Incidence rate of vitamin D deficiency and FGF23 levels in 12- to 13-year-old adolescents in Japan.
The incidence rate of vitamin D deficiency is increasing throughout the world. We measured the incidence rate of vitamin D deficiency and fibroblast growth factor 23 (FGF23) levels in 12- to 13-year-old adolescents in Japan. A total of 492 adolescents (247 boys and 245 girls) from Japanese community enrolled in this study. 25 hydroxyvitamin D (25(OH)D) was measured with radioimmunoassay. In the subjects with low 25(OH)D levels (≦ 20 ng/ml), intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), albumin (Alb), alkaline phosphatase (ALP) and FGF23 were measured. 25(OH)D levels were significantly lower in girls (20.9 ± 3.1 ng/ml) than in boys (22.2 ± 3.3 ng/ml) (p < 0.0001). Fifty-five boys (22.3%) and 83 (33.9%) girls showed vitamin D deficiency (< 20 ng/ml). One-hundred eighty-six (75.3%) boys and 162 (66.1%) girls showed vitamin D insufficiency (≧ 20 ng/ml, < 30 ng/ml). In the subjects whose 25(OH)D levels were ≦ 20 ng/ml, the levels of iPTH, Ca, P, Alb, ALP and FGF23 were 22.3 ± 9.0 pg/ml, 9.5 ± 0.4 mg/dl, 4.7 ± 0.6 mg/dl, 4.6 ± 0.3 g/dl, 920.8 ± 339.3 U/l and 42.6 ± 26.0 pg/ml, respectively. There was a significant negative association between serum 25(OH)D levels and iPTH [r = - 0.290 (p < 0.0001)]. There was no significant association between serum 25(OH)D levels and FGF23. We show that 28% of Japanese 12- to 13-year-old early adolescents suffer from vitamin D deficiency. Findings from this study indicate that vitamin D deficiency requires close oversight in public health during adolescence to ensure proper bone health.


Exact analysis of dispersive SAW devices on ZnO/diamond/si-layered structures.
In this paper, a formulation for calculating the effective permittivity of a piezoelectric layered SAW structure is given, and the exact frequency response of ZnO/diamond/Si-layered SAW is calculated. The effective permittivity and phase velocity dispersion of a ZnO/diamond/Si-layered half space are calculated and discussed. The frequency response of an unapodized SAW transducer is calculated, and the center frequency shift caused by the velocity dispersion is explained. In addition, the electromechanical coupling coefficients of the ZnO/diamond/Si -layered half space based on two different formulas are calculated and discussed. Finally, based on the results of the study, we propose an exact analysis for modeling the layered SAW device. The advantage of using the effective permittivity method is that, not only the null frequency bandwidth, but also the center frequency shift and insertion loss can be evaluated.


Presentation and outcomes of patients with clinically T1-2, N0 supraglottic squamous cell carcinoma: The role of definitive radiotherapy compared to primary partial laryngectomy.
Early-stage supraglottic squamous cell carcinoma (SCC) is usually treated with a single modality. The aim of this study is to examine the role of radiotherapy (RT) versus partial laryngectomy (open, robotic-assisted, or endoscopic) with elective neck dissection (PL + END). A retrospective analysis of the National Cancer Database, 2010-2016. The study population included adult patients with clinically T1-2, N0 supraglottic SCC. 3301 patients were included. RT was performed in 93.52%, open PL + END in 2.64%, robotic-assisted PL + END in 1.33%, and endoscopic surgical resection in 2.51%. In the surgery group, T was upstaged in 23.36% and N was upstage in 16.36%. Five-year survival in the primary surgery group compared to RT group was 61.89% versus 77.46% (HR: 0.56, 95%CI: 0.43, 0.72). T was upstaged in 23% of surgical patients. This accurate staging is likely missed in patients who undergo RT and possibly contributes to lower overall survival of this treatment group.


Is endometrial apoptosis evidence of endometrial aging in unexplained infertility? a preliminary report.
To investigate spontaneous endometrial apoptosis in women with unexplained infertility and to find out whether there is a possible relationship between endometrial apoptosis, age, and hormonal parameters. This study was designed as a prospective, case-controlled study in a University Hospital setting. A total of 34 endometrial biopsies were performed from 17 women with unexplained infertility and 17 fertile controls, who were admitted for tubal ligation. Endometrium was sampled on the seventh post-ovulatory day. On the same day of endometrial sampling, serum levels of FSH, LH, PRL, TSH, E2, progesterone, 17alpha-hydroxyprogesterone, testosterone and DHEA-S were determined. Endometrial glandular and stromal apoptosis were investigated by DNA nick end labeling (TUNEL) method on each sample. Endometrial apoptotic index was calculated and correlated with age and hormonal parameters. There was no difference in either endometrial glandular apoptotic index (AI) or stromal AI between the groups. However, the mean glandular AI was significantly higher than the mean stromal AI (p = 0.0001). There was a strong correlation between endometrial AI and age (r = 0.91, p = 0.02). Serum T levels were significantly found to be decreased in the unexplained infertility group (p = 0.0001). In addition, serum TSH levels were positively correlated with AI in the glandular endometrium in women with unexplained infertility (r = 0.611, p = 0.009). Endometrial apoptosis increases with age. Serum levels of testosterone were lower in unexplained infertility. The effect of serum TSH levels on apoptosis in the glandular epithelium of the endometrium needs further studies.


Deep learning combined with radiomics for the classification of enlarged cervical lymph nodes.
To investigate the application of deep learning combined with traditional radiomics methods for classifying enlarged cervical lymph nodes. The clinical and computed tomography (CT) imaging data of 276 patients with enlarged cervical lymph nodes (150 with lymph-node metastasis, 65 with lymphoma, and 61 with benign lymphadenopathy) who were treated at the hospital from January 2015 to January 2021 were retrospectively analysed. The patients were randomly divided into a training group and a test group at a ratio of 8:2. The radiomics features were extracted using one-by-one convolution and neural network activation, filtered with the least absolute shrinkage and selection operator (LASSO) model, and used to construct a discrimination model with PyTorch. Then, the performance of the model was compared with the radiologists' diagnostic performance. The neural network model was evaluated using the area under the receiver-operator characteristic curve (AUC), and the accuracy, sensitivity, and specificity were analysed. A total of 102 features, comprising five traditional radiomic features and 97 deep learning features, were selected with LASSO and used to construct a discrimination model, which achieved a total accuracy of 87.50%. The AUC value, specificity, and sensitivity were, respectively, 0.92, 92.30%, and 90.00% for metastatic lymph nodes, 0.87, 95.45%, and 83.33% for benign lymphadenopathy, and 0.88, 90.47%, and 85.71% for lymphoma. The accuracies of the radiologists' diagnoses were 62.68% and 62.68%. The diagnostic performance of the model was significantly different from that of the radiologists (p < 0.05). CT-based deep learning combined with the traditional radiomics methods has a high diagnostic value for the classification of cervical enlarged lymph nodes.


Beyond path diagrams: Enhancing applied structural equation modeling research through data visualization.
Structural equation modeling (SEM) is a multivariate data analytic technique used in many domains of addictive behaviors research. SEM results are usually summarized and communicated through statistical tables and path diagrams, which emphasize path coefficients and global fit without showing specific quantitative values of data points that underlie the model results. Data visualization methods are often absent in SEM research, which may limit the quality and impact of SEM research by reducing data transparency, obscuring unexpected data anomalies and unmodeled heterogeneity, and inhibiting the communication of SEM research findings to research stakeholders who do not have advanced statistical training in SEM. In this report, we show how data visualization methods can address these limitations and improve the quality of SEM-based addictive behaviors research. We first introduce SEM and data visualization methodologies and differentiate data visualizations from model visualizations that are commonly used in SEM, such as path diagrams. We then discuss ways researchers may utilize data visualization in SEM research, including by obtaining estimates of latent variables and by visualizing multivariate relations in two-dimensional figures. R syntax is provided to help others generate data visualizations for several types of effects commonly modeled in SEM, including correlation, regression, moderation, and simple mediation. The techniques outlined here may help spur the use of data visualization in SEM-based addictive behaviors research. Using data visualization in SEM may enhance methodological transparency and improve communication of research findings.


Muscle force and power following tendon repair at altered tendon length.
While a great deal is known regarding the performance of muscle with intact tendon, little is known about muscle performance when tendon is surgically lengthened or shortened. This knowledge may allow surgeons to more accurately predict functional outcome following tendon repair when correcting a simple tendon laceration or performing a more complex vascularized neuromuscular transfer. We studied muscle performance 12 wk following extensor tendon repairs producing altered tendon lengths. Forty male Fischer 344 rats underwent division of the proximal and distal tendons of the extensor digitorum longus muscle. Tendons were immediately repaired producing tendons with increased length, decreased length, or presurgical length (control). Observation confirmed that altered tendon length produced inverse changes in initial resting muscle tension. Muscle in the decreased tendon length group demonstrated a 15.2% greater muscle mass, 4.9% greater muscle length, 9.6% greater physiological cross-sectional area, 12.6% greater maximum isometric force, and 31.9% greater maximum power relative to the control tendon length group (P < 0.05). The increased tendon length group did not differ significantly from the control tendon length group for any measurement. Histologically, muscles set with a decreased tendon length demonstrated normal appearing hypertrophied fibers, without evidence of detrimental histological effects such as fibrosis, denervation, necrosis, inflammation, fiber type changes, or fiber splitting. These data support the clinical practice of setting muscles with increased passive tension when performing tendon transfer surgeries. Conversely, setting muscles with decreased tension does not necessarily result in a force or power deficit.


Vaginal repair of neobladder-vaginal fistula: a case report and review of the literature.
Neobladder substitution after radical cystectomy for invasive cancer has become commonplace as it preserves normal volitional voiding through the native urethra and avoids urinary diversion. Neobladder-vaginal fistula (NVF) is a rare postoperative complication of this procedure that results in decreased quality of life. We describe a case of vaginal repair of a NVF and present a review of the literature.


Comparison of the antimicrobial activity of Listerine and Corsodyl on orthodontic brackets in vitro.
The aim of this study was to evaluate the antimicrobial efficacy of 2 commercially available mouth rinses on a monospecies-biofilm model on orthodontic brackets in vitro. The antimicrobial effects of the 2 mouth rinses, Listerine (tartar control; IDS Manufacturing, Bangkok, Thailand) and Corsodyl (SmithKline Beecham, Maidenhead, United Kingdom), on the planktonic Streptococcus mutans were tested by maximum inhibitory dilution assay. The cell viability of S mutans biofilm on Damon3 MX brackets (Ormco, Glendora, Calif) after exposure to the 2 mouth rinses was quantified by 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) reduction assay. Visualization of the biofilm samples was performed by fluorescence microscopy and confocal laser scanning microscopy. The maximum inhibitory dilution assays of S mutans were 1:5 for Listerine and 1:320 for Corsodyl. The optical density values, which were measured by XTT reduction assay from S mutans biofilms after 1 minute of exposure to the different test agents, demonstrated that the cell viability of S mutans biofilms exposed to Listerine was less than that for Corsodyl, which was less than that for brain-heart infusion (P <0.001). Listerine caused more dead cells on the surface of the brackets than did Corsodyl when examined with the 2 microscope systems. Both mouth rinses showed marked antimicrobial effects on the monospecies biofilm in vitro. Listerine showed a stronger bactericidal effect but had less bacterial inhibitory effect than did Corsodyl.


Occurrence and role of phosphoenolpyruvate carboxykinase in procyclic Trypanosoma brucei brucei glycosomes.
Phosphoenolpyruvate carboxykinase (EC 184.108.40.206) was detected in a particulate fraction of Trypanosoma brucei brucei procyclic culture form. It requires ADP rather than GDP for activity in the direction of carboxylation and is located in the glycosomes. Since phosphoenolpyruvate can serve to furnish ATP for glycolysis and can promote 3-phosphoglycerate or 1,3-bisphosphoglycerate formation without simultaneous alpha-glycerophosphate production, we suggest that the glycosomal phosphoenolpyruvate carboxykinase-malate dehydrogenase tandem contributes to ATP regeneration and NADH re-oxidation in the glycosome, and regulates alpha-glycerophosphate production.


Local and systemic adaptive immune responses toward viral infection via gills in ginbuna crucian carp.
Recent studies on fish immunity highlighted the significance of gills as mucosal immune tissues. To understand potential of gills as vaccination sites for inducing adaptive systemic immunity, we investigated virus-specific cell-mediated and humoral immune responses following a "per-gill infection method", which directly exposes virus only to gills. The viral load in crucian carp hematopoietic necrosis virus (CHNV)-infected gills decreased after peaking at a particular time point. Furthermore, the viral titers in the gills following the secondary infection were lower than that after the primary infection, indicating that local adaptive immunity helped the elimination of virus. Gene expression analysis demonstrated that IFN-γ in gills and perforin in kidney were increased after the gill infection. CD8(+) cells in kidney leukocytes increased after the secondary infection, whereas IgM(+) cells decreased. These results suggest that IFN-γ and CTL contribute in controlling CHNV-replication in gills and kidney. Gill infection could induce specific cell-mediated cytotoxicity of peripheral blood leukocytes (PBL) and secretion of CHNV-specific IgM in serum, indicating that local priming of the gill site can generate adaptive systemic immunity. Thus, the gills could be prospective antigen-sensitization sites for mucosal vaccination.


Global DNA methylation profile at LINE-1 repeats and promoter methylation of genes involved in DNA damage response and repair pathways in human peripheral blood mononuclear cells in response to γ-radiation.
DNA methylation is an epigenetic mechanism, which plays an important role in gene regulation. The present study evaluated DNA methylation profile of LINE1 repeats and promoter methylation of DNA damage response (DDR) and DNA repair (DR) genes (PARP1, ATM, BRCA1, MLH1, XPC, RAD23B, APC, TNFα, DNMT3A, MRE11A, MGMT, CDKN2A, MTHFR) in human peripheral blood mononuclear cells (PBMCs) of healthy donors in response to γ-radiation. Methylation level was correlated with gene expression profile of selected DDR and DR genes (APC, MLH1, PARP1, MRE11A, TNFα, MGMT) to understand their role in gene regulation. Blood samples were collected from 15 random healthy donors, PBMCs were isolated, exposed to 0.1 Gy (low) and 2.0 Gy (high) doses of γ-radiation and proliferated for 48 h and 72 h. Genomic DNA and total RNA were isolated from irradiated PBMCs along with un-irradiated control. Methylation profile was determined from bisulphite converted DNA and amplified by methylation sensitive high resolution melting (MS-HRM) method. Total RNA was converted to cDNA and relative expression was analysed using real time quantitative-PCR. Our results revealed that at 0.1 Gy, MRE11A and TNFα showed significant (P < 0.05) increase in methylation at 72 h. At 2.0 Gy, significant increase (P < 0.05) in methylation profile was observed at LINE1, MRE11A, PARP1, BRCA1, DNMT3A and RAD23B at 48 h and 72 h. PARP1 showed significant positive correlation of methylation status with gene expression. In conclusion, low and high doses of γ-radiation have significant influence on DNA methylation status of LINE1, DDR and DR genes suggesting their potential role as epigenetic signatures in human PBMCs, which can be further explored in human populations.


Role of concomitant resistance in the development of murine lung metastases.
An attempt was made to explain the distinct lung metastatic patterns of 2 mammary adenocarcinomas with a common BALB/c origin: M3, which does not induce spontaneous metastases, and MM3 with an almost 100% incidence. No difference between the 2 tumors was detected with respect to host mononuclear cell content, degree of immunogenicity or lung-colony-forming ability. Conversely, there was a marked difference in the capacity to induce concomitant resistance: M3-bearing mice induced stronger and earlier resistance against i.v. challenge of both M3 and MM3 tumor cells than MM3-bearing mice; this resistance was expressed as lower number of lung metastases and lower tumor-cell proliferation in metastatic nodules. M3 was also able to control the development of spontaneous metastases: metastases developed in all M3-excised mice, compared with none in M3-bearing mice, while MM3-bearing mice also bearing a secondary M3 tumor developed fewer metastases than mice bearing MM3 only. This anti-metastatic effect does not appear to depend on classical immunological mechanisms since no difference could be detected between the 2 tumors in response to T cells, NK, macrophages or antibodies.


Estrogen receptor beta in breast cancer.
Estrogen is essential for growth and development of the mammary glands and has been associated with the promotion and growth of breast cancer and in line with this, most human breast cancers are initially estrogen-dependent and undergo regression when deprived of their supporting hormone. Estrogen exerts many of its effects via two nuclear estrogen receptors (ERs), ERα and ERβ. The discovery of a second ER, ERβ, demanded a full re-evaluation of estrogen action in all target tissues and different estrogen associated diseases, including human breast cancer. However, despite over 15 years of research, the exact role, if any, of ERβ in human breast cancer remains elusive. The main challenges now are to develop highly selective anti-ERβ antibodies that are applied to large well characterized human breast cancer samples to validate their diagnostic potential and to explore ERβ-selective agonists in animal models of breast cancer to validate their therapeutic potential.


Chrysin mitigates diclofenac-induced hepatotoxicity by modulating oxidative stress, apoptosis, autophagy and endoplasmic reticulum stress in rats.
Diclofenac (DF) is a non-steroidal anti-inflammatory drug (NSAID) generally prescribed for the treatment of pain. In spite of the widespread use of DF, hepatotoxicity has been reported after its administration. The current study discloses new evidence as regards of the curative effects of chrysin (CHR) on DF-induced hepatotoxicity by regulating oxidative stress, apoptosis, autophagy, and endoplasmic reticulum (ER) stress. The animals were separated into five different groups. Group-I was in control. Group-II received CHR-only (50 mg/kg bw, p.o.) on all 5 days. Group-III received DF-only (50 mg/kg bw, i.p.) on 4th and 5th day. Group-IV received DF (50 mg/kg bw) + CHR (25 mg/kg, bw) and group-V received DF (50 mg/kg, bw) + CHR (50 mg/kg, bw) for 5 days. DF injection was associated with increased MDA while reduced GSH level, activities of superoxide dismutase, glutathione peroxidase, and catalase and mRNA levels of HO-1 and Nrf2 in the liver. DF injection caused apoptosis and autophagy in the liver by up-regulating caspase-3, Bax, LC3A, and LC3B levels and down-regulating Bcl-2. DF also caused ER stress by increasing mRNA transcript levels of ATF-6, IRE1, PERK, and GRP78. Additionally, it was observed that DF administration up-regulated MMP2 and MMP9. However, treatment with CHR at a dose of 25 and 50 mg/kg considerably ameliorated oxidative stress, apoptosis, autophagy, and ER stress in liver tissue. Overall, the data of this study indicate that liver damage associated with DF toxicity could be ameliorated by CHR administration.


Peripheral proliferative retinopathy without oxygen therapy in a full-term infant.
A 2,948-g full-term male infant, the product of an uncomplicated pregnancy, developed fundus changes consistent with retrolental fibroplasia in the absence of supplemental oxygen therapy. He had no associated illnesses or congenital anomalies, and had not received exchange transfusions. There was no family history of ocular disease. Changes similar to those of retrolental fibroplasia do occasionally occur in fullterm infants who have had no supplemental oxygen therapy. A relative hyperoxia caused by the increase in arterial oxygen saturation occurring at birth is one possible explanation for these events. This rise, plus susceptibility factors apart from prematurity, may account for these unusual cases. Additionally, these cases may represent sporadic examples of familial exudative vitreoretinopathy.


Functional outcomes after radiotherapy or laser surgery in early glottic carcinoma: a systematic review.
Early glottic carcinoma is treated with laser surgery or radiotherapy, but which treatment has better functional outcomes is unclear. This systematic review compared functional outcomes (voice, swallowing, quality of life [QOL]) in more extended T1a and limited T2 tumors (1) between treatments and (2) between greater and lesser laser resections. A systematic literature search covered relevant databases from 1990 to 2009, combining all patient/problem, intervention, comparison, outcome (PICO) keyword variations. A total of 19 papers met the inclusion criteria, all of which were level IV evidence. Papers reported only voice and QOL. Heterogeneity of outcome measures prevented data pooling. Uncertainty about tumor comparability (depth, extent) between the 2 treatments, small subject numbers, and poor-quality reporting hindered interpretation. To allow comparison of laser surgery versus radiotherapy, a standardized method is needed that accurately measures tumor extent and depth. Agreement on functional outcome measures is necessary to allow comparison of treatments and resection types. Multicenter studies should be encouraged to guarantee adequate subject numbers.


Neither long-term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in healthy postmenopausal women: two randomized, placebo-controlled, 2-year studies.
Our purpose was to investigate the long-term effects of raloxifene, compared with opposed and unopposed estrogen replacement therapy, on echocardiographic parameters of left ventricular systolic function in healthy postmenopausal women. A total of 157 women were studied in 2 randomized, double-blind, placebo-controlled, 2-year studies. In study I, 60 postmenopausal women who had undergone hysterectomy received daily raloxifene, 60 mg (n = 15); raloxifene, 150 mg (n = 15); conjugated equine estrogens (CEE), 0.625 mg (n = 15); or placebo (n = 15). In study II, 97 postmenopausal women who had not undergone hysterectomy received daily raloxifene, 60 mg (n = 24); raloxifene, 150 mg (n = 24); CEE, 0.625 mg, plus medroxyprogesterone acetate (MPA), 2.5 mg (n = 24); or placebo (n = 25). M-mode, quantitative 2-dimensional and Doppler echocardiographic measurements were performed at baseline and after 1 and 2 years. Neither after 1 year nor after 2 years of treatment were echocardiographic parameters found to differ from baseline in both raloxifene groups, as well as in the unopposed CEE and the CEE/MPA groups, compared with the placebo group. Within 2 years of raloxifene treatment, no effect on echocardiographic parameters of left ventricular systolic function was found. Unopposed CEE or CEE/MPA also showed no effect.


Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy.
We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40-75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P < 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P < 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P < 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P < 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P < 0.01 for both variables). Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina.


The influence of economic incentives linked to road safety indicators on accidents: the case of toll concessions in Spain.
The goal of this paper is to evaluate whether the incentives incorporated in toll highway concession contracts in order to encourage private operators to adopt measures to reduce accidents are actually effective at improving safety. To this end, we implemented negative binomial regression models using information about highway characteristics and accident data from toll highway concessions in Spain from 2007 to 2009. Our results show that even though road safety is highly influenced by variables that are not managed by the contractor, such as the annual average daily traffic (AADT), the percentage of heavy vehicles on the highway, number of lanes, number of intersections and average speed; the implementation of these incentives has a positive influence on the reduction of accidents and injuries. Consequently, this measure seems to be an effective way of improving safety performance in road networks.


[Long-term results of the treatment of acute suppurative destruction of the lungs in children].
The results of the treatment of acute purulent destruction of the lungs were studied. The period of follow-up ranged from 6 mos to 10 yrs. Unsatisfactory results were obtained in 4.8% of the patients, satisfactory--in 27%, good--in 68.2%.


[Relationship between the quantities of H substance before, and B substance after conversion of red blood cells by alpha-D-galactosyl transferase].
The authors determined the agglutination percentages with anti-B, eel and Ulex europeus anti-H reagents for the kinetic study of the in vitro conversion O red blood cells in B. The agglutination with the anti-B increases in proportion as the agglutination with eel anti-H decreases; the agglutination with Ulex anti-H remains constant. They converted (time=18 h) O red blood cells with a more or less high substance H content (adults in good health, africans and europeans, patients, newborn and one "Bombay" phenotype). They showed that there is a good correlation between the agglutination percentages with eel anti-H or Ulex anti-H before conversion and the agglutination percentages with anti-B after conversion. These "O converted" look like the B phenotype defined by a check sample of B subjects.


Overexpression of the toll-like receptor (TLR) signaling adaptor MYD88, but lack of genetic mutation, in myelodysplastic syndromes.
MYD88 is a key mediator of Toll-like receptor innate immunity signaling. Oncogenically active MYD88 mutations have recently been reported in lymphoid malignancies, but has not been described in MDS. To characterize MYD88 in MDS, we sequenced the coding region of the MYD88 gene in 40 MDS patients. No MYD88 mutation was detected. We next characterized MYD88 expression in bone marrow CD34+ cells (N = 64). Increased MYD88 RNA was detected in 40% of patients. Patients with higher MYD88 expression in CD34+ cells had a tendency for shorter survival compared to the ones with lower MYD88, which was significant when controlled for IPSS and age. We then evaluated effect of MYD88 blockade in the CD34+ cells of patients with lower-risk MDS. Colony formation assays indicated that MYD88 blockade using a MYD88 inhibitor resulted in increased erythroid colony formation. MYD88 blockade also negatively regulated the secretion of interleukin-8. Treatment of MDS CD34+ cells with an IL-8 antibody also increased formation of erythroid colonies. These results indicate that MYD88 plays a role in the pathobiology of MDS and may have prognostic and therapeutic value in the management of patients with this disease.


Chromosomal effects in lymphocytes of 400 kV-substation workers.
In a previous study we found an increased rate of chromosomal aberrations in substation workers. To follow up this finding we in this study present data from 38 employees of electric power companies; 19 of the subjects worked with the repair and maintenance of circuit breakers and disconnectors in 400 kV-substations. The other 19 served as controls and were only exposed to normal environmental electromagnetic fields. Coded blood samples were sent to a laboratory for determination of the rate of chromosomal aberrations (CA), sister chromatid exchanges (SCE), and cells with micronuclei (MN). Compared to the control group the exposed men displayed a statistically significant increase in CA and cells with MN. No increase was found in the frequency of SCE. Since "in vitro" studies of lymphocytes exposed to transient electric currents (spark discharges) produced similar results the increase in chromosomal damage in substation workers may be associated with exposure to transient electric currents during work.


Cardiopulmonary bypass in the newborn: effects of circulatory cell-free hemoglobin and hyperoxia evaluated in a novel rat pup model.
Infants with congenital heart defects (CHD) are at risk for white matter brain injury. This novel rat pup model characterizes the systemic effects of intravasal cell-free hemoglobin and hyperoxia, hypothesizing that immature endogenous scavenging systems relate to increased vulnerability to conditions present during cardiopulmonary bypass (CPB). Plasma pharmacokinetics of cell-free human hemoglobin (Hb) was determined after intraperitoneal (i.p.) administration in postnatal day 6 (P6) rat pups. Cell-free hemoglobin degradation, scavenger- and oxidative stress responses in altered oxygen environments were evaluated in P6 rat pups exposed to i.p. cell-free Hb or vehicle and subjected to hyperoxia or normoxia for 24 h. Plasma and liver were analyzed for free heme, haptoglobin, hemopexin, heme-oxygenase 1, and 8-OHdG at 3-120 h post-injection. Baseline scavenging properties were evaluated in P0-P12 rat pups. Cell-free Hb displayed peak plasma concentrations of 3.6 ± 0.5 mg/mL (mean ± SD) at 3 h post-administration. Animals exposed to cell-free Hb demonstrated a 30-fold increase in plasma haptoglobin and a decrease in plasma hemopexin to 1/6 of concentrations observed in pups exposed to vehicle. Exposure to cell-free Hb and hyperoxia mediated increased plasma concentrations of free heme (72.7 ± 19.5 μM, mean ± SD) compared to exposure to cell-free Hb and normoxia (49.3 ± 13.1 μM) at 3 h, and an elevated hepatic mRNA expression of heme-oxygenase 1. mRNA expression of haptoglobin and hemopexin was increased in animals exposed to hemoglobin with a mitigated response in pups exposed to hemoglobin and hyperoxia. Animals exposed to hyperoxia displayed an increase in hepatic transcription of scavenger proteins at 24 h. Combined exposure to cell-free Hb and hyperoxia mediated an increased DNA-oxidation at 6 h, whereas all insults conveyed a decrease in DNA-oxidation at 120 h. In this study, we present a novel rat pup model with scavenging characteristics and brain maturation similar to newborns with CHD. We have confirmed a distinct scavenger response after exposure to systemic cell-free hemoglobin. We have indications of an accelerated metabolism of cell-free Hb and of an altered transcription of scavenger proteins in a hyperoxic environment. We believe that this model will prove valuable in future delineation of inflammatory and oxidative end-organ damage following CPB.


Serum lipids, metabolic syndrome and lifetime suicide attempts in patients with bipolar disorder.
Bipolar disorder is associated with a high risk of suicide. Many clinical characteristics and, recently, biomarkers have been studied with the aim to find useful predictors of suicidality. The role of serum lipids has also been explored albeit with conflicting results; however, few studies have been focused on patients with bipolar disorder. Aim of our study is to investigate whether serum cholesterol, triglycerides, HDL-c and metabolic syndrome are associated with lifetime suicide attempts in a large naturalistic sample of patients with bipolar disorder. 220 patients with bipolar disorder were included. History of lifetime suicide attempts was systematically and retrospectively assessed for each patient. Blood exams testing total cholesterol, triglycerides, and HDL-c levels were performed, and metabolic syndrome was diagnosed according to NCEP ATP-III modified criteria. Serum lipid levels and metabolic syndrome were compared in patients with or without history of suicide attempt. According to a theory that links impulsivity and violence with low cholesterol, the association between lipid levels and violent suicidal behavior was also assessed. Lifetime suicide attempts rate was 32.3%. There were no statistically significant differences between patients with and without lifetime suicide attempts in cholesterol, triglycerides, HDL-c levels, and the prevalence of metabolic syndrome. No differences in the same variables were found in violent suicide attempters compared with nonviolent ones. Clinical characteristics such as gender, low education, higher number of manic and depressive episodes, and taking more medications for bipolar disorder were associated with lifetime suicide attempts. Our results do not support the hypothesis of a strong association between serum lipid levels and suicide in patients with bipolar disorder.


Asymmetric total syntheses of marine cyclic depsipeptide halipeptins A-D.
Halipeptins A-D (1 a-d) are a family of natural cyclic depsipeptides isolated from marine sponges. Total syntheses of these four compounds are detailed in this report. The key elements in this synthesis include the elaboration of the polysubstituted decanoic acid parts by two asymmetric aldol reactions, assembly of the N-methyl-delta-hydroxyisoleucine residue by using either aza-Claisen rearrangement or methylation of aspartates as the key steps, and macrocyclization at the polysubstituted decanoic acid alanine site.


Direct in vivo transfer of plasmid DNA into murine tumors: effects of endotoxin presence and transgene localization.
The purpose of this study was to investigate the effect of endotoxin presence in plasmid DNA preparations on the efficiency of transfection achieved in vivo with B16(F10) and Renca tumors and to determine transgene localization. Our data show that endotoxin markedly decreases the efficiency of transfection. Furthermore, the transgene transferred in vivo can be found in both neoplastic and normal (most likely myofibroblast) cells lying in proximity of the administration site.


What are the best routes to effectively model human colorectal cancer?
Colorectal cancer (CRC) is the third most common cancer in the UK, with over 37,500 people being diagnosed every year. Survival rates for CRC have doubled in the last 30 years and it is now curable if diagnosed early, but still over half of all sufferers do not survive for longer than 5 years after diagnosis. The major complication to treating this disease is that of metastasis, specifically to the liver, which is associated with a 5 year survival of less than 5%. These statistics highlight the importance of the development of earlier detection techniques and more targeted therapeutics. The future of treating this disease therefore lies in increasing understanding of the mutations which cause tumourigenesis, and insight into the development and progression of this complex disease. This can only be achieved through the use of functional models which recapitulate all aspects of the human disease. There is a wide range of models of CRC available to researchers, but all have their own strengths and weaknesses. Here we review how CRC can be modelled and discuss the future of modelling this complex disease, with a particular focus on how genetically engineered mouse models have revolutionised this area of research.


Effects of cold stress during pupal diapause on the survival and development of Mamestra configurata (Lepidoptera: Noctuidae).
The effects of exposing diapausing pupae of Mamestra configurata Wlk. to temperatures from -5° C to-20° C during a 140-day experimental period were reduced survival to post-diapause stages, reduced survival to emergence as malformed or normal adults, and a reduced rate of post-diapause development. Pupae given a continuous exposure of variable length to -10° C and pupae given the same exposure to -10° C, interrupted by 28 days at 0° or -5° C, had the same survival, indicating that repair of cold injury does not occur at 0° or-5° C. Assuming that the effects of low temperatures were additive, not only for exposures to one temperature but also for exposures to different combinations of temperatures, survival was decribed by a polynomial: [Formula: see text] where p=the proportion in post-diapause stages and t=the number of days of exposure to the temperature given by the subscript. The values of the coefficients (C) were inversely related to the temperature of exposure (T): log10 C=-2.87-0.159 T. In validation experiments, the model accurately predicted survival of pupae in the laboratory and in soil under natural snow-cover or in soil where snow cover was maintained at <2 cm through a complete winter. Our results suggest that: (1) symptoms of cold injury, from death in the stage exposed through death, malformation or retarded development in post-exposure stages represent a continuum that can be produced by varying the exposure time at temperatures that cause cold injury; (2) repair does not occur at these temperatures nor at slightly warmer temperatures (e.g. at 0° C for M. configurata pupae); (3) the total amount of injury is not affected by the sequence of temperatures to which the insect is exposed; (4) freezing is not responsible for the observed cold injury.


Gonadotropin and prostaglandins binding sites in nuclei of bovine corpora lutea.
Highly purified nuclei isolated from bovine corpora lutea showed marked enrichment of NAD pyrophosphorylase, a marker for this organelle. Rough endoplasmic reticulum and lysosomal markers were undetectable, whereas plasma membrane and Golgi markers were detectable but not enriched in nuclei. These highly puridied nuclei exhibited specific binding with 125I-labeled human choriogonadotropin, [3H]prostaglandin E1 and [3H]prostaglandin F2 alpha. However, these bindings were only 15.4% (human choriogonadotropin), 7.9% (prostaglandin E1) and 8.9% (prostaglandin F2 alpha) of the plasma membrane binding observed under the same conditions. Washing of nuclei and plasma membranes twice with buffer containing 0.1% Triton X-100 resulted in gonadotropin and prostaglandin F2 alpha binding site and 5'-nucleotidase (EC 126.96.36.199) losses from nuclei that were different from those observed for plasma membranes. More importantly, the washed nuclei exhibited 44% (human choriogonadotropin), 21--26% (prostaglandins) of original specific binding despite virtual disappearance of 5'-nucleotidase activity. The nuclear membranes isolated from nuclei, specifically bound 125I-labeled human choriogonadotropin and [3H]prostaglandin F2 alpha to the same extent or significantly more ([3H]prostaglandin E1, P less than 0.05) than nuclei themselves, despite the marked losses of chromatin. In summary, our data suggest that gonadotropin and prostaglandins bind to nuclei and that this binding was intrinsic and was primarily associated with the nuclear membrane.


Hip preserving procedures for osteonecrosis of the femoral head after collapse.
Osteonecrosis of the femoral head (ONFH) affects mainly young patients and causes secondary hip osteoarthritis if remains untreated. Several operative treatments have been introduced with successful outcomes in the early stages. However, in late stages of ONFH treatment may be challenging due to the progressive nature of disease and many surgeons prefer arthroplasty option after collapse. Considering the size, age and etiology an effort should be made to preserve hip joint selected patients with early collapse or minimal arthritic changes. The purpose of the current review is to discuss the results of joint preserving procedures for late stages of ONFH.


Anaesthesia and Rett syndrome: a case report.
Rett syndrome is a neurological disorder of females characterized by dementia, autism, movement disorders and an abnormality of respiratory control. A 14-year-old girl with Rett Syndrome underwent spinal fusion surgery under general anaesthesia. No exacerbation of the respiratory control defect with surgery and anaesthesia was observed. Hypothermia, ongoing blood loss and a normal anion gap acidosis were encountered, but were not attributable to features of this disorder.


Cellular requirements for antigen processing by antigen-presenting cells: evidence for different pathways in forming the same antigenic determinants.
In this report we examined the antigen-presenting cell (APC) requirements for activation of T-cell hybridomas specific for the protein antigen PPD (purified protein derivative of tuberculin). During the course of these studies we observed that glutaraldehyde fixation of Ia-positive A20.2JAD (A20) and P388D1 stimulator cells had different effects on T-cell activation. A20 cells fixed with glutaraldehyde stimulated the T cells in the presence of PPD as efficiently as nonfixed A20 cells. By contrast, glutaraldehyde treatment of Ia-positive P388D1 cells dramatically inhibited their ability to process and/or present PPD to T cells. This was not due to nonspecific effects on the P388D1 cells since cells prepulsed with PPD prior to glutaraldehyde treatment stimulated T cells as efficiently as non-glutaraldehyde-treated P388D1 cells. In addition, there was no apparent difference in "fixing" of the two cell types as determined by the uptake of radiolabeled thymidine. These observations suggested that P388D1, but not A20, cells required PPD internalization to form the relevant antigenic determinants. This was substantiated by showing that treatment of P388D1 cells with chloroquine prior to PPD pulsing eliminated their stimulatory capacity, but had no effect on P388D1 cells previously pulsed with PPD. Chloroquine treatment had no effect on stimulation by A20 cells. Since PPD internalization appeared not to be required for presentation by A20 cells, we next determined if isolated A20 plasma membranes would substitute for the intact cell. We observed that the isolated plasma membranes from PPD-pulsed A20 cells stimulated the T hybridoma cells, and that this stimulation was antigen-specific and was inhibited by anti-Ia monoclonal antibodies. Taken together, the results presented here suggest that for the PPD-specific T-cell responses examined here, different APC utilize distinct pathways to present the same antigenic determinant for T-cell recognition.


Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes.
Survival of lung cancer patients has been dismal. Glutathione enzymes are directly involved in the metabolism of platinum compounds, a group of important chemotherapeutic drugs in cancer treatment. We tested the hypothesis that genes encoding glutathione enzymes may predict lung cancer short-term survival. We studied DNA polymorphisms of 250 primary lung cancer patients at four glutathione-related loci: GSTP1, GSTM1, GSTT1 and gamma-GCS that encode glutathione-S-transferase-pi, glutathione-S-transferase-mu, glutathione-S-transferase-theta, and gamma-glutamylcysteine synthetase, respectively. Pearson's chi(2)-square tests, Kaplan-Meier survival curves, log rank tests, and Cox regression models were applied in the analysis. There were 150 (60%) men and 100 (40%) women in this study. Seventeen percent of the patients had never smoked cigarettes, and 61% had stopped smoking at least 6 months prior to their lung cancer diagnosis. Among never smokers, those with null (N) or low (L) genotype experienced a better 1-year-survival rate than those with a positive (P) or high (H) genotype. Patients with P or H at two loci (PP or PH) were compared with patients with N or L at one or both loci (other). Among never smokers, 1-year-survival rates were 60-78% for patients with PP or PH genotypes compared with 89-100% for other types. The survival advantage was greater among advanced-stage patients who were NL or NN than low-stage patients. Similar results were not observed among smokers. Glutathione-related genes may determine lung cancer survival. Our results, if confirmed, would suggest new directions to enhance cancer treatment, and provide easily measurable markers for clinicians to plan patient-specific therapy.


Biliary spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) in dogs.
The spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) on the biliary tract was investigated in anesthetized dogs. Intravenous administration of AA-149 at 2 mg/kg and higher doses produced a dose-dependent reduction in passage resistance through the choledochoduodenal junction and in gallbladder pressure, and a dose-dependent increase in bile flow. AA-149, like cholecystokinin, decreased biliary ductal pressure in spite of increasing the bile flow in dogs with ligation of the cystic duct of the gallbladder, whereas taurocholate increased the pressure as well as the bile flow. Moreover, the spasmic response of the choledochoduodenal junction to morphine was depressed strongly by AA-149, BUT NOT CONSISTENTLY BY ATROPINE. The effects of AA-149 were not influenced by pretreatment with atropine, phentolamine or propranolol. These findings strongly suggest that AA-149 relaxed the biliary tract and depressed the morphine-induced spasm by a mechanism different from those of anticholinergic and sympathomimetic agents.


Inhibition of glucagon secretion by diazoxide in vitro.
The effect of diazoxide on the secretion of glucagon and insulin was studied using the isolated perfused rat pancreas. The perfusate concentration of D-glucose was kept constant at 5.6 mM. Five secretagogues of both glucagon and insulin--10 mM L-arginine, 5 mM L-leucine, 1.4 muM prostaglandin F2alpha, 100 nM bovine growth hormone, and 10 nM theophylline--were administered individually in the presence or absence of 325 muM diazoxide. Basal secretion of glucagon or insulin was not discernibly affected by diazoxide. With diazoxide the secretion of glucagon was (a) abolished completely in response to L-arginine or L-leucine; (b) inhibited partially in response to prostaglandin F2alpha; (c) unaltered in response to growth hormone; and (d) unchanged or, at times, enhanced in response to theophylline. On the other hand, the secretion of insulin induced by each of these agents was inhibited effectively by diazoxide. (a) Diazoxide inhibits the secretion of glucagon as well as insulin in response to certain secretagogues independent of any changes in prevailing levels of glucose. (b) At the concentration tested, diazoxide is a more potent and consistent inhibitor of the release of insulin than of glucagon.


Daily hassles and emotional eating in obese adolescents under restricted dietary conditions--the role of ruminative thinking.
Emotional eating is conceptualized as eating in response to negative affect or distress and is discussed as a mechanism leading to eating binges. Recent evidence suggests that eating may not only be triggered by negative affect, but also ruminative thinking. We report results of an experience sampling study examining the role of rumination for emotional eating in 16 obese adolescents (M=15.5 years, S.D.=1.4; range 14-17, body mass index M = 31.1 kgm(-2), S.D.=5.5) under restricted dietary conditions. We hypothesized that daily hassles type of stress predicted the individuals' desire to eat, with the predictive value further increased when negative affect and rumination were accounted for. The results of mixed regression modeling were in line with our predictions, suggesting a significant contribution of ruminative thinking to the mechanisms of negative affect induced eating.


The NO-cGMP-PKG pathway plays an essential role in the acquisition of ethanol resistance by cerebellar granule neurons.
When the developing brain is exposed to alcohol, neuronal death is a prominent pathologic effect. This loss of neurons may underlie many of the behavioral deficits observed in fetal alcohol syndrome (FAS). Previous studies using whole animals and cultured neurons have demonstrated that the vulnerability of neurons to alcohol-induced death changes with development and can diminish markedly over the course of several days. This study examined the possibility that developmental stage-dependent alcohol resistance depends on a unique signaling pathway involving nitric oxide (NO), the NO-cyclic GMP (cGMP)-cGMP-dependent protein kinase (PKG) pathway. Cerebellar granule neuron (CGN) cultures were established from neonatal rats. The cultures were exposed to alcohol (400 mg/dl) either when they were newly established (1 day in vitro, 1-DIV) or when they were more mature (4 days in vitro, 4-DIV). Viable neurons were quantified 24 h later. Although both 1-DIV and 4-DIV cultures were exposed to alcohol for an identical length of time (24 h), the 1-DIV cultures were much more vulnerable to alcohol-induced neuronal death (22.9% neuronal loss) than the 4-DIV cultures (2.3% neuronal loss). Thus, the cultures have a developmental stage-dependent alcohol resistance. To determine the role of the NO-cGMP-PKG pathway in this developmental stage-dependent alcohol resistance, the CGN cultures at 4-DIV were exposed to agents that either activated or inhibited the pathway, either in the presence or in the absence of alcohol. Inhibition of the pathway at its first step with N(G)-nitro-l-arginine-methyl ester (NAME) or at its second step with LY83583 converted the 4-DIV cultures from alcohol resistant to alcohol sensitive. Alcohol-induced neuronal losses were as severe in the 4-DIV cultures treated with pathway inhibitors as they were in the 1-DIV cultures. Treatment of the CGN cultures with agents that activate the NO-cGMP-PKG pathway reduced background cell death, and this neurotrophic effect was not inhibited by the presence of alcohol. Furthermore, activation of the NO-cGMP-PKG pathway at sites downstream from sites of pathway inhibition restored alcohol resistance. Thus, the developmental stage-dependent alcohol resistance acquired by CGN cultures depends on a functional NO-cGMP-PKG pathway.


Corrigendum: A comprehensively prognostic and immunological analysis of actin-related protein 2/3 complex subunit 5 in pan-cancer and identification in hepatocellular carcinoma.
[This corrects the article DOI: 10.3389/fimmu.2022.944898.].


Effect of gold nanosphere surface chemistry on protein adsorption and cell uptake in vitro.
Gold nanoparticles exhibit unique spectral properties that make them ideal for biosensing, imaging, drug delivery, and other therapeutic applications. Interaction of gold nanoparticles within biological environments is dependent on surface characteristics, which may rely on particular capping agents. In this study, gold nanospheres (GNS) synthesized with different capping agents--specifically citric acid (CA) and tannic acid (TA)--were compared for serum protein adsorption and cellular uptake into a lung epithelial cell line (A549). Both GNS samples exhibited noticeable protein adsorption based on surface charge data after exposure to serum proteins. Light scattering measurements revealed that GNS-CA-protein composites were smaller and less dense compared to GNS-TA-protein composites. The cell uptake characteristics of these nanoparticles were also different. GNS-CA formed large clusters and elicited high uptake, while GNS-TA were taken up as discrete particles, possibly through nonendosomal mechanisms. These results indicate that the capping agents used for GNS synthesis result in unique biological interactions.


External versus endoscopic ultrasound: Non-inferiority assessment for visualization of various structures of interest in the shoulder.
Certain structures and pathologies can be difficult to reveal under videoscopy alone during arthroscopic surgery. Ultrasound can be a useful contribution in arthroscopic diagnostic and therapeutic procedures. The main aim of the present study was to assess equivalence between endoscopic and external ultrasound for shoulder exploration. Secondary objectives comprised qualitative assessment of endoscopic ultrasound images and comparative assessment of acquisition time between the two techniques. An anatomic non-inferiority study was conducted on 6 shoulders from 3 subjects with a mean age of 84 years. After ultrasound examination by a radiologist specializing in osteoarticular imaging, shoulder arthroscopy was performed by a single specialized surgeon, using an ultrasound endoscope. Number of visualized structures and image quality were assessed by independent observers. Ten of the 11 structures of interest (91%) were visualizable on endoscopic ultrasound, versus 4 (36%) on external ultrasound (p<0.05). Mean endoscopic acquisition time was 9.5±6.3minutes [range, 5;22]. In the 11 structures, image quality was better on endoscopic than external ultrasound, except for the acromioclavicular joint, where quality was better on external ultrasound, and the lateral side of the rotator cuff, where quality was equivalent. The present study demonstrated equivalence between endoscopic and external ultrasound for shoulder exploration. IV, Non-inferiority cadaver study.


The Emerging Role of Liquid Biopsies in Lymphoproliferative Disorders.
Lymphomas represent clinically and molecularly heterogeneous diseases with variable presentations, treatment algorithms, and outcomes. As treatment options continue to expand, more sophisticated prognostic and predictive biomarkers are needed to guide personalized treatment approaches. Liquid biopsies, in which the sequencing of circulating tumor DNA (ctDNA) in peripheral blood serves as a surrogate for a tumor biopsy, are now being studied across cancer subtypes, including in lymphoid malignancies. Recent studies have demonstrated the potential of these techniques to improve prognostication and guide individualized treatment strategies, providing a significant advance in the field of precision medicine. In this review, we describe the sequencing platforms currently available for analysis of ctDNA in lymphoma and their potential applications in clinical practice, which seem poised to refine treatment paradigms across lymphoma subtypes.


Evidence and causation in mental capacity assessments PC v City of York Council [2013] EWCA CIV 478.
McFarlane LJ's leading judgment in PC v City of York Council consistently stresses the 'plain' statutory language of the Mental Capacity Act 2005. In doing so, it reveals how intractably difficult performing an assessment in accord with the Act can sometimes be. In particular, it raises questions about the sources of evidence upon which a finding of incapacity can be based, illustrates that causation under the Act may have been widely neglected, and highlights contestable assumptions that underlie the Act's 'decision-specific' approach to assessment.


The Role of Diabetes Mellitus as an Effect Modifier of the Association Between Smoking Cessation and Its Clinical Prognoses: An Observational Cohort Study.
The smoker's paradox refers to an increased risk of adverse clinical outcomes after smoking cessation in patients with coronary artery disease. The mechanisms involved are controversial. The present study evaluated the effect of delay in smoking cessation on clinical outcomes among patients after percutaneous coronary intervention (PCI) stratified by diabetes mellitus (DM). Patients included in this study came from an established Fu Wai hospital PCI cohort. Smoking behavior was recorded; clinical end points included all-cause mortality and repeat revascularization. The analyses were based on 8489 smokers who underwent PCI. Patients with and without DM were examined separately. Multivariable model analysis suggested that smoking cessation was associated with significant lower all-cause mortality both for non-DM and DM patients. The smoking paradox was observed for revascularization. However, the increased risk of repeat revascularization correlated with quitting time among non-DM patients only, especially if they stopped smoking late (>90 days) after their index procedure (adjusted hazard ratio, 3.40; 95% CI: 2.45-4.72). In conclusion, smoking cessation is associated with a lower mortality rate for PCI patients. However, the relative benefit on repeated revascularization was only observed among non-DM patients if they quit smoking early.


Awareness Among Undergraduate Students of Mangalore City Regarding Novel Coronavirus (COVID-19): A Questionnaire Study.
COVID-19 outbreak has surfaced as an imminent threat for the public health. Because India is a populous country, it is important for Indians to be aware of the basic modes of prevention that can diminish the spread of the coronavirus disease 2019 (COVID-19) infection. The present questionnaire study was carried out among the undergraduate students to assess the awareness regarding the spread and control of COVID-19. The questionnaire was circulated among the undergraduate students as a Google form. The study included responses of 868 undergraduate students belonging to 2 university colleges. The majority of the participants were females (63%; n = 547) in the age range of 18-23 y. Approximately 98.3% (853) had awareness regarding COVID-19. Approximately 94.7% (822) were washing their hands after visiting public places, out of which only 90.6% (786) were aware of proper steps to be followed in hand washing. It was concluded that it is required to create awareness among 20.8% (181) of our study participants regarding the importance of hand washing to control COVID-19. Awareness regarding COVID-19 among study participants was good. However, a small part of the study population is required to be educated on proper steps to be followed in hand washing.


Radiation Therapy for Prostate Cancer.
Randomized controlled trials provide evidence-driven clinical decision making in the management of newly diagnosed nonmetastatic and oligometastatic prostate cancer. Advances in technology (eg, multiparametric MRI, MR/transrectal ultrasound fusion biopsy, image-guided radiation therapy, stereotactic body radiation therapy) have transformed diagnosis and treatment of prostate cancer while improving cancer control and quality-of-life outcomes. Exciting breakthroughs are revealing possible new indications for radiotherapy, particularly with respect to oligometastatic prostate cancer. Ongoing studies using next-generation androgen receptor-targeted agents hold promise to continue to improve important clinical outcomes, including metastasis-free prostate cancer-specific and overall survival in addition to health-related quality of life.


Cryptosporidium secretome sheds new light on host-parasite interactions.
Invasive Cryptosporidium sporozoites contain organelles that secrete unique proteins to facilitate invasion and remodeling of the infected cell. By identifying a novel secretory organelle, 'small granules', and defining the global content of all the secretory organelles, Guérin et al. set the stage to uncover molecular determinants of virulence at the host cell interface.


Delftia sp. JD2: a potential Cr(VI)-reducing agent with plant growth-promoting activity.
A chromium (Cr)-resistant bacterium isolated from soil containing 6,000 mg/kg of Cr was identified based on 16S rRNA gene sequence analysis as Delftia, and designated as JD2. Growth of JD2 was accompanied with reduction of Cr(VI) to Cr(III) in liquid medium initially containing 100 mg/L Cr(VI), the maximum concentration allowing growth. JD2 showed NADH/NADPH-dependent reductase activity associated with the soluble fraction of cells. The results suggest that JD2 might be a good candidate for the treatment of highly Cr(VI)-contaminated water and/or industrial effluents. The isolate produced indole-3-acetic acid in the presence and absence of Cr(VI) and showed free-living nitrogen-fixing activity possibly attributable to a V-nitrogenase. JD2 did not counteract the harmful effect of Cr(VI) during leguminous plant growth and nodulation by rhizobial strains but functioned as a "helper" bacterium to enhance the performance of rhizobial inoculant strains during inoculation of alfalfa and clover (used as model plants to study plant growth-promoting activity) in the absence of Cr(VI).


Anticancer activity of Momordica cochinchinensis (red gac) aril and the impact of varietal diversity.
Momordica cochinchinensis (Cucurbitaceae) is a nutritionally and medicinally important fruit restricted to South East Asia with diverse morphological and genetic variations but there is limited information on its medicinal potential. M. cochinchinensis aril from 44 different samples in Australia, Thailand and Vietnam were extracted using different solvents and tested for its anticancer potential. Anticancer activity of M. cochinchinensis aril on breast cancer (MCF7 and BT474) and melanoma (MM418C1 and D24) cells were compared to control fibroblasts (NHDF). The cytotoxicity of the cells following treatment with the aril extract was determined using CCK-8 assay. Biochemical and morphological changes were analysed using flow cytometry, confocal and transmission electron microscopy to determine the mechanism of cell death. The water extract from the aril of M. cochinchinensis elicited significantly higher cytotoxicity towards breast cancer and melanoma cells than the HAE extract. The IC50 concentration for the crude water extract ranged from 0.49 to 0.73 mg/mL and induced both apoptotic and necrotic cell death in a dose- and time-dependant manner with typical biochemical and morphological characteristics. The greatest cytotoxicity was observed from Northern Vietnam samples which caused 70 and 50% melanoma and breast cancer cell death, respectively. The water extract of M. cochinchinensis aril caused significant apoptosis and necrosis of breast cancer and melanoma cells, with varieties from Northern Vietnam possessing superior activity. This highlights the potential of this fruit in the development of novel anticancer agents against such tumours, with specific regions on where to collect the best variety and extraction solvent for optimum activity.


Using European naturalistic driving data to assess secondary task engagement when stopped at a red light.
Some evidence exists that drivers choose to engage in secondary tasks when the driving demand is low (e.g., when the car is stopped). While such a behavior might generally be considered as rather safe, it could be argued that the associated diversion of attention away from the road still leads to a reduction of situational awareness, which might increase collision risk once the car regains motion. This is especially relevant for texting, which is associated with considerable eyes-off-the-road-time. Nonetheless, it seems that previous research has barely addressed the actual engagement in secondary tasks while waiting at a red light (as compared to just addressing the tasks' mere prevalence). The present study investigated secondary task engagement while stopped at a red light using European naturalistic driving data collected through the UDRIVE project. Attention was given to the whole engagement process, including simple prevalence and the tasks' relation (in terms of start/end) to the red light period. Moreover, given that texting is one of the most problematic forms of distraction, it was characterized in more detail regarding glance behavior. Videos of 804 red light episodes from 159 drivers were annotated. Glance behavior was also coded for a sub-set of 75 texting events and their matched baselines. Results, conclusions and practical applications: Drivers engaged in at least one secondary task across almost half of the annotated red light episodes. Drivers who texted while stopped spent most of the time looking at their cell phone. Consequently, drivers might not have been prepared for potentially unexpected events once the light turned green. Further, drivers concluded texting a considerable number of times well after the red light period, which has potential implications for traffic safety.


Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits.
Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors.


Visual status after transsphenoidal surgery at the Mayo Clinic, 1971-1982.
In 1,003 patients who underwent transsphenoidal surgery for sellar and parasellar lesions, the surgical mortality was 0.7% (seven patients). Only 25 patients experienced visual complications. Pituitary adenomas were found in 851 patients, of whom 714 underwent visual acuity and visual field testing both before and after their transsphenoidal operations. Among this group, visual acuity had been reduced in 115; postoperatively it was restored to normal or improved in 53, remained the same in 60, and became worse in two. Visual fields, which had been abnormal preoperatively in 230 cases, were restored to normal or improved in 168, remained the same in 52, and became worse in ten. There were also five patients whose vision was normal preoperatively but not postoperatively; thus, the total of those whose sight became worse after transsphenoidal surgery was 17. Surgical mortality in the group with adenomas was 0.5% (four of 851 patients). Nine adenomas recurred during follow-up. Of 40 patients with craniopharyngiomas, 21 had abnormal vision preoperatively; postoperatively, nine were improved and two were worse. In 40 cases surgical exploration failed to disclose any abnormality. There were 12 patients with chordomas and 60 with miscellaneous sellar and parasellar tumors.


Stimulation artifact correction method for estimation of early cortico-cortical evoked potentials.
Effective connectivity can be explored using direct electrical stimulations in patients suffering from drug-resistant focal epilepsies and investigated with intracranial electrodes. Responses to brief electrical pulses mimic the physiological propagation of signals and manifest as cortico-cortical evoked potentials (CCEP). The first CCEP component is believed to reflect direct connectivity with the stimulated region but the stimulation artifact, a sharp deflection occurring during a few milliseconds, frequently contaminates it. In order to recover the characteristics of early CCEP responses, we developed an artifact correction method based on electrical modeling of the electrode-tissue interface. The biophysically motivated artifact templates are then regressed out of the recorded data as in any classical template-matching removal artifact methods. Our approach is able to make the distinction between the physiological responses time-locked to the stimulation pulses and the non-physiological component. We tested the correction on simulated CCEP data in order to quantify its efficiency for different stimulation and recording parameters. We demonstrated the efficiency of the new correction method on simulations of single trial recordings for early responses contaminated with the stimulation artifact. The results highlight the importance of sampling frequency for an accurate analysis of CCEP. We then applied the approach to experimental data. The model-based template removal was compared to a correction based on the subtraction of the averaged artifact. This new correction method of stimulation artifact will enable investigators to better analyze early CCEP components and infer direct effective connectivity in future CCEP studies.


Clinically relevant preservation conditions for mesenchymal stem/stromal cells derived from perinatal and adult tissue sources.
The interplay between mesenchymal stem/stromal cells (MSCs) and preservation conditions is critical to maintain the viability and functionality of these cells before administration. We observed that Ringer lactate (RL) maintained high viability of bone marrow-derived MSCs for up to 72 h at room temperature (18°C-22°C), whereas adipose-derived and umbilical cord-derived MSCs showed the highest viability for 72 h at a cold temperature (4°C-8°C). These cells maintained their adherence ability with an improved recovery rate and metabolic profiles (glycolysis and mitochondrial respiration) similar to those of freshly harvested cells. Growth factor and cytokine analyses revealed that the preserved cells released substantial amounts of leukaemia inhibitory factors (LIFs), hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A), as well as multiple cytokines (eg IL-4, IL-6, IL-8, MPC-1 and TNF-α). Our data provide the simplest clinically relevant preservation conditions that maintain the viability, stemness and functionality of MSCs from perinatal and adult tissue sources.


Docosahexaenoic acid and cognitive function: Is the link mediated by the autonomic nervous system?
Docosahexaenoic acid is a long-chain polyunsaturated fatty acid that is found in large quantity in the brain and which has repeatedly been observed to be related in positive ways to both cognitive function and cardiovascular health. The mechanisms through which docosahexaenoic acid affects cognition are not well understood, but in this article, we propose a hypothesis that integrates the positive effects of docosahexaenoic acid in the cognitive and cardiovascular realms through the autonomic nervous system. The autonomic nervous system is known to regulate vital functions such as heart rate and respiration, and has also been linked to basic cognitive components related to arousal and attention. We review the literature from this perspective, and delineate the predictions generated by the hypothesis. In addition, we provide new data showing a link between docosahexaenoic acid and fetal heart rate that is consistent with the hypothesis.


Plasma levels and vascular effects of endothelin and big endothelin in patients with stable and unstable angina pectoris undergoing coronary bypass grafting.
The aim of this study was to determine the plasma and pericardial levels of endothelin-1 (ET-1) and its precursor big endothelin-1 (Big ET-1) in patients with unstable and stable angina prior to and following coronary bypass surgery. To further investigate the content of ET-1, tissue levels were studied in the internal mammary artery (IMA) in patients with stable and unstable angina pectoris. Finally, the difference in reactivity of the IMA to ET-1 and Big ET-1 in stable and unstable patients was evaluated. Plasma and pericardial levels of ET-1 and Big ET-1 were determined with radioimmunoassay in 81 patients (33 unstable) immediately before coronary bypass surgery, and at 6, 14, 40 and 64 h following the procedure. Specimens of the distal IMA from 12 patients (six unstable) were collected at the beginning of surgery for determination of tissue levels of ET-1. Additionally, distal internal mammary arteries were obtained from another 24 patients (12 unstable). These vessels were mounted in organ baths for functional studies on vascular reactivity to ET-1 and Big ET-1. The peripheral plasma levels of ET-1 in unstable patients were significantly lower in patients with unstable angina compared with patients with stable angina pectoris at all points of measurement. The levels of Big ET-1 were significantly higher pre-operatively in the unstable group, but decreased to similar levels to those of stable patients following coronary bypass grafting. There was no difference in ET-1 tissue content in the IMA between the patients. ET-1 and Big ET-1 caused an endothelin(A) (ET(A))-receptor blocker sensitive, concentration-dependent contraction of the IMA obtained from stable as well as unstable patients. It is concluded that unstable angina pectoris is associated with an increased ET-1 turnover. This increased turnover may participate in the local regulation of coronary vascular tone with subsequent influence of the condition of the patients. The present investigation also implies that ET(A)-blockade may be useful as an additional pharmacological principal in the treatment of unstable angina pectoris prior to revascularization, as well as to prevent post-operative arterial graft spasm.


Identification of novel Pyrrolo[2,3-d]Pyrimidine-based KRAS G12C inhibitors with anticancer effects.
Oncogene KRAS plays predominant roles in human cancers by regulating cell proliferation, differentiation, and migration. Recent progress revealed that directly target KRAS G12C with allosteric inhibitors that covalently bind to the switch Ⅱ pocket is feasible. Herein, series of pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized through systematic structural optimization, leading to the discovery of compound 2-((S)-1-acryloyl-4-(2-(((2R,7aS)-2-fluorohexahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-methyl-6-(8-methylnaphthalen-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-2-yl)acetonitrile (50) with high KRAS/SOS1 inhibitory potency (IC50 = 0.21 μM) and strong anti-proliferation activities on cancer cells harboring KRAS p.G12C. Compound 50 also exhibited satisfactory selectivity, moderate pharmacokinetic characters, and good anticancer effects in vivo. Meaningfully, the identification of these compounds highlights the necessity of an appropriate conformational constraint for acquiring the applicable binding pose in the cryptic pocket of KRAS, and the results support efforts toward design of KRAS inhibitors with novel skeleton and binding mechanism could be beneficial for targeting the acquired drug resistance.


Truth Be Told: Adolescents' Disclosure of Sexual Activity to Healthcare Providers.
The purpose of this study was to describe whether adolescent and young adult patients truthfully disclose sexual activity to providers during a sexual history and explore associations between disclosure and receipt of recommended services. Data from the 2018 National Survey of Sexual Health and Behavior were used to describe self-reported disclsoure of sexually active 14- to 24-year-olds who had a health care visit in the previous year where a sexual history was taken (n = 196). We examined bivariate associations between disclosure and age, race/ethnicity, sex, sexual identity, and receipt of sexual health services. Most (88%) respondents reported telling their provider the truth about sexual activity. A higher proportion of the younger adolescents (14- to 17-year-olds) did not disclose compared with the 18- to 24-year-old respondents (25.4% vs 3.9%; p < .001). A higher proportion of patients who disclosed reported having a sexually transmitted disease test (69.6% vs 26.7%; p < .001); being offered a sexually transmitted disease test (44.3% vs 4.5%; p < .001); and being asked by providers about number of partners (54.3% vs 15.4%; p < .01). Most young patients disclose their sexual history to their provider, but younger patients might be less likely to do so. Positive patient-provider relationships may encourage disclosure of sexual activity and support receipt of indicated sexual and reproductive health services.


Pancreas abscess: a fatal complication of endoscopic cholangiopancreatography (ERCP).
Endoscopic retrograde cholangiopancreatography (ERCP) is a popular and extremely useful technique for investigating the pancreatico-biliary tree. While the mortality is low, rare complications i.e., pancreatic abscess, may prove lethal. Surgical backup must be available to obviate recognized complications following ERCP.


Application of targeted exome and whole-exome sequencing for Chinese families with Stargardt disease.
The aim of this study was to investigate pathogenic variants and molecular etiologies of Stargardt disease (STGD) in a cohort of Chinese families. A cohort of 12 unrelated STGD families diagnosed on the basis of clinical manifestations underwent analysis by targeted exome or whole-exome sequencing. Bioinformatics analysis, Sanger sequencing, and cosegregation analysis of available family members were used to validate sequencing data and confirm the presence of disease-causing genes. Using targeted exome and whole-exome sequencing, we found that eight families had disease-causing variants in the ABCA4 gene, one family had only one heterozygous variant in the ABCA4 gene, and the remaining three families have not been identified with any disease-causing variants for STGD. We identified 15 variants in the ABCA4 gene; of these, five variants have not been previously described for STGD. The findings in this study expand the data regarding the frequency and spectrum of variants in the ABCA4 gene, thus potentially enriching our understanding of the molecular basis of STGD. Moreover, they constitute clues for future STGD diagnosis and therapy.


Isolation of a novel retina-specific clone (MEKA cDNA) encoding a photoreceptor soluble protein.
We have reported the isolation of clones which are candidates for retina-specific cDNAs. One of the cDNA clones, pCR-470, was further characterized. We found that mRNA corresponding to the pCR-470 was expressed only in the retina and encodes an unknown soluble protein whose molecular weight and pI are calculated to be 26,935 and 5.35, respectively. We designated it as a MEKA protein, because its amino acid sequence starts from M-E-K-A. It was found by in situ hybridization that MEKA mRNA was transcribed only in the photoreceptor cells and accumulated in the inner segments just like opsin mRNA. The MEKA cDNA was ligated with expression vector PEX 1, and a MEKA-fusion protein synthesized in E. coli was purified and used as an antigen. By the Western blot analysis anti-MEKA protein serum reacted with a soluble 32 kDa protein from bovine retina and 33 kDa for chick, but not with proteins from other tissues. Immunohistochemical study showed that anti-MEKA stained only the photoreceptor cells in bovine, chick, rat and mouse retinas.


Observational study of cerebral hemodynamics during dopamine treatment in hypotensive ELBW infants on the first day of life.
To evaluate cerebral hemodynamics during dopamine treatment in hypotensive (mean arterial blood pressure (MABP)<gestational age) extremely low birth weight (ELBW) infants. Continuous monitoring of cerebral blood flow velocity (CBFv), MABP and PCO2 was performed in hypotensive ELBW infants on the first day of life, beginning with an ∼15-min baseline reading and continued during advancing dopamine infusion until MABP was optimized. Physiological variables and CBFv reactivity were compared before and after MABP was optimized. Fifteen hypotensive ELBW infants (625±174 g; 24 (23 to 24.8) weeks) were studied. Mean CBFv increased from 10.9±3.7 to 15.7±5.7 cm s(-1) (P=0.001) simultaneously as MABP increased from 22.3±2.8 to 35.2±9.7 mm Hg (P<0.001). Mean CBFv reactivity (95% confidence interval (CI)) was 3.9 (1.6 to 6.2) %mm Hg(-1). Nine infants died and/or developed severe intraventricular hemorrhage (IVH). Mean CBFv increased pressure-passively as MABP was optimized by dopamine treatment in very sick hypotensive ELBW infants on the first day of life.


Combination therapy to treat moderate to severe psoriasis.
In patients with moderate-to-severe psoriasis, remission can be difficult to achieve and sustain. Both acutely acting and long-term maintenance agents are needed. Speed and efficiency of available monotherapies tend to be inversely proportional to safety. Combination, rotational, and sequential approaches are often more effective and safer than single-agent therapy. Combining agents with complementary adverse effect profiles is preferable. Apparent synergistic enhancement is seen with most paired combinations of the four major therapies: acitretin, phototherapy (ultraviolet B/psoralen plus ultraviolet A), cyclosporine, and methotrexate. Of those, only cyclosporine in combination with psoralen plus ultraviolet A is contraindicated because of increased cancer risk. Combinations of each of those major therapies with topical agents (retinoids, steroids, vitamin D derivatives, and others) have been used with varying efficacy and safety. The immunomodulators, hydroxyurea and thioguanine, have also shown some success in combination therapy. The new biologic agents with their novel modes of action and adverse effect profiles may prove to be important adjuncts in combination/rotational/sequential approaches. In some cases, monotherapy (with either systemic agents or phototherapy) adequately controls moderate to severe disease. A regimen using a single agent has the advantages of lower cost and greater adherence by the patient. For any number of reasons, however, including loss of efficacy, adverse effects, or cumulative or acute toxicity-and especially the inability to clear resistant lesions-a single modality will not be adequate. Using two or more therapies is thus the rule rather than the exception for most patients with moderate-to-severe psoriasis, but picking a combination that serves to balance safety and efficacy needs careful consideration, especially since no evidence-based treatment guidelines exist.


Novel treatments for vasospasm after subarachnoid hemorrhage.
Cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage remains a considerable challenge in neurocritical care medicine. This review aims to cover the recent novel aspects and results in CVS treatment. On the basis of the recent literature, treatment focusing on CVS alone is outdated. A considerable amount of evidence suggests CVS not to be the sole cause of delayed cerebral ischemia (DCI) and poor outcome. Early brain injury, cortical spreading depolarization, inflammation and microthrombosis have recently been discussed as additional factors. The results of a well designed phase III trial, using an endothelin-1 antagonist, indicated a decrease in the occurrence of CVS but did not change the clinical outcome significantly. Induced hypertension is currently recommended for treating suspected DCI, whereas hemodilution and hypervolemia are not. Endovascular intervention is only recommended in case of refractory symptomatic CVS. A couple of newer treatment strategies are under evaluation. Phase III trials are underway for magnesium sulfate and statins. Clinical trials aiming specifically at recently discussed factors other than CVS have not been reported. Reviewing the recent literature, there have been some updates on recommendations and newer treatment modalities are under evaluation. However, a novel treatment with convincing evidence has not been reported so far.


Postural control and head stability during natural gaze behaviour in 6- to 12-year-old children.
We investigated how the influence of natural exploratory gaze behaviour on postural control develops from childhood into adulthood. In a cross-sectional design, we compared four age groups: 6-, 9-, 12-year-olds and young adults. Two experimental trials were performed: quiet stance with a fixed gaze (fixed) and quiet stance with natural exploratory gaze behaviour (exploratory). The latter was elicited by having participants watch an animated short film on a large screen in front of them. 3D head rotations in space and centre of pressure (COP) excursions on the ground plane were measured. Across conditions, both head rotation and COP displacement decreased with increasing age. Head movement was greater in the exploratory condition in all age groups. In all children-but not in adults-COP displacement was markedly greater in the exploratory condition. Bivariate correlations across groups showed highly significant positive correlations between COP displacement in ML direction and head rotation in yaw, roll, and pitch in both conditions. The regularity of COP displacements did not show a clear developmental trend, which indicates that COP dynamics were qualitatively similar across age groups. Together, the results suggest that the contribution of head movement to eye-head saccades decreases with age and that head instability-in part resulting from such gaze-related head movements-is an important limiting factor in children's postural control. The lack of head stabilisation might particularly affect children in everyday activities in which both postural control and visual exploration are required.


Novel keratinolytic enzymes, discovered from a talented and efficient bacterial keratin degrader.
Huge quantities of keratinaceous waste are a substantial and almost totally unexploited protein resource which could be upgraded for use as high value-added products by efficient keratinolytic enzymes. In this study, we found that Bacillus sp. 8A6 can efficiently degrade chicken feather after 24 h growth. According to phylogenetic analysis, the strain (formerly identified as Bacillus pumilus 8A6) belongs to the B. pumilus species clade but it is more closely related to B. safensis. Hotpep predicted 233 putative proteases from Bacillus sp. 8A6 genome. Proteomic analysis of culture broths from Bacillus sp. 8A6 cultured on chicken feathers or on a mixture of bristles and hooves showed high abundance of proteins with functions related to peptidase activity. Five proteases (one from family M12, one from family S01A, two from family S08A and one from family T3) and four oligopeptide and dipeptide binding proteins were highly expressed when Bacillus sp. 8A6 was grown in keratin media compared to LB medium. This study is the first to report that bacterial proteases in families M12, S01A and T3 are involved in keratin degradation together with proteases from family S08.


The syndrome of partial mole.
One hundred and six patients with complete mole and 35 patients with partial mole were analysed. The clinical behaviour of complete mole was more florid. The clinical diagnosis of partial mole was more difficult. 20.7% of the complete mole patients and 11.4% of the partial mole patients required chemotherapy because of persistent or metastatic trophoblastic disease. The response to chemotherapy was more favourable in the partial moles. All patients with either partial or complete mole needed hCG assay monitor because of the risk of malignant sequelae.


Detection of all human Plasmodium species by a telomeric DNA fragment cloned from Plasmodium berghei.
A telomeric DNA fragment that was cloned from Plasmodium berghei was used to detect the genomic DNA of P. falciparum, P. vivax, P. malariae, and P. ovale. The fragment hybridized to the DNA of all four of these human Plasmodium species and can be used as an interspecific probe to detect human malaria.


Assessing the Role of Urban Green Areas for Students' Quality of Life during the COVID-19 Pandemic.
The COVID-19 pandemic and social distancing measures have limited outdoor activities for many people, including university students who live inside the campus and far from their families. We investigated if and how the fear of COVID-19 had impacted visiting green areas and consequently the quality of life. The assessments were taken through a questionnaire-based survey of the university students living inside the campus in two universities (Konkuk and Sejong universities) in Seoul, South Korea in 2021 (n=255). Measuring three variables, the participants were asked to self-estimate their fear of COVID-19 and quality of life during the pandemic, and the time and frequency of the park visit. Structural equation modeling (SEM) and confirmatory factor analysis (CFA) were conducted to explore the potential relationship between the three main observed variables. In the case of the campus students, visiting the green area cannot play a mediating impact on the effect of the COVID-19 fear and quality of life. Likewise, the data did not support the effect of COVID-19 fear on the quality of life for this group of students, however, significant correlations were found between the COVID-19fear and visiting green spaces (P<0.05) (positive effect on visiting, and negative effect on the time of visit). Students perceived not a considerable improvement in their quality of life after visiting green areas. It might be due to the fear of staying outdoor for a long time (frequency) during the pandemic, and students' lifestyles. However, the quality of life for the students is likely to be influenced by other factors, rather than the fear of COVID-19.


Mathematical analysis of magnetohydrodynamic (MHD) flow of micropolar nanofluid under buoyancy effects past a vertical shrinking surface: dual solutions.
In this paper, we explore dual solutions of MHD flow, heat and mass transfer of micropolar nanofluid over a linear vertical shrinking surface with buoyancy effects, which was not considered in the previous works. The governing fluid flow equations of this problem are transformed into nonlinear boundary value problems (BVPs) of ordinary differential equations (ODEs) by applying similarity variables. The resultant BVPs are converted into initial value problems (IVPs) by using shooting method which then resolved by employing Runge Kutta of order four. The impacts of the governing parameters, such as suction parameter, material parameter, Richardson number, magnetic parameter, Prandtl number, thermophoresis and Brownian motion parameters on velocity, angular velocity, temperature, and concentration are illustrated graphically. The results indicate that the existence of a range of dual solutions and no-solutions. When Richardson number ( δ ) is increased, the reduction of the velocity of micropolar nanofluid has occurred in the second solution. The stability analysis on dual solutions, however, reveals that only the first solution is stable.


Factors influencing the use of public dental services: an application of the Theory of Planned Behaviour.
There is limited evidence of the influence of psychosocial factors and health beliefs on public dental patient's patterns of service use in Australia. The research aims were to examine associations between dental attitudes and beliefs of public dental service users and dental visiting intention and behaviour using the Theory of Planned Behaviour. 517 randomly selected adult public dental patients completed a questionnaire assessing dental attitudes and beliefs which was matched with electronic records for past and future dental service use. A questionnaire measured intentions, attitudes, subjective norms and perceptions of behavioural control and self-efficacy in relation to visiting public dentists. A measure of dental attendance at public dental clinics was obtained retrospectively (over 3 1/2 years) and prospectively (over a one year period following the return of the questionnaire) by accessing electronic patient clinical records. Participants had positive attitudes, subjective norms and self-efficacy beliefs towards dental visiting but perceived a lack of control over visiting the dentist. Attitudes, subjective norms, self-efficacy and perceived control were significant predictors of intention (P < 0.05). Intentions, self-efficacy and past dental attendance were significant predictors of actual dental attendance (P < 0.05). Public dental patients held favourable attitudes and beliefs but perceived a lack of control towards dental visiting. Reducing structural barriers may therefore improve access to public dental services.


Century-long changes and drivers of soil nitrous oxide (N2 O) emissions across the contiguous United States.
The atmospheric concentration of nitrous oxide (N2 O) has increased by 23% since the pre-industrial era, which substantially destructed the stratospheric ozone layer and changed the global climate. However, it remains uncertain about the reasons behind the increase and the spatiotemporal patterns of soil N2 O emissions, a primary biogenic source. Here, we used an integrative land ecosystem model, Dynamic Land Ecosystem Model (DLEM), to quantify direct (i.e., emitted from local soil) and indirect (i.e., emissions related to local practices but occurring elsewhere) N2 O emissions in the contiguous United States during 1900-2019. Newly developed geospatial data of land-use history and crop-specific agricultural management practices were used to force DLEM at a spatial resolution of 5 arc-min by 5 arc-min. The model simulation indicates that the U.S. soil N2 O emissions totaled 0.97 ± 0.06 Tg N year-1 during the 2010s, with 94% and 6% from direct and indirect emissions, respectively. Hot spots of soil N2 O emission are found in the US Corn Belt and Rice Belt. We find a threefold increase in total soil N2 O emission in the United States since 1900, 74% of which is from agricultural soil emissions, increasing by 12 times from 0.04 Tg N year-1 in the 1900s to 0.51 Tg N year-1 in the 2010s. More than 90% of soil N2 O emission increase in agricultural soils is attributed to human land-use change and agricultural management practices, while increases in N deposition and climate warming are the dominant drivers for N2 O emission increase from natural soils. Across the cropped acres, corn production stands out with a large amount of fertilizer consumption and high-emission factors, responsible for nearly two-thirds of direct agricultural soil N2 O emission increase since 1900. Our study suggests a large N2 O mitigation potential in cropland and the importance of exploring crop-specific mitigation strategies and prioritizing management alternatives for targeted crop types.


In vitro apatite formation on organic polymers modified with a silane coupling reagent.
Gamma-methacryloxypropyltrimethoxysilane (gamma-MPS) was grafted to high-density polyethylene, polyamide and silicone rubber substrates by the emulsion polymerization procedure in order to provide these organic polymers with in vitro apatite-forming ability. The contact angles towards distilled water of the gamma-MPS-grafted specimens were lower than those of the original organic polymer specimens, indicating that the grafted substrates were more hydrophilic. The in vitro apatite formation in a simulated body fluid (Kokubo solution) was confirmed for several of the gamma-MPS-grafted specimens.