Evaluation of Color-matching Ability of a Structural Colored Resin Composite.
The present study evaluated the color-matching ability of a structural colored resin composite to compare it with resin composites employing pigments. A structural colored resin composite (Omnichroma [OMC]), a supranano-filled resin composite (Estelite ∑ Quick [ELQ]), and a nano-filled resin composite (Filtek Supreme Ultra [FSU]) were used. Each resin composite was packed into a Teflon mold and pressed down with a clear strip under a glass slide. The specimens were light irradiated through the slide with a light-emitting diode curing unit. The thickness of the specimens (n=6) was measured with a digital caliper before being transferred to distilled water and stored at 37°C for 24 hours. The measurements of the optical characteristics of the specimens on a black-and-white background were performed using a spectrophotometer. D65 (CIE D65) was used as a light source for the spectrophotometer. Measurements were repeated three times for each specimen under each color-measurement condition, and average values for three same-shade specimens were calculated. One-way analysis of variance and Tukey post hoc tests were used (α=0.05). To determine its ability to match the color of artificial teeth, each shade of resin composite was placed in a cavity before performing color measurements. Using a spectrophotometer (CMS-35F S/C) with a flexible sensor, L*, a*, and b* values were obtained. The spectral reflectance curve of OMC showed that it reflected light wavelengths from 430-700 nm regardless of the background color and thickness of the specimens. The percentage of reflectance of ELQ decreased near wavelengths of 550-580 nm. Regarding the influence of background color on CIE L*, a*, b* values, the L* level showed significantly higher values for all tested materials with white backgrounds, and OMC was most affected by the difference in background color. However, a* values of ELQ and FSU were significantly higher with a black background than with a white background, and OMC showed a significantly higher value with a white background than with a black background. The b* values were higher with a white background than with a black background and were significantly higher for all three products, and these tendencies were much greater for ELQ and FSU. The ability of OMC to match the color of artificial teeth showed acceptable color compatibility, regardless of the shade of the artificial teeth and the depth of the cavity. However, ELQ and FSU showed reduced color compatibility, especially for a cavity depth of 3.0 mm. Excellent color matching ability was confirmed for the structural colored resin composite OMC, resulting in reduced color differences and therefore improving the esthetic appearance of the restoration, simplifying shade matching, and compensating for any color mismatch.


Self-assembly and mineralization of full-length human amelogenin and its functional fragments in vitro.
To investigate the dynamic process of the self-assembly behaviors of a full-length human amelogenin (AM) and its functional fragments tyrosine-rich amelogenin peptide (TRAP) and leucine-rich amelogenin peptide(LRAP) in vitro and its role in hydroxyapatite (HA) crystal formation. The full-length human AM and its functional fragments, TRAP and LRAP, were reassembled and purified in vitro. The protein solution of 100 µg‧mL-1, pH=8, was prepared in Tris-HCl and incubated at room temperature for 1-15 min. Their self-assembly behaviors were observed and compared under a transmission electron microscope (TEM). The full-length AM was added to artificial saliva and incubated for 3 days. A scanning electron microscope (SEM) was used in observing the morphology of the induced new crystals. Then, TARP and LRAP were added. The resulting solution was incubated for 3 days and then observed again. When pH=8, the full-length human AM and TRAP assembly started spontaneously and formed "nanospheres" after 15 min.The nanospheres formed by TRAP existed independently, with a uniform size but without obvious internal structures. The full-length AM was assembled hierarchically, which formed "nanospheres" and further extended in all directions, formed a chain structure, and then aggregated into a net. The self-assembly behavior of LRAP was not obvious. Proteins mostly existed in the form of monomers without "nanosphere" formation. Only few oligomers were observed. The full-length AM was induced independently for 3 days to form rod-shaped HA crystals. TRAP and LRAP proteins were added, after 3 days the crystal elongation was obvious in the c axis, but the growth in plane A and plane B was poor. The self-assembly and mineralization behaviors of full-length human AM, TRAP, and LRAP were consistent with the directional growth mechanism of HA crystals in vivo, providing a theoretical basis for the role of the fragments in the growth and maturation of HA crystals.


MRI findings of working and non-working TMJ during unilateral molar clenching on hard bolus.
The aim of this study is to evaluate with MRI the TMJs behavior during one-side clenching on a hard bolus. The sample consisted of 13 patients. an MRI of TMJ using a 1.5 Tesla superconducting magnet and a dedicated surface coil was performed in all patients. Parasagittal scans of the TMJ (perpendicular to the long axis of the condyles) were made with the mouth closed, open and with a plastic thickness 10 mm high, 15 mm wide and 20 mm long always interposed between the molars of the left side; TSE T2W and DPW sequences were used. The working condyle is always positioned behind the non-working contralateral condyle and the morphology of the retrodiscal tissue upper lamina was curvilinear in all TMJs examined. This work confirmed that, during clenching on a unilateral hard bolus, the working condyle translates less than the balancing one and that the condyle-disc ratios are substantially the same in both sides. The study of the retrodiscal tissue imaging in the different functional phases, suggest that it does not exert any pulling force towards the disc.


Growth and senescence of Medicago truncatula cultured cells are associated with characteristic mitochondrial morphology.
Here mitochondrial morphology and dynamics were investigated in Medicago truncatula cell-suspension cultures during growth and senescence. Cell biology techniques were used to measure cell growth and death in culture. Mitochondrial morphology was investigated in vivo using a membrane potential sensor probe coupled with confocal microscopy. Expression of a senescence-associated gene (MtSAG) was evaluated in different cell-growth phases. Mitochondria appeared as numerous, punctuate organelles in cells at the beginning of the subculture cycle, while interconnected networks were observed in actively growing cells. In senescent cells, giant mitochondria were associated with dying cells. The release of cytochrome c from mitochondria was detected in different growth phases of cultured cells. Studies on plant cell cultures allowed us to identify physiological and molecular markers of senescence and cell death, and to associate distinct mitochondrial morphology with cells under different physiological conditions.


Dicer recognizes the 5' end of RNA for efficient and accurate processing.
A hallmark of RNA silencing is a class of approximately 22-nucleotide RNAs that are processed from double-stranded RNA precursors by Dicer. Accurate processing by Dicer is crucial for the functionality of microRNAs (miRNAs). The current model posits that Dicer selects cleavage sites by measuring a set distance from the 3' overhang of the double-stranded RNA terminus. Here we report that human Dicer anchors not only the 3' end but also the 5' end, with the cleavage site determined mainly by the distance (∼22 nucleotides) from the 5' end (5' counting rule). This cleavage requires a 5'-terminal phosphate group. Further, we identify a novel basic motif (5' pocket) in human Dicer that recognizes the 5'-phosphorylated end. The 5' counting rule and the 5' anchoring residues are conserved in Drosophila Dicer-1, but not in Giardia Dicer. Mutations in the 5' pocket reduce processing efficiency and alter cleavage sites in vitro. Consistently, miRNA biogenesis is perturbed in vivo when Dicer-null embryonic stem cells are replenished with the 5'-pocket mutant. Thus, 5'-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs.


Validating a Scale of Health Beliefs in Preventive Health Screenings Among Chinese Older Adults.
We aimed to examine the psychometric properties of a modified 16-item Attitudinal Index (AI), a measure of Chinese older adults' beliefs about preventive health screenings. We used the 2013 Shanghai Elderly Life and Opinion data including 3,418 respondents age 60+ who were randomly split into training and validation samples. We examined the validity and reliability of the modified AI. Psychometric evaluation of the modified AI revealed good response patterns. The overall scale had good reliability (Cronbach's α = .835). Exploratory factor analysis yielded four factors: barriers, fatalism, unnecessary, and detects (Cronbach's α = .815-.908). Confirmatory factor analysis of the modified AI's factor structure verified its four-factor structure (comparative fit index = 0.913, standardized root mean square residual = 0.048). The validity and reliability of the modified AI support its cultural appropriateness in measuring health beliefs among Chinese elderly. Further psychometric evaluation should focus on testing concurrent and criterion validity.


The Pivotal Role of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Hypertension Management and Cardiovascular and Renal Protection: A Critical Appraisal and Comparison of International Guidelines.
Arterial hypertension is the main preventable cause of premature mortality worldwide. Across Latin America, hypertension has an estimated prevalence of 25.5-52.5%, although many hypertensive patients remain untreated. Appropriate treatment, started early and continued for the remaining lifespan, significantly reduces the risk of complications and mortality. All international and most regional guidelines emphasize a central role for renin-angiotensin-aldosterone system inhibitors (RAASis) in antihypertensive treatment. The two main RAASi options are angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Although equivalent in terms of blood pressure reduction, ACEis are preferably recommended by some guidelines to manage other cardiovascular comorbidities, with ARBs considered as an alternative when ACEis are not tolerated. This review summarizes the differences between ACEis and ARBs and their place in the international guidelines. It provides a critical appraisal of the guidelines based on available evidence from randomized controlled trials (RCTs) and meta-analyses, especially considering that hypertensive patients in daily practice often have other comorbidities. The observed differences in cardiovascular and renal outcomes in RCTs may be attributed to the different mechanisms of action of ACEis and ARBs, including increased bradykinin levels, potentiated bradykinin response, and stimulated nitric oxide production with ACEis. It may therefore be appropriate to consider ACEis and ARBs as different antihypertensive drugs classes within the same RAASi group. Although guideline recommendations only differentiate between ACEis and ARBs in patients with cardiovascular comorbidities, clinical evidence suggests that ACEis provide benefits in many hypertensive patients, as well as those with other cardiovascular conditions.


cAMP potentiates ATP-evoked calcium signaling in human parotid acinar cells.
In salivary acinar cells, intracellular calcium ([Ca(2+)](i)) signaling plays an important role in eliciting fluid secretion through the activation of Ca(2+)-activated ionic conductances. Ca(2+) and cAMP have synergistic effects on fluid secretion such that peak secretion is elicited following activation of both parasympathetic and sympathetic pathways. We have recently demonstrated that cAMP exerts effects on Ca(2+) release, through protein kinase A (PKA)-mediated phosphorylation of inositol 1,4,5-trisphosphate receptors (InsP(3)R) in mouse parotid acinar cells. To extend these findings, in the present study cross-talk between Ca(2+) signaling and cAMP pathways in human parotid acinar cells was investigated. In human parotid acinar cells, carbachol stimulation evoked increases in the [Ca(2+)](i) and the initial peak amplitude was enhanced following PKA activation, consistent with reports from mouse parotid. Stimulation with ATP also evoked an increase in [Ca(2+)](i). The ATP-evoked Ca(2+) elevation was largely dependent on extracellular Ca(2+), suggesting the involvement of the P2X family of purinergic receptors. Pharmacological elevation of cAMP resulted in a approximately 5-fold increase in the peak [Ca(2+)](i) change evoked by ATP stimulation. This enhanced [Ca(2+)](i) increase was not dependent on intracellular release from InsP(3)R or ryanodine receptors, suggesting a direct effect on P2XR. Reverse transcription-polymerase chain reaction and Western blot analysis confirmed the presence of P2X(4)R and P2X(7)R mRNA and protein in human parotid acinar cells. ATP-activated cation currents were studied using whole cell patch clamp techniques in HEK-293 cells, a null background for P2XR. Raising cAMP resulted in a approximately 4.5-fold enhancement of ATP-activated current in HEK-293 cells transfected with P2X(4)R DNA but had no effects on currents in cells expressing P2X(7)R. These data indicate that in human parotid acinar cells, in addition to modulation of Ca(2+) release, Ca(2+) influx through P2X(4)R may constitute a further locus for the synergistic effects of Ca(2+) and PKA activation.


A modified Ce/Mg-BCIP-NBT formazan/indigoblue technique for demonstration of non-specific alkaline phosphatase activity.
The wide ranged structurally variability of formazans and their accessibility for auxiliary additives as redoxmediators or metals provide an easy tunable chromogenic visualization technique. We present here an improved nitro blue tetrazolium (NBT) 5-bromo-4-chloro-3-indolyl phosphate (BCIP) method which is superior to the classical McGadey's procedure regarding proper precipitation and localization as well as sensitivity. Different metal additives as well as the overall reaction course modifying additives (redox mediators, chelating additives, buffer) were optimized.


Securing chemotherapies: fabrication, prescription, administration and complete traceability.
Decision support, order entry, drug and care administration with their respective documentation cannot be seen as independent actions, especially in term of medical approach and patient safety. Chemotherapy treatment is a good example to illustrate the various implication of technology information in these multifaceted and intricate processes. Chemotherapy administration can be a highly complex process. It can take place over a variable period of time, from hours to months. Chemotherapies can be produced specifically for a given patient and can have dramatic effects in case of errors. Chemotherapy treatment will depend from various information including patient specific data such as temperature, weight or laboratory or drug specific knowledge such as side effects or administration directives. At the University Hospitals of Geneva (HUG), processes reengineering accompanied with new applications covering the whole chain of the processes involved in chemotherapy treatment (prescription preparation, administration, control) have been developed. This paper presents the overall approach leading the computerization of these processes and the first evaluations about the potential benefits of the computer-aided controls during the administration phase.


Optically Active Particles with Tunable Morphology: Prepared by Embedding Graphene Oxide/Fe3O4 in Helical Polyacetylene.
We report a novel and straightforward methodology for constructing hybrid particles with tunable morphology (spherical vs nonspherical) by embedding inorganic components (graphene oxide and/or Fe3O4 nanoparticles) inside chiral helical polyacetylene. Scanning electron microscopic images ascertain the spherical or nonspherical morphology of the particles. The intense circular dichroism effects demonstrate that the hybrid particles (spherical, ellipsoid-like, and cake-like) possess remarkable optical activity. The use of the chiral magnetic hybrid particles in enantioselective crystallization of racemic phenylalanine demonstrates the kind of particles' significant potential applications in chiral technologies and chiral processes. The study not only creates an unprecedented type of chiral hybrid particles, but also provides a versatile strategy for preparing advanced functional hybrid particles with tunable morphology from polymers and even from inorganic and metallic materials.


Assessment of Knee Cartilage Stress Distribution and Deformation Using Motion Capture System and Wearable Sensors for Force Ratio Detection.
Knowledge about the knee cartilage deformation ratio as well as the knee cartilage stress distribution is of particular importance in clinical studies due to the fact that these represent some of the basic indicators of cartilage state and that they also provide information about joint cartilage wear so medical doctors can predict when it is necessary to perform surgery on a patient. In this research, we apply various kinds of sensors such as a system of infrared cameras and reflective markers, three-axis accelerometer, and force plate. The fluorescent marker and accelerometers are placed on the patient's hip, knee, and ankle, respectively. During a normal walk we are recording the space position of markers, acceleration, and ground reaction force by force plate. Measured data are included in the biomechanical model of the knee joint. Geometry for this model is defined from CT images. This model includes the impact of ground reaction forces, contact force between femur and tibia, patient body weight, ligaments, and muscle forces. The boundary conditions are created for the finite element method in order to noninvasively determine the cartilage stress distribution.


Epidermodysplasia Verruciformis: A Study of Clinicopathologic Features, Biomarkers, and Associated Malignancies in Indian Patients.
Epidermodysplasia verruciformis (EDV) is a rare cutaneous manifestation of human papilloma virus infection, which has a potential for malignant transformation. The characteristic histologic features of EDV may not always be present and may often be overlooked. The use of a panel of novel biomarkers may aid in differentiating EDV from their clinical and pathologic mimics. We reviewed 20 cases histologically diagnosed as EDV from 2013 to 2022. Sections were reviewed for histopathologic features, and immunohistochemistry for p16 and Ki67 was performed. There were 20 cases, ranging in age from 6 to 52 years with a male predominance. Four patients were immunosuppressed, and 4 patients had a positive family history. The most common presentation was hypopigmented papules and macules. In all the cases, epidermal keratinocytes showed dysmaturation, enlargement, and a blue-gray cytoplasm. These changes were very focal and superficial in 15 cases (75%). Associated malignancies included carcinoma in situ (1), trichilemmoma (2), and trichilemmal carcinoma (1). The trichilemmal tumors were seen in 2 siblings. p16 was expressed in the parabasal and basal layers in 7 of 17 cases (41%), in keratinocytes with and without inclusions. Ki67 was increased and localized to suprabasal and parabasal keratinocytes in 15 of 17 cases (88%). Although striking and characteristic, the keratinocyte changes are often focal and superficial, requiring multiple step-sections. Association of EDV with familial trichilemmal neoplasms is a novel finding requiring further genetic testing. In cases of clinically suspected EDV with negative histopathologic findings, p16 and Ki67 seem useful as adjunct biomarkers and could serve as cost-effective alternatives to genotyping.


Effects of supplemental zinc source and level on growth performance, carcass traits, and meat quality of broilers.
The objective of this study was to investigate the effects of dietary supplemental Zn on growth performance, carcass traits, and meat quality of broilers. Dietary treatments included the corn-soybean meal-based diet (control) and the basal diet supplemented with 60, 120, or 180 mg of Zn/kg as ZnSO(4), Zn amino acid A, Zn proteinate B, or Zn proteinate A. The results showed that birds fed diets supplemented with Zn had higher ADFI, ADG, and percentage of eviscerated yield than birds fed the control diet. Supplemental Zn significantly increased the redness value in breast muscle and pH values in thigh muscle, decreased shear force in thigh muscle, and decreased drip loss in breast and thigh muscle. The DM and intramuscular fat contents of the breast muscle in broilers fed diets with supplemental Zn were higher than those of the control. Results from this study indicated that Zn could promote growth and improve production performance of broilers independent of Zn source.


Design and validation of non-metal oxo complexes for C-H activation.
We use our recent discovery of the reduction-coupled oxo activation (ROA) principle to design a series of organometallic molecules that activate C-H bonds through this unique proton/electron-decoupled hydrogen abstraction mechanism, in which the main group oxo moiety binds to the proton while the electron is transferred to the transition metal. Here we illustrate this general class of catalyst clusters with several examples that are validated through quantum mechanics calculations.


Finding the space between east and west: the emotional impact of teaching in St Petersburg.
The paper describes our experience of teaching analytical psychology to a group of graduates of the East European Institute of Psychoanalysis in St Petersburg, our developing partnership as we struggled to teach and learn, each with our own assumptions, preconceptions and projections about the other, and the emotional impact of our radically different social, intellectual and political histories. We had to be affected to become effective. It draws on contemporary Jungian ideas to unpack the interpersonal dynamics involved when there are culturally different styles of learning, which created a complicated transference/countertransference matrix. We believe we have by now witnessed a process of individuation among our students and at the same time they too have witnessed some change and growth in us.


Brownmillerite-type Ca2 FeCoO5 as a Practicable Oxygen Evolution Reaction Catalyst.
Here, we report remarkable oxygen evolution reaction (OER) catalytic activity of brownmillerite (BM)-type Ca2 FeCoO5 . The OER activity of this oxide is comparable to or beyond those of the state-of-the-art perovskite (PV)-catalyst Ba0.5 Sr0.5 Co0.8 Fe0.2 O3-δ (BSCF) and a precious-metal catalyst RuO2 , emphasizing the importance of the characteristic BM structure with multiple coordination environments of transition metal (TM) species. Also, Ca2 FeCoO5 is clearly advantageous in terms of expense/laboriousness of the material synthesis. These facts make this oxide a promising OER catalyst used in many energy conversion technologies such as metal-air secondary batteries and hydrogen production from electrochemical/photocatalytic water splitting.


Carotid endarterectomy at Royal Brisbane Hospital and Princess Alexandra Hospital, Brisbane.
A retrospective study was made of carotid endarterectomies performed at Royal Brisbane and Princess Alexandra Public Hospitals, the 2 major teaching hospitals in Brisbane, between 1st July 1973 and 30th June 1978. The case histories of the patients undergoing the procedure during the period were studied and the immediate mortality and morbidity associated with the procedure were determined. Records of 38 operations at Royal Brisbane Hospital were found. From these operations there were 3 deaths and 1 completed stroke, a major complication rate of 11%. From 83 operations at Princess Alexandra Hospital there was 1 death and 3 completed strokes, a major complication rate of 5%. Significant delays were noted from the time of referral to the hospitals to the time when endarterectomy was performed.


Binding interaction and gelation in aqueous mixtures of poly(N-isopropylacrylamide) and hectorite clay.
The binding interaction between poly(N-isopropylacrylamide) (PNIPAm) chains and hectorite clay platelets was directly detected by quartz crystal microbalance with dissipation (QCM-D) to explore the cross-linking mechanism in the strong nanocomposite hydrogel (NC gel), which is in situ polymerized with NIPAm in the clay suspension. PNIPAm chains were allowed to be adsorbed on the gold surface of the QCM electrode. A large frequency shift Δf in the QCM as introducing the clay indicated that a large amount of clay platelets were adsorbed on the deposited PNIPAm layer. The relationship between the dissipation shift ΔD and Δf revealed that the adsorption included two steps of fast initial buildup and following densification of the clay platelets. In dilute aqueous mixtures, the PNIPAm chain and clay formed aggregates as observed from the hydrodynamic diameter. A gelation state diagram was established for concentrated aqueous PNIPAm-clay mixtures. The Raman spectrum pointed out the conformation change of the PNIPAm chains in aqueous solutions when the clay was added, which would be caused by the adsorption of PNIPAm chains to the clay platelets.


[Steady-state plasma and saliva concentrations of procainamide and N-acetyl-procainamide after a sustained release preparation].
With ordinary procainamide tablets a dosing interval of 3-4 hours must be chosen to achieve therapeutically useful plasma concentrations during the entire interval. The concentrations of procainamide and its N-acetylated metabolite, NAPA, have been studied in the plasma of 10 normal volunteers and 11 patients who were given a new sustained release preparation at 8 hour intervals. Blood samples were taken between two doses on the fourth day of treatment. Procainamide showed levels within the accepted therapeutic range during the entire dosing interval. A dose of 4.5 g per day per 70 kg body-weight is necessary in order to achieve adequate levels. NAPA concentrations did not fluctuate during the dosing interval and mean steady-state concentrations were influenced predominantly by the degree of renal function. Saliva to plasma concentration ratio, measured in four patients, showed huge inter- and intraindividual variability. Therefore, saliva concentrations measurements of procainamide and NAPA are of little clinical use.


IL-12 Signaling Contributes to the Reprogramming of Neonatal CD8+ T Cells.
Neonates are highly susceptible to intracellular pathogens, leading to high morbidity and mortality rates. CD8+ T lymphocytes are responsible for the elimination of infected cells. Understanding the response of these cells to normal and high stimulatory conditions is important to propose better treatments and vaccine formulations for neonates. We have previously shown that human neonatal CD8+ T cells overexpress innate inflammatory genes and have a low expression of cytotoxic and cell signaling genes. To investigate the activation potential of these cells, we evaluated the transcriptome of human neonatal and adult naïve CD8+ T cells after TCR/CD28 signals ± IL-12. We found that in neonatal cells, IL-12 signals contribute to the adult-like expression of genes associated with cell-signaling, T-cell cytokines, metabolism, and cell division. Additionally, IL-12 signals contributed to the downregulation of the neutrophil signature transcription factor CEBPE and other immaturity related genes. To validate the transcriptome results, we evaluated the expression of a series of genes by RT-qPCR and the promoter methylation status on independent samples. We found that in agreement with the transcriptome, IL-12 signals contributed to the chromatin closure of neutrophil-like genes and the opening of cytotoxicity genes, suggesting that IL-12 signals contribute to the epigenetic reprogramming of neonatal lymphocytes. Furthermore, high expression of some inflammatory genes was observed in naïve and stimulated neonatal cells, in agreement with the high inflammatory profile of neonates to infections. Altogether our results point to an important contribution of IL-12 signals to the reprogramming of the neonatal CD8+ T cells.


Frameshift mutation in the V2 domain of human keratin 1 results in striate palmoplantar keratoderma.
The striate form of palmoplantar keratoderma is a rare autosomal dominant disorder affecting palm and sole skin. Genetic heterogeneity of striate palmoplantar keratoderma has been demonstrated with pathogenic mutations in the desmosomal proteins desmoplakin and desmoglein 1. We have studied a four-generation family of British descent with striate palmoplantar keratoderma. Ultrastructural studies show that intermediate filaments of suprabasal keratinocytes are finer than those of the basal layer. In addition, desmosome numbers are normal, but their inner plaques and midline structures are attenuated. Microsatellite markers were used to screen candidate loci including the epidermal differentiation complex on 1q, the desmoplakin locus on 6p, the type I and II keratin gene clusters on chromosomes 12q and 17q, and the desmosomal cadherin gene cluster on chromosome 18q. Significant genetic linkage to chromosome 12q was observed using marker D12S368, with a maximum two-point lod score of 3.496 at a recombination fraction of 0. Direct sequencing of the keratin 1 gene revealed a frameshift mutation in exon 9 that leads to the partial loss of the glycine loop motif in the V2 domain and the gain of a novel 70 amino acid peptide. Using expression studies we show that the V2 domain is essential for normal function of keratin intermediate filaments.


Properties of pertussis toxin mutant PT-9K/129G after formaldehyde treatment.
Formaldehyde treatment is a method routinely used to detoxify diphtheria, tetanus, and pertussis toxins as well as other molecules suitable for vaccine production. To investigate whether chemical detoxification alters the immunological properties of vaccine components, we have treated the pertussis toxin mutant PT-9K/129G with formaldehyde and tested the properties of the resulting molecules. Very low concentrations of formaldehyde stabilize the molecule without affecting the physicochemical and immunological parameters. Increasing doses of formaldehyde abolish the mitogenic and hemagglutinating activities of PT-9K/129G. At the same time, the molecule loses the ability to be recognized by a monoclonal antibody specific for a major protective epitope on the S1 subunit of pertussis toxin and its affinity for anti-pertussis toxin polyclonal antibodies is also reduced. In marked contrast, the ability of PT-9K/129G to be recognized by human T-cell clones is not affected by Formalin treatment. In vivo, the formaldehyde-treated molecules induce amounts of specific antibodies comparable with those of untreated molecules but significantly lower levels of toxin-neutralizing antibodies. Furthermore, the formaldehyde-treated molecules also show a reduced protective activity in the intracerebral challenge assay.


[Development of "Patient Friendly Formulations" to Counter the Side Effects of Cancer Chemotherapy].
Anticancer drug-induced stomatitis develops in 30% to 40% of cancer patients undergoing chemotherapy. However, medications for this condition are not commercially available in Japan. The "hospital formulation" is a customized medicine which hospital pharmacists prepare when doctors cannot carry out the medical therapy most suitable for a patient using commercial medicines. However, as the duties of pharmacists increase, use of the "hospital fomulation" decreases. Therefore, development of "hospital fomulations" based on individual evidence has a limit. Irsogladine maleate (IM) is a drug with gastric mucosal protective properties. IM increases intracellular cAMP levels in the gastric mucosa and activates communication between cells. It has been reported that the oral administration of IM reduces the incidence of 5-FU-based chemotherapy-induced stomatitis. However, there have been no reports on the effect of the direct use of IM in treating stomatitis. Therefore, we studied the development of an IM oral spray for stomatitis treatment, and obtained evidence of a direct effect in an animal experiment using a stomatitis model. Next, rebamipide mouthwash was administered to patients who had stomatitis caused by cancer chemotherapy. The total scores were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). When comparing SES and changes in the stomatitis area in patients, gradual reductions in the extent of stomatitis were observed, even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.


Lower extremity amputations in the county of Aalborg 1961-1971. Population study and follow-up.
All lower extremities amputations in the county of Aalborg, Denmark, during the period 1961-1971 were analysed. During this 10-year period the amputation rate did not increase. Those requiring amputation were predominantly arteriosclerotics followed by diabetics. The diabetics underwent amputation 3 years younger on average than the arteriosclerotics, but it was more often possible to preserve the knee in diabetics. There was a far higher rate of successful prosthetic fitting among patients in whom the knee had been preserved. Despite a high mortality, also beyond the first postoperative months, prosthetic fitting was of such psychological and social value, that every effort should be made to amr homes. This was the most positive finding in the present study.


Alpha-1-antitrypsin deficiency-associated cervical artery dissection: report of three cases.
The pathogenesis of cervical artery dissection is poorly understood. Deficiency of the elastase inhibitor alpha-1-antitrypsin may represent a predisposing condition. Biochemical and genetic analyses in a series of 12 consecutive patients with spontaneous dissection of the neck vessels showed 3 cases associated to alpha-1-antitrypsin deficiency, in combination with transient precipitating factors. A disequilibrium between proteolytic enzymes and protease inhibitors may contribute to the pathogenesis of cervical artery dissection leading to structural abnormalities of the extracellular matrix and increasing the susceptibility of the vessel wall to additional short-lived trigger mechanisms.


Efflux and uptake transporters as determinants of statin response.
The important role of drug transporters in drug absorption and disposition has been well documented. Statins are subjected to active transport of membrane proteins of the superfamilies ATP-binding cassette and solute carrier, and there is limited understanding of the mechanisms by which differences in transporter expression and activity contributes to variability of pharmacokinetics (PKs)/pharmacodynamics (PDs) of statins. This review aims to discuss the roles of drug transporters in the PKs and PDs of statins, and in drug interactions with statins. A comprehensive summary of the literature on this subject including in vitro and in vivo observations. In vivo and in vitro studies have shown that efflux and uptake transporters modulate the PKs/PDs of statins. Until now organic anion transporting polypeptides (OATP)1B1 variants have been considered major factors in limiting the uptake of statins and increasing statin exposure, and, consequently, increasing risk of myopathy. Further studies in pharmacogenetics and in vitro models to assess statin disposition and toxicity are required to understand the contribution of others transporters, such as multidrug resistance-associated protein (MRP)1, MRP2, breast cancer resistance protein, OATP2B1, OAT1B3 and OATP1A2, in interindividual variability to statins efficacy and safety.


Cell cycle control by natural phenols in cisplatin-resistant cell lines.
Fifteen plant polyphenols, including flavonoids, cinnamic acids, coumarins and capsaicin, were investigated for their capacity to suppress cell growth and regulate the cell cycle of in vitro human ovarian carcinoma (2008 cell line) and cervix squamous carcinoma cells (A431), and their cisplatin (CDDP)-resistant subclones (C13 and A431Pt, respectively). Evaluation of the cytotoxic effects of the polyphenols (0.01-100 μM) indicated that especially rhein and quercetin were almost equiactive in wild type and CDDP-resistant cells, indicating lack of cross-resistance with cisplatin. Capsaicin was more potent in CDDP-resistant subclones than in wild type cells. The order of their potencies is flavonoids > anthraquinones > vanilloids > coumarins > phenols, cinnamic acids. The natural phenols which were most cytotoxic (rhein, quercetin and capsaicin) were able to cause the arrest of the cancer cell cycle, suggesting that specific cell cycle regulatory proteins are possibly involved in their intracellular mechanism of action. In particular, the natural compounds were revealed to be more active in CDDP-resistant cells than in wild types, especially inducing apoptotic death.


Hepatectomy for hepatocellular carcinoma in elderly patients aged 75 years or more.
The aim of this study was to clarify the characteristics of elderly hepatocellular carcinoma (HCC) patients aged 75 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Between January 1990 and December 2006, 570 patients underwent curative hepatectomy for HCC. Elderly patients were defined as those aged 75 years or more. Clinicopathological data and outcomes after hepatectomy for 64 elderly and 502 younger patients were prospectively collected and compared. The proportion of elderly patients with chronic viral infection was less than that of younger patients (p < 0.001). Cirrhotic patients in the elderly group were less than those in the younger group (p = 0.03). The elderly patients had better liver function than did the younger patients (p = 0.007) but had more advanced HCC with microscopic vascular invasion than did the younger patients (p = 0.04). There was no operative mortality in the elderly patients and there was no significant difference in postoperative complication rates and long-term survival after hepatectomy between the two groups. Hepatectomy for elderly patients with resectable HCC is safe and feasible. Selected elderly patients with HCC might benefit from hepatectomy.


Real-Time Approach to Flow Cell Imaging of Candida albicans Biofilm Development.
The ability of Candida albicans to form biofilms is a virulence factor that allows tissue attachment and subsequent infection of host tissues. Fungal biofilms have been particularly well studied, however the vast majority of these studies have been conducted under static conditions. Oral biofilms form in the presence of salivary flow, therefore we developed a novel flow system used for real-time imaging of fungal biofilm development. C. albicans wild-type (WT) cells readily attached to the substrate surface during the 2 h attachment phase, then formed heterogeneous biofilms after 18 h flow. Quantitative values for biomass, rates of attachment and detachment, and cell-cell adhesion events were obtained for C. albicans WT cells and for a hyperfilamentous mutant Δhog1. Attachment rates of C. albicans WT cells were nearly 2-fold higher than C. albicans Δhog1 cells, although Δhog1 cells formed 4-fold higher biomass. The reduced normalized detachment rate was the primary factor responsible for the increased biomass of Δhog1 biofilm, showing that cell detachment rates are an important predictor for ultimate biofilm mass under flow. Unlike static biofilms, C. albicans cells under constant laminar flow undergo continuous detachment and seeding that may be more representative of the development of in vivo biofilms.


Experimental and Simulation Study of the Fracture Instability Behavior in Polypropylene Fiber-Reinforced Concrete.
This study investigated the fracture characteristics of plain concrete and polypropylene fiber-reinforced concrete (PFRC) using pre-notched three-point bending beam tests with the digital speckle correlation method (DSCM). Then, the fracture instability behavior of the two types of beams was simulated in finite elements based on the plastic damage model and the cohesion model, for which the applicability was assessed. Furthermore, the stability of the Big Gang Mountain Dam made from plain concrete or PFRC subjected to the earth-quake loading was simulated with the plastic damage model. The results show that the limiting length of the non-local deformation zone can be used as an indicator of instability damage in a concrete structure. The simulation results of the plastic damage model agreed well with the local deformation in the pre-notched three-point bending beam test obtained from the DSCM. The plastic damage model was found to be capable of describing the residual strength phenomenon, which the cohesive model was not capable of. The damage evolution regions of the PFRC dam are strictly constrained in some regions without the occurrence of the local deformation band across the dam, and PFRC can dramatically reduce the failure risk under earthquake loading. The numerical solution proves that PFRC is an advisable material for avoiding failure in concrete dams.


[The glial endothelin-nitric oxide system in ischemia-related neuronal cell death].
Both endothelin and nitric oxide (NO) have been proposed to act as pathophysiological factors in ischemia-related neural damage. This review is concerned with the participation of the glial endothelin-NO system in ischemia-related neuronal cell death. In the rat brain with cerebral apoplexy, endothelin, endothelin receptors and NO synthase (NOS) were rich in the glial cells of damaged brain areas. The brain subjected to transient forebrain ischemia contained astrocytic endothelins and microglial expressions of the ETB-receptor and NOS aggregating in the damaged CA1 subfield of the hippocampus at 7 days after the ischemia. Astrocytic endothelin, ETB-receptor and NOS became more apparent at 28 days after the ischemia, corresponding to a time when neural tissue-repair/remodeling after damage occurs, whereas no activities of the endothelin-NO system are observed in microglia. In the in vitro experiment, endothelin was found to modulate the release of NO from the hippocampal slices subjected to transient forebrain ischemia. There may be a cross-talk between the endothelin system and NO in the astrocytes and microglia during the process of ischemia-related neuronal cell death and neural tissue-remodeling.


Derivatives of 9-phosphorylated acridine as butyrylcholinesterase inhibitors with antioxidant activity and the ability to inhibit β-amyloid self-aggregation: potential therapeutic agents for Alzheimer's disease.
We investigated the inhibitory activities of novel 9-phosphoryl-9,10-dihydroacridines and 9-phosphorylacridines against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CES). We also studied the abilities of the new compounds to interfere with the self-aggregation of β-amyloid (Aβ42) in the thioflavin test as well as their antioxidant activities in the ABTS and FRAP assays. We used molecular docking, molecular dynamics simulations, and quantum-chemical calculations to explain experimental results. All new compounds weakly inhibited AChE and off-target CES. Dihydroacridines with aryl substituents in the phosphoryl moiety inhibited BChE; the most active were the dibenzyloxy derivative 1d and its diphenethyl bioisostere 1e (IC50 = 2.90 ± 0.23 µM and 3.22 ± 0.25 µM, respectively). Only one acridine, 2d, an analog of dihydroacridine, 1d, was an effective BChE inhibitor (IC50 = 6.90 ± 0.55 μM), consistent with docking results. Dihydroacridines inhibited Aβ42 self-aggregation; 1d and 1e were the most active (58.9% ± 4.7% and 46.9% ± 4.2%, respectively). All dihydroacridines 1 demonstrated high ABTS•+-scavenging and iron-reducing activities comparable to Trolox, but acridines 2 were almost inactive. Observed features were well explained by quantum-chemical calculations. ADMET parameters calculated for all compounds predicted favorable intestinal absorption, good blood-brain barrier permeability, and low cardiac toxicity. Overall, the best results were obtained for two dihydroacridine derivatives 1d and 1e with dibenzyloxy and diphenethyl substituents in the phosphoryl moiety. These compounds displayed high inhibition of BChE activity and Aβ42 self-aggregation, high antioxidant activity, and favorable predicted ADMET profiles. Therefore, we consider 1d and 1e as lead compounds for further in-depth studies as potential anti-AD preparations.


Isolation of bacteria-containing phagosomes by magnetic selection.
There is a growing awareness of the importance of intracellular events in determining the outcome of infectious disease. To improve the understanding of such events, like phagosome maturation, we set out to develop a versatile technique for phagosome isolation that is rapid and widely applicable to different pathogens. We developed two different protocols to isolate phagosomes containing dead or live bacteria modified with small magnetic particles, in conjunction with a synchronized phagocytosis protocol and nitrogen cavitation. For dead bacteria, we performed analysis of the phagosome samples by microscopy and immunoblot, and demonstrated the appearance of maturation markers on isolated phagosomes. We have presented detailed protocols for phagosome isolation, which can be adapted for use with different cell types and prey. The versatility and simplicity of the approach allow better control of phagosome isolation, the parameters of which are critical in studies of host-bacteria interaction and phagosome maturation.


Medical mentorship deconstructed: an analysis and structural recommendation for high value mentorship.
Background: Mentorship is an important component for young students interested in pursuing a career in medicine. In medically underserved areas, such as rural areas, mentorship can be sparse due to the lack of access to healthcare professionals. The purpose of this project was to gain an understanding of the mentorship received by practicing medical students. Methods: The authors conducted structured, one-on-one interviews with 10 current medical students about their perceptions and experiences with mentorship. Interviews were transcribed, coded, and analyzed for themes and subthemes. Results: Our findings revolve around three time periods of mentorship: 1) Before Obtaining a Mentor; 2) During the Mentorship; and 3) After the Mentorship. In our findings we describe key characteristics such as professional development, personal qualities of the mentor, and professional and personal guidance as important components in guiding the mentee starting from the undergraduate level and continuing to their current level of education. Conclusion: Interviewees' experiences with and perspectives on the mentorship they received were generally positive, though it was evident there are some aspects of the mentee-mentor relationship that can be improved. Building on the results obtained, setting expectations, providing mentor training, and pairing mentors/mentees from similar backgrounds are what we propose to create fulfilling and meaningful relationships between a mentee and mentor.


A new model of epidermal differentiation: induction by mechanical stimulation.
In vivo, epidermal cells are committed to terminal differentiation in which they undergo a series of morphological and biochemical changes. In vitro, keratinocytes are able to undergo some steps of this differentiation process only. In view of the fact that in vivo skin is continuously subjected to mechanical stress, we investigated the stimulation of differentiation of transformed keratinocytes by mechanical stimulation. The cells, grown in plastic culture dishes, were periodically treated with weights exerting a pressure of 0.015 Ncm-2. This stimulation lasted from 1 to 4 days. Then keratinocytes were examined using indirect immunofluorescence, 3H-thymidine and 14C-amino acid incorporation, SDS polyacrylamide gel electrophoresis, and Western blotting. Following pressure treatment, the previously monolayered keratinocytes locally grew up to several layers, the number of horny scales increased and, after 4 days, the pattern of cytokeratin was modified. The total amount of keratin increased, forming granular accumulations, while the proliferation rate of the cells decreased. Both the 67 kDa and 49.5 kDa keratin subunits increased in stimulated cells. Moreover, a weak keratin band of 44 kDa appeared that was not present in controls. The results demonstrate that cyclic pressure promotes differentiation of cultivated epidermal cells.


Pulsed radiofrequency to the great occipital nerve for the treatment of intractable postherpetic itch: a case report.
A patient with intractable postherpetic itch lasting for 1 year was reported. The itch was mainly from the left vertex, frontal and ophthalmic regions and extended to the left neck area. The patient had negative response to the ophthalmic nerve block. Under the initial positive response to the great occipital nerve block, pulsed radiofrequency (PRF) was performed on the position of the great occipital nerve. After 4 months treatment, the itch was completely vanished. This case study demonstrates the effectiveness of PRF for intractable postherpetic itch originating in the head and neck. However, more samples needed to verify this management.


Effects of low glycaemic index/low glycaemic load vs. high glycaemic index/ high glycaemic load diets on overweight/obesity and associated risk factors in children and adolescents: a systematic review and meta-analysis.
The objective of the present systematic review and meta-analysis was to synthesize the available literature data investigating the effects of low glycaemic index/low glycamic load dietary regimens on anthropometric parameters, blood lipid profiles, and indicators of glucose metabolism in children and adolescents. Literature search was performed using the electronic databases MEDLINE, EMBASE, and the Cochrane Central Register of trials with restrictions to randomized controlled trials, but no limitations concerning language and publication date. Parameters taken into account were: body weight, body mass index, z-score of body mass index, fat mass, fat-free mass, height, waist cicrumference, hip circumference, waist-to-hip ratio, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, diastolic and systolic blood pressure, fasting serum glucose, fasting serum insulin, HOMA-index, glycosylated haemoglobin, and C-reactive protein. Meta-analyses were performed for each parameter to assess pooled effect in terms of weighted mean differences between the post-intervention (or differences in means) of the low glycaemic index diets and the respective high glycaemic index counterparts. Data analysis was performed using the Review Manager 5.3. software. Nine studies enrolling 1.065 children or adolescents met the inclusion criteria. Compared to diets providing a high gylcaemic index, low glycaemic index protocols resulted in significantly more pronounced decreases in serum triglycerides [mean differences -15.14 mg/dl, 95%-CI (-26.26, -4.00)] and HOMA-index [mean difference -0.70, 95%-CI (-1.37, -0.04), fixed-effects model only]. Other parameters under investigation were not affected by either low or high glycaemic indices. The present systematic review and meta-analysis provides evidence of a beneficial effect of a low glycaemic index/load diet in children and adolescents being either overweight or obese. Regarding the limitations of this analysis, further studies adopting a homogenous design are necessary to assure the present findings. Since low glycaemic index/load regimens were not associated with a deterioration of the outcome parameters, these diets should not be categorically excluded when looking for alternatives to change lifestyle habits in this age group.


Antibiotic-taking experiences of undergraduate college students.
The purpose of this qualitative descriptive study was to explore the medication-taking experiences of undergraduate college students prescribed short-term antibiotic therapies and to describe factors influencing their adherence. Thirty-four undergraduate students prescribed antibiotics for treatment of an acute infectious illness at a large university health center were recruited to participate in this study. Semistructured telephone interviews were conducted after students finished their course of treatment. Qualitative descriptive content analysis was used to analyze the transcripts typed from the audio-taped phone interviews. The main theme that emerged from the data was antibiotic-taking self-management. Most participants were able to adapt medication regimens into their daily routines, and used events in their day and specific reminder strategies to help them to remember to take their medications. This occurred despite an ever-changing class and work schedule and being prescribed complex, lengthy antibiotic regimens. Most dosing errors occurred during times when schedules changed or students were off campus during weekends or college breaks. A small number of students discontinued therapy early because of side effects or forgetfulness. By understanding factors that influence antibiotic adherence from a college student perspective, healthcare providers can suggest strategies to promote adherence that are tailored to the specific needs of this unique population.


Fibronectin in aging extracellular matrix fibrils is progressively unfolded by cells and elicits an enhanced rigidity response.
While the mechanical properties of a substrate or engineered scaffold can govern numerous aspects of cell behavior, cells quickly start to assemble their own matrix and will ultimately respond to their self-made extracellular matrix (ECM) microenvironments. Using fluorescence resonance energy transfer (FRET), we detected major changes in the conformation of a constituent ECM protein, fibronectin (Fn), as cells fabricated a thick three-dimensional (3D) matrix over the course of three days. These data provide the first evidence that matrix maturation occurs and that aging is associated with increased stretching of fibronectin fibrils, which leads to at least partial unfolding of the secondary structure of individual protein modules. A comparison of the conformations of Fn in these 3D matrices with those constructed by cells on rigid and flexible polyacrylamide surfaces suggests that cells in maturing matrices experience a microenviroment of gradually increasing rigidity. In addition, further matrix stiffening is caused by active Fn fiber alignment parallel to the contractile axis of the elongated fibroblasts, a cell-driven effect previously described for other fibrillar matrices. The fibroblasts, therefore, not only cause matrix unfolding, but reciprocally respond to the altered Fn matrix properties by up-regulating their own rigidity response. Consequently, our data demonstrate for the first time that a matured and aged matrix has distinctly different physical and biochemical properties compared to a newly assembled matrix. This might allow cells to specifically recognise the age of a matrix.


Diagnosis and management of interstitial lung disease.
The complex tasks of making a confident diagnosis of a specific form of interstitial lung disease (ILD) and formulating a patient-centered, personalized management plan in an attempt to achieve remission or stabilization of the disease process can pose formidable challenges to clinicians. When patients are evaluated for suspected ILD, an accurate diagnosis of the specific form of ILD that a patient has developed must be made to provide the patient with useful prognostic information and to formulate an appropriate management plan that can relieve symptoms and restore or significantly improve quality of life. A well-performed patient history and physical examination provides invaluable information that can be combined with appropriate laboratory testing, imaging, and, if needed, tissue biopsy to reach a confident ILD diagnosis, and high-resolution computed tomography (HRCT) of the thorax is usually a key component of the diagnostic evaluation. If treatment is indicated, many forms of ILD can respond significantly to immunosuppressive anti-inflammatory therapies. However, ILD accompanied by extensive fibrosis may be difficult to treat, and the identification of an effective pharmacologic therapy for idiopathic pulmonary fibrosis (IPF) has remained elusive despite the completion of many phase 3 clinical trials over the past decade. Nonetheless, patients with IPF or advanced forms of non-IPF ILD can benefit significantly from detection and treatment of various co-morbid conditions that are often found in patients (especially the elderly patient), and supportive care (oxygen therapy, pulmonary rehabilitation) can have a beneficial impact on quality of life and symptom palliation. Finally, lung transplantation is an option for patients with progressive, advanced disease that does not respond to other therapies, but only a relatively small subset of patients with end-stage ILD are able to meet wait listing requirements and eventually undergo successful lung transplantation.


Creation of Highly Ordered "Nano-Mille-Feuille" Hard/Soft Nanoparticle Multilayers with Interparticle Cross-Linking by Diacetylene-Containing Chains.
In this study, we attempted to create a precise nanostructure in which hard and soft layers were alternately stacked with a period of 5 nm. Such a periodically stacked structure can be used as a model material to elucidate the origin of the innovative mechanical property improvement proposed for Mg alloy systems. The soft layer was a single layer of nanoparticles made of a ternary copolymer containing a carbazole ring and both hydrocarbon and fluorocarbon chains. The hard layer was a single-particle layer made of magnetite nanoparticles; the surface of these particles was modified with long-chain diynoic acid. The multilayers of each single-particle layer were 54% crystalline and ordered with a D001 crystallite size of approximately 20 nm. The nano-mille-feuille structure, in which the hard and soft layers are repeated in a single-digit nanoperiod, was 56% crystalline and ordered with a D001 crystallite size of approximately 15 nm. Infrared absorption spectroscopy and X-ray photoelectron spectroscopy did not show any loss of both hard and soft layers. Even when the thickness/number of layers was changed variously, no remarkable decrease was observed in the order. Cross-linking between particles by ultraviolet irradiation polymerization was performed for the direct evaluation of the mechanical properties of this structure in the future. Even after topochemical polymerization between the modified chains, the order of the particle stacking structure was maintained.


Precise Delivery Into Chronic Spinal Cord Injury Syringomyelic Cysts with Magnetic Nanoparticles MRI Visualization.
Traumatic spinal cord injury (SCI) often results in the deficiency of glia and neurons in cystic cavities. These syringomyelic cysts can prevent axonal regeneration and sprouting. Details of the mechanism of syringomyelic cyst formation are unknown and an effective treatment for overcoming syringomyelic cysts is not available. Ten adult female Wistar rats underwent contusion SCI modeling resulting in syringomyelic cyst formation. A novel method for locating the cysts was developed and employed. MRI safe silver needles were inserted through the erector spinae of anesthetized rats to create a stable reference point. MRI images of the rodent spine were taken with the needles in situ. This information was used to accurately locate the cyst and determine the 3-dimensional entry point coordinates for nanoparticle delivery. Nanoparticles were injected into the cyst during a primary injection of 8 ul and a secondary injection of 8 ul, to prove the procedure can be accurately repeated. None of the rats died intra- or post-operatively. The syringomyelic cysts were accurately located with the 3-dimensional entry point coordinates. After nanoparticle delivery twice into each rat, the visualized syringomyelic cyst volume significantly decreased from 5.71±0.21 mm3 to 3.23±0.364 mm3 and to 1.48±0.722 mm3. The present study describes a novel strategy for precise nanoparticle delivery into a syringomyelic cyst, using measurements obtained from MRI images. This strategy may aid in developing a new method for studying chronic spinal cord injury and a novel treatment for syringomyelic cysts.


Shape memory alloy smart knee spacer to enhance knee functionality: model design and finite element analysis.
In this paper we introduce Shape Memory Alloy (SMA) for designing the tibial part of Total Knee Arthroplasty (TKA) by exploiting the shape-memory and pseudo-elasticity property of the SMA (e.g. NiTi). This would eliminate the drawbacks of the state-of-the art PMMA based knee-spacer including fracture, sustainability, dislocation, tilting, translation and subluxation for tackling the Osteoarthritis especially for the aged people of 45-plus or the athletes. In this paper a Computer Aided Design (CAD) model using SolidWorks for the knee-spacer is presented based on the proposed SMA adopting the state-of-the art industry-standard geometry that is used in the PMMA based spacer design. Subsequently Ansys based Finite Element Analysis is carried out to measure and compare the performance between the proposed SMA based model with the state-of-the art PMMA ones. 81% more bending is noticed in the PMMA based spacer compared to the proposed SMA that would eventually cause fracture and tilting or translation of spacer. Permanent shape deformation of approximately 58.75% in PMMA based spacer is observed compared to recoverable 11% deformation in SMA when same load is applied on both separately.


Changing compliance of poly(vinyl alcohol) tubular scaffold for vascular graft applications through modifying interlayer adhesion and crosslinking density.
Poly(vinyl alcohol) (PVA) is a water-soluble polymer and forms a hydrogel that has been studied as a potential small-diameter (<6 mm) vascular graft implant. The PVA hydrogel crosslinked using sodium trimetaphosphate (STMP) has been shown to have many beneficial properties such as bioinert, low-thrombogenicity, and easy surface modification. Compared to conventional synthetic vascular graft materials, PVA has also shown to possess better mechanical properties; however, the compliance and other mechanical properties of PVA grafts are yet to be optimized compared to the native blood vessels. Mechanical compliance has been an important parameter to be studied for small-diameter vascular grafts, as compliance has been proposed to play an important role in intimal hyperplasia formation. PVA grafts are made using dip-casting a cylindrical mold into crosslinking solution. The number of dipping can be used to control the wall thickness of the resulting PVA grafts. In this study, we hypothesized that the number of dip layer and wall thickness, the chemical crosslinking, and interlayer adhesive strength could be important parameters in the fabrication process that would affect compliance. This work provides the relationship between the wall thickness, burst pressure, and compliance of PVA. Furthermore, our data showed that interlayer adhesion as well as chemical and physical crosslinking density can increase the compliance of PVA grafts.


Apoptotic endothelial cells demonstrate increased adhesiveness for human mesenchymal stem cells.
Mesenchymal stem cells (MSCs) participate in the wound healing process in mammalians. Adhesion of MSCs to endothelium is a key step in the homing of MSCs circulating in the bloodstream to the sites of injury and inflammation. Because endothelial cells (ECs) may become apoptotic under certain pro-inflammatory conditions, we investigated the effects of pro-inflammatory, TNF-alpha and IL-1 beta, and pro-apoptotic agents, actinomycin D, cycloheximide, okadaic acid, wortmannin, and staurosporine, on human MSCs (hMSCs) adhesion to ECs. Treatment of ECs with pro-apoptotic agents markedly increased adhesion of hMSCs to ECs. This adhesion correlated with reduction of mitochondrial membrane potential, inhibition of NADH dehydrogenases, and release of von Willebrand factor (vWF) by ECs. Treatment of ECs with exogenous vWF also stimulated hMSC adhesion. These data provide evidence that apoptosis of ECs may regulate homing of hMSCs to the sites of tissue injury. These results are consistent with the hypothesis that activation of apoptotic signaling pathways in ECs releases vWF which regulates hMSC adhesion to ECs.


Use of proteomic differential displays to assess functional discrepancies and adjustments of human bone marrow- and Wharton jelly-derived mesenchymal stem cells.
Mesenchymal stem cells (MSCs) from bone marrow are suitable for the reconstruction of connective tissues and even brain tissue but have limitations in terms of cell expansion and fully specific differentiation. In our current study, we have attempted to adjust and improve the cell expansion and differentiation properties of human MSCs from different tissues. MSCs from normal bone marrow and Wharton jelly were subjected to proteomic differential displays, followed by functional adjustments based on these displays. Bone marrow MSCs expressed more transgelin-2 and differentiated more rapidly into bone nodules but showed a slower growth rate. A knockdown of transgelin-2 expression by specific small interfering RNA (siRNA) significantly increased the growth rate of these cells, the G1/S phase cell cycle transition, and the interaction of cyclin D1 with cdk2. Wharton jelly MSCs expressed the chaperone protein HSP90β at higher levels and differentiated slowly toward an osteogenic lineage. However, the knockdown of HSP90β expression significantly increased bone nodule formation, inhibited cell growth, decreased the number of cells in the G1/S phase of the cell cycle, and decreased the interaction of cyclin D1 with cdk2 and of cyclin E with cdk2. These results were validated by the in vivo repair of segmental bone defects in a mouse model with severe combined immunodeficiency. We thus demonstrate an improvement in the cell expansion and tissue regeneration properties of human MSCs through specific adjustments.


[Use of a new inotropic agent, enoximone, in heart surgery].
We report our experience with the use of enoximone in 5 patients with severely depressed preoperative myocardial function who underwent cardiac surgery. In patients 1 and 2, enoximone was administered as the inotropic of choice before cardiopulmonary bypass (CPB) and a substantial improvement of cardiac index was achieved; in these patients, enoximone administration after CPB permitted to overcome low cardiac output which persisted after high dose dobutamine in patient 1, and in patient 2 right ventricular contractility improved. In patient 3 the use of enoximone permitted the discontinuation of CPB, which had not been previously possible with the association of dopamine and dobutamine. In this patient, adrenaline perfusion improved the low cardiac output syndrome but resulted in poorly tolerated side effects. However, in patient 4 the administration of enoximone during pre-CPB did not improve in a reduction in filling pressures without an increase in the cardiac index because the patient was hypovolemic. In patient 5, the administration of enoximone permitted to interrupt the infusion of dobutamine and to reduce the dose of sodium nitroprusside, which had resulted in significant tachycardia, with increased myocardial contractility and a reduction of vascular peripheral and pulmonary resistances. We conclude that enoximone, single or in association with other inotropics, should be considered a drug of choice in patients undergoing cardiac surgery who develop a low cardiac output syndrome.


The value of myocardial perfusion imaging in screening coronary artery disease before kidney transplantation.
The value of myocardial single-photon emission computed tomography (SPECT) in pre-transplant evaluation of kidney transplant recipients is controversial. We assessed whether myocardial SPECT predicts major adverse cardiac events (MACE) and determined whether SPECT findings affected transplant recipients' medical and invasive treatment. We analyzed 301 patients referred for myocardial SPECT before kidney transplantation and combined the results with information from patient files and the Transplantation Registry. During the median follow-up time of 96 months (IQR 70.75-118.25 months), the incidence of MACE was higher in patients (n = 37) with severely abnormal SPECT (>10% reversible perfusion defect) than in patients (n = 35) with mildly abnormal or normal SPECT (51.4%, 29.4%, and 27.0%, respectively, P = .011). Severely abnormal SPECT findings predicted long-term MACE in a univariable analysis but not after adjusting for other risk factors. Following SPECT, 29 patients (9.6%) underwent coronary angiography and 14 (4.6%) were revascularized. New antithrombotic or statin medication was prescribed to 7.3% of patients with ischemia in SPECT. Kidney transplantation patients are at high long-term risk of MACE even with normal preoperative myocardial SPECT. Abnormal SPECT did not predict MACE when adjusted for other risk factors. Minority of the patients underwent coronary revascularization or had changes in preventive medication before transplantation.


Regulation of low affinity neurotrophin receptor (p75(NTR)) by early growth response (Egr) transcriptional regulators.
The low affinity neurotrophin receptor p75(NTR) is a multifunctional receptor with important roles in neurotrophin signaling, axon outgrowth, and oligodendroglia and neuron survival. It is transcriptionally regulated with spatial and temporal precision during nervous system development, injury and regeneration. Very little is known about how p75(NTR) expression is dynamically regulated but it is likely to influence how p75(NTR) signals in particular cellular contexts. Here, we identify the early growth response (Egr) transcriptional regulators, Egr1 and Egr3, as direct modulators of p75(NTR) gene expression. Egr1 and Egr3 bind and transactivate the p75(NTR) promoter in vitro and in vivo, using distinct response elements on the p75(NTR) promoter. Consistent with these results, p75(NTR) expression is greatly diminished in muscle spindle stretch receptors and in peripheral nerve Schwann cells in Egr gene deficient mice. Taken together, the results elucidate a novel mechanism whereby Egr proteins can directly modulate p75(NTR) expression and signaling in vivo.


Molecular and Clinical Aspects of Angelman Syndrome.
The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2-q13 genomic region identifies 75-80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5-10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity.


The influence of sex steroids on Sjögren's syndrome.
Sjögren's syndrome is an autoimmune disease affecting the exocrine glands, most typically salivary and lacrimal glands. In Sjögren's syndrome, the acinar cells of these glands are damaged and destroyed, leading to diminished secretion of saliva and tear fluid. Accordingly, the current American-European criteria of Sjögren's syndrome include xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). In addition to these sicca symptoms and signs, the diagnostic criteria require autoimmune features in the form of Sjögren's syndrome SS-A and/or SS-B autoantibodies and lymphocyte infiltrates in labial salivary glands. Majority of patients with Sjögren's syndrome are women and the diagnosis is usually done when they are 40-50 years old. The cause of Sjögren's syndrome is unknown, but taking into account the female dominance and the late onset, our hypothesis is that sex steroids play a key role in the etiology of Sjögren's syndrome. More specifically, we believe that the driving factor behind Sjögren's syndrome could be lack of androgens. It has been shown that patients with Sjögren's syndrome have low concentrations of circulating dehydroepiandrosterone sulfate (DHEA-S) compared to age-matched healthy controls. Our hypothesis is that patients with Sjögren's syndrome suffer from an insufficient local androgen effect in the exocrine target tissues of the disease because of low systemic levels and/or ineffective local intracrine handling of DHEA-S prohormone. To further clarify the role of sex steroids and the eventual deficiency of androgens, salivary glands are studied using protein markers regulated by androgens or estrogens.


The Origins of Food Supplied to an Australian Public Hospital.
Local food procurement by public institutions such as hospitals offers multiple benefits including stimulating the local economy, creating jobs, and building resilience within the food supply. Yet no published study has attempted to quantify the local food purchase by hospitals. This baseline is needed to identify gaps, set targets, and monitor change. The objective of this study was to investigate the origin of food supplied to a metro tertiary public hospital and to describe the proportion of food budget spent on items with ingredients grown in Australia and "locally" within the state of Victoria. Food procurement data were collected and analyzed during October 2020-April 2021. All items purchased by the cook fresh kitchen supplying meals to inpatients and two childcare centres during an 8-day menu cycle period were audited. Following an inspection of food packaging labels to determine country of origin, data on the proportion of Victorian content were collected from manufacturers and suppliers of foods containing Australian ingredient. Almost 80% of the food budget (AU $17,748 and 200 items) was spent on items containing significant (at least 75%) Australian content, while 11% was spent on entirely imported foods. The specific geographic origins of 55% of the budget spent on "Australian" food remain unknown as information from manufacturers and suppliers was not available. Where data were available, 3% of food budget was attributed to entirely Victorian grown foods, including fresh fruit, vegetables, and poultry. A considerable proportion of Australian grown foods are purchased by this hospital, but it is largely unknown whether these are local, from the state of Victoria, or not. Tracing and sharing of food origin data, a clear definition for "local" food, and an understanding of Victorian food growing industries are needed to progress the "local food to hospital" agenda.


Fetal mouse alveolar type II cells in culture express several type II cell characteristics found in vivo, together with major histocompatibility antigens.
Alveolar type II cells were isolated from fetal mouse lung by differential adherence and obtained in monolayer culture. Cultures display a high degree of purity as shown by histochemical and immunocytochemical staining procedures. Seventy-five percent of cells stained positive with specific anti-lavage serum mouse (SALS-M), an antiserum specific for (pre)alveolar type II cells of the mouse, and osmiophilic bodies were present in 82% of cells. These and other characteristics of type II cells in culture correspond to those of alveolar type II cells in fetal mouse lung. The pattern of reactivity of these cells with various anti-cytokeratin antibodies is described, and we show that, in contrast to rat type II cells, they do not exhibit alkaline phosphatase activity. Identity of the type II cell cultures was shown by their specific phospholipid composition and surfactant protein A (SP-A) content. The fetal alveolar type II cells in culture were found to synthesize and express class I but not class II major histocompatibility complex (MHC) antigens. The possibility to culture fetal alveolar type II cells of the mouse and the availability of genetically well-defined inbred and transgenic mouse strains opens ways to study the genetics of type II cell differentiation and function. Also, the in vitro availability of alveolar type II cells, the progenitor cells of mouse lung tumors, will enable us to study in vitro several of the processes involved in lung tumorigenesis in the mouse.


Is COPD a rare disease? Prevalence and identification rates in smokers aged 40 years and over within general practice in Germany.
According to literature, COPD rates are high in spite of decreasing rates of main risk factors smoking and air pollution in developed countries. general practice is a good place to survey unbiased prevalence rates. Ten studies done in general practice over the last 20 years found prevalence rates among smokers between 13.1% and 92.1%. Prevalence and detection rates of COPD in smokers in German general practice. Twenty-eight of 34 invited and eligible GP surgeries in/around Duesseldorf, Germany, took part in the non-announced 2-day investigation of all smokers (> or =40 years) who visited the surgeries. Lung function test by hand-held spirometer, peak flow, sympton part of St George's Respiratory Questionnaire, and data on smoking habits were used. GOLD criteria for COPD were employed. GPs had to give their diagnosis not knowing the test results. Of 3157 patients attending the 28 surgeries, 538 were smokers. Four hundred and thirty-seven of these agreed to participate, 5 had to be excluded for medical reasons/unacceptable spirometry. Three hundred and ninety-eight patients have not been previously diagnosed with COPD or asthma. Thirty patients were disgnosed with COPD, making a prevalence of 6.9%, of which 15 patients were already known as having COPD. Our result of low prevalence differs strongly from all other studies in general practice. Considering our study design which avoids selection bias found in nearly all other studies (no pre-announcement, no self-selection of patients or GPs, high participation rate and testing all patients), we strongly believe that our findings reflect the current situation of COPD in German general practice.


[Exploration of the high-risk factors of catheter-related thrombosis in breast cancer].
Objective: To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies. Methods: A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed. Results: The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old (OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC (OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein (OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position (OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level (OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions: The CRT problem can't be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.


Quantum mechanical/molecular mechanical study on the mechanisms of compound I formation in the catalytic cycle of chloroperoxidase: an overview on heme enzymes.
The formation of Compound I (Cpd I), the active species of the enzyme chloroperoxidase (CPO), was studied using QM/MM calculation. Starting from the substrate complex with hydrogen peroxide, FeIII-HOOH, we examined two alternative mechanisms on the three lowest spin-state surfaces. The calculations showed that the preferred pathway involves heterolytic O-O cleavage that proceeds via the iron hydroperoxide species, i.e., Compound 0 (Cpd 0), on the doublet-state surface. This process is effectively concerted, with a barrier of 12.4 kcal/mol, and is catalyzed by protonation of the distal OH group of Cpd 0. By comparison, the path that involves a direct O-O cleavage from FeIII-HOOH is less favored. A proton coupled electron transfer (PCET) feature was found to play an important role in the mechanism nascent from Cpd 0. Initially, the O-O cleavage progresses in a homolytic sense, but as soon as the proton is transferred to the distal OH, it triggers an electron transfer from the heme-oxo moiety to form water and Cpd I. This study enables us to generalize the mechanisms of O-O activation, elucidated so far by QM/MM calculations, for other heme enzymes, e.g., cytochrome P450cam, horseradish peroxidase (HRP), nitric oxide synthase (NOS), and heme oxygenase (HO). Much like for CPO, in the cases of P450 and HRP, the PCET lowers the barrier below the purely homolytic cleavage alternative (in our case, the homolytic mechanism is calculated directly from FeIII-HOOH). By contrast, the absence of PCET in HO, along with the robust water cluster, prefers a homolytic cleavage mechanism.


[Polymorphism of 5,10-methylenetetrahydropholate reductase, prothrombin, and coagulation factor V genes in young patients with ischemic stroke].
The study included 142 patients (87 women, 55 men) (mean age 36.2 +/- 8.3 yr) after ischemic stroke caused by dissection of cerebral arteries (D) (n = 37), anti-phospholipid syndrome (APS) (n = 55) or cardiogenic embolism (CE) (n = 11). Stroke of unknown origin (cryptogenic) was diagnosed in 39 patients. Mutations of 5,10-methylenetetrahydropholate reductase (MTGPR), prothrombin, and coagulation factor V genes were documented by PCR in 38, 0, 3% of D cases, 55.9, 9, 13% of APS cases, 73, 9, 0 CE cases, 57, 5, 0% of cases with cryptogenic stroke compared with 43, 0, 0% in controls. Mutations in MTGPR gene in CE cases, prothrombin gene in APS and CE cases, coagulation factor V gene in APS cases occurred more frequently than in control (p < 0.05). They, were more frequent in APS/CE than in D (p < 0.05). Mutation rate in cryptogenic stroke was not significantly different from that in control (p < 0.05). It is concluded that the above mutations are not involved in pathogenesis of cryptogenic stroke, whereas those of prothrombin and coagulation factor V genes may enhance the thrombogenic potential in APS and CE patients. The role of MTGPR gene mutation in pathogenesis of cardiogenic stroke needs clarification.


Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.
Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT) in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL) and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS) innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG) and VLDL particles (VLDL-P) was tested in men with spinal cord injury (SCI). One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4); 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5)] and 53 able-bodied (AB) subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package. Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (p<0.01) and 112±8 mg/dl (p<0.05), respectively]. VLDL-P concentration was significantly elevated in ↓T5 group compared to AB and ↑T4 groups [74±4 vs. 58±4 (p<0.05) and 55±4 μmol/l (p<0.05)]. VAT volume was significantly higher in both SCI groups than in the AB group, and HOMA-IR was higher and approached significance in the SCI groups compared to the AB group. A linear relationship between triglyceride rich lipoproteins (i.e., TG or Large VLDL-P) and VAT volume or HOMA-IR was significant only in the ↓T5 group. Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB control groups. Thus, level of injury is an important determinate of the concentration of circulating triglyceride rich lipoproteins, which may play a role in the genesis of cardiometabolic dysfunction.


[Individualized pharmaceutical consultations in the management of chemotherapy-induced nausea and vomiting].
In order to prevent and control the chemotherapy-induced nausea and vomiting (CINV), the military hospital Percy (Clamart, France) developed a systematic "CINV consultation". With 1.500 consultations conducted in 2013, the aim of this study was to confront professional practices and the patient's point of view to assess the efficiency of this procedure and consider a restructuring to optimize it. A preliminary study was conducted: 30 medical records of patients who had chemotherapy cure during 2013 have been analysed and 30 patients have completed an evaluation questionnaire anonymously. Patients were very satisfied (63%) or satisfied (37%) of these consultations. Most of them (71%) said the consultations were useful before every cure, while 27% thought that the consultation at first cure or when the chemotherapy protocol changed was enough. CINV consultations were estimated as complementary of the medical consultation for 93% of the patients. Most of the patients (70%) never had CINV or just at the first cure. Furthermore, the anti-emetic treatment was adapted to the new chemotherapy emetic level in only 53% of protocol changes. Patients have expressed a real interest in these CINV consultations and the benefits they could get from them. Moreover, patients' side effects are stabilized faster thanks to those pharmaceutical interviews. In fact, it seems that these consultations are mostly needed for the first cure (until patient stabilization) and when there is a chemotherapy protocol change.


Validation of the Dimensions of Anger Reactions Scale (the DAR-5) in non-clinical South Korean adults.
Posttraumatic anger is a commonly reported emotion among people who have experienced traumatic events. The current study aimed to demonstrate the reliability and validity of the South Korean version of the DAR-5 (DAR-5-K). The DAR-5 is a single scale with 5 items which measures posttraumatic anger. The DAR-5 is composed of five items that measure anger frequency, intensity, duration, aggression, and its interference with social relations. Data were collected from 814 South Korean adults who had experienced traumatic events and participated in the study and analyzed via the combination of exploratory factor analysis (n = 405) and confirmatory factor analysis (n = 409). Results supported the one-factor structure, as reported in previous validation studies. The scale demonstrated robust internal reliability and concurrent validity with measures of posttraumatic stress disorder (PTSD) symptoms, depression, anxiety, and self-esteem. The DAR-5 cut-off score of 12 that was established in the original validation study successfully differentiated high from low scorers with regard to PTSD symptoms, depression, anxiety, and self-esteem. The results confirm that the DAR-5-K is a brief and psychometrically robust measure of anger that can be used to examine South Korean adults who have experienced traumatic events.


Comparison of physical and social risk-reducing factors for the development of disability in older adults: a population-based cohort study.
Considerations of modifiable risk factors for the development of disability in older age have traditionally focused on physical activity. However, there is increasing evidence that psychological, social, and cognitive factors also help to maintain functional independence. This study compared the protective associations between physical and social activities and disability onset. We analysed data from 5434 adults aged 50+ years tracked biennially from 2004/2005 to 2016/2017, measuring self-reported difficulty in carrying out any basic activities of daily living (ADLs) or instrumental ADLs. Exposures included mild, moderate and vigorous physical activity, frequency of socialising with friends/family, cultural engagement (eg, going to the theatre/museums/concerts), and participation in community groups. Over the 12-year follow-up, 1945 adults developed disability. Using Cox proportional hazards regression models adjusted for all identified demographic and health-related variables, vigorous exercise or activity once a month or more (HR 0.82, 95% CI 0.71 to 0.96), moderate exercise or activity more than once a week (HR 0.81, 95% CI 0.67 to 0.97) or cultural engagement once or twice a year or more (HR 0.84, 95% CI 0.73 to 0.97) were associated with a lower hazard of developing disability. Other exposures did not show independent protective associations. Results were robust to sensitivity analyses considering reverse causality and exploring the potential confounding role of time-invariant factors, such as socioeconomic status. These results suggest the importance of either developing multimodal interventions to protect against disability and promote healthy ageing or promoting greater physical and social engagement with existing community activities among older adults.


MICROMORPHOLOGY OF DERMATOPHILUS CONGOLENSIS.
Gordon, Morris A. (Division of Laboratories and Research, New York State Department of Health, Albany), and Mercedes R. Edwards. Micromorphology of Dermatophilus congolensis. J. Bacteriol. 86:1101-1115. 1963.-As seen in electron micrographs of thin sections, Dermatophilus congolensis is a holocarpic actinomycete that fragments, after formation of septa in several planes, into Sarcina-like packets and then into individual cocci. Release of coccal forms from the filaments and packets is by dissolution of a capsular matrix, which is a product of degradation of the cell wall. The plasmalemma is a "unit membrane." Regularly occurring plasmalemmosomes ("onion bodies") of uniform structure are apparently related to septum formation. A typical bacterial nucleoid is seen in most sections, and ribosomes are scattered throughout the cytoplasm. Specimens for electron microscopy were prepared by a modification of Kellenberger's method.


Functional health literacy, chemotherapy decisions, and outcomes among a colorectal cancer cohort.
Functional health literacy is essential for the self-management of chronic diseases and preventive health behaviors. Patients with cancer who have a low level of health literacy may be at greater risk for poor care and poor outcomes. We assessed health literacy using the Short Test of Functional Health Literacy in Adults in 347 participants with colorectal cancer who were nested within a prospective observational study of system, health care provider, and participant characteristics influencing cancer outcomes. Having adequate health literacy increased the likelihood that participants with stage 3/4 disease received chemotherapy (odds ratio, 3.29; 95% confidence interval, 1.23-8.80) but had no effect on cancer stage at diagnosis or vital status at last observation during postenrollment follow-up. No difference was seen in health literacy status regarding participant beliefs and preferences about chemotherapy among those with stage 3/4 disease, nor in participant roles in deciding whether to receive chemotherapy. Patients with lower levels of health literacy were less likely to receive chemotherapy compared with participants with higher levels of health literacy. Therefore, clear communication related to key health care decisions may lead to fewer disparities due to a patient's level of health literacy.


Ultrasound Phantom Using Sodium Alginate as a Gelling Agent.
For medical workers, ultrasound phantoms for human soft tissue are used not only for accuracy management of ultrasound diagnosis but also to aid ultrasound-guided needle and blind catheter insertion training without risk to real patients. For the phantoms, ultrasound characteristics and a texture are required to mimic the human soft tissue. The proposed phantom was composed of sodium alginate, calcium sulfate dihydrate, trisodium phosphate 12-hydrate, glycerol, and water. The propagation speed, attenuation coefficient, acoustic impedance, and texture of the proposed phantom were almost the same as those of human soft tissue. Expensive chemicals and special equipment are not required.


Effect of pH on Aβ42 Monomer and Fibril-like Oligomers-Decoding in Silico of the Roles of pK Values of Charged Residues.
Amyloid beta-peptide (Aβ) is the key to developing Alzheimer's disease. Experiments have confirmed that different acidity influences directly not only the structural morphology and population of Aβ oligomers, but also the toxicity. The atomic-level association between the pH, charged residues, and Aβ properties remains obscure. Herein, conformational changes of Aβ42 monomer, fibril-like trimer, and pentamer in the medium pH range of 4.0-7.5 are studied. The results reveal that, as the pH changes from 7.5 to the isoelectric pH, His6, His13, and His14 are protonated in turn, successively approach the center of mass of folded Aβ monomer, trigger ionic interactions and changes of neighboring turns (Asp7-Ser8, His14-Lys16) and even a distant one (Leu34-Met35), as well as concomitant changes of secondary structure, and promote the conformation transition from unfolded to folded. This observation discloses that protonation can convert these charged residues from originally hydrophilic to "hydrophobic-like". For fibril-like oligomers, the pH susceptibility essentially stems from the pK values of charged residues in the context of the Aβ fibril, and in turn one can predict the dynamic behavior of these residues in the processes of dissociation or stabilization of a fibril by comparing the pK values of residues involved in salt bridges in the normal state with those in the current context. This idea is justified by two fibril models and appears to be applicable to other peptides and their fibril systems.


Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer.
Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).