Role of carbon monoxide in glutamate receptor-induced dilation of newborn pig pial arterioles.
The hypothesis that glutamate dilates pial arterioles of newborn pigs through the production of carbon monoxide (CO) was addressed. Anesthesized newborn pigs were equipped with cranial windows to measure pial arteriolar responses to stimuli. Heme oxygenase (HO) inhibitors added topically inhibited dilation to glutamate and to specific glutamate receptor agonists. The initial dilation to glutamate (10(-5) M) was 22% from baseline without an inhibitor and decreased to 9% with the HO inhibitor chromium mesoporphyrin (CrMP). Inhibition of dilation upon HO inhibition was similar when specific glutamate receptor agonists were employed. RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid caused 24% dilation from the baseline without an inhibitor, and the dilation was decreased to 1% with tin protoporphyrin (SnPP). (RS)-2-amino-3-(3-hydroxy-5-t-butylisoxazol-4-yl)propionic acid (kainate receptors) caused dilation of 18% from baseline without an inhibitor, but only 2% when tin mesoporphyrin was applied. 1-Aminocyclopropanecarboxylic acid (N-methyl-D-aspartate receptors) dilated pial arterioles 33% from baseline in control, but only to 2% in the presence of SnPP. Neither copper mesoporphyrin, which does not inhibit HO, nor light-inactivated CrMP affected the dilations. Furthermore, cerebral microvessels removed from the brain produced CO (stable isotope dilution gas chromatography-mass spectrometry), and this production was dose dependently increased by glutamate and inhibited by metal porphyrin HO inhibitors. These data suggest that dilation of newborn pig pial arterioles to glutamate and specific glutamate receptor agonists involves vascular production of CO. Additional cerebral sources of CO also could be stimulated by glutamate and contribute to the dilation.


Menkes disease in affected females: the clinical disease spectrum.
Menkes disease (MD; OMIM 309400) is an X-linked, neurodegenerative disorder resulting from deficient activity of copper-dependent enzymes and caused by alterations in the APT7A gene. In its classic form, it manifests in boys with hypotonia, seizures, skin and joint laxity, hair twisting (pili torti), cerebrovascular tortuosity, and bladder diverticulae. Menkes disease phenotypes have been reported in females with X; autosome translocations-disrupting ATP7A gene function- or ATP7A gene alterations. Those females manifest variable clinical findings, some of which, such as pili torti, seizure presence and/or age of onset, cerebrovascular tortuosity, degree of intellectual disability, and bladder divericulae are largely under-reported and under-studied. Here, we report on three females with Menkes disease and variant phenotypes, sharing characteristic features, one with classic Menkes disease and two with Menkes disease variants. We conclude that Menkes disease in females manifests with a variable spectrum of clinical findings but a few are uniformly present such as neurodevelopmental disability, hypotonia, and connective tissue findings. Others, such as seizures, cerebral atrophy, and cerebrovascular tortuosity may be present but are under-reported and under- studied. We propose that the diagnosis of Menkes disease or variants in females with suspicious clinical findings is an important one to consider as early treatment with parenteral copper may be considered. The effect of this treatment on the disease course in females with MD is unknown and remains to be seen.


Doppler assessment of tracheal and nasal fluid flow during fetal breathing movements: preliminary observations.
Our aim was to determine if it was technically possible to assess fetal tracheal fluid flow during fetal breathing movements, and to compare the data obtained with those recorded in the fetal nasopharynx. Tracheal and nasal fluid flow was analyzed in ten uncomplicated pregnancies, the gestational age ranging between 28 and 38 weeks. Color Doppler was used to detect the fluid displacement in the trachea generated by fetal breathing movements. Spectral Doppler was then used to analyze the fluid flow velocity waveforms. During the same breathing episode, nasal fluid flow was assessed by the same technique. The inspiration and expiration times were variable and not statistically comparable for both nasal and tracheal flow. Peak velocities of inspired and expired fluid were higher in the trachea than in the nose (p < 0.05). We found that the peak velocity of tracheal flow waveforms was significantly higher for inspiration than expiration (p < 0.05). No significant differences were found in the time velocity integral between inspiration and expiration (p = 0.79). The calculated intratracheal flow volume displaced during one breathing cycle increased from 1.3 to 5.0 ml with advancing gestation. Assessment of nasal and tracheal flow, using color and spectral Doppler, is feasible in the human fetus. Intratracheal flow measurements may provide an insight into the effect of fetal breathing movements on lung fluid in the human fetus.


Renoportal anastomosis in living donor liver transplantation with prior proximal splenorenal shunt.
For transplant surgeons, end-stage liver disease with portal venous thrombosis and a previous splenorenal shunt (SRS) is a significant challenge during liver transplantation. Thrombosis of the portal vein can be corrected by surgical interventions, such as portal venous thrombectomy or surgical removal of the thrombosed portal vein. Even also placement of a graft between the mesenteric vein and the graft portal vein can be performed. If these maneuvers fail, a renoportal anastomosis (RPA) can be performed to achieve adequate graft inflow. A 51-year-old male patient who had a history of proximal SRS and splenectomy underwent living donor liver transplantation (LDLT) due to cryptogenic cirrhosis. LDLT was performed with RPA using a cadaveric iliac vein graft. The early postoperative course of the patient was completely uneventful and he was discharged 20 d after transplantation. To the best of our knowledge, this was the first patient to receive LDLT with RPA after surgical proximal SRS and splenectomy.


Detection of trichothecene mycotoxins in sera from individuals exposed to Stachybotrys chartarum in indoor environments.
To date, no study has effectively demonstrated a direct human exposure to mycotoxins in mold-contaminated buildings. Therefore, the authors investigated the presence of trichothecene mycotoxins in sera from individuals exposed to indoor molds (specifically Stachybotrys chartarum). Sera from occupants of contaminated (test samples, n=44) and uncontaminated (control samples, n=26) buildings were analyzed using a competitive enzyme-linked immunosorbent assay (ELISA) highly specific for macrocyclic trichothecenes. Twenty-three samples were significantly different (p < 0.05) from normal human serum tested in the same manner, whereas only 1 of the control samples tested positive. Mass spectrometry analysis could not confirm the presence of intact S. chartarum macrocyclic trichothecenes. The authors hypothesize that this result was caused by uncharacterized ELISA-reactive metabolic breakdown products. Data from this study suggest that trichothecene mycotoxins can be demonstrated in the tissues of certain individuals exposed to S. chartarum in contaminated buildings.


Lactate clearance for assessing response to resuscitation in severe sepsis.
Severe sepsis remains a major public health problem both with a high hospital mortality rate and with staggering associated health care expenditures. The past decade has seen new insights into the early resuscitation of severe sepsis and this is an important, controversial, and constantly changing topic to emergency physicians. In this article, the recent support for lactate clearance as a measure of early sepsis resuscitation effectiveness is summarized, lactate-derived to oxygen-derived resuscitation variables are compared, and the shortcomings of lactate-derived variables are described. As summarized in this article, the best available experimental evidence suggests that lactate clearance of at least 10% at a minimum of 2 hours after resuscitation initiation is a valid way to assess initial response to resuscitation in severe sepsis. Associative data suggest that lactate normalization during resuscitation is a more powerful indicator of resuscitative adequacy; however, further research on the optimal lactate clearance parameters to use during resuscitation is needed, and many other important questions have yet to be answered.


A vascular patch prepared from Thai silk fibroin and gelatin hydrogel incorporating simvastatin-micelles to recruit endothelial progenitor cells.
Delayed re-endothelialization is one of the major disadvantages in synthetic vascular grafts, especially in small-diameter grafts (inner diameter <6 mm), leading to thrombosis and stenosis of the grafts. Simvastatin, a serum cholesterol-lowering drug, has promotional effects on endothelial progenitor cell (EPC) mobilization from bone marrow and recruitment to sites of vascular injury exhibiting acceleration of re-endothelialization. In this study, we prepared double-layer vascular patches from Thai silk fibroin/gelatin with gelatin hydrogel incorporating simvastatin-micelles (SM) for sustained release of simvastatin to recruit circulation EPCs. To enhance simvastatin solubility, simvastatin was entrapped in micelles of l-lactic acid oligomer-grafted gelatin. The drug loading efficiency was at 4.1 ± 0.5 μg/mg micelles. SM had a chemoattractive effect on EPCs comparable to nonmodified simvastatin. Gelatin hydrogel incorporating SM at 100 μM of simvastatin (GSM100) could enhance in vitro EPC activities of adhesion and proliferation. In vitro results showed the initial cell adhesion of 86%, specific growth rate of 15.33×10(-3) h(-1), and population doubling time of 46.21 h. In vivo implantation of the patches incorporating SM significantly increased the recruitment of circulating EPCs. From the results of immunofluorescence staining, they demonstrated the complete re-endothelialization on the implanted patches containing SM at 2 weeks after implantation in rat carotid arteries. The gelatin hydrogel incorporating SM could be an effective inner layer of multifunctional vascular grafts to accelerate re-endothelialization in vascular tissue engineering.


Extrinsic innervation of the pelvic organs in the lesser pelvis of human embryos.
Realistic models to understand the developmental appearance of the pelvic nervous system in mammals are scarce. We visualized the development of the inferior hypogastric plexus and its preganglionic connections in human embryos at 4-8 weeks post-fertilization, using Amira 3D reconstruction and Cinema 4D-remodelling software. We defined the embryonic lesser pelvis as the pelvic area caudal to both umbilical arteries and containing the hindgut. Neural crest cells (NCCs) appeared dorsolateral to the median sacral artery near vertebra S1 at ~5 weeks and had extended to vertebra S5 1 day later. Once para-arterial, NCCs either formed sympathetic ganglia or continued to migrate ventrally to the pre-arterial region, where they formed large bilateral inferior hypogastric ganglionic cell clusters (IHGCs). Unlike more cranial pre-aortic plexuses, both IHGCs did not merge because the 'pelvic pouch', a temporary caudal extension of the peritoneal cavity, interposed. Although NCCs in the sacral area started to migrate later, they reached their pre-arterial position simultaneously with the NCCs in the thoracolumbar regions. Accordingly, the superior hypogastric nerve, a caudal extension of the lumbar splanchnic nerves along the superior rectal artery, contacted the IHGCs only 1 day later than the lumbar splanchnic nerves contacted the inferior mesenteric ganglion. The superior hypogastric nerve subsequently splits to become the superior hypogastric plexus. The IHGCs had two additional sources of preganglionic innervation, of which the pelvic splanchnic nerves arrived at ~6.5 weeks and the sacral splanchnic nerves only at ~8 weeks. After all preganglionic connections had formed, separate parts of the inferior hypogastric plexus formed at the bladder neck and distal hindgut.


Specific selection of antigen-reactive lymphocytes into antigenically stimulated lymph nodes in sheep.
Sheep were primed to a variety of antigens and the efferent lymphatic from a popliteal lymph node was cannulated. The cannulated node was challenged repeatedly with PPD and all the lymph and cells removed from the animal. During this time the PBL were monitored for reactivity to all antigens (purified protein derivative of tuberculin [PPD], johnin, and keyhole limpet hemocyanin [KLH]) by the vitro transformation assay. The response of these cells to PPD was found to be gradually eliminated after repeated challenge of the cannulated node with that antigen. The response to the other antigens was unimpaired. No depletion of this response to PPD occurred in cannulated sheep when the antigen was given into a noncannulated node. In vivo delayed-type hypersensitivity skin test and helper T cell assays confirmed that there is a specific selection of antigen-reactive cells from the recirculating lymphocyte pool into antigen-stimulated lymph nodes.


The Adverse Impact of Glaucoma on Psychological Function and Daily Physical Activity.
To evaluate the impact of glaucoma on vision-related quality of life and physical activity. This study included 50 glaucoma patients and 50 healthy control subjects. Sociodemographic and clinical data were collected from all subjects. A Chinese version of the NEI VFQ-25 was used to evaluate the quality of life. Objective physical activity was assessed by wearing an accelerometer for 7 consecutive days. No significant difference was found in sociodemographic data between the two groups (all p < 0.05). Visual acuity and visual field scores were worse in the glaucoma group than in the control group (all p < 0.001). The VFQ-25 scores indicated significantly lower scores for ocular pain, social function, mental health, role difficulties, and color vision in the glaucoma group than in the normal group (all p < 0.05). The average daily step count was lower in the glaucoma group than in the normal group. High, moderate, and low average daily step counts in the glaucoma group were associated with early-, moderate-, and advanced-stage glaucoma, respectively, while the step count was significantly lower in the advanced-stage glaucoma group than in the control group (p=0.037). A positive relationship was found between the average daily step count and social function and mental health (both p < 0.05). We demonstrated an adverse impact of glaucoma on psychological function and daily physical activity. Social function and mental health showed declines in glaucoma patients, and physical activity was limited in patients with advanced-stage glaucoma.


Transplantation of liver grafts from older donors: impact on recipients with hepatitis C virus infection.
Older donor allografts are being accepted for liver transplantation (LTx) due to shortage of organs. Hepatitis C virus (HCV) infection-related disease is presently the most common indication of LT in the United States. We studied the impact of donor age on patient and graft survivals in patients with HCV infection. One hundred fifty four consecutive HCV(+) LTx recipients (117 men, 37 women) were studied. The mean follow-up period was 41.0 +/- 30.2 months. The population was divided into four groups according to donor age: group I (< or =20 years); group II (21 to 40 years); group III (41 to 60 years); group IV (>60 years). Thirty-two (20.8%) patients died during follow-up and 16 patients (10.4%) required retransplantation. The actuarial 7-year patient survivals for groups I, II, III, and IV were 87.1%, 73.7%, 69.3%, and 68.5%, respectively (P = .4). Patient survivals for donor age groups III + IV (n = 95) and groups I + II (n = 59) were 68.9% and 77.2%, respectively (P = .19). The 7-year graft survivals for groups I, II, III, and IV were 82.7%, 71.8%, 65.8%, and 62.5%, respectively (P = .17). Graft survivals for groups III + IV and groups I + II were 58.4% and 76.2%, respectively (P = .03). Patient and graft survivals for HCV-positive liver transplant recipients in this study decreased progressively as the donor age increased. Patient and graft survivals were best for group I recipients. There were significant differences in graft survivals when recipients were grouped with a cutoff donor age of 40 years.


Development of high-resolution cathodoluminescence system for STEM and application to plasmonic nanostructures.
A high-resolution cathodoluminescence (CL) system for scanning transmission electron microscope (STEM) has been developed by employing a field emission gun and a spherical aberration corrector, which realizes a probe size of 1 nm even at an accelerating voltage of 80 kV and beam current of the order of 1 nA. Angle resolved measurement of light emission from a sample in the STEM is possible by combining a parabolic mirror and position-controlled pinhole. CL spectra are successively acquired by a highly sensitive charge-coupled device while scanning the incident electron beam or pinhole, which enables various detection modes, i.e. (i) angle resolved spectral pattern, (ii) beam scan spectral image and (iii) photon map. In order to calibrate the acquired spectrum, the correction function is created from the comparison between the observed and theoretical spectra of the transition radiation. Furthermore, the modification of polarization by the parabolic mirror is discussed. Some examples of the applications of the STEM-CL system to plasmonics are presented to demonstrate the unique measurement features of the CL system, i.e. (i) multipole modes in silver nanoparticles, (ii) surface plasmon polariton modes in a 2D plasmonic crystal and (iii) localized surface plasmon modes in a gold bow tie nano-antenna.


A Case of Adams-Oliver Syndrome.
Adams-Oliver syndrome (AOS) is a rare congenital disorder with unknown etiology commonly presented with aplasia cutis and terminal limb defects. Central nervous and cardiopulmonary systems may also be affected. It is commonly inherited as an autosomal dominant disorder but autosomal recessive and sporadic cases have also been reported. Here, we present a 10-year-old boy with extensive aplasia cutis congenita and limb anomalies as well as mild pachygyria and focal acrania in neuroimaging. No other internal organ involvement was obvious in this patient. Family history was negative for this syndrome. AOS is a multisystem disorder, and so it is crucial to investigate for internal organ involvements.


[Detection of tumor circulating cells in patients with ocular melanoma].
The authors investigated a group of 51 patients (29 men and 22 women) with intraocular melanoma: 41 patients with melanoma of the chorioid, 10 patients with melanoma of the ciliary body. They evaluated the clinical and pathological finding according to the TNM classification recommended by UICC (International Union Against Cancer). In all investigated patients they assessed circulating tumour cells (melanocytes) in the peripheral blood stream based on the detection of mRNA tyrosinase and marker MART 1. When evaluating the presence of markers according to the diagnosis irrespective of time, they found in patients in the clinical stage of T2 choroidal melanoma a 19% positivity of different markers and very rare a concurrent positivity of both markers. Patients in the clinical stage T3 had a 51% positivity of one marker and 34% concurrent positivity of both markers. In melanoma of the ciliary body evidence of individual markers was positive in 17% and only in 11% both markers were positive concurrently. On comparison of therapeutic procedures from the aspect of development in time in patients treated by brachytherapy only rare positivity was found at the time of administration the radioactive plaque, following an eight-month interval after brachytherapy the positivity of markers increased to 28%. On evaluation of markers of choroidal melanoma and ciliary body melanoma resolved by enucleation had their positivity at the time of operation was 36%, and during check-ups up to one year or longer it persisted at similar levels. Concurrent presence of both markers before this operation was rare, during postoperative check-up examinations it was within a range of 23 and 33%. The presence of both markers was repeatedly proved in five patients with chooidal melanoma after enucleation of the eye, in four of them in direct correlation with a metastatic process.


[A case of para-aortic lymph node metastasis from gastric cancer treated with chemoradiotherapy].
A 64-year-old man was diagnosed as having advanced gastric cancer with peritoneal and para-aortic lymph node metastases. He received 2 courses of chemotherapy with S-1 and cisplatin( CDDP) and 5 courses of combination chemotherapy with capecitabine, CDDP, and trastuzumab. The peritoneal and para-aortic lymph node metastases disappeared after chemotherapy, and subsequently, total gastrectomy was performed (pT2N3aM0, stage IIIA). Although the patient received combination chemotherapy with capecitabine and trastuzumab, para-aortic lymph node recurrence was noted 6 months after the operation. Radiation therapy at a total dose of 50 Gy targeted at the para-aortic lymph node metastasis along with S-1 and trastuzumab chemotherapy was administered. No serious adverse effects were observed during chemoradiotherapy. Following chemoradiation therapy, tumor recurrence was not observed. Therefore, chemoradiotherapy is considered an effective treatment for lymph node metastasis from gastric cancer.


Circ_0003732 promotes osteosarcoma progression through regulating miR-377-3p/CPEB1 axis and Wnt/β-catenin signaling pathway.
Osteosarcoma is a prevalent malignant bone cancer. This study aimed to explore the biologic role and potential mechanism of circ_0003732 in osteosarcoma carcinogenesis. Quantitative real-time PCR was implemented to detect the RNA expression of circ_0003732, microRNA-377-3p (miR-377-3p) and cytoplasmic polyadenylation element-binding protein 1 (CPEB1). Cell proliferation was evaluated by cell counting kit-8 assay and colony formation assay. Transwell, wound healing and flow cytometry assays were employed to assess cell migration, invasion and apoptosis. In addition, the interaction between miR-377-3p and circ_0003732 or CPEB1 was validated by dual-luciferase reporter assay. The protein expression was detected by western blot assay or immunohistochemistry assay. Xenograft tumor assay was performed to explore the regulation of circ_0003732 on osteosarcoma tumor growth in vivo. Circ_0003732 was upregulated in osteosarcoma tissues and cells. Knockdown of circ_0003732 suppressed osteosarcoma cell proliferation, migration, invasion and triggered cell apoptosis in vitro, as well as reduced osteosarcoma tumor growth in vivo. Meanwhile, miR-377-3p could bind to circ_0003732 and CPEB1 and miR-377-3p inhibitor could reverse the effects of circ_0003732 silence on osteosarcoma cell progression. Furthermore, CPEB1 overexpression could overturn the suppressive impacts of miR-377-3p on osteosarcoma progression. In addition, circ_0003732 silence restrained Wnt/β-catenin signaling pathway via regulating miR-377-3p in osteosarcoma cells. Circ_0003732 might play a positive role in the malignant progression of osteosarcoma by regulating the miR-377-3p/CPEB1 axis and activating the Wnt/β-catenin signaling pathway, which might provide new insights for osteosarcoma therapy.


Genome-wide binding analysis of AtGNC and AtCGA1 demonstrates their cross-regulation and common and specific functions.
GATA transcription factors are involved in multiple processes in plant growth and development. Two GATA factors, NITRATE-INDUCIBLE,CARBON METABOLISM-INVOLVED (GNC) and CYTOKININ-RESPONSIVE GATA FACTOR 1 (CGA1, also named GNL), are important regulators in greening, flowering, senescence, and hormone signaling. However, their direct target genes related to these biological processes are poorly characterized. Here, GNC and CGA1 are shown to be transcription activators and by using chromatin immunoprecipitation sequencing (ChIP-seq), 1475 and 638 genes are identified to be associated with GNC and CGA1 binding, respectively. Enrichment of diverse motifs in the peak binding regions for GNC and CGA1 suggests the possibility that these two transcription factors also interact with other transcription factors and in addition genes coding for DNA-binding proteins are highly enriched among GNC- and CGA1-associated genes. Despite the fact that these two GATA factors are known to share a large portion of co-expressed genes, our analysis revealed a low percentage of overlapping binding-associated genes for these two homologues. This suggests a possible cross-regulation between these, which is verified using ChIP-qPCR. The common and specific biological processes regulated by GNC and CGA1 also support this notion. Functional analysis of the binding-associated genes revealed that those encoding transcription factors, E3 ligase, as well as genes with roles in plant development are highly enriched, indicating that GNC and CGA1 mediate complex genetic networks in regulating different aspects of plant growth and development.


Melanoma stem cell maintenance and chemo-resistance are mediated by CD133 signal to PI3K-dependent pathways.
Melanoma stem cells (MSCs) are characterized by their unique cell surface proteins and aberrant signaling pathways. These stemness properties are either in a causal or consequential relationship to melanoma progression, treatment resistance and recurrence. The functional analysis of CD133+ and CD133- cells in vitro and in vivo revealed that melanoma progression and treatment resistance are the consequences of CD133 signal to PI3K pathway. CD133 signal to PI3K pathway drives two downstream pathways, the PI3K/Akt/MDM2 and the PI3K/Akt/MKP-1 pathways. Activation of PI3K/Akt/MDM2 pathway results in the destabilization of p53 protein, while the activation of PI3K/Akt/MKP-1 pathway results in the inhibition of mitogen-activated protein kinases (MAPKs) JNK and p38. Activation of both pathways leads to the inhibition of fotemustine-induced apoptosis. Thus, the disruption of CD133 signal to PI3K pathway is essential to overcome Melanoma resistance to fotemustine. The pre-clinical verification of in vitro data using xenograft mouse model of MSCs confirmed the clinical relevance of CD133 signal as a therapeutic target for melanoma treatment. In conclusion, our study provides an insight into the mechanisms regulating MSCs growth and chemo-resistance and suggested a clinically relevant approach for melanoma treatment.


Anomalously low endemic goiter prevalence among Efe pygmies.
The existence of endemic goiter, caused by iodine deficiency and the presence of a dietary goitrogen, has been noted in eastern Zaire by a number of authors (De Visscher et al.: Journal of Clinical Endocrinology and Metabolism 21:175-188, 1961; Delange et al.: Journal of Clinical Endocrinology and Metabolism 34:1059, 1972). In the Ituri Forest of Huate-Zaire, two distinct populations, the Efe (pygmy) and Lese (Bantu), live in association with each other and have similar diets. The goiter survey reported here documents differences in goiter prevalence and severity between the nomadic pygmy and village-living Bantu populations. While the Efe have an overall goiter prevalence of 9.4%, the Lese have a goiter prevalence of 42.9%. Furthermore, Efe women living in Lese villages and subsisting on a Lese diet have a prevalence of goiter similar to that of forest-living Efe women. Village-living individuals born of Efe mothers and Lese fathers have a prevalence of goiter greater than that of pure Efe but less than that of Lese. While our data cannot exclude dietary explanations for the difference in goiter prevalence between the Efe and Lese, they do support the hypothesis that the Efe possess an adaptation to an iodine-deficient environment that does not result in the development of goiters.


Growing Safe: Acute Size Escape from Desiccation in Juvenile Crepipatella peruviana (Mollusca: Gastropoda).
Desiccation is an important limiting factor in the intertidal zone. Generally decreasing seaward, desiccation stress can also be alleviated in wet microhabitats. Juvenile snails are generally more susceptible to desiccation than adults, and, for some species, juveniles must therefore hide in microhabitats to survive emersion. The transition from hiding in safe microhabitats to being able to survive fully exposed for the duration of low tide is not well documented. In this study, we investigated the influence of size on desiccation tolerance in juveniles of the calyptraeid gastropod Crepipatella peruviana to determine the size at which they can first survive exposure to air. Juveniles 2-13 mm long were exposed to 75% or 100% relative humidity for 0.5-6.5 hours. Juveniles smaller than 5 mm in shell length did not survive emersion at 75% relative humidity for even 0.5 hours; surprisingly, most also perished after short exposures to air at 100% relative humidity, suggesting that something other than desiccation stress may also be at play. In marked contrast, 82% of juveniles larger than 6 mm in shell length survived exposure to 75% relative humidity for the full 6.5 hours. In a field survey, no juveniles smaller than 9 mm were found on exposed rock but rather were found only in wet microhabitats. We suggest that the clearly defined size escape from desiccation may reflect a change in gill functioning or a newfound ability to retain water more effectively within the mantle cavity at low tide.


Induction of a hypertrophic growth status of coronary smooth muscle cells is associated with an overexpression of TGF-beta.
Hypertrophy of vascular smooth muscle cells occurs during hypertension-induced remodelling of arteries and during development of arteriosclerosis and restenosis following angioplasty but the pathogenesis of the hypertrophic status is not yet fully understood. In a previous study we demonstrated that the synthetic non-sulfated, non-toxic heparin-mimicking compound RG-13577 is capable of inducing a cell cycle-arrested hypertrophic phenotype of coronary smooth muscle cells. In this study we clarify the mode of action of RG-13577 and demonstrate that the RG-13577-induced hypertrophy is associated with an increased expression of TGF-beta1 as indicated by an increase in TGF-beta1-specific protein and mRNA level. Furthermore we show that RG-13577-treated hypertrophic smooth muscle cells maintain full metabolic activity as indicated by a continuous de novo synthesis of protein and proteoglycans and that the RG-13577-induced growth arrest is caused not only by a higher expression of TGF-beta, but also by a reduced response of RG-treated cells to the mitogenic activity of bFGF, PDGF and EGF. The growth inhibitory activity of RG-13577 is reduced in the presence of neutralizing antibodies against TGF-beta. TGF-beta itself has anti-proliferative activity in serum-depleted medium. The RG-13577 effect is reversible since incubation of hypertrophic cells in RG-13577-free medium restores cell volume and [3H]thymidine incorporation to the values of untreated control cells within 4 days. We conclude, that the active metabolic status of RG-13577-treated cells in association with the overexpression of TGF-beta could promote repair processes of injured arteries after angioplasty without stimulating cell proliferation.


Phase Behavior and Dynamics of the Liquid Crystal 4'-butyl-4-(2-methylbutoxy)azoxybenzene (4ABO5*).
The results of dielectric relaxation spectroscopy and polarizing microscope observation of the 4'-butyl-4-(2-methylbutoxy)azoxybenzene (abbreviated as 4ABO5*) are presented. Numerical analysis of the dielectric spectra results points to complex dynamics of 4ABO5* molecules in isotropic, cholesteric, and crystalline phases. Two well-separated maxima on the imaginary part of dielectric permittivity and the third low frequency relaxation process, hidden in the conductivity region, were detected and described in cholesteric and crystalline phases. Temperature dependence of mean relaxation times characterizing flip-flop motions and rotation around long axes, observed in all phases, is of the Arrhenius type.


The marine intertidal zone shapes oyster and clam digestive bacterial microbiota.
Digestive microbiota provide a wide range of beneficial effects on host physiology and are therefore likely to play a key role in marine intertidal bivalve ability to acclimatize to the intertidal zone. This study investigated the effect of intertidal levels on the digestive bacterial microbiota of oysters (Crassostrea gigas) and clams (Ruditapes philippinarum), two bivalves with different ecological niches. Based on 16S rRNA region sequencing, digestive glands, seawater and sediments harbored specific bacterial communities, dominated by operational taxonomic units assigned to the Mycoplasmatales,Desulfobacterales and Rhodobacterales orders, respectively. Field implantation modified digestive bacterial microbiota of both bivalve species according to their intertidal position. Rhodospirillales and Legionellales abundances increased in oysters and clams from the low intertidal level, respectively. After a 14-day depuration process, these effects were still observed, especially for clams, while digestive bacterial microbiota of oysters were subjected to more short-term environmental changes. Nevertheless, 3.5 months stay on an intertidal zone was enough to leave an environmental footprint on the digestive bacterial microbiota, suggesting the existence of autochthonous bivalve bacteria. When comparing clams from the three intertidal levels, 20% of the bacterial assemblage was shared among the levels and it was dominated by an operational taxonomic unit affiliated to the Mycoplasmataceae and Spirochaetaceae families.


Exploring binding stability of hydroxy-3-(4-hydroxyphenyl)-5-(4-nitrophenyl)-5,5a,7,8,9,9a-hexahydrothiazolo[2,3-b] quinazolin-6-one with T790M/L858R EGFR-TKD.
Cancer causes innumerable deaths every year globally. Breast cancer and non-small cell lung carcinoma are the most prevalent worldwide. EGFR-TKD is a neoplastic survival therapeutic target in a wide array of carcinoma cells. Various non-specific tyrosine kinase inhibitors lead to hyperphosphorylation and overexpression of EGFR-TKD and further mutations recognise deletion of exon 19. In this work, we study the binding affinity, binding stability, and strength of hydroxy-3-(4-hydroxyphenyl)-5-(4-nitrophenyl)-5,5a,7,8,9,9a-hexahydrothiazolo[2,3-b] quinazolin-6-one with TMLR mutated EGFR-TKD (T790M/L858R). The collective motions, residual mobility, and flexibility of TMLR mutated EGFR-TKD bound with reference and title molecule were calculated by principal component analysis. The meta-state conformations of both the simulated complexes were determined by Gibb's energy landscape analysis. The binding affinity exhibited by thiazolo-[2,3-b] quinazolinone and the reference molecule was found to be -7.95 ± 0.088 Kcal/mol and -9.13 ± 0.018 kcal/mol with TMLR mutated EGFR-TKD. The alignment of both the docked complexes was done by blosum40 matrix. Similar spatial orientations were exhibited by the synthesised ligand in the binding pocket of TMLR mutated EGFR-TKD, corresponding to the reference ligand. The ligand stability was computed for 100 ns. In addition, the radius of gyration, solvent accessible surface area, hydrogen bonds formed was calculated. The average ΔGbind of thiazolo-[2,3-b] quinazolinone was -41.212 ± 0.834 kJ/mol and for reference ligand -71.938 ± 0.367 kJ/mol, calculated by MM-PBSA. ADMET analysis concludes thiazolo-[2,3-b] quinazolinone derivative is safe. Further research work is encouraged to determine the efficacy of thiazolo-[2,3-b] quinazolinone against in vivo models.Communicated by Ramaswamy H. Sarma.


Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies.
The scientific literature presents conflicting data on a possible causal relationship between marijuana users and the development of head and neck cancer. This study performed a systematic review with meta-analysis. Articles were selected from various electronic databases using keywords obtained from the Medical Subject Headings (MeSH). After reading by three reviewers and scoring of methodological quality, six articles (totaling nine case-control studies) were assessed with Comprehensive Meta-Analysis(®) software. The value of effect (odds ratio) was calculated, which represented the chance of developing head and neck cancer between individuals who had smoked marijuana in their lifetime in models controlled for age, gender, race, and tobacco consumption. Approximately 12.6% of cases and 14.3% of controls were marijuana users. The meta-analysis found no association between exposure and disease (OR=1.021; IC 95%=0.912-1.14; p=0.718). No association between lifetime marijuana use and the development of head and neck cancer was found. The different methods of collection/presentation of results in the selected articles prevented other analyzes from being conducted. Additional studies are needed to assess for long-term effects.


[Predictive factors of facial palsy of the acoustic neurinoma after retrosigmoid surgery: 230 cases].
To determine predictive factors influencing postoperative facial palsy during retro sigmoid approach in vestibular schwannoma surgery. Retrospective study over 230 patients with vestibular schwannoma, mostly stade I and II, operated by retro sigmoid approach, by the same oto neuro chirurgical team between 1993 and 2004. Pre and post operative parameters taken into consideration: quantitative: age and sex, audiometric parameters, duration of clinical symptoms; qualitative: tumor anatomic factors and facial nerve function according to House Brackmann classification. 8 days after surgery, 92% of patients have a normal or subnormal facial nerve function, 5% a facial paresis and 3% a paralysis. After one year, only 4% of patients still have a grade III to VI paralysis. Latency of vertigo with facial nerve paralysis is 4.33 vs. 1.97 year in absence of paralysis. Hearing conservation is 85% without facial nerve paralysis vs. 58% with facial nerve paralysis; Wave III latency (PEAP) with facial nerve paralysis is 4.54 vs. 4.28 ms if not. Significant predictive factors of facial nerve palsy outcome are: age, post surgery hearing conservation, wave III latency, difficulty in tumor dissection, vertigo latency.


Inhibition of NAMPT decreases cell growth and enhances susceptibility to oxidative stress.
Nicotinamide adenine dinucleotide (NAD) is an essential molecule for living organisms and plays a vital role in aging and age-associated diseases. In eukaryotic cells, cellular NAD is mainly generated by the scavenge pathway in which nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the formation of nicotinamide mononucleotide. Inhibition of NAMPT is a therapeutic strategy for cancer treatment. To explore the effects of NAMPT inhibition on cellular processes, cells were treated with 10 nM FK866, an NAMPT inhibitor, resulting in a decrease in the cellular NAD level, a lower growth rate, and enhanced susceptivity to oxidative stress as compared to the untreated cells. Quantitative proteomics revealed that 325 proteins were downregulated in the FK866-treated cells, and were involved in diverse cellular processes including nucleobase-containing compound metabolic process, protein metabolic process, antioxidant and DNA repair processes. Downregulation of 4 selected proteins was confirmed by western blotting and quantitative PCR. Downregulation of antioxidant proteins GRX1 and catalase, and DNA-repair proteins PCNA and PARP1 contributed to the enhanced susceptibility of FK866-treated cells to oxidative stress. FK866 treatment also caused mitochondrial dysfunction through downregulation of mitochondrial ribosomal proteins. Taken together, these results demonstrate that FK866 treatment efficiently decreases the cellular NAD level and induces autonomous changes in proteostasis, leading to cell growth inhibition and increased susceptibility to oxidative stress.


The transcriptional regulator RovS controls the attachment of Streptococcus agalactiae to human epithelial cells and the expression of virulence genes.
Streptococcus agalactiae is part of the normal flora of the human gastrointestinal tract and also the leading cause of bacterial infections in human newborns and immunocompromised adults. The colonization and infection of different regions within the human host require a regulatory network in S. agalactiae that senses environmental stimuli and controls the formation of specific virulence factors. In the present study, we characterized an Rgg-like transcriptional regulator, designated RovS (regulator of virulence in Streptococcus agalactiae). Deletion of the rovS gene in the genome of S. agalactiae resulted in strain 6313 DeltarovS, which exhibited an increased attachment to immobilized fibrinogen and a significant increase in adherence to the eukaryotic lung epithelial cell line A549. Quantification of expression levels of known and putative S. agalactiae virulence genes by real-time PCR revealed that RovS influences the expression of fbsA, gbs0230, sodA, rogB, and the cyl operon. The altered gene expression in mutant 6313 DeltarovS was restored by plasmid-mediated expression of rovS, confirming the RovS deficiency as the cause for the observed changes in virulence gene expression in S. agalactiae. DNA electrophoretic mobility shift assays showed that RovS specifically binds to the promoter regions of fbsA, gbs0230, sodA, and the cyl operon, indicating that RovS directly regulates their expression. Deletion and mutation studies in the promoter region of fbsA, encoding the main fibrinogen receptor in S. agalactiae, identified a RovS DNA motif. Similar motifs were also found in the promoter regions of gbs0230, sodA, and the cyl operon, and alignments allowed us to propose a consensus sequence for the DNA-binding site of RovS.


New Insights on the Role of Marinobufagenin from Bench to Bedside in Cardiovascular and Kidney Diseases.
Marinobufagenin (MBG) is a member of the bufadienolide family of compounds, which are natural cardiac glycosides found in a variety of animal species, including man, which have different physiological and biochemical functions but have a common action on the inhibition of the adenosine triphosphatase sodium-potassium pump (Na+/K+-ATPase). MBG acts as an endogenous cardiotonic steroid, and in the last decade, its role as a pathogenic factor in various human diseases has emerged. In this paper, we have collated major evidence regarding the biological characteristics and functions of MBG and its implications in human pathology. This review focused on MBG involvement in chronic kidney disease, including end-stage renal disease, cardiovascular diseases, sex and gender medicine, and its actions on the nervous and immune systems. The role of MBG in pathogenesis and the development of a wide range of pathological conditions indicate that this endogenous peptide could be used in the future as a diagnostic biomarker and/or therapeutic target, opening important avenues of scientific research.


Estimation of L-threonine requirements for Longyan laying ducks.
A study was conducted to test six threonine (Thr) levels (0.39%, 0.44%, 0.49%, 0.54%, 0.59%, and 0.64%) to estimate the optimal dietary Thr requirements for Longyan laying ducks from 17 to 45 wk of age. Nine hundred Longyan ducks aged 17 wk were assigned randomly to the six dietary treatments, where each treatment comprised six replicate pens with 25 ducks per pen. Increasing the Thr level enhanced egg production, egg weight, egg mass, and the feed conversion ratio (FCR) (linearly or quadratically; p<0.05). The Haugh unit score, yolk color, albumen height, and the weight, percentage, thickness, and breaking strength of the eggshell did not response to increases in the Thr levels, but the albumen weight and its proportion increased significantly (p<0.05), whereas the yolk weight and its proportion decreased significantly as the Thr levels increased. According to a regression model, the optimal Thr requirement for egg production, egg mass, and FCR in Longyan ducks is 0.57%, while 0.58% is the optimal level for egg weight from 17 to 45 wk of age.


Technique for CT Fluoroscopy-Guided Lumbar Medial Branch Blocks and Radiofrequency Ablation.
The purpose of this study is to describe the procedure for CT fluoroscopy-guided lumbar medial branch blocks and facet radiofrequency ablation. CT fluoroscopic guidance allows more-precise needle tip positioning and is an alternative method for performing medial branch blocks and facet radiofrequency ablation.


Gold catalyzed cyclization of alkyne-tethered dihydropyrimidones.
Dihydropyrimidones are an important class of biologically active heterocycles accessible from the multicomponent Biginelli condensation. Further manipulation of the dihydropyrimidone skeleton gives access to unique heterocycles. Presented herein is a Au-catalyzed cyclization of alkyne-tethered dihydropyrimidones to yield pyridopyrimidones.


Local conformation and intermolecular interaction of rigid ring polymers are not always the same as the linear analogue: cyclic amylose tris(phenylcarbamate) in Θ solvents.
Small-angle X-ray scattering and static and dynamic light scattering measurements were made for cyclic amylose tris(phenylcarbamate) (cATPC) of which weight-average molar mass M(w) ranges from 1.3 × 10(4) to 1.5 × 10(5) to determine their z-average mean square radius of gyration <S(2)>z, particle scattering function P(q), hydrodynamic radius R(H), and second virial coefficient A2 in methyl acetate (MEA), ethyl acetate (EA), and 4-methyl-2-pentanone (MIBK). The obtained <S(2)>z, P(q), and R(H) data were analyzed in terms of the wormlike ring to estimate the helix pitch per residue h and the Kuhn segment length λ(-1) (the stiffness parameter, twice the persistence length). Both h and λ(-1) for cATPC in MEA, EA, and MIBK are smaller than those for linear amylose tris(phenylcarbamate) (ATPC) in the corresponding solvent and the discrepancy becomes more significant with increasing the molar volume of the solvent. This indicates that not every rigid ring has the same local helical structure and chain stiffness as that for the linear polymer in the M(w) range investigated while infinitely long ring chains should have the same local conformation. This conformational difference also affects A2. In actuality, negative A2 was observed for cATPC in MIBK at the Θ temperature of linear ATPC whereas intermolecular topological interaction of ring polymers increases A2.


The isolation of two different lipopolysaccharide fractions from various Proteus mirabilis strains.
Four distinct Proteus mirabilis strains were extracted by the phenol/water procedure. After ultracentrifugation of the dialyzed water phase, the pelleted lipopolysaccharide was purified and analyzed. The sugar composition of this lipopolysaccharide fraction I was similar for all four strains, containing only small amounts of strain-specific constituents. A second lipopolysaccharide fraction was isolated from the supernatant above (termed L1 fraction) after removal of nucleic acids. DEAE-cellulose chromatography indicated that this material is not a polysaccharide but rather a water-soluble lipopolysaccharide containing strain-specific constituents such as uronic acids, amino acids, amino sugars, neutral sugars, ethanolamine and phosphate, depending on the strain from which lipopolysaccharide II was isolated.


Successful Control of Massive Bleeding in a Child with Burkitt's Lymphoma via a Biosimilar Recombinant Activated Factor VII (AryoSeven™).
We describe a case of a 4-year-old girl with Burkitt's lymphoma, who suffered from a massive gastrointestinal hemorrhage 3 days after chemotherapy. In spite of applying the common practice in correction of coagulopathy, thrombocytopenia persisted and bleeding became life-threatening. In the present case report, we report a successful control of bleeding with a single-dose administration of a biosimilar recombinant activated human factor VII (AryoSeven).


A melanopsin ganglion cell subtype forms a dorsal retinal mosaic projecting to the supraoptic nucleus.
Visual input to the hypothalamus from intrinsically photosensitive retinal ganglion cells (ipRGCs) influences several functions including circadian entrainment, body temperature, and sleep. ipRGCs also project to nuclei such as the supraoptic nucleus (SON), which is involved in systemic fluid homeostasis, maternal behavior, social behaviors, and appetite. However, little is known about the SON-projecting ipRGCs or their relationship to well-characterized ipRGC subtypes. Using a GlyT2Cre mouse line, we show a subtype of ipRGCs restricted to the dorsal retina that selectively projects to the SON. These ipRGCs tile a dorsal region of the retina, forming a substrate for encoding ground luminance. Optogenetic activation of their axons demonstrates they release the neurotransmitter glutamate in multiple regions, including the suprachiasmatic nucleus (SCN) and SON. Our results challenge the idea that ipRGC dendrites overlap to optimize photon capture and suggests non-image forming vision operates to sample local regions of the visual field to influence diverse behaviors.


The experience of transportation to visit a nursing home resident: A case study.
Maintaining social connections in the community can be accomplished through transportation access and opportunities. This includes relationships between family and residents in nursing homes. Previous research supports the relationship between transportation, social support, and visitation of residents in nursing homes (NHs), however no empirical research to date explores this relationship of family member transportation as a means to visit their loved one in this setting. Guided by a case study approach, a sample of 11 (N = 11) family members of residents in nursing homes across North Central Texas were selected to develop an in-depth understanding of transportation access and mobility, as it relates to visitation of residents in nursing facilities. Analyses revealed the following seven themes: Car access, Alternative modes, Flexibility, Travel time, Actual cost, Collateral cost, and Health and Mobility. Findings from this study uncover how cost, both actual cost and collateral cost, are greatly linked to car access, transportation access, and opportunities to visit, as well as the impact each of these features, and emergent themes, related to transportation have on maintained or fractured relationships of family and residents in nursing homes. This article concludes with implications for future research and social work practice.


One-step route to wurtzite-structured ZnS thin nanorods in pure ethylenediamine or mixed solvent.
In the paper, we report one-step synthesis of novel wurtzite-structured ZnS three dimensional architectures assembled from thin nanorods in mixed solvent of ethylenediamine (en) and ethylene glycol, and wurtzite ZnS nanorods in a pure en solvent, both adopting Zn(CH3COO)2 x 2H2O and (NH2)2CS as raw materials. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy and selected area electron diffraction were applied to characterize the samples. It was found that the volume ratio of solvents and the concentration of (NH2)2CS played important roles in the formation of wurtzite-structured ZnS nanorods, and the thin wurtzite ZnS nanorods with mean diameter of 6 nm were successfully synthesized. The optical absorption edges of the thin ZnS nanorods were found to be blue-shifted compared with that of the bulk ZnS due to the quantum confinement effect.


Health promotion approach for the control of food-borne parasitic zoonoses in Nepal: emphasis on an environmental assessment.
Green and Kreuter define health promotion as the use of both education and ecology to encourage and support living conditions conducive to good health. Their PRECEDE-PROCEED model delineates a practical way to cope with health problems using this definition. Applying PRECEDE to Nepal helps identify the steps needed to control the ever-increasing incidence of food-borne parasitic zoonoses (FBPZ) there and in other South Asian countries. In executing the first five steps of the model, we focused on behavioral and environmental assessments to find a method for controlling FBPZ. Through these two assessments, we identified the following behavioral and environmental objectives: establish a meat inspection system by 2003, establish training programs on safe meat production and selling practices by 2003, improve slaughterhouses and slaughtering practices by 2003. The educational and ecological assessments revealed that the necessary predisposing, reinforcing and enabling factors for appropriate control of FBPZ are present in Nepal, while an administration and policy assessment shows Nepal meets PRECEDE requirements through its recent meat inspection legislation. Although the data for each element of the PRECEDE-PROCEED model are limited in Nepal, they clearly tell us to move forward to the PROCEED stage to control FBPZ there as well as in all of South Asia.


Control of Solvent Dynamics around the B12-Dependent Ethanolamine Ammonia-Lyase Enzyme in Frozen Aqueous Solution by Using Dimethyl Sulfoxide Modulation of Mesodomain Volume.
The temperature-dependent structure and dynamics of two concentric solvent phases, the protein-associated domain (PAD) and the mesodomain, that surround the ethanolamine ammonia-lyase (EAL) protein from Salmonella typhimurium in frozen polycrystalline aqueous solution are addressed by using electron paramagnetic resonance spectroscopy of the paramagnetic nitroxide spin probe, TEMPOL, over the temperature ( T) range 190-265 K. Dimethyl sulfoxide (DMSO), added at 0.5, 2.0, and 4.0% v/v and present at the maximum freeze concentration at T ≤ 245 K, varies the volume of the interstitial aqueous DMSO mesodomain ( Vmeso) relative to a fixed PAD volume ( VPAD). The increase in Vmeso/ VPAD from 0.8 to 6.0 is quantified by the partitioning of TEMPOL between the two phases. As Vmeso/ VPAD is increased, the Arrhenius parameters for activated TEMPOL rotational motion in the mesodomain remain uniform, whereas the parameters for TEMPOL in the PAD show a progressive transformation toward the mesodomain values (higher mobility). An order-disorder transition (ODT) in the PAD is detected by the exclusion of TEMPOL from the PAD into the mesodomain. The ODT T value is systematically lowered by increased Vmeso/ VPAD (from 215 to 200 K), and PAD ordering kinks the mesodomain Arrhenius dependence. Thus there is reciprocity in PAD-mesodomain solvent coupling. The results are interpreted as a dominant influence of ice-boundary confinement on the PAD solvent structure and dynamics, which is transmitted through the mesodomain and which decreases with mesodomain volume at increased added DMSO. The systematic tuning of PAD and mesodomain solvent dynamics by the variation of added DMSO is an incisive approach for the resolution of contributions of protein-solvent dynamical coupling to EAL catalysis.


Clinical characteristics and outcomes of Chinese patients with coronary heart disease and resistant hypertension.
There is currently few research on clinical characteristics and outcomes of coronary heart disease (CHD) with resistant hypertension in central region of China. This study aimed to assess the risk factors and outcomes of CHD and resistant hypertension in population of central region of China. A total of 1467 CHD patients with hypertension were included and considered to three groups according to blood pressure control: controlled group (blood pressure < 140/90 mmHg on three or less antihypertensive drugs); uncontrolled group (blood pressure ≥ 140/90 mmHg on two or less antihypertensive drugs); or resistant group (blood pressure ≥ 140/90 mmHg on three antihypertensive drugs or < 140/90 mmHg on at least four antihypertensive drugs including diuretic). The authors evaluated the clinical outcomes of three groups at 1-year follow-up. The prevalence of resistant hypertension was 21.8%. Significant adjusted associated factors of resistant hypertension included per unit changes body mass index (BMI, OR 1.12), and four categorical variable diagnosis by yes or no: heart failure (HF, OR 2.62), left ventricular hypertrophy (LVH, OR 2.83), diabetes (OR 1.55), and chronic kidney disease (CKD, OR 1.63). In multiple adjusted Cox regression analysis, patients in resistant group had a higher risk of the primary outcome (HR, 2.14 [95% CI, 1.47-3.11]; p < .001). Moreover, the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with resistant hypertension is also significantly increased (HR, 2.11 [95% CI, 1.39-3.20]; p < .001). In conclusion, resistant hypertension was a quite common and high proportion finding in patients with CHD and hypertension in central region of China, and these patients have a worse clinical prognosis.


[Extraction of respiratory signals from chest tomosynthesis].
To analyze the respiratory motion of the scanned object during acquisition of digital chest tomosynthesis (CTS) using a linear model. Respiratory signals were generated by extracting the motion of the diaphragm from the projection radiographs. The diaphragm trajectory obtained by dynamic programming (DP) was modeled and fitted, and according to the fitting of the data, the base motion curve and respiratory signal curve of the diaphragm were separated. Multipurpose chest phantom data, simulated digital Xcat phantom data and the datasets of 3 clinical patients were used to validate the performance of the proposed method. The motion trajectory of the diaphragm extracted from multipurpose chest phantom simulation data was linear. The respiratory signals could be effectively extracted from the 3 datasets of clinical patients in different respiratory states. The correlation coefficient between the respiratory signal extracted in Xcat simulation experiment and the original design was 0.9797. The linear model can effectively obtain the respiratory motion information of patients in real time, thus enabling the physicians to make clinical decisions on a rescan.


High current table-top setup for femtosecond gas electron diffraction.
We have constructed an experimental setup for gas phase electron diffraction with femtosecond resolution and a high average beam current. While gas electron diffraction has been successful at determining molecular structures, it has been a challenge to reach femtosecond resolution while maintaining sufficient beam current to retrieve structures with high spatial resolution. The main challenges are the Coulomb force that leads to broadening of the electron pulses and the temporal blurring that results from the velocity mismatch between the laser and electron pulses as they traverse the sample. We present here a device that uses pulse compression to overcome the Coulomb broadening and deliver femtosecond electron pulses on a gas target. The velocity mismatch can be compensated using laser pulses with a tilted intensity front to excite the sample. The temporal resolution of the setup was determined with a streak camera to be better than 400 fs for pulses with up to half a million electrons and a kinetic energy of 90 keV. The high charge per pulse, combined with a repetition rate of 5 kHz, results in an average beam current that is between one and two orders of magnitude higher than previously demonstrated.


[Therapeutic development in myotonic dystrophy].
Myotonic dystrophy (DM), the commonest form of muscular dystrophy in adults, is a multisystem disease caused by repeat expansions located in untranslated regions of the affected genes. Its pathogenesis results from expression of RNAs with these expanded repeats, which causes sequestration of splicing factors and thus series of splicing misregulation. An increased understanding of the disease mechanism has accelerated the development of therapeutic strategies, including correction of individual missplicing by antisense oligonucleotides (ASOs), ASO- or small molecule-mediated neutralization of the RNA toxicity by preventing sequestration of splicing factors, degradation of the toxic RNA by ASOs, and stabilization of the expanded repeats. ASOs targeting the toxic RNA have exhibited promising results in animal models, and a clinical trial has recently been launched. With the advent of clinical trials, we are confronting several challenges. As with other rare diseases, we must identify eligible patients. It may be more important in Japan to establish a standardized best practice management of currently available approaches (e.g., pacemaker use) followed by nationwide dissemination. The national DM registry, about to be launched shortly, might be a promising tool to overcome these issues and lead to improved management of DM.


Vaccination of swine against H3N2-influenza field isolates using the human Philippines-strain.
Intratracheal inoculation of 2 Belgian H3N2-influenza viral strains, isolated from sick swine in the field, caused high fever, anorexia and dyspnoea in unvaccinated swine. The strains are related to the human A/Port Chalmers/1/73 (H3N2)-strain. In a limited study, 2 subunit vaccines, both derived from the human A/Philippines/2/82 (H3N2)-strain, were tested for efficacy in protecting swine against these Belgian field isolates. Vaccine A was a commercial vaccine, vaccine B an experimental vaccine. For evaluation of the efficacy of the vaccines, clinical as well as virological parameters were used. It was found that 2 spaced injections of the experimental vaccine (B) resulted in very high serum hemagglutination-inhibition (HI) titres against the Philippines-strain. Nevertheless, only partial protection was obtained, as indicated by the milder clinical signs and the decreased viral replication at challenge. One injection of the experimental vaccine (B) and 2 spaced injections of the commercial vaccine (A) did not result in any protection at challenge, even though moderate HI titres against the Philippines-strain were obtained. It was concluded that if an H3N2-strain is included in vaccines for use in swine, a strain should be selected which is identical or very closely related to the strain(s) prevalent in the swine population of the country in which the vaccine will be used.


Evaluation of angiography performed by radiographers and nurses.
To evaluate out-patient angiography performed by nurses and radiographers. A protocol for out-patient angiography performed by nurses and radiographers was drawn up and approved by the Trust's Risk Management Committee. Following training, two experienced radiographers and one nurse undertook elective peripheral or renal angiography according to the protocol on 187 patients. Angiograms were performed using a 3F catheter introduced into the abdominal aorta from a femoral approach. Patients were discharged after 2 hours and contacted by telephone the following morning. No patient refused consent for the procedure. One hundred and seventy-two patients underwent successful catheterization without assistance from a radiologist. Radiologist assistance was required with femoral puncture or catheter/guidewire manipulation in 15 cases (8%). Images were considered diagnostic by the reporting radiologist in all but one case. This patient was recalled for further aortogram and pressure measurements. There was a single puncture site complication due to transient stenosis of the common femoral artery at the puncture site. This is thought to have been the result of subintimal injection of local anaesthetic, and it resolved spontaneously over 30 minutes. There were no delayed complications. Experienced nurses and radiographers can rapidly acquire the skills to perform diagnostic angiography safely and efficiently.


Characteristics of social smoking among college students.
Social smoking is a newly identified phenomenon in the young adult population that is poorly understood. We investigated differences in social smoking (smoking most commonly while partying or socializing) and other smoking within a convenience sample of college smokers (n = 351) from a large midwestern university. Results revealed that 70% of 351 current (past 30-day) smokers reported social smoking. No significant difference was found in motivation to quit between smoking groups. However, a significant difference was found between groups in confidence to quit, the number of days smoked, and the number of cigarettes smoked on those days. More social smokers than expected did not perceive themselves as smokers. Logistic regression analysis revealed that lower physical and psychological dependence and higher social support scores predicted social smoking.


Emerging Role of Stem Cells - Derived Exosomes as Valuable Tools for Cardiovascular Therapy.
In modern society, myocardial infarction is a major cause of mortality, morbidity and deterioration of quality of life. Although various therapeutic approaches are available, none of them lead to the regeneration of infarcted tissue. The use of mesenchymal stem cells in cell therapy for myocardial infarction showed a beneficial effect consisting in reduced infarcted area and improved cardiac function, which can be explained by paracrine mechanism. It has been shown that stem cells are able to release a very complex range of factors including growth factors, cytokines and chemokines, along with an abundant mixture of membrane vesicles. These secreted elements contribute to the beneficial effect of stem cells therapy observed both in vitro and in vivo. Recent studies have shown that exosomes, which are small membrane vesicles originating in the endocytic pathway of the cells and carry a complex cargo consisting in mRNA, microRNA and various other anti-apoptotic and pro-angiogenic factors, are the main mediators of stem cells paracrine effect. In this review, we discuss the capacity of mesenchymal stem cells to protect the ischemic myocardium, the role of exosomes as protective factors secreted by stem cells and the possibility to use these vesicles in developing a novel approach in cardiovascular therapy, involving a non-cellular use of mesenchymal stem cells paracrine activity.


Tender, loving care.
Early diagnosis and treatment of retinopathy can save premature babies' sight. In one neonatal clinic, nurses are at the forefront of providing a service which reflects the unit's caring ethos.


[Platelet aggregation and various coagulation parameters in liver cirrhosis].
Twenty eight patients affected by liver cirrhosis were studied in comparison with 44 control subjects, matched for age. The following parameters were carried out: a) platelet aggregation (by Born's method) induced by increasing concentrations of ADP and epinephrine; b) PF3 ( Spaet - Cintron method) and antithrombin III, aPTT, prothrombin ratio, fibrinogen, platelet count. Platelet aggregation and availability of PF3 are lower in cirrhotic patients, suggesting an intrinsic defect of platelets. Moreover prolongation of aPTT and prothrombin ratio, lower levels of antithrombin III, fibrinogen and platelet count were detected.


Increased body mass in infancy and early toddlerhood in Angelman syndrome patients with uniparental disomy and imprinting center defects.
The diagnosis of Angelman syndrome (AS) is based on clinical features and genetic testing. Developmental delay, severe speech impairment, ataxia, atypical behavior and microcephaly by two years of age are typical. Feeding difficulties in young infants and obesity in late childhood can also be seen. The NIH Angelman-Rett-Prader-Willi Consortium and others have documented genotype-phenotype associations including an increased body mass index in children with uniparental disomy (UPD) or imprinting center (IC) defects. We recently encountered four cases of infantile obesity in non-deletion AS cases, and therefore examined body mass measures in a cohort of non-deletion AS cases. We report on 16 infants and toddlers (ages 6 to 44 months; 6 female, and 10 male) with severe developmental delay. Birth weights were appropriate for gestational age in most cases, >97th% in one case and not available in four cases. The molecular subclass case distribution consisted of: UPD (n = 2), IC defect (n = 3), UPD or IC defect (n = 3), and UBE3A mutation (n = 8). Almost all (7 out of 8) UPD, IC and UPD/IC cases went on to exhibit >90th% age- and gender-appropriate weight for height or BMI within the first 44 months. In contrast, no UBE3A mutation cases exhibited obesity or pre-obesity measures (percentiles ranged from <3% to 55%). These findings demonstrate that increased body mass may be evident as early as the first year of life and highlight the utility of considering the diagnosis of AS in the obese infant or toddler with developmental delay, especially when severe. Although a mechanism explaining the association of UPD, and IC defects with obesity has not been identified, recognition of this correlation may inform investigation of imprinting at the PWS/AS locus and obesity.


Characterization of a 7,8-benzoflavone double effect on CFTR Cl(-) channel activity.
The human cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the superfamily of adenosine triphosphate (ATP)-binding cassette (ABC) transporter ATPases. This protein forms a Cl(-) channel with a complex regulation; gene mutations cause cystic fibrosis disease. We investigated the interaction between the protein and the flavone UCCF-029 using the patch-clamp technique in the excised inside-out configuration in order to study the molecular mechanism of action for this potentiator on completely phosphorylated channel (25 U/ml protein kinase A) and a relatively low level of ATP (0.3 mM: ). Low concentrations of UCCF-029 (<50 nM: ) increase the open probability (p (o)), favoring the channel transition to an activated state, while high UCCF-029 (>50 nM: ) levels determine inhibition of the CFTR by a reduction of the total open time. Our data suggest that this drug can potentiate CFTR by binding to a specific site on the nucleotide binding domain, promoting dimer formation. The response of CFTR to variable concentrations of ATP is not modified by application of the potentiator UCCF-029 at either low, activatory, concentration or high, inhibitory, levels. Hence, we conclude that the potentiator may not interfere with binding of ATP but probably acts at an independent site in the protein, interacting directly with CFTR to modulate channel activity.


Silicone catheter fracture secondary to stress events and a dressing technique to reduce those events.
In vitro experiments describe how two specific stresses result in weakened and thus more easily fractured silicone catheters. The two stresses studied are stretching and kinking of the catheters. A dressing method for flexible peripherally inserted catheters that eliminates kinking and significantly reduces stretching is described. The dressing method is compared experimentally with a standard dressing method.


Reduction quality in lateral view of X-ray and hypoalbuminemia are associated with postoperative mortality in elderly pertrochanteric fracture patients.
Pertrochanteric fracture is one of the most prevalent public health issues across the world for the elderly population. The purpose of this study was to investigate the association between surgical factors and postoperative mortality in patients with intramedullary nail-treated pertrochanteric fractures. A retrospective cohort study was designed to evaluate the pertrochanteric fracture patients treated with intramedullary nail between January 2016 to February 2021. The surgical factors included the Dorr morphology, Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association (AO/OTA) classification of fractures, the tip-apex distance (TAD), location of the cephalic screw, reduction quality in anterior-posterior (AP) and lateral views, the integrity of the lateral wall, and the design of cephalic screws. Using univariate and multivariate Cox proportional hazard models, the association between these risk factors and postoperative mortality in patients with this type of fractures was evaluated. A total of 169 pertrochanteric fracture patients treated with intramedullary nails were included in our study, with the average age of 82.68±5.93 years. The mortality rates at 3 months, 1 year, and the end of follow-up were 4.14%, 11.24%, and 26.04%, respectively. According to the univariate Cox analysis, age, gender, preoperative levels of hemoglobin (Hb) and albumin (Alb) were associated with a poor overall survival (OS) (P<0.05). After multivariate adjustment, the pre-operative level of Alb (P<0.001) and the reduction in lateral view (P<0.001) were shown to be independent risk factors for poor OS. The preoperative hypoalbuminemia and reduction quality in lateral view were associated with postoperative mortality in our study. Therefore, optimizing both parameters could improve the prognosis in elderly pertrochanteric fracture patients.


Publication guidelines for structural modelling of small-angle scattering data from biomolecules in solution.
Small-angle scattering is becoming a mainstream technique for structural molecular biology. As such, it is important to establish guidelines for publication that will ensure that there is adequate reporting of the data and its treatment so that reviewers and readers can independently assess the quality of the data and the basis for any interpretations presented. This article presents a set of preliminary guidelines that emerged after consultation with the IUCr Commission on Small-Angle Scattering and other experts in the field and discusses the rationale for their application. At the 2011 Congress of the IUCr in Madrid, the Commission on Journals agreed to adopt these preliminary guidelines for the presentation of biomolecular structures from small-angle scattering data in IUCr publications. Here, these guidelines are outlined and the reasons for standardizing the way in which small-angle scattering data are presented.


Physical Activity and Its Associated Factors among Patients with Hypertension at Amhara Region Comprehensive Specialised Hospitals, Northwest Ethiopia: An Institutional Based Cross-Sectional Study.
Accurate evaluation of physical activity for patients with hypertension is important to determine patients' health outcomes and intervention measures. Information about physical activity among patients with hypertension in Ethiopia is not well known. This study was aimed to assess the physical activity and associated factors among patients with hypertension. An institution-based cross-sectional study was conducted. The study was conducted at the Tertiary Hospital Northwest, Ethiopia. Physical activity was assessed by Global Physical Activity Questionnaire as the primary outcome and factors significantly associated with physical activity were secondary outcomes. Four hundred and twenty patients with hypertension took part in the study; among those 233 were men and 187 were women. The study participants were chosen using a systematic random sampling method. SPSS V.20 statistical software was used to analyse the data. In the multivariable logistic regression analysis model, adjusted OR (AOR) with a 95% CI and p value<0.05 were used to identify the associated factors with physical activities. Our study showed that 19.1% of study participants had inadequate physical activity, being old age with AOR: 10.27 (3.21 to 33.01), low or poor self-efficacy with AOR: 10.34 (4.89 to 21.84), poor self-rated health with AOR: 5.91 (1.73 to 20.13) and lack of adequate facilities with AOR: 4.07 (1.72 to 9.66) were significantly associated with inadequate physical activity. Inadequate physical activity was detected in one-fifth of the study participants, according to our research. Being elderly, having low self-efficacy, having inadequate facilities and having poor self-rated health were all linked to inadequate physical activity.


Transvaginal evisceration after hysterectomy: is vaginal cuff closure associated with a reduced risk?
To evaluate the overall incidence of transvaginal evisceration following hysterectomy and to assess the risk associated with indication, route of surgery, age and vaginal cuff closure technique. A database was used to identify all patients undergoing hysterectomy from 1995 to 2001 at our institution and all the patients admitted for vaginal evisceration during the same period. Each vaginal evisceration was analyzed for time of onset, trigger event, presenting symptoms, details of prolapsed organs and type of repair surgery. Of the 3593 patients enrolled in the study, 63.5% underwent abdominal hysterectomy, 33.0% vaginal hysterectomy, and 3.5% laparoscopic hysterectomy. Ten patients (0.28%) presented to the emergency room with vaginal evisceration. No statistical differences in evisceration rates were seen according to the route of surgery. No differences were found between the 1440 patients who had closure of the vaginal cuff and the 2153 who had an unclosed cuff closure technique. Our data suggest that, in young patients, sexual intercourse is to be considered the main trigger event before the complete healing of the vaginal cuff while, in elderly patients, the evisceration is a spontaneous event. Uterine prolapse was not associated with a higher rate and the route of surgery or vaginal cuff closure technique did not influence the dehiscence rate.


Questions and answers in chronic urticaria: where do we stand and where do we go?
This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. In 2011, a report of the GA(2) LEN task force on urticaria outlined important and unanswered questions in chronic urticaria (CU). These included, but were not limited to, questions on the epidemiology and course of chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], the resources allocated for the diagnosis and treatment of CSU, whether patients with angioedema as an isolated symptom can be regarded as a subgroup of CSU, and the efficacy and long-term safety of therapies. Many of these questions have been addressed by recent studies. Some of the answers obtained raise new questions. Here, we summarize some of the key insights on CU obtained over recent years, and we discuss old and new unmet needs and how to address them with future studies. We need to analyze the influence of recent advances in understanding of the burden of CU on patients and society, disease management and the CU patient journey. Our increased understanding of urticarial pathophysiology and consideration of the patient as a whole will need to be translated to better treatment algorithms and protocols. Actions to address these challenges include the 5th International Consensus Meeting on Urticaria, which will take place later this year. The formation of a global network of Urticaria Centers of Reference and Excellence over the next few years has also been proposed, with the aim of providing consistent excellence in urticaria management and a clear referral route, furthering knowledge of urticaria through additional research and educating/promoting awareness of urticaria.


Comparison of the Mortality of Non-COVID Hospitalized Patients during the COVID Pandemic: A Retrospective Cohort Study in a Tertiary Medical Center in Israel.
At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems. To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel. We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group). Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function. Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.


Knowledge and attitudes about attention-deficit/hyperactivity disorder (ADHD) and its treatment: the views of children, adolescents, parents, teachers and healthcare professionals.
Attention-deficit/hyperactivity disorder (ADHD) is a common neuro-developmental disorder that causes controversy; this may have a negative effect on the ability of families, teachers and healthcare professionals to achieve shared understanding and goals. This article reviews recent research of the knowledge and attitudes of children, adolescents, parents, teachers, healthcare professionals and the public about ADHD. Findings suggest that misconceptions about ADHD persist, and children with ADHD and their parents report stigmatizing experiences. Educational interventions to improve the knowledge of teachers about ADHD appeared to be effective in the short term. Parents and professionals working together in the diagnosis and treatment of children with ADHD may have different views about their roles in the shared decision-making process. Studies have reported both similarities and differences in parents' and professionals' views about the effectiveness of treatments for ADHD, but all stakeholders supported the principles of information-sharing and working in partnership.


Single-cell transcriptome analysis illuminating the characteristics of species-specific innate immune responses against viral infections.
Bats harbor various viruses without severe symptoms and act as their natural reservoirs. The tolerance of bats against viral infections is assumed to originate from the uniqueness of their immune system. However, how immune responses vary between primates and bats remains unclear. Here, we characterized differences in the immune responses by peripheral blood mononuclear cells to various pathogenic stimuli between primates (humans, chimpanzees, and macaques) and bats (Egyptian fruit bats) using single-cell RNA sequencing. We show that the induction patterns of key cytosolic DNA/RNA sensors and antiviral genes differed between primates and bats. A novel subset of monocytes induced by pathogenic stimuli specifically in bats was identified. Furthermore, bats robustly respond to DNA virus infection even though major DNA sensors are dampened in bats. Overall, our data suggest that immune responses are substantially different between primates and bats, presumably underlying the difference in viral pathogenicity among the mammalian species tested.


[Clinical observation of gelfoam in preventing cement leakage via the anterior vertebral wall in Kümmell's patients treated with percutaneous kyphoplasty].
To evaluate the efficacy of gelfoam granules application in prevention of cement leakage via anterior vertebral wall in Kümmell's patients treated with percutaneous kyphoplasty (PKP). From June 2017 to December 2019, 13 patients with Kümmell disease were treated with PKP, and gelatin sponge was inserted into the anterior wall of vertebral body to prevent bone cement leakage. There were 3 males and 10 females, with an average age of (73.84±8.44) years. The visual analogue scale (VAS) was used to record the degree of pain before treatment and 1 day and 3 months after treatment; Oswestry Disability Index (ODI) was used to evaluate the thoracolumbar function before treatment and 3 monthsafter treatment;X-ray was used to observe the bone cement leakage after operation. The VAS scores were 7.31±0.83, 2.92±1.13 and 1.69±1.11 before treatment and 1 day and 3 months after treatment, respectively. The VAS scores on the 1st day and 3 months after treatment were lower than those before treatment (P<0.05), and the postoperative pain was significantly relieved. The ODI before treatment and 3 months after treatment were (71.08±9.46)%, (17.85±7.82)%, respectively. The ODI at 3 months after treatment was improved compared with that before treatment (P<0.05), and the postoperative thoracolumbar function was significantly improved compared with that before treatment. Postoperative X-ray showed no leakage of bone cement in the anterior wall of vertebral body. The application of gelfoam granules in PKP can effectively prevent the leakage of bone cement via the anterior vertebral wall of Kümmell patients, and reduce the risk of thermal and mechanical injury of soft tissues such as the aorta in front of the vertebral body, and does not affect the postoperative pain relief and the recovery of thoracolumbar function.


Real time quantitative methylation detection of PAX1 gene in cervical cancer screening.
DNA methylation is currently found to be associated with the progression of cervical intraepithelial neoplasia and the development of cervical cancer. The aim of this study was to analyze the role of real time quantitative methylation detection of the PAX1 gene in cervical cancer screening. All eligible patients who underwent multiple detections for cervical cancer were assigned to the normal cervical group (n=21), cervical intraepithelial neoplasia I group (n=7), cervical intraepithelial neoplasia II+III group (n=12), or invasive cervical cancer group (n=14) based on pathological gradings. The methylation level of the PAX1 gene was detected using the real time quantitative methylation specific polymerase chain reaction assay and assessed by △Cp value. The diagnostic performance of PAX1 methylation detection was compared with folic acid receptor mediated diagnosis, the Thinprep cytology test, and human papilloma virus (HPV) testing. The △Cp value in the invasive cervical cancer group was (6.15±4.07), significantly lower than that in the other groups (F=26.45, p<0.001). The area under the curve (AUC) of PAX1 methylation detection was 0.902 (95% confidence interval (CI) 0.817-0.986; p<0.001), and sensitivity and specificity were 92.30% and 78.60% when the cut-off value of △Cp was 13.28. The AUC of PAX1 methylation detection was notably larger compared with 0.709 for folic acid receptor mediated diagnosis (95% CI 0.568-0.849, p=0.009), 0.702 for the Thinprep cytology test (95% CI 0.559-0.844, p=0.015), and 0.655 for HPV testing (95% CI 0.508-0.802, p=0.014). Through quantitative methylation specific polymerase chain reaction assay characterized by rapid screening and simple operation, the methylation detection of the PAX1 gene exhibited a higher diagnostic performance and may be a promising method for cervical cancer screening.


Neoagarooligosaccharides prevent septic shock by modulating A20-and cyclooxygenase-2-mediated interleukin-10 secretion in a septic-shock mouse model.
Analysis of the signaling mechanism triggered by endotoxin-mediated toll-like receptor-4 activation using immune cell systems or rodent models may help identify potential agents for the prevention of Gram-negative bacteria infection. β-agarase cleaves the β-1,4-linkages of agar to produce neoagarooligosaccharides (NAOs), which have various physiological functions. The aim of this study was to investigate the efficacy of NAOs in preventing experimental sepsis caused by the administration of endotoxin or Gram-negative bacteria. Organ damage and neutrophil infiltration in an endotoxemia and septic-shock mouse model were suppressed by NAOs. Pro-inflammatory cytokine level was decreased, but IL-10 level was increased by NAO-treatment. Further induction by NAOs in the presence of endotoxin was associated with a significant induction of A20 and cyclooxygenase (COX)-2 expressions. Our data suggest that NAOs have a beneficial preventive effect in septic shock correlated with the enhancement of IL-10 via the induction of A20 and COX-2.


Phospholipid-exchange proteins as membrane probes.
Phospholipid-exchange proteins, first discovered in rat liver, have now been identified in a variety of animal and plant tissues. In rat liver one protein transfers phosphatidylcholine with a high degree of specificity. Another protein fraction is capable of transferring all major types of phospholipids as well as cholesterol. Beef heart is a good source of phospholipid-exchange protein, which transfers phosphatidylinositol and phosphatidylcholine. Studies with phospholipid-exchange protein from beef heart, beef liver and rat liver show that these proteins are useful for the study of membrane structure. When unilamellar vesicles of isotopically labeled phosphatidylcholine are incubated with nonlabeled mitochondria in the presence of phospholipid-exchange protein, only the outer portion of the phosphatidylcholine bilayer is exchangeable and translocation of lipids between inner and outer parts of the bilayer is exceedingly slow. Resealed red blood cell ghosts show an equilibration of phosphatidylcholine between the inner and outer portions of the bilayer with a t1/2 of two hours. An even faster equilibration of various phospholipids in the microsomal mmebrane appears to take place in rat-liver microsomes.


The role of surgery in recurrent endometrial cancer.
Endometrial cancer is a common gynecologic malignancy in the United States, and the recurrence rate depends on the disease stage at diagnosis. Recurrence can affect several areas and follow different patterns. The role of surgery at the time of recurrence is not clearly defined. In this review, we fully describe the current evidence available. In particular, we describe how surgical treatment might be recommended for 1) vaginal or pelvic recurrences; 2) retroperitoneal or localized intra-abdominal recurrence, when a maximal cytoreductive effort is more likely to be successful; or 3) isolated distant recurrences when microscopically tumor-free margins can be achieved. Expert commentary: Cases should be evaluated individually, considering factors such as comorbidities, risks of intervention, and impact of treatment on quality of life.


Drug concentrations in post-mortem femoral blood compared with therapeutic concentrations in plasma.
Therapeutic drug concentrations measured in plasma are of limited value as reference intervals for interpretation in post-mortem (PM) toxicology. In this study, drug concentration distributions were studied in PM femoral venous blood from 57 903 Finnish autopsy cases representing all causes of death during an 11-year period. Cause-of-death information was obtained from death certificates issued by forensic pathologists. Median, mean, and upper percentile (90th, 95th, 97.5th) concentrations were calculated for 129 drugs. To illustrate how PM median concentrations relate to established therapeutic ranges in plasma, a PM blood/plasma relationship was calculated for each drug. Males represented 75% of the subjects and showed a lower median age (55 yrs) than females (59 yrs). In 43% of these cases, blood alcohol concentration was higher than 0.2‰, and the median was 1.8‰. Sixty-one (47%) of the 129 drugs showed a PM blood/plasma relationship of 1. For 22 drugs (17%), the relationship was <1, and for 46 drugs (35%), the relationship was >1. No marked correlation was found between the PM blood/plasma relationship and the volume of distribution (Vd ). For 36 drugs, more than 10% of cases were fatal poisonings attributed to this drug as the main finding. These drug concentration distributions based on a large database provide a helpful reference not only to forensic toxicologists and pathologists but also to clinical pharmacologists in charge of interpreting drug concentrations in PM cases.


In vitro cellular testing of strontium/calcium substituted phosphate glass discs and microspheres shows potential for bone regeneration.
Phosphate-based glasses (PBGs) are ideal materials for regenerative medicine strategies because their composition, degradation rates, and ion release profiles can easily be controlled. Strontium has previously been found to simultaneously affect bone resorption and deposition. Therefore, by combining the inherent properties of resorbable PBG and therapeutic activity of strontium, these glasses could be used as a delivery device of therapeutic factors for the treatment of orthopaedic diseases such as osteoporosis. This study shows the cytocompatibility and osteogenic potential of PBGs where CaO is gradually replaced by SrO in the near invert glass system 40P2 O5 ·(16-x)CaO·20Na2 O·24MgO·xSrO (x = 0, 4, 8, 12, and 16 mol%). Direct seeding of MG63 cells onto glass discs showed no significant difference in cell metabolic activity and DNA amount measurement across the different formulations studied. Cell attachment and spreading was confirmed via scanning electron microscopy (SEM) imaging at Days 3 and 14. Alkaline phosphatase (ALP) activity was similarly maintained across the glass compositions. Follow-on studies explored the effect of each glass composition in microsphere conformation (size: 63-125 μm) on human mesenchymal stem cells (hMSCs) in 3D cultures, and analysis of cell metabolic activity and ALP activity showed no significant differences at Day 14 over the compositional range investigated, in line with the observations from MG63 cell culture studies. Environmental SEM and live cell imaging at Day 14 of hMSCs seeded on the microspheres showed cell attachment and colonisation of the microsphere surfaces, confirming these formulations as promising candidates for regenerative medicine strategies addressing compromised musculoskeletal/orthopaedic diseases.


Automatic Detection of Negated Findings in Radiological Reports for Spanish Language: Methodology Based on Lexicon-Grammatical Information Processing.
We present a methodology for the automatic recognition of negated findings in radiological reports considering morphological, syntactic, and semantic information. In order to achieve this goal, a series of rules for processing lexical and syntactic information was elaborated. This required development of an electronic dictionary of medical terminology and informatics grammars. Pertinent information for the assembly of the specialized dictionary was extracted from the ontology SNOMED CT and a medical dictionary (RANM, 2012). Likewise, a general language dictionary was also included. Lexicon-Grammar (LG), proposed by Gross (1975; Cahiers de l'institut de linguistique de Louvain, 24. 23-41 1998), was used to set up the database, which allowed an exhaustive description of the argument structure of predicates projected by lexical units. Computational framework was carried out with NooJ, a free software developed by Silberztein (Silberztein and Noo 2018, 2016), which has various utilities for treating natural language, such as morphological and syntactic grammar, as well as dictionaries. This methodology was compared with a Spanish version of NegEx (Chapman et al. Journal of Biomedical Informatics, 34(5):301-310 2001; Stricker 2016). Results show that there are minimal differences in favor of the algorithm developed using NooJ, but the quality and specificity of the data improves if lexical-grammatical information is added.


Clinical and pathological course of renal disease in non-insulin-dependent diabetes mellitus: the Pima Indian experience.
Non-insulin-dependent diabetes mellitus (NIDDM) and the renal disease attributable to it have been characterized extensively in the Pima Indians, a group of American Indians who form the Gila River Indian Community in Arizona. Both of these diseases are common in this community, and their onset and duration are known with greater certainty than in other populations because research examinations, which include oral glucose tolerance tests and measures of urinary protein excretion, have been performed frequently on most members of the population for the past 30 years. Studies of glomerular structure and hemodynamic function in diabetic Pima Indians indicate that glomerular hyperfiltration often develops at the onset of NIDDM and remains elevated until after overt nephropathy appears. Structurally, the glomeruli in subjects with microalbuminuria are not clearly distinguishable from those in subjects with normoalbuminuria, but macroalbuminuria is characterized by extensive glomerular sclerosis, mesangial expansion, and widening of epithelial cell foot processes that together lead to a rapid decline in the glomerular filtration rate. The decline in glomerular function in subjects with macroalbuminuria is due both to a loss of ultrafiltration surface area and to reduction in glomerular hydraulic permeability.


Changes in RNA and protein synthesis in the neural retina during lens regeneration in newts.
Since neural retina stimulates regeneration of a lens from the dorsal iris in newts, RNA and protein synthesis in the neural retina was investigated during this process. Incorporation of 3H-uridine and 3H-leucine using liquid scintillation counting was employed to compare RNA and protein synthesis in the neural retina from sham-operated control eyes with that in eyes during lens regeneration. An initial increase in 3H-uridine uptake was seen one to three days after lentectomy. This was followed by greater incorporation of 3H-leucine, indicating increased protein synthesis between 5 to 15 days after lens removal. A decrease in 3H-uridine uptake was also seen at 5 to 12 days after lentectomy. After 20 days both the RNA and protein synthesis returned to the normal level. Since the increase in protein synthesis is preceded by an increase in RNA synthesis, the two processes might be related. The results indicate significant changes in the synthesis of macromolecules by the neural retina following lentectomy. These may be indirectly related to the production of the neural retinal factor with stimulates lens differentiation.