Stabilization of the Distal Radioulnar Joint Using the TightRope Implant: A Distal Oblique Bundle Augmentation.
Background Triangular fibrocartilage complex (TFCC) injury often results in distal radioulnar joint (DRUJ) instability. However, not all patients with a ruptured TFCC have an unstable DRUJ as in these patients a distal oblique bundle (DOB) may be present. We assumed that augmentation of the DOB leads to a more stable situation following reinsertion of the TFCC. We present the clinical results of a new surgical technique using the TightRope system as a DOB augmentation. Description of Technique All cases were treated under regional anesthesia with the TightRope implant for which a tunnel was drilled from the distal ulna through the radius along the path of the DOB. The TightRope was passed through the tunnel and secured with buttons on either side. X-rays were made during surgery to confirm correct positioning. Methods A retrospective study was performed analyzing 21 cases treated with a TightRope augmentation of the DOB. The primary outcome was measured using the patient-rated wrist evaluation (PRWE) score at least 12 months after surgery. Results Postoperatively, the DRUJ was stable in all patients. The median PRWE score was 16 for the injured side compared to zero for the uninjured side ( p -value: < 0.001). The median pronation and supination were not statistically significant when we compared the injured side to the uninjured side. The median grip strength was 31 kg for the injured side compared to 38 kg for the uninjured side ( p -value: 0.015). There were two minor postoperative complications (10%). Conclusion This technique is capable of restoring DRUJ stability with a short immobilization period resulting in good patient-related outcomes and a low complication rate.


The formation of complexes with albumin increases the stability of the protoporphyrin IX spectra.
Photodynamic therapy is a high-target, low-invasive treatment utilized to manage a variety of malignant diseases and precancerous lesions. Protoporphyrin IX (PpIX) is one of the most important photosensitizers used in photodynamic therapy, carried to the cancer tissue by serum albumin. Its delivery by transport protein is one of the major factors in determining the efficacy of photodynamic therapy. The distribution of the albumin-PpIX complexes to the target tissue enables the accomplishment of an optimal PDT effect. This study aimed to assess in vitro the stability of spectrofluorimetric spectra of albumin-PpIX complexes. The experiment used three chemicals: PpIX, human serum albumin (HSA), and bovine serum albumin (BSA). Spectral data was recorded using a Kontron SFM-25 Instrument AG, at two excitation wavelengths λex=280 nm and 295 nm. A concentration of 1x10-5M of PpIX, in combination with 1.25x10-6M of HSA and 4x10-7M of BSA, have been recorded repetitively for ten days and compared to the initial spectrum. The maximum of PpIX fluorescence changed significantly on the first day following sample preparation. The maximum of PpIX - serum albumin complex was stable 10 and 4 days for HSA and 5 and 2 days for BSA for λex=280 nm and 295 nm, respectively. The formation of a complex between PpIX and serum albumin was seen to extend the stability of the spectrofluorimetric spectrum. However, a less significant effect was observed in the case of BSA, which could most plausibly be attributed to the variations in primary structure between HSA and BSA, leading to discernible variations in spectroscopic measurements.


Anthropogenic and naturally occurring organobrominated compounds in fish oil dietary supplements.
Fish oil dietary supplements (FODS) are recommended to increase the intake of polyunsaturated fatty acids (PUFAs), renowned for their beneficial effects on human health. However, FODS also contain anthropogenic contaminants, such as polychlorinated biphenyls and polybrominated diphenyl ethers (PBDEs). Sixty-nine (n=69) PUFA-enriched FODS from 37 producers were collected in 2006 and then analyzed for their levels of organobrominated compounds. Levels of the sum of tri- to hepta-BDEs (BDEs 28, 47, 49, 66, 85, 99, 100, 153, 154, and 183) were typically below 5 ng/g oil, while only a few had higher values of up to 44 ng/g oil. Several peaks in the chromatograms were identified as methoxylated PBDEs (MeO-PBDEs) and polybrominated hexahydroxanthene derivatives (PBHDs). These two groups of compounds have been suggested to be produced by marine organisms (e.g., algae and sponges) and have also been reported in marine samples, such as fish and marine mammals. Median concentrations of MeO-PBDEs and PBHDs (6.2 and 5.3 ng/g oil, respectively) were higher than median concentrations of PBDEs (0.6 ng/g oil), and their maximum values were 1670 and 200 ng/g oil, respectively. FODS are intended to be consumed on a daily basis, and the median daily intakes of MeO-PBDEs and PBHDs from FODS were 3 and 6 times higher than the median intake of PBDEs (3 ng/day). Consumption of FODS does not appear to substantially increase the total dietary intake of PBDEs since the median daily intake


Surgical treatment of Freiberg's infraction in athletes.
Ten patients with 11 cases of Freiberg's infraction were studied retrospectively. The patients had varying amounts of sports participation. All cases were treated surgically, most after some form of nonoperative intervention. Surgery consisted of metatarsophalangeal joint debridement, except in 1 patient where the metatarsal head was resected. All patients had improvement of their symptoms and 80% of normal joint range of motion was restored. No patient had joint space narrowing or major arthritic changes on follow-up roentgenographic studies.


Evaluation of amoxicillin clavulanate twice daily versus thrice daily in the treatment of otitis media in children. Danish-Swedish Study Group.
A total of 311 children who had recurrent otitis media or who had experienced failure of initial treatment of acute otitis media with phenoxymethylpenicillin, amoxicillin, ampicillin esters or cefaclor were entered into a single-blind study in two parallel groups in order to compare the clinical efficacy and safety of amoxicillin/clavulanate suspension given b.i.d. or t.i.d. for seven days. The patients were examined prior to the start of treatment, at an early follow-up visit 9 to 12 days after the start of treatment and at a late follow-up visit about three weeks later. Specimens for bacteriological culture were taken from the nasopharynx at entry, at the early follow-up visit, and at the late follow-up visit if there were symptoms of otitis. Both treatment groups showed a similar response, 90% or more of the patients being cured or showing improvement at the time of the early follow-up visit. The initial nasopharyngeal cultures showed growth of Haemophilus influenzae in 53% of the patients, Moraxella catarrhalis in 43% and Streptococcus pneumoniae in 39%. After treatment, cultures showed elimination of the initial pathogens in 30% of patients in both groups and recolonization in 23% in both groups. Haemophilus influenzae was the bacteria most frequently found in the nasopharynx at the first follow-up visit. Adverse effects, which consisted mostly of gastrointestinal and dermatological reactions, tended to be more common in the b.i.d. group but the difference was not statistically significant.


The effects of calcium chloride and sodium chloride on the electroporation-mediated skin permeation of fluorescein isothiocyanate (FITC)-dextrans in vitro.
We previously reported the substantial synergic effects of electroporation and electrolytes, particularly those containing CaCl(2) on the skin permeation of the model low-molecular weight compound, calcein. We then investigated the effects of electroporation (300 V, 10 msx10 times) and 150 mM NaCl or CaCl(2) on skin permeation of higher molecular weight compounds, fluorescein isothiocyanate (FITC)-dextrans (FD-4, FD-10 and FD-40; average molecular weight, 4.4, 9.6 and 35.6 kDa, respectively) using excised hairless rat skin. The observed steady state flux of FD-4 was 1.3 pmol/cm(2)/h after electroporation without NaCl or CaCl(2). The flux did not differ greatly from that without electroporation. In contrast, a much higher steady state flux was observed after electroporation with NaCl or CaCl(2) (2.5 and 8.2 pmol/cm(2)/h, respectively). For FD-10 and FD-40, no flux was detected with electroporation in water (without electrolytes) or without electroporation. On the other hand, high skin permeation was observed after electroporation in NaCl or CaCl(2) solution (FD-10: 7.5 and 18.2 pmol/cm(2)/h, FD-40: 4.5 and 9.3 pmol/cm(2)/h in NaCl and CaCl(2), respectively). The effects of CaCl(2) on FD permeation were greater than those of NaCl. The present finding suggests that electroporation application in the presence of electrolytes, particularly CaCl(2), was very effective in increasing transdermal delivery of water-soluble macromolecules.


Hydrophobic pulmonary surfactant proteins SP-B and SP-C induce pore formation in planar lipid membranes: evidence for proteolipid pores.
Pulmonary surfactant is a complex mixture of lipids and specific surfactant proteins, including the hydrophobic proteins SP-B and SP-C, in charge of stabilizing the respiratory surface of mammalian lungs. The combined action of both proteins is responsible for the proper structure and dynamics of membrane arrays in the pulmonary surfactant network that covers the respiratory surface. In this study, we explore the possibility that proteins SP-B and SP-C induce the permeabilization of phospholipid membranes via pore formation. To this end, electrophysiological measurements have been carried out in planar lipid membranes prepared with different lipid/protein mixtures. Our main result is that channel-like structures are detected in the presence of SP-B, SP-C, or the native mixture of both proteins. Current traces show a high variety of conductance states (from pS to nS) that are dependent both on the lipid composition and the applied potential. We also show that the type of host lipid crucially determines the ionic selectivity of the observed pores: the anionic selectivity observed in zwitterionic membranes is inverted to cationic selectivity in the presence of negatively charged lipids. All those results suggest that SP-B and SP-C proteins promote the formation of proteolipid channels in which lipid molecules are functionally involved. We propose that proteolipidic membrane-permeabilizing structures may have an important role to tune ionic and lipidic flows through the pulmonary surfactant membrane network at the alveolar surfaces.


Authority as coercion:when authority figures abuse their positions to perpetrate child sexual abuse.
ABSTRACT. This article discusses child sexual abuse by a person in a position of authority, such as the child's teacher, guardian, relative, sports coach, or other person with authority over a child because of his/her particular position. The article tracks the recent trend toward recognizing position of authority in both state legislation and judicial precedent. Understanding the confusion and intimidation surrounding a child's experiences as a result of being sexually abused by a person in a position of authority often explains why children often fail to report or delay in reporting such abuse. Thus, existence of a perpetrator's position of authority in a particular case of child sexual abuse should influence a court's rulings on the elements of sexual abuse or assault in particular state statutes, as well as what evidence should be admissible. Ultimately, the author concludes that all states should recognize position of authority in their child abuse statutes, that such statutes should be interpreted broadly by the courts, and, finally, that evidence of the defendant's prior acts of sexual abuse should almost always be admissible at trial.


Principles of design of active and removable appliances.
Removable orthodontic appliances, perhaps more than any other form of mechanical therapy for the movement of teeth, are applicable to general practice. Far too frequently, however, the clinician limits his appliance design to a selective number of appliances with which he is conversant and attempts to modify any one of them to fit a specific situation. This article suggests a different approach. A specific appliance has not been recommended for a specific situation. Instead, the principles of removable appliance design have been elaborated upon according to an established plan. Adherence to the principles should enhance the clinician's ability to provide a more effective and efficient service for his young patients.


Giant liposomes: a model system in which to obtain patch-clamp recordings of ionic channels.
Cell-size, giant liposomes have been formed by submitting a mixture of asolectin lipid vesicles and native membranes from Torpedo, highly enriched in acetylcholine receptor (AcChR), to a partial dehydration/rehydration cycle [Criado, M., & Keller, B. U. (1987) FEBS Lett. 224, 172-176]. Giant liposomes can be prepared in bulk quantities, in the absence of potentially damaging detergents or organic solvents, and their formation is mediated by membrane fusion phenomena. In fact, fluorescence microscopy and freeze-fracture data indicate that protein and lipid components of the initial membranes and lipid vesicles are homogenously distributed in the resulting liposomes. Giant liposomes containing AcChR have been used as a model to evaluate whether this system can be used to monitor the activity of ionic channels by using high-resolution, patch-clamp techniques. Excised liposome patches in an "inside-out" configuration have been used in this work. We find that the most frequent pattern of electrical activity in response to the presence of acetylcholine in the patch pipet corresponds to a cation-specific channel exhibiting a dominant conductance level and a sublevel of approximately 78 and 25 pS, respectively. Such channel activity exhibits the pharmacological specificity, ion channel activation, ion selectivity, and desensitization properties expected from native Torpedo AcChR. Thus, it appears that the giant liposome technique offers a distinct advantage over other reconstitution procedures in that it provides a unique opportunity to undertake simultaneous biochemical, morphological, and electrophysiological studies of the incorporated ionic channel proteins.


Crosslinked polymer nanoparticles containing single conjugated polymer chains.
Conjugated polymer nanoparticles are widely used in fluorescent labeling and sensing, as they have mean radii between 5 and 100 nm, narrow size dispersion, high brightness, and are photochemically stable, allowing single particle detection with high spatial and temporal resolution. Highly crosslinked polymers formed by linking individual chains through covalent bonds yield high-strength rigid materials capable of withstanding dissolution by organic solvents. Hence, the combination of crosslinked polymers and conjugated polymers in a nanoparticulated material presents the possibility of interesting applications that require the combined properties of constituent polymers and nanosized dimension. In the present work, F8BT@pEGDMA nanoparticles composed of poly(ethylene glycol dimethacrylate) (pEGDMA; a crosslinked polymer) and containing the commercial conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) were synthesized and characterized. Microemulsion polymerization was applied to produce F8BT@pEDGMA particles with nanosized dimensions in a ∼25% yield. Photophysical and size distribution properties of F8BT@pEDGMA nanoparticles were evaluated by various methods, in particular single particle fluorescence microscopy techniques. The results demonstrate that the crosslinking/polymerization process imparts structural rigidity to the F8BT@pEDGMA particles by providing resistance against dissolution/disintegration in organic solvents. The synthesized fluorescent crosslinked nanoparticles contain (for the most part) single F8BT chains and can be detected at the single particle level, using fluorescence microscopy, which bodes well for their potential application as molecularly imprinted polymer fluorescent nanosensors with high spatial and temporal resolution.


Photosynthetic electron transport regulates the stability of the transcript for the protochlorophyllide oxidoreductase gene in the liverwort, Marchantia paleacea var. diptera.
The transfer of Marchantia paleacea var. diptera cells to darkness caused a reversible repression in the accumulation of transcript for a gene, por, encoding the NADPH: protochlorophyllide oxidoreductase (EC 18.104.22.168). The photosynthetic inhibitor DCMU and DBMIB repressed the accumulation in light. In the presence of transcription inhibitor cordycepin, not only incubation in the dark but also addition of DCMU or DBMIB in light stimulated the degradation of the por transcript. These findings suggest that photosynthetic electron transport is involved in regulating the stability of the por transcript.


Heterologous expression, characterization and possible functions of the chitin deacetylases, Cda1 and Cda2, from mushroom Coprinopsis cinerea.
Two chitin deacetylases, Cda1 and Cda2, from Coprinopsis cinerea were expressed and characterized. Cda1 preferably deacetylates the nonreducing end residue of (GlcNAc)2, the internal or nonreducing end residue of (GlcNAc)3 and the nonreducing residue of (GlcNAc)6 after deacetylating the internal residues. In contrast, Cda2 preferably deacetylates the reducing end residue of (GlcNAc)2, the internal or reducing end residue of (GlcNAc)3 and the reducing residue of (GlcNAc)6 after deacetylating the internal residues. Furthermore, Cda1 prefers chitohexaose with higher degrees of acetylation for deacetylation, while Cda2 shows a weaker preference for chitohexaose with varying degrees of acetylation. The predicted Cda1 structure shows more hydrophobic aromatic amino acids on the surface near subsite +1 in the active site than on the surface near subsite -1, whereas the predicted Cda2 structure has more hydrophobic aromatic amino acids on the surface near subsite -1 than on the surface near subsite +1, which may be the molecular basis of the distinctive catalytic features between Cda1 and Cda2. Notably, Cda1 has a high transcription level in the nonelongating basal stipe region, whereas Cda2 has a high transcription level in the elongating apical stipe region, and the transcription level of the former is approximately five times that of the latter. Correspondingly, the molar ratio of GlcN/GlcNAc increased from 0.15 in the cell wall of the apical stipe region to 0.22 in the cell wall of the basal stipe region. Different modes of action of Cda1 and Cda2 may be related to their functions in the different stipe regions.


Nanoelectrospray ion mobility spectrometry online with inductively coupled plasma-mass spectrometry for sizing large proteins, DNA, and nanoparticles.
Recently it has been demonstrated that nanoelectrospray (nES) in conjunction with macro-ion mobility spectrometry (macroIMS) and condensed particle detection can be used to size various types of nanoparticles, including large biomolecules (proteins, DNA, etc.), having electrophoretic mobility diameters ranging from 3 nm to well over 100 nm. The technique is extremely sensitive; however, it lacks specificity as a result of the detector used. To explore the possibility to overcome this limitation, we demonstrate the direct coupling of the nES-macroIMS system to an inductively coupled plasma mass spectrometer (ICPMS). Technical challenges involving the coupling of the air-based nES-macroIMS with the argon-based ICPMS are addressed and overcome. The resulting novel hyphenated technique is used to determine the elemental composition of nanoparticles resulting from the electrospraying of solutions containing inorganic salts and acids (CsI and dimethylarsinic acid). Even though the sensitivity of the used ICPMS does not allow for the simultaneous sizing of proteins and the determination of their metal, metalloid, or halogen content, we have shown that it is feasible to detect and accurately size proteins at femtomole levels by adding CsI to their solutions and detecting the resulting Cs adducts. This is also possible with DNA molecules. A linear relationship between protein amount and ICPMS response for (133)Cs(+) is observed, thus hinting at the possibility of further developing the technique for quantitative analysis of large biomolecules.


IL-34 exacerbates pathogenic features of Alzheimer's disease and calvaria osteolysis in triple transgenic (3x-Tg) female mice.
Hallmark features of Alzheimer's disease (AD) include elevated accumulation of aggregated Aβ40 and Aβ42 peptides, hyperphosphorylated Tau (p-Tau), and neuroinflammation. Emerging evidence indicated that interleukin-34 (IL-34) contributes to AD and inflammatory osteolysis via the colony-stimulating factor-1 receptor (CSF-1r). In addition, CSF-1r is also activated by macrophage colony-stimulating factor-1 (M-CSF). While the role of M-CSF in bone physiology and pathology is well addressed, it remains controversial whether IL-34-mediated signaling promotes osteolysis, neurodegeneration, and neuroinflammation in relation to AD. In this study, we injected 3x-Tg mice with mouse recombinant IL-34 protein over the calvaria bone every other day for 42 days. Then, behavioral changes, brain pathology, and calvaria osteolysis were evaluated using various behavioral maze and histological assays. We demonstrated that IL-34 administration dramatically elevated AD-like anxiety and memory loss, pathogenic amyloidogenesis, p-Tau, and RAGE expression in female 3x-Tg mice. Furthermore, IL-34 delivery promoted calvaria inflammatory osteolysis compared to the control group. In addition, we also compared the effects of IL-34 and M-CSF on macrophages, microglia, and RANKL-mediated osteoclastogenesis in relation to AD pathology in vitro. We observed that IL-34-exposed SIM-A9 microglia and 3x-Tg bone marrow-derived macrophages released significantly elevated amounts of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, compared to M-CSF treatment in vitro. Furthermore, IL-34, but not M-CSF, elevated RANKL-primed osteoclastogenesis in the presence of Aβ40 and Aβ42 peptides in bone marrow derived macrophages isolated from female 3x-Tg mice. Collectively, our data indicated that IL-34 elevates AD-like features, including behavioral changes and neuroinflammation, as well as osteoclastogenesis in female 3x-Tg mice.


Investigating the effectiveness of monitoring relevant variations during IMRT and VMAT treatments by EPID-based 3D in vivo verification performed using planning CTs.
The goal of this study was to investigate the effectiveness of monitoring relevant variations during treatments for electronic portal imaging device (EPID)-based 3D in vivo verification performed using planning CTs. Experiments on two simple phantoms (uniform and nonuniform phantoms) and a thoracic phantom were analyzed in this study, and six relevant variations including the machine output, planning target volume (PTV) deformation, multileaf collimator (MLC) and Phantom shift (set-up errors), and gantry and couch angle shifts were evaluated. 3D gamma and dose-volume histogram (DVH) methods were used to evaluate the detection sensitivity of the EPID-based 3D in vivo dosimetry and the dose accuracy of the EPID reconstruction, respectively, as affected by the variations, and the results were validated by determining the consistency with TPS simulated results. The results of the simple phantoms showed that the gamma failure rates and DVH trend of EPID reconstructions were consistent with the results of TPS simulations for machine output and MLC shifts and inconsistent for phantom shift, gantry/couch angle shift and PTV deformation variations. The results of the thoracic phantom showed that CBCT-guided EPID reconstruction sensitively detected 3-mm Phantom shift in thoracic phantom and its gamma failure rates and DVH trend were consistent with the results of TPS simulations. The variations, such as machine output and MLC shift, that are phantom unrelated and cause changes in the beam of the linear accelerator can be sensitively detected by EPID-based 3D in vivo dosimetry and do not affect the accuracy of the EPID reconstruction dose. Planning CT will limit the detection sensitivity and the accuracy of the reconstruction dose of the EPID-based 3D in vivo dosimetry for phantom-related variations (such as Phantom shift and gantry/couch angle shift). EPID reconstruction combined with IGRT technology is a more effective method to monitor phantom shift variations.


MACF1, versatility in tissue-specific function and in human disease.
Spectraplakins are a family of evolutionarily conserved gigantic proteins and play critical roles in many cytoskeleton-related processes. Microtubule actin crosslinking factor 1 (MACF1) is one of the most versatile spectraplakin with multiple isoforms. As a broadly expressed mammalian spectraplakin, MACF1 is important in maintaining normal functions of many tissues. The loss-of-function studies using knockout mouse models reveal the pivotal roles of MACF1 in embryo development, skin integrity maintenance, neural development, bone formation, and colonic paracellular permeability. Mutation in the human MACF1 gene causes a novel myopathy genetic disease. In addition, abnormal expression of MACF1 is associated with schizophrenia, Parkinson's disease, cancer and osteoporosis. This demonstrates the crucial roles of MACF1 in physiology and pathology. Here, we review the research advances of MACF1's roles in specific tissue and in human diseases, providing the perspectives of MACF1 for future studies.


Full-Dimensional Potential Energy Surface and Ro-vibrational Levels of Dioxirane.
A full-dimensional potential energy surface is developed for dioxirane based on a high-fidelity fit of ∼46,000 ab initio points at the CCSD(T)-F12a/AVTZ level. The ro-vibrational levels of dioxirane were computed using the MULTIMODE method on this potential energy surface, and the agreement with the available experimental microwave spectrum is quite satisfactory. In addition, dipole moment surfaces have been constructed from ab initio data, and they allow the prediction of the infrared (IR) spectrum.


Effects of genetic variations within goat PITX2 gene on growth traits and mRNA expression.
Paired-like homeodomain 2 (PITX2), a key gene in hypothalamic-pituitary-adrena axis, influences animal growth and development. The objective of this study was to identify the association of the functional genetic variations within goat PITX2 gene with growth traits and mRNA expression levels. According to the reported single nucleotide polymorphisms (SNPs) information in Guanzhong dairy goat (GZDG), we identified genotypes of the known SNPs in Hainan black goat (HNBG). Association analysis uncovered that the SNPs of AC_000163: g.18117T > C, g.18161C > G and g.18353T > C loci were significantly associated with several growth traits (e.g., body height and body length) in HNBG and GZDG breeds. According to the quantitative real-time PCR assay, β-Actin and ribosomal protein L19 (RPL19) were the most stable expressed housekeeping genes in heart and skeletal muscle, respectively; meanwhile, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was the most stable expressed housekeeping gene in the other tissues. Based on the best housekeeping gene of varied tissues, we found the different genotypes of above loci were significantly associated with PITX2 mRNA expression in heart, muscle and small intestine. Briefly, the genetic variants of goat PITX2 associating with mRNA expression affected growth traits significantly, which would benefit for goat breeding in the future.


Role of pigment epithelium-derived factor on proliferation and migration of choroidal capillary endothelium induced by vascular endothelial growth factor in vitro.
Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization. Microdissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays. Cells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However, the concentration of PEDF which we used has little effect on normal CECs. PEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell. These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.


The kaleidoscope of the glass ceiling: experiences of Pakistani female doctors - a qualitative narrative inquiry.
To explore the extent and factors leading to the glass ceiling for Pakistani female doctors in leadership positions. The qualitative narrative study was conducted the Department of Medical Education, Riphah International University, Islamabad, Pakistan from March to July 2021, and comprised female doctors with 10-15 years of professional experience who were either currently at top leadership position or had retired from such a position in public and private medical clinical setups and medical colleges. Data was collected using in-depth interviews conducted through Zoom due to the coronavirus disease-2019 pandemic. The transcribed data was processed using ATLAS.ti.9 software for thematic analysis with an inductive approach. Of the 9 subjects aged 47-72 years having professional experience of 11-39 years, 4(44.4%) were clinicians, 3(33.3%) had basic medical science background and 2(22.2%) were health profession educationists. In terms of qualifications, 4(44.4%) were PhDs, 4(44.4%) were Fellows of the College of Physicians and Surgeons, Pakistan, and 1(11.1%) had an M. Phil. Besides, 4(44.4%) subjects were from the public sector, and 5(55.5%) from the private sector, 1(11.1%) had retired from service. The extent of experiencing the glass ceiling was common to all but 1(11.1%) participant. Factors identified included 'institutional challenges', 'family support issues', 'personal challenges' and 'societal unacceptance'. Detailed analysis revealed that women in leadership positions faced 'malintent of seniors', 'discrimination', 'stereotyping', 'lack of mentors' and 'ethnic background conditioning' at the institutional level. On the personal front, they faced 'lack of support of in-laws', 'insecurity of husbands', 'need of personal attributes' and 'beauty as a barrier'. The glass ceiling was found to be a challenge faced by Pakistani female doctors in leadership positions in both clinical settings and academia.


[Relationships between basic sciences and medicine revisited].
1. The role of basic research in medical institutions and in particular in Medical Schools is discussed. 2. Clinical practice is characterized, in its technical aspects, as a branch of biological technology. 3. It is suggested that the main functions of basic research practiced in medical institutions is to promote the interaction between physicians and scientists in other fields and to train physicians in the practices of other scientists. 4. It is suggested that the introduction of basic research in medical institutions implies: the recruitment of scientists from non-medical disciplines; a policy of funding that does not favour exclusively the clinical sector; the setting up of a regular graduate program, based on the scientifically active groups and adequately regulated.


[Separate evaluation of left and right-sided renal function (author's transl)].
The PAH extraction of the kidneys was determined separately on each side after catheterisation of both renal veins and the femoral artery during PAH infusion in eleven patients with normal or diminished renal function due to bilateral renal disease and in five patients with only one kidney with normal or diminished renal function. A significant positive correlation was found between PAH extraction and inulin clearance and a significant negative correlation between PAH extraction and the log of the serum creatinine. PAH extraction is a suitable method for quantitative evaluation of right and left renal function.


New infrared-assisted method for sol-gel derived ZnO:Ag thin films: Structural and bacterial inhibition properties.
A new sol-gel method, based on crystallization with Infrared heating, was developed to obtain ZnO:Ag thin films. The common sol, with zinc acetate as precursor and silver nitrate as doping source (1, 3 and 5 % molar), isopropanol and distilled water as solvents and monoethanolamine as stabilizer agent; was modified with Pluronic F127 and diethylene glycol as rheological agents, and with urea as fuel to produce enough energy to the combustion and to promote the crystallization process. Later, Corning glass-substrates were dipped into the sol at a constant speed of 3mms-1. To provide the necessary energy for obtaining the hexagonal ZnO structure of the coatings during the drying and consolidation process, instead of using the common furnace heat-treatment, the films were heated by means of an infrared (IR) ceramic lamp (800W) for 15, 30, 45, 60 and 180 minutes, and the effect of this annealing method was analyzed. The structural properties were examined by means of X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), whereas morphology was studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The examination revealed a homogeneous distribution of particles with the characteristic pores of pluronic F127, and the coating roughness had an average value of 100nm by AFM. To evaluate the effect on the number of dipping cycles and the IR-treatment on the thickness, ellipsometry results for 1, 3 and 5 deposits were analyzed and showed increments of 780, 945 and 1082nm, respectively. Finally, to test of the antibacterial activity, instead of the common one-microorganism approach, environmental microorganisms that grow with expose of the broth to the ambient conditions were employed (microbial consortium), which is a real environmental condition. The biological test was carried out by kinetic growth inhibition (optical density) of heterotrophic bacteria in culture liquid media under conditions of light, light-dark and darkness, to analyze the effect of light. A significance reduction in growth was obtained for doped coatings with silver in comparison with the control ZnO substrate. Furthermore, the analysis bacteria growth inhibition on a solid surface showed that the films effectively present antibacterial activity. The best result was obtained with ZnO:Ag 1% in light conditions, about 67%, but all the coatings inhibited the bacterial activity.


Innovative prevention strategies for radiation necrosis of the central nervous system.
The authors have reviewed the experimental data on the radio-response of the central nervous system (CNS) and summarize the development of rational prevention strategies for radiation necrosis. Currently, radiation necrosis is thought to result from complex dynamic interactions between parenchymal and vascular endothelial cells within the CNS. The latent time, preceding the clinical manifestation of damage, is viewed as an active phase where cytokines and growth factors play important roles in inter- and intracellular communication. The present pathogenetic model forms the basis of rational innovative prevention strategies, which are now being studied in vivo. They include treatment with growth factors as well as neural stem cell transplantation and neoangiogenesis.


The effect of cyclophosphamide, methotrexate and X-irradiation on the ultrastructure and endocytic capacity of murine peritoneal macrophages.
100 mg/kg cyclophosphamide given subcutaneously daily for 5 days and whole-body X-irradiation (500 r) had an appreciable effect on the phagocytosis of E. coli by mouse peritoneal macrophages. Less bacteria were ingested by cells from the treated mice as compared with control cells. In contrast, whole-body X-irradiation had a stimulatory effect on pinocytosis as compared with cells from cyclophosphamide treated mice or control mice. Morphological changes in the cells from animals treated with cyclophosphamide or X-rays were evident. The cells were larger than normal macrophages and contained large amounts of lipid and phagolysosomes and had more vacuoles as compared with control cells. Many giant cells were present in the treated mice. Treatment of mice with methotrexate for 5 days, although affecting the cells morphologically in that they were larger than normal cells and had many vacuoles did not appear to have any effect on either phagocytosis or pinocytosis. Cells from methotrexate treated animals did not contain the large quantities of lipid seen in cells from the cyclophosphamide treated and X-irradiated mice.


Teaching an old dog new tricks: new directions in fundamental and applied closo-carborane anion chemistry.
This feature article covers new directions in the fundamental and applied chemistry of the closo-carborane anions [HCB11H11]- and [HCB9H9]-, as well as some related chemistry with the dicarbolide ion [H2C2B9]2-. Specifically the manuscript will focus on summarizing the authors' as well as related novel contributions to the field. The application of such clusters as solution based electolytes for Mg batteries and related materials for ionic liquids will be discussed. In addition, the preparation of heterocycles and radicals fused to carborane anions will be discussed as well as various novel chemical transformations. Furthermore, new developments in anionic carboranyl phosphines and N-heterocyclic carbenes in the context of catalysis will be summarized.


Nanocrystals modified with peptide nucleic acids (PNAs) for selective self-assembly and DNA detection.
Gold nanocrystals modified with peptide nucleic acids (PNAs) have been prepared and applied to self-assembly and DNA sensing. Experiments with different PNA structural motifs show that (1). the versatility in PNA synthetic design can be used to modulate the electrostatic surface properties of nanocrystals, presenting an opportunity to control assembly rate and aggregate size, (2). short (6 base) PNAs can hybridize effectively while attached to nanoparticles, providing a route to generating materials with small interparticle spacings, and (3). the superior base pair mismatch selectivity of PNAs is further enhanced on nanosurfaces, enabling PNA-modified nanoparticles to act as highly selective nanoscale sensors, as well as synthons for defect-free self-assembly. This last feature was coupled with a substantial change in colloidal stability upon DNA hybridization to develop a novel colorimetric DNA assay that detects the presence of single base imperfections within minutes. Various modes of PNA hybridization, including the first practical application of PNA-PNA interactions, were used to direct the assembly of nanoparticles into macroscopic arrangements. Shorter duplex interconnects and greater specificity in assembly were obtained compared to similar experiments with DNA-modified nanocrystals.


Metal accumulation varies with life history, size, and development of larval amphibians.
Amphibian larvae are commonly used as indicators of aquatic ecosystem health because they are susceptible to contaminants. However, there is limited information on how species characteristics and trophic position influence contaminant loads in larval amphibians. Importantly, there remains a need to understand whether grazers (frogs and toads [anurans]) and predators (salamanders) provide comparable information on contaminant accumulation or if they are each indicative of unique environmental processes and risks. To better understand the role of trophic position in contaminant accumulation, we analyzed composite tissues for 10 metals from larvae of multiple co-occurring anuran and salamander species from 20 wetlands across the United States. We examined how metal concentrations varied with body size (anurans and salamanders) and developmental stage (anurans) and how the digestive tract (gut) influenced observed metal concentrations. Across all wetlands, metal concentrations were greater in anurans than salamanders for all metals tested except mercury (Hg), selenium (Se), and zinc (Zn). Concentrations of individual metals in anurans decreased with increasing weight and developmental stage. In salamanders, metal concentrations were less correlated with weight, indicating diet played a role in contaminant accumulation. Based on batches of similarly sized whole-body larvae compared to larvae with their digestive tracts removed, our results indicated that tissue type strongly affected perceived concentrations, especially for anurans (gut represented an estimated 46-97% of all metals except Se and Zn). This suggests the reliability of results based on whole-body sampling could be biased by metal, larval size, and development. Overall, our data shows that metal concentrations differs between anurans and salamanders, which suggests that metal accumulation is unique to feeding behavior and potentially trophic position. To truly characterize exposure risk in wetlands, species of different life histories, sizes and developmental stages should be included in biomonitoring efforts.


The Response Regulator Slr1588 Regulates spsA But Is Not Crucial for Salt Acclimation of Synechocystis sp. PCC 6803.
Cyanobacterial sucrose biosynthesis is stimulated under salt stress, which could be used for biotechnological sugar production. It has been shown that the response regulator Slr1588 negatively regulates the spsA gene encoding sucrose-phosphate synthase and mutation of the slr1588 gene also affected the salt tolerance of Synechocystis (Chen et al., 2014). The latter finding is contrary to earlier observations (Hagemann et al., 1997b). Here, we observed that ectopic expression of slr1588 did not restore the salt tolerance of the slr1588 mutant, making the essential function of this response regulator for salt tolerance questionable. Subsequent experiments showed that deletion of the entire coding sequence of slr1588 compromised the expression of the downstream situated ggpP gene, which encodes glucosylglycerol-phosphate phosphatase for synthesis of the primary osmolyte glucosylglycerol. Mutation of slr1588 by deleting the N-terminal part of this protein (Δslr1588-F976) did not affect ggpP expression, glucosylglycerol accumulation as well as salt tolerance, while the mutation of ggpP resulted in the previously reported salt-sensitive phenotype. In the Δslr1588-F976 mutant spsA was up-regulated but sucrose content was lowered due to increased invertase activity. Our results reveal that Slr1588 is acting as a repressor for spsA as previously suggested but it is not crucial for the overall salt acclimation of Synechocystis.


ELISA subtypization of anti-ENA autoantibodies in clinical management of autoimmune diseases in Bosnia and Herzegovina.
The basis of autoimmune diseases such as SLE (Systemic Lupus Eritematodes), Sjogren's syndrome, scleroderma, dermatomyositis and polymiositis is the creation of auto-antibodies to the following specific extractable nuclear antigens (ENA):Jo-1, Ssl-70, SS-A, SS-B, Sm and Sm/RNPs. Some of these antigens are in fact enzymes (Jo-1-histidil-tRNA synthetase, Scl-70-topoisomerase) which are inhibited by specific autoantibodies--this leads to disturbance in the metabolism of DNA and protein biosynthesis. During 2009, we analyzed total of 87 serum samples of patients suspected for autoimmune disorder using ANA-IFA and ELISA-ENA-6 methods. After establishing IFA-ANA positivity (83.9%), all serum specimens; ANA positive and negative, were subtypized by ELISA ENA-6 test. Analysis showed the highest incidence of anti-SS-A (56%), and incidence of anti-SS-B (29.8%), anti-Sm/ RNP (11.5%), anti-Jo-1 (2.3%) and anti-Scl-70 (1,1%) auto-antibodies. Also, 78.5% of IFA-ANA negative serum specimens showed high level of positivity (212.50 and 277.0 IU/ml) to SS-A (78.5%) and SS-B (21.4%) antigenes using ELISA-ENA-6 subtypization. Following these results, we conclude that it is necessary to introduce Western blot confirmation testing. After comparing with other clinical findings, we diagnosed the following autoimmune diseases: SLE, Sjogren's syndrome and dermatomiosytis.


Vitreomacular traction syndrome confused with pseudophakic cystoid macular edema.
Vitreomacular traction syndrome causes visual loss as a consequence of persistent traction on the fovea from an attached posterior hyaloid. The diagnosis can be challenging because the attachment may be subtle. Cystoid macular edema secondary to cataract extraction is well known and can occur in the absence of any surgical complication. Herein, a patient is described who had vitreomacular traction syndrome diagnosed after uneventful cataract surgery. Pars plana vitrectomy with detachment of the posterior hyaloid restored vision to an acceptable level. Careful examination and clinical suspicion are important because recognition and surgical intervention will benefit the majority of these patients.


Anatomy and physiology of visual evoked potentials and electroretinograms.
ERGs are electrical potentials originating in the retina and recorded directly from the corneal surface of the eyes. Flash ERGs are elicited by high intensity flashes either on scotopic or photopic conditions. The origin of the A and B waves of ERG are a combination of photoreceptor potentials, K+ mediated current flow and DC potentials within Müller cells, whereas the C waves are altered K+ fluxes induced by light in the pigment epithelia. Oscillatory potentials are probably related to feedback circuits of the inner layer of the retina. Electroretinograms evoked by pattern are mostly originated in ganglion cells. The use of various visual stimuli allow the selective activation of different retinal structures. Flashes selectively activate retina luminance and color detectors, whereas small pattern stimuli preferentially activate contrast and edge detectors. Visual evoked potentials recorded from the scalp probably originate from multiple cortical visual areas. P-100 response of the visual evoked potential to pattern stimulation is a cortically originated wave either produced exclusively by area 17 or 18 or by a multiplicity of cortical neuronal pools. Visual evoked potentials have important application for the diagnosis of optic nerve disease, assessment in conjunction with pattern ERG of the prognosis of recovery of visual function, and the evaluation of visual physiology and physiopathology.


Excessive cytokine response to rapid proliferation of highly pathogenic avian influenza viruses leads to fatal systemic capillary leakage in chickens.
Highly pathogenic avian influenza viruses (HPAIVs) cause lethal infection in chickens. Severe cases of HPAIV infections have been also reported in mammals, including humans. In both mammals and birds, the relationship between host cytokine response to the infection with HPAIVs and lethal outcome has not been well understood. In the present study, the highly pathogenic avian influenza viruses A/turkey/Italy/4580/1999 (H7N1) (Ty/Italy) and A/chicken/Netherlands/2586/2003 (H7N7) (Ck/NL) and the low pathogenic avian influenza virus (LPAIV) A/chicken/Ibaraki/1/2005 (H5N2) (Ck/Ibaraki) were intranasally inoculated into chickens. Ty/Italy replicated more extensively than Ck/NL in systemic tissues of the chickens, especially in the brain, and induced excessive mRNA expression of inflammatory and antiviral cytokines (IFN-γ, IL-1β, IL-6, and IFN-α) in proportion to its proliferation. Using in situ hybridization, IL-6 mRNA was detected mainly in microglial nodules in the brain of the chickens infected with Ty/Italy. Capillary leakage assessed by Evans blue staining was observed in multiple organs, especially in the brains of the chickens infected with Ty/Italy, and was not observed in those infected with Ck/NL. In contrast, LPAIV caused only local infection in the chickens, with neither apparent cytokine expression nor capillary leakage in any tissue of the chickens. The present results indicate that an excessive cytokine response is induced by rapid and extensive proliferation of HPAIV and causes fatal multiple organ failure in chickens.


[Pharmacokinetics of ampicillin in lambs and guinea pigs].
Comparative studies were carried out on the sodium salt of ampicillin and ampicillintrihydrate with the use of guinea pigs and lambs. Ampicillintrihydrate was applied to guinea pigs singly, muscularly and orally, at the rate of 0.025 per kilogram With lambs the two forms of the preparation were used--muscularly at rates of 0.005, 0.01, 0.015, and 0.02/kg; ampicillintrihydrate was tested orally at rates of 0.02, 0.03, and 0.05 kg/weight. For venous application ampicillin-sodium was used at the rate of 0.02/kg under the form of 4 per cent water solution (prepared with distilled water). Data referring to the comparative studies on the two forms of ampicillin--ampicillin-sodium and ampicillintrihydrate--showed that these preparations, after single parenteral and oral administration, are resorbed from the site of application and penetrate into all investigated organs and tissues. Ampicillin developed very soon bacteriostatic concentration in the blood serum in the course of 4-6-8 hours, depending on the amount applied and the route of application.


Combination of Pembrolizumab With Platinum-containing Chemotherapy for Pleomorphic Carcinoma of the Lung.
Pleomorphic carcinoma of the lung is a rare, highly malignant subtype of lung cancer, with a more aggressive clinical course compared with other types of non-small-cell lung cancer (NSCLC). Platinum-containing chemotherapy has been the standard therapy for patients with NSCLC and pembrolizumab is one of the novel and reliable agents for these patients. We herein report the case of a 60-year-old man with advanced chemo-naïve pleomorphic carcinoma of the lung who was successfully treated with a combination of pembrolizumab with platinum-containing chemotherapy. In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of this tumor, our case demonstrates the potential utility of the combination of pembrolizumab with platinum-containing chemotherapy. Our result also suggest that this combination of therapy may be key to the treatment of pleomorphic carcinoma of the lung.


Active hair bundle movements and the cochlear amplifier.
The "active process" is a term used to describe amplification and filtering processes that are essential for obtaining the exquisite sensitivity of hearing organs. Understanding the components of the active process is important both for our understanding of the normal physiology of hearing and because perturbations of the cochlear amplifier may lead to such maladies as threshold shifts (both temporary and permanent), tinnitus, sensorineural hearing loss and presbicusis. To date the cochlear amplifier has largely been attributed to outer hair cell electromotility; however, recent evidence suggests, that active properties of the hair bundle may also be important. Most likely both somatic motility and active hair bundle movements contribute to establishing the cochlear active process. This paper reviews recent evidence regarding known active processes in the hair bundle gating compliance, and fast and slow adaptation.


Configurational probabilities for symmetric dimers on a lattice: an analytical approximation with exact limits at low and high densities.
A new approach is developed for lattice density functional theory of interacting symmetric dimers at high temperatures. Equations of equilibrium for two-dimensional square and three-dimensional cubic lattices are derived for the complete set of configurations in the first three shells around the central dimer, and rules of truncation for higher shells are based on exact results from the mathematical theory of domino tilings. This provides exact limits for both low and high densities. The new model predicts contributions of particular configurations which are in agreement with Monte Carlo simulations over the whole range of densities, including agreement with pocket Monte Carlo simulations at high densities.


The association between neurocognition and sexual abuse within a children's psychiatric inpatient program.
Objective: The aim of this study was to understand the detrimental effects of sexual abuse on neuropsychological variables including child's intelligence, executive functioning (EF), and learning/memory within a pediatric inpatient population.Method: This study examined the effect of sexual abuse on children's intelligence, EF, and learning/memory by conducting a retrospective chart review for 144 children (aged 7-12) who completed a neuropsychological assessment during a psychiatric inpatient hospitalization. Of the 144 children, participants were matched two to one by gender and age, with one group (n = 52) categorized by reported sexual abuse and the other group (n = 92) categorized by no reported sexual abuse. The neuropsychological measures included the Wechsler Abbreviated Scale of Intelligence (WASI-I/II) or Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), Wide Range Assessment of Memory and Learning - Second Edition (WRAML-2): Story Memory Immediate/Delayed Recall and Delayed Recognition, Trail Making Test-B, Stroop Interference Test: Color-Word Condition, WRAML-2: Sentence Memory and Conners Continuous Performance Test-Second Edition.Results: Statistical analysis showed that participants with reported sexual abuse had significantly (p< .05) lower intelligence, EF, and learning/memory skills than those without reported sexual abuse. Only working memory and cognitive flexibility differences remained after controlling for clinical variables (e.g., PTSD, amount of total abuse types).Conclusions: These findings contributed to the limited research on the detrimental effects of sexual abuse in a pediatric inpatient population. They demonstrated a relationship between early sexual abuse and neuropsychological deficits, specifically executive function and IQ deficits.


The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial.
Delayed cord clamping has been shown to decrease the need for transfusion in preterm neonates, but may delay resuscitation. The aim of this study was to determine whether umbilical cord milking compared with immediate cord clamping in extremely preterm deliveries reduces the need for neonatal red blood cell transfusion. Women admitted to a tertiary care center and expected to deliver between 24 to 28 completed weeks of gestation were randomized to cord milking before clamping or immediate cord clamping. The primary outcome was the risk of neonatal transfusion, reported as risk ratio (RR) and 95% confidence interval (CI). Of 113 women who were enrolled and randomized, 56 were assigned to cord milking with 36 remaining eligible and completing the study and 57 were assigned to the control group with 39 remaining eligible and completing the study. Albeit not statistically significant, neonates in the cord milking group were less likely to require transfusion compared with those in the control group (RR: 0.86; 95% CI: 0.73 to 1.0). Neonates whose cords were milked had higher hematocrits at birth (P=0.004) and were less likely to develop an intraventricular hemorrhage (P=0.0195). Milking the umbilical cord of a preterm neonate is an easy intervention with the potential to improve perinatal outcomes. Our results suggest that milking of the cord increases the neonate's initial hematocrit and may lessen the need for transfusion in the neonatal period. The observed reduction in the incidence of intraventricular hemorrhage may have important long-term implications that warrant further study.


Mechanism and significance of early, rapid shortening in sensitized airway smooth muscle.
It has been reported that sensitization of animals to allergens increases both early shortening velocity and myosin light-chain kinase of their airway smooth muscle without increasing force generated by these muscles. Since early shortening sets muscle length for the duration of a contraction, these responses might be expected to produce greater airway obstruction. Here, it is explained how the more rapid early shortening without increased force production is predicted by the 2-stage process of activation followed by contraction posited by the crossbridge theory of contraction when the rate, but not the extent, of activation is increased. The experimental results are reproduced by a simple model in which activation rate is increased 1.6-fold without any other changes in contractile parameters. These results reinforce suggestions that sensitized animals are a model for reactive airway disease.


[The social status of schizophrenic patients].
In the German multicenter ANI study comparing continuous prophylactic treatment with intermittent medication, the social situation of a large sample of 364 schizophrenic patients was investigated and followed up over a 2-year period of outpatient aftercare. Effective therapy and prophylaxis substantially reduced relapses and rehospitalization. On the other hand, the psychosocial situation still showed considerable disadvantages. Of the patients (35 years old on average), 60% were still unmarried. Almost one-half of the patients still lived alone or with their parents, and one-third lived a very solitary life. At the end of the 2-year aftercare period, one-third was able to earn their own living. Almost one-half retired early from their occupations. Predictors and intervening variables are presented in order to stimulate early rehabilitation approaches. Schizophrenics are particularly placed at a disadvantage by tighter competition in the employment market, even though the course of illness can be improve. Social psychiatry must to be involved in helping to improve social contacts, accommodation and employment in order to prevent major distress.


Age differences in personality structure: a cluster analytic approach.
A cluster analytic approach was used to determine possible age differences in the structure of personality as measured by the Cattell Sixteen Personality Factor Questionnaire. Subjects were 969 adult male volunteers, originally divided into three groups: 25 to 34, 35 to 54, and 55 to 82. Two familiar dimensions of personality, Anxiety-Adjustment and Introversion-Extraversion, were found to be cross sectionally stable. A third cluster dimension, interpreted as openness to experience, showed age-related differences. Young subjects showed openness to feelings; middle-aged subjects showed openness to ideas; and old subjects showed a balanced openness to both feelings and ideas. Repartitioning of the sample into two groups (ages 25 to 43 and 44 to 82), and three groups (25 to 39, 40 to 47, and 48 to 82) confirmed these age differences in the third cluster. The interpretation of the third cluster is discussed in terms of Jung's concepts of psychological functions.


[Studies on purification and properties of antagonistic protein from bacteria SS02 of Paenibacillus daejeonensis].
The antifungal, anti-bacterical, anti-brine shrimp activities of SD22 isolated from Paenibacillus daejeonensis Bacteria SS02 were studied. The separation steps included ultracentrifugation, ultrafiltration and (NH4)2SO4 fractional precipitation, further purification was performed by SephadexG-75 and DEAE-32 chromatography. Its molecular weight determined by SDS-PAGE was 56.0 kD and its isoelectfic point was 6.4. SD22 was thermostable to some extent and stable to ultraviolet, but sensitive to some of the enzyme. SD22 could kill most pathogens from propagation, such as Rhizoctonia cerealis, Sclerotinia sclerotiorum Physalospora piricala, Trichodema viride, Gliocladium viride, Curvularia leaf spot, Fusarium sp, Fusarium head blight, Beauveria Bassiana, Escherichia coli, Staphylococcus aureus, Bacillus subtilis , Candidal vaginitis, Fusarium oxysporum Schl. emend. Sayder & Hansem et al. The results will be helpful to find out a novel antifungal protein.


Quality Information Detection of Agaricus bisporus Based on a Portable Spectrum Acquisition Device.
As one of the most popular edible fungi in the market, the quality of Agaricus bisporus will determine its sales volume. Therefore, to achieve rapid and nondestructive testing of the quality of Agaricus bisporus, this study first built a portable spectrum acquisition device for Agaricus bisporus. The Ocean Spectromeper was used to calibrate the spectral data of the device, and the linear regression analysis method was combined to analyze the two. The results showed that the Pearson correlation coefficient of significance between the two was 0.98. Then, the spectral data of Agaricus bisporus were collected, the spectral characteristic wavelength of Agaricus bisporus was extracted by the SPA and PCA algorithms, and the moisture content and whiteness prediction models based on a BP neural network and PLSR, respectively, were built. The parameters of the BP neural network model were optimized by SSA. The R2 values for the final moisture content and the predicted whiteness were 0.95 and 0.99, and the RMSE values were 5.04% and 0.60, respectively. The results show that the portable spectral acquisition and analysis device can be used for the accurate and rapid quality detection of Agaricus bisporus.


Systemic fungal infections: diagnosis and treatment. I. Histoplasmosis.
Histoplasmosis is a fungus disease of nearly worldwide distribution. Because of its wide distribution and tendency to be endemic near large cities, it is the most common systemic mycosis in the United States, with an estimated 500,000 new infections per year. Although millions of persons in the United States have been infected with this fungus, few show signs of disease. Histoplasmosis has emerged as an important opportunistic infection in immunocompromised patients, including those with AIDS. This review of histoplasmosis builds upon basic descriptions found in standard texts, incorporating important recent observations.


Coherent modulation imaging using a physics-driven neural network.
Coherent modulation imaging (CMI) is a lessness diffraction imaging technique, which uses an iterative algorithm to reconstruct a complex field from a single intensity diffraction pattern. Deep learning as a powerful optimization method can be used to solve highly ill-conditioned problems, including complex field phase retrieval. In this study, a physics-driven neural network for CMI is developed, termed CMINet, to reconstruct the complex-valued object from a single diffraction pattern. The developed approach optimizes the network's weights by a customized physical-model-based loss function, instead of using any ground truth of the reconstructed object for training beforehand. Simulation experiment results show that the developed CMINet has a high reconstruction quality with less noise and robustness to physical parameters. Besides, a trained CMINet can be used to reconstruct a dynamic process with a fast speed instead of iterations frame-by-frame. The biological experiment results show that CMINet can reconstruct high-quality amplitude and phase images with more sharp details, which is practical for biological imaging applications.


High power enzymatic biofuel cell based on naphthoquinone-mediated oxidation of glucose by glucose oxidase in a carbon nanotube 3D matrix.
We report the design of a novel glucose/O2 biofuel cell (GBFC) integrating carbon nanotube-based 3D bioelectrodes and using naphthoquinone-mediated oxidation of glucose by glucose oxidase and direct oxygen reduction by laccase. The GBFCs exhibit high open circuit voltages of 0.76 V, high current densities of 4.47 mA cm(-2), and maximum power output of 1.54 mW cm(-2), 1.92 mW mL(-1) and 2.67 mW g(-1). The GBFC is able to constantly deliver 0.56 mW h cm(-2) under discharge at 0.5 V, showing among the best in vitro performances for a GBFC. Using a charge pump, the GBFC finally powered a Light Emitting Diode (LED), demonstrating its ability to amplify micro watts to power mW-demanding electronic devices.


Buprenorphine physician supply: Relationship with state-level prescription opioid mortality.
Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation's prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states. The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of prescription opioid overdose mortality in 2013 at or above the median (>5.5 deaths per 100,000 population) and those with rates below the median. State-level growth curves were estimated using mixed-effects regression to compare rates of growth between high and low overdose states. The total supply and the supply of 100-patient buprenorphine physicians grew significantly (total supply from 7.7 to 9.9 per 100,000 population, p<0.001; 100-patient supply from 2.2 to 3.4 per 100,000 population, p<0.001). Rates of growth were significantly greater in high overdose states when compared to low overdose states (total supply b=0.033, p<0.01; 100-patient b=0.022, p<0.01). The magnitude of the US prescription opioid crisis, as measured by the rate of prescription opioid overdose mortality, is associated with growth in the number of buprenorphine physicians. Because this observational design cannot establish causality, further research is needed to elucidate the factors influencing physicians' decisions to begin prescribing buprenorphine.


Simple nonsingular control approach to fed-batch fermentation optimization.
Determination of the optimal feed rate for fed-batch fermentation is normally a problem in singular control with a state inequality constraint and as such is, in general, difficult to solve, especially for those described by a large number of dynamic mass balance equations. In this article we use a new set of state variables and the culture volume as the control variable. In this way the problem is converted to one of nonsingular control with the magnitude and rate constraints on the manipulated variable and can be numerically solved by a gradient-based technique, thus avoiding the difficulty associated with singular control problems. Examples are given to illustrate the method.


CD10 in diffuse uterine leiomyomatosis: a case report along with a few comments on histogenesis.
Diffuse uterine leiomyomatosis (DUL) is a rare entity with an unknown etiopathogenesis. A 24 years old female presented with abdominal discomfort and menorrhagia. Clinical and ultrasonographic examination revealed an enlarged uterus. The hysterectomy specimen showed a symmetrically enlarged uterus with a bosselated external surface. The cut surface showed multiple nodules of varying sizes diffusely involving the myometrium. Microscopically, the nodules were leiomyomas of varying degrees of cellularity. Some of the leiomyomas showed an increased vascularity either in the form of congeries of blood vessels with a lobular arrangement or occasionally as foci of 2-3 vessels. The vessels were surrounded by whorls of spindle cells. On immunohistochemistry the leiomyomas expressed vimentin, smooth muscle actin (SMA), desmin and CD10: the cells whorling around the blood vessels expressed vimentin, SMA and focally desmin and were negative for CD10 and HMB-45. The aim of this paper is to document that CD10 is expressed in diffuse uterine leiomyomatosis and discuss the histogenesis of DUL.


Synaptic integration in excitatory and inhibitory crayfish motoneurons.
The passive integrative properties of two crayfish abdominal motoneurons, the fast flexor inhibitor (FI) and a posterior, ipsilateral fast flexor excitor (FE), were studied electrophysiologically and through simulations with multicompartment models of their electrotonic structures. Responses of the models to simulated giant neuron input were quite similar to the motoneurons' responses to giant neuron stimulation, which suggests that differences in the electrotonic structures and the sites of synaptic input to the two cells can account in large part for differences in their responses to a common input. A full action potential created in the initial axon compartment of the FI model produced attenuated potentials in the adjacent integrating segment compartment and contralateral soma compartment. These potentials are similar in amplitude and time course to attenuated antidromic action potentials recorded in the corresponding regions of the FI neuron. A location of the spike initiation zone of the FI at the initial axon segment is consistent with this result. The responses of FI to ipsi- and contralateral inputs are different. Shock of a single abdominal second root produced a larger, faster rising excitatory postsynaptic potential in the ipsilateral FI soma than in the contralateral soma. Second root shock also caused the contralateral FI to produce an action potential either alone or before the ipsilateral FI neuron. Responses of the FI model to ipsilateral and contralateral inputs differ in the same way as the cell's responses. Inputs to the FI model that are ipsilateral to the soma compartment produce larger responses there than do contralateral inputs. Conversely, those contralateral inputs produce larger responses in the initial axon compartment than do ipsilateral inputs. This difference results from the long integrating segment that connects the soma compartment to the initial axon compartment. These results can account for the FI responses to lateralized inputs. Unlike the responses of FIs, the soma responses of contralaterally homologous FEs to ipsilateral and contralateral second root shocks were similar in waveform and amplitude, with the ipsilateral root producing the larger response. This result is consistent with theoretical results from the FE model simulations. We conclude that a smaller size, larger input resistance and shorter membrane time constant allow the FE to respond to giant neuron input before the FI, and so help to achieve the proper timing of flexor contraction and relaxation during a tailflip.(ABSTRACT TRUNCATED AT 400 WORDS)


Single fraction radiosurgery/stereotactic body radiation therapy (SBRT) for spine metastasis: A dosimetric comparison of multiple delivery platforms.
There are numerous commercial radiotherapy systems capable of delivering single fraction spine radiosurgery/SBRT. We aim to compare the capabilities of several of these systems to deliver this treatment when following standardized criteria from a national protocol. Four distinct target lesions representing various case presentations of spine metastases were contoured in both the thoracic and lumbar spine of an anthropomorphic SBRT phantom. Single fraction radiosurgery/SBRT plans were designed for each target with each of our treatment platforms. Plans were prescribed to 16 Gy in one fraction to cover 90% of the target volume using normal tissue and target constraints from RTOG 0631. We analyzed these plans with priority on the dose to 10% of the partial spinal cord and dose to 0.03 cc of the spinal cord. Each system was able to maintain 90% target coverage while meeting all the constraints of RTOG 0631. On average, CyberKnife was able to achieve the lowest spinal cord doses overall and also generated the sharpest dose falloff as indicated by the Paddick gradient index. Treatment times varied widely depending on the modality utilized. On average, treatment can be delivered faster with Flattening Filter Free RapidArc and Tomotherapy, compared to Vero and Cyberknife. While all systems analyzed were able to meet the dose constraints of RTOG 0631, unique characteristics of individual treatment modalities may guide modality selection. Specifically, certain modalities performed better than the others for specific target shapes and locations, and delivery time varied significantly among the different modalities. These findings could provide guidance in determining which of the available modalities would be preferable for the treatment of spine metastases based on individualized treatment goals.


Performance analysis of valveless piezoelectric pump with dome composite structures.
Valveless piezoelectric pumps are used in the field of drug delivery. However, the output performances are limited by severe reflux. This article is aimed at reducing the reflux and improving the output performances. We use different pressure loss coefficients in the forward and reverse directions and design dome composite structures within the chamber of the valveless pump. The structures and working principles are described. Then, we use the fluid simulation software CFX to simulate the flow state inside the chamber under different parameters such as the dome length, 2 mm, 4 mm, 6 mm, and 8 mm; the trapezoidal one-sided angle, 1°, 3°, 5°, 7°, and 9°; and the rounded corner, from 0 to 6 mm. Finally, we also make the prototypes and test the output performances. The results show that the output flow rate can reach a maximum of 220.6 ml/min; the measured variance is 80.7 in the three experiment tests for the optimal flow rate at the dome length of 8 mm, angle of 5°, and rounded corner of 6 mm under the driving voltage of 190 V at a frequency of 45 Hz; the highest output pressure is 670.0 Pa under the voltage of 190 V at a frequency of 130 Hz. Moreover, the precision is 5.85% of the highest tested pressure compared to the simulated pressure. The output flow rate has a great improvement, and the effectiveness of the structures is proved.


DIANA: A deep learning-based paprika plant disease and pest phenotyping system with disease severity analysis.
The emergence of deep neural networks has allowed the development of fully automated and efficient diagnostic systems for plant disease and pest phenotyping. Although previous approaches have proven to be promising, they are limited, especially in real-life scenarios, to properly diagnose and characterize the problem. In this work, we propose a framework which besides recognizing and localizing various plant abnormalities also informs the user about the severity of the diseases infecting the plant. By taking a single image as input, our algorithm is able to generate detailed descriptive phrases (user-defined) that display the location, severity stage, and visual attributes of all the abnormalities that are present in the image. Our framework is composed of three main components. One of them is a detector that accurately and efficiently recognizes and localizes the abnormalities in plants by extracting region-based anomaly features using a deep neural network-based feature extractor. The second one is an encoder-decoder network that performs pixel-level analysis to generate abnormality-specific severity levels. Lastly is an integration unit which aggregates the information of these units and assigns unique IDs to all the detected anomaly instances, thus generating descriptive sentences describing the location, severity, and class of anomalies infecting plants. We discuss two possible ways of utilizing the abovementioned units in a single framework. We evaluate and analyze the efficacy of both approaches on newly constructed diverse paprika disease and pest recognition datasets, comprising six anomaly categories along with 11 different severity levels. Our algorithm achieves mean average precision of 91.7% for the abnormality detection task and a mean panoptic quality score of 70.78% for severity level prediction. Our algorithm provides a practical and cost-efficient solution to farmers that facilitates proper handling of crops.


Dioxin-like activity in the blood of Greenlandic Inuit and Danish women: a pilot study.
(1) To determine whether plasma dioxin-like (DL) bioactivity differs between Inuit living in different Greenlandic districts, (2) to compare the DL activity of the Inuit having high burdens of POPs with a low-burden study group (Danish volunteers), and (3) to evaluate DL activity associations to POP exposure biomarkers and/or lifestyle factors. The study was a cross-sectional survey, including randomized inhabitants (70) from 6 different Greenlandic districts and young Danish volunteers (22). POPs and fatty acids profiles were analysed. Aryl hydrocarbon receptor (AhR) mediated DL-activity was determined by exposure of Hepa1.12cR AhR-CALUX reporter cell line to hexane: ethanol plasma extracts. The sum PCBs/POPs level of Inuit was more than 10 times higher than the levels found in Danish volunteers, and for both study groups the level was positively associated with age. The TCDD equivalent of the determined DL-activity, AhR-TEQ, differed between the Greenlandic districts. The AhR-TEQ data of the combined Inuit was significantly higher compared with the Danish women. AhR-TEQ of Inuit were positively associated with plasma POPs after adjustment for age and/or the ratio of n-3 to n-6 fatty acids, whereas no correlations were found for the Danish samples. AhR-TEQ differs between Inuit and Danish plasma samples. Plasma POP levels alone cannot be used as a biomarker for DL-activity. We suggest that the profile and level of plasma POPs, geographical location and diet have the greatest impact on plasma dioxin activity. Further studies are needed to elucidate the differences in geographical determinants of blood DL-activity.


Physiological and pathological functions of the prion protein homologue Dpl.
A misfolded version of the prion protein PrP(C), known as PrP(Sc), is the major component of scrapie infectivity, the pathological agent in transmissible spongiform encephalopathies. The Prnp gene that encodes the cellular PrP(C) protein was cloned almost 20 years ago, but remained without sequence or structural relatives for over a decade. Only recently a novel protein, named Doppel (Dpl), was identified, which shares significant biochemical and structural homology with PrP(C). When overexpressed, Dpl is neurotoxic and causes a neurological disease. Strikingly, Dpl neurotoxicity is counteracted and prevented by PrP(C). In contrast to its homologue PrP(C), Dpl is dispensable for prion disease progression and for the generation of PrP(Sc), but Dpl appears to have an essential function in male spermatogenesis. Although Dpl research is still in its infancy, the discovery of Dpl has already solved some enigmas of prion biology and an understanding of its physiological function is emerging.


Ginkgo biloba extract (EGb 761) improves postischemic function in isolated preconditioned working rat hearts.
We studied the effect of preconditioning and Gikgo biloba extract (EGb 761) in relation to the recovery of contractile function after global ischemia in the isolated working rat heart. Hearts (n = 12 in each group) were randomly divided into five groups: In group I, hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion; in group II, they were subjected to one cycle of preconditioning consisting of 5 min ischemia and 10 min reperfusion before the induction of 30 min of ischemia and 30 min of reperfusion; group III hearts underwent two cycles of preconditioning; group IV hearts underwent three cycles of preconditioning; and group hearts underwent four cycles of preconditioning before the onset of 30 min ischemia followed by 30 min of reperfusion. Ventricular fibrillation (total) and ventricular tachycardia (no preconditioning) both fell from 100% to 50% (P < 0.05) after four cycles of preconditioning. In relation to ventricular fibrillation, preconditioning significantly reduced the formation of oxygen free radicals, measured by electron spin resonance spectroscopy (ESR), but recovery of cardiac function was low in all preconditioned groups. Because of the relatively low incidence of arrhythmias (50% ventricular fibrillation and 50% ventricular tachycardia) and relatively low cardiac function in Group V, EGb 761, a free-radical scavenger, was chosen to improve myocardial contractile function in preconditioned hearts. Fifty and 100 mg/kg of EGb 761 (per os) significantly improved coronary flow, aortic flow, left ventricular developed pressure (LVDP), and the first derivative of LVDP (LVDdP/dtmax) in the four-cycle preconditioned group. Thus, after 30 min of reperfusion, aortic flow was improved from 11.6 +/- 0.9 ml/min to 19.7 +/- 1.2 ml/min (P < 0.05) with a dose of 50 mg/kg of EGb 761 and to 22.0 +/- 1.5 ml/min (P < 0.05) with a dose 100 mg/kg of EGb 761, in the four-cycle preconditioned group. During reperfusion, the formation of free radicals was reduced by approximately 50 and 60% using 50 mg/kg and 100 mg/kg of EGb 761, respectively, when compared with the four-cycle preconditioned drug-free control group. We have demonstrated that EGb 761 can improve contractile function after global ischemia in the isolated working rat heart by reducing the formation of oxygen free radicals, and we have shown that this protection is additive to that of ischemia-induced preconditioning.


The clinical manifestations and risk factors of a delayed diagnosis of Kawasaki disease.
Kawasaki disease (KD) is an acute febrile vasculitis and may cause coronary artery abnormalities. Due to the higher incidence in Asian countries, most pediatricians in Taiwan are familiar with KD. However, there are still some patients being diagnosed 10 days after the onset of the illness and not receiving a highly effective therapy. In this study, we analyzed the risk factors and clinical manifestations of patients with a delayed diagnosis of KD. A retrospective review was made of the medical records of the patients diagnosed with KD at our institution between January 1996 and December 2005. The patients were divided into 2 groups: early-diagnosis group (EDG: diagnosis was made within 10 days after the onset of the fever) and delayed-diagnosis group (DDG: diagnosis was made 10 days after the onset of the fever). Fourteen of a total of 78 children (17.9%) were grouped into the DDG group, and 64 into the EDG group. There were no statistical differences between the 2 groups in terms of age, gender, number of antibiotics used, day of the first medical visit, total days of skin rash, conjunctivitis, mucosa changes, lymphadenopathy or laboratory examinations except for the higher white blood cell count and serum immunoglobulin G level in the DDG group. The patients in the EDG group had a clustered onset of symptoms as compared to the DDG group with a dispersed and late onset of symptoms. There was a higher risk of coronary artery abnormalities in the DDG group than the EDG group (42.9% vs. 14.1%; p = 0.036), and in the patients with KD who were younger than 1 year (29.0% vs. 12.7%; p = 0.043). Patients with delayed diagnosis of KD were associated with higher risk of developing coronary arterial lesions. It is necessary to develop a diagnostic test for KD and provide more education to health care providers for early recognition of KD.


Identification of host receptor and receptor-binding module of a newly sequenced T5-like phage EPS7.
The virulent bacteriophage EPS7 active against a number of Salmonella serovar and Escherichia coli strains, isolated from the local sewage in Korea, belongs to the family Siphoviridae. The ESP7 genome constitutes a linear double-stranded DNA of 111 382 bp. DNA sequencing and genomic analysis of EPS7 showed that it belongs to the phage T5 family. We identified the EPS7 genes involved in DNA repair, replication, viral structure and bacterial lysis by comparing the EPS7 genome with that of T5. In contrast, the tail genes encoding for putative host receptor-binding protein and the putative receptor-blocking lipoprotein precursor of EPS7 exhibit high homologies with the corresponding gene products of BF23, another member of the T5-family. BF23 binds to BtuB, a surface receptor in the host and involved in vitamin B12 uptake, but its infection is independent of TonB. By constructing a series of deletion mutants in Salmonella and in E. coli and studying phage infection in the mutant hosts, we showed that BtuB is also the host receptor of the phage EPS7. Whether EPS7 infection depends on TonB needs to be further studied.


Glomerulocystic kidney: one hundred-year perspective.
Glomerular cysts, defined as Bowman space dilatation greater than 2 to 3 times normal size, are found in disorders of diverse etiology and with a spectrum of clinical manifestations. The term glomerulocystic kidney (GCK) refers to a kidney with greater than 5% cystic glomeruli. Although usually a disease of the young, GCK also occurs in adults. To assess the recent molecular genetics of GCK, review our files, revisit the literature, and perform in silico experiments. We retrieved 20 cases from our files and identified more than 230 cases published in the literature under several designations. Although GCK is at least in part a variant of autosomal dominant or recessive polycystic kidney disease (PKD), linkage analysis has excluded PKD-associated gene mutations in many cases of GCK. A subtype of familial GCK, presenting with cystic kidneys, hyperuricemia, and isosthenuria is due to uromodullin mutations. In addition, the familial hypoplastic variant of GCK that is associated with diabetes is caused by mutations in TCF2, the gene encoding hepatocyte nuclear factor-1beta. The term GCK disease (GCKD) should be reserved for the latter molecularly recognized/inherited subtypes of GCK (not to include PKD). Review of our cases, the literature, and our in silico analysis of the overlapping genetic entities integrates established molecular-genetic functions into a proposed model of glomerulocystogenesis; a classification scheme emerged that (1) emphasizes the clinical significance of glomerular cysts, (2) provides a pertinent differential diagnosis, and (3) suggests screening for probable mutations.


A comparative study of serum lipid profile and gallstone disease.
The diseased gallbladder is one of the commonest specimens submitted to the surgical pathology laboratory in North India. Obesity is associated with a linear increase in gallstone formation. It has been observed that the plasma lipoprotein profile of patients with gallstones differs markedly from that of healthy subjects. Serum lipid profile was done by enzyme kit method. All the gallstones received were categorized morphologically and examined biochemically. The age range of 200 cases was 13 to 77 years with a mean of43.75 +/- 13.39 years. There were 171 females (85.5%) and 29 males (14.5%) with male to female ratio of 1: 5.8. The stones containing both cholesterol and bile pigments were the most common (129 cases, 84.87%); while pure cholesterol stones were seen in 23 cases (11.50%) and pigment stones were infrequent (1 case, 0.65%). On lipidogram of patients in the study group, mean serum total cholesterol was 155.50 +/- 43.03 mg/dL, mean serum triglycerides was 100.49 +/- 45.23 mg/dL, mean HDL cholesterol was 46.71 +/- 15.20 mg/dL, mean LDL cholesterol was 87.94 +/- 36.85 mg/dL and mean VLDL cholesterol was 20.84 +/- 11.97 mg/dL. Serum total cholesterol values were significantly higher in patients older than 39 years as compared to patients < or =39 years (161.44 +/- 42.32 mg/dL vs. 145.79 +/- 32.96 mg/dL, p < 0.05). But the observed mean values in both of these subgroups were within the normal range i.e. <200 mg/dL. No significant difference was observed in the mean serum triglyceride values between male and female patients. The findings of this study did not indicate any role of serum lipid profile in the formation of gallstones. However the higher mean values of serum total cholesterol and serum triglycerides in patients older than 39 years of age may be explained by increasing age.


Characterization of rat aortic fragment within collagen gel as an angiogenesis model; capillary morphology may reflect the action mechanisms of angiogenesis inhibitors.
A fragment of rat thoracic aorta within type I collagen gel was employed as a model of angiogenesis, including the processes of cell migration, proliferation and capillary tube formation. Endogenous angiogenic factors in this model were studied. Expressions of vascular endothelial growth factor (VEGF) and its receptor, and proteolytic enzyme activities (matrix metalloprotease-2; MMP-2 and plasminogen activator; PA) increased during angiogenesis. The angiogenesis was inhibited by VEGF receptor kinase inhibitor and MMP inhibitor, confirming that these endogenous factors played an important role in angiogenesis. Interestingly, these inhibitors induced different capillary morphologies, including differences of cell migration and sprouting. Furthermore, dexamethasone (a down-regulator of MMP and PA) and TNP-470 (an endothelial cell growth inhibitor) induced another capillary morphology. The results suggest that the capillary structure in this model is dramatically influenced by the inhibition of angiogenic signalling and extracellular matrix (ECM) degradation. We also found that a novel angiogenesis inhibitor, the microbial metabolite luminacin, which was recently identified by us (Wakabayashi et al., J. Antiobiot., 53, 591-596 (2000)), induced a different morphology compared with other inhibitors examined, suggesting that it has a unique mechanism of action. Our results indicate that this rat aorta model should be useful for screening novel angiogenesis inhibitors.


Development and application of a double-antigen sandwich enzyme-linked immunosorbent assay for detection of antibodies to porcine circovirus 2.
A double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) is described for detection of porcine circovirus 2 (PCV2) antibodies using the well-characterized recombinant PCV2 capsid protein. In a comparative test of 394 pig sera against an indirect immunofluorescence (IIF) test and a commercial ELISA kit (also based on the recombinant PCV2 capsid protein), the results showed that the diagnostic sensitivity, specificity, and accuracy of the assay were, respectively, 90.61, 94.02, and 91.62% compared with IIF and 94.38, 95.28, and 94.67% compared with the commercial ELISA kit. Assay of 12 PCV-free pigs over a 5-week period produced only PCV2-negative titers by all 3 methods. These results and the seroprofiles of 4 pig farms obtained by both the commercial ELISA kit and the double-antigen sandwich ELISA indicate that the sandwich ELISA is a reliable method for detection of antibodies to PCV2. Additionally, the method described here permits the use of undiluted test serum samples simultaneously loaded with horseradish peroxidase (HRP)-conjugated antigen into the test well, and the complete test procedure can be performed in less than 90 min. This double-antigen sandwich ELISA should be a useful tool to aid swine industry professionals in deciding the intervention strategies for the control of PCV2-associated diseases.


Stress and Burnout Among Frontline Nurses During COVID-19 Pandemic in a Middle Eastern Country.
The COVID-19 pandemic has resulted in an unanticipated shift in nursing practice to meet the sudden increase in demand for pandemic-related care, leaving nurses unable to provide acceptable services to patients in the way they were taught and expected to do. It put the nurses under more stress and most of them were dissatisfied with their work due to excessive burnout. The study determined the level of stress and burnout among front-line nurses working at the Ministry of Health Hospitals in Najran, Saudi Arabia during the COVID-19 pandemic. A total of 1594 nurses were chosen using a convenience sampling approach. Google Forms were used to collect data from the nurses. COVID-19 stressors questionnaire and an abbreviated Maslach Burnout Inventory were used to assess stress and burnout among nurses. Our study reported that the majority of nurses experienced extreme levels of stress as their colleagues became ill; that they would spread COVID-19 infection to their family and friends; upsetting to see COVID-19 patients dying in front of them; not knowing when the COVID-19 pandemic will be under control; and emotional exhaustion and physical fatigue. A vast majority of nurses felt there were not adequate protective measures; there was a shortage of staff at times; were nervous and scared and thought of quitting their job; and they would quit their job if a COVID-19 outbreak recur and they would fall sick. Likewise, 41.9% of the nurses experienced a high level of burnout. A significant association was found between the area of working and the level of burnout among nurses. As nurses experienced extreme levels of stress and severe burnout, it is vital to design regular programs to assist frontline nurses in maintaining their mental health.


Mother's age at delivery and daughters' risk of preeclampsia.
Some cardiovascular disease risk factors are associated with both risk of preeclampsia and having been born to a younger or older mother. We examined whether mother's age at delivery predicts a primiparous daughter's risk of preeclampsia. The analysis included 39 803 Sister Study participants (designated as "daughters") born between 1930 and 1974. Using log-binomial regression, we estimated relative risks (RR) of preeclampsia in the first pregnancy ending in birth ("primiparous preeclampsia") associated with mother's age at the daughter's birth. Models included: number of older full and maternal half-siblings, income level growing up, daughter's age at delivery, race/ethnicity, and 5-year birth cohort. We examined self-reported relative weight at age 10 (heavier than peers versus not) as a potential effect measure modifier. Overall, 6.2% of daughters reported preeclampsia. Compared with those who had been born to 20-24-year old mothers, daughters of teenage mothers had a relative risk of 1.20 (95% confidence interval (CI) 1.01, 1.43) and daughters of mothers ≥25 had a ~10% lower risk. Relative weight at age 10 modified the association, with an inverse association between mother's age at delivery and preeclampsia seen only among daughters with low/normal childhood relative weight. In this subset, results were consistent across strata of daughter's age at menarche and age at first birth. These findings, based on self-reported data, require replication. Nevertheless, as women increasingly delay childbearing, they provide some reassurance that having been born to an older mother is not, per se, a risk factor for primiparous preeclampsia.


Apoptosis of Oligodendrocytes during Early Development Delays Myelination and Impairs Subsequent Responses to Demyelination.
During mammalian development, myelin-forming oligodendrocytes are generated and axons ensheathed according to a tightly regulated sequence of events. Excess premyelinating oligodendrocytes are eliminated by apoptosis and the timing of the onset of myelination in any specific CNS region is highly reproducible. Although the developing CNS recovers more effectively than the adult CNS from similar insults, it is unknown whether early loss of oligodendrocyte lineage cells leads to long-term functional deficits. To directly assess whether the loss of oligodendrocytes during early postnatal spinal cord development impacted oligodendrogenesis, myelination, and remyelination, transgenic mouse lines were generated in which a modified caspase-9 molecule allowed spatial and temporal control of the apoptotic pathway specifically in mature, myelin basic protein expressing oligodendrocytes (MBP-iCP9). Activating apoptosis in MBP(+) cells of the developing spinal cord during the first postnatal week inhibited myelination. This inhibition was transient, and the levels of myelination largely returned to normal after 2 weeks. Despite robust developmental plasticity, MBP-iCP9-induced oligodendrocyte apoptosis compromised the rate and extent of adult remyelination. Remyelination failure correlated with a truncated proliferative response of oligodendrocyte progenitor cells, suggesting that depleting the oligodendrocyte pool during critical developmental periods compromises the regenerative response to subsequent demyelinating lesions. This manuscript demonstrates that early insults leading to oligodendrocyte apoptosis result in the impairment of recovery from demyelinating diseases in the adult. These studies begin to provide an initial understanding of the potential failure of recovery in insults, such as periventricular leukomalacia and multiple sclerosis.


Elevated substance P and accelerated cartilage degradation in rabbit knees injected with interleukin-1 and tumor necrosis factor.
Cytokines, interleukin-1 (IL-1), tumor necrosis factor alpha, and the neurotransmitter, substance P, have been implicated in the pathogenesis of arthritis because they stimulate synovial cells to secrete prostaglandin E2 and collagenase in vitro. We investigated in vivo changes in intraarticular substance P and the degradation of cartilage proteoglycan in response to intraarticular cytokine injections in rabbits. Twenty-four hours after a single injection of 10 ng, 30 ng, or 100 ng of recombinant human IL-1 alpha (rHuIL-1 alpha) per joint, the mean +/- SEM levels of substance P detected in the cell-free joint lavage fluid were 250 +/- 67 fmoles, 480 +/- 60 fmoles, and 530 +/- 130 fmoles (n = 4-5), respectively. The level of substance P in the contralateral knees injected with diluent was 58 +/- 8 fmoles (n = 12). The level of substance P had increased by 2 hours after IL-1 injection and remained elevated in the joint 48 hours after injection. Cytokine-induced proteoglycan depletion was also time- and dose-dependent. Proteoglycan concentrations in articular cartilage dissected from the weight-bearing condyles were calculated as the ratio of sulfated glycosaminoglycan measured using 1,9-dimethylmethylene blue: hydroxyproline. After 48 hours, 10 ng, 30 ng, or 100 ng of rHuIL-1 alpha per joint decreased proteoglycan levels by 9 +/- 4%, 14 +/- 4%, and 21 +/- 3% (n = 8), respectively. Likewise, the injection of recombinant human tumor necrosis factor alpha induced depletion of intraarticular substance P and cartilage proteoglycan.