Applying quantitative spatial phenotypes analysis to the investigation of peltate glandular trichomes development pattern in Perilla frutescens.
Glandular trichomes, often referred to as "phytochemical factories", plays a crucial role in plant growth and metabolism. As the site for secretion and storage, the development of glandular trichomes is related to the dynamic biosynthesis of specialised metabolites. The study aims to explore the relationship between spatial phenotype and dynamic metabolism of glandular trichomes, and establish a novel approach for the exploration and study of the regulatory mechanism governing the development of glandular trichomes. In this study, we proposed a technical route based on the relative deviation value to distinguish the peltate glandular trichomes (PGTs) from the background tissues and extract their spatial phenotype. By defining glandular trichome developmental stages based on the leaf vein growth axis, we found that young PGTs were densely distributed near the proximal end of growth axis of the leaf veins, where perillaketone, a primary metabolite of PGTs, is predominantly accumulated. Conversely, mature PGTs are typically found near the distal end of the mid-vein growth axis and the lateral end of the secondary vein growth axis, where the accumulation rate of isoegomaketone and egomaketone exceeds that of perillaketone in PGTs. We further identified spatial phenotypic parameters, Lsum and d, as independent variables to construct a linear regression model that illustrates the relationship between the spatial phenotypes and metabolite content of PGTs, including perillaketone (R2 = 0.698), egomaketone (R2 = 0.593), isoegomaketone (R2 = 0.662) and the sum of the amount (R2 = 0.773). This model proved that the development of PGTs was correlated with the growth of the entire leaf, and the development stage of PGTs can be identifined by spatial phenotypes based on the leaf veins. In conclusion, the findings of this study enhance our understanding of correlation between spatial phenotype and development of glandular trichomes and offer a new approach to explore and study the regulatory mechanism of glandular trichome development.


Level of liver fibrosis and immune status of mice of different age after heroin treatment and long abstinence.
Young and middle-aged CBA mice were injected with "street" heroin in increasing doses for 14 days. Volume density of perisinusoid argirophilic fibers increased in both age groups (the increase being more pronounced in middle-aged mice), while the levels of spontaneous, LPS- and ConA-stimulated splenocyte proliferation decreased in young mice. Six months after heroin discontinuation further progress of liver fibrosis was observed in young mice.


Oesophageal cancer: how radical should surgery be?
Oesophagectomy for carcinoma can be viewed as comprising two components: resection of the oesophagus and resection of the enveloping lymphatics. Controversy exists regarding how extensive these two components should be. Through a literature overview, the aim of this educational article is to provide surgeons with arguments to understand which operation is the most oncologically sound according to patient and tumour parameters. Non-randomised comparative studies evaluating radical lymphadenectomy have reported controversial survival benefit. Independent association found between the number of surgically removed lymph nodes and overall survival is an indirect evidence supporting radical lymphadenectomy. The only phase III trial comparing non-radical transhiatal oesophagectomy with transthoracic oesophagectomy for patients with oesophageal adenocarcinoma found 5-year survival rates of 29% vs. 39%, respectively. Although not statistically significant due to underpowered study, specialists would consider less of an increase in survival to be clinically relevant. For squamous OC, the first small randomised controlled trial comparing 2-field lymphadenectomy to 3-field lymphadenectomy did not found significant 5-year survival difference (48% vs. 66%) and the second one comparing 2-field lymphadenectomy to lymph node sampling identified a survival benefit favoring radical resection (36% vs. 25%). Radical transthoracic oesophagectomy with two-field lymphadenectomy appears to offer an optimal balance between benefits and risks to a majority of OC patients, especially in the growing area of neoadjuvant treatments. Non-radical resection should be probably reserved for patients with a poor general status whereas 3-field lymphadenectomy may be reserved to selected patients with loco-regional disease in experienced hands, surely for patients with upper OC.


Effect of sodium cellulose phosphate therapy on crystallization of calcium oxalate in urine.
Effects of oral sodium cellulose phosphate therapy (5 g three times a day with meals for 4 days) on renal excretion of oxalate and on the crystallization of calcium oxalate in urine were examined in six patients with absorptive hypercalciuria on a constant metabolic dietary regimen. During treatment, urinary oxalate increased by 9-50 mg/day. However, urinary calcium decreased by 138-225 mg/day (50%-70%). Thus, the state of saturation of urine with respect to calcium oxalate decreased or did not change significantly. There was no consistent or significant change in the formation product ratio (limit of metastability) or in the crystal growth of calcium oxalate in urine.


Preparation of monoclonal antibodies against methamphetamine.
15 monoclonal antibodies against methamphetamine (MA) were obtained from hybridoma clones by the fusion of mouse 653 myeloma cells with the spleen cells of the immunized mice. The monoclonal antibodies exhibited different cross-reactivities against MA-related compounds and one antibody (MA-15 Ab) was highly specific against MA. A competitive inhibition enzyme-linked immunosorbent assay was established and the detection limit for MA was approximately 20 ng/ml.


Factors determining copper concentration in tea leaves produced at Yuyao County, China.
Over consumption of copper (Cu) from food and beverages is detrimental to human health. In this study, we investigated Cu accumulation in tea leaves produced in Yuyao County in China. Copper concentrations in all tea leaves sampled from tea gardens were below 60mgkg(-1), the permissible level given by the Chinese Ministry of Health; however, 15% of the samples were over 15mgkg(-1), the allowable level of 'green food' as defined by the Chinese Ministry of Agriculture. These observations indicate that Cu concentrations in tea leaves from the investigated producing areas are acceptable, but still a concern. To understand what factors affect the Cu accumulation in the tea leaves, we further analyzed soils from the tea gardens for Cu availability, pH and organic matter content. The Cu availability in soil was found to be closely correlated with the soil's H+ activity, followed by organic matter content. The soils in the tea gardens were also found to be severely acidic with the lowest pH of 3.58. The tea garden soils, if fertilized with animal manure, could also contribute to the risk of Cu contamination. Additionally, Cu concentrations in the final products of tea leaves were greatly increased by the machinery processing in factories that used copper boards at the twisting stage. In one factory, the Cu level was increased by 32.1mgkg(-1). This study suggests that both edaphic and non-edaphic factors can contribute to the final Cu accumulation in tea leaves used by consumers.


Factors associated with antidiabetic medication non-adherence in patients with incident comorbid depression.
To identify factors associated with antidiabetic drug (AD) non-adherence among patients with type 2 diabetes and depression. We conducted a population-based retrospective cohort study among new AD users with a diagnosis of depression following AD initiation. We used public health insurance data from Quebec. The dependent variable was non-adherence (i.e., <90% of days covered by ≥1AD) in the year after a depression diagnosis. Different sociodemographic, clinical and medication-related variables were assessed as potential factors of non-adherence to AD treatment. We performed univariate and multivariate logistic regressions. We identified 3106 new users of ADs with a diagnosis of depression between 2000 and 2006. Of these individuals, 52% were considered non-adherent to their ADs. Baseline non-adherence, younger age, the addition of another AD to the initial treatment, <4 drug claims, visits with several different physicians, high socioeconomic status, and a small number of diabetes complications were associated with AD non-adherence. The factors identified in the present study may help clinicians recognize patients with type 2 diabetes and incident depression at increased risk for non-adherence. In these patients, close follow-up and targeted interventions could help improve adherence to AD treatment, improve glycemic control and reduce complications.


Relation between mechanical and densimetric properties to fractal dimension in human rib cortical bone.
Numerous prior studies hypothesized a power-law relationship (E∝ρα) between cortical bone Young's modulus (E) and density (ρ) with an exponent 2.3≤α≤3.0, that has not been previously justified in the literature on a theoretical level. Moreover, despite the fact microstructure have been extensively studied, the material correlate of Fractal Dimension (FD) as a descriptor of bone microstructure was not clear in previous studies. This study examined the effect of mineral content and density on the mechanical properties of a large number of human rib cortical bone samples. The mechanical properties were calculated using Digital Image Correlation and uniaxial tensile tests. CT scans were used to calculate the Fractal Dimension (FD) of each specimen. For each specimen, the mineral (fmin), organic (forg) and water (fwat) weight fractions were determined. In addition, density was measured after a drying-and-ashing process. Then, Regression Analysis was employed to investigate the relationship between anthropometric variables, weight fractions, density and FD, as well as its impact on the mechanical properties. Young's modulus exhibited a power-law relationship with an exponent of α>2.3 when using the conventional density (wet density), but α=2 when using dry density (desecated specimens). In addition, FD increases with decreasing cortical bone density. A significant relationship has been found between FD and density, whereby FD is correlated with the embedding of low density regions in cortical bone. This study provides a new insight in the exponent value of the power-law relation between Young's Modulus and density, and relates bone behavior with the fragile fracture theory in ceramic materials. Moreover, the results suggest that Fractal Dimension is related to presence of low-density regions.


Tibiofemoral Contact Mechanics After Horizontal or Ripstop Suture in Inside-Out and Transtibial Repair for Meniscus Radial Tears in a Porcine Model.
To compare tibiofemoral contact mechanics after horizontal or ripstop (horizontal plus vertical) sutures in inside-out and transtibial repair for meniscal radial tears with 10 porcine knees in each group. Ten matched pairs of porcine knees were tested under a 1500-N axial compressive load at 0°, 30°, 60°, and 90° of knee flexion. Each knee underwent 4 testing conditions consecutively: (1) intact, (2) medial meniscal radial tear, (3) horizontal suture repair configuration, and (4) ripstop suture repair configuration. Tekscan sensors measured tibiofemoral contact pressure and contact area in the medial and lateral compartments. All repair groups improved their contact mechanics when compared with the tear state among all flexion angles analyzed (all P < .05). Furthermore, ripstop sutures with both inside-out and transtibial repairs restored intact knee contact area and pressures (peak and mean) in the medial compartment at all flexion angles, whereas the horizontal sutures alone failed to do so for contact pressures at 60° and 90° and for contact surface areas at all flexion angles. However, the aforementioned parameters were not significantly different between inside-out sutures and transtibial sutures, regardless of horizontal or ripstop configuration (P > .05). Radial tears of the meniscus in a porcine model significantly decreased medial contact area and increased mean and peak contact pressure. Both inside-out and transtibial ripstop repairs for radial tears aid in restoring intact tibiofemoral contact mechanics at all assessed knee flexion angles. Our results suggest that both inside-out and transtibial ripstop repairs for radial tears can restore tibiofemoral contact mechanics to the intact state. Since the study were performed in an open fashion porcine model, the results should be carefully used in clinical practices, and the efficacy of the techniques through arthroscopic method should be further explored.


Sesquiterpenoids and phenolics from Crepis conyzifolia.
From the roots of Crepis conyzifolia, two new and two known guaianolides were isolated together with three known phenylpropanoids. Structures of the new compounds were established as 8beta-hydroxy-4beta, 15-dihydrozaluzanin C and 4beta, 15, 11beta, 13-tetrahydrozaluzanin C-3-O-beta-glucopyranoside by spectral methods. The identity of 8-epiisolippidiol and dentalactone was also discussed.


Using max standardized uptake value from positron emission tomography to assess tumor responses after lung stereotactic body radiotherapy for different prescriptions.
To retrospectively investigate tumor responses of lung SBRT patients for different prescriptions. To analyze the relation between optimal biologically equivalent dose (BED) and tumor responses. Tumor responses after lung SBRT were compared by examining 48 treatments used four prescriptions. This study used simplified tumor response criteria: (a) Complete Response (CR) - post max SUV (SUVpost ) after SBRT in the treated tumor region was almost the same as the SUVs in the surrounding regions; (b) Partial Response (PR) - SUVpost was smaller than previous max SUV (SUVpre ), but was greater than the SUVs in the surrounding regions; (c) No Response (NR) - SUVpost was the same as or greater than SUVpre . Some SUVpost reported as mild or favorable responses were classified as CR/PR. BED calculated using α/β of 10 Gy were analyzed with assessments of tumor responses for SBRT prescriptions. For the prescriptions (9 Gy × 5, 10 Gy × 5, 11 Gy × 5, and 12 Gy × 4) historically recommended by RTOG, we observed that higher BED10 and lower tumor volume would achieve a higher complete response rate. The highest complete response rate was observed for smallest tumor volume (PTVave = 6.8 cc) with higher BED10 (105.6) of 12 Gy × 4 prescription. For 11 Gy × 5 prescription, the BED10 (115.5) was the highest, but its complete response rate (58%) was lower than 79% of 12 Gy × 4 prescription. We observed the PTVave of 11 Gy × 5 prescription was more than double of the PTVave of 12 Gy × 4 prescription. For the same lung SBRT prescription (BED10 > 100) earlier staging tumor had more favorable local control. We demonstrated post max SUV read from PET/CT could efficiently and accurately assess tumor response after lung SBRT. Although SBRT with prescriptions resulting in a BED10 > 100 experienced favorable tumor responses for early staging cancer, escalation of BED10 to higher levels would be beneficial for lung cancer patients with later staging and larger volume tumors.


A single step purification for recombinant proteins. Characterization of a microtubule associated protein (MAP 2) fragment which associates with the type II cAMP-dependent protein kinase.
A 167 base pair DNA cassette has been constructed to facilitate the detection and purification of recombinant proteins. This cassette, kfc, encodes three distinct peptide units: a phosphorylation site for the cAMP-dependent protein kinase (PKA), called kemptide, a factor Xa cleavage site, and a calmodulin-binding peptide. Expressed kfc fusion proteins can be purified from bacterial lysates in one step by affinity chromatography on calmodulin-agarose using EGTA as eluant. As a test of this system, we describe the expression, purification and characterization of the PKA binding domain of the microtubule associated protein (MAP 2).


Global burden of rabies in 204 countries and territories, from 1990 to 2019: results from the Global Burden of Disease Study 2019.
Rabies is an acute lethal infectious disease caused by a lyssavirus infection. In 2018, the World Health Organization proposed a global strategic plan to end human rabies deaths by 2030. However, systematic studies on the global rabies disease burden and epidemiological trends are scarce. We extracted the disease burden and epidemiological data of rabies worldwide in the preceding 30 years from the Global Burden of Disease Study 2019 and performed a comprehensive analysis. In 2019, the incident cases of rabies worldwide were 14,075.51 (95% uncertainty interval: 6124.33-21,618.11), and the number of deaths was 13,743.44 (95% uncertainty interval: 6019.13-17,938.53), both of which were lower than that in 1990. With the improvement of the sociodemographic index, the incident cases, the number of deaths, age-standardized incidence rate, age-standardized incidence death rate, and disability-adjusted life years of rabies all showed downward trends. Adolescents and adults aged <50 years represented the majority of rabies cases worldwide. The global disease burden of rabies has declined over the past 30 years. Furthermore, the disease burden of rabies was closely related to the sociodemographic index level.


Potential for variability through multiple gene products of bacteriophage phiX174.
The small single-stranded DNA phages phiX174 and S13 produce multiple products of certain phage genes, as observed by electrophoresis on SDS-polyacrylamide slab gels. Two A protein products, two A products and four G products are observed. The multiple gene products may arise from multiple sites for initiation or termination of translation, or by protein modification. Some of the variant products may provide a substitute for heterozygosity without a concomitant increase in the size of the genome.


Structures for the care of people with dementia: a European comparison.
Dementia is a disease that impacts people with dementia, their families, and the healthcare system. In 2018, the number of people with dementia in the EU, the European Free Trade Association (EFTA), and the UK was estimated to be 9.1 million. National dementia strategies and publications by organisations such as Alzheimer Europe outline how dementia-specific care should be designed. This study aims to provide insights into existing formal care structures, models of good practise, and gaps in dementia-specific care for people with dementia in 17 European countries. The research is based on guided interviews with country-specific care experts. A mixed-methods approach with a combination of open and closed questions was used. All interviews were recorded and transcribed verbatim based on the transcription rules of Kuckarts (2010). For data evaluation, the qualitative content analysis model of Mayring (2014) was used. In all 17 countries, efforts for dementia-friendly care and models of good care practise exist. However, there are large differences between European countries regarding the spread of dementia-specific services. In nine countries (Bulgaria, Finland, Italy, Liechtenstein, Luxembourg, the Netherlands, Norway, Sweden, the UK), there are already nationwide structures, while in five countries (Belgium, Greece, Ireland, Portugal, Romania), services are only available in certain regions. In three countries (Austria, Denmark, Germany) dementia-specific outpatient services are widespread nationwide, whereas inpatient services are not. Simultaneously, in all countries, areas with major care gaps exist. Several European states have an urgent need for action concerning the expansion of the provision of dementia-specific services, the reduction of regional differences regarding the provision of care, the elimination of barriers to access to care, the dementia-friendliness of services, and the participation of people with dementia and their relatives in care and research. To reduce the existing structural inequalities in care between and within European countries, and to establish quality-related minimum standards in the care of people with dementia, transnational concepts are needed. The EU, in cooperation with care planners, research institutions, care providers, and patient organisations, should develop European care guidelines or dementia plans that contain concrete measures, schedules, and budgets.


Extractive determination of ephedrine hydrochloride and bromhexine hydrochloride in pure solutions, pharmaceutical dosage form and urine samples.
Simple, rapid, sensitive, precise and accurate spectrophotometeric methods for the determination of ephedrine hydrochloride (E-HCl) and bromhexine hydrochloride (Br-HCl) in bulk samples, dosage form and in spiked urine samples were investigated. The methods are based on the formation of a yellow colored ion-associates due to the interaction between the examined drugs with picric acid (PA), chlorophyllin coppered trisodium salt (CLPH), alizarin red (AR) and ammonium reineckate (Rk) reagents. A buffer solution had been used and the extraction was carried out using organic solvent, the ion associates exhibit absorption maxima at 410, 410, 430 and 530 nm of (Br-HCl)with PA, CLPH, AR and Rk respectively; 410, 410, 435 and 530 of (E-HCl) with PA, CLPH, AR and Rk respectively. (E-HCl) and (Br-HCl) could be determined up to 13, 121, 120 and 160; 25, 200, 92 and 206 μg mL(-1), using PA, CLPH, AR and Rk respectively. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity, Sandell sensitivity were determined for the investigated drug. The correlation coefficient was ≥0.995 (n=6) with a relative standard deviation (RSD) ≤1.15 for five selected concentrations of the reagents. Therefore the concentration of Br-HCl and E-HCl drugs in their pharmaceutical formulations and spiked urine samples had been determined successfully.


Docking-complex-independent alignment of Chlamydomonas outer dynein arms with 24-nm periodicity in vitro.
The docking complex is a molecular complex necessary for assembly of outer dynein arms (ODAs) on the axonemal doublet microtubules (DMTs) in cilia and flagella. The docking complex is hypothesized to be a 24-nm molecular ruler because ODAs align along the DMTs with 24-nm periodicity. In this study, we rigorously tested this hypothesis using structural and genetic methods. We found that the ODAs can bind to DMTs and porcine microtubules with 24-nm periodicities even in the absence of the docking complexin vitro Using cryo-electron tomography and structural labeling, we observed that the docking complex took an unexpectedly flexible conformation and did not lie along the length of DMTs. In the absence of docking complex, ODAs were released from the DMT at relatively low ionic strength conditions, suggesting that the docking complex strengthens the electrostatic interactions between the ODA and DMT. Based on these results, we conclude that the docking complex serves as a flexible stabilizer of the ODA rather than as a molecular ruler.


Effects of plant diversity and time of colonization on an herbivore-plant interaction.
Experimental field plantings showed that plant diversity strongly affected the population dynamics of a specialist herbivore, the striped cucumber beetle, Acalymma vittata (Fab.) (Coleoptera: Chrysomelidae). Population densities over time were characterized by two peaks in numbers (from colonization and reproduction, respectively) and were consistently higher in cucumber monocultures (Cucumis sativus L.) than in polycultures of cucumbers, corn (Zea mays L.), and broccoli (Brassica oleracea L.). Greater abundances in monocultures appear to result from two factors: (1) per individual reproductive rates were greater in monocultures than in polycultures, and (2) mark-recapture studies confirmed that beetles stay in monocultures for a longer period of time than in polycultures. Differences in predation did not appear to contribute to the overall differences in herbivore abundances.The primary impact of A. vittata on its host plant, C. sativus, is the dissemination of bacterial wilt disease, Erwinia tracheiphila (E.F.Sm.). Greater numbers of beetles led to greater plant mortality in monocultures. It is suggested that factors other than numbers of beetles (e.g., shading, allelopathy, microclimate) are more important in influencing plant reproduction, since cucumber plants in monocultures had greater yields than did plants grown in polycultures. However, time of beetle colonization strongly affected plant parameters, indicating that the length of time during which herbivores are interacting with plants is of critical importance to plant survivorship, and thus reproduction.


Production of primary human CD4⁺ T cell lines and clones.
Tetramer staining of CD4(+) T cells is a valuable technique in immunology for detecting rare autoreactive T cells. Generating clones or cell lines from autoantigen tetramer-positive CD4(+) T cells allows further characterization and phenotyping of autoreactive cells.


Interface between the meningioma and the brain.
Though meningiomas are usually well demarcated from the brain, their interfaces with the brain take various forms. Based on 27 nonoperated supratentorial meningiomas from autopsies, the interfaces were classified into four types, that is, smooth, lobular, finger-like expansion, and invasive. Relationships between the types of interfaces and the so-called capsule of the tumor and subarachnoid vessels are discussed. Additionally, three surgical cases which showed more or less the invasive form are presented with neuroradiological findings.


Autistic children exposed to simultaneous communication training: a follow-up.
Fourteen originally mute, low-functioning autistic children, exposed to intensive simultaneous communication training, were followed up 1 to 4 years later. Psychometric testing, communication assessment, and teacher and parent interviews were employed. Results showed that at least half of the children who had become verbal by program termination remained verbal at follow-up. Higher-functioning and verbal children performed overall better than their lower-functioning and mute peers. Children exposed longer to the intensive program and those exposed to good schooling after termination fared better at follow-up, as did those whose parents were more involved in their training. Yet teachers and parents employed mainly speech rather than signs to communicate with these children, despite the children's difficulty with speech. Compared to the verbal children, who recalled signs and words equally well, the mute children recalled signs better than words. The findings are discussed for their relevance to choice of communication training with different subgroups of autistic children.


The effect and mechanism of Qingre Huashi formula in the treatment of chronic hepatitis B with Gan-dan-shi-Re syndrome: An integrated transcriptomic and targeted metabolomic analysis.
Qingre Huashi (QRHS) formula is an empirical prescription for the treatment of Gan-Dan-Shi-Re syndrome (GDSR) syndrome in traditional Chinese medicine (TCM). GDSR is one of the typical TCM syndromes in chronic hepatitis B (CHB). However, little is known about the mechanism of the QRHS formula in treating CHB patients with GDSR. The biological basis of GDSR also remains largely unknown. GDSR mostly occurs in the acute and early stages of chronic liver disease. Effectively alleviating GDSR stalls disease development and benefits patients. The purpose of this study was to explore the molecular basis of GDSR in CHB and then study the mechanism of the QRHS formula treating GDSR using transcriptomics and metabolomics. The transcriptome and metabolome of CHB patients with GDSR syndrome were detected using RNA microarray combined with ultra-high performance liquid chromatography/mass spectrometry and information mining. The potential biomarkers were identified from differentially expressed genes and metabolites, and the metabolic pathway was analyzed. We also investigated the callback of metabolic biomarkers after treatment with the QRHS formula, an empirical prescription for the treatment of GDSR syndrome. RT-PCR analysis was carried out in an independent patient cohort of CHB for validation. Four candidate genes-GPT2, HK2, DDIT3, and HIF1A-and 14 candidate metabolic biomarkers, including L-alpha-aminobutyric acid, selenomethionine, and fructose 1,6-bisphosphate, were identified and validated. All four transcripts of GPT2, HK2, DDIT3, and HIF1A were significantly differentially expressed between the GDSR and non-GDSR groups through independent microarray data and RT-PCR. After treatment with the QRHS formula, the clinical indexes and TCM syndrome were significantly improved, and the 14 disturbed biomarkers were obviously corrected. Three metabolic pathways were confirmed to be perturbed in CHB GDSR patients: alanine, aspartate, and glutamate metabolism, arginine biosynthesis, and aminoacyl-tRNA biosynthesis. Using integrated transcriptomic and targeted metabolomic methods, we identified the potential biomarkers and dysregulated metabolic pathways in CHB patients with GDSR syndrome, which was alleviated by the QRHS formula treatment. These results may provide the mechanism of metabolic dysregulation in GDSR syndrome as well as that underlying the curative effect of the QRHS formula.


The function of host discrimination and superparasitization in parasitoids.
Host discrimination, i.e. the ability to distinguish unparasitized hosts from parasitized ones, and to reject the latter for egg laying is present in many parasitic wasp species. This property is classically considered as an example of contest competition, and is supposed to have a number of functions. However, different species do not react to each other's marks and lay eggs in hosts parasitized by the other species. Apparently the marks used for recognition are specific.Multiparasitization is the best strategy when hosts are scarce and the egg supplies of the parasitoids are not limited. Interspecific host discrimination is not an ESS.Superparasitization within one species would have selective advantage if the number of unparasitized hosts is small and the wasp has a reasonable chance to lay her egg in a host that is not parasitized by herself, and if the chance for her offspring to survive the competitive battle with the first parasitoid larva is not too small. This is shown to be the case.However, marks are not individual and wasps cannot distinguish hosts parasitized by themselves from those parasitized by others. The hypothesis is tested that the egg laying strategy (i.e. the decision to superparasitize) of wasps is dependent on the number of conspecifics that is searching simultaneously for hosts, since this determines the chance that a parasitized host encountered by a wasp is parasitized by herself.It is shown that host discrimination cannot be regarded as a case of contest competition. Other aspects of superparasitization, related to interference and population regulation, sex allocation and encapsulation are briefly discussed.


Low-cost Mn-Fe/SAPO-34 catalyst from natural ferromanganese ore and lithium-silicon-powder waste for efficient low-temperature NH3-SCR removal of NOx.
The development of low-temperature selective catalytic reduction of NOx with NH3 (NH3-SCR) catalysts is desirable but still challenging. Herein, a low-cost Mn-Fe/SAPO-34 catalyst was successfully synthesized using natural ferromanganese ore (FO) and industrial waste lithium-silicon-powder (LSP) by solid-state ion exchange (SSIE) method, and showed high NH3-SCR activity at low temperature range (150-200 °C) with high N2 selectivity. After loading FO, Mn-O and Fe-O bonds on Mn-Fe/SAPO-34 were weakened, which were beneficial to electron transfer and the oxidation-reduction cycle of SCR. The coexisting of Mn and Fe promoted the dispersion of Fe, resulted in high amounts of Oa, Mn4+ and Fe3+ which facilitated the adsorption and activization of NH3 over Mn-Fe/SAPO-34 catalyst. The Brønsted and Lewis acid sites participate in NH3-SCR, and the adsorbed nitrate species could quickly react with the adsorbed NH3 species via the Langmuir-Hinshelwood (L-H) mechanism. The Mn-Fe/SAPO-34 integrated the advantages of low-cost, resource saving and environment friendly, giving a low-carbon and sustainable choice for the industrial application of NOx abatement.


Temporary Skeletal Anchorage Techniques.
As orthodontic treatment has advanced in complexity and in frequency, more recent techniques, using temporary skeletal anchorage, were developed to help correct more severe occlusal and dentofacial discrepancies that were treated with orthognathic surgery alone previously. These techniques have allowed the orthodontist to move teeth against a rigid fixation, allowing for more focused movements of teeth and for orthopedic growth modification. These types of treatments using rigid fixation have allowed for greater interaction between the orthodontist and the oral and maxillofacial surgeon, and have vastly enhanced the treatment planning for the orthodontist in today's society.


E2A proteins: essential regulators at multiple stages of B-cell development.
The development of mature B lymphocytes from multipotent progenitor cells requires the co-ordinated activities of a number of transcriptional regulatory proteins. The transcription factors encoded by the E2A gene are required for the development of committed B-lineage cells and regulate the expression of essential B-lineage genes at multiple stages of differentiation and activation. In this review we discuss the evidence that the E2A gene products function in the regulation of 1) transcription factors required for B-lineage determination, 2) essential proteins involved in pro-B and pre-B-cell development, 3) accessibilty and recombination of the IgH and IgL chain loci, and 4) isotype switching in activated, mature B lymphocytes.


[Psychotherapy and public institutions. The first year's experience of the "three-year training course in psychotherapy" of the Valenza Po National Health Unit].
The article begins by examining the position of psychotherapy in Italy's current cultural climate. This is followed by a brief review of an experiment in the training of National Health Service psychiatrists at National Health Unit 71 in Valenza Po (Piedmont). The experiment was designed and conducted as the first year of a "3-year Course in Psychotherapy" intended to offer training in the practice of psychotherapy within the National Health Service. It was therefore necessary to teach the correct approach both to relations with the patient and to the complex network of relations arising in team work in such cases.


Modulating pH through lysine integrated dental adhesives.
The objective of this study was to explore the effect of lysine integration to dental adhesives with respect to the polymerization kinetics, neutralization capacities in the acidic microenvironment, dynamic mechanical properties, and thermal properties. Lysine was incorporated into liquid resin formulations at 2.5 and 5.0wt % with additional water/ethanol co-solvents. The co-monomer system contained 2-hydroxyethyl-methacrylate (HEMA) and Bisphenol A glycerolate dimethacrylate (BisGMA) with a mass ratio of 45/55. The kinetics of photopolymerization, neutralization capacities, lysine-leaching, dynamic mechanical properties and thermal properties of the control and experimental adhesives were analyzed. The degree of conversion of the experimental adhesive was increased substantially at 2.5wt% lysine as compared to the control. The experimental polymers provided acute neutralization of the acidic microenvironment. Approximately half of the lysine was released from the polymer network within one month. Under dry conditions and physiologic temperatures, the incorporation of lysine did not compromise the storage modulus. Comparison of the thermal properties suggests that the more compact structure of the control adhesive inhibits movement of the polymer chains resulting in increased Tg. Incorporating lysine in the adhesive formulations led to promising results regarding modulating pH, which may serve as one aspect of a multi-spectrum approach for enhancing the durability of composite restorations. The results provide insight and lay a foundation for incorporating amino acids or peptides into adhesive formulations for pH modulation or desired bioactivity at the interfacial margin between the composite and tooth.


An improved system for the surface immobilisation of proteins on Bacillus thuringiensis vegetative cells and spores through a new spore cortex-lytic enzyme anchor.
An improved surface-immobilisation system was engineered to target heterologous proteins onto vegetative cells and spores of Bacillus thuringiensis plasmid-free recipient strain BMB171. The sporulation-dependent spore cortex-lytic enzyme from B. thuringiensis YBT-1520, SceA, was expressed in vegetative cells and used as the surface anchoring motif. Green fluorescent protein (GFP) and a Bacillus endo-β-1,3-1,4-glucanase (BglS) were used as the fusion partners to test the binding efficiency and the functional activities of immobilised surface proteins. The surface localisation of the SceA-GFP fusion protein on vegetative cells and spores was confirmed by Western blot, immunofluorescence microscopy and flow cytometry. The GFP fluorescence intensity from both vegetative cells and spores was measured and compared to a previously characterised surface display system using a peptidoglycan hydrolase anchor (Mbg). Results demonstrated comparable efficiency of SceA- and Mbg-mediated immobilisation on vegetative cells but a more efficient immobilisation on spores using the SceA anchor, suggesting SceA has greater potential for spore-based applications. The SceA protein was then applied to target BglS onto vegetative cells and spores, and the surface immobilisation was verified by the substantial whole-cell enzymatic activity and enhanced whole-spore enzymatic activity compared to vegetative cells. A dually active B. thuringiensis vegetative cell and spore display system could prove especially valuable for the development of regenerable and heat-stable biocatalysts that function under adverse environmental conditions, for example, an effective feed additive for improved digestion and nutrient absorption by livestock.


Timing of therapy for latent tuberculosis infection among immigrants presenting to a U.S. public health clinic: a retrospective study.
In the U.S. more than half of incident tuberculosis (TB) cases occur in immigrants. Current guidelines recommend screening and treatment for latent TB infection (LTBI) within 5 years of arrival to the U.S. This study evaluates the timing of LTBI therapy among immigrants presenting for care to a public health TB clinic. Retrospective chart review of patients prescribed LTBI treatment based on medical records from Prince Georges County Health Department. 1882 immigrants received LTBI therapy at Prince Georges County Health Department between 1999 and 2004. 417 of these patients were diagnosed with LTBI through contact investigations and were excluded from the analysis. Among the remaining 1465 individuals, median time from arrival to the U.S. until initiation of LTBI therapy was 5 months (range 0-42.4 years). 16% of all immigrants initiated therapy more than 5 years after arrival to the U.S. A logistic regression model using risks identified on univariate analysis revealed that referral for therapy by non-immigration proceedings was the strongest predictor of initiation of therapy more than 5 years after arrival to the U.S. Other factors associated with > 5 year U.S. residence prior to initiation of LTBI therapy included female gender (adjusted odds ratio (AOR) 1.8, 95% CI 1.2-2.6), age > or = 35 (AOR = 4.1, 95% 2.5-6.6), and originating from Latin American and the Caribbean (AOR = 1.9, 95% CI 1.3-3.0). Foreign-born individuals who are not referred for LTBI therapy through immigration proceedings are less likely to receive LTBI therapy within 5 years of arrival to the U.S. These data highlight the need to explore other mechanisms for timely LTBI screening beyond services provided by immigration.


The biochemical and immunochemical characterisation of the 30 kilodalton surface antigen of Brugia pahangi.
The major surface antigen (30 kDa) of Brugia pahangi has been characterised by a number of biochemical and immunochemical means. The 30 kDa polypeptide is a glycoprotein which can be extracted from the worm surface by homogenization in the absence of detergents. The 30 kDa polypeptide can be metabolically labelled with [35S]methionine in adult male and female parasites. In addition small amounts of the 35S-labelled 30 kDa antigen can be detected in the medium of worms cultured in vitro. 125I labelling of the excretory-secretory (ES) products of adult male and female parasites followed by immunoprecipitation and peptide mapping has confirmed the relationship between the surface located 30 kDa polypeptide and that released in vitro.


Responses to exercise in the pregnant pygmy goat.
Pregnant Pygmy goats were trained to walk on a treadmill up a 10 degree grade at a rate of 1.5 mile/hr for 10 min. Hemodynamic measurements were made in duplicate during late pregnancy and postpartum, at rest and after 3 min of exercise. All kids were weighed within 12 hr of delivery to assess the effect of exercise on fetal growth. Pulse rate, cardiac output and oxygen consumption were higher during pregnancy than postpartum, at rest and also during exercise. Stroke volume increased significantly with exercise. Peripheral vascular resistance (pvr) at rest was lower during pregnancy than postpartum, and decreased significantly during exercise, especially in pregnancy. Exercise was associated with a fall in arterial P(CO2) during pregnancy and postpartum. In goats, as in humans, the increased oxygen demands of pregnancy, during exercise and at rest, are met by an increased cardiac output rather than by increased peripheral oxygen extraction. The individual birth weights of twins, triplets and quadruplets from Pygmy goats who were exercised during late pregnancy were smaller than birth weights of matched newborns from control animals.


Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis.
The pathogenesis of ischemic cerebrovascular disease has revealed that ischemia-reperfusion (I/R) injury often leads to aggravation of metabolic oxidative stress and blood-brain barrier (BBB) destruction, eventually causing secondary brain tissue damage. Accumulated reactive oxygen species (ROS) in focal ischemia activate mitochondria-mediated apoptosis and damage the BBB by degrading tight junction proteins (TJPs). Herein, we report macrophage-derived exosomes (Ex) loaded with curcumin (cur) as a multifunctional biomimetic delivery vehicle (Ex-cur) for targeting ischemic brain tissue and alleviating cerebral I/R injury by inhibiting ROS-mediated mitochondrial apoptosis in a transient cerebral ischemia rat model. The design principle relies on unique features of macrophage-derived exosomes and the natural ingredient cur. Specifically, cur can be entrapped within exosomes when incubated with murine macrophage RAW264.7 cells, and its stability is subsequently significantly improved. The resultant Ex-cur can target ischemic regions by leveraging the targeting migration capability of Ex driven by inflammation. Accumulated Ex-cur in ischemic regions is experimentally proven to be highly effective at reducing ROS accumulation by virtue of the antioxidant properties of cur. Using Ex-cur to down-regulate ROS accumulation in lesions, we alleviate BBB damage and suppress mitochondria-mediated neuronal apoptosis, which is confirmed by a series of relevant protein analysis. These findings demonstrate good therapeutic efficacy of Ex-cur for treating I/R injury, providing experimental evidence for the potential clinical benefits of Ex-cur for other modes of neuroprotection.


A fructose bisphosphate activated lactate dehydrogenase in the liver fluke Fasciola hepatica.
Lactate dehydrogenase of Fasciola hepatica showed typical Michaelis-Menten kinetics at pH 7.2, with respect to pyruvate. Addition of physiological levels of fructose bisphosphate activated the enzyme at all substrate concentrations tested; the response to this effector being hyperbolic in nature. As well as depending upon the fructose bisphosphate concentration, the Vmax and Km are modified by different buffers. The degree of activation is much greater using Tris-HCl than phosphate buffer. The pH optimum occurs at pH 6.5 whether using physiological levels of substrate in the presence or absence of fructose bisphosphate, or high levels of substrate. Of the potential effectors tested, significant inhibition was shown by the nucleoside triphosphates, especially ATP. The importance of this inhibition, coupled with the activation by fructose bisphosphate is discussed. Fasciola hepatica lactate dehydrogenase is unusual in that it does not catalyse the reverse reaction to any measurable extent. That is, lactate oxidation is negligible unless the effector fructose bisphosphate is present. Use was made of this fact to visualise the isoenzymes of lactate dehydrogenase separated by polyacrylamide disc gel electrophoresis. Five isoenzyme bands became apparent when stained in this manner.


The subcommissural organ of Lacerta s. sicula Raf.: functional studies.
The secretory activity of the subcommissural organ (SCO) is affected by adrenalectomy, adrenalectomy + castration, and by an increase in ambient temperature in adrenalectomized and adrenalectomized + castrated animals. Adrenalectomy inhibits the activity of the SCO. After adrenalectomy + castration the decrease in the secretory activity of the SCO is more rapid. In contrast, an increase in the ambient temperature in adrenalectomized animals induces a recrudescence of the activity of the SCO. The increase in temperature in castrated + adrenalectomized lizards does not affect the inhibition produced by this type of surgical treatment. The histological changes are discussed on the basis of results obtained in the present study and in previous experiments.


Coronavirus-like particles in Aboriginals and non-Aboriginals in Western Australia.
Pleomorphic virus-like particles which resemble coronaviruses in morphology were found in faecal specimens from Aboriginal and non-Aboriginal children in Western Australia. They were equally prevalent in those with or without symptoms of diarrhoea. A much greater proportion of Aboriginal than non-Aboriginal children were found to be excreting the particles. The proportion of children who excreted the virus-like particles increased with age. Coronavirus-like particles, indistinguishable from those found in humans, were found in a number of Aboriginals' dogs.


Rapid determination of methandrostenolone in equine urine by isotope dilution liquid chromatography-tandem mass spectrometry.
Urine samples were spiked with [17-methyl-2H3]methandrostenolone as internal standard and extracted with a mixture of dichloromethane and cyclohexane. The organic phase was concentrated and injected onto a short octyl-silica column (30 mm x 4.6 mm I.D.) for separation of methandrostenolone and 17-epimethandrostenolone. The effluent from the column was connected to a Sciex TAGA 6000E triple quadrupole mass spectrometer equipped with an atmospheric pressure ion source for sampling of ions generated by a heated pneumatic nebulizer with corona discharge ionization. This ion source produced abundant [M + H]+ ions and a weak fragment ion due to loss of water. The protonated molecular ions at m/z 301 and 304 for methandrostenolone, 17-epimethandrostenolone and the internal standard were transmitted to the second quadrupole for collision-induced dissociation. Quantification was obtained by selected reaction monitoring of three daughter ions. Methandrostenolone and 17-epimethandrostenolone were separated by liquid chromatography, but gave identical mass spectra. The method detection limit by injection of a urine extract corresponding to 2.8 ml urine was 180 pg/ml at the 99% confidence level. The precision (relative standard deviation) was 3% at the 16 ng/ml level and the linear dynamic range was at least 3 orders of magnitude. Screening for unknown metabolites in urine after administration of methandrostenolone to horses and humans was accomplished by a parent ion scan of m/z 121, a fragment corresponding to the intact A-ring of the steroids.


Functional physical training improves women's military occupational performance.
The U.S. Armed Forces have recently approved full integration of women into combat roles. Physical fitness demands for executing Military Occupational Specialties (MOS) are substantial; thus lifting and load carriage capability improvements are desirable. To determine if a specially-designed physical conditioning program could lessen the gap between the performance of male and female Soldiers in lifting and load carriage and thereby enable women to meet the requirements of most, if not all, Army MOSs. Forty women participated in a 24-week physical training program, which included resistance training, long-distance running, backpacking, and specialized drills. Pre- and post-tests of occupational and physical performance measures were conducted before and after training. Repeated measures analysis of variance were used to determine statistically significant differences among the pre-, mid- and posttests. Women increased maximal occupational lifting strength 12-20 kg, added 9-34 repetitions in lifting endurance, increased 0.23 m in jumping performance, added 46 repetitions in local muscular endurance, and decreased load carriage for time by 3.7-8.6 min. Women scored within 82-94% of untrained male scores for aerobic capacity and muscular endurance after training. Women's ability to perform physically-demanding military occupational tasks was significantly improved following 6 months of concurrent training, with emphasis on load carriage and lifting. The percentage of women that qualified for current "heavy" and "very heavy" MOSs was initially 24%, but increased to 78% after training. A resistance training program of 6+ months can adequately prepare women for "heavy" to "very heavy" MOS's.


Phylogenetic position of Indian termites (Isoptera: Termitidae) with their respective genera inferred from DNA sequence analysis of the mitochondrial cytochrome oxidase gene subunit I compared to subunit II.
The present work was aimed to investigate the phylogenetic analysis of different species of Indian termites belonging to the family termitidae based on mitochondrial genes COI and COII. The sequences so obtained from public database revealed grouping of termites according to their ecological distribution. The sequences of the species under investigation were characterized on the basis of frequencies of nucleotide bases and in most of the species, a significantly high percentage of A+T base composition was observed. Phylogenetic tree revealed positioning of species according to the analysis of their cytochrome oxidase subunits.


The diagnostic performance of 18F-FDG PET/CT, CT and MRI in the treatment evaluation of ablation therapy for colorectal liver metastases: A systematic review and meta-analysis.
Uncertainty exists regarding the optimal imaging modality for timely detection of disease progression (DP) after ablation therapy for colorectal liver metastases. We evaluated the diagnostic accuracy of 18F-FDG PET(/CT), CT and MRI for detection of DP following ablation therapy. A systematic search was performed on May 18, 2016. The analysis included studies that reported on the diagnostic accuracy of 18F-FDG PET(/CT), CT and/or MRI for post-ablative evaluation of patients with liver metastases. Primary outcome was the diagnostic accuracy of the imaging modalities for detection of DP. Methodological quality was assessed using the QUADAS-2 tool. Pooled sensitivities and specificities were estimated using bivariate random-effects models. Ten studies were included in the meta-analysis, including seven comparative studies. Nine reported data on diagnostic accuracy of 18F-FDG PET(/CT), seven on CT imaging. Only two studies reported the diagnostic accuracy of MRI, hence not included in the meta-analysis. Quality assessment raised concerns about the risk of bias regarding the use of the reference standard, blinding of the index tests and the follow-up time. Pooled sensitivity was respectively 84.6% (75.0-90.6) and 53.4% (29.0-76.4) for 18F-FDG PET(/CT) and CT (P = 0.005). Pooled specificity was respectively 92.4% (86.5-95.9) and 95.7% (87.5-98.6) (P = 0.392). 18F-FDG PET/(CT) yields a higher sensitivity for detecting DP after ablation therapy compared with CT and has a comparably high specificity. These findings indicate that the use of 18F-FDG PET(/CT) in this setting particularly allows for minimization of the false-negative rate compared with CT without compromising the low false-positive rate.


Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases.
Over the past decade, Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have arisen as a novel and promising targeted therapy for breast cancer gene (BRCA)-mutated ovarian and breast cancer patients. Therapies targeting the enzyme, PARP-1, have since established their place as maintenance drugs for cancer. Here, we present existing evidence that implicates PARP-1 as a player in the development and progression of both malignancy and demyelinating disease. These findings, together with the proven clinical efficacy and marketed success of PARP-1 inhibitors in cancer, present the repurposing of these drugs for demyelinating diseases as a desirable therapeutic concept. Indeed, PARP-1 inhibitors are noted to demonstrate neuroprotective effects in demyelinating disorders such as multiple sclerosis and Parkinson's disease, further supporting the use of these drugs in demyelinating, neuroinflammatory, and neurodegenerative diseases. In this review, we discuss the potential for repurposing PARP-1 inhibitors, with a focus on rare demyelinating diseases. In particular, we address the possible use of PARP-1 inhibitors in examples of rare leukodystrophies, for which there are a paucity of treatment options and an urgent need for novel therapeutic approaches.


Medication Errors and Their Correlation with Nurse's Satisfaction. The Case of the Hospitals of Lasithi, Crete.
Medication errors have been recognized as a real problem for all health systems worldwide and are the most common category of nursing errors. The aim of this study was to investigate the prevalence of medication errors and their correlation with the job satisfaction of nurses. A prospective cross-sectional study was carried out and the sample of the study consisted of 189 nurses. To investigate medication errors, an anonymous structured questionnaire of 34 questions was used and Job Satisfaction Survey (JSS) questionnaire was used to measure job satisfaction. The IBM SPSS 25.0 program was used for statistical analysis of the data. 63.0% of nurses have been errors in the administration of medication, more often by the wrong time of administration (34.4%), missed dose (22.8%), and wrong dose (21.7%). The likelihood of an error is similar in all shifts, its devaluation is a non-reference reason, and if reported to a greater frequency in the attending physician. A significant difference in the frequency of errors was found only in the marital status and the job, while under the working conditions no significant variation was recorded. Job satisfaction is statistically significantly low for financial earnings and high for the management supervision. Based on the findings, the correlation between total job satisfaction and medication errors was not significant. Nursing medication errors continue to happen. Continuing education, formal recording, and improvement of working conditions could help prevent and minimize errors and at the same time increase the job satisfaction of nurses.


A global reference model of Curie-point depths based on EMAG2.
In this paper, we use a robust inversion algorithm, which we have tested in many regional studies, to obtain the first global model of Curie-point depth (GCDM) from magnetic anomaly inversion based on fractal magnetization. Statistically, the oceanic Curie depth mean is smaller than the continental one, but continental Curie depths are almost bimodal, showing shallow Curie points in some old cratons. Oceanic Curie depths show modifications by hydrothermal circulations in young oceanic lithosphere and thermal perturbations in old oceanic lithosphere. Oceanic Curie depths also show strong dependence on the spreading rate along active spreading centers. Curie depths and heat flow are correlated, following optimal theoretical curves of average thermal conductivities K = ~2.0 W(m°C)-1 for the ocean and K = ~2.5 W(m°C)-1 for the continent. The calculated heat flow from Curie depths and large-interval gridding of measured heat flow all indicate that the global heat flow average is about 70.0 mW/m2, leading to a global heat loss ranging from ~34.6 to 36.6 TW.


Visual loss due to central serous chorioretinopathy during corticosteroid treatment for giant cell arteritis.
Giant cell arteritis (GCA) can be a devastating disease resulting in blindness if not promptly diagnosed and treated. The only proven treatment for GCA is systemic corticosteroids; however, there are many side-effects associated with this therapy including ocular side-effects such as ocular hypertension, cataract formation and central serous chorioretinopathy. To raise physician awareness, a patient with biopsy-proven GCA is reported who lost vision during corticosteroid therapy because of central serous chorioretinopathy.


Biosimilars: Rationale and current regulatory landscape.
To discuss current terminology and the regulatory standards and processes involved in the development of biosimilars. An Internet-based literature search through April 2015 was performed for information related to biosimilars in chronic inflammatory disorders. Keywords were as follows: biosimilar, development, manufacturing, characterization, structural, functional, preclinical, clinical, immunogenicity, rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, Crohn׳s disease, ulcerative colitis, and ankylosing spondylitis. The European Medicines Agency (EMA) and US Food and Drug Administration (FDA) websites were searched for guidelines and information related to biosimilars. Biosimilars are products that are highly similar to the reference product regarding quality, biological activity, safety, and efficacy. Biosimilars are biological products and not generic drugs and, thus, do not follow the same regulatory pathways as generic molecules. Rigorous early-stage structural, functional, and analytical testing, followed by nonclinical and clinical analyses comparing a biosimilar with its reference product, are required to demonstrate biosimilarity in regulatory markets worldwide. The addition of biosimilars to the market has the potential to improve access to biologic therapies. Many regulatory agencies have enacted stringent pathways, which must be followed for a biosimilar to be labeled and approved as such; following the pathways will help protect and maintain the integrity, quality, and safety of the biosimilar product.


Trace elements found to be variable in two coral reef species, Heliofungia actiniformis and Galaxea fascicularis, collected from the Ryukyu Islands.
Biominerals and metals of intertidal corals of two species (Heliofungia actiniformis, Quoy and Gaimard; Galaxea fascicularis, Linnaeus), collected from the Iriomote Island of Ryukyu, were examined with an inductively coupled plasma atomic emission spectrometer (ICP-AES). Twelve elements were detectable in the coralline skeletons dissected radially along the growth axis. The relative content (RC) of Hg periodically fluctuated and was minimum at the hollow sites of the coralline slab of Heliofungia sp., corresponding to the cyclic growth. There were two types of elements: constant elements and variable elements along the growth axis. RCs of Ca, Mg, Al, Si, and P were nearly constant. RCs of Fe, Mn, Cu, and Ba were variable, but not as regularly changed as Hg. There were positive mass correlations of Hg to Mn, Cu and Zn, but not to Ba and Fe. In contrast, these relationships were not prominent and were likely degraded by aging in the skeleton of Galaxea sp., suggesting a different mode from that of the Heliofungia sp.


Extramammary Paget's diseases in men from the Shanghai area: its association with PSA level increase.
The aim of this study was to determine the incidence of prostate cancer in patients with extramammary Paget's disease (EMPD). All cases of EMPD diagnosed between 1992 and 2007 in Shanghai Cancer Hospital were collected and analyzed for the incidence of prostate cancer. The median follow-up was 78 months. In total, 38 cases of invasive and 10 cases of in situ EMPD had been registered. A second malignancy was found in 28.9% (11/38) of patients with invasive EMPD and in 30% (3/10) of patients with in situ EMPD. Patients had an increased risk of developing a second cancer compared with the general population (standardized incidence ratio: 1.7; 95% confidence interval 1.2-2.4). Sixteen patients had serum prostate-specific antigen (PSA) level above 4 ng/mL; five developed prostate cancer, three of them with PSA levels beyond 100 ng/mL. The incidence of prostate cancer is 10.4% in this patient group. Patients with EMPD were more likely to have prostate cancer than the general population. Although the prognosis of EMPD is fairly good, a thorough search for a second tumor is recommended.


The effect of exogenous transforming growth factor-beta 2 on healing fractures in the rabbit.
The effects of exogenous TGF-beta 2 on normally healing fractures were investigated to see if healing can be accelerated; TGF-beta s stimulate bone and cartilage formation on calvariae and long bones. TGF-beta 2 (60 or 600 ng) was injected around the developing callus of rabbit tibial fractures healing under stable, or unstable, mechanical conditions 4 days after fracture. The fractures were examined 5, 7, 10, and 14 days after fracture. A large amount of edema developed around the injection sites. The callus of fractures healing under stable mechanical conditions consists almost entirely of bone. The effects of 60-ng injections of TGF-beta 2 are minimal, but 600-ng doses lead to a small increase in the size of the callus. The callus of fractures healing under unstable mechanical conditions has a large area of cartilage over the fracture site with bone on each side. The effects of TGF-beta 2 on unstable fractures are to retard and reduce bone and cartilage formation in the callus. The overall size of the callus is not affected. In conclusion, TGF-beta 2 does not stimulate fracture healing under either stable, or unstable, mechanical conditions during the initial healing phase. It is argued that agents which stimulate bone formation can retard remodeling when treatment is extended into the remodeling phase of healing.


Novel Sca-1+ macrophages modulate the pathogenic progress of endotoxemia.
Macrophages are important innate immune cells that play crucial roles in inflammatory responses. Accumulating evidence has demonstrated macrophage heterogeneity based on biomarkers, functions, and localization. Here, we report a novel stem cell antigen-1 (Sca-1)-positive macrophage population induced in the pathological conditions caused by lipopolysaccharide (LPS). Sca-1 is only upregulated in macrophages but not in monocytes and neutrophils upon LPS injection. Sca-1+ macrophages develop from resident peritoneal macrophages. LPS-induced Sca-1+ macrophage generation was partly blocked by anti-IFN-γ antibody, suggesting a role of IFN-γ in the process. LPS-stimulated production of IL-6, TNF-α, and CCL2 is significantly lower in Sca-1+ macrophages compared to their counterpart Sca-1- macrophages. Depletion of Sca-1+ macrophages using anti-Sca-1 antibody significantly increased survival rate and reduced lung and kidney damage in an LPS-induced sepsis model. Taken together, we discovered a novel population of Sca-1+ macrophages in LPS-induced septic conditions.


Detection of chitinase activity by 2-aminobenzoic acid labeling of chito-oligosaccharides.
Chitinases are hydrolases capable of hydrolyzing the abundant natural polysaccharide chitin. Next to artificial fluorescent substrates, more physiological chito-oligomers are commonly used in chitinase assays. Analysis of chito-oligosaccharides products is generally accomplished by UV detection. However, the relatively poor sensitivity poses a serious limitation. Here we report on a novel, much more sensitive assay for the detection of chito-oligosaccharide reaction products released by chitinases, based on fluorescent detection, following chemical labeling by 2-aminobenzoic acid. Comparison with existing UV-based assays, shows that the novel assay offers the same advantages yet allows detection of chito-oligosaccharides in the low picomolar range.


Phlaeothripidae (Thysanoptera) diversity in Australia, with three new generic records and two new species.
The genera Ponticulothrips, Trichinothrips and Tylothrips are newly recorded from Australia. Litotetothrips symplocosae sp.n. is described as the fourth species from Australia of this Asian genus, and Ponticulothrips mudloi sp.n. is described as the second known species in this genus that was previously known only from Japan. Trichinothrips and Tylothrips are each represented in Australia by single species, each of which is known from several countries.


Validation of the Polish version of the Western Ontario Rotator Cuff Index in patients following arthroscopic rotator cuff repair.
The Western Ontario Rotator Cuff Index (WORC) is a joint specific outcome tool that assesses the quality of life in patients with various rotator cuff problems. Our purpose was to evaluate selected psychometric characteristics (internal consistency, validity, reliability and agreement) of the Polish version of WORC in patients undergoing rotator cuff repair. Sixty-nine subjects took part in the study with a mean age 55.5 (range 40-65). All had undergone arthroscopic rotator cuff repair in 2015-2016. Data from 57 patients in whom symptoms in the shoulder joint had not changed within 10-14 days were analyzed in a WORC test-retest using the Intraclass Correlation Coefficient (ICC), Standard Error of Measurement (SEM) and Minimal Detectable Change (MDC). WORC was compared to the short version of the Disabilities of Arm, Shoulder and Hand Questionnaire (QuickDash) and the Short Form-36 v. 2.0 (SF-36). High internal consistency of 0.94 was found using Cronbach's alpha coefficient. Reliability of the WORC resulted in ICC = 0.99, agreement assessed with SEM and MDC amounted to 1.62 and 4.48 respectively. The validity analysis of WORC showed strong correlations with QuickDash and SF-36 PCS (Physical Component Summary), while moderate with SF-36 MCS (Mental Component Summary). WORC had no floor or ceiling effect. The Polish version of the WORC is a reliable and valid tool with high internal consistency for assessing the quality of life in patients undergoing arthroscopic rotator cuff repair.


Online gambling venues as relational actors in addiction: Applying the actor-network approach to life stories of online gamblers.
With the emerging technologies of the Internet and smartphones during the last decades, the gambling environment has undergone a massive transformation. In Sweden, and Europe in general, online gambling has more than doubled since 2007. The paper studies online gambling venues (OGVs) as relational actors of addiction. By drawing on the actor-network theory (ANT) and assemblage thinking, we examine how OGVs, as actors in specific networks of attachment, enable the development of gambling addiction and facilitate its continuation. The data consists of life story interviews with 34 online gamblers. Online gambling venues extend the scope of gambling opportunities through space, providing an easy portable 24-hours-a-day access to gambling online and on smartphones. This increases the spatial mobility of gambling to diverse contexts. By linking gambling to more unpredictably evolving patterns of relations, online gambling venues also increase gambling's temporal mobility to intrude in the habitual trajectories of everyday life. By enhancing the gambling mobility through space and time, OGVs simultaneously extend the scope of situations in which gambling may transform from a controlled activity into an addiction. It is then that the actor-networks of gambling infiltrate in the actor-networks of work, domestic life and leisure, and start to feed processes where they are translated to serve the interests of gambling. By giving us tools to challenge simplistic and taken-for-granted explanations of gambling addiction and by allowing us to grasp the flux and changing nature of addiction as a relational pattern of heterogeneous contextual attachments, the actor-network theory can help us to understand the complexity and multiplicity of gambling problems. The knowledge on what kinds of contextual attachments in diverse actor-networks enable harmful gambling and sustain unhealthy relations helps practitioners to focus treatment interventions especially on these contextual linkages and their configurations.


Carbohydrate-deficient glycoprotein syndrome with previously unreported features.
A boy with carbohydrate-deficient glycoprotein syndrome died at five months of age in status epilepticus. Postmortem examination failed to show the classically observed olivopontocerebellar atrophy. Two previously unreported features were present: cataracts from the first week of life and lysosomal storage affecting mainly the anterior horn neurons of the spinal cord.


Psychometric analyses of the Bangla version of the Dark Triad Dirty Dozen.
Three undesirable social traits (Machiavellianism, psychopathy, and narcissism) collectively known as the'Dark Triad' have gained huge empirical attention during the past decades. The Dark Triad Dirty Dozen (DTDD) is a brief and psychometrically sound tool for assessing dark traits. In the present study, the psychometric properties of the DTDD-Bangla were assessed (n = 371) as there no information about its psychometric adequacy in the Bangladesh context. The item analysis results demonstrated that the DTDD-Bangla had good item discrimination indices in both CTT and IRT. The confirmatory factor analysis results supported the three factors first-order model in terms of model fits and items' factor loadings over the bi-factor model. Scale level analyses revealed that this scale and its subscales had good internal consistency reliabilities and composite reliability. The MGCFA supported scalar invariance between males and females. Overall, the DTDD-Bangla seems psychometrically sound measure to assess the dark traits and can be used in further researches in the Bangladesh context.


[Screen for natural benzylisoquinoline alkaloids against tumor].
To search for natural benzylisoquinoline alkaloids against tumor. In this study, taken DNA as target, a method was developed for screening of natural benzylisoquinoline alkaloids against tumor from traditional Chinese medicine by the use of centrifugal ultrafiltration combined with HPLC technology. The anti-tumor activity for the compounds screened was evaluated in vitro. Nine compounds interacted with DNA were discovered and identified from Macleaya cordata, Chelidonium majus, Coptis chinensis, and the proliferation of four types of human solid cancer cell lines was markedly inhibited by these compounds. The developed method was considered to be suitable for screening of natural benzylisoquinoline alkaloids against tumor from traditional Chinese medicine.


Superior Suppressive Capacity of Skin Tregs Compared with Lung Tregs in a Model of Epicutaneous Priming.
We have previously shown that T helper type 2 (Th2)-polarized airway inflammation can facilitate priming to new antigens in the lungs, which we called "collateral priming". To investigate whether allergic skin inflammation can also facilitate priming toward new antigens, we developed an allergic skin inflammation model based on an allergic lung inflammation model. Mice were sensitized intraperitoneally toward the primary antigen, ovalbumin. Challenge was subsequently performed intranasally or epicutaneously with ovalbumin and a secondary antigen, keyhole limpet hemocyanin (KLH). Re-challenge consisted of local application of either antigen alone. Analysis of KLH-specific antibody responses, KLH-specific cytokines, and local inflammation demonstrated tolerance induction toward the secondary antigen in the skin, whereas in the lung priming had occurred. Flow-cytometric analysis revealed increased numbers of regulatory T cells (Tregs), increased cytotoxic T lymphocyte antigen-4 (CTLA-4) expression, and an enhanced suppressive capacity of Tregs from skin-draining lymph nodes when compared with Tregs from the lung-draining lymph nodes. Furthermore, depletion of Tregs resulted in restoration of collateral priming in the skin. These results demonstrate crucial local differences between the Treg function in the skin and lung to repetitive antigen exposure, which can decisively influence the immune response toward new antigens.


[Viscosity of pure pancreatic juice in chronic pancreatitis (author's transl)].
In patients with chronic pancreatitis viscosity is significantly increasesed compared to controls when pure pancreatic juice aspirated in the course of duodenoscopy is analysed. This parameter may represent a simple method for the diagnosis of chronic pancreatitis.


Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis.
There are currently 10 licensed biologic therapies for the treatment of rheumatoid arthritis in 2014. In this article, we review the risk of serious infection (SI) for biologic therapies. This risk has been closely studied over the last 15 years within randomised controlled trials, long-term extension studies and observational drug registers, especially for the first three antitumour necrosis factor (TNF) drugs, namely infliximab, etanercept and adalimumab. The risk of SI with the newer biologics rituximab, tocilizumab, abatacept and tofacitinib is also reviewed, although further data from long-term observational studies are awaited. Beyond all-site SI, we review the risk of tuberculosis, other opportunistic infections and herpes zoster, and the effect of screening on TB rates. Lastly, we review emerging opportunities for stratifying the risk. Patients can be risk-stratified based on both modifiable and non-modifiable patient characteristics such as age, co-morbidity, glucocorticoid use, functional status and recent previous SI.


Electric and antiferromagnetic chiral textures at multiferroic domain walls.
Chirality, a foundational concept throughout science, may arise at ferromagnetic domain walls1 and in related objects such as skyrmions2. However, chiral textures should also exist in other types of ferroic materials, such as antiferromagnets, for which theory predicts that they should move faster for lower power3, and ferroelectrics, where they should be extremely small and possess unusual topologies4,5. Here, we report the concomitant observation of antiferromagnetic and electric chiral textures at domain walls in the room-temperature ferroelectric antiferromagnet BiFeO3. Combining reciprocal and real-space characterization techniques, we reveal the presence of periodic chiral antiferromagnetic objects along the domain walls as well as a priori energetically unfavourable chiral ferroelectric domain walls. We discuss the mechanisms underlying their formation and their relevance for electrically controlled topological oxide electronics and spintronics.


The effects of microRNAs on human neural stem cell differentiation in two- and three-dimensional cultures.
Stem cells have the ability to self-renew or to differentiate into numerous cell types; however, our understanding of how to control and exploit this potential is currently limited. An emerging hypothesis is that microRNAs (miRNAs) play a central role in controlling stem cell-fate determination. Herein, we have characterized the effects of miRNAs in differentiated human neural stem cells (hNSCs) by using a cell line currently being tested in clinical trials for stroke disability (NCT01151124, Clinicaltrials.gov). HNSCs were differentiated on 2- (2D) and 3-dimensional (3D) cultures for 1 and 3 weeks. Quantification of hNSC differentiation was measured with real-time PCR and axon outgrowth. The miRNA PCR arrays were implemented to investigate differential expression profiles in differentiated hNSCs. Evaluation of miRNA effects on hNSCs was performed by using transfection of miRNA mimics, real-time PCR, Western blot, and immunocytochemistry. The 3D substrate promoted enhanced hNSC differentiation coupled with a loss of cell proliferation. Differentiated hNSCs exhibited a similar miRNA profiling. However, in 3D samples, the degree and timing of regulation were significantly different in miRNA members of cluster mi-R17 and miR-96-182, and hsa-miR-302a. Overall, hNSC 3D cultures demonstrated differential regulation of miRNAs involved in hNSC stemness, cell proliferation, and differentiation. The miRNA mimic analysis of hsa-miR-146b-5p and hsa-miR-99a confirmed induction of lineage-committed progenitors. Downregulated miRNAs were more abundant; those most significantly downregulated were selected, and their putative target mRNAs analyzed with the aim of unraveling their functionality. In differentiated hNSCs, downregulated hsa-miR-96 correlated with SOX5 upregulation of gene and protein expression; similar results were obtained for hsa-miR-302a, hsa-miR-182, hsa-miR-7, hsa-miR-20a/b, and hsa-miR-17 and their target NR4A3. Moreover, SOX5 was identified as a direct target gene of hsa-miR-96, and NR43A, a direct target of hsa-miR-7 and hsa-mir-17 by luciferase reporter assays. Therefore, the regulatory role of these miRNAs may occur through targeting NR4A3 and SOX5, both reported as modulators of cell-cycle progression and axon length. The results provide new insight into the identification of specific miRNAs implicated in hNSC differentiation. These strategies may be exploited to optimize in vitro hNSC differentiation potential for use in preclinical studies and future clinical applications.


N-terminal myristoylation alters the calcium binding pathways in neuronal calcium sensor-1.
Neuronal calcium sensor-1 (NCS-1) interacts with many membranes and cytosolic proteins, both in a Ca(2+)-dependent and in a Ca(2+)-independent manner, and its physiological role is governed by its N-terminal myristoylation. To understand the role of myristoylation in altering Ca(2+) response and other basic biophysical properties, we have characterized the Ca(2+) filling pathways in both myristoylated (myr) and non-myristoylated (non-myr) forms of NCS-1. We have observed that Ca(2+) binds simultaneously to all three active EF-hands in non-myr NCS-1, whereas in the case of myr NCS-1, the process is sequential, where the second EF-hand is filled first, followed by the third and fourth EF-hands. In the case of myr NCS-1, the observed sequential Ca(2+) binding process becomes more prominent in the presence of Mg(2+). Besides, the analysis of (15)N-relaxation data reveals that non-myr NCS-1 is more dynamic than myr NCS-1. The overall molecular tumbling correlation time increases by approximately 20% upon myristoylation. Comparing the apo forms of non-myr NCS-1 and myr NCS-1, we found the possibility of existence of some substates, which are structurally closer to the holo form of the protein. There are more such substates in the case of non-myr NCS-1 than in the case of the myr NCS-1, suggesting that the former accesses larger volumes of conformational substates compared with the latter. Further, the study reveals that the possibility of Ca(2+) binding simultaneously to different parts of the protein is more favourable in non-myr NCS-1 than in myr NCS-1.


Isolation, cloning and sequence analysis of the cDNA for the alpha-subunit of human chorionic gonadotropin.
A 621-base pair fragment of the cDNA for the alpha-subunit of human chorionic gonadotropin has been isolated by cloning in a plasmid vector, and the complete nucleotide sequence determined. The entire coding region, including the 24-amino acid pre-sequence and most of the untranslated regions, are present in the fragment.


Women with lipoedema: a national survey on their health, health-related quality of life, and sense of coherence.
Lipoedema is a chronic disease in adipose tissue that almost exclusively affects women during periods of hormonal alterations. Its main symptoms include an abnormal accumulation of subcutaneous fat in the buttock, hips, and legs, which is associated with pain, swelling, and easy bruising. Herein, a grading in three stages is used to determine disease progression. Problematically, lipoedema manifestations are often confused with lifestyle-induced obesity, which is why the various health problems among affected women often remain unrecognized. Overall, research on lipoedema is scarce. As such, this study examined the health, health-related quality of life (HRQOL), and sense of coherence (SOC) among women with lipoedema. We conducted a national cross-sectional study using an online survey assessing sociodemographic data, lipoedema characteristics, symptom severity, comorbidities, HRQOL (RAND-36), and SOC (SOC-13). In total, 245 women with lipoedema, recruited from all Lipoedema Association groups in Sweden, participated. Data were compiled with descriptive statistics, and mean differences between groups were analysed by using parametric and non-parametric tests. Moderate and severe leg heaviness, pain, numbness, cold skin, feeling cold, easy bruising, and sleep problems were found to occur in all lipoedema stages. Moreover, almost all participants reported having comorbidities. Worse physical health and most substantial limitations in daily life were reported among women with the most progressive lipoedema (i.e., stage 3). Social and emotional functioning and SOC were found to be, on the other hand, primarily related to respondents' sociodemographic data and their ages at lipoedema onset. Even though approximately 70% of the women had experienced lipoedema onset before age 30, only three (1.6%) had been diagnosed by a healthcare professional before that age. Having lipoedema is associated with several health problems and a lower HRQOL. In addition, the extent of delay in diagnosis within this sample indicates that many women with lipoedema are often underdiagnosed and are left without support from healthcare. These findings call for the need for greater attention on lipoedema. Moreover, further studies on how women with lipoedema manage their health and symptoms, as well as on their experiences of healthcare services and lipoedema treatments, are needed.


Ectopic formation of primordial germ cells by transplantation of the germ plasm: direct evidence for germ cell determinant in Xenopus.
In many animals, the germ line is specified by a distinct cytoplasmic structure called germ plasm (GP). GP is necessary for primordial germ cell (PGC) formation in anuran amphibians including Xenopus. However, it is unclear whether GP is a direct germ cell determinant in vertebrates. Here we demonstrate that GP acts autonomously for germ cell formation in Xenopus. EGFP-labeled GP from the vegetal pole was transplanted into animal hemisphere of recipient embryos. Cells carrying transplanted GP (T-GP) at the ectopic position showed characteristics similar to the endogenous normal PGCs in subcellular distribution of GP and presence of germ plasm specific molecules. However, T-GP-carrying-cells in the ectopic tissue did not migrate towards the genital ridge. T-GP-carrying cells from gastrula or tailbud embryos were transferred into the endoderm of wild-type hosts. From there, they migrated into the developing gonad. To clarify whether ectopic T-GP-carrying cells can produce functional germ cells, they were identified by changing the recipients, from the wild-type Xenopus to transgenic Xenopus expressing DsRed2. After transferring T-GP carrying cells labeled genetically with DsRed2 into wild-type hosts, we could find chimeric gonads in mature hosts. Furthermore, the spermatozoa and eggs derived from T-GP-carrying cells were fertile. Thus, we have demonstrated that Xenopus germ plasm is sufficient for germ cell determination.


Concomitant complete atrioventricular block and left main coronary artery occlusion during transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI) is now considered a viable alternative therapy to surgery in patients with severe symptomatic aortic stenosis, considered to have a high risk for surgery. Herein, we present a case of severe aortic stenosis treated with transfemoral aortic valve implantation and complicated by complete atrioventrciular block and left main coronary artery obstruction that was successfully managed with permanent pacemaker implantation and left main coronary artery stenting. Although less invasive, TAVI can be associated with major complications. Therefore, extra care is required when performing TAVI in patients with borderline valve to coronary ostia distance.


Acute Brain Infarction in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Korean Single-Center Study.
This study investigated the clinical and radiological features of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with acute brain infarction, using a cohort of Korean patients with AAV. This study included 263 patients with AAV. Acute brain infarction was defined as infarction that occurred within 7 days or less. The brain territories affected by acute brain infarction were investigated. Active AAV was arbitrarily defined as the highest tertile of Birmingham Vasculitis Activity Score (BVAS). The median age at diagnosis was 59.0 years, and 35.4% were male. Fourteen cases of acute brain infarction occurred in 12 patients (4.6%), which was calculated as 1332.2 per 100,000 patient-years and 10 times higher than the incidence rate in the Korean general population. Patients with AAV with acute brain infarction exhibited significantly older age, increased BVAS at diagnosis, and a more frequent history of prior brain infarction compared with those without. The brain territories affected in AAV patients were middle cerebral artery (50.0%), multiple territories (35.7%), and posterior cerebral artery (14.3%). Lacunar infarction and microhemorrhage were observed in 42.9% and 71.4% of cases, respectively. Prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction (hazard ratios, 7.037 and 1.089). Patients with AAV with prior brain infarction or BVAS for active AAV exhibited significantly lower cumulative acute brain infarction-free survival rates than those without. Acute brain infarction was observed in 4.6% of AAV patients, and both prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction.


Reproductive factors, exogenous hormone use and incidence of melanoma among women in the United States.
Although the photosensitising effects of oestrogens may increase the impact of ultraviolet radiation (UVR) on melanoma risk, few prospective studies have comprehensively assessed the association between oestrogen-related factors and melanoma. We examined the associations between reproductive factors, exogenous oestrogen use and first primary invasive melanoma among 167 503 non-Hispanic white, postmenopausal women in the NIH-AARP Diet and Health Study. Satellite-based ambient UVR estimates were linked to geocoded residential locations of participants at study baseline. Increased risk of melanoma was associated with early age at menarche (≤10 vs ≥15 years: HR = 1.25, 95% CI: 0.92, 1.71; P for trend = 0.04) and late age at menopause (≥50 vs <45 years: HR = 1.34, 95% CI: 1.13, 1.59; P for trend = 0.001). The relationship between ambient UVR and melanoma risk was highest among women with age at menarche ≤10 years (HR per UVR quartile increase = 1.29; 95% CI: 1.05, 1.58; P-interaction = 0.02). Melanoma risk was not associated with parity, age at first birth, use of oral contraceptives or use of menopausal hormone therapy. Our findings suggest that increased melanoma risk is associated with early age at menarche and late age at menopause. Effect modification findings support the hypothesis that endogenous oestrogen exposure in childhood increases photocarcinogenicity. Future studies should include information on personal UVR exposure and sun sensitivity.


Techniques of tympanomastoidectomy.
The authors describe the various techniques of tympanomastoidectomy that can be used to eradicate chronic disease processes. The techniques are either open or closed operations; the factors in determining the choice of technique for specific conditions are presented.


Yolk sac cholesteryl ester secretion rates can be manipulated in the Golden Syrian hamster: effect of yolk sac cholesterol concentrations.
The yolk sac is one of two extra-embryonic fetal tissues that separates the fetal and maternal circulations. The yolk sac can secrete lipoprotein particles to the vitelline vessels, which supply yolk sac-derived nutrients to the embryo. The amount and composition of lipoproteins secreted from the rat yolk sac can be manipulated by fatty acid content and gestational age. The goals of the current studies were to determine, first, if tissue cholesterol concentration could mediate cholesterol secretion rate from the yolk sac and, second, if some of the secreted cholesterol could be derived from the maternal circulation. Golden Syrian hamsters were fed 2% added cholesterol to increase the yolk sac cholesterol concentration. Yolk sac explants secreted similar amounts of triglyceride and apolipoproteins B and E into the media regardless of yolk sac cholesterol concentration. In contrast, yolk sacs with greater cholesterol concentrations secreted 2.3-fold more cholesterol into the media as compared to control yolk sacs; the increase was found mostly as cholesteryl ester. At least part of the secreted cholesterol was maternally derived. These data demonstrate that yolk sac cholesterol concentration influences cholesterol secretion rates, and that at least some of the cholesterol secreted originates from the maternal circulation.


[Characteristics of the effect of estradiol on prolactin secretion by adenohyophyseal cells from intact and ovariectomized rats in primary monolayer cultures].
Estradiol directly stimulated the secretion of prolactin by the adenohypophyseal cells of intact rats in a monolayer culture. Complex interactions between estradiol and some other regulators of the hypophyseal lactotropic function were revealed. It was established that changes in prolactin synthesis and secretion in ovariectomized rats persisted for 3--4 days of adenohypophyseal cell cultivation in vitro.


Regulatory effects of a novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae on mice immune cells.
The giant panda (Ailuropoda melanoleuca) is a well-known, rare and endangered species. Baylisascaris schroederi is a pathogenic ascarid. Infection with B. schroederi may cause death in giant pandas. At present, the immune evasion mechanism of B. schroederi is little known. Cysteine protease inhibitors (CPI) play important roles in the regulation of host immune responses against certain nematodes. In this study, we focused on the analysis of the regulation of B. schroederi migratory larvae CPI (rBsCPI-1) on mice immune cells. First, the pattern recognition receptors on the surface of peripheral blood mononuclear cells (PBMCs) and the signal pathways that transduce extracellular signals into the nucleus activated by rBsCPI-1 were identified. Then, the regulatory effects of rBsCPI-1 on PBMCs physiological activities were detected. Finally, the effects of rBsCPI-1 on TLR signaling pathway activation and NF-κB phosphorylation in mice immunized with recombinant protein were analysed. The results suggested that rBsCPI-1 secreted by B. schroederi migratory larvae is mainly recognized by TLR2 and TLR4 on PBMCs. Extracellular signals are transduced into the nucleus through the MAPK and NF-κB signaling pathways, enhancing the phagocytosis, migration, and apoptosis of PBMCs; meanwhile, rBsCPI-1 induces high expression of NO. Thus, rBsCPI-1 plays a role in immune regulation. In addition, the high expression of negative regulatory factors also ensured that TLR activation is maintained at the optimal level. rBsCPI-1 can transduce regulatory signals into immune cells by activating the TLR2/4-NF-κB/MAPK signaling pathway, having a certain regulatory effect on the physiological activities. Meanwhile, rBsCPI-1 can maintain the immune response in a balance by limiting the over-activation of the TLRs signaling pathway and thus contributes to B. schroederi immune evasion.


Posttraumatic stress disorder and depression among new mothers at 8 months later of the 2008 Sichuan earthquake in China.
On May 12, 2008, a magnitude 8.0 earthquake struck China's southwestern Sichuan province. Recent studies have identified mental health problems among the survivors, but little is known about the impact of the Sichuan earthquake on the mental health of new mothers in the area. The main objective was to assess the impact of the Sichuan earthquake on the posttraumatic stress disorders (PTSD) and depression of new mothers. A total of 317 new mothers were interviewed in the hospital from January 2009 to March 2009. Symptoms of PTSD were measured using the impact of event scale-revised, and symptoms of postpartum depression were measured using the Center for Epidemiologic Studies Depression scale. The prevalence rates of PTSD and postpartum depression were 19.9% and 29.0%, respectively. Women with high earthquake exposure had higher risks of PTSD (odds ratio (OR), 5.91; 95% confidence interval (CI), 1.75-19.97; P < 0.001) and postpartum depression (OR, 7.28; 95% CI, 2.51-21.08; P < 0.001) than women without earthquake experience. In addition, women with low monthly family income and farm workers had a higher risk of having PTSD; women who were unemployed or with lower monthly family income and poor sleep had a higher risk of having depression. Earthquake experience increased the risks of having PTSD and depression among new mothers at 8 months later of the earthquake.


A robust deep learning approach for tomato plant leaf disease localization and classification.
Tomato plants' disease detection and classification at the earliest stage can save the farmers from expensive crop sprays and can assist in increasing the food quantity. Although, extensive work has been presented by the researcher for the tomato plant disease classification, however, the timely localization and identification of various tomato leaf diseases is a complex job as a consequence of the huge similarity among the healthy and affected portion of plant leaves. Furthermore, the low contrast information between the background and foreground of the suspected sample has further complicated the plant leaf disease detection process. To deal with the aforementioned challenges, we have presented a robust deep learning (DL)-based approach namely ResNet-34-based Faster-RCNN for tomato plant leaf disease classification. The proposed method includes three basic steps. Firstly, we generate the annotations of the suspected images to specify the region of interest (RoI). In the next step, we have introduced ResNet-34 along with Convolutional Block Attention Module (CBAM) as a feature extractor module of Faster-RCNN to extract the deep key points. Finally, the calculated features are utilized for the Faster-RCNN model training to locate and categorize the numerous tomato plant leaf anomalies. We tested the presented work on an accessible standard database, the PlantVillage Kaggle dataset. More specifically, we have obtained the mAP and accuracy values of 0.981, and 99.97% respectively along with the test time of 0.23 s. Both qualitative and quantitative results confirm that the presented solution is robust to the detection of plant leaf disease and can replace the manual systems. Moreover, the proposed method shows a low-cost solution to tomato leaf disease classification which is robust to several image transformations like the variations in the size, color, and orientation of the leaf diseased portion. Furthermore, the framework can locate the affected plant leaves under the occurrence of blurring, noise, chrominance, and brightness variations. We have confirmed through the reported results that our approach is robust to several tomato leaf diseases classification under the varying image capturing conditions. In the future, we plan to extend our approach to apply it to other parts of plants as well.


Extremophiles: the species that evolve and survive under hostile conditions.
Extremophiles possess unique cellular and molecular mechanisms to assist, tolerate, and sustain their lives in extreme habitats. These habitats are dominated by one or more extreme physical or chemical parameters that shape existing microbial communities and their cellular and genomic features. The diversity of extremophiles reflects a long list of adaptations over millions of years. Growing research on extremophiles has considerably uncovered and increased our understanding of life and its limits on our planet. Many extremophiles have been greatly explored for their application in various industrial processes. In this review, we focused on the characteristics that microorganisms have acquired to optimally thrive in extreme environments. We have discussed cellular and molecular mechanisms involved in stability at respective extreme conditions like thermophiles, psychrophiles, acidophiles, barophiles, etc., which highlight evolutionary aspects and the significance of extremophiles for the benefit of mankind.