Trajectory tracking nonlinear H∞ controller for wheeled mobile robots with disturbances observer.
Wheeled Mobile Robots (WMRs) are systems with multiple industrial and civilian applications. Trajectory tracking is essential in many applications, such as surveillance, monitoring, and autonomous driving. However, in practical applications, a WMR is always affected by kinematic disturbances, state estimation error, and measurement noise, which may diminish the system's performance. Hence, this work proposes a novel observer-based H∞ controller that is robust against matched and unmatched disturbances. The proposed methodology compensates for disturbances through a disturbance observer, transforming the closed-loop system into a new one affected by uniformly bounded disturbances. Then, an H∞ controller is designed to make the WMR track a desired reference signal. A formal stability proof demonstrates the feasibility of the new proposal. Also, feedback and finite-time controllers are used to assess the novel controller. Numerical simulations and experimental results with a scaled autonomous car-like robot demonstrate the novel controller's efficiency and outstanding performance, despite disturbances when compared against finite-time and feedback controllers.


Light-Directed Migration of D. discoideum Slugs in Microfabricated Confinements.
This paper investigates the light-driven migration of the multi-cellular microorganism Dictyostelium discoideum as a potential bio-actuation mechanism in microsystems. As a platform for slug migration we use microscale confinements, which consist of intersecting microchannels fabricated from solidified agar-water solution. The agar surface provides necessary moisture to the slugs during the experiment while remaining sufficiently stiff to allow effective slug migration. The movements of the slugs in the microchannels are driven and guided by phototaxis via controlling light transmitted through optical fibers. The microchannels impose geometrical confinements on the migrating slugs, improving the spatial precision of the migration. We demonstrate that slugs that form in a microchamber can be driven to migrate through the microchannels, as well as steered to a particular direction at microchannel intersections. Our experimental results indicate that slug movements can be more effectively controlled in microchannels, and potentially useful for bio-actuation applications.


In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice.
We determined whether the implantation of human pancreatic cancer cells into the pancreas of nude mice can be used to select variants with increasing metastatic potential. COLO 357 line fast-growing cells were injected into the spleen or pancreas of nude mice. Hepatic metastases were harvested, and tumor cells were reinjected into the spleen or pancreas. This cycle was repeated several times to yield cell lines L3.6sl (spleen to liver) and L3.6pl (pancreas to liver). The variant cells produced significantly higher incidence and number of lymph node and liver metastases than the parental cells. Their increased metastatic potential was associated with increased expression (mRNA and protein) of the proangiogenic molecules basic fibroblast growth factor, vascular endothelial growth factor, and interleukin-8. The metastatic cells also exhibited increased motility and invasiveness, which were associated with increased expression of collagenase type IV (MMP-9) and decreased expression of E-cadherin. Collectively, the data show that the orthotopic implantation of human pancreatic cancer cells in nude mice is a relevant model with which to study the biology of pancreatic cancer metastasis and to select variant cell lines with enhanced metastatic potential.


Cerebrospinal fluid JC virus antibody index for diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV ) in the diagnosis of natalizumab-associated PML. AIJCV was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as published. Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5. Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML.


A new insight into the aryl hydrocarbon receptor/cytochrome 450 signaling pathway in MG63, HOS, SAOS2, and U2OS cell lines.
Osteosarcoma is the most common malignant tumor of bone, with rapid progressive growth, early distant metastases, and frequent recurrence after surgical treatment. Osteosarcoma is characterized by changes in the ratio and expression of different cytochrome P450 (CYP) isoforms that can affect the effectiveness of anticancer therapies. The inducible expression of CYP1 genes depends on the ligand-dependent functionality of the aryl hydrocarbon receptor (AHR). In this study, we examined the AHR/CYP1 signaling pathway in four osteosarcoma cell lines (MG63, HOS, SAOS2, and U2OS) induced by the known AHR ligands: indirubin, indole-3-carbinol, and beta-naphthoflavone. Using qPCR and Western blot analysis, we explored the effects of these ligands on the expression of the CYP1 genes and studied the correlation between these responses and the changes in the mRNA and protein levels of AHR and the AHR nuclear translocator (ARNT) in these osteosarcoma cell lines. The results show that the AHR/CYP1 signaling pathway retains its function only in MG63 and HOS cells, and is impaired in SAOS2 and U2OS cells. Our data should be taken into account when recommending new strategies for the treatment of osteosarcoma and when evaluating new drugs against osteosarcoma in vitro.


In Vitro Study of a Stentless Aortic Bioprosthesis Made of Bacterial Cellulose.
The paper present findings from an in vitro experimental study of a stentless human aortic bioprosthesis (HAB) made of bacterial cellulose (BC). Three variants of the basic model were designed and tested to identify the valve prosthesis with the best performance parameters. The modified models were made of BC, and the basic model of pericardium. Each model (named V1, V2 and V3) was implanted into a 90 mm porcine aorta. Effective Orifice Area (EOA), rapid valve opening time (RVOT) and rapid valve closing time (RVCT) were determined. The flow resistance of each bioprosthesis model during the simulated heart systole, i.e. for the mean differential pressure (ΔP) at the time of full valve opening was measured. All experimental specimens were exposed to a mean blood pressure (MBP) of 90.5 ± 2.3 mmHg. The V3 model demonstrated the best performance. The index defining the maximum opening of the bioprosthesis during systole for models V1, V2 and V3 was 2.67 ± 0.59, 2.04 ± 0.23 and 2.85 ± 0.59 cm2, respectively. The mean flow rate through the V3 valve was 5.7 ± 1, 6.9 ± 0.7 and 8.9 ± 1.4 l/min for stroke volume (SV) of 65, 90 and 110 mL, respectively. The phase of immediate opening and closure for models V1, V2 and V3 was 8, 7 and 5% of the cycle duration, respectively. The mean flow resistance of the models was: 4.07 ± 2.1, 4.28 ± 2.51 and 5.6 ± 2.32 mmHg. The V3 model of the aortic valve prosthesis is the most effective. In vivo tests using BC as a structural material for this model are recommended. The response time of the V3 model to changed work conditions is comparable to that of a healthy human heart. The model functions as an aortic valve prosthesis in in vitro conditions.


Dominant lethal study of sulfur mustard in male and female rats.
Sulfur mustard (HD) (bis(2-chloroethyl)sulfide) is a strong alkylating agent with known mutagenic and suspected carcinogenic properties, but occupational health standards have not been established. The purpose of this study was to determine the dominant lethal effect in male and female rats dosed orally with HD, for which currently available data are ambiguous. Sprague-Dawley rats of each sex, 6-7 weeks old, were orally administered 0, 0.08, 0.20 or 0.50 mg kg-1 HD 5 days a week for 10 weeks, after which dominant lethal studies were conducted during the post-exposure period. The studies were conducted in two phases: a female dominant lethal phase in which treated or untreated males were mated with treated females and their fetuses were evaluated 14 days after copulation; and a male dominant lethal phase in which treated males cohabited with untreated females for 5 days and fetuses were evaluated 14 days after the mid-point of the week of cohabitation, for each of 10 weeks. In addition, motility, population size and morphology were measured in sperm obtained from the cauda epididymis. Parental growth rates were reduced in both sexes treated with the high level of HD. Female dominant lethal effects were not observed, although significant male dominant lethal effects were observed in HD-exposed male rats mated to untreated females at 2 and 3 weeks' post-exposure. These effects, which included increases of early fetal resorptions and preimplantation losses and decrease in total live embryo implants, were most consistently observed at a dose of 0.50 mg kg-1. A significant P(P < 0.05) increase in the percentage of abnormal sperm was detected in males exposed to 0.50 mg kg-1 HD. The timing of dominant lethal effects is consistent with an effect during the post-meiotic stages of spermatogenesis, possibly involving the generally sensitive spermatids.


Commonsense advice on treating nail disorders.
Most nail disorders seen by primary care physicians are due to maceration, dryness, trauma, or infection. Some cases may be treated simply by having the patient remove a bandage to allow the skin to dry; other cases, such as subungual abscess, require local anesthesia and drainage for relief. Fungal infections may need to be treated for as long as a year. Patients with a tumor under the nail should be referred to a specialist.


Recovery of carbon fiber-reinforced polymer waste using dimethylacetamide base on the resin swelling principle.
The mechanical recycling method of the carbon fiber-reinforced polymer (CFRP) has the advantages of simple process, less pollution and low cost, but only low utilization value of carbon fibers in powder or short fibers form can be obtained. To reduce the length and strength loss of the recycled carbon fibers, a novel and cost-effective dimethylacetamide (DMAC) swelling technique was developed to achieve rapid delamination of the CFRP laminates under mild conditions (120°C-160°C, 1 h). The corresponding swelling ratios and mass-loss rates of cured epoxy resin (CEP) were about 121.39%-157.39% and 0-0.69%, respectively. Excessive swelling of CEP in DMAC resulted in the cracking of the resin matrix between the adjacent carbon fiber layers. Thus the CFRP laminates were delaminated into soft single carbon fiber layers, which showed excellent cutting performance and reinforcing properties. The delamination products were cut into thin strips of different sizes and vacuum bag molded into new CFRP laminates. The flexural strength and tensile strength of the newly produced CFRP laminates were about 76.38%-90.98% and 94.61%-98.54% of the original CFRP laminates, respectively. More importantly, the chemical compositions of DMAC and CEP were unchanged during the physical swelling process. No organic pollutants (caused by resin degradation) were generated. And the used DMAC can be easily recycled by filtration. Therefore, this study provides a strategy for low-cost and high-valued recycling of CFRP waste.


Computational models of ventricular- and atrial-like human induced pluripotent stem cell derived cardiomyocytes.
The clear importance of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) as an in-vitro model highlights the relevance of studying these cells and their function also in-silico. Moreover, the phenotypical differences between the hiPSC-CM and adult myocyte action potentials (APs) call for understanding of how hiPSC-CMs are maturing towards adult myocytes. Using recently published experimental data, we developed two computational models of the hiPSC-CM AP, distinguishing between the ventricular-like and atrial-like phenotypes, emerging during the differentiation process of hiPSC-CMs. Also, we used the computational approach to quantitatively assess the role of ionic mechanisms which are likely responsible for the not completely mature phenotype of hiPSC-CMs. Our models reproduce the typical hiPSC-CM ventricular-like and atrial-like spontaneous APs and the response to prototypical current blockers, namely tetrodotoxine, nifedipine, E4041 and 3R4S-Chromanol 293B. Moreover, simulations using our ventricular-like model suggest that the interplay of immature I Na, I f and I K1 currents has a fundamental role in the hiPSC-CM spontaneous beating whereas a negative shift in I CaL activation causes the observed long lasting AP. In conclusion, this work provides two novel tools useful in investigating the electrophysiological features of hiPSC-CMs, whose importance is growing fast as in-vitro models for pharmacological studies.


Isolation, identification and oenological characterization of non-Saccharomyces yeasts in a Mediterranean island.
We isolated, identified and characterized yeast strains from grapes, and their fermented musts, sampled in the small island of Linosa, where there are no wineries and therefore the possibility of territory contamination by industrial strains is minimal. By traditional culture-dependent methods, we isolated 3805 colonies, distinguished by molecular methods in 17 different species. Five hundred and forty-four isolates were analysed for the main oenological characteristics such as fermentative vigour with and without sulphites, sugar consumption and production of alcohol, volatile acidity, hydrogen sulphide, glycerol and β-glucosidase. This analysis identified Kluyveromyces marxianus (seldomly used in winemaking) as the most interesting candidate yeast for the production of innovative wines. In recent years, interest is growing for wine production by non-Saccharomyces yeasts, both in research and in the industry. This study describes the yeast population of the grapes in a small-secluded island in the Mediterranean Sea, useful site for the search of new strains. Evaluation of fundamental oenological characters identifies potential best yeasts to assay in experimental vinifications. We also describe, for the first time, 14 new colony morphologies on WL Nutrient Agar, culture medium used to monitor the yeast population dynamics.


A feasible method for linkage studies avoiding clerical review: linkage of the national HIV/AIDS surveillance databases with the National Death Index in Australia.
To assess the sensitivity and specificity of linkage of HIV/AIDS diagnoses in Australia to the National Death Index (NDI). An aggregated file containing 19,772 matched HIV/AIDS diagnoses reported to the national HIV/AIDS databases from 1980 to 30 June 2004 was linked to the NDI using probabilistic linkage methods based on the namecode, date of birth, and sex as identifiers. Based on the 6,900 HIV/AIDS known deaths reported by 1 January 2003 and 1,455 known non-deaths with an active follow-up beyond 1 January 2003, the different combinations of weights assigned to matched pairs were examined to obtain maximum sensitivity and specificity. The trade-off between sensitivity and specificity was used to obtain an optimal linkage. The optimal linkage was found to link 5,658 of the 6,900 HIV/AIDS known deaths (a sensitivity of 82%), and 116 false positives of the 1,455 known not deaths (specificity of 92%). Causes of deaths were recorded for 86.5% of deaths that were linked to the NDI. This is a feasible method for conducting linkage studies if both the identifying deaths and non-deaths are available. The relatively poor sensitivity could be due to limited identifiers available for linkage on the HIV/AIDS databases.


[Clinical assessment of toothpaste with vitamin A in patients with periodontal diseases].
The effectiveness was assessed of a toothpaste with vitamin A and a toothpaste without this vitamin in the treatment of parodontal disease. Significant differences in the therapeutic action of both pastes were observed in patients with superficial inflammatory periodontopathy. The toothpaste with vitamin A had a more favourable effect.


Fine-needle trucut biopsy versus fine-needle aspiration cytology with ultrasound guidance in the abdomen.
Historically, fine-needle aspiration cytology (FNAC) has varying sensitivity, specificity and accuracy in the diagnosis of abdominal lesions with a high insufficient sampling rate. We compared 20-G fine-needle trucut biopsy (FNTB) with FNAC results in the biopsy of solid abdominal tumours. A retrospective review of 171 (128x 20-G FNTB and 43x FNAC) ultrasound-guided biopsies of abdominal tumours on 157 patients (male : female 85:72, mean age 61.25 years) were carried out. One hundred and seventy-one biopsies were carried out: liver 109, pancreas 19, lymph node 10, omentum 5, right iliac fossa mass 6, adrenal 6 and others 16. An average of 2.06 and 1.97 passes (range 1-4) were carried out per FNTB and FNAC, respectively. A definitive diagnosis was made in 122/128 biopsies (95.3%) and 32/43 biopsies (74.4%) for FNTB and FNAC, respectively. Diagnoses consisted of metastatic liver disease (74/171), pancreatic adenocarcinoma (10/171), lymphoma (8/171) and others (33/171) and benign (29/171). No significant complications occurred in either group. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87, 100, 100, 50, 84.4 and 93.1, 100, 100, 60, 71.4 for FNTB and FNAC, respectively. A greater and more consistent positive diagnosis rate is yielded by 20-G FNTB (95.3%) than FNAC (74.4%). The diagnostic accuracy of FNTB is 84.4% compared with 69.8% for FNAC. A greater insufficient sampling rate occurs with FNAC (25.6%) than with FNTB (4.7%). For abdominal biopsy, 20-G FNTB needles have a much higher yield than FNAC with no increase in complications. FNTB is the preferred choice, particularly where cytological assistance at the time of biopsy is unavailable.


The structure of the KtrAB potassium transporter.
In bacteria, archaea, fungi and plants the Trk, Ktr and HKT ion transporters are key components of osmotic regulation, pH homeostasis and resistance to drought and high salinity. These ion transporters are functionally diverse: they can function as Na(+) or K(+) channels and possibly as cation/K(+) symporters. They are closely related to potassium channels both at the level of the membrane protein and at the level of the cytosolic regulatory domains. Here we describe the crystal structure of a Ktr K(+) transporter, the KtrAB complex from Bacillus subtilis. The structure shows the dimeric membrane protein KtrB assembled with a cytosolic octameric KtrA ring bound to ATP, an activating ligand. A comparison between the structure of KtrAB-ATP and the structures of the isolated full-length KtrA protein with ATP or ADP reveals a ligand-dependent conformational change in the octameric ring, raising new ideas about the mechanism of activation in these transporters.


Maintenance of human pluripotent stem cells using 4SP-hFGF2-secreting STO cells.
Human embryonic stem cells (hESCs) are typically cultured on fibroblast feeder cells or in fibroblast conditioned medium supplemented with fibroblast growth factor 2 (FGF2, also known as bFGF). FGF signaling appears to be important for hESC self-renewal and is required to enable the culture of hESCs in an undifferentiated state. In this study, we generated a transgenic fibroblast feeder line stably expressing a secretable FGF4 signal peptide tagged hFGF2 (4SP-hFGF2). The expression of this transgene functionally replaced the requirement for exogenous FGF2 when using these cells as feeders for the maintenance of hESCs. Under these conditions, hESCs maintained the typical marker of pluripotency assessed after long term culture, while still retaining the capacity for differentiation to all three germ layers. This transgene could be applied to mass produce 4SP-hFGF2 protein, serving to be an economical and effective strategy for culturing pluripotent stem cells as feeder cells.


Development of an abdominal magnetic resonance (MR) contrast agent formulation with Oral Magnetic Particles (OMP, Ferristene).
A formulation for fast dispersible granules with the magnetic resonance (MR) contrast agent, Oral Magnetic Particles (OMP), was developed. The formulation contained viscosity-increasing agents (xanthan gum and a mixture of microcrystalline cellulose and sodium carboxymethylcellulose). The granules were dispersed easily in water when stirred by hand and became a viscous OMP suspension with apparent homogeneity, but does not form granule aggregates (lump), within 10 min. The dispersibiility was greatly affected by the binder type and addition of disintegrant. Hydroxypropylcellulose and low-substituted hydroxypropylcellulose were preferable. The preparation method to incorporate OMP into the granules also greatly influenced the dispersibility of the granules. A fluidized bed granulation of the base granules containing additives and subsequent coating of OMP onto the granules was eventually utilized. The formulation was able to control the viscosity of the suspension by regulating the content of viscosity-increasing agent while maintaining dispersibility. The developed formulation gave a good MR contrast image in rats and no magnetic susceptibility artifact was observed.


Reprogramming of Human Fibroblasts with Non-integrating RNA Virus on Feeder-Free or Xeno-Free Conditions.
Recent advances in generating induced pluripotent stem cells have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from somatic cells. However, a major obstacle to the use of iPSC for therapeutic applications is the potential genomic modifications resulted from viral insertion of transgenes in the cellular genome. Second, the culture of iPSCs and adult cells often requires the use of animal products, which hinder the generation of clinical-grade iPSCs. We report here the generation of iPSCs by an RNA Sendai virus vector that does not integrate transgenes into the cell's genome. In addition, reprogramming can be performed on a feeder-free or xeno-free condition without containing animal products. Generation of an integrant-free iPSCs in these conditions will facilitate the studies of iPSCs in cell-based therapies.


The Prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension.
The cytochrome P450 (CYP) epoxygenase pathway produces arachidonic acid metabolites that are vasoactive, that affect renal sodium handling, and that have been proposed to play a mechanistic role in hypertension. Multiple single nucleotide polymorphisms (SNP) in CYP2C8, 2C9, 2J2 and soluble epoxide hydrolase (sEH) have been identified, many of which have altered functional activity in vitro. We performed a case-control study to determine the prevalence of epoxygenase-related SNP in African American individuals and to evaluate whether these SNP are associated with increased risk of hypertension. Normotensive African American individuals (N = 107) and African American patients with hypertension (N = 108) were recruited. DNA was extracted from a venous blood sample and genotyped for CYP2C8*2,*3, CYP2C9*2-*5,*8,*11, CYP2J2 *2-*7, L50L, R49S, V113M, N124S, sEH R287Q, and sEH 403Rins variant alleles by allelic discrimination using real-time polymerase chain reaction. Genotype and allele frequencies were calculated and associations with hypertension were estimated using unconditional logistic regression, adjusting for age and sex. No association was found between any of the variant alleles and hypertension. We did find that only the CYP2C8*3and CYP2C9*2 alleles were in strong linkage disequilibrium in both the hypertensive and healthy African American groups, a finding that was reported previously in healthy individuals of white ethnicity. These results suggest that these epoxygenase-related SNP are not associated with increased risk of hypertension in the African American population. There was significant linkage disequilibrium between CYP2C8*3 and CYP2C9*2 alleles that was not associated with hypertension.


Intravital 2-Photon Microscopy of Diverse Cell Types in the Murine Tibia.
Intravital imaging allows the visualization of fluorescently labeled structures like cells, blood flow, and pathogens in a living organism. Nowadays, numerous methods for imaging in several organs are available. In this chapter, we present a method for intravital 2-photon microscopy of the murine tibial bone marrow. It enables the observation of hematopoietic cells including cells of the innate and adaptive immune system under physiological conditions. Motility analyses within this complex environment led to insights into their migratory potential as well as their interactions with other cells or blood vessels.


Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype: case series of a new entity.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (pHGG) is a rare and aggressive brain tumor characterized by a specific DNA methylation profile. It was recently introduced in the 5th World Health Organization classification of central nervous system tumors of 2021. Clinical data on this tumor is scarce. This is a case series, which presents the first clinical experience with this entity. We compiled a retrospective case series on pHGG patients treated between 2015 and 2022 at our institution. Data collected include patients' clinical course, surgical procedure, histopathology, genome-wide DNA methylation analysis, imaging and adjuvant therapy. Eight pHGG were identified, ranging in age from 8 to 71 years. On MRI tumors presented with an unspecific intensity profile, T1w hypo- to isointense and T2w hyperintense, with inhomogeneous contrast enhancement, often with rim enhancement. Three patients died of the disease, with overall survival of 19, 28 and 30 months. Four patients were alive at the time of the last follow-up, 4, 5, 6 and 79 months after the initial surgery. One patient was lost to follow-up. Findings indicate that pHGG prevalence might be underestimated in the elderly population.


Neurological complications of chemotherapy to the central nervous system.
One of the most common complications of chemotherapeutic drugs is toxicity to the central nervous system (CNS). This toxicity can manifest in many ways, including encephalopathy syndromes and confusional states, seizure activity, headache, cerebrovascular complications and stroke, visual loss, cerebellar dysfunction, and spinal cord damage with myelopathy. For many drugs, the toxicity is related to route of administration and cumulative dose, and can vary from brief, transient episodes to more severe, chronic sequelae. However, the neurotoxicity can be idiosyncratic and unpredictable in some cases. Among the antimetabolite drugs, methotrexate, 5-fluorouracil, and cytosine arabinoside are most likely to cause CNS toxicity. Of the alkylating agent chemotherapeutic drugs, the nitrosoureas (e.g., BCNU) and cisplatin most frequently cause toxicity to the CNS, especially when given via the intra-arterial route. Ifosfamide is also likely to cause neurotoxicity at high intravenous doses. Other alkylating agents, such as busulfan, cyclophosphamide, procarbazine, and temozolomide, are better tolerated by the CNS at moderate doses. The retinoid drugs are known to cause severe headaches at high doses. l-Asparaginase can induce an encephalopathy syndrome, as well as cerebrovascular complications such as stroke.


Fundus autofluorescence imaging patterns in central serous chorioretinopathy according to chronicity.
PurposeTo investigate the time-period characteristics associated with morphologic changes in central serous chorioretinopathy (CSC) using fundus autofluorescence (FAF).Patients and methodsRetrospective, cross-sectional observational case series. Patients were classified into three groups: acute and chronic according to the onset of subjective symptoms of 6 weeks and sequelae patients who have history and symptoms but no serous retinal detachment (SRD). We compared FAF images to obtain characteristic findings according to the chronicity.ResultsA total of 52 eyes were included in this study. Acute CSC eyes were characterized by decreased FAF intensity at the leakage point in 13/22 eyes (56.5%) and staining patterns with various levels of fluorescence signal (hyperautofluorescent (10 eyes, 43.5%), hypoautofluorescent (1 eye, 4.3%), and minimal changes (12 eyes, 52.2%)) in the area of SRD. In chronic CSC eyes, hyperautofluorescent (14 eyes, 63.6%) or minimal changes (8 eyes, 36.4%) were observed in the area of SRD. Discrete dots with increased FAF intensity were observed in chronic CSC eyes (P<0.001). Eyes with sequelae of CSC had mixed FAF patterns over areas of retinal pigment epithelium (RPE) atrophy in seven eyes (100%, P<0.001)) and descending tracts which showed various FAF intensities according to the RPE and photoreceptor status (P<0.001).ConclusionFAF imaging patterns in CSC eyes differ according to the course of the disease, reflecting RPE and outer retinal changes. Detailed investigation using FAF could help to estimate the duration of CSC and determine the proper treatment modality.


Corrigendum: Chloroplast genome sequencing, comparative analysis, and discovery of unique cytoplasmic variants in pomegranate (Punica granatum L.).
[This corrects the article DOI: 10.3389/fgene.2021.704075.].


Single atom iron implanted polydopamine-modified hollow leaf-like N-doped carbon catalyst for improving oxygen reduction reaction and zinc-air batteries.
Metal-nitrogen-carbon (MNC) catalysts, especially FeNC catalysts, are considered promising candidates to replace Pt-based catalysts, but FeNC catalysts still present certain challenges in controlled-synthesis and energy device applications. In this paper, through the modification strategy of poly-dopamine (PDA) to maintain 2D leaf morphology to obtain more active sites and further adjust the N content, N-doped porous carbon monatomic iron catalyst (FeSA/NPCs) with rich-nitrogen content was prepared. XPS analysis showed that compared with C-ZIF-Fe, the contents of graphite nitrogen and pyridine nitrogen increased in FeSA/NPCs. The hollow structure with defects and Fe-N4 configuration of Fe single atom show more active sites for the catalyst, and positively promote the diffusion of reactants, oxygen exchange and electron transport, thus changing the reaction kinetics and promoting the improvement of ORR activity. FeSA/NPCs electrocatalyst exhibits good half-wave potential and onset potential at low loading (E1/2 = 0.93 V, Eonset = 1.0 V). In addition, the methanol tolerance, stability and Tafel slope are better than those of commercial Pt/C. Excitingly, the zinc-air cell with FeSA/NPCs as cathode material achieves a power density of 223 mW cm-2 and exhibits a long-term stability higher than 200 h. This work shows that nitrogen-doped porous carbon materials as well as iron monoatoms play important roles in improving electrocatalytic performance.


X-ray photographs of the sun on March 7, 1970.
The Sun was photographed from an Aerobee rocket by means of equipment responding to the wavelength interval 3-60 angstroms, revealing interesting relationships between structures in the corona.


Novel 5beta-hydroxyspirostan-6-ones ecdysteroid antagonists: synthesis and biological testing.
Eight new 5beta-hydroxy-spirostan-6-ones bearing hydroxy and amino functions in the A ring, i.e., 3beta-OH, 3alpha-OH, 2beta,3beta-OH, 2alpha,3beta-OH, 3beta-NH2, 2alpha-NH2-3beta-OH, 2beta-NH2-3beta-OH, and 2beta-OH-3beta-NH2, were efficiently synthesized, and their antiecdysteroid activities were evaluated on the metamorphosis bioassay of mosquito Aedes aegypti. To our knowledge, these new steroids represent the first 5beta-hydroxy-spirostanes which have been tested for antiecdysteroid activity in mosquitoes. The higher antagonistic effect was found for compounds bearing the 3beta-hydroxy and 2beta,3beta-dihydroxy functionality, which show promise as environmental friendly insecticides.


Antimigration versus conventional fully covered metal stents in the endoscopic treatment of anastomotic biliary strictures after deceased-donor liver transplantation.
Migration of fully covered metal stents (FCMS) remains a limitation of the endoscopic treatment of anastomotic biliary strictures (ABS) following orthotopic liver transplantation (OLT). The use of antimigration FCMS (A-FCMS) might enhance endoscopic treatment outcomes for ABS. Single center retrospective study. Consecutive patients with ABS following OLT who underwent ERCP with FCMS placement between January 2005 and December 2020 were eligible. Subjects were grouped into conventional-FCMS (C-FCMS) and A-FCMS. The primary outcome was stent migration rates. Secondary outcomes were stricture resolution, adverse event, and recurrence rates. A total of 102 (40 C-FCMS; 62 A-FCMS) patients were included. Stent migration was identified at the first revision in 24 C-FCMS patients (63.2%) and in 21 A-FCMS patients (36.2%) (p = 0.01). The overall migration rate, including the first and subsequent endoscopic revisions, was 65.8% in C-FCMS and 37.3% in A-FCMS (p = 0.006). The stricture resolution rate at the first endoscopic revision was similar in both groups (60.0 vs 61.3%, p = 0.87). Final stricture resolution was achieved in 95 patients (93.1%), with no difference across groups (92.5 vs 93.5%; p = 0.84). Adverse events were identified in 13 patients (12.1%) with no difference across groups. At a median follow-up of 52 (IQR: 19-85.5) months after stricture resolution, 25 patients (24.5%) developed recurrences, with no difference across groups (C-FCMS 30% vs A-FCMS 21%; p = 0.28). The use of A-FCMS during ERCP for ABS following OLT results in significantly lower stent migration rates compared to C-FCMS. However, the clinical benefit of reduced stent migration is unclear. Larger studies focusing on stricture resolution and recurrence rates are needed.


Improving the esthetic replacement of missing anterior teeth: interaction between periodontics and a rotational path removable partial denture.
The rotational path of insertion concept for removable partial dentures (RPDs) can be used in esthetically demanding situations. This clinical report describes the treatment of a patient with an anterior maxillary edentulous area using a rotational path RPD. To optimally improve gingival esthetics and to allow proximal retention on the surveyors, a crown-lengthening surgical procedure was performed prior to prosthetic treatment on all teeth involved in this rehabilitation. When correctly planned and fabricated, this prosthesis allows excellent functional and esthetic results, minimizes tooth preparation, and reduces the tendency toward plaque accumulation.


Comparison of mouth guard designs and concussion prevention in contact sports: a multicenter randomized controlled trial.
To compare the effectiveness of the WIPSS mouth guard to other currently used mouth guards in the prevention of concussion injuries in athletes participating in varsity football and rugby. : Multicenter, cluster-randomized, controlled trial comparing the WIPSS Brain-Pad mouth guard against the standard use mouth guard of choice. Teams were monitored by their respective athletic therapist, trainer, or sports physician for 1 playing season to diagnose and record incident concussion injuries and dental trauma. Concussion symptoms were also recorded at the time of injury. Five Ontario universities. University male football (394) and university male (129) and female (123) rugby athletes reporting to 2003 fall training camps. The primary end point was the incidence of any diagnosed concussion events during the 2003 playing season as defined by the American Academy of Neurology Concussion Guidelines. Secondary endpoints included the incidence of dental trauma events and observed concussion symptoms. There was no significant difference in the number of concussions observed between the intervention and control arms of this trial (P = 0.79; odds ratio, 1.06, in favor of controls; 95% CI, 0.51, <<1.61). No dental trauma events occurred. The 5 most common symptoms experienced by concussed athletes were dizziness, general headache, nausea, loss of visual focus, and personality changes. In this study, concussion rates were not significantly different for varsity football and rugby players who wore the WIPSS Brain-Pad mouth guard compared with other types of mouth guards.


'I Have Had to Stop Singing Because I Can't Take the Pain': Experiences of Voice, Ability, and Loss in Singers With Hypermobility Spectrum Disorders.
This study explored the voice experience, singing ability, and wellbeing of singers diagnosed with Hypermobility Spectrum Disorder (HSD) or hypermobile Ehlers-Danlos Syndrome (h-EDS). This was a mixed-method study. A purposive sampling strategy was used. Data were collected via an online survey, using written closed and open-ended questions. 276 adults completed the survey. This study focuses on a subset of professionally-trained singers (n=71). Responses elicited information about participants' voice health and function, symptoms of hypermobility, singing experiences and training. Data were analysed using template analysis. Many participants reported wide vocal ranges and enjoyment of singing but 74.6% of participants across all age groups (18-60 years) experienced voice difficulties. Three common themes were identified: (1) 'My unreliable voice': The ups and downs; (2) Wider effects of HSD/h-EDS on singers, and (3) Need for acknowledgment and support. Voice difficulties and hypermobility-related health conditions affected the participants' abilities to sing and perform; this impacted their professional and personal opportunities, communication, relationships, and wellbeing. Our results indicate that symptoms of voice disorder worsen over time. We suggest practical strategies that singers and training providers could implement to support hypermobile singers. More research is needed to fully understand voice difficulties in singers with HSD/H-EDS and to inform tuition and support.


Where midwives are not yet recognised: a feasibility study of professional midwives in Nepal.
the professional midwife is a key person for promoting maternal and family health. Not all countries have yet reached the professional standard for midwives set by the International Confederation of Midwives (ICM) and Nepal is one of these countries. This study explores the feasibility to establish a professional midwifery cadre in Nepal that meets the global standards of competencies, and to define a strategy to reach this. a mixed-methods study comprised (1) policy-review (2) interviews and (3) observations. An assessment tool was designed for data collection and analysis using variables from three sources: ICM's Global Standards, the skilled birth attendant programme in Nepal, and JHPIEGO's site assessment tool for maternal health and new-born programmes. Data were collected in a desk review of education and policy documents, interviews with stakeholders, and site assessment of five higher education institutions and their hospital-based maternity departments. The analysis resulted in a recommended strategy. six levels of education of nurse staff providing midwifery care were identified; all regulated under the Nepal Nursing Council. No legislation was in place authorising midwifery as an autonomous profession. A post-basic midwifery programme on first cycle-bachelor level was under development. A well-organised midwifery association was established consisting of nurses providing maternal health care. Four university colleges offering higher education for nurses and clinicians had a capability to run a midwifery programme and the fifth had a genuine interest in starting a midwifery programme at bachelor level. The proposed strategy includes four strategic objectives and interventions in relation to four components identified by UNFPA: Legislation and regulation; Training and education; Deployment and utilisation; and Professional associations. the study has delivered a proposed strategy for the Government of Nepal for effective management of the midwifery workforce in order to enhance midwives' contribution in maternity care and thus promoting improved maternal and new-born health. The developed analytical framework could be used as an assessment tool also in other countries to establish professional midwifery cadres that meets the global standards of competencies.


Diverse nature of the seasonally coastal eutrophication dominated by oceanic nutrients: An eco-system based analysis characterized by salmon migration and aquaculture.
Previously, studies of coastal eutrophication have usually focused on the nutrients input from adjacent land sectors, such as rivers, submarine-ground discharges, and atmospheric depositions. Here we report two examples of well-managed seasonal eutrophication phenomena in coastal marine environments, where nutrients come predominantly from offshore: one by humans and the other by nature (higher trophic animals). In the Sanggou Bay of North China, the total amount of incoming nutrients from the open Yellow Sea is taken up by seaweeds. Seaweed, in turn, supports bivalves culture activities and absorbs nutrients emitted by finfish. In the Academy Bay of Russian Far East, a relatively high plankton primary production sustains throughout the salmon-returning season when nutrients are released from the massive carcasses of dead fish after return from the ocean to their natal streams to spawn and die. This high plankton productivity, in turn, fuels higher trophic ecosystem constituents, including whale populations of global importance. In the future, dominance of nutrients from marine sources needs to be seriously considered in studies of coastal eutrophication.


Find the Word! - But Where?: Maturana's 'Coordination' and Sartre's 'Reflection' around Naming.
'Behavioral coordination' theory of language of Maturana (1928-) does not give a clear explanation for the questions of how naming takes place and where a word adequate for our experience comes from. This flaw may be alleviated by Sartre (1905-1980)s 'reflection' theory. According to Sartre's theory, we can make two types of sentences from the same data: for example, "I am conscious of this chair" and "There is consciousness of this chair." The difference between the two sentences is the existence of 'I' in the first or its lack in the second. Where did 'I' come from or how was it removed? There must be a field in which 'I' is brought forth, and it may also be a field where naming can take place. This essay concerns a naming process with special reference to Sartre's philosophy. At first, Maturana's biology and his linguistic theory are explained, and Sartre's fundamental ontology and in relation to this, his theory of reflection (two types of reflection) are introduced. Next, Sartre's notions of language (words and naming) are explained. Then, after operational correspondences between Maturana's 'coordination' and Sartre's 'reflection' are examined, our primary questions are answered. Finally, constraints burdened on our cognition with language and the possibility of liberation from them are discussed. Main arguments: (1) Maturana's 'coordination' and Sartre's 'reflection' are operationally equivalent concepts; (2) Sartre can complement Maturana's languaging theory of naming by providing both the domain for naming (the domain for the synthesis of identification, or for universalizing synthesis) and a mediator of naming (the cogito, namely the consciousness, of a languaging person).


Semiquantitative analysis using thallium-201 SPECT for differential diagnosis between tumor recurrence and radiation necrosis after gamma knife surgery for malignant brain tumors.
Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography (201Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of 201Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. A total of 107 tumors were analyzed with 201Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. Semiquantitative analysis of 201Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most valuable index for this purpose.


[Posterior interosseous nerve entrapment syndrome following distal rupture of the biceps tendon: physiopathology and literature review, an unreported case report].
We report a unique and previously unreported case of motor paralysis of the posterior interosseous nerve of rapid onset in a context of hypertrophy of the short supinator muscle, occurring 2 years after a distal rupture of the biceps in a 62 year-old man. The ruptured tendon had received functional treatment due to the patient's age and low functional requirements. Operatively, the deep branch of the radial nerve was released within the arcade of Frohse with complete recovery from symptoms at 5 months. The unrepaired rupture of the distal portion of the biceps could be a risk factor for posterior interosseous nerve compression in active subjects.


Multispectral versus texture features from ZiYuan-3 for recognizing on deciduous tree species with cloud and SVM models.
Tree species recognition accuracy greatly affects forest remote sensing mapping and forestry resource monitoring. The multispectral and texture features of the remote sensing images from the ZiYuan-3 (ZY-3) satellite at two phenological phases of autumn and winter (September 29th and December 7th) were selected for constructing and optimizing sensitive spectral indices and texture indices. Multidimensional cloud model and support vector machine (SVM) model were constructed by the screened spectral and texture indices for remote sensing recognition of Quercus acutissima (Q. acutissima) and Robinia pseudoacacia (R. pseudoacacia) on Mount Tai. The results showed that, the correlation intensities of the constructed spectral indices with tree species were preferable in winter than in autumn. The spectral indices constructed by band 4 showed the superior correlation compared with other bands, both in the autumn and winter time phases. The optimal sensitive texture indices for both phases were mean, homogeneity and contrast for Q. acutissima, and contrast, dissimilarity and second moment for R. pseudoacacia. Spectral features were found to have a higher recognition accuracy than textural features for recognizing on both Q. acutissima and R. pseudoacacia, and winter showing superior recognition accuracy than autumn, especially for Q. acutissima. The recognition accuracy of the multidimensional cloud model (89.98%) does not show a superior advantage over the one-dimensional cloud model (90.57%). The highest recognition accuracy derived from a three-dimensional SVM was 84.86%, which was lower than the cloud model (89.98%) in the same dimension. This study is expected to provide technical support for the precise recognition and forestry management on Mount Tai.


Evidence on the nature of sectarian animosity from a geographically representative survey of Iraqi and Iranian Shia pilgrims.
Sectarian tensions underlie conflicts across the Middle East, but little is known about their roots and associated beliefs. We conducted a large-scale empirical analysis, drawing on an original, geographically representative survey of over 4,000 devout Shiites across Iran and Iraq. We find that sectarian animosity is linked to economic deprivation, political disillusionment, lack of out-group contact and a sect-based view of domestic politics-paralleling patterns seen in ethno-nationalism elsewhere. In contrast, two alternative accounts are largely unsupported: sectarian animosity is not consistently associated with solidarity with a transnational sect-based community, nor does it seem to stem from disputes over religious doctrine. Nonetheless, this identity's religious roots manifest in differences from typical ethno-nationalism; practising men are less sectarian, consistent with official doctrine encouraging unity, whereas practising women are more sectarian. These gendered patterns suggest an understudied mechanism: religiously mediated socialization, or the transmission of non-religious norms through religious practice.


Hypothalamic temperature and deep body temperature during copulation in the male rat.
The medial preoptic area (MPOA) of the hypothalamus is involved in both the expression of male sexual behavior and the regulation of physiological temperature. This duality of function led us to ask whether arousal, intromission, and ejaculation are accompanied by a distinctive temperature profile. Using telemetric thermosensors, we monitored MPOA temperature and deep body temperature during copulation in the male rat. Changes in MPOA temperature were highly uniform, more so than changes in body temperature. The MPOA heated prior to ejaculation, cooled rapidly following ejaculation and then began to heat again coincident with the termination of the post-ejaculatory refractory period. These changes could not be related to variations in general activity. The most striking change in MPOA temperature, rapid cooling following ejaculation, was explained in terms of certain behaviorally-induced hemodynamic events.


Detection of occult cobalamin deficiency by magnetic resonance imaging.
We present a case of cobalamin deficiency in an elderly woman who presented with peripheral neuropathy without evidence of anemia or macrocytosis; her diagnosis was suspected with cervical magnetic resonance imaging. This imaging modality may identify patients with cobalamin deficiency who have neurologic abnormalities with normal hematologic parameters.


Adenoacanthoma of the colon.
The clinical and pathologic features of five cases of adenoacanthoma of the colon are presented. Although the lesion is rare, both the pathologist and the surgeon should be aware of this unusual neoplasm in order to avoid error in diagnosis, especially when metastatic lesions are being evaluated. In our experience, these rare colonic lesions are more aggressive than ordinary carcinomas of the colon.


The use of prohibited substances for therapeutic reasons in athletes affected by endocrine diseases and disorders: the therapeutic use exemption (TUE) in clinical endocrinology.
To protect sporting ethics and athletes' health, the World Anti-Doping Agency (WADA) produced the World Anti-Doping Code and The Prohibited List of substances and methods forbidden in sports. In accordance with the International Standards for Therapeutic Use Exemption (ISTUE), to avoid rule violations and sanctions, athletes affected by different endocrine diseases and disorders (e.g., adrenal insufficiency, diabetes, male hypogonadisms, pituitary deficit, thyroid diseases, etc.) who need to use a prohibited substance for therapeutic reasons (e.g., medical treatments, surgical procedures, clinical diagnostic investigations) must apply to their respective Anti-Doping Organizations (ADOs) to obtain a Therapeutic Use Exemption (TUE), if specific criteria are respected. The physicians who treat these athletes (i.e., endocrinologists, andrologists and diabetologists) are highly involved in these procedures and should be aware of their specific role and responsibility in applying for a TUE, and in adequately monitoring unhealthy athletes treated with prohibited substances. In this paper, the prohibited substances commonly used for therapeutic reasons in endocrine diseases and disorders (e.g., corticotropins, beta-blockers, glucocorticoids, hCG, insulin, GnRH, rhGH, testosterone, etc.), the role of physicians in the TUE application process and the general criteria used by ADO-Therapeutic Use Exemption Committees (TUECs) for granting a TUE are described.


Role of through-the-scope catheter-based EUS in inflammatory bowel disease diagnosis and activity assessment.
Distinguishing Crohn's disease (CD) from ulcerative colitis (UC) may be difficult when the disease is limited to the colon. Transmural healing is an important adjunctive measure of inflammatory bowel disease activity. The aim of this study was to examine the role of EUS in differentiating CD versus UC and evaluating transmural disease activity. This prospective cohort study enrolled 20 patients with CD (10 active [aCD], 10 inactive), 20 patients with UC (10 active [aUC], 10 inactive), and 20 control subjects who underwent colonoscopy from 2019 to 2021 at a tertiary care center. Measurements of bowel wall layer thickness from the rectum and cecum were obtained using a through-the-scope US catheter (UM-3R-3; Olympus, Center Valley, Penn, USA) at the time of colonoscopy. Compared with control subjects, patients with aCD had thicker rectal submucosa and total wall layer (submucosa median, 1.80 mm [interquartile range {IQR}, 1.40-2.00] vs .60 mm [IQR, .40-.70]; total wall median, 3.70 mm [IQR, 3.52-4.62] vs 2.10 mm [IQR, 1.70-2.40], respectively; P < .01). Similar significant findings were observed for the cecal wall layers. Compared with control subjects, patients with aUC had thicker rectal mucosa and total wall but not submucosa or muscularis propria layers (mucosa median, 1.35 mm [IQR, 1.12-1.47] vs .60 mm [IQR, .57-.70]; total wall median, 3.45 mm [IQR, 2.85-3.75] vs 2.10 mm [IQR, 1.70-2.40], respectively; P < .01). Patients with aCD compared with those with aUC had a significantly thicker rectal submucosa layer (median, 1.80 mm [IQR, 1.40-2.00] vs .55 mm [IQR, .40-.75], respectively, P < .01). Cutoff values of 1.1 mm for rectal submucosa in CD (sensitivity, 1.0; specificity, 1.0) and 1.1 mm for rectal mucosa in UC (sensitivity, .8; specificity, .9) were found to differentiate active from inactive disease. EUS measurements of colon wall layers can help diagnose aCD versus aUC and assess transmural disease activity. (Clinical trial registration number: NCT03863886.).


Endoscopic-Assisted Flexor Hallucis Longus Transfer: Harvest of the Tendon at Zone 2 or Zone 3.
Flexor hallucis longus (FHL) tendon transfer is indicated for reconstruction of the Achilles tendon with a gap larger than 5 cm. The tendon can be harvested at zone 2 or zone 3 by minimally invasive techniques with the advantage of minimal soft-tissue dissection. The tendon can be harvested under the sustentaculum tali by zone 2 FHL tendoscopy. It is adequate for FHL transfer to the posterior calcaneal tubercle. If a double-thickness reconstruction of a huge gap of the Achilles tendon is indicated, the tendon can be harvested at the level of the hallux by means of a tendon stripper. However, the interconnection tendon of the master knot of Henry can be split together with the FHL or flexor digitorum longus tendon instead of being cut. Zone 2 FHL tendoscopy can be used to release the split tendon to complete the FHL harvest.


Adverse fetal outcomes in pregnant rabbits experimentally infected with rabbit hepatitis E virus.
Hepatitis E virus (HEV) causes severe hepatitis in pregnant women, with associated poor fetal outcomes. To study HEV viral pathogenesis, pregnant rabbits were infected with low- and high-dose rabbit HEV at 2 weeks gestation. HEV was identified in the serum, feces, and liver tissue of infected rabbits, and dose-dependent fetal mortality rates ranging from 67% to 80% were observed. The aspartate transaminase (AST)/alanine transaminase ratio was significantly higher (P < 0.01) in high-dose infected rabbits than low-dose infected and negative control rabbits 14 days post infection (dpi). Tumor necrosis factor-α (TNF-α) was significantly higher in low-dose (P < 0.01) and high-dose infected rabbits (P < 0.001) than in negative controls 7 dpi. High-dose HEV-infected rabbits produced significantly more interferon-γ (IFN-γ; P < 0.05) than negative control rabbits at 7 and 14 dpi. High levels of AST, TNF-α, and IFN-γ may substantially influence adverse fetal outcomes in pregnant rabbits infected with high-dose HEV.


Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines.
A spent medium antigen was prepared from the avirulent RIA strain of Salmonella typhimurium. Lymph node cells isolated from female BALB/c mice injected subcutaneously with the spent medium antigen exhibited antigen-specific proliferation. By using these cells and T-cell growth factor, continuous spent medium antigen-specific, Thy 1.2-sensitive lines were generated. These cells exhibited antigen-specific proliferation in vitro and were effective in inducing significant (P less than 0.01) host protection when adoptively transferred to naive syngeneic mice.


AUGIST: inferring species trees while accommodating gene tree uncertainty.
AUGIST (accomodating uncertainty in genealogies while inferring species tress) is a new software package for inferring species trees while accommodating uncertainty in gene genealogies. It is written for the Mesquite software system and provides sampling procedures to incorporate uncertainty in gene tree reconstruction while providing confidence estimates for inferred species trees. http://www.lycaenid.org/augist/


Noise and Vibration in the Vivarium: Recommendations for Developing a Measurement Plan.
Noise and vibration are present in every room of laboratory animal vivaria, with great variability from room-to-room and facility-to-facility. Such stimuli are rarely measured. As a result, the many stakeholders involved in biomedical research, (for example, funding agencies, construction personnel, equipment manufacturers, animal facility administrators, veterinarians, technicians, and scientists) have little awareness of the effects such stimuli may have on their research animals. Noise and vibration present a potential source of unrecognized animal distress, and a significant, uncontrolled and confounding variable in scientific studies. Unmeasured and unrecognized noise and vibration can therefore undermine the fundamental goals of the 3R's to refine animal models and reduce the number of animals used in biomedical and behavioral research. This overview serves to highlight the scope of this problem and proposes a series of recommended practices to limit its negative effects on research animals and the scientific data derived from them. These practices consist of developing a written plan for managing noise and vibration concerns, assessment of noise and vibration both annually and whenever unexpected changes in the facility or animals are observed, and for maintaining levels of chronic noise below thresholds that might cause animal welfare concerns or disruptions in ongoing studies.


Continuous, real-time, noninvasive monitor of blood pressure: Penaz methodology applied to the finger.
The finger blood pressure monitor measures blood pressure continuously and noninvasively by means of a technique described by J. Penaz. The size of the artery is measured when its internal pressure (arterial pressure) equals the external pressure. (At this point, transmural pressure equals zero and the arterial wall is said to be "unloaded.") This unloaded condition is maintained by continuous, automatic adjustments of external pressure on the artery, adjustments that are made simultaneously with and parallel to intraarterial pressure variations. The external pressure then constantly equals internal pressure (arterial blood pressure) and is reported by the monitor as values for systolic, mean, and diastolic pressure. A finger cuff with a built-in light source and detector is used to measure finger artery size, and an inflatable bladder is used to apply the external pressure to the artery. The monitor is microprocessor based; algorithms determine the unloaded artery size approximately every minute and automatically correct for changes possibly induced by smooth muscle contraction or relaxation, and a high-speed electropneumatic servo control system enables automatic calibration and adjustment.


Balearic archipelago: three islands, three beta-thalassemia population patterns.
The mutation spectrum of 175 β-thalassemia (β-thal) carriers, identified in pilot carrier screening on 22,713 individuals from Balearic Islands (Spain), is reported. The β(0) CD39 (C>T) mutation is the most frequent (61.1%), followed by β(+) IVS-I-110 (G>A) (12.0%), β(+) IVS-I-6 (T>C) and β(0) IVS-1-1 (G>A) (3.4% both) and eight other rare mutations (2.9-0.6%); with a distinct prevalence and distribution between islands. Minorca shows the highest prevalence in Iberian populations, with a single mutation, CD39 (C>T), present in most β-thal carriers. Ibiza is the only Western Mediterranean population where the most frequent β-thal mutation is IVS-I-110 (G>A). These results can be explained by a combination of historical-demographic characteristics together with evolutionary forces such as founder effect, genetic drift and probably selection by malaria. Knowledge of the mutational spectrum in the Balearic Islands will enable to optimize mutation detection strategy for genetic diagnosis of β-thal in these islands.


Molecular breeding of white rot fungus Pleurotus ostreatus by homologous expression of its versatile peroxidase MnP2.
Using a DNA-mediated transformation technique, a molecular breeding approach to isolate Pleurotus ostreatus strains with enhanced productivity of its versatile peroxidase MnP2 was conducted. A recombinant mnp2 construct under the control of P. ostreatus sdi1 expression signals was introduced into the wild-type P. ostreatus strain by cotransformation with a carboxin-resistant marker plasmid. A total of 32 transformants containing the recombinant mnp2 sequence were isolated in a screening with specific amplification by PCR. Productivity of MnP2 in the recombinants was evaluated by the decolorization ability of Poly R-478 on agar plates in the absence of Mn2+. Recombinant P. ostreatus strains with elevated manganese peroxidase (MnP) productivity were successfully isolated. One of the recombinants, TM2-10, was demonstrated to secrete recombinant MnP2 predominantly on a synthetic medium containing 15 mM ammonium oxalate, which was confirmed by reverse transcription PCR (RT-PCR) and isozyme profile analysis using anion-exchange chromatography. The benzo[a]pyrene-removing activity by fungal treatment was also analyzed using the isolated recombinant strains.


Long-term effects of an intergenerational program on functional capacity in older adults: Results from a seven-year follow-up of the REPRINTS study.
Social engagement activities can help older adults maintain mental and physical functioning levels. This study examined the long-term effects of the intergenerational picture-book reading program "REPRINTS" (Research of Productivity by Intergenerational Sympathy) on older adults. After baseline assessment, participants were allowed to decide which condition they wanted to participate in: the REPRINTS intervention or control group involving only assessments. REPRINTS participants participated in group activities that involved playing a hand game and reading picture books to children at kindergartens, elementary schools, and public childcare centers, once every one-two weeks. A follow-up assessment, which focused on functional capacity (i.e., instrumental activities of daily living, intellectual activity, and social function), was conducted after seven years. The analysis included responses from 62 REPRINTS (mean age [SD]=66.2 [5.7]) and 100 control-group participants (mean age [SD]=68.0 [4.7]). A logistic regression analysis examining intervention effects revealed that control-group participants were more likely to reduce intellectual activity and interactions with children compared to REPRINTS participants (p=.013 and .003, respectively). Furthermore, the REPRINTS group maintained greater functional reach compared to the control group (p<.001). However, the REPRINTS group was likely to stay indoors more often, compared to the control group (p=.045). The present study indicates that the REPRINTS intergenerational program has long-term, positive effects that help maintain and promote intellectual activity, physical functioning, and intergenerational exchange, although the effect of the increasing amount of physical activity is unclear.


Effect of Entamoeba histolytica infection on gut microbial diversity and composition in diarrheal patients from New Delhi.
During amoebiasis, colonization of the gut by Entamoeba histolytica can lead to alterations of the host microbiota. In this study, we have compared the gut microbiota of patients of amoebiasis with healthy controls using 16S rRNA gene variable regions, (V1-V3) and (V3-V5), of the bacterial genome. From this 16S rRNA gene amplicon data, one paired-end and two single-end datasets were selected and compared by the number of OTUs obtained, sequence count, and diversity analysis. Our results showed that the V1-V3-paired-end dataset gave the maximum number of OTUs in comparison to the two single-end datasets studied. The amoebiasis samples showed a significant drop in richness in the alpha diversity measurements and lower intra group similarity compared to the healthy controls. Bacteria of genus Prevotella, Sutterella, and Collinsella were more abundant in healthy controls whereas Escherichia, Klebsiella, and Ruminococcus were more abundant in the E. histolytica-positive patients. All the healthy controls harbored bacteria belonging to Faecalibacterium, Prevotella, Ruminococcus, Subdoligranulum, and Escherichia genera while all the E. histolytica-positive patient samples contained genus Enterobacter. The compositional changes in the gut microbiome observed in our study indicated a higher prevalence of pathogenic bacteria along with a depletion of beneficial bacteria in E. histolytica-infected individuals when compared with healthy controls. These results underline the interplay between E. histolytica and the human gut microbiome, giving important inputs for future studies and treatments.


Synergy of peptide and sugar in O-GlcNAcase substrate recognition.
Protein O-GlcNAcylation is an essential reversible posttranslational modification in higher eukaryotes. O-GlcNAc addition and removal is catalyzed by O-GlcNAc transferase and O-GlcNAcase, respectively. We report the molecular details of the interaction of a bacterial O-GlcNAcase homolog with three different synthetic glycopeptides derived from characterized O-GlcNAc sites in the human proteome. Strikingly, the peptides bind a conserved O-GlcNAcase substrate binding groove with similar orientation and conformation. In addition to extensive contacts with the sugar, O-GlcNAcase recognizes the peptide backbone through hydrophobic interactions and intramolecular hydrogen bonds, while avoiding interactions with the glycopeptide side chains. These findings elucidate the molecular basis of O-GlcNAcase substrate specificity, explaining how a single enzyme achieves cycling of the complete O-GlcNAc proteome. In addition, this work will aid development of O-GlcNAcase inhibitors that target the peptide binding site.


Effect of socioeconomic status on hepatocellular carcinoma incidence and stage at diagnosis, a population-based cohort study.
Hepatocellular carcinoma (HCC) incidence is increasing worldwide and cirrhosis is the most important risk factor predominantly caused by chronic viral hepatitis infection. We studied the impact of socioeconomic status (SES) on HCC incidence and stage at diagnosis among viral hepatitis cases. A population-based retrospective cohort study was conducted through the Ontario Cancer Registry linked data. Incidence rates were calculated using person-time methodology. Association between SES (income quintile) and HCC incidence was assessed using proportional-hazards regression. The impact of SES on HCC stage was investigated using logistic regression. Among 11 350 individuals diagnosed with viral hepatitis between 1991 and 2010, a crude HCC incidence rate of 21.4 cases per 1000 person-years was observed. Adjusting for age, gender, urban/rural residence and year of viral hepatitis diagnosis, a significant association was found between SES and HCC incidence, with an increased risk among individuals in the lowest three income quintiles (incidence rate ratio, IRR = 1.235; 95% CI: 1.074-1.420; IRR = 1.183; 95% CI: 1.026-1.364; IRR = 1.158; 95% CI: 1.000-1.340 respectively). No significant association between SES and HCC incidence was found after additionally adjusting for risk factors associated with HCC. However, HCC risk factors such as cirrhosis and HIV are associated with SES. Furthermore, no association was found between SES and HCC stage. The association between SES and HCC incidence is likely because of differences in risk factors across income quintiles. Investigating how SES affects HCC incidence facilitates an understanding of which populations are at elevated risk for HCC.


Computational models for wall shear stress estimation in scaffolds: a comparative study of two complete geometries.
Fluid mechanical stimuli are known to upregulate cell differentiation and matrix formation. Since wall shear stress plays an important role various studies tried to estimate the scaffold fluid dynamic environment. However, because of the geometrical complexity, nearly all studies created their CFD model based on a submodel of the entire scaffold assuming that the model covers heterogeneity sufficiently. However to the authors' knowledge no study exist providing guidelines in this matter. In a previous study we demonstrated that submodels are influenced by the boundary conditions, inevitable when flow channels are chopped off. For the current study we therefore developed μCT based models of two complete scaffold geometries (one titanium and one hydroxyapatite). Imposing a 0.04 ml/min flow rate resulted in a surface area averaged wall shear stress of 1.41 mPa for titanium and 1.09 mPa for hydroxyapatite. In order to get insight in required model size we subdivided the domain in regions of different size. From our results we propose a model size between 6 and 10 times the average pore size. The wall shears stress should be calculated on a region at least one pore size away from the boundaries. These guidelines could be of use for computationally more costly simulations where it is not possible to simulate the complete scaffold domain.


Association of Angiotensin Converting Enzyme gene Polymorphism and Indian Army Triathletes Performance.
It is well known that the effects of exercise training gives inter individual differences which might be due to genetic diversity. This study aims to explore the probable relation between angiotensin converting enzyme (ACE) alleles and physical fitness parameters in elite athletes. Twenty-nine national level Indian Army Triathletes who volunteered for the study were taken as subjects and 101 healthy age matched control group subjects were taken for comparison of genotype frequencies. The following parameters were checked in triathletes: blood pressure, body mass index, VO(2 max), muscular endurance, flexibility and power. DNA was extracted from blood using standard phenol-chloroform method. Genotyping was done using PCR specific for ACE (I/D) polymorphism, followed by agarose gel electrophoresis method. Variation of the parameters among different genotypes was compared. Genotype frequencies of triathletes were compared with the control group as well. No difference was observed between fitness parameters of three genotype groups' triathletes, while the frequency of I allele was found to be very high in triathletes compared with the control group. It can be concluded that there might be a positive association between I allele of ACE gene and endurance.


Ultrasound-guided percutaneous laser ablation of papillary thyroid microcarcinoma: a feasibility study on three cases with pathological and immunohistochemical evaluation.
Ultrasound-guided thermal laser ablation (LA) is a nonsurgical technique that has been proposed, but not fully assessed, for papillary thyroid microcarcinoma (PTMC) treatment. The objectives of this study were to evaluate the clinical feasibility of LA on PTMC as a primary treatment and to prove histologically the absence of residual viable tumor after LA procedure. Three patients with a Thy 6 diagnosis at fine-needle aspiration cytology with a single PTMC smaller than 10 mm volunteered after full explanation of the protocol. At ultrasound examination, patients had no extrathyroid extension and no evidence of lymph node metastasis. Patients underwent percutaneous ultrasound-assisted LA of the PTMC in the operating room under general anesthesia. One 300 μm plane-cut optic fiber was inserted through the sheath of 21G Chiba needle, exposing 5 mm of the nude fiber in direct contact with tumor tissue, and connected with a laser source operating at 1.064 μm with 3 W output power. Total energy delivery was 1800 J. The surgeon directly started a standard total thyroidectomy. During surgical inspection, no remarkable laser sign was observed in the muscles, the perithyroidal tissues, or the recurrent laryngeal nerves. Conventional histology showed destructured and carbonized tissue. Lack of vitality was demonstrated by complete loss of TTF1 and antimitochondria antibody expression in the whole ablated area and in the rim of normal tissue surrounding the tumor. BRAF V600E mutation was detected in cases 1 and 2. Furthermore, in cases 2 and 3, incidental papillary microfoci were found. A lymph node micrometastasis (200 μm) was observed in case 2. This study demonstrates that percutaneous LA is technically feasible for complete PTMC destruction. Now, LA may be useful in selected patients with PTMC, either when the surgeon or a patient refuses surgery, or when the patient is at high risk for an operation. LA may become a primary choice of treatment for PTMC only if future new knowledge would permit preoperative recognition of multifocality and lymph node metastasis.


Hostile Hartlepool and genteel Guildford: hostility and health in 10 English towns.
Research from the USA suggests that cities with high mortality rates have high levels of hostility. Our aim was to replicate this research in English towns. A telephone questionnaire, based on the Cook-Medley hostility scale, was administered to random samples of adults in 10 English towns: five with high standardized mortality ratios (SMR) and five with low SMRs. The point estimate for the age-sex-weighted mean hostility score of high SMR towns was higher than that of low SMR towns (mean difference 0.2). However, the 95% confidence interval on the estimate included no difference between the two groups (-0.3-0.8). Our study does not confirm beyond doubt the findings of earlier research in the USA.


Red/NIR G-Quadruplex Sensing, Harvesting Blue Light by a Coumarin-Naphthalene Diimide Dyad.
A conceptually new light-up nucleic acid fluorescent probe resulting from the conjugation of a coumarin to a naphthalene diimide exhibits a single wavelength emission at 498 nm when free in solution and an additional red/NIR emission when bound to G-quadruplex DNA. The light-up response centred at 666 nm is highly specific for quadruplex DNA when compared to duplex DNA or to RNA quadruplexes.


Self-testing for contact allergy to hair dyes - a 5-year follow-up multicentre study.
In 2011, a multicentre study was conducted in order to determine how hair dye manufacturers instructed consumers to perform a self-test prior to dyeing their hair, in order to identify individuals who are likely to react upon subsequent hair dyeing. A number of concerns were raised concerning the variability in instructions between products and producers, and the safety and validity of this tool. To perform a 5-year follow-up study in order to determine whether manufacturers still recommend a self-test, and if so, whether the procedures have been changed. During March 2016, a total of 40 oxidative hair dye products from 21 different manufacturers were bought in retail stores in 8 European countries. The consumers were instructed to perform a self-test prior to hair dyeing for 39 of the products; however, the procedures varied greatly regarding the method of application, the amount of hair dye applied, the location and size of the application area, the number of applications, whether or not rinsing was performed after application, the reading times, and how a positive reaction was defined. Self-testing is still recommended by almost all manufacturers of permanent hair dyes. There are major variations in the instructions, even in products from the same manufacturer. The previously raised concerns regarding safety and validity still remain.


Fixation and effect on bone strain pattern of a stemless hip prosthesis.
Given the relatively short survival time of total hip replacement in young patients, a different concept of femoral implant was designed and evaluated biomechanically prior to clinical application. The femoral component has no intramedullary stem and fits into an angular resection of the femoral neck. A trans-trochanteric screw provides immediate strong fixation. A comparative biomechanical study with cadaver femora and a dynamic hip simulator was performed. The study had three objectives. (1) The strains generated under loading in the intact proximal femur were compared to those generated in the presence of the experimental implant and a classic cemented implant. (2) The short-term stability of the experimental prosthesis under loading conditions encountered during fast walking was evaluated. (3) Most importantly, the implant design was improved in the light of the experimental observations prior to any clinical trial. Indeed, the prototype underwent several important modifications in the course of the study. With the modified design, later used in a clinical trial, it was demonstrated that if accurate fit and position of the prosthesis were provided, fixation remained sound for over one million loading cycles with peak loads of three times the body weight. The measured interface micromotion was compatible with direct bone apposition and ingrowth. No statistical difference was found between the strain measurements obtained before and after implantation of the experimental prosthesis whereas significant stress shielding was observed with a stemmed, cemented prosthesis.


Hysterosalpingography with a balloon catheter versus a cannula: evaluation of patient pain.
The amount of procedural and post-procedural pain due to hysterosalpingography performed with a standard cannula (28 patients) versus a balloon catheter (23 patients) was compared. Patients completed questionnaires in which they rated the pain they experienced during insertion of the instrument, during injection of contrast material, immediately after the examination, several hours after the examination, and over the next 6 days. The balloon catheter produced less discomfort during the procedure but significantly more discomfort after the procedure than did the standard cannula. These results indicate that hysterosalpingography with the balloon catheter is not as painless as has been claimed.


The kidney of a teleost, Spinachia spinachia. II. Histochemical identification of sialic acid-containing glycoprotein and fine structure of mucus secreting cells.
Kidney cells of the marine stickleback Spinachia have been studied with histochemical methods for the demonstration of glycoconjugates. The fine structure of epithelial cells is described. Mucus threads in the nephronic tubule of sexually mature consist of neutral glycoprotein which corresponds with the secretory granules in proximal tubule segment II cells. Large lysosome-like inclusions, which also react with PAS, are present in many P II cells. All cells of the collecting duct epithelium differentiate into mucous cells in male Spinachia. The nature of their secretory products, which are well preserved by freeze-drying, is discussed. Sialylated glycoprotein is present in mucus granules and sulphated glycoprotein can be demonstrated at the apex of collecting duct cells. Collecting duct cell mucus can be digested with testicular hyaluronidase indicating that proteoglycans may be involved in the structure of macromolecules. The observations are compared with studies of mucus production in the urinary apparatus of several other vertebrates.


Current Status and Future Prospects of Copper Oxide Heterojunction Solar Cells.
The current state of thin film heterojunction solar cells based on cuprous oxide (Cu₂O), cupric oxide (CuO) and copper (III) oxide (Cu₄O₃) is reviewed. These p-type semiconducting oxides prepared by Cu oxidation, sputtering or electrochemical deposition are non-toxic, sustainable photovoltaic materials with application potential for solar electricity. However, defects at the copper oxide heterojunction and film quality are still major constraining factors for achieving high power conversion efficiency, η. Amongst the Cu₂O heterojunction devices, a maximum η of 6.1% has been obtained by using pulsed laser deposition (PLD) of AlxGa1-xO onto thermal Cu₂O doped with Na. The performance of CuO/n-Si heterojunction solar cells formed by magnetron sputtering of CuO is presently limited by both native oxide and Cu rich copper oxide layers at the heterointerface. These interfacial layers can be reduced by using a two-step sputtering process. A high η of 2.88% for CuO heterojunction solar cells has been achieved by incorporation of mixed phase CuO/Cu₂O nanopowder. CuO/Cu₂O heterojunction solar cells fabricated by electrodeposition and electrochemical doping has a maximum efficiency of 0.64% after surface defect passivation and annealing. Finally, early stage study of Cu₄O₃/GaN deposited on sapphire substrate has shown a photovoltaic effect and an η of ~10-2%.


Cutaneous collagenous vasculopathy: A report of three cases.
Cutaneous collagenous vasculopathy is a rare pauci-inflammatory, superficial, cutaneous vasculopathy characterized by progressive fine-branching telangiectasias clinically, while light microscopically one observes dilated venules and capillaries within the superficial dermis exhibiting excessive Type IV collagen within the vessel wall. We present three cases of collagenous vasculopathy. Two cases were associated with certain autoimmune stigmata, including a positive serologic anti-endothelial cell antibody assay and positive lupus anticoagulant in one, while the third case had positive anti-ribonucleoprotein (RNP) antibodies. The latter case was associated with chronic hydroxyurea therapy for an underlying myeloproliferative disorder. We explore the role of immune- and non-immune-based endothelial cell injury in the pathogenesis of collagenous vasculopathy.


An effect of corticosteroids and 100% oxygen on aryl hydrocarbon hydroxylase, cytochrome-c reductase, and free radical formation by rat lung microsomes.
Activity of aryl hydrocarbon hydroxylase (AHH), cytochrome c-reductase, and NADPH oxidase, and epinephrine oxidation to adrenochrome were determined in lung microsomes from intact, adrenalectomized, and adrenalectomized cortisol-treated female rats under ambient and hyperoxic conditions. Microsomal adrenochrome formation, which is initiated by superoxide anion or other free radicals, was increased by adrenalectomy and decreased by cortisol treatment. Exposure of animals to 100% oxygen caused a further increase in adrenochrome formation. NADPH-cytochrome c-reductase and AHH activities were increased in incubations of microsomes from animals which had received cortisol in vivo while adrenalectomy led to decreases activity. NADPH oxidase activity was increased by cortisol in lung microsomes in the presence of either epinephrine or cytochrome c. Epinephrine conversion to adrenochrome in the presence of lung microsomes was blocked by SOD, but NADPH-cytrochrome c-reductase and AHH activity were unaffected.


Methotrexate and corticosteroids in the treatment of localized scleroderma: a standardized prospective longitudinal single-center study.
To evaluate the effectiveness of a uniform single-center treatment protocol composed of high-dose methotrexate (MTX) and oral corticosteroids in a pediatric localized scleroderma (LS) cohort. Thirty-six patients with LS were recruited. Patients with active disease, defined as erythematous lesions and/or new lesions, or expansion of existing lesions, were started on oral prednisone 2 mg/kg/day (maximum 60 mg/day) and subcutaneous (SC) MTX at 1 mg/kg/week (maximum 25 mg/week). Prednisone was tapered and kept at 0.25 mg/kg/day for 12 months. MTX SC was continued for 24 months, and then switched to oral administration to complete 36 months of therapy. Modified LS Skin Severity Index (mLoSSI) and the physician global assessment of disease activity (PGA-A) were used as outcome measures. Twenty-five patients with LS were female with a median age at onset of 7.86 years [interquartile range (IQR) 4.63-11.91]. Median disease duration from onset until start of this treatment regimen was 19.2 months (IQR 8.96-35.35). Median duration of followup was 36.40 months (IQR 29.39-45.36). All patients demonstrated significant improvement in mLoSSI at median 1.77 months (IQR 0.76-2.37, 95% CI 1.54, 2.01). PGA-A followed the same trend. No significant adverse reactions or flares were observed during therapy. This single-center LS treatment protocol was effective and well tolerated. Clinical outcome in LS is affected by dose and route of administration of immunosuppressive regimens. Daily tapering dose of corticosteroids and parenteral MTX were effective in controlling LS activity without significant adverse reaction. This regimen should be considered as one of the therapies for LS clinical trials.


New WGS data and annotation of the heterosomal vs. autosomal localization of Ostrinia scapulalis (Lepidoptera, Crambidae) nuclear genomic scaffolds.
Here, we introduce new whole-genome shotgun sequencing and annotation data describing the autosomal vs. Z-heterosomal localization of nuclear genomic scaffolds of the moth species Ostrinia scapulalis. Four WGS libraries (corresponding to 2 males and 2 females) were sequenced with an Illumina HiSeq2500 sequencing technology, and the so-called 'AD-ratio' method was applied to distinguish between autosomal and Z-heterosomal scaffolds based on sequencing depth comparisons between homogametic (male) and heterogametic (female) libraries. A total of 25,760 scaffolds (corresponding to 341.69 Mb) were labelled as autosomal and 1273 scaffolds (15.29 Mb) were labelled as Z-heterosomal, totaling about 357 Mb. Besides, 4874 scaffolds (29.07 Mb) remain ambiguous because of a lack of AD-ratio reproducibility between the two replicates. The annotation method was evaluated a posteriori, by comparing depth-based annotation with the exact localization of known genes. Raw genomic data have been deposited and made accessible via the EMBL ENA BioProject id PRJEB26557. Comprehensive annotation is made accessible via the LepidoDB database (http://bipaa.genouest.org/sp/ostrinia_scapulalis/download/genome/v1.2/).


Measurement of cell death in Mammalian cells.
Methods for assessing mammalian cell death are presented in this unit. The unit is divided into six sections: (1) a brief overview of cytotoxicity and pathways of cell death, (2) a method to measure cell death using lactate dehydrogenase (LDH) release as a marker of membrane integrity, (3) a flow cytometry method that simultaneously measures two types of cell death, necrosis, and apoptosis, (4) use of fluorescence microscopy and nuclear morphology to assess apoptosis and necrosis, (5) the use of multi-well plates and high-content analysis imaging systems to assess nuclear morphology, and (6) a discussion of the use of cytotoxicity assays to determine the mechanisms of cell death.


Mantle cell lymphoma involving the oral and maxillofacial region: a study of 20 cases.
To investigate the clinicopathologic features of mantle cell lymphoma (MCL) involving the oral and maxillofacial region. The MCL cases were retrieved from the pathosis database of 6 pathology laboratories. Original hematoxylin and eosin slides and immunohistochemical reactions were reviewed for confirmation of the initial diagnosis. Clinical data of the cases were obtained from the patients' pathosis and/or medical charts. Twenty cases were included in the study, showing a male predominance and a mean age of 66 years. The oral cavity (12 cases) and the oropharynx (5 cases) were the most commonly involved subsites. Most cases presented as asymptomatic swellings, with 2 cases showing bilateral involvement of the palate. The classic histologic variant predominated (12/20 cases). All cases expressed CD20 with nuclear cyclin D1 positivity. SOX11 was seen in 9/13 cases, CD5 in 6/16 cases, Bcl2 in 16/19 cases, CD10 in 2/20 cases, and Bcl6 in 4/16 cases. Ki67 showed a mean proliferation index of 40.6%. The Epstein-Barr virus (EBV) was negative in all cases investigated. Follow-up data was available for 7 patients, with 5 currently alive and 2 deceased. Mantle cell lymphoma, albeit rare, may manifest in the oral and maxillofacial region. Its histologic heterogeneity demands a high degree of diagnostic skill from pathologists.


Spatial resolution of anthropogenic heat fluxes into urban aquifers.
Urban heat islands in the subsurface contain large quantities of energy in the form of elevated groundwater temperatures caused by anthropogenic heat fluxes (AHFS) into the subsurface. The objective of this study is to quantify these AHFS and the heat flow they generate in two German cities, Karlsruhe and Cologne. Thus, statistical and spatial analytical heat flux models were developed for both cities. The models include the spatial representation of various sources of AHFS: (1) elevated ground surface temperatures, (2) basements, (3) sewage systems, (4) sewage leakage, (5) subway tunnels, and (6) district heating networks. The results show that the district heating networks induce the largest AHFS with values greater than 60 W/m(2) and one order of magnitude higher than fluxes from other sources. A covariance analysis indicates that the spatial distribution of the total flux depends mainly on the thermal gradient in the unsaturated zone. On a citywide scale, basements and elevated ground surface temperatures are the dominant sources of heat flow. Overall, 2.1 PJ/a and 1.0 PJ/a of heat are accumulated on average in Karlsruhe and the western part of Cologne, respectively. Extracting this anthropogenically originated energy could sustainably supply significant parts of the urban heating demand. Furthermore, using this heat could also keep groundwater temperatures from rising further.


[Echocardiographic representation of the fetal heart (time-motion registration) (author's transl)].
With time-motion registration of the fetal heart it is possible to get information about the size of the ventricles, the left atrium and the aorta. First results of this method of investigation are demonstrated.


Buteyko breathing techniques in asthma: a blinded randomised controlled trial.
To evaluate the effect of Buteyko breathing techniques (BBT) in the management of asthma. Prospective, blinded, randomised study comparing the effect of BBT with control classes in 39 subjects with asthma. The study was conducted from January 1995 to April 1995. Subjects recruited from the community, aged 12 to 70 years, with asthma and substantial medication use. Medication use; morning peak expiratory flow (PEF); forced expiratory volume in one second (FEV1); end-tidal (ET) CO2; resting minute volume (MV); and quality of life (QOL) score, measured at three months. No change in daily PEF or FEV1 was noted in either group. At three months, the BBT group had a median reduction in daily beta 2-agonist dose of 904 micrograms (range, 29 micrograms to 3129 micrograms), whereas the control group had a median reduction of 57 micrograms (range, -2343 micrograms to 1143 micrograms) (P = 0.002). Daily inhaled steroid dose fell 49% (range, -100% to 150%) for the BBT group and 0 (range, -82% to +100%) for the control group (P = 0.06). A trend towards greater improvement in QOL score was noted for BBT subjects (P = 0.09). Initial MV was high and similar in both groups; by three months, MV was lower in the BBT group than in the control group (P = 0.004). ET CO2 was low in both groups and did not change with treatment. Those practising BBT reduced hyperventilation and their use of beta 2-agonists. A trend toward reduced inhaled steroid use and better quality of life was observed in these patients without objective changes in measures of airway calibre.


Single unit activity in cat prefrontal and posterior association cortex during performance of spatial reversal tasks .
Relationships between the performance of complex learning tasks and the firing patterns of single unites in prefrontal and posterior association areas of the neocortex were studied in 9 cats. Recording data from 2 additional cats served as controls for sensory and motor aspects of the tasks employed. During recordings, animals sat in a box, their heads fixed to a stereotaxic instrument, and performed a non-sensory spatial reversal or delayed-alternation task by pressing 1 of 2 lateralized retractable levers. Units obtained were classified into 5 basic types according to their correlation with aspects of the tasks. The first 3 types were related directly to sensory, motor and motivational aspects of the tasks. The fourth type was named associative, as it contained units which changed firing rates in advance or as a consequence of environmental events, rather than in direct relation. Discharge changes of units of the fifth type were rated as non-specific or non-specifiable. Between recording areas and tasks a striking similarity of unit firing patterns was obtained. Differences were observed only between the reactivity of polymodal cells in prefrontal and in posterior fields, and in the proportions of units revealing mnemonic and motor response aspects. It was concluded that a considerable functional overlap between prefrontal and posterior association areas of the cat with respect to processing of complex learning tasks exists on the single neuron level.


Noninvasive assessment of cardiac function and ventricular dyssynergy by precordial Q wave mapping in anterior myocardial infarction.
To determine whether multiple lead precordial electrocardiographic recordings offer an improved index for noninvasive estimation of left ventricular hemodynamic function and segmental dyssynergy, precordial mapping was performed in patients with anterior myocardial infarction, and the number of pathologic Q waves (greater than or equal to 0.04 sec) was counted (Q-Index). Left ventricular function was determined by cardiac catheterization and angiography and correlated with the Q-Index. The Q-Index correlated well with dyssynergy extent (r = 0.84) and inversely with ejection fraction (r= -0.87), stroke work index (r = -0.79) and cardiac index (r = =0.66). Three patient groups were defined by Q-Index; group I, 0.04 sec Q complexes less than 15; group II, 15-25; group III, 26-35. Q-Index related closely to functional classification and survival (mean follow-up 12.2 months): group I, 91%; group II, 81%; group III, 40%. Thus 35-lead precordial Q wave mapping with determination of total number of pathologic Q waves permits practical, atraumatic assessment of hemodynamic and functional status and allows prediction of survival in acute and chronic anterior myocardial infarction.