The Aphelenchus avenae genome highlights evolutionary adaptation to desiccation.
Some organisms can withstand complete body water loss (losing up to 99% of body water) and stay in ametabolic state for decades until rehydration, which is known as anhydrobiosis. Few multicellular eukaryotes on their adult stage can withstand life without water. We still have an incomplete understanding of the mechanism for metazoan survival of anhydrobiosis. Here we report the 255-Mb genome of Aphelenchus avenae, which can endure relative zero humidity for years. Gene duplications arose genome-wide and contributed to the expansion and diversification of 763 kinases, which represents the second largest metazoan kinome to date. Transcriptome analyses of ametabolic state of A. avenae indicate the elevation of ATP level for global recycling of macromolecules and enhancement of autophagy in the early stage of anhydrobiosis. We catalogue 74 species-specific intrinsically disordered proteins, which may facilitate A. avenae to survive through desiccation stress. Our findings refine a molecular basis evolving for survival in extreme water loss and open the way for discovering new anti-desiccation strategies.


How to improve infraorbital hollows with neuromodulators-A clinical prospective interventional study about the application of facial biomechanics.
A previous injection algorithm termed the "Toxin Lift" was recently introduced and described volume increases in the midface following neuromodulator treatments of the jawline. Increase in midfacial volume due to soft tissue repositioning could also affect the severity of infraorbital hollows. The objective is therefore to evaluate whether the severity of infraorbital hollows can be improved by injecting neuromodulators in the supra-mandibular segment of the platysma. A total of 35 volunteers (11 males/24 females) with a mean age of 39.8 (9.6) years and a mean BMI of 25.2 (5.2) kg/m2 were investigated. Bilateral infraorbital regions were evaluated via clinical assessment and semi-quantitative 3D imaging. The applied injection technique targeted the platysma via four injection points administering 5 I.U. per injection point resulting in a total of 20 I.U. per facial side. Volume increase of the infraorbital region was 0.13 cc at 15 days (p = 0.001) and was 0.02 cc at 30 days (p = 0.452) whereas the skin displacement in cranial direction was 0.54 mm at 15 days (p < 0.001) and was 0.31 mm at 30 days (p < 0.001). Clinical evaluation revealed a highly statistically significant improvement of the tear trough, palpaebromalar groove, and of the lid-cheek junction when compared to baseline with all p < 0.001. The results of this clinical prospective interventional analysis revealed that the "Toxin Lift" injection technique is capable to improve the clinical appearance of infraorbital hollows. The effects can be explained by the concepts of facial biomechanics.


Administration of the Rho-kinase inhibitor fasudil before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium in swine.
We assessed the effect of administration time for fasudil treatment of the stunned myocardium in 40 anesthetized open chest swine. All swine were subjected to 12 min ischemia followed by reperfusion to generate stunned myocardium. Group A (n = 11) received saline in place of fasudil both before ischemia and after reperfusion. Group B (n = 10) received 30 min intravenous fasudil at a rate of 13 mug/kg/min starting 45 min before ischemia and received saline after reperfusion. Groups C (n = 10) and D (n = 9) received saline before ischemia, and received fasudil at a rate of 13 microg kg(-1) min(-1) starting just before reperfusion in group C and 30 min after reperfusion in group D. In both groups, treatment lasted 30 min. Myocardial contractility was assessed by percent segment shortening (%SS). Three swine in group A, 2 swine in each of groups B and C, and one swine in group D had ventricular fibrillation or tachycardia after reperfusion and were excluded from further analysis. The changes of %SS from baseline at 90 min after reperfusion in groups B and C were 68 +/- 8% and 75 +/- 8%, respectively, which were significantly higher than in group A or D (47 +/- 10% or 43 +/- 8%). We conclude that fasudil administered before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium.


Trauma History as a Significant Predictor of Posttraumatic Growth Beyond Mental Health Symptoms in Women-Identifying Survivors of Undergraduate Non-Consensual Sexual Experiences.
There is little data on what influences posttraumatic growth for women who experienced non-consensual sexual contact (NCSC) as an undergraduate college student. The purpose of this study is to garner a better understanding of posttraumatic growth among women-identifying survivors of undergraduate NCSC by addressing the following aims: 1) evaluate the mediating role of NCSC-related shame on the relationship between perceived peer rape myth acceptance and posttraumatic growth (n = 174); and 2) evaluate the shared and independent variance contributions of mental health symptoms and trauma history clusters on posttraumatic growth (n = 151).NCSC-related shame did not mediate the relationship between perceived peer rape myth acceptance and posttraumatic growth. Mental health symptoms and trauma history significantly contributed to 35.27% of posttraumatic growth variance, with the trauma history cluster significantly influencing posttraumatic growth scores beyond mental health symptoms. Based on these findings, it is important that clinicians assess for a history of trauma and the impact of that trauma in addition to mental health symptoms when trying to understand posttraumatic growth after campus sexual violence.


A sensitive fluorescent assay for N-acetyltransferase activity in human lymphocytes from newborns and adults.
We have developed a simplified assay for the enzyme N-acetyltransferase, based upon the loss of fluorescence after acetylation of the substrate p-aminobenzoic acid. This method is sufficiently sensitive to permit the quantitation of N-acetyltransferase activity in 10(5) human lymphocytes. Using this method, we have compared the level of N-acetyltransferase activity in lymphocytes from adult peripheral blood and from cord blood samples.


Bipolar electrochemiluminescence on thread: A new class of electroanalytical sensors.
This paper introduces a new and simple concept for fabricating low-cost, easy-to-use capillary microchannel (CMC) assisted thread-based microfluidic analytical devices (CMCA-μTADs) for bipolar electrochemiluminescence (BP-ECL) application. The thread with patterns of carbon screen-printed electrodes and bare thread zones (BTZs) is embedded into a CMC. Such CMCA-μTADs can produce a strong and stable BP-ECL signal, and have an extremely low cost ($0.01 per device). Interestingly, the CMCA-μTADs are ultraflexible, and can be bent with a 135° bending angle at the BTZ or with a 150° bending angle at the middle of bipolar electrode (BPE), with no loss of analytical performance. Additionally, the two commonly-used ECL systems of Ru(bpy)32+/TPA and luminol/H2O2 are applied to demonstrate the quantitative ability of the BP-ECL CMCA-μTADs. It has been shown that the proposed devices have successfully fulfilled the detection of TPA and H2O2, with detection limits of 0.00432mM and 0.00603mM, respectively. Based on the luminol/H2O2 ECL system, the CMCA-μTADs are further applied for the glucose measurement, with the detection limit of 0.0205mM. Finally, the applicability and validity of the CMCA-μTADs are demonstrated for the measurements of H2O2 in milk, and glucose in human urine and serum. The results indicate that the proposed devices have the potential to become an important new tool for a wide range of applications.


An echocardiographic survey of primary school children for bicuspid aortic valve.
Primary school students (817 apparently healthy 10-year olds) were screened by transthoracic 2-dimensional echocardiography to assess for the prevalence of bicuspid aortic valve. Bicuspid aortic valve was found in 0.5% of cases, with a higher prevalence in males than females (0.75% vs 0.24%), and was significantly associated with aortic root enlargement compared with children who had tricuspid aortic valves.


Theory of Fighting the Epidemic with Traditional Chinese Medicine Qigong () Therapy.
Qigong () therapy is an active self-paced exercise therapy and it has a long history in traditional Chinese medicine (TCM). As early as the mention of it in the Huang Di Nei Jing ( Huangdi's Internal Classic), there is a record of using qigong therapy to prevent and treat pestilence. This thesis discusses the idea and methods of qigong therapy in TCM, such as daoyin (), expiration and inspiration, and meditation. These methods purpose to have the functions of strengthening and consolidating the primordial qi, improving health conditions, and resisting pestilent qi. Therefore, the core idea of fighting the epidemic with qigong therapy is to enhance the healthy qi, and to prevent the intrusion of pestilent qi into the human body. It embodies the TCM thought of "when there is sufficient healthy qi inside the body, the evil cannot invade the body."


Trisomy 8 in B-cell chronic lymphocytic leukemia.
Association between trisomy 8 and myeloid disorders/malignancies has been well documented. We report on two patients with a known history of B-cell chronic lymphocytic leukemia (B-CLL) with bone marrow involvement. In addition to the classic B-CLL cytogenetic abnormalities in one of the patients, both showed a trisomy 8 clone in their bone marrow specimens. Using a BioView Duet automated scanning system, which allowed us to combine histology with fluorescence in situ hybridization, we showed that the trisomy 8 clone was restricted to the myeloid lineage. We believe that this finding signifies the development of myelodysplastic syndrome (de novo or therapy related), rather than progression of B-CLL with the occurrence of a new clone, and that in general, it has implications for the finding of trisomy 8 in CLL.


Knockout of bone sialoprotein in cementoblasts cell lines affects specific gene expression in unstimulated and mechanically stimulated conditions.
One of the major components in cementum extracellular matrix is bone sialoprotein (BSP). BSP knockout (Ibsp) mice were reported to have a nonfunctional hypo-mineralized cementum, as well as detachment and disorganization of the periodontal ligament tissue. However, studies investigating the influence of Ibsp in cementoblasts are missing yet. This study investigates the influences of Bsp in three cementoblasts cell lines (OCCM.30-WT,IbspΔNterm, and IbspKAE). The mRNA expression of cementoblast and osteoclast markers (Col1a1, Alpl, Ocn, Runx2, Ctsk, Rankl and Opg) and the cell morphology were compared. Additionally, a functional monocyte adhesion assay was performed. To understand the influence of external stimuli, the effect of Ibsp was investigated under static compressive force, mimicking the compression side of orthodontic tooth movement. Cementoblasts with genotype IbspΔNterm and IbspKAE showed slight differences in cell morphology compared to OCCM.30-WT, as well as different gene expression. Under compressive force, the Ibsp cell lines presented expression pattern markers similar to the OCCM.30-WT cell line. However, Cathepsin K was strongly upregulated in IbspΔNterm cementoblasts under compressive force. This study provides insight into the role of BSP in cementoblasts and explores the influence of BSP on periodontal ligament tissues. BSP markers in cementoblasts seem to be involved in the regulation of cementum organization as an important factor for a functional periodontium. In summary, our findings provide a basis for investigations regarding molecular biology interactions of BSP in cementoblasts, and a supporting input for understanding the periodontal and cellular cementum remodeling.


Synopsis of the species of the genus Sphaeromyxa Thélohan, 1892 (Myxosporea: Bivalvulida: Variisporina: Sphaeromyxidae).
Sphaeromyxa spp. are parasites of marine fishes, infecting the gall-bladders or bile ducts. The spores of these species possess characteristic ribbon-like polar filaments, a unique character among myxozoans. This unique character is also a synapomorphy consistent with estimates of phylogeny for this group which forms a lineage distinct from other myxozoans. There are 49 nominal species of Sphaeromyxa Thélohan, 1892 for which a synopsis is provided, reporting spore dimensions, spore shape, locality, and host species. A line drawing is also provided for each species.


Association of mean corpuscular volume with sarcopenia and visceral obesity in individuals without anemia.
Sarcopenia and visceral obesity are major global public health issues, and higher mean corpuscular volume (MCV) levels are related to adverse outcomes. Nevertheless, no study has determined the association between MCV and body composition. Therefore, we evaluated the association between MCV levels and trunk muscle quality, muscle quantity and visceral fat area. In our cross-sectional study, we investigated 702 middle-aged Japanese individuals without anemia and with normal MCV levels who underwent physical checkups. The cross-sectional area of skeletal muscle or visceral fat was analyzed by computed tomography. In the adjusted model, the MCV was independently associated with the visceral fat area index (β = -0.107, P = 0.0007), total skeletal muscle index (β = 0.053, P = 0.0341) and total skeletal muscle density (β = 0.099, P = 0.0012). MCV as a continuous variable was related to the prevalence of sarcopenia (odds ratios [OR] 0.93, 95% confidence intervals (CI) 0.88-0.98, per 1.0 fL increment; P = 0.0097) and visceral obesity (OR 0.91, 95% CI 0.86-0.97, per 1.0 fL increment; P = 0.0046). The highest MCV quartile was independently associated with the prevalence of sarcopenia (OR 0.48, 95% CI 0.27-0.83; P = 0.0089) and visceral obesity (OR 0.49, 95% CI 0.27-0.88; P = 0.0170), compared with the lowest quartile. In individuals without anemia and with normal MCV levels, a lower MCV was associated with unfavorable body composition, including lower muscle quality, lower muscle quantity, sarcopenia and visceral obesity.


Placenta accreta spectrum - variations in clinical practice and maternal morbidity between the UK and France: a population-based comparative study.
To compare the management and outcomes of women with placenta accreta spectrum (PAS) in France and the UK. Two population-based cohorts. All obstetrician-led hospitals in the UK and maternity hospitals in eight French regions. A cohort of 219 women with PAS in France and a cohort of 154 women with PAS in the UK. The management and outcomes of women with PAS were compared between the UK and France. Median blood loss, severe postpartum haemorrhage (≥3 l), postpartum infection and damage to surrounding organs. The management of PAS differed between the two countries: a larger proportion of women with PAS in the UK had a caesarean hysterectomy compared with France (43% vs 26%, p < 0.001), whereas in France a larger proportion of women with PAS received a uterus-preserving approach compared with the UK (36% vs 19%, p < 0.001). The total median blood loss in the UK was 3 l (IQR 1.7-6.5 l), compared with 1 l (IQR 0.5-2.5 l) in France; more women with PAS had a severe postpartum haemorrhage (PPH) in the UK compared with women with PAS in France (58% vs 21%, p < 0.001) [Correction added on 06 May 2022, after first online publication: '24 hour' has been changed to 'total' in the preceding sentence]. There was no difference between the UK and French populations for postpartum infection or organ damage. The UK and France have very different approaches to managing PAS, with more women in France receiving a uterine-conserving approach and more women in the UK undergoing caesarean hysterectomy. A life-threatening haemorrhage was more common in the UK than in France, which may be the result of differential management and/or the organisation of the healthcare systems. In women with placenta accreta spectrum, severe haemorrhage was more common in the UK than in France. In women with placenta accreta spectrum, severe haemorrhage was more common in the UK than in France.


Statistical modelling of data showing pandemic H1N1 2009 swine influenza a virus infection kinetics in vaccinated pigs.
A swine influenza A pandemic 2009 H1N1 (pH1N1) virus was used in a pig challenge model to investigate the efficacy of whole inactivated vaccines homologous or heterologous to the challenge virus as well as a commercial vaccine. Nasal shedding of viral RNA was monitored daily by real-time, quantitative RT-PCR (RRT-qPCR) as detailed (1). Here we report the statistical modelling of the viral RNA shedding kinetics.


A phase I study of everolimus and CHOP in newly diagnosed peripheral T-cell lymphomas.
We performed a phase I study to determine the dose and safety of everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL). Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with CHOP (750 mg/m(2) cyclophosphamide, 50 mg/m(2) doxorubicin, and 1.4 mg/m(2) (maximum 2 mg) vincristine on day 1, and 100 mg/day prednisone on days 1 to 5) every 21 days were planned. Fifteen patients newly diagnosed with stage III/IV PTCL were enrolled. One of 6 patients at dose level 2 (5 mg everolimus) had grade 3 hepatotoxicity and 3 of 6 patients at level 3 (7.5 mg everolimus) had grade 4 hematologic toxicities (two grade 4 thrombocytopenia and one grade 4 neutropenia with fever lasting more than 3 days). The recommended dose of everolimus for combination was 5 mg. There were no differences in steady state trough concentrations of everolimus between cycles 1 and 2 for all three dose levels. All evaluable patients achieved response (8 complete and 6 partial). Everolimus (5 mg) can be safely combined with CHOP leading to a feasible and effective regimen for PTCL. The subsequent phase II is now in progress.


Early, aggressive therapy for rheumatoid arthritis: concerns, descriptions, and estimate of outcome.
The past few years have witnessed changing perceptions about rheumatoid arthritis (RA); it is now considered a serious systemic disease that confers not only physical and social morbidity but also earlier mortality. The long-term outcome of sequential monotherapy based on the therapeutic pyramid has been disappointing. A review of prognostic factors, acute disease activity measures, functional measures, and the results of preliminary trials with combination therapy suggests that specific goals of treatment can be established and that logical, aggressive treatment in early disease can be accomplished. These goals should include prompt control and continuous reduction of the active joint count to < or = 4 and normalization of acute-phase reactants. The "graduated-step paradigm" of treatment designed with these goals in mind is described, and a retrospective series that gives an estimate of outcome with its use is reported.


[Literature and own strategies concerning soft-tissue reconstruction and exposed osteosynthetic hardware].
In the event of exposed hardware from reconstructive surgery, it must be decided whether to retain or remove it prior to plastic surgical soft-tissue reconstruction to ensure long-term freedom from infection and stable wound closure. Treatment options and results in the literature are reviewed. A treatment algorithm is proposed under consideration of our personal experience. Hardware used in spine surgery is commonly left in situ until bony consolidation has been achieved. The indications for hardware removal depend on length of exposure or infection, implant failure, and location. Osteosynthetic devices in the extremities may be removed and replaced by external fixators or immobilisation. Removal of prostheses requires complex second-stage reimplantation or arthrodesis. A treatment algorithm is suggested that might ease the decision whether exposed hardware can remain or requires removal before reconstruction of soft-tissue defects.


M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae.
Intracellular pathogens have developed various strategies to escape immunity to enable their survival in host cells, and many bacterial pathogens preferentially reside inside macrophages, using diverse mechanisms to penetrate their defenses and to exploit their high degree of metabolic diversity and plasticity. Here, we characterized the interactions of the intracellular pathogen Chlamydia pneumoniae with polarized human macrophages. Primary human monocytes were pre-differentiated with granulocyte macrophage colony-stimulating factor or macrophage colony-stimulating factor for 7 days to yield M1-like and M2-like macrophages, which were further treated with interferon-γ and lipopolysaccharide or with interleukin-4 for 48 h to obtain fully polarized M1 and M2 macrophages. M1 and M2 cells exhibited distinct morphology with round or spindle-shaped appearance for M1 and M2, respectively, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophage polarization did not influence uptake of C. pneumoniae, since comparable copy numbers of chlamydial DNA were detected in M1 and M2 at 6 h post infection, but an increase in chlamydial DNA over time indicating proliferation was only observed in M2. Accordingly, 72±5% of M2 vs. 48±7% of M1 stained positive for chlamydial lipopolysaccharide, with large perinuclear inclusions in M2 and less clearly bordered inclusions for M1. Viable C. pneumoniae was present in lysates from M2, but not from M1 macrophages. The ability of M1 to restrict chlamydial replication was not observed in M1-like macrophages, since chlamydial load showed an equal increase over time for M1-like and M2-like macrophages. Our findings support the importance of macrophage polarization for the control of intracellular infection, and show that M2 are the preferred survival niche for C. pneumoniae. M1 did not allow for chlamydial proliferation, but failed to completely eliminate chlamydial infection, giving further evidence for the ability of C. pneumoniae to evade cellular defense and to persist in human macrophages.


Identification of novel genes involved in gingival epithelial cells responding to Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infections.
This study aimed to identify the differentially expressed genes (DEGs) in gingiva epithelial cells responding to Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infections using bioinformatics method. GSE9723 dataset was downloaded from Gene Expression Omnibus, and DEGs between the infected cells and controls were identified using unpaired t-test. Overlapping DEGs in responding to Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infections were extracted. Protein-protein interaction networks were constructed and functional modules were isolated using Molecular Complex Detection algorithm. Key genes in protein-protein interaction network and Molecular Complex Detection modules were subjected to functional enrichment analyses. In addition, the transcriptional factors were predicted. A total of 533 co-up-regulated and 202 co-down-regulated genes were identified. The up-regulated genes, including IL6, CCL19, EDN1, ADCY9, and BCL2 and the down-regulated genes, including CCNB1, PLK1, and CCNA2 were the key genes in the protein-protein interaction network and modules. They were intensively enriched in chemokine signaling pathway, calcium signaling pathway and cell cycle. Finally, two transcriptional factors, E12 and NRSF, targeting to the up-regulated genes and one transcriptional factor, NRP1, targeting the down-regulated genes, were predicted. CCNB1, PLK1, and CCNA2 might play important roles in the response of host epithelial cells to Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis.


Peli1 facilitates NLRP3 inflammasome activation by mediating ASC ubiquitination.
Inflammasomes are crucial for innate immunity against infections and, when deregulated, also contribute to inflammatory diseases. Here, we identify a critical function of the E3 ubiquitin ligase Peli1 in regulating the activation of NLRP3 inflammasome. Peli1 deficiency impairs induction of interleukin-1β (IL-1β) secretion by different NLRP3 inducers, but not by inducers of the Aim2, NLRP1, and NLRC4 inflammasomes. Peli1-deficient mice have alleviated peritonitis induction by alum and display increased resistance to lipopolysaccharide (LPS) endotoxin shock, coupled with decreased serum concentration of IL-1β. Peli1 is required for NLRP3-induced caspase-1 activation and IL-1β maturation. Mechanistically, Peli1 conjugates K63 ubiquitin chain to lysine 55 of the inflammasome adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which in turn facilitates ASC/NLRP3 interaction and ASC oligomerization, thereby contributing to inflammasome activation. Peli1 deficiency impairs the ubiquitination of ASC and inhibits inflammasome activation. Our findings establish Peli1 as an important inflammasome regulator and suggest a mechanism by which Peli1 mediates inflammatory responses.


Diagnostic and Therapeutic Dilemmas with Arrhythmic Right Ventricular Cardiomyopathy.
The diagnosis of arrhythmic right ventricular cardiomyopathy (ARVC) can be difficult, particularly in patients who have early manifestations of the disease. Modification of the 1994 Diagnostic Test Task Force criteria has recently been published. The most frequent cause for misdiagnosis is incorrect interpretation of a cardiac imaging test, particularly magnetic resonance imaging. The results of genetic testing must be interpreted with caution. Genetic abnormalities may be absent in 50% of patients with ARVC and penetrance is variable.


Maternal Exposure to Ozone Modulates the Endophyte-Conferred Resistance to Aphids in Lolium multiflorum Plants.
Plants are challenged by biotic and abiotic stress factors and the incidence of one can increase or decrease resistance to another. These relations can also occur transgenerationally. For instance, progeny plants whose mothers experienced herbivory can be more resistant to herbivores. Certain fungal endophytes that are vertically transmitted endow plants with alkaloids and resistance to herbivores. However, endophyte-symbiotic plants exposed to the oxidative agent ozone became susceptible to aphids. Here, we explored whether this effect persists transgenerationally. We exposed Lolium multiflorum plants with and without fungal endophyte Epichloë occultans to ozone (120 or 0 ppb), and then, challenged the progeny with aphids (Rhopalosiphum padi). The endophyte was the main factor determining the resistance to aphids, but its importance diminished in plants with ozone history. This negative ozone effect on the endophyte-mediated resistance was apparent on aphid individual weights. Phenolic compounds in seeds were increased by the symbiosis and diminished by the ozone. The endophyte effect on phenolics vanished in progeny plants while the negative ozone effect persisted. Independently of ozone, the symbiosis increased the plant biomass (≈24%). Although ozone can diminish the importance of endophyte symbiosis for plant resistance to herbivores, it would be compensated by host growth stimulation.


Milk consumption decreases activity of human serum alkaline phosphatase: a cross-sectional study.
Since the Japanese have not reached the recommended daily allowance (RDA) for calcium (600 mg), milk is recommended as a Ca-rich food to increase Ca intake and prevent osteoporosis in Japan. To determine whether milk consumption influences Ca/bone metabolism in the Ca-deficient population, relationships between milk consumption and serum alkaline phosphatase (Al-P) activity were analyzed in 3,098 premenopausal and 1,182 postmenopausal women and 13,141 men aged 30 to 69 years. Milk consumption was classified into no/yes groups by a self-administered questionnaire that asked "Do you drink a glass of milk (180 to 200 mL) or more everyday?". Regardless of age or sex, the "yes" group had a lower activity of serum Al-P than the "no" group. Milk consumption decreased the activity to a greater degree in women, especially perimenopausal/postmenopausal women, than in men. These results were confirmed in a multivariate analysis considering age, body mass index (BMI), and smoking and drinking habits as confounding factors. Although menopause obviously increased serum Al-P activity in perimenopausal women, it could not influence the effects of milk consumption on the activity. These results suggest that milk has osteostatic effects on humans via a mechanism different from that of estrogens. Milk consumption, even one glass per day, may be an easy and effective strategy for prevention of osteoporosis in the Ca-deficient population, especially perimenopausal/postmenopausal women.


Phosphorylation of synaptic-membrane proteins from ox cerebral cortex in vitro. Preparation of fractions enriched in phosphorylated proteins by using extraction with detergents and urea, and gel filtration.
Synaptic-membrane fragments from ox cerebral cortex contain basal and cyclic AMP-stimulated protein kinase(s) that transfer 32P from [gamma-32P]ATP to hydroxyl groups of serine and threonine residues in membrane-protein substrates. In the present work, labelled membrane fragments were partitioned into soluble and insoluble fractions with Triton X-100, Nonidet P. 40, sodium deoxycholate and urea, and the distribution of 32P-labelled protein in the fractions was determined by polyacrylamide-gel electrophoresis and radioautography. A high percentage of phosphorylated protein sustrates remained insoluble, including those whose phosphorylation was most highly stimulated by cyclic AMP. Whole membrane fragments and samples prepared by detergent extraction were fractionated on Sepharose 6B columns in the presence of low concentrations of sodium dodecyl sulphate and pooled fractions were analysed by polyacrylamide-gel electrophoresis and radioautography. Phosphorylated proteins were fractionated on the basis of their molecular weight, but homogeneous protein was not obtained. The results are discussed in relation to the techniques used and the results obtained in other laboratories.


Stable isotopes reveal the formation diversity of humic substances derived from different cotton straw-based materials.
Humic substances (HS) are essential in environment processes and carbon (C) sequestration in soils. In this study, organic materials such as cotton straw and its derived compost and biochar were added to the soil on a C-equivalent basis and incubated for 30 and 180 days in order to investigate the different forms of plant biomass derived C sequestration in HS. The C distribution in humic acid (HA), fulvic acid (FA), and humin (Hu) derived from organic materials was investigated using the 13C isotope method, while the catalase, sucrose, and β-glucosidase activities were also determined. The results showed that C3 distribution of Hu derived from straw, compost and biochar increased from 40.94% to 67.12%, 74.47% and 80.75%, respectively. In addition, the increase of C3 distribution of HA or FA derived from straw, compost and biochar were 4.69%, 10.09% and 1.49%, respectively. There were significantly positive correlations between catalase, sucrase and β-glucosidase activities and C3 derived HA and FA. The principal component analysis showed that catalase, sucrase and β-glucosidase were explained mainly by the first principal component indicating a significant correlation. These findings suggest that straw, compost and biochar are mainly sequestrated in Hu. Comparatively, the straw and compost are more likely to contribute to the formation of HA and FA in soil, but biochar favors the Hu, which helps in soil C sequestration. The formation of HA and FA derived from organic materials was supported by catalase, sucrase and β-glucosidase activities.


Deep learning for diffusion in porous media.
We adopt convolutional neural networks (CNN) to predict the basic properties of the porous media. Two different media types are considered: one mimics the sand packings, and the other mimics the systems derived from the extracellular space of biological tissues. The Lattice Boltzmann Method is used to obtain the labeled data necessary for performing supervised learning. We distinguish two tasks. In the first, networks based on the analysis of the system's geometry predict porosity and effective diffusion coefficient. In the second, networks reconstruct the concentration map. In the first task, we propose two types of CNN models: the C-Net and the encoder part of the U-Net. Both networks are modified by adding a self-normalization module [Graczyk et al. in Sci Rep 12, 10583 (2022)]. The models predict with reasonable accuracy but only within the data type, they are trained on. For instance, the model trained on sand packings-like samples overshoots or undershoots for biological-like samples. In the second task, we propose the usage of the U-Net architecture. It accurately reconstructs the concentration fields. In contrast to the first task, the network trained on one data type works well for the other. For instance, the model trained on sand packings-like samples works perfectly on biological-like samples. Eventually, for both types of the data, we fit exponents in the Archie's law to find tortuosity that is used to describe the dependence of the effective diffusion on porosity.


Genetically Diversity of Pseudomonas aeruginosa Isolated from Chronic Suppurative Otitis Media with Respect to Their Antibiotic Sensitivity Pattern.
Pseudomonas aeruginosa is an important chronic suppurative otitis media (CSOM) pathogen that exhibits multiple resistances to antibiotics with increasing frequency, making patient treatment more difficult. The aim of the study is to ascertain the genetically diversity of this clinically isolated P. aeruginosa with inter simple sequence repeat (ISSR) markers. All 25 P. aeruginosa were isolated from CSOM patients by taking their ear swabs and culturing on blood agar and MacConkey agar. All strains were identified with morphological characters and biochemical testing. The antimicrobial susceptibility testing was carried out according to National Committee for Clinical Laboratory Standards. ISSR was used to study the genetic diversity of P. aeruginosa. Clinically CSOM isolated 25 P. aeruginosa were 88% Ciprofloxacin resistant and similarly resistant to other antibiotics were documented. The study has been made using ISSR marker to find out the genomic relation among the strains/populations of P. aeruginosa. The result was shown that maximum similarity (80%) was between S-11 and S-13 and minimum (28.2%) was between S-4 and S-16 with an average similarity of 53.2%. The dendogram showed a distinct separation in between all the strains/populations of P. aeruginosa. The strains/populations were broken up into two main clusters in which small one bear two strains/populations (S-4 and S-9) and another cluster have another 23 strains/populations. These 23 strains were also separated to form subcluster by having different range of small clades. The genetically diversity of pathogenic P. aeruginosa present in CSOM at our hospital indicates the coexistence different strains due to different antibiotic sensitivity patterns. The conventional culture and sensitivity methods are time consuming whereas in PCR, it will detect within 4-6 h for effective antibiotic. Basing upon the banding pattern with ISSR primers, clinicians can prescribe the effective antibiotics accordingly for CSOM patients in the same day.


LC determination and pharmacokinetic study of the main phenolic components of Portulaca oleracea L. extract in rat plasma after oral administration.
This study investigated the pharmacokinetics of hesperidin (HP), ferulic acid (FA) and p-coumaric acid (CA) in rat plasma after oral administration of Portulaca oleracea L. extract (POE). The plasma concentrations were determined by HPLC with vitexin-2″-O-rhamnoside (VR) as internal standard. The calibration curves were linear over the range 0.1-5 µg mL(-1), 0.1-5 µg mL(-1)and 0.015-3 µg mL(-1) for HP, FA and CA, respectively. The validated method was suitable to the pharmacokinetic study of HP, FA and CA in rats after oral administration at a single dose of POE.


Comparison of weight- vs body surface area-based growth hormone dosing for children: implications for response.
To compare weight (per kg)- vs body surface area (BSA, per m(2) )-based growth hormone (GH) dosing formats in children and to derive a useful conversion formula between the two formats. Growth hormone doses (>33,000) from 1874 children were obtained from the national Australian database (OZGROW) and used to derive conversion formulae and to confirm the accuracy of a conversion formula based on a weight-only BSA estimate. A further 27,000 doses were used to test the accuracy of all formulae. The best conversion formula was used to compare weight- and surface area-based GH dosing, which included an analysis of first year response (∆SDS height or growth velocity, GV). Growth hormone doses in mg/m(2) /wk and mg/kg/wk, dose estimates, residuals, first year ∆SDS, first year GV. The formula, [Formula: see text] based on a weight-only BSA estimate, provides accurate dose conversion (mean residual, 0·005 mg/kg/week). A constant mg/m(2) /week dose expressed in terms of mg/kg/week declines quickly with increasing body weight to approximately 15 kg after which the decline continues although less dramatically. For Australian patients, despite an increase in mean per m(2) dose with increased starting weight/age, the per kg dose decreased. This was associated with a greater decline in first year GV than estimated if a per kg dose had been maintained. Growth hormone doses can be accurately converted between formats. Surface area-based GH dosing is likely to result in a reduced height response as children become heavier when compared with weight-based GH dosing.


Assessing the suitability of stream water for five different uses and its aquatic environment.
Surface water is one of the essential resources for supporting sustainable development. The suitability of such water for a given use depends both on the available quantity and tolerable quality. Temporary status for a surface water quality has been identified extensively. Still the suitability of the water for different purposes needs to be verified. This study proposes a water quality evaluation system to assess the aptitude of the Selangor River water for aquatic biota, drinking water production, leisure and aquatic sport, irrigation use, livestock watering, and aquaculture use. Aptitude of the water has been classified in many parts of the river segment as unsuitable for aquatic biota, drinking water production, leisure and aquatic sport as well as aquaculture use. The water quality aptitude classes of the stream water for nine locations along the river are evaluated to contribute to decision support system. The suitability of the water for five different uses and its aquatic ecosystem are verified.


Microfluidic Cell Deformability Assay for Rapid and Efficient Kinase Screening with the CRISPR-Cas9 System.
Herein we report a CRISPR-Cas9-mediated loss-of-function kinase screen for cancer cell deformability and invasive potential in a high-throughput microfluidic chip. In this microfluidic cell separation platform, flexible cells with high deformability and metastatic propensity flowed out, while stiff cells remained trapped. Through deep sequencing, we found that loss of certain kinases resulted in cells becoming more deformable and invasive. High-ranking candidates identified included well-reported tumor suppressor kinases, such as chk2, IKK-α, p38 MAPKs, and DAPK2. A high-ranking candidate STK4 was chosen for functional validation and identified to play an important role in the regulation of cell deformability and tumor suppression. Collectively, we have demonstrated that CRISPR-based on-chip mechanical screening is a potentially powerful strategy to facilitate systematic genetic analyses.


A single receptor identical with that from intestine/T47D cells mediates the action of 1,25-dihydroxyvitamin D-3 in HL-60 cells.
Two anti-vitamin D receptor monoclonal antibodies binding to two different epitopes immunoprecipitate 100% of the HL-60 1,25-dihydroxyvitamin D-3 binding activity, while another monoclonal antibody specific for the porcine receptor precipitates none. Using a rat receptor cDNA probe, a single mRNA species of 4.6 kb was detected by Northern analysis of HL-60 mRNA. Using a cDNA probe from the cloned rat receptor, 10(7) recombinants from a lambda gt11 cDNA library constructed from mRNA isolated from HL-60 cells was screened yielding two positive clones. These clones had sequences identical with the known human receptor sequence from intestinal/T47D sources. Using PCR technology, the entire sequence of the HL-60 1,25-dihydroxyvitamin D-3 receptor was determined. This sequence was found identical with that reported for the human intestinal/T47D cDNA encoding the vitamin D receptor except for a single base. The substitution of this particular base does not alter the amino acid sequence however. Thus, the same receptor likely operates in differentiation and calcium transport functions.


In vitro activity of a serine protease from Monacrosporium thaumasium fungus against first-stage larvae of Angiostrongylus vasorum.
A serine protease from the nematophagous fungus Monacrosporium thaumasium (NF34a) was purified, partially characterized and tested in vitro in control of the first larval stage of Angiostrongylus vasorum. NF34a grew in liquid culture medium, producing its crude extract that was purified by ion exchange chromatography. The fractions with high protease activity were collected in a pool, and elution of proteases was monitored by enzymatic assay and protein content. Purification steps were monitored by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Protease activity was determined under different pH and temperature conditions, and the inhibitor effects of metal ions and phenylmethylsulfonyl fluoride (PMSF) were assessed. In an experimental test, the infection process of NF34a on first-stage larvae of A. vasorum was investigated. A purified serine protease (Mt1) was identified, with an approximate molecular mass of 40 kDa and apparent homogeneity in SDS-PAGE, having optimal activity at pH 7.0 to 8.0 and temperature of 60°C. Mg(2+) and Zn(2+) partially inhibited the activity of Mt1 while PMSF inhibited it completely. Mt1 production was observed when NF34a was grown using first-stage larvae of A. vasorum as the only source of carbon and nitrogen. These results show that the enzyme may have a possible role in the infection process of the larvae. In the in vitro test of applicability against A. vasorum L(1), we observed a reduction in the number of larvae of 23.9% (p < 0.05) in the group treated with Mt1 compared with the control group. However, even this low reduction demonstrates that the Mt1 is important in the infection process.


The X-ray Correlation Spectroscopy instrument at the Linac Coherent Light Source.
The X-ray Correlation Spectroscopy instrument is dedicated to the study of dynamics in condensed matter systems using the unique coherence properties of free-electron lasers. It covers a photon energy range of 4-25 keV. The intrinsic temporal characteristics of the Linac Coherent Light Source, in particular the 120 Hz repetition rate, allow for the investigation of slow dynamics (milliseconds) by means of X-ray photon correlation spectroscopy. Double-pulse schemes could probe dynamics on the picosecond timescale. A description of the instrument capabilities and recent achievements is presented.


Systematic review of prostate cancer's association with body size in childhood and young adulthood.
Body size relatively early in life may influence men's later rate of prostate cancer. We searched for published, English-language studies of the association between prostate cancer incidence or mortality and body size between ages 5 and 29 years. We summarized analyses of childhood body size, early-adult waist circumference, and early-adult body mass index (BMI). Most study designs were case-control or retrospective cohort studies, in which body size was self-reported and recalled. The few studies of childhood body size and early-adult waist circumference indicated null or weak associations. The results from studies of early-adult BMI were heterogeneous (p = 0.04) and showed evidence of funnel plot asymmetry. The random-effects rate ratio (RR) was 1.06 (95% confidence interval [CI]: 0.99, 1.14) per five-unit increase in BMI. Studies using measured (as opposed to self-recalled) height and weight (n = 3) tended to produce stronger associations: fixed-effects summary RR = 1.22 (1.06, 1.39). The same was true for studies that did not adjust for later-life BMI (n = 13): fixed-effects RR = 1.13 (1.06, 1.21). Examining only analyses of advanced or high-grade prostate cancers, results were heterogeneous (p < 0.01). The random-effects summary RR per five units of BMI was 1.01 (95% CI: 0.89, 1.15). In all the reviewed studies, the vast majority of men were of normal weight in childhood and early adulthood. Few studies presented data describing the association between prostate cancer and obesity (e.g., early-adult BMI > or = 30). The exact relationships between early-life body size and prostate cancer remain unclear but appear to be weak.


Fast simultaneous determination of main components and impurity sodium ion in PAMA injection by mixed-mode chromatography.
This study describes an analytical method to control the quality of potassium aspartate and magnesium aspartate (PAMA) injection based on the simultaneous detection of the main components (K+, Mg2+ and Asp) and impurities (Na+) using a mixed-mode chromatography coupled with charged aerosol detector. To obtain optimal chromatographic separation, the effects of organic content, column temperature, buffer types, pH and concentrations were evaluated. A Response Surface Methodology (RSM) optimal design was performed after single factor experiment. The mixed-mode HPLC method is proved to be a complementary approach to the conventional ion chromatography (IC). The optimized method was successfully validated and applied to the analysis of Asp, K+, Na+ and Mg2+ in PAMA injection with good specificity, linearity, accuracy, and repeatability. The method would be useful for quality control in PAMA injection and other similar drugs, which can provide references for the analysis of drug quality by enterprises and drug regulatory department.


Determination of the luminal diameter of the radial artery in man by high frequency ultrasound: a methodological study.
The validity and reproducibility of measurements of the luminal diameter of the radial artery in man were investigated with Dermascan A, a 20 MHz ultrasound scanner. The luminal diameter of a reference object, a plastic tube, was measured with ultrasound to be 99.0% of stereomicroscopic measurements. By comparing the diameter of the reference object either filled with water or blood at 37 degrees C, the ultrasound velocity in human blood at 37 degrees C was calculated to be 1605 m/s. The intraobserver repeatability coefficients of in-vivo measurements of the radial artery in man were in the same range, whether measurements were repeated after 30 min (14%) or from day to day (12%). The interobserver repeatability coefficient was acceptable (15%) when the site of measurements was marked, whereas measurements without a mark resulted in a repeatability coefficient of 24%. The intravenous administration of 0.5 mg ergotamine tartrate to 5 subjects caused a decrease in the mean luminal diameter of the radial artery from 2.94 mm to 2.42 mm 1 h after ergotamine (p less than 0.05). This ultrasound method for measurements of the luminal diameter should thus be suitable for investigating the effects of physiological and pharmacological stimuli on the arteries per se.


Morphology, composition and aggregation mechanisms of soft bioflocs in marine snow and activated sludge: A comparative review.
Conditions that lead to marine snow formation and aggregates that constitute the marine snow have similarities with the soft bioflocs that form during wastewater treatment by activated sludge process. Analysis of the conditions and similarities of the soft bioflocs in these two aquatic environments provide insight for the processes that lead to formation and growth of hydrated aggregates consisting of both living and nonliving particles, their chemical and biolocial composition, settling/suspension behavior, and contributing factors for their structure and morphology. This literature review provides a comparative analysis of the soft aggregates that form in marine and wastewater environments to characterize the conditions for formation and growth of highly hydrated aggregates consisting of microorganisms, suspended solids and large molecules. The marine snow and bioflocs that form in wastewater are visually similar and even contain microorganisms that are of similar type (i.e., Zoogloea, filamentous bacteria). During wastewater treatment, the microorganisms are not stressed and exopolymeric substances (EPS) produced have shorter molecules and higher protein content while EPS produced by the marine organisms are significantly larger in molecular size (by orders of magnitude) and have higher carbohydrate content.


Controlled polymorphic transformation of continuously crystallized solid lipid nanoparticles in a microstructured device: a feasibility study.
The contribution describes the transfer from a batch to a micro-continuous process for the production of stable solid lipid nanoparticles as drug carrier systems. Solid lipid nanoparticles are commonly prepared batch-wise often resulting in poorly defined product qualities with regard to the polymorphic state of their lipid matrix. In order to obtain solid lipid nanoparticle dispersions that meet the requirements for an acceptable pharmaceutical product, the manufacture of reproducible product qualities preferably containing the stable crystal form of the respective matrix lipid is necessary. These requests are addressed by the continuous preparation process of solid lipid nanoparticles. A four step feasibility study for the standardized evaluation whether or not a colloidal lipid dispersion is suitable for continuous crystallization of the particles resulting in stable crystal forms is presented. The process is based on the continuous crystallization and subsequent thermal treatment of differently stabilized, tripalmitin-based nanoparticle formulations in microstructured devices. The successful production of the stable crystal form by means of a continuous process chain is shown for a dispersion stabilized with a blend of hydrogenated soybean lecithin and sodium glycocholate.


Application of micro-solid-phase extraction for the determination of persistent organic pollutants in tissue samples.
A novel, simple and efficient method for determining persistent organic pollutants (POPs) in tissue samples has been developed. This technique involves the use of simultaneous microwave-assisted digestion (MAD) and micro-solid-phase extraction (micro-SPE), in which the sorbent is held within a propylene membrane envelope, with gas chromatographic-mass spectrometric (GC-MS) analysis. The POPs studied included eleven organochlorine pesticides and five polychlorinated biphenyl congeners. Optimization of the MAD-micro-SPE parameters was performed. The relative standard deviations (RSDs) of the method ranged from 0.14 to 12.7%. Correlation coefficients up to 0.9999 were obtained across a concentration range of 1.25-50 ng g(-1). The method detection limits for POPs ranged from 0.002 to 0.009 ng g(-1). A preliminary study applying the MAD-micro-SPE procedure to human ovarian cancer tissue showed that it was capable of detecting the presence of a wide spectrum of different POPs in benign and malignant tumors.


Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement.
The objectives of this study were to analyze the clinical and angiographic outcome of diabetic patients with successful coronary stent placement and to compare these results with those achieved after stenting in nondiabetic patients. The outcome of diabetic patients treated with stent placement due to coronary artery disease has not been assessed comprehensively. This study analyzes a consecutive series of patients with successful stent placement comprising 715 patients with diabetes and 2,839 patients without diabetes. Clinical one year follow-up and angiographic control at 6 months were part of the protocol. Death, myocardial infarction and target lesion revascularization were considered as adverse events. An automated edge detection system was used for the angiographic assessment. The primary clinical endpoint was event-free survival at one year. The primary angiographic endpoint was restenosis rate at 6 months (> or = 50% diameter stenosis). Event-free survival was significantly lower in diabetic than in nondiabetic patients (73.1 vs. 78.5%, p < 0.001). Survival free of myocardial infarction was also significantly reduced in the diabetic group (89.9 vs. 94.4% in nondiabetics, p < 0.001). The incidence of both restenosis (37.5 vs. 28.3%, p < 0.001) and stent vessel occlusion (5.3 vs. 3.4%, p = 0.037) was significantly higher in diabetic patients. Diabetes was identified as an independent risk factor for adverse clinical events and restenosis in multivariate analyses. Patients with diabetes mellitus have a less favorable clinical outcome at one year after successful stent placement as compared to the nondiabetic patients. The clinical follow-up was characterized by a higher incidence of death, myocardial infarction and reinterventions. Diabetic patients also demonstrated an increased risk for restenosis.


Changes in total body surface area and the distribution of skin surfaces in relation to body mass index.
A correct estimation of total burn surface area is important since it is used for determining fluid resuscitation volumes, nutritional estimates and hospital admission criteria. Wallace's rule of nines is the most commonly used methods for this purpose. However, fat distribution is non-uniform and the total body surface area changes with obesity. The aim of this study was to determine if the rule of nines applies to all body mass index groups. A total of 217 individuals were included in the study. The patients were divided into 4 groups according to their BMI (18.5-25kg/m2 (60 persons)), 25-29.9kg/m2 (61 individuals)), 30-34.9kg/m2 (55 persons)), >35kg/m2 (41 persons)). Each patient underwent a complete duel-energy X-ray absorptiometry body scan to determine the surface area (cm2) of the various regions of the body. We found no statistically significant variations between the Wallace body percentage distributions and our results in the men for all BMI ranges (head p=0.331, arms p=0.861, legs p=0.282, trunk p=0.696). In contrast, among women we found a statistically significant change in body surface area percentage distribution between the BMI groups and specific body regions (head p=0.000, legs p=0.000 and trunk p=0.001). The Wallace rule of nines is a quick and acceptable method for estimating the total burn surface area percentage in men of all BMI ranges. However, for women, a more accurate method of burn area estimation is required as proposed by our BMI adjusted charts.


Polyuric urinary tract dilatation with renal damage.
Polyuria of diabetes insipidus and psychogenic polydipsia can produce massive dilatation of the urinary tract in the absence of any mechanical obstruction. Renal failure in these cases is rare. We report the second case of nephrogenic diabetes insipidus with nonobstructive hydronephrotic renal damage. Temporary suprapubic drainage restored renal function to normal and decreased the upper tract dilatation. Renal function has been preserved for more than 10 years. Surgical intervention beyond temporary vesical drainage is unnecessary.


Crystal structure of bis-[μ-N-(η2-prop-2-en-1-yl)piperidine-1-carbo-thio-amide-κ2 S:S]bis-[(thio-cyanato-κN)copper(I)].
The title crystalline compound, [Cu2(NCS)2(C9H16N2)2], was obtained from the reaction of copper(I) thio-cyanate (CuSCN) with (N-prop-2-en-1-yl)piperidine-1-carbo-thio-amide as a chelating and bridging thio-urea ligand in chloro-benzene. The Cu2S2 core of the dimeric mol-ecule is situated on a crystallographic inversion centre. The copper atom is coordinated by a thio-cyanate nitro-gen atom, each sulfur atom of the two thio-urea ligands, and the C=C double bond of the ligand in a distorted tetra-hedral geometry. The dimers are linked by N-H⋯S hydrogen bonds, forming a network extending in two dimensions parallel to (100).


Graph-based automatic detection and classification of lesion changes in pairs of CT studies for oncology follow-up.
Radiological follow-up of oncology patients requires the quantitative analysis of lesion changes in longitudinal imaging studies, which is time-consuming, requires expertise, and is subject to variability. This paper presents a comprehensive graph-based method for the automatic detection and classification of lesion changes in current and prior CT scans. The inputs are the current and prior CT scans and their organ and lesion segmentations. Classification of lesion changes is formalized as bipartite graph matching where lesion pairings are computed by adaptive overlap-based lesion matching. Six types of lesion changes are computed by connected components analysis. The method was evaluated on 208 pairs of lung and liver CT scans from 57 patients with 4600 lesions, 1713 lesion matchings and 2887 lesion changes. Ground-truth lesion segmentations, lesion matchings and lesion changes were created by an expert radiologist. Our method yields a lesion matching rate accuracy of 99.7% (394/395) and 95.0% (1252/1318) for the lung and liver datasets. Precision and recall are > 0.99 and 0.94 and 0.95 (respectively) for the detection of lesion changes. The analysis of lesion changes helped the radiologist detect 48 missed lesions and 8 spurious lesions in the input ground-truth lesion datasets. The classification of lesion classification provides the clinician with a readily accessible and intuitive identification and classification of the lesion changes and their patterns in support of clinical decision making. Comprehensive automatic computer-aided lesion matching and analysis of lesion changes may improve quantitative follow-up and evaluation of disease status, assessment of treatment efficacy and response to therapy.


Qualitative assessment of selective blockade of M(4)-cholinoreceptors in the whole organism.
Quantitative assessment of selective blockade of M4-subtype muscarinic receptors was performed by the number of pilocarpine-induced movements of lower jaw in rats. Three antagonists (atropine, cyclodol, and glipin) were used in the experiments. Glipin produced the most potent blockade of M4 receptors in the whole organism compared to other test antagonist.


Proteolytic activities in yeast.
Studies on the mechanism and time course of the activation of proteinases A (EC 126.96.36.199), B (EC 220.127.116.11) and C (EC 3.4.12.--) in crude yeast extracts at pH 5.1 and 25 degrees C showed that the increase in proteinase B activity is paralleled with the disappearance of proteinase B inhibitor. Addition of purified proteinase A to fresh crude extracts accelerates the inactivation of the proteinase B inhibitor and the appearance of maximal activities of proteinases B and C. The decrease of proteinase B inhibitor activity and the increase of proteinase B activity are markedly retarded by the addition of pepstatin. Because 10-minus 7 M pepstatin completely inhibits proteinase A without affecting proteinase B activity, this is another indication for the role of proteinase A during the activation of proteinase B. Whereas extracts of yeast grown on minimal medium reached maximal activation of proteinases B and C after 20 h of incubation at pH 5.1 and 25 degrees C, extracts of yeast grown on complete medium had to be incubated for about 100 h. In the latter case, the addition of proteinas A results in maximal activation of proteinases B and C and disappearance of proteinase B inhibitor activity only after 10--20 h of incubation. With the optimal conditions, the maximal activities of proteinases A, B and C, as well as of the proteinase B inhibitor, were determined in crude extracts of yeast that had been grown batchwise for different lengths of time either on minimal or on complete medium. Upon incubation, all three proteinases were activated by several times their initial activity. This reflects the existence of proteolytically degradable inhibitors of the three proteinases and together with the above mentioned observations it demonstrates that the "activation" of yeast proteinases A, B and C upon incubation results from the proteolytic digestion of inhibitors rather than from activation of inactive zymogens by limited proteolysis.


Influencing factors and mechanism by which DOM in groundwater releases Fe from sediment.
The groundwater in many aquifers contains elevated concentrations of iron (Fe). Although much of this Fe is from its release from water-bearing sediments under natural environmental conditions, sufficient evidence is lacking to clarify whether anthropogenic pollutants, such as dissolved organic matter (DOM), can increase this natural release. In this time series and comparative analysis study, an Fe increasing effect was verified through laboratory leaching tests. The influences of the aqueous environmental conditions, such as pH, were also investigated. DOM can promote the release of Fe from sediments and increase the concentration of Fe in groundwater. In addition, lower or higher pH and temperature can enhance the release of Fe to some extent. Higher concentrations of DOM provided a more thorough release of Fe from the sediment; additional ions such as Cu also affected Fe release. It is possible that complexation between DOM and Fe occurs through ligand dissolution and reduction, thus promoting the release of Fe. The findings indicate that DOM imported through anthropogenic activities can increase the release of Fe from aquifer sediments into groundwater, thus worsening Fe pollution in groundwater. This study explored the mechanism by which different types of DOM release Fe from aquifer sediments and investigated the factors that influence this process. The findings provide insights into the geochemical processes of Fe in the groundwater.


Impulse control disorders in patients with prolactinoma receiving dopamine agonist therapy: a prospective study with 1 year follow-up.
To assess prospectively the prevalence of impulse control disorders (ICD), psychiatric symptoms, and their clinical correlates in patients with prolactinoma receiving dopamine agonists (DA) in comparison to those with non-functioning pituitary adenomas (NFA) and healthy controls (HC). A total of 25 patients with prolactinoma, 31 with NFA, and 32 HCs were included in the study. All patients and controls were screened for the presence of ICDs and other psychiatric disorders using revised version of Minnesota Impulsive Disorders Interview (MIDI-R), Barratt Impulsiveness Scale (BIS-11), Symptom Check List (SCL-90-R) questionnaire and Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). We detected two new cases (8%) of ICD associated with DAs. Both cases presented with hypersexuality, which reversed totally or decreased upon discontinuation of the drug. The re-challenge of the DA in a smaller dose has led to either no symptoms or weaker symptoms than before. There was an increase in the number of patients who screened positive on obsession, interpersonal sensitivity, paranoid ideation, and additional items subscales of SCL-90-R in comparison to HCs at the end of the study period (p < 0.05 for all). Likewise, cumulative DA dose was positively correlated to obsession, interpersonal sensitivity, paranoid ideation, hostility, phobic anxiety subscales, and GSI scores of SCL-90-R (p < 0.05 for all). DAs are associated with a small but substantial short-term risk of ICD development and a broad range of psychiatric symptoms in patients with prolactinoma receiving DAs.


Peripheral axons of Wlds mice, which regenerate after a delay of several weeks, do so readily when transcription is inhibited in the distal stump.
We have raised the hypothesis that differentiated Schwann cells repress regrowth of axons but become permissive upon dedifferentiation. WId(S) mouse is a strain in which severed peripheral nerves do not degenerate for several weeks, and axonal regeneration does not occur either [5,11]. In this strain, we studied the role of resident cells upon axonal regeneration by inhibiting transcription. Regeneration was assessed with the pinch test, electron microscopy and Dil (a fluorescent lipid soluble dye). After a crush, WId(S) axons did not regenerate but they did so when the crush was made through a nerve segment treated with actinomycin D (ActD), an inhibitor of transcription. In contrast, when the crush was made distal to the treated segment no regeneration ensued. Our results support the notion that normal resident cells of peripheral nerves repress axonal growth.


The sulfatase pathway as estrogen supply in endometrial cancer.
Contradictory results are reported about the level of steroid sulfatase (STS), estrogen sulfotransferase (SULT1E1; together, the sulfatase pathway) and aromatase (CYP19A1) in endometrial cancer (EC). The aim of this study was to explore the levels of these enzymes in a well-characterized cohort of EC patients and postmenopausal controls. Endometrial tissues from 31 EC patients (21 grade 1 and 10 grade 2-3) and 19 postmenopausal controls were collected. Levels of mRNA (RT-qPCR) and protein (immunohistochemistry) were determined. STS enzyme activity was measured by HPLC, whereas SULT1E1 enzyme activity was determined using a novel method based on liquid chromatography-mass spectrometry (LC-MS/MS). No significant differences in STS, SULT1E1 mRNA or protein levels and STS:SULT1E1 ratio were found. STS enzyme activity and STS:SULT1E1 activity ratio were significantly decreased in ECs compared with controls. CYP19A1 mRNA levels were lower in ECs than in controls. A novel highly sensitive and accurate protocol to assess SULT1E1 activity is presented. STS enzyme activity and the STS:SULT1E1 activity ratio seem to be lower in ECs than in controls. STS is an important route for estrogen supply in endometrial cells.


The effect of mucolytic agents and topical decongestants on the ciliary activity of chicken tracheal organ cultures.
The chicken tracheal organ culture system was used to study the effect on cilia function of two frequently used topical decongestants and four mucolytic agents. The agents used were: phenylephrine hydrochloride spray 0.25%, oxymetazoline 0.05%, sodium bicarbonate 7.5%, acetylcysteine 10%, pancreatic dornase 50,000 units/ml, and L-arginine 5.6%. The tracheal rings were given two kinds of exposure to the test drugs. Only pancreatic dornase was not ciliotoxic. Until further data are available, including studies with human organ cultures, it would perhaps be wise to discourage the topical use of phenylephrine hydroxhloride spray 0.25% and oxymetazoline 0.05%, and to consider pancreatic dornase as the mucolytic agent of choice.


Advanced glycation end products accelerate calcification in VSMCs through HIF-1α/PDK4 activation and suppress glucose metabolism.
Arterial media calcification is associated with diabetes mellitus. Previous studies have shown that advanced glycation end products (AGEs) are responsible for vascular smooth muscle cell (VSMC) calcification, but the underlying mechanisms remain unclear. Hypoxia-inducible factor-1α (HIF-1α), one of the major factors during hypoxia, and pyruvate dehydrogenase kinase 4 (PDK4), an important mitochondrial matrix enzyme in cellular metabolism shift, have been reported in VSMC calcification. The potential link among HIF-1α, PDK4, and AGEs-induced vascular calcification was investigated in this study. We observed that AGEs elevated HIF-1α and PDK4 expression levels in a dose-dependent manner and that maximal stimulation was attained at 24 h. Two important HIF-1α-regulated genes, vascular endothelial growth factor A (VEGFA) and glucose transporter 1 (GLUT-1), were significantly increased after AGEs exposure. Stabilization or nuclear translocation of HIF-1α increased PDK4 expression. PDK4 inhibition attenuated AGEs-induced VSMC calcification, which was evaluated by measuring the calcium content, alkaline phosphatase (ALP) activity and runt-related transcription factor 2 (RUNX2) expression levels and by Alizarin red S staining. In addition, the glucose consumption, lactate production, key enzymes of glucose metabolism and oxygen consumption rate (OCR) were decreased during AGEs-induced VSMC calcification. In conclusion, this study suggests that AGEs accelerate vascular calcification partly through the HIF-1α/PDK4 pathway and suppress glucose metabolism.


Evaluation of the water quality of a highly polluted stream with water quality indices and health risk assessment methods.
The water quality of Çorlu Stream, located in the Thrace region of Türkiye, and exposed to intense industrial pressure, was evaluated by monitoring 10 toxic metals and 13 other water quality variables in the dry and wet seasons of 2021. Seven different water quality indices were applied to determine the pollution level at the sampling stations in the stream. In addition, human health risks from exposure to toxic metals in stream water via ingestion and dermal contact were evaluated. The results showed that the water quality at stations S2 and S3 of Çorlu Stream receiving domestic and industrial discharges are seriously polluted by NH4-N, PO4-P, COD, BOD5 and suspended solids according to surface water quality standards. In addition, these stations were highly polluted and had poor water quality according to the results of the water quality indices. The average Cr level at station S3 exceeded the permissible levels set for the protection of aquatic life due to effluent discharges from the leather factories. Considering the results of the health risk assessment methods, non-carcinogenic risks from ingestion of combined metals in stream water can be expected at station S3 for both children and adults and at station S2 for children. Also, it was estimated that Cr and As at station S3 may cause carcinogenic health risks for residents.


A plant RNA virus inhibits NPR1 sumoylation and subverts NPR1-mediated plant immunity.
NONEXPRESSER OF PATHOGENESIS-RELATED GENES 1 (NPR1) is the master regulator of salicylic acid-mediated basal and systemic acquired resistance in plants. Here, we report that NPR1 plays a pivotal role in restricting compatible infection by turnip mosaic virus, a member of the largest plant RNA virus genus Potyvirus, and that such resistance is counteracted by NUCLEAR INCLUSION B (NIb), the viral RNA-dependent RNA polymerase. We demonstrate that NIb binds to the SUMO-interacting motif 3 (SIM3) of NPR1 to prevent SUMO3 interaction and sumoylation, while sumoylation of NIb by SUMO3 is not essential but can intensify the NIb-NPR1 interaction. We discover that the interaction also impedes the phosphorylation of NPR1 at Ser11/Ser15. Moreover, we show that targeting NPR1 SIM3 is a conserved ability of NIb from diverse potyviruses. These data reveal a molecular "arms race" by which potyviruses deploy NIb to suppress NPR1-mediated resistance through disrupting NPR1 sumoylation.


Robust perceptual-load-dependent audiovisual integration in adult ADHD.
We perceive our daily-life surrounded by different senses (e.g., visual, and auditory). For a coherent percept, our brain binds those multiple streams of sensory stimulations, i.e., multisensory integration (MI). Dependent on stimulus complexity, early MI is triggered by bottom-up or late via top-down attentional deployment. Adult attention-deficit/hyperactivity disorder (ADHD) is associated with successful bottom-up MI and deficient top-down MI. In the current study, we investigated the robustness of the bottom-up MI by adding additional task demand varying the perceptual load. We hypothesized diminished bottom-up MI for high perceptual load for patients with ADHD. 18 adult patients with ADHD and 18 age- and gender-matched healthy controls participated in this study. In the visual search paradigm, a target letter was surrounded by uniform distractors (low load) or by different letters (high load). Additionally, either unimodal (visual flash, auditory beep) or multimodal (audiovisual) flanked the visual search. Linear-mixed modeling was used to investigate the influence of load on reaction times. Further, the race model inequality was calculated. Patients with ADHD showed a similar degree of MI performance like healthy controls, irrespective of perceptual load manipulation. ADHD patients violated the race model for the low load but not for the high-load condition. There seems to be robust bottom-up MI independent of perceptual load in ADHD patients. However, the sensory accumulation might be altered when attentional demands are high.


Antioxidant status during the course of Eimeria tenella infection in broiler chickens.
The antioxidant status of broiler chickens (Cobb 500 hybrids) infected with Eimeria tenella was monitored by determining blood plasma malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT). The results of the experiment showed an increase in MDA - a marker of radical-induced damage of E. tenella-infected birds, compared to healthy chickens (3.01 micro mol/L vs. 2.55 micro mol/L, P<0.05). Correspondingly, a decreased SOD activity was observed in infected birds compared to controls (2429.0 U/g Hb vs. 3044.6 U/g Hb, P<0.05). Furthermore, CAT activity in infected birds was higher than in healthy ones (2242.2 U/g Hb vs. 1367.0 U/g Hb, P<0.001). The observed enzyme changes suggest an impaired antioxidant status of chickens during the course of an E. tenella infection and the occurrence of oxidative stress following infection. Alterations in the caecum, oocyst production, weight gain and feed conversion ratio were indicative of a severe infection involving pathogenic oxidative stress and impaired ecological oxidative balance.


Bacterial antioxidant mechanism in calcium peroxide aided sludge anaerobic fermentation.
Although calcium peroxide (CaO2) can enhance the short-chain fatty acids (SCFAs) production in sludge anaerobic fermentation, the microbiological mechanisms underlying this process remain unclear. In this study, it is aimed to elucidate the bacterial protective mechanisms in response to the oxidative stress induced by CaO2. Results show that extracellular polymeric substance (EPS) and anti-oxidant enzymes play vital roles in protecting bacterial cells from CaO2. The addition of CaO2 resulted in increased relative abundances of genes exoP and SRP54, which are associated with EPS secretion and transportation. Superoxide dismutase (SOD) played a crucial in alleviating oxidative stress. The dosage of CaO2 significantly influences the succession of the bacterial community in the anaerobic fermentation system. With 0.3 g CaO2/g VSS, the net income was approximately 4 USD/ton of sludge treated. The CaO2-assisted anaerobic fermentation process has the potential to recover more resources from sludge and thus, benefit the environment.


Orexin/hypocretin receptor 1 signaling mediates Pavlovian cue-food conditioning and extinction.
Learned food cues can drive feeding in the absence of hunger, and orexin/hypocretin signaling is necessary for this type of overeating. The current study examined whether orexin also mediates cue-food learning during the acquisition and extinction of these associations. In Experiment 1, rats underwent two sessions of Pavlovian appetitive conditioning, consisting of tone-food presentations. Prior to each session, rats received either the orexin 1 receptor antagonist SB-334867 (SB) or vehicle systemically. SB treatment did not affect conditioned responses during the first conditioning session, measured as food cup behavior during the tone and latency to approach the food cup after the tone onset, compared to the vehicle group. During the second conditioning session, SB treatment attenuated learning. All groups that received SB, prior to either the first or second conditioning session, displayed significantly less food cup behavior and had longer latencies to approach the food cup after tone onset compared to the vehicle group. These findings suggest orexin signaling at the 1 receptor mediates the consolidation and recall of cue-food acquisition. In Experiment 2, another group of rats underwent tone-food conditioning sessions (drug free), followed by two extinction sessions under either SB or vehicle treatment. Similar to Experiment 1, SB did not affect conditioned responses during the first session. During the second extinction session, the group that received SB prior to the first extinction session, but vehicle prior to the second, expressed conditioned food cup responses longer after tone offset, when the pellets were previously delivered during conditioning, and maintained shorter latencies to approach the food cup compared to the other groups. The persistence of these conditioned behaviors indicates impairment in extinction consolidation due to SB treatment during the first extinction session. Together, these results demonstrate an important role for orexin signaling during Pavlovian appetitive conditioning and extinction.


Survival analysis with incomplete genetic data.
Genetic data are now collected frequently in clinical studies and epidemiological cohort studies. For a large study, it may be prohibitively expensive to genotype all study subjects, especially with the next-generation sequencing technology. Two-phase sampling, such as case-cohort and nested case-control sampling, is cost-effective in such settings but entails considerable analysis challenges, especially if efficient estimators are desired. Another type of missing data arises when the investigators are interested in the haplotypes or the genetic markers that are not on the genotyping platform used for the current study. Valid and efficient analysis of such missing data is also interesting and challenging. This article provides an overview of these issues and outlines some directions for future research.


Ischemic preconditioning and long-chain acyl carnitine in the canine heart.
This study investigated the effects of ischemic preconditioning on myocardial carnitine-linked metabolism and high-energy phosphates in the canine model of ischemia and reperfusion. Anesthetized dogs underwent 1 hour of coronary artery occlusion and 4.5 hours of reperfusion. The dogs were randomly assigned to a control group (no intervention for 30 minutes), a preconditioned group (four repeated episodes of 3 minutes of mechanical coronary occlusion, each followed by 5 minutes of reperfusion), and a coronary cyclic flow variation (CFV) group (coronary artery stenosis and endothelial injury, resulting in an average of four episodes of platelet thrombosis and dislodgment). After completion of the protocol, ATP, creatine phosphate, and long-chain acyl carnitine concentrations were studied in both nonischemic and previously ischemic myocardium. In Part I of this study (Ovize et al., Circulation 1992, 85:779-789), it was reported that both mechanical occlusion and CFV before sustained occlusion resulted in a decrease in infarct size. In the present paper, we report changes in high-energy phosphates and long-chain acyl carnitine in these groups. Control, preconditioned, and CFV groups showed similar depletion in ATP content and "overshoot" in creatine phosphate stores. Control dogs exhibited a significant accumulation of long-chain acyl carnitine in the previously ischemic tissue (219 +/- 61 vs 131 +/- 38 nmoles/g wet weight in the nonischemic tissue; P < 0.05). No significant increase in long-chain acyl carnitine occurred in the mechanically preconditioned and CFV groups. These results indicate that brief episodes of transient ischemia before sustained coronary occlusion prevent long-chain acyl carnitine accumulation in the ischemic and reperfused canine myocardium.


Immunogenicity and protective efficacy of recombinant Modified Vaccinia virus Ankara candidate vaccines delivering West Nile virus envelope antigens.
West Nile virus (WNV) cycles between insects and wild birds, and is transmitted via mosquito vectors to horses and humans, potentially causing severe neuroinvasive disease. Modified Vaccinia virus Ankara (MVA) is an advanced viral vector for developing new recombinant vaccines against infectious diseases and cancer. Here, we generated and evaluated recombinant MVA candidate vaccines that deliver WNV envelope (E) antigens and fulfil all the requirements to proceed to clinical testing in humans. Infections of human and equine cell cultures with recombinant MVA demonstrated efficient synthesis and secretion of WNV envelope proteins in mammalian cells non-permissive for MVA replication. Prime-boost immunizations in BALB/c mice readily induced circulating serum antibodies binding to recombinant WNV E protein and neutralizing WNV in tissue culture infections. Vaccinations in HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice elicited WNV E-specific CD8+ T cell responses. Moreover, the MVA-WNV candidate vaccines protected C57BL/6 mice against lineage 1 and lineage 2 WNV infection and induced heterologous neutralizing antibodies. Thus, further studies are warranted to evaluate these recombinant MVA-WNV vaccines in other preclinical models and use them as candidate vaccine in humans.


Discovery of a dsRNA virus infecting the marine photosynthetic protist Micromonas pusilla.
We report the isolation of the first double-stranded (ds) RNA virus in the family Reoviridae that infects a protist (microalga Micromonas pusilla, Prasinophyceae). The dsRNA genome was composed of 11 segments ranging between 0.8 and 5.8 kb, with a total size of approximately 25.5 kb. The virus (MpRNAV-01B) could not be assigned to the genus level because host type, genome size, and number of segments smaller than 2 kb did not correspond to either of the two existing 11-segmented dsRNA genera Rotavirus and Aquareovirus. MpRNAV-01B has a particle size of 65-80 nm, a narrow host range, a latent period of 36 h, and contains five major proteins (120, 95, 67, 53, and 32 kDa). MpRNAV-01B was stable to freeze-thawing, resistant to chloroform, ether, nonionic detergents, chelating and reducing agents. The virus was inactivated at temperatures above 35 degrees C and by ionic detergent, ethanol, acetone, and acidic conditions (pH 2-5).


Multiomics implicate gut microbiota in low cypermethrin (CP) exposure induced multiorgan toxicological effects in pubertal male rats.
Cypermethrin (CP), widely used as a broad-spectrum pesticide, has raised concerns over its frequent presence in the environment and potential health risks. The present study focused on incorporating the gut-organ axis theory to reinterpret the toxicological effects and mechanisms following CP exposure at environmentally relevant concentrations (0.1 mg/kg/d and 0.5 mg/kg/d) in pubertal male rats. The results showed alterations in histopathological and organosomatic indices in the liver, brain, and epididymis. Through multiomics network analysis, it was found that Lachnospiraceae and Ruminococcaceae may contribute to the alteration in serum L-carnitine and trigonelline, leading to hepatic lipid accumulation following CP exposure. Additionally, Ruminococcaceae, Lachnospiraceae, and Porphyromonadaceae were associated with CP-induced glutamatergic hypofunction and overproduction of TNF-α, potentially contributing to the brain neurotoxicity. Overall, the study provides important insights into the potential mechanisms underlying CP-induced toxicity and highlights the need for continued research to fully understand the implications for CP-induced health risks. The incorporation of the gut-organ axis theory in the study provides a promising avenue for future research into the potential interactions between gut microbiota and organ toxicity, and the potential for targeted interventions to mitigate the adverse effects of environmental toxins.


A multicenter study on the preoperative prediction of gastric cancer microsatellite instability status based on computed tomography radiomics.
To construct and validate a radiomics feature model based on computed tomography (CT) images and clinical characteristics to predict the microsatellite instability (MSI) status of gastric cancer patients before surgery. We retrospectively collected the upper abdominal or the entire abdominal-enhanced CT scans of 189 gastric cancer patients before surgery. The patients underwent postoperative gastric cancer MSI status testing, and the dates of their radiologic images and clinicopathological data were from January 2015 to August 2021. These 189 patients were divided into a training set (n = 90) and an external validation set (n = 99). The patients were divided by MSI status into the MSI-high (H) arm (30 and 33 patients in the training set and external validation set, respectively) and MSI-low/stable (L/S) arm (60 and 66 patients in the training set and external validation set, respectively). In the training set, the clinical characteristics and tumor radiologic characteristics of the patients were extracted, and the tenfold cross-validation method was used for internal validation of the training set. The external validation set was used to assess its generalized performance. A receiver-operating characteristic (ROC) curve was plotted to assess the model performance, and the area under the curve (AUC) was calculated. The AUC of the radiomics model in the training set and external validation set was 0.8228 [95% confidence interval (CI) 0.7355-0.9101] and 0.7603 [95% CI 0.6625-0.8581], respectively, showing that the constructed radiomics model exhibited satisfactory generalization capabilities. The accuracy, sensitivity, and specificity of the training dataset were 0.72, 0.63, and 0.77, respectively. The accuracy, sensitivity, and specificity of the external validation dataset were 0.67, 0.79, and 0.60, respectively. Statistical analysis was carried out on the clinical data, and there was statistical significance for the tumor site and age (p < 0.05). MSI-H gastric cancer was mostly seen in the gastric antrum and older patients. Radiomics markers based on CT images and clinical characteristics have the potential to be a non-invasive auxiliary diagnostic tool for preoperative assessment of gastric cancer MSI status, and they can aid in clinical decision-making and improve patient outcomes.


Genome-wide analysis of AP2/ERF transcription factors in pineapple reveals functional divergence during flowering induction mediated by ethylene and floral organ development.
The APETALA2/ethylene-responsive factor (AP2/ERF) has important roles in regulating developmental processes and hormone signaling transduction in plants. Pineapple demonstrates a special sensitivity to ethylene, and AP2/ERFs may contribute to this distinct sensitivity of pineapples to ethylene. However, little information is available on the AP2/ERF of pineapple. In this study, 97 AP2/ERF family members were identified from the pineapple genome. The AcAP2/ERF superfamily could be further divided into five subfamilies, and different subfamily existed functional divergence in multifarious biological processes. ERF and RAV subfamily genes might play important roles in the process of ethylene response of pineapple; ERF and DREB subfamily genes had particular functions in the floral organ development. This study is the first to provide detailed information on the features of AP2/ERFs in pineapple, provide new insights into the potential functional roles of the AP2/ERF superfamily members, and will facilitate a better understanding of the molecular mechanism of flower in pineapple.


Hormonal influences on the relationships between body fatness, body fat distribution, lipids, lipoproteins, glucose and blood pressure in French working women.
The independent associations between overall obesity, body fat distribution, lipids, lipoproteins, glucose, blood pressure and some hormonal factors (sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG) and fasting insulin) were cross-sectionally examined in 205 French working women. After adjustment for age, overall adiposity assessed by body mass index (BMI) was significantly associated with most metabolic parameters, whereas regional adiposity assessed by the waist-hip ratio (WHR) was significantly associated only with triglyceride, systolic and diastolic blood pressure. Blood pressure, glucose but not triglyceride, were also negatively and significantly correlated with SHBG and positively with fasting insulin. Negative independent associations were found between SHBG and both BMI and WHR, whereas CBG was positively associated only with WHR. Fasting insulin was no longer related to WHR after adjustment for BMI. After controlling for the effect of SHBG or insulin, the associations between triglyceride, blood pressure and both BMI and WHR were not substantially modified. After adjustment for BMI and WHR, fasting insulin was independently associated with both HDL cholesterol and diastolic blood pressure. In conclusion, in these French women, hormonal factors under study appeared to have little influence on the relationships between body fatness, body fat distribution, metabolic variables and blood pressure.


Biochemical effects on combined gases of nitrogen dioxide and ozone. I. Species differences of lipid peroxides and phospholipids in lungs.
In the present study, changes of lipid peroxides, phospholipids and antioxidant levels in lungs of 4 animal species exposed to the combined gases of NO2 and O3 were compared. Male mice, hamsters, rats and guinea pigs were used. Lipid peroxides were increased significantly in the lungs of mice and guinea pigs exposed to the combined gases, but not in hamsters and rats. Changes of alpha-tocopherol (VE) contents were slight. On the other hand, non-protein sulfhydryl (NPSH) contents were increased strikingly, especially in hamsters, but were not increased in guinea pigs. Phosphatidylcholine (PC) contents were increased and phosphatidylethanolamine (PE) contents were decreased by the exposure to the combined gases, with the order guinea pig greater than mouse greater than rat. In hamsters no changes were seen. The changes of fatty acid composition in guinea pigs and mice were marked, the increases of palmitate and palmitolate and the decreases of polyunsaturated fatty acid were especially characteristic. These changes in phospholipid class and fatty acid composition may be a "a kind of adaptation phenomenon" to avoid further lipid peroxidation. On the other hand, the changes in hamsters and rats were small. The results show the existence of species differences in lipid peroxide formation by exposure to the combined gases of NO2 and O3. They were found to be related to the contents of antioxidants and the compositions of phospholipids and their fatty acids.


The 1α,25-dihydroxy-vitamin D3 reduces dengue virus infection in human myelomonocyte (U937) and hepatic (Huh-7) cell lines and cytokine production in the infected monocytes.
Dengue is the most important mosquito-borne viral infection in humans. Recent evidence suggests that vitamin D influences virus replication. In this work, the effect of vitamin D treatment on dengue virus infection in human hepatic Huh-7 cells and on virus infection and cytokine production in the human monocytic U937 cells was evaluated. Exposure to 1α,25-dihydroxy-vitamin D3, resulted in a significant reduction in the number of infected cells, in conditions where cell viability was not affected. Viral replication in monocytic cells was more susceptible to vitamin D3 than replication in the hepatic cells. Moreover, vitamin D3 significantly reduced the levels of proinflammatory cytokines (TNF-α, IL-6, IL-12p70 and IL-1β) produced by infected U937 cells. These results suggest that vitamin D3 may represent a potentially useful antiviral compound.


Clinical pharmacy services are reimbursed in Germany: challenges of real world implementation remain.
Over the last two decades, community pharmacy has experienced major changes as the role of pharmacists is evolving from a product to a service and a patient focus. As part of this change, new and innovative clinical pharmacy services aimed at improving medicines use and patient outcomes have been designed, both nationally and internationally. Since June 2022, five services are reimbursed by all statutory health insurance funds and private insurance companies in Germany: medication review for patients with polymedication; blood pressure control in hypertension; assuring proper inhalation techniques for patients receiving a new device or a device change; medication review including a follow-up for patients taking oral anticancer drugs or immunosuppressants post-transplantation. Beyond reimbursement, the upscaling and sustainable provision of these professional services are now the main challenges. Implementation research will provide important information for the further development of pharmaceutical care programs.


ESR spin label and ultrastructural monitoring of protein-lipid interactions in the lens fiber-cell plasma membranes in relation to human ageing and cataractogenesis.
The Electron Spin Resonance (ESR) technique and the protein spin labels 2,2,4,4,9-pentamethyl-1,2,3,4-tetrahydro-gamma-carboline-3-oxyl and 4-(N-maleimido)-2,2,6,6-tetramethylpiperidine-1-oxyl were used in this study to probe the fluidity and binding ability to protein functional groups in human lens membranes. The image and the stage of cataract as well as the ultrastructural characteristics of the lens fiber cell membranes were evaluated in parallel studies. ESR measurements in membrane structures of the transparent lenses of different ages have shown that the sorbtion parameter of the carboline label on the surface of protein-lipid components was usually weakly expressed but increased with aging and the extent of immobilization of the bound label was not significant. At different stages of the lens opacification the carboline analogue spin label increasingly bound to the lens membranous structures. A spin label signal can be enhanced by addition to the samples of the paramagnetic probe K3Fe(CN)6. The maleimide spin label bound to the protein SH-groups in the cataractous lens membranes at a slow rate, however in transparent lenses a gradual increase of the rapidly binding phase of this label could be detected. The results show an appearance of at least two types of the reactive SH-groups in membranes of human transparent lenses. The electron microscopic studies suggested that the age-related and cataractogenic changes in the lens matter are accompanied by deterioration of the lenticular fiber plasma membranes and formation of the coalescing globules with a diameter of 220-500 nm. At the stage of cataract with advanced opacities, which is biochemically characterized by the increase in number of the carboline label binding sites with the surface proteins and annular lipids of membranes, a mass of amorphous aggregates filled with the electron-grey debris is formed contributing to significant scatter of light. It appears, therefore, that the suggested ESR spin label technique can be effectively used to monitor the aggregation process of protein membrane components which takes place during human cataractogenesis.


Intestinal permeability and systemic endotoxemia after laparotomic or laparoscopic cholecystectomy.
Because laparoscopic cholecystectomy (LC) is widely recognized as a "mild" or "mini-invasive" kind of surgery, in this prospective nonrandomized study, we investigated the effect of intestinal manipulation on intestinal permeability and endotoxemia, in patients undergoing elective cholecystectomy by comparing the laparoscopic with the laparotomic approach. The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. Forty-three patients undergoing elective cholecystectomy were divided into either the laparotomic (n = 22) or laparoscopic (n = 21) approach. Intestinal permeability was measured preoperatively and at day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. Intestinal permeability was significantly increased at day 1 [0.106 +/- 0.005 (mean +/- SEM)] in the laparotomic group compared with the preoperative level (0.019 +/- 0.005, P < 0.05) and to the laparoscopic group at day 1 (0.019 +/- 0.005, P < 0.05), which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison to the laparoscopic group (P < 0.05). There was a significant positive correlation between systemic endotoxemia and intestinal permeability (r(s) = 0.958; P = 0.001). An increase in intestinal permeability and a greater degree of systemic endotoxemia are observed during laparotomic cholecystectomy. This suggests that intestinal manipulation may impair gut mucosal barrier function and contribute to the systemic inflammatory response see in open cholecystectomy.


Evolution of highly repeated DNA within the genusTriturus (Amphibia, Urodela).
Highly repeated DNA is a main feature of urodele amphibian genomes. InTriturus this class of DNA consists of several sequence families differently arranged at both the molecular and the chromosomal level, showing varying degrees of conservation across species. Present data on highly repeated DNA inTriturus are here summarized and discussed with regard to the evolution and possible functional role of these sequences.