A genetic selection for isolating cDNAs encoding secreted proteins.
We describe a simple, rapid technique for simultaneously isolating large numbers of cDNAs encoding secreted proteins. The technique makes use of a facile genetic selection performed in a strain of Saccharomyces cerevisiae deleted for its endogenous invertase gene. A cDNA cloning vector which carries a modified invertase gene lacking its leader sequence is used in conjunction with this strain. Heterologous secreted genes fused appropriately upstream of this defective invertase provide the necessary signals to restore secretion, allowing the yeast to grow on sugars such as sucrose or raffinose. This microbial growth selection facilitates scanning cDNA libraries containing millions of clones, enabling the wholesale identification of novel secreted proteins without the need for specific bioassays. The technique is similar to one previously described (Klein et al. (1996) Proc. Natl. Acad. Sci. USA 93, 7108-7113). We describe results using a cDNA library derived from activated human peripheral blood mononuclear cells (PBMC). Genes identified from this library encoded signal sequences of proteins of diverse structure, function, and cellular location such as cytokines, type 1 and type 2 transmembrane proteins, and proteins found in intracellular organelles. In addition, a number of novel secreted proteins were identified, including a chemokine and a novel G-protein-coupled receptor. Since signal sequences possess features conserved throughout evolution, the procedure can be used to isolate genes encoding secreted proteins from both eukaryotes and prokaryotes.


Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice.
B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region, and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for the successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an open chromatin state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacked both GCN5 and PCAF in B cells. Double-deficient mice possessed low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We concluded that both GCN5 and PCAF are required for B-cell development in vivo.


Stiffness Measurement of Drosophila Egg Chambers by Atomic Force Microscopy.
Drosophila egg chamber development requires cellular and molecular mechanisms controlling morphogenesis. Previous research has shown that the mechanical properties of the basement membrane contribute to tissue elongation of the egg chamber. Here, we discuss how indentation with the microindenter of an atomic force microscope can be used to determine an effective stiffness value of a Drosophila egg chamber. We provide information on the preparation of egg chambers prior to the measurement, dish coating, the actual atomic force microscope measurement process, and data analysis. Furthermore, we discuss how to interpret acquired data and which mechanical components are expected to influence measured stiffness values.


Does hysteroscopic resection of polyps require cycle cancellation in women undergoing controlled ovarian hyperstimulation in the ICSI cycle?
Endometrial polyps are one of the most extensive pathologies in the uterus and can be detected incidentally during assisted reproductive therapy in asymptomatic women. In patients planned for in vitro fertilization or intracytoplasmic sperm injection (ICSI) treatment, embryo freezing, or cycle cancelation options are mandatory in many clinics when detected at the beginning of the cycle. In our study, in ICSI treatment, patients with a single endometrial polyp smaller than 1.5 cm, who underwent hysteroscopic polyp resection at the beginning of the cycle and underwent fresh embryo transfer without canceling the treatment (n=31), and patients with the same characteristics of endometrial polyp who underwent hysteroscopic polyp resection before the cycle (n=34) are compared within the pregnancy, abortion and live birth rates. As a result, no statistical difference was found between the two groups' pregnancy, abortion, and live birth rates. Hysteroscopic resection of polyps during ovarian stimulation in ICSI treatment does not affect pregnancy and live birth rates and may eliminate the necessity of freezing.


Development and evaluation of a facile mesh-to-surface tool for customised wheelchair cushions.
Custom orthoses are becoming more commonly prescribed for upper and lower limbs. They require some form of shape-capture of the body parts they will be in contact with, which generates an STL file that designers prepare for manufacturing. For larger devices such as custom-contoured wheelchair cushions, the STL created during shape-capture can contain hundreds of thousands of tessellations, making them difficult to alter and prepare for manufacturing using mesh-editing software. This study covers the development and testing of a mesh-to-surface workflow in a parametric computer-aided design software using its visual programming language such that STL files of custom wheelchair cushions can be efficiently converted into a parametric single surface. A volunteer in the clinical space with expertise in computer-aided design aided was interviewed to understand and document the current workflow for creating a single surface from an STL file of a custom wheelchair cushion. To understand the user needs of typical clinical workers with little computer-aided design experience, potential end-users of the process were tasked with completing the workflow and providing feedback during the experience. This feedback was used to automate part of the computer-aided design process using a visual programming tool, creating a new semi-automated workflow for mesh-to-surface translation. Both the original and semi-automated process were then evaluated by nine volunteers with varying levels of computer-aided design experience. The semi-automated process showed a 37% reduction in the total number of steps required to convert an STL model to a parametric surface. Regardless of previous computer-aided design experience, volunteers completed the semi-automated workflow 31% faster on average than the manual workflow. The creation of a semi-automated process for creating a single parametric surface of a custom wheelchair cushion from an STL mesh makes mesh-to-surface conversion more efficient and more user-friendly to all, regardless of computer-aided design experience levels. The steps followed in this study may guide others in the development of their own mesh-to-surface tools in the wheelchair sector, as well as those creating other large custom prosthetic devices.


Soft tissue coverage of the arm.
The latissimus dorsi muscle is the main flap used for soft tissue coverage of the arm. It can be tailored to size or tissue type (skin and/or muscle), and can provide function for elbow flexion and extension. When required it can cover both the arm and elbow.


Quantum dots enhance Cu2+ -induced hepatic L02 cells toxicity.
As a new class of xenogenous nanoparticle, quantum dots (QDs) possess the potential to co-exist with CU2+ in human liver. The combined toxicity is thus concerned. Considering QDs and Cu2+ are known ROS (reactive oxygen species) inducer, we investigated the combined oxidative stress and corresponding protective strategy using human hepatic L02 cells. The results demonstrated that the presence of a small amount of MPA-CdTe QDs (2 microg/mL) in a Cu2+ solution (2.5-20 microg/mL) resulted in a higher toxicity with up to 8-fold cell viability decrease, which was accompanied by cell morphology changes. The combined toxicity was then confirmed as ROS associated oxidative stress with up to 300% and 35% increase of the intracellular ROS level and glutathione S-transferase (GST) activity, respectively. N-acetylcysteine (NAC) can also provide almost complete protection against the induced toxicity. Therefore, the ROS associated oxidant injury might be responsible for the QDs-Cu2+/CU2+ induced toxicity and could be balanced through cytoprotective antioxidant enzyme GST.


Long non-coding RNA BRE-AS1 inhibits the proliferation, migration, and invasion of cancer cells in triple-negative breast cancer and predicts patients' survival by downregulating miR-21.
BRE-AS1 is a recently identified tumor suppressor in non-small cell lung cancer. It role in other human diseases remains elusive. Differential expression of BRE-AS1 in with triple-negative breast cancer (TNBC) patients (n = 74, patient group) and healthy volunteers (n = 58, control group) was studied with RT-qPCR. The direct interaction between BRE-AS1 and premature microRNA-21 (miR-21) was assessed by RNA pull-down assay. The interactions among BRE-AS1, miR-21 and PTEN were evaluated by overexpression assays. CCK-8 assay and Transwell assay were used to evaluate cell behaviors. BRE-AS1 was downregulated in TNBC, while miR-21 was highly expressed in TNBC. Low expression levels of lncRNA BRE-AS1 and high expression levels of miR-21 were significantly correlated with unfavorable survival outcomes. BRE-AS1 and miRNA-21 were inversely correlated across TNBC samples, not control samples. BRE-AS1 decreased miR-21 expression and increased PTEN expression while miR-21showed no role in BRE-AS1 expression. RNA pull-down assay illustrated that BRE-AS1 may sponge premature miR-21 to suppress it maturation. Overexpression of BRE-AS1 decreased cell behaviors, while overexpression of miR-21 promoted cell behaviors. MiR-21 suppressed the role of BRE-AS1 in cancer cell behaviors. Therefore, BRE-AS1 may inhibit TNBC by downregulating miR-21.


The RLCK-VND6 module coordinates secondary cell wall formation and adaptive growth in rice.
The orderly deposition of secondary cell wall (SCW) in plants is implicated in various biological programs and is precisely controlled. Although many positive and negative regulators of SCW have been documented, the molecular mechanisms underlying SCW formation coordinated with distinct cellular physiological processes during plant adaptive growth remain largely unclear. Here, we report the identification of Cellulose Synthase co-expressed Kinase1 (CSK1), which encodes a receptor-like cytoplasmic kinase, as a negative regulator of SCW formation and its signaling cascade in rice. Transcriptome deep sequencing of developing internodes and genome-wide co-expression assays revealed that CSK1 is co-expressed with cellulose synthase genes and is responsive to various stress stimuli. The increased SCW thickness and vigorous vessel transport in csk1 indicate that CSK1 functions as a negative regulator of SCW biosynthesis. Through observation of green fluorescent protein-tagged CSK1 in rice protoplasts and stable transgenic plants, we found that CSK1 is localized in the nucleus and cytoplasm adjacent to the plasma membrane. Biochemical and molecular assays demonstrated that CSK1 phosphorylates VASCULAR-RELATED NAC-DOMAIN 6 (VND6), a master SCW-associated transcription factor, in the nucleus, which reduces the transcription of a suite of SCW-related genes, thereby attenuating SCW accumulation. Consistently, genetic analyses show that CSK1 functions upstream of VND6 in regulating SCW formation. Interestingly, our physiological analyses revealed that CSK1 and VND6 are involved in abscisic acid-mediated regulation of cell growth and SCW deposition. Taken together, these results indicate that the CSK1-VND6 module is an important component of the SCW biosynthesis machinery, which coordinates SCW accumulation and adaptive growth in rice. Our study not only identifies a new regulator of SCW biosynthesis but also reveals a fine-tuned mechanism for precise control of SCW deposition, offering tools for rationally tailoring agronomic traits.


Energy status determines hindbrain signal transduction pathway transcriptional reactivity to AMPK in the estradiol-treated ovariectomized female rat.
Dorsal vagal complex (DVC) AMPK regulation of food intake in the estradiol-treated ovariectomized (OVX) female rat is energy state-dependent. Here, RT-PCR array technology was used to identify estradiol-sensitive AMPK-regulated DVC signal transduction pathways that exhibit differential reactivity to sensor activation during energy balance versus imbalance. The AMP mimetic AICAR correspondingly reduced or stimulated cDVC phosphoAMPK (pAMPK) and estrogen receptor-beta (ERβ) proteins in full-fed (F) versus 12-h food-deprived (D) estradiol-treated ovariectomized (OVX) rats, but elevated ER-alpha (ERα) in F only. Estradiol suppressed DVC ERβ protein and hypoxia, NFκB, STAT3, STAT6, and Hedgehog signaling pathway marker genes against oil-implanted OVX controls. F+(A)ICAR and D+(S)aline groups each exhibited further inhibition of NFκB, STAT3, and Hedgehog pathway genes, and diminished PPAR, Notch, and STAT5 transcripts versus F+S. Conversely, genes in these six pathways were up-regulated by AICAR treatment of D. Results show that in this animal model, acute AMP augmentation or feeding cessation each inhibit both pAMPK and ERβ expression, but in combination increase these protein profiles. pAMPK protein and DVC TNF (NFκB), SOCS3 (JAK/STAT), WNT6 (Hedgehog), and FABP1 (PPAR) mRNAs were down- or upregulated in parallel by AICAR in F versus D states, respectively. Further research is needed to determine the impact of ERβ on opposing directionality of these responses, and to characterize the role of the aforementioned signaling pathways in hyperphagic responses in the female to AICAR-induced DVC AMPK activation during acute interruption of feeding.


Induction of cyclooxygenase-2 following anoxic stress in piglet cerebral arteries.
Ischemic stress causes damage to cerebrovascular endothelium and alters arteriolar responses to prostanoid-dependent stimuli. However, effects of ischemic stress on cyclooxygenase (COX) levels in endothelium are unclear. We examined the effect of ischemia and reperfusion and asphyxia and reventilation on production of COX isoforms in cerebral vascular endothelium. Neonatal pigs were exposed to global ischemia (n = 4) or asphyxia (n = 3) for 5-10 min. Following 2-6 h of recovery, the animals were killed, and the cerebral arteries and arterioles were removed. Cerebral arteries and arterioles were also removed from untreated control animals (n = 1) and from time control animals (n = 3). Cerebral vessels were fixed in 4% formalin and paraffin embedded, and constitutive and inducible COX (COX-1 and COX-2, respectively) levels were assessed using indirect immunofluorescence. Hemotoxylin and eosin staining indicated that anoxic stress leads to enlargement of endothelial cells. Immunofluorescence for COX-1 in endothelium was minimal in cerebral arteries and arterioles from control animals and did not show an increase in animals exposed to anoxic stress. Similarly, cerebral vessels from control animals showed little immunostaining for COX-2. In contrast, immunofluorescence for COX-2 was greatly increased in cerebral arteries and arterioles from animals exposed to asphyxia or ischemia. We concluded that anoxic stress increases COX-2 but not COX-1 levels in cerebral endothelium.


What do cancer support groups provide which other supportive relationships do not? The experience of peer support groups for people with cancer.
This qualitative study examined the questions of what cancer support groups provide that other supportive relationships do not, and what the self perceived consequences are of support group attendance. Nine representative Australian cancer peer support groups, consisting of a total of 93 interviewees, 75 women, and 18 men, with a mean age of 62, took part in participant observation and focus group interviews, with the data analysed using positioning theory. Support groups were positioned by participants as providing a unique sense of community, unconditional acceptance, and information about cancer and its treatment, in contrast to the isolation, rejection, and lack of knowledge about cancer frequently experienced outside the group. Groups were also positioned as occasionally emotionally challenging, in contrast to the experience of normalising support from family and friends. Increased empowerment and agency were positioned as the most significant consequences of group support, consisting of increased confidence and a sense of control in relation to self, living with cancer, and interactions with others, in particular the medical profession. The support group was also positioned as facilitating positive relationships with family and friends because of relieving their burden of care, by providing a safe space for the expression of emotion. No difference was found between professionally led and peer led support groups, suggesting that it is not the professional background of the leader which is of importance, but whether the group provides a supportive environment, mutuality, and a sense of belonging, and whether it meets the perceived needs of those attending. It is suggested that future research should examine the construction and experience of social support in those who drop out of, or who do not attend, cancer support groups, in order to provide further insight into the contrast between social support within groups and support in other contexts.


Montmorillonite-iron crosslinked alginate beads for aqueous phosphate removal.
Phosphate runoff from agriculture fields leads to eutrophication of the water bodies with devastating effects on the aquatic ecosystem. In this study, naturally occurring montmorillonite clay-incorporated iron crosslinked alginate biopolymer (MtIA) beads were synthesized and evaluated for aqueous phosphate removal. Batch experiment data showed an efficient phosphate removal (>99%) by the MtIA beads from solutions with different initial phosphate concentrations (1 and 5 mg PO43--P/L, and 100 μg PO43--P/L). The kinetic data fitted well into the pseudo-second-order kinetic model indicating chemisorption played an important role in phosphate removal. Based on analyses of results from the Elovich and intra-particulate diffusion models, phosphate removal by the MtIA beads was found to be chemisorption where both film diffusion and intra-particulate diffusion participated. The isotherm studies indicate that MtIA surfaces were heterogeneous, and the adsorption capacity of the beads calculated from Langmuir model was 48.7 mg PO43--P/g of dry beads which is ~2.3 times higher than values reported for other clay-metal-alginate beads. Electron microscopy (SEM-EDS) data from the beads showed a rough-textured surface which helped the beads achieve better contact with the phosphate ions. Fourier-transform infrared spectroscopy (FTIR) indicated that both iron and montmorillonite clay participated in crosslinking with the alginate chain. The MtIA beads worked effectively (>98% phosphate removal) over a wide pH range of 2-10 making it a robust adsorbent. The beads can potentially be used for phosphate recovery from eutrophic lakes, agricultural run-off, and municipal wastewater.


RGD peptides grafting onto poly(ethylene terephthalate) with well controlled densities.
The aim of this study was to graft RGD peptides with well controlled densities onto poly(ethylene terephthalate) (PET) film surfaces. Biomimetic modifications were performed by means of a four-step reaction procedure: surface modification in order to create -COOH groups onto polymer surface, coupling agent grafting and finally immobilization of peptides. The originality of this work is to evaluate several grafted densities peptides. Toluidine blue and high-resolution mu-imager (using [(3)H]-Lys) were used to evaluate densities. Moreover, mu-imager has exhibited the stability of peptides grafted onto the surface when treated under harsh conditions. Benefits of the as-proposed method were related to the different concentrations of peptides grafted onto the surface as well as the capacity of RGD peptide to interact with integrin receptors.


[Efficacy of disinfectants in contamination of eggs].
Good hygiene practices are essential in livestock production. Likewise hygienic production and storage of hatching eggs contribute to improve hatchability and to obtain healthier fowls. This study was designed to compare three methods of disinfection commonly used in poultry houses: fumigation with formaldehyde, pulverization of an iodophore and synthetic phenols. By washing eggs in sterile bags to determine the bacterial contamination on shells, the best results were obtained with formaldehyde, and the smallest bacterial decrease with the iodophore.


The imbalance of biliary microflora in hepatolithiasis.
The imbalance of microbial flora is thought to be associated with many diseases. However, the characteristics of the biliary microflora and its relation to in hepatolithiasis are unknown. This study included 40 patients with hepatolithiasis and 10 control patients. Bile samples were taken during hepatectomy surgeries and 16S rRNA sequencing was performed. The sequencing results were analyzed by operational taxonomic unit (OTU) clustering, species annotation and abundance analyses, sample complexity analyses, diversity analyses, and environmental factor correlation analyses. There were significant differences in bile microflora between the hepatolithiasis group and the control group. We found that the abundance of microflora in the bile of patients with hepatolithiasis was relatively high (52.4% versus 40.2% and 42.1% versus 29.6%). The diversity of microflora in the bile of patients with hepatolithiasis decreased significantly (Shannon (P = 0.004), Observed species (P = 0.001), PD-whole-tree (P = 0.001)). These differences are mainly associated with Enterococcus(P<0.001), Enterobacter(P = 0.003). In addition, we found that there were intra-group differences in hepatolithiasis, but the differences in the hepatolithiasis group were generally smaller than the differences in the non-hepatolithiasis group. There is an imbalance of microflora in the bile duct of patients with hepatolithiasis. The imbalance of biliary flora may be associated with hepatolithiasis pathogenesis.


Medicare reform and your practice: what you need to know.
Reimbursements for Medicare Part B physician-administered medications have been cut and will be further reduced in the years to come. Physician groups have supported the prescription benefit within the Medicare reform package. However, physician and patient advocacy groups alike are concerned about how other portions of the legislation will change the administration of Medicare Part B-covered drugs in the office setting. This article explores the payment changes built into the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, what the proponents and opposition have been saying, and how these changes will impact the practice of urology and patients with prostate cancer.


Efficacy of different designs of mandibular expanders: A 3-dimensional finite element study.
Nonsurgical mandibular expansion has been increasingly performed in recent years because it can effectively expand the mandibular dental arch. However, many types of mandibular expanders have been used in previous studies. No relevant studies have compared the biomechanical responses of different designs of mandibular expansion appliances with screws. Therefore, the purpose of this study was to analyze the stress distribution and displacement of the dentoalveolar structures according to different designs of mandibular screw expanders. Cone-beam computed tomography scans were used for 3-dimensional reconstruction of the mandibular finite element model. Four different designs of mandibular expanders, 1 removable expander (type A) and 3 fixed expanders (types B, C, and D), were added to the finite element models. Expanders were activated transversely for 0.2 mm. The initial tooth displacement and von Mises stress distribution were evaluated. All the expanders enlarged the arch dimensions. In types A and B, the stress was mainly concentrated in the region of the anterior teeth, along with greater tooth displacement, whereas in types C and D, greater stress and displacement occurred in the region of the posterior teeth. Type A showed the greatest amount of transverse displacement. Type D was more efficient in the region of the posterior teeth. Types A and B should be used with great caution in the clinic because of their incompatible expansion pattern. Type D is the recommended mandibular expansion appliance because of its appropriate expansion pattern.


Crosstalk in the non-classical signal transduction of testosterone and retinol in immature rat testes.
This study aimed to investigate the effects of the interaction between testosterone and retinol on the rapid responses of cultured Sertoli cells obtained from 10-day-old immature rat testes. Non-classical actions of testosterone and retinol were investigated, and the activities of L-type voltage-dependent calcium channels (L-VDCC) and voltage-dependent potassium channels (Kv) were determined by measuring 45Ca2+ influx in whole testis. Additionally, the effects of testosterone and retinol on these channels were studied in primary culture of Sertoli cells using the patch-clamp technique. 45Ca2+ influx was used to observe a dose-response curve on tissues treated with retinol and/or testosterone for 2 min (10-12, 10-9 and 10-6 M and 10-9 and 10-6 M), and a concentration of 10-6 M was selected to investigate the mechanism of action of testosterone and retinol on rapid responses. Participation of the L-VDCC and Kv channels was investigated using nifedipine and tetraethylammonium chloride (TEA) inhibitors, respectively. Both, testosterone and retinol act through non-classical mechanisms, stimulating 45Ca2+ influx in immature rat testes. The response to testosterone was abolished by nifedipine and TEA, whereas the effects of retinol were partially blocked by nifedipine and completely inhibited by TEA. Retinol amplified the testosterone-induced effect on 45Ca2+ influx in the testes, suggesting a crosstalk between rapid responses (calcium influx) and cell repolarization via activation of Kv channels. Whole-cell electrophysiology data demonstrated that testosterone and retinol increased voltage-dependent potassium currents (Kv) in Sertoli cells; inhibition of these responses by TEA confirmed the involvement of TEA-sensitive K+ channels in these effects. Taken together, we demonstrate, for the first time, crosstalk between testosterone and retinol that is mediated by a non-classical mechanism involving the L-VDCC-triggered cell depolarization and activation of repolarization by Kv currents in Sertoli cells. These ionic modulations play a physiological role in Sertoli cells and male fertility via stimulation of secretory activities.


Protein Intake, Adherence to Vitamin-Mineral Supplementation, and Dumping Syndrome in Patients Undergoing One Anastomosis Gastric Bypass.
One anastomosis gastric bypass (OAGB) is an effective bariatric procedure. However, nutritional deficiencies or dumping syndrome (DS) may occur. The aim of this study was to assess adherence to nutritional recommendations and development of DS in a 3-year OAGB patient follow-up. For 150 OAGB patients, in our center, data were collected through the electronic platform and by an individual telephone interview. The inclusion criterion is OAGB as a primary bariatric procedure, no revisional surgery, or no pregnancy. The adequacy of daily protein intake cutoff was defined as 60 g. Adherence to micronutrient supplementation protocol was considered if a minimum of 5 takes/week were reported. To evaluate the occurrence of DS, the Sigstad score questionnaire was used. For statistical analysis, a significance level less than 5% (p < 0.05) was considered. A total of 150 patients (80% females), BMI 44.3 ± 21.3 kg/m2, were subjected to the OAGB procedure. Of those, 128 fulfilled the study inclusion criteria. After 3 years, the mean %EBMIL was 78.4 ± 14.4. During the 3-year follow-up, the average protein intake was 60 g/day, and 48% reported an adequate daily protein intake. Adherence to the micronutrient supplementation protocol was reported by 70%. According to the Sigstad score questionnaire, DS was present in 24% of patients. A significant part of OAGB patients does not comply with the nutrition prescription assessed, emphasizing the need to improve team/patient communication strategies. Long-term studies are needed to characterize and assess the health impact of protein, vitamin, and mineral malnutrition in patients undergoing OAGB.


Automated data analysis of unstructured grey literature in health research: A mapping review.
The amount of grey literature and 'softer' intelligence from social media or websites is vast. Given the long lead-times of producing high-quality peer-reviewed health information, this is causing a demand for new ways to provide prompt input for secondary research. To our knowledge, this is the first review of automated data extraction methods or tools for health-related grey literature and soft data, with a focus on (semi)automating horizon scans, health technology assessments (HTA), evidence maps, or other literature reviews. We searched six databases to cover both health- and computer-science literature. After deduplication, 10% of the search results were screened by two reviewers, the remainder was single-screened up to an estimated 95% sensitivity; screening was stopped early after screening an additional 1000 results with no new includes. All full texts were retrieved, screened, and extracted by a single reviewer and 10% were checked in duplicate. We included 84 papers covering automation for health-related social media, internet fora, news, patents, government agencies and charities, or trial registers. From each paper, we extracted data about important functionalities for users of the tool or method; information about the level of support and reliability; and about practical challenges and research gaps. Poor availability of code, data, and usable tools leads to low transparency regarding performance and duplication of work. Financial implications, scalability, integration into downstream workflows, and meaningful evaluations should be carefully planned before starting to develop a tool, given the vast amounts of data and opportunities those tools offer to expedite research.


Factors associated with blood carnitine levels in adult epilepsy patients with chronic valproic acid therapy.
Valproic acid (VPA) is a widely used antiepileptic drug for the treatment of epilepsy, seizures, and bipolar and psychiatric disorders. A deficiency of carnitine, a compound involved in energy production, is associated with chronic VPA use. However, the clinical factors affecting blood carnitine levels and their pathophysiology remain unclear. Hence, we aimed to identify the factors that correlated with serum carnitine levels in epilepsy patients receiving chronic VPA therapy. This observational study included 138 epilepsy patients receiving chronic VPA therapy. Serum total and free carnitine levels, routine blood tests and drug concentrations were assessed. The correlation between carnitine levels and other factors were calculated using Spearman's rank correlation coefficients, and a principal component analysis (PCA) and a multiple linear regression analysis were performed. Overall, serum free carnitine levels showed significant negative correlations with epilepsy duration, VPA treatment duration, daily VPA dose, and blood VPA concentration. A significant positive correlation was observed with erythrocyte count, hemoglobin levels, and creatinine levels. Of the 138 patients, 21 (15.2 %) with serum free carnitine levels of <20 μmol/L had significantly longer disease duration, a higher daily VPA dose, and lower blood clobazam concentrations. In the 48 VPA monotherapy patients, serum free carnitine levels showed a significant negative correlation with disease duration and duration of VPA therapy. Furthermore, in the 2.1 % patients receiving VPA monotherapy, serum free carnitine levels were <20 μmol/L. PCA resulted in seven factor solution (eigenvalue >1; 71.67 % explained variance). Component 1 clearly revealed the maximal loading for serum free carnitine level (.792) and the most negative loading for disease duration of epilepsy (-.595). A linear regression analysis revealed that the duration of epilepsy, serum creatinine level, and daily dose of VPA were significant (p < .01) factors that affected serum free carnitine levels. The effects of combination therapy with VPA and other anti-epileptic drug(s) on carnitine levels are higher than that of VPA monotherapy. Additionally, epilepsy duration may affect serum free carnitine level.


Color Doppler ultrasound in renal transplant: role of resistive index versus renal cortical ratio in the evaluation of renal transplant diseases.
Ultrasound (US) and color Doppler are not sensitive enough to detect anomalies in cortical perfusion, which is affected in most graft dysfunctions. The renal cortical ratio (RCR) is a variation in the resistive index (RI) values from the renal artery to cortical vessels, expressed in percent. The aim of this study was to compare the RI and RCR in the differentiation of normal and pathological grafts, to assess the positive predictive value of RCR and show that RCR enables earlier diagnosis than RI. Based on clinical, biochemical and histological examinations, 494 renal allografts were divided into 3 groups (normal grafts, acute and chronic pathologies). All patients underwent US color Doppler. RI was measured and RCR calculated. Follow-up confirmed the initial division in groups. Statistical significance was calculated using the two-tailed Student's t test. The positive predictive value was calculated for each group. 24 h after transplant, RCR differentiated normal grafts from acute dysfunctions despite confusing biochemical values and clinical symptoms. In chronic patients, RCR variations occurred later but always before the serum creatinine level increased. RCR presented a higher positive predictive value than RI. RCR curves were already altered in the early stages of transplant pathologies. RCR calculation is easy and makes a significant contribution towards a correct early diagnosis.


Sepsis in the Postpneumonectomy Space: Pathogenesis, Recognition, and Management.
Empyema may occur in the pleural space after pulmonary resection. Subsequent bacterial contamination results in infection and development of frank empyema. Pneumonectomy-surgical removal of the entire lung-is the treatment of choice for centrally located bronchogenic carcinoma, diffuse malignant mesothelioma, and chronic inflammatory lung diseases with destroyed lung from pulmonary tuberculosis, fungal infections, and bronchiectasis. In the uncomplicated case, on the pneumonectomy side, the diaphragm becomes elevated as the air-fluid level decreases with chest wall deformation and gradual disappearance of hydrothorax. The pneumonectomy space is at potential risk for getting infected from bacterial contamination and developing empyema.


Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes.
Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an "endothelial hyperglycemic memory" model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo.


Relation Between Body Composition, Systemic Inflammatory Response, and Clinical Outcomes in Patients Admitted to an Urban Teaching Hospital with COVID-19.
COVID-19 has been associated with cases of severe respiratory illness, admissions to intensive therapy units (ITUs), and high mortality rates. The aim of the present study was to examine the relation between computed tomography- body composition (CT-BC) measurements, systemic inflammation, and clinical outcomes in those with COVID-19. Patients who presented to our institution between March 17 and May 1, 2020, with a positive PCR test for COVID-19 or characteristic radiological changes, were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, poGPS, NLR , CT-BC measurements, and clinical outcomes including ITU admission and 30-d mortality, of those admitted. Sixty-three patients met the study inclusion criteria. Forty-two patients (67%) were aged ≥70 y, 30 (47.6%) were male and 34.9% ( n = 22) had a poGPS ≥1. ITU admission was significantly associated with a high VFA ( P < 0.05). Thirty-day mortality was associated with high VFA (P < 0.05) and low SMI (P < 0.05). Sarcopenia in the presence of obesity was associated with clinical outcomes including greater 30-d mortality.


Genomic sequencing of SARS-CoV-2 in Rwanda reveals the importance of incoming travelers on lineage diversity.
COVID-19 transmission rates are often linked to locally circulating strains of SARS-CoV-2. Here we describe 203 SARS-CoV-2 whole genome sequences analyzed from strains circulating in Rwanda from May 2020 to February 2021. In particular, we report a shift in variant distribution towards the emerging sub-lineage A.23.1 that is currently dominating. Furthermore, we report the detection of the first Rwandan cases of the B.1.1.7 and B.1.351 variants of concern among incoming travelers tested at Kigali International Airport. To assess the importance of viral introductions from neighboring countries and local transmission, we exploit available individual travel history metadata to inform spatio-temporal phylogeographic inference, enabling us to take into account infections from unsampled locations. We uncover an important role of neighboring countries in seeding introductions into Rwanda, including those from which no genomic sequences were available. Our results highlight the importance of systematic genomic surveillance and regional collaborations for a durable response towards combating COVID-19.


Chronic stress conditions do explain posttraumatic brain injury depression.
Psychosocial and biologic mechanisms are implicated in depression after traumatic brain injury (TBI). Using McEwen's stress theory of allostasis as a guidepost, this study examined whether pre- and postinjury chronic stress conditions could explain post-TBI depressive symptoms. Seventy-five community-dwelling persons who sustained a mild-to-moderate TBI and were within 2 years of the injury participated in this cross-sectional study. The participants completed measures of chronic stress and depression, measured with the Neurobehavioral Functioning Inventory. Data were collected also on brain injury severity. Using multiple regression analysis, the frequency of childhood adversities and postinjury stress explained post-TBI depression. When time-since-injury was in the regression model, the frequency of preinjury stressors and postinjury stress significantly explained post-TBI depressive symptoms while the combined effect of childhood adversity with postinjury stress was not significant in explaining depressive symptoms. Pre- and postinjury chronic stress explained post-TBI depressive symptoms. These findings support stress-diathesis theory within the psychiatric literature and a linkage between chronic stress, an indicator of allostatic load, and post-TBI depression. These findings are important for nurse specialists working with persons who sustained brain injury, for chronic stress can be buffered by efficient and effective support systems.


AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia.
Chimeric antigen receptor (CAR) T-cell therapy is the most active field in immuno-oncology and brings substantial benefit to patients with B cell malignancies. However, the complex procedure for CAR T-cell generation hampers its widespread applications. Here, we describe a novel approach in which human CAR T cells can be generated within the host upon injecting an Adeno-associated virus (AAV) vector carrying the CAR gene, which we call AAV delivering CAR gene therapy (ACG). Upon single infusion into a humanized NOD.Cg-Prkdcscid Il2rgem26/Nju tumor mouse model of human T-cell leukemia, AAV generates sufficient numbers of potent in vivo CAR cells, resulting in tumor regression; these in vivo-generated CAR cells produce antitumor immunological characteristics. This instantaneous generation of in vivo CAR T cells may bypass the need for patient lymphodepletion, as well as the β processes of traditional CAR T-cell production, which may make CAR therapy simpler and less expensive. It may allow the development of intricate, individualized treatments in the form of on-demand and diverse therapies.


A simple Norrish Type II actinometer for flow photoreactions.
This contribution addresses a frequent problem in flow photochemistry, where methodologies to determine the quantum efficiency of photoreactions are totally lacking. In spite of numerous studies being available in the literature, product reaction yields are never accompanied by measurements to determine their quantum yields. Basically, the key reagent in the reaction, light, is not measured under the experimental conditions of exposure. We report here a flow actinometer based on the photochemistry of valerophenone that can be readily implemented in the organic laboratory for irradiations in the UV region. For example for UVB lamps used in our work, the irradiance was measured as 1.1 × 10-4 einstein l-1 s-1. Our photoreactor design involves wrapping low-pressure lamps with Teflon tubbing, where the photochemistry takes place. Similar strategies could be implemented with other geometries or with lamps (e.g. LED) and actinometers with sensitivity in other spectral regions.


The genetics of retinoblastoma. Relevance to the patient.
The understanding of the molecular biology of human cancer has advanced rapidly in the last decade, in part due to discoveries in the rare, pediatric ocular tumor, retinoblastoma. RB studies have led to recognition of a class of human genes, the tumor suppressor genes, that are critical in the initiation and progression of the malignant process. Mutations in the RB1 gene initiate RB and other specific tumors. They may also contribute to progressive stages of many other malignancies. The protein product of RB1 (p110RB1) is a basic regulator of the cell cycle. In the absence of normal protein, the cell proceeds to the next cell division without the potential to become quiescent. Understanding the genetics of RB has benefited the patients, as the precise identification of the RB1 mutations in families has led to accurate prediction of individuals at risk for RB tumors. It seems unlikely, in the foreseeable future, that direct genetic manipulation of mutant RB1 genes will play a role in therapy, but complete understanding of the function of p110RB1 may eventually allow exploitation of its powerful antiproliferative effect. Other molecular genetic events in addition to RB1 mutations are documented in RB tumors, and may play a critical role in the full malignant phenotype. The oncogene, N-myc, is amplified in some RB tumors and is expressed in normal fetal retina. The cytogenetic abnormality, i(6p), is almost unique to RB tumors. The molecular and tissue-specific roles of these abnormalities are not yet known. Many RB tumors also acquire excessive expression of the cell surface membrane glycoprotein, p170, linked to multidrug resistance, whether or not the RB tumor has been exposed to chemotherapy. We anticipate that ways to avoid or counteract the drug resistance of excessive p170 expression will be developed for other pediatric tumors and eventually will be applied to chemotherapy for RB patients.


Tissue distribution of Red Spotted Grouper Nervous Necrosis Virus (RGNNV) genome in experimentally infected juvenile European seabass (Dicentrarchus labrax).
The distribution of viral genome in the tissues of juvenile European seabass (Dicentrarchus labrax) during the course of a Red Spotted Grouper Nervous Necrosis Virus (RGNNV) infection has not yet been described. The present study addresses this and indicates which target organs may be involved in viral replication. This information should enable more accurate detection of virus in asymptomatic carriers, and in turn help to control the spread of the disease. The aim of this study was to examine the pattern of expression of viral genomic segments RNA1 and RNA2, using two absolute real-time PCRs (RT-qPCR), over the course of a RGNNV infection after administering the virus by intramuscular injection. In situ hybridization was also used to locate the RNA2 viral segment in different organs throughout the infection. The experimental challenge provoked an acute form of viral nervous necrosis (VNN), with a resulting cumulative mortality of 37%. The RT-qPCRs designed allowed the detection of both genomic segments in all the organs tested (nervous and non-nervous tissues) at all sampling times examined. The highest viral RNA copy number was found in eyes, although viral replication appeared to begin in the brain. Viral replication was also recorded in pooled internal organs and in caudal fin. However, the increase in the viral RNA copy number in these organs did not result in an increased viral titre, which may indicate that a productive infection does not take place in non-nervous tissues, possibly due to a failure in a viral post-replication step.


Zirconia-reinforced lithium silicate (ZLS) mechanical and biological properties: A literature review.
This paper aimed to provide a literature review of the mechanical and biological properties of zirconia-reinforced lithium silicate glass-ceramics (ZLS) in Computer-aided design / Computer-aided manufacturing (CAD/CAM) systems. An extensive search of the literature for papers related to ZLS was made on the databases of PubMed/Medline, Scopus, Embase, Google Scholar, Dynamed, and Open Grey. The papers were selected by 3 independent calibrated reviewers. The search strategy produced 937 records. After the removal of duplicates and the exclusion of papers that did not meet the inclusion criteria, 71 papers were included. After reviewing the included records, it was found that two types of ZLS (Vita Suprinity PC; Vita Zahnfabrik and Celtra Duo; Dentsply Sirona) are nowadays available on the market for CAD/CAM systems, similar in their chemical composition, microstructure, and biological-mechanical properties. ZLS is reported to be a biocompatible material, whose fracture resistance can withstand physiological chewing loads. The firing process influences the improvements of strength and fatigue failure load, with a volumetric shrinkage. To date, ZLS can be considered a viable alternative to other glass-ceramics for fixed single restorations. . As to biocompatibility and mechanical properties of ZLS, data are still scarce, often controversial and limited to short-term observational periods. These promising ceramics require further in vitro/in vivo studies to accurately define mechanical and biological properties, mainly in the long-term performance of restorations produced with such materials.


Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis.
Cancer stem cell (CSC) epithelial cell adhesion molecule (Ep-CAM) is frequently expressed in colorectal cancer (CRC). However, the clinical significance of Ep-CAM expression in CRC is not clear. This study evaluated whether Ep-CAM provided valuable insight as a molecular biomarker for CRC diagnosis and prognosis and the potential of Ep-CAM as a novel therapeutic target in CRC. Publications were selected online using electronic databases. The pooled odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs), and the combined sensitivity, specificity, and area under the curve (AUC) were calculated and summarized. Eleven eligible articles published in English involving 4561 cases were analyzed in this study. Ep-CAM expression was significantly higher in CRC compared with normal controls, and its overexpression was negatively linked to tumor differentiation, tumor stage, vascular invasion, depth of tumor invasion, lymph node metastasis, distant metastasis, and tumor budding in CRC patients. The loss of Ep-CAM expression positively correlated with these characteristics. Multivariate analysis of loss of Ep-CAM expression correlated with a poor prognosis in disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). The pooled sensitivity, specificity and AUC values of Ep-CAM expression in patients with CRC vs. normal controls were 0.93, 0.90, and 0.94, respectively. The present findings suggest that Ep-CAM expression may be associated with CRC carcinogenesis, while the loss of Ep-CAM expression is correlated with the progression, metastasis, and poor prognosis of CRC. Ep-CAM expression may be a useful biomarker for the clinical diagnosis of CRC.


Deinococcus radiodurans strain R1 contains N6-methyladenine in its genome.
Methylation of DNA is known to be involved in DNA repair mechanisms in bacteria. Deinococcus radiodurans strain R1 on exposure to high radiation undergoes significant DNA damage, which is repaired without mutations. However, the presence of modified nucleotides has not been reported in its genome. We report here the detection of N6-methyladenine in the genome of D. radiodurans strain R1 using immunochemical techniques. This N6-methyladenine is not a part of GATC restriction-modification system. D. radiodurans cell extract also exhibited a DNA adenine methyltransferase activity which was reduced in the early post-irradiation recovery phase.


Association of genetic polymorphisms of VAX1, MAFB, and NTN1 with nonsyndromic cleft lip with or without cleft palate in Chinese population.
Nonsyndromic cleft lip with or without palate (NSCL/P) is a common birth defect involving genetic factors. We conducted this case-control study to verify the association of ten single-nucleotide polymorphisms (SNPs) of six genes (VAX1, MAFB, PAX7, ABCA4, NTN1, and NOG) with NSCL/P in the Chinese population. The study included 249 NSCL/P patients, 62 nonsyndromic cleft palate only (NSCPO) patients and 480 controls. Three loci, namely, VAX1 rs7078160, MAFB rs11696257, and NTN1 rs4791774, were associated with NSCL/P (Bonferroni method adjusted p values were 0.020, 0.00031, and 0.030, respectively). We also found that the disease risk of individuals carrying both VAX1 rs7078160 and NTN1 rs4791774 was higher than those carrying only one of them (p = 4.50 × 10-4 and 6.03 × 10-3, respectively). SNPs of genes VAX1 rs7078160, MAFB rs11696257, and NTN1 rs4791774 increased NSCL/P risk in the Chinese population.


Different Tridacnins in different Tridacnid clams: a comparative study.
1. Haemolymph samples from different Tridacnid clams were tested for haemagglutinin activity, using normal and enzyme-treated red cells from different sources. 2. Precipitin reactions with these haemolymph fluids were performed in agar gel, using several defined glycosubstances of different origin. 3. In several experiments it could be demonstrated that in all Tridacnid haemolymph samples anti-galactosyl ("anti-galactan") specific lectins do occur, however, they definitely differ from each other.


[Postirradiation change in the radiosensitivity of rats in relation to the preliminary radiation dose in the cutaneous form of radiation injury].
The experimental animals were exposed two times to soft 17kV X-radiation. Post-irradiation changes in radiosensitivity were shown to depend upon dose of preliminary irradiation (10, 18 and 25 Gy). The state of radiosensitive tissues was studied and a comparison was made of a residual damage curve with a change in the proliferative activity of dividing tissue elements during 30 days after irradiation.


The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant.
Thyroid hormone is crucial for brain development during foetal and neonatal life. In very preterm infants, transient low levels of plasma T4 and T3 are commonly found, a phenomenon referred to as transient hypothyroxinaemia of prematurity. We investigated whether breast milk is a substantial resource of thyroid hormone for very preterm neonates and can alleviate transient hypothyroxinaemia. Both the influence of breast feeding on plasma thyroid hormone levels and the thyroid hormone concentration in preterm human milk were studied. Two groups were formed from the placebo group of a randomized thyroxine supplementation trial in infants born at < 30 weeks' gestational age on the basis of the mean breast milk intake during the third, fourth and fifth weeks of life. One group received more than 50% breast milk (mean breast milk intake 84%, n = 32) and the other group less than 25% breast milk (mean breast milk intake 3.3%, n = 25). Plasma thyroid hormone concentrations were compared between the two groups. Breast milk was collected from mothers of infants participating in the same trial and the thyroxine concentration in breast milk was measured with RIA after extraction. No significant differences were found between both groups in plasma concentrations of T4, free T4, T3, TSH, rT3 and thyroxine-binding globulin (TBG), which were measured once a week. Thyroxine concentration in breast milk ranged between 0.17 microg/l and 1.83 microg/l (mean 0.83, SD 0.3 microg/l) resulting in a maximum T4 supply of 0.3 microg/kg via ingested breast milk. In formula milk, the T4 concentration was equally low. Protease treatment did not influence the measured T4 concentrations. No differences in plasma thyroid hormone between breast milk-fed and formula-fed infants were found. The amount of T4 present in human milk and formula milk is too low to alter the hypothyroxinaemic state of preterm infants.


Barriers and facilitators of sport and physical activity for Aboriginal and Torres Strait Islander children and adolescents: a mixed studies systematic review.
Participation in sport and physical activity could minimise the inflated risk of poor physical health outcomes for Aboriginal and Torres Strait Islander children and adolescents. This review aimed to synthesise existing quantitative and qualitative literature regarding barriers and facilitators to physical activity and sports participation in Aboriginal and Torres Strait Islander children. Literature was systematically searched to include studies reporting barriers or facilitators to physical activity and/or sports participation in Aboriginal and Torres Strait Islander children aged 0-18 years. Using a pre-established taxonomy based on the social-ecological model, a deductive analysis was performed. Quality appraisal was performed using the Mixed Methods Appraisal Tool. Of 3440 unique articles, nine studies were included with n = 10,061 total participants. Of the nine included studies one reported on participants from urban areas, two from regional and three from remote areas. Three were from representative samples of the Aboriginal and Torres Strait Islander population. Barriers were reported in all nine studies: 18 individual, 9 interpersonal, 27 community and 4 at the policy level (58 total); Facilitators were reported in five studies: 12 individual, 11 interpersonal, 11 community and 3 policy level (37 total). Research in this area is lacking with some states in Australia not represented and small samples. Strategies for improving participation in sport and physical activity by Aboriginal and Torres Strait Islander children and adolescents need to integrate a comprehensive identification of barriers and facilitators with a social-ecological understanding of how community and cultural factors can impact individual participation.


[Progress of antibiotic therapy in pediatrics].
The advances in the antibiotic therapy of acute bacterial infections can be shown by the decreasing frequency of complications and fatalities in children. The annual death-rate from pneumonia in children aged one month to 15 years has fallen in Schleswig-Holstein from 1.8 (1954-1958) to 0.6 per 10,000 (1969-1973). At the same time the total death-rate in the same age group has fallen from 14.5 to 9.3 per 10,000 children. The percentage of pneumonia in the total death-rate was 5.3% in 1971-1973: 1.6% in the first month of life and after the sixteenth year 2.3%. Pneumonia was in fourth place (after accident, malformation and neoplasm) as a cause of death in children more than one month old. Of 245 children operated on for congenital heart disease in 1983-1984, bacterial and fungal infections occurred in 3.6% compared to 17.8% of 469 in 1968-1972. Staphylococcal infections decreased from 3.4% to 0.8% and those caused by gram-negative bacteria from 6.9% to 0. Perioperative prophylaxis was performed with cefotaxime plus piperacillin in 1983-1984 versus oxacillin plus ampicillin in 1968-1972. Between 1984 and 1989, 944 children (premature babies and term babies) were treated in the intensive care unit of the University Children's Hospital of Kiel. The incidence of sepsis was 5% (congenital sepsis 4%, sepsis acquired after birth 1%). Early diagnosis and treatment of severe bacterial infections with cefotaxime plus piperacillin reduced the mortality rate of sepsis to 2%. Sepsis never developed under treatment with cefotaxime plus piperacillin.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasmacytoid dendritic cells: in search of their niche in immune responses.
Plasmacytoid dendritic cells (pDCs) have been associated with several names and functions over time, reflecting the limited availability of specific markers and their ability to produce large amounts of type I interferons, present antigens, as well as prime disparate T-cell helper responses. Yet, there is increasing evidence that pDCs are a distinct cell type in the innate immune system. This review highlights aspects in which pDCs are unique in comparison to other antigen-presenting cells in regulating innate and adaptive immune responses.


Role of blood mSEPT9 in evaluating tumor burden and disease monitoring in colorectal cancer patients.
This study aimed to investigate the correlation between mSEPT9 and tumor burden as well as the role of mSEPT9 in monitoring colorectal cancer (CRC) patients. A total of 309 patients were recruited and received mSEPT9 detection in this retrospective study. Clinicopathologic characteristics were collected, including age, gender, differentiation, gene mutation, stage, and tumor markers. The correlation between mSEPT9 and clinical tumor burden was analyzed. A relative mSEPT9 value was determined using the ΔΔCt method. The overall positivity rate of mSEPT9 was 39.8% in CRC patients. mSEPT9 status was significantly associated with disease status and tumor markers (CEA and CA19-9). The mSEPT9 positivity rates were 15.6%, 50.0%, 64.4%, and 70.0% for P0M0, P1M0, P0M1, and P1M1 patients, respectively (p < 0.001). Among 137 CRC patients who received mSEPT9 assay before surgery, the pre-operation mSEPT9 positivity rate increased significantly from stage I to stage IV (Stage I vs. II vs. III vs. IV 25% vs. 59.1% vs. 57.1% vs. 70.0%, respectively). Consecutive blood samples were obtained from 26 patients during therapy. The patients with increased mSEPT9 levels showed a higher progression rate. mSEPT9 was a biomarker reflecting tumor burden, and serial detections of mSEPT9 could be a promising strategy for disease monitoring in CRC patients.


Developmental changes in hepatic activation of dietary mutagens by mice.
Metabolic activation of the food mutagens 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and aflatoxin B1 by female BALB/c mice of different ages (2-24 weeks) was investigated in vivo and in vitro using Salmonella typhimurium TA98 as the indicator organism. The in vivo activation of the three mutagens was investigated in 4- and 24-week-old mice using an intrasanguineous host-mediated assay. All three compounds showed reduced levels of activation with the older hosts. Hepatic S9 fractions from female mice of varying ages between 2 and 24 weeks were used in the in vitro mutagenicity assay. To achieve optimal activation to bacterial mutagens, 5% S9 was required for aflatoxin B1 and Trp-P-2 and 10% S9 for MeIQ; age of donor generally had little effect on the profile of these protein activation curves. Under these optimal conditions MeIQ and Trp-P-2 both exhibited, as before, age-dependent decreases in activation over a wide range of mutagen concentrations, however the in vitro activation of aflatoxin showed no consistent change with age. Spectrophotometric measurements of S9 cytochrome P-450 content showed a decrease in concentration with increasing age, but this was not sufficient to account for changes observed in hepatic mutagen activation. However, changes in the activities of certain cytochrome P-450 isoenzymes and cytosolic GSH-transferases, which in turn result in changes in the activation and detoxification capacity of the liver, would appear to explain age-dependent changes in the activity of mutagens in vivo.


The treatment of intervertebral disc degeneration using Traditional Chinese Medicine.
Intervertebral disc degeneration (IDD) is one of the most common causes of chronic low back pain that spending a lot of workforces and financial resources, seriously affecting human physical and mental health. Clinically used drug treatments and surgical treatments cannot fundamentally relieve the disease and have a risk of recurrence. Traditional Chinese Medicine (TCM) has a history of more than a thousand years in the prevention and treatment of IDD. However, so far, there are few reviews on the treatment of IDD by TCM. Therefore, it is crucial and necessary to systematically mine the existing literature on the treatment of IDD with TCM. This paper strives to systematically describe the modern medicine and TCM theoretical research on IDD, progress in the treatment of IDD and focuses on the treatment of IDD by TCM, which would lay some theoretical foundation and provide new directions for future research. Information on clinical observations, animal experiments and relevant pharmacology data about the treatment of IDD were gathered from various sources including traditional Chinese books and Chinese Pharmacopoeia, scientific databases (Elsevier, PubMed, Science Direct, Baidu Scholar, CNKI, Spring Link, Web of Science) and from different professional websites. This review mainly introduces the current research on the theoretical research on IDD, the combination principle of the TCM formula, and the underlying mechanism of the formula and active ingredients. At present, domestic and foreign scholars have carried out a lot of research in different ways, such as the molecular mechanism and predisposing factors of IDD, which provides theoretical development and clinical practice significance for future research. TCM, as a multi-component and multi-targeted drug, can produce synergistic effects to exert its efficacy. Therefore, the development of TCM with more specific functions and practical data will not only become a significant trend in the world market but also has an irreplaceable role in the future treatment of IDD.


Long-Term Safety and Tolerability of Fremanezumab for Migraine Preventive Treatment in Japanese Outpatients: A Multicenter, Randomized, Open-Label Study.
Early discontinuation and poor adherence are common limitations of conventional preventive migraine medications that limit their long-term efficacy. Therefore, a migraine preventive medication with favorable long-term safety is warranted. This study aimed to evaluate the long-term safety and tolerability of fremanezumab for the preventive treatment of chronic or episodic migraine in Japanese patients. In this 52-week, randomized, open-label, parallel-group study, fremanezumab monthly or quarterly was administered in newly enrolled Japanese patients with chronic migraine or episodic migraine. Safety was assessed by monitoring of treatment-emergent adverse events, including injection-site reactions, laboratory and vital sign assessments. Newly enrolled patients and rollover patients from previous phase IIb/III trials who did not receive fremanezumab in this study were included in the immunogenicity testing cohort (n = 587). Efficacy outcomes included changes from baseline in the average monthly migraine days and headache days of at least moderate severity. Other efficacy outcomes included changes in disability scores. A total of 50 patients were enrolled with chronic migraine (monthly, n = 17; quarterly, n = 17) or episodic migraine (monthly, n = 8; quarterly, n = 8). The most commonly reported treatment-emergent adverse events were nasopharyngitis (64.0%) and injection-site reactions (erythema, 24.0%; induration, 10.0%; pain, 8.0%; pruritus, 6.0%). The discontinuation rate was low (4.0% from adverse events, 2.0% from a lack of efficacy) and no deaths were reported. The incidence of anti-drug antibody development was low (2.4%). Fremanezumab reduced monthly migraine days and headache days of at least moderate severity from 1 month after initial administration, and this effect was maintained with no worsening throughout 12 months. Fremanezumab also led to sustained reductions in any acute headache medication use and headache-related disability at 12 months. Fremanezumab administered monthly and quarterly was well tolerated in patients with chronic migraine and episodic migraine and led to sustained improvements in monthly migraine days and headache days of at least moderate severity throughout 12 months. ClinicalTrials.gov Identifier: NCT03303105.


Knowledge, attitudes and experience associated with testing for prostate cancer: a comparison between male doctors and men in the community.
Debate about testing for prostate cancer using prostate-specific antigen (PSA) and digital rectal examination (DRE) continues. The evidence of benefit from screening for prostate cancer using PSA tests is inconclusive, and it is unclear how PSA can be used most effectively in the detection of prostate cancer. Given the lack of consensus, it is important that consumers understand the issues in a way that will permit them to decide whether or not to have a test and, if symptomatic, how their condition is managed. To compare prostate cancer knowledge, attitudes and testing experiences reported by male doctors and men in the community, despite the lack of evidence of a benefit. The primary method for ascertaining the attitudes of male doctors (MD) was a telephone survey, with some doctors electing to complete a written survey. Each MD was selected, at random, from a register of male practitioners aged > or = 49 years of age. A total of 266 MD participated in the survey. The community sample (CS) was accessed using a telephone survey. Five hundred male Victorian residents aged > or = 49 years of age participated in the study. Knowledge - Overall, 55% of the CS indicated correctly that prostate disease is sometimes cancer, compared to 83% of MD. Attitudes - Fifty-five per cent of MD believed men should be tested for prostate disease at least every 2 years, compared to 68% of men in the CS. Testing experience - Forty-five per cent of MD had been tested for prostate cancer in the past, and 92% of those tests were reported as negative. In the CS, 56% had been tested for prostate cancer in the past, and 78% of the results were reported as negative. The significant independent predictors of having had a prostate test among MD were: (i) age (> or = 60 years; odds ratio (OR): 1.59; 95% confidence intervals (CI): 1.30-1.88) and (ii) positive attitudes towards regular testing for prostate cancer (OR: 2.27; 95% CI: 1.98-2.56). The significant independent predictors for the CS were: (i) age (> or = 60 years; OR: 1.65; 95% CI: 1.40-1.89), (ii) being married (OR: 1.30; 95% CI: 1.00-1.60), (iii) knowledge that prostate disease was sometimes cancer (OR: 1.46; 95% CI: 1.26-1.66) and (iv) positive attitudes towards regular testing for prostate cancer (OR: 2.12; 95% CI: 1.90-2.34). The results highlight that testing for prostate cancer is widespread in the community and in the medical profession. Further research should be undertaken to identify how to help men make fully informed decisions about prostate cancer testing.


Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1 protease inhibitors possessing augmented P2' side chains.
A series of monopyrrolinone-based HIV-1 protease inhibitors possessing rationally designed P2' side chains have been synthesized and evaluated for activity against wild-type HIV-1 protease. The most potent inhibitor displays subnanomolar potency in vitro for the wild-type HIV-1 protease. Additionally, the monopyrrolinone inhibitors retain potency in cellular assays against clinically significant mutant forms of the virus. X-ray structures of these inhibitors bound in the wild-type enzyme reveal important insights into the observed biological activity.


Fractionation of enzymatic hydrolysis lignin by sequential extraction for enhancing antioxidant performance.
The heterogeneity of lignin chemical structure and molecular weight results in the lignin inhomogeneous properties which also covers the antioxidant performance. In order to evaluate the effects of lignin heterogeneity on its antioxidant activity, four lignin fractions from enzymatic hydrolysis lignin were classified by sequential organic solvent extraction and further evaluated by DPPH (1,1-Diphenyl-2-Picrylhydrazyl) free radical scavenging capacity and reducing power analysis. The characterization including FTIR, 1H NMR and GPC showed that the fractionation process could effectively separate lignin fractions with distinctly different molecular weight and weaken the heterogeneity of unfractionated lignin. The antioxidant performance comparison of lignin fractions indicated that the dichloromethane fraction (F1) with lowest molecular weight (4585g/mol) and highest total phenolics content (246.13mg GAE/g) exhibited the highest antioxidant activity whose value was close to commercial antioxidant BHT (butylated hydroxytoluene). Moreover, the relationship between the antioxidant activity and the structure of lignin was further discussed to elucidate the mechanism of antioxidant activity improvement of lignin fractionation. Consequently, this study suggested that the sequential extraction was an effective way to obtain relatively homogeneous enzymatic hydrolysis lignin fractions which showed the potential for the value-added antioxidant application.


The video laryngoscopes blind spots and possible lingual nerve injury by the Gliderite rigid stylet--case presentation and review of literature.
We report the first case of near serious lingual nerve injury in an 80-y-old female caused by the Rigid GlideScope Stylet. This complication was discovered during oral surgery and may have been missed if the site of surgery was not oral cavity.


One-pot synthesis of zinc oxide nanoparticles via chemical precipitation for bromophenol blue adsorption and the antifungal activity against filamentous fungi.
In this research, zinc oxide nanoparticles (ZnONPs) were prepared via a facile one-pot chemical precipitation approach and applied in the adsorption of bromophenol blue (BRB) and as antifungal agents against the filamentous fungi and plant pathogens; Alternaria alternata CGJM3078, Alternaria alternata CGJM3006 and Fusarium verticilliodes CGJM3823. The ZnONPs were characterized by the UV-Vis, FTIR, XRD, TGA, BET, SEM, TEM, and EDX techniques, which showed efficient synthesis. The characteristics ZnO UV-Vis absorption band was observed at 375 nm, while the XRD showed an average ZnONPs crystalline size of 47.2 nm. The SEM and TEM images showed an irregular shaped and aggregated porous structure of 65.3 nm average-sized ZnONPs. The TGA showed 22.9% weight loss at 800 °C indicating the high thermal stability of ZnONPs, while BET analysis revealed a surface area, pore volume and pore diameter of 9.259 m2/g, 0.03745 cm3/g and 9.87 nm respectively. The Freundlich, pseudo-second-order, and intra-particle diffusion models showed R2 > 0.9494 and SSE < 0.7412, thus, exhibited the best fit to the isotherm and kinetics models. Thermodynamics revealed feasible, endothermic, random, and spontaneous adsorption of BRB onto the synthesized ZnONPs. The antifungal assay conducted depicts strong antifungal activities against all three tested fungi. Noticeably, ZnONPs (0.002-5 mg/mL) showed maximum activities with the largest zone of inhibition against A. alternata CGJM 3006 from 25.09 to 36.28 mm. This was followed by the strain F. verticilliodes CGJM 3823 (range from 23.77 to 34.77 mm) > A. alternata CGJM3078 (range from 22.73 to 30.63 mm) in comparison to Bleach 5% (positive control). Additionally a model was proposed based on the possible underlying mechanisms for the antifungal effect. This research demonstrated the potent use of ZnONPs for the adsorption of BRB and as effective antifungal agents.


A kinome-wide CRISPR screen identifies CK1α as a target to overcome enzalutamide resistance of prostate cancer.
Enzalutamide (ENZA), a second-generation androgen receptor antagonist, has significantly increased progression-free and overall survival of patients with metastatic prostate cancer (PCa). However, resistance remains a prominent obstacle in treatment. Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1α (CK1α) as a therapeutic target to overcome ENZA resistance. Depletion or pharmacologic inhibition of CK1α enhanced ENZA efficacy in ENZA-resistant cells and patient-derived xenografts. Mechanistically, CK1α phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of CK1α stabilizes ATM, resulting in the restoration of DSB signaling, and thus increases ENZA-induced cell death and growth arrest. Our study details a therapeutic approach for ENZA-resistant PCa and characterizes a particular perspective for the function of CK1α in the regulation of DNA-damage response.


Cross-species regulation of Plasmodium parasitemia in semi-immune children from Papua New Guinea.
Malariologists have long been fascinated by the question of whether Plasmodium spp. interact in the human host. The first genetic study of the longitudinal dynamics of multiple Plasmodium spp. and genotypes in humans has been completed in Papua New Guinea, where all four Plasmodium spp. that infect humans are present. The broad implications of the data from this study are covered here and they show that the total parasite density of Plasmodium species oscillates around a threshold and that peaks of infection with each species do not coincide. It is proposed that malaria parasitemia is controlled in a density-dependent manner in these semi-immune children and that a cross-species mechanism of parasite regulation exists. A model of how multiple immune responses could act in concert to explain these within-host dynamics are discussed here in relation to observed epidemiological patterns of mixed-species infections.


Mortality trends and access to care for cardiovascular diseases in Agincourt, rural South Africa: a mixed-methods analysis of verbal autopsy data.
Cardiovascular diseases are the second leading cause of mortality behind HIV/AIDS in South Africa. This study investigates cardiovascular disease mortality trends in rural South Africa over 20+ years and the associated barriers to accessing care, using verbal autopsy data. A mixed-methods approach was used, combining descriptive analysis of mortality rates over time, by condition, sex and age group, quantitative analysis of circumstances of mortality (CoM) indicators and free text narratives of the final illness, and qualitative analysis of free texts. This study was done using verbal autopsy data from the Health and Socio-Demographic Surveillance System site in Agincourt, rural South Africa. Deaths attributable to cardiovascular diseases (acute cardiac disease, stroke, renal failure and other unspecified cardiac disease) from 1993 to 2015 were extracted from verbal autopsy data. Between 1993 and 2015, of 15 305 registered deaths over 1 851 449 person-years of follow-up, 1434 (9.4%) were attributable to cardiovascular disease, corresponding to a crude mortality rate of 0.77 per 1000 person-years. Cardiovascular disease mortality rate increased from 0.34 to 1.12 between 1993 and 2015. Stroke was the dominant cause of death, responsible for 41.0% (588/1434) of all cardiovascular deaths across all years. Cardiovascular disease mortality rate was significantly higher in women and increased with age. The main delays in access to care during the final illness were in seeking and receiving care. Qualitative free-text analysis highlighted delays not captured in the CoM, principally communication between the clinician and patient or family. Half of cases initially sought care outside a hospital setting (50.9%, 199/391). The temporal increase in deaths due to cardiovascular disease highlights the need for greater prevention and management strategies for these conditions, particularly for the women. Strategies to improve seeking and receiving care during the final illness are needed.


Validity and reliability of the instrument Performance and Satisfaction in Activities of Daily Living (PS-ADL) and its clinical applicability to adults with rheumatoid arthritis.
This study set out to evaluate the validity and reliability of the instrument Performance and Satisfaction of Activities of Daily Living (PS-ADL) in patients with rheumatoid arthritis (RA). The PS-ADL is a questionnaire including 39 actions divided into 12 activities measuring the degree of difficulty and satisfaction with activity performance. Construct validity was examined by factor analysis. For convergent and discriminant validity evaluation, the Performance and the Satisfaction scales were correlated to the Health Assessment Questionnaire (HAQ), the Rheumatoid Arthritis Self-Conception (RASC), pain, fatigue, and mobility. Internal consistency was tested and repeated measurements were taken to establish the Percentage Agreement (PA) and correlation coefficients for test-retest reliability. The factor analysis revealed the PS-ADL scale to be unidimensional. Significant correlations were seen between the Performance and Satisfaction scales and the HAQ (r(s) 0.78, 0.67), and between the RASC and Satisfaction scale (r(s) 0.45). Cronbach's alpha level ranged from 0.41 to 0.92 for the Performance scale and 0.66 to 0.94 for the Satisfaction scale. The percentage agreement (PA) at action level ranged from 68% to 91% for the Performance scale and from 59% to 91% for the Satisfaction scale. The PS-ADL is a valid instrument with satisfactory reliability. It is easy to handle and can be recommended for use in RA patients.


Alcohol consumption as a risk factor for atrial fibrillation: a systematic review and meta-analysis.
Alcohol exposure is one of the major risk factors for global burden of disease, but atrial fibrillation (AF) had not yet been included in these estimates. The purpose of this contribution was to examine the dose–response relationship between alcohol consumption and AF and to explore potential causal pathways. Systematic literature review and meta-analyses. Overall, a consistent dose–response relationship between the amount of alcohol consumed daily and the probability of the onset of AF was found. Women consuming 24, 60 and 120 g of alcohol daily had relative risks of 1.07 [95%confidence interval (CI): 1.04–1.10], 1.42 (95% CI: 1.23–1.64) and 2.02 (95% CI: 1.60–2.97), respectively, relative to nondrinkers. Among men, the corresponding relative risks were 1.08 (95% CI: 1.04–1.11), 1.44 (95% CI: 1.23–1.69) and 2.09(95% CI: 1.52–2.86). Based on the categorical analyses, we could not exclude the existence of a threshold (three drinks a day for men and two drinks a day for women). Several pathogenic mechanisms for the development of AF in alcohol users were identified. Epidemiological criteria for causality were met to conclude a causal impact of alcohol consumption on the onset of AF with a monotonic dose–response relationship. However, the impact of light drinking is not clear.


Surgical management of diaphragmatic and thoracic endometriosis': A French multicentric descriptive study.
Surgical management of Diaphragmatic and thoracic endometriosis (DTE) is still controversial, a thoracic or an abdominal approach can be proposed. We conducted a multicentric retrospective study in 8 thoracic, gynecology or digestive surgery units in 5 French university hospitals. The main objective was to review the current management of DTE. 50 patients operated for DTE from 2010 to 2017 were included: 26 with a thoracic approach and 24 with an abdominal approach. Preoperative pelvic endometriosis (PE) concerned 25 patients. In 38 patients, DTE diagnosis was made on clinical symptoms (pneumothorax (n = 19), chronic or catamenial chest pain (n = 18) or hemopneumothorax (n = 1)). Median time from onset of symptoms to diagnosis was 47 months (0-212). PE surgery concurrently occurred in 22 patients. We report diaphragmatic nodules, pleuropulmonary nodules and diaphragmatic perforations in 42, 5 and 22 women respectively. Lesions were right-sided in 45 patients. Nodules were destructed in 12 cases and resected in 38 cases. When a diaphragmatic reconstruction was needed (n = 31), a simple suture was performed in 26 patients, while 5 patients needed a mesh repair. Pleural symphysis was performed for all patients who received a thoracic approach. DTE resection was considered complete in 46 patients. Three patients had severe 30-days complications of DTE surgery. Median follow-up was 20 months (range 1-69). Recurrence occurred in 10 patients. The results emphasize the importance of systematically looking for chest pain in patients suffering from PE and underline the lack of a standardized procedure and treatment in DTE.


Microsolvation of lysine by water: computational study of stabilized zwitterion.
We present calculations for Lys-(H(2)O)(n) (n = 2, 3) to examine the effects of microsolvating water on the relative stability of the zwitterionic vs canonical forms of Lys. We calculate the structures, energies, and Gibbs free energies of the conformers at the B3LYP/6-311++G(d,p), wB97XD/6-311++G(d,p), and MP2/aug-cc-pvdz levels of theory, finding that three water molecules are required to stabilize the Lys zwitterion. By calculating the barriers of the canonical ↔ zwitterionic pathways of Lys-(H(2)O)(3) conformers, we suggest that both forms of Lys-(H(2)O)(3) may be observed in low temperature gas phase.


Methyl 2-(1H-indole-3-carboxamido)-acetate.
The title compound, C(12)H(12)N(2)O(3), was synthesized by condensation of methyl amino-acetate with 3-trichloro-acetyl-indole. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains parallel to the b axis. The chains are further connected into a three-dimensional network by N-H⋯O hydrogen bonds involving the indole N atom. In the molecule, the indole skeleton is nearly planar [maximum deviation = 0.012 (1) Å] and the mean plane of the amido group is twisted from the mean plane of indole ring by 17.2 (1)°.


[Accumulation of magnetic nanoparticles in plants grown on soils of Apsheron peninsula].
The disclosure of magnetic nanoparticles in five plant species growing in Apsheron peninsula have been detected by the EPR method. The EPR spectra of these nanoparticles proved to be similar to those of synthesized magnetic nanoparticles. The result demonstrated that plants are capable of absorbing magnetic nanoparticles from the soil. The accumulation of nanoparticles in plants is confirmed by the presence of a broad EPR signal whose maximum position of the low-field component changes from g = 2.38 and halfwidth of the signal of 32 mT at room temperature to g = 2.71 and 50-55 mT at 80 K. The intensity of the broad EPR signal for plants grown in radioactively contaminated areas (170-220 mkR per h) was substantially lower compared with plants grown on clean soil. The parameters of the broad EPR signal and its dependence on the temperature of recording were identical with those for synthetic magnetic nanoparticles. The photosynthetic activity and changes in the genome of irradiated plants by the analysis of PCR products were studied.


M6P/IGF2R modulates the invasiveness of liver cells via its capacity to bind mannose 6-phosphate residues.
The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R), a multifunctional protein, plays a central role in intracellular targeting of lysosomal enzymes and control of insulin-like growth factor II (IGF-II) bioactivity. Importantly, the gene encoding this receptor is frequently inactivated in a wide range of malignant tumors including hepatocellular carcinomas. Thus, M6P/IGF2R is considered a putative liver tumor suppressor. The aim of this study was to establish the impact of the receptor on the invasive properties of liver cells. Reconstitution experiments were performed by expression of wild type and mutant M6P/IGF2R in receptor-deficient FRL14 fetal rat liver cells. RNA interference was used to induce M6P/IGF2R downregulation in receptor-positive MIM-1-4 mouse hepatocytes. We show that the M6P/IGF2R status exerts a strong impact on the invasiveness of tumorigenic rodent liver cells. M6P/IGF2R-deficient fetal rat liver cells hypersecrete lysosomal cathepsins and penetrate extracellular matrix barriers in a cathepsin-dependent manner. Forced expression of M6P/IGF2R restores intracellular transport of cathepsins to lysosomes and concomitantly reduces the tumorigenicity and invasive potential of these cells. Conversely, M6P/IGF2R knock-down in receptor-positive mouse hepatocytes causes increased cathepsin secretion as well as enhanced cell motility and invasiveness. We also demonstrate that functional M6P-binding sites are important for the anti-invasive properties of M6P/IGF2R, whereas the capacity to bind IGF-II is dispensable for the anti-invasive activity of the receptor in liver cells. M6P/IGF2R restricts liver cell invasion by preventing the pericellular action of M6P-modified proteins.


Development of a gel-in-oil emulsion as a transdermal drug delivery system for successful delivery of growth factors.
Growth factors (GFs) are indispensable in regenerative medicine because of their high effectiveness. However, as GFs degenerate easily, the development of a suitable carrier with improved stability for GFs is necessary. In this study, we developed a gel-in-oil (G/O) emulsion technology for the transdermal delivery of growth factors. Nanogel particles prepared with heparin-immobilized gelatin that can bind growth factors were dispersed in isopropyl myristate. The particle size of the G/O emulsion could be controlled by changing the surfactant concentration, volume ratio of the water phase to the oil phase, and gelatin concentration. In vitro skin penetration studies showed better penetration through the stratum corneum of fluorescent proteins containing G/O emulsions than of the aqueous solution of GF. Similarly, an in vivo study showed an angiogenesis-inducing effect after transdermal application of GF-immobilized G/O emulsion. Angiogenesis in mice was confirmed owing to both an increased blood vessel network and higher hemoglobin content in the blood. Therefore, the G/O emulsion could be a promising carrier for GFs with better stability and can effectively deliver GFs at the target site.


Summary of the National Institute of Standards and Technology and US Food And Drug Administration cell counting workshop: Sharing practices in cell counting measurements.
The emergence of cell-based therapeutics has increased the need for high-quality, robust and validated measurements for cell characterization. Cell count, being one of the most fundamental measures for cell-based therapeutics, now requires increased levels of measurement confidence. The National Institute of Standards and Technology (NIST) and the US Food and Drug Administration (FDA) jointly hosted a workshop focused on cell counting in April 2017 entitled "NIST-FDA Cell Counting Workshop: Sharing Practices in Cell Counting Measurements." The focus of the workshop was on approaches for selecting, designing and validating cell counting methods and overcoming gaps in obtaining sufficient measurement assurance for cell counting. Key workshop discussion points, representing approximately 50 subject matter experts from industry, academia and government agencies, are summarized here. A key conclusion is the need to design the most appropriate cell counting method, including control/measurement assurance strategies, for a specific counting purposes. There remains a need for documentary standards for streamlining the process to develop, qualify and validate cell counting measurements as well as community-driven efforts to develop new or improved biological and non-biological reference materials.


A voltage-dependent gate in series with the inwardly rectifying potassium channel in frog striated muscle.
1. The degree of tubular potassium depletion and the decrease of potassium conductance due to hyperpolarizing pulses in striated muscular fibres have been examined with the three micro-electrode voltage-clamp technique. 2. The conductance of the fibre membrane has been measured in different extracellular K+ concentrations from 1 to 10 mM. 3. Comparison of the two sets of measurements shows that changes in tubular K+ concentration are not sufficient to account for the conductance decrease associated with hyperpolarization. 4. The presence of a voltage-dependent gate in series with the inwardly rectifying channel for K+ ions, suggested by Almers (1972a, b), is thus confirmed.


CD35 expression on peripheral blood granulocytes of patients with atopic dermatitis.
We examined CD35 expression on granulocytes from 45 patients with atopic dermatitis (AD) (male, 21, female, 24) and 25 age and sex-matched controls (male, 15; female, 10). There was no significant difference in the peripheral blood neutrophil count between AD patients and controls, whereas the eosinophil count in AD patients was significantly higher than that of controls. The percentages of CD35 positive eosinophils and neutrophils were determined by using two-color flow cytometric analysis. As regards eosinophils, we found CD35 expression from AD patients to be lower than that of controls (P < 0.05), but there was no correlation between the CD35 expression and disease severity. In contrast, the CD35 expression on neutrophils from AD patients was much lower than that of controls (P < 0.005). Furthermore, CD35 expression on neutrophils of severe AD group was significantly higher than that of the mild AD group (P < 0.05). This suggests that the CD35 expression of neutrophils but not eosinophils reflects disease severity in AD patients and the CD35 expression on neutrophils in AD patients may associate with susceptibility to bacterial infection.


A robust and anticorrosion non-fluorinated superhydrophobic aluminium surface for microplastic removal.
Solid particulate pollutants such as microplastics constitute a global environmental issue in the 21st century. Many studies are exploring ways of removing these particles from marine environments such as seas and oceans. Here, we present a superhydrophobic surface obtained by combining anodisation and the liquid-phase deposition of lauric acid. The superhydrophobic surface was examined by field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) to elucidate its hierarchical structure and wetting state, while time-of-flight secondary ion mass spectrometry (TOF-SIMS) and high-resolution X-ray photoelectron spectroscopy (HR-XPS) were applied to identify the chemical composition of the surface, which revealed that aluminium laurate decreased the surface free energy. As microplastics are usually found in saline water, it was important to study the anticorrosion properties of the surface. Polarisation curves of the anodised surface showed excellent anticorrosion properties in 3.5 wt% NaCl aqueous solution, which was enhanced by the superhydrophobic properties when the aluminium surface was anodised for 60 min. The functionalised surface was superhydrophobic (154°) and superoleophilic (0°). These wetting properties allowed the surface to remove microplastics from the NaCl aqueous solution with an efficiency higher than 99%. Thus, we present a novel application of a superhydrophobic and anticorrosive surface in the removal of microplastics. This has not been reported previously and provides a new scope for superwettable materials and their environmental applications.


Human impact on C/N/P accumulation in lake sediments from northeast China during the last 150 years.
Lakes and lake sediments are significant components of the global carbon (C) cycle, and may store very large amounts of organic matter. Carbon sequestration in lakes is subject to substantial temporal and spatial variation and may be strongly affected by human activities. Here, we report accumulation rates (AR) of organic C (OC), total nitrogen (TN) and total phosphorous (TP), and investigate their responses to anthropogenic impact over the past 150 years by analyzing 62 sediment cores from 11 shallow lakes in the Songnen Plain, northeast China. From the center of each of the lakes, we selected one master core for age determination by 210Pb and 137Cs radioisotopes. The contents of OC, TN, TP, dry bulk density and mass specific magnetic susceptibility were then determined for all cores. The regional OCAR, TNAR and TPAR up-scaling from the multiple cores yielded mean values of 51.63 ± 15.13, 2.50 ± 0.98, and 0.90 ± 0.21 g m-2 yr-1, respectively. Nutrient AR in the studied lakes increased by a factor of approximately 2 × from the middle 19th century to the 1950s, and approximately 5 × after the 1950s. Elemental ratios show that the increase in OCAR is mainly the result of C autogenesis from the growth of aquatic plants stimulated by agricultural intensification, including increased chemical fertilizer application and farmland expansion. Significantly enhanced nutrient burial by these lakes after the 1950s resulted from increased anthropogenic impacts in northeast China. More sustainable agricultural practises, including a decrease in P fertilizer use, would result in a lowering of OCAR, TNAR and TPAR in the future.


CXC chemokines influence immune surveillance in immunological disorders: Polycystic ovary syndrome and endometriosis.
Reproductive health is a worldwide challenge, but it is of particular significance to women during their reproductive age. Several female reproductive problems, including polycystic ovary syndrome (PCOS) and endometriosis, affect about 10 % of women and have a negative impact on their health, fertility, and quality of life. Small, chemotactic, and secreted cytokines are CXC chemokines. Both PCOS and endometriosis demonstrate dysregulation of CXC chemokines, which are critical to the development and progression of both diseases. Recent research has shown that both in humans and animals, CXC chemokines tend to cause inflammation. It has also been found that CXC chemokines are necessary for promoting angiogenesis and inflammatory responses. CXC chemokine overexpression is frequently associated with poor survival and prognosis. CXC chemokine levels in PCOS and endometriosis patients impact their circumstances significantly. Hence, CXC chemokines have significant potential as diagnostic and prognostic biomarkers and therapeutic targets. The molecular mechanisms through which CXC chemokines promote inflammation and the development of PCOS and endometriosis are currently unknown. This article will discuss the functions of CXC chemokines in the promotion, development, and therapy of PCOS and endometriosis, as well as future research directions. The current state and future prospects of CXC chemokine -based therapeutic strategies in the management of PCOS and endometriosis are also highlighted.