[Implantation of an ARTISANtrade mark toric phakic intraocular lens to correct high astigmatism after penetrating keratoplasty].
Visual outcome after penetrating keratoplasty is often Iimited by residual astigmatism. Sometimes conservative treatment modalities like glasses or contact lenses fail to correct the keratoplasty-associated astigmatism. Refractive options are arcuate keratotomy, photorefractive keratectomy or laser in situ keratomileusis. The implantation of an ARTISAN toric intraocular lens presents an additive option to correct corneal astigmatism in phakic eyes. This toric intraocular lens (IOL) has an optical zone of 5.0 mm with a sphericaI front and a toric back. The torus of the IOL is available up to 7 D in half dioper steps. A 27-year old female presented with a bestcorrected visual acuity of 20/32. Penetrating keratoplasty was performed in 1997 because of a decompensated keratoconus. Despite a clear allgraft visual acuity was limited because of a keratoplasty-related high astigmatism of 7.6 D/124 degrees, which could not be sucessfully treated with glasses or contact lenses. An ARTISAN toric intraocular lens with - 3 D spherical and 7.0 D/0 degrees cylindrical power (individually manufactured) was implanted via a sclerocorneal tunnel incision into the anterior chamber. Postoperatively an optimal graft clarity with a well-centered and stable-positioned IOL was found. After 3 months uncorrected visual acuity was 20/25. Six months after implantation the IOL was still well-centered and uncorrected visual acuity was 20/20. Implantation of an ARTISAN toric intraocular lens in phakic eyes is an alternative and new option to correct higher astigmatism. In contrast to the keratorefractive option minor manipulation on the allograft can be expected. For a final conclusion of the endothelial cell loss longer follow-up is necessary.


Wuchereria bancrofti infection in Haitian immigrants and the risk of re-emergence of lymphatic filariasis in the Brazilian Amazon.
Lymphatic filariasis (LF) is a public health problem in Haiti. Thus, the emigration of Haitians to Brazil is worrisome because of the risk for LF re-emergence. Blood samples of Haitian immigrants, aged ≥18 years, who emigrated to Manaus (Brazilian Amazon), were examined using thick blood smears, membrane blood filtration, and immunochromatography. Of the 244 immigrants evaluated, 1 (0.4%) tested positive for W. bancrofti; 11.5% reported as having received LF treatment in Haiti. The re-emergence of LF in Manaus is unlikely, due to its low prevalence and low density of microfilaremia among the assessed Haitian immigrants.


Detecting the presence and absence of causal relationships between expression of yeast genes with very few samples.
Inference of biological networks from high-throughput data is a central problem in bioinformatics. Particularly powerful for network reconstruction is data collected by recent studies that contain both genetic variation information and gene expression profiles from genetically distinct strains of an organism. Various statistical approaches have been applied to these data to tease out the underlying biological networks that govern how individual genetic variation mediates gene expression and how genes regulate and interact with each other. Extracting meaningful causal relationships from these networks remains a challenging but important problem. In this article, we use causal inference techniques to infer the presence or absence of causal relationships between yeast gene expressions in the framework of graphical causal models. We evaluate our method using a well studied dataset consisting of both genetic variations and gene expressions collected over randomly segregated yeast strains. Our predictions of causal regulators, genes that control the expression of a large number of target genes, are consistent with previously known experimental evidence. In addition, our method can detect the absence of causal relationships and can distinguish between direct and indirect effects of variation on a gene expression level.


Biomechanical Study of Two Peripheral Suture Methods on Repaired Tendons.
Flexor digitorum tendon injuries are challenging conditions to manage to ensure optimal patient outcomes. While several surgical approaches with high success rates have been developed, there remains no gold standard for suture technique for the repair of flexor tendon injuries. In this study, we compared two distinct peripheral suture methods on the strength of repaired tendons. Pig flexor digitorum profundus tendons were used in biomechanical studies and the biomechanical influence on tendon repair of continuous running peripheral suture (CRPS) and continuous locking peripheral suture (CLPS), were compared, using stitch length ranging from 1mm to 5mm. In CRPS, the 1mm stitch length group displayed the highest maximum load and breaking power, which was 1.57 fold higher than the 2mm stitch length group. Pairwise comparison revealed that the 1 and 2mm groups were statistically different from the 3, 4, and 5mm stitch length groups while comparison among the latter groups was not statistically significant. For CLPS, the 1mm group exhibited consistently the highest maximum load strength and breaking power, which was twice the strength displayed by the 2mm group. Pairwise comparisons between groups showed statistical significance. For future repairs of flexor tendon injuries, 1mm stitch length is highly recommended for simple peripheral suture.


Characterization of the human homolog of the IL-4 induced gene-1 (Fig1).
Mouse interleukin-four induced gene-1 (mFig1) maps to a region of susceptibility for systemic lupus erythematosus (SLE) that includes the Sle3 locus. To begin examining this relationship in humans, we have isolated and characterized the human homolog of mFig1. Human Fig1 (hFig1) has the same eight exon genomic structure as mFig1. The predicted 63-kDa protein, like mFig1, contains a signal peptide, a large internal sequence that is most similar (43% identical over 484 amino acids) to L-amino acid oxidase (LAAO), and a carboxy terminal domain with no similarity to known genes. When compared to the LAAO crystal structure, hFig1 conserves key residues thought to be involved in catalysis and binding of the flavin adenine dinucleotide cofactor. Surprisingly, the carboxy terminal domains of hFig1 and mFig1 have little similarity (<11% identity), different lengths and amino acid composition. Like mFig1, hFig1 RNA is induced by interleukin-4 (IL-4) in B lymphocytes, and is primarily found in immune tissues. Finally, hFig1 maps to the predicted mFig1 syntenic region on human chromosome 19q13.3-19q13.4, a hot spot for susceptibility to several autoimmune diseases, including SLE.


Transfer of Magnetic Order and Anisotropy through Epitaxial Integration of 3d and 4f Spin Systems.
Resonant x-ray scattering at the Dy M_{5} and Ni L_{3} absorption edges was used to probe the temperature and magnetic field dependence of magnetic order in epitaxial LaNiO_{3}-DyScO_{3} superlattices. For superlattices with 2 unit cell thick LaNiO_{3} layers, a commensurate spiral state develops in the Ni spin system below 100 K. Upon cooling below T_{ind}=18 K, Dy-Ni exchange interactions across the LaNiO_{3}-DyScO_{3} interfaces induce collinear magnetic order of interfacial Dy moments as well as a reorientation of the Ni spins to a direction dictated by the strong magnetocrystalline anisotropy of Dy. This transition is reversible by an external magnetic field of 3 T. Tailored exchange interactions between rare-earth and transition-metal ions thus open up new perspectives for the manipulation of spin structures in metal-oxide heterostructures and devices.


The Small GTPase RHOA Links SLP65 Activation to PTEN Function in Pre B Cells and Is Essential for the Generation and Survival of Normal and Malignant B Cells.
The generation, differentiation, survival and activation of B cells are coordinated by signals emerging from the B cell antigen receptor (BCR) or its precursor, the pre-BCR. The adaptor protein SLP65 (also known as BLNK) is an important signaling factor that controls pre-B cell differentiation by down-regulation of PI3K signaling. Here, we investigated the mechanism by which SLP65 interferes with PI3K signaling. We found that SLP65 induces the activity of the small GTPase RHOA, which activates PTEN, a negative regulator of PI3K signaling, by enabling its translocation to the plasma membrane. The essential role of RHOA is confirmed by the complete block in early B cell development in conditional RhoA-deficient mice. The RhoA-deficient progenitor B cells showed defects in activation of immunoglobulin gene rearrangement and fail to survive both in vitro and in vivo. Reconstituting the RhoA-deficient cells with RhoA or Foxo1, a transcription factor repressed by PI3K signaling and activated by PTEN, completely restores the survival defect. However, the defect in differentiation can only be restored by RhoA suggesting a unique role for RHOA in B cell generation and selection. In full agreement, conditional RhoA-deficient mice develop increased amounts of autoreactive antibodies with age. RHOA function is also required at later stage, as inactivation of RhoA in peripheral B cells or in a transformed mature B cell line resulted in cell loss. Together, these data show that RHOA is the key signaling factor for B cell development and function by providing a crucial SLP65-activated link between BCR signaling and activation of PTEN. Moreover, the identified essential role of RHOA for the survival of transformed B cells offers the opportunity for targeting B cell malignancies by blocking RHOA function.


Hepatitis C virus genotype 7, a new genotype originating from central Africa.
We report a new hepatitis C virus (HCV) genotype identified in patients originating from the Democratic Republic of Congo. The prototype QC69 virus is shown to be a new lineage distinct from genotypes 1 to 6. Three additional patients were also found to be infected by a virus from this lineage, confirming its circulation in humans. We propose that these viruses be classified into HCV genotype 7.


Ethics of trial drug use: to give or not to give?
The 2014 outbreak of Ebola viral disease in some West African countries, which later spread to the USA and Spain, has continued to be a subject of global public health debate. While there is no approved vaccine or drug for Ebola cure yet, moral questions of bioethical significance are emerging even as vaccine studies are at different clinical trial phases. This paper, through a normative and critical approach, focuses on the question of whether it is ethical to give any experimental drugs to Ebola victims in West Africa or not. Given the global panic and deadly contagious nature of Ebola, this paper argues on three major compassionate grounds that it is ethical to use experimental drugs on the dying African victims of Ebola. Besides respecting patients and family consent in the intervention process, this paper argues that the use of Ebola trial drugs on West African population will be ethical if it promotes the common good, and does not violate the fundamental principles of transparency and integrity in human research ethics. Using Kantian ethical framework of universality as a basis for moral defense of allowing access to yet approved drugs. This paper provides argument to strengthen the compassionate ground provisional recommendation of the WHO's Strategic Advisory Group of Experts on Immunization (SAGE) on Ebola vaccines and vaccination.


DNA analysis by flow cytometry in cutaneous T-cell lymphomas.
DNA histograms of skin and blood specimens from 64 patients with known or suspected cutaneous T-cell lymphoma (CTCL) have been examined and compared with normal blood mononuclear cells and skin biopsy samples from 50 patients with various benign cutaneous conditions (i.e. patch test infiltrates, eczema, psoriasis, lichen planus, atopic dermatitis) in an attempt to establish whether DNA measurements by flow cytometry may improve the early recognition of CTCL. The results indicate that right-skewed G0/G1 peaks are seen frequently in both benign disorders and known and suspected CTCL. Such peaks may reflect increased stainability of DNA due to chromatin dispersion during cell activation and/or cell proliferation and do not constitute reliable evidence of malignancy. In contrast, discrete aneuploid DNA peaks are confined to malignant lesions, but are seen almost exclusively in the advanced stages in which the diagnosis can be established easily based on routine histological criteria. These data indicate that DNA measurements by flow cytometry is of only limited help in the early recognition of CTCL and support the view that the lymphoid infiltrate in early CTCL may be reactive (rather than neoplastic) or alternatively may contain only minor reactive (rather than neoplastic) or alternatively may contain only minor populations of abnormal (malignant) cells which cannot be detected by currently available DNA measurement techniques.


Strain-engineered indirect-direct band-gap transitions of PbPdO2 slab with preferred (0 0 2) orientation.
Layered transition metal oxide PbPdO2 has great potential application in electronic devices because of its unique electronic structure and large thermoelectric power at room temperature. In this work, strain effect on the electronic structure of PbPdO2 slab with preferred (0 0 2) orientation was systematically investigated using first-principles calculation. The calculated results indicate that PbPdO2 ultrathin slab possesses a small indirect gap while an indirect-direct band gap transition occurs when a moderate 2% compression or tensile strain is applied on the slab. Moreover, this strain induced indirect-direct band gap transition was analyzed in detail using the charge density difference at different point of valence band. The charge transfer and energy barrier with charge polarization resulting from the changes of bond length and angle for Pd-O bonding under the strain, have been accounted for this transition. Remarkablely, for the (0 0 2) preferred orientation PbPdO2 slab, the predicted carrier mobilities of electrons and holes are 11 645.31 and 694.60 cm2 V-1 s-1 along the x-axis direction, 935.05 and 16.05 cm2 V-1 s-1 along the y -axis direction, respectively. These calculated mobilities of electrons along the x-axis direction are larger than those for 2D MoS2 (~400 cm2 V-1 s-1), and being comparable to those for InSe (103 cm2 V-1 s-1) and black phosphorene (103-104 cm2 V-1 s-1). It is strong suggested that the (0 0 2) orientated PbPdO2 slab with high mobility should be an ideal candidate material for the application of electronics devices.


Skin autofluorescence, arterial stiffness and Framingham risk score as predictors of clinical outcome in chronic kidney disease patients: a cohort study.
The risk of cardiovascular disease (CVD) is predicted by Framingham's CVD risk scores (FRS) but the high CVD-related mortality in patients with chronic kidney disease (CKD) is only partially explained by traditional CVD risk markers. Therefore, there is a need to explore whether other CVD risk markers may improve risk prediction. Although arterial stiffness measured by augmentation index (AIx) and tissue content of advanced glycation end-products (AGEs) measured by skin autofluorescence (SAF) are two biomarkers that associate with CVD and mortality in CKD, it is not known how they compare with FRS. We evaluated associations between SAF, AIx and FRS, and their associations with CVD and mortality in CKD patients. SAF (AGE Reader) and AIx (SphygmoCor; adjusted for 75 heart beats per minute) were measured in 261 clinically stable and extensively phenotyped patients with CKD Stage 5 (median age 56 years, 66% male, 20% diabetes; 130 non-dialysed, 93 patients on peritoneal dialysis and 38 patients on haemodialysis). Multivariate receiver operator characteristics (ROC) curve analysis and multivariate Cox models followed by C-statistics were used to evaluate CVD-related and all-cause mortality risk associated with SAF, AIx and FRS during follow-up for median 25 months with 46 deaths. In multivariate regression analysis, SAF associated with FRS, haemoglobin, fat body mass index and CVD, and inversely with per cent handgrip strength (HGS). AIx associated with FRS, and inversely with per cent HGS. Associations of SAF and AIx with high-sensitivity C-reactive protein (hsCRP), serum albumin, statin therapy and renal replacement therapy were not statistically significant. In ROC analysis, area under the curve (AUC) for CVD mortality ranged from AUC = 0.72 (AIx and FRS, respectively) to AUC = 0.78 (FRS + AIx), and for all-cause mortality from AUC = 0.70 (AIx) to AUC = 0.79 (FRS + AIx). In multivariate Cox analysis, after adjusting for 1-standard deviation (1-SD) of FRS, 1-SD increase of SAF associated with all-cause mortality and 1-SD increase of AIx associated with CVD mortality and all-cause mortality. After further adjustments for hsCRP, albumin and presence of CVD, AIx (but not SAF) remained independently associated with CVD mortality, hazard ratio (HR) 2.14 [95% confidence interval (95% CI) 1.18-3.89] and all-cause mortality, HR 1.74 (95% CI 1.16-2.60). In patients with CKD Stage 5, SAF and aortic stiffness associated with mortality, independently of FRS. After adjusting for additional confounders including inflammation, aortic stiffness remained as an independent predictor of outcome. Since the contribution of SAF and aortic stiffness compared with FRS in ROC curve analysis was relatively modest, this underlines the importance of traditional CVD risk factors in CKD.


Aerobic oxidative coupling of arenes and olefins through a biomimetic approach.
Arenes and electron-deficient olefins can be oxidatively coupled through a biomimetic Pd(OAc)2-catalyzed transformation. C-H activation of the arene partner is effected under reaction conditions of low catalyst loading, normal oxygen pressure, and using p-benzoquinone and iron phthalocyanine as electron-transfer mediators (ETMs). By controlling catalyst loading, the reaction can be made selective for either mono- or diarylation.


Diagnostic yield and safety of C-TBNA in elderly patients with lung cancer.
Conventional transbronchial needle aspiration (C-TBNA) is a minimally invasive technique used primarily in the diagnosis and staging of lung cancer. Currently lung cancer is mostly considered a disease of the elderly and the management of this disease in older patients is a growing concern. In this study we aimed to assess the diagnostic yield and safety of C-TBNA in elderly patients. A retrospective review of 88 consecutive C-TBNA procedures for nodal staging in suspected or confirmed primary lung cancer or pathological confirmation in suspected advanced lung cancer was performed. Patients were divided into less than 70 (<70yrs) or 70 and older (≥70yrs) age groups for analysis. There were no significant differences either in the diagnostic yield (69% in patients aged < 70 yrs and 74% patients aged ≥ 70 yrs (p=0.5) nor in the complication rate (respectively 8.8% in patients aged < 70 yrs and 6.9% in patients aged ≥ 70 yrs (p=0.7) between the two age groups. Reported complications were minor bleeding and poor tolerance; no major complications were observed. Based on our experience, C-TBNA represents a useful and safe alternative procedure for the diagnosis and staging of lung cancer in elderly patients.


Investigation of the haemolytic effects of Ancylostoma ceylanicum: observations on infected dogs in vivo and human and dog blood in vitro.
Investigations into the probable role of haemolysins in the causation of hookworm anaemia have been undertaken in living infected dogs. Secondly, the effects of living hookworms and various worm products on erythrocytes in vitro have been assessed. In dogs infected with varying numbers of A. ceylanicum, severe microcytic anaemia developed in the most heavily infected animals six weeks after infection. Erythrocytes from the latter animals showed significantly greater autohaemolysis in the presence of added glucose. When serum bilirubin and methaemalbumin, plasma haemoglobin, urinary urobilinogin and osmotic fragility of their red cells were measured, however, no evidence of haemolysis was detected. Erythrocytes from these animals appeared normal under scanning electron microscopy. In in vitro studies varying concentrations of adult worm extract had no effect on the haemolysis of either dog or human erythrocytes in the presence or absence of glucose nor on their mechanical fragility. There was no increase in 51Cr release from dog or human labelled red cells when incubated with either adult worm extract or excretory/secretory products of worms. Living adult worms caused an increase in 51Cr release from human but not dog labelled erythrocytes. Thus, the role of haemolysins in the genesis of hookworm anaemia is minimal.


[Multi- and single-port laparoscopic surgery in the treatment of hydatid liver disease].
To compare the effectiveness of multi-port and single-port laparoscopic surgery in the treatment of hydatid cyst of the liver. There were 25 children with solitary hydatid cyst of the liver (CL-CE2) who underwent surgery in 2013-2017. Mean age was 10.1±2.05 years. There were 17 boys and 8 girls. Patients were divided into 2 groups: group 1 (multi-port laparoscopy) - 19 patients, group 2 (single-port laparoscopic surgery) - 6 patients. Duration of ultrasound-assisted laparoscopy (G11 generator) was significantly shorter in the group 1 compared with group 2 (62.2±5.4 vs. 85.3±9.7 min, p<0.05). Intraoperative complications were absent. Biliary fistula in postoperative period was observed in 1 (5.3%) patient of the group 1. External drainage was effective. Residual cavity in 6 months after laparoscopic resection was observed in 1 (16.7%) patient of the group 2. Recurrent liver echinococcosis was not recorded. Hydatid cyst (CL-CE2) of the liver is an indication for laparoscopic echinococcectomy. Multi-port laparoscopy is characterized by reduced duration of surgery and postoperative morbidity compared with single-port procedures.


Reversing Stimulus Timing in Visual Conditioning Leads to Memories with Opposite Valence in Drosophila.
Animals need to associate different environmental stimuli with each other regardless of whether they temporally overlap or not. Drosophila melanogaster displays olfactory trace conditioning, where an odor is followed by electric shock reinforcement after a temporal gap, leading to conditioned odor avoidance. Reversing the stimulus timing in olfactory conditioning results in the reversal of memory valence such that an odor that follows shock is later on approached (i.e. relief conditioning). Here, we explored the effects of stimulus timing on memory in another sensory modality, using a visual conditioning paradigm. We found that flies form visual memories of opposite valence depending on stimulus timing and can associate a visual stimulus with reinforcement despite being presented with a temporal gap. These results suggest that associative memories with non-overlapping stimuli and the effect of stimulus timing on memory valence are shared across sensory modalities.


Topological alternation from structurally adaptable to mechanically stable crosslinked polymer.
Stimuli-responsive polymers with complicated but controllable shape-morphing behaviors are critically desirable in several engineering fields. Among the various shape-morphing materials, cross-linked polymers with exchangeable bonds in dynamic network topology can undergo on-demand geometric change via solid-state plasticity while maintaining the advantageous properties of cross-linked polymers. However, these dynamic polymers are susceptible to creep deformation that results in their dimensional instability, a highly undesirable drawback that limits their service longevity and applications. Inspired by the natural ice strategy, which realizes creep reduction using crystal structure transformation, we evaluate a dynamic cross-linked polymer with tunable creep behavior through topological alternation. This alternation mechanism uses the thermally triggered disulfide-ene reaction to convert the network topology - from dynamic to static - in a polymerized bulk material. Thus, such a dynamic polymer can exhibit topological rearrangement for thermal plasticity at 130°C to resemble typical dynamic cross-linked polymers. Following the topological alternation at 180°C, the formation of a static topology reduces creep deformation by more than 85% in the same polymer. Owing to temperature-dependent selectivity, our cross-linked polymer exhibits a shape-morphing ability while enhancing its creep resistance for dimensional stability and service longevity after sequentially topological alternation. Our design enriches the design of dynamic covalent polymers, which potentially expands their utility in fabricating geometrically sophisticated multifunctional devices.


SRA-domain proteins required for DRM2-mediated de novo DNA methylation.
De novo DNA methylation and the maintenance of DNA methylation in asymmetrical sequence contexts is catalyzed by homologous proteins in plants (DRM2) and animals (DNMT3a/b). In plants, targeting of DRM2 depends on small interfering RNAs (siRNAs), although the molecular details are still unclear. Here, we show that two SRA-domain proteins (SUVH9 and SUVH2) are also essential for DRM2-mediated de novo and maintenance DNA methylation in Arabidopsis thaliana. At some loci, SUVH9 and SUVH2 act redundantly, while at other loci only SUVH2 is required, and this locus specificity correlates with the differing DNA-binding affinity of the SRA domains within SUVH9 and SUVH2. Specifically, SUVH9 preferentially binds methylated asymmetric sites, while SUVH2 preferentially binds methylated CG sites. The suvh9 and suvh2 mutations do not eliminate siRNAs, suggesting a role for SUVH9 and SUVH2 late in the RNA-directed DNA methylation pathway. With these new results, it is clear that SRA-domain proteins are involved in each of the three pathways leading to DNA methylation in Arabidopsis.


[PROBLEM OF END EFFECTOR OF ISCHEMIC POSTCONDITIONING OF THE HEART].
It is well known that cardiovascular disease and in particular acute myocardial infarction are a major cause of death among working-age population in Russia. Some of the patients die after successful recanalization of the infarct-related coronary artery as a result of ischemic and reperfusion injury of the heart. It is obvious that there is an urgent need to develop new approaches to prevention reoxygenation heart damages. In this regard the study of adaptive phenomenon postconditioning is of particular interest. This analysis of literature source preformed by authors of the article indicates that main pretenders to the role of end-effectors of ischemic postconditioning of the heart are: (1) Ca(2+)-dependent K+ channel of BK-type (big conductance K+ channel), (2) mitoKATp channel (mitochondrial ATP-sensitive K+ channel), (3) MPT pore (mitochondrial permeability transition pore). At the same time, some investigators consider that mitoK(ATP) channel is only an intermediate link in the series of signaling events ensured an increase in cardiac tolerance to impact of ischemia-reperfusion. The most likely end effector of these three structures is MPT pore. Alternatively, it is possible, that unique molecular complex appearing a single end effector of postconditioning does not exist. Perhaps, that there are several effectors ensured cardioprotective effect of an adaptive phenomenon of postconditioning.


CRISPR-Cas9 editing of TLR4 to improve the outcome of cardiac cell therapy.
Inflammation and fibrosis limit the reparative properties of human mesenchymal stromal cells (hMSCs). We hypothesized that disrupting the toll-like receptor 4 (TLR4) gene would switch hMSCs toward a reparative phenotype and improve the outcome of cell therapy for infarct repair. We developed and optimized an improved electroporation protocol for CRISPR-Cas9 gene editing. This protocol achieved a 68% success rate when applied to isolated hMSCs from the heart and epicardial fat of patients with ischemic heart disease. While cell editing lowered TLR4 expression in hMSCs, it did not affect classical markers of hMSCs, proliferation, and migration rate. Protein mass spectrometry analysis revealed that edited cells secreted fewer proteins involved in inflammation. Analysis of biological processes revealed that TLR4 editing reduced processes linked to inflammation and extracellular organization. Furthermore, edited cells expressed less NF-ƙB and secreted lower amounts of extracellular vesicles and pro-inflammatory and pro-fibrotic cytokines than unedited hMSCs. Cell therapy with both edited and unedited hMSCs improved survival, left ventricular remodeling, and cardiac function after myocardial infarction (MI) in mice. Postmortem histologic analysis revealed clusters of edited cells that survived in the scar tissue 28 days after MI. Morphometric analysis showed that implantation of edited cells increased the area of myocardial islands in the scar tissue, reduced the occurrence of transmural scar, increased scar thickness, and decreased expansion index. We show, for the first time, that CRISPR-Cas9-based disruption of the TLR4-gene reduces pro-inflammatory polarization of hMSCs and improves infarct healing and remodeling in mice. Our results provide a new approach to improving the outcomes of cell therapy for cardiovascular diseases.


Comparison Of Efficacy Of Phenytoin And Levetiracetam For Prevention Of Early Post Traumatic Seizures.
The incidence of early post-traumatic seizures after civilian traumatic brain injury ranges 4-25%. The control of early post-traumatic seizure is mandatory because these acute insults may add secondary damage to the already damaged brain with poor outcome. Prophylactic use of anti-epileptic drugs have been found to be have variable efficacy against early post-traumatic seizures. The objective of this study was to compare the efficacy of Phenytion and Levetiracetam in prevention of early post-traumatic seizures in moderate to severe traumatic brain injury. This randomized controlled trial was conducted in department of Neurosurgery, Ayub Medical College, Abbottabad from March, 2012 to March 2013. The patients with moderate to severe head injury were randomly allocated in two groups. Patients in group A were given phenytoin and patients in group B were given Levetiracetam. Patients were followed for one week to detect efficacy of drug in terms of early post traumatic seizures. The 154 patients included in the study were equally divided into two groups. Out of 154 patients 115 (74.7%) were male while 29 (25.3%) were females. Age of patients ranges from 7-48 (24.15±9.56) years. Ninety one (59.1%) patients had moderate head injury while 63 (40.9%) patients had severe head injury. Phenytoin was effective in preventing early post traumatic seizures in 73 (94.8%) patients whereas Levetiracetam effectively controlled seizures in 70 (90.95%) cases (p-value of .348). There is no statistically significant difference in the efficacy of Phenytoin and Levetiracetam in prophylaxis of early posttraumatic seizures in cases of moderate to severe traumatic brain injury.


Administration of human urinary colony stimulating factor after bone marrow transplantation.
A phase II study of the use of colony stimulating factor derived from human urine (CSF-HU) was performed after bone marrow transplantation (BMT). Steady and rapid recovery of leukocyte and granulocyte numbers was observed. In most patients who received CSF-HU from day 1, leukocyte numbers started to increase on day 6 and monocytes and granulocytes on day 11. Significant differences in the days to recovery of leukocytes over 1 x 10(9)/l and of granulocytes over 0.5 x 10(9)/l were observed in comparison with non-randomized control patients. In some patients in whom recovery of leukocytes was delayed, CSF also seemed to be effective in increasing leukocyte numbers from 8 days after the start of administration. There was no significant difference in the rate of relapse of leukemia between the two groups. CSF-HU seems very promising as a treatment of patients after BMT by shortening the period of leukopenia or granulocytopenia.


The photosynthetic apparatus of Prochlorococcus: Insights through comparative genomics.
Within the vast oceanic gyres, a significant fraction of the total chlorophyll belongs to the light-harvesting antenna systems of a single genus, Prochlorococcus. This organism, discovered only about 10 years ago, is an extremely small, Chl b-containing cyanobacterium that sometimes constitutes up to 50% of the photosynthetic biomass in the oceans. Various Prochlorococcus strains are known to have significantly different conditions for optimal growth and survival. Strains which dominate the surface waters, for example, have an irradiance optimum for photosynthesis of 200 mumol photons m(-2) s(-1), whereas those that dominate the deeper waters photosynthesize optimally at 30-50 mumol photons m(-2) s(-1). These high and low light adapted 'ecotypes' are very closely related - less than 3% divergent in their 16S rRNA sequences - inviting speculation as to what features of their photosynthetic mechanisms might account for the differences in photosynthetic performance. Here, we compare information obtained from the complete genome sequences of two Prochlorococcus strains, with special emphasis on genes for the photosynthetic apparatus. These two strains, Prochlorococcus MED4 and MIT 9313, are representatives of high- and low-light adapted ecotypes, characterized by their low or high Chl b/a ratio, respectively. Both genomes appear to be significantly smaller (1700 and 2400 kbp) than those of other cyanobacteria, and the low-light-adapted strain has significantly more genes than its high light counterpart. In keeping with their comparative light-dependent physiologies, MED4 has many more genes encoding putative high-light-inducible proteins (HLIP) and photolyases to repair UV-induced DNA damage, whereas MIT 9313 possesses more genes associated with the photosynthetic apparatus. These include two pcb genes encoding Chl-binding proteins and a second copy of the gene psbA, encoding the Photosystem II reaction center protein D1. In addition, MIT 9313 contains a gene cluster to produce chromophorylated phycoerythrin. The latter represents an intermediate form between the phycobiliproteins of non-Chl b containing cyanobacteria and an extremely modified beta phycoerythrin as the sole derivative of phycobiliproteins still present in MED4. Intriguing features found in both Prochlorococcus strains include a gene cluster for Rubisco and carboxysomal proteins that is likely of non-cyanobacterial origin and two genes for a putative varepsilon and beta lycopene cyclase, respectively, explaining how Prochlorococcus may synthesize the alpha branch of carotenoids that are common in green organisms but not in other cyanobacteria.


Line element for the perceptual color space.
It is generally accepted that the perceptual color space is not Euclidean. A new line element for a 3-dimensional Riemannian color space was developed. This line element is based on the Friele line elements and psychophysical color discrimination models, and comprises both the first and second stage of color vision. The line element is expressed in a contrast space based on the MacLeod-Boynton chromaticities. New equations for the contrast thresholds along the cardinal axes and new metric tensor elements were determined. Visual adaptation effects were incorporated into the model. Color discrimination threshold ellipsoids were calculated with the new line element. Adequate agreement with experimental threshold ellipsoids reported in literature was demonstrated. From a comparison with other color difference metrics a better overall predictability of threshold ellipsoids was found with the new line element.


Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors.
Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods. We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as α-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration. We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also for in vitro applications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.


Electrochemical sensors based on metal nanoparticles with biocatalytic activity.
Biosensors have attracted a great deal of attention, as they allow for the translation of the standard laboratory-based methods into small, portable devices. The field of biosensors has been growing, introducing innovations into their design to improve their sensing characteristics and reduce sample volume and user intervention. Enzymes are commonly used for determination purposes providing a high selectivity and sensitivity; however, their poor shelf-life is a limiting factor. Researchers have been studying the possibility of substituting enzymes with other materials with an enzyme-like activity and improved long-term stability and suitability for point-of-care biosensors. Extra attention is paid to metal and metal oxide nanoparticles, which are essential components of numerous enzyme-less catalytic sensors. The bottleneck of utilising metal-containing nanoparticles in sensing devices is achieving high selectivity and sensitivity. This review demonstrates similarities and differences between numerous metal nanoparticle-based sensors described in the literature to pinpoint the crucial factors determining their catalytic performance. Unlike other reviews, sensors are categorised by the type of metal to study their catalytic activity dependency on the environmental conditions. The results are based on studies on nanoparticle properties to narrow the gap between fundamental and applied research. The analysis shows that the catalytic activity of nanozymes is strongly dependent on their intrinsic properties (e.g. composition, size, shape) and external conditions (e.g. pH, type of electrolyte, and its chemical composition). Understanding the mechanisms behind the metal catalytic activity and how it can be improved helps designing a nanozyme-based sensor with the performance matching those of an enzyme-based device.


Pathogenesis of experimental salmonellosis: inhibition of protein synthesis by cytotoxin.
Salmonella cytotoxin present in cell lysates inhibited protein synthesis in both Vero cells and isolated rabbit intestinal epithelial cells. A time-course experiment with Vero cells revealed progressive inhibition of protein synthesis beginning as early as 1 h after exposure to the Salmonella cell lysate. Significant loss of membrane integrity of Vero cells (measured by release of [3H]uridine) did not appear before 24 h. To demonstrate inhibited protein synthesis in intestinal tissue during experimental salmonellosis, we isolated rabbit epithelial cells from Salmonella-infected and control intestinal loops. Measurement of [3H]leucine incorporation showed a similar decrease in protein synthesis in epithelial cells from the Salmonella-infected intestinal loop as that from an adjacent control loop. A similar pattern of protein synthesis inhibition was observed when isolated epithelial cells from normal rabbit intestine were exposed to the Salmonella cell lysate. The inhibited protein synthesis in the intestinal cells provides a molecular basis for the cellular damage caused by Salmonella cytotoxin during experimental salmonellosis.


Multifocal Tuberculosis Verrucosa Cutis: A Manifestation Extraordinary of Reactivation Secondary Tuberculosis.
A BCG (Bacillus Calmette-Guérin)-vaccinated 78-year-old man, a native Indian, reported with numerous asymptomatic, peanut-sized, dirty gray, elevated eruptions of 1 year's duration appearing over apparently normal skin on the upper and lower extremities (Figure 1). The onset of the eruptions had been sudden, but they had progressed slowly. A history of cough and/or expectoration, evening rise of temperature, night sweats, or loss of appetite and weight was denied.


Low concentrations of the recombinant toxin protein rLj-RGD3 suppress TNF-α-induced human renal carcinoma cell invasion.
A hallmark of renal cell carcinoma (RCC) invasion is the degradation of the extracellular matrix (ECM) by the local production of gelatinase enzymes. Matrix metalloproteinase-9 (MMP-9)-induced cancer cell invasion is one of the pivotal steps in cancer metastasis. It has been reported that tumor necrosis factor-α (TNF-α), a regulator of MMP-9, can induce invasion in human renal carcinoma cells. Previous work in our laboratory has shown that rLj-RGD3, a recombinant RGD (Arg-Gly-Asp)-toxin protein from the buccal gland secretion of Lampetra japonica, possesses anti-tumor activity. In this study, we demonstrated that rLj-RGD3 suppressed TNF-α-induced MMP-9 secretion in 786-0 cells (human renal carcinoma cells). To investigate the regulatory effect of rLj-RGD3 on TNF-α-induced MMP-9 secretion, we pre-treated cells with rLj-RGD3. Interestingly, rLj-RGD3 had no significant effect on the constitutive secretion of MMPs. However, low concentrations of rLj-RGD3 decreased TNF-α-induced MMP-9 secretion. Functional studies revealed that rLj-RGD3 induced apoptosis and significantly inhibited the proliferation, migration, and invasion of 786-0 cells. Furthermore, the actin architecture in cells pre-treated with rLj-RGD3 was aggregated and disorganized. Our findings suggest that rLj-RGD3 may be used as a potential drug in renal cancer therapy.


Mediation of most atypical effects by species homologues of the beta 3-adrenoceptor.
1. A wide panel of compounds acting on beta-adrenoceptors active either in mammalian heart or in rodent digestive tract and adipose tissues, were investigated for their effects on Chinese hamster ovary cells transfected with the human or murine beta 3-adrenoceptor gene. 2. The beta 3-agonists, bucindolol, CGP 12177A and pindolol exhibited the highest binding affinities; BRL 37344, LY 79771, ICI 201651 and SR 58611A presented high potencies in stimulating adenylyl cyclase; bupranolol appeared as the most efficient beta 3-antagonist. 3. This pharmacological analysis further established that the beta 3-adrenoceptor is the prototype of the adipose tissue atypical beta-adrenoceptor, since these receptors share a number of pharmacological properties which differ strikingly from those of beta 1- and beta 2-adrenoceptors: low affinities for conventional beta-adrenoceptor agonists and antagonists, high potencies for novel compounds active in adipose tissues, partial agonistic activities for several beta 1/beta 2-antagonists. 4. Although the pharmacological profiles of the human and murine beta 3-receptor were very similar, some quantitative or even qualitative differences were observed for particular compounds such as propranolol, which exhibited weak and partial agonistic effects at the human beta 3-receptors and antagonistic effects at the murine beta 3-receptors. These differences may result from key amino-acid substitutions between the human and the murine beta 3-receptor sequences, which may alter the binding site or signal processing. 5. Compounds active on atypical beta-sites of other tissues such as heart and digestive tract were also potent on the beta 3-adrenoceptor expressed in Chinese hamster ovary cells, suggesting that this receptor mediates most of the atypical properties described in various tissues, and that differences in ligand effects may result from tissue-related specificities.


Relative position of the mandibular foramen in different age groups of children: a radiographic study.
To assess the relative position of the mandibular foramen (MF) and to evaluate the measurement of gonial angle (GoA) and its relationship with distances between different mandibular borders in growing children between 3 and 13 years of dental age. The radiographs were traced to arrive at six linear and two angular measurements from which the relative position of the MF was assessed and compared in different age groups to determine the growth pattern of the mandible and changes in the location of the MF. The distances between the MF and the anterior plane of the ramus were greater than that between MF and posterior plane of the ramus through all stages. There was a maximum increase in the vertical dimensions of the mandible compared with the horizontal dimensions, particularly in the late mixed dentition period. The mandible and its growth did not alter the position of the MF, both vertically and horizontally, in relation to different landmarks, and more obtuse GoA indicated an increased growth potential of the mandible. This has major implications in the inferior alveolar nerve block technique when used in children.


Remineralization effect of a low-concentration fluoride rinse in an intraoral model.
A previous study showed that a sodium hexafluorosilicate-calcium chloride-based two-solution fluoride (F) rinse containing 6 mmol/l of F was more effective than a 12 mmol/l F sodium fluoride rinse in depositing F on tooth surfaces and increasing oral F levels. The present study compared the remineralization effects of these two rinses in an intraoral de- and remineralization model. The results showed that the 6 mmol/l F two-solution rinse produced greater remineralization in increasing lesion mineral contents and reducing lesion depths. The results demonstrated that the effectiveness of an F regimen depends less on the F dose and more on the ability of the treatment to utilize F efficiently for remineralization.


Drainless Abdominoplasty Using Barbed Progressive Tension Sutures.
We describe our current technique of drainless abdominoplasty using barbed progressive tension sutures. The perioperative management and detailed steps of procedure are outlined, including indications for concomitantly performing liposuction and repair of diastasis of the rectus abdominis muscles. This approach reliably improves abdominal contour, minimizes complications, and is straightforward to learn and perform.


Use of Various UVC Photofunctionalization Times to Modify Surface Characteristics and Enhance the Biologic Activity of SLA Titanium.
To evaluate the effect of ultraviolet-C light (UVC) photofunctionalization treatment time on the biologic activity of airborne particle-abraded and acid-etched (SLA) titanium surfaces and to analyze its physical and chemical mechanisms. SLA titanium was treated with UVC light for different lengths of time (10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours), and then changes to its surface characteristics were evaluated via electron microscope scanning, X-ray photoelectron spectroscopy (XPS), water contact angle measurement, and zeta potential measurement. The effect of UVC photofunctionalization on the biologic processes of SLA titanium surfaces was assessed by analyzing the bovine serum albumin adsorption, adhesion, proliferation, morphology, and alkaline phosphatase activity of MG-63 cells. UVC irradiation did not change the topography of SLA titanium surfaces. As treatment times increased, the water contact angle decreased from 120 degrees to 0 degrees, and the hydrocarbon content decreased. Zeta potential testing showed increased surface potential of photofunctionalized titanium. In vitro testing showed that cell adhesion, proliferation, morphology, and alkaline phosphate (ALP) activity on titanium surfaces were significantly improved by UVC photofunctionalization. UVC photofunctionalization can improve the biologic activity of SLA titanium surfaces by removing hydrocarbons and increasing the surface potential of titanium.


Electrical stimulation of the brain. II. Effects on the blood-brain barrier.
Acute and chronic studies of the effects of electrical stimulation on the blood-brain barrier (BBB) of the cat cerebral cortex are reported. The findings emphasize the importance of avoiding direct-coupled, monophasic waveforms in stimulating nervous tissue. Biphasic waveforms with balanced charges in each half-wave of the stimulating pulse can be used for up to 36 hours of continuous stimulation if the charge per phase (Q/ph) does not exceed 0.45 microcoulombs. Charge density (QD) is also an important parameter. When stimulating in the bipolar mode, BBB breakdown will occur first beneath the smaller electrode of the pair. Following electrical injury, the BBB will be partially restored within one week, and, with rare exceptions, be completely intact after one month.


Photooxygenation of allylic alcohols: kinetic comparison of unfunctionalized alkenes with prenol-type allylic alcohols, ethers and acetates.
The kinetics of the chemical and physical quenching of the first excited singlet state of oxygen [1O2 (1delta(g))] by unfunctionalized alkenes 1-4, allylic alcohols 5-7 and 9, allylic acetates 8 and 11, and the allylic ether 10 display small solvent-polarity effects on the reactivity. The regioselectivity of the singlet oxygen ene reaction is solvent independent for the unfunctionalized alkenes as well as the prenol-type substrates, the latter showing substantial solvent effects on the diastereoselectivity. Pronounced physical quenching is detected only for the allylic alcohols 5 and 6. These results are interpreted in terms of the interactions between singlet oxygen and the allylic hydroxy groups, conformationally promoted by allylic strain which lead either to chemical activation or to physical quenching. The results for substrate 9 in deuterated v.s non-deuterated methanol are in accord with hydrogen bonding between the allylic alcohol and 1O2, which directs the diastereoselectivity of the ene reaction with chiral allylic alcohols.


Genetic association between single nucleotide polymorphisms in the paraoxonase 1 (PON1) gene and small-for-gestational-age birth in related and unrelated subjects.
Paraoxonase 1 (PON1) protects against oxidative modification of low density lipoproteins. The PON1 gene has 3 polymorphisms considered strong determinants of PON1 levels: Q192R and L55M in the coding region and C-108T in the promoter region. PON1 levels are also influenced by smoking. The authors hypothesized that PON1 variants could increase the risk of vascular thrombosis, leading in turn to placental insufficiency and small-for-gestational-age (SGA) birth. The author compared PON1 variants and haplotypes between 448 newborn SGA cases and 431 newborn controls from Montréal, Québec, Canada (1998-2000) and studied the effects of interaction with maternal smoking. Transmission of the variants in case-parent trios was used as validation of the case-control results; the authors combined case-control and family data to analyze the associations of variants with SGA birth. In the case-control analysis, the T allele from C-108T increased the risk of SGA birth (additive odds ratio = 1.30, 95% confidence interval (CI): 1.06, 1.59), and the TRL haplotype (T from C-108T, R from Q192R, and L from L55M) was associated with an odds ratio of 1.51 (95% CI: 1.07, 2.15). Among smokers, the CRL haplotype was protective (odds ratio = 0.48, 95% CI: 0.28, 0.82). Case-parent trio results were compatible with case-control results.


[Willingness of Psychotherapists in Private Practice to Treat Patients With Complex Post-Traumatic Stress and Dissociative Disorders].
Analyses of patient care with severe mental disorders. Psychotherapists in private praxis were interviewed about their willingness to treat patients with a range of diagnoses in the context of post-traumatic disorders. Therapists were found more willing to treat "less severe" disorders, independent of years in practice, school of psychotherapy, a rural or urban practice setting. Therapists criticized the quality of their training and the health insurance review process. Therapists are generally willing to treat patients with severe mental disorders, but experience limits of competency attributed to training deficits. They further experience the bureaucratic procedures of the health insurance review process as barriers to accepting these patients into treatment.These results indicate that recently developed concepts of psychotherapy for these patient groups should be more intensively integrated into the existing training curricula. Furthermore, a simplified health insurance review process ought to be considered.


Allele-specific control of Ia molecule surface expression and conformation: implications for a general model of Ia structure-function relationships.
Sequence polymorphism of class II major histocompatibility complex-encoded molecules (Ia) not only accounts for the allelic variability in Ia structure relevant to T-lymphocyte responses but also seems to result in differential quantitative expression of particular Ia heterodimers. The contributions of different allelically variable regions of Ia molecules to both of these processes were analyzed by transfection of L cells with various A beta and A alpha gene pairs. The results show that, with regard to quantitative and qualitative aspects of Ia expression, the polymorphisms in the A beta chain segregate into two groups. Those in the NH2-terminal half of A beta 1 have a consistent role in controlling beta-alpha chain interactions, efficiency of dimer expression, and Ia conformation and probably are in the interior of the Ia molecule at the site of beta-alpha domain interaction. Polymorphisms in the COOH-terminal half of A beta 1 contribute to those structures that directly interact with antibodies, antigen, and/or T-cell receptors, consistent with their presence on the surface of the Ia heterodimer. This analysis provides a model for understanding both overall class II molecular structure and the relationship between this structure and immune recognition. It also suggests an explanation for the evolution of certain features of class II genes.


Protein and ribonucleic acid synthesis during the diploid life cycle of Allomyces arbuscula.
The diploid life cycle of Allomyces arbuscula may be divided into four parts: spore induction, germination, vegetative growth, and mitosporangium formation. Spore induction, germination, and mitosporangium formation are insensitive to inhibition of actinomycin D, probably indicating that stable, pre-existing messenger ribonucleic acid (RNA) is responsible for these developmental events. Protein synthesis is necessary during the entire life cycle except for cyst formation. A system for obtaining synchronous germination of mitospores is described. During germination there is a characteristic increase in the rate of synthesis of RNA and protein although none of the other morphogenetic changes occurring during the life cycle are necessarily accompanied by an appreciable change in the rate of macromolecular synthesis.


PD-L1 correlated gene expression profiles and tumor infiltrating lymphocytes in pancreatic cancer.
Objective: To study the expression and clinical value of PD-L1 gene in pancreatic cancer, and to predict the role of PD-L1 gene in the development of pancreatic cancer. Methods: The pancreatic cancer datasets were downloaded from the Cancer Genome Atlas (TCGA) and the Oncomine to obtain the PD-L1 gene expression profile and clinical information. Bioinformatics methods were used to analyze the correlation between the expression level of PD-L1 gene in pancreatic cancer and clinicopathological indicators, as well as its influence on prognosis. GSEA and WGCNA analysis was performed to predict the possible pathways of PD-L1 gene regulation in pancreatic cancer. TIMER and MCP-counter were used for PD-L1 with immune infiltration. The genes interact with PD-L1 were also investigated by STING and immunoco-precipitation combined with mass spectrometry analysis (IP-MS). Results: In TCGA database, the overall survival of patients with high expression of PD-L1 gene was significantly lower than that of patients with low expression of PD-L1 gene (χ2 = 12.52, P < 0.001). The samples with high expression of PD-L1 gene showed enrichment of 8 pathways including toll-like receptor signaling pathway and NOD receptor signaling pathway (P < 0.01, FDR < 0.05). Immune infiltration analysis suggested that PD-L1 were associated with monocytic lineage (r = 0.5). The proteins interacting with PD-L1 are mainly concentrated in RNA binding, ribosome, spliceosome and other biological processes or pathways. Conclusion: PD-L1 gene may play an important role in the development of pancreatic cancer and is expected to be a prognostic indicator of pancreatic cancer.


Atrial septal defect in a patient with congenital disorder of glycosylation type 1a: a case report.
Atrial septal defect often become more severe when encountered in genetic syndromes. Congenital disorder of glycosylation type 1a is an inherited metabolic disorder associated with mutations in PMM2 gene and can affect almost all organs. Cardiac abnormalities vary greatly in congenital disorder of glycosylation type 1a and congenital heart defects have already been reported, but there is little knowledge about the effect of this inherited disorder on an existing congenital heart defect. Herein we report for the first time on a baby with congenital disorder of glycosylation type 1a with atrial septal defect and make a comparison of changes in atrial septal defect by follow-ups to the age of 3. Our patient was an 8-month-old Han Chinese boy. At the initial visit, he presented with recurrent lower respiratory infection, heart murmur, psychomotor retardation, inverted nipples, and cerebellar atrophy. Echocardiography revealed a 8 mm secundum atrial septal defect with left-to-right shunt (Qp/Qs ratio 1.6). Enzyme testing of phosphomannomutase 2 demonstrated decreased levels of phosphomannomutase 2 activities in fibroblasts. Whole exon sequencing showed he was heterozygous for a frameshift mutation (p.I153X) and a missense mutation (p.I132T) in PMM2 gene. The diagnosis of congenital disorder of glycosylation type 1a with atrial septal defect was issued. Now, he is 3-years old at the time of this writing, with the development of congenital disorder of glycosylation type 1a (cerebellar atrophy become more severe and the symptom of nystagmus emerged), the size of atrial septal defect increased to 10 mm and the Qp/Qs ratio increased to 1.9, which suggested exacerbation of the atrial septal defect. Congenital heart defect-associated gene sequencing is then performed and shows there are no pathogenic mutations, which suggested intrinsic cardiac factors are not the cause of exacerbation of the atrial septal defect in our patient and it is reasonable to assume congenital disorder of glycosylation type 1a can worsen the situation of the existing atrial septal defect. This report highlights the view that congenital disorders of glycosylation type 1a should be excluded when faced with congenital heart defect with cerebellar atrophy or neurodevelopmental delay, especially when the situation of congenital heart defect becomes more and more severe.


Mapping clinical outcomes to generic preference-based outcome measures: development and comparison of methods.
Cost-effectiveness analysis using quality-adjusted life-years as the measure of health benefit is commonly used to aid decision-makers. Clinical studies often do not include preference-based measures that allow the calculation of quality-adjusted life-years, or the data are insufficient. 'Mapping' can bridge this evidence gap; it entails estimating the relationship between outcomes measured in clinical studies and the required preference-based measures using a different data set. However, many methods for mapping yield biased results, distorting cost-effectiveness estimates. Develop existing and new methods for mapping; test their performance in case studies spanning different preference-based measures; and develop methods for mapping between preference-based measures. Fifteen data sets for mapping from non-preference-based measures to preference-based measures for patients with head injury, breast cancer, asthma, heart disease, knee surgery and varicose veins were used. Four preference-based measures were covered: the EuroQoL-5 Dimensions, three-level version (n = 11), EuroQoL-5 Dimensions, five-level version (n = 2), Short Form questionnaire-6 Dimensions (n = 1) and Health Utility Index Mark 3 (n = 1). Sample sizes ranged from 852 to 136,327. For mapping between generic preference-based measures, data from FORWARD, the National Databank for Rheumatic Diseases (which includes the EuroQoL-5 Dimensions, three-level version, and EuroQoL-5 Dimensions, five-level version, in its 2011 wave), were used. Mixture-model-based approaches for direct mapping, in which the dependent variable is the health utility value, including adaptations of methods developed to model the EuroQoL-5 Dimensions, three-level version, and beta regression mixtures, were developed, as were indirect methods, in which responses to the descriptive systems are modelled, for consistent multidirectional mapping between preference-based measures. A highly flexible approach was designed, using copulas to specify the bivariate distribution of each pair of EuroQoL-5 Dimensions, three-level version, and EuroQoL-5 Dimensions, five-level version, responses. A range of criteria for assessing model performance is proposed. Theoretically, linear regression is inappropriate for mapping. Case studies confirm this. Flexible, direct mapping methods, based on different variants of mixture models with appropriate underlying distributions, perform very well for all preference-based measures. The precise form is important. Case studies show that a minimum of three components are required. Covariates representing disease severity are required as predictors of component membership. Beta-based mixtures perform similarly to the bespoke mixture approaches but necessitate detailed consideration of the number and location of probability masses. The flexible, bi-directional indirect approach performs well for testing differences between preference-based measures. Case studies drew heavily on EuroQoL-5 Dimensions. Indirect methods could not be undertaken for several case studies because of a lack of coverage. These methods will often be unfeasible for preference-based measures with complex descriptive systems. Mapping requires appropriate methods to yield reliable results. Evidence shows that widely used methods such as linear regression are inappropriate. More flexible methods developed specifically for mapping show that close-fitting results can be achieved. Approaches based on mixture models are appropriate for all preference-based measures. Some features are universally required (such as the minimum number of components) but others must be assessed on a case-by-case basis (such as the location and number of probability mass points). Further research is recommended on (1) the use of the monotonicity concept, (2) the mismatch of trial and mapping distributions and measurement error and (3) the development of indirect methods drawing on methods developed for mapping between preference-based measures. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 34. See the NIHR Journals Library website for further project information. This project was also funded by a Medical Research Council grant (MR/L022575/1).


Contemporary Prevalence and risk factors of carotid artery stenosis in asymptomatic low-income Chinese individuals: a population-based study.
Carotid artery stenosis (CAS) is an established risk factor for cerebrovascular disease. However, the contemporary prevalence and risk factors of CAS in asymptomatic rural Chinese individuals, especially low-income populations, remains unclear. Therefore, we aimed to explore the present prevalence and risk factors of CAS in a low-income Chinese population. A total of 3126 people aged ≥ 45 years without history of stroke or cardiovascular disease were recruited for this study. B-mode ultrasonography was performed to evaluate the presence of CAS. We used multivariate analysis to determine potential risk factors for CAS. The overall prevalence of CAS in this population was 6.7%, with a prevalence of 8.8% for men and 5.0% for women. The risk of CAS increased with older age and a higher level of low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and fasting blood glucose (FBG) (all P < 0.05). Each 1-mmHg increase in SBP increased the risk of CAS by 0.011 times, each 1-mmol/L increase in LDL-C increased the risk of CAS by 0.192 times, and each 1-mmol/L increase in FBG increased the risk of CAS by 0.067 times. In addition, the risk of CAS increased 52.9% in men compared to that in women, increased 100.2% in current drinkers compared to that in never drinkers, and increased 38.9% in patients with diabetes compared to those without diabetes (all P < 0.05). These findings suggest that the prevalence of CAS remains high in low-income individuals. Male sex, older age, current drinking, diabetes, and high levels of LDL-C, SBP, and FBG increase the risk of CAS. Thus, to prevent cerebrovascular disease and reduce the severe disease-associated burden for low-income individuals, there is a definitive need to control the risk factors of CAS.


Effect of Deformity and Malunion of the Anterior Pelvic Ring.
Pelvic fractures are common after high-energy trauma and are often associated with ligamentous injury. Treatment is guided by assessing stability of the pelvic ring, and unstable injuries frequently require surgery to achieve a desirable outcome. Assessment of pelvic ring stability is often possible with physical examination and standard imaging studies (plain radiographs and computed tomography); however, these "static" imaging modalities may not adequately identify dynamically unstable pelvic injuries that require surgery. Cadaveric and clinical data suggest that the injured pelvis may recoil significantly from the point of maximal displacement, and some unstable injuries may not be recognized until patients present with clinical symptoms. This article presents the case of a patient who sustained a minimally displaced pelvic ring injury that was stable on bedside examination and static imaging, but ultimately was unstable. She developed a substantial pelvic malunion with significant pain and activity limitations. The patient subsequently underwent successful pelvic ring reconstruction, and she remains asymptomatic at 2 years.


Modifying the Schwarz Bayesian information criterion to locate multiple interacting quantitative trait loci.
The problem of locating multiple interacting quantitative trait loci (QTL) can be addressed as a multiple regression problem, with marker genotypes being the regressor variables. An important and difficult part in fitting such a regression model is the estimation of the QTL number and respective interactions. Among the many model selection criteria that can be used to estimate the number of regressor variables, none are used to estimate the number of interactions. Our simulations demonstrate that epistatic terms appearing in a model without the related main effects cause the standard model selection criteria to have a strong tendency to overestimate the number of interactions, and so the QTL number. With this as our motivation we investigate the behavior of the Schwarz Bayesian information criterion (BIC) by explaining the phenomenon of the overestimation and proposing a novel modification of BIC that allows the detection of main effects and pairwise interactions in a backcross population. Results of an extensive simulation study demonstrate that our modified version of BIC performs very well in practice. Our methodology can be extended to general populations and higher-order interactions.


HTLV-1 Tax-mediated inhibition of FOXO3a activity is critical for the persistence of terminally differentiated CD4+ T cells.
The mechanisms involved in the persistence of activated CD4+ T lymphocytes following primary human T leukemia/lymphoma virus type 1 (HTLV-1) infection remain unclear. Here, we demonstrate that the HTLV-1 Tax oncoprotein modulates phosphorylation and transcriptional activity of the FOXO3a transcription factor, via upstream activation of the AKT pathway. De novo HTLV-1 infection of CD4+ T cells or direct lentiviral-mediated introduction of Tax led to AKT activation and AKT-dependent inactivation of FOXO3a, via phosphorylation of residues Ser253 and Thr32. Inhibition of FOXO3a signalling led to the long-term survival of a population of highly activated, terminally differentiated CD4+Tax+CD27negCCR7neg T cells that maintained the capacity to disseminate infectious HTLV-1. CD4+ T cell persistence was reversed by chemical inhibition of AKT activity, lentiviral-mediated expression of a dominant-negative form of FOXO3a or by specific small interfering RNA (siRNA)-mediated silencing of FOXO3a. Overall this study provides new mechanistic insight into the strategies used by HTLV-1 to increase long-term maintenance of Tax+CD4+ T lymphocytes during the early stages of HTLV-1 pathogenesis.


Blood volume responses in partially dehydrated subjects working in the cold.
The effects of high-salt diets, cold, and heavy exercise have been examined in 33 Marine Corps volunteers living and working in a cold chamber. Temperatures varied from -29 degrees C during working hours to -4 degrees C, simulating partly warmed shelters, at night. Dehydrated operational rations were eaten and fluid intakes were controlled. When quantities of water were consumed at or above the amounts determined in previous studies in this series to prevent symptoms of cold-induced dehydration with these diets, ie., 2.5-3.0 L/d with diets containing 24 g of NaCl/d or about 2.0 L/d with 8 g NaCl/d, blood volumes increased 5-10%, primarily as a result of plasma volume expansion. This finding apparently confirms the results of earlier workers who have noted plasma volume increases in subjects undergoing vigorous exercise training. In subjects receiving 0.5 L/d or more below recommended quantities of water, intravascular volume increases developed slowly and quite erratically during 5 d of exercise. Intravascular volume increases responded within 1-2 d when fluid levels became appropriate for either high- or low-salt intakes. Besides confirming recommendations concerning water needed with dehydrated diets under conditions of the experiment, the observation of intravascular fluid volume increases during exercise training--despite limiting fluid intakes--raises the question of whether there are any physiological advantages from this adaptive mechanism.


Low genetic variability in a natural alpine marmot population (Marmota marmota, Sciuridae) revealed by DNA fingerprinting.
Genetic heterogeneity is usually considered an important factor for the viability of a population, yet there are cases in which populations sustain themselves despite virtual homozygosity. A prior step to studying the effects of such low levels of genetic variability can be the analysis of its causes. We analysed a population of the highly social alpine marmot (Marmota marmota, Sciuridae) by multilocus DNA fingerprinting. The fingerprint patterns revealed a very low degree of polymorphism in our main study population. We show that this lack of hypervariability is caused by a low effective population size, rather than by an unusual low mutation rate of the fingerprint loci studied. However, the current number of breeding pairs was found to be about an order of magnitude larger than the one that would be expected to lead to such a low degree of heterozygosity. We conclude that there must have been bottlenecks in the history of the Berchtesgaden marmot population that have severely affected its genetic heterozygosity.


Allelic imbalance in the diagnosis of benign, atypical and malignant Spitz tumours.
To test the diagnostic usefulness of allelic imbalance (AI) analysis based on routinely paraffin-embedded tissue, a series of 55 benign Spitz naevi, Spitz tumours with uncertain malignant potential, and malignant Spitzoid melanomas was investigated. Laser microdissection was used to ensure representative sampling of lesional cells and to investigate AI in separate tumour areas of four melanomas. AI was found in 2/12 (17%) typical Spitz naevi, 3/9 (33%) atypical Spitz tumours, 12/17 (65%) atypical Spitz tumours suspicious for melanoma and 15/17 (88%) Spitzoid melanomas. Additional immunohistochemical staining for Ki-67 using the MIB-1 antibody revealed positive deeply situated lesional cells in 0/6 (0%) Spitz naevi, 1/8 (13%) atypical Spitz tumours, 5/14 (35%) atypical Spitz tumours suspicious for melanoma, and 7/14 (50%) Spitzoid melanomas, respectively. Two of the melanomas examined for AI in separate tumour areas showed intratumoural genetic heterogeneity. In view of the finding of AI and deeply situated Ki-67 positive cells not only in melanomas but also in Spitz tumours with uncertain malignant potential, these approaches appear to have no direct diagnostic applicability for the distinction between benign and malignant Spitz tumours. Further molecular studies will be required to determine whether Spitz tumours and Spitzoid melanomas are unrelated entities, or whether there is a true spectrum of tumour progression.


Sustained low catheter related infection (CRI) incidence in an observational follow-up study of 9924 catheters using automated data scripts as quality assurance for central venous catheter (CVC) management.
To maintain a low incidence of Catheter Related Infections (CRI) and Catheter Related Bloodstream Infections (CRBSI), continuous follow-up studies on catheter management are necessary. The aims of the present study were to investigate the incidence of catheter tip colonisation, CRI and CRBSI in the Region, to further explore the feasibility of automatic data collection and to investigate associations between independent variables and CRI. Data from electronic patient charts on all documented central venous catheter (CVC) insertions from multiple hospitals in southern Sweden, between March 2019 and August 2020, were automatically extracted. Multivariable regression analyses were used to identify associated risk factors. In total, 9924 CVC insertions were included. The prevalence of CRI and CRBSI were 0.7% (n = 74) and 0.02% (n = 20) with incidences of 1.2/1000 catheter days and 0.3/1000 catheter days, respectively. We found a sustained low incidence of CRI and CRBSI in the Region. Catheter tips were less likely to be colonised when the subclavian route was used compared to the internal jugular route and male sex as well as increased number of catheter lumens were associated with both catheter tip colonisation and CRI. By using automated scripts, data extraction was efficient and feasible but also demonstrated that real-time quality assurance should be recommended, since this is superior to current standard.


Spondyloepiphyseal dysplasia tarda: report of one case.
We report the clinical assessment and mutational analysis of one boy with spondyloepiphyseal dysplasia tarda (SEDT). His short stature manifested between age 5 and 10. As his growth slowed, his height fell from the mean for his age at 5 to the 2nd percentile at age 10.5. His bone age was retarded at 8 years, thus his predicted adult height was 164.9 cm, not far from his target height of 170cm. However, upon physical examination, he presented markedly short trunk. We suspected SEDT and X-ray finding of his spine supported this diagnosis. We performed DNA analysis on the SEDL gene and detected a 5-bp deletion in exon 5 which has been previously reported by Mumm et al. and Gedeon et al. in cases of SEDT.


[Occurrence of AmpC-positive Klebsiella pneumoniae strains in patients with haematological malignancies].
Currently, important bacterial beta-lactamases of increasing clinical significance include AmpC enzymes. The aim was to assess their occurrence in Klebsiella pneumoniae strains isolated from patients with haematological malignancies in a prospective study. Over a 2-month period, strains of the species were isolated from clinical material obtained from patients hospitalized at the Department of Haemato-Oncology of the University Hospital Olomouc. The strains were identified using standard microbiological techniques and the Vitek 2 automated system. Production of AmpC beta-lactamases was roughly determined by phenotypic tests and subsequently confirmed by PCR detection of genes encoding these enzymes. During the above-mentioned period, a total of 35 K. pneumoniae isolates were collected. In 7 of them, production of AmpC beta-lactamases was preliminarily detected by phenotypic test. The multiplex PCR method confirmed phenotyping and determined DHA types in all the isolates. All AmpC-positive isolates were false-susceptible to at least one of the tested third-generation cephalosporins. In one patient, clinically apparent infection caused by this strain was documented. The reported results suggest the possibility of occurrence of AmpC-beta-lactamases in K. pneumoniae strains with clinical significance.


Assessment of Scanning Mobility Particle Sizer (SMPS) for online monitoring of delivered dose in an in vitro aerosol exposure system.
Real-time monitoring of dosimetry is critical to mitigating the constraints of offline measurements. To address this need, the use of the Scanning Mobility Particle Sizer (SMPS) to estimate the dose delivered through the Dosimetric Aerosol in Vitro Inhalation Device (DAVID) was assessed. CuO nanoparticles suspended in ethanol at different concentrations (0.01-10 mg/mL) were aerosolized using a Collison nebulizer and diluted with air at a ratio of either 1:3 (setup 1) or 1:18 (setup 2). From the aerosol volume concentrations measured by the SMPS, density of CuO (6.4 g/cm3), collection time (5-30 min), flow rate (0.5 LPM) and deposition area (0.28 cm2), the mass doses (DoseSMPS) were observed to increase exponentially over time and ranged from 0.02 ± 0.001 to 84.75 ± 3.49 μg/cm2. The doses calculated from the Cu concentrations determined by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) (DoseICP) also increased exponentially over time (0.01 ± 0.01-97.25 ± 1.30 μg/cm2). Regression analysis between DoseICP and DoseSMPS showed R2 ≥ 0.90 for 0.1-10 mg/mL. As demonstrated, the SMPS can be used to monitor the delivered dose in real-time, and controlled delivery of mass doses with a 226-fold range can be attained in ≤30 min in DAVID by adjusting the nebulizer concentration, dilution air and time.


Exposure to air pollutants and the gut microbiota: a potential link between exposure, obesity, and type 2 diabetes.
Work has shown that increased exposure to air pollutants independently contributes to obesity and type 2 diabetes risk, yet the exact mechanisms underlying these associations have not been fully characterized. The current review summarizes recent findings regarding the impact of inhaled and ingested air pollutants on the gut microbiota. Animal and human studies provide evidence that air pollutants, such as particulate matter, nitrogen oxides, and ozone, have the potential to alter the gut microbiota. Further, studies suggest that such exposure-induced alterations to the gut microbiota may contribute to increased risk for obesity and type 2 diabetes through inflammatory pathways. Future work is needed to fully understand the complex interactions between air pollution, the gut microbiome, and human health. Additionally, advanced sequencing methods for gut microbiome research present unique opportunities to study the underlying pathways that link increased air pollution exposure with obesity and type 2 diabetes risk.


[Idiopathic hemochromatosis--diagnosis and therapy].
The excessive storage of iron in idiopathic haemochromatosis leads to severe organic lesion up to life-threatening conditions (cardiac insufficiency, portal decompensation). The symptoms melanodermia , diabetes mellitus and other endocrine failures, liver cirrhosis, cardiac insufficiency and arthropathy appear together or in various combinations. The diagnosis is ascertained by the proof of iron storage, the multiple organic affection and by familial accumulation of the various laboratory diagnostic possibilities are particularly to be emphasized the serum iron value together with the percetal transferrin saturation (as search test), serum ferritin, the desferrioxamine test, simple ferrokinetic investigations and the quantitative determination of iron in the liver in the bioptate . For family examinations, apart from the search test, a HLA typisation is reasonable, in order to estimate the risk of the disease (particularly of brothers and sisters). The therapy of choice are blood- lettings (0.5 l once to twice a week) up to obtaining a permanent easy iron deficiency anaemia. The maintenance therapy should be performed with monthly to quarterly blood- lettings . Only in cases exception a desferal treatment is indicated. Endocrine failures and cardiac disturbances need a particular therapy.


Electronic stress tensor description of chemical bonds using nonclassical bond order concept.
The stress tensors are used widely for description of internal forces of matter. For some time it is also applied in quantum theory in studies of molecular properties in chemical systems. Electronic stress tensors measure effects caused by internal forces acting on electrons in molecules and particularly those between bonded atoms. Utilized here stress tensor originated bond orders express bond strengths in terms of these internal forces. The unique concept of energy density and electronic chemical potential based bond orders gives natural evaluation of interaction strength compared with classical definition, considering delocalized nature of electrons. In addition to other causes, the relation to electronic energy may be used to predict relative stabilities of geometrical isomers or even conformers.


Preoperative Symptoms in Femoroacetabular Impingement Patients Are More Related to Mental Health Scores Than the Severity of Labral Tear or Magnitude of Bony Deformity.
The purpose of this study was to determine the relationships between patient factors, mental health status, the condition of the local tissue, magnitude of bony deformity, and preoperative symptoms in a series of femoroacetabular impingement (FAI) patients. From our prospective outcomes registry, we identified 64 patients with arthroscopically-treated labral tears and cam deformities. We assessed the correlations between patient factors (age, sex, body mass index, level of education), surgical findings (size of labral tear, presence of chondral lesions), mental health factors (VR-12 mental component score [MCS], depression, and preoperative use of psychotropic and/or opioid drugs), magnitude of FAI deformity (alpha and lateral center edge angles), and preoperative hip dysfunction and osteoarthritis outcome score (HOOS) subscales. Patient factors, surgical and radiographic findings, and preoperative HOOS scores were compared between patients with low and high MCS. Neither hip pathology nor patient-related factors significantly correlated with HOOS scores. On the contrary, MCS significantly correlated with HOOS symptom (ρ = 0.45, P < .001) and pain scores (ρ = 0.52, P < .001). Low MCS patients had significantly lower preoperative scores for all 5 HOOS subscales (P ≤ .002) and more frequent chondral lesions and comorbid depression (P ≤ .01). Symptom severity was significantly more related to mental health status than either the size of labral tear or FAI deformity. Patients with low MCS had significantly worse preoperative pain and self-reported function, and a greater prevalence of concomitant chondral lesions. Future studies are necessary to determine if earlier surgical treatment or preoperative psychological and/or pain coping interventions may improve outcomes for those with low MCS.


Application of photoconversion technique for correlated confocal and ultrastructural studies in organotypic slice cultures.
Photoconversion of fluorescent staining into stable diaminobenzidine (DAB) precipitate is widely used for neuroanatomical and developmental studies. An important advantage of the approach is to make correlations between light and electron microscopy analyses possible, the DAB reaction product formed during photoconversion being electron dense. By combining a photoconversion approach with biolistic transfection of neurons in organotypic hippocampal slice cultures, we describe here a methodology that allowed us to study at the electron microscopy level the fine details of cells expressing specific genes of interest. The same approach has also been used to analyze the ultrastructural characteristics of specific cells such as neurons recorded with patch clamp techniques. This approach revealed particularly useful for studies of dendritic arborisation, dendritic spines, and axon varicosities of identified cells, as precise morphometric parameters of these structures can only be obtained by electron microscopy. The techniques used for fluorescent staining and photoconversion of these different cell structures and the results obtained by electron microscopic analyses are described.


[Immunologic activity of human lymph cells in the lymphocyte blast transformation reaction].
The immunologic activity of lymph cells obtained by curative draining of the chest lymph drainage was studied in 14 patients with subhepatogenous jaundice of different origin. The lymphocyte blast transformation reaction showed that lymphocytes of the lymph can form blasts under the effect of phytohemagglutinin, antilymphocyte gamma-globulin and some bacterial antigens. The reaction of the highest intensity was recorded in lymphocyte cultures of the lymph collected for this purpose on the 2--3d day from the commencement of lymph drainage. Lymphorrhea produces a decrease in the capacity of stimulated lymph cells for blastformation. During lymph drainage no blastformation takes place in stimulated blood cell cultures of the patients. Therefore, the fundamental part of antigen sensitive lymphocytes is stored in the lymphoid tissue.


Inhibitory effect of topical application of polymerized ferulic acid, a synthetic lignin, on tumor promotion in mouse skin two-stage tumorigenesis.
A dehydrogenation polymer of ferulic acid (DHP-FA), a synthetic lignin, was evaluated for its ability to inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the 7,12-dimethylbenz[a]anthracene-treated skin of female ICR mice. Topical application of DHP-FA inhibits TPA-induced tumor promotion, whereas a monomeric ferulic acid does not show the inhibitory effect.


Immune response to acute diarrhea seen as circulating antibody-secreting cells.
We studied the immune response to acute diarrhea by examining antibody-secreting cells among peripheral blood lymphocytes, which are believed to be derived from the intestinal mucosa and to be on their way back there. In 23 of 24 patients, a dramatic increase in the total number of cells actively secreting immunoglobulins was detected one week after onset of diarrhea, and most of the cells were secreting IgA. Cells secreting antibody specific to the pathogen (Campylobacter jejuni or Salmonella spp.) also appeared at this time but accounted for only a part of the total response. The data suggest that diarrhea induces a vigorous, apparently polyclonal response, including antibodies to normal intestinal flora. The response to the infective agent was outstanding and suggests that this method can be used to identify the causative agent of an infection.


Systematic development of a block copolymer adjuvant for trivalent influenza virus vaccine.
The current influenza virus vaccines induce systemic humoral immunity and short lived cellular immunity in young adults. Unfortunately these vaccines are only 50% efficacious in the elderly (> 65 years) and high risk groups of the very young. The use of a vaccine adjuvant to correct this deficit would therefore be very beneficial to these population groups. We have developed high molecular weight synthetic non-ionic block copolymers with adjuvant activity. These copolymers are compatible with, and active in, aqueous, physiological formulations in which they spontaneously assemble into 500-3000 nm particles. By varying both the molecular weight and the proportions of hydrophilic and hydrophobic components of the molecule, we have designed the optimal copolymer adjuvant for use with influenza hemagglutinin. This copolymer, termed CRL-1005, was investigated for its ability to augment the immune response of mice to the commercially-available human influenza vaccine, Fluogen. Co-formulation of CRL-1005 with the vaccine resulted in markedly increased antibody titres measured by both ELISA and the functional haemagglutination inhibition assay, indicating that critical immunogen epitopes were not destroyed. A single dose of copolymer and vaccine produced both long term rising antibody titres (six months) and primed for a potent secondary response. This high molecular weight copolymer is non-toxic and should therefore be well suited for widespread use.


Modulation of ischemic excitatory neurotransmitter and gamma-aminobutyric acid release during global temporary cerebral ischemia by local nitric oxide synthase inhibition.
Systemic nitric oxide synthase inhibition (NOSI) decreases cerebral blood flow, which may worsen ischemic insults. To examine the local effects of NOSI without this confounding effect, we examined the role of a locally administered NOSI, NG-nitro-L-arginine-methyl-ester (L-NAME), on neurotransmitter recovery during cerebral ischemia. Rats were assigned to one of three groups: locally administered L-NAME via a striatal microdialysis probe (n = 11), systemic L-NAME (n = 5), or control (n = 11). Temporary global forebrain ischemia was induced for 15 min, followed by 60 min of reperfusion. L-NAME resulted in decreases of basal aspartate (ASP; 74% of basal) and glutamate (GLU; 60% of basal) recovery. While systemic L-NAME caused significant increases in ischemic ASP and GLU recovery (by 224% and 110%, respectively, compared with ischemic controls), local NOSI administration resulted in a significant attenuation of peak ASP, GLU, glycine, and gamma-aminobutyric acid recovery (43%, 38%, 53%, and 72%, respectively, compared with ischemic controls). We conclude that local NOSI attenuated ischemic neurotransmitter recovery during ischemia/reperfusion. Our results emphasize the importance of the systemic effects of NOSI and suggest both deleterious and beneficial effects of NOSI during ischemia/reperfusion.


School Counselor and Administrator Perceptions of Response to the COVID-19 Pandemic.
Collaborative efforts by school counselors and school administrators that are grounded in social capital principles have the potential to better support students' educational success, health, and well-being in the wake of challenging and adverse events, such as the COVID-19 pandemic. The purpose of this study was to assess perceptions of school counselors and administrators to determine the extent to which they had a shared vision of the challenges and strengths in their school's initial response to the pandemic. We also explored their sense of the anticipated future needs within the context of social capital theory and trauma-informed practices. Participants included 381 current pre-K-12 school administrators and school counselors throughout the United States who completed a mixed-methods survey in spring 2020. Use of these findings can help school stakeholders continue to foster students' social/emotional, academic, and career and college readiness development during continued and future mass trauma events.


Rotational and translational dynamics of rhodamine 6G in a pyrrolidinium ionic liquid: a combined time-resolved fluorescence anisotropy decay and NMR study.
NMR spectroscopy and time-resolved fluorescence anisotropy decay (TRFAD) are two of the most commonly used methods to study solute-solvent interactions. However, only a few studies have been reported to date using a combined NMR and TRFAD approach to systematically investigate the overall picture of diffusional and rotational dynamics of both the solute and solvent. In this paper, we combined NMR and TRFAD to probe fluorescent rhodamine dye in a pyrrolidinium-based room temperature ionic liquid (RTIL), an emergent environmentally friendly solvent type used in several energy-related applications. A specific interaction of the R6G cation and [Tf2N] anion was identified, resulting in near-stick boundary condition rotation of R6G in this RTIL. The diffusional rates of the R6G solute and [C4mpyr][Tf2N] solvent derived from (1)H NMR suggest the rates are proportional to their corresponding hydrodynamic radii. The (1)H and (13)C NMR studies of self-rotational dynamics of [C4mpyr][Tf2N] showed that the self-rotational correlation time of [C4mpyr](+) is 47 ± 2 ps at 300 K. At the same temperature, we find that the correlation time for N-CH3 rotation in [C4mpyr](+) is 77 ± 2 ps, comparable to overall molecular reorientation. This slow motion is attributed to properties of the cation structure.


Genetic and structural analyses of Escherichia coli O107 and O117 O-antigens.
The O-antigen, consisting of many repeats of an oligosaccharide, is an essential component of the lipopolysaccharide on the surface of Gram-negative bacteria. The O-antigen is one of the most variable cell constituents, and different O-antigen forms are almost entirely due to genetic variations in O-antigen gene clusters. In this paper, we present structural and genetic evidence for a close relationship between Escherichia coli O107 and E. coli O117 O antigens. The O-antigen of E. coli O107 has a pentasaccharide repeating unit with the following structure: -->4)-beta-D-GalpNAc-(1-->3)-alpha-L-Rhap-(1-->4)-alpha-D-GlcpNAc-(1-->4)-beta-D-Galp-(1-->3)-alpha-D-GalpNAc-(1-->, which differs from the known repeating unit of E. coli O117 only in the substitution of D-GlcNAc for D-Glc. The O-antigen gene clusters of E. coli O107 and O117 share 98.6% overall DNA identity and contain the same set of genes in the same organization. It is proposed that one cluster was evolved from another via mutations, and the substitution of a few amino acids residues in predicted glycosyltransferases resulted in the functional change of one such protein for transferring different sugars in O107 (D-GlcNAc) and O117 (D-Glc), leading to different O-antigen structures. This is an example of the O-antigen alteration caused by nucleotide mutations, which is less commonly reported for O-antigen variations.


Biomechanical evaluation of injury severity associated with patient falls from bed.
This study investigated the severity of injuries associated with falling from bed and the effectiveness of injury-prevention strategies. Injury criteria were calculated for head- and feet-first falls from six bed heights onto a tiled surface and floor mat. These values indicated a 25% chance of experiencing a serious head injury as a result of falling feet-first from a bed height of 97.5 cm onto a tiled surface. Risk of injury increased to 40% when extrapolated for the height added by bedrails. Using a floor mat decreased this risk to less than 1% for bedrail height for feet-first falls. Calculated impact forces indicated a risk of skull fracture when hitting the tiled surface. Floor mats and height-adjustable beds positioned to the lowest height should be used to decrease the risk of injury associated with falling from bed.


[Clinical effect of recombinant human G-CSF on neutropenia induced by chemotherapy for lung cancer. rG.CSF Cooperation Study Group].
The therapeutic evaluation of rG.CSF has been studied on neutropenic patients receiving lung cancer chemotherapy with focusing the change in the absolute neutrophil counting (ANC) in the patients during chemotherapy and subsequent rG.CSF treatment by daily dosing either at 0.4, 2.0, 5.0 and 10.0 micrograms/kg intravenously or at 2.0 and 5.0 micrograms/kg subcutaneously. The daily rG.CSF dosing for 14 consecutive days was performed on the patients upon completion of the 28-day chemotherapy for lung cancer. As a result, remarkable recovery of ANC was observed in the patients administered at doses of more than 5 and 2.0 micrograms/kg intravenously and subcutaneously, respectively. Additionally, the shortening of the neutropenia (ANC: below 1,000/cmm) was observed in the patients at doses of not less than 2.0 micrograms/kg in both administration routes. In conclusion, rG.CSF treatment demonstrates the completion and/or shortening of the chemotherapy cycle for lung cancer at a subcutaneous dose of 2.0 micrograms/kg and at a intravenous dose of 5.0 micrograms/kg. No adverse drug effects were observed in all patients during the study.