Pulmonary sarcoidosis-like reactions induced by sintilimab in esophageal cancer: A case report.
Esophageal cancer is one of the deadliest cancers in the world, with high incidence and mortality rates ranking among the top ten in China. The efficacy of conventional treatments is limited and often accompanied by severe adverse reactions, which results in unsatisfactory outcomes. The mechanism of immune checkpoint inhibitors (ICIs) is to activate cytotoxic T cells to kill tumor cells expressing tumor antigens. The application of ICIs has profoundly changed the mode of cancer treatment. However, the use of ICIs also induces a series of adverse reactions similar to autoimmune reactions, called immune-related adverse events (irAEs). Some ICIs can cause manifestations similar to those in the development of sarcoidosis, which are called sarcoidosis-like reactions or granulomatosis. We report a 50-year-old Chinese male patient. The patient had been diagnosed with advanced esophageal squamous cell carcinoma , and was confirmed to have pulmonary sarcoidosis-like reactions associated with sintilimab, a human programmed cell death protein 1 (PD-1) inhibitor. The patient was administered corticosteroid treatment. After receiving steroid treatment, the patient's systemic and pulmonary symptoms improved rapidly. To our knowledge, this is the first report of pulmonary sarcoidosis-like reaction in a patient with esophageal squamous cell carcinoma. The patient then continued to receive 1 year of follow-up antitumor treatment after the appearance of lung pulmonary sarcoidosis-like reactions. The prognosis was good and the patient's condition is currently stable. The diagnosis of ICI-induced sarcoidosis often requires comprehensive evaluation through clinical, pathological, and radiological assessment. A subset of patients with sarcoidosis-like reactions may not require treatment unless there is organ dysfunction or severe clinical symptoms, and these reactions generally respond well to treatment. The occurrence of sarcoidosis-like reactions after immunotherapy is positively correlated with the long-term prognosis of cancer patients. However, this hypothesis requires larger prospective studies for validation.


Protective effects of ACE inhibitors on vascular endothelial dysfunction induced by exogenous advanced oxidation protein products in rats.
To explore detrimental effects of advanced oxidation protein products-bovine serum albumin (BSA) on endothelial function and compare the favorable effects of angiotensin-converting enzyme (ACE) inhibitors: captopril and enalapril. Male Sprague-Dawley rats were randomly divided into groups: control, advanced oxidation protein products-BSA, captopril (10, 20 mg/kg/day), enalapril (15 mg/kg/day), and N(G)-nitro-l-arginine methyl ester (l-NAME, 300 mg/kg/day) plus captopril (20 mg/kg/day) groups. All animals were given advanced oxidation protein products-BSA (100 mg/kg/day, i.v.) except for control group (iv. equal volume of PBS). Rats in other groups were received different drugs intragastrically after advanced oxidation protein products-BSA administration. Endothelium-dependent relaxation of thoracic aorta was assayed. Content of nitrite/nitrate (NO), malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and of ACE in Sera, as well as renal function index including blood urea nitrogen and creatinine were measured. After 30 days, the endothelium-dependent relaxation of blood vessels in received advanced oxidation protein products-BSA rats was significantly impaired compared with control rats. The impairment was accompanied by decreases of serum NO, activity of GSH-Px and SOD. Administration of captopril and enalapril not only decreased damage of endothelium-dependent relaxation, but also reverse the changes of MDA levels, NO content and activity of SOD. The protective effect of captopril was abolished by L-NAME. Blood urea nitrogen and creatinine had no significant differences between various groups. ACE activities were decreased in high captopril and enalapril groups, but did not significantly change in other groups. The results suggested that captopril and enalapril have similar effects on endothelial dysfunction induced by advanced oxidation protein products-BSA, which indicated that protective effects of captopril are not related to sulfhydryl group.


Legal aspects of open disclosure II: attitudes of health professionals - findings from a national survey.
To assess the attitudes of health care professionals engaged in open disclosure (OD) to the legal risks and protections that surround this activity. National cross-sectional survey of 51 experienced OD practitioners conducted in mid 2009. Perceived barriers to OD; awareness of and attitudes towards medicolegal protections; recommendations for reform. The vast majority of participants rated fears about the medicolegal risks (45/51) and inadequate education and training in OD skills (43/51) as major or moderate barriers to OD. A majority (30/51) of participants viewed qualified privilege laws as having limited or no effect on health professionals' willingness to conduct OD, whereas opinion was divided about the effect of apology laws (state laws protecting expressions of regret from subsequent use in legal proceedings). In four states and territories (Western Australia, South Australia, Tasmania and the Northern Territory), a majority of participants were unaware that their own jurisdiction had apology laws that applied to OD. The most frequent recommendations for legal reform to improve OD were strengthening existing protections (23), improving education and awareness of applicable laws (11), fundamental reform of the medical negligence system (8), and better alignment of the activities of certain legal actors (eg, coroners) with OD practice (6). Concerns about both the medicolegal implications of OD and the skills needed to conduct it effectively are prevalent among health professionals at the leading edge of the OD movement in Australia. The ability of current laws to protect against use of this information in legal proceedings is perceived as inadequate.


Hypertriglyceridemia as a possible risk factor for prostate cancer.
We retrospectively studied anthropometric and laboratory parameters (including serum triglycerides, cholesterol), as well as comedication in 504 patients diagnosed with prostate cancer between January 1997 and August 2002 at a single referral center, and compared these patients with 565 age-matched patients with benign prostatic hyperplasia. A positive correlation was found between serum triglycerides and prostate cancer (odds ratio: 1.148/mmol/l; 95% confidence interval (CI) 1.003-1.315; P<0.05) after correcting for age, body mass index, diabetes and comedication with statins. Hypertriglyceridemia may increase the risk of prostate cancer, and the prognostic relevancy of serum triglycerides should be studied prospectively.


The clinical response and systemic effects of non-surgical periodontal therapy in end-stage renal disease patients: a 6-month randomized controlled clinical trial.
Scientific evidence on the effects of chronic periodontitis on end-stage renal disease (ESRD) remains inadequate and inconclusive. This intervention study was designed to evaluate the effects of non-surgical periodontal therapy on the clinical response and systemic status of ESRD patients. Patients in the intervention group (n = 48) received non-surgical periodontal therapy and then a supragingival prophylaxis at the 3-month follow up, and those in the control group (n = 49) received no intervention throughout the study. At 6 weeks, 3 months, and 6 months after therapy, clinical periodontal examinations were conducted and blood samples were taken to evaluate inflammatory, nutritional and lipid profiles. The results showed a significant improvement in clinical periodontal parameters (p < 0.05) in the intervention group. Compared to the control group, the intervention group had significantly lower high-sensitivity C-reactive protein at 3 months and 6 months. Significant improvements were found (p < 0.05) in interleukin-6, ferritin, albumin, creatinine, blood urea nitrogen, and transferrin after therapy. Non-surgical periodontal therapy can effectively improve periodontal, circulating inflammatory and nutritional status in ESRD patients. Non-surgical periodontal therapy, as a relatively simple intervention, has beneficial systemic effects in ESRD patients.


Low IGF-I in synovial fluid and serum in patients with aseptic prosthesis loosening.
We have previously shown that proliferation in primary cultures of human osteoblast-like cells is lower after exposure to synovial fluid from patients with aseptic prosthesis loosening than after exposure to synovial fluid from patients with osteoarthrosis. Insulin-like growth factors (IGF) I and II and IGF binding proteins (IGFBP) 3-6, were measured with radioimmunoassy in synovial fluid and in serum from patients with aseptic prosthesis loosening or osteoarthrosis. Proliferation in osteoblast-like MG-63 cells was studied with the CyQUANT assay. IGF-I and IGFBP-4 concentrations were lower whereas the concentration of IGFBP-6 was higher in synovial fluids from patients with prosthesis loosening than in synovial fluid from patients with osteoarthrosis. IGF-I concentrations in serum from patients with prosthesis loosening were also lower than in the osteoarthrosis group, and were even below the normal range in most cases (72%). Synovial fluid from patients with aseptic loosening had a weaker stimulatory effect on MG63 osteoblast-like cell proliferation than synovial fluid from patients with osteoarthrosis, but there was no difference between the two groups when a human IGF-I antibody was added. Low levels of IGF-I in synovial fluid possibly result from low serum levels and may be a mechanism leading to aseptic prosthesis loosening.


Calorimetric studies of flavin binding protein: flavin analog binding.
The effect of flavin structure variation upon the overall binding reaction of flavin to hen egg white riboflavin binding protein (WRBP) was correlated to thermodynamic parameters obtained via titration calorimetry. This effect was measured by determining a reference binding enthalpy (delta Href) for 3-carboxymethylriboflavin and subsequently comparing delta Href to the binding enthalpies determined for all other flavin analogs in this study. The reference enthalpy change was measured in detail under a variety of temperatures (14, 25, and 38 degrees C), pH's (5.5, 6.5, 7.4, 8.5), and buffer types. The reference enthalpy for the binding of N(3)-carboxymethylriboflavin to WRBP was measured as delta H = -20.9 kcal/mol at 25.0 degrees C and pH 7.4. Evaluation of the binding thermodynamic values for the reference flavin indicates that there is no H+ flux concomitant with binding. A small negative change in heat capacity (delta Cp) occurs during the binding process suggesting a contraction of the protein. Finally, the reaction appears to be independent of pH and buffer type indicating little, if any, involvement of charged residues in the binding of flavin to apoWRBP. Thermodynamic values for the binding of an additional eight flavin analogs were then measured at pH 7.4 and 25.0 degrees C. The thermodynamic binding parameters for these analogs were evaluated by comparison to those determined for the reference flavin. The results indicate that the ribityl C2' position is a major influence in the interaction between the ribityl side chain and the protein; the C9 position of the isoalloxazine ring is sterically restricted in a manner similar to positions C7 and C8; and the positions C7 and C8 appear to be unequal with regard to enthalpy release, suggesting that the C8 position is the most restricted region in the aromatic ring. These various findings indicate the unique ability of titration calorimetry to evaluate structural variation of ligands to their corresponding binding site interactions.


Osculatory packing of finite areas with circles.
Osculatory packing of a finite area by circles requires that any uncovered area or interstice be filled always with the largest possible non-overlapping circle. The strength of this requirement makes it possible to derive a general analytic expression that approximates closely to the distributions of radii calculated for various sets of boundary conditions.


Dibutyltin dichloride exposure affects mouse oocyte quality by inducing spindle defects and mitochondria dysfunction.
Dibutyltin dichloride (DBTCl) is a widespread environmental pollutant that is frequently employed as a light and heat sustainer for polyvinyl chloride (PVC) plastics and is a teratogen in vivo. Nevertheless, its destructiveness in mammalian oocytes remains unclear. This study highlighted the consequences of DBTCl vulnerability on mouse oocyte. Our results revealed that exposure to 5.0 mg/kg/day of DBTCl for ten days reduced the number of mature follicles and oocytes in the ovaries and inhibited the meiotic maturation of oocytes. Single-cell transcriptomic analysis indicated that DBTCl exposure interfered with the expression of more than 400 genes in oocytes, including those involved in multiple biological pathways. Specifically, DBTCl exposure impaired spindle assembly and chromosome alignment. In addition, DBTCl exposure caused mitochondrial dysfunction, which led to the accumulation of reactive oxygen species (ROS) and induced apoptosis. In summary, our study illustrates that mitochondrial dysfunction and redox perturbation are the major causes of the reduced quality of oocytes exposed to DBTCl.


Dielectric property measurements as a method to determine the physiological state of Kluyveromyces marxianus and Saccharomyces cerevisiae stressed with furan aldehydes.
Cell physiology parameters are essential aspects of biological processes; however, they are difficult to determine on-line. Dielectric spectroscopy allows the on-line estimation of viable cells and can provide important information about cell physiology during culture. In this study, we investigated the dielectric property variations in Kluyveromyces marxianus SLP1 and Saccharomyces cerevisiae ERD yeasts stressed by 5-hydroxymethyl-2-furaldehyde and 2-furaldehyde during aerobic growth. The dielectric properties of cell permittivity, specific membrane capacitance (Cm), and intracellular conductivity (σIn) were considerably affected by furan aldehydes in the same way that the cell population, viability, cell size, substrate consumption, organic acid production, and respiratory parameters were. The yeasts stressed with furan aldehydes exhibited three physiological states (φ): adaptation, replicating, and nonreplicating states. During the adaptation state, there were small and stable signs of permittivity, Cm, and σIn; additionally, no cell growth was observed. During the replicating state, cell growth was restored, and the cell viability increased; in addition, the permittivity and σIn increased rapidly and reached their maximum values, while the Cm decreased. In the nonreplicating state, the permittivity and σIn were stable, and Cm decreased to its minimum value. Our results demonstrated that knowing dielectric properties allowed us to obtain information about the physiological state of the cells under control and stressed conditions. Since the permittivity, Cm, and σIn are directly associated with the physiological state of the yeast, these results should contribute to a better understanding of the stress response of yeasts and open the possibility to on-line monitor and control the physiological state of the cell in the near future.


Design, synthesis and pharmacological characterization of new highly selective CRF(2) antagonists: development of 123I-K31440 as a potential SPECT ligand.
Novel analogs of antisauvagine-30 (aSvg-30), a specific antagonist for corticotropin-releasing factor (CRF) receptor, type 2 (CRF(2)), have been synthesized and characterized in vitro and in vivo. The N-terminal amino acid D-phenylalanine in aSvg-30 was replaced by a D-tyrosine residue for specific radioactive labeling with 123I. Additionally, Met(17) of aSvg-30 was substituted by norleucine and the N-terminus of the peptide was acetylated to increase in vivo metabolic stability. The aSvg-30 analogs were tested for their ability to displace [125I-Tyr(0)]Svg in binding experiments and to inhibit Svg-stimulated adenylate cyclase activity in human embryonic kidney (HEK) 293 cells, permanently transfected with cDNA coding for the human CRF(1) (hCRF(1)), hCRF(2alpha) and hCRF(2beta) receptor. Ac-[D-Tyr(11), His(12), Nle(17)Svg(11-40), named K31440, showed high specific binding to hCRF(2alpha) (K(i) = 1.48 +/- 0.34 nM) and hCRF(2beta) (K(i) = 2.05 +/- 0.61 nM) but not the hCRF(1) receptor (K(i) = 288 +/- 13 nM) and decreased Svg-stimulated cAMP activity in hCRF(2)-expressing cells in a similar fashion as aSvg-30. In biodistribution studies specific uptake of 123I-K31440 was detected after 1 h in small intestine of BALB/c nude mice. These data demonstrate that 123I-K31440 may serve as a useful tool to detect native CRF(2) receptors and elucidate their role in gastrointestinal disorders and diseases such as irritable bowel syndrome or cancer.


Design and synthesis of benzoxazole derivatives as novel melatoninergic ligands.
A novel series of benzoxazole derivatives was synthesized and evaluated as melatoninergic ligands. The binding affinity of these compounds for human MT(1) and MT(2) receptors was determined using 2-[(125)I]-iodomelatonin as the radioligand. The results of the SAR studies in this series led to the identification of compound 28, which exhibited better MT(1) and MT(2) receptor affinities than melatonin itself. This work also established the benzoxazole nucleus as a melatoninergic pharmacophore, which served as an isosteric replacement to the previously established alkoxyaryl core.


The receptive-field spatial structure of cat retinal Y cells.
1. Y-type ganglion cells in the cat's retina were stimulated with bars of light and grating patterns at photopic luminances. Stimuli were stationary, and luminance at each point was varied sinusoidally in time at 2 Hz. Impulse rates were recorded from single cells. 2. When the stimulus was a narrow bar of light, the impulse rate approached a sinusoidal function of time as contrast was reduced. The linear behaviour of each cell was therefore characterized by taking the limit of response parameters as contrast approached zero. 3. The ratio of surround strength to centre strength varied widely between cells but the two strengths were approximately equal on average. The difference between surround phase and centre phase averaged 168 deg. 4. As contrast increased, responses became rectified. Rectifier output was well described by a power law of stimulus amplitude, where the power was usually 1.4 or 1.5. 5. Response phase advanced with increasing contrast, and at high response amplitudes grew less than proportionally with contrast. These effects were assumed due to the contrast gain control described by Shapley & Victor (1978). 6. Gratings in which luminance varied sinusoidally with distance were used to determine Y cell spatial resolution. The second-harmonic amplitude of the response diminished rapidly with increasing spatial frequency: the radius of the best-fitting Gaussian mechanism was about 0.25 deg for a cell at 10 deg eccentricity. 7. This spatial resolution is close to the linear resolution of X cells as determined by Linsenmeier, Frishman, Jakiela & Enroth-Cugell (1982). 8. A receptive field model incorporating both linear and non-linear elements is described. The model consists of an array of subunit pathways, each of which has a centre-surround organization followed by a rectifier; a pool weights and sums subunit outputs, and signals are then passed through a contrast gain control. 9. The model accounts qualitatively for the over-all centre-surround organization of Y cell linear responses, the dependence of frequency-doubled responses on spatial frequency, and impulse rate as a function of time for a variety of bar and grating stimuli.


MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.
Histone epigenetic modification disorder is an important predisposing factor for the occurrence and development of many cancers, including colorectal cancer (CRC). The role of MYSM1, a metalloprotease that deubiquitinates monoubiquitinated histone H2A, in colorectal cancer was identified to evaluate its potential clinical application value. MYSM1 expression levels in CRC cell lines and tumor tissues were detected, and their associations with patient survival rate and clinical stage were analyzed using databases and tissue microarrays. Gain- and loss-of-function studies were performed to identify the roles of MYSM1 in CRC cell proliferation, apoptosis, cell cycle progression, epithelial-mesenchymal transition (EMT) and metastasis in vitro and in vivo. ChIP, rescue assays and signal pathway verification were conducted for mechanistic study. Immunohistochemistry (IHC) was used to further assess the relationship of MYSM1 with CRC diagnosis and prognosis. MYSM1 was significantly downregulated and was related to the overall survival (OS) of CRC patients. MYSM1 served as a CRC suppressor by inducing apoptosis and inhibiting cell proliferation, EMT, tumorigenic potential and metastasis. Mechanistically, MYSM1 directly bound to the promoter region of miR-200/CDH1, impaired the enrichment of repressive H2AK119ub1 modification and epigenetically enhanced miR-200/CDH1 expression. Testing of paired CRC patient samples confirmed the positive regulatory relationship between MYSM1 and miR-200/CDH1. Furthermore, silencing MYSM1 stimulated PI3K/AKT signaling and promoted EMT in CRC cells. More importantly, a positive association existed between MYSM1 expression and a favorable CRC prognosis. MYSM1 plays essential suppressive roles in CRC tumorigenesis and is a potential target for reducing CRC progression and distant metastasis.


Population dynamics of gyrinid beetles : III. Survival of adults.
Survival chances have been estimated for populations of the waterbeetle Gyrinus marinus Gyll. from capture-recapture sequences in 1974-1978. The average weekly survival chance is estimated as 0.9247 in spring, decreasing to 0.7701 in autumn; males survive longer than females. Survival shows little variation in time or space (variation coefficient V<0.1). Survival chance did not significantly decrease with age. Freshly emerged tenerals apparently have a lower survival chance than older beetles. The survival chance during hibernation (October-April) is about 0.33, with a greater variation between years (V=0.7) than between populations (V=0.4).


The neonicotinoid thiacloprid causes transcriptional alteration of genes associated with mitochondria at environmental concentrations in honey bees.
Thiacloprid is widely used in agriculture and may affect pollinators. However, its molecular effects are poorly known. Here, we report the global gene expression profile in the brain of honey bee foragers assessed by RNA-sequencing. Bees were exposed for 72 h to nominal concentrations of 25 and 250 ng/bee via sucrose solution. Determined residue concentrations by LC-MS/MS were 0.59 and 5.49 ng/bee, respectively. Thiacloprid exposure led to 5 and 71 differentially expressed genes (DEGs), respectively. Nuclear genes encoding mitochondrial ribosomal proteins and enzymes involved in oxidative phosphorylation, as well as metabolism enzymes and transporters were altered at 5.49 ng/bee. Kyoto Encylopedia of Genes and Genomes (KEGG) analysis revealed that mitochondrial ribosome proteins, mitochondrial oxidative phosphorylation, pyrimidine, nicotinate and nicotinamide metabolism and additional metabolic pathways were altered. Among 21 genes assessed by RT-qPCR, the transcript of farnesol dehydrogenase involved in juvenile hormone III synthesis was significantly down-regulated. Transcripts of cyp6a14-like and apolipophorin-II like protein, cytochrome oxidase (cox17) and the non-coding RNA (LOC102654625) were significantly up-regulated at 5.49 ng/bee. Our findings indicate that thiacloprid causes transcriptional changes of genes prominently associated with mitochondria, particularly oxidative phosphorylation. This highlight potential effects of this neonicotinoid on energy metabolism, which may compromise bee foraging and thriving populations at environmentally relevant concentrations.


A pilot study to test the validity of a piezoelectric intra-splint force detector for monitoring of sleep bruxism in comparison to portable polysomnography.
To test the validity of a force-based detection system (ISFD: intra-splint force detector) to record sleep bruxism (SB) in comparison to portable polysomnography (PSG). Simultaneous portable PSG recordings with a masseter electromyography (EMG) channel and ISFD with a deformation-sensitive piezoelectric film were performed on six participants with definite SB. First, simulated bruxism behaviors (static clenching, grinding, tapping, and rhythmic clenching) were recorded using both EMG and ISFD. Using these data, interval and duration criteria for ISFD data conditioning were established. Then, portable PSG recordings were conducted with the ISFD during sleep. Using the above criteria, ISFD events were compared with EMG-based SB episodes (the gold standard), and the sensitivity and positive predictive value of ISFD events were calculated. Spearman's correlation coefficients between true-positive ISFD events and SB episodes were then calculated. Among the tested conditioning criteria, a 3-s interval combined with a 1-s duration was selected. The median sensitivity and positive predictive value for the ISFD were 0.861 and 0.585, respectively. The duration of true-positive ISFD events was correlated with that of EMG-based SB episodes (rho = 0.658, P < 0.01). ISFD has validity for SB detection and could be an alternative to single-channel EMG-based recordings.


A twelve month study of sports injuries in one Irish school.
A literature review suggested that both acute and overuse injuries were common in body contact sports. This hypothesis was tested on a group of 266 Irish adolescents in an investigation that examined the incidence of injury amongst these individuals over a twelve months period. The mean age of the subjects was:- males 14.3 +/- 0.85 years and females 14.1 +/- 0.90 years. The responses of the subjects to a questionnaire on their sporting involvement, training and sports injuries were analysed. A total of 230 injuries were incurred by the subjects during the twelve month period: 181 of these were to males. However, the number of injuries per hour of participation was similar in the two sexes. Subjects involved in body contact sports incurred the highest number of overuse injuries. The injury rate per 10,000 hours of participation was highest in badminton (70.85 injuries per 10,000 hours), gymnastics (68.18), rugby (59.77) and basketball (56.22). The rate of overuse injuries was high in swimming, badminton and athletics. The most common injuries was found to be common. The results of the study suggests that injury prevention programmes should be targeted to a wider range of sports, to females as well as to males, and that rehabilitation programmes need to be improved.


Inhibiting and catalysing amyloid fibrillation at dynamic lipid interfaces.
Proteins are naturally exposed to diverse interfaces in living organisms, from static solid to dynamic fluid. Solid interfaces can enrich proteins as corona, and then catalyze, retard or hinder amyloid fibrillation. But fluid interfaces abundant in biology have rarely been studied for their correlation with protein fibrillation. Unsaturated fatty acids own growing essential roles in diet, whose fluid interfaces are found in vitro to catalyze amyloid fibrillation under certain physiologic conditions. It is determined by the location of double bonds within alkyl chains as well as the presence of physical shear. Docosahexaenoic acid (DHA) shows low catalysis because its unique alkyl chain does not favor to stabilize cross-β nucleus. Mixtures of different fatty acids also decelerate their catalytic activity. High catalysis poses an unprecedented approach to synthesize biologic nanofibrils as one-dimensional (1D) building blocks of functional hybrids. Fibrillation inhibition implied that appropriate diet would be a preventive strategy for amyloid-related diseases. Thus these results may find their significances in diverse fields of science as chemistry, biotechnology, nanotechnology, nutrition, amyloid pathobiology and nanomedicine.


Transcriptional variation in Babesia gibsoni (Wuhan isolate) between in vivo and in vitro cultures in blood stage.
Babesia gibsoni, the causative agent of canine babesiosis, belongs to the phylum Apicomplexa. The development of in vitro culture technology has driven research progress in various kinds of omics studies, including transcriptomic analysis of Plasmodium spp. between in vitro and in vivo environments, which has prompted the observation of diagnostic antigens and vaccine development. Nevertheless, no information on Babesia spp. could be obtained in this respect, which greatly hinders the further understanding of parasite growth and development in the blood stage. In this study, considerable changes in the morphology and infectivity of continuous in vitro cultured B. gibsoni (Wuhan isolate) were observed compared to in vivo parasites. Based on these changes, B. gibsoni (Wuhan isolate) was collected from both in vivo and in vitro cultures, followed by total RNA extraction and Illumina transcriptome sequencing. The acquired differentially expressed genes (DEGs) were validated using qRT-PCR, and then functionally annotated through several databases. The gene with the greatest upregulation after in vitro culture was cloned from the genome of B. gibsoni (Wuhan isolate) and characterized by western blotting and indirect immunofluorescence assay for detecting the native form and cellular localization. Through laboratory cultivation, multiple forms of parasites were observed, and the infectivity of in vitro cultured parasites in dogs was found to be lower. Based on these changes, Illumina transcriptome sequencing was conducted, showing that 377 unigenes were upregulated and 334 unigenes were downregulated. Notably, an AP2 transcription factor family, essential for all developmental stages of parasites, was screened, and the transcriptional changes in these family members were tested. Thus, the novel AP2 transcription factor gene (BgAP2-M) with the highest upregulated expression after in vitro adaptation was selected. This gene comprises an open reading frame (ORF) of 1989 base pairs encoding a full-length protein of 662 amino acids. BgAP2-M contains one AP2 domain and one ACDC conserved domain, which may be involved in the nuclear biology of parasites. The prepared polyclonal antibodies against the BgAP2-M peptides further detected a native size of ~ 73 kDa and were localized to the nuclei of B. gibsoni. This study presents a thorough transcriptome analysis of B. gibsoni in vivo and in vitro for the first time, contributing to a detailed understanding of the effects of environmental changes on the growth and development of parasites in the blood stage. Moreover, it also provides a deeper investigation for the different members of the ApiAP2 transcription factor family as various life stage regulators in Babesia spp.


Correlation between the duration of maternal rest in the left lateral decubitus position and the amniotic fluid volume increase.
The purpose of this study was to show the relationship between amniotic fluid volume changes and the duration of maternal rest in the left lateral decubitus position. Pregnant women (n = 34) with an amniotic fluid index between 6 and 24 cm and an uncomplicated singleton pregnancy at 35 to 40 weeks' gestation were included in the study. After the initial amniotic fluid index measurements, the women were instructed to rest in the left lateral position, and the measurements were repeated at 15, 30, 45, 60, 75, and 90 minutes. The amniotic fluid index increased at each sequential interval. Although each amniotic fluid index value was higher than the preceding one, only the 15- and 30-minute values were significantly higher than the preceding measurements (P < .001; P < .01, respectively). At the beginning of maternal rest in the left lateral position, 15 minutes of rest was sufficient to create significant changes (P < .001). However, after 30 minutes of rest, an additional 45 minutes was needed to create a significant amniotic fluid index increase (P < .01). The curve describing the amniotic fluid index increases caused by maternal rest resembled a saturation curve, and the maximum increase in the amniotic fluid volume was projected to be achieved approximately at the end of the second hour of the rest period. The correlation between the duration of maternal rest and amniotic fluid volume changes is not linear. However, maternal rest in the left lateral decubitus position significantly increases the amniotic fluid volume, particularly in the first 30 minutes (maximum increase in the first 15 minutes).


Resolving a Prickly Situation: Involving Stakeholders in Invasive Cactus Management in South Africa.
The regulation and management of alien species can be contentious, particularly when the stakeholders who benefit from alien species are different from those who suffer the costs. We propose a consultative process involving relevant stakeholders in invasive species management decisions. The process involves (1) the identification of relevant stakeholders, (2) assessing their perceptions, (3) enhancing interaction between stakeholders, (4) assessing changes in stakeholders' perceptions following interactions with other stakeholders, and (5) developing management recommendations in collaboration with stakeholders. We demonstrate the application of the process using the family Cactaceae ('cacti') in South Africa. Many species of cacti have been introduced to the country over the past two centuries, mostly for horticulture, food and fodder, and hundreds of other species have been introduced in the past few decades (or are likely to be introduced soon) for horticulture. Using the proposed process enabled the negotiation and participation of all stakeholders in decision making and helped minimize contentious situations by clarifying stakeholder's beliefs and exploring consensus solutions. Consequently, management objectives were broadly supported by all stakeholders. These results will be included in a national cactus management strategy for South Africa.


An algorithm for identifiable parameters and parameter bounds for a class of cascaded mammillary models.
A complex structural identifiability problem for a class of unidirectionally interconnected n-compartment linear mammillary models with multiple inputs is discussed. This class is particularly useful in the study of drug/metabolite kinetics and other interconversion kinetic processes. An explicit algorithm is developed for this model class that provides identifiable parameter combinations, parameter bounds, steady-state pool sizes, and production rates, with input forcing and output measurements in central compartments. A six-compartment model of the combined dynamics of the prohormone thyroxine (T4) and hormone triiodothyronine (T3) illustrates how physiological parameter values or their smallest ranges, such as tissue T4 to T3 conversion rates and separate T4 and T3 production rates, can be determined from stimulus-response measurements in plasma alone.


The effect of live feeds bathed with the red seaweed Asparagopsis armata on the survival, growth and physiology status of Sparus aurata larvae.
Larval rearing is affected by a wide range of microorganisms that thrive in larviculture systems. Some seaweed species have metabolites capable of reducing the bacterial load. However, no studies have yet tested whether including seaweed metabolites on larval rearing systems has any effects on the larvae development. This work assessed the development of Sparus aurata larvae fed preys treated with an Asparagopsis armata product. Live prey, Brachionus spp. and Artemia sp., were immersed in a solution containing 0.5% of a commercial extract of A. armata (Ysaline 100, YSA) for 30 min, before being fed to seabream larvae (n = 4 each). In the control, the live feed was immersed in clear water. Larval parameters such as growth, survival, digestive capacity (structural-histology and functional-enzymatic activity), stress level (cortisol content), non-specific immune response (lysozyme activity), anti-bacterial activity (disc-diffusion assay) and microbiota quantification (fish larvae gut and rearing water) were monitored. Fish larvae digestive capacity, stress level and non-specific immune response were not affected by the use of YSA. The number of Vibrionaceae was significantly reduced both in water and larval gut when using YSA. Growth was enhanced for YSA treatment, but higher mortality was also observed, especially until 10 days after hatching (DAH). The mortality peak observed at 8 DAH for both treatments, but higher for YSA, indicates larval higher susceptibility at this development stage, suggesting that lower concentrations of YSA should be used until 10 DAH. The application of YSA after 10 DAH onwards promotes a safer rearing environment.


Staphylococcal septicemia and adult respiratory distress syndrome in pregnancy treated with extracorporeal carbon dioxide removal.
Septicemia in pregnancy may take an especially fulminant course. Adult respiratory distress syndrome (RDS) and disseminated intravascular coagulation (DIC) are associated life-threatening complications. Treatment consists of appropriate antibiotic coverage and supportive measures. A previously healthy 21-year-old woman presented at 26 weeks' gestation with staphylococcal sepsis of undetermined origin. Her course was complicated by the rapid onset of adult RDS, DIC, and multi-organ-system failure, resulting in preterm delivery. Despite maximal ventilatory support, her pulmonary status continued to deteriorate. She was treated ultimately with extracorporeal carbon dioxide removal and survived without serious sequelae. Extracorporeal carbon dioxide removal may improve survival in gravidas with adult RDS by decreasing the required airway pressures for ventilation, thus permitting pulmonary recovery.


Suppression of remyelination in the CNS by X-irradiation.
Rat and cat spinal cords were exposed to 2000, 3000 or 4000 rads of x-irradiation prior to producing an area of primary demyelination in the dorsal columns by the injection of lysolecithin. In animals irradiated with 4000 rads no remyelination by either Schwann cells or oligodendrocytes occurred. With 2000 rads both types of remyelination occurred, but when compared to unirradiated controls, central remyelination was less extensive, while Schwann cells remyelinated a greater percentage of axons. With 3000 rads the results were variable, some animals responded similarly to those in the 4000 rad group, whereas others responded as the 2000 rad animals. Oligodendrocytes were found among the persistently demyelinated axons in the 4000 rad animals and their processes were associated with, but only rarely formed a myelin sheath round, the demyelinated axons. It was concluded that irradiation damage to local cells was responsible for the inhibition of remyelination but it could not be determined if this was due to its effect on the oligodendrocytes alone. The origin of the oligodendrocytes found among the demyelinated axons is discussed in this context.


Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis.
We have examined the role of caspase-mediated cleavage of the Ste20-like kinases, mammalian sterile 20-like 1 and 2 (Mst1/Mst2), in the mechanism of human eosinophil and neutrophil apoptosis. Initial measurements of kinase activity, using myelin basic protein (MBP) as a substrate in "in-gel" renaturation assays, showed that constitutive eosinophil and neutrophil apoptosis were associated temporally with the activation of a 36-kd MBP kinase (p36 MBPK) and a 34-kd MBP kinase (p34 MBPK), respectively. A constitutively active 63-kd MBP kinase (p63 MBPK) was also detected in freshly prepared eosinophils but not neutrophils, whose activity was transiently augmented during spontaneous apoptosis. Immunoblotting studies demonstrated the expression of Mst1 and Mst2 in eosinophils but not neutrophils whereas immunoprecipitation studies identified the p63 MBPK activity as being Mst1 and Mst2 and showed that the p36 MBPK activity represented the N-terminal catalytic fragment of Mst1. A role for the p36 MBPK in eosinophil cell death was supported by studies showing increased activation upon exposure to the proapoptotic Fas/CD95-activating antibody, CH-11, and attenuation in the presence of the survival-promoting cytokine, interleukin-5. Furthermore, spontaneous and Fas-induced activation of p36 MBPK was inhibited by catalase and the general caspase inhibitor, z-Asp-CH(2)-DCB, at concentrations that suppressed eosinophil apoptosis. These studies therefore implicate a role for caspase- and H(2)O(2)-mediated cleavage of the Mst1 and the subsequent release of the 36-kd catalytic fragment in the mechanism of eosinophil apoptosis. In contrast, neutrophil apoptosis occurs independently of Mst1 and Mst2 but instead is correlated with the activation of an as-yet-unidentified 34-kd MBPK.


Titanocene(II)-promoted carbonyl allenation utilizing 1,1-dichloroalk-1-enes.
Treatment of 1,1-dichloroalk-1-enes with Cp2Ti[P(OEt)3]2 produced organotitanium species, which afford allenes on treatment with aldehydes and ketones.


WINTER FIXATION OF NITROGEN IN SCOTCH BROOM (CYTISUS SCOPARIUS L.).
The retention of green lateral branches by Scotch Broom allows nitrogen fixation to continue during mild winters. Tolerance of low soil temperatures is suggested to be a major factor contributing to the occurrence of winter nitrogen fixation.


Molecular identification of differential expression genes associated with sex pheromone biosynthesis in Spodoptera exigua.
Species-specific sex pheromone is biosynthesized and released in most female moths as a chemical cue in mating communication. However, information on genes involved in this pathway is limited. The beet armyworm, Spodoptera exigua, is a cosmopolitan agricultural pest that causes severe economic losses to many crops. In China, the female sex pheromones in sex pheromone glands (PGs) of S. exigua have been measured which comprises (Z,E)-9,12-tetradecadienyl acetate, (Z)-9-tetradecen-l-ol, (Z)-9-tetradecenyl acetate, and (Z,E)-9,12-tetradecadien-1-ol in a ratio of 47:18:18:17. Fifty-nine putative genes related to sex pheromone biosynthesis were identified in the present study by sequencing and analyzing the sex pheromone gland (PG) transcriptome of S. exigua. Expression profiles revealed that two desaturase (SexiDes5 and SexiDes11) and three fatty acyl reductase (SexiFAR2, 3, and 9) genes had PG-specific expression, and phylogenetic analysis demonstrated that they clustered with genes known to be involved in pheromone synthesis in other moth species. Our results provide crucial background information that could facilitate the elucidation of sex pheromone biosynthesis pathway of S. exigua as well as other Spodoptera species and help identify potential targets for disrupting sexual communication in S. exigua for developing novel environment-friendly pesticides.


Microwave-assisted CVD-like synthesis of dispersed monolayer/few-layer N-doped graphene encapsulated metal nanocrystals for efficient electrocatalytic oxygen evolution.
Herein a novel and general microwave-assisted chemical vapor deposition (CVD)-like synthetic strategy was developed to realize the ultrafast synthesis of a series of well-dispersed monolayer/few-layer N-doped graphene shell encapsulated metal nanocrystals (M@NC) by using a metal-organic framework (MOF) on graphene as precursors for the first time. Unlike traditional programmed heat treatment, this microwave-assisted method decomposed the MOF into separated metal and carbon- and nitrogen-containing gases rather than aggregated metal and carbon composites during the initial thermal transformation stages. This change ensured the effective control of the subsequent formation process of carbon on the surface of metal and led to the formation of well-dispersed M@NC with monolayer/few-layer NC. Moreover, the graphene substrate promoted the full exposure of all active monolayer/few-layer NC, and thus the obtained FeNi@NC/graphene displays the best electrocatalytic properties for the oxygen evolution reaction of all of the previously reported M@NC based catalysts, including the lowest overpotential (261 mV) at 10 mA cm-2 in alkaline electrolyte (1 M KOH), the smallest Tafel slope (40 mV dec-1) and excellent durability for at least 120 h.


Mucosal maxillary cysts: long-term subjective outcomes after surgical treatment.
Mucosal maxillary cysts (MMCs) are usually asymptomatic and are often diagnosed as an incidental finding. The aim of this study is to assess clinical significance of MMCs and the long-term effect of surgical treatment on the symptoms initially addressed to MMCs. The study included a retrospective analysis of 64 patients who had undergone surgery for MMC using a questionnaire focused mainly on the effect surgery had on symptoms. Mean time of follow-up was 79 months. Patients were also divided and compared according to the presence of rhinitic symptoms. Twenty-six patients (63.4%) reported complete disappearance of symptoms, 8 (19.5%) reported improvement, 4 (9.7%) reported no change in symptoms following surgery and 3 (7.3%) reported that symptoms reappeared. Significantly (p = 0.0365) better results were achieved in patients without preexisting rhinitic symptoms. This study supports the opinion that in some cases, MMCs are involved in the development of sinonasal symptoms. Surgical treatment leads, in most patients, to disappearance or improvement of symptoms and the effect is better in patients without rhinitic symptoms.


Comparison of initial distribution volume of glucose and intrathoracic blood volume during hemodynamically unstable States early after esophagectomy.
We have reported that initial distribution volume of glucose (IDVG) measures the central extracellular fluid volume in the presence of fluid gain or loss without apparent modification of glucose metabolism. We hypothesized that IDVG has a close relationship with intrathoracic blood volume (ITBV). We examined whether IDVG can correlate with ITBV during hemodynamically unstable states early after esophagectomy. Prospective clinical study. General ICU. Twelve consecutive hypotensive patients who required volume loading during the first 10 postoperative hours after admission to the ICU. Indexed ITBV (ITBVI) and cardiac index (CI) were measured by single transpulmonary thermodilution technique using 10 mL of cold saline solution. Indexed IDVG (IDVGI) was then determined by the administration of 5 g of glucose and calculated by applying a one-compartment model. Three sets of measurements were performed: immediately after admission to the ICU, during hypotension, and after subsequent volume loading. When hypotension developed, stroke volume index (SVI), central venous pressure, and ITBVI were decreased but IDVGI and CI were not. All these variables were increased after volume loading. IDVGI was correlated only slightly with either ITBVI (r2 = 0.23) or SVI (r2 = 0.38) but moderately with CI (r2 = 0.61). Results does not support that IDVGI can be equivalently used as an alternative measure of ITBVI or SVI, but IDVG may be clinically relevant as a measure of the fluid volume affecting CI even during hemodynamically unstable states after esophagectomy.


Inflammaging and body composition: New insights in diabetic and hypertensive elderly men.
Age-related changes in the body's physiological responses play a critical role in systemic arterial hypertension (SAH) and type 2 Diabetes mellitus (T2DM). SAH and T2DM have clinically silent low-grade inflammation as a common risk factor. This inflammation has a relevant element, the excess of fatty tissue. In this scenario, little is known about how inflammatory markers interact with each other. Therefore, this work evaluated the interplay among anthropometric, biochemical, and inflammatory markers in the elderly with SAH and T2DM. Men aged 60-80 years old with SAH and T2DM were classified by body mass index (BMI) as eutrophic elderly (EE, 24 individuals) or overweight elderly (OE, 25 individuals). Body composition analysis was performed using bioimpedance. Blood samples were collected to perform inflammatory and biochemical evaluations. The cytokines IL-17A, IL-1β, IFN-y, TNF-α, and IL-10, were evaluated by ELISA. Triglycerides, total and fractions of cholesterol, and glucose were measured by spectrophotometry. Overweight elderly men had a higher glycemic index and an increase in most anthropometric markers, as well as higher means for all pro-inflammatory cytokines analyzed (IL-17A, IL-1β, IFN-y, and TNF-α) in comparison to their eutrophic elderly counterparts. However, there was a decrease in IL-10 anti-inflammatory cytokine and IL-10/IL-17A ratio compared to their eutrophic elderly counterparts. Although overweight elderly men have worsening inflammatory parameters, the magnitude of their correlations with anthropometric and biochemical parameters becomes less evident. The Bayesian networks highlight that in the eutrophic elderly, IL-17A and TNF-α are the cytokines most associated with interactions, and most of these interactions occur with biochemical parameters. It is worth highlighting the role of IFN-y in overweight elderly men. This cytokine influences IL-10 and TNF-α production, contributing to the inflammatory profile exacerbated in this group.


Characterization of a novel cDNA encoding a short venom peptide derived from venom gland of scorpion Buthus martensii Karsch: trans-splicing may play an important role in the diversification of scorpion venom peptides.
A novel cDNA clone (named BmKT-u) which is a hybrid molecule of the 5'-terminal region of BmKT' cDNA and the 3'-terminal region of an undocumented cDNA (named BmKu), was isolated from a cDNA library made from the venom gland of scorpion Buthus martensii Karsch. BmKT-u codes for a 30 amino acid residue precursor peptide composed of a 20-residue signal sequence, and a putative 10-residue novel mature peptide. Northern blot hybridization showed BmKT-u cDNA is generated from a transcript. RT-PCR experiments excluded the possibility that BmKT-u cDNA is an artifact generated during reverse transcription. Genomic amplifications performed with three pairs of BmKT-u gene-specific primers showed the BmKT-u gene does not exist in the genome of the scorpion as a single transcriptional unit. Genomic cloning for BmKT' showed that the BmKT' gene contains an intron of 509 bp inserted into the region encoding the C-terminal region of the signal peptide. A sequence alignment comparison of the cDNA of BmKT-u with genomic BmKT' revealed that the junction site of the hybrid molecule is located at the 5'-splicing site of the intron. The data suggest that the BmKT-u transcript is a naturally occurring mature mRNA that is generated by trans-splicing. Trans-splicing may contribute to the diversity of venom peptides from venomous animals.


A clinical and pathologic study of chronic sinusitis: the role of the eosinophil.
Evidence exists that the eosinophil plays an important role in mediating injury to bronchial epithelium in chronic asthma. Here, the role of the eosinophil in chronic inflammatory disease of the paranasal sinuses was studied with tissue from patients who underwent surgery for chronic sinusitis. Paranasal tissue from patients with chronic asthma and/or allergic rhinitis was extensively infiltrated with eosinophils. Immunofluorescent studies demonstrated a striking association between the presence of extracellular deposition of major basic protein and damage to sinus mucosa. The histopathology of paranasal respiratory epithelium appeared similar to that described in bronchial asthma. These findings suggest that the eosinophil acts as an effector cell in chronic inflammatory disease of paranasal respiratory epithelium. Thus, sinus disease in patients with asthma may be due to the same mechanisms that cause damage to bronchial epithelium.


Facile Synthesis of Folic Acid-Modified Iron Oxide Nanoparticles for Targeted MR Imaging in Pulmonary Tumor Xenografts.
The purpose of this study was to develop folic acid (FA)-modified iron oxide (Fe3O4) nanoparticles (NPs) for targeted magnetic resonance imaging (MRI) of H460 lung carcinoma cells. Water-dispersible Fe3O4 NPs synthesized via a mild reduction method were conjugated with FA to generate FA-targeted Fe3O4 NPs. The specificity of FA-targeted Fe3O4 NPs to bind FA receptor was investigated in vitro by cellular uptake and cell MRI and in vivo by MRI of H460 tumors. The formed NPs displayed good biocompatibility and ultrahigh r 2 relaxivity (440.01/mM/s). The targeting effect of the NPs to H460 cells was confirmed by in vitro cellular uptake and cell MRI. H460 tumors showed a significant reduction in T2 signal intensity at 0.85 h, which then recovered and returned to control at 2.35 h. The results indicate that the prepared FA-targeted Fe3O4 NPs have potential to be used as T2 negative contrast agents in targeted MRI.


Blood-brain Barrier Permeable and Multi-stimuli Responsive Nanoplatform for Orthotopic Glioma Inhibition by Synergistic Enhanced Chemo-/Chemodynamic/Photothermal/Starvation Therapy.
Glioblastoma (GBM) is a common malignant tumor in brain, and the treatment is still a challenge owing to the high invasiveness and the existence of blood-brain barrier (BBB). Although temozolomide (TMZ) is the first line medication, its efficacy is not ideal, which is related to the defect of dose distribution and drug resistance. It is urgent to develop a novel BBB-permeable nanoagent with multiple therapeutic modalities for improving the treatment effect of GBM. In this work, we constructed an intelligent BBB-permeable nanoplatform (CTHG-Lf NPs) with hollow mesoporous copper sulfide nanoparticles (HM-CuS NPs) as temozolomide (TMZ) carrier and hyaluronic acid (HA) as gatekeeper, as well as further modification with glucose oxidase (GOx) and lactoferrin (Lf) for highly efficient synergistic therapy of orthotopic GBM. The modification of Lf endows CTHG-Lf NPs with good target and BBB-permeable ability. HA not only prevents the TMZ leakage during circulation, but also achieves responsive drug release at tumor site for effective chemotherapy (CT). GOx provides high hydrogen peroxide (H2O2) and gluconic acid for improving the treatment effect of chemodynamic therapy (CDT), and realizes the starvation therapy (ST) by consuming glucose. The good photothermal effect of CTHG-Lf NPs achieves the "mild" photothermal therapy (PTT), while enhancing the efficiency of Fenton-like reaction. The synergistic strategy with CT/CDT/PTT/ST can not only promote brain drug delivery, but also realize the combination of multiple mechanisms for effective tumor growth suppression in vivo.


The binding affinity of human pediatric respiratory syncytial virus Phosphoprotein's C-terminal tail to nucleocapsid can be improved by a rationally designed halogen-bonded system.
Human respiratory syncytial virus (hRSV) is a common contagious virus that causes infections of pediatric pneumonia and specifically impacts infants and small children. The hRSV phosphoprotein is a key component of the viral RNA polymerase, which can interact with nucleocapsid and other partners through its C-terminal tail (CTT) to promote the formation of viral transcriptase complex, where the Phe241 is a key anchor residue. Based on the crystal template-modeled complex structure of hRSV nucleocapsid with a peptidic segment derived from the phosphoprotein's CTT, we successfully introduced a rationally designed halogen-bonded system to the complex interface by substituting para (p)-position of the side-chain phenyl moiety of CTT Phe241 residue with a halogen atom X (X = F, Cl, Br or I). The halogen-bonded system consists of a halogen bond (X-bond) between nucleocapsid Ser131 residue and CTT Phe241 residue as well as a hydrogen bond (H-bond) between nucleocapsid Ser131 residue and nucleocapsid Glu128 residue; the X-bond and H-bond share a common hydroxyl group of nucleocapsid Ser131 residue. High-level theoretical calculations suggested that bromine Br is the best choice that can render strong potency for the X-bond and can confer high affinity to the nucleocapsid-CTT binding. Affinity analysis revealed that the p-brominated CTT ([p]bCTT) exhibited 6.3-fold affinity improvement relative to its nonhalogenated counterpart. In contrast, the Br-substitutions at ortho (o)- and meta (m)-positions, which resulted in two negative controls of o-brominated [o]bCTT and m-brominated [m]bCTT, respectively, were unable to form effective X-bond with nucleocapsid according to theoretical investigation and did not improve the binding affinity essentially relative to native CTT.


Experimental study of reflectance spectrophotometric analysis of the dog's dural sac--in the open decompressed state and after the application of external dural pressure.
Haemoperfusion and oxygen saturation were studied by tissue reflection spectra on the dural sac of dogs, Experimentally, decompression laminectomy and external pressure on the dural sac were carried out. Haemoperfusion and oxygen saturation were investigated in the open state, and after an external pressure was applied. After the application of external pressure, paraplegia occurred. The tissue Spectrum Analyser 'TS-200' (Sumitomo Electric Industries Co. Ltd, Japan) was used for the measurement of haemoperfusion and oxygen saturation. With this apparatus, an optical fibre probe is applied to irradiate tissue with white light, and the absorption spectrum of the reflected light from tissue is analysed. It has been confirmed that oxygen saturation was not changed in either state, however, haemoperfusion was decreased when external pressure was applied.


Paromomycin: A potential dual targeted drug effectively inhibits both spike (S1) and main protease of COVID-19.
With the increasing number of people suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dire need to look for effective remedies against this pandemic. Drug repurposing seems to be the solution for the current situation. In a quest to find a potential drug against this virus, 15 antimalarial drugs (including chloroquine) and 2413 US Food and Drug Administration-approved drugs were investigated for activity against both the protease and spike proteins of SARS-CoV-2 using an in silico approach. Molecular docking analysis followed by molecular dynamics simulation was performed to estimate the binding and stability of the complexes. This study identified a single drug - paromomycin - with activity against two targets of SARS-CoV-2, i.e., spike protein (S1) and protease domain. Paromomycin was found to have strong binding affinity for both targets of coronavirus. The results also showed that no antimalarial drug exhibited effective binding for either S1 or protease. This study found that paromomycin may be an effective dual targeting drug against coronavirus, as it binds not only to the protease domain of the virion, but also to the spike domain, with high stability. Furthermore, none of the antimalarial drugs showed strong binding affinity for either protease or the receptor binding domain (RBD).


Glucose phosphate isomerase deficiency with hereditary hemolytic anemia in a Spanish family: clinical and familial studies.
A new case of glucose phosphate isomerase deficiency associated with cogenital nonspherocytic hemolytic anemia is described in a 12-year-old girl of Spanish origin. The parents exhibited erythrocyte glucose phosphate isomerase activity between 50 and 60% of normal. The enzyme of the propositus had normal Michaelis-Menten constants both for F-6-P and G-6-P, but abnormal pH optimum and decreased heat stability at 48 degrees C. On starch-gel electrophoresis the father's enzyme was normal but the mother's showed a cathodic migrating band in addition to the normal one. The enzyme from the propositus exhibited only one band with cathodal mobility of 116% of the main band found in normal subjects. It is postulated that the propositus is double heterozygous for two abnormal alleles, and the mother contributes a mutant allele with abnormal electrophoretic mobility and thermolability at 48 degrees C whereas the father contributes an allele without enzymatic activity.


Acinetobacter radioresistens and Microbacterium paraoxydans endocarditis in patient with indwelling catheter and metastatic carcinoma.
Acinetobacter radioresistens is a rare cause of nosocomial infection and is believed to confer antibiotic resistance to aggressive bacterial species. We present the first reported case of polymicrobial endocarditis caused by A. radioresistens and Microbacterium paraoxydans co-infection, a case of a woman in her late 60s with bacteraemia and ultimate finding of endometrial carcinoma. Bacteraemia with either agent in a previously healthy patient should prompt providers to search for underlying malignancy or immunological problem.We support the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for identifying these organisms in cultures, as well as the development of faster isolation techniques through PCR. Furthermore, we advocate for providers to order early antibiotic susceptibility testing, since our patient's Microbacterium sp was not susceptible to meropenem unlike most Microbacterium reported in literature.


Association Between the A118G Polymorphism of the OPRM1 Gene and Suicidal Depression in a Large Cohort of Outpatients with Depression.
Growing evidences suggest that depression with suicidal ideation (SI) could be a specific phenotype with its own characteristics. Moreover, opioid system deregulation might be implicated in suicidal behaviour (SB). The aim of this study was to determine whether the A118G polymorphism (rs1799971) in ORPM1 (the gene encoding opioid receptor mu 1) is associated with suicidal depression (ie, moderate to severe depression with SI) in a large cohort of outpatients with depression. GENESE is a large, prospective, naturalistic cohort of French adult outpatients with depression (DSM-IV criteria), treated and followed for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale (HADS), and SI with the suicidal item of the Montgomery-Åsberg Depression Rating Scale (MADRS-SI). From this cohort, patients with moderate or severe depression (HADS-D subscale score >11) were selected and classified as without SI (MADRS-SI < 2), or with SI (MADRS-SI ≥ 2). The AA/AG genotypes of the A118G polymorphism were significantly associated with suicidal depression in the non-adjusted (OR = 2.32, 95% CI = [1.28; 4.18]; p-value = 0.005) and in the adjusted models (OR = 2.54, 95% CI = [1.35; 4.78]; p-value = 0.004). Outpatients with depression harbouring the A allele are at higher risk of SI (and possibly SB) than those carrying the G allele. More studies are needed to better understand the link between this polymorphism and SB.


[Identification of oligopeptides mimicking the virus attachment protein of hantaan virus].
To identify and characterize the epitope associated with the virus attachment protein (VAP) of hantaan virus. The monoclonal antibody 3G1 was used as the ligand to biospan from a phage-displayed 12-amino acid peptide library, then the positive phage clones were chosen and sequenced. The amino acid sequences of them were compared with that of hantaan virus G2 in homology. The characteristics of positive phage were studied by IFA and ELISA. A decapeptide combining to cell membrane was observed under laser scanning confocal microscope (LSCM). The conservative motif PX(1-2) HX(0-2) H displaying on positive clones shared homologous amino acid sequence with G2 96YPWHTAKCHY105. G2 96YPWHTAKCHY105 might play some roles in virus binding to host cell, and might be a possible key epitope of hantaan virus VAP.


Auditory adaptation in voice perception.
Perceptual aftereffects following adaptation to simple stimulus attributes (e.g., motion, color) have been studied for hundreds of years. A striking recent discovery was that adaptation also elicits contrastive aftereffects in visual perception of complex stimuli and faces [1-6]. Here, we show for the first time that adaptation to nonlinguistic information in voices elicits systematic auditory aftereffects. Prior adaptation to male voices causes a voice to be perceived as more female (and vice versa), and these auditory aftereffects were measurable even minutes after adaptation. By contrast, crossmodal adaptation effects were absent, both when male or female first names and when silently articulating male or female faces were used as adaptors. When sinusoidal tones (with frequencies matched to male and female voice fundamental frequencies) were used as adaptors, no aftereffects on voice perception were observed. This excludes explanations for the voice aftereffect in terms of both pitch adaptation and postperceptual adaptation to gender concepts and suggests that contrastive voice-coding mechanisms may routinely influence voice perception. The role of adaptation in calibrating properties of high-level voice representations indicates that adaptation is not confined to vision but is a ubiquitous mechanism in the perception of nonlinguistic social information from both faces and voices.


Effects of caudal sufentanil supplemented with levobupivacaine on blocking spermatic cord traction response in pediatric orchidopexy.
Caudal block is one of the most commonly used anesthetic techniques in subumbilical and genitourinary procedures. However, traditional administration of caudal levobupivacaine was inadequate on blocking peritoneal response during spermatic cord traction. The aim of this study was to evaluate whether the addition of caudal sufentanil to levobupivacaine provided better analgesia for children undergoing orchidopexy. Sixty-two patients, scheduled for right orchidopexy, received caudal block after induction. Group LS (n = 31) received levobupivacaine 0.25% 1 ml/kg plus sufentanil 0.5 μg/kg, and group L (n = 31) received levobupivacaine 0.25% 1 ml/kg only. HR or MAP fluctuation >20% or entropy increase >15% during spermatic cord traction was defined as inadequate anesthesia and was treated with increasing sevoflurane concentration. The number of children who needed sevoflurane rescue was counted, and postoperative side effects and quality of sleep were also recorded. There were no statistically significant differences between the two groups in age, weight, and duration of surgery. Two (6.45%) children in group LS required inspired sevoflurane rescue to block hemodynamic fluctuation during spermatic cord traction, as compared with 12 (38.71%) patients in group L (P < 0.001). At the time of exerting spermatic cord traction, the median HR was, respectively, 134 and 145 (P < 0.001); the corresponding response entropy (RE) and state entropy (SE) was 65 and 54, respectively, in group LS versus 76 and 65 in group L (P < 0.001). In pediatric orchidopexy, the addition of sufentanil to levobupivacaine for caudal blockade offers clinical benefit over levobupivacaine alone in blocking the spermatic cord traction response.


Blood-derived macrophages prone to accumulate lysosomal lipids trigger oxLDL-dependent murine hepatic inflammation.
Despite the consistent rise of non-alcoholic steatohepatitis (NASH) worldwide, the mechanisms that govern the inflammatory aspect of this disease remain unknown. Previous research showed an association between hepatic inflammation and lysosomal lipid accumulation in blood-derived hepatic macrophages. Additionally, in vitro findings indicated that lipids, specifically derived from the oxidized low-density lipoprotein (oxLDL) particle, are resistant to removal from lysosomes. On this basis, we investigated whether lysosomal lipid accumulation in blood-derived hepatic macrophages is causally linked to hepatic inflammation and assessed to what extent increasing anti-oxLDL IgM autoantibodies can affect this mechanism. By creating a proof-of-concept mouse model, we demonstrate a causal role for lysosomal lipids in blood-derived hepatic macrophages in mediating hepatic inflammation and initiation of fibrosis. Furthermore, our findings show that increasing anti-oxLDL IgM autoantibody levels reduces inflammation. Hence, therapies aimed at improving lipid-induced lysosomal dysfunction and blocking oxLDL-formation deserve further investigation in the context of NASH.


Effect of maternal malnutrition on matrix cell proliferation in the cerebrum of mouse embryo: an autoradiographic study.
Thirty pregnant mice were undernourished by providing low protein diets (PM) or providing approximately one-third their normal diets (PCM) for 9 days from the 8th to the 16th day of gestation. Another 15 pregnant mice, which were fed a normal diet, served as the control. On the 16th day of gestation, all animals were injected with a single does of [3H]thymidine and were killed one by one at 1- or 2-hr intervals. Mean litter size was statistically insignificant between the control group and two malnourished groups. There was, however, a significant difference in mean body weight between the control group and two malnourished groups (P less than 0.005). The cerebral cortex at this stage of development consisted of three different layers, i.e., the cortical plate, the migratory zone, and the matrix layer. The width of the cortical plate of the malnourished embryos was significantly smaller (P less than 0.001). There was, however, no significant difference in width of the migratory zone between the control and the malnourished groups. The width of the matrix layer in PM was significantly smaller (P less than 0.001), but that of PCM showed no significant difference from the control (P greater than 0.1). Coronal section of the brains of the embryos were processed for autoradiography. Labeled cells were found almost exclusively at the matrix layer surrounding the lateral ventricels. Labeling index counted in the matrix layer after 1 or 2 hr of [3H]thymidine injection indicated that more than 30% of the cells in this layer were always synthesizing DNA in each group of embryos. The generation times of the matrix cell, precursor of the neurons, in the matrix layer were approximately 18.5 hr in the control and 21.5 hr and 21.8 hr in the malnourished embryos, thus indicating about 3 hr of prolongation in the latter. DNA synthetic time was about 6.5 hr in the control and 7.0 hr and 7.0 hr in the two malnourished groups. The postduplication time was about 2.5 hr in the control and 3.0 hr and 3.5 hr in the malnourished. The preduplication time was about 8.8 hr in the control and 10.6 hr and 10.3 hr in the malnourished.


Usefulness of procalcitonin clearance as a prognostic biomarker in septic shock. A prospective pilot study.
To evaluate procalcitonin clearance as a prognostic biomarker in septic shock. Prospective, observational pilot study. Intensive care unit. Patients admitted to the ICU due to septic shock and multiorgan dysfunction. Serum concentrations of procalcitonin were determined within 12h of onset of septic shock and multiorgan dysfunction (coinciding with admission to the ICU), and the following extractions were obtained after 24, 48 and 72h in patients who survived. Demographic data, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score, data on the primary focus of infection, and patient outcome (ICU mortality). Procalcitonin clearance was higher in survivors than in non-survivors, with significant differences at 24h (73.9 [56.4-83.8]% vs 22.7 [-331-58.4], p<0.05) and 48h (81.6 [71.6-91.3]% vs -7.29 [-108.2-82.3], p<0.05). The area under the ROC curve was 0.74 (95%CI, 0.54-0.95, p<0.05) for procalcitonin clearance at 24h, and 0.86 (95%CI, 0.69-1.0, p<0.05) at 48h. ICU mortality was associated to sustained high procalcitonin levels, suggesting that procalcitonin clearance at 48h may be a valuable prognostic biomarker.


Three challenges described for identifying participants with missing data in trials reports, and potential solutions suggested to systematic reviewers.
To categorize the challenges in determining the extent of missing participant data in randomized trials and suggest potential solutions for systematic review authors. During the process of updating a series of Cochrane systematic reviews on the topic of anticoagulation in patients with cancer, we identified challenges and used an iterative approach to improve, and a consensus process to agree on the challenges identified, and to suggest potential ways of dealing with them. The five systematic reviews included 58 trials and 75 meta-analyses for patient-important dichotomous outcomes with 27,037 randomized participants. We identified three categories of challenges: (1) Although systematic reviewers require information about missing data to be reported by outcome, trialists typically report the information by participant; (2) It is not always clear whether the trialists followed up participants in certain categories (e.g., noncompliers), that is, whether some categories of participants did or did not have missing data; (3) It is not always clear how the trialists dealt with missing data in their analysis (e.g., exclusion from the denominator vs. assumptions made for the numerator). We discuss potential solutions for each one of these challenges and suggest further research work. Current reporting of missing data is often not explicit and transparent, and although our potential solutions to problems of suboptimal reporting may be helpful, reliable and valid characterization of the extent and nature of missing data remains elusive. Reporting of missing data in trials needs further improvement.


Predictors of interhospital transfer delays in acute surgical patient deaths in Australia: a retrospective study.
Interhospital transfers in Australia facilitate access to acute surgical services, however transfer delays can occur. The aims of this study were to examine Australian mortality audit data on acute surgical patients who were transferred after presenting with a surgical emergency, and to identify modifiable predictors of transfer delay. Surgical admissions between 1 January 2001 and 18 August 2020 were retrospectively extracted from the Australian and New Zealand Audit of Surgical Mortality database. Relevant factors and themes of interest were collated. Results were presented as odds ratios (OR) and 95% confidence intervals (CI), with statistical significance defined as P <0.05. After exclusion, a final 8270 cases were analysed. Non-modifiable predictors identified were female gender (OR 1.34, 95% CI 1.05-1.70, P = 0.0184), comorbidities (OR 1.50, 95% CI 1.40-161, P <0.0001) and major non-trauma non-vascular specialty (OR 1.54 to 7.77, depending on specialty, P < 0.05). Modifiable predictors were inadequate clinical assessment (OR 49.48, 95% CI 32.91-74.38, P <0.0001), poor communication (OR 6.62, 95% CI 3.70-11.85, P <0.0001) and multiple transfers (OR 6.30, OR 95% 4.31-9.21, P <0.0001). Age, lack of bed and after-hours transfer did not predict transfer delays. Metropolitan transfers was protective against transfer delays (OR 0.64, 95% CI 0.47-0.86, P = 0.0035). In the view of the receiving surgeon or assessor, all transfer delays potentially contributed to patient deaths, and may have been preventable. Strategies directed at modifiable factors could minimize delays. Increased surgical services in non-metropolitan regions could reduce need for transfer. Prospective data is required to examine if the same predictors are observed in surgical patients who survive.


[A case of metachronous carcinoma of the colon diagnosed and radical operated with restorative anastomosis after more than 5 years from the first left hemicolectomy].
The authors described their observation about the female patient with an advanced carcinoma (T4) of the descendent colon where left hemicolectomy was done in the beginning of 1998. The patient is operated again after more than 5 years because of the cancer in the site of the anastomosis. Radical reresection with restorative anasomosis is performed and for this reason the colon is putting via mesenteric radix. The case is analyzed and there are suggestion about is this a local recurrence or "de novo" carcinoma It is important to follow up the patients during lifetime for early uncovering of local recurrence. Endocoloscopy and scener are preferable for this aim.


A patient with HIV infection presenting with diffuse membranous glomerulonephritis in a country with a low HIV prevalence--remarkable remission with therapy.
The most common manifestation of HIV in the kidney is HIV-associated nephropathy (HIVAN). In this report, we describe the first documented case of membranous glomerulonephritis in an HIV-positive individual in Turkey, the country with the lowest HIV prevalence in the region. The case occurred in an HIV-positive, hepatitis C (HCV)-negative, and hepatitis B (HBV)-negative Caucasian male, who presented with nephrotic-range proteinuria. The patient had a favorable response to HAART and an angiotensin-receptor blocker.


Synthesis of 6-O-methotrexylhyaluronan as a drug delivery system.
Selective halogenation of hyaluronan and partial halogen substitution by methotrexate led to 6-chloro-6-deoxy-6-O-methotrexylhyaluronan, a potential antitumor drug. The remaining halogen could be further substituted by a second organic carboxylate, leading to mixed esters. 6-O-Acetyl-6-O-methotrexylhyaluronan and 6-O-butyryl-6-O-methotrexylhyaluronan were thus synthesized and characterized by NMR spectroscopy.


Activation cross-sections of deuteron induced reaction of natural Ni up to 40 MeV.
Production cross-sections of (nat)Ni(d,x)(56,57)Ni, (55,56,57,58)Co, (52,54)Mn, and (51)Cr nuclear reactions were measured up to 40 MeV by using the stacked foil technique. The results were compared with the literature values, TALYS 1.4 and TENDL-2012. Spline fits were made on the selected data, from which physical yields were calculated and compared with the literature and our directly measured thick target yield values. (nat)Ni(d,x)(56,57,58)Co reactions were analyzed for beam monitoring and thin layer activation (TLA). Rate of production of (55)Co was compared between proton and deuteron induced reactions.


Design and construction of an innovative brain phantom prototype for MRI.
The purpose of this project was to construct a physical brain phantom for MRI, mimicking structure and T1 relaxation properties of white matter (WM) and gray matter (GM). The phantom design comprised 2 compartments, 1 resembling the WM and 1 resembling the GM. Their T1 relaxation times, as assessed using an inversion recovery turbo spin echo sequence, were reproduced using an agar gel doped with contrast agent (CA) and their folding patterns were simulated through a molding-casting procedure using 3D-printed casts and flexible silicone molds. Three versions of the assembling procedure were adopted to build: Phantom1 without any separation; Phantom2 with a varnish layer; and Phantom3 with a thin wax layer between the compartments. Phantom1 was characterized by an immediate diffusion of CA between the 2 compartments. Phantom2 and Phantom3, instead, showed relaxation times and shape comparable with the target ones identified in a healthy control subject (WM: 754 ± 40 ms; GM: 1277 ± 96 ms). Moreover, both compartments revealed intact gyri and sulci. However, the diffusion of CA made Phantom2 stable only for a short period of time. Phantom3 showed stability within a time window of several days but the wax layer between the WM and GM was visible in the MRI. Structural and intensity properties of the constructed phantoms are useful in evaluating and validating steps from image acquisition to image processing. Moreover, the described constructing procedure and its modular design make it adjustable to a variety of applications.


How does the polyhexamethylene guanidine interact with waste activated sludge and affect the metabolic functions in anaerobic fermentation for volatile fatty acids production.
Antibacterial agents are frequently used to ensure public hygiene. Most of the massively consumed chemicals are discarded and accumulated in waste activated sludge (WAS), which might influence the subsequent anaerobic fermentation process for WAS treatment. This study mainly investigated the impacts of polyhexamethylene guanidine (PHMG, considered as a safe and efficient broad-spectrum antibacterial agent) on the volatile fatty acids (VFAs) production derived from WAS anaerobic fermentation and disclosed the key mechanisms. Results demonstrated that low level of PHMG evidently increased the VFAs accumulation as well as the acetic acid proportion, while the excessive dose posed evident negative effects. Further analysis found that appropriate PHMG synchronously stimulated the solubilization/hydrolysis and acidification processes but inhibited methanogenesis. Mechanistic exploration revealed that PHMG firstly absorbed on WAS due to electric attraction but then interacted with WAS to promote extracellular polymeric substance (EPS) disintegration and organics release (especially proteinaceous matter). Moreover, PHMG affected the microbial community structure and metabolic functions. The low level of PHMG evidently enriched functional VFAs producers (i.e., Desulfobulbus, Macellibacteroides and Sporanaerobacter) and upregulated the critical genes expression responsible for substrates metabolism (particularly the proteins) and VFAs biosynthesis (i.e., aldehyde dehydrogenase (NAD+) (K00128) and molybdopterin oxidoreductase (K00184)). This study provides an in-depth understanding of emerging pollutant impacts on WAS fermentation and provides insightful guidance on WAS disposal.


N5-Scaling Excited-State-Specific Perturbation Theory.
We show that by working in a basis similar to that of the natural transition orbitals and using a modified zeroth-order Hamiltonian, the cost of a recently introduced perturbative correction to excited-state mean field theory can be reduced from seventh to fifth order in the system size. The (occupied)2(virtual)3 asymptotic scaling matches that of ground-state second-order Møller-Plesset theory but with a significantly higher prefactor because the bottleneck is iterative: it appears in the Krylov-subspace-based solution of the linear equation that yields the first-order wave function. Here, we discuss the details of the modified zeroth-order Hamiltonian we use to reduce the cost and the automatic code generation process we used to derive and verify the cost scaling of the different terms. Overall, we find that our modifications have little impact on the method's accuracy, which remains competitive with singles and doubles equation-of-motion coupled cluster.


Role of cholangitis in predicting survival in patients with carcinoma of the ampulla of vater.
There have been strong suggestions that acute inflammation promotes tumour growth, and has a tendency for increased invasiveness, leading to poor survival after surgery. When cholangitis coexists with ampulla of vater cancer, the patient's prognosis may be influenced by the acute inflammatory status of the bile duct. We evaluated the relationship between the severity of acute cholangitis, preoperative CRP levels and survival. We retrospectively analysed 154 patients who underwent surgical resection for AOV cancer between January 2003 and November 2018. Cholangitis was graded according to Tokyo Guidelines 2018. Patients were categorised into two groups based on their CRP levels: CRP > 1 mg/L and CRP ≤ 1 mg/L. Relationship of cholangitis grade and CRP >1 mg/L with survival was assessed. The mean age of the patients was 65.8 years. Preoperative cholangitis was present in 40 (25.9%) patients, of which 28 (18.2%) had mild cholangitis, 11 (7.1%) had moderate cholangitis, and one (0.6%) had severe cholangitis. CRP was elevated preoperatively in 56 (36.4%) patients. The median follow-up period was 33.5 months. Severity of cholangitis significantly affected the overall survival (P < 0.001) and disease-free survival (P < 0.001). Patients with mild cholangitis had a median overall survival of 43 months compared to 14 months in those with moderate cholangitis. A preoperative CRP level of >1 mg/L was significantly associated with poor overall survival (P = 0.023) but not with disease-free survival (P = 0.128), although it was associated with a trend towards poorer survival. The survival rate of patients with CRP ≤1 mg/L was 77.4%, whereas that of patients with CRP >1 mg/L was 56.7%. In multivariable analysis, age >65 years (P = 0.015), cholangitis grade (P = 0.050), CRP > 1 mg/L (P = 0.045), venous invasion (P = 0.005), and perineural invasion (P = 0.034) were independent prognostic factors for overall survival while cholangitis grade (P = 0.049) and perineural invasion (P = 0.004) were independent prognostic factors for disease-free survival. Acute inflammation when associated with cancer can have a negative effect on patient's survival. Patients with higher grades of cholangitis should be adequately treated to improve the inflammatory status.


Ectopic Cushing's syndrome secondary to pulmonary carcinoid tumor.
Adrenocorticotropic hormone (ACTH) overproduction within the pituitary gland or ectopically leads to hypercortisolism. In this study a case of Cushing's syndrome caused by an ectopic ACTH-secreting carcinoid tumor in lung is discussed, as are the available diagnostic procedures. The patient was a 28-year-old woman with clinical features starting about 6 months previously. The results of her biochemical tests suggested ectopic Cushing's syndrome. Full-body computed tomography revealed a single nodule in the inferior lobe of the right lung. After removal of the nodule, the patient's symptoms subsided clinically, and laboratory tests confirmed remission of the hypercortisolism.


Studies on the biology, histology and cytogenetics of two sublines of a murine ovarian reticular cell sarcoma : Biology of M5 and R16 murine tumor.
Two sublines of the ovarian reticular cell sarcoma M5 in C57BL mice respond differently to cyclophosphamide and other alkylating agents. The subline R16, which is resistant to cyclophosphamide, was obtained by treating M5 mice repeatedly with this compound and subsequently transplanting the regrowing tumor for 16 passages. The R16 subline shows biological characteristics perfectly superimposable to those of the parent line and histologically resembles an undifferentiated mesenchymal neoplasia with numerous atypical nuclei and karyokinetic figures with large necrotic areas. The cytogenetic examination of the distribution in the chromosomal number of R16 indicates that this subline may be considered a clone of the parent line with a modal class of 35 chromosomes (34-37) versus a class of 34 (31-37) in the M5 tumor line. The presence of metacentric chromosomes characterizes the modal class of the two lines, 23 in the R16, and 25 in the M5 tumor lines.


Preliminaries on pollution risk factors related to mining and ore processing in the Cu-rich pollymetallic belt of Eastern Carpathians, Romania.
The present study focuses on the mineralogical and geochemical patterns of mining and ore-processing wastes from some occurrences in the Eastern Carpathians; its aim is to identify the main factors and processes that could lead to the pollution of the environment. In this respect, the following types of solid waste were investigated: efflorescent salts developed on the surface of rock blocks from a quarry, ore-processing waste from two tailings ponds, and salt crusts developed at the surface of a tailings pond. The potential risks emphasized by these preliminary investigations are the following: (1) the risk of wind-driven removal and transport of the waste from the surface of tailings ponds, given that fine grains prevail (up to 80%); (2) the risk of tailings removal through mechanical transport by water, during heavy rainfall; (3) the appearance of hydrated sulfates on the rock fragments from the mining waste, sulfates which are highly susceptible to the generation of acid mine drainage (pH<4); (4) the high amount of toxic elements (Pb, Cd, Cu, Zn, As, etc.) that acid mine drainage leachates contain; and (5) the development of a salt crust on the flat, horizontal surfaces of the waste deposit, due to this very shape. Statistical data regarding the amount of both major and minor elements in the tailings have revealed two statistical populations for nearly all the toxic metals. This suggests that, beyond the effect that the tailings have upon the environment through their mere presence in a given area, there are alleged additional factors and processes which intensify the pollution: the location of the waste deposit relative to the topography of the area; the shape of the waste deposit; the development of low areas on the surface of the deposit, areas which favor the appearance of salt crusts; and the mineralogy of efflorescent aggregates.


Effects of PD-1/PD-L1 signaling pathway on intestinal flora in patients with colorectal cancer.
To explore the effects of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway on the intestinal flora in patients with colorectal cancer (CRC). A total of 30 CRC patients treated with PD-1 monoclonal antibody therapy in the Oncology Department of our hospital from January 2018 to January 2019, and another 30 patients treated with routine non-immune therapy were enrolled. The feces specimens were collected for sequencing, the CRC model was established, and the 16S rRNA gene sequences in intestinal flora in feces specimens of mice were analyzed. The 3-month progression-free survival could not be predicted through the gene count or abundance of metagenomic species (MGS) in intestinal microflora of patients. The gene count or MGS abundance was related to the clinical progression-free response. There were abundant unclassified Escherichia coli, s_lactobacillus and s_unclassified parasutterella in patients treated with PD-1. The reflection curve of microbiota had an obvious difference in richness (Chao1), but had no apparent difference in diversity (Shannon). The PD-1/PD-L1 signaling pathway can regulate the metabolic activity of intestinal flora, thereby promoting immune surveillance of tumors.


Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.
Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood. We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy. Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells. The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.


Roxithromycin-loaded lipid nanoparticles for follicular targeting.
Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm.


Comparison of means.
This chapter describes statistical methods to test for differences between means or other measures of central tendency of 2 or more populations. Parametric tests and nonparametric tests are included. Methods for pairwise comparisons when more than 2 groups are being compared are included.


catena-Poly[[tetra-aqua-cadmium]-μ-5,5'-(1,4-phenyl-ene)di(tetra-zol-2-ido)-κ(2) N (2):N (2')].
In the title compound, [Cd(C8H4N8)(H2O)4] n , 5,5'-(1,4-phenyl-ene)di(tetra-zol-2-ide) (L) ligands bridge Cd(II) atoms into polymeric chains along [201]. The Cd(II) atom is situated on an inversion centre and is coordinated by two N atoms from two L ligands and by four water O atoms in a distorted octa-hedral geometry. In the L ligand, the benzene ring resides on an inversion centre and the tetra-zole rings are twisted from its plane by 22.3 (1)°. An extensive hydrogen-bonding network formed by classical O-H⋯N and O-H⋯O inter-actions consolidates the crystal packing, linking the poymeric chains into a three-dimensional structure.


The potential impact of prostate volume in the planning of optimal number of cores in the systematic transperineal prostate biopsy.
We compared the detection rates of different transperineal prostate biopsy protocols with the aim to optimize the number of cores to sample according to prostate volume. From October 2002 to October 2004 we evaluated 480 consecutive patients with PSA between 2.5 and 20 ng/ml undergoing the first set of prostate biopsy. All patients underwent a 14-core TRUS-guided transperineal prostate biopsy, including 12 cores in the peripheral and two in the transitional zone. The detection rate of the 14-core scheme was compared to the one of the other biopsy schemes obtained through the exclusion of pairs of cores. Data were stratified according to the different TRUS estimated prostate volumes. The detection rate of the standard sextant was 35.2%, while those of the 8-core schemes ranged from 37.1 to 38.8%. The 10-core schemes yielded detection rates of 39.6-40.8% and the protocol with 12 biopsies in the peripheral zone diagnosed prostate cancer in 42.1% of the patients. In patients with <30 cc prostate volume, the detection rate of the 14-core scheme was 43.8% and resulted statistically overlapping to the 8-peripheral cores protocol. In patients with 30.1-50 cc prostate volume a 12-peripheral core biopsy reproduced the results of the 14-core sampling. In prostates larger than 50 cc, an even more extensive procedure was mandatory, considering the low detection rate of the 14-core scheme (24.2%). Transperineal prostate biopsy is a safe procedure with a very low complication rate and high cancer detection rate. Prostate volume is the most relevant variable in the planning of the optimal number of cores in the extensive first biopsy set. A protocol with more than 8 peripheral cores) is recommended only in patients with prostate volume larger than 30 cc.


Extended Right Hepatectomy and Inferior Vena Cava Graft Replacement for En Bloc Resection of Hepatocellular Carcinoma with Cavo-Hepatic Venous Confluence Invasion.
Hepatocellular carcinoma (HCC) associated with tumor extension in the portal vein, hepatic vein, or inferior vena cava (IVC) is traditionally considered an advanced stage of disease to which palliative radiotherapy or sorafenib chemotherapy is proposed.1,2 Recent studies have shown a significant survival benefit in patients treated with R0 liver resection.3-5 METHODS: We describe the case of a 45-year-old female patient presenting with a voluminous HCC developed in a non-cirrhotic liver with a tumor thrombus obstructing the retrohepatic IVC and the middle hepatic vein termination. Initial treatment included two cycles of selective internal radiation therapy with Yttrium 90 and sorafenib treatment for 1 year. Re-evaluation revealed a significant reduction of the tumor and compensative hypertrophy of the left liver lobe, enabling surgical resection. The procedure included anatomic right hepatic trisectionectomy with caudate lobectomy and retrohepatic IVC graft replacement. Total liver vascular exclusion with intrapericardial IVC control enabled en bloc R0 resection of the tumor and the floating tumor thrombus in the cavo-hepatic venous confluence. Total liver vascular exclusion duration was 20 min, for a total warm liver ischemia of 40 min. The duration of the operation was 240 min and blood loss was 700 mL. The patient was discharged on postoperative day 15 and was free of disease 6 months post-surgery. Liver surgery with complex vascular resections for HCC with major vascular invasion should be considered a valid therapeutic option in high-volume hepatobiliary centers.