SkyPole-A method for locating the north celestial pole from skylight polarization patterns.
True north can be determined on Earth by three means: magnetic compasses, stars, and via the global navigation satellite systems (GNSS), each of which has its own drawbacks. GNSS are sensitive to jamming and spoofing, magnetic compasses are vulnerable to magnetic interferences, and the stars can be used only at night with a clear sky. As an alternative to these methods, nature-inspired navigational cues are of particular interest. Celestial polarization, which is used by insects such as Cataglyphis ants, can provide useful directional cues. Migrating birds calibrate their magnetic compasses by observing the celestial rotation at night. By combining these cues, we have developed a bioinspired optical method for finding the celestial pole during the daytime. This method, which we have named SkyPole, is based on the rotation of the skylight polarization pattern. A polarimetric camera was used to measure the degree of skylight polarization rotating with the Sun. Image difference processes were then applied to the time-varying measurements in order to determine the north celestial pole's position and thus the observer's latitude and bearing with respect to the true north.


KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway.
The Krüppel-like factor 13 (KLF13) has emerged as an important transcription factor involved in essential processes of the central nervous system (CNS). It predominantly functions as a transcriptional repressor, impacting the activity of several signaling pathways with essential roles in the CNS, including the JAK/STAT pathway, which is the canonical mediator of growth hormone (GH) signaling. It is now recognized that GH has important actions as a neurotrophic factor. Therefore, we analyzed the effects of KLF13 on the activity of the JAK/STAT signaling pathway in the hippocampus-derived cell line HT22. Results showed that KLF13 directly regulates the expression of several genes involved in the JAK-STAT pathway, including Jak1, Jak2, Jak3, and Socs1, by associating with their proximal gene promoters. In addition, it was found that in KLF13-deficient HT22 neurons, the expression of Jak1, Stat3, Socs1, Socs3, and Igf1 was dysregulated, exhibiting mRNA levels that went up to 7-fold higher than the control cell line. KLF13 displayed a differential effect on the GH-induced JAK/STAT pathway activity, decreasing the STAT3 branch while enhancing the STAT5 branch. In KLF13-deficient HT22 cells, the activity of the STAT3 branch was enhanced, mediating the GH-dependent augmented expression of the JAK/STAT output genes Socs1, Socs3, Igf1, and Bdnf. Furthermore, GH treatment increased both the nuclear content of KLF13 and Klf13 mRNA levels, suggesting that KLF13 could be part of the mechanisms that maintain the homeostatic state of this pathway. These findings support the notion that KLF13 is a regulator of JAK/STAT activity.


Rest vertical dimension determined by electromyography with biofeedback as compared to conventional methods.
This study was undertaken to determine if electromyography with biofeedback can be utilized to produce a more reliable determination of rest vertical dimension than conventional methods such as phonetics and swallowing. It was found that: 1. Electromyography with biofeedback appeared to produce a more consistently reliable determination of rest vertical dimension than conventional methods when used with edentulous subjects. 2. Determinations of rest vertical dimension by individual dentists using phonetics and swallowing had wide variations in two of the five patients in a range of up to 6 mm. An error of this magnitude could easily cause an intrusion upon the interocclusal distance and resultant failure of treatment. Since this study was limited to five patients, a more expanded study is necessary to determine the validity of electromyography vs. conventional methods for determining rest vertical dimension. Both methods have questionable aspects in relation to the time of day, patient's understanding of each technique, and past dental history. However, the most critical problem of the electromyographic technique is the feasibility of its use in a private practice in light of the excessive cost of the required equipment.


Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes.
Familial cases of hematological malignancies are associated with germline mutations. In particular, heterozygous mutations of SRP72 correlate with the development of myelodysplasia and bone marrow aplasia in two families. The signal recognition particle 72 kDa protein (SRP72) is part of the SRP complex, responsible for targeting of proteins to the endoplasmic reticulum. The main objective of this study is to investigate the role of SRP72 in the hematopoietic system, thus explaining why a reduced dose could increase susceptibility to hematological malignancies. We developed an Srp72 null mouse model and characterized its hematopoietic system using flow cytometry, bone marrow transplantations, and gene expression analysis. Heterozygous loss of Srp72 in mice is not associated with major changes in hematopoiesis, although causes mild reductions in blood and BM cellularity and minor changes within the stem/progenitor compartment. We did not observe any hematological disorder. Interestingly, gene expression analysis demonstrated that genes encoding secreted factors, including cytokines and receptors, were transcriptionally down-regulated in Srp72+/- animals. The Srp72+/- mouse model only partially recapitulates the phenotype observed in families with inherited SRP72 lesions. Nonetheless, these results can provide mechanistic insights into why SRP72 mutations are associated with aplasia and myelodysplasia in humans.


A Mutant Isoform of ObgE Causes Cell Death by Interfering with Cell Division.
Cell division is a vital part of the cell cycle that is fundamental to all life. Despite decades of intense investigation, this process is still incompletely understood. Previously, the essential GTPase ObgE, which plays a role in a myriad of basic cellular processes (such as initiation of DNA replication, chromosome segregation, and ribosome assembly), was proposed to act as a cell cycle checkpoint in Escherichia coli by licensing chromosome segregation. We here describe the effect of a mutant isoform of ObgE (ObgE∗) that causes cell death by irreversible arrest of the cell cycle at the stage of cell division. Notably, chromosome segregation is allowed to proceed normally in the presence of ObgE∗, after which cell division is blocked. Under conditions of rapid growth, ongoing cell cycles are completed before cell cycle arrest by ObgE∗ becomes effective. However, cell division defects caused by ObgE∗ then elicit lysis through formation of membrane blebs at aberrant division sites. Based on our results, and because ObgE was previously implicated in cell cycle regulation, we hypothesize that the mutation in ObgE∗ disrupts the normal role of ObgE in cell division. We discuss how ObgE∗ could reveal more about the intricate role of wild-type ObgE in division and cell cycle control. Moreover, since Obg is widely conserved and essential for viability, also in eukaryotes, our findings might be applicable to other organisms as well.


Training nurses to place tunnelled central venous catheters.
In recent years experienced nurses working in radiology and haematology have expanded their roles to encompass placing tunnelled central venous catheters using real-time sonography and fluoroscopy. With training and supervised practice, such nurses can increase their knowledge and skills and improve services for patients requiring CVCs.


The role of vitamin D in subjective tinnitus-A case-control study.
Regarding the high prevalence of vitamin D (25(OH)D) deficiency in the population and its possible association with ear diseases, we aimed to investigate the 25(OH)Dserum level in patients with subjective, nonpulsating tinnitus and its effect on tinnitus severity. The study included 201 tinnitus patients and 99 controls. Patient clinical information, including tinnitus characteristics and severity according to Tinnitus Handicap Inventory (THI), loudness assessed by Visual Analogue Scale (VAS), audiometry, and the blood level of vitamin D, was recorded. The level of 25(OH)D in tinnitus patients was significantly decreased compared with the controls (19.86 ± 7.53 and 27.43 ± 8.85 ng/ml, respectively; P value < 0.0001). More patients in the tinnitus group were deficient in vitamin D, compared with the controls (50.7% vs. 22.2% respectively, p < 0.0001). Tinnitus patients with a lower serum level of 25(OH)D (≤15 ng/dl) were significantly younger, had a higher degree of tinnitus severity measured with THI and VAS scales, had higher triglyceride and TSH levels, and a lower HDL level compared with individuals who had higher 25(OH)D level (>15 ng/dl). There was a strong correlation between the 25(OH)D level and THI. Our findings suggest that a large proportion of tinnitus patients suffers from vitamin D deficiency and that the vitamin D level correlates with tinnitus impact. We recommend a vitamin D assessment for all tinnitus patients.


Copper(I) Alkynyl Clusters with Crystallization-Induced Emission Enhancement.
Four copper(I) alkynyl complexes incorporating phosphate ligands, namely, [Cu16(tBuC≡C)12(PhOPO3)2]n (1; PhOPO3 = phenyl phosphate), [Cu16(tBuC≡C)12(1-NaphOPO3)2]n (2; 1-NaphOPO3 = 1-naphthyl phosphate), [VO4@Cu25(tBuC≡C)19(1-NaphOPO3)](PF6)0.5(F)0.5 (3), and [PO4@Cu25(tBuC≡C)19(1-NaphOPO3)](PF6)0.5(F)0.5 (4), were solvothermally synthesized and well-characterized by IR spectroscopy, powder X-ray diffraction, and single-crystal X-ray diffraction. Single-crystal X-ray analysis revealed that the Cu16 cluster-based coordination chain polymers 1 and 2 are formed by assembly during crystallization, while 3 and 4 contain high-nuclearity copper(I) composite clusters enclosing orthovanadate and phosphate template ions, respectively, that are supported by ROPO32- ligands. Complexes 1-4 exhibit crystallization-induced emission enhancement. Their crystalline state shows strong luminescence, in striking contrast to the weak emission of the amorphous state and solution phase. A detailed investigation of the crystal structure suggests that well-arranged C-H···π and π···π interactions between the ligands are the major factors for this enhanced emission. Clusters 3 and 4 also exhibit photocurrent responses upon visible-light illumination.


A rare case of nevus sebaceous of the bilateral labia minora: A case report and review of literature.
Nevus sebaceous (NS) is a lesion caused by congenital hyperplastic disorder of the sebaceous glands. It commonly noted in the scalp and face and rarely in the trunk, neck, or oral mucosa. We present a rare case of a lesion arising in the genital region. A 47-year-old woman complained of a gradual increase in the size of her bilateral labia minora over 2 years, which affected her sexual life and caused walking difficulty. She was admitted to the Department of Obstetrics and Gynecology. On physical examination, no ulcer, discharge, and vulval or vaginal bleeding were found. The bilateral inguinal lymph nodes were not palpable, bilateral labia minora were asymmetric, and the right side was evidently bigger than the left. The labia minora had serrated edges and numerous papillae with a maximum diameter of 0.5 cm. The vagina, cervix, and uterus with its attachments were normal. Blood samples tested negative for human immunodeficiency virus, human papilloma virus, hepatitis B virus, and hepatitis C virus. A diagnosis of NS of the bilateral labia minora was made following histopathological examination of the resected specimen. The bilateral labia minora lesions were resected general anesthesia on August 29, 2016. The operation was successful, and intraoperative blood loss was about 10 ml. After 40 months of postoperative follow-up, no recurrence or appearance of other tumors were noted. We recommend surgical removal of lesions in the genital area during adolescence or before adulthood. Adolescence may be the best period for surgical intervention owing to a greater risk of malignant change in adulthood. On the other hand, surgical risk should be avoided in children considering the low incidence of malignant transformation.


Olfactory dysfunction in patients with Wilson's Disease.
Many neurodegenerative disorders are associated with olfactory dysfunction (OD), but little is known about OD in Wilson's Disease (WD). We evaluated olfactory function in patients with WD. OD was examined in 68 patients with WD and 70 sex- and age-matched healthy controls using subjective testing with 'Sniffin Sticks'. Threshold discrimination identification (TDI) score and its three components (odour detection threshold, discrimination, and identification) were assessed. Compared to controls, patients with WD had a significantly weaker sense of smell in terms of TDI (p < 0.01), odour discrimination (p < 0.01), and identification (p < 0.01), but not in terms of odour detection threshold (p = 0.27). Patients with predominantly neurological symptoms were characterised by greater OD by TDI (p < 0.01), odour detection threshold (p = 0.01), and discrimination (p = 0.03). The presence of pathological lesions (p = 0.04) in brain magnetic resonance imaging and generalised brain atrophy (p = 0.02) predisposed to worse TDI. In the WD group, weak inverse correlations between age and TDI score (r = -0.27), odour detection threshold (r = -0.3), and discrimination (r = -0.3) were found. Male gender was a risk factor for abnormal TDI in both WD and controls (both p = 0.02). Patients with WD, particularly older individuals, more frequently had OD than healthy volunteers. Predominantly neurological symptoms, and the presence of typical brain MRI changes, predisposed patients with WD to smell disorders.


Measurement and optimization of the beam coupling impedance of a novel 3D-printed titanium alloy cage inside the thin-wall vacuum chamber.
Dipole magnet vacuum chambers are among the most critical and costly components of rapid-cycling accelerator facilities. Alternative approaches to traditional ceramic chambers have been explored for the implementation of fast-ramping dipole-magnet vacuum chambers, including thin-wall metallic beam pipe chambers strengthened with transverse ribs and ceramic rings inside thin-walled chambers. Here, we report a novel 3D-printed titanium alloy cage inside the thin-wall vacuum chamber, which is designed for high-intensity heavy ion accelerator facility (HIAF) to reduce manufacturing difficulty and cost, shorten the production cycle, and improve the quality. Comprehensive studies were undertaken to characterize the impedance of the 3D-printed titanium alloy cage inside the thin-wall vacuum chamber. The beam-coupling impedance and eddy currents of the new thin-wall vacuum chamber were studied mostly numerically. Strategies for further reducing the beam-coupling impedance were explored. In addition, impedance bench measurements using the "half wavelength" resonant method were conducted to identify the longitudinal and transverse impedances of the 3D-printed titanium alloy cage inside the thin-wall vacuum chamber prototype experimentally. The simulated and measured results for the impedance were consistent. Furthermore, a campaign for resonance-check measurements on the 3D-printed titanium alloy ring loaded inside a thin-wall vacuum chamber prototype was launched. This novel thin-wall vacuum chamber structure is now entering the fabrication stage and will soon be ready for installation in the Booster Ring (BRing).


Creatinine reduction ratio and 24-hour creatinine excretion on posttransplant day two: simple and objective tools to define graft function.
To devise objective criteria for early diagnosis of delayed graft function (DGF), 59 adult living donor kidney transplants with immediate graft function (IGF) and 51 cadaveric kidney transplants were investigated for creatinine reduction ratio (CRR2) from posttransplant day 1 to day 2 and 24-h urine creatinine excretion (UC2) on day 2. The mean CRR2 in living donor transplants was 53% (SD +/- 11); the distribution of CRR2 was gaussian, and all of them had UC2 >1000 mg. Criteria for DGF were developed on the basis of living donor transplant: CRR2 < or =30% (2SD below 53%) +/- UC2 < or =1000 mg. Overall, 24 cadaver transplant recipients (47%) developed DGF (CRR2 < or =30%); 13 patients (25%) had mild DGF (UC2 >1000 mg), and the remaining 11 (22%) had severe DGF (UC2 < or =1000 mg). All the patients with severe DGF had a measured creatinine clearance <25 ml/min on day 7, and 8 of 11 were dialyzed within the first week of transplantation. Patients with IGF and mild DGF had a creatinine clearance of > or =25 ml/min on or before day 7, and none of them were dialyzed. Calcineurin inhibitors were avoided or delayed in five patients with mild DGF and all patients with severe DGF. In conclusion, diagnosing DGF within 48-h after transplantation is simple and may be valuable in the management of these patients.


Accurate standard hydrogen electrode potential and applications to the redox potentials of vitamin C and NAD/NADH.
We computationally evaluated the standard hydrogen electrode (SHE) potential in aqueous phase and the Gibbs energy of a proton from the experimental pKa values of alcohol molecules. From the "golden standard" CCSD(T)/aug-cc-pVTZ level calculation, we estimated the SHE potential as 4.48 V, which is very close to the IUPAC-recommended experimental value of 4.44 V. As applications to the Gaussian-3 (G3) methods, which also reproduce the "golden standard" level calculations, we computed various pKa values and redox potentials for a vitamin series. For vitamin C, we support the experimental result of +0.35 V and predict the pKa value of d-ascorbic acid to be 3.7-3.9. Using a model molecule for nicotinamide adenine dinucleotide (NAD), we reproduced the redox potential and determined the order of the proton/electron addition, based on both the proton affinity and redox potential.


An RNA extraction protocol for shellfish-borne viruses.
The GPTT virus RNA extraction method, originally developed for extraction of human norovirus and hepatitis A virus RNAs from contaminated shellfish, was evaluated for extraction of RNA from Aichi virus strain A846/88 (AiV), coxsackievirus strains A9 (CAV9) and B5 (CBV5), murine norovirus (strain MNV-1), and the norovirus surrogate, feline calicivirus (FCV) strain KCD, for the purpose of RT-PCR detection within seeded oyster (Crassostrea virginica) extracts. The RT-PCR equivalent sensitivities observed within seeded oysters as compared to virus stocks were 0.68, 6.8, 26, 5.6, and 14.5 RT-PCR(50) units when assaying 10% of total RNA extracted from seeded oyster extracts for CAV9, CBV5, AiV, FCV, and MNV-1, respectively. For oysters exposed to virus-contaminated seawater, the detection equivalent sensitivities observed were 680, 68, 2600, 560, and 14.5 RT-PCR(50) for CAV9, CBV5, AiV and FCV, and MNV-1, respectively. These results indicate that the GPTT method can be used as a general viral RNA extraction method for multiple picornaviruses and caliciviruses that could potentially contaminate shellfish.


Opioid Prescribing Patterns and Costs in a Large Group of Patients in Colombia.
The potential for development of tolerance and dependence and the risk of side effects of opioids make it necessary to monitor their prescribing patterns in order to decrease the morbidity and mortality associated with their continued use. The objective of this study was to determine prescription patterns of opioid medication in a group of patients through a cross-sectional study on a population database of 3.5 million people. Patients with three months of continuous opioid use were identified. Pharmacological, co-medication and cost variables were analyzed. We conducted a multivariate analysis. A total of 7,457 patients were included; 72.1% were women, the mean age was 65.1 years, and 3.8% had a diagnosis of cancer. 10.2% of the patients received opioids in combination therapy. The most prescribed opioids were codeine (57.7%), tramadol (30.9%), and hydrocodone (10.4%). The great majority of patients (91.8%) received pharmacological co-medication with antihypertensive agents (54.4%), statins (38.2%) and acetaminophen (35.4%). The use of other analgesics such as acetaminophen (OR: 1.45, 95% CI: 1.22 -1.75) or nonsteroidal anti-inflammatory drugs (OR: 1.98, 95% CI: 1.60 -2.44) was associated with increased risk of receiving opioids in combination therapy. Prescribing habits of weak agonists and short-acting opioids predominate, mainly in monotherapy and at lower than recommended doses.


Is there any benefit using low-intensity inspiratory and peripheral muscle training in heart failure? A randomized clinical trial.
Inspiratory and peripheral muscle training improves muscle strength, exercise tolerance, and quality of life in patients with chronic heart failure (HF). However, studies investigating different workloads for these exercise modalities are still lacking. To examine the effects of low and moderate intensities on muscle strength, functional capacity, and quality of life. A randomized controlled trial. Thirty-five patients with stable HF (aged >18 years, NYHA II/III, LVEF <40%) were randomized to: non-exercise control group (n = 9), low-intensity training group (LIPRT, n = 13, 15% maximal inspiratory workload, and 0.5 kg of peripheral muscle workload) or moderate-intensity training group (MIPRT, n = 13, 30% maximal inspiratory workload and 50% of one maximum repetition of peripheral muscle workload). The outcomes were: respiratory and peripheral muscle strength, pulmonary function, exercise tolerance by the 6-minute walk test, symptoms based on the NYHA functional class, and quality of life using the Minnesota Living with Heart Failure Questionnaire. All groups showed similar quality-of-life improvements. Low and moderate intensities training programs improved inspiratory muscle strength, peripheral muscle strength, and walking distance. However, only moderate intensity improved expiratory muscle strength and NYHA functional class in HF patients. The low-intensity inspiratory and peripheral resistance muscle training improved inspiratory and peripheral muscle strength and walking distance, demonstrating that LIPRT is an efficient rehabilitation method for debilitated HF patients. In addition, the moderate-intensity resistance training also improved expiratory muscle strength and NYHA functional class in HF patients.


Changes in activity and structure of jaw muscles in Parkinson's disease model rats.
Parkinson's disease (PD), a major neurological disease, is characterised by a marked loss of dopaminergic neurons in the substantia nigra. Patients with PD frequently show chewing and swallowing dysfunctions, but little is known about the characteristics of their stomatognathic functions. The purpose of this study was to evaluate the influence of PD on jaw muscle fibre and functions. PD model rats were made by means of the injection of 6-hydroxydopamine (6-OHDA) into the striatum of 8-week-old Sprague-Dawley male rats. Five weeks after the injection, a radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter and anterior belly of digastric muscles. Muscle activity was recorded for 3 days and was evaluated by the total duration of muscle activity per day (duty time). After recording the muscle activities, jaw muscles were isolated for immunohistochemical and PCR analyses. In PD model rats, the following findings of the digastrics muscles verify that compared to the control group: (i) the higher duty time exceeding 5% of the peak activity level, (ii) the higher expression of the mRNA of myosin heavy chain type I, and (iii) the tendency for fast to slow fibre-type transition. With respect to the masseter muscle, there were no significant differences in all analyses. In conclusion, PD leads to the changes in the jaw behaviours, resulting in a PD-specific chewing and swallowing dysfunctions.


Bridging sulfur substitutions in the analysis of pre-mRNA splicing.
Accurate excision of intervening sequences (introns) from messenger RNA precursors is accomplished by a very large and complicated ribonucleoprotein complex called the spliceosome. Elucidating the mechanisms of the two phosphotransesterification reactions that result in intron removal is important for our understanding of the molecular evolution of early genetic systems, as well as our knowledge of contemporary eukaryotic gene expression. The functional consequences of systematic alterations in the reactive groups can be invaluable for understanding catalytic mechanisms, especially for enzymes, such as the spliceosome, whose size and complexity place them beyond the reach of crystallographic and spectroscopic analysis. One type of modification that can be incorporated into a scissile phosphate linkage is the phosphorothiolate, in which a bridging phosphate oxygen is substituted with sulfur. Phosphorothiolate substitutions can be used to detect metal ion-ligand interactions by a "metal specificity switch" strategy. I review recent advances in the synthesis, incorporation, and manipulation of nucleoside phosphorothiolates (with an emphasis on 3'-S-phosphorothiolates), and describe their utility in the study of pre-mRNA splicing.


Loss of Gata4 in Sertoli cells impairs the spermatogonial stem cell niche and causes germ cell exhaustion by attenuating chemokine signaling.
Sertoli cells, the primary somatic cell in the seminiferous epithelium, provide the spermatogonial stem cell (SSC) microenvironment (niche) through physical support and the expression of paracrine factors. However, the regulatory mechanisms within the SSC niche, which is primarily controlled by Sertoli cells, remain largely unknown. GATA4 is a Sertoli cell marker, involved in genital ridge initiation, sex determination and differentiation during the embryonic stage. Here, we showed that neonatal mice with a targeted disruption of Gata4 in Sertoli cells (Gata4(flox/flox); Amh-Cre; hereafter termed Gata4 cKO) displayed a loss of the establishment and maintenance of the SSC pool and apoptosis of both gonocyte-derived differentiating spermatogonia and meiotic spermatocytes. Thus, progressive germ cell depletion and a Sertoli-cell-only syndrome were observed as early as the first wave of murine spermatogenesis. Transplantation of germ cells from postnatal day 5 (P5) Gata4 cKO mice into Kit(W/W-v) recipient seminiferous tubules restored spermatogenesis. In addition, microarray analyses of P5 Gata4 cKO mouse testes showed alterations in chemokine signaling factors, including Cxcl12, Ccl3, Cxcr4 (CXCL12 receptor), Ccr1 (CCL3 receptor), Ccl9, Xcl1 and Ccrl2. Deletion of Gata4 in Sertoli cells markedly attenuated Sertoli cell chemotaxis, which guides SSCs or prospermatogonia to the stem cell niche. Finally, we showed that GATA4 transcriptionally regulated Cxcl12 and Ccl9, and the addition of CXCL12 and CCL9 to an in vitro testis tissue culture system increased the number of PLZF+ undifferentiated spermatogonia within Gata4 cKO testes. Together, these results reveal a novel role for GATA4 in controlling the SSC niche via the transcriptional regulation of chemokine signaling shortly after birth.


Outcome of phacoemulsification in patients with and without Pseudoexfoliation syndrome in Kashmir.
The aim of the study is to compare the outcome of phacoemulsification in patients with and without pseudoexfoliation syndrome in Kashmir. 200 patients were prospectively evaluated and divided into 2 groups. Group 1 comprised 100 cases with pseudoexfoliation and Group 2 (control) 100 cases without pseudoexfoliation. Phacoemulsification with posterior chamber intraocular lens implantation was performed by 3 surgeons. Intraoperative and postoperative observations were made in both the groups at regular intervals upto 6 months. A chi square test was used for statistical analysis. Patients with pseudoexfoliation were significantly older (P = 0.000), had harder cataract(P = 0.030) and smaller mean pupil diameter(P = 0.000) than the control group. Intraoperative complications were comparable between the 2 groups except the occurrence of zonular dehiscence which was seen in 7% patients of Group 1 compared to 0% in Group 2. Higher postoperative inflammatory response was seen in Group 1(P = 0.000). Decrease in intraocular pressure (IOP) at all postoperative measurements was more in Group 1(P = 0.000). The visual acuity was better in the control group in the early postoperative period (P = 0.029), however the final visual acuity at 6 months was comparable between the 2 groups. Phacoemulsification in presence of pseudoexfoliation necessitates appropriate surgical technique to avoid intraoperative complications. Pseudoexfoliation is associated with higher inflammatory response, significant postoperative IOP drop and satisfactory visual outcome.


Australian Adolescents and Young Adults-Trends in Cancer Incidence, Mortality, and Survival Over Three Decades.
Cancer is a significant health concern for adolescents and young adults (AYAs; aged 15-24 years). Monitoring population-level changes in incidence, mortality, and survival is complicated by the lack of published data presenting statistics separately for AYAs. This study synthesizes and reviews data on AYA cancers in Australia, including trends in incidence and mortality. National data were extracted for 1980-2012, primarily from the Australian Cancer Database and Australian National Mortality Database. Incidence, mortality, and survival trends are described, and incidence and mortality projections are reported. In 2000-2009, the annual all-cancer incidence was 31.7 cases per 100,000 population, and the mortality rate was 4.1 per 100,000. Incidence, mortality, and survival varied widely, indicating areas of concern. Melanoma was the most common cancer, and bone cancer had the highest mortality and poorest survival rates. All-cancer incidence rates peaked in the late 1990s, but then declined, largely due to melanoma. All-cancer mortality decreased throughout the study period, but showed no improvements for some common sites (i.e., brain, bone, soft tissue). Further reductions in all-cancer incidence and mortality are projected for the next decade, although specific cancers (colorectal cancers and lymphomas) were projected to increase in incidence. Observed Australian cancer trends are largely consistent with trends for other high-income populations. While overall decreases in incidence and mortality are encouraging, consistently high mortality and poor survival for some cancers remain concerning. Planned data initiatives for AYAs with cancer will aid in resolving whether trends continue and projections are realized in the future.


Glass-Forming Ability and Soft Magnetic Properties of (Co75Ti25)100-xFex (x; 0-20 at.%) Systems Fabricated by SPS of Mechanically Alloyed Nanopowders.
Due to their outstanding mechanical properties and soft magnetic characteristics, cobalt-based metallic glassy alloys have stimulated much interesting research. These metastable ferromagnetic materials possess very small magnetocrystalline anisotropy, and almost zero magnetostriction. They reveal low coercivity, extremely low core loss, moderate saturation polarization, and very high magnetism. Despite these attractive physical behaviors, Co-based metallic glasses are difficult to obtain by the melting/casting and conventional rapid solidification techniques due to their poor glass-forming ability. In the present study, we succeed in preparing (Co75Ti25)100-xFex (x; 0-20 at.%) metallic glassy powders, using a mechanical alloying approach. The end product of the as-prepared powders was consolidated into full dense cylinders with large-diameter and thickness (2 × 2 cm), using spark plasma sintering technique. The results have shown that the consolidation step did not lead to any undesired crystallizations or phase transformations, and the as-consolidated buttons maintained their unique short-range order structure. These bulk metallic glassy systems possessed high glass-transition and crystallization temperatures, suggesting their high thermal stability. However, they showed low values of the reduced glass-transition temperatures, indicating that this system is difficult to prepare by the conventional way of preparations.


Using a 3D Culture System to Differentiate Visceral Adipocytes In Vitro.
It has long been recognized that body fat distribution and regional adiposity play a major role in the control of metabolic homeostasis. However, the ability to study and compare the cell autonomous regulation and response of adipocytes from different fat depots has been hampered by the difficulty of inducing preadipocytes isolated from the visceral depot to differentiate into mature adipocytes in culture. Here, we present an easily created 3-dimensional (3D) culture system that can be used to differentiate preadipocytes from the visceral depot as robustly as those from the sc depot. The cells differentiated in these 3D collagen gels are mature adipocytes that retain depot-specific characteristics, as determined by imaging, gene expression, and functional assays. This 3D culture system therefore allows for study of the development and function of adipocytes from both depots in vitro and may ultimately lead to a greater understanding of site-specific functional differences of adipose tissues to metabolic dysregulation.


Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice.
Ras oncogenes owe their transforming properties to single point mutations in the sequence coding for the active site of the p21 protein. These mutations lead to changes in cellular proliferation and induce tumorigenic properties. Point mutations represent a well-defined target for antisense oligonucleotides that can specifically suppress the translation of the targeted mutant mRNA. We show that the stability and cellular disponibility of antisense oligonucleotides can be markedly improved by adsorption to polyalkylcyanoacrylate nanoparticles. Nanoparticle-adsorbed antisense oligonucleotides directed to a point mutation (G-->U) in codon 12 of the Ha-ras mRNA selectively inhibited the proliferation of cells expressing the point-mutated Ha-ras gene at a concentration 100 times lower than free oligonucleotides. In addition they markedly inhibited Ha-ras-dependent tumor growth in nude mice after subcutaneous injection. These experiments show that inhibition of ras oncogenes by antisense oligonucleotides can block tumor development even though ras oncogenic activation might be an early event in tumor progression.


Accumulation and effects of 90-day oral exposure to Dechlorane Plus in quail (Coturnix coturnix).
While a number of studies have addressed bioaccumulation of the flame retardant Dechlorane Plus (DP), little information is available regarding the adverse effects of DP on animals, especially on bird species. In the present study, male common quails (Coturnix coturnix) were consecutively exposed to commercial DP-25 by gavage for 90 d at 1-mg/kg/d, 10-mg/kg/d, and 100-mg/kg/d dosages. Concentrations of DP isomers in liver, muscle, and serum were determined after exposure. Liver enzyme activity involved in xenobiotic biotransformation processes and oxidative stress was measured, as well as glutathione and maleic dialdehyde content. The results showed that DP was more prone to accumulate in the liver than in muscle and serum in all exposed groups. In tested tissues, syn-DP dominated in the high-exposure groups (10 and 100 mg/kg/d), whereas anti-DP tended to accumulate in the low-exposure group (1 mg/kg/d). The concentration ratios of anti-DP to total DP (fanti values) in the tissues examined were close to commercial DP in the low-exposure group; however, the fanti values were significantly decreased in the high-exposure groups. Enzyme activity of 7-pentoxyresorufin-O-demethylase (PROD) decreased significantly in all exposed groups compared with the control group, whereas activity of erythromycin N-demethylase (ERND) and the antioxidant enzyme catalase significantly increased in high-exposure groups. The results implied that DP exposure levels influenced isomeric compositions in organs and that DP exposure altered hepatic alkoxyresorufin O-dealkylase (AROD) activity and contributed to the biological effects of DP.


Fungal co-culture increases ligninolytic enzyme activities: statistical optimization using response surface methodology.
The optimization of ligninolytic enzyme (LE) activities in a novel fungal co-culture between Pycnoporus sanguineus and Beauveria brongniartii were studied using a Plackett-Burman experimental design (PBED) and a central composite design (CCD). In addition, H2O2 role was analyzed. Laccase (EC. 18.104.22.168) and MnP (EC 22.214.171.124) activities of P. sanguineus increased 6.0- and 2.3-fold, respectively, in the co-culture with B. brongniartii. The H2O2 content was higher in the co-culture (0.33-7.12-fold) than in the P. sanguineus monoculture. The PBED revealed that yeast extract (YE), FeSO4, and inoculum amount were significant factors for laccase and MnP activities and H2O2 production in the co-culture, which increased by 8.2-, 5.2- and 1.03-fold, respectively. The YE and FeSO4 were studied using a CCD to optimize the studied response variables. Laccase activity was enhanced 1.5-fold by CCD, the optimal amount of YE was 0.366 g L-1. Quadratic term of FeSO4 modulated MnP activity and was associated with a 4.28-fold increase compared to the PBED. Both YE and its quadratic term significantly affected H2O2 production; however, the CCD did not enable an increase in H2O2 production. Pearson correlation indicated an increase in laccase (r2=0.4411, p = 0.0436) and MnP (r2=0.5186, p = 0.0198) activities following increases in H2O2 in the co-culture system.


Hollow Bragg fiber bundles: when coupling helps and when it hurts.
Coupling between leaky modes of collinear hollow-core Bragg fibers is considered. It is found that coupling is unusually strong because of resonant effects in the interfiber cavity when the fibers are touching each other and decreases dramatically with the first tens of nanometers of fiber separation. However, residual coupling with a strength proportional to the fiber radiation loss is long range, decreasing as an inverse square root of the interfiber separation and exhibiting periodic variation. The possibility of building a directional coupler from touching Bragg fibers is discussed in view of the findings.


High-efficiency large-bandgap material for polymer solar cells.
High-molecular-weight conjugated polymer HD-PDFC-DTBT with N-(2-hexyldecyl)-3,6-difluorocarbazole as the donor unit, 5,6-bis(octyloxy)benzothiadiazole as the acceptor unit, and thiophene as the spacer is synthesized by Suzuki polycondensation. HD-PDFC-DTBT shows a large bandgap of 1.96 eV and a high hole mobility of 0.16 cm(2) V(-1) s(-1) . HD-PDFC-DTBT:PC71 BM-based inverted polymer solar cells (PSCs) give a power conversion efficiency (PCE) of 7.39% with a Voc of 0.93 V, a Jsc of 14.11 mA cm(-2) , and an FF of 0.56.


Evaluation of Salivary Opiorphin, pH and Flow Rate in Oral Submucous Fibrosis - A Case - Control Observational Study.
The aim of the study was to evaluate the salivary pH, flow rate and opiorphin in Oral submucous fibrosis patients and to compare them with healthy individuals. A comparative study was conducted to evaluate the salivary opiorphin levels, pH and flow rate among 78 patients (39 Oral submucous fibrosis + 39 control). Burning sensation was assessed using VAS score. Opiorphin levels were assessed using Cusabio Human Salivary Opiorphin ELISA kit. Salivary flow rate was assessed using graduated syringes and salivary pH was assessed using Hydrion salivary pH strips. Kolmogorov-Smirnov and Shapiro Wilk test were assessed for normality testing and distribution. Inferential statistics was done by using Unpaired t test/Independent sample t test to compare the mean values of variables included in the study among the OSMF and healthy patients. There was statistically significant difference in pH and flow rate with a reduction in the mean pH (p=0.024) and flow rate (p<0.01) among the oral submucous fibrosis patients compared to the control group. A statistically significant increase (p<0.01) in salivary opiorphin levels was noted in the oral submucous fibrosis patients. Majority of the study participants had mild to moderate burning sensation. This study was a pilot evaluation of salivary opiorphin in OSMF. Salivary opiorphin could be used as an objective marker for chronic subjective conditions The pre-treatment and post treatment evaluation of salivary opiorphin could provide more insight on its role.


The application of prolonged electroencephalographic monitoring and video recording to the diagnosis of epilepsy.
This study reports the results of the application of intensive monitoring by electroencephalogram (EEG) combined with video recording as an aid to the diagnosis of epilepsy. A group of 622 patients was investigated; useful information was obtained in approximately 50% of these patients. Ten per cent of the patients with suspected epilepsy had a seizure during the period of recording. The combined analysis of the video recording and the EEG provided valuable evidence in the analysis of complex partial seizures and highlights the high prevalence of pseudoseizures in patients who are suspected of having epilepsy.


Efficient compressive sensing of ECG segments based on machine learning for QRS-based arrhythmia detection.
A novel method for efficient telemonitoring of arrhythmia based on using QRS complexes is proposed. Two features, namely, sum of absolute differences (SAD) and maximum of absolute differences (MAD) are efficiently computed for each ECG segment in the bio-sensor. The computed features can be transmitted from the bio-sensor using wireless channel, and they can be used in the receiver for determining the absence of QRS complex in the segment. By avoiding computationally expensive signal reconstruction for the ECG segments without QRS complex, it is shown, using simulation results, that computation time can be reduced by approximately 7.4% for long-term telemonitoring of QRS-based arrhythmia. Detection of the absence of QRS complex can be carried out in around 7 milliseconds in a standard laptop computer with 2.2GHz processor and 8GB RAM.


Aldosterone-reversible decrease in the density of renal peripheral benzodiazepine receptors in the rat after adrenalectomy.
A statistically significant decrease in the density of peripheral benzodiazepine receptors was observed in renal membranes of rats beginning 2 weeks after adrenalectomy when compared with sham-operated controls. This decrease in peripheral benzodiazepine receptor density was manifest as a decrease in the maximum binding of two ligands, [3H]Ro 5-4864 and [3H]PK 11195, without accompanying changes in their Kd for this site. Similar changes were not seen in another aldosterone-sensitive organ, the submandibular salivary gland. The decrease in peripheral benzodiazepine receptor density observed in adrenalectomized rat renal membranes was restored to control levels after 1 week of aldosterone administration using a dose (12.5 micrograms/kg/day) that had no effect on peripheral benzodiazepine receptor density in sham-operated animals. In contrast, dexamethasone administration (50 micrograms/kg/day, 1 week) had no effect on renal peripheral benzodiazepine receptor density when administered to either adrenalectomized or sham-operated rats. Further, adrenal demedullation had no effect on renal peripheral benzodiazepine receptor density or affinity. The decrease in peripheral benzodiazepine receptor density was localized to the renal cortex and the outer stripe of the medulla by gross dissection of renal slices and renal tissue section autoradiography. The specific effect of adrenalectomy on renal peripheral benzodiazepine receptor density, the lack of direct effect of aldosterone on [3H] Ro 5-4864 binding and the localization of the change in peripheral benzodiazepine receptor density to the renal cortex and outer stripe suggest that these changes may reflect an adaptation of the renal nephron (possibly the distal convoluted tubule, intermediate tubule and/or the collecting duct) to the loss of mineralocorticoid hormones.


Surgical Delay of the Nipple-Areolar Complex in High-risk Nipple-sparing Mastectomy Reconstruction.
As nipple-sparing mastectomy gains increasing popularity, minimizing the risk of nipple necrosis continues to be of critical importance to patients and surgeons. Patients with large or ptotic breasts, scars from previous cosmetic and/or oncologic breast surgery, or previous irradiation have often been denied nipple-sparing mastectomy (NSM) because of increased risk of nipple necrosis. A variety of interventions have been suggested to minimize the ischemic insult to the nipple-areolar complex (NAC). This article presents our experience in 26 high-risk patients with surgical delay of the NAC.


The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective.
Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a rare recessively inherited disease that is associated with early dementia and bone cysts with fractures. Here, we review the genetic causes of PLOSL with loss-of-function mutations or deletions in one of two genes, TYROBP and TREM2, encoding for two proteins DNAX-activating protein 12 (DAP12) and triggering receptor expressed on myeloid cells-2 (TREM2). TREM2 and DAP12 form an immunoreceptor signaling complex that mediates myeloid cell, including microglia and osteoclasts, development, activation, and function. Functionally, TREM2-DAP12 mediates osteoclast multi-nucleation, migration, and resorption. In microglia, TREM2-DAP12 participates in recognition and apoptosis of neuronal debris and amyloid deposits. Review of the complex immunoregulatory roles of TREM2-DAP12 in the innate immune system, where it can both promote and inhibit pro-inflammatory responses, is given. Little is known about the function of TREM2-DAP12 in normal brain homeostasis or in pathological central nervous system diseases. Based on the state of the field, genetic testing now aids in diagnosis of PLOSL, but therapeutics and interventions are still under development.


Distinct roles for the mTOR pathway in postnatal morphogenesis, maturation and function of pancreatic islets.
While much is known about the molecular pathways that regulate embryonic development and adult homeostasis of the endocrine pancreas, little is known about what regulates early postnatal development and maturation of islets. Given that birth marks the first exposure to enteral nutrition, we investigated how nutrient-regulated signaling pathways influence postnatal islet development in mice. We performed loss-of-function studies of mechanistic target of rapamycin (mTOR), a highly conserved kinase within a nutrient-sensing pathway known to regulate cellular growth, morphogenesis and metabolism. Deletion of Mtor in pancreatic endocrine cells had no significant effect on their embryonic development. However, within the first 2 weeks after birth, mTOR-deficient islets became dysmorphic, β-cell maturation and function were impaired, and animals lost islet mass. Moreover, we discovered that these distinct functions of mTOR are mediated by separate downstream branches of the pathway, in that mTORC1 (with adaptor protein Raptor) is the main complex mediating the maturation and function of islets, whereas mTORC2 (with adaptor protein Rictor) impacts islet mass and architecture. Taken together, these findings suggest that nutrient sensing may be an essential trigger for postnatal β-cell maturation and islet development.


Association of Resting Heart Rate with Infrarenal Aortic Diameter: A Cross Sectional Study in Chinese Hypertensive Adults.
Elevated resting heart rate (RHR) has been shown to be a risk marker for cardiovascular disease. Results from studies on the effects of RHR in large arteries are limited to the functional changes of those arteries, while the association between RHR and aortic diameter remains largely understudied. This was a cross sectional study of hypertensive Chinese adults from rural areas. The maximum infrarenal aortic diameter (maxIAD) from renal arteries to the iliac bifurcation was obtained by ultrasound. MaxIADs in different RHR groups were compared in males and females separately because of the significant differences between sexes. Multiple regression analysis was used to determinate the correlation between RHR and maxIAD. Further interactions between three factors (BMI, smoking, and anti-hypertensive regimens) and RHR for maxIAD were examined using subgroup analysis. 19,200 subjects were enrolled in the study, with an average age of 64.8±7.4 years and 61.6% females. Only 22 cases (0.11%) were detected with AAA, with males (n = 17) presenting a higher AAA incidence than females (n = 5). In subjects ≥65 years, there were 18 (0.19%) AAA, and 15 (83.3%) had a history of smoking. In the total subjects, the mean maxIAD ranged from 15.7±2.1 mm to 15.2±2.2 mm as RHR changed from the lowest quartile to the highest (≥84 bpm) in males, with a similar tendency observed in females. The correlation coefficient of RHR on maxIAD was -0.17 in males and -0.12 in females. Further subgroup analysis revealed that smoking exaggerated the correlation between RHR and maxIAD, but only in females. A low AAA incidence was observed in this hypertensive Chinese population. There was a negative association between RHR and maxIAD, potentially exaggerated by smoking, especially in females.


[IgG4-related lung disease: analysis of 8 cases and literature review].
Objective: To improve the understanding and treatment of IgG4-related lung disease (IgG4-RLD). Methods: The clinical characteristics, serum IgG4 levels, pathological features, chest CT, therapy and prognosis of 8 patients with IgG4-RLD were retrospectively analyzed. These patients were admitted to the People's Liberation Army General Hospital and the pathological diagnosis was made between December 2005 and March 2016. Relevant literatures were reviewed. Results: The 8 patients with IgG4-RLD included 4 men and 4 women, with an average age of (59±4) years (range, 37-74). The respiratory symptoms included shortness of breath, cough, and expectoration. Extra-pulmonary symptoms included abdominal pain, facial edema, and fever. Extrapulmonary organs were involved in 7 cases. Serum IgG4 levels were elevated in 8 cases, with an average concentration of(17±6)g/L. Chest CT showed solid lung nodules in 6, alveolar-interstitial infiltration in 5, bronchovascular lesions in 3 and ground glass shadows in 2 cases. PET/CT was performed in 2 cases and it showed multiple organ involvement with higher radioactivity uptake(SUVmax2.9-4.2). The pathological examination found lymphocyte and plasma cell infiltration in 7, fibrous tissue hyperplasia in 5, and occlusive vasculitis in 2 cases. On immunohistochemical staining, the ratio of IgG4-positive plasma cells to IgG-positive plasma cells was higher than 40%in 3 cases. The number of IgG4-positive plasma cells was 10-50/HP in 8 cases. The misdiagnosis rate was 100% before the final diagnosis was made. Three cases received glucocorticoids with immunosuppressant therapy, 2 received surgery combined with glucocorticoid therapy, 2 received glucocorticoid therapy alone, and 1 only received surgery. The follow-up time was 4-132 months, with remission in 7 cases, and disease progression in 1 case, but no death. A total of 195 cases of IgG4-RLD were reviewed from the literature, among whom 111 cases were admitted with respiratory symptoms, 144 with extra-pulmonary involvement. Serum IgG4 levels were detected in 179 cases, with an average concentration of 5.408 g/L. The nodular type was predominant, accounting for 36.9%. Of these cases, 178 received glucocorticoid treatment with disease remission. Conclusions: The major clinical manifestations of IgG4-RLD were shortness of breath, cough and expectoration. Multiple organ lesions were common. The misdiagnosis rate was extremely high. The diagnosis could be made based on pathological features and IgG4 serum levels . Glucocorticoid treatment was effective.


Use of metal-based contrast agents for in vivo MR and CT imaging of phagocytic cells in neurological pathologies.
The activation of phagocytic cells is a hallmark of many neurological diseases. Imaging them in their 3-dimensional cerebral environment over time is crucial to better understand their role in disease pathogenesis and to monitor their potential therapeutic effects. Phagocytic cells have the ability to internalize metal-based contrast agents both in vitro and in vivo and can thus be tracked by magnetic resonance imaging (MRI) or computed tomography (CT). In this review article, we summarize the different labelling strategies, contrast agents, and in vivo imaging modalities that can be used to monitor cells with phagocytic activity in the central nervous system using MRI and CT, with a focus on clinical applications. Metal-based nanoparticle contrast agents such as gadolinium, gold and iron are ideal candidates for these applications as they have favourable magnetic and/or radiopaque properties and can be fine-tuned for optimal uptake by phagocytic cells. However, they also come with downsides due to their potential toxicity, especially in the brain where they might accumulate. We therefore conclude our review by discussing the pitfalls, safety and potential for clinical translation of these metal-based neuroimaging techniques. Early results in patients with neuropathologies such as multiple sclerosis, stroke, trauma, cerebral aneurysm and glioblastoma are promising. If the challenges represented by safety issues are overcome, phagocytic cells imaging will be a very valuable tool for studying and understanding the inflammatory response and evaluating treatments that aim at mitigating this response in patients with neurological diseases.


High juvenile body weight and low insulin levels as markers preceding early diabetes in the BB rat.
Diabetes incidence in BB rats is 60-80% and our aim was to investigate whether it is possible to characterize those rats destined to develop diabetes. While the genetic background as well as the environmental factors affecting BB-rat littermates are very similar, body weight reflects some existing variance. The study involved 151 BB rats, and the body weight of each animal was measured daily from birth. Thirty-four animals became diabetic before 100 days of age, and their body weight showed a 5-10% increase compared to the non-diabetic animals for each day of life from day 1 to day 45 (p values 0.0001 to 0.05). This increased body weight in individuals destined for diabetes was seen in both sexes. When investigating whether juvenile body weight has any predictive value, we found that the incidence of diabetes at 100 days of age increased from 22.5% to 46.7% (p < 0.01) when the heaviest animals in each litter were selected. Insulin content in pancreas was examined at day 10 and 20, and was found to be significantly reduced in the BB rats with highest body weight compared with rest of the litter (p = 0.02 and p = 0.0005, respectively). The insulin concentration in peripheral blood was significantly reduced in the BB rats with highest body weight at 20 days of age (p = 0.002). When early and late diabetic BB rats were compared at time of diagnosis regarding blood glucose, degree of insulitis and number of small and large islets, no significant differences were found between the groups.


Common variable immunodeficiency in vitiligo.
Three cases of adult, non-segmental vitiligo patients in which primary, common variable immunodeficiency (CVID) was present are described. In two of the three cases, psoriasis was also present. Onset of CVID was diagnosed before vitiligo in two patients, and subsequent to the onset of vitiligo in the remaining patient. A family history of CVID was negative in all three cases. In contrast, a family history of vitiligo was present in two cases and a family history of psoriasis was present in one case. In regards to vitiligo, disease onset was gradual, with active disease in two cases, while the third case had an abrupt disease onset with borderline activity during clinical presentation. Cutaneous disease extension ranged from 2% to 12.3% in the three cases. Upon physical exam, Koebner phenomenon and signs of inflammation, such as pruritus were present in two patients; one of whom had scalp leukotrikia as well. Stress was a triggering factor in the development of vitiligo in two cases. The presence of CVID due to drugs or diseases known to cause secondary antibody deficiency were excluded in all three patients. Lastly, all patients were under treatment with immunoglobulin replacement therapy, which did not change the outcourse of vitiligo.


Toxicities of Four Parabens and Their Mixtures to Daphnia magna and Aliivibrio fischeri.
The objective of this study was to determine toxicities of four parabens (methyl paraben, MP; ethyl paraben, EP; n-propyl paraben, PP; and n-butyl paraben; BP) and their mixtures to two aquatic microorganisms, Daphnia magna and Aliivibrio fischeri. Parabens are one of the widely used preservatives for personal care products, such as cosmetics, pharmaceuticals and food also. First, each paraben was treated to D. magna to measure the toxicity levels as LC20 and LC50. The results showed their value of MP (25.2 mg/L, 73.4 mg/L), EP (18.4 mg/L, 43.7 mg/L), PP (10.4 mg/L, 21.1 mg/L) and BP (3.3 mg/L, 11.2 mg/L). Then, each of the parabens was treated to A. fischeri and calculated their EC20 and EC50 by bioluminescence inhibition test. The results showed the values of MP (2.93 mg/L, 16.8 mg/L), EP (1.18 mg/L, 6.74 mg/L), PP (0.51 mg/L, 5.85 mg/L) and BP (0.21 mg/L, 2.34 mg/L). These four parabens belong to the group classified as being 'harmful to aquatic organisms' (above 10 mg/L, below 100 mg/L). After measuring the toxicity, EC20 values of two or more parabens were tested in order to investigate their toxicity. A total of ten combinations of four parabens were tested. As a result, the bioluminescence inhibition test of A. fischeri showed that the toxicity of mixture parabens was stronger than that of a single compound and combinations of three parabens showed the highest bioluminescence inhibition. These results showed that independent toxicity of paraben was maintained. Therefore, it can be predictable that the toxicity of paraben is getting stronger by the addition of other parabens.


[Allergy and hypersensitivity to drugs: anaphylaxis].
Anaphylaxis due to allergic or non-allergic hypersensitivity to drugs is an acute fatal or potentially fatal reaction. The estimate rate of 3.2 cases of drug-associated fatal anaphylaxis per 100.000 inhabitants per year seems to be approximately 10 times greater in hospitalised patients. The most common agents that are responsible for anaphylaxis in hospitalised patients are muscle relaxants, latex, antibiotics, anaesthesia-inducing drugs, plasma expanders followed by local anaesthetics and iodinated radio contrast media, and many others. Antibiotics and non-steroid anti-inflammatory drugs (NSAID) are the common cause of anaphylaxis in non-hospitalised patients. Predictive tests for high-risk patients have not been established. However, several procedures for prevention are proposed. These include preoperative screening to detect sensitisation to anaesthetic drugs and latex, or pre-treatment with antihistamines and corticosteroids to prevent anaphylaxis to iodinated contrast media. Challenge tests are useful for the determination of a safe anaesthetic or NSAID. Unfortunately, the causative agents cannot be identified in all cases of anaphylaxis. Subjects at risk for idiopathic anaphylaxis should have epinephrine available for self-administration.


[The advertisements of drug in newspaper by Ginkou Kishida].
Ginko Kishida, who was a journalist formerly, took advantage of newpaper to publicize ophthalmicus. He put an advertisement expressed by only characters in Yokohama-mainichi-shinbun just founded. After that, he employed advertisement with illustration. In the beginning, the advertisement laid stress on spreading the name of the ophthalmicus, "Seikisui." The advertisement published in Meiji 8th, appealed variation of ophthalmic diseases and their causes, besides it expressed effective of "Seikisui." His contributions to convey the information of drug were difficult to distinguish between advertisement and articles. Nowadays, advertisement of drug imitating the articles are popular. Needless to say, Ginko Kishida was the pioneer of the style of present advertisement of drug.


Longitudinal associations between gratitude and depression 1 year later among adult cystic fibrosis patients.
Individuals with cystic fibrosis (CF) are confronted by a range of difficult physical and psychosocial sequelae. Gratitude has drawn growing attention as a psychosocial resource, but it has yet to be examined among adults with CF. The current investigation evaluated longitudinal associations between trait gratitude and subsequent outcomes from depression screening 12 months later, adjusting for disease severity (FEV1% predicted) and other significant clinical or demographic covariates. Participants were 69 adult CF patients recruited from a regional adult treatment center. They completed a validated measure of gratitude (Gratitude Questionnaire-6) at baseline and a screening measure of depression (Hospital Anxiety and Depression Scale) at 12-month follow-up. In a logistic regression analysis controlling for disease severity, higher levels of baseline gratitude were associated with reduced likelihood of depression caseness at 12 months (OR .83, 95% CI .73-.91, p = .001). Gratitude remained predictive after adjusting for other psychosocial resource variables (i.e., perceived social support and positive reframing coping). Findings offer an initial indication of the potential salutary role of dispositional gratitude in an understudied clinical population.


Characteristics of follicular cell-derived thyroid carcinomas occurring after external radiation exposure: results of a case control study nested in a cohort.
Radiation exposure is the only well-established risk factor for follicular cell-derived thyroid carcinoma. To compare the clinical characteristics and outcome of thyroid carcinoma in patients with and without a history of radiation exposure, we performed a case control study nested in a cohort of 2,196 patients treated for a papillary or a follicular thyroid cancer at the Institut Gustave Roussy. The study was performed on 91 cases (71% females) and their 273 controls matched for gender, age at thyroid cancer diagnosis (+/-3 years), and period of initial thyroid cancer treatment (+/-6 years). More than 85% of the cases have been first exposed to external radiation before the age of 30 years. Thyroid cancers were more frequently multifocal in cases than in controls (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.3-4.8), and local residual tumor was more frequently observed in cases, but the other clinical features did not differ overall. Female cases with a history of radiation exposure more frequently had a tumor of follicular histology than female controls (OR = 2.7, 95% CI: 1.1-6.5), and conversely the frequency of follicular histology was similar in male cases and in male controls (OR = 0.3, 95% CI: 0.1-1.4). The risks of recurrence and of thyroid cancer related death were similar in cases and in controls.


Cell death by apoptosis in epidermal biology.
Homeostasis in continually renewing tissues is maintained by a tightly regulated balance between cell proliferation, cell differentiation, and cell death. Until recently, proliferation was thought to be the primary point of control in the regulation of normal tissue kinetic homeostasis and as such has been the major focus of both understanding the etiology of disease and developing therapeutic strategies. Now, physiologic cell death, known as apoptosis (ă-pŏp-to' sĭs, ă-po-to' sĭs [Thomas CL (ed.): Taber's Cyclopedic Medical Dictionary. F.A. Davis, Co., Philadelphia, 1989)] has gained scientific recognition as an active regulatory mechanism, complementary, but functionally opposite, to proliferation with important roles in shaping and maintaining tissue size and prevention of disease. In this review we will describe the concept of apoptosis and discuss possible molecular mechanisms of its regulation that may have implications for skin biology.


Evaluation of cancer chemopreventive agents using clones derived from a human prostate cancer cell line.
The successful use of clonal selection through fluctuation analysis of human cancer cells as a means for studying tumor progression has been previously reported. Three clones derived from a parental population of human prostate cancer (LNCaP) cells were selected based on proliferation, hormone sensitivity and anchorage-independent growth. The effects of five potential cancer preventive agents were evaluated using cell proliferation, anchorage-independent growth and apoptosis as end-points. Clone 21 cells, which represent a presumptive normal phenotype, were generally more sensitive than Clone 17 and Clone 6 cells, which represent a more malignant phenotype, to fluasterone, 7beta-HF, L-selenomethionine and troglitazone in assays for proliferation and/or apoptosis. The results confirm the efficacy of the above agents as cancer chemopreventive agents and support our contention that clonal selection of established human cancer cells provides a model to study the efficacy of chemopreventive agents.


[Foreign body-induced angiosarcoma 60 years after a shell splinter injury].
An 84-year-old gentleman developed an angiosarcoma in the lateral temporal fossa 60 years after a World War II injury. The tumour resection confirmed the close spatial relationship of the tumour and a shell splinter. Analysis of the metallic composition showed no clear carcinogenic potential of the ingredients; an inflammation-related carcinogenesis seems more probable. A review of the literature revealed two similar cases.


Formation of a covalent complex between the terminal protein of pneumococcal bacteriophage Cp-1 and 5'-dAMP.
Incubation of extracts of Cp-1-infected Streptococcus pneumoniae with [alpha-32P]dATP produced a labeled treatment with micrococcal nuclease and sensitive to treatment with proteinase K. Incubation of the 32P-labeled protein with 5 M piperidine for 4 h at 50 degrees C released 5'-dAMP, indicating that a covalent complex between the terminal protein and 5'-dAMP was formed in vitro. When the four deoxynucleoside triphosphates were included in the reaction mixture, a labeled complex of slower electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels than the terminal protein-dAMP complex was also found, indicating that the Cp-1 terminal protein-dAMP complex can be elongated and, therefore, that it is an initiation complex. Treatment of the 32P-labeled terminal protein-dAMP complex with 5.8 M HCl at 110 degrees C for 2 h yielded phosphothreonine. These results, together with the resistance of the terminal protein-DNA linkage to hydroxylamine, suggest that the Cp-1 terminal protein is covalently linked to the DNA through a phosphoester bond between L-threonine and 5'-dAMP, namely, a O-5'-deoxyadenylyl-L-threonine bond.


An Overview of Hypoglycemia in Children Including a Comprehensive Practical Diagnostic Flowchart for Clinical Use.
Hypoglycemia is the result of defects/impairment in glucose homeostasis. The main etiological causes are metabolic and/or endocrine and/or other congenital disorders. Despite hypoglycemia is one of the most common emergencies in neonatal age and childhood, no consensus on the definition and diagnostic work-up exists yet. Aims of this review are to present the current age-related definitions of hypoglycemia in neonatal-pediatric age, to offer a concise and practical overview of its main causes and management and to discuss the current diagnostic-therapeutic approaches. Since a systematic and prompt approach to diagnosis and therapy is essential to prevent hypoglycemic brain injury and long-term neurological complications in children, a comprehensive diagnostic flowchart is also proposed.


Effects of steroid blockers on LH-induced ovulation in the domestic fowl, Gallus domesticus.
The spontaneous ovulation of hens was suppressed by daily injection of PMSG. The LH injected to overcome the block was accompanied by one of 4 compounds known to inhibit steroidogenesis at different sites in the biosynthetic pathway. A dose of 300 mg aminoglutethimide phosphate, which inhibits the conversion of cholesterol to 20 alpha-hydroxycholesterol, blocked the LH-induced ovulation and prevented the normal rise in plasma progesterone. Metyrapone, an inhibitor of 11 beta-hydroxylase, and SC 12937 and AY 9944, inhibitors of cholesterol synthesis, did not prevent ovulation or the progesterone rise induced by exogenous LH. Administration of progesterone overcame the inhibitory effect of aminoglutethimide, and it is suggested that progesterone is involved in the ovulatory process of the fowl.


Keratan sulphate as a secretory product of human endometrium: cyclic expression in normal women.
The distribution of keratan sulphate (KS) in normal endometrium has been studied by immunohistochemistry using monoclonal antibody 5D4. KS is present in association with glandular epithelium throughout the normal cycle. Production is hormonally regulated, as indicated by the significant increase observed in the secretory phase of the cycle. Intracellular immunoreactivity increases to a maximum 3 days after the luteinizing hormone (LH) peak. This is followed by an increase in secreted KS from 4 days after the LH peak, and essentially all endometrial glands showed immunoreactive deposits by 5 days after the LH peak. Beginning on day 7 after the LH peak, a fraction of glands was observed to have lost the epitope. Nevertheless, KS remained in a significant proportion of the gland lumens 9 days after the LH peak. The data suggest that analysis of secretory KS in women gives an index of hormonally regulated epithelial differentiation in the peri-implantation phase.


Technology-enhanced Interactive Teaching of Marginal, Joint and Conditional Probabilities: The Special Case of Bivariate Normal Distribution.
Data analysis requires subtle probability reasoning to answer questions like What is the chance of event A occurring, given that event B was observed? This generic question arises in discussions of many intriguing scientific questions such as What is the probability that an adolescent weighs between 120 and 140 pounds given that they are of average height? and What is the probability of (monetary) inflation exceeding 4% and housing price index below 110? To address such problems, learning some applied, theoretical or cross-disciplinary probability concepts is necessary. Teaching such courses can be improved by utilizing modern information technology resources. Students' understanding of multivariate distributions, conditional probabilities, correlation and causation can be significantly strengthened by employing interactive web-based science educational resources. Independent of the type of a probability course (e.g. majors, minors or service probability course, rigorous measure-theoretic, applied or statistics course) student motivation, learning experiences and knowledge retention may be enhanced by blending modern technological tools within the classical conceptual pedagogical models. We have designed, implemented and disseminated a portable open-source web-application for teaching multivariate distributions, marginal, joint and conditional probabilities using the special case of bivariate Normal distribution. A real adolescent height and weight dataset is used to demonstrate the classroom utilization of the new web-application to address problems of parameter estimation, univariate and multivariate inference.


Haematological malignancies and acute kidney injury requiring nephrology consultation: challenging the worst of the worst.
Acute kidney injury (AKI) often complicates the course of haematological malignancies (HMs) and confers a worse prognosis. The majority of these patients are managed by the attending physician, yet, a small group, mostly coincident with the worst presentation and outcomes, requires nephrology consultation, challenging the clinician with ethical issues regarding the decision to initiate or forgo renal support therapy. The purpose of this work is to identify the prognostic determinants for in-hospital mortality in this population. A retrospective, observational chart review was undertaken at a single tertiary referral oncological centre. We reviewed the medical records of in-hospital patients with AKI and HM between 1 January 1995 and 31 December 2014 who met the criteria for RIFLE (Risk, Injury, and Failure; and Loss; and End-stage kidney disease) classification of I or higher and were followed by a nephrologist. Three hundred and forty-five patients were included in the study. Predictors of in-hospital death in patients with HM and AKI were septic shock [odds ratio (OR) 4.290 (95% CI 2.058-8.943)], invasive mechanical ventilation (IMV) [OR 4.305 (95% CI 2.075-8.928)] and allogeneic stem cell transplantation (SCT) [OR 2.232 (95% CI 1.260-3.953)]. The combination of each risk factor was used to estimate the probability of dying. Patients with all three risk factors had a risk of death of 86%. Septic shock, IMV and allogeneic SCT were identified as independent predictors of death in patients with HM and AKI, with only a small chance of survival if all three were present. Depending on the combination of risk factors, the indication for aggressive life support therapies, such as RST, might be questionable.


Shedding light on auxin movement: light-regulation of polar auxin transport in the photocontrol of plant development.
By being sessile, plants have evolved a remarkable capacity to perceive and respond to changes in environmental conditions throughout their life cycle. Light represents probably the most important environmental factor that impinge on plant development because, other than supplying the energy source for photosynthesis, it also provides seasonal and positional information that are essential for the plant survival and fitness. Changes in the light environment can dramatically alter plant morphogenesis, especially during the early phases of plant life, and a compelling amount of evidence indicates that light-mediated changes in auxin homeostasis are central in these processes. Auxin exerts its morphogenetic action through instructive hormone gradients that drive developmental programs of plants. Such gradients are formed and maintained via an accurate control on directional auxin transport. This review summarizes the recent advances in understanding the influence of the light environment on polar auxin transport.


A modified version of the Molly rumen model to quantify methane emissions from sheep.
We modified the rumen submodel of the Molly dairy cow model to simulate the rumen of a sheep and predict its methane emissions. We introduced a rumen hydrogen (H2) pool as a dynamic variable, which (together with the microbial pool in Molly) was used to predict methane production, to facilitate future consideration of thermodynamic control of methanogenesis. The new model corrected a misspecification of the equation of microbial H2 utilization in Molly95, which could potentially give rise to unrealistic predictions under conditions of low intake rates. The new model included a function to correct biases in the estimation of net H2 production based on the default stoichiometric relationships in Molly95, with this function specified in terms of level of intake. Model parameters for H2 and methane production were fitted to experimental data that included fresh temperate forages offered to sheep at a wide range of intake levels and then tested against independent data. The new model provided reasonable estimates relative to the calibration data set, but a different parameterization was needed to improve its predicted ability relative to the validation data set. Our results indicate that, although feedback inhibition on H2 production and methanogen activity increased with feeding level, other feedback effects that vary with diet composition need to be considered in future work on modeling rumen digestion in Molly.


Echocardiographic and phonocardiographic confirmation of suspected caged mitral valve malfunction.
Seven patients studied by echocardiography with and without simultaneous phonocardiography for suspected malfunction of a caged mitral valve prosthesis are presented. In case 1, with inaudible prosthetic clicks, thrombosis of the cage and immobility of the ball were suggested by echocardiographic studies and confirmed at surgery. In case 2, simultaneous echocardiographic and phonocardiographic studies demonstrated wide and variable intervals between the aortic second sound the the opening click and also "sticking" of the ball. In case 3 a thrombus prevented full motion of the ball to the apex of the cage, which was seen on the echocardiogram, while in case 4, with a thrombus within the ventricle and prosthesis, the prosthetic opening click was present intermittently and was associated with only subtle echocardiographic changes. In case 5, echocardiographic studies demonstrated abnormal rocking of the cage secondary to severe prosthetic dehiscence. In case 6, dul prosthetic clicks were to be secondary to a low cardiac-output state. In case 7, with multiple valve prostheses, simultaneous echocardiographic and phonocardiographic studies allowed identification of individual valve sounds and abnormal timing of valve opening. Based on these studies, we believe that echocardiography and simultaneous phonocardiography can yield very useful information in the evaluation of patients with suspected malfunction of a caged mitral valve prosthesis.


Holistic nursing can improve family engagement.
Family engagement is relevant to patient outcomes and ensures patient efficacy, support, and quality of life. Such engagement is facilitated by holistic nursing methods. This article discusses the importance of and barriers to family engagement and practical strategies for its implementation.


[Application of DNA fingerprinting to investigation of genetic relationships between laboratory rabbit strains].
It is well known that laboratory rabbits are not controlled genetically like laboratory mice and rats. In order to test the usefulness of DNA fingerprinting in investigation of genetic uniformity of the laboratory rabbits strains and their relationships, we applied DNA fingerprinting using bacteriophage M13 probe to five strains (2 inbreds (JWY-NIBS and DuY-NIBS) and 3 outbreds (JW-NIBS, Icl:JW and WHHL)). DNA fingerprints of 2 inbred strains showed the same banding patterns within each strain but the strain-specific patterns. Although there were no rabbits showing the same banding patterns in 3 outbred strains, average percent differences (APD) were 13.7 to 18.6. A dendrogram based on APD of DNA fingerprints was constructed by 2 large clusters, JW group and DuY. The dendrogram was essentially similar to that based on rabbit mandible measurements. These results suggest that DNA fingerprinting is available not only for the genetic monitoring of the laboratory rabbit strains but also for the investigation of their genetic relationships.


Pulmonary surfactant.
Pulmonary surfactant reduces the surface tension of the alveolar air-liquid interface, thereby providing mechanical stability and preventing alveolar atelectasis. More than 50% of surfactant is dipalmitoyl phosphatidylcholine, a material that is capable of reducing the surface tension of the alveolar interface to uniquely low values. The functions of the remaining 25% unsaturated phosphatidylcholines, 5-10% phosphatidylglycerol, 5% cholesterol, and 8-10% protein are unknown. Surfactant is synthesized by alveolar epithelial type II cells and is probably secreted as a lipoprotein complex. Lamellar bodies, which distinguish type II cells, are likely to be intracellular sites of transport of processing. The catabolism of surfactant after it is secreted into the alveolar lumen is complicated and involves different turnover times for the phosphatidylcholines, phosphatidylglycerol, and the proteins. The metabolic events are under hormonal control and may involve an interplay between beta-adrenergic agonists cAMP, and prostaglandins. In disease, such as the neonatal and adult respiratory distress syndromes, derangements in the metabolic processes may produce surfactant that is abnormal with respect to its chemical and physical properties.


Free and coordinated biarsolyls.
A trace side product from the reaction of [Mo(AsC4Me4)(CO)3(η-C5H5)] with [Mn(THF)(CO)2(η5-C5H4Me)] was identified as the biarsolyl complex [Mn2{μ-(AsC4Me4)2}(CO)4(C5H4Me)2] on the basis of a strategic synthesis from [Mn(THF)(CO)2(η5-C5H4Me)] and the pre-formed and structurally characterised biarsolyl (AsC4Me4)2. Crystallographic and computational data for this first example of a biarsolyl complex and free biarsolyls are discussed in the context of those for free biarsolyls.


Simultaneous determination of codeine and pyridoxine in pharmaceutical preparations by first-derivative spectrofluorimetry.
A method for the simultaneous determination of codeine and pyridoxine was developed, based on the measurement of their native fluorescence signals, by using first-derivative spectrofluorimetry to resolve the mixture. Codeine was measured at lambda(em) = 309 nm, and pyridoxine was measured at lambda(em) = 450 nm. Instrumental parameters were optimized, and the emission spectra were recorded between 275 and 475 nm, at lambda(ex) = 255 nm and excitation and emission slit widths of 2.5 and 10 nm, respectively. Systematic studies on the influence of species usually present along with the analytes (such as caffeine, ascorbic acid, paracetamol, and thiamine) were also performed. The calibration graphs were linear over the ranges of 0.5-7.0 and 0.1-1.0 microg/mL for codeine and pyridoxine, respectively, and the relative standard deviations (n = 10) were about 3%. The method was successfully applied to the determination of codeine and pyridoxine in solutions of synthetic mixtures and in synthetic and semisynthetic pharmaceutical formulations.


Is the prophylactic antidepressant efficacy of lithium in bipolar I disorder dependent on study design and lithium level?
In the 1970s, several randomized controlled trials demonstrated significant antimanic and antidepressant properties of lithium in the prophylactic treatment of bipolar disorder. However, a recent meta-analysis of randomized, placebo-controlled trials of lithium in bipolar disorder found that its protective effect against depressive relapse/recurrence was equivocal. By examining potentially relevant parameters of recent randomized controlled trials with regard to lithium's prophylactic antidepressant efficacy, we try to identify factors which might help to explain these discrepant results across the different trials. Lithium's efficacy against manic relapse/recurrence appears rather robust at plasma levels between 0.8 and 1.2 mmol/L, whereas lithium's efficacy against depressive relapse/recurrence may be more modest and dependent on whether a response during the preceding acute episode was achieved by lithium treatment. Furthermore, it might be advisable to continue lithium without interruption at the same dose/plasma level, which yielded the initial response. A lithium level between 0.5 and 0.8 mmol/L may be equally efficacious against overall relapse and associated with equal or even superior efficacy regarding depressive relapse/recurrence. To provide evidence-based guidelines on this issue, large prospective, randomized, double-blind, placebo-controlled trials are needed comparing the efficacy of lithium at different plasma levels against manic and depressive relapse/recurrence. In these trials, factors previously associated with predicting response to lithium should also be assessed.


Three-dimensional in situ photocurrent mapping for nanowire photovoltaics.
Devices based upon semiconductor nanowires provide many well-known advantages for next-generation photovoltaics, however, limited experimental techniques exist to determine essential electrical parameters within these devices. We present a novel application of a technique based upon two-photon induced photocurrent that provides a submicrometer resolution, three-dimensional reconstruction of photovoltaic parameters. This tool is used to characterize two GaAs nanowire-based devices, revealing the detail of current generation and collection, providing a path toward achieving the promise of nanowire-based photovoltaic devices.


Complementary metal-oxide-semiconductor compatible 1060 nm photodetector with ultrahigh gain under low bias.
Falling on the tail of the absorption spectrum of silicon, 1060 nm Si detectors often suffer from low responsivity unless an exceedingly thick absorption layer is used, a design that requires high operation voltage and high purity epitaxial or substrate material. We report an all-silicon 1060 nm detector with ultrahigh gain to allow for low operation voltage (<4 V) and thin (200 nm) effective absorption layer, using the recently discovered cycling excitation process. With 1% external quantum efficiency, a responsivity of 93 A/W was demonstrated in a p/n junction device compatible with the complementary metal-oxide-semiconductor process.


Elders' nonadherence, its assessment, and computer assisted instruction for medication recall training.
This study investigates three questions related to the problem of medication nonadherence among elders. First, does recall failure play a significant role in nonadherence? Recent research suggests that it may not. Second, can the new portable bar code scanner technology be used to study nonadherence? Other forms of monitoring are obtrusive or inaccurate. Finally, can inexpensive computer assisted instructions (CAI) be used to teach mnemonic techniques specifically designed to improve medication schedule recall? Current research on memory training teaches nonspecific mnemonics and uses the expensive classroom approach. Results of the present study suggest that physically active and cognitively alert elders do have significant nonadherence (control group = 32.0%) problems related to forgetting and that CAI courseware can significantly reduce (medication recall training group = 10.0%) this form of nonadherence. Portable bar code technology proved easy to use by elderly patients and provided detailed information about the type of forgetting underlying nonadherence. Most significant recall failure was in the complete forgetting to take medication rather than delays in medicating or overmedicating.


Comparison of the long-term efficacy between entecavir and tenofovir in treatment- naïve chronic hepatitis B patients.
There have been limited studies directly comparing the long-term efficacy between entecavir (ETV) and tenofovir disoproxil fumarate (TDF). This study was aimed to compare the long-term efficacy between them in treatment-naïve chronic hepatitis B (CHB). Out of 345 CHB patients who received first line therapy with ETV (n = 200) or TDF (n = 145) in a cohort, 210 patients were analyzed using propensity score matching, at a ratio of 1:1. Two groups showed no difference in baseline characteristics. During the follow-up of 12 months, HBV DNA levels were similarly suppressed in both groups (ETV vs. TDF; -5.01 vs. -5.242 log10IU/mL, P = 0.559). At month 12, both groups showed no difference in terms of the serologic, biochemical and virologic (VR) response. In multivariate analysis, the initial virologic response at 3 months (IVR-3) was independent factor for VR at 1 year. During the long-term follow-up, HBV DNA levels were more strongly suppressed by TDF than ETV in hepatitis B e antigen (HBeAg) positive patients (P = 0.035), especially with high viral load (P = 0.012), although there was no significant difference in overall VR between two groups. The type of antivirals was not an independent factor for long-term VR. Although either ETV or TDF, overall, may show a comparable long-term antiviral efficacy in treatment-naïve CHB, TDF might be better regimen than ETV in the subgroup of HBeAg-positive CHB, especially with a higher HBV DNA levels.


A quartz crystal microbalance method for rapid detection and differentiation of shiga toxins by applying a monoalkyl globobioside as the toxin ligand.
A simple globobiosyl (Gb2) ceramide mimic carrying a monoalkyl chain (C18) was applied for a monolayer Langmuir-Blodgett (L-B) technique to detect Shiga toxins (Stxs) by a quartz crystal microbalance (QCM) method. The artificial glycolipid, synthesized from penta-O-acetyl-D-galactopyranose via a conventional glycosidation pathway, was developed at the air-water surface for the formation of the monolayer film. Then, the film was transferred onto a QCM cell surface modified with alkanethiols. Upon the addition of each of Stx-1 and Stx-2, the decrease of frequency reached saturation within 45 min at a few nanogram order per quartz cell. Binding constants (Ka) estimated for each of Stx-1 and Stx-2 showed little difference between the two toxins. On the other hand, in the presence of an artificial acrylamido Gb2 copolymer as a competitive inhibitor, the two toxins showed a large difference in the binding behavior to the L-B monolayer.


Open questions concerning influences on clinical decision making.
Efforts to influence utilization of services to bring down spending and to improve quality of care have largely failed. A critical reason is that most attention has focused on dysfunctional financial incentives without considering other factors that also influence physicians' utilization decisions. In this article, after providing a framework for ideal physician-patient interactions, questions are also raised about other influences, including physicians' impulse to help patients, professional codes of ethics, the threat of malpractice claims, and the leadership of health care organizations. An Appendix contains a summary of the literature on these factors.


[Decrease of plasma prolactin in valproate therapy--expression of an increase in the activity of the central GABAergic system].
The effect of Valproat on plasma prolactin level in epileptic children with long term medication was investigated. Valproat was able to decrease plasma prolactin level significantly. This result is a sign of an increase in the central GABAergic system activity.


Cohort study on predicting grades: is performance on early MBChB assessments predictive of later undergraduate grades?
Timely intervention, based on early identification of poor performance, is likely to help weaker medical students improve their performance. We wished to identify if poor performance in degree assessments early in the medical degree predicts later undergraduate grades. If it does, this information could be used to signpost strategically placed supportive interventions for our students. We carried out a retrospective, observational study of anonymised databases of student assessment outcomes at the University of Aberdeen Medical School. Data were accessed for students who graduated in the years 2003-07 (n = 861). The main outcome measure was marks for summative degree assessments from the end of Year 2 to the end of Year 5. After adjustment for cohort, maturity, gender, funding source, intercalation and graduate status, poor performance (fail and borderline pass) in the Year 2 first semester written examination Principles of Medicine II was found to be a significant predictor of poor performance in all subsequent written examinations (all P < 0.001). Poor performance in the Year 3 objective structured clinical examination (OSCE) was a significant predictor of poor performance in Year 4 and 5 OSCEs. Relationships between essay-based summative assessments were not significantly predictive. Male gender appeared to significantly predict poor performance. Examinations taken as early as mid-Year 2 can be used to identify medical students who would benefit from intervention and support. Strategic delivery of appropriate intervention at this time may enable poorer students to perform better in subsequent examinations. We can then monitor the impact of remedial support on subsequent performance.


Video-based reflection on neonatal interventions during COVID-19 using eye-tracking glasses: an observational study.
The aim of this study was to determine the experience with, and the feasibility of, point-of-view video recordings using eye-tracking glasses for training and reviewing neonatal interventions during the COVID-19 pandemic. Observational prospective single-centre study. Neonatal intensive care unit at the Leiden University Medical Center. All local neonatal healthcare providers. There were two groups of participants: proceduralists, who wore eye-tracking glasses during procedures, and observers who later watched the procedures as part of a video-based reflection. The primary outcome was the feasibility of, and the proceduralists and observers' experience with, the point-of-view eye-tracking videos as an additional tool for bedside teaching and video-based reflection. We conducted 12 point-of-view recordings on 10 different patients (median gestational age of 30.9±3.5 weeks and weight of 1764 g) undergoing neonatal intubation (n=5), minimally invasive surfactant therapy (n=5) and umbilical line insertion (n=2). We conducted nine video-based observations with a total of 88 observers. The use of point-of-view recordings was perceived as feasible. Observers further reported the point-of-view recordings to be an educational benefit for them and a potentially instructional tool during COVID-19. We proved the practicability of eye-tracking glasses for point-of-view recordings of neonatal procedures and videos for observation, educational sessions and logistics considerations, especially with the COVID-19 pandemic distancing measures reducing bedside teaching opportunities.


Induction of c-fos transcription in the medaka brain (Oryzias latipes) in response to mating stimuli.
Immediate-early genes (IEGs) are useful for mapping active brain regions in various vertebrates. Here we identified a c-fos homologue gene in medaka and demonstrated that the amounts of c-fos transcripts and proteins in the medaka brain increased in relation to an artificially evoked seizure, suggesting that the homologue gene has the characteristics of IEGs, which are used as markers of neural activity. Next, quantitative reverse-transcription-polymerase chain reaction revealed that female mating behaviors upregulated c-fos transcription in some brain regions including the telencephalon, optic tectum, and cerebellum. In addition, we performed in situ hybridization with a c-fos intron probe to detect the de novo synthesis of c-fos transcripts and confirmed induction of c-fos transcription in these brain regions after mating. This is the first report of IEG induction in response to mating stimuli in teleost fish. Our results indicated that c-fos expression was induced in response to behavioral stimuli in the medaka brain and that medaka c-fos could be a useful marker of neural activity.


Measuring the 3D motion space of the human ankle.
The 3D motion space of the human ankle is an important area of study in medicine. The 3D motion space can provide significant information for establishing more reasonable rehabilitation procedures and standards of ankle injury care. This study aims to measure the 3D motion space of the human ankle and to use mathematical methods to quantify it. A motion capturing system was used to simultaneously capture the 3D coordinates of points marked on the foot, and convert these coordinate values into rotation angles through trigonometric functions and vectors. The mathematical expression of the ankle's motion space was obtained by screening, arranging, and fitting the converted data. The mathematical expression of the 3D motion space of the participants was obtained. We statistically analyzed the data and learned that, in terms of 3D motion space, the right foot is more flexible than the left foot and the female foot is more flexible than the male foot. The adduction and abduction rotation ranges are affected by the plantar flexion or dorsal flexure rotation angles. This relationship can be expressed mathematically, which is significant in the study of the ankle joint.


Fundus-Vascular Responses to Color Deviation Caused by Non-Oxidative Blue Filtering.
Short-wavelength blue light damaged retina by the oxidative stress in the retinal pigment epithelial (RPE) cells. Filtering blue light from screen could reduce blue hazard, whereas it inevitably altered color-gamut coverage and color-deviation level. Although abnormal fundus-vascular density (FVD) sometimes indicated fundus disease, few researchers noticed its responses to the variation of color-gamut coverage and color-deviation level. In this study, we performed cellular experiments and analyzed the RPE cell viabilities (CVs) in spectrums with different blue (455-475 nm) ratios to describe the corresponding oxidative-stress levels. Further, we investigated the effects of color-gamut and deviation on FVD variations during the screen-watching task using human factor experiments with 30 participants (university students, including 17 males and 13 females, 21 to 30 years old). RPE CVs were similar in different spectrums, implying that non-oxidative blue filtering hardly contributed to CV improvement. Color-deviation level seems to induce more significant effects on the visual function compared to color-gamut coverage, and MTF and FVD presents similar variation trends during the visual task. Oxidative-free blue filtering contributed little to decrease retinal oxidative stress yet caused color-deviation increase, which caused significant FVD reduction.