65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review.
Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gathered the vast evidence of the role of dopamine in the simplest forms of aversive learning: classical fear conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic and optogenetic approaches now provide causal evidence for dopamine's role in these learning processes. Dopamine neurons encode conditioned stimuli during fear conditioning and extinction and convey the signal via activation of D1-4 receptor sites particularly in the amygdala, prefrontal cortex and striatum. The coordinated activation of dopamine receptors allows for the continuous formation, consolidation, retrieval and updating of fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of classical fear conditioning and extinction and contributes in a way that is comparable to its role in encoding reward.


Tropical plant supplementation effects on the performance and parasite burden of goats.
Examine the effects of supplementing bahiagrass hay (BG) with potentially anthelmintic quantities of hays of perennial peanut (PEA) or sericea lespedeza (LES) or seeds of velvet bean (Mucuna pruriens L.; MUC) or papaya (PAP) on the intake and nutritive value (Experiment 1), and the performance and parasite burden (Experiment 2) of goats. In Experiment 1, 38 male goats (27.4±5.7 kg body weight) were randomly assigned to each of 5 treatments: i) BG alone and BG plus; ii) PEA; iii) LES; iv) MUC; and v) PAP. Goats were fed for ad libitum consumption and adapted to the diets for 14 d followed by 7 d of measurement. The PEA, LES, MUC (50%, 50%, and 10% of the diet dry matter [DM], respectively), and PAP (forced-fed at 10 g/d) were fed at rates that would elicit anthelmintic effects. In Experiment 2, goats remained in the same treatments but were allocated to 15 pens (3 pens per treatment) from d 22 to 63. All goats were infected with parasites by grazing an infected bahiagrass pasture from 0800 to 1500 h daily and then returned to the pens. Dry matter intake tended to be greater in goats fed PEA and LES than those fed BG (757 and 745 vs 612 g/d, respectively). Digestibility of DM (59.5% vs 54.9%) and organic matter (60.8% vs 56.0%) were greater in goats fed MUC vs BG, respectively. In Experiment 2, feeding PAP, LES, and PEA to goats reduced nematode fecal egg counts by 72%, 52%, and 32%, reduced abomasal adult worm counts by 78%, 52%, and 42%, and decreased plasma haptoglobin concentrations by 42%, 40%, and 45% relative to feeding BG alone, respectively. Supplementation with PEA, LES, and PAP decreased the parasite burden of goats but did not increase their performance. PAP was the most effective anthelmintic supplement.


Novel multipurpose bipolar instrument for endoscopic neurosurgery.
Hemorrhage control in endoscopic neurosurgery is critical because of the lack of suitable instruments for coagulation. One reason for this problem is that miniaturization of the instruments is still a technical problem. In this article, we present a solution: the use of bipolar microforceps with a small diameter of 1.5 mm. With the use of modern synthetic and metallic materials, the construction of the bipolar microforceps was designed without the use of mechanical joints. All movable elements are integrated within the instrument shaft. This design provides optimal visibility of the operating field because the sheath has a diameter of only 1.5 mm along its entire length. Therefore, this instrument is compatible with most working channels of neuroendoscopes. The new, joint-free design of the forceps and the electric insulation of the branches were the technical innovations that led to the development of this novel, multipurpose instrument. This new instrument may enhance endoscopic resection and shrinkage of cystic lesions and may offer new possibilities in endoscopic tumor resection and the treatment of hemorrhage.


A ZYGOTE-SPECIFIC PROTEIN WITH HYDROXYPROLINE-RICH GLYCOPROTEIN DOMAINS AND LECTIN-LIKE DOMAINS INVOLVED IN THE ASSEMBLY OF THE CELL WALL OF CHLAMYDOMONAS REINHARDTII (CHLOROPHYTA).
The cell wall of Chlamydomonas reinhardtii zygotes, which forms rapidly after the fusion of wall-free gametes, provides a tractable system for studying the properties and assembly of hydroxyproline-rich glycoproteins, the major proteinaceous components of green algal and plant cell walls. We report the cloning of the zsp2 gene and the analysis of its ZSP-2 product, a 58.9 kDa polypeptide that is synthesized exclusively by zygotes. The protein contains two (SP)x repeats, establishing it as a member of the cell wall hydroxyproline-rich glycoproteins family. It also contains a 4-fold iteration of an amino acid sequence centered around cysteine residues, a configuration found in both plant and animal lectins. Furthermore, we report four observations on pellicle composition and production. First, cell-free preparations of the pellicle matrix are rich in hydroxyproline, arabinose, and galactose and contain bundles of very long fibrils. Second, glutathione blocks pellicle formation and results in the accumulation of long fibrils in the growth medium. Third, antibody to ZSP-2 also blocks pellicle formation. Fourth, ZSP-2 immunolocalizes to the boundary between the outer layers of the wall proper and the pellicle matrix. These observations are consistent with the possibility that the Cys-rich (glutathione-sensitive) lectin-like domains of ZSP-2 may bind to sugar residues on the long fibrils and anchor them to the cell wall, thereby initiating and maintaining pellicle formation.


[Primary cardiac lymphoma: a case report].
Primary cardiac lymphomas are rare entities (1.3% of all primary cardiac tumors) of difficult clinical identification. We report a case of a primitive cardiac lymphoma in a 35-year-old immunocompetent patient, presenting with signs and symptoms of cardiac tamponade. Echocardiography revealed a lateral atrioventricular mass associated with large pericardial effusion. After pericardiocentesis, surgical excision was performed. Chemotherapy regimens were administered according to established protocols and were effective in inducing complete remission at 6 months.


Plasticity of astrocytes.
It is becoming apparent that astrocytes carry out a large number of different functions in brain and are able to modify their characteristics throughout life, that is they exhibit a high degree of plasticity in their phenotype. For example, the morphology of astrocytes changes markedly during neuronal migration, maturation, and degeneration. It is conceivable that these cells must constantly adjust their abilities to meet changes in brain environment. Several examples of astrocytic plasticity are presented in this review. First, the ability of astrocytes to recognize neuronal signals can change qualitatively as well as quantitatively; evidence suggests that the expression of glial receptors may be developmentally regulated by both intrinsic and extrinsic signals. Second, the expression of adrenergic receptors by astrocytes in adult brain can change in response to neuronal degeneration. The up-regulation of beta-adrenergic receptors in this case suggests that these receptors play a role in function of reactive astrocytes. Finally, glial morphology can be reciprocally regulated by neurotransmitters such as norepinephrine and glutamate. This reciprocal regulation may be significant since both beta-adrenergic receptors and glutamate transporters are found predominantly in astrocytes in the brain. The change in glial morphology may also affect neuronal activity by changing the volume of the extracellular space.


Unexplained recurrent shock in peripheral T-cell lymphoma: A case report.
Malignant lymphoma sometimes manifests with septic-like shock symptoms. We report a case of peripheral T-cell lymphoma presenting with unexplained recurrent shock in absence of apparent lymphadenopathy. The patient also experienced varied symptoms, including severe chest and back pain, respiratory distress due to tracheobronchomalacia, skin rash, and fever.


Cytokeratins in induced epidermoid formations and cholesteatoma lesions.
The expression of cytokeratins varies with the type of epithelium, the state of differentiation, and pathological conditions. In this study, the differential expression of cytokeratins in external meatal skin and middle ear epithelium was used for a pathogenetic study of cholesteatoma lesions and infection-induced epidermoid formations in the middle ear of the rat. Immunocytochemistry generally revealed an epidermal-type cytokeratin profile in the cholesteatoma matrix, except for the focal expression of nonepidermal cytokeratins at the invasion front. Comparable observations were made in the middle ear of the rat after an infection-induced invasion of epidermal cells from the meatal skin. An infection-induced-cornifying metaplastic lesion of the middle ear epithelium revealed nonepidermal cytokeratin expression. The results of this combined study suggested that the cholesteatoma specimens studied had an epidermal origin. The expression of nonepidermal cytokeratins was considered to result from a state of hyperproliferation rather than from metaplasia.


Segmental anatomy of the liver: utility of a nomenclature accepted worldwide.
A major use of imaging techniques in the preoperative evaluation of hepatic tumors is to help the surgeon determine the feasibility of hepatic resection. Although the segmental location of tumors is not the sole criterion for determining resectability, such information is crucial for the preoperative planning of the type of resection.


Pathologic fracture of the mandible resulting from osteomyelitis: report of cases.
Two cases of pathologic fracture of the mandible resulting from chronic osteomyelitis are described. The first case was treated successfully by antibiotic therapy followed by resection of the affected bone and iliac bone grafting after six months of follow-up care. In the second case, a patient with a history of diabetes mellitus, a fracture of the condyloid process occurred because of extension of the Actinomyces infection after extraction of the third molar. Because antibiotics failed to prevent exacerbation of the disease, the patient was given human gamma globulin. Then, all the signs of inflammation disappeared gradually with no evidence of recurrence for more than a year. There was no spontaneous bony healing of the fractured site.


RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage.
The NLRP3 inflammasome functions as a crucial component of the inflammatory response in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the activation of NLRP3 inflammasome has not been well elucidated. In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection. SAH grade, neurological function, brain water content, Western blot, ROS assay, immunofluorescence and transmission electron microscopy were performed. SAH led to the upregulation of RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome. Nec-1 treatment reduced RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome, subsequently alleviated brain edema and neurological deficits at 24h following SAH. The treatment with Mdivi-1 inhibited the expression of DRP1 protein, attenuated mitochondria damage and the generation of ROS, inhibited NLRP3 inflammasome and ameliorated brain edema and neurological deficits at 24h after SAH. The activation of the NLRP3 inflammasome in EBI after SAH was mediated by RIP1-RIP3-DRP1 pathway. Nec-1 and Mdivi-1 can inhibit inflammation and improve neurological function after SAH.


Local and regional anesthesia and analgesia.
Many benefits can be obtained from the use of drugs applied locally or regionally when treating dogs and cats that are in pain or will be in pain because of surgical trauma. These techniques often use less medication than for systemic administration with a reduction in the likelihood of toxic effects from these compounds. Complete relief of pain can be achieved by blocking nerves originating from the site of injury by using local anesthetics, but this may entail loss of all sensation and motor paralysis. Other drugs, such as the opioids, may decrease the nociceptive input with minimal effect on motor activity. This report discusses the use of local anesthetics and other drugs for analgesia of the skin, mucous membranes, joints, pleura, and peritoneum, and the application of these drugs for regional blocks of peripheral nerves and epidural/intrathecal injection.


Behavioral and electrophysiological studies of peptide-induced emesis in dogs.
The electrophysiological responses of neurons in the canine area postrema (AP) to ionophoretic application of neuropeptides and transmitters were studied and correlated with the presence or absence of an emetic response on systemic administration. Of 17 common neuropeptides 11 were emetic when applied systemically at doses of 0.03-0.35 mg/kg. The emesis was dose dependent and was no longer observed in animals with chronic ablation of the AP. The responses of 122 AP single units were recorded. Neurons were silent at rest, and most were excited by glutamate, apomorphine, and dopamine. Excitatory responses to each of eight emetic peptides were recorded in 22-65% of cells studied; no responses were found to two peptides that were not emetic. The response to glutamate was always a brief, high-frequency discharge; the responses to all 13 other excitatory substances were of long latency, low frequency, and long duration. With high ionophoretic current or multiple applications, units would frequently become spontaneously active for many minutes or longer. The similarity of response of so many substances on small neurons suggests a common ionic or metabolic mechanism underlying the response. The direct correlation between the occurrence of emesis on systemic administration and the presence of excitatory receptors on AP neurons provides strong support for the proposed role of the AP as the chemoreceptor trigger zone for emesis.


Full-electric microfluidic platform to capture, analyze and selectively release single cells.
Current single-cell technologies require large and expensive equipment, limiting their use to specialized labs. In this paper, we present for the first time a microfluidic device which demonstrates a combined method for full-electric cell capturing, analyzing, and selectively releasing with single-cell resolution. All functionalities are experimentally demonstrated on Saccharomyces cerevisiae. Our microfluidic platform consists of traps centered around a pair of individually accessible coplanar electrodes, positioned under a microfluidic channel. Using this device, we validate our novel Two-Voltage method for trapping single cells by positive dielectrophoresis (pDEP). Cells are attracted to the trap when a high voltage (VH) is applied. A low voltage (VL) holds the already trapped cell in place without attracting additional cells, allowing full control over the number of trapped cells. After trapping, the cells are analyzed by broadband electrochemical impedance spectroscopy. These measurements allow the detection of single cells and the extraction of cell parameters. Additionally, these measurements show a strong correlation between average phase change and cell size, enabling the use of our system for size measurements in biological applications. Finally, our device allows selectively releasing trapped cells by turning off the pDEP signal in their trap. The experimental results show the techniques potential as a full-electric single-cell analysis tool with potential for miniaturization and automation which opens new avenues towards small-scale, high throughput single-cell analysis and sorting lab-on-CMOS devices.


Detection and elimination of product inhibition from the asymmetric catalytic hydrogenation of enamines.
[reaction: see text] The catalytic asymmetric hydrogenation of enamine amides and esters with catalyst Rh-1a, prepared from ferrocenyl based ligand 1a or 1b and [(COD)RhCl](2), has been shown through kinetic studies to suffer from product inhibition. Enamine ester substrates have also been shown to be incompatible with the amine products of the reaction in methanol. In situ protection of the amine products with di-tert-butyl dicarbonate eliminates functional group incompatibility of ester substrates and eliminates product inhibition in the reaction.


Near-infrared organic compounds and emerging applications.
This Focus Review describes the emerging class of near-infrared (NIR) organic compounds containing the conjugated polyene, polymethine, and donor-acceptor chromophores and exploration of their NIR-absorbing, NIR-fluorescence, and NIR-photosensitizing properties for potential applications in heat absorbers, solar cells, and NIR light-emitting diodes. Examples of NIR organic compounds are reviewed with emphasis on the molecular design, NIR absorption, and fluorescence and particular emerging applications. The donor-acceptor type of NIR chromophores are particularly introduced owing to some unique features, including the designer-made energy gaps, facile synthesis, good processability, and controllable morphology and properties in the solid state. Future directions in research and development of NIR organic materials and applications are then offered from a personal perspective.


Cancer-Related Triplets of mRNA-lncRNA-miRNA Revealed by Integrative Network in Uterine Corpus Endometrial Carcinoma.
The regulation of transcriptome expression level is a complex process involving multiple-level interactions among molecules such as protein coding RNA (mRNA), long noncoding RNA (lncRNA), and microRNA (miRNA), which are essential for the transcriptome stability and maintenance and regulation of body homeostasis. The availability of multilevel expression data enables a comprehensive view of the regulatory network. In this study, we analyzed the coding and noncoding gene expression profiles of 301 patients with uterine corpus endometrial carcinoma (UCEC). A new method was proposed to construct a genome-wide integrative network based on variance inflation factor (VIF) regression method. The cross-regulation relations of mRNA, lncRNA, and miRNA were then selected based on clique-searching algorithm from the network, when any two molecules of the three were shown as interacting according to the integrative network. Such relation, which we call the mRNA-lncRNA-miRNA triplet, demonstrated the complexity in transcriptome regulation process. Finally, six UCEC-related triplets were selected in which the mRNA participates in endometrial carcinoma pathway, such as CDH1 and TP53. The multi-type RNAs are proved to be cross-regulated as to each of the six triplets according to literature. All the triplets demonstrated the association with the initiation and progression of UCEC. Our method provides a comprehensive strategy for the investigation of transcriptome regulation mechanism.


Fast-track elective colectomy: single-surgeon experience of 100 consecutive cases.
In 2005, the senior author (AGH) initiated an Enhanced Recovery After Surgery (ERAS) or 'fast-track' programme for elective colonic surgery at the Manukau Surgery Centre aimed at improving perioperative care. We reviewed the senior author's experience of elective colectomy conducted within the ERAS programme and evaluated clinical outcomes. Using a prospectively maintained database, consecutive patients who underwent elective colonic resection by the senior author within the ERAS programme at the Manukau Surgery Centre between December 2005 and March 2012 were reviewed. Demographic and operative data were recorded and clinical outcomes including complications, hospital stay and readmissions were evaluated for 30 days postoperatively. 100 consecutive patients were reviewed. The median age of patients was 70 years (range: 16-92) and the most common indication for surgery was malignancy (81 cases). Right-sided colectomy was performed in 52 cases while 45 patients had a left-sided colectomy and 3 patients underwent subtotal colectomy. The median day to discharge was 3 days while total hospital stay was 4 days which incorporated 21 readmissions for mostly minor complications. Major complications occurred in only 8 patients and included 4 anastomotic leaks. In one surgeon's experience, elective colectomy performed within an optimised perioperative care environment achieves shorter hospital stay with a low rate of major complications.


Immune reconstitution in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy: a cohort study.
Highly active antiretroviral therapy (HAART) has brought about rapid declines in HIV-1 RNA concentrations and an increase in CD4+ counts in HIV-1-infected children. These changes are often accompanied by clinical improvement; however, the extent to which immune reconstitution occurs is not known. We compared two cohorts (n = 35) of HIV-1-infected children to evaluate the effects of HAART on immune recovery. Cohort 1 (C1) included clinically well children receiving HAART with a CD4 >22% at study initiation. Before HAART all children had moderately to severely suppressed immune function by CDC criteria (CD4 <25%) or CDC Category B or C disease. Cohort 2 (C2) included children with no current or past evidence of immunosuppression based on CDC criteria (CD4 >25%) and no evidence of clinical disease. Children in C2 were receiving a non-HAART regimen. Immunophenotyping was performed to characterize CD4+ and CD8+ subsets with regard to maturation and activation. T cell rearrangement excision circles (TRECs) were measured to quantify recent thymic emigrants. No difference was found in percent CD4+ or percent CD8+ T cells or maturation markers between C1 and C2. There was significantly less expression of activation markers in both CD4+ and CD8+ cells in C1. There was no difference in TREC production between C1 and C2. Moderately to severely suppressed HIV-1-infected children receiving HAART are able to reconstitute their immune systems to a degree that is indistinguishable from that of stable, CDC Class A1 HIV-1-infected children with regard to CD4+ and CD8+ T cell subsets, expression of cellular maturation markers and TREC production.


Recurrent flexural exanthema (SDRIFE or baboon syndrome) after administration of two different iodinated radio contrast media.
In 1984, the baboon syndrome was described as a particular form of systemic contact dermatitis that occurred after the administration of a contact allergen in individuals previously sensitized by topical exposure to the same allergen. Its clinical picture presents as an erythema of the buttocks and upper inner thighs resembling the red bottom of baboons. This specific reaction was originally observed with mercury, nickel and ampicillin. Since then over 100 cases have been described, most of them without known prior sensitization to the causative agent. In 2004, our group proposed the acronym SDRIFE specifically for cases associated with systemic drugs; it stands for symmetrical drug-related intertriginous and flexural exanthema, as a distinct reaction pattern related to systemic drugs. Here we describe a case of SDRIFE after administration of the iodinated radio contrast medium (RCM) iomeprol (Iomeron), accidentally reproduced by the RCM iopromide (Ultravist). Positive delayed skin tests with both drugs were observed indicating that the pathomechanism of SDRIFE is likely a cell-mediated type IV allergy. Oral potassium iodide and a skin-test-negative RCM were administered and both tolerated, indicating that the antigen is related to the molecules and not to iodine itself. Therefore, in our case skin tests had a good positive and negative predictive value.


Computational Analysis Reveals the Association of Threonine 118 Methionine Mutation in PMP22 Resulting in CMT-1A.
The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A). CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures.


[Continuous hemodilution using a low-molecular hydroxyethyl starch solution. Pilot studies in patients with acute cerebral ischemia].
The intention of this study was to examine whether it is possible to induce an acute and long-time hemodilution by a 6% Hydroxyethyl Starch solution (HES 40). This study was investigated in 30 patients with acute cerebral ischemia. Primarily a isovolemic infusion of HES 40 was made in order to reduce the hematocrit nearly 40%. Secondly, a hypervolemic infusion of 1,000 ml/24 h followed during 4 days. Then 500 ml/24 h for the next 6 days, respectively. The neurological staging was estimated by special scores, the rheological effects by changing of values of hematocrit, hemoglobin, plasma viscosity, number of blood cells, concentration of total plasma protein and fibrinogen concentration. It can be stated that HES 40 induced a significant acute and long time decrease of blood parameters (4 weeks later). After this time, the symptoms of cerebral ischemia could not be observed in 54% of cases and were reduced significantly in 31 percent. 2 patients had transitory ischemic attacks and 4 patients died during therapy. These results demonstrate that this new therapy (long time hemodilution with HES 40) is ingenious for patients with acute cerebral ischemia, because HES 40 has lower undesired effects than HES 200.


Measurement of body composition: applications in hormone research.
Measurements of body composition are fundamental to the diagnosis and management of a number of diseases. However, these measurements must be appropriate and accurate. Accuracy can now be achieved, but at the expense of invasiveness (mainly radiation) and cost. Some methods for measuring body composition, such as bioimpedance analysis, are inexpensive, simple, harmless and infinitely repeatable. The remaining methods fall within a scale of increasing discriminating power and increasing cost/risk/difficulty. In this review, a number of methods of measuring body composition are discussed. Both traditional and new methods are included, which vary in ease of use, invasiveness and cost. The choice of technique depends on the needs of a particular study.


Peptide binding prediction for the human class II MHC allele HLA-DP2: a molecular docking approach.
MHC class II proteins bind oligopeptide fragments derived from proteolysis of pathogen antigens, presenting them at the cell surface for recognition by CD4+ T cells. Human MHC class II alleles are grouped into three loci: HLA-DP, HLA-DQ and HLA-DR. In contrast to HLA-DR and HLA-DQ, HLA-DP proteins have not been studied extensively, as they have been viewed as less important in immune responses than DRs and DQs. However, it is now known that HLA-DP alleles are associated with many autoimmune diseases. Quite recently, the X-ray structure of the HLA-DP2 molecule (DPA*0103, DPB1*0201) in complex with a self-peptide derived from the HLA-DR α-chain has been determined. In the present study, we applied a validated molecular docking protocol to a library of 247 modelled peptide-DP2 complexes, seeking to assess the contribution made by each of the 20 naturally occurred amino acids at each of the nine binding core peptide positions and the four flanking residues (two on both sides). The free binding energies (FBEs) derived from the docking experiments were normalized on a position-dependent (npp) and on an overall basis (nap), and two docking score-based quantitative matrices (DS-QMs) were derived: QMnpp and QMnap. They reveal the amino acid preferences at each of the 13 positions considered in the study. Apart from the leading role of anchor positions p1 and p6, the binding to HLA-DP2 depends on the preferences at p2. No effect of the flanking residues was found on the peptide binding predictions to DP2, although all four of them show strong preferences for particular amino acids. The predictive ability of the DS-QMs was tested using a set of 457 known binders to HLA-DP2, originating from 24 proteins. The sensitivities of the predictions at five different thresholds (5%, 10%, 15%, 20% and 25%) were calculated and compared to the predictions made by the NetMHCII and IEDB servers. Analysis of the DS-QMs indicated an improvement in performance. Additionally, DS-QMs identified the binding cores of several known DP2 binders. The molecular docking protocol, as applied to a combinatorial library of peptides, models the peptide-HLA-DP2 protein interaction effectively, generating reliable predictions in a quantitative assessment. The method is structure-based and does not require extensive experimental sequence-based data. Thus, it is universal and can be applied to model any peptide - protein interaction.


Interaction between dietary content of protein and sodium chloride on milk urea concentration, urinary urea excretion, renal recycling of urea, and urea transfer to the gastrointestinal tract in dairy cows.
Dietary protein and salt affect the concentration of milk urea nitrogen (MUN; mg of N/dL) and the relationship between MUN and excretion of urea nitrogen in urine (UUN; g of N/d) of dairy cattle. The aim of the present study was to examine the effects of dietary protein and sodium chloride (NaCl) intake separately, and their interaction, on MUN and UUN, on the relationship between UUN and MUN, on renal recycling of urea, and on urea transfer to the gastrointestinal tract. Twelve second-parity cows (body weight of 645±37 kg, 146±29 d in milk, and a milk production of 34.0±3.28 kg/d), of which 8 were previously fitted with a rumen cannula, were fitted with catheters in the urine bladder and jugular vein. The experiment had a split-plot arrangement with dietary crude protein (CP) content as the main plot factor [116 and 154 g of CP/kg of dry matter (DM)] and dietary NaCl content as the subplot factor (3.1 and 13.5 g of Na/kg of DM). Cows were fed at 95% of the average ad libitum feed intake of cows receiving the low protein diets. Average MUN and UUN were, respectively, 3.90 mg of N/dL and 45 g of N/d higher for the high protein diets compared with the low protein diets. Compared with the low NaCl diets, MUN was, on average, 1.74 mg of N/dL lower for the high NaCl diets, whereas UUN was unaffected. We found no interaction between dietary content of protein and NaCl on performance characteristics or on MUN, UUN, urine production, and renal clearance characteristics. The creatinine clearance rate was not affected by dietary content of protein and NaCl. Urea transfer to the gastrointestinal tract, expressed as a fraction of plasma urea entry rate, was negatively related to dietary protein, whereas it was not affected by dietary NaCl content. We found no interaction between dietary protein and NaCl content on plasma urea entry rate and gastrointestinal urea entry rate or their ratio. The relationship between MUN and UUN was significantly affected by the class variable dietary NaCl content: UUN=-17.7±7.24 + 10.09±1.016 × MUN + 2.26±0.729 × MUN (for high NaCl); R(2)=0.85. Removal of the MUN × NaCl interaction term lowered the coefficient of determination from 0.85 to 0.77. In conclusion, dietary protein content is positively related to MUN and UUN, whereas dietary NaCl content is negatively correlated to MUN but NaCl content is not related to UUN. We found no interaction between dietary protein and NaCl content on performance, MUN, UUN, or renal urea recycling, nor on plasma urea entry rate and urea transfer to the gastrointestinal tract. For a proper interpretation of the relationship between MUN and UUN, the effect of dietary NaCl should be taken into account, but we found no evidence that the effect of dietary NaCl on MUN is dependent on dietary protein content.


The systemic administration of intravenous melphalan.
Melphalan (L-phenylalanine mustard) is a bifunctional alkylating agent that is commonly administered orally to treat a wide variety of malignancies, including cancers of the breast and ovary, as well as multiple myeloma. Although commercially available in Europe and Canada, intravenous (IV) melphalan remains investigational in the United States. The role of IV melphalan in cancer chemotherapy is not well defined, despite its manageable toxicity and higher and more predictable blood levels following IV administration compared with oral administration. In addition, unlike oral melphalan, an extensive phase I evaluation of IV melphalan has not been undertaken. At lower doses (eg, 30 to 70 mg/m2), both as a single agent and in combination, the activity of IV melphalan has been evaluated in only a limited number of diseases. However, striking activity has been observed in previously untreated patients with rhabdomyosarcoma, a disease not generally considered responsive to alkylating agents. When administered at high doses (greater than 140 mg/m2) requiring bone marrow reinfusion, melphalan effects a high response rate (but no improvement in survival) in a variety of nonhematologic tumor types, including resistant tumors such as melanoma and colon carcinoma. In contrast, in poor-prognosis patients with non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or neuroblastoma, high-dose melphalan-containing regimens have yielded both high response rates and improved survival, despite considerable toxicity. Additional clinical trials will be necessary to define the spectrum of activity of lower doses of IV melphalan and to define subgroups of patients most likely to benefit from high-dose melphalan.


Hydrogel-Forming Microneedles with Applications in Oral Diseases Management.
Controlled drug delivery in the oral cavity poses challenges such as bacterial contamination, saliva dilution, and inactivation by salivary enzymes upon ingestion. Microneedles offer a location-specific, minimally invasive, and retentive approach. Hydrogel-forming microneedles (HFMs) have emerged for dental diagnostics and therapeutics. HFMs penetrate the stratum corneum, undergo swelling upon contact, secure attachment, and enable sustained transdermal or transmucosal drug delivery. Commonly employed polymers such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone are crosslinked with tartaric acid or its derivatives while incorporating therapeutic agents. Microneedle patches provide suture-free and painless drug delivery to keratinized or non-keratinized mucosa, facilitating site-specific treatment and patient compliance. This review comprehensively discusses HFMs' applications in dentistry such as local anesthesia, oral ulcer management, periodontal treatment, etc., encompassing animal experiments, clinical trials, and their fundamental impact and limitations, for example, restricted drug carrying capacity and, until now, a low number of dental clinical trial reports. The review explores the advantages and future perspectives of HFMs for oral drug delivery.


Behavioural consequences of withdrawal from three different administration schedules of amphetamine.
Different administration schedules of amphetamine (AMPH) lead to different behavioural consequences, neurochemical changes and gene expression patterns in a variety of brain areas during drug withdrawal. However, direct comparisons of these different effects within the same experiment are rare in the literature. Accordingly, in this study, rats were tested in relevant behavioural paradigms during withdrawal from three different administration schedules of AMPH. The intermittent schedule (INT) consisted of one daily injection of 1.5 mg/kg AMPH for 6 days. The escalating administration schedule consisted of three daily injections for 6 days with increasing dosages from 1 to 5 mg/kg AMPH during the first five injections and 5 mg/kg for the following 13 injections (ESC-5). A second more severe escalating administration schedule (three injections per day for 3 days escalating from 1 to 9 mg/kg AMPH and a final 10 mg/kg AMPH injection on day 4, ESC-10) was also investigated. Control animals received saline injections according to the three administration schedules. Rats pretreated with AMPH according to the ESC-10 administration schedule exhibited a transient reduction of locomotor activity on day 1, but not day 5, of withdrawal, as well as a permanent disruption of prepulse inhibition (PPI) on days 4, 20, and 40 of withdrawal. There was no effect on anxiety measured by the elevated plus-maze on withdrawal day 2, and all the AMPH pretreated animals exhibited a similar magnitude of behavioural sensitization following an AMPH challenge irrespective of administration schedule on withdrawal day 42. These data suggest that, based on their persistent disruption of PPI, animals withdrawn from AMPH ESC-10 might model specific symptoms of schizophrenic patients.


Carotid atherosclerotic plaque instability and cognition determined by ultrasound-measured plaque strain in asymptomatic patients with significant stenosis.
OBJECTIVE This article describes the use of ultrasound measurements of physical strain within carotid atherosclerotic plaques as a measure of instability and the potential for vascular cognitive decline, microemboli, and white matter changes. METHODS Asymptomatic patients with significant (> 60%) carotid artery stenosis were studied for dynamic measures of plaque instability, presence of microemboli, white matter changes, and vascular cognitive decline in comparison with normative controls and premorbid state. RESULTS Although classically asymptomatic, these patients showed vascular cognitive decline. The degree of strain instability measured within the atherosclerotic plaque directly predicted vascular cognitive decline in these patients thought previously to be asymptomatic according to classic criteria. Furthermore, 26% of patients showed microemboli, and patients had twice as much white matter hyperintensity as controls. CONCLUSIONS These data show that physical measures of plaque instability are possible through interpretation of ultrasound strain data during pulsation, which may be more clinically relevant than solely measuring degree of stenosis. The data also highlight the importance of understanding that the definition of symptoms should not be limited to motor, speech, and vision function but underscore the role of vascular cognitive decline in the pathophysiology of carotid atherosclerotic disease. Clinical trial registration no.: NCT02476396 (clinicaltrials.gov).


Characterizing the Diversity of the CDR-H3 Loop Conformational Ensembles in Relationship to Antibody Binding Properties.
We present an approach to assess antibody CDR-H3 loops according to their dynamic properties using molecular dynamics simulations. We selected six antibodies in three pairs differing substantially in their individual promiscuity respectively specificity. For two pairs of antibodies crystal structures are available in different states of maturation and used as starting structures for the analyses. For a third pair we chose two antibody CDR sequences obtained from a synthetic library and predicted the respective structures. For all three pairs of antibodies we performed metadynamics simulations to overcome the limitations in conformational sampling imposed by high energy barriers. Additionally, we used classic molecular dynamics simulations to describe nano- to microsecond flexibility and to estimate up to millisecond kinetics of captured conformational transitions. The methodology represents the antibodies as conformational ensembles and allows comprehensive analysis of structural diversity, thermodynamics of conformations and kinetics of structural transitions. Referring to the concept of conformational selection we investigated the link between promiscuity and flexibility of the antibodies' binding interfaces. The obtained detailed characterization of the binding interface clearly indicates a link between structural flexibility and binding promiscuity for this set of antibodies.


Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates.
Postsurgical administration of opiates in patients with obstructive sleep apnea (OSA) has recently been linked to an increased risk for respiratory complications. The authors have attributed this association to an effect of recurrent oxygen desaturation accompanying OSA on endogenous opioid mechanisms that, in turn, alter responsiveness to subsequent administration of exogenous opiates. In a retrospective study, the authors have shown that oxygen desaturation and young age in children with OSA are correlated with a reduced opiate requirement for postoperative analgesia. The current study was designed to test that conclusion prospectively in 22 children with OSA scheduled to undergo adenotonsillectomy. The children were stratified to those having displayed < 85% or > or = 85% oxygen saturation nadir during sleep preoperatively. Using a blinded design, the children were given morphine postoperatively to achieve an identical behavioral pain score. As compared with children in the > or = 85% group, the < 85% oxygen saturation nadir group required one half the total analgesic morphine dose postoperatively, indicating heightened analgesic sensitivity to morphine after recurrent hypoxemia. Previous recurrent hypoxemia in OSA is associated with increased analgesic sensitivity to subsequent morphine administration. Therefore, opiate dosing in children with OSA must take into account a history of recurrent hypoxemia.


Re-entry using anatomically determined isthmuses: a curable ventricular tachycardia in repaired congenital heart disease.
Ventricular tachycardia (VT) is an important cause of late morbidity and mortality in repaired congenital heart disease. The substrate often includes anatomic isthmuses that can be transected by radiofrequency catheter ablation similar to isthmus block for atrial flutter. This study evaluates the long-term efficacy of isthmus block for treatment of re-entry VT in adults with repaired congenital heart disease. Thirty-four patients (49±13 years; 74% male) with repaired congenital heart disease who underwent radiofrequency catheter ablation of VT in 2 centers were included. Twenty-two (65%) had a preserved left and right ventricular function. Patients were inducible for 1 (interquartile range, 1-2) VT, median cycle length: 295 ms (interquartile range, 242-346). Ablation aimed to transect anatomic isthmuses containing VT re-entry circuit isthmuses. Procedural success was defined as noninducibility of any VT and transection of the anatomic isthmus and was achieved in 25 (74%) patients. During long-term follow-up (46±29 months), all patients with procedural success (18/25 with internal cardiac defibrillators) were free of VT recurrence but 7 of 18 experienced internal cardiac defibrillator-related complications. One patient with procedural success and depressed cardiac function received an internal cardiac defibrillator shock for ventricular fibrillation. None of the 18 patients (12/18 with internal cardiac defibrillators) with complete success and preserved cardiac function experienced any ventricular arrhythmia. In contrast, VT recurred in 4 of 9 patients without procedural success. Four patients died from nonarrhythmic causes. In patients with repaired congenital heart disease with preserved ventricular function and isthmus-dependent re-entry, VT isthmus ablation can be curative.


A liquid chromatography with tandem mass spectrometry method to simultaneously determinate chlorpyrifos, imidacloprid and imidacloprid metabolites in wheat.
A liquid chromatography with tandem mass spectrometry method was developed and validated to simultaneously determine chlorpyrifos, imidacloprid, and imidacloprid metabolites in soil, wheat grain, and wheat straw matrices. Satisfactory linearity (R2 ≥ 0.9965) of the method was obtained for all analytes. The ranges of limits of detection and limits of quantification for seven analytes in three matrices were 0.17-66.7 and 0.5-200 μg/kg, respectively. Average recoveries were 72.85-81.25% for chlorpyrifos, 78.54-84.70% for imidacloprid, 73.83-81.03% for imidacloprid olefin, 71.47-80.61% for 5-hydroxy imidacloprid, 71.79-81.32% for imidacloprid urea, 70.42-82.20% for imidacloprid nitroguanidine, and 70.91-82.46% for imidacloprid 6-chloronicotinic acid in soil, wheat grain, and wheat straw. The intra- and interday relative standard deviations were less than 8%. The established method was successfully applied for the residual analysis of chlorpyrifos, imidacloprid, and imidacloprid metabolites in actual soil, wheat grain, and wheat straw samples. The results indicated that the established method could be used to detect trace amounts of chlorpyrifos, imidacloprid, and imidacloprid metabolites in wheat and that the method might be able to provide some data on the detection of these seven compounds in other crops.


Inorganic Triphenylphosphine.
A completely inorganic version of one of the most famous organophosphorus compounds, triphenylphosphine, has been prepared. A comparison of the crystal structures of inorganic triphenylphosphine, PBaz3 (where Baz=B3 H2 N3 H3 ) and PPh3 shows that they have superficial similarities and furthermore, the Lewis basicities of the two compounds are remarkably similar. However, their oxygenation and hydrolysis reactions are starkly different. PBaz3 reacts quantitatively with water to give PH3 and with the oxidizing agent ONMe3 to give the triply-O-inserted product P(OBaz)3 , an inorganic version of triphenyl phosphite; a corresponding transformation with PPh3 is inconceivable. Thermodynamically, what drives these striking differences in the chemistry of PBaz3 and PPh3 is the great strength of the B-O bond.


Surgical Treatment of Portal Hypertension in Children.
Introduction: Portal hypertension is a syndrome characterized by increased pressure in the portal vein system and can be caused by impaired blood flow in the portal vein, hepatic veins, or inferior vena cava. The main complications of this condition are bleeding from varicose veins of the esophagus (in our study in 100% of patients), splenomegaly with hypersplenism (in our study in 98% of patients), ascites (in our study in 1 patient). The main goal of treating portal hypertension is to prevent bleeding from esophageal varices. However, today the goal of surgical treatment of portal hypertension in children is not only to prevent the development of bleeding but also the possible restoration of intrahepatic blood flow. Materials and Methods: A retrospective analysis of the results of treatment of portal hypertension in 75 children (41 boys, 34 girls) operated in our Center for the period from 2019 to 2022 was carried out. The mean age of the patients was 7 ± 1 years. Sixty-nine patients had an extrahepatic form of portal hypertension, and 6 patients had an intrahepatic form (liver fibrosis). In 14 patients (18.6%), the operation was repeated (a vascular shunt was previously applied in another hospital; 4 children were operated on repeatedly). Results: A good result was obtained in all children, and the risk of bleeding from varicose veins of the esophagus was eliminated. Vascular bypass surgery was performed in all cases: mesoportal bypass in 17 (22.7%) patients, splenorenal bypass in 37 (49.3%) patients, mesocaval bypass in 21 (28%) patients. In 10 (13%) cases, repeated bypass surgery was required due to dysfunction or thrombosis of the previously performed bypass. In 14 (18.6%) patients with mesoportal shunts, blood flow in the liver was completely restored. Conclusions: The main method of surgical treatment of portal hypertension today is portosystemic bypass surgery, which effectively prevents bleeding from varicose veins of the esophagus. Mesoportal shunting is a definitive treatment for extrahepatic portal hypertension that restores portal perfusion of the liver.


Mucoepidermoid Carcinoma of the Breast With MAML2 Rearrangement: A Case Report and Literature Review.
Mucoepidermoid carcinoma is one of the most common malignancies in salivary glands. In comparison, breast mucoepidermoid carcinoma is a very rare entity, with limited reports and understanding of its clinical behaviors to date. In this article, we report a case of low-grade breast mucoepidermoid carcinoma of a 60-year-old female patient. Histologic and immunohistochemical patterns were demonstrated. Fluorescence in situ hybridization test was also conducted to identify MAML2 rearrangement in this case, indicating a similar molecular abnormality as mucoepidermoid carcinoma in the salivary gland. Five-year follow-up of the patient showed no local recurrence or distant metastasis of the carcinoma, indicating the indolent behavior of low-grade breast mucoepidermoid carcinoma. Besides, a 40-year literature review from 1979 to 2019 was also performed to better characterize the prognosis and molecular abnormalities of the lesion.


A radiographic evaluation of microporosity in a nickel base casting allow.
Three series of tensile test pieces were produced using a nickel base partial denture casting alloy. For the first series induction heating was employed, for the second a resistance crucible, and for the third an oxy-acetylene torch. All specimens were radiographed and a classification developed to indicate the radiographic soundness of each specimen. Radiographic soundness was subsequently related to the results obtained from mechanical testing.


A polymer network architecture provides superior cushioning and lubrication of soft tissue compared to a linear architecture.
We report the relationships between linear vs. network polymer architecture and biomechanical outcomes including lubrication and cushioning when the polymers are applied to the surface of articulating knee cartilage. Aqueous formulations of the bioinspired polymer poly(2-methacryloyloxylethyl phosphorylcholine) (pMPC) exhibit tuneable rheological properties, with network pMPC exhibiting increased elasticity and viscosity compared to linear pMPC. Application of a polymer network, compared to a linear one, to articulating tissue surfaces reduces friction, lessens tissue strain, minimizes wear, and protects tissue - thereby improving overall tissue performance. Administration of the network pMPC to the middle carpal joint of skeletally mature horses elicits a safe response similar to saline as monitored over a 70 day period.


[From a Ph.D. Thesis: Understanding the Past, Predicting the Future].
Posey et al. have reported multiple molecular diagnoses in 4.5% of cases (101/2076) in which whole-exome sequencing was informative. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within the same pathway. My research projects at the Niigata University of Pharmacy have investigated underlying mechanisms involved in human disease, including fatty acid metabolism, diabetic cardiomyopathy, atopic dermatitis, colitis, hepatitis, etc. Three students from abroad graduated this year from the Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences. These students reported on treatments for heart disease, non-alcoholic steatohepatitis and atopic dermatitis, as well as the underlying mechanisms involved in each. The titles of these reports are "Study of the role of cardiac 14-3-3η protein in cardiac inflammation and adverse cardiac remodeling during heart failure in mice", "Non-alcoholic steatohepatitis: onset of mechanisms under diabetic background and treatment strategies" and "The role of HMGB1 and its cascade signaling pathway in atopic dermatitis". It can be concluded from these three theses that oxidative stress and inflammation are among the principal mechanisms underlying these diseases.


Interactions between chronic ethanol consumption and thiamine deficiency on neural plasticity, spatial memory, and cognitive flexibility.
Many alcoholics display moderate to severe cognitive dysfunction accompanied by brain pathology. A factor confounded with prolonged heavy alcohol consumption is poor nutrition, and many alcoholics are thiamine deficient. Thus, thiamine deficiency (TD) has emerged as a key factor underlying alcohol-related brain damage (ARBD). TD in humans can lead to Wernicke Encephalitis that can progress into Wernicke-Korsakoff syndrome and these disorders have a high prevalence among alcoholics. Animal models are critical for determining the exact contributions of ethanol (EtOH)- and TD-induced neurotoxicity, as well as the interactions of those factors to brain and cognitive dysfunction. Adult rats were randomly assigned to 1 of 6 treatment conditions: chronic EtOH treatment (CET) where rats consumed a 20% v/v solution of EtOH over 6 months; severe pyrithiamine-induced TD (PTD-moderate acute stage); moderate PTD (PTD-early acute stage); moderate PTD followed by CET (PTD-CET); moderate PTD during CET (CET-PTD); and pair-fed (PF) control. After recovery from treatment, all rats were tested on spontaneous alternation and attentional set-shifting. After behavioral testing, brains were harvested for determination of mature brain-derived neurotrophic factor (BDNF) and thalamic pathology. Moderate TD combined with CET, regardless of treatment order, produced significant impairments in spatial memory, cognitive flexibility, and reductions in brain plasticity as measured by BDNF levels in the frontal cortex and hippocampus. These alterations are greater than those seen in moderate TD alone, and the synergistic effects of moderate TD with CET lead to a unique cognitive profile. However, CET did not exacerbate thalamic pathology seen after moderate TD. These data support the emerging theory that subclinical TD during chronic heavy alcohol consumption is critical for the development of significant cognitive impairment associated with ARBD.


Heterogeneity in non-epitope loop sequence and outer membrane protein complexes alters antibody binding to the major porin protein PorB in serogroup B Neisseria meningitidis.
PorB is a well-characterized outer membrane protein that is common among Neisseria species and is required for survival. A vaccine candidate, PorB induces antibody responses that are directed against six variable surface-exposed loops that differ in sequence depending on serotype. Although Neisseria meningitidis is naturally competent and porB genetic mosaicism provides evidence for strong positive selection, the sequences of PorB serotypes commonly associated with invasive disease are often conserved, calling into question the interaction of specific PorB loop sequences in immune engagement. In this report, we provide evidence that antibody binding to a PorB epitope can be altered by sequence mutations in non-epitope loops. Through the construction of hybrid PorB types and PorB molecular dynamics simulations, we demonstrate that loops both adjacent and non-adjacent to the epitope loop can enhance or diminish antibody binding, a phenotype that correlates with serum bactericidal activity. We further examine the interaction of PorB with outer membrane-associated proteins, including PorA and RmpM. Deletion of these proteins alters the composition of PorB-containing native complexes and reduces antibody binding and serum killing relative to the parental strain, suggesting that both intramolecular and intermolecular PorB interactions contribute to host adaptive immune evasion.


[Vaccines: a public affair?] [corrected].
In spite of the expectation that the development of vaccines would help in the control of some of the main transmissible diseases in Brazil, which are responsible for a large share of endemic illness in the country, efficient and safe vaccines against no less serious contagious diseases are available, yet underutilized. The reason is simple: some vaccines are not included in the National Immunization Program (PNI) and are this not the object of government campaigns. Despite the competence with which the National Health Foundation has acted-through the PNI-in reducing prevalence of diseases such as diphteria, whooping cough, measles, and polio, lack of information and prejudice make several vaccines inaccessible to a major share of the Brazilian population. Since the government-through its vaccination campaigns-exerts the most important influence on public opinion in this area, a vaccine procedure which is not the object of such campaigns will obviously not become part of popular culture. The result of this lack of information is that the population fails to utilize vaccines against such diseases as rubella, mumps, and hepatitis B or against Haemophilus influenza type b and pneumococcus infections. We therefore argue for information on the existence and availability of these vaccines, so that not only the part of the population that has access to private medicine can benefit, but mainly so that pressure can be brought to bear on the government for all public health care services to supply them to the neediest portion of the population. We suggest that strategies for the socialization of immunoprophylatics should be defined with participation by all segments of society, incorporating measures such as the gradual expansion of the National Immunization Program, coverage of vaccine costs by health insurance policies, and granting of fiscal incentives to companies that vaccinate their employees and families. Finally, we propose a struggle against the prejudice surrounding participation by private initiative in collective health actions, as well as defense of the interaction between private and public sectors in all aspects of health throughout Brazil.


Conbercept combined with laser photocoagulation in the treatment of diabetic macular edema and its influence on intraocular cytokines.
The prevalence of diabetes mellitus (DM) in China is high, and the base is broad. Diabetic retinopathy (DR) is a critical condition affecting the life and health of a nation and its economic development. DR is a common complication of DM. To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema. Overall, 130 patients with diabetic macular edema (DME) hospitalized in The Third People's Hospital of Changzhou from January 2019 to June 2022 were retrospectively included. According to the treatment plan, 130 patients with DME were categorized into an observation and a control group, with 65 patients in each group. The control group received laser photocoagulation, and the observation group received laser photocoagulation with intravitreal injection of conbercept. Observe changes in vision, cytokines in the eye and so on. The total efficacy rate in the observation group (93.85%) was higher than that in the control group (78.46%) (P < 0.05). In both groups, the best corrected visual acuity correction effect improved after treatment, and the observation group was superior to the control group (P < 0.05). Retinal thickness and central macular thickness improved after treatment, and the observation group was superior to the control group (P < 0.05). The levels of vascular endothelial growth factor, interleukin-6, soluble intercellular adhesion molecule-1, and basic fibroblast growth factor in both groups improved after treatment, and the observation group was superior to the control group (P < 0.05). In patients with macular edema, combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision, and lower intraocular cytokine levels.


Home Healthcare Nurses' Job Satisfaction Scale: refinement and psychometric testing.
This paper describes a study to further develop and test the psychometric properties of the Home Healthcare Nurses' Job Satisfaction Scale, including reliability and construct and criterion validity. Numerous scales have been developed to measure nurses' job satisfaction. Only one, the Home Healthcare Nurses' Job Satisfaction Scale, has been designed specifically to measure job satisfaction of home healthcare nurses. The Home Healthcare Nurses' Job Satisfaction Scale is based on a theoretical model that integrates the findings of empirical research related to job satisfaction. A convenience sample of 340 home healthcare nurses completed the Home Healthcare Nurses' Job Satisfaction Scale and the Mueller and McCloskey Satisfaction Scale, which was used to test criterion validity. Factor analysis was used for testing and refinement of the theory-based assignment of items to constructs. Reliability was assessed by Cronbach's alpha internal consistency reliability coefficients. The data were collected in 2003. Nine factors contributing to home healthcare nurses' job satisfaction emerged from the factor analysis and were strongly supported by the underlying theory. Factor loadings were all above 0.4. Cronbach's alpha coefficients for each of the nine subscales ranged from 0.64 to 0.83; the alpha for the global scale was 0.89. The correlations between the Home Healthcare Nurses' Job Satisfaction Scale and Mueller and McCloskey Satisfaction Scale was 0.79, indicating good criterion-related validity. The Home Healthcare Nurses' Job Satisfaction Scale has potential as a reliable and valid scale for measurement of job satisfaction of home healthcare nurses.


The endovascular treatment of juxta-renal abdominal aortic aneurysm using fenestrated endograft: early and mid-term results.
The aim of the present study was to evaluate the early and mid-term results of the endovascular treatment of juxta-renal abdominal aortic aneurysms (j-AAA) using fenestrated endograft (FEVAR). Between 2008 to 2013 all consecutive patients underwent FEVAR using Cook-Zenith fenestrated endograft for treating j-AAA (proximal neck length <5 mm) with renal aortic α/β angle <60°, were prospectively collected in a database. Cardiovascular risk factors, comorbidities, aortic-iliac morphological features, intra and post-procedural data were analyzed. Preoperative FEVAR planning was performed by a thoraco-abdominal computer tomography angiography (CTA) and the 3D/Center Lumen Line reconstructions (3mensio Medical Imaging, Bilthoven, The Netherlands). Follow-up was conducted by duplex ultrasound (DUS)/ contrast enhancement DUS (CEUS) and/or CTA at 1, 6, and 12 months, and yearly thereafter. Early endpoints were technical (TS) and clinical success (CS), renal function worsening (≥30% of preoperative creatinine value) and type I/III endoleak. Mid-term endpoints were: type I/III endoleak, target visceral vessels patency, j-AAA shrinkage, freedom from reintervention and survival. Twenty patients (94.7% of whom male; mean age: 73.4±5.9 years; ASA≥3: 100%) were enrolled. The mean neck length and j-AAA diameter were 2±1.4 mm (range: 0-4 mm) and 54.9±5 mm, respectively. Eleven (55%) endograft with two fenestrations and a scallop, 8 (45%) with three fenestrations and a scallop, and one (5%) with one fenestration and a scallop were implanted. Sixty-seven visceral vessels were re-vascularized. TS and CS were 100% and 95%, respectively (1/20 30-day mortality). Perioperative renal function worsening was observed in 15% of cases. The mean follow-up was 25±20 months (range: 2-72 months). No type I/III endoleak or occlusion of target visceral vessels occurred. There was j-AAA shrinkage in 65% of patients and no cases of j-AAA enlargement were observed. There were no FEVAR-related reinterventions. Survival at 12, 24, and 36 months were 89.4%, 80.5%, and 80.5%, respectively. According to our results, the endovascular treatment for j-AAA, with α/β angle <60°, is safe and effective.


Salinomycin: A new paradigm in cancer therapy.
The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate-binding cassette transporter in multidrug resistance cells and interferes with Akt signaling pathway, Wnt/β-catenin, Hedgehog, and Notch pathways of cancer progression. Salinomycin selectively targets cancer stem cells. The potential of salinomycin to eliminate both cancer stem cells and therapy-resistant cancer cells may characterize the compound as a novel and an efficient chemotherapeutic drug.


Testicular damage due to cytotoxic drugs and recovery after cessation of therapy.
Testicular function was assessed in 32 patients who received standard chemotherapy regimens for disseminated lymphomas. Thirty-one had evidence of germ cell damage, as assessed by the finding of azoospermia and/or high plasma levels of follicle-stimulating hormone (FSH). In addition, five patients had persistently low plasma testosterone levels associated in three with elevated plasma luteinising hormone (LH) levels. Reproductive function did not recover in any patient while chemotherapy continued. Cessation of therapy was possible in 16 patients with prolonged remissions of disease. Among these, recovery of germinal epithelium differed greatly between the cyclophosphamide / vincristine / prednisone treated group and the mustine/procarbazine/vincristine/prednisone treated group. Seventy per cent of the former patients had evidence of recovery after 34 months of follow-up while only one (17%) of the latter had begun to recover at 52 months post-therapy. Serial measurement of plasma FSH levels proved useful in predicting likely recovery of spermatogenesis.


The comparison of Se(IV) and Se(VI) sequestration by nanoscale zero-valent iron in aqueous solutions: The roles of solution chemistry.
The sequestration of Se(IV) and Se(VI) by nanoscale zero-valent iron (NZVI) particles were compared under different solution conditions. Firstly, the comparison was conducted at three pH values (4.0, 6.0 and 8.0) in deionized water. Generally, the removal of Se(IV)/Se(VI) by NZVI was more rapid under acidic conditions and the removal efficiency of Se(IV) was much higher than that of Se(VI). Moreover, the pH variation exhibited much larger influence on the sequestration of Se(VI) than that of Se(IV) by NZVI. The spectroscopic analysis showed that both the Se(IV) and Se(VI) were reduced to Se0 and Se2-, while NZVI was transformed into iron (hydr)oxides. When the selenium-NZVI reactions occurred in synthetic groundwater, all the reaction systems were inhibited in varying degrees. The individual effects of humic acid (HA) and typical inorganic ions were also examined. It seems that HA could substantially hinder the sequestration of Se(IV) compared with that in deionized water, while sulfate (SO42-) and bicarbonate (HCO3-) inhibited the Se(VI) removal significantly. Notably, the presence of cations (i.e., Na+ or Ca2+) ions did not cause obvious interference to the Se(IV)/Se(VI) removal by NZVI, while the presence of Ca2+ could alleviate the adverse effect of HA on Se(IV) removal to some degree.


PET/CT imaging of skeletal muscle metastases.
Skeletal muscle metastases (SMM) are very rare because of complex resistance of the musculature to metastatic invasion. Previously, positron emission tomography (PET) imaging of SMM has been reported only in few reports. A systematic analysis of SMM features in PET/CT has not been performed before. To study PET/CT findings of SMM in a larger group of patients with known malignancies and to determine PET/CT patterns of SMM in different primary tumors. Between January 2009 and December 2011 581 patients with lung cancer were investigated by PET with 18 F-fluordeoxyglucose (FDG PET) and computed tomography (CT) at the Center of Fusion Imaging, Halle. In five patients SMM were identified. Furthermore, PubMed database was screened for muscle metastases. Only articles containing SUV of SMM were considered in the study. Twenty-one articles with 33 patients could be included in this meta-analysis from the literature. At our center the prevalence of SMM was 0.9%. Our analysis comprised 38 patients with 67 muscle metastases. All identified SMM presented as intramuscular focal abnormal activity with SUV ranging from 2.4 to 25.9, median SUV 7.8. The median size of the muscle metastases was 2.5 cm (range, 0.6-6.5 cm). There were no significant differences between SUV and size of SMM arising from lung cancer, renal cell carcinoma, and esophageal cancer. Also, there was no correlation between SUV and size of SMM (r = 0.101, P = 0.558) and between SUV of SMM and primary tumors (r = 0.138, P = 0.686). In nine (23.7%) of the 38 patients, the identified SMM were isolated distant metastases or isolated tumor recurrence. SMM manifested on PET/CT as focal hypermetabolic intramuscular areas with different SUV. There were no significant differences between SUV or size of the identified SMM in esophageal cancer, renal cell carcinoma, and lung cancer.


Inhibitor-induced structural change in the HCV IRES domain IIa RNA.
Translation of the hepatitis C virus (HCV) RNA is initiated from a highly structured internal ribosomal entry site (IRES) in the 5' untranslated region (5' UTR) of the RNA genome. An important structural feature of the native RNA is an approximately 90 degrees helical bend localized to domain IIa that positions the apical loop of domain IIb of the IRES near the 40S ribosomal E-site to promote eIF2-GDP release, facilitating 80S ribosome assembly. We report here the NMR structure of a domain IIa construct in complex with a potent small-molecule inhibitor of HCV replication. Molecular dynamics refinement in explicit solvent and subsequent energetic analysis indicated that each inhibitor stereoisomer bound with comparable affinity and in an equivalent binding mode. The in silico analysis was substantiated by fluorescence-based assays showing that the relative binding free energies differed by only 0.7 kcal/mol. Binding of the inhibitor displaces key nucleotide residues within the bulge region, effecting a major conformational change that eliminates the bent RNA helical trajectory, providing a mechanism for the antiviral activity of this inhibitor class.


How to Use TeleSimBox "Off the Shelf" to Connect Remote Content Experts With In-Person Simulation Participants.
In this technical report, we describe how to use TeleSimBox to run a remotely facilitated simulation to connect the facilitator with learners at a distant site. This method was developed to comply with safety measures imposed during the coronavirus disease-19 (COVID-19) pandemic to reduce the risk of viral exposure and transmission. Here, we present one example where a telesimulation naïve facilitator was trained as an in-person facilitator to enable the in-situ medical student and resident learners to participate in a pediatric emergency simulation exercise remotely guided by an off-site content expert. The case of neonatal shock was run five times during a half-day emergency department (ED) educational program with one to four participants per session. 14/15 (93%) participants completed evaluations and felt that the simulation met the case learning objectives and that connecting with the remote facilitator was useful for their learning. Feedback from the one newly trained in-person facilitator was that the tool was easy to learn how to use quickly, and the process of connecting with a remote expert was worthwhile for learners. To grab this web-based toolkit off the proverbial shelf and successfully run a telesimulation session from start to finish took approximately one hour; 20 minutes were spent in preparation the day prior and 40 minutes to set up and run the simulations the day of. We believe that this is a low-cost, efficient, and perceived to be an effective method to connect remotely located content experts and learners to engage in a simulation-based education activity when access to in-person resources and personnel is limited.


Resin Cement/Enamel Interface: A Morphological Evaluation of the Acid-Base Resistant Zone, Enamel Etching Pattern, and Effect of Thermocycling on the Microshear Bond Strength.
To evaluate the effects of etching mode (self-etch and etch-and-rinse) on acid-base resistant zone (ABRZ) formation at the resin cement/enamel interface and enamel etching pattern, as well as the effects of thermocycling (0, 5000, and 10,000 cycles) on the enamel microshear bond strength (μSBS) mediated by dual-cure resin cements (DCRC). Two DCRC were used in 4 groups: Panavia V5 in self-etch (V5NE) and etch-and-rinse mode (V5E); and Estecem II in self-etch (ENE) and etch-and-rinse mode (EE). For ABRZ observation, the bonded interface was subjected to a demineralizing solution. The morphological attributes of the interface and etching patterns were observed using FE-SEM. For μ-SBS, cylinders with a 0.79-mm internal diameter and 0.5-mm height were made with DCRC and tested in shear after 0, 5000, and 10,000 thermal cycles (TC) (5°C and 55°C) (n = 10). The formation of an enamel ABRZ was observed in all groups with different morphological features between self-etch and etch-and-rinse groups. A funnel-shaped erosion beneath the interface was present using V5NE and ENE modes where enamel was dissolved, while ABRZ formation was confirmed and no funnel-shaped erosion was noticed using V5E and EE. No significant differences in μSBS were observed between resin cements. However, significantly lower µSBSs were recorded when the self-etching mode was used. Thermocycling resulted in a significant reduction in µSBS for all groups. Selective enamel etching should be recommended to improve the interfacial quality when dual-cure resin luting cements are used.


Effect of the Molecular Structure Change of a Matrix Polymer (Nylon 6) on the Deformation of Dispersed Phase (a Thermotropic Liquid Crystalline Polymer) Droplets in Shear Flow.
In this work, we investigated the effect of a change in the molecular structure and ensuing molar mass change of a matrix polymer (polyamide 6, Ny 6) on droplet deformation of a dispersed thermotropic liquid crystalline polymer (TLCP, a poly(ester amide)) in shear flow. This study focuses on a total capillary number (the sum of the shear capillary number and the elasticity capillary number) and the viscosity ratio between the TLCP and Ny 6, for the morphological development and mechanical performance of TLCP/Ny 6 blends. In contrast to Ny 6, which has a lower melt viscosity than the TLCP melt, a modified Ny 6 (m-Ny 6) with ca. 2 orders higher melt viscosity than that of Ny 6 at a shear rate of 1 s-1 was found to facilitate the deformation of the TLCP phase. A total capillary number was defined to characterize the viscoelasticity effect on droplet deformation in the blend system. The first normal stress difference obtained from the viscosity curve using Steller's method was used for the evaluation of the elasticity capillary number. The total capillary number for the Ny 6 blend was far less than the critical capillary number and was insufficient for the dispersed TLCP droplets to be deformed. The shear capillary number of the m-Ny 6 blend was greater than the critical capillary number but was still insufficient for droplet deformation into fibril shapes. The total capillary number, including the elastic capillary number, was sufficiently greater than the critical capillary number for deformation of the dispersed TLCP droplets. Morphological observations and a comparison with the theoretical work confirmed the importance of the viscoelasticity of the melt in the immiscible Ny 6/TLCP blends for in situ composite fabrication in shear flow. Both the high viscosity and the first normal stress difference of m-Ny 6 promote the deformation and fibrillation of the dispersed TLCP droplets.


IgA deficiency in one of identical twins.
A disease resembling childhood coeliac disease occurred in one of identical twins. When the twins were investigated at the age of 23 the initial diagnosis could not be substantiated but the twin who had been ill had selective IgA deficiency. Differences dating from early infancy may have been a result of the discordance for IgA deficiency. Thus in some patients environmental influences may be important in either the initiation or the perpetuation of the deficiency.


Evidence of alternative or concomitant use of perforin- and Fas-dependent pathways in a T cell-mediated negative regulation of Ig production.
To study the possible involvement of perforin (Pfp)- and/or Fas-dependent cytotoxicity pathways in a T cell-mediated negative regulation of Ig production, we used the T cell-induced Ig-allotype suppression model. T splenocytes from Igha/a mice, when neonatally transferred into histocompatible Igha/b F1 or Ighb/b congenic hosts, are intrinsically able to totally, specifically, and chronically suppress the production of IgG2a of the Ighb haplotype (IgG2ab). It has not been established whether the suppression effectors, which are anti-IgG2ab MHC class I-restricted CD8+ T cells, cytolyse IgG2ab+ B targets or whether they only silence Ig production. In this study, using T cells from Igha/a Pfp+/+ or Pfpo/o mice, the latter obtained by crossbreeding, and B cells from Ighb/b Fas+/+ or Faslpr/lpr (lymphoproliferation) mice in appropriate adoptive transfer models, we demonstrated that: 1) under blockage of the Pfp-mediated pathway, Igha/a T cells were still able to induce suppression against wild-type IgG2ab+ B cells, 2) IgG2ab+ B cells with impaired Fas expression were also subjected to suppression by WT Igha/a T splenocytes, and 3) the suppression establishment was totally inhibited when both Pfp- and Fas-dependent mechanisms were simultaneously blocked, i.e., when Igha/a Pfpo/o T cells were used to induce suppression against Ighb/b Faslpr/lpr B cells. These results provide the first demonstration of the existence of alternative or simultaneous use of the major cytotoxic mechanisms in a T cell-mediated down-regulation of an Ig production.


Biological aspects of the Dm 28c clone of Trypanosoma cruzi after metacyclogenesis in chemically defined media.
The biological characterization of the Trypanosoma cruzi clone Dm 28c in terms of its growth in LIT medium, cell-cycle, infectivity to mice and interaction with professional and non-professional phagocytic cells shows that it behaves as a bona fide T. cruzi representant. The biological properties of this myotropic clone do not change according to the origin of the trypomastigote forms (i. e., from triatomines, infected mice, cell-culture or from the chemically defined TAUP and TAU3AAG media). In addition Dm 28c metacyclic trypomastigotes from TAU3AAG medium display a high infectivity level to fibroblasts and muscle cells. Experiments on binding of cationized ferritin to trypomastigotes surface show the existence of cap-like structures of ferritin in regions near the kinetoplast, however the nature and role of these anionic sites remain to be determined. The results indicate that metacyclic trypomastigotes from the Dm 28c clone obtained under chemically defined conditions reproduce the biological behaviour of T. cruzi, rendering this system very suitable for the study of cell-parasite interactions and for the isolation of trypanosome relevant macromolecules.


Italian medical students quality of life: years 2005-2015.
Quality of Life (QoL) is a concept used to indicate the general wellness of persons or societies. University students report a low quality of life and a worse perception of their health status, because of a situation of greater discomfort in which they live during the course of the study, especially in faculties with an important emotional burden, such as medical schools. The aim of the study was to evaluate the perceived health status of first year medical students. We conducted a cross sectional study in the time span 2005-2015, administering the questionnaire Short Form 36 (SF-36) to first-year students of the School of Medicine of the University of Siena, Italy. In addition to demographic information such as gender and the age we investigated the region of residence, marital status, employment status, and smoking habits; height and weight were required to calculate the body mass index (BMI) to evaluate a possible physical discomfort connected with the perception of health status. The data from the questionnaires were organized and processed by software Stata® SE, version 12.1. 1,104 questionnaires were collected. Medical students reported lower SF-36 scores, compared to the Italian population of the same age. Female gender and smoking habits influence negatively the score of several scales. Body Mass Index is positively correlated with the Physical Activity, while Age is negatively correlated with Social Activities. The perceived quality of life of the Italian medical students is lower when compared to the general population. This confirms that the condition of student implies additional problems, as other studies reports. It would be better to improve it, developing students' resilience. It would be interesting to extend this research to students of other years, from other faculties and other locations, to gain a broader view about the QoL of the Italian students.


Travel intentions of travelers in the COVID-19 context: The moderation of fear of COVID-19.
The spread of COVID-19 pandemic in early 2020 has significantly affected the tourism industry. Most current tourism research on emergencies focuses on issues such as the revitalization of the tourism economy. However, research on aspects such as visitor perception has not received sufficient attention, This study contributes to the literature by analyzing the effects of social interactions, multidimensional perceived value, fear of COVID-19, and age on travelers' travel intentions during the COVID-19 pandemic. This study constructs a structural equation model, formulates the corresponding hypotheses, investigates Chinese travelers, and verifies the moderating effect of COVID-19 fear. All of the proposed hypotheses were verified. The three dimensions of perceived value and satisfaction had a significant mediating effect in the relationship between perceived quality and travel intention, and that fear of COVID-19 had a significant moderating effect in the relationship between satisfaction and travel intention. With the moderation of fear of COVID-19, age had a significantly negative effect on travel intention. Given extant research demonstrating that both math activities and math talk predict children's math skills, our results stress the need for multimethod studies that differentiate among these HME opportunitiesThe findings confirmed a significant mediating effect of the three dimensions of perceived value and satisfaction on perceived quality and travel intention. fear of COVID-19 had a significant moderating effect on satisfaction and travel intention. In addition, age had a significant negative effect on travel intention under the moderation of fear of COVID-19; thus, travel intention decreases with age.


[2nd revised consensus skin melanoma. De Nederlandse Melanoom Werkgroep].
The 'Guideline melanoma of the skin, second revised consensus' was published in March 1997. Some of the contents are cited: Over 1600 new melanomas are diagnosed in the Netherlands each year; by now the mean 5-year survival amounts to over 80%. In examination of a pigmented lesion a dermatoscope is a valuable tool. The recommended margin of the diagnostic excision was reduced from 5 mm to 2 mm of macroscopically normal skin round the lesion; the margins in definite excision are: 1 cm of normal skin for a Breslow thickness < or = 2 mm; 2 cm for a Breslow thickness > 2 and < or = 4 mm. A margin of at least 2 cm seems also justified for thicker melanomas. Elective (prophylactic) regional lymph node dissection is advised against. Sentinel node biopsy appears to be an attractive method to detect occult metastasis in regional nodes. In lymph node metastasis a (therapeutic) regional lymph node dissection should be performed. In case of inoperable tumourgrowth in an extremity regional isolated perfusion is indicated. Radiotherapy may be applied curatively (e.g. if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy in melanoma patients is still experimental; the earliest results of high doses of interferon alpha are encouraging. Atypical (dysplastic) naevi and congenital naevi are important risk factors for melanoma. No consensus was reached regarding prophylactic removal of all congenital naevi. Regarding the duration of the follow-up period, 5 years suffices in patients with a melanoma with a Breslow thickness < or = 1.5 mm (provided there are no histological signs of regression), while 10 years is required for melanomas with a Breslow thickness > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Routine blood testing, roentgen examination or ultrasonography are considered to be useless. There are no indications that hormonal alterations during pregnancy or use of the pill stimulate the growth of micrometastases that may be present. Excessive exposure to ultraviolet rays is discouraged.


Oral Candida carriage, quantification, and species characterization in oral submucous fibrosis patients and healthy individuals.
To determine the prevalence of oral Candida carriage, candidal quantification, and various subtypes of Candida species in oral submucous fibrosis patients and healthy individuals. The study comprised 30 clinically-diagnosed and -staged oral submucous fibrosis patients aged 20-40 years, and 20 age- and sex-matched controls. Buccal mucosa was sampled by sterile swab technique. Each sample was inoculated on Sabouraud's dextrose agar and CHROMagar culture media. Candida species identification was done using the KB006 Candida identification kit. Eleven (36.67%) cases in the study group, and two (10%) cases in the control group, yielded Candida on culture. The value of CFU/mL increased with an increased duration of betel quid chewing habit. All Candida-positive oral submucous fibrosis patients complained of a burning sensation. Candida albicans and Candida tropicalis were the most common species in the oral submucous fibrosis cases. Candida dubliniensis was isolated in both the study and control groups. Our observations in this study affirm that oral submucous fibrosis favors the colonization of Candida. Mucosal alterations due to the underlying disease process or betel quid chewing, coupled with other factors, might lead to candidal colonization, even in the absence of clinically-related mycotic manifestations.


Cytosolic phosphoglucose isomerase is essential for microsporogenesis and embryogenesis in Arabidopsis.
Phosphoglucose isomerase (PGI) catalyzes the interconversion of fructose-6-phosphate and glucose-6-phosphate, which impacts cell carbon metabolic flow. Arabidopsis (Arabidopsis thaliana) contains two nuclear PGI genes respectively encoding plastidial PGI1 and cytosolic PGI (cPGI). The loss of PGI1 impairs the conversion of F6P of the Calvin-Benson cycle to G6P for the synthesis of transitory starch in leaf chloroplasts. Since cpgi knockout mutants have not yet been obtained, they are thought to be lethal. The cpgi lethality can be rescued by expressing CaMV 35S promoter (p35S)-driven cPGI; however, the complemented line is completely sterile due to pollen degeneration. Here, we generated a cpgi mutant expressing p35S::cPGI-YFP in which YFP fluorescence in developing anthers was undetectable specifically in the tapetum and in pollen, which could be associated with male sterility. We also generated RNAi-cPGI knockdown lines with strong cPGI repression in floral buds that exhibited reduced male fertility due to the degeneration of most pollen. Histological analyses indicated that the synthesis of intersporal callose walls was impaired, causing microsporocytes to fail to separate haploid daughter nuclei to form tetrads, which might be responsible for subsequent pollen degeneration. We successfully isolated cpgi knockout mutants in the progeny of a heterozygous cpgi mutant floral-dipped with sugar solutions. The rescued cpgi mutants exhibited diminished young vegetative growth, reduced female fertility, and impaired intersporal callose wall formation in a meiocyte, and, thus, male sterility. Collectively, our data suggest that cPGI plays a vital role in carbohydrate partitioning, which is indispensable for microsporogenesis and early embryogenesis.


Determination of blood cyanide by HPLC-MS.
An original high-performance liquid chromatographic-mass spectrometric (HPLC-MS) procedure was developed for the determination of cyanide (CN) in whole blood. After the addition of K13C15N as internal standard, blood was placed in a microdiffusion device, the inner well of which was filled with a mixture of taurine (50mM in water)/naphthalene-2,3-dicarboxaldehyde (NDA, 10mM in methanol)/methanol/ concentrated (approximately 20%) ammonia solution (25:25:45:5, v/v). Concentrated H2SO4 was added to the blood sample, and the microdiffusion chamber was sealed. After 30 min of gentle agitation, 2 microL of the contents of the inner vial were pipetted and directly injected onto a NovaPak C18 HPLC column. Separation was performed by a gradient of acetonitrile in 2mM NH4COOH, pH 3.0 buffer (35-80% in 10 min). Detection was done with a Perkin-Elmer Sciex API-100 mass analyzer with an ionspray interface, operated in the negative ionization mode. MS data were collected as either TIC or SIM at m/z (299 + 191) and (301 + 193) for the derivatives formed with CN and 13C15N, respectively. Inspired by previous works dealing with the complexation of CN by NDA + taurine to form a 1-cyano [f] benzoisoindole derivative analyzed by HPLC-fluorimetry, this method appears simple, rapid, and extremely specific. Limits of detection and quantitation for blood CN are 5 and 15 ng/mL, respectively. The use of 13C15N as internal standard allows the quantitation of CN with elegance and accuracy in comparison with previously reported methods.


Relationship between the kidney and parathyroid hormone.
This report reviews the interrelationship between the activity of the parathyroid glands and renal function. Among the topics discussed are: effects of parathyroid hormone on various aspects of renal function such as: (1) glomerular filtration rate and renal blood flow; (2) renal handling of phosphorus, calcium, magnesium, sodium and potassium; (3) renal production of 1,25-dihydroxycholecalciferol; (4) renal handling of bicarbonate and acid-base metabolism, and (5) mechanism of action of parathyroid hormone on the renal cell. Further topics include: renal metabolism of parathyroid hormone; the kidney in hyperparathyroidism, and effects of renal failure on structure and function of the parathyroid glands.


Single-Particle ICP-MS as a Screening Technique for the Presence of Potential Inorganic Nanoparticles in Food.
In this work, we show the potential of single-particle inductively coupled plasma-mass spectrometry (spICP-MS) as a screening technique for detection of inorganic nanoparticles (NPs) that are expected to be present in food. We demonstrate that the spICP-MS/MS method in combination with collision/reaction cell gases and microsecond dwell times offers sensitive and interference-free detection of NPs. We present the steps that have to be considered to correctly assess the presence of NPs in food, for example, setting a suitable threshold for discriminating particle events from the baseline and analyzing a sufficient number of blank samples to minimize false-positive results. We applied the proposed screening approach to the sequential detection of NPs containing 8 selected elements that could be potentially present in 13 different food products. The highest mass concentrations of NPs (in the mg/g range) were found in the samples with food additives which are known to contain a fraction of NPs. The presence of (nano)particles in some of the investigated food samples was also confirmed by scanning electron microscopy analysis. Moreover, for the example of Al-containing NPs in Chinese noodles, we demonstrate that identification of the source of NPs with an unknown composition can be challenging when using only spICP-MS as particle mass concentration and size distribution can only be estimated by assuming a certain particle composition/shape. Other complementary techniques for particle characterization, such as electron microscopy in combination with elemental analysis, are therefore required.


Ru(II) multinuclear metallosupramolecular rack-type architectures of polytopic hydrazone-based ligands: synthesis, structural features, absorption spectra, redox behavior, and near-infrared luminescence.
A novel class of polytopic hydrazone-based ligands was synthesized. They gave heteroleptic Ru(II) polynuclear rack-like complexes of formula [Ru(n)terpy(n)(bridging molecular strand)](2n+) (terpy=2,2':6',2''-terpyridine). The new rack-like systems can be viewed as being made of two identical or roughly identical peripheral subunits separated by several similar metal-containing spacer subunits. The presence of pyrazine or pyrimidine units within the molecular multitopic strands introduces additional chemical diversity: whereas a pyrimidine unit leads to appended orthogonal subunits that are on the same side with regard to the main molecular strand, a pyrazine unit leads to orthogonal subunits that lie on different sides. Mixing pyrazine and pyrimidine units within the same (bridging) molecular strand also allows peculiar and topographically controlled geometries to be obtained. Redox studies provided evidence that each species undergoes reversible redox processes at mild potentials, which can be assigned to specific subunits of the multicomponent arrays. Non-negligible electronic coupling takes place among the various subunits, and some electron delocalization extending over the overall bridging molecular strand takes place. In particular, oxidation data suggest that the systems can behave as p-type "molecular wires" and reduction data indicate that n-type electron conduction can occur within the multimetallic framework. All the multinuclear racks exhibit (3)MLCT emission, both at 77 K in rigid matrix and at 298 K in fluid solution, which takes place in the near-infrared region (emission maxima in the 1000-1100 nm region), and is quite structured. Rigidity of the molecular structures and delocalization within the large bridging ligands are proposed to contribute to the occurrence of the rather uncommon MLCT infrared emission, which is potentially interesting for optical communication devices.


Recovery education for people experiencing housing instability: An evaluation protocol.
Recovery education centers (RECs) offer recovery supports through education rather than traditional health services. The Supporting Transitions and Recovery Learning Centre (STAR) in Toronto, Canada, is among the few that are internationally focused on individuals with histories of homelessness. Although research suggests that RECs positively impact participants, there is a paucity of rigorous studies and none address the engagement and impacts on homeless individuals. This protocol describes a realist-informed evaluation of STAR, specifically examining (1) if STAR participation is more effective in promoting 12-month recovery outcomes than participation in usual services for individuals experiencing housing instability and mental health challenges and (2) how STAR participation promotes recovery and other positive outcomes. This study uses a quasi-experimental mixed methods design. Personal empowerment (primary outcome) and recovery, housing stability, social functioning, health service use and quality of life (secondary outcomes) data were collected at baseline, and 6 and 12 months. Intervention group participants were recruited at the time of STAR registration while control group participants were recruited from community agencies serving this population after screening for age and histories of housing instability. Interviews and focus groups with service users and providers will identify the key intervention ingredients that support the process of recovery. From January 2017 to July 2018, 92 individuals were recruited to each of the intervention and control groups. The groups were mostly similar at baseline; the intervention group's total empowerment score was slightly higher than the control group's (M (SD): 2.94 (0.23) vs 2.84 (0.28), p = .02), and so was the level of education. A subset of STAR participants (n = 20) and nine service providers participated in the qualitative interviews and focus groups. This study will offer important new insights into the effectiveness of RECs, and expose how key REC ingredients support the process of recovery for people experiencing housing instability.


Functionally Graded Bismuth Oxide/Zirconia Bilayer Electrolytes for High-Performance Intermediate-Temperature Solid Oxide Fuel Cells (IT-SOFCs).
A functionally graded Bi1.6Er0.4O3 (ESB)/Y0.16Zr0.84O1.92 (YSZ) bilayer electrolyte is successfully developed via a cost-effective screen printing process using nanoscale ESB powders on the tape-cast NiO-YSZ anode support. Because of the highly enhanced oxygen incorporation process at the cathode/electrolyte interface, a novel bilayer solid oxide fuel cell (SOFC) yields extremely high power density of ∼2.1 W cm-2 at 700 °C, which is a 2.4 times increase compared to that of the YSZ single electrolyte SOFC.