Measurements and modelling of base station power consumption under real traffic loads.
Base stations represent the main contributor to the energy consumption of a mobile cellular network. Since traffic load in mobile networks significantly varies during a working or weekend day, it is important to quantify the influence of these variations on the base station power consumption. Therefore, this paper investigates changes in the instantaneous power consumption of GSM (Global System for Mobile Communications) and UMTS (Universal Mobile Telecommunications System) base stations according to their respective traffic load. The real data in terms of the power consumption and traffic load have been obtained from continuous measurements performed on a fully operated base station site. Measurements show the existence of a direct relationship between base station traffic load and power consumption. According to this relationship, we develop a linear power consumption model for base stations of both technologies. This paper also gives an overview of the most important concepts which are being proposed to make cellular networks more energy-efficient.


[Effect of saponins extracted from Panax japonicus on inhibiting cardiomyocyte apoptosis by AMPK/Sirt1/NF-κB signaling pathway in aging rats].
To investigate the effects of saponins extracted from Panax japonicus(SPJ) on cardiomyocyte apoptosis in natural aging rats and explore its underlying mechanisms. SD male rats were randomly divided into four groups: young control group, natural aging group, SPJ low dose group and SPJ high dose group, with 10 rats in each group. The rats in natural aging group, SPJ low and high dose groups were respectively treated with normal saline, SPJ 10 and 60 mg•kg-1•d-1 from the beginning of 18 month-old, 6 days per week for 6 months till 24 month-old. Then the animals were sacrificed. Their myocardial morphology changes were observed by using haematoxylin-eoin(HE) staining; cardiomyocyte apoptosis was tested by using Tunel assays; and the protein expression levels of Bcl-2, Bax, IL-1β, TNF-α, AMPK, p-AMPK, Sirt1, and Ac-NF-κB p65 in myocardial tissues of rats were detected by Western blot. The results showed that SPJ could effectively improve the arrangement disorder of myocardial fibers, reduce the infiltration of inflammatory cells and inhibit cardiomyocyte apoptosis in natural aging rats. At the same time, SPJ could significantly inhibit the protein expression of Bax, IL-1β, TNF-α and Ac-NF-κB p65, and increase the expression of Bcl-2, Bcl-2/Bax, p-AMPK/AMPK and Sirt1 in the heart tissues of natural aging rats. SPJ can effectively inhibit cardiomyocyte apoptosis in natural aging rats, and its mechanisms may be related with the regulation of inflammatory reaction by AMPK/Sirt1/NF-κB signaling pathway.


The closure of a long-stay psychiatric hospital: a longitudinal study of patients' behavior.
This paper summarises longitudinal data based on repeat assessments of the behavioural functioning of 90 long-stay psychiatric patients. Data were gathered over a period of 4-5 years that spanned a hospital closure and the resettlement of patients in various alternative settings. Time-series analyses of individual data sets showed that resettlement led to no significant behavioural change in the majority of patients. However, some significant behavioural improvements were evidenced for approximately 20% of the group, while behavioural deterioration occurred in approximately 12%. Supplementary findings showed that following resettlement the quality of care provided significantly improved in many respects. However, access to social, recreational or vocational activities was reduced. In addition, the level of physical health symptomatology was shown to increase for this group of patients.


Controversies in postoperative atrial fibrillation after noncardiothoracic surgery: clinical and research implications.
Post operative atrial fibrillation after non-cardiothoracic surgery is an increasingly common problem. There is little high quality data to guide clinicians in risk prediction as well as short term and long term management. There appears to be a significant risk of recurrent atrial fibrillation and stroke but effective screening strategies have not been tested. In this commentary, we delineate various controversies in the management of post operative atrial fibrillation and briefly review the available evidence. Prospective studies in this clinically important area of cardiology should be encouraged.


Comparative Analysis of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells between Preeclampsia and Normal Pregnant Women.
Preeclampsia is a syndrome characterized by deterioration of either the maternal condition or the fetal condition. The adverse intrauterine environment made by preeclampsia results into intrauterine growth restriction and increased risk of a variety of diseases in future life. Given the adverse environment of fetal circulation made in the preeclamptic condition, and the role of mesenchymal stem cell (MSC) as a multipotent progenitor cell, we hypothesized that MSCs derived from human umbilical cord blood (hUCB-MSCs) obtained from preeclampsia are adversely altered or affected compared with normal pregnancy. The aim of this study was to analyze the biological characteristics and compare the functional abilities and gene expression patterns of hUCB-MSCs originating from pregnant women with and without severe preeclampsia. hUCB-MSCs were isolated and cultured from 28 pregnant women with severe preeclampsia and 30 normal pregnant women. hUCB-MSCs obtained from women with preeclampsia were less proliferative and more senescent and had lower telomerase activity and higher ROS activity than cells from women with normal pregnancy. In addition, many senescence-related differentially expressed genes (DEGs) were identified by analysis of microarray gene expression profiles and significantly associated with the Gene Ontology term cell aging. In conclusion, hUCB-MSCs obtained from women with preeclampsia showed the poorly proliferative, more senescent, and decreased telomerase activity, and these characters may be related with functional impairment of MSC from preeclampsia compared with cells from normal pregnancy.


Does the media matter to suicide?: Examining the social dynamics surrounding media reporting on suicide in a suicide-prone community.
Despite the widespread acknowledgement by public health organizations that media reporting matters to suicide, this link has been much debated and the mechanisms undergirding it poorly understood. With this study, I combine a media analysis with ethnographic data collected during 2014-2016 (N = 91) to examine the social dynamics surrounding media reporting on suicide in a community (that I call Poplar Grove, USA) with an enduring adolescent suicide problem. I illustrate how the media crafted a particular story about why youth die by suicide that emphasized academic pressure over other plausible causes. In so doing, the media may have broadened ideas about when suicide is seen as an option. However, I also provide evidence that cautions against attributing too much causal power to the media. The media coverage in Poplar Grove reflected conditions that were already present in the community; it was already a high-pressure place for youth to live with widespread mental health stigma. These factors likely shaped media reporting, while also contributing independently to the suicide problem. Finally, I found that the suicide deaths that received media coverage were those that triggered significant cognitive dissonance and thus were much discussed among youth, independent of the media reporting. This generated ample opportunities for peer role modeling of suicide. Thus, while the media may have helped solidify a certain view of suicide in the community, it was not the only social force contributing to suicide in Poplar Grove. While the findings from this study do not negate the importance of responsible reporting on suicide, they do contextualize the role of the media in suicide and suggest that researchers must take a broader view of how suicide suggestion operates in the media and in social contexts.


Finding the Hurt in Pain.
Pain is unique to every person, and difficult to quantify and treat. Whether it is delivered as a jolt or a persistent, dull ache, pain is guaranteed to affect one's quality of life. Our author examines how brain imaging is opening our eyes to the richness and complexity of the pain experience, giving us extraordinary insight into the neurochemistry, network activity, wiring, and structures relevant to producing and modulating painful experiences in all their various guises.


The impact of the use of immunosuppressive treatment after an embryo transfer in increasing the rate of live birth.
The tolerance of the immune system for the semi-allogeneic embryo is promoted by several factors and the cells involved in the immune system and factors in the mother during pregnancy. The dysregulation of the immune responses between the mother and fetus is a risk factor that raises the likelihood of rejection of the embryo and reproductive failure. To safeguard embryos and prevent immunological attacks, it is critical to suppress immunological rejection and encourage immunological tolerance. Based on current medical literature, it seems that immune cell management through immunosuppressive therapies can address reproductive failures. Immunosuppressive treatment has demonstrated encouraging results in terms of enhancing outcomes related to pregnancy and rates of live birth by regulating the immune responses of mothers and positively impacting the reproductive processes of humans. Currently, there is scarcity of high-quality data regarding the safety and efficacy of immunosuppressive therapies for children and mothers. Therefore, it is important to exercise caution while selecting use of any immunosuppressive therapy in pregnancy. This mini review provides a comprehensive overview of the existing literature regarding the impact of Calcineurin Inhibitors and anti-TNF treatment on improving the live birth rate following embryo transfer.


We have your daughter.
Virtual kidnappers attempt to extort money from their victims by saying they've kidnapped a member of the victim's family. While no actual kidnapping occurred, the callers use coconspirators, who sometimes scream for help in the background, to convince their victims of the legitimacy of the threat. During June and July of this year, the FBI received multiple reports indicating physicians in McAllen, Laredo, Brownsville, and Del Rio were contacted in attempts to collect extortion payments in "virtual kidnapping" schemes.


Altererythrobacter gangjinensis sp. nov., a marine bacterium isolated from a tidal flat.
A Gram-stain-negative, ochre-pigmented, strictly aerobic bacterium, designated strain KJ7(T), was isolated from a tidal flat of the Gangjin bay in South Korea. Cells were halotolerant, non-motile, catalase- and oxidase-positive rods. Growth of strain KJ7(T) was observed at 5-35 °C (optimum, 25 °C), at pH 6.0-9.5 (optimum, pH 6.5-7.0) and in the presence of 0-9 % (w/v) NaCl (optimum, 2 %). The major cellular fatty acids were C18 : 1ω7c, C17 : 1ω6c, summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The polar lipid pattern indicated the presence of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, a sphingoglycolipid, an unidentified phospholipid and two unidentified lipids. The G+C content of the genomic DNA was 60.2±0.9 mol% and the predominant respiratory quinone was Q-10. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain KJ7(T) formed a phyletic lineage distinct from other members of the genus Altererythrobacter and was most closely related to Altererythrobacter luteolus SW-109(T) and Altererythrobacter namhicola KYW48(T) (95.6 and 95.0 % 16S rRNA gene sequence similarity, respectively). On the basis of phenotypic, chemotaxonomic and molecular features, strain KJ7(T) represents a novel species of the genus Altererythrobacter, for which the name Altererythrobacter gangjinensis sp. nov. is proposed. The type strain is KJ7(T) ( = KACC 16190(T) = JCM 17802(T)).


Validity and reliability of Japanese version of the pressure ulcer knowledge assessment tool.
To develop Japanese version of the pressure ulcer knowledge assessment tool, a tool for measuring nurses' pressure ulcer knowledge to effectively evaluate the efficacy of current educational programs, resulting in prevention and early treatment, and to verify its validity and reliability among Japanese nurses. A total of 1716 nurses across three university hospitals participated in this study. All had been employed for at least one year. Managers, part-timers, and those in the operating room and the outpatient ward were excluded from the study as it is limited to bedside preventive care. The original tool was translated into Japanese using the Brislin's translation model. A cross-sectional study was used to examine the reliability and validity of the measure within a Japanese sample. Assessment of the multiple-choice test items included analysis of the validity (item difficulty and discriminating index), construct validity, internal consistency, and stability (test-retest reliability). The item difficulty indices ranged from 0.17 to 0.95, whereas values for item discrimination ranged from 0.15 to 0.45. Known group validity of the scale was confirmed; therefore, the higher-expertize group consisting of wound, ostomy, and continence nurses significantly outperformed nurses certified in other fields. The overall internal consistency reliability was 0.86 with a two-week test-retest intraclass correlation of 0.60. The instrument may be applied as a reliable and valid measure to assess nurses' pressure ulcer knowledge in the fields of nursing education, research, and practice in Japan.


Congenital fibrosarcoma: a congenital fibrous histiocytoma.
Using immunoperoxidase PAP technique in 2 cases of congenital fibrosarcoma, a great number of cells showed positive stain for alpha-1-antitrypsin (A1AT) and alpha-1-antichymotrypsin (A1ACT), both considered to be good histiocytic markers. The ultrastructure in 1 case also provides evidence of histiocytic differentiation. These findings suggest that congenital fibrosarcomas are actually congenital fibrous histiocytomas and may explain the presence of inflammatory infiltrates as in some malignant fibrous histiocytomas.


Human cytomegalovirus infection of tumor cells downregulates NCAM (CD56): a novel mechanism for virus-induced tumor invasiveness.
Pathologic data indicate that human cytomegalovirus (HCMV) infection might be associated with the pathogenesis of several human malignancies. However, no definitive evidence of a causal link between HCMV infection and cancer dissemination has been established to date. This study describes the modulation of the invasive behavior of NCAM-expressing tumor cell lines by HCMV. Neuroblastoma (NB) cells, persistently infected with the HCMV strain AD169 (UKF-NB-4AD169 and MHH-NB-11AD169), were added to endothelial cell monolayers and adhesion and penetration kinetics were measured. The 140- and 180-kDa isoforms of the adhesion receptor NCAM were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). The relevance of NCAM for tumor cell binding was proven by treating NB with NCAM antisense oligonucleotides or NCAM transfection. HCMV infection profoundly increased the number of adherent and penetrated NB, compared to controls. Surface expression of NCAM was significantly lower on UKF-NB-4AD169 and MHH-NB-11AD169, compared to mock-infected cells. Western-blot and RT-PCR demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoform. An inverse correlation between NCAM expression and adhesion capacity of NB has been shown by antisense and transfection experiments. We conclude that HCMV infection leads to downregulation of NCAM receptors, which is associated with enhanced tumor cell invasiveness.


Absorption and chemopreventive targets of sulforaphane in humans following consumption of broccoli sprouts or a myrosinase-treated broccoli sprout extract.
Sulforaphane (SFN), an isothiocyanate derived from crucifers, has numerous health benefits. SFN bioavailability from dietary sources is a critical determinant of its efficacy in humans. A key factor in SFN absorption is the release of SFN from its glucosinolate precursor, glucoraphanin, by myrosinase. Dietary supplements are used in clinical trials to deliver consistent SFN doses, but myrosinase is often inactivated in available supplements. We evaluated SFN absorption from a myrosinase-treated broccoli sprout extract (BSE) and are the first to report effects of twice daily, oral dosing on SFN exposure in healthy adults. Subjects consumed fresh broccoli sprouts or the BSE, each providing 200 μmol SFN daily, as a single dose and as two 100-μmol doses taken 12 h apart. Using HPLC-MS/MS, we detected ∼3 x higher SFN metabolite levels in plasma and urine of sprout consumers, indicating enhanced SFN absorption from sprouts. Twelve-hour dosing retained higher plasma SFN metabolite levels at later time points than 24-hour dosing. No dose responses were observed for molecular targets of SFN (i.e. heme oxygenase-1, histone deacetylase activity, p21). We conclude that the dietary form and dosing schedule of SFN may impact SFN absorption and efficacy in human trials.


Spermine modulates fungal morphogenesis and activates plasma membrane H+-ATPase during yeast to hyphae transition.
Polyamines play a regulatory role in eukaryotic cell growth and morphogenesis. Despite many molecular advances, the underlying mechanism of action remains unclear. Here, we investigate a mechanism by which spermine affects the morphogenesis of a dimorphic fungal model of emerging relevance in plant interactions, Yarrowia lipolytica, through the recruitment of a phytohormone-like pathway involving activation of the plasma membrane P-type H+-ATPase. Morphological transition was followed microscopically, and the H+-ATPase activity was analyzed in isolated membrane vesicles. Proton flux and acidification were directly probed at living cell surfaces by a non-invasive selective ion electrode technique. Spermine and indol-3-acetic acid (IAA) induced the yeast-hypha transition, influencing the colony architecture. Spermine induced H+-ATPase activity and H+ efflux in living cells correlating with yeast-hypha dynamics. Pharmacological inhibition of spermine and IAA pathways prevented the physio-morphological responses, and indicated that spermine could act upstream of the IAA pathway. This study provides the first compelling evidence on the fungal morphogenesis and colony development as modulated by a spermine-induced acid growth mechanism analogous to that previously postulated for the multicellular growth regulation of plants.


Development of transcriptomic biomarker signature in human saliva to detect lung cancer.
Lung cancer is the leading cause of cancer death for both men and women worldwide. Since most of the symptoms found for lung cancer are nonspecific, diagnosis is mostly done at late and progressed stage with the consecutive poor therapy outcome. Effective early detection techniques are sorely needed. The emerging field of salivary diagnostics could provide scientifically credible, easy-to-use, non-invasive and cost-effective detection methods. Recent advances have allowed us to develop discriminatory salivary biomarkers for a variety of diseases from oral to systematic diseases. In this study, salivary transcriptomes of lung cancer patients were profiled and led to the discovery and pre-validation of seven highly discriminatory transcriptomic salivary biomarkers (BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and LZTS1). The logistic regression model combining five of the mRNA biomarkers (CCNI, EGFR, FGF19, FRS2, and GREB1) could differentiate lung cancer patients from normal control subjects, yielding AUC value of 0.925 with 93.75 % sensitivity and 82.81 % specificity in the pre-validation sample set. These salivary mRNA biomarkers possess the discriminatory power for the detection of lung cancer. This report provides the proof of concept of salivary biomarkers for the non-invasive detection of the systematic disease. These results poised the salivary biomarkers for the initiation of a multi-center validation in a definitive clinical context.


Trackable Mitochondria-Targeting Nanomicellar Loaded with Doxorubicin for Overcoming Drug Resistance.
Multidrug resistance (MDR) has been recognized as a major obstacle to successful chemotherapy for cancer in the clinic. In recent years, more and more nanoscaled drug delivery systems (DDS) are constructed to modulate drug efflux protein (P-gp) and deliver chemotherapeutic drugs for overcoming MDR. Among them, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely used as a drug carrier due to its capability of inhibiting overexpression of P-gp and good amphiphilicity favorable for improving permeation and long-circulation property of DDS. In the present work, a novel kind of mitochondria-targeting nanomicelles-based DDS is developed to integrate chemotherapeutics delivery with fluorescence imaging functionalities on a comprehensive nanoplatform. The mitochondria-targeting nanomicelles are prepared by self-assembly of triphenylphosphine (TPP)-modified TPGS and fluorescent carbon quantum dots (CQDs) in an n-hexane/H2O mixed solution, named CQDs-TPGS-TPP. Notably, although the drug loading content of doxorubicin (DOX) in the as-prepared nanomicelles is as low as 3.4%, the calculated resistant index (RI) is greatly decreased from 66.23 of free DOX to 7.16 of DOX-loaded nanomicelles while treating both parental MCF-7 cells and drug-resistant MCF-7/ADR cells. Compared with free DOX, the penetration efficiency of DOX-loaded nanomicelles in three-dimensional multicellular spheroids (MCs) of MCF-7/ADR is obviously increased. Moreover, the released DOX from the nanomicelles can cause much more damage to cells of drug-resistant MCs. These results demonstrate that our constructed mitochondria-targeting nanomicelles-based DDS have potential application in overcoming MDR of cancer cells as well as their MCs that mimic in vivo tumor tissues. The MDR-reversal mechanism of the DOX-loaded CQDs-TPGS-TPP nanomicelles is also discussed.


Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine 5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway.
Opioids, such as morphine, are the most potent drugs used to treat pain. Long-term use results in high tolerance to morphine. High mobility group box-1 (HMGB1) has been shown to participate in neuropathic or inflammatory pain, but its role in morphine tolerance is unclear. In this study, we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days. We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1. HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4 receptor expression in microglia, thereby inducing morphine tolerance. Glycyrrhizin, an HMGB1 inhibitor, markedly attenuated chronic morphine tolerance in the mouse model. Finally, compound C (adenosine 5'-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin (heme oxygenase-1 inhibitor) alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tolerance, and alleviated morphine tolerance in the mouse model. These findings suggest that morphine induces HMGB1 release via the adenosine 5'-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway, and that inhibiting this signaling pathway can effectively reduce morphine tolerance.


Remembering Professor Benito Casu (1927-2016).
Heparin and related drugs have contributed in so many different ways to the drug discovery process, and have provided a platform to understand the pathophysiology of vascular and inflammatory diseases for nearly 100 years.


C34T AMP deaminase 1 gene mutation protects cardiac function in donors.
Dysfunction of the donor heart is an important clinical problem that could be affected by genetic factors. We tested the hypothesis that possession of the C34T nonsense mutation in AMPD1 gene, which is known to improve survival in chronic heart failure, protects against cardiac dysfunction in donors. Genetic analysis for C34T mutation was performed by single-stranded conformational polymorphism (SSCP) in 22 donor hearts used for transplantation, 10 unused donor hearts with acute heart failure (HF), 37 patients with chronic HF, and 207 healthy controls. We found a significantly higher frequency of the mutation among donors with healthy hearts used for transplantation (31.8%) as compared to control population (13.5%, P < 0.001) and a lower frequency in dysfunctional donor hearts (5.0% P = 0.025); the frequency of the C34T mutation in patients with chronic heart failure (14.8%) was not different from that of a control population. The presence of the C34T mutation in AMPD1 gene appears to be protective against acute heart failure in cardiac donors.


Molecular genetics and the characterization of steroid 21-hydroxylase deficiency.
Classical 21-hydroxylase deficiency congenital adrenal hyperplasia is a monogenic autosomal recessive disorder that has been conclusively shown by family HLA-typing studies to be in close genetic linkage with the human major histocompatibility complex. More recently recognized is the nonclassical disorder, an attenuated form of 21-hydroxylase deficiency characterized variably by late onset or absence of symptoms. Certain of the mild 21-hydroxylase deficiency allotypes involved in the nonclassical disorder have also been shown to be genetically linked with HLA, exhibiting distinct (B and B,DR) antigen associations. The nonclassical disorder is now also known to result from different genotypes: two mild 21-hydroxylase defects in conjunction, or a mild defect occurring with a sever (classical) defect. Restriction mapping and hybridization analysis have located two highly homologous base sequences, one structural gene coding for 21-hydroxylase and one pseudogene, in the Class III region of the MHC in tandem with the A and B genes for C4, the fourth component of complement. Current work documenting and characterizing gene abnormalities, as well as elucidating the molecular genetic basis of the mutations that have arisen, is aimed at developing better cDNA probes for prenatal diagnosis by amniocentesis and chorionic villus biopsy. In addition, because of the close association of the C4 and 21-hydroxylase genes, coordination of data on C4 variants and null alleles with altered 21-hydroxylase activity is improving understanding of the genetic mechanisms generating disease alleles of this enzyme crucial for normal endocrine function.


The Influence of Turmeric and Curcumin on Female Reproductive Processes.
The present review summarizes the available knowledge concerning the action of curcumin, the best-known polyphenol among the rhizomes of Curcumas, on female reproductive processes and their dysfunctions. Curcumin affects a number of physiological processes, including female reproduction (puberty, reproductive aging, ovarian follicullogenesis and oogenesis, and fecundity). Curcumin can affect these processes via changes in the release and reception of pituitary and ovarian hormones, growth factors and cytokines. Furthermore, it can influence the response of ovarian cells to these substances and external environmental factors. Finally, curcumin can affect oxidative processes within the ovary and numerous intracellular signalling pathways related to ovarian cell proliferation and apoptosis. These effects suggest the applicability of curcumin for stimulation of female reproductive processes in vivo and in vitro, as well as for the prevention, mitigation, and treatment of various reproductive disorders from ovarian insufficiency and infertility to polycystic ovarian syndrome and ovarian cancer.


[Toxicological evaluation of nanosized colloidal silver, stabilized with polyvinylpyrrolidone. I. Characterization of nanomaterial, integral, hematological parameters, level of thiol compounds and liver cell apoptosis].
Nano-sized colloidal silver (NCS) is currently one of the most widely used nanomaterials in medicine and consumer's products. Nanoparticles (NPs) of silver, in addition to the direct exposition through products may expose human via various environmental objects. The aim of the study is to assess the safe doses of silver NP received orally. The investigated NCS contained silver NPs with diameter of 10–60 nm, predominantly with a nearly spherical form stabilized with polyvinylpyrrolidone (PVP). The experiment was performed during 92 days in 5 groups of male Wistar rats (n=15 in each group), receiving a balanced semisynthetic diet. Animal of group 1 (control) received vehicle (deionized water) intragastrically for 30 days and then with food, groups from 2nd to 4th – PVP and groups from 3rd to 5th NCS, in doses respectively, 0.1; 1.0 and 10 mg/kg body weight (b.w.) in terms of silver. The dose of PVP in groups from 2nd to 5th did not differ, amounting to 200 mg/kg b.w. During the experiment, the weight gain, skin condition, activity, stool, cognitive function were assessed. At the end of the feeding period weight of internal organs, intestinal wall permeability to protein macromolecules, liver thiols, standard values of blood erythrocytes, leukocytes and platelets, hepatocyte apoptosis by flow cytometry were studied. These results suggest that in terms of weight gain, lung relative mass, average erythrocyte volume, hemoglobin content and concentration in erythrocytes, the relative proportion of lymphocytes and neutrophils adverse changes have been observed at a dose of 10 mg NPs per kg of b.w. At lower levels of exposure (0.1 and 1.0 mg/kg b.w.) some specific changes were also observed (in terms of thiols pool in liver, cognitive function, relative abundance of monocytes, the number of dead hepatocytes), which, however, did not possess an unambiguous dependence on the dose. Possible mechanisms of the toxic action of the NCS have been discussed.


[Patients admitted with decubital lesions: the experience of the Milanese hospital in Garbagnate].
Patients may develop a pressure sore while in hospital, but some are admitted with a pressure sore. In Garbagnate hospital all patients are assessed for the risk of pressure sores. The ad hoc forms of patients with multiple lesions, in very poor conditions and with "sentinel" symptoms such as poor hygiene, malnutrition, bruises, are specifically assessed and further data from the head nurse and the family are collected to understand and reconstruct the patients' stories. From January 1999, 26 patients with pressure sores were admitted; 80% were over 75 years: 42.4% came from their homes and 7 from nursing homes. Half of the patients presented severe malnutrition. All the cases had some common characteristics: lack of well defined management of pressure sores; delays in the requests for special mattresses due to lack of attention or bureaucratic problems; or use of ineffective treatments or medications; lack of contacts between hospital and district, leading to a fragmented patient care. Two of the 26 cases are presented and their significance discussed in details.


Irreducible Lisfranc injury by tibialis anterior tendon entrapment: A case report.
Lisfranc injuries are a dislocation of the metatarsal bones from the tarsal bone. Although closed reduction is possible in most cases of Lisfranc injury when attempted in the early stage, there are some rare cases for which open reduction is required. Herein we report a case of irreducible Lisfranc injury in a 34-year-old man who presented to our institution with painful swelling. We report a 34-year-old man presented to our institution with painful swelling after a fall from 1.0 m height. We diagnosed it as irreducible Lisfranc injury by tibialis anterior tendon entrapment through plain radiologic study and surgical findings. Plain X-ray, C-arm fluoroscopy and open surgery were performed. We did a closed reduction under a C-arm fluoroscopic guide, but it was not successful. Thus, we had to do an open reduction of a Lisfranc dislocation. Upon exposure, we observed the entrapment of the tibialis anterior tendon between the medial and intermediate cuneiform bones. Our report is valuable in that it can contribute to the diagnosis and suggest a clue to the treatment of such a rare pathology. The knowledge in the rare case of entrapment of the tibialis tendon and the understanding of management will be useful when a irreducible Lisfranc dislocation is unsuccessful after an attempt at closed reduction.


Evidence for a folic acid binding protein in human cell membrane.
Cell membranes were prepared by sucrose discontinuous gradient from human liver and human peripheral leukocytes and erythrocytes and from circulating leukocytes from patients with chronic granulocytic leukemia (CGL) and acute myeloblastic leukemia (AML). The membrane preparations from liver and from leukemic leukocytes were shown to bind tritiated folic acid. The membranes from normal leukocytes and erythrocytes did not show this binding capacity. The membrane preparation from liver and CGL leukocytes showed two peaks of binding eluting with proteins from Sephadex G-200. However, protein extracts of these membrane preparations showed only a single peak for labelled folic acid, eluting near but just after albumin. The binding capacity of the membranes for folic acid was partially inhibited by reduced folate analogues. It is concluded that the liver plasma cell membrane and the membranes of myeloblasts in AML and circulating leukocytes in CGL contain a binding protein for folic acid which may be concerned in the transport of folates into these cells.


Acute megakaryoblastic leukaemia shows high frequency of chromosome 1q aberrations and dismal outcome.
Acute megakaryoblastic leukaemia (AMKL) is associated with poor prognosis. Limited information is available on its cytogenetics, molecular genetics and clinical outcome. We performed genetic analyses, evaluated prognostic factors and the value of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in a homogenous adult AMKL patient cohort. We retrospectively analysed 38 adult patients with AMKL (median age: 58 years, range: 21-80). Most received intensive treatment in AML Cooperative Group (AMLCG) trials between 2001 and 2016. Cytogenetic data showed an accumulation of adverse risk markers according to ELN 2017 and an unexpected high frequency of structural aberrations on chromosome arm 1q (33%). Most frequently, mutations occurred in TET2 (23%), TP53 (23%), JAK2 (19%), PTPN11 (19%) and RUNX1 (15%). Complete remission rate in 33 patients receiving intensive chemotherapy was 33% and median overall survival (OS) was 33 weeks (95% CI: 21-45). Patients undergoing allo-HSCT (n = 14) had a superior median OS (68 weeks; 95% CI: 11-126) and relapse-free survival (RFS) of 27 weeks (95% CI: 4-50), although cumulative incidence of relapse after allo-HSCT was high (62%). The prognosis of AMKL is determined by adverse genetic risk factors and therapy resistance. So far allo-HSCT is the only potentially curative treatment option in this dismal AML subgroup.


Thiophenol-mediated 1,5-hydrogen transfer for the preparation of pyrrolizidines, indolizidines, and related compounds.
The efficient preparation of 1-azabicyclic alkanes is described. Highly functionalized skeletons are prepared in a concise manner using a radical tin-free 1,5-hydrogen transfer-cyclization process. The precursors for the radical reactions are readily assembled either from pyrrolidine/piperidine/hexahydro-1H-azepine or via condensation of a properly designed N-alkylimine with an allenylzinc species.


Degradation of native feathers by a novel keratinase-producing, thermophilic isolate, Brevibacillus thermoruber T1E.
Strain T1E, isolated and identified as Brevibacillus thermoruber, and evolutionally distant from the known keratinolytic isolates, proved to have feather-degrading ability. During the 7-day fermentation period, T1E consumed 10 g/l native goose feathers as the sole source of carbon and energy at 50 degrees C under aerobic conditions. The isolate secreted a thermostable, keratinolytic protease, which exhibited activity optimally at pH 6.5, whilst it was inhibited at alkaline pH. The keratin cleavage and catabolism resulted in the accumulation of free aspartic acid and soluble peptides with maximum values of 31.6 and 720 mg/l, respectively. The majority of the fermentation end-products were found to be small oligopeptides with an average molecular mass of 2275 Da.


The operating room of the future: a view from Europe.
The Operating Room of the Future will be characterized by meticulous preoperative planning, full integration of the operating room into the general flow of information, more comprehensive intraoperative diagnostic imaging procedures, and the use of sophisticated visualization processes including augmented reality. Mechatronic support (partially autonomous robots) enhances safety and allows reduction of staff. Integrated operating room systems will allow the wide spectrum of new devices and functionalities to be easily controlled by the operating team. The Operating Room of the Future will no longer be isolated from the rest of the clinical endeavor. Intraoperative teleconsultation and telepresence will help to promote and teach safer evidence-based endoscopic therapeutic surgery. Traditional surgical intervention will expand its definitions by procedures via an interdisciplinary, cooperative approach that will replace the sequential therapeutic process of today.


Magnetic resonance imaging of non-specific inflammatory granulation involving the skull base--two case reports.
A 55-year-old male presented with a 20-day history of nuchal pain and hypoglossal nerve paresis on the right. T2-weighted magnetic resonance (MR) imaging showed an isointense lesion with a small hypointense part in the hypoglossal canal and caudal clivus. A 66-year-old female presented with a long-standing history of left orbital pain. T2-weighted MR imaging showed a hypointense lesion occupying the orbital apex which on recurrence became isointense. The histological diagnosis of both lesions was non-specific inflammatory granulation. The T2-weighted MR imaging appearance of this entity is variable, and can change within the clinical course of the same lesion.


The indirect effect of somatic complaints on report of posttraumatic psychological symptomatology among Somali refugees.
Somali refugees are a growing population of displaced persons at risk for considerable traumatic exposure and its subsequent psychological symptomatology. Two hypotheses were proposed to evaluate the relationships between somatic complaints and posttraumatic psychological symptoms in a community-based sample of 74 adult Somali participants. As hypothesized, traumatic exposure predicted increased symptoms of posttraumatic stress disorder (PTSD; r = .64, p < .01), depression (r = .31, p < .01), and anxiety (r = .38, p < .01) in the basal model. In evaluation of the second hypothesis, somatic complaints were found to have a statistically significant indirect effect on the predictive relationship between traumatic life events and mood disturbance, accounting for 9% of the variance in depression and 14% of the variance in anxiety. However, somatic complaints failed to have an indirect effect on the relationship between traumatic exposure and symptoms of PTSD. Post hoc analyses revealed that, consistent with research conducted with nonrefugee populations, PTSD had a statistically significant indirect effect that accounted for 13% of the variance in the relationship between trauma and somatic complaints. These findings provide preliminary data regarding the influence of somatic complaints on the self-reported psychological symptoms of internationally displaced Somali refugees.


Location of subunit-subunit contact sites on RNA polymerase II subunit 3 from the fission yeast Schizosaccharomyces pombe.
RNA polymerase II from the fission yeast Schizosaccharomyces pombe consists of 10 putative subunits. Subunit 3 (Rpb3) is a homologue of prokaryotic alpha subunit, which plays a key role in the assembly of core enzyme subunits. Previously we indicated that Rpb3 also plays an essential role in subunit assembly because it interacts with at least four subunits, two large subunits (Rpb1 and Rpb2) and two medium-sized subunits (Rpb3 and Rpb5) (1), and it constitutes a core subassembly consisting of Rpb2, Rpb3, and Rpb11 (2). Using a synthetic mixture of equimolar amounts of individual subunits, which were all purified from cDNA-expressed Escherichia coli, we found here that Rpb3 also interacts with Rpb11, another alpha homologue. By making a set of Rpb3 deletion derivatives, we carried out mapping of the Rpb5- and Rpb11-contact sites on Rpb3. By far-Western blot and GST pull-down assays, we found that the amino acid sequence between residues 105-263 of Rpb3 is involved in binding Rpb5, and the sequence between residues 105-297 is required for binding Rpb11. Although the Rpb5- and Rpb11-contact sites on Rpb3 overlap each other, both subunits are able to associate with Rpb3 simultaneously. The binding of Rpb5 stabilizes the Rpb3-Rpb11 heterodimer.


Efficacy of Acetylshikonin in Preventing Obesity and Hepatic Steatosis in db/db Mice.
Zicao (Lithospermum erythrorhizon) has been used in clinics as a traditional Chinese medicine for thousands of years. Acetylshikonin (AS) is the main ingredient of Zicao, Xinjiang, China. The objective of this study was to investigate the anti-obesity and anti-nonalcoholic fatty liver disease (NAFLD) efficacy of AS in a model of spontaneous obese db/db mice. Mice were divided into Wild Type (WT) groups and db/db groups, which received no treatment or treatment with 100 mg/kg/day clenbuterol (CL) hydrochloride or 540 mg/kg/day AS by oral gavage for eight weeks. The results provided the evidence that AS prevented obesity and NAFLD including reduction in body weight, food efficiency ratio, serum triglyceride (TG) and free fatty acid (FFA) levels in db/db mice. Administration of AS markedly suppressed the levels of hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory cytokines in treated groups when compared with that of db/db groups. Further investigation of the lipid synthesis-related protein using Western blotting revealed that hepatic protein expression of sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthetase (FAS) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) were significantly downregulated by AS treatment. These findings suggest that AS exerts anti-obesity and anti-NAFLD effects through the regulation of lipid metabolism and anti-inflammatory effects.


An express sexual health service: in and out in a jiffy.
Objectives The aims of the present study were to assess client satisfaction with existing services, gauge the interest in an express service option and to compare waiting times before and after the introduction of an express service. Methods A survey evaluating satisfaction with existing services, waiting times and interest in an express service was offered to all clients attending the Western Sydney Sexual Health Centre in May 2013. A pilot of the express service ran from May to December 2013, and a follow-up survey was conducted in December 2013. Results There was a high level of interest in the express service. Median waiting times and satisfaction with waiting times improved following introduction of the express clinic. A high level of satisfaction was reported in those who had used the express service. Conclusions The express service was well received by clients and has the potential to improve client waiting times, increase clinic capacity and improve the overall client journey through the clinic. What is known about the topic? Express service options for testing for sexually transmitted infections (STIs) are being introduced both in Australia and overseas. Express services have been shown to increase clinic capacity and can create cost savings. They appear to be acceptable to clients. What does this paper add? This paper demonstrates that an express service option can be successfully introduced in an at-risk multicultural population. What are the implications for practitioners? The present study helps show that new models can be successfully introduced into long-standing traditional service models. Such models can help improve efficiency, clinic capacity and may produce cost savings. An express clinic is an option for screening asymptomatic clients for STIs. Clients complete a self-collected history and take self-collected specimens, and clinician-collected blood tests and throat swabs are advised accordingly.


DOTS implementation in a post-war, United Nations-administered territory: lessons from Kosovo.
The WHO-recommended strategy of tuberculosis control (DOTS strategy) has been shown to be effective in reducing tuberculosis incidence in a variety of countries/ settings. Little evidence exists on the implementation, and effectiveness of DOTS in a transitional, post-war setting To describe the process of establishing a National Tuberculosis Control Program (NTP) and implementing DOTS throughout Kosovo, and the outcomes achieved by this international collaboration in a post-war transitional setting during 1999-2005. In 1999, as part of the re-organization of health services, a DOTS-based NTP was established and operationalized through a collaboration of several international partners in Kosovo. Five key steps supported these activities. Kosovo has reached the World Health Assembly targets, having achieved 75% case detection rate (sputum smear-positive cases) and 93% treatment success rate. During 2000-2005, new smear-positive tuberculosis case notifications decreased by 44.5% (median annual decrease for all cases: 7.6%). Kosovo's success story is a collaborative tale, each partner involved playing a unique role in supporting NTP activities. The Kosovo example provides yet another setting in which DOTS implementation has resulted in successful patient outcomes. The international TB control community would be well-served by formal guidelines for implementing DOTS and the new STOP TB Strategy in these settings.


Mouse Models of Alzheimer's Disease.
Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology. Then, transgenic mouse lines harboring mutated human genes at several loci such as APP, PSEN1, APOEɛ4, and ob (leptin) are reviewed. Therefore, not only the accumulation of the Aβ peptide is emulated but also cholesterol and insulin metabolism. Further novel information about the disease will allow for the development of more accurate animal models, which in turn will undoubtedly be helpful for bringing preclinical research closer to clinical trials in humans.


Natural History of Patients Presenting with Autoimmune Hepatitis and Coincident Nonalcoholic Fatty Liver Disease.
Given the increase of nonalcoholic fatty liver disease (NAFLD) in the general population, a similar rise might be expected in autoimmune hepatitis (AIH) patients. We sought to determine the clinical outcome of patients with coincident AIH and NAFLD. We identified all intradepartmental AIH cases, and those meeting study criteria were placed into one of three cohorts: AIH only, AIH and simple steatosis (SS), and AIH and nonalcoholic steatohepatitis (NASH). The following outcome and clinical data were analyzed: incidence of all-cause mortality, incidence of liver-related mortality, incidence of liver-related adverse outcomes, and prevalence of cirrhosis at index biopsy. Out of a total 73 study patients, 14 % classified as AIH with SS and 16 % as AIH and NASH. Fifty percent of AIH and NASH patients had cirrhosis at index biopsy as compared to 18 % of AIH-only patients (p = 0.032). Patients with AIH and NASH had a relative risk of 7.65 (95 % CI 1.43-40.8) for liver-related mortality and 2.55 (95 % CI 0.92-7.09) for liver-related adverse outcomes, as compared to the AIH-only cohort. No significant difference in outcome measures existed in comparing (AIH only) with (AIH and SS) cohorts. Patients with coincident AIH and NASH were more likely to present with cirrhosis and more likely to develop adverse clinical outcome with decreased survival as compared to AIH-only patients. These findings suggest that simultaneous exposure confers a clinically significant increased risk, which may warrant closer follow-up and surveillance.


Clinical characteristics and diabetes associated autoantibodies in patients with both type 1 diabetes mellitus and asthma.
Type 1 diabetes mellitus (DM1) and asthma are mediated by opposite arms of the cellular immune system, namely T helper (Th)1 and Th2 CD4+ cells, respectively. It is not known whether their coexistence affects their clinical manifestations. The number of asthma exacerbations, frequency of hypoglycemic events, HbA1c levels, diabetes associated autoantibody status and diabetes associated late complications were determined in three paired groups of patients (n = 11) matched by gender and age: DM1 and asthma, asthma only, and DM1 only. Patients with both diseases had a higher prevalence of hypoglycemic events per month compared to patients with DM1 only: 5.67 +/- 4.27 vs 1.45 +/- 2.06, respectively (p = 0.008). The co-existence of the two diseases did not modify the remaining clinical and laboratory parameters. Patients with both DM1 and asthma have similar clinical characteristics to patients with only one of these diseases apart from a higher rate of hypoglycemic events compared to patients with DM1 without asthma.


Antioxidant therapy is associated with a reduction in the serum levels of mediators of renal injury following lithotripsy for renal calculi.
To investigate the effects of antioxidant therapy on the levels of mediators of shock wave induced renal injury in patients with renal calculi treated with extracorporeal shock wave lithotripsy (ESWL). One hundred and twenty patients with renal calculi were divided into three treatment groups: Group A patients (n = 39) served as a control group; Group B patients (n = 41) were given 2 capsules of Nature Made((R)) antioxidants 2 hours before, and 2 and 8 hours after ESWL and Group C patients (n = 40) were given 2 capsules of the antioxidants at 2 and 8 hours after ESWL. Blood and urine samples were obtained from all patients just before the start of treatment with ESWL, and at 2 and 24 hours and on day 7 and 28 after ESWL. Levels of mediators of renal injury such as serum alkaline phosphatase (ALP), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were measured. Urinary levels of albumin and ALP were also determined as measures of renal tubular injury. Patients given antioxidants had significantly reduced mean serum concentration of ALP (p < 0.001) at 24 hours, lower serum ALP and LDH on day 7 and 28, and lowest CRP on day 28 after ESWL. They also had higher urine albumin (p < 0.001) and ALP (p < 0.001) levels (from 24 hours to day 28) compared with patients who were not given antioxidants. These findings suggest that oral antioxidant therapy prior to lithotripsy may reduce the severity of long term renal injury caused by the shock waves.


Measuring the effectiveness of cataract surgery: the reliability and validity of a visual function outcomes instrument.
To assess test-retest reliability and validity of the "TyPE" patient self assessed visual function questionnaire, as part of a study in two hospitals measuring the effectiveness of cataract surgery. The American TyPE questionnaire had minor adaptations made for use in Britain. Test-retest reliability was assessed on 63 out of 378 adult cataract surgery patients in the study, using Spearman correlation coefficients and kappa coefficients of agreement. "Construct" validity was evaluated by comparing the association between changes in visual function questionnaire scores after surgery, with patients' perception of change in visual function obtained by independent interview of 24 patients. The TyPE questionnaire items showed very good test-retest reliability. Average Spearman and kappa coefficients for 39 patients from hospital 1 were 0.93 and 0.84 respectively. Spearman and kappa coefficients of 0.9 and 0.81 were obtained for those nine patients in hospital 2 where both the test and retest questionnaires were filled in by the same people. However, for the 15 patients from hospital 2, where the questionnaire was filled in by different people in the retest, reliability was less good: the Spearman coefficients were still high, average 0.72, but the kappa coefficients were poor, 0.27. Good construct validity was exhibited, with a correlation of 0.79 between change in distance vision score from the questionnaires and the independent interview. The adapted TyPE questionnaire is both very reliable and has good construct validity. The kappa coefficient should be used wherever possible to evaluate reliability. The test-retest reliability and validity and practicability of other visual function questionnaires have not been assessed adequately, and further development should be carried out of all such questionnaires, so that they may be introduced into routine clinical care.


Transmuscular quadratus lumborum (TQL) block for laparoscopic colorectal surgery: study protocol for a double-blind, prospective randomized placebo-controlled trial.
Thoracic epidural anesthesia is no longer considered the gold standard for perioperative analgesia in laparoscopic colorectal procedures. In the search for alternatives, the efficacy of the transverse abdominal plane (TAP) block and other abdominal wall blocks such as the transmuscular quadratus lumborum (TQL) block continues to be investigated for postoperative pain management. Most of the initial studies on TAP blocks reported positive effects; however, the amount of studies with negative outcomes is increasing, most probably due to the fact that the majority of abdominal wall blocks fail to mitigate visceral pain. The TQL block could prove attractive in the search for better postoperative pain relief after laparoscopic colorectal surgery. In several cadaveric studies of the TQL, a spread of dye into the thoracic paravertebral space, the intercostal spaces, and even the thoracic sympathetic trunk was reported. Given the advantage of possibly reaching the thoracic paravertebral space, the potential to reach nerves transmitting visceral pain, and the possible coverage of dermatomes T4-L1, we hypothesize that the TQL provides superior postoperative analgesia for laparoscopic colorectal surgery as compared to patient-controlled intravenous analgesia with morphine alone. In this prospective, randomized, double-blind controlled clinical trial, 150 patients undergoing laparoscopic colorectal surgery will be included. Patients will be randomly allocated to two different analgesic strategies: a bilateral TQL with 30 ml ropivacaine 0.375% each on both sides, administered before induction of anesthesia, plus postoperative patient-controlled intravenous analgesia with morphine (TQL group, n = 75), or a bilateral TQL block with 30 ml saline each on both sides plus postoperative patient-controlled intravenous analgesia with morphine (placebo group, n = 75). Our primary outcome parameter will be the morphine consumption during the first 24 h postsurgery. Secondary endpoints include pain intensity as assessed with the numerical rating scale (NRS) for pain, time to return of intestinal function (defined as the time to first flatus and the time to the first postoperative intake of solid food), time to first mobilization, the incidence of postoperative nausea and vomiting during the first 24 h, length of stay on the post anesthesia care unit (PACU) and in the hospital, the extent of sensory block at two time points (admission to and discharge from the PACU), the doses of morphine IV as requested by the patient from the PCA pump, the total dosage of morphine administered IV, the need for and dose of rescue analgesics (ketamine, clonidine), free plasma ropivacaine levels after induction and at discharge from the PACU, and the incidence of adverse events during treatment (in particular, signs of local anesthetic systemic toxicity (LAST)). Epidural analgesia is no longer the standard of care for postoperative analgesia in laparoscopic colorectal surgery. Until now, the most effective analgesic strategy in these patients especially in an enhanced recovery program is still unknown. Several abdominal wall blocks (TAP, fascia transversalis plane block) are known to have an analgesic effect only on somatic pain. Recognizing the importance of procedure-specific pain management, we aim to investigate whether a transmuscular quadratus lumborum block delivers superior pain control in comparison to patient-controlled intravenous analgesia with morphine alone. EudraCT identifier 2019-002304-40. Registered on 17 September 2019.


Localization of Charcot-Leyden crystal protein in individual morphological phenotypes of human basophils stimulated by f-Met peptide.
Human basophils undergo anaphylactic degranulation, characterized by extrusion of membrane-free granules, and piecemeal degranulation, characterized by progressive removal of granule contents in the absence of granule extrusion. F-Met peptide stimulates a degranulation continuum in human basophils that includes both forms of secretion. Charcot-Leyden crystal protein is stored in the granules of unstimulated human basophils. The objective of this study was to determine the subcellular localization of the Charcot-Leyden crystal protein in individual morphological basophil phenotypes that are stimulated by f-Met peptide and are associated with secretion. A post-embedding immunogold analysis was used to detect changes in the subcellular sites of Charcot-Leyden crystal protein in human basophils stimulated with f-Met peptide. Human basophils from normal donors were purified by countercurrent centrifugal elutriation and Percoll density gradients, stimulated to degranulate with 1 micron f-Met peptide (or incubated in buffer controls), and recovered for histamine assay, electron microscopy and immunogold labelling. Specificity controls included omission of the primary antibody and substitution of the primary antibody with non-immune normal rabbit IgG or with Charcot-Leyden crystal protein-Sepharose-absorbed primary antibody. The results showed new sites of labelling and different densities of labelling for Charcot-Leyden crystal protein in distinctive basophil phenotypes stimulated by f-Met peptide. New sites for Charcot-Leyden crystal protein included nucleus, cytoplasm, degranulation channel, degranulation channel membrane, plasma membrane, and a newly recognized granule population similar to primary granules in eosinophils. These new sites, as well as previously documented sites of Charcot-Leyden crystal protein (granules, intragranular Charcot-Leyden crystals, cytoplasmic vesicles) showed variable labelling when analysed by phenotype. Other sites (besides intragranular Charcot-Leyden crystals) of formed Charcot-Leyden crystals included cytoplasm, degranulation channel, extracellular space and, rarely, nucleus. Analysis of cytoplasmic vesicles, total granules and altered granules, and gold particles in subcellular compartments in seven identifiable phenotypes revealed that f-Met peptide stimulated human basophils to empty their granules by transporting Charcot-Leyden crystal protein in vesicles to the plasma membrane in the absence of granule extrusion in cells exhibiting piecemeal degranulation. In cells exhibiting anaphylactic degranulation, gold-labelled Charcot-Leyden crystals were extruded to the cells' exterior in concert with granule particles and concentric dense membranes contained within granules. Completely degranulated cells had a high density of plasma membrane gold label that was associated with numerous gold-laden endocytotic cytoplasmic vesicles. Basophils reconstituted their main granule population, within which Charcot-Leyden crystals resided, in part by endocytosis of previously released plasma membrane-bound Charcot-Leyden crystal protein. Completely recovered cells displayed decreased Charcot-Leyden crystal protein labelling of the plasma membrane and vesicle compartments, the presence of a highly labelled new granule subset that resembled Charcot-Leyden crystal protein-containing primary granules in eosinophils, and the highest density of granule and intragranular Charcot-Leyden crystal gold labelling of all phenotypes that developed after stimulation. Seven individual f-Met peptide-activated human basophil phenotypes labelled by an ultrastructural immunogold method to detect subcellular sites of Charcot-Leyden crystal protein showed changing distributions of this protein which document the capability of human basophils to undergo complex release and recovery reactions that may be pertinent to the functions of Charcot-Leyden crystal protein and the capabilit


Interresidue contacts in proteins and protein-protein interfaces and their use in characterizing the homodimeric interface.
The environment of amino acid residues in protein tertiary structures and three types of interfaces formed by protein-protein association--in complexes, homodimers, and crystal lattices of monomeric proteins--has been analyzed in terms of the propensity values of the 20 amino acid residues to be in contact with a given residue. On the basis of the similarity of the environment, twenty residues can be divided into nine classes, which may correspond to a set of reduced amino acid alphabet. There is no appreciable change in the environment in going from the tertiary structure to the interface, those participating in the crystal contacts showing the maximum deviation. Contacts between identical residues are very prominent in homodimers and crystal dimers and arise due to 2-fold related association of residues lining the axis of rotation. These two types of interfaces, representing specific and nonspecific associations, are characterized by the types of residues that partake in "self-contacts"--most notably Leu in the former and Glu in the latter. The relative preference of residues to be involved in "self-contacts" can be used to develop a scoring function to identify homodimeric proteins from crystal structures. Thirty-four percent of such residues are fully conserved among homologous proteins in the homodimer dataset, as opposed to only 20% in crystal dimers. Results point to Leu being the stickiest of all amino acid residues, hence its widespread use in motifs, such as leucine zippers.


[Disseminated histoplasmosis].
We describe two cases of disseminated histoplasmosis, which are of interest due to their severity and the infrequency of this infection in our environment. Both children were immunocompromised immigrants from Latin America who developed prolonged fever, weight loss, hepatosplenomegaly and pancytopenia. One patient had respiratory symptoms with associated alterations on x-ray, while no radiological alterations were found in the other patient. Despite administration of broad-spectrum antibiotics and extraction of samples for microbiological analysis, both patients had a rapid and fatal outcome and the diagnosis was made post mortem. Because of its severity, disseminated histoplasmosis should be considered in the differential diagnosis of fever, hepatosplenomegaly and pancytopenia, with or without alterations on chest x-ray, in immunosuppressed children who were born in or have visited endemic regions. In these patients, therapy should be started immediately without waiting for the results of diagnostic tests.


Hippocampal metaplasticity is required for the formation of temporal associative memories.
Metaplasticity regulates the threshold for modification of synaptic strength and is an important regulator of learning rules; however, it is not known whether these cellular mechanisms for homeostatic regulation of synapses contribute to particular forms of learning. Conditional ablation of mGluR5 in CA1 pyramidal neurons resulted in the inability of low-frequency trains of afferent activation to prime synapses for subsequent theta burst potentiation. Priming-induced metaplasticity requires mGluR5-mediated mobilization of endocannabinoids during the priming train to induce long-term depression of inhibition (I-LTD). Mice lacking priming-induced plasticity had no deficit in spatial reference memory tasks, but were impaired in an associative task with a temporal component. Conversely, enhancing endocannabinoid signaling facilitated temporal associative memory acquisition and, after training animals in these tasks, ex vivo I-LTD was partially occluded and theta burst LTP was enhanced. Together, these results suggest a link between metaplasticity mechanisms in the hippocampus and the formation of temporal associative memories.


The power of scenario.
Teaching wilderness medicine to medical students comes alive when nontraditional methods are used. In our wilderness medicine elective at the University of Massachusetts Medical School, the teaching is primarily experientially based. The following anecdote illustrates the magic that can happen when teaching is done via the scenario-debriefing method.


[The Urinary Tract Diseases Dispensary and Clinic of the Instituto Rubio (1885). !st hospital service specializing in urologic pathology in the history of Spanish medicine. 2nd period. The Instituto Rubio in Moncloa (1896-1936).(II)].
In 1896, for different reasons and requirements, the Institute of Operative Therapy of the Hospital de la Princesa was transferred to a new and ample site in the Moncloa district in Madrid, with building complexes and pavillions for the dispensaries and policlinics for practically all surgical specialties, with all the necessary equipment. This came to be known as the "Rubio Institute". Luis González Bravo y Serrano, Suender's assistant, was in charge of the new Dispensary and Clinic for Diseases of the Urinary Tract of the Institute until 1929; Carlos Negrete de los Reyes was his assistant. Both specialists' initiative and drive led to the creation of the Spanish Urological Society in 1911. They were elected President and Secretary, respectively, to the first Board of the Society. This article reviews the activities of the specialists in Diseases of the Urinary Tract of the new Institute in the provision of care, in the field of teaching and research, from their brilliant beginnings to their decline in 1936, when the Spanish Civil War broke out. In my view, for all the contributions of those who worked in this Section and its significant influence on the Spanish specialists during its existence of more than 50 years, the Dispensary and Clinic of Diseases of the Urinary Tract of the Rubio Institute should be considered the catalyst and essence of Spanish urology and the Spanish Urological Society.


A critique of utilitarian and instrumentalist concepts for the teaching of gross anatomy to medical and dental students: Provoking debate.
Medical and dental curricula, together with anatomical sciences courses, are increasingly having to change, mainly because there is a drive to being what is termed, without adequate definition, "clinically relevant." The concept of "clinical anatomy" has accordingly been invented and it is expected that, at all times, the teaching of anatomy is directly focused on clinical scenarios, meaning almost invariably the disease-based model of medicine and dentistry. Furthermore, students are not expected to have a detailed knowledge of gross anatomy and the time devoted to teaching and learning the subject has decreased significantly. The notion being fostered is that knowledge is not required "just in case" but "just in time." However, the absence of agreed core syllabuses that are internationally accepted complicates a discussion about what is relevant practically and what does not need to be taught. In this article, we critique such an utilitarian and instrumentalist approach to the teaching of gross anatomy within medical and dental curricula. We draw attention to the need to embrace the functionality-based model of medicine and dentistry by returning to an understanding that the role of the medical or dental practitioner is to value health and to restore to functionality the ill person or the pathologically affected region/organ/system. A fuller knowledge of anatomy than is presently taught is regarded as a prerequisite for appreciating normality and health. A further problem with the instrumentalist approach to medical education is that, by concentrating on what is seen to be at the time "useful" or "clinically relevant," there is the danger of undermining, or discouraging, future developments that rely on what contemporaneously seems "useless" and "irrelevant" knowledge. Finally, the reliance instrumentalism has on just what is pragmatic and regardless of scientific validity is contrary to the ethos and practice of a university education that values deep learning and the development of learnèd professions. Clin. Anat. 30:912-921, 2017. © 2017 Wiley Periodicals, Inc.


Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles.
Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca(2+). However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca(2+) signals, and at elevated Ca(2+) concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca(2+)-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion.


Assessment of xerostomia and its impact on quality of life in head and neck cancer patients undergoing radiation therapy.
Xerostomia in head and neck (H&N) cancer patients significantly affects their quality of life (QoL). The aim of the present study was to investigate the associations among QoL, xerostomia and quantity of saliva in a sample of H&N cancer patients who had received conventional radiotherapy (RT). A total of 60 H&N adult patients were enrolled in this prospective study. The patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30), the Quality of Life Questionnaire Head and Neck Module (QLQ-H&N35) and the Greek version of the XQ questionnaire at 4 timepoints: At the beginning of RT, at the end of RT, 6 months after RT completion and 1 year after RT completion. Patients with distant metastases or serious comorbidities were excluded from the study. Salivary pH, and stimulated and unstimulated salivary flow rate were assessed. All functional scales and symptom scales, apart from cognitive functioning in QLQ-C30 and feeding tube in H&N35 exhibited an abrupt deterioration at timepoint 3 and were then gradually restored over time. The difference was statistically significant (P<0.001). XQ scores at different timepoints exhibited a statistically significant negative correlation with salivary flow rates. Salivary flow rate and XQ scores almost parallelled one another. Flow rates recovered at a mean level of 20% below baseline values at the end of the follow-up period. The subjective symptom of xerostomia parallelled salivary flow and QoL. Despite receiving conventional RT, the participants exhibited a considerable preservation of salivary gland function after 12 months, allowing some optimism regarding the course of xerostomia in selected patients.


Contagion dynamics on hypergraphs with nested hyperedges.
In complex social systems encoded as hypergraphs, higher-order (i.e., group) interactions taking place among more than two individuals are represented by hyperedges. One of the higher-order correlation structures native to hypergraphs is the nestedness: Some hyperedges can be entirely contained (that is, nested) within another larger hyperedge, which itself can also be nested further in a hierarchical manner. Yet the effect of such hierarchical structure of hyperedges on the dynamics has remained unexplored. In this context, here we propose a random nested-hypergraph model with a tunable level of nestedness and investigate the effects of nestedness on a higher-order susceptible-infected-susceptible process. By developing an analytic framework called the facet approximation, we obtain the steady-state fraction of infected nodes on the random nested-hypergraph model more accurately than existing methods. Our results show that the hyperedge-nestedness affects the phase diagram significantly. Monte Carlo simulations support the analytical results.


Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4.
Breast cancer remains the second largest cause of mortality in women with cancer and does not respond well to conventional therapies. Regulator of G-protein signaling 4 (RGS4) is a GTPase-activating protein of the heterotrimeric Gq and Gi proteins. Altered levels of RGS4 are reportedly linked with several human diseases, including cancer. The present study investigated whether overexpression of RGS4 inhibited the growth of human breast cancer cells. Protein expression was investigated by western blot analysis. Cell viability and apoptosis were analyzed by MTT assay and flow cytometric analysis, respectively. Cell cycle analysis was performed using propidium iodide staining in order to examine the anti-proliferative function of increased RGS4 levels. Next, changes in the expression levels of G2/M cell cycle-related proteins were examined. Overexpression of RGS4 led to the upregulation of phosphorylayed (p)-Ser216 cell division cycle (Cdc)25C and p-Tyr15 Cdc2. Importantly, MG132-induced proteasome blockade prevented degradation of RGS4. Suppression of proliferation was associated with G2/M-phase cell cycle arrest. Furthermore, enhanced endogenous RGS4 protein levels significantly inhibited breast cancer cell growth, which was reversed by a pharmacological inhibitor of RGS4. Taken together, these results suggest that overexpression of RGS4 in human breast cancer cells by molecular means may offer a potential therapeutic approach.


Teratogenicity of zinc chloride, 1,10-phenanthroline, and a zinc-1,10-phenanthroline complex in mice.
Zinc chloride, in single doses of 12.5, 20.5 and 25 mg/kg ip on Day 8,9,10, or 11 of gestation in CF-1 albino mice, produced skeletal anomalies without accompanying soft tissue defects. Ripple ribs, the most unusual anomaly, first appeared when the zinc salt was given on Day 9 of gestation in a dose of 20.5 mg/kg, becoming more prevalent when 25 mg/kg of the drug was administered on Day 11.1,10-Phenanthroline, in single doses of 30 mg/kg ip on Day 8,9,10, or 11 of gestation elicited skeletal defects comparable to those caused by zinc chloride as well as soft tissue anomalies, but a significant incidence of the former occurred with this agent only following its injection on Day 8 of gestation. A zinc-1,10-phenanthroline complex in single doses of 50 mg/kg on Day 8,9,10, or 11 of gestation yielded significant incidences of skeletal and soft tissue anomalies only when the complex was administered on Day 8 or 9 of gestation. This dosage level was toxic to both the mother and fetus when given on Day 10 of gestation. However, when the complex was given on Day 8,9,10, or 11 in a dose of 25 mg/kg, neither toxic nor teratogenic effects were observed in the mother or fetus, respectively.


Synthesis and in vitro evaluation of West Nile virus protease inhibitors based on the 1,3,4,5-tetrasubstituted 1H-pyrrol-2(5H)-one scaffold.
West Nile virus (WNV), a member of the Flaviviridae family, is a mosquito-borne pathogen that causes a large number of human infections each year. There are currently no vaccines or antiviral therapies available for human use against WNV. Therefore, efforts to develop new chemotherapeutics against this virus are highly desired. In this study, a WNV NS2B-NS3 protease inhibitor with a 1,3,4,5-tetrasubstituted 1H-pyrrol-2(5H)-one scaffold was identified by screening a small library of nonpeptidic compounds. Optimization of this initial hit by the synthesis and screening of a focused library of compounds with this scaffold led to the identification of a novel uncompetitive inhibitor ((-)-1a16, IC₅₀ =2.2±0.7 μM) of the WNV NS2B-NS3 protease. Molecular docking of the chiral compound onto the WNV protease indicates that the R enantiomer of 1a16 interferes with the productive interactions between the NS2B cofactor and the NS3 protease domain and is thus the preferred isomer for inhibition of the WNV NS2B-NS3 protease.


Effect of Osmolytes on Water Mobility Correlates with Their Stabilizing Effect on Proteins.
There is a long, ongoing debate on how small molecules (osmolytes) affect the stability of proteins. The present study found that change in collective rotational dynamics of water in osmolyte solutions likely has a dominant effect on protein denaturation. According to THz spectroscopy analysis, osmolytes that stabilize proteins are accompanied by bound hydration water with slow dynamics, while the collective rotational dynamics of water is accelerated in the case of denaturant osmolytes. Among 15 osmolytes studied here, there is a good correlation between the change in mobility in terms of water rotational dynamics and the denaturation temperature of ribonuclease A. The changes in water dynamics due to osmolytes can be regarded as a pseudo-temperature-change, which agrees well with the change in protein denaturation temperature. These results indicate that the molecular dynamics of water around the protein is a key factor for protein denaturation.


The potential DNA toxic changes among workers exposed to antimony trioxide.
Occupational exposure to antimony has gained much interest when specific toxic effects were noticed among workers processing antimony. Thus, the aim of the present work was to investigate the potential DNA oxidative damage occurring among Egyptian workers occupationally exposed to antimony trioxide. The study was conducted on 25 subjects exposed to antimony trioxide while working in the polymerization process of polyester in Misrayon and Polyester Fiber Company, KafrEldawwar, Beheira, Egypt. Urinary antimony levels were assessed using inductive coupled plasma-optical emission spectrometry (ICP-OES) and considered as a biological exposure index. DNA damage and total oxidant capacity (TOC) were assessed using ELISA. DNA damage was detected in the form of increased apurinic/apyrimidinic (AP) sites among antimony trioxide-exposed workers compared to control subjects, but it could not be explained by oxidative mechanisms due to lack of significant correlation between DNA damage and measured TOC. Antimony trioxide might have a genotoxic impact on occupationally exposed workers which could not be attributed to oxidative stress in the studied cases.


Salivary cortisol and IgA levels in patients with myofascial pain treated with occlusal appliances in the short term.
In many studies, the endocrinological response of individuals to different kinds of stresses has been tested. There seems to be widespread agreement that stress, depression, disability and dysfunctional illness behaviors are critical aspects of patients suffering from symptoms like pain, arising out of temporomandibular disorders (TMD). We aimed to explore treatment-induced changes in salivary cortisol, IgA and flow rate values in TMD patients suffering from myofascial pain. Temporomandibular disorders patients (n = 39) were randomized into two groups and treated with two different occlusal appliances. Perceived stress regarding family, work, economy, relationships, general health and stress in general was evaluated at baseline according to a verbal scale. Paraffin-stimulated saliva samples were collected before treatment and during follow-up at 6 and 10 weeks. Flow rate was measured immediately after the saliva collection while salivary cortisol and IgA were determined from samples stored at -70 degrees C. No clear association between reported stress and cortisol or IgA values could be observed at baseline. At 10 weeks follow-up, 92% of the patients felt 'better, much better, symptom-free' and no difference was found between the two appliance groups. Cortisol, IgA and flow rate values showed no systematic between appliance groups' differences. All salivary parameters showed interindividual differences but stayed intra-individually on a similar level throughout the study and no statistically significant changes could be observed when comparing before and after treatment levels. To conclude, there were no treatment-induced changes in saliva parameters despite successful appliance therapy in myofascial pain patients.


An analysis of sampling errors for the Demographic Health Surveys.
"Sampling errors and design effects from 48 nationally representative surveys conducted under the Demographic and Health Surveys Program for a large number of variables concerning fertility, family planning, fertility intentions, child health and mortality etc. are analysed for the total sample, and for urban-rural domains, sub-national regions and various demographic and socio-economic subclasses.... At the country level, overall design effect (the ratio of actual to simple random sampling standard error) averaged over all variables and countries is around 1.5. Variation among countries is high, but less so than among variables. Urban-rural and regional differentials in design effects are small, and can be attributed to the fact that similar sample designs and cluster sizes were used across those domains within each country. Design effects for estimates over other subclasses are smaller, and tend towards 1.0 for small subclasses and differences, apart from the effect of sample weights which tends to persist undiminished across variables and subclasses." (SUMMARY IN FRE)


Rapid enrichment of bioactive milk proteins and iterative, consolidated protein identification by multidimensional protein identification technology.
Direct injection of complex protein mixtures, e.g. those derived from crude biological fluids, is often incompatible with conventional LC supports, because of column clogging and rapid deterioration of chromatographic performance. In this paper, we report the use of restricted access media to rapidly enrich and fractionate human breast milk. This resin, combining size exclusion and anion exchange functionalities, yielded a fraction enriched in soluble CD14 and showing specific sCD14-dependant activity. This fraction was split into five aliquots, which were individually characterized using multidimensional protein identification technology. Reproducibility of the results was addressed by analysing and comparing five datasets using different protein identification tools available within the Sequest software. Furthermore, a comparison of three major releases of the Ensembl human protein database was performed to examine the effect of database updates on our results. We report here the benefit of repeated analysis of aliquots of the same fraction: first to increase the confidence in peptide identification by repeated confirmation in several aliquots; and second to assess experimental reproducibility. We demonstrate furthermore the effect of database modifications on the results and the importance of constantly re-analysing data with new releases to keep them consistent and up to date with the latest protein identities and predictions available.


Phosphate Additive Avoidance in Chronic Kidney Disease.
IN BRIEF Dietary guidelines for patients with diabetes extend beyond glycemic management to include recommendations for mitigating chronic disease risk. This review summarizes the literature suggesting that excess dietary phosphorus intake may increase the risk of skeletal and cardiovascular disease in patients who are in the early stages of chronic kidney disease (CKD) despite having normal serum phosphorus concentrations. It explores strategies for limiting dietary phosphorus, emphasizing that food additives, as a major source of highly bioavailable dietary phosphorus, may be a suitable target. Although the evidence for restricting phosphorus-based food additives in early CKD is limited, diabetes clinicians should monitor ongoing research aimed at assessing its efficacy.


Aqueous and ethanolic extracts of welsh onion, Allium fistulosum, attenuate high-fat diet-induced obesity.
Allium fistulosum (Welsh onion) is a traditional medicinal plant used for the treatment of colds, influenza, abdominal pain, headache, and heart disease. This study evaluated the effects of A. fistulosum ethanolic extract (AFE) and aqueous extract (AFW) on body weight and other obesity-related parameters. Male 8-week-old C57BL/6 J mice were fed either a standard chow diet (normal control) or a high-fat diet (HFD) either alone (HFD-control) or in combination with G. cambogia extract containing hydroxycitric acid (HCA, an herbal weight-loss supplement), conjugated linoleic acid (CLA, a weight-loss supplement), orlistat (a clinically available anti-obesity drug), AFW, or AFE (n = 6 mice per group) for 6 weeks. At the end of 6 weeks, several body weight and obesity-related parameters were examined, including: liver and adipose weight, adipocyte size, serum lipid profiles, liver expression of adenosine monophosphate-activated protein kinase (AMPK), and adipose tissue expression of uncoupling protein 2 (UCP2). High-performance liquid chromatography showed that both AFE and AFW contain ferulic acid and quercetin. Oral administration of AFW and AFE to HFD-fed mice decreased body weight as well as liver and adipose tissue weight and adipocyte size. Serum lipid profiles and adiponectin levels were improved in HFD-fed mice treated with AFE but not AFW. However, both AFW and AFE significantly attenuated HFD-induced changes in serum leptin and insulin-like growth factor 1 levels, liver expression of AMPK, and adipose tissue expression of UCP2. The findings from this study suggest that A. fistulosum extracts have potential as functional food materials for weight control in obesity.


Pre-operative scanning of the liver for colorectal liver metastases.
The comparative value of staging the extent of colorectal liver metastases by isotope, ultrasound and CT imaging has been assessed in 20 patients considered for inclusion into a randomized trial. Metastases were identified in all patients by CT, but failed in 4 by isotope and 2 by ultrasound scanning. There was often a discrepancy of 25% in estimating tumour replacement between the different modalities and surgical evaluation. As the extent of tumour is an important prognostic factor, initial evaluation should incorporate all three imaging techniques. Relative regional blood flow in tumour and normal liver regions was measured by dynamic liver scintigraphy, showing that 60% have a predominantly arterial blood supply.


Validation of SPECT equilibrium radionuclide angiographic right ventricular parameters by cardiac magnetic resonance imaging.
Recent advances in the treatment of primary pulmonary hypertension (PPH), and in surgery to correct tetralogy of Fallot (TOF), have rekindled interest in evaluating right ventricular (RV) volume and ejection fraction (EF). The purpose of this investigation was to determine the accuracy of RV functional parameters assessed by single photon emission computed tomography (SPECT) equilibrium radionuclide angiography (ERNA). Twenty-eight patients with PPH (n = 15) or TOF (n = 13) (aged 28 +/- 14 years; 57% male) were analyzed by means of SPECT ERNA algorithms that automatically identified mid-RV tomographic planes, generated regions isolating the right ventricle from other structures, and presented RV-segmented regions as a cinematic display. RV EF and volumes were computed and compared with values obtained by magnetic resonance imaging (MRI). Mean values were not different between SPECT ERNA and MRI for RV EF, end-diastolic volume, and end-systolic volume (42% +/- 11% vs 41% +/- 10%, 135 +/- 67 mL vs 139 +/- 91 mL, and 87 +/- 54 mL vs 85 +/- 61 mL, respectively; P = not significant for all comparisons). Significant linear correlation (P <.0001) was found between SPECT ERNA and MRI for RV EF, end-diastolic volume, and end-systolic volume (r = 0.85, r = 0.94, and r = 0.93, respectively). No statistically significant trends or biases for RV EF were found. Intraobserver and interobserver comparisons demonstrated good reproducibility. As expected, RV volume was significantly higher and RV EF was significantly lower for patients with PPH and TOF than were values for individuals at low likelihood for coronary artery disease or other cardiac disease. SPECT ERNA provides accurate, reproducible assessment of RV volumes and EF and should prove useful in evaluating the magnitude of RV dysfunction in patients and in providing an objective means with which to assess the results of therapeutic interventions.


Inner-hydrogen tautomerism in some 5,15-unsymmetrically disubstituted and beta-unsubstituted porphyrins.
5,15-Unsymmetrically disubstituted and beta-unsubstituted porphyrins such as 5-R, 15-(3,5-dimethoxyphenyl) porphyrins [where R=2-benzyloxy-1-naphthyl (1), 2-(2-naphthylmethoxy)-1-naphthyl (2), anthryl (3), or 2,4,6-triphenylphenyl (4)] and 5-(2-benzyloxy-1-naphthyl), 10,15,20-tri(3,5-dimethoxyphenyl) porphyrin (1') were synthesized and studied by (1)H-NMR spectroscopy. At room temperature, 1, 2, 3 and 4 showed doubling of the inner-hydrogen resonances with equal intensities, whereas the pyrrolic betaH signals were completely averaged. For 1 and 1', variable-temperature (1)H-NMR experiments were also performed. For 1, the two peaks of the inner hydrogen coalesced at about 313 K. In contrast, the pyrrolic betaH signals were only slightly broadened even at 213 K. On the other hand, 1' showed ordinary singlets of the inner hydrogens at room temperature, and the resonances of both the inner hydrogens and the pyrrolic betaH coalesced at about 233 K. We interpret these results as indicating the existence of two distinct paths, one slow and the other fast, leading to NH tautomerization in 1. We discuss the structures and energies of cis-tautomers as transition intermediates in relation to the two paths of NH tautomerization.


Clinical Presentation of Adult Pulmonary Tuberculosis (PTB): A Study of 103 Cases from a Tertiary Care Hospital.
Tuberculosis, one of the oldest diseases known to affect humans, is a major cause of death worldwide. The disease, which is caused by the bacteria Mycobacterium tuberculosis complex, usually affects the lungs, although other organs are involved in up to one-third of causes. If properly treated, tuberculosis caused by drug-susceptible strains is curable in virtually all cases. If untreated, the disease may be fatal within five years in 50-65% of cases. Transmission usually takes place through the airborne spread of droplet nuclei produced by patients with infectious pulmonary tuberculosis. This cross sectional observational study was conducted to detect various clinical presentations of pulmonary tuberculosis patients in the Department of Medicine, Sir Salimullah Medical College and Hospital from January 2009 to December 2009. Sample was selected through inclusion methods from patients who was admitted in to hospital and confirmed as pulmonary tuberculosis after appropriate investigations and who gave informed written consent was finally enrolled in this study. A total 103 patients were selected for the study. Out of 103 cases 34.9% were above 50 years old, followed by 26.2% between 30-40 years old, 22.3% between 40-50 years old and remaining 16.5% bellow 30 years old. The male to female ratio was roughly 1.2:1. The most of the patients were housewife and farmer which were 31% and 28.1% respectively. The most of the patients came from low socio-economic group. About 55.3% cases were smoker and 43.7 were non smoker. Among the frequency of symptoms 73.7% were chronic cough for above one month followed by 70.8% were low grade fever, 41.8% were night sweats and the 2% were admitted in hospital for other complaints and after evaluation diagnosed as PTB. The most of the patients about 67% were suffering from less than six weeks duration. Among the physical findings the 67% cases were lost significant weight, 56.3% had fever and 56.3% had apical crepitation over chest. There was sputum positive for acid fast bacilli about 64.7%. The traditional TB diagnosis methods are time consuming and the most of the patients are poor in our country, they are unable to afford the modern costly investigations. Therefore we should more emphasis on clinical examinations, so that we can diagnosis pulmonary TB rapidly and can start treatment as early as possible.


Maternal transfer of xenobiotics and effects on larval striped bass in the San Francisco Estuary.
Aquatic ecosystems around the world face serious threats from anthropogenic contaminants. Results from 8 years of field and laboratory investigations indicate that sublethal contaminant exposure is occurring in the early life stages of striped bass in the San Francisco Estuary, a population in continual decline since its initial collapse during the 1970s. Biologically significant levels of polychlorinated biphenyls, polybrominated diphenyl ethers, and current-use/legacy pesticides were found in all egg samples from river-collected fish. Developmental changes previously unseen with standard methods were detected with a technique using the principles of unbiased stereology. Abnormal yolk utilization, brain and liver development, and overall growth were observed in larvae from river-collected fish. Histopathological analyses confirmed and identified developmental alterations. Using this methodology enabled us to present a conclusive line of evidence for the maternal transfer of xenobiotics and their adverse effects on larval striped bass in this estuary.


Complete Genome Sequence of Bacillus subtilis GQJK2, a Plant Growth-Promoting Rhizobacterium with Antifungal Activity.
Bacillus subtilis GQJK2 is a plant growth-promoting rhizobacterium with antifungal activity which was isolated from Lycium barbarum L. rhizosphere. Here, we report the complete genome sequence of B. subtilis GQJK2. Ten gene clusters involved in the biosynthesis of antagonistic compounds were predicted.


Intra-Subject Variability of 5 km Time Trial Performance Completed by Competitive Trained Runners.
Time-trials represent an ecologically valid approach to assessment of endurance performance. Such information is useful in the application of testing protocols and estimation of sample sizes required for research/magnitude based inference methods. The present study aimed to investigate the intra-subject variability of 5 km time-trial running performance in trained runners. Six competitive trained male runners (age = 33.8 ± 10.1 years; stature = 1.78 ± 0.01 m; body mass = 69.0 ± 10.4 kg, [Formula: see text]O2max = 62.6 ± 11.0 ml·kg·min-1) completed an incremental exercise test to volitional exhaustion followed by 5 x 5 km time-trials (including a familiarisation trial), individually spaced by 48 hours. The time taken to complete each trial, heart rate, rating of perceived exertion and speed were all assessed. Intra-subject absolute standard error of measurement and the coefficient of variance were calculated for time-trial variables in addition to the intra-class correlation coefficient for time taken to complete the time-trial. For the primary measure time, results showed a coefficient of variation score across all participants of 1.5 ± 0.59% with an intra-class correlation coefficient score of 0.990. Heart rate, rating of perceived exertion and speed data showed a variance range between 0.8 and 3.05%. It was concluded that when compared with related research, there was observed low intra-subject variability in trained runners over a 5 km distance. This supports the use of this protocol for 5 km time-trial performance for assessment of nutritional strategies, ergogenic aids or training interventions on endurance running performance.