Reliability and validity of King's Health Questionnaire in patients with symptoms of overactive bladder with urge incontinence in Japan.
The purpose of this study is to evaluate the psychometric properties of the Japanese version of the King's Health Questionnaire (KHQ) in patients with symptoms of overactive bladder (OAB) with urge incontinence. Data from a 12-week, randomized, double-blind, placebo-controlled clinical trial comparing tolterodine with oxybutynin in patients with symptoms of OAB in Japan were analyzed. Cronbach's alpha coefficient was calculated as a reliability index. Inter-domain correlation was calculated for convergent and discriminant validity assessment. A factor analysis was conducted to explore the underlying factor structure of the KHQ. Sensitivity to clinical change was also evaluated. The psychometric properties and clinical validity of the KHQ Japanese version were confirmed in this study population, and were similar between males and females. The KHQ's good reliability was evidenced by Cronbach's alpha coefficients of >0.60, indicating reasonable consistency except for the personal relationship domain in males (0.47) and severity (coping) measure domain in females (0.59). Discriminant, convergent, and construct validity of the KHQ were also good, with the factor analysis identifying those factors which the KHQ was intended to measure. Finally, KHQ domains were generally responsive to clinical efficacy variables; the KHQ also showed statistically significant sensitivity to change in patients' perception of bladder condition in all domains, except General Health Perception. Our analyses confirm psychometric properties and clinical validity of the KHQ Japanese version, which appears to offer a valid and reliable HRQoL instrument for use in clinical trials of antimuscarinics in Japan.


Eosinophilic COPD Patients Display a Distinctive Serum miRNA Profile From Asthma and Non-eosinophilic COPD.
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases that may overlap in some individuals. Asthma COPD overlap (ACO) is a heterogeneous conditions that includes smoking-asthma (SA) and COPD with eosinophilia (COPDe). MicroRNAs (miRNA) are regulators of gene expression with a great potential as biomarkers. The objective of this study was to identify distinctive miRNA signatures in patients from the whole spectrum of chronic obstructive bronchial disease (SA, COPDe, non-smoking asthmatics (NSA), and COPD) that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. From a previously characterized cohort of ACO, COPD and asthma patients, we selected a discovery group of 40 patients for miRNA expression profiling by means of microarray technology. Differential expression of miRNAs were validated by quantitative PCR in the complete cohort (n=274). Thirty differentially expressed miRNAs (eBAYES p<0.05, fold change ≥2) were found among the different groups of patients regarding COPDe: 19 COPD-vs-COPDe, 13 NSA-vs-COPDe, 11 SA-vs-COPDe. A characteristic down-regulated miRNA expression pattern was identified in COPDe patients. Differential expression of miR-619-5p and miR-4486 in COPDe patients were validated in the complete cohort (n=274). We postulate that COPDe patients show a characteristic expression profile of miRNAs distinctive from asthma and COPD. Also that SA and COPDe patients, which have been typically clustered in the ACO group, display distinct molecular events.


Testosterone deficiency and the aging male.
Testosterone deficiency (TD), also known as male hypogonadism, is a complex syndrome encompassing physical, biochemical, and social aspects that increasingly affects the aging population. TD has been analyzed over recent decades, with an enhanced focus on etiologies relating to aging males. There is debate whether testosterone decline leading to hypogonadism is directly and primarily related to age-specific processes or if it is the subsequent result of accumulating comorbidities throughout a lifetime. Several studies have been done to further characterize this distinction. Chronic comorbidities that have commonly been associated with TD include hypertension (HTN), cardiovascular disease (CVD), diabetes mellitus (DM), obesity, metabolic syndrome (MetS), chronic kidney disease (CKD), and tobacco use. Although clear associations between hypogonadism and aging have been biochemically demonstrated, many large studies have illustrated the concomitant effects of highly prevalent chronic diseases and social behaviors in aging men. Given the significant impact of hypogonadism on the physical and mental health of men, this paper aims to delve into these studies and further define the complex relationship of testosterone deficiency in the aging male.


Detection of the cross-linking amino acid, histidinoalanine, in human brown cataractous lens protein.
In human nuclear cataract, with its progression, high polymers protein mass, which is aggregated and strengthened by disulfide cross-links and other covalent cross-links, accumulates in the nuclear region to cause hardening of the lens nucleus. However, the structure of non-disulfide covalent cross-links has not been clearly confirmed yet. Recently a cross-linking amino acid, histidinoalanine, was discovered in connective tissue and is thought to cause hardening of the tissue with aging. The content of this amino acid in the lens nucleus was studied. Nuclear cataract was classified on the basis of nuclear color as described by Pirie (1986). The content of histidinoalanine was found to be 0.05 +/- 0.03 nmol mg-1 in normal nucleus; 0.06 +/- 0.03 nmol mg-1 in grade I (uniform pale yellow); 0.05 +/- 0.03 nmol mg-1 in grade II (deep yellow nucleus); 0.38 +/- 0.07 nmol mg-1 (P less than 0.01) in grade III (hazel-brown nucleus) and 3.35 +/- 2.76 nmol mg-1 (P less than 0.01) in grade IV (deep brown nucleus). The result suggests that histidinoalanine is one of the non-disulfide cross-links of lens proteins in nuclear cataract and is closely related to the grade of cataract.


The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care--an observational analysis on non-small-cell lung cancer patients.
To evaluate frequency and severity of adverse drug reactions (ADRs) and its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC). Subanalysis of a prospective, multicentre, longitudinal, observational cohort study; data were collected from patient interviews and pre-planned chart reviews. Costs were aggregated per CT line and presented from provider perspective. A total of 120 consecutive NSCLC patients (mean age, 63.0 ± 8.4 (SD) years; men, 64.2%; ECOG (Eastern Cooperative Oncology Group) performance status <2, 84.3%; tumour stage III/IV, 85%; history of comorbidity, 93.3%) receiving 130 CT lines were evaluated. 80% of CT lines were associated with grade 3 or 4 ADRs, 22.3% developed potential life-threatening complications, 77.7% were associated with at least one hospital stay (inpatient, 63.9%; outpatient/day clinic 39.2%, ICU 6.9%), with a mean cumulative number of 12.8 (±14.0 SD) hospital days. Mean (median) toxicity management costs per CT line (TMC-TL) amounted to €3,366 (€1,406) and were found to be higher for first-line compared to second-line treatment: €3,677 (€1,599) vs. €2,475 (€518). TMC-TL were particularly high in CT lines with ICU care €12,207 (€9,960). Eight out of 11 ICU stays were associated with grade 3 or 4 infections. Nine CT lines with ICU care accounted for 25% of total expenses (€109,861 out of €437,580). In first-line NSCLC treatment, in particular, CT toxicity management is expensive. Asymmetric cost distribution seems to be triggered by infection associated ICU care. Its avoidance should reduce patients' clinical burden and have considerable economic implications. Nevertheless, comparative observational studies have to confirm estimated savings.


Perylene tetra-(alkoxycarbonyl) derivative and its copper chelate for selective sensing of fluoride ions.
Two novel fluoride ion fluorescent probes (P1 and P2) containing perylene tetra-(alkoxycarbonyl) derivative (PTAC) and its copper chelate were designed and synthesized. The identification properties of the probes were studied by absorption and fluorescence methods. The results showed that the probes were highly selective and sensitive to fluoride ions. 1H NMR titration confirmed that the sensing mechanism involved the formation of H-bond between the O-H moiety and fluoride ions, and the coordination of copper ion could enhance the H-bond donor capacity of the receptor unit (O-H). The corresponding orbital electron distributions were calculated by density functional theory (DFT). In addition, fluoride ion can be easily detected by probe-coated Whatman filter paper without the need for expensive equipment. Until now, there have been few reports of such probes enhancing the capacity of the H-bond donor based on metal ion chelation. This study will contribute to the design and synthesis of novel sensitive perylene fluoride probes.


Assessment of the related factors of blood loss and blood ingredients among patients under hypotensive anesthesia in orthognathic surgery.
The objective of the study was to understand the factors associated with presurgical and postsurgical blood loss and blood ingredients among patients in the treatment of mandibular prognathism by intraoral vertical ramus osteotomy combined genioplasty. Preoperative and postoperative values of blood loss and blood ingredients were collected from 30 mandibular prognathic patients who underwent orthognathic surgery. The linear regression models and correlation coefficients were used to identify factors with respect to patients' blood loss level and 3 types of blood ingredients (ie, red blood cells, hemoglobin, and hematocrit). The mean blood loss and operation time were 179.2 mL and 311.7 minutes, respectively. No blood transfusion was received by our patients. After adjusting for potential factors, the regression models showed that no significant factor was found to be associated with blood loss and reduce blood ingredients. Moreover, female patients were found to be more likely to have a low level of presurgical blood ingredients (β = -0.293 to -3.551; P < 0.05), whereas female sex (β = -1.606 to -4.008; P < 0.001), a high blood loss level (β = -0.003 to -0.009; P < 0.05), and long operation time (β = -0.005 to -0.018; P < 0.05) were associated with a low level of postsurgical blood ingredients (ie, hemoglobin and hematocrit). No significant factor was associated with blood loss and reduced blood ingredients among patients in orthognathic surgery with hypotenstive anesthesia. Improvements in anesthesia provided surgeons with more time to promote hemostasis during surgery. Hypotensive anesthesia was a well-accepted method to reduce blood loss during orthognathic surgery.


Influence of belt pretensioning on dummy responses in 40 km/h rear-impact sled tests.
This study compares dummy kinematics and biomechanical responses with and without belt pretensioning in matched rear sled tests. Two rear-impact sled tests were run at 40 km/h (25 mph) rear delta V with a lap-shoulder-belted Hybrid III 50th percentile male dummy on Ford F-150 driver seats. One test was with the standard lap-shoulder belts and the other with a buckle pretensioner activated at 20 ms. The head, chest, and pelvis were instrumented with triaxial accelerometers. The upper and lower neck, thoracic spine, and lumbar spine had transducers measuring triaxial loads and moments. Lap and shoulder belt loads were measured. High-speed video recorded different views of the dummy motion. Dummy kinematics and biomechanical responses were compared to study the influence of belt pretensioning. The dummy kinematics and biomechanical responses were essentially similar with and without belt pretensioning in the rear-impact sled tests. There were higher belt loads with pretensioning, but they did not result in different dummy lumbar loads or pelvic, chest, and head accelerations. In a rear impact, the dummy moves rearward away from the belts that wrap around the chest and pelvis. The occupant loads the seat, which yields rearward restraining dummy motion. Though pretensioning caused a transient increase in belt load, it was of short duration and there was no sustained effect on occupant dynamics until late in rebound. The matched tests showed no difference in occupant restraint with and without buckle pretensioning in 40 km/h (25 mph) rear-impact sled tests. Belt pretensioning did not influence occupant responses in these rear impacts because the seat supported the occupant.


Primary clear cell adenocarcinoma of the vagina not associated with diethylstilbestrol metastasizing to the lung: a case report.
Primary clear cell carcinoma of the vagina (PCCAV) is a rare form of vaginal cancer that typically affects young women with a history of prenatal exposure to DES. However, data on non-DES PCCAV cases are limited. This report describes a case of PCCAV in a 47-year-old patient who presented with post-coital bleeding and was diagnosed with clear cell adenocarcinoma via biopsy and MRI. The patient had no history of DES exposure and further testing showed no signs of metastasis, leading to surgery and chemotherapy. Four years later, the patient presented with dyspnea, and a chest CT scan revealed a lung nodule, later confirmed to be a metastasis of clear cell adenocarcinoma from the vaginal cancer. The patient passed away a month later due to complications from COVID-19.


Biphasic effects of amphetamine on striatal dopamine dynamics.
S(+)-Amphetamine (AMPH) was administered to rats over the dose range 0.15-10.0 mg/kg (1.74(3)mumoles/kg) at various times before sacrifice. 15 min before sacrifice rats received an intraventricular injection of 3H-tyrosine, and the accumulation of striatal 3H-dopamine (DA) was assessed as an index of striatal DA formation and utilization. 3H-DA formation exhibited a biphasic dose response to AMPH. At 16 and 31 min after AMPH administration, 3H-DA accumulation increased linearly in response to AMPH to a maximal rate of 200% of control values at 1.0 mg/kg, then declined to less than 50% of control values at AMPH doses of 5 and 10 mg/kg. As a function of time, low doses of AMPH (to 2.0 mg/kg)) only increased 3H-DA accumulation, whereas high doses of AMPH (greater than 2.5 mg/kg) only decreased 3H-DA accumulation. All doses of AMPH increased endogenous levels of striatal DA. The data are discussed in terms of compensatory adaptive mechanisms of the nigrostriatal dopaminergic pathway.


Practical clinical guidelines for contouring the trigeminal nerve (V) and its branches in head and neck cancers.
The trigeminal nerve (V) is a major route of tumor spread in several head and neck cancers. However, only limited data are currently available for its precise contouring, although this is absolutely necessary in the era of intensity-modulated radiation therapy (IMRT). The purpose of this article is to present practical clinical guidelines for contouring the trigeminal nerve (V) in head and neck cancers at risk of spread along this nerve. The main types of head and neck cancers associated with risks of spread along the trigeminal nerve (V) and its branches were comprehensively reviewed based on clinical experience, literature-based patterns of failure, anatomy and radio-anatomy. A consensus for contouring was proposed based on a multidisciplinary approach among head and neck oncology experts including radiation oncologists (JBi, ML, MO, VG and JB), a radiologist (VD) and a surgeon (CS). These practical clinical guidelines have been endorsed by the GORTEC (Head and Neck Radiation Oncology Group). We provided contouring and treatment guidelines, supported by detailed figures and tables to help, for the trigeminal nerve and its branches: the ophthalmic nerve (V1), the maxillary nerve (V2) and the manidibular nerve (V3). A CT- and MRI-based atlas was proposed to illustrate the whole trigeminal nerve pathway with its main branches. Trigeminal nerve (V) invasion is an important component of the natural history of various head and neck cancers. Recognizing the radio-anatomy and potential routes of invasion is essential for optimal contouring, as presented in these guidelines.


Mono-Oxidation of Bidentate Bis-phosphines in Catalyst Activation: Kinetic and Mechanistic Studies of a Pd/Xantphos-Catalyzed C-H Functionalization.
Kinetic, spectroscopic, crystallographic, and computational studies probing a Pd-catalyzed C-H arylation reaction reveal that mono-oxidation of the bis-phosphine ligand is critical for the formation of the active catalyst. The bis-phosphine mono-oxide is shown to be a hemilabile, bidentate ligand for palladium. Isolation of the oxidative addition adduct, with structural elucidation by X-ray analysis, showed that the mono-oxide was catalytically competent, giving the same reaction rate in the productive reaction as the Pd(II)/xantphos precursor. A dual role for the carboxylate base in both catalyst activation and reaction turnover was demonstrated, along with the inhibiting effect of excess phosphine ligand. The generality of the role of phosphine mono-oxide complexes in Pd-catalyzed coupling processes is discussed.


Correction to: Understanding the survival mechanisms of Deinococcus radiodurans against oxidative stress by targeting thioredoxin reductase redox system.
The correction does not affect the discussion or conclusions of the article. The correct image is given below.


[Primary open-angle glaucoma (POAG), retinal vein occlusions (RVO) and central corneal thickness (CCT): what is the relationship?].
To investigate the relationship between various types of glaucoma, retinal vein occlusion (RVO), and central corneal thickness (CCT) METHODS: We followed 48 known glaucoma patients who developed any type of retinal vein occlusion. Mean follow-up was 4.2 years. At all visits, patients had a detailed ocular history, as well as thorough bilateral evaluation, including dynamic gonioscopy, CCT measurement, retinal nerve fiber layer (RNFL) measurement by OCT, and automated visual field. Student's t-test and Chi(2) test were used to evaluate continuous and categorical data, respectively, with comparison of the means of paired series. Mean age at time of diagnosis was 68.1 ± 11.8 years (range 40-85 years). Six patients were black (12.5%), while the others were white (87.5%, P=0,0001). Various types of glaucoma were found in the 48 patients (22 men, 26 women, P=0.564) who developed RVO. No significant difference was found between mean CCT of eyes with RVO and fellow eyes (537.7 ± 39.8 μM and 538.4 ± 36.4 μM, respectively) (P=0.527). By stratifying our results according to the various types of glaucoma, mean CCT of involved and fellow eyes was 542.7 ± 37.6 μM and 540.6 ± 33.2 μM, respectively in the primary open-angle glaucoma (POAG) group, 530.4 ± 45.2 μM and 535 ± 43.6 μM in the chronic angle-closure glaucoma (CACG) group, 549.3 ± 24.8 μM and 558 ± 37.3 μM in the pseudo-exfoliation glaucoma (PXG) group, and 490 ± 56.6 μM and 495 ± 35.4 μM in the normal-tension glaucoma (NTG) group. Contrary to some recently-published studies, our results showed no statistically significant difference between CCT of eyes involved with RVO and fellow eyes. The NTG group seems to have the thinnest CCT.


ProPred analysis and experimental evaluation of promiscuous T-cell epitopes of three major secreted antigens of Mycobacterium tuberculosis.
In the search for safe vaccine candidates against tuberculosis (TB), subunit vaccines including peptide-based candidates deserve consideration. However, an important requirement for such vaccine candidates is their promiscuous presentation to Th1 cells mediating protective immunity against TB, i.e. Th1 cells secreting IFN-gamma. The aim of the present study was to identify promiscuous Th1 cell epitopes of three major secreted antigens of Mycobacterium tuberculosis, i.e. ESAT-6, CFP10 and MPT70 by using a virtual matrix-based prediction program (ProPred) for peptide binding to 51 HLA-DR alleles. The ProPred analysis of these proteins was performed using the server (http:www.imtech.res.in/raghava/ProPed/). The peptides predicted to bind > 50% HLA-DR alleles included in the ProPred were considered promiscuous for binding predictions. Based on this criteria, one region in ESAT-6 (aa 69-77), two regions in CFP10 (aa 55-66 and aa 76-84) and four regions in MPT70 (aa 1-11, aa 81-95, aa 124-140 and aa 182-191) were considered promiscuous HLA-DR binders. The experimental evaluation of these regions, by using overlapping synthetic peptides for presentation to T-cells, confirmed the promiscuous nature of peptides covering the regions aa 69-77, aa 76-84 and aa 182-191 of ESAT-6, CFP10 and MPT70, respectively. These results demonstrate that the ProPred analysis can facilitate the selection of promiscuous peptides recognized by Th1 cells, and thus it can be useful in the identification of peptide-based vaccine candidates against TB.


Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22-p21.3.
Human prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high-resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy-resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22-p21.3 flanked by markers cMSR-32 and C18-1051. A second region of common deletion was identified between C18-1312 and C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early-stage tumors (11/27, 40%; P < 0.01, Fisher's exact test). In two out of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer.


Structure of fumarate hydratase from Rickettsia prowazekii, the agent of typhus and suspected relative of the mitochondria.
Rickettsiae are obligate intracellular parasites of eukaryotic cells that are the causative agents responsible for spotted fever and typhus. Their small genome (about 800 protein-coding genes) is highly conserved across species and has been postulated as the ancestor of the mitochondria. No genes that are required for glycolysis are found in the Rickettsia prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in both. A 2.4 Å resolution crystal structure of R. prowazekii fumarate hydratase, an enzyme catalyzing the third step of the tricarboxylic acid cycle pathway that ultimately converts phosphoenolpyruvate into succinyl-CoA, has been solved. A structure alignment with human mitochondrial fumarate hydratase highlights the close similarity between R. prowazekii and mitochondrial enzymes.


The computerised tomographic findings in paediatric orbital tumours.
Forty-two patients with histologically proven orbital tumours are presented. CT is of value in the pretreatment assessment and in delineating the extent of the orbital tumour. The surrounding bony destruction and intracranial extension are easily assessed. Post-treatment follow-up can be closely monitored using CT.


Towards a sustainable transformation of municipal wastewater treatment plants into biofactories using advanced NH3-N recovery technologies: A review.
Ammonia (NH3), as a prevalent pollutant in municipal wastewater discharges, can impair aquatic life and have a negatively impact on the environment. Proper wastewater treatment and management practices are essential to protect ecosystems and keep human populations healthy. Therefore, using highly effective NH3-N recovery technologies at wastewater treatment plants (WWTPs) is widely acknowledged as a necessity. In order to improve the overall efficiency of NH3 removal/recovery processes, innovative technologies have been generally applied to reduce its concentration when discharged into natural water bodies. This study reviews the current status of the main issues affecting NH3 recovery from municipal/domestic wastewater discharges. The current study investigated the ability to recover valuable resources, e.g., nutrients, regenerated water, and energy in the form of biogas through advanced and innovative methods in tertiary treatment to achieve higher efficiency towards sustainable wastewater and resource recovery facilities (W&RRFs). In addition, the concept of paradigm shifts from WWTP to a large/full scale W&RRF has been studied with several examples of conversion to innovative bio-factories producing materials. On the other hand, the carbon footprint and the high-energy consumption of the WWTPs were also considered to assess the sustainability of these facilities.


Non-thermal plasma activated peroxide and percarbonate for tetracycline and oxytetracycline degradation: Synergistic performance, degradation pathways, and toxicity evaluation.
Tetracycline (TC) and Oxytetracycline (OTC) are common antibiotics increasingly detected in the environment, posing a potential risk to human and aquatic lives. Although conventional methods such as adsorption and photocatalysis are used for the degradation of TC and OTC, they are inefficient in removal efficiency, energy yield, and toxic byproduct generation. Herein, a falling-film dielectric barrier discharge (DBD) reactor coupled with environmentally friendly oxidants (hydrogen peroxide (HPO), sodium percarbonate (SPC), and HPO + SPC) was applied, and the treatment efficiency of TC and OTC was investigated. Experimental results showed that moderate addition of the HPO and SPC exhibited a synergistic effect (SF > 2), significantly improving the antibiotic removal ratio, total organic removal ratio (TOC), and energy yield by more than 50%, 52%, and 180%, respectively. After 10 min of DBD treatment, the introduction of 0.2 mM SPC led to a 100% antibiotic removal ratio and a TOC removal of 53.4% and 61.2% for 200 mg/L TC and 200 mg/L OTC, respectively. Also, 1 mM HPO dosage led to 100% antibiotic removal ratios after 10 min of DBD treatment and a TOC removal of 62.4% and 71.9% for 200 mg/L TC and 200 mg/L OTC, respectively. However, the DBD + HPO + SPC treatment method had a detrimental effect on the performance of the DBD reactor. After 10 min of DBD plasma discharge, the removal ratios for TC and OTC were 80.8% and 84.1%, respectively, when 0.5 mM HPO + 0.5 mM SPC was added. Moreover, principal component and hierarchical cluster analysis confirmed the differences between the treatment methods. Furthermore, the concentration of oxidant-induced in-situ generated ozone and hydrogen peroxide were quantitatively determined, and their indispensable roles during the degradation process were established via radical scavenger tests. Finally, the synergetic antibiotic degradation mechanisms and pathways were proposed, and the toxicities of the intermediate byproducts were evaluated.


[Application of three-dimensional digital technology in the diagnosis and treatment planning in orthodontics].
Three-dimensional(3D)digital technology has been widely used in the field of orthodontics in clinical examination, diagnosis, treatment and curative effect evaluation. 3D digital technology greatly improves the accuracy of diagnosis and treatment, and provides effective means for personalized orthodontic treatment. This review focuses on the application of 3D digital technology in the field of orthodontics.


Scaling law and microstructure of alginate hydrogel.
The gelation of alginate in aqueous solution was studied as a function of Ca(2+) concentration. At each given concentration of alginate, a critical gel concentration [Formula: see text] , was successfully determined for the first time using the Winter-Chambon criterion. The critical gel concentration [Formula: see text] was found to increase linearly with alginate concentration. At the same time, the critical relaxation exponent n decreased and the critical gel strength Sg increased linearly with alginate concentration. An improved egg-box model was proposed to describe the change in gel junction and gel network. In the stable gel state, the plateau modulus Ge of alginate gel depended on Ca(2+) concentration according to a power-law scaling, Ge=kɛ(1.5), where ɛ is the relative distance of a gelling variable (Ca(2+) concentration in this case) from the gel point ( [Formula: see text] ). The FESEM images verified the microstructure of alginate gel in which alginate chains associated into fibrils in the presence of Ca(2+) ions. The fibrillar diameter and network density increased with increasing Ca(2+) ion concentration while alginate concentration had a weak influence on fibrillar diameter.


Modulation of the beta-adrenergic receptor system of vascular smooth muscle cells in vitro and in vivo by chronically elevated endothelin-1 levels.
Endothelin-1 (ET-1) levels are chronically elevated in several cardiovascular diseases and correlate with an increased mortality. However, in contrast to acute biological activities such as vasoconstriction, little is known about long-term effects of ET-1. In this study we determined the effects of ET-1 on the beta(2)-adrenergic receptor (AR) system. Incubation of smooth muscle cells with ET-1 for 72 hr led to increased beta(2)AR density as determined by radioligand binding. Experiments with inhibitors of protein and RNA synthesis as well as RT-PCR revealed that beta(2)AR upregulation required de novo synthesis. In addition, protein kinase C but neither NO nor prostaglandin metabolism were involved in this effect. The enhanced expression of beta(2)AR was associated with an increased expression of its stimulatory G-protein and the receptor's ability to stimulate adenylyl cyclase. To study chronic effects of ET-1 in vivo, rats were infused with ET-1 for 3 weeks. Similarly as in cultured cells, prolonged ET-1 exposure led to increased betaAR expression in vivo. As a consequence, beta(2)AR-induced vasodilatation was increased in aortic rings from ET-1-treated animals. Our results therefore suggest that chronically elevated ET-1 levels in vitro and in vivo induce counterregulatory mechanisms by increasing betaARs that attenuate the vasoconstrictive effects of ET-1.


Effect of linear alkylbenzene sulphonates (LAS) on the anaerobic digestion of sewage sludge.
Batch anaerobic biodegradation tests with different alkylbenzene sulphonates (LAS) at increasing concentrations were performed in order to investigate the effect of LAS homologues on the anaerobic digestion process of sewage sludge. Addition of LAS homologues to the anaerobic digesters increased the biogas production at surfactant concentrations 5-10 g/kg dry sludge and gave rise to a partial or total inhibition of the methanogenic activity at higher surfactant loads. Therefore, at the usual LAS concentration range in sewage sludge, no adverse effects on the anaerobic digesters functioning of a wastewater treatment plant (WWTP) can be expected. The increase of biogas production at low surfactant concentrations was attributed to an increase of the bioavailability and subsequent biodegradation of organic pollutants associated with the sludge, promoted by the surfactant adsorption at the solid/liquid interface. When the available surfactant fraction in the aqueous phase instead of the nominal surfactant concentration was used to evaluate the toxicity of LAS homologues, a highly significant relationship between toxicity and alkyl chain length was obtained. Taking into account the homologue distribution of commercial LAS in the liquid phase of the anaerobic digesters of a WWTP, an EC(50) value of 14 mg/L can be considered for LAS toxicity on the anaerobic microorganisms.


Monoamine neurocircuitry in depression and strategies for new treatments.
Extensive studies showed that monoaminergic neurotransmission that involves serotonin (5-HT), norepinephrine (NE) and dopamine (DA) exerts major influence on brain circuits concerned by the regulation of mood, reactivity to psychological stress, self-control, motivation, drive, and cognitive performance. Antidepressants targeting monoamines directly affect the functional tone of these circuits, notably in limbic and frontocortical areas, and evidence has been provided that this action plays a key role in their therapeutic efficacy. Indeed, at least some of functional changes detected by functional magnetic resonance imaging in emotion- and cognitive-related circuits such as the one involving limbic-cortical-striatal-pallidal-thalamic connections in depressed patients can be reversed by monoamine-targeted antidepressants. However, antidepressants acting selectively on only one monoamine, such as selective inhibitors of 5-HT or NE reuptake, alleviate depression symptoms in a limited percentage of patients, and are poorly effective to prevent recurrence. Thorough investigations for the last 30 years allowed the demonstration of the existence of functional interactions between 5-HT, NE and DA systems, and the identification of the specific receptors involved. In particular, 5-HT systems were shown to exert negative influence on NE and DA systems through 5-HT2A and 5-HT2C receptor- mediated mechanisms, respectively. On the other hand, complex positive and negative influences of NE system on 5-HT neurotransmission are mediated through α1- and α2-adrenergic receptors, respectively. These data provided a rationale for the design of new, multimodal, therapeutic strategies involving drugs acting not only at the "historical" targets such as the 5-HT and/or the NE transporter, but also at other molecular targets to improve their efficacy and their tolerability.


Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate.
Indoleamine 2,3-dioxygenase purified to apparent homogeneity from rabbit intestine was inhibited by scavengers for superoxide anion such as superoxide dismutase and 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron). On the other hand, beta-carotene and 1,4-diazobicyclo-(2,2,2)-octane, scavengers for singlet oxygen, did not affect the enzyme activity significantly. The degree of inhibition of the dioxygenase by superoxide dismutase preparations from bovine erythrocytes, green peas, spinach leaves, and Escherichia coli paralleled that observed with these dismutase preparations on the aerobic reduction of cytochrome c by xanthine oxidase and its substrate. The pH profiles of the inhibition by dismutase of the dioxygenase and cytochrome c reduction were also similar and the maximal inhibition was observed around pH 10 in both cases. The degree of inhibition was not affected by the concentration of substrate but was a function of the concentration of dismutase. It was inversely related to the concentrations of the dioxygenase and its cofactors, ascorbic acid and methylene blue, both of which were required for maximum activity. Ascorbic acid could be replaced either by xanthine oxidase and its substrate, or by tetrabutylammonium superoxide prepared by electrolytic reduction of molecular oxygen, or by potassium superoxide. When limited amounts of superoxide anion were added to the reaction mixture containing a substrate amount of the dioxygenase, the ratio of the amount of superoxide anion added to that of the product formed was approximately unity both under aerobic and anaerobic conditions. Taken together, these findings indicate that superoxide anion, rather than molecular oxygen, is utilized as substrate by indoleamine 2,3-dioxygenase.


Oxidative stress induction by short time exposure to ozone on THP-1 cells.
Ozone is a major component of air pollution mainly formed by photochemical reactions of nitrogen oxides with volatile organic compounds and/or carbon monoxide. Numerous studies have shown the association between ozone exposure with pulmonary injuries. This pollutant is a strong oxidant exerting its biological action either by direct reaction with target molecules or by generating reactive oxygen species which result in its biological effects and its toxicity. In order to study the effects of an induced oxidative stress by ozone on THP-1 cell, a human macrophage-like cell line, we used an in vitro system which has been previously used to study the rapid responses to ozone exposure. Using this system, THP-1 cells were subjected to short time exposure (30 min) followed by different incubation times ranging from 4 to 24 h. Our results show that ozone exposure provokes an alteration of the cell membrane translating an induction of lipid peroxidation resulting in a 3.2-fold increase of thiobarbituric reactive substances (TBARS), an increase by 35% of heme oxygenase-1 (HO-1) expression, and significant modifications of the redox status evaluated by glutathione measurement and of antioxidant enzyme activities in THP-1 cells. Our in vitro model constitutes a very interesting tool for the measurement of ozone effect on rapid modifications induced by this pollutant as well as intracellular modifications due to an oxidative stress.


Reversible escitalopram-induced hypothyroidism.
Some drugs can cause alterations in the concentration of thyroid hormones in blood even without clinical signs of dysfunction or pathology of the thyroid gland. Apart from the well-known relationship between depression and hypothalamic-pituitary-thyroid (HPT) axis, and the impact of selective serotonin reuptake inhibitors (SSRIs) on thyroid indices, hypothyroidism is a very rare adverse effect of SSRI treatment. However, the case presented here demonstrates that escitalopram may have the potential to induce hypothyroidism without any significant clinical signs and symptoms. Therefore, the possibility of SSRI-induced asymptomatic hypothyroidism presented here may help clinicians in this regard.


T and R states in the crystals of bacterial L-lactate dehydrogenase reveal the mechanism for allosteric control.
The crystal structure of L-lactate dehydrogenase from Bifidobacterium longum, determined to 2.5 A resolution, contains a regular 1:1 complex of T- and R-state tetramers. A comparison of these two structures within the same crystal lattice and kinetical characterization of the T-R transition in solution provide an explanation for the molecular mechanism of allosteric activation. Substrate affinity is controlled by helix sliding between subunits which is triggered by the binding of the activator, fructose 1,6-bisphosphate. The proposed mechanism can explain activation by chemical modification and mutagenesis, as well as suggesting why vertebrate counterparts are not allosteric.


Computational and experimental study of the mechanics of embryonic wound healing.
Wounds in the embryo show a remarkable ability to heal quickly without leaving a scar. Previous studies have found that an actomyosin ring (purse string) forms around the wound perimeter and contracts to close the wound over the course of several dozens of minutes. Here, we report experiments that reveal an even faster mechanism which remarkably closes wounds by more than 50% within the first 30s. Circular and elliptical wounds (~100μm in size) were made in the blastoderm of early chick embryos and allowed to heal, with wound area and shape characterized as functions of time. The closure rate displayed a biphasic behavior, with rapid constriction lasting about a minute, followed by a period of more gradual closure to complete healing. Fluorescent staining suggests that both healing phases are driven by actomyosin contraction, with relatively rapid contraction of fibers at cell borders within a relatively thick ring of tissue (several cells wide) around the wound followed by slower contraction of a thin supracellular actomyosin ring along the margin, consistent with a purse string mechanism. Finite-element modeling showed that this idea is biophysically plausible, with relatively isotropic contraction within the thick ring giving way to tangential contraction in the thin ring. In addition, consistent with experimental results, simulated elliptical wounds heal with little change in aspect ratio, and decreased membrane tension can cause these wounds to open briefly before going on to heal. These results provide new insight into the healing mechanism in embryonic epithelia.


A simple and rapid procedure for the isolation of intact bovine rod outer segments (ROS).
A method is described which allows the rapid isolation and purification of intact rod outer segments (ROS) from cattle eyes. It requires very fresh retinal material and can be completed within less than 2 h of the death of the animals. Cattle eyes are dissected in the usual manner, the retinae are isolated and the ROS are separated from the rest of the retina by gentle vortexing and filtration through a nylon mesh. The resulting crude ROS suspension is purified on a discontinuous sucrose density gradient. Two fractions are obtained, the major one consisting of mostly intact ROS, the minor one of RIS-ROS, i.e. of ROS which are still connected to part of their inner segment. The ROS are washed once and can be stored on ice for several days without loosing their intact plasma membrane. They can be transformed to leaky ROS by a quick freeze/thawing cycle or, if one wants unobstructed access to the interdiskal space, they can be subjected to a mild lysis treatment. The resulting ROS material is characterised using light microscopy, electron microscopy, light scattering, gel electrophoresis and absorption spectroscopy. It contains unusually low levels of 48k-protein and very high levels of G-protein. The latter cannot be washed out in the presence of GTP-gamma-S, even in the case of leaky ROS.


Pharmacokinetics and Pharmacodynamics of Burixafor Hydrobromide (GPC-100), a Novel C-X-C Chemokine Receptor 4 Antagonist and Mobilizer of Hematopoietic Stem/Progenitor Cells, in Mice and Healthy Subjects.
Adequate mobilization of hematopoietic stem cells (HSCs), especially CD34+ cells, is necessary for stem cell transplantation in patients with hematological malignancies or autoimmune diseases. Burixafor is an inhibitor of the C-X-C Chemokine Receptor 4 that disrupts the C-X-C motif chemokine 12 (CXCL12)/CXCR4 axis in the bone marrow, releasing HSCs into circulation. In mice, a single intravenous dose of burixafor was rapidly absorbed (time to maximum concentration, 5 minutes) and increased peripheral white blood cell counts within 30 minutes. Additionally, burixafor was administered to 64 healthy subjects in a randomized, double-blind, placebo-controlled, single-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics. Subjects received burixafor intravenous doses ranging from 0.10 to 4.40 mg/kg in 8 cohorts. Single doses were generally safe and well tolerated. Gastrointestinal events were reported at doses of 2.24 mg/kg or greater. Exposure (maximum concentration and area under the concentration-time curve) increased in an approximately dose-proportional manner. Time to maximum concentration occurred with a median of 0.26-0.30 hours that was not dose proportional. As expected, white blood cell, CD133+ cell, and CD34+ cell concentrations generally increased with the increases in burixafor dose from 0.10 to 3.14 mg/kg. At maximal levels, the CD34+ cell counts increased 3- to 14-fold from baseline levels. These results provide support for continued clinical development of burixafor.


Extraction and decontamination of microplastics from high organic matter soils: A simple, cost-saving and high efficient method.
This article introduces a simple, cost-saving and high efficient for the extraction and separation of microplastics (MPs) from soil with a high organic matter (SOM) content. In this study, MP with particle sizes of 154-600 μm of polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC) and polyethylene terephthalate (PET) were artificially added into the five Mollisols with the high SOM. Three flotation solutions were used to extract these MPs from soils, and four digestion solutions were used to digest the SOM. As well, their destruction effects on MPs were also examined. The results showed that the flotation recovery rates of PE, PP, PS, PVC and PET were 96.1%-99.0% by ZnCl2 solution, while were 102.0%-107.2% by rapeseed oil, were 100.0%-104.7% by soybean oil. The digestion rate of SOM was 89.3% by H2SO4:H2O2 (1:40, v:v) at 70 °C for 48 h, and this was higher than by H2O2 (30%), NaOH and Fenton's reagent. However, the digestion rate of PE, PP, PS, PVC and PET were 0.0%-0.54% by H2SO4:H2O2 (1:40, v:v), and this was lower than by H2O2 (30%), NaOH and Fenton's reagent. As well, the factors influencing on MP extraction was also discussed. Generally, the best flotation solution was ZnCl2 (ρ > 1.6 g cm-3) and the best digestion method was H2SO4:H2O2 (1:40, v:v) at 70 °C for 48 h. The optimal extraction and digestion method were verified by the known concentrations of MPs (recovery rate of MPs was 95.7-101.7%), and this method was also used to extract MPs from long-term mulching vegetable fields in Mollisols of Northeast China.


Full automation in allergy testing: measurement of specific IgE by the ENEA System.
We evaluated the ENEA System, a fully automated instrument for the measurement of specific IgE antibodies. The instrument dispenses sera and reagents, incubates, washes, and reads and prints results automatically. The "core" of the instrument is the reactive unit called ACE (Allergy Chamber Enzymatic), which is a new solid phase to which the allergens are linked. The system uses calibration curves specific for the major allergen families, and data are supplied qualitatively (five classes) and quantitatively. We evaluated the analytic efficiency of the system and its correlation with the in vivo test (skin prick test (SPT)) results in 60 patients with inhalant allergic diseases and in 20 controls. 450 results were available within 4 h. A satisfactory within-run (CVs between 1.58 and 6.2%) and between-run (CVs 6.3-11.5%) precision was found. No significant carry-over was observed. A wide linearity of the assay was demonstrated. With the concordance between the clinical history and SPT as the reference value, the clinical sensitivity of the ENEA System was 84.1%, the specificity 82.8%, and the overall efficiency 83.4%. Finally, a good agreement with the results of another technique for the in vitro measurement of specific IgE (Pharmacia CAP System) was proven.


High-Frequency 0.36BiScO3-0.64PbTiO3 Ultrasonic Transducer for High-Temperature Imaging Application.
( 1- x )BiScO3- x PbTiO3 (BS-PT) ceramics have excellent piezoelectricity and high Curie temperature at its morphotropic phase boundary (MPB) ( x = 0.64 ), so it is a promising piezoelectric material for fabricating high-temperature ultrasonic transducer (HTUT). Electric properties of 0.36BS-0.64PT ceramics were characterized at different temperatures, and an HTUT with the center frequency of about 15 MHz was designed by PiezoCAD based on the measuring results. The prepared HTUT was tested in a silicone oil bath at different temperatures systematically. The test results show that the HTUT can maintain a stable electrical resonance until 290 °C and get a clear echo response until 250 °C with slight changes of the center frequency. Then, a stepped metal block submerged in silicone oil was imaged by the HTUT until 250 °C. Velocity of silicone oil and axial resolution of the HTUT at different temperatures was calculated. The results verify the capability of 0.36BS-0.64PT-based HTUT for high-temperature ultrasonic imaging applications.


Patient-controlled analgesia vs. conventional intramuscular analgesia following colon surgery.
Though patient-controlled analgesia (PCA) has been in use for over a decade, it has been popularized only recently. Conventional techniques of intermittent intramuscular (IM) administration of analgesia have fallen short of meeting the needs of patients following major abdominal surgery. This has prompted a search for methods to improve postoperative pain management. Though PCA has been accepted in many hospitals, few studies comparing conventional IM administration of morphine with PCA have been performed. A prospective randomized study comparing IM- and PCA-administered morphine in 62 patients undergoing colon surgery was performed. A comparison of the efficacy of analgesia and extent of sedation using these approaches shows that PCA allows for analgesia with less sedation and less drug requirement than that of IM administration. No differences were noted in postoperative duration of ileus, duration of hospitalization, and total hospital costs. This study confirms the safety and efficacy of PCA, and should be considered the current optimal method of controlling pain following major colonic surgery.


Effect of Metabolic and Bariatric Surgery on the Clinical Course of Multiple Sclerosis in Patients with Severe Obesity: a Systematic Review.
Multiple sclerosis (MS) is an autoimmune inflammatory condition affecting the central nervous system (CNS). A systematic review following the PRISMA guidelines was performed to explore the effect of metabolic and bariatric surgery (MBS) on the clinical course and outcomes in patients with multiple sclerosis. Eleven articles examining 394 patients were included in the final analysis. The mean MS duration at the time of surgery was 7.6 ± 4.6 years, and the mean postoperative follow-up was 35.5 ± 5.3 months. MBS leads to the same weight loss with the same complication rate as in patients without MS. Most of patients experienced improvement in clinical course of MS after MBS, compared to non-surgical group. However, there is a risk for MS exacerbation in a number of patients after MBS; they should not be disadvantaged from having MBS, since surgery leads to the same weight loss outcomes with the same complication rate as in patients without MS.


Heat-shock proteins DnaK and GroEL facilitate export of LacZ hybrid proteins in E. coli.
The use of lacZ gene fusions, producing a hybrid protein containing an amino terminus specified by a target gene fused to the functional carboxy terminus of beta-galactosidase, has facilitated the study of protein targeting in various organisms. One of the best characterized fusions in Escherichia coli is phi(lamB-lacZ)42-1(Hyb), which produces a hybrid protein with the signal sequence and 181 N-terminal amino acids of the exported protein LamB, attached to LacZ. In common with other LacZ hybrids, the LamB-LacZ(42-1) protein is poorly exported from E. coli, conferring a Lac+ phenotype. beta-Galactosidase activity decreases markedly when cells producing the LamB-LacZ protein are grown at 42 degrees C or when a heat-shock response is induced at lower temperatures by overproducing heat-shock factor RpoH3, indicating the LacZ hybrids are being efficiently targeted to the cell envelope. We now report that the heat-shock proteins DnaK and GroEL can, in sufficient amounts, decrease beta-galactosidase activity and facilitate the export of lacZ-hybrid proteins.


Short communication: The biological value of transition milk: analyses of immunoglobulin G, IGF-I and lactoferrin in primiparous and multiparous dairy cows.
Colostrum (the first mammary gland secretion after calving) is known to contain high concentrations of nutrients as well as bioactive substances (including immunoglobulins, growth factors, and antimicrobial factors) to ensure neonatal survival. Due to its immunomodulatory, antibacterial, and antiviral activities, bovine colostrum has been used not only in calves but also in the prevention and treatment of human gastrointestinal and respiratory infections. Transition milk is the mammary secretion from the second milking to the sixth, which may contain these bioactive compounds to a lesser extent. The objective of the present study was to measure IGF-I, immunoglobulin G (IgG), and lactoferrin (LTF) concentrations in colostrum and transition milk of primiparous and multiparous cows to further assess its potential use in veterinary and nutraceutical applications. The results demonstrated that the concentrations of these three bioactive molecules decrease from the first milking to the tenth. Concentrations of IGF-I and LTF were greater in multiparous than in primiparous cows. Also, lactation number interacted with milking number in IGF-I, since primiparous cows had a smoother decline of IGF-I concentrations than multiparous ones. Overall, transition milk from the second milking showed a 46% decrease in the analysed colostrum bioactive molecules. Therefore, further studies are needed to apply this knowledge in neonate farm management practices or in developing pharmaceutical supplements from farm surpluses.


Coaching Non-technical Skills Improves Surgical Residents' Performance in a Simulated Operating Room.
To investigate the effect of coaching on non-technical skills and performance during laparoscopic cholecystectomy in a simulated operating room (OR). Non-technical skills (situation awareness, decision making, teamwork, and leadership) underpin technical ability and are critical to the success of operations and the safety of patients in the OR. The rate of developing assessment tools in this area has outpaced development of workable interventions to improve non-technical skills in surgical training and beyond. A randomized trial was conducted with senior surgical residents (n = 16). Participants were randomized to receive either non-technical skills coaching (intervention) or to self-reflect (control) after each of 5 simulated operations. Coaching was based on the Non-Technical Skills For Surgeons (NOTSS) behavior observation system. Surgeon-coaches trained in this method coached participants in the intervention group for 10 minutes after each simulation. Primary outcome measure was non-technical skills, assessed from video by a surgeon using the NOTSS system. Secondary outcomes were time to call for help during bleeding, operative time, and path length of laparoscopic instruments. Non-technical skills improved in the intervention group from scenario 1 to scenario 5 compared with those in the control group (p = 0.04). The intervention group was faster to call for help when faced with unstoppable bleeding in the final scenario (no. 5; p = 0.03). Coaching improved residents' non-technical skills in the simulated OR compared with those in the control group. Important next steps are to implement non-technical skills coaching in the real OR and assess effect on clinically important process measures and patient outcomes.


Cytochemical localization of adenylate cyclase in the dense tubule system of human blood platelets stimulated by forskolin, prostacyclin and prostaglandin D2.
Platelets were briefly fixed in paraformaldehyde/glutaraldehyde and then incubated with 5'-adenylyl imidodiphosphate under conditions suitable for the cytochemical detection of adenylate cyclase activity. The adenylate cyclase activity of these platelets retains the ability to respond to prostaglandins E1, D2, I2 (prostacyclin), forskolin and fluoride. Sites of stimulated adenylate cyclase activity were localized cytochemically by the reaction of lead with the reaction product imidodiphosphate to form deposits of lead imidodiphosphate that are visible in the electron microscope. Reaction product deposition was seen only in the dense tubule system of human platelets when the incubation medium contained forskolin, prostacyclin, or prostaglandin D2 at concentrations known to stimulate the enzyme in intact platelets. Epinephrine, an antagonist of adenylate cyclase inhibited the cytochemical reaction stimulated by prostacyclin. The fact that the cytochemical reaction was induced by agonists that stimulate the enzyme through two different types of prostaglandin receptors and by forskolin, which acts distal to the receptors, confirms that the method specifically detects adenylate cyclase. The presence of adenylate cyclase in the dense tubules may be significant for the regulation of intracellular Ca2+ and arachidonic acid metabolism by this membrane system.


Influenza vaccine effectiveness: Maintained protection throughout the duration of influenza seasons 2010-2011 through 2013-2014.
Factors, such as age, comorbidities, vaccine type, herd immunity, previous influenza exposure, and antigenic shift may impact the immune response to the influenza vaccine, protection against circulating strains, and antibody waning. Evaluating vaccine effectiveness (VE) is important for informing timing of vaccine administration and evaluating overall vaccine benefit. VE was assessed using febrile respiratory illness surveillance among Department of Defense non-active duty beneficiaries from influenza seasons 2010-2011 through 2013-2014. Respiratory specimens were taken from participants meeting the case definition and tested by polymerase chain reaction for influenza. VE was calculated using logistic regression and by taking 1 minus the odds ratio of being vaccinated in the laboratory confirmed positive influenza cases versus laboratory confirmed negative controls. This study included 1486 participants. We found an overall adjusted VE that provided significant and fairly consistent protection ranging from 54% to 67% during 0-180days postvaccination. This VE dropped to -11% (95% confidence interval: -102% to 39%) during 181-365days. Our study found moderate VE up to 6months postvaccination. Since the influenza season starts at different times each year, optimal timing is difficult to predict. Consequently, early influenza vaccination may still offer the best overall protection.


Effect of sodium butyrate on the antiviral and anticellular action of interferon in normal and MSV-transformed cells.
Sodium butyrate enhances the antiviral and anticellular action of interferon in MSV-transformed cells but has no such effect in normal cells. The increased sensitivity could be mediated at least partially by the butyrate-induced elaboration of the microtubule and microfilament network.


An automated controlled-release device for intravaginal hormone delivery.
Our objective was to develop and validate an electronically controlled hormone-delivery device for reproductive control of cattle. After development and in vitro testing of a prototype device for intravaginal (IVG) hormone release, we aimed to demonstrate the feasibility of inducing luteal regression by automated treatment with PGF2α. The IVG device comprises an outer 3D-printed plastic housing, fluid reservoirs connected to delivery pumps and tubing, a programmable circuit board, and a retention mechanism. For in vitro testing, 4 pumps were programmed to release different target volumes (0.1, 0.2, 0.5, 1.0, and 2.0 mL) in 4 replicates (n = 80). A Bland-Altman plot was constructed to assess the magnitude of disagreement between expected and delivered volumes. Observations fell within acceptable limits of agreement (1.96 standard deviations) >95% of the time, indicating overall good agreement (mean difference = -0.005 mL). To assess in vivo performance of the IVG device, lactating Holstein cows with at least 1 corpus luteum ≥15 mm in diameter were randomly allocated to 1 of 3 treatments: (1) IM-PGF (n = 6): two 25-mg intramuscular doses of PGF2α 24 h apart; (2) DEV-PGF (n = 6): four 25-mg doses of PGF2α released automatically by the IVG device at 10- or 12-h intervals; and (3) DEV-CTL (n = 4): insertion of an empty IVG device (placebo control). Blood samples were collected at 0, 12, 24, 36, 48, and 72 h after treatment. Data were analyzed by ANOVA with repeated measures. All devices (10/10) remained in situ until removed at 48 h. Progesterone (P4) concentrations from 0 to 72 h were affected by treatment, time, and their interaction. Concentrations of P4 did not differ at time 0 but differed from 24 to 72 h: cows in IM-PGF and DEV-PGF had lesser P4 than cows in DEV-CTL. Conversely, P4 did not differ for IM-PGF and DEV-PGF during the experiment. We conclude that the current IVG hormone-releasing device prototype can be programmed to automatically release PGF2α for successful induction of luteal regression in lactating dairy cows.


Use of Diagnostic Performance of Clinical Examination Measures and Pain Presentation to Identify Patellofemoral Joint Osteoarthritis.
To assess the diagnostic performance of a comprehensive set of tests and measures to discriminate patellofemoral (PF) from tibiofemoral (TF) osteoarthritis (OA). The Clinical Assessment of the Knee Study is a study of knee pain in the general population. The presence of PF crepitus and pain with PF compression were assessed. Anterior knee pain was determined using a knee pain map. Pain with climbing/descending stairs and walking on level ground were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index. Radiographs were used to define the compartment(s) of the knee affected by OA (no OA, isolated/predominant PF joint OA, and isolated/predominant TF joint OA). In knees with mixed OA, knees with more severe PF joint OA were included in the isolated/predominant PF group (the same was done for TF joint OA). We determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and positive likelihood ratio (LR+) for each test and measure individually, and the combination of these measures, in distinguishing knees with PF joint OA from knees with TF joint OA or no OA. There were 745 knees included in the study. No measure had high sensitivity and specificity. Pain with climbing/descending stairs had the greatest sensitivity (90%) but poor specificity (15%). The combination of definite crepitus with no pain on walking had the greatest specificity (96%), PPV (53%), and LR+ (1.8), but poor sensitivity (7%). Typical clinical examination findings and knee pain patterns commonly thought to represent underlying PF joint pathology do not discriminate knees with PF joint OA from knees without OA or TF joint OA.


Automating behavioral analysis in neuroscience: Development of an open-source python software for more consistent and reliable results.
The application of automated analyses in neuroscience has become a practical approach. With automation, the algorithms and tools employed perform fast and accurate data analysis. It minimizes the inherent errors of manual analysis performed by a human experimenter. It also reduces the time required to analyze a large amount of data and the need for human and financial resources. In this work, we describe a protocol for the automated analysis of the Morris Water Maze (MWM) and the Open Field (OF) test using the OpenCV library in Python. This simple protocol tracks mice navigation with high accuracy. In the MWM, both automated and manual analysis revealed similar results regarding the time the mice stayed in the target quadrant (p = 0.109). In the OF test, both automated and manual analysis revealed similar results regarding the time the mice stayed in the center (p = 0.520) and in the border (p = 0.503) of the field. The automated analysis protocol has several advantages over manual analysis. It saves time, reduces human errors, can be customized, and provides more consistent information about animal behavior during tests. We conclude that the automated protocol described here is reliable and provides consistent behavioral analysis in mice. This automated protocol could lead to deeper insight into behavioral neuroscience.


Neuropsychological performance of a clinical sample of extremely obese individuals.
Obesity is a leading cause of preventable death in America and its prevalence is increasing at an alarming rate. While it is known that individuals with specific obesity-related medical conditions perform poorly on neuropsychological tasks, recent evidence suggests that cognitive dysfunction in obese individuals may occur independently of medical co-morbidities. This study examined neuropsychological performance in a clinical sample of extremely obese patients. Individuals seeking surgical treatment of obesity (N=68) were administered cognitive tests as part of a standard pre-surgical evaluation. Results indicated significant differences in performances of extremely obese individuals on tests of executive functioning (planning, problem solving, mental flexibility) in comparison to normative data. No significant differences emerged between obese patients with and without co-morbid medical conditions of hypertension, type II diabetes, and obstructive sleep apnea on the neuropsychological tasks specific to executive functioning. Taken together, these results provide further evidence of specific cognitive dysfunction in extremely obese individuals.


Polymorphic ventricular tachycardia and other complex arrhythmias in organophosphate insecticide poisoning.
Organophosphate insecticide intoxication produces endogenous acetylcholine poisoning which may precipitate complex ventricular arrhythmias, a relatively unrecognized and potentially lethal aspect of this condition. A case is described in which sinus bradycardia, A-V dissociation, idioventricular rhythms, multiform ventricular extrasystoles, and prolongation of the PR, QRS, and QT intervals were observed. Polymorphic ventricular tachycardia--a chaotic ventricular rhythm characterized by extreme variability of QRS morphology and the R-R interval--which previously has not been reported with organophosphate poisoning, was also present in our case. Metabolic and electrolyte derangements, myocardial injury, autonomic dysfunction, and asynchronous repolarization variously may be involved in the genesis of arrhythmias in organophosphate intoxication. Management of these cases should take into account the possible occurrence of conduction abnormalities and arrhythmias, including polymorphic ventricular tachycardia.


Simultaneous asymmetrical bilateral hip dislocations - A report of three cases with different presentations and management.
Simultaneous traumatic dislocation of both the hips in an individual is an uncommon injury. It accounts for only 1-2% of all traumatic hip dislocations. Simultaneous traumatic dislocation of both the hips in opposite directions i.e., anterior dislocation of one hip and posterior of the other is even rarer. These asymmetric dislocations need prompt identification for appropriate management. While their management should proceed in a manner commensurate with the accepted management of isolated dislocations to avoid complications, it is the timely identification which is essential. Retrospectively the details of three patients with asymmetric bilateral hip dislocations were collected. The article describes the clinical presentation of each patient and the management offered to them. The follow up duration ranged from 15 months to 24 months. In the short term, the outcomes in terms of hip pain, movements at the hips and radiological parameters like absence of arthritic or avascular changes were found to be satisfactory in each patient. Early diagnosis and prompt reduction is the essential first step in the appropriate management of these patients to prevent the possible complications. The associated fractures must be managed as per the established principles of trauma care. Long term follow up is essential for identifying if complications like avascular necrosis and secondary osteoarthritis develop after this uncommon injury.


A record of Diplozoon nipponicum Goto, 1891 found from Cyprinus carpio nudus in Korea.
Diplozoon nipponicum, a monogenean trematode from Cyprinus carpio was described according to the characteristic findings of X-form adult, metrical data, and presence of a pair of sticky glands. It is the first record of the presence of Diplozoon nipponicum in Korea.


Is There Any Association between the Severity of Disc Degeneration and Low Back Pain?
Objective To access the possibility that higher degrees of disc degeneration lead to higher levels of pain and dysfunction. Methods Magnetic resonance imaging (MRI) scans of 85 patients with low back pain lasting for more than 12 weeks were evaluated, and the degree of disc degeneration was quantified according to the Pfirrmann grading system. The Pfirrmann degree in each disc space from L1-L2 to L5-S1, the maximum degree of Pfirrmann (Pfirrmann-max) between the lumbar discs, and the sum of Pfirrmann (Pfirrmann-sum) degrees were correlated (through the Spearman test) with the Oswestry Disability Index (ODI) and the Visual Analogical Scale (VAS) for pain. Results In total, 87% of the patients had moderate to severe lumbar disc degeneration measured by Pfirrmann-max, and the most degenerated discs were L4-L5 and L5-S1. There was a week to moderate correlation regarding the Pfirrmann-max (r = 0,330; p = 0.002) and the Pfirrmann-sum (r = 0,266; p = 0,037) and the ODI, and the Pfirrmann scores in L1-L2 were correlated with the ODI and the VAS. Conclusion Patients with chronic idiopathic low back pain frequently have moderate to severe lumbar disc degeneration, which has a negative impact on the quality of life of the patients. Low degrees of degeneration in L1-L2 might be related with higher degrees of pain and of functional disability.


Enthalpy relaxation in binary amorphous mixtures containing sucrose.
To compare the enthalpy relaxation of amorphous sucrose and co-lyophilized sucrose-additive mixtures near the calorimetric glass transition temperature, so as to measure the effects of additives on the molecular mobility of sucrose. Amorphous sucrose and sucrose-additive mixtures, containing poly(vinylpyrrolidone) (PVP), poly(vinylpyrrolidone-co-vinyl-acetate) (PVPNA) dextran or trehalose, were prepared by lyophilization. Differential scanning calorimetry (DSC) was used to determine the area of the enthalpy recovery endotherm following aging times of up to 750 hours for the various systems. This technique was also used to compare the enthalpy relaxation of a physical mixture of amorphous sucrose and PVP. Relative to sucrose alone, the enthalpy relaxation of co-lyophilized sucrose-additive mixtures was reduced when aged for the same length of time at a comparable degree of undercooling in the order: dextran approximately PVP > PVPNA > trehalose. Calculated estimates of the total enthalpy change required for sucrose and the mixtures to relax to an equilibrium supercooled liquid state (deltaHinfinity) were essentially the same and were in agreement with enthalpy changes measured at longer aging times (750 hours). The observed decrease in the enthalpy relaxation of the mixtures relative to sucrose alone indicates that the mobility of sucrose is reduced by the presence of additives having a Tg that is greater than that of sucrose. Comparison with a physically mixed amorphous system revealed no such effects on sucrose. The formation of a molecular dispersion of sucrose with a second component, present at a level as low as 10%, thus reduces the mobility of sucrose below Tg, most likely due to the coupling of the molecular motions of sucrose to those of the additive through molecular interactions.


Secreted microRNAs: a new form of intercellular communication.
In multicellular organisms, cell-to-cell communication is of particular importance for the proper development and function of the organism as a whole. Intensive studies over the past three years suggesting horizontal transfer of secreted microRNAs (miRNAs) between cells point to a potentially novel role for these molecules in intercellular communication. Using a microvesicle-dependent, or RNA-binding protein-associated, active trafficking system, secreted miRNAs can be delivered into recipient cells where they function as endogenous miRNAs, simultaneously regulating multiple target genes or signaling events. In this Opinion, we summarize recent literature on the biogenesis and uptake of secreted miRNAs, propose a possible working model for how secreted miRNAs might be sorted and transferred between cells and speculate on their biological significance.


The coverage and detection limit of a sampling point for robotics radiation mapping.
The sensor coverage problem aims to maximize the coverage of a target area with a fixed or minimum number of sensors. However, the sampling point coverage for radiation mapping has yet to be specified or adequately established. When dealing with unknown radiation fields, it is critical that the placements of sampling points will ensure that all hotspots are detected and accurately identified. Therefore, the concept of coverage and detection limit for a sampling point in radiation mapping is proposed in this paper. The proposed concept relates the angular dependency of the radiation measurement instruments with the detector detection limit or minimum detectable amount (MDA). To demonstrate the implementation, the concept is used to compute the sensitivity of the radiation map for coverage radiation mapping with mobile robot. Simulation results showed that hotspots with intensity equal to or above the sampling point detection limit were successfully detected regardless of their position within the coverage circle. Moreover, the experimental results of coverage radiation mapping showed that the concept can be used to compute the resolution of the radiation map. This will help the user to efficiently configure the appropriate grid size that suit their mapping situation and requirements.


Active water management brings possibility restoration to degraded lakes in dryland regions: a case study of Lop Nur, China.
Protecting and restoring the degraded arid lakes are globally urgent issues. We document a potential recovery of the dried salt-lake, Lop Nur called "the Sea of Death" which is located at the terminus of the largest inland basin in China, the Tarim River Basin. The changes and relationship of surface water with climate parameters and groundwater in the basin over the last 30 years are analyzed, by using satellite remote sensing and land data assimilation products. We find that with increased surface water in the basin, the groundwater level in Lop Nur began to show an obvious positive response in 2015; and the rate of decline of the groundwater level is slowing down. We argue that after a balance is achieved between regional groundwater recharge and evapotranspiration, the Lop Nur ecosystem will gradually recover. This study shows an encouraging case for the protection and restoration of degraded lakes in dryland regions around the world.


Malaysian dental therapists' job motivation, job satisfaction, intention to leave and perceived future roles.
To assess Malaysian dental therapists' job satisfaction, motivation, turnover intention and perceived future roles, following recent changes in the regulations that allow them to provide dental care within their scope of practice in the private sector. A self-administered questionnaire was distributed to public dental therapists who were selected using a stratified random sampling technique. Questions included items on social structure, job satisfaction and motivation (based on the Warr-Cook-Wall scale), turnover intention (based on four cognitive processes) and perceived future roles. Multiple logistic regression was used to assess the predictors of dental therapists' turnover intention. Overall, a majority (>90%) of the participants had high job satisfaction and job motivation, with total mean scores of 45.70 ± 6.86 and 21.16 ± 2.63, respectively. A total of 8.3% intended to leave the public sector to work in a different organization. Of those who chose to remain as a dental therapist in the next five years, only 7% considered working in the private sector. The significant predictors for turnover intention were educational attainment, years of working experience, job satisfaction level and future preferred working sector. Although the newly introduced Dental Act allows dental therapists to expand their roles to the private setting, very few intended to do so. This could be related to them having a high level of job satisfaction and job motivation while serving in the public sector.


Atomically Dispersed Cu Sites on Dual-Mesoporous N-Doped Carbon for Efficient Ammonia Electrosynthesis from Nitrate.
The industrial Haber-Bosch process for ammonia synthesis is extremely important in modern society. However, it is energy intensive and leads to severe pollution, which has motivated eco-friendly NH3 synthesis research. Electroreduction of contaminant nitrate ions back to NH3 is an effective complement but is still limited by low NH3 yields and nitrate-to-NH3 selectivities. In this study, the electrochemical nitrate reduction reaction (NTRR) is carried out over a single-atom Cu catalyst. Atomically dispersed Cu sites anchored on dual-mesoporous N-doped carbon framework display excellent NTRR performance with NH3 production rate of 13.8 mol NH 3 gcat -1 h-1 and NO3 - -to-NH3 faradaic efficiency (FE) of 95.5 % at -1.0 V. Cu-N-C catalyst can sustain continuous 120 h NTRR test in the simulated NH3 synthesis scenarios with large current density (about 200 mA cm-2 ) and amplified volume of NO3 - solution (9 times). Theoretical calculations reveal that atomically dispersed Cu1 -N4 sites reduce the energy barrier of potential-determining step in NTRR and promote the decomposition of primary intermediate in NO3 - -to-N2 process. These findings provide a guideline for the rational design of highly active, selective and durable electrocatalysts for the NTRR.


Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension.
Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism).


Synergism between fluconazole and methylene blue-photodynamic therapy against fluconazole-resistant Candida strains.
Photodynamic therapy (PDT) has been proved to be effective against fungi and it may be employed as a coadjutant to conventional antifungal agents, leading to a more effective microbial control minimising side effects. This work evaluates the combined effect of PDT and fluconazole against resistant Candida albicans, Candida glabrata and Candida krusei. The yeasts were submitted to methylene blue-PDT (MB-PDT) in sub-inhibitory concentrations. In the present work, MB-PDT combined with fluconazole was more efficient in the inhibition of the C. albicans and C. glabrata than each treatment alone, being possible to infer that the treatments are synergic.


Isolation and estimation of flavonoid compound(s) of Baccharoides anthelmintica (L.) Moench.
Based on ethnobotanical surveys, an Indian traditional plant, i.e., Baccharoides anthelmintica (L.) Moench (Family - Asteraceae) was selected for detailed phytochemical investigations. B. anthelmintica seeds, purchased from local market, were extracted exhaustively in a Soxhlet apparatus using methanol as solvent. A well-established method was adopted to obtain phenolic compounds and flavonoids rich fraction of methanol extract. This fraction yielded two isolates (AK-1 and AK-2) upon purification by column chromatographic process. AK-1 was characterized as mixture of two isomeric compounds - 3',4',5,6,7- and 3',4',5,7,8-pentahydroxy flavanone, and AK-2 as butein (chalcone derivative) by UV, IR and NMR spectral analysis. A TLC densitometric method was developed and validated to estimate the content of butein in B. anthelmintica seeds, and was found to be 1.252 mg/g. Bioactive Marker (butein) based standardized B. anthelmintica seeds will ensure reproducibility in efficacy and safety of the plant or authenticity of its products.


NTCP model for hypothyroidism after supraclavicular-directed radiation therapy for breast cancer.
Hypothyroidism (HT) is a well-known complication of radiation (RT) that includes supraclavicular (SCV) fields. We analyzed breast cancer patients who received SCV-directed RT to evaluate predictors of HT and developed the first normal tissue complication probability (NTCP) model for HT specific to breast cancer patients. 192 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines as well as minimum, mean, and maximum doses. Multivariable logistic regression was performed to assess potential clinical and treatment factors for the development of hypothyroidism. An NTCP model was created, and model validation was performed. Thirty-seven patients (19.3%) developed HT following SCV-directed RT at a median 25 months (range: 2-83 months). Multivariable analysis revealed longer length of follow-up (p = 0.015) and larger thyroid volume receiving less than 20 Gy (CV20Gy[cc]; p = 0.045) were significant prognostic factors (p = 0.039). IMRT was not associated with an increased risk of hypothyroidism (p = 0.28) despite lower CV20Gy[cc] (p = 0.0002). On NTCP modeling, CV20Gy[cc] ≥ 8.5 cc was associated with a risk of HT < 15%. For smaller thyroids, mean dose and thyroid volume were found to be predictive of HT risk. Model validation demonstrated comparable performances between our model and other published models (AUC 0.69-0.72). NTCP modeling within our patient cohort suggested that greater than 8.5 cc thyroid volume receiving less than 20 Gy may be a recommended dosimetric guideline to minimize HT risk in breast cancer patients receiving SCV-directed RT.


[Spatial Genetic Structure of the Crested Auklet (Aethia cristatella Pallas, 1769) Colony as Inferred from Data on the Mitochondrial DNA Control Region and Microsatellite Loci].
The effect of philopatry on the formation of the intrapopulation structure in the crested auklet colony of the Talan Island, Taui Bay of the Sea of Okhotsk, was examined. The nucleotide sequences of the mitochondrial DNA control region fragment (408 bp) and five microsatellite loci (Apy03, Apy04, Apy06, Apy07, Apy10) in individuals from two study plots of the colony were examined. A high genetic diversity (h = 0.999 ± 0.003) and the absence of intrapopulation genetic differentiation was observed at both types of markers. Thus, despite the high level of nest-area fidelity in breeding adults, no genetic isolation was revealed for crested auklets from different parts of the Talan Island colony.


Glycosylated hemoglobin, but not advanced glycation end products, predicts severity of coronary artery disease in patients with or without diabetes.
The association between coronary artery disease (CAD) and diabetes mellitus (DM) is strong but the physiologic mechanisms responsible for this association remain unclear. Patients with DM exhibit high circulating levels of glycated proteins and lipoproteins called advanced glycation end products (AGEs) which have been implicated in the development of oxidative damage to vascular endothelium. We examined the relationships between the presence and extent of CAD and AGEs in patients undergoing elective coronary artery catheterization in an urban teaching hospital. Patients with possible CAD (n = 364) were recruited prior to elective cardiac catheterization (52% male, 48% diabetic). Regression and correlation analyses were used to examine the relationship between serum AGE concentrations, soluble AGE receptor (sRAGE) concentration, HbA1c, LDL and the presence of obstructive CAD along with the burden of CAD measured by SYNTAX and SYNTAX II scores. AGE and sRAGE levels did not significantly correlate with any of the studied coronary artery disease parameters. HbA1c showed positive correlation with both SYNTAX and SYNTAX II scores in patients with and without diabetes. In this cross-sectional study of patients with possible CAD, serum AGEs and sRAGE concentrations did not correlate with SYNTAX or SYNTAX II scores regardless of diabetic status. HbA1C correlated positively with the SYNTAX and SYNTAX II scores in both diabetic and non-diabetic populations.


Early local recurrence of rectal cancer showing extremely rapid growth after curative surgery: report of a case.
We report herein the case of a 59-year-old woman who developed a local recurrence of rectal cancer which showed extremely rapid growth. The patient had undergone a curative low anterior resection with total mesoexcision, and was discharged on postoperative day 25 after an uneventful recovery. However, 2 months after the operation, she developed bleeding from the rectum during defecation, the quantity of which gradually increased. A colonoscopy performed during the fifth postoperative month revealed a circular tumor at the suture line. The tumor was unresectable because it had firmly invaded not only the sacrum, but also the right ureter. Despite the administration of 5-fluorouracil and leucovorin, the patient died of cancer 18 months after her initial surgery. Considering that local recurrence of rectal cancer does not usually occur within 1 year after surgery, this case is unusual because the local recurrence developed very early and showed extremely rapid growth, occupying the entire lumen of the rectum by the time it was detected by colonoscopy during the fifth postoperative month.


An intelligent recognition method of chromosome rearrangement patterns based on information entropy.
Chromosome rearrangements play an important role in the speciation of plants and animals, and the recognition of chromosome rearrangement patterns is helpful to elucidate the mechanism of species differentiation at the chromosome level. However, the existing chromosome rearrangement recognition methods have some major limitations, such as low quality, barriers to parental selection, and inability to identify specific rearrangement patterns. Based on the whole genome protein sequences, we constructed the combined figure according to the slope of the collinear fragment, the number of homologous genes, the coordinates in the top left and bottom right of the collinear fragment. The standardized combination figure is compared with the four standard pattern figures, and then combined with the information entropy analysis strategy to automatically classify the chromosome images and identify the chromosome rearrangement pattern. This paper proposes an automatic karyotype analysis method EntroCR (intelligent recognition method of chromosome rearrangement based on information entropy), which integrates rearrangement pattern recognition, result recommendation and related chromosome determination, so as to infer the evolution process of ancestral chromosomes to the existing chromosomes. Validation experiments were conducted using whole-genome data of Gossypium raimondii and Gossypium arboreum, Oryza sativa and Sorghum bicolor. The conclusions were consistent with previous results. EntroCR provides a reference for researchers in species evolution and molecular marker assisted breeding as well as new methods for analyzing karyotype evolution in other species.


Correlation between the clinical diagnosis of bacterial vaginosis and the results of a proline aminopeptidase assay.
The object of this study was to develop a simple and inexpensive test for detection of bacterial vaginosis (BV) in pregnant patients and to test its accuracy in a clinic population. We developed a modified proline aminopeptidase (PAMP) assay to detect BV and compared the results of the assay with the clinical diagnosis of BV. The results of the PAMP assay in 55 asymptomatic and 50 symptomatic subjects significantly correlated with a clinical diagnosis of BV. The prevalence of BV in the asymptomatic population was 42% (PAMP assay) and 38% (clinical diagnosis). In the symptomatic population, it was 50% (PAMP assay) and 54% (clinical diagnosis). The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the PAMP assay were 86, 85, 86, 78, and 91%, respectively, in asymptomatic patients and 89, 96, 92, 96, and 88%, respectively, in symptomatic patients. The modified PAMP assay, which we describe, met our goals for simplicity, cost, and accuracy. We feel it could be best used as a screening test for BV in asymptomatic pregnant patients.


Age-specific onset and distribution of the natural anticoagulant deficiency in pediatric thromboembolism.
The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation. We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis. Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism. Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.


Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome.
Chordomas are rare neoplasms arising from notochord remnants. Tyrosine kinase receptors (RTK) are altered in these lesions. We used a tissue microarray containing 58 chordomas to examine the expression of platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β, epidermal growth factor receptor (EGFR), c-Met, c-Kit, pAKT, mammalian target of rapamycin, and HER2 by immunohistochemistry and fluorescence in situ hybridization. Most tumors were positive for PDGFR-α (92%), PDGFR-β (85%), c-Kit (77.4%), c-Met (96%), pAKT (82%), mammalian target of rapamycin (56%), HER2 (24%), and EGFR (26%) by immunohistochemistry. Amplifications or deletions could not be identified for HER2 or EGFR in the 13 cases available for fluorescence in situ hybridization analysis; however, chromosome 7 polysomy was detected in 29% of the cases. The only factor directly associated with a poorer survival rate was pAKT positivity (P = .042). The 5-year survival rate for patients with pAKT-negative chordomas was 100%, whereas it was 45% for patients with pAKT-positive chordomas. Our results confirm that RTKs are frequently altered in chordomas. Given the implications of pAKT positivity, RTK inhibitors might be efficacious, and drugs that inhibit AKT, alone or in combination with radiotherapy, could be an effective treatment for patients with refractory chordomas.


Early identification of drug-induced impairment of gastric emptying through physiologically based pharmacokinetic (PBPK) simulation of plasma concentration-time profiles in rat.
Inhibition of gastric emptying rate can have adverse effects on the absorption of food and nutrients. The absorption phase of the plasma concentration-time profile of a compound administered orally to pre-clinical species reflects among others, the gastric and intestinal transit kinetics, and can thus assist in the early identification of delayed gastric emptying. The purpose of this article is to demonstrate the value of Physiologically Based Pharmacokinetic (PBPK) modelling in the early identification of drug induced impairment of gastric emptying from pharmacokinetic profiles. To our knowledge, this is first time that the value of a generic PBPK model for hypothesis testing has been demonstrated with examples. A PBPK model built in-house using MATLAB package and incorporating absorption, metabolism, distribution, biliary and renal elimination models has been employed for the simulation of concentration-time profiles. PBPK simulations of a few compounds that are currently in drug discovery projects show that the observed initial absorption phase of their concentration-time profiles in rat were consistent with reduced gastric emptying rates. The slow uptake of these compounds into the systemic circulation is reflected in their pharmacokinetic profiles but it is not obvious until PBPK simulations are done. Delayed gastric emptying rates of these compounds in rats were also independently observed in x-ray imaging. PBPK simulations can provide early alerts to drug discovery projects, besides aiding the understanding of complex mechanisms that determine the lineshapes of pharmacokinetic profiles. The application of PBPK simulations in the early detection of gastric emptying problems with existing data and without the need to resort to additional animal studies, is appealing both from an economic and ethical standpoint.


Immune thrombocytopenic purpura increased risk of subsequent pancreatitis: A Nationwide population cohort study.
Immune thrombocytopenic purpura (ITP) is characterized by thrombocytopenia and bleeding diathesis. Pancreatitis is a very rare complication but may be fatal. We analyzed data of newly diagnosed ITP patients, excluding those with a history of splenectomy, unknown sex or date of birth, or preexisting pancreatitis at the time of ITP diagnosis, and compared these with selected age-, gender-, and index-year-matched controls, using the Taiwan National Health Insurance Research Database from 1996 to 2013. The study enrolled 100,177 ITP patients and 100,177 controls. We found that pancreatitis risk was higher in secondary ITP patients, regardless of age group, gender, baseline Charlson comorbidity index (CCI) score, history of biliary stone, hyperlipidemia, or alcoholism, than in the control population. Primary ITP patients with CCI score 1 and without biliary tract stone history also showed a higher pancreatitis risk than the controls. The incidence rate and cumulative incidence of pancreatitis were increased in primary, secondary, and unspecified ITP cases. These phenomena may be related to the presence of autoantibodies against glycoprotein IIb/IIIa, or to IgG4, microparticle obstruction, or sclerosis. We noted a direct association between ITP and the development of pancreatitis in Taiwan population.


Sudden Unexpected Postnatal Collapse of the Newborn.
Sudden unexpected postnatal collapse is a rare but devastating neonatal event. A well-appearing, full-term newborn with Agpar scores of eight or more suddenly crashes, often with full respiratory and cardiac arrest. Up to half of newborns with sudden unexpected postnatal collapse die, with many survivors suffering serious neurological damage. The first 2 hours of life are the hours of greatest risk, coinciding with the time frame when nurses encourage breastfeeding and uninterrupted skin-to-skin contact between women and newborns. Nursing assessments and measures to promote neonates' optimal transition to extrauterine life through skin-to-skin contact and early breastfeeding while decreasing the risk of this catastrophic event are described. Nursing surveillance to promote optimal transition in a safe environment is essential, and birth facilities should allocate staffing resources accordingly.


Inhibition of human immunodeficiency virus (HIV) type 1 multiplication by an avian cellular factor.
A factor secreted from avian cells infected non productively with a non cytopathogenic mutant of vesicular stomatitis virus (VSV ts 1026) interferes with HIV replication in CEM cells and peripheral blood monocytes (PBL). Production of infectious particles is decreased and many virions lack cores and/or spikes. In CEM cells the prmRNA is spliced into 7.5, 4, and 2 kb mRNA. Residual virus contains less env encoded proteins and p 18; p 25 appears as several bands. The processing of tat, rev. and nef proteins differs in treated cells and in controls.


Phytochemical and biological studies of Adiantum capillus-veneris L.
Chromatographic fractionation of the alcoholic extract of the dried fronds of Adiantum capillus-veneris L. (Adiantaceae) yielded seven compounds: four triterpenoidal compounds belonging to adiantane and filicane groups were isolated from the hexane fraction and identified as isoadiantone (1); isoadiantol-B (2); 3-methoxy-4-hydroxyfilicane (3) and 3,4-dihydroxyfilicane (4) and three flavonoids were isolated from the ethyl acetate fraction and identified as: quercetin (5), quercetin-3-O-glucoside (6) and quercetin-3-O-rutinoside (rutin) (7). The identification of the isolated compounds has been established through their physical, chemical and spectroscopic methods including IR, (1)H NMR, (13)C NMR, HSQC, HMBC, NOESY and MS. Biological studies of the total alcoholic extract, hexane fraction and some of the isolated compounds showed an anti-inflammatory activity while the hypoglycemic study of the total alcoholic extract showed a significant activity.