Insecticidal activity of a Moroccan strain of Streptomyces phaeochromogenes LD-37 on larvae, pupae and adults of the Mediterranean fruit fly, Ceratitis capitata (Diptera: Tephritidae).
The Mediterranean fruit fly (medfly), Ceratitis capitata, is considered the most important fruit pest worldwide. Its management is mainly based on the use of chemical insecticides. Although these conventional pesticides are effective at high doses, they cause considerable human health and environment problems. Thus, the aim of this study was to assess insecticidal activity of Moroccan actinobacteria against C. capitata. A total of 12 preselected actinobacteria isolated from various Moroccan habitats were screened for their insecticidal activity against larvae, pupae and adults of C. capitata. Four actinobacteria isolates were significantly active against the first-instar larvae, and nine were active against the medfly adult, while no significant mortality was obtained against the third-instar larval and pupal stages. Among the selected isolates, the biological screening revealed that strain Streptomyces LD-37, which showed 99.4% similarity with Streptomyces phaeochromogenes, exhibited the maximal corrected larval mortality of 98%. Moreover, the isolates AS1 and LD-37 showed the maximum significant corrected mortality against adults of 32.5 and 28.2%, respectively. The crude extract obtained from a fermented culture of strain S. phaeochromogenes LD-37 was separated into six fractions by thin layer chromatography. Fractions F3 and F4 caused a significant corrected larval mortality of 66.7 and 53.3%, respectively; whereas the maximum reduction in adult emergence was obtained with fraction F4. This finding could be useful for utilizing S. phaeochromogenes LD-37 as an alternative to chemical insecticides in pest management of C. capitata.


Effect of dehydrating agents on DNA organization in herpes viruses.
With routine procedures of Epon- or GMA-embedding and a stain specific for DNA, the nucleoid of mature herpes simplex virus-type 1 (HSV-1) assumes the well-known form of a short, compact, hollow cylinder or torus. A new, more complex organization of DNA filaments in encapsidated HSV-1 was found in infected cells after aldehyde fixation, methanol dehydration, and Lowicryl embedment. We have determined that it is the use of methanol as dehydrating agent that permits visualization of this internal structure. The same new spatial organization of DNA can be seen in Epon and GMA sections when methanol dehydration is used. This organization is lost in a methanol-ethanol sequence of dehydration but can be restored in an ethanol-methanol sequence. Dimethylsulfoxide (DMSO) is the only other agent among several reviewed here which resembles methanol in its effect on HSV-1 DNA. Methanol had the same effect on five subfamilies of the herpes group (HSV-1, HSV-2, CCV, CMV, CTHV) but did not alter the nucleoid ultrastructure in simian virus 40 (SV40) and adenovirus type 5 (Ad 5). Therefore, it may sometimes, but not always, provide additional information about the organization of biological structures.


Long noncoding RNAs show differential expression profiles and display ceRNA potential in cholesteatoma pathogenesis.
Cholesteatoma is a pathologically benign but clinically destructive middle ear disease, which is caused by excessive epidermal migration and uncontrolled hyperproliferation of keratinocytes of squamous epithelium, leading to various clinical manifestations and serious complications, such as hearing loss, dizziness, facial paralysis, meningitis, and hydrocephalus. However, the pathogenesis of cholesteatoma is still not fully understood. Herein, we performed microarray analysis to identify the differentially expressed patterns of lncRNAs in cholesteatoma for the first time. Our data indicated that compared with matched normal skin tissue, lncRNA expression profiles were significantly altered in cholesteatoma. A total of 787 lncRNAs were identified (fold change ≥2.0, P<0.05), consisting of 181 upregulated and 606 downregulated lncRNAs. Furthermore, by constructing an lncRNA/miRNA/mRNA competing endogenous RNA (ceRNA) network, we found that lncRNAs, such as lncRNA‑uc001kfc.1, had ceRNA potential in cholesteatoma formation. In conclusion, lncRNAs were aberrantly expressed in cholesteatoma compared with normal skin tissues and may play important roles in cholesteatoma formation. Our findings shed novel light on the molecular mechanism of cholesteatoma pathogenesis and suggest that lncRNAs may be potential therapeutic targets for cholesteatoma.


Evaluation of luteal phase in normal and infertile women.
Evaluation of luteal phase function is an important part of fertility evaluation in the female. Among fifty clinically identified patients with primary infertility certain well-established laboratory methods were used to identify the luteal phase defect. These methods included serum progesterone assays, endometrial biopsy, vaginal cytology, basal body temperatures and cervical mucus scoring, with appropriate controls. Based on both endometrial biopsy which was two or more days out of phase and the serum progesterone level of less than 2.5 ng/ml, luteal phase defect was found in five patients among the 50 patients (10 percent). It was found that an endometrial biopsy which was well dated showed a definite correlation with the progesterone assays and could be considered as the most easily performed and reliable indicator, useful in detecting a luteal phase defect.


Effect of Welding Defects on Fatigue Properties of SWA490BW Steel Cruciform Welded Joints.
Welding is prone to several defects. To test the fatigue properties of the welded defective joints of high-speed rail bogies, SMA490BW steel cruciform welded joints were employed with artificial defects treatment. Consequently, fatigue tests were conducted on the specimens. Fatigue fracture morphology was studied via scanning electron microscopy. The ABAQUS (version 2022) finite element software was used to calculate the stress distribution and concentration factor of cruciform welded joints with defects. The results show that the fatigue limits of 1 and 2.4 mm defect specimens were approximately 57.2 and 53.75 Mpa, respectively. Furthermore, the stress concentration factor of no, 1 mm, and 2.4 mm defects were 2.246, 4.441, and 6.684, respectively, indicating that the stress concentration factor of 1 and 2.4 mm defects increased by 98 and 198%, respectively, with respect to the no-defect case.


Loss of Cep72 affects the morphology of spermatozoa in mice.
The centrosome regulates mammalian meiosis by affecting recombination, synapsis, chromosome segregation, and spermiogenesis. Cep72 is one of the critical components of the centrosome. However, the physiological role of Cep72 in spermatogenesis and fertility remains unclear. In this study, we identify Cep72 as a testis-specific expression protein. Although Cep72 knockout mice were viable and fertile, their sperms were morphologically abnormal with incomplete flagellum structures. Transcriptome analysis reveals significant differences in six genes (Gm49527, Hbb-bt, Hba-a2, Rps27a-ps2, Gm29647, and Gm8430), which were not previously associated with spermatogenesis. Overall, these results indicate that Cep72 participates in regulating sperm morphology and yet is dispensable for fertility in mice.


Nitric oxide acts as an antioxidant and delays programmed cell death in barley aleurone layers.
Nitric oxide (NO) is a freely diffusible, gaseous free radical and an important signaling molecule in animals. In plants, NO influences aspects of growth and development, and can affect plant responses to stress. In some cases, the effects of NO are the result of its interaction with reactive oxygen species (ROS). These interactions can be cytotoxic or protective. Because gibberellin (GA)-induced programmed cell death (PCD) in barley (Hordeum vulgare cv Himalaya) aleurone layers is mediated by ROS, we examined the effects of NO donors on PCD and ROS-metabolizing enzymes in this system. NO donors delay PCD in layers treated with GA, but do not inhibit metabolism in general, or the GA-induced synthesis and secretion of alpha-amylase. alpha-Amylase secretion is stimulated slightly by NO donors. The effects of NO donors are specific for NO, because they can be blocked completely by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. The antioxidant butylated hydroxy toluene also slowed PCD, and these data support our hypothesis that NO is a protective antioxidant in aleurone cells. The amounts of CAT and SOD, two enzymes that metabolize ROS, are greatly reduced in aleurone layers treated with GA. Treatment with GA in the presence of NO donors delays the loss of CAT and SOD. We speculate that NO may be an endogenous modulator of PCD in barley aleurone cells.


Obtaining consent: the use of a consent form.
A consent form provides clear, unambiguous proof that a patient consented to treatment. Consent forms do not reveal the content of discussions with a patient. Staff awareness needs to be raised of the importance of providing information, obtaining consent and demonstrating that this has occurred.


Factors that may determine the targeting accuracy of image-guided radiosurgery.
The AAPM TG-135 report is a landmark recommendation for the quality assurance (QA) of image-guided robotic radiosurgery. The purpose of this paper is to present results pertaining to intentionally offsetting the phantom as recommended by TG-135 and to present data on targeting algorithm accuracy as a function of imager parameters in less than ideal circumstances, which had not been available at the time of publication of TG-135. All tests in this study were performed at the Cooper University Hospital CyberKnife Center in Mt. Laurel, NJ. For intentional offsets, initial tests were performed on the Accuray-supplied anthropomorphic head and neck phantom, whereas for subsequent tests, the Accuray-supplied alignment quality assurance (AQA) phantom was used. To simulate the effects of imager parameters for larger patients, slabs of Blue Water (Standard Imaging, Inc., Middleton, WI) were added to attenuate the x-ray images in some of the tests. In conjunction with attenuated x-ray tests, the number of fiducials was varied by systematically deselecting them one at a time at the CyberKnife console. Tests using the AQA phantom verified that submillimeter alignments were consistently achieved even with intentional shifts and rotations of up to 10.0 mm and 1.0°, respectively. An analysis of 17 months of daily QA alignment tests showed that submillimeter alignments were achieved more than 99% of the time even with such intentional shifts and rotations of the phantom. When additional slabs of Blue Water were added to simulate patient attenuation of the x-ray images, targeting errors could be induced depending on imager parameters and the amount of Blue Water used. A series of consecutive tests showed that two helpful variables to ensure good accuracy of the system were (1) the fiducial extraction confidence level (FECL) system parameter and (2) the number of targeted fiducials. When fewer than four fiducials were used, the FECL reported by the CyberKnife was sometimes high even when a false lock occurred, so using multiple fiducials helped to ensure reliable targeting. Radiosurgery requires the highest degree of targeting accuracy, and in our experience, the CyberKnife has been able to maintain submillimeter accuracy consistently. It has been verified that our CyberKnife can correct for phantom shifts of up to 10.0 mm and rotations of up to 1.0°. It has also been discovered that false locks are more likely to occur with a single fiducial than with multiple fiducials. Although targeting accuracy can only be measured on a phantom, the insight gained from analyzing the QA tests can help us in devising better strategies for achieving the best treatment for our patients.


Quantitative surface-enhanced Raman spectroscopy chemical analysis using citrate as an in situ calibrant.
Direct detection, or inferring the presence of illicit substances, is of great forensic and toxicological value. Surface-enhanced Raman spectroscopy (SERS) has been shown capable of detecting such molecules in a quick and sensitive manner. Herein we describe an analysis strategy for quantitation of low concentrations of three analytes (methamphetamine, cocaine, and papaverine) by SERS analysis using the citrate capping agent that initially saturates the silver nanoparticles' surface as an in situ standard. The citrate is subsequently displaced by the analyte to an extent dependent on the analyte's concentration in the analyte solution. A general model for the competitive adsorption of citrate and a target analyte was developed and used to determine the relative concentrations of the two species coexisting on the surface of the silver nanoparticles. To apply this model, classical least squares (CLS) was used to extract the relative SERS contribution of each of the two species in a given SERS spectrum, thereby accurately determining the analyte concentration in the sample solution. This approach, in essence, transforms citrate into a local standard against which the concentration of an analyte can be reliably determined.


Dynamics of homogeneous nucleation.
The classical nucleation theory for homogeneous nucleation is formulated as a theory for a density fluctuation in a supersaturated gas at a given temperature. But molecular dynamics simulations reveal that it is small cold clusters which initiates the nucleation. The temperature in the nucleating clusters fluctuates, but the mean temperature remains below the temperature in the supersaturated gas until they reach the critical nucleation size. The critical nuclei have, however, a temperature equal to the supersaturated gas. The kinetics of homogeneous nucleation is not only caused by a grow or shrink by accretion or evaporation of monomers only but also by an exponentially declining change in cluster size per time step equal to the cluster distribution in the supersaturated gas.


Differential detection of classical swine fever virus challenge strains in C-strain vaccinated pigs.
Control of classical swine fever (CSF) by vaccination ideally requires that field strain infection can be detected irrespective of the vaccination status of the herd. To inform on the usefulness of molecular tests compatible with genetic Differentiation of Infected from Vaccinated Animals (DIVA) principles when using live-attenuated vaccines, tonsil homogenates from a vaccination-challenge experiment were analyzed using a differential real-time qRT-PCR for the C-strain vaccine or real-time qRT-PCR assays developed to specifically detect the challenge strains used. In animals with high or moderate levels of blood viraemia, which were not, or not fully, protected by vaccination, challenge virus RNA was readily detected in tonsil homogenates. In three out of the seven vaccinated animals that had high or moderate viraemia, the vaccine strain RNA also could be detected but at lower levels. Lower but varying levels of challenge and/or vaccine virus RNA were detected in tonsil homogenate samples from animals with no or low-level viraemia, and in groups solely consisting of such animals, no transmission of infection to naïve in-contact animals occurred. In one group of animals that were vaccinated 3 days prior to challenge, viraemia levels varied from high to absent and transmission of challenge virus to naïve in-contact animals occurred. The DIVA assay revealed challenge virus in all tonsil homogenates from this group, even in those animals that did not have viraemia and were protected from clinical disease by vaccination. Such animals, particularly in a low biosecurity/informal farm setting, could constitute a risk for disease control in the field. Genetic DIVA testing is useful for detecting the presence of field virus infection especially in non-viraemic animals without overt clinical signs but which are incompletely protected by vaccination. Such tests could particularly be useful to inform decisions prior to and during cessation of a control strategy that employs vaccination.


Mammalian target of rapamycin inhibition in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin (mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase III studies, mTORC1 inhibitors demonstrate anti-tumor activity in advanced HCC, but dual mTOR (mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.


An Oncolytic Adenovirus Encoding Decorin and Granulocyte Macrophage Colony Stimulating Factor Inhibits Tumor Growth in a Colorectal Tumor Model by Targeting Pro-Tumorigenic Signals and via Immune Activation.
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA), were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while there were increased Met and VEGFA levels. To develop a novel therapy for CRC, rAd.DCN.GM, an oncolytic adenovirus encoding decorin and granulocyte macrophage colony stimulating factor (GM-CSF), has been created. Several therapeutic strategies expressing GM-CSF have been employed in clinical trials for treating metastatic colorectal cancer. In this study, infection of CRC cells with rAd.DCN.GM expressed decorin and GM-CSF, and produced cytotoxicity. In murine CT26 xenografts, rAd.DCN.GM and control adenoviruses were administrated intratumorally on days 7 and 10, and tumor volumes were monitored over time. The study showed that rAd.DCN.GM inhibited the tumor growth and lung metastases significantly. rAd.DCN.GM induced apoptosis, inhibited proliferation, and downregulated angiogenesis and epithelial mesenchymal transition markers in the tumors. On day 12 and day 29, the immune-activation in the peripheral blood, tumors, and spleens were analyzed. rAd.DCN.GM increased CD8+ T lymphocytes in the blood, upregulated perforin and granzyme B in the tumors, inhibited transforming growth factor beta expression, and promoted dendritic-cell production in the spleen. In conclusion, rAd.DCN.GM inhibited the tumor growth and metastasis of CT26 tumors, downregulated multiple pro-tumorigenic pathways, and activated antitumor immune responses.


Vulvar squamous intraepithelial neoplasia epithelial thickness in hairy and non-hairy sites: a single center experience from China.
A large-sample study focusing on VIN lesions of a more precise thickness is needed to help guide clinical treatment. This study aimed to investigate the depth of vulvar intraepithelial neoplasia (VIN) and involved skin appendages to provide evidence for laser surgery. The study retrospectively enrolled and analyzed the clinical characteristics of VIN patients in the obstetrics and gynecology department of a university hospital between January 1, 2019 and December 30, 2021. The study further explored the thickness of epithelium and skin appendages of 285 women with low-grade VIN (VIN1) and 285 women with high-grade VIN (VIN2/3). The study included 1,139 (80%) VIN1 and 335 (20%) VIN2/3 cases. The VIN1 and VIN2/3 groups showed a significant difference in human papillomavirus infection (P<0.01) but not in cytology (P = 0.499). Most (89.90%, 1,325) cases occurred in one area of the vulva, whereas 10.11% were multifocal. VIN commonly occurred on the posterior fourchette (76.85%), labia majora (11.61%), and labia minora (9.92%). The VIN2/3 group reported a significantly higher positive rate for concurrent cervical and vaginal intraepithelial neoplasia (160 of 285) than the VIN1 group (321 of 953) (P=0.000). The involved epithelial thicknesses in VIN2/3 and VIN1 were 0.69 ± 0.44 and 0.49 ± 0.23 mm, respectively, both of which were greater than the corresponding noninvolved epithelial thickness (0.31 ± 0.19 and 0.32 ± 0.10 mm, P<0.001 and P<0.001, respectively). In cases of appendage involvement, the VIN thickness was 1.98 ± 0.64 mm. VIN thickness was generally ≤1 mm for the superficial lesions in non-hairy areas. However, for lesions extending onto hairy areas, the thickness was approximately 3 mm, leading to the destruction of involved skin appendages.


Biokinetics and Dosimetry of 177Lu-Pentixather.
The chemokine receptor 4 (CXCR4), which is overexpressed in many solid and hematologic malignancies, can be targeted for radiopeptide therapy via the antagonist pentixather. The biokinetics and dosimetry of 177Lu-pentixather and 90Y-pentixather were analyzed in this study. Methods: This retrospective study was a standardized reevaluation of data collected for treatment planning. Nineteen patients with complete sets of planar whole-body scans over at least 4 d and a single SPECT/CT scan after administration of 200 MBq of 177Lu-pentixather were included. Kinetics were measured in the whole body, in tissues with activity retention, and in 10 individuals in the blood. Time-integrated activity coefficients and tissue-absorbed doses were derived. Results: Increased uptake of pentixather was observed in the kidneys, liver, spleen, and bone marrow, inducing respective median absorbed doses of 0.91 Gy (range, 0.38-3.47 Gy), 0.71 Gy (range, 0.39-1.17 Gy), 0.58 Gy (range, 0.34-2.26 Gy), and 0.47 Gy (range, 0.14-2.33 Gy) per GBq of 177Lu-pentixather and 3.75 Gy (range, 1.48-12.2 Gy), 1.61 Gy (range, 1.14-2.97 Gy), 1.66 Gy (range, 0.97-6.69 Gy), and 1.06 Gy (range, 0.27-4.45 Gy) per GBq of 90Y-pentixather. In most tissues, activity increased during the first day after the administration of 177Lu-pentixather and afterward decayed with mean effective half-lives of 41 ± 10 h (range, 24-64 h) in the kidneys and median half-lives of 109, 86, and 92 h in the liver, spleen, and bone marrow, respectively. Maximum uptake per kidney was 2.2% ± 1.0% (range, 0.6%-5.1%). In organs showing no specific uptake, absorbed doses exceeding 0.3 Gy/GBq of 90Y-pentixather were estimated for the urinary bladder and for tissues adjacent to accumulating organs such as the adrenal glands, bone surface, and gallbladder. Dose estimates for tumors and extramedullary lesions ranged from 1.5 to 18.2 Gy/GBq of 90Y-pentixather. Conclusion: In patients with hematologic neoplasms, absorbed doses calculated for bone marrow and extramedullary lesions are sufficient to be effective as an adjunct to high-dose chemotherapies before stem cell transplantation.


[New concepts in the pathophysiology, diagnosis and treatment of neuropathic pain].
We here summarize five articles bringing new advances in our knowledge on neuropathic pain and put them into perspective with our current understanding. The first uses a mechanism-based approach with a capsaicin test to stratify patients suffering from painful diabetic neuropathy before starting a topical clonidine treatment. The second reviews disinhibition as a critical mechanism and a promising target for chronic pain. The third evokes neuroglial interactions and its implication regarding the interplay between injuries in childhood and hypersensitivity in adulthood. The last articles remind us that interventional therapies, not always very invasive, have a future potential in the therapy of frequent conditions such as head pain disorders.


Off-the-shelf multibranched endograft for urgent endovascular repair of thoracoabdominal aortic aneurysms.
The aim of this paper was to report early and midterm results of endovascular repair of urgent thoracoabdominal aortic aneurysms (TAAAs) by the off-the-shelf multibranched Zenith t-Branch endograft (Cook Medical, Bloomington, Ind). Between January 2014 and April 2016, all patients with urgent TAAAs (asymptomatic with diameter >8 cm, symptomatic, or ruptured TAAAs) and aortoiliac anatomic feasibility underwent endovascular repair by t-Branch and were prospectively enrolled. Clinical, morphologic, intraoperative, and postoperative data were recorded. Follow-up was performed by duplex ultrasound, contrast-enhanced duplex ultrasound, and computed tomography angiography. Early end points were technical success (absence of type I or type III endoleak, loss of target visceral vessels [TVVs], conversion to open repair, or 24-hour mortality), spinal cord ischemia, and 30-day mortality. Follow-up end points were survival, TVV patency, type I or type III endoleaks, and freedom from reintervention. Seventeen patients (male, 71%; age, 73 ± 6 years; American Society of Anesthesiologists class 3/4, 60%/40%) affected by type II (47%), III (29%), and IV (24%) TAAAs were enrolled. The indications for t-Branch were as follows: contained TAAA rupture, four (24%); symptomatic TAAA (pain or peripheral embolism), four (24%); and TAAA diameter ≥8 cm, nine (52%). The mean TAAA diameter was 80 ± 19 mm, with 63 TVVs. Fifteen patients (87%) needed adjunctive intraoperative procedures: 14 proximal thoracic endografts (thoracic endovascular aortic repair), 1 left carotid-subclavian bypass, 2 endovascular hypogastric branches, and 2 surgical iliac conduits. In four cases (24%), a significant malorientation (≥60 degrees) of the main body occurred during t-Branch deployment. Technical success was achieved in 14 cases (82%), with technical failures consisting of the loss of three renal arteries (TVV patency, 95%). Spinal cord ischemia occurred in one case (6%) with temporary paraparesis. The 30-day mortality was 6% (one patient with ruptured type II TAAA died on postoperative day 7 of respiratory failure). Renal function worsening occurred in four patients (25%), with one case requiring permanent hemodialysis. The mean follow-up was 11 ± 9 months. Survival at 1 month, 6 months, and 12 months was 94%, 82%, 82%, respectively. No TAAA-related mortality and TVV occlusion occurred in the follow-up. One type III endoleak was detected at 3 months and successfully treated. Freedom from reintervention at 1 month, 6 months, and 12 months was 88%, 82%, and 82%, respectively. The off-the-shelf multibranched endograft is a safe and effective therapeutic option for urgent total endovascular TAAA repair for which a custom-made endograft is not obtainable in due time. However, the complex anatomy of these aneurysms needs a number of adjunctive and complex intraoperative procedures to achieve a durable repair.


Cardiac magnetic resonance imaging in patients with systemic lupus erythematosus.
To delineate the cardiac magnetic resonance (MR) appearances of cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE), in comparison with transthoracic echocardiographs. Cardiac MR was performed on 22 patients with SLE-11 with previous CVD and 11 matched controls-using late gadolinium contrast enhancement (LGE) to identify areas of myocardial scarring; Transthoracic echocardiography (TTE) was performed on the same day. Twenty female and two male patients participated. LGE was seen in 5/11 subjects in the CVD group (4/5 with previous myocardial infarction) and 1/11 in the control group. TTE detected myocardial abnormalities in 2/6 patients with LGE. The cardiac MR appearance of CVD in these patients with SLE was suggestive of coronary disease, rather than cumulative inflammatory muscle damage. Cardiac MR detected more abnormalities than TTE. Further studies of cardiac MR in patients with SLE are warranted to investigate these preliminary findings.


The regulation of tissue eosinophil chemotactic factor and inhibitor in allergic skin lesions of Freund's complete adjuvant-treated guinea-pigs.
The regulation of tissue eosinophilia induced by dinitrophenyl-ascaris extract (DNP-As) was investigated in guinea-pigs. Biphasic tissue eosinophilia peaking at 6 and 24 hr was observed in the skin lesions in Bordetella pertussis vaccine (Bp)-treated animals. In contrast, only the early phase of tissue eosinophilia was observed in Freund's complete adjuvant (FCA)-treated animals. Although less eosinophil chemotactic activity was detected in 24-hr-old skin extract of FCA-treated animals (FCA-extract), evident activity was recovered in the concanavalin A eluate (Con A-eluate) when FCA-extract was fractionated by Con A Sepharose. The chemotactic factor in Con A-eluate of FCA-extract was confirmed to be the T cell-derived eosinophil chemotactic factor, termed Delayed ECF-a, which has been isolated from allergic skin lesions by immunoadsorption. Another factor from the same skin lesions, Delayed ECF-b (which is a serum-derived one), was not detected in the FCA-extract. When eosinophils were mixed or pretreated with Con A-effluent of FCA-extract, the treated cells failed to be attracted by Delayed ECF-a, while the response to Delayed ECF-b was not affected, indicating that the inhibition was selective for Delayed ECF-a but not for Delayed ECF-b, and the eosinophil chemotactic inhibitory factor (ECIF) acts on eosinophils directly. Major ECIF activity was associated with a mol. wt. of 70,000 and minor with 12,500. Furthermore, the activity was absorbed by eosinophils but not by macrophages suggesting that eosinophils have receptor sites for ECIF. It was thus suggested that the appearance of ECIF, which is selective for the response of eosinophils to Delayed ECF-a, and decreased Delayed ECF-b production resulted in the inhibition of delayed tissue eosinophilia in FCA-treated guinea-pigs.


Hormonally induced changes in apocrine secretion of transglutaminase in the rat dorsal prostate and coagulating gland.
Coagulating gland and dorsal prostate of the rat are peculiar in secreting transglutaminase, a protein-cross linking enzyme that is released in an apocrine fashion. To elucidate whether or not the intracellular pathway and the unusual extrusion mechanism proceed constitutively or were differentially regulated, transglutaminase immunoreactivity was studied both at the light and electron microscopic levels. In addition, ultrastructural morphometry and scanning densitometry were applied to quantitate hormone-dependent distribution of transglutaminase. Coagulating glands and dorsal prostate, respectively, from sexually active rats were compared to those from sexually inactive, castrated, estradiol-treated or testosterone-substituted castrated animals. In intact, sexually active animals, no labeling of the cisternae of rough endoplasmic reticulum was seen, but instead the hyaloplasm was labeled. In the supranuclear portions of the cells an increase in labeling density of the hyaloplasm subjacent to the plasma membrane was found, whereas no labeling of either Golgi stacks or vesicles was observed. Apical blebs projecting into the acinar lumen were densely labeled. In castrated animals, epithelium showed a reduction of rough endoplasmic reticulum, loss of secretory blebs, and a decrease in cell size. Morphometric analysis of immunolabeling of coagulating gland epithelium from experimental animals resulted in a highly significant reduction of labeling of the hyaloplasm and apical blebs which was reversed by testosterone supplementation of castrated animals. After estrogen treatment, the reduction in immunolabeling was less pronounced, but morphology of apical blebs was obviously changed. Results from scanning densitometry of Western blots correlated with quantitative immunoelectron microscopical findings. Northern blot analysis using a secretory transglutaminase cDNA probe showed characteristic changes at the RNA levels. Our results indicate that apocrine secretion of transglutaminase in rat coagulating gland and dorsal prostate is a hormonally controlled process, where androgen deprivation results in impaired biosynthesis and release of transglutaminase, whereas estradiol treatment only partially inhibits secretion, but changes morphological features of the glandular epithelium, especially apocrine bleb formation.


Overexpression of gibberellin 20-oxidase1 from Pinus densiflora results in enhanced wood formation with gelatinous fiber development in a transgenic hybrid poplar.
Gibberellins (GAs) are important regulators of plant shoot biomass growth, and GA 20-oxidase (GA20ox) is one of the major regulatory enzymes in the GA biosynthetic pathway. Previously, we showed that the expression levels of a putative GA20ox1 (i.e., PdGA20ox1) in stem tissue of 3-month-old seedlings of 12 families of Pinus densiflora were positively correlated with stem diameter growth across those same families growing in an even-aged 32-year-old pine forest (Park EJ, Lee WY, Kurepin LV, Zhang R, Janzen L, Pharis RP (2015) Plant hormone-assisted early family selection in Pinus densiflora via a retrospective approach. Tree Physiol 35:86-94). To further investigate the molecular function of this gene in the stem wood growth of forest trees, we produced transgenic poplar lines expressing PdGA20ox1 under the control of the 35S promoter (designated as 35S::PdGA20ox1). By age 3 months, most of the 35S::PdGA20ox1 poplar trees were showing an exceptional enhancement of stem wood growth, i.e., up to fourfold increases in stem dry weight, compared with the nontransformed control poplar plants. Significant increases in endogenous GA1, its immediate precursor (GA20) and its catabolite (GA8) in elongating internode tissue accompanied the increased stem growth in the transgenic lines. Additionally, the development of gelatinous fibers occurred in vertically grown stems of the 35S::PdGA20ox1 poplars. An analysis of the cell wall monosaccharide composition of the 35S::PdGA20ox1 poplars showed significant increases in xylose and glucose contents, indicating a qualitative increase in secondary wall depositions. Microarray analyses led us to find a total of 276 probe sets that were upregulated (using threefold as a threshold) in the stem tissues of 35S::PdGA20ox1 poplars relative to the controls. 'Cell organization or biogenesis'- and 'cell wall'-related genes were overrepresented, including many of genes that are involved in cell wall modification. Several transcriptional regulators, which positively regulate cell elongation through GA signaling, were also upregulated. In contrast, genes involved in defense signaling were appreciably downregulated in the 35S::PdGA20ox1 stem tissues, suggesting a growth versus defense trade-off. Taken together, our results suggest that PdGA20ox1 functions to promote stem growth and wood formation in poplar, probably by activating GA signaling while coincidentally depressing defense signaling.


Tuberculosis screening among persons with diabetes mellitus in Pune, India.
Diabetes mellitus (DM) increases tuberculosis (TB) risk, and there is increasing concern over the public health implications of the convergence of these two epidemics. Screening for TB among people with DM is now recommended in India. People with DM seeking care at a large public sector tertiary care hospital clinic in Pune, India, were screened for TB from June 2015 to May 2016. All consenting people with DM were screened for TB at each clinic visit using a five-item, WHO-recommended questionnaire and those with TB symptoms and/or risk factors were tested for active TB using sputum smear microscopty, Xpert® MTB/RIF and TB culture. Categorical data and continuous variables were summarized using descriptive statistics. The x 2 test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. Among 630 adults approached for screening, median age was 60 (interquartile range (IQR), 57-64) years and 350 (56%) were females. Median hemoglobin A1c (HbA1c) was 8.7% (IQR, 6.7-9.9) and 444 (70.5%) were poorly controlled DM (HbA1c > 7). Forty-four (7%) had prior history of TB but the proportion with TB risk factors at screening was low (<5%). While 18% of participants reported any TB symptoms, none of these patients were diagnosed with culture confirmed TB. Our study failed to yield any active TB cases using a WHO-recommended questionnaire among people with DM. High TB risk populations among people with DM must be identified if TB screening is to be feasible in settings such as India where the DM epidemic continues to rise.


Arabidopsis acyl-CoA-binding protein ACBP3 participates in plant response to hypoxia by modulating very-long-chain fatty acid metabolism.
In Arabidopsis thaliana, acyl-CoA-binding proteins (ACBPs) are encoded by a family of six genes (ACBP1 to ACBP6), and are essential for diverse cellular activities. Recent investigations suggest that the membrane-anchored ACBPs are involved in oxygen sensing by sequestration of group VII ethylene-responsive factors under normoxia. Here, we demonstrate the involvement of Arabidopsis ACBP3 in hypoxic tolerance. ACBP3 transcription was remarkably induced following submergence under both dark (DS) and light (LS) conditions. ACBP3-overexpressors (ACBP3-OEs) showed hypersensitivity to DS, LS and ethanolic stresses, with reduced transcription of hypoxia-responsive genes as well as accumulation of hydrogen peroxide in the rosettes. In contrast, suppression of ACBP3 in ACBP3-KOs enhanced plant tolerance to DS, LS and ethanol treatments. By analyses of double combinations of OE-1 with npr1-5, coi1-2, ein3-1 as well as ctr1-1 mutants, we observed that the attenuated hypoxic tolerance in ACBP3-OEs was dependent on NPR1- and CTR1-mediated signaling pathways. Lipid profiling revealed that both the total amounts and very-long-chain species of phosphatidylserine (C42:2- and C42:3-PS) and glucosylinositolphosphorylceramides (C22:0-, C22:1-, C24:0-, C24:1-, and C26:1-GIPC) were significantly lower in ACBP3-OEs but increased in ACBP3-KOs upon LS exposure. By microscale thermophoresis analysis, the recombinant ACBP3 protein bound VLC acyl-CoA esters with high affinities in vitro. Further, a knockout mutant of MYB30, a master regulator of very-long-chain fatty acid (VLCFA) biosynthesis, exhibited enhanced sensitivities to LS and ethanolic stresses, phenotypes that were ameliorated by ACBP3-RNAi. Taken together, these findings suggest that Arabidopsis ACBP3 participates in plant response to hypoxia by modulating VLCFA metabolism.


[Evaluation of selected serum protein markers as early detectors of ovarian cancer].
an attempt to determine the value of the simultaneous quantization of osteopontin (OPN), insulin-growth factor II (IGF II), leptin, prolactin and CA 125 for early detection of ovarian cancer. Prospective study of 69 women including: 15 females with ovarian cancer; 33 females with benign ovarian neoplasm; 21 disease-free females; The levels of IGF II, prolactin, leptin and CA 125 were determined in serum, while the level of OPN was checked in plasma. The concentrations of IGF II, leptin and prolactin do not let us distinguish among disease-free females, females with ovarian cancer and those with benign ovarian neoplasms on the basis of biochemical markers. The comparison of OPN and CA 125 levels showed significant differences in the concentrations of the biomarkers between disease-free females and females with ovarian cancer, as well as between females with benign ovarian neoplasms and females with ovarian cancer. The ROC curves for two groups: disease-free females and females with ovarian cancer, proved the diagnostic value of OPN and CA 125. The simultaneous quantization of OPN, IGF II leptin and prolactin has not been proved useful for the early detection of ovarian cancer. Statistically significant increase of OPN & CA 125 levels was noted in case of women with ovarian cancer diagnosed through microscopic examination. The analysis of ROC curves showed comparable diagnostic usefulness of both markers. Quantization of OPN may have an additional value for treatment monitoring of women diagnosed with ovarian cancer but with concentration of CA 125 within the reference value.


Uterine artery score and perinatal outcome.
To evaluate a modified uterine artery score based on the pulsatility index and presence or absence of notching in the Doppler velocity waveform recorded from both uterine arteries in relation to the perinatal outcome. A retrospective analysis was performed in 741 third-trimester high-risk pregnancies. The uterine artery score was constructed assigning one point to each abnormal parameter-high pulsatility index and presence of notch-thus ranging from 0 (normal findings in both uterine arteries) to 4 (notch and high pulsatility index in both uterine arteries). In a subgroup with lateral placenta (n = 359), two definitions of abnormal pulsatility index were compared. In the uniform uterine artery score, a pulsatility index > 1.20 in both uterine arteries was considered abnormal, disregarding the placental location; in the subgroup with lateral placenta, the high pulsatility index was defined as > 1.00 on the placental side and > 1.40 on the non-placental side. Receiver-operating characteristic curves did not reveal any difference in the diagnostic capacity between the group with a uniform uterine artery score and the subgroup with lateral placenta (P = 0.54). In the total material, the odds ratios and linear regression analysis showed an increased risk for an adverse perinatal outcome with increasing uterine artery score (P < 0.01). At a uterine artery score > 2, there was a significantly increased risk for operative delivery for fetal distress, neonatal intensive care unit admission, 5-min Apgar score < 7, preterm delivery and delivery of a small-for-gestational age fetus. In high-risk third-trimester pregnancies, Doppler velocity waveforms of the uterine arteries can be evaluated using the uterine artery score disregarding the placental location. The uterine artery score possesses a high predictive value regarding adverse perinatal outcome.


Surgical Drains in Chronic Subdural Hematoma Surgery: From the Cheapest to the Most Expensive Drains.
Among the various neurosurgical techniques currently being used in chronic subdural hematoma (CSDH) surgery, bur hole craniostomy is the most popular worldwide. Recent studies have strongly recommended that a drain be placed after surgical evacuation of a hematoma, and a broad spectrum of preformed surgical drains is widely available for this purpose. If preformed drains are unavailable, a surgeon-made drain can be used and various methods are available to develop a drain in the operating room. Using a case report, we demonstrate how to develop a surgeon-made drain. Next, we retrospectively screened for subdural drain usage in consecutive patients undergoing bur hole drainage for CSDH at Adiyaman University Hospital between January 2017 and April 2017, and data from only those patients in whom a surgeon-made drain was used were included for analyses. A 74-year-old male was operated with the diagnosis of CSDH. Assembly of a surgeon-made drain was explained step by step. Our review identified 6 unilateral and 2 bilateral cases in which 10 surgeon-made drains were used. Mean age of the patients was 72, and mean follow-up period was 7 months, 23 days. No instances of infection or drain-related complications had been recorded. The recurrence rate was 0%, and the average drainage period was 3.4 days. In case of unavailability of a preformed drain, a surgeon-made drain can be used during CSDH surgery. Different methods are available and can be further diversified using various combinations of simple medical materials.


Divergent regulation of Wnt-mediated development of the dorsomedial and ventrolateral dermomyotomal lips.
The dermomyotome is the dorsal compartment of the somite which gives rise to multiple cell fates including skeletal muscle, connective tissue, and endothelia. It consists of a pseudostratified, roughly rectangular epithelial sheet, the margins of which are called the dermomyotomal lips. The dermomyotomal lips are blastema-like epithelial growth zones, which continuously give rise to resident dermomyotomal cells and emigrating muscle precursor cells, which populate the subjacent myotomal compartment. Wnt signaling has been shown to regulate both dermomyotome formation and maintenance of the dermomyotomal lips. Whereas the epithelialization of the dermomyotome is regulated via canonical, β-catenin-dependent Wnt signaling, the downstream signaling mechanisms suppressing epithelial-mesenchymal transition (EMT) in the mature dermomyotomal lips have been unknown. Here, we present evidence that dermomyotomal lip sustainment is differentially regulated. Whereas the dorsomedial dermomyotomal lip is maintained by canonical Wnt signaling, development of the ventrolateral dermomyotomal lip is regulated by non-canonical, PCP-like Wnt signaling. We discuss our results in the light of the different developmental prerequisites in the dorsomedial and ventrolateral lips, respectively, thus providing a new perspective on the regulation of dermomyotomal EMT.


Individual differences in autobiographical memory predict the tendency to engage in spontaneous thoughts.
Individual differences in autobiographical memory have become a research area of interest, but little is known about its associations with other individual differences dimensions, such as the tendency to engage in spontaneous cognition. We report two studies examining individual differences in autobiographical memory, as measured by the Autobiographical Recollection Test (ART), in relation to eight trait-like measures of spontaneous thought and, in Study 2, also a measure of fantasy proneness. In Study 1, the ART correlated positively and systematically with six out of eight measures of spontaneous thought, even when controlling for age, gender, and trait positive and negative affect. The two exceptions concerned spontaneous thoughts specifically related to attentional deficits. Study 2 replicated these findings and extended them to a measure of fantasy proneness. The findings demonstrate that people who generally consider their autobiographical memories to be vivid, detailed, relevant, and coherent, report a higher tendency to engage in various forms of spontaneous cognition, including positive constructive daydreaming, spontaneous mind wandering, involuntary mental time travel, and vivid and immersive fantasy. We discuss these findings in terms of the role autobiographical memory plays in spontaneous thoughts.


Sepsis caused by acute phlegmonous gastritis based on a group A Streptococcus.
We present a case of 45-year-old male with acute phlegmonous gastritis (APG) based on a hemolytic group A Streptococcus. APG is a rare and often a potentially fatal disease, which is characterized by a severe bacterial infection of the gastric wall. Because APG is a rapidly progressive disease, it comes with high mortality rates. Patients with an early diagnosis may undergo successful treatment and have a survival benefit. As soon as the diagnosis of APG is suspected, aggressive and adequate antibiotic treatment in combination with surgical intervention should be considered.


Enantioselective Synthesis of Spiro[indolizidine-1,3'-oxindoles].
A three-step procedure for the enantioselective synthesis of spiro[indolizidine-1,3'-oxindoles], consisting of a stereoselective cyclocondensation reaction between (S)-tryptophanol and a prochiral or racemic δ-oxoester, bromination of the resulting oxazolopiperidone lactam, and a final stereoselective spirocyclization, is reported.


Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma.
Although lymphoid tissue is absent in normal gastric mucosa, primary lymphomas arise in the stomach and most of these recapitulate the features of mucosa-associated lymphoid tissue (MALT). Gastric lymphoid tissue is known to be acquired in response to local infection by Helicobacter pylori, and we have confirmed this in 450 patients with H pylori-associated gastritis of whom 125 showed mucosal lymphoid follicles. In 8 patients, B lymphocytes infiltrated epithelium, which is a feature characteristic of MALT. We also examined 110 cases of gastric MALT lymphoma and found H pylori infection in 101 of these (92%). We conclude that gastric MALT is acquired in H pylori infection and that this provides the necessary background in which MALT lymphoma might develop.


Mini-implant stability at the initial healing period: a clinical pilot study.
To evaluate the changes of mini-implant stability over the initial healing period in humans. A sample of 19 consecutively treated patients (mean age 15.5 ± 7.3 years) was examined. In each patient, a mini-implant of a size of 2 × 9 mm was inserted into the anterior palate. Implant stability was assessed using resonance frequency analysis (RFA) immediately after insertion (T0), 2 weeks later (T1), 4 weeks later (T2), and 6 weeks later (T3). Insertion depth (ID) and the maximum insertion torque (IT) were measured. Data were tested for correlations between RFA, ID, and IT. All RFA values were tested for statistically significant differences between the different times. The mean ID was 7.5 ± 0.6 mm, and the mean IT was 16.8 ± 0.6 Ncm. A correlation was found between RFA and ID (r = .726, P < .0001), whereas no correlations between RFA and IT or between IT and ID were observed. From T0 to T1, the stability (36.1 ± 6.1 implant stability quotient [ISQ]) decreased nonsignificantly by 4.9 ± 6.1 ISQ values (P > .05). Between T1 and T2, the stability decreased highly significantly (P < .001) by 7.9 ± 5.9 ISQ values. From T2 on, RFA remained nearly unchanged (-1.7 ± 3.5 ISQ; P > .05). Mini-implant stability is subject to changes during the healing process. During weeks 3 and 4, a significant decrease of the stability was observed. After 4 weeks, the stability did not change significantly.


2002 global update of available data on visual impairment: a compilation of population-based prevalence studies.
For the past 25 years, the WHO Programme for the Prevention of Blindness and Deafness has maintained a Global Data Bank on visual impairment with the purpose of storing the available epidemiological data on blindness and low vision. The Data Bank has now been updated to include studies conducted since the last update in 1994. An extensive literature search was conducted in international and national scientific and medical journals to identify epidemiological studies that fulfilled basic criteria for inclusion in the Data Bank, namely a clearly stated definition of blindness and low vision, and prevalence rates derived from population-based surveys. Sources such as National Prevention of Blindness Programmes, academic institutions or WHO country or regional reports were also investigated. Two-hundred-and-eight population-based studies on visual impairment for 68 countries are reported in detail, providing an up-to-date, comprehensive compilation of the available information on visual impairment and its causes globally.


Hyperbaric oxygen therapy of cerebral ischemia.
Hyperbaric oxygen (HBO) therapy of cerebral ischemia has been evaluated in a number of human and animal studies; however, there is presently no consensus on its efficacy. We present a review of animal and human studies on HBO therapy of cerebral ischemia as well as present potential mechanisms of action of HBO. Animal studies of HBO have shown promise by reducing infarct size and improving neurologic outcome. HBO has also been shown to inhibit inflammation and apoptosis after cerebral ischemia. Early reports in humans also suggested benefit in stroke patients treated with HBO. Recent randomized, controlled human studies, however, have not shown benefit, although all were limited by small sample size. Important differences between animal and human studies suggest HBO might be more effective in stroke within the first few hours and at a pressure of 2-3 ATA. The clinical usefulness of HBO in the treatment of cerebral ischemia is not yet certain. Attention to emerging pathophysiologic data should be taken into consideration in design of any future clinical trials of HBO in acute ischemic stroke.


Continuous culture of sessile human oropharyngeal microbiotas.
The microbiota of the human oropharynx plays an important role in health through involvement in the aetiology of infection and the carriage of adventitious pathogens. Despite this, there are few models available for the preclinical assessment of novel antimicrobials directed to the human throat. We have profiled bacterial consortia sampled from the palatine tonsil and posterior pharyngeal wall microbiotas of healthy adult volunteers (n = 10) using differential culture and 16S rRNA gene sequencing, together with PCR-denaturing gradient gel electrophoresis. The data generated were used to assess the validity of an oropharyngeal microcosm system based on replicated constant-depth film fermenters (CDFFs; n = 5), which were continuously fed using an artificial airway surface liquid. Developed microcosms exhibited significant homology to ex situ consortia according to principal components analysis, whilst compositional reproducibility was apparent in replicated models for tonsillar and pharyngeal inocula. Differential viable count data and Shannon-Weiner diversity indices indicated that representative tonsil and pharyngeal model systems achieved dynamic compositional stability about 6 days after inoculation which could be maintained for ≥20 days. In conclusion, the CDFF facilitated the continuous maintenance of bacteriologically stable microcosms that were compositionally similar to ex situ inocula.


Transcriptional upregulation of breast cancer resistance protein by 17beta-estradiol in ERalpha-positive MCF-7 breast cancer cells.
Breast cancer resistance protein (BCRP) confers resistance to certain anticancer drugs such as mitoxantrone, topotecan and SN-38. A putative estrogen response element (ERE) was located in the promoter region of the BCRP gene. The present study aimed to investigate whether human BCRP expression is regulated pretranscriptionally by 17beta-estradiol. Two recombinant plasmids (pcDNA3-promoter-BCRP and pcDNA3-CMV-BCRP) were designed to express the full-length BCRP cDNA enforced driven by its endogenous promoter containing a functional ERE and a control constitutive cytomegalovirus (CMV) promoter, respectively, which were transfected into estrogen receptor alpha (ERalpha)-positive MCF-7 and ERalpha-negative MDA-MB-231 breast cancer cell lines. 17beta-estradiol significantly upregulated BCRP mRNA and protein expression in a dose-dependent manner, and the effect was abolished by the antiestrogen tamoxifen. Furthermore, electrophoretic mobility shift assays demonstrated that the putative ERE in the promoter region of the BCRP gene and ERalpha are essential for transcriptional activation of BCRP by 17beta-estradiol. Taken together, our findings indicate that BCRP expression is upregulated by 17beta-estradiol via a novel pretranscriptional mechanism which might be involved in 17beta-estradiol-ER complexes binding to the ERE of BCRP promoter via the classical pathway to activate transcription of the BCRP gene.


The guanylyl cyclase-receptor family.
Guanylyl cyclase activity exists in the soluble and particulate fractions of most tissue homogenates. Recently, the mRNA encoding members of the enzyme family from both the soluble and particulate fraction have been cloned. The soluble form exists as a heterodimer, both subunits containing cyclase catalytic-like amino acid sequences. Both subunits must be expressed to observe enzyme activity. The particulate (plasma membrane) forms contain a single putative transmembrane domain that separates an extracellular, ligand-binding domain from an intracellular, protein kinase-like and cyclase catalytic region. The protein kinase-like domain appears to serve as an important regulatory element of the receptor.


Structure, stability, and electronic property of carbon-doped gold clusters Au(n)C- (n = 1-10): a density functional theory study.
The equilibrium geometric structures, relative stabilities, and electronic properties of Au(n)C(-) and Au(n+1)(-) (n = 1-10) clusters are systematically investigated using density functional theory with hyper-generalized gradient approximation. The optimized geometries show that one Au atom capped on Au(n-1)C(-) clusters is a dominant growth pattern for Au(n)C(-) clusters. In contrast to Au(n+1)(-) clusters, Au(n)C(-) clusters are most stable in a quasi-planar or three-dimensional structure because C doping induces the local non-planarity while the rest of the structure continues to grow in a planar mode, resulting in an overall non-2D configuration. The relative stability calculations show that the impurity C atom can significantly enhance the thermodynamic stability of pure gold clusters. Moreover, the effect of C atom on the Au(n)(-) host decreases with the increase of cluster size. The HOMO-LUMO gap curves show that the interaction of the C atom with Au(n)(-) clusters improves the chemical stability of pure gold clusters, except for Au3(-) and Au4(-) clusters. In addition, a natural population analysis shows that the charges in corresponding Au(n)C(-) clusters transfer from the Au(n)(-) host to the C atom. Meanwhile, a natural electronic configuration analysis also shows that the charges mainly transfer between the 2s and 2p orbitals within the C atom.


A model of enzyme adsorption and hydrolysis of microcrystalline cellulose with slow deactivation of the adsorbed enzyme.
Reduction in the activity and the concentration of the adsorbed enzyme are noted in the experimental data. Two alternative mechanisms, inactivation of the adsorbed enzyme and mass transfer of the enzyme from the bulk solution to the solution within the cellulose fibril where the cellulase is assumed to be inactive, are used to represent the decline in activity. The decline in concentration of the adsorbed enzyme is represented by a modest product inhibition and, more importantly, the assumption that the concentration of the adsorption sites is proportional to the square of the remaining substrate concentration. Measurements of both adsorbed enzyme and product concentration over time are used in determining parameter values. The model is applied to a series of experiments having a 10-fold range of substrate concentration and to an experiment in which the product is removed continuously. For both deactivation mechanisms, a very good representation of product concentration (standard deviation 3.6%) is obtained over the full period (168 h) of hydrolysis; the representation of adsorbed enzyme is, however, less accurate (standard deviation 6.7-6.8%).


Impact of unfavorable factors on outcomes among inoperable stage II-IV Nonsmall cell lung cancer patients treated with proton therapy.
To investigate the impact of unfavorable risk factors among patients with locally advanced nonsmall cell lung cancer (LA-NSCLC) treated with proton therapy (PT). From May 2008 through July 2015, 90 consecutive patients with unresectable stage II-IV (oligometastatic) NSCLC were treated with PT. Unfavorable factors including age ≥80 years, stage IV, weight loss >10% in 3 months, performance status (PS) ≥2, FEV1 < 1.0 or O2 dependency, prior lung cancer, prior lung surgery, prior 2nd cancer in the past 3 years, and prior chest irradiation were evaluated. All patients received standard fractionation of 1.8-2 Gy(RBE) (median dose, 70 Gy[RBE]). Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method. The impact of unfavorable factors was analyzed in Cox regression models. Twenty-six percent were favorable-risk, while 42%, 22%, and 10% had 1-, 2-, or ≥3 unfavorable factors. The 2-year OS was 52% and 45% (p = .8522), and 2-year PFS was 21% and 44% (p = .0207), for favorable and unfavorable risk patients, respectively. Among patients with stage III-IV, only PS ≥2 adversely impacted OS (p = .0015). Most patients treated with PT for LA-NSCLC have unfavorable risk factors. These patients had similar outcomes to favorable-risk patients. Enrollment in future clinical trials may improve if eligibility is less restrictive.


Laminin-5 gamma 2 chain expression in cervical intraepithelial neoplasia and invasive cervical carcinoma.
To analyze the expression of laminin-5 gamma 2 chain, a protein which plays a major role in keratinocyte migration, in cervical intraepithelial neoplasia (CIN), and invasive cervical carcinoma associated with high-risk oncogenic human papillomaviruses (HR-HPVs). The expression of laminin-5 gamma 2 chain protein has been analyzed by immunohistochemistry in 17 cases of low-grade squamous intraepithelial lesions (LSIL-CIN1), 35 high-grade squamous intraepithelial lesions (HSIL-CIN2/3), 18 microinvasive or invasive carcinomas, and three metastatic lymph nodes. All these lesions have been proved to contain HR-HPVs and were also positive for p16 protein which classically is overexpressed at all stages of cervical neoplasia and dysplasia linked with HR-HPVs. 20 cases of normal cervix served as controls. The expression of laminin-5 gamma 2 chain protein was observed in 100% of invasive or microinvasive carcinoma and in their related lymph node metastasis with an immunoreactivity located preferentially at the invasive front of the lesions. All the HSILs (100%) associated with invasive carcinoma were also positive. In contrast, in HSILs without associated invasive component, the expression of the protein has been found in only 34% of cases. In positive HSILs, laminin-5 gamma 2 protein was expressed in basal layers. In LSILs and normal epithelium, no expression of the protein was noted. We conclude the following: (i) the expression of laminin-5 gamma 2 is a late event in cervical carcinogenesis increasing with the grade of dysplastic lesions; (ii) laminin-5 gamma 2 expression facilitates the identification of invasive and microinvasive lesions which could be difficult to diagnose on the basis of routine stains; (iii) laminin-5 gamma 2 expression in HSILs could potentially identify those lesions with a more increased risk of tumor progression.


Paenibacillus lemnae sp. nov., an endophytic bacterium of duckweed (Lemna aequinoctialis).
A Gram-stain-variable, rod-shaped and endospore-forming bacterium, designated strain L7-75, was isolated from duckweed (Lemna aequinoctialis). Cells were motile with a monopolar flagellum. Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain L7-75(T) belonged to the genus Paenibacillus, and the closest phylogenetically related species were Paenibacillus uliginis N3/975(T) (98.5% 16S rRNA gene sequence similarity), Paenibacillus purispatii ES_M17(T) (98.5%), Paenibacillus lactis MB 1871(T) (98.2%), Paenibacillus campinasensis 324(T) (97.7%), Paenibacillus glucanolyticus S93(T) (97.7%) and Paenibacillus lautus ATCC 43898(T) (97.4%). Growth of strain L7-75(T) was observed at pH 7-10 and at 20-40 °C, and NaCl concentrations up to 5% (w/v) were tolerated. Major cellular fatty acids included anteiso-C15 : 0, C16 : 0 and anteiso-C17:0 that were present at 36.0%, 14.2 % and 10.0% of the total cellular fatty acid profile, respectively. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidyl-N-methylethanolamine. MK-7 was the predominant menaquinone. The diamino acid found in the cell-wall peptidoglycan was meso-diaminopimelic acid. The DNA G+C content was 49.1 mol% (Tm). DNA-DNA relatedness values between strain L7-75(T) and its closest relatives ranged from 4.4 to 47.8%. These results indicate that strain L7-75(T) represents a novel species of the genus Paenibacillus, for which the name Paenibacillus lemnae sp. nov. is proposed. The type strain is L7-75(T) ( = BCC 67838(T) = NBRC 109972(T)).


Anaesthetic management of a patient with severe pulmonary arterial hypertension for renal transplantation.
We describe a patient with severe pulmonary arterial hypertension scheduled to undergo live-related renal transplantation. We emphasise on meticulous anaesthetic management and early renal transplantation to prevent the progression of disease which would become refractory to treatment, leading to right ventricular failure. Regional (continuous epidural) anaesthesia has been used as technique of choice, where the selective advantages of this technique have been put to good use.


[Let's get indignant. Nursing memorandum for the 150 years anniversary of Italy: a perspective from its South].
Let's get indignant. Nursing memorandum for the 150 years anniversary of Italy: a perspective from its South. The 150th anniversary of the declaration of Italy as one nation is the occasion for a reflection on the historical and present gaps between various regions, considered from the perspective of the South and with a focus on what could/should be done by the health, and specifically, nursing profession. Proposals and initiatives to fill this gap are listed, such as the analysis of the differences, not for a mere description but for a discussion and implementation of strategies to try to overcome them, as well as an occasion to learn from each others; the creation of research networks, as a permanent resource for confrontation; the rise of a movement of indignation among nurses, to contrast the different answers to patients' rights and needs.


Nurse Informaticians Report Low Satisfaction and Multi-level Concerns with Electronic Health Records: Results from an International Survey.
This study presents a qualitative content analysis of nurses' satisfaction and issues with current electronic health record (EHR) systems, as reflected in one of the largest international surveys of nursing informatics. Study participants from 45 countries (n=469) ranked their satisfaction with the current state of nursing functionality in EHRs as relatively low. Two-thirds of the participants (n=283) provided disconcerting comments when explaining their low satisfaction rankings. More than one half of the comments identified issues at the system level (e.g., poor system usability; non-integrated systems and poor interoperability; lack of standards; and limited functionality/missing components), followed by user-task issues (e.g., failure of systems to meet nursing clinical needs; non nursing-specific systems) and environment issues (e.g., low prevalence of EHRs; lack of user training). The study results call for the attention of international stakeholders (educators, managers, policy makers) to improve the current issues with EHRs from a nursing perspective.


[Serum variations of 2 markers of fibrogenesis in chronic hepatitis C treated with alpha interferon].
We evaluated variations in serum levels of N-terminal peptide of type III procollagen (PIIIP) and laminin (Lam-P1) in 36 anti-HCV positive patients, confirmed by RIBA II, with chronic hepatitis treated with alpha interferon (IFN) at a dose of 6 million units (MU) three times for week for 6 months, followed by 3 MU three times for week for a further 6 months. We consider responders (R) those patients who after one year of therapy had normalized ALT levels, and non-responders (NR) the remaining subjects. Serum PIIIP and Lam-P1 were determined by RIA on entry to the study and at 12 months. Ten patients underwent a percutaneous liver biopsy also at the end of the therapy for the histological evaluation of the necroinflammatory activity and fibrosis according to the Knodell score system. Overall, at the end of therapy, the mean levels of both markers were lower than at entry to the study, with a statistically significance only for the Lam-P1 values (p < 0.05). When, however, we divided the patients into R (n = 15) and NR (n = 21) subgroups, the mean baseline values of both markers were significantly higher in NR vs controls and after therapy there was a significantly reduction only for PIIIP values (p < 0.01). In the group of R there is a slight, but not significantly reduction of both markers. The comparison of the Knodell's score before and after IFN treatment showed an improvement of the necroinflammatory activity, but not of fibrosis. In conclusion patients R to IFN therapy have lower baseline values of PIIIP and Lam-P1 than NR and therapy with IFN improves the serum values of PIIIP as well as the score of the necroinflammatory activity.


Changing What You Like: Modifying Contour Properties Shifts Aesthetic Valuations of Scenes.
To what extent do aesthetic experiences arise from the human ability to perceive and extract meaning from visual features? Ordinary scenes, such as a beach sunset, can elicit a sense of beauty in most observers. Although it appears that aesthetic responses can be shared among humans, little is known about the cognitive mechanisms that underlie this phenomenon. We developed a contour model of aesthetics that assigns values to visual properties in scenes, allowing us to predict aesthetic responses in adults from around the world. Through a series of experiments, we manipulate contours to increase or decrease aesthetic value while preserving scene semantic identity. Contour manipulations directly shift subjective aesthetic judgments. This provides the first experimental evidence for a causal relationship between contour properties and aesthetic valuation. Our findings support the notion that visual regularities underlie the human capacity to derive pleasure from visual information.


Nanoemulsions as an effective medium for encapsulation and stabilization of cholesterol/β-cyclodextrin inclusion complex.
Inclusion complex formation between β-cyclodextrin (β-CD) and suitable guest molecules such as cholesterol (Ch) has regularly been exploited to design self-assembled structures. In the present study an effective nanoemulsion medium (lecithin/Tween 80/ethyl oleate/water) was selected for solubilizing and stabilizing Ch and Ch/β-CD inclusion complex. Phase solubility, spectroscopic, thermodynamic, Z-average diameter and morphological analyses were conducted. Phase solubility data analysis demonstrated an increase in Ch solubility at low β-CD concentrations (0.01-0.35 mmol L(-1) ). Transmission electron microscopy and Z-average diameter data indicated the spherical nature of the droplets and confirmed the formation of nanoemulsions with an average size of less than 50 nm. The negative value of ΔG obtained during analysis further indicated that the binding was spontaneous in nature. Primarily, this research demonstrates the use of nanoemulsions as a medium in food matrices, instead of water, for hosting Ch in β-CD.


Diversity and population structure of northern switchgrass as revealed through exome capture sequencing.
Panicum virgatum L. (switchgrass) is a polyploid, perennial grass species that is native to North America, and is being developed as a future biofuel feedstock crop. Switchgrass is present primarily in two ecotypes: a northern upland ecotype, composed of tetraploid and octoploid accessions, and a southern lowland ecotype, composed of primarily tetraploid accessions. We employed high-coverage exome capture sequencing (~2.4 Tb) to genotype 537 individuals from 45 upland and 21 lowland populations. From these data, we identified ~27 million single-nucleotide polymorphisms (SNPs), of which 1 590 653 high-confidence SNPs were used in downstream analyses of diversity within and between the populations. From the 66 populations, we identified five primary population groups within the upland and lowland ecotypes, a result that was further supported through genetic distance analysis. We identified conserved, ecotype-restricted, non-synonymous SNPs that are predicted to affect the protein function of CONSTANS (CO) and EARLY HEADING DATE 1 (EHD1), key genes involved in flowering, which may contribute to the phenotypic differences between the two ecotypes. We also identified, relative to the near-reference Kanlow population, 17 228 genes present in more copies than in the reference genome (up-CNVs), 112 630 genes present in fewer copies than in the reference genome (down-CNVs) and 14 430 presence/absence variants (PAVs), affecting a total of 9979 genes, including two upland-specific CNV clusters. In total, 45 719 genes were affected by an SNP, CNV, or PAV across the panel, providing a firm foundation to identify functional variation associated with phenotypic traits of interest for biofuel feedstock production.


[Comparison of diagnostic value of coronary artery disease between ATP-stress and exercise-stress thallium myocardial SPECT images].
A study was made between adenosine triphosphate disodium (ATP)-stress thallium myocardial scintigrams and exercise-stress scintigrams to compare their respective extents and degree of defects. The subjects of the study were 33 ischemic heart disease patients, who received ATP stress and treadmill exercise stress with a mean interval of 25 days. ATP was infused for 5 minutes with an infusion rate of 0.16 or 0.18 mg per kg of body weight per minute. Thallium was injected three minutes after infusion. The percent-defect index (percentage of the extent and degree of the defects for all 33 patients), was calculated with visual scoring using a five-zone myocardial division method and semi-quantitative four-grade representation method for both the ATP and exercise SPECT images. The extent of the defects in ATP- and exercise-stress images was 51.5% and 44.2%, and that in redistribution images was 36.4% and 33.9%, respectively. The degree of defects in ATP- and exercise-stress images was 35.8% and 32.3%, while that in redistribution images was 20.8% and 17.2%, respectively (p = NS in all cases). In conclusion, the image quality of thallium SPECT with ATP stress was equivalent to that of exercise stress, indicating identical diagnostic values for coronary lesions.


Regularization of least squares problems in CHARMM parameter optimization by truncated singular value decompositions.
We examine the use of the truncated singular value decomposition and Tikhonov regularization in standard form to address ill-posed least squares problems Ax = b that frequently arise in molecular mechanics force field parameter optimization. We illustrate these approaches by applying them to dihedral parameter optimization of genotoxic polycyclic aromatic hydrocarbon-DNA adducts that are of interest in the study of chemical carcinogenesis. Utilizing the discrete Picard condition and/or a well-defined gap in the singular value spectrum when A has a well-determined numerical rank, we are able to systematically determine truncation and in turn regularization parameters that are correspondingly used to produce truncated and regularized solutions to the ill-posed least squares problem at hand. These solutions in turn result in optimized force field dihedral terms that accurately parameterize the torsional energy landscape. As the solutions produced by this approach are unique, it has the advantage of avoiding the multiple iterations and guess and check work often required to optimize molecular mechanics force field parameters.


[7 Tesla MRI for visualisation of small cerebral vessels].
Due to its higher resolution, MRI in which a magnet with a field strength of 7 Tesla (7T MRI) is used, is able to image smaller abnormalities. 7T MRI is a promising tool for research into the causes of cerebral small vessel disease. Originally this technique was aimed at imaging the small perforating brain vessels and in particular at the micro-thrombi present there. Although 7T MRI has not proved effective in showing thrombi in small blood vessels, it has proved itself to be effective on other fronts. Functional measurements of the small brain vessels can be reliably determined and abnormalities of the vessel wall can be imaged. However, the most promising development is the possibility of diagnosing so-called micro-infarctions of the cortex. These extremely small infarctions are an expression of ischaemic damage in degenerating small brain vessels, which for this reason are an important marker of brain ageing.


The Association Between Depression and Invasive and In-situ Cervical Tumors: A Large Population Based Cohort Study.
Depression has been shown to be associated with cervical tumors (CTs), an association mostly demonstrated in studies in which temporality could not have been ascertained. To study the association between depression and CTs and the influence of co-morbidities of this association in a large cohort study. A retrospective computer-based cohort study was conducted. The cohort included 357,450 female members of Maccabi Healthcare Services. The cohort was classified as depressed or non-depressed using the International Classification of Diseases 9/10 codes. For each subgroup, demographic characteristics, behavioral characteristics, co-morbidities, and CTs diagnosis were obtained. The burden of co-morbidities was defined as the sum of major co-morbidities. We used zero-inflated negative binomial regression analysis due to over-dispersion to estimate the relative risk (RR) for CTs with 95% confidence interval (95%CI). Depression was diagnosed in 15,789 women. Among this group, CTs were diagnosed in 1585 (10.0%). Among the 341,661 non-depressed, CTs were diagnosed in 4185 (1.2%). After adjustment to age and socioeconomic status, the association between depression and CTs was RR=9.2 (95%CI 8.7-9.9, P-value < 0.0001). The association between depression and CTs increased as the burden of clinical conditions increased (P-value < 0.0001). Women with depression are at a higher risk for CTs, especially among those who have several co-morbidities. Tighter gynecology surveillance is crucial among these women.


Histamine release induced by himan leukocyte lysates: implication of a specific, complement-independent, noncytotoxic reaction.
The characteristics of histamine release induced by human leukocyte lysates were determined. Intact human leukocytes released histamine during incubation with leukocyte lysates. Maximal release occurred under physiological conditions of temperature and pH, and both Ca(2+) and Mg(2+) were required. The addition of ethylenediaminetetraacetic acid abruptly inhibited release. Complement was not required, and serum actually inhibited release. Histamine release was maximal at lysate concentrations of 0.25 to 1.0 mug of protein per ml, and it was reduced at either higher or lower concentrations. Leukocytes continued to exclude trypan blue and maintained chemotactic activity after histamine release. Leukocytes released histamine independently of cellular protein or enzymes. Histamine release induced by leukocyte lysates was interrupted by subsequent removal of the lysate. The data suggest that this histamine release occurs by a specific, complement-independent, noncytotoxic process which resembles, but is not identical with, antigen-induced histamine release. The system has several unique characteristics which suggest that it is a novel form of inflammatory histamine release. This system should provide a useful in vitro model for studies of cellular processes in human inflammation.


Recapturing the art of therapeutic breast massage during breastfeeding.
Milk expression is a normal part of breastfeeding, but in developed countries in particular, the focus tends to center on mechanical expression. In Russia, there is a long tradition of hands-on techniques that continues in the present day and includes mothers turning to providers trained in hand expression and breast massage techniques to resolve breastfeeding complications including engorgement, plugged ducts, and mastitis. As observed over the course of several trips to Russia, Russian clinicians routinely combine hand expression with breast massage for the treatment of milk stasis, engorgement, and plugged ducts. A better understanding of these hands-on techniques to assist in resolution of complications may provide additional treatment options for the lactation community.


Third trimester growth restriction patterns: individualized assessment using a fetal growth pathology score.
To qualitatively and quantitatively characterize third trimester growth patterns in fetuses/neonates with growth restriction using Individualized Growth Assessment. Serial fetal size measurements from 73 fetuses with proven growth restriction were evaluated using a novel composite parameter, the Fetal Growth Pathology Score (FGPS1). Third trimester FGPS1 measurements plotted against fetal age were examined for patterns. Identified patterns were characterized using the four components of the FGP1 [head circumference (HC), abdominal circumference (AC), femur diaphysis length (FDL), estimated weight (EWT)]. A secondary characterization using age of onset, duration and magnitude of the growth abnormality process was also performed. Frequencies and magnitudes of abnormal values in different FGPS1 patterns were compared. Five growth restriction patterns were found in 70/73 (95.9%) of the cases, with progressive worsening [Pattern 1 (37.0%)] and abnormal growth identified only at last scan [Pattern 2 (27.4%)] being the most common. These two patterns were usually statistically different from each other and the other three with respect to size parameter abnormalities and abnormal growth process characteristics (MANOVA). Growth abnormalities in all parameters of the FGPS1 contributed to the five abnormality patterns although AC and EWT were most important. The age of onset, duration and magnitude were similar between patterns except for Pattern 2, which had a late onset and a short duration (GLM + contrasts). Our study represents the first detailed evaluation of third trimester growth restriction using methods that consider the growth potential of each fetus. Five distinctive and repetitive patterns were found, suggesting that fetal growth restriction evolves in different ways. Further research is needed to determine the relationships of these patterns to physiological/biochemical changes and adverse outcomes associated with growth restriction.


Memory T cells have gene expression patterns intermediate between naive and effector.
The biological basis underlying differentiation of naive (NAI) T cells into effector (EFFE) and memory (MEM) cells is incompletely understood. Furthermore, whether NAI T cells serially differentiate into EFFE and then MEM cells (linear differentiation) or whether they concurrently differentiate into either EFFE or MEM cells (parallel differentiation) remains unresolved. We isolated NAI, EFFE, and MEM CD8(+) T cell subsets from human peripheral blood and analyzed their gene expression by using microarrays. We identified 156 genes that strongly differentiate NAI, EFFE, and MEM CD8(+) T cells; these genes provide previously unrecognized markers to help identify each cell type. Using several statistical approaches to analyze and group the data (standard heat-map and hierarchical clustering, a unique circular representation, multivariate analyses based on principal components, and a clustering method based on phylogenetic parsimony analysis), we assessed the lineage relationships between these subsets and showed that MEM cells have gene expression patterns intermediate between NAI and EFFE T cells. Our analysis suggests a common differentiation pathway to an intermediate state followed by a split into EFFE or MEM cells, hence supporting the parallel differentiation model. As such, conditions under which NAI T cells are activated may determine the magnitude of both EFFE and MEM cells, which arise subsequently. A better understanding of these conditions may be very useful in the design of future vaccine strategies to maximize MEM cell generation.


[Socio-demographic and clinical characteristics of a patient population with diabetes mellitus].
To describe sociodemographic and clinical characteristics of a diabetic population. To relate sociodemographic and clinical evolutionaries variables. Descriptive transversal study. Three urban Primary Health Centers (PHC). Participants. Diabetic patients attended in these PHC.Measurements. sociodemographic and clinical through an individualized survey and a medical record review. 1495 patients were studied from whom 96% were diabetic type 2. Age: 66 years old (SD 12). Sex: 56% were women. Education level: 62 didn't have finished their primary studies. Family: 71% live together with a partner. Years of evolution: Diabetes (DM) < 10 years: 47% in type 1; 64% in type 2. DM 1: smokers 40%; hypertension (HTA) 7%; DM 2: smokers 12%; HTA 51%; obesity 26%; hypercholesterolemia 28%; hypertriglyceridemia 17%. Chronic complications: DM 1: retinopathy (DR) 26%; nephropathy (Nf) 3.5%; ischemic heart disease (IHD) 3.5%; periferic arteriopathy (PA) 7%; Cerebrovascular accident (CVA) 2%; peripheric neuropathy (PN) 5%. DM 2: DR 14%; Nf 13%; IHD 12%; PA 9%; CVA 5%; PN 4%; autonomic neuropathy 3%. Metabolic control DM 2: 67% HbA1c 7.5. Best metabolic control in DM with less years of evolution (p = 0.001). Treatment DM 2: 32% diet, 51% oral treatment, 13% insulin, 4% mixed. No relation with cultural level and family situation with metabolic control. In chronic complications only DR were more prevalent in patients with less cultural level (p = 0.037). Less cultural level doesn't influence neither metabolic control nor appearance chronic complications, except DR. The knowledge of diabetic population attended has allowed to detect the need of reinforce the intervention for decrease smoking and increase chronic complications detection.


Reply to the Comment on "Realization of Lewis Basic Sodium Anion in the NaBH3 - Cluster".
We reply to the comment by S. Pan and G. Frenking who challenged our interpretation of the Na- :→BH3 dative bond in the recently synthesized NaBH3 - cluster. Our conclusion remains the same as that in our original paper (https://doi.org/10.1002/anie.201907089 and https://doi.org/10.1002/ange.201907089). This conclusion is additionally supported by the energetic pathways and NBO charges calculated at UCCSD and CASMP2(4,4) levels of theory. We also discussed the suitability of the Laplacian of electron density (QTAIM) and Adaptive Natural Density Partitioning (AdNDP) method for bond type assignment. It seems that AdNDP yields more sensible results. This discussion reveals that the complex realm of bonding is full of semantic inconsistencies, and we invite experimentalists and theoreticians to elaborate this topic and find solutions incorporating different views on the dative bond.


Edge-Preserving Decomposition-Based Single Image Haze Removal.
Single image haze removal is under-constrained, because the number of freedoms is larger than the number of observations. In this paper, a novel edge-preserving decomposition-based method is introduced to estimate transmission map for a haze image so as to design a single image haze removal algorithm from the Koschmiedars law without using any prior. In particular, weighted guided image filter is adopted to decompose simplified dark channel of the haze image into a base layer and a detail layer. The transmission map is estimated from the base layer, and it is applied to restore the haze-free image. The experimental results on different types of images, including haze images, underwater images, and normal images without haze, show the performance of the proposed algorithm.


Pregnancy related issues in inflammatory bowel disease: evidence base and patients' perspective.
Inflammatory bowel disease (IBD) affects women of childbearing age and can influence fertility, pregnancy and decisions regarding breastfeeding. Women with IBD need to consider the possible course of disease during pregnancy, the benefits and risks associated with medications required for disease management during pregnancy and breastfeeding and the effects of mode of delivery on their disease. When indicated, aminosalicylates and thiopurines can be safely used during pregnancy. Infliximab and Adalimumab are considered probably safe during the first two trimesters. During the third trimester the placenta can be crossed and caution should be applied. Methotrexate is associated with severe teratogenicity due to its folate antagonism and is strictly contraindicated. Women with IBD tend to deliver earlier than healthy women, but can have a vaginal delivery in most cases. Caesarean sections are generally recommended for women with active perianal disease or after ileo-anal pouch surgery.While the impact of disease activity and medication has been addressed in several studies, there are minimal studies evaluating patients' perspective on these issues. Women's attitudes may influence their decision to have children and can positively or negatively influence the chance of conceiving, and their beliefs regarding therapies may impact on the course of their disease during pregnancy and/or breastfeeding. This review article outlines the impact of IBD and its treatment on pregnancy, and examines the available data on patients' views on this subject.


Moving beyond transition outcomes: meta-analysis of remission rates in individuals at high clinical risk for psychosis.
Recent evidence suggests that transition risks from initial clinical high risk (CHR) status to psychosis are decreasing. The role played by remission in this context is mostly unknown. The present study addresses this issue by means of a meta-analysis including eight relevant studies published up to January 2012 that reported remission rates from an initial CHR status. The primary effect size measure was the longitudinal proportion of remissions compared to non-remission in subjects with a baseline CHR state. Random effect models were employed to address the high heterogeneity across studies included. To assess the robustness of the results, we performed sensitivity analyses by sequentially removing each study and rerunning the analysis. Of 773 subjects who met initial CHR criteria, 73% did not convert to psychosis along a 2-year follow. Of these, about 46% fully remitted from the baseline attenuated psychotic symptoms, as evaluated on the psychometric measures usually employed by prodromal services. The corresponding clinical remission was estimated as high as 35% of the baseline CHR sample. The CHR state is associated with a significant proportion of remitting subjects that can be accounted by the effective treatments received, a lead time bias, a dilution effect, a comorbid effect of other psychiatric diagnoses.


[Sports and coronary heart disease].
The effectivity of an endurance physical training must not be ignored any longer as it is known that physical activity as well in the job as in the leisure time diminishes the risk of coronary artery disease and their consequences. The training should be put through according to the vigorous exercise training with 70 to 80% of the maximal work load in a dynamic work continuously for at least 10 minutes. The optimum duration appears to be about 30 to 40 minutes a day, repeated 3 to 4 times weekly. The best sports for coronary patients are jogging, cycling or bicycle ergometry, country cross skiing, walking in the mountains as well as at diminished performance capacity, gymnastic, walking, golf and with some restrictions swimming.


Screening for new MTHFR polymorphisms and NTD risk.
The enzyme, 5,10-methylenetetrahydrofolate reductase (MTHFR) plays a key role in cellular folate metabolism. The A222V (677C->T) polymorphism is a confirmed neural tube defect (NTD) risk factor within Irish and other populations. To search for other unknown single nucleotide polymorphisms (SNPs) that might play a role in the etiology of NTDs, we examined the entire MTHFR coding region in healthy individuals (n = 100). SNPs were identified using sequencing and database analysis and allele frequencies were determined in our Irish population. We identified P39P (116C->T; T allele frequency 0.13) and previously reported R594Q (1793G->A; Q allele frequency 0.07). We screened a large ethnically homogeneous Irish NTD cohort (n>1,300) for P39P and R594Q. A possible association between NTD cases and P39P (P = 0.034) was found but this was not confirmed by transmission disequilibrium testing. R594Q also showed some evidence of a NTD case association (P = 0.07). Further analysis indicated these observations are due to linkage disequilibrium with A222V (677C->T), and therefore these new SNPs are unlikely to be independent risk factors for NTDs. As rates of NTDs differ between ethnic groups, we examined allele and genotype frequencies of P39P and R594Q within African-American and American-Caucasian populations. This is the first NTD association study of both R594Q and the novel P39P. The association with NTD risk reported for these SNPs is driven by the linkage disequilibrium with the A222V (677C->T) NTD risk factor.


Mechanical Leeching with Venocutaneous Fistula and Monitoring with Near-infrared Spectroscopy.
The report herein describes the use of a venocutaneous fistula with angiocatheter attachment and near-infrared spectroscopy device to correct venous congestion of a vertical upper gracilis free flap used for breast reconstruction. This method of mechanical leeching was precisely controlled through monitoring trends in the tissue oxygen saturation levels of the flap, allowing venous congestion to be relieved before it became clinically apparent.


Early 3‑day course of remdesivir for the prevention of the progression to severe COVID‑19 in the elderly: A single‑centre, real‑life cohort study.
Remdesivir, a viral RNA polymerase inhibitor, has constituted a key component of therapeutic regimens against the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Originally approved for administration in hospitalized patients, remdesivir leads to improved outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving to be effective in hospitalized patients, its use gained approval in early-stage disease for symptomatic outpatients who are at a high risk of progression to severe disease. The present study is a real-life prospective cohort study involving 143 elderly non-hospitalized patients with SARS-CoV-2 (≥65 years of age) who attended the emergency department of the authors' hospital seeking care for COVID-19 symptoms appearing within the prior 7 days. Eligible patients received intravenous remdesivir at a dose of 200 mg on the first day and 100 mg on days 2 and 3. The efficacy endpoints were set as the need for COVID-19-related hospitalization and all-cause mortality in the following 28 days. A total of 143 patients participated in the study. Of these patients, 118 (82.5%) patients were vaccinated with at least two doses. All patients enrolled completed the 3-day course, with a total of 6 out of 143 patients (4.2%) having a COVID-19-related hospitalization by day 28, and 5 patients (3.5%) succumbing to the disease within the study period. In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio and haematological malignancy were identified as predictors of progression to severe disease, and albumin levels, the C-reactive protein-to-albumin ratio (CAR) and haematological malignancy were identified as predictors of 28-day mortality. On the whole, the findings of the present study demonstrated that among the elderly outpatients, a 3-day course of intravenous remdesivir was associated with favourable outcomes.


A Series of Linear {FeIII2 FeII } Complexes with Paramagnetic Building-Block-Modified Spin Crossover Behaviors.
Tuning of the spin crossover (SCO) behavior through paramagnetic building blocks with different steric hindrance effects is of great interest in terms of the synergy between SCO and magnetic interactions. Herein, the steric effect of specified FeIII building blocks is modified, from the large Tp* (hydridotris(3,5-dimethylpyrazol-1-yl)borate) analogue to a small Tp (hydrotris(pyrazolyl)borate) derivative; the FeII SCO unit and FeIII paramagnetic ions are incorporated into three well isolated trinuclear complexes featuring thermally induced and light-induced SCO properties. Reanalysis of the structures reveals that π-π stacking interactions play a key role in the thermal hysteresis and anomalous octahedral distortion parameter Σ around the FeII ion. The Tp* ligand showing the largest steric hindrance induces elongated FeII -N bond lengths and bending of the C≡N-FeII angle in 1, as well as having a relatively large electron donor effect, which leads to the lowest thermal transition temperature among the three compounds.