): Effects of acute cold stress on potential reference targets.
The Nile tilapia (Oreochromis niloticus) is one of the most important cultured fish worldwide, but tilapia culture is largely affected by low temperatures. Recent studies suggest that microRNAs (miRNAs) regulate cold tolerance traits in fish. In general, qPCR-based methods are the simplest and most accurate forms of miRNA quantification. However, qPCR data heavily depends on appropriate normalization. Therefore, the aim of the present study is to determine whether the expression of previously tested, stably expressed miRNAs are affected by acute cold stress in Nile tilapia. For this purpose, one small nuclear RNA (U6) and six candidate reference miRNAs (miR-23a, miR-25-3, Let-7a, miR-103, miR-99-5, and miR-455) were evaluated in four tissues (blood, brain, liver, and gills) under two experimental conditions (acute cold stress and control) in O. niloticus. The stability of the expression of each candidate reference miRNA was analyzed by four independent methods (the delta Ct method, geNorm, NormFinder, and BestKeeper). Further, consensual comprehensive ranking of stability was built with RefFinder. Overall, miR-103 was the most stable reference miRNA in this study, and miR-103 and Let-7a were the best combination of reference targets. Equally important, Let-7a, miR-23a, and miR-25-3 remained consistently stable across different tissues and experimental groups. Considering all variables, U6, miR-99-5, and miR-455 were the least stable candidates under acute cold stress. Most important, suitable reference miRNAs were validated in O. niloticus, facilitating further accurate miRNA quantification in this species.