Expert consensus document on arterial stiffness: methodological issues and clinical applications.
In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.


Effects of different desensitizers and lasers on dentine tubules: An in-vitro analysis.
Dentin hypersensitivity is an important clinical problem affecting a large percentage of the population, and various therapies have been suggested for its treatment-among them desensitizing agents and lasers. The aim of this study was to evaluate the in vitro effects of different in-office desensitizing agents and different type lasers, alone or in combination, on human dentinal tubules. Eighty-four dentinal specimens obtained from freshly extracted impacted third molars were included and subsequently divided into seven groups: Group 1 (Control), Group 2 (Gluma desensitizer), Group 3 (Teethmate desensitizer), Group 4 (Nd:YAG laser), Group 5 (Er:YAG laser), Group 6 (Gluma desensitizer + Er:YAG laser), and Group 7 (Teethmate desensitizer + Er:YAG laser). The dentinal specimens of all groups were evaluated using SEM. A total of 12 images per sample were taken, and the numbers of open, partially occluded, and totally visible (open + partially occluded) dentinal tubules were counted. AFM was used to further substantiate the blocking mechanism. The data were analyzed by one-way ANOVA and Dunnett-C tests. Comparison of the number of occluded dentinal tubules per 100 µm2 revealed that the laser and laser combined-treated groups showed the most occluded dentinal tubules. Gluma desensitizer + Er:YAG laser combination demonstrated significantly more tubule occlusion than all the other groups (p < .05). The results of this study show that combined treatment methods were effective in the occlusion of dentinal tubules.


Gene expression mediated by bacteriophage T3 and T7 RNA polymerases in transgenic trypanosomes.
Messenger RNAs of higher eukaryotes share a functionally essential 5' monomethyl CAP structure generated during a reaction that is linked exclusively to RNA polymerase II transcription. In unicellular parasites belonging to the Kinetoplastida, however, mRNAs acquire their 5' CAP through a trans-splicing reaction which effectively uncouples pol II transcription and capping. Consequently functional mRNAs can be produced by endogenous RNA polymerase I. Here we demonstrate the extension of this flexibility to heterologous bacteriophage polymerases. Transgenic Trypanosoma brucei cell lines stably expressing functional, nuclearly localized T3 or T7 RNA polymerase were established and assayed using reporter plasmids bearing the corresponding phage promoters. In these cell lines the levels of phage promoter-driven gene expression ranges from one half to greater than 5 times that mediated by endogenous pol I. Analysis of 5' ends of transcripts synthesized by the T7 polymerase revealed that they are trans-spliced. Thus the usual eukaryotic link between mRNA production and pol II transcription can be by-passed by the introduced phage polymerases, thereby significantly expanding the critically small panel of promoters currently available for exploitation in reverse genetic approaches in T. brucei.


Bilateral appendicular bone tumors in four dogs.
Bilateral synchronous appendicular bone tumors, occurring in the same bone and same anatomic site within the bone are very rare. This report describes the clinical presentation and oncologic outcome for four dogs with this rare presentation. All cases presented to the authors following a history of unilateral lameness for several weeks. On presentation, case 1 had pain elicited in the contralateral proximal humerus but all the other cases had no abnormalities detectable on physical examination of the contralateral limb. All dogs had technetium 99m ((99m)Tc) nuclear scintigraphy performed that identified bilateral lesions of the distal radii in two dogs, proximal humeri and distal tibiae in one dog each. Thoracic radiographs performed on all dogs showed no evidence of pulmonary metastases. Three dogs were treated with palliative radiation therapy (two dogs received concurrent bisphosphonates) resulting in survival times from initial presentation of 50 days, 193 days, and 523 days, respectively. One dog had stereotactic radiation therapy (SRT) and a surgical limb-salvage performed followed by carboplatin chemotherapy, resulting in a survival time of 926 days from initial presentation. Palliative and curative-intent treatments for the bilateral synchronous appendicular bone tumors resulted in survival times similar to those reported for treatment of a single primary appendicular bone tumor.


BAG5 Interacts with DJ-1 and Inhibits the Neuroprotective Effects of DJ-1 to Combat Mitochondrial Oxidative Damage.
Loss-of-function mutations in gene encoding DJ-1 contribute to the pathogenesis of autosomal recessive early-onset familial forms of Parkinson's disease (PD). DJ-1 is a multifunctional protein and plays a protective role against oxidative stress-induced mitochondrial damage and cell death, but the exact mechanism underlying this is not yet clearly understood. Here, using coimmunoprecipitation (Co-IP) and immunofluorescence methods, we prove that Bcl-2-associated athanogene 5 (BAG5), a BAG family member, interacts with DJ-1 in mammalian cells. Moreover, we show that BAG5 could decrease stability of DJ-1 and weaken its role in mitochondrial protection probably by influencing dimerization in stress condition. Our study reveals the relationship of BAG5 and DJ-1 suggesting a potential role for BAG5 in the pathogenesis of PD through its functional interactions with DJ-1.


[The possible carcinogenic action of a protein concentrate from Saccharomyces yeasts grown on molasses].
A testing was done in a chronic experiment on 300 rats and 360 mice of both sexes for carcinogenic potential of a new protein product from Saccharomyces yeast grown in melasse. The production procedures and techniques of the above product have been worked out at the Ukrainian Research Institute of Spirits and Biotechnology of Food Stuffs of Gospishcheprom (State Food Industry) of Ukraine. The studies made showed the new protein product has no carcinogenic effect.


Acute effects of acephate and methamidophos and interleukin-1 on corticotropin-releasing factor (CRF) synthesis in and release from the hypothalamus in vitro.
Acute effects of Ace, Meth and IL-1 on AChE activity, ACh and CRF mRNA levels in, and CRF-release from the hypothalamus were studied in vitro. The hypothalamus samples were dissected from the rat brain and were incubated in vitro with IL-1, Ace or Meth in the presence or absence of Dex, Atrop, PTL, PROP and GABA. Ace and Meth, but not IL-1, inhibited AChE activity, while all three compounds; (1) increased ACh and CRF mRNA levels in and CRF release from; (2) activated the CRE promoter region of CRF-gene in: and (3) increased cFos binding to the AP-1 region of the CRF-gene in the hypothalamus. Dex suppressed the effects of IL-1, possibly by inducing the nGRE regulatory sites of the CRF-gene. Dex, however, did not modulate the effects of Ace and Meth on the hypothalamus, which may be attributed to the failure of Dex to modulate the CRF-gene's nGRE regulatory sites. Atrop caused 80-90% inhibition of the effects of IL-1, but caused only 50-65% inhibition of the effects of Ace or Meth on CRF mRNA levels in and CRF release from the hypothalamus. PTL did not affect, while PROP slightly attenuated the effects of IL-1 and the insecticides on the hypothalamus. GABA attenuated the effects of the insecticides but not the effects of IL-1 on the hypothalamus. This suggests that the IL-1-induced augmentation of CRF synthesis in and release from the hypothalamus is mediated through a cholinergic pathway, while the insecticide-induced augmentation of CRF synthesis in and release from the hypothalamus is mediated through the cholinergic and GABAergic pathways. The insecticides, but not IL-1, disrupt feedback regulation of CRF synthesis in and release from the hypothalamus.


Characterization of eubacterial communities by Denaturing Gradient Gel Electrophoresis (DGGE) and Next Generation Sequencing (NGS) in a desulfurization biotrickling filter using progressive changes of nitrate and nitrite as final electron acceptors.
Anoxic biotrickling filters (BTFs) represent a technology with high H2S elimination capacity and removal efficiencies widely studied for biogas desulfurization. Three changes in the final electron acceptors were made using nitrate and nitrite during an operating period of 520 days. The stability and performance of the anoxic BTF were maintained when a significant perturbation was applied to the system that involved the progressive change of nitrate to nitrite and vice versa. Here the impact of electron acceptor changes on the microbial community was characterized by denaturing gel gradient electrophoresis (DGGE) and next generation sequencing (NGS). Both platforms revealed that the community underwent changes during the perturbations but was resilient because the removal capacity did not significantly change. Proteobacteria and Bacteroidetes were the main Phyla and Sulfurimonas and Thiobacillus the main nitrate-reducing sulfide-oxidizing bacteria (NR-SOB) genera involved in the biodesulfurization process.


Thyroid treatment and its possible influence on occurrence of malignant tumors after diagnostic 131I.
The extent to which thyroid surgery, thyroid hormone medication or other forms of thyroid therapy were applied after diagnostic administration of 131I has been determined in 871 patients of the 10 133 patients reported previously. The relevant information was obtained from questionnaires and from hospital records. Of the 871 patients at least 58 per cent had received no form of thyroid treatment and 33 per cent had had some form of treatment, while in 9 per cent no information could be obtained. The large difference between the number of malignant tumors observed in the 10 133 patients after exposure to 131I and the number expected from UNSCEAR's risk figures for radiation-induced thyroid carcinoma (47--124 cases) cannot be ascribed to the various forms of thyroid treatment given after the 131I administration.


Evaluation of Curcumin (Turmeric Extract) Effect on Prevention of CIN in Patient Under Elective Coronary Angiography, a Randomized Double Blind Placebocontrolled Clinical Trial.
Curcumin is turmeric extract that have antiproliferative, anti-cancer, and anti-oxidant effects and has been shown that it may have reno-protective properties. This study conducted to evaluate the efficacy of curcumin in the prevention of CIN. This randomized placebo-controlled clinical trial was carried out on 138 patients with chronic stable angina scheduled for elective coronary angiography that had renal insufficiency. Patients were randomized to receive curcumin or placebo in addition to standard hydration with saline 0.9% before nonionic iso-osmolar contrast agent administration for angiography. Serum creatinine was measured 12h before, 24h and 48h after contrast injection. CIN, mainly, defined as increase in creatinine of ≥ 0.5 mg/dL or ≥ 25% from the baseline. Serum creatinine change was 0.19 ± 0.31 mg/dL which was 0.22 ± 0.33 and 0.16 ± 0.29 in placebo and curcumin group, respectively. In 'repeated measure analysis' no statistically difference was found in serum creatinine level between pre-intervention, and 24 hours and 48 hours after intervention. CIN was occurred less frequently, though statistically insignificant, in curcumin group (22.7%) compared with placebo group (32.3%). It was found that although curcumin reduced the incidence of CIN, this difference was not statistically significant. It seems that, like other antioxidant substances studied in previous studies, although curcumin can reduce apoptosis and oxidative stress at cellular level, but in high risk patients for CIN, such as patients with renal insufficiency, it does not produce more protective effects than hydration with normal saline.


Serum osteopontin levels in relation to bone mineral density and bone turnover markers in postmenopausal women.
Osteopontin (OPN) is an extracellular matrix protein that is expressed in bone cells such as osteoblast and osteocytes and associated with bone turnover and bone mineral density (BMD) in postmenopausal women. Here, we aimed to investigate the relationship between circulating OPN levels and BMD in postmenopausal women in Southern China. A total of 362 postmenopausal women were consecutively recruited into this study from 2011-2013. Serum levels of OPN, receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL), and bone turnover markers were analyzed. BMD was measured by dual energy X-ray absorptiometry. Osteoporosis and osteopenia were diagnosed according to the World Health Organization criteria. Serum OPN levels were remarkably higher in the osteoporotic group than those in the osteopenic and normal groups (all p < 0.001). The cut-off value of OPN for diagnosing postmenopausal osteoporosis was 10.1 ng/mL, which had a sensitivity of 89.5%, a specificity of 70.8%, and an area under curve of 0.953. Serum OPN was negatively correlated with parathyroid hormone (PTH), lumbar spine BMD, and femoral neck BMD (r = -0.25, p = 0.004; r = -0.66, p < 0.001; r = -0.28, p = 0.001; respectively) and positively associated with type I procollagen amino-terminal propeptide (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX), and RANKL (r = 0.20, p = 0.020; r = 0.17, p = 0.036; r = 0.19, p = 0.028, respectively) in the osteoporotic group. In multiple regression analyses, lumbar spine BMD, PTH and RANKL were the predictors for serum OPN levels. In conclusion, OPN serum levels are negatively related to BMD and positively correlated with bone turnover levels in this group of Chinese postmenopausal women.


50 to 30-Hz triplet and singlet down sweep vocalizations produced by sei whales (Balaenoptera borealis) in the western North Atlantic Ocean.
The life history, distribution, and acoustic ecology of the sei whale (Balaenoptera borealis) in the western North Atlantic Ocean remains poorly understood. In this study an array of bottom-mounted recorders captured previously undocumented low frequency 50 to 30-Hz triplet and singlet down sweep vocalizations in close association with signature 82 to 34-Hz sei whale down sweep vocalizations. Spatiotemporal correlations of acoustically tracked sei whales confirm the original vocalizations are produced by sei whales. The 50 to 34-Hz down sweep call types were characterized with a suite of five spectral and temporal measurements. The pattern and repetition of the full acoustic suite is suggestive of song structure and warrants further investigation. The discovery of vocalizations attributed specifically to sei whales enables historic acoustic records to be re-evaluated for the presence of this species throughout its range.


Nesfatin-1 suppresses fish reproductive axis and gonadal steroidogenesis.
Nesfatin-1 is a naturally occurring orphan ligand in fish and mammals. Research in our lab resulted in the identification of an inhibitory role for nesfatin-1 on pituitary hormones (goldfish) and oocyte maturation (zebrafish). The present study is an extension of these original findings and aimed to determine whether nesfatin-1 has any additional effects on HPG genes in male and female goldfish. We found that a single i.p. injection of synthetic nesfatin-1 (50 ng/g body weight) downregulated the expression of salmon gonadotropin-releasing hormone (sgnrh), chicken gnrh-II (cgnrh-II), kisspeptin receptor (gpr54a) and brain aromatase (cyp19a1b) mRNAs in the hypothalamus of both male and female goldfish at 15 min post-administration. In the pituitary of both males and females, nesfatin-1 reduced luteinizing hormone beta (lhβ) and follicle stimulating hormone beta (fshβ) mRNA expression at 60 min and gpr54a mRNA at 15 min. Similarly, the gonadotropin receptors lhr and fshr were downregulated in the gonads. Meanwhile, gonadotropin inhibiting hormone (gnih), gnih receptor, kisspeptin 1 (kiss1) and gpr54a mRNA expression in the gonads were increased post-nesfatin-1 treatment. Nesfatin-1 negatively influences the star, cytochrome P450 family 11 subfamily A member 1, anti-mullerian hormone and aromatase mRNAs. In agreement with these results, nesfatin-1 reduced plasma estradiol and testosterone in female and male goldfish circulation at 60 min post-injection. The information generated through this research further solidified nesfatin-1 as an inhibitor of reproductive hormones in fish. Targeting nesfatin-1 and related peptides could yield beneficial effects in fish reproduction and aquaculture.


Prognostic Factors of Prostate Cancer in Tunisian Men: Immunohistochemical Study.
Prostate cancer is the second most common male cancer and remains a leading cause of cancer death worldwide. Heterogeneity regarding recurrence, tumor progression and therapeutic response reflects the inadequacy of traditional prognostic factors and underlies interest in new genetic and molecular markers. In this work, we studied the prognostic value of the expression of 9 proteins, Ki-67, p53, Bcl-2, PSA, HER2, E-cadherin, p21WAF1/Cip1, p27Kip1 and p16ink4a in prostate cancer. We conducted a retrospective study of 50 prostate cancers diagnosed in Pathology Department of Farhet Hached Hospital, Sousse, Tunisia, during a period of 12 months. Clinico-pathological data and survival were investigated. Protein expression was analyzed by immunohistochemistry on archived material. Expression or over-expression of Ki-67, p53, Bcl-2, PSA, HER2, E-Cadherin, p21WAF1/Cip1, p27Kip1 and p16ink4a was observed in 68%, 24%, 32%, 78%, 12%, 90%, 20%, 44% and 56% of cases, respectively. Overall five-year survival was 68%. A statistically significant correlation was observed between death occurrence and advanced age (p=0.018), degree of tumor differentiation (p=0.0001), perineural invasion (p=0.016) and metastasis occurrence (p=0.05). Death occurrence was significantly correlated with the expression of p53 (p=0.007), Bcl-2 (p=0.02), Ki-67 (p=0.05) and p27Kip1 (p=0.04). The p53, Bcl-2, Ki-67 and p27Kip1 proteins may be useful additional prognostic markers for prostate cancer. The use of these proteins in clinical practice can improve prognosis prediction, disease screening and treatment response of prostatic cancer.


Phenotype of combined Duchenne and facioscapulohumeral muscular dystrophy.
This case report describes a young boy with concomitant genetically-confirmed Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy with a novel dystrophin mutation in exon 6 and a D4Z4 fragment of 31 kb. This child presented with a more severe phenotype than expected for either individual disease process and underscores the role for thorough diagnostic investigation in identifying atypical clinical presentations.


Lung cancer patients with synchronous colon cancer.
Lung and colon cancers are two of the most common malignancies, which, in some cases, may develop synchronously. In the present study, the treatment and outcome of patients with synchronous lung and colon cancers were reviewed. During a 76-month study period, from April 2009 up to July 2016, 17 (0.54%) of 3,102 patients with lung cancer were diagnosed with colon cancer within 1 month. Heavy smoking and obesity were not specific factors in these patients. A total of 9 patients succumbed to lung cancer during the study period. Survival in asymptomatic patients was longer compared with that in symptomatic patients (median survival, 80 vs. 23.2 months, respectively; P=0.007). Although the incidence of synchronous occurrence of these two cancers may be low, particularly in patients diagnosed incidentally, such patients should be treated accordingly. Future genetic and epidemiological studies are required to elucidate the potential connection between lung and colon cancer.


A Phase II Study of Dose-reductive XELOX Plus Bevacizumab in Elderly or Vulnerable Patients With Metastatic Colorectal Cancer (MCSGO-1202).
This phase II study (MCSGO-1202) aimed to evaluate the initial dose reduction of oxaliplatin in XELOX plus bevacizumab therapy. This was a phase II, multicenter, open-label, single-arm, prospective, study conducted at 14 Japanese institutions. The study included patients with metastatic colorectal cancer (mCRC) with performance status (PS) of 1 or 2 who had not undergone chemotherapy. Patients received oxaliplatin (100 mg/m2) plus bevacizumab (7.5 mg/kg) on day 1 and capecitabine (2,000 mg/m2/day) on days 1-14 of a 21-day cycle. The primary endpoint was the objective response rate. The secondary endpoints were progression-free and overall survival, 1-year survival rate, disease control rate, dose intensity, and adverse events. Between April 2012 and March 2016, 56 patients were enrolled. The median age was 71 years (range=44-85 years), and the majority (90.6%) had a PS of 1. A complete response was observed in three patients (5.7%), partial response in 24 (45.3%), stable disease in 22 (43.4%), and progressive disease in one (1.9%). The median progression-free survival and overall survival were 11.4 and 26.5 months, respectively. The most common grade 3-4 adverse events were leucopenia (15.1%), neutropenia (9.4%), neuropathy (9.4%). The dose-reduction strategy of oxaliplatin was effective for elderly or vulnerable patients with mCRC.


Immunohistochemical localization of phosphoenolpyruvate carboxykinase in adult and developing mouse tissues.
We used immunohistochemical techniques to analyze the cell distribution of phosphoenolpyruvate carboxykinase (PEPCK) in adult and developing mouse tissues. PEPCK immunoreactivity was detected in many tissues, including some that had not been previously reported to contain PEPCK enzyme activity (bladder, stomach, ovary, vagina, parotid gland, submaxillary gland, and eye). In some multicellular tissues, PEPCK immunoreactivity was observed in multiple cell types. Several tissues (spleen, thyroid, and submaxillary gland) contained no detectable PEPCK immunoreactivity. During development, PEPCK immunoreactivity was associated with the developing nervous system and somites in 15-day embryos. At prenatal day 18, PEPCK immunoreactivity was detected only in the nervous system. At prenatal day 20, PEPCK immunoreactivity was observed in many of the tissues that contain PEPCK in the adult, with the exception of liver, lung, and stomach. PEPCK immunoreactivity was detected in liver at postnatal day 1, lung at postnatal day 7, and stomach after postnatal day 21. The only tissue in which PEPCK immunoreactivity decreased during development was the pancreas, where PEPCK immunoreactivity was detected at prenatal day 20 and was present until postnatal day 21. These results suggest that PEPCK expression is cell-type specific, more widespread than previously thought, and differentially expressed during development.


A bipartite NLS at the SHP-1 C-terminus mediates cytokine-induced SHP-1 nuclear localization in cell growth control.
SHP-1 protein tyrosine phosphatase is a critical regulator of signaling in hematopoietic cells as illustrated by the lethal hematopoietic disorders in SHP-1-deficient mice. We and others have shown in previous studies that SHP-1 regulates membrane receptor signaling: it binds via its N-terminal region SH2 domains to tyrosine phosphorylated membrane receptors to dephosphorylate key substrates in the receptor complexes. Here we demonstrate that the SHP-1 C-terminal region contains a bipartite NLS that mediates SHP-1 nuclear localization in response to cytokines. This NLS was located within amino acids 576-595 of the PTPase and, when fused by itself to EGFP, targeted the fluorescent protein into the nuclei of transiently transfected NIH3T3 fibroblasts and Bac1.2f5 macrophage cells. When positioned within SHP-1, the activity of the NSL was under tight regulation as indicated by the predominant cytoplasmic distribution of the EGFP/SHP-1 fusion protein in NIH3T3 transfectants and the exclusive cytoplasmic localization of the endogenous SHP-1 in hematopoietic cell line PBLC-1. Activation of the NLS in SHP-1 by IL-4 was demonstrated by increased nuclear localization of the EGFP/SHP-1 fusion protein in NIH3T3 transfectants and of the endogenous SHP-1 protein in PBCL-1 cells at 4, 6 and 8 h post-IL-4 stimulation. SHP-1 nuclear localization in PBCL-1 cells was also induced by IL-7 in a similar manner, suggesting it as a common event in cytokine signaling. In comparison to that of the wild-type phosphatase, an SHP-1 mutant lacking the NLS showed only approximately half of the activity in inhibiting proliferation of NIH3T3 transfectants. These results provide evidence of cytokine-regulated SHP-1 nuclear localization mediated by a bipartite NLS and suggest that SHP-1 regulates nuclear signaling in cell growth control.


Symptomatic C-cell hyperplasia associated with chronic lymphocytic thyroiditis.
A 58-year-old euthyroid man with episodic flushing and a 2-year history of progressive wheezing was found to have a hypoechoic lesion in one lobe of his thyroid and hypercalcitoninemia in response to pentagastrin stimulation. Thyroidectomy revealed bilateral C-cell hyperplasia unexpectedly associated with chronic lymphocytic thyroiditis. The C-cells exhibited positive immunohistochemical staining for calcitonin and polyclonal carcinoembryonic antigen (CEA). Postoperatively, the wheezing and flushing subsided and the serum calcitonin level was not elevated with pentagastrin stimulation. The substance or substances responsible for the wheezing and flushing were not specifically identified. Nine other specimens of chronic lymphocytic thyroiditis were examined for C-cell hyperplasia and two had small hyperplastic foci, but of a lesser degree than the index case. These patients did not exhibit wheezing and flushing. The development of C-cell hyperplasia in chronic lymphocytic thyroiditis is uncommon and the mechanism for its occurrence is unexplained. This patient appears to be the first reported case of symptomatic C-cell hyperplasia associated with chronic lymphocytic thyroiditis. The substance or substances responsible for the clinical symptoms remain to be identified.


Anti-IL5 Monoclonal Antibodies Reduce Asthma Exacerbations and Corticosteroids Dose in Three Eosinophilic Granulomatosis with Polyangiitis Case Reports.
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystem necrotizing small and medium-sized vessel vasculitis with eosinophilic adult-onset asthma as part of its spectrum. Therapeutic choices include corticosteroids, immunosuppressive agents, and novel immunomodulators. Mepolizumab and benralizumab are monoclonal antibodies targeting Interleukin-5 (IL-5), which plays a leading role in every stage of production and maturation of eosinophils and are recently undergoing evaluation and administered in steroid-dependent, relapsing and/or refractory EGPA. Herein we describe the cases of three patients with a prior EGPA diagnosis, experiencing frequent asthmatic exacerbations despite oral and inhaled corticosteroid treatment (two patients) and adverse effects of corticosteroids (one patient). Two patients are under treatment with mepolizumab and one patient with benralizumab as an add-on supplemental regimen. In our case series anti-IL5 monoclonal antibodies proved efficient asthma-controlling and corticosteroid-sparing agents.


Skin incision-induced receptive field responses of mechanosensitive peripheral neurons are developmentally regulated in the rat.
Maturation of the nervous system results in changes in both central and peripheral processing. To better understand responses to injury in the young, developmental differences in the acute response to incision were investigated in both tactile and nociceptive myelinated peripheral mechanosensitive afferent neurons in vivo. Neuronal intrasomal recordings were performed in juvenile and infant rats in 34 L5 dorsal root ganglia, and each neuron was phenotypically defined. Neurons had a mechanosensitive receptive field in the glabrous skin on the plantar surface of the hind paw, which was characterized at baseline and for up to 45 min after incision. Fundamental maturational differences in the effect of incision were clear: in high-threshold nociceptive mechanoreceptors, the mechanical threshold decreased immediately and the receptive field size increased rapidly in juvenile rats but not in infant rats. Additionally, a divergence in changes in the instantaneous response frequency of tactile afferents occurred between the two ages. These differences may help explain maturational differences in responses to peripheral injury and suggest that differences in central nervous system responses may be partially mitigated by spatially confined and frequency-dependent differences resulting from tactile and nociceptive mechanosensitive input.


[Severe light dermatosis following photo therapy in a newborn infant with congenital erythropoietic urophyria].
A newborn infant with hemolytic anemia and hepatosplenomegaly was treated by phototherapy for early jaundice. After 18 h, a dark brown pigmentation of the skin was noticed, leading to the assumption of a bronze baby syndrome. Indeed, the child was suffering from a severe disturbance of liver function. 4 days later, a severe bullous dermatosis with blody imbibition developed, covering all exposed parts of the body surface and reoccurring in many bursts over several weeks despite protection against light. A severe hemolytic anemia was constantly present. The baby died on the 50th day. The diagnosis of erythropoietic porphyria was suggested immediately after the onset of the bullous exanthema and proved by laboratory data as follows: uro- and coproporphyrin in the urine were extremely high, uroporphyrin being mainly of type-I isomer. In red cells, increased amounts of uro-, copro- and protoporphyrins were detected. Massive red fluorescence of erythroblasts (so-called porphyroblasts) in the bone marrow and in the blood could be observed. At autopsy, the liver showed multiple blood-forming areas and severe diffuse hemosiderosis, which is to be explained by a long existing, i.e. fetal hemolysis. Erythropoietic porphyria is such a rare disease that there is no reason to consider it as a general contraindication for phototherapy.


Genetics and hypogonadotrophic hypogonadism.
Hypothalamic pulsatile gonadotrophin-releasing hormone secretion, stimulating pituitary gonadotrophin secretion, is essential for adult reproductive function. This neuroendocrine drive to the reproductive axis is critically dependent on a sequence of developmental events in utero. During early foetal life, gonadotrophin-releasing hormone neurones migrate from the nasal placode to the medial basal hypothalamus where gonadotrophin-releasing hormone can be transported down portal vessels to the anterior pituitary. Gonadotrophin-releasing hormone secretion is active fleetingly neonatally but soon becomes quiescent throughout childhood. At the time of puberty activation of gonadotrophin-releasing hormone secretion reawakens the hypothalamic pituitary-gonadal axis and secondary sexual maturation is triggered. Any disruption in gonadotrophin-releasing hormone secretion will result in hypogonadotrophic hypogonadism. The clinical manifestations of this become apparent with secondary sexual maturation. Genetic mutations have been identified in a minority of cases. These include Kallmann syndrome, adrenal hypoplasia congenital, gonadotropin-releasing hormone receptor and luteinizing hormone or follicle-stimulating hormone beta-subunit gene mutations. The importance of these discoveries is important not only in relation to the conditions that result, but also for our better understanding of normal reproductive function.


Nursing and justice as a basic human need.
This paper explores the idea that justice is a basic human need akin to those famously depicted in Maslow's hierarchy of human needs and, as such, warrants recognition as a core element in representative ideas about nursing. Early nurse theorists positioned the principles and practice of nursing as having their origins in 'universal human needs'. The principle of deriving nursing care from human needs was thought to provide a guide not only for promoting health, but for preventing disease and illness. The nursing profession has had a longstanding commitment to social justice as a core professional value and ideal, obligating nurses to address the social conditions that undermine people's health. The idea of justice as a universal human need per se and its possible relationship to people's health outcomes has, however, not been considered. One reason for this is that justice in nursing discourse has more commonly been associated with law and ethics, and the legal and ethical responsibilities of nurses in relation to individualized patient care and, more recently, changing systems of care to improve health and health outcomes. Although this association is not incorrect, it is incomplete. A key aim of this paper is to redress this oversight and to encourage a broader conceptualization of justice as necessary for human survival, health and development, not merely as a professional value, or legal or ethical principle for guiding human conduct.


Treadmill training increases the size of A cells from the L5 dorsal root ganglia in diabetic rats.
The aim of this study was to evaluate the effects of physical training on the L5 dorsal root ganglion (DRG) cells in streptozotocin diabetic rats. Male adult rats were divided into 3 groups: (control, diabetic and trained diabetic). Treadmill training was performed for 10 weeks (5 days/week, twice a day). Blood glucose concentrations and body weight were evaluated 48h after diabetes induction and every 30 days thereafter. Then, animals were killed and the right L5 DRG removed. Histological and morphometric analysis consisted of evaluating nuclear and cellular volumes and areas in A and B cells at light and ultrastructural levels. Blood glucose concentrations were higher in both diabetic groups vs controls at all periods. Body weights were lower in all diabetics vs controls at all periods after diabetes induction, with a significant time vs group interaction. In A cells, the cellular and nuclear volumes were lower than control animals only in the diabetic group; control and trained diabetic animals did not differ; in B cells the cellular and nuclear volumes were lower in diabetic and trained diabetic rats. The cellular areas of A cells were smaller in diabetic rats than in control and trained diabetic rats, while the cellular areas of B cells were smaller in the diabetic and trained groups. In conclusion, treadmill training was able to increase the size of A cells from the DRG in diabetic rats and improved the morphological features of these cells.


Promoting health among perimenopausal women through diet and exercise.
To review the literature related to health promotion during the perimenopausal years and suggest methods for integrating those changes into the lifestyles of women in primary care. Selected scientific literature and guidelines for exercise programs. The transition into perimenopause presents an opportunity for addressing health promotion issues, such as diet and exercise. As a woman senses perimenopausal changes, health awareness emerges. Such personal insight motivates the woman to implement lifestyle changes. Considering the average women will spend approximately one third of her life past menopause, a concerted effort is needed to ensure her well-being. Diet and exercise represent two modifiable areas of concern for perimenopausal women. Dietary selections of phytoestrogens, calcium, fiber and fat along with exercises plans are relatively simple interventions to begin the process of change.


Identification of the SS-A/Ro intracellular antigen with autoimmune sera.
Autoantibodies to SS-A/Ro antigen have been described in the sera of certain patients with Sjögren's syndrome, systemic lupus erythematosus and in neonates with lupus and/or congenital heart block. SS-A/Ro is a trypsin-sensitive intracellular antigen which appears to be associated with another intracellular antigen SS-B/La in tissue extracts. This study describes a simple method of separation of SS-A/Ro and SS-B/La antigenic activity by differential salt elution in polybuffer ion exchange chromatography. The partially purified SS-A/Ro antigen was separated by polyacrylamide gel electrophoresis under non-denaturing conditions and identified by Western blot analysis as a single polypeptide of 61,000 Da. The pI of SS-A/Ro antigen was 4.67. The partially purified SS-A/Ro antigen derived from gel electrophoresis could be adapted to an enzyme linked immunosorbent assay (ELISA) for the detection of antibody.


Mycoplasma suppression of THP-1 Cell TLR responses is corrected with antibiotics.
Mycoplasma contamination of cultured cell lines is a serious problem in research, altering cellular response to different stimuli thus compromising experimental results. We found that chronic mycoplasma contamination of THP-1 cells suppresses responses of THP-1 cells to TLR stimuli. For example, E. coli LPS induced IL-1 beta was suppressed by 6 fold and IL-8 by 10 fold in mycoplasma positive THP-1 cells. Responses to live F. novicida challenge were suppressed by 50-fold and 40-fold respectively for IL-1beta and IL-8. Basal TLR4 expression level in THP-1 cells was decreased by mycoplasma by 2.4-fold (p = 0.0003). Importantly, cell responses to pathogen associated molecular patterns are completely restored by mycoplasma clearance with Plasmocin. Thus, routine screening of cell lines for mycoplasma is important for the maintenance of reliable experimental data and contaminated cell lines can be restored to their baseline function with antibiotic clearance of mycoplasma.


Kinetics of hepatic accumulation of dextrans in isolated perfused rat livers.
The role of various processes (uptake, release, metabolism, and excretion) in the hepatic accumulation of dextrans was investigated in isolated perfused rat livers (IPRLs). Single-pass IPRLs were infused with fluorescein-dextran (FD) with a molecular weight (MW) of 70,000 (FD-70) for 15, 30, 45, or 60 min, and inlet and outlet samples and livers were collected. In addition, two groups of livers were infused with FD-70 for 60 min, followed by 30 or 60 min of drug-free perfusion. The concentrations of the macromolecule in the samples were measured by a size exclusion chromatographic method. Similar, but limited, experiments were also conducted for FDs with MWs of 4,000 (FD-4) and 150,000 (FD-150). In addition, the metabolism of all three FDs were investigated using liver homogenates. Because of low hepatic extraction, the concentrations of dextrans in the inlet and outlet perfusates were almost the same during the entire perfusion. However, liver concentrations increased almost linearly during the infusion of FD-70 (0-60 min) and declined slowly thereafter (60-120 min). The apparent hepatic extraction ratio (Eapp) values, estimated directly from the concentrations of FDs in the liver, were MW dependent; Eapp of FD-4 (0.124% +/- 0.015%) was significantly (p < 0.05) less than that for FD-70 (0.677% +/- 0.193%) or FD-150 (0.711% +/- 0.022%). The metabolism and biliary excretion of all FDs were negligible during the perfusion time. The mean residence time of FD-70 in the liver, estimated by nonlinear regression analysis of experimental data, was 248 min. These studies define the role of various processes involved in the slow (but substantial) and MW dependent hepatic accumulation of dextrans.


Evaluation of constipation.
The evaluation of the chronically constipated patient is multifaceted and challenging. Many clinicians define constipation according to the latest Rome III diagnostic criteria for functional gastrointestinal disorders. Female sex, older age, low fiber diet, a sedentary life style, malnutrition, polypharmacy, and a lower socioeconomic status have all been identified as risk factors for functional constipation. In elderly patients, it is important to rule out a colonic malignancy as the cause of constipation. The initial evaluation of the constipated patient includes a detailed history to elicit symptoms distinguishing slow transit constipation from obstructive defecation. Slow transit and obstructive defecation are the two major subtypes of functional constipation. In addition, the clinician should identify any secondary causes of constipation. The office examination of the constipated patient includes an abdominal, perineal, and a rectal exam. Many patients improve with lifestyle modification. When dietary interventions and lifestyle modifications fail, many diagnostic studies are available to further evaluate the constipated patient. Sitzmark transit study, nuclear scintigraphic defecography, electromyography, anorectal manometry, balloon expulsion test, paradoxical puborectalis contraction, cinedefecography, and dynamic magnetic resonance imaging defecography have all been used to diagnose the underlying causes of functional constipation.


The being a patient effect: negative expectations based on group labeling and corresponding treatment affect patient performance.
Patient studies provide insights into mechanisms underlying diseases and thus represent a cornerstone of clinical research. In this study, we report evidence that differences between patients and controls might partly be based on expectations generated by the patients' knowledge of being invited and treated as a patient: the Being a Patient effect (BP effect). This finding extends previous neuropsychological reports on diagnosis threat. Participants with mild allergies were addressed either as patients or control subjects in a clinical study. We measured the impact of this group labeling and corresponding instructions on pain perception and cognitive performance. Our results provide evidence that the BP effect can indeed affect physiological and cognitive measures in clinical settings. Importantly, these effects can lead to systematic overestimation of genuine disease effects and should be taken into account when disease effects are investigated. Finally, we propose strategies to avoid or minimize this critical confound.


Use of detector tubes under extreme conditions (humidity, pressure, temperature).
Detector tubes are mainly used in a temperature range between 0 degrees C and 40 degrees. At lower temperatures systematic minus indications may occur, high temperatures cause plus indications. By utilizing simple warming-up methods or cooling devices the temperature of the gas to be tested can be adjusted to a temperature which which is suitable for detector tubes. Humidity often influences chemical reagents. In detector tubes this interfering effect can be eliminated by special drying preparations. The reading of most of the detector tubes is directly proportional to the absolute air pressure. Pressure correction can be done easily by the gas law.


Fatigue-Induced Scapular Dyskinesis in Healthy Overhead Athletes.
Alterations of scapular kinematics affect the whole kinematic chain, potentially leading to the impingement syndrome. This is crucial in overhead sports, where athletes perform frequent and quick upper limb actions. In this manuscript, we aimed to assess the extent to which fatigue alters scapulo-thoracic and scapulo-humeral ranges of motion (RoM), as well as scapulo-humeral movement onset during different upper limb actions. Twenty-four young healthy males aged 22 ± 2 years (height: 1.82 ± 0.06 m, body mass: 78.0 ± 7.8 kg) performed three movements (upper limb elevation, scapular-plane abduction, and intra-extra rotation) before and after an isokinetic fatigue protocol (upper limb intra/extra rotation, 32 repetitions at 120 degrees/s). Pre vs. post fatigue RoM of humeral elevation and rotation, scapular retraction/protraction, and rotation and tilt were computed. Humerus-scapula movement delay was also determined. Humerus elevation range reduced during intra/extra humerus rotation in fatigued conditions (p = 0.006). Scapular tilt RoM increased after the fatigue protocol (p = 0.063, large effect). Humerus-scapular movement onset delay reduced in fatigued conditions of about 80 ms (p < 0.001, large effect). In sum, fatigued intra/extra upper limb rotators altered the scapulohumeral rhythm, and joints RoM in movements outside the scapular plane. Rather, movements close to the scapular plane were less prone to fatigue-induced alterations.


Post-crizotinib management of effective ceritinib therapy in a patient with ALK-positive non-small cell lung cancer.
We report the re-biopsied diagnosis of a patient with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive lung adenocarcinoma successfully treated with ceritinib 450 mg/day taken with food following disease progression and gastrointestinal intolerance to crizotinib. A 74-year old female patient initially diagnosed with ALK-negative lung adenocarcinoma responded to initial standard chemotherapy. The patient was subsequently re-tested by next generation sequencing (NGS) and found to have ALK EIF2AK3-ALK fusion, and responded to crizotinib, but ultimately progressed and showed intolerance to this ALK inhibitor. She was then successfully treated with ceritinib 450 mg/day taken with food, has not suffered from any further gastrointestinal side-effects, and remains on ceritinib treatment after 12 months. Second-line ceritinib treatment, when administered at 450 mg/day with food, is both well tolerated and efficacious in a patient with previously treated lung adenocarcinoma who had discontinued crizotinib due to disease progression and gastrointestinal adverse effects (AEs).


Body surface area as a key determinant of aortic root and arch dimensions in a population-based study.
The associations between the aortic dimensions (of the aortic sinus, aortic annulus and aortic arch) and physiological variables have not been established in the Chinese population. The present study examined the associations among physiological variables to determine the aortic root and arch dimensions echocardiographically. The diameters of the aortic sinus, annulus and arch were measured in 1,010 subjects via 2-D echocardiography with a 3.5-MHz transducer in a trans-thoracic position. The images of the aortic sinus and aortic annulus were obtained from a standard parasternal long-axis view. The maximum diameter of the valve orifice was measured at the end of systole. The aortic arch dimension was visualized in the long-axis using a suprasternal notch window and the maximum transverse diameter was measured. Epidata 3.0, Excel 2007 and SPSS version 17.0 were used to collect and analyze the data. A total of 1,010 subjects were enrolled. The mean age was 55.0±17.0 years (range of 18 to 90 years). The body surface area (BSA) was the best predictor of all the studied physiological variables and may be used to predict aortic sinus, annulus and arch dimensions independently (r=0.54, 0.37 and 0.39, respectively). Gender, blood pressure, age and BSA are significant predictors of the aortic dimensions. Of these, BSA was the best predictor.


Deposition of C3, C9 neoantigen and vitronectin (S-protein of complement) in lichen planus pemphigoides.
We have compared the distribution of C3, C9 neoantigen (C9n) and vitronectin at the dermoepidermal junction in lichen planus pemphigoides with that in bullous pemphigoid. Eight out of 30 biopsies from patients with lichenoid lesions had linear C3 deposition at the basement membrane zone (BMZ); four of these patients had bullae and fulfilled the criteria for lichen planus pemphigoides. C9n immunoreactivity was detected as a linear or an intermittent linear/granular band at the BMZ only in these four patients, suggesting a role for the membrane attack complex of complement (MAC) in the pathogenesis of blister formation in lichen planus pemphigoides. Faint linear deposition of vitronectin, in addition to C9n, at the BMZ was seen in two of the four cases of lichen planus pemphigoides and three of six cases of bullous pemphigoid. This suggests that vitronectin may be deposited in association with C9n not only as part of the non-lytic SC5b-9 complex, but also as a regulatory step following the lytic action of MAC. A regulatory function for vitronectin in limiting tissue damage following activation of MAC is supported by our finding of a heavy deposition of vitronectin in association with C9n in a lichen planus pemphigoides patient in whom bulla formation had ceased.


[Thrombopoietic activity induced by blood withdrawal and administration of antithrombocyte serum in nephrectomized rats. Role of kidneys in the production of thrombopoietin].
The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms.


Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711].
This study was designed to determine if a natural mineral supplement, sierrasil, alone and in combination with a cat's claw extract (Uncaria guianensis), vincaria, has therapeutic potential in mild to moderate osteoarthritis of the knee. Patients (n = 107) with mild to moderate osteoarthritis of the knee were randomly assigned to one of 4 groups; high dose sierrasil (3 g/day), low dose sierrasil (2 g/day), low dose sierrasil (2 g/day) + cat's claw extract (100 mg/day) or placebo, administered for 8 weeks. Treatment was double blinded. Primary efficacy variables were WOMAC scores (A, B, C and total). Visual analog score (VAS) for pain, consumption of rescue medication (paracetamol), and tolerability were secondary variables. Safety measures included vital signs and laboratory-based assays. Ninety-one of the 107 patients successfully completed the protocol. All four groups showed improvement in WOMAC and VAS scores after 8 weeks (p < 0.001), in all 3 groups receiving sierrasil the magnitude of benefits were greater vs. placebo (WOMAC Total 38-43% vs. 27%) but this was not statistically significant. In reference to baseline values sierrasil treated groups had a considerably faster onset of benefits. Placebo-treated individuals failed to show significant benefits at 4 weeks (11% reduction in total WOMAC). In contrast, after 1 or 2 weeks of therapy all the sierrasil groups displayed significant reductions in WOMAC scores (p < 0.05) and at week 4 displayed a 38-43% improvement. VAS was significantly improved at 4 weeks in all groups (p < 0.001) but was significantly greater in all sierrasil groups compared to placebo (p < 0.05). Rescue medication use was 28-23% lower in the herbomineral combination and high dose sierrasil groups although not statistically different from placebo (P = 0.101 and P = 0.193, respectively). Tolerability was good for all groups, no serious adverse events were noted and safety parameters remained unchanged. The natural mineral supplement, sierrasil alone and in combination with a cat's claw extract, improved joint health and function within 1-2 weeks of treatment but significant benefits over placebo were not sustained, possibly due to rescue medication masking. Sierrasil may offer an alternative therapy in subjects with joint pain and dysfunction.


Sequence-Selective Protection of Peptides from Proteolysis.
Proteolysis of proteins and peptides is involved in the infection of cells by enveloped viruses and also in the invasion and spread of cancer cells. Shutting down broad-specificity proteases, however, is problematic because normal functions by these proteases will be affected. Herein, nanoparticle receptors were prepared from molecular imprinting for complex biological peptides. Their strong and selective binding enabled them to protect their targeted sequences from proteolysis in aqueous solution at stoichiometric amounts. Generality of the method was demonstrated by the protection of hydrophobic and hydrophilic peptides from different proteases, selective protection of a segment of a long peptide, and selective protection of a targeted peptide in a mixture. Most interestingly, two receptors targeting different parts of a long peptide could work in cooperation to protect the overall sequence, highlighting the versatility of the method.


Heritability of liver enzyme levels estimated from genome-wide SNP data.
Variation in the liver enzyme levels in humans is moderately heritable, as indicated by twin-family studies. At present, genome-wide association studies have traced <2% of the variance back to genome-wide significant single-nucleotide polymorphisms (SNPs). We estimated the SNP-based heritability of levels of three liver enzymes (gamma-glutamyl transferase (GGT); alanine aminotransferase (ALT); and aspartate aminotransferase (AST)) using genome-wide SNP data in a sample of 5421 unrelated Dutch individuals. Two estimation methods for SNP-based heritability were compared, one based on the distant genetic relatedness among all subjects as summarized in a Genetic Relatedness Matrix (GRM), and the other one based on density estimation (DE). The DE method was also applied to meta-analysis results on GGT and ALT. GRM-derived SNP-based heritability estimates were significant for GGT (16%) and AST (11%), but not for ALT (6%). DE estimates in the same sample varied as a function of pruning and were around 23% for all liver enzymes. Application of the DE approach to meta-analysis results for GGT and ALT gave SNP-based heritability estimates of 6 and 3%. The significant results in the Dutch sample indicate that genome-wide SNP platforms contain substantial information regarding the underlying genetic variation in the liver enzyme levels. A major part of this genetic variation remains however undetected. SNP-based heritability estimates, based on meta-analysis results, may point at substantial heterogeneity among cohorts contributing to the meta-analysis. This type of analysis may provide useful information to guide future gene searches.


Utility of bedside sonography to distinguish soft tissue abnormalities from joint effusions in the emergency department.
The purpose of this study was to determine the utility of bedside sonography to differentiate soft tissue abnormalities from joint effusions. We conducted a retrospective review of emergency department (ED) patients presenting with joint pain, erythema, and swelling who received bedside sonography. The ED sonographic examinations were performed by emergency physician sonologists who were not involved in clinical assessment and management of these patients. The treating physician's opinions regarding the probability of joint effusion and need for aspiration were documented in the sonography log before the sonographic examination was performed. The bedside sonograms of all patients included in this study were also reviewed for accuracy. Descriptive statistics were used to summarize the data. A total of 54 patients (mean age +/- SD, 41 +/- 18.9 years) were identified over a 1-year period. The symptomatic joints in our study subjects were as follows: knee, 24 of 54 (44%); elbow, 21 of 54 (38%); ankle, 8 of 54 (15%); and metatarsophalangeal joint, 1 of 54 (2%). Twenty-two of 54 patients (40.7%; 95% confidence interval [CI], 27.6%-53.8%) were found to have joint effusions on sonography. Sonography altered management in 35 of 54 patients (65%; 95% CI, 52%-77.5%). Joint aspiration was planned in 39 of 54 cases (72.2%; 95% CI, 60.2%-84.1%) before sonography. After sonography, only 20 of these patients (37%; 95% CI, 24.1%-49.9%) underwent joint aspiration. There was a statistically significant difference in treatment plans after the addition of bedside sonographic results (P < .01). Our study suggests that bedside sonography is useful in differentiating joint effusions from soft tissue abnormalities and directing appropriate therapy.


Comparison of 5 Rectal Preparation Strategies for Prostate MRI and Impact on Image Quality.
To compare 5 different rectal preparation strategies for prostate MRI. This 5-arm quality-assurance study evaluated 56 patients per arm (280 patients) including: no preparation, clear-fluids diet (CFD) beginning at 00:00 hours on the day of MRI, Fleet®-enema, enema + CFD, enema + CFD + IV-antispasmodic agent. The study was powered to 0.80 with alpha-error of 0.05. Three blinded radiologists independently evaluated T2-Weighted (T2W) and Diffusion Weighed Imaging (DWI) for: rectal diameter (maximal AP diameter), rectal content (stool, fluid, gas), rectal motion, T2W/DWI image quality, T2W image sharpness and DWI susceptibility artifact using 5-point Likert scales. Overall comparisons were performed using analysis of variance (ANOVA) and Kruskal-Wallis, with pair-wise comparisons using paired t-tests and Wilcoxon sign-rank tests. Rectal diameter and amount of gas were lower in enema compared to non-enema groups (p < 0.001), with smallest diameter and least gas in the enema + CFD + IV-antispasmodic group (p = 0.022-<0.001). T2W image quality and sharpness were highest in the enema + CFD groups (p < 0.001) with no difference comparing enema + CFD with/without IV-antispasmodic (p = 0.064, 0.084). Motion artifact was least in enema + CFD + IV-antispasmodic group compared to all other groups (p < 0.001), followed by the enema + CFD group (p = 0.008-<0.001). DWI image quality was highest (p < 0.001) and DWI susceptibility artifact lowest (p < 0.001) in the enema + CFD groups (p < 0.001) and did not differ comparing enema + CFD with/without anti-spasmodic (p = 0.058-0.202). Use of enema + clear-fluids diet before prostate MRI yields the highest T2W and DWI image quality with the least DWI artifact. IV-antispasmodic use reduces motion on T2W but does not improve image quality on T2W or DWI, or lessen DWI artifact compared to enema + clear-fluids diet.


Facile synthesis of hydrangea flower-like hierarchical gold nanostructures with tunable surface topographies for single-particle surface-enhanced Raman scattering.
The physicochemical properties of noble metal nanocrystals depend strongly on their size and shape, and it is becoming clear that the design and facile synthesis of particular nanostructures with tailored shape and size is especially important. Herein a novel class of hydrangea flower-like hierarchical gold nanostructures with tunable surface topographies and optical properties are prepared for the first time by a facile, one-pot, seedless synthesis using ascorbic acid (AA) to reduce hydrogen tetrachloroaurate (HAuCl4) in the presence of (1-hexadecyl)trimethylammonium chloride (CTAC). The morphologies of the synthesized gold nanoflowers are controlled and fine-tuned by varying the synthetic conditions such as the concentration of reagents and the growth temperature. Due to their unique hierarchical three-dimensional (3D) structures with rich hot spots, these gold nanoflowers exhibit an efficient performance in single-particle surface-enhanced Raman scattering (SERS). The work stands out as an interesting approach for anisotropic particle synthesis and morphological control, and the proposed novel, hierarchical gold nanoflowers have a number of exciting potential applications in SERS-based sensors.


Sinonasal malignancies and charged particle radiation treatment: a systematic literature review.
Background. Paranasal and nasal cavity malignancies are rare tumors that frequently present at advanced stages. Tumor extension and anatomic complexity pose a challenge for their treatment. Due to their peculiar physical and biological properties particle radiation therapy, i.e. protons and ions can have a role in their management. We performed a systematic literature review to gather clinical evidence about their use to treat sinonasal malignancies. Materials and Methods. We searched the browsers PubMed and Medline as well as specific journals and conference proceedings. Inclusion criteria were: at least 10 patients, English language, reporting outcome and/or toxicity data. Results. We found six studies with data on clinical outcome. Carbon and helium ions were each used in one study, protons in four. Toxicity was specifically described in five studies. One reported acute toxicity of carbon ions, one dealt with brain toxicity from both carbon ions and protons. Three papers reported on visual toxicity: one from carbon ions, one from protons and one from both. Specific data were extracted and compared with the most pertinent literature. Conclusion. Particle radiation therapy is in its early phase of development. Promising results achieved so far must be confirmed in further studies.


Carbodiimide Conjugation of Latent Transforming Growth Factor β1 to Superparamagnetic Iron Oxide Nanoparticles for Remote Activation.
Conjugation of latent growth factors to superparamagnetic iron oxide nanoparticles (SPIONs) is potentially useful for magnetically triggered release of bioactive macromolecules. Thus, the goal of this work was to trigger the release of active Transforming Growth-Factor Beta (TGF-β) via magnetic hyperthermia by binding SPIONs to the latent form of TGF-β, since heat has been shown to induce release of TGF-β from the latent complex. Commercially available SPIONS with high specific absorption rates (SAR) were hydrolyzed in 70% ethanol to create surface carboxylic acid conjugation sites for carbodiimide chemistry. Fourier-Transform Infra-Red (FTIR) analysis verified the conversion of maleic anhydride to maleic acid. 1-Ethyl-2-(3-dimethyulaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS) were used to bind to the open conjugation sites of the SPION in order to graft latent TGF-β onto the particles. The resulting conjugated particles were imaged with transmission electron microscopy (TEM), and the complexed particles were characterized by dynamic light scattering (DLS) and superconducting quantum interference device (SQUID) magnetometry. Enzyme-linked immunosorbent assay (ELISA) was used to assess the thermally triggered release of active TGF-β from the latent complex, demonstrating that conjugation did not interfere with release. Results showed that latent TGF-β was successfully conjugated to the iron oxide nanoparticles, and magnetically triggered release of active TGF-β was achieved.


Assessment of the performance of DFT functionals in the fulfillment of off-diagonal hypervirial relationships.
Off-diagonal hypervirial relationships, combined with quantum mechanical sum rules of charge-current conservation, offer a way to test electronic excited-state transition energies and moments, which does not need any external reference. A number of fundamental relationships were recast into absolute deviations from zero, which have been used to assess the performance of some popular DFT functionals. Extended TD-DFT calculations have been carried out for a pool of molecules chosen for this purpose, adopting a large basis set to ensure high quality results. A partial agreement with previous benchmarks is observed.


Transport distraction osteogenesis using nitinol spring: an exploration in canine mandible.
Some experiments in rabbits have presented the potential feasibility of using shape memory alloy spring for continuous distraction osteogenesis. To confirm the effectiveness of such method, we established canine models for the exploratory experiments of transport distraction osteogenesis using nitinol springs. Simple devices, including an internal 60-mm long sinusoid-shaped nitinol springs were used in the study. All dogs needed only one operation. In the operation, osteotomy was performed to create a 40-mm unilateral segmental mandibular body defect and a tooth-bearing transport bone disc. After reconstructive fixation of the remnant mandible, the spring was constricted and anchored across the distraction gap to activate transport distraction immediately. At the second experimental stage, an ePTFE sheet was further fixed to protect the defect and distraction gap before closing the incision. Control dogs underwent the same operation except for anchoring of the spring to examine the spontaneous bone regeneration. Automatic bone transportation, as a gradual slowdown process, was observed under the effect of the spring. The transport disc could get to the opposite side of the defect, or stopped halfway when ePTFE sheet intervened. Mandibular reconstruction was achieved in all these dogs and better in dogs with sheet protection. No integrated bone mass was found in the defect of control dogs. The study further proves that continuous distraction osteogenesis using nitinol springs is a practical technique, although the devices need more improvement for better control of the process of distraction and the quality of regenerated bone.


[Direct effect of contemporary health education programmes on the knowledge about hand hygiene and technique of hand washing in primary school age children].
In the case of primary school children in Budapest (n = 165), data on their social status and their previous knowledge on hand hygiene were elicited with the help of pre-knowledge questionnaires issued by students of higher education. The aim of the research was introducing a novel pedagogical procedure - application and optimization of peer education in the development of proper hand hygiene among primary school students. The knowledge-based survey was conducted after four (n = 85) and eight hours of teaching (n = 36). In addition, the effectiveness of hand washing was tested immediately before (n = 166) and after the four (n = 74) and eight hours of teaching (n = 35) with Semmelweis Scanner after rubbing the hand with fluorescent cream. Prior knowledge of hand hygiene significantly increased after the four-hour and eight-hour trainings. In the case of smaller children, the effect of the eight-hour training was more pronounced. Similar results were obtained with regards to the changes in the number of areas missed while rubbing the surface of the hand as a result of the teaching. Sociological surveys on hand hygiene knowledge and direct physical measurements indicate that training with appropriate pedagogical procedures is effective and contributes to the environmentally conscious hygiene culture of children aged 6 to 10. Orv Hetil. 2018; 159(12): 485-490.


Phospholipid composition of the mammalian red cell membrane can be rationalized by a superlattice model.
Although the phospholipid composition of the erythrocyte membrane has been studied extensively, it remains an enigma as to how the observed composition arises and is maintained. We show here that the phospholipid composition of the human erythrocyte membrane as a whole, as well as the composition of its individual leaflets, is closely predicted by a model proposing that phospholipid head groups tend to adopt regular, superlattice-like lateral distributions. The phospholipid composition of the erythrocyte membrane from most other mammalian species, as well as of the platelet plasma membrane, also agrees closely with the predictions of the superlattice model. Statistical analyses indicate that the agreement between the observed and predicted compositions is highly significant, thus suggesting that head group superlattices may indeed play a central role in the maintenance of the phospholipid composition of the erythrocyte membrane.


Perspectives on signet ring stromal cell tumor and related signet ring cell lesions of the gonads.
In this article, we discuss advances in our knowledge of the pathology of signet ring stromal cell tumor and related signet ring cell lesions of the ovary and a single case of signet ring stromal cell tumor of the testis. We divide ovarian signet ring cell lesions into 3 categories that reflect differences in their pathogenesis and histologic appearance. With 1 exception, all authentic cases of signet ring stromal cell tumor have been unilateral. Cases of ovarian signet ring stromal cell tumor from the literature can arise in 2 ways. The majority of cases arise multifocally from fibroma, whereas the remainder likely arise directly from the ovarian stroma. In difficult cases, immunocytochemistry provides improved diagnostic accuracy in distinguishing signet ring stromal cell tumor and its mimics from Krukenberg tumor. The most useful antibodies in this regard are epithelial membrane antigen and vimentin.


An astable multivibrator model of binocular rivalry.
The behavior of a neural network model for binocular rivalry is explored through the development of an analogy between it and an electronic astable multivibrator circuit. The model incorporates reciprocal feedback inhibition between signals from the left and the right eyes prior to binocular convergence. The strength of inhibitory coupling determines whether the system undergoes rivalrous oscillations or remains in stable fusion: strong coupling leads to oscillations, weak coupling to fusion. This implies that correlation between spatial patterns presented to the two eyes can affect the strength of binocular inhibition. Finally, computer simulations are presented which show that a reciprocal inhibition model can reproduce the stochastic behavior of rivalry. The model described is a counterexample to claims that reciprocal inhibition models as a class cannot exhibit many of the experimentally observed properties of rivalry.


Trends in overweight and obesity and changes in the distribution of body mass index in schoolchildren of Jena, East Germany.
Data of Jena children (Germany) show increases in the prevalence estimates of overweight and obesity between 1975 and 2001. Our objective was to determine if these increases contribute to changes in the distribution of body mass index (BMI) in the entire population of children. The decade 1985-1995, which includes the time of German reunification, is of particular interest because of the significant socio-economic changes in East Germany, in which Jena is located. The analyses were based on data from four cross-sectional growth studies in 7- to 14-year-old children performed in Jena, Germany, in 1975 (n=2013), 1985 (n=1534), 1995 (n=1906) and 2001 (n=1918). Overweight and obesity were estimated by German reference data and the reference of Cole et al. Mean difference plots were used to investigate the changes in the BMI distributions within sexes between the studies. Between 1985 and 1995, the prevalence of overweight and obesity increased significantly in both sexes, whereas nonsignificant changes were found between 1975 and 1985. Although there is a tendency towards increased overweight between 1995 and 2001, the differences were nonsignificant. Comparing data from 1975 and 1985, the mean difference plots showed virtually no changes in the BMI distribution. In the plots comparing the BMI distribution for 1985 data and 1995 data, the whole distribution tended to shift upwards with a greater shift in the upper BMI range. The entire population of children in Jena gained weight during this period of time. This increase may be linked to a transition towards a more Western lifestyle, that is, usually by lower energy expenditure and nutritional transitions, caused by the process of reunification of Germany in 1989. Weight gain appears to be a characteristic feature of the entire population studied and does not seem to be a separate problem of the obese children. This suggests that reported changes in the prevalence may be underestimating the looming public health crisis.


Mitigation of immunosuppressive and oxidative stress effect of dietary gelatinized starch in Labeo rohita fingerlings by elevation of rearing temperature within optimum range.
The present study was conducted to investigate the strategy to mitigate the immunosuppressive and oxidative stress effect of gelatinized starch in fingerling of Labeo rohita. Fingerlings were either maintained at ambient water temperature (26 °C) or exposed to 32 °C for one week and then subjected to 26 °C for four weeks. Both groups were fed with isoproteinous (30% crude protein) diets containing gelatinized (G) or non-gelatinized (NG) starch. After 5 weeks of feeding trial, fingerlings were challenged by Aeromonas hydrophila and survival rate was recorded for the next 7 days. Serum cortisol and glucose content was significantly (p < 0.05) higher in G starch fed group and decreased with the increase in temperature from 26 to 32 °C, which was consistent for next four week after decrease in temperature from 32 to 26 °C. Lower respiratory burst activity and serum total protein and globulin content in G starch fed group at 26 °C significantly (p < 0.05) increased after elevation of temperature from 26 to 32 °C and levelled off to NG starch fed group. Liver superoxide dismutase (SOD) and catalase (CAT) activity of G starch fed group was significantly higher in group reared at 32 °C compared to 26 °C. After challenge, fish fed G starch showed lower survival rate than that of fish fed NG starch. Subsequently, exposure of elevated temperature (32 °C) for one week significantly increased the survival rate of G starch fed group and levelled off to NG starch fed group. The results of this study indicated that dietary G starch may cause metabolic stress of fingerling L. rohita, as might consequently lead to the decrease antioxidant abilities, depressed immunity and reduced resistance to A. hydrophila infection. Subsequently, exposure of elevated temperature (32 °C) for one week mitigate immunosuppressive and oxidative stress effect of dietary G starch.


[The vascular pattern in solid and cystic basal cell tumors (author's transl)].
In addition to other criteria, the growth pattern, macroscopic form, and histologic examination of a tumor are heavily influenced by the tumor's blood supply. Rapid size increases of basal cell carcinomas in certain of our patients has led us to examine the capillary network of such tumors. Known histologic patterns were summarized, and the tumor vascular patterns evaluated by scanning electron microscopy of corrosion preparations. For this, an artery leading to the tumor was cannulated, and a thin synthetic resin ("Mercox" liquid) injected. After precipitation, the preparation was macerated in aqueous sodium hydroxide. The vascular changes encountered could thus be illustrated in three-dimensional form. In addition to changes specific in the tumors (i.e., caliber fluctuations, cyst formation at vessel ends, and degeneration forms), peculiar formations could be found in various sites, suggesting that capillary neogenesis was taking place within the tumors.


Risk stratification to predict pain during unsedated colonoscopy: results of a multicenter cohort study.
Colonoscopy without sedation has several advantages over sedated colonoscopy, but a considerable proportion of patients experience pain. The aim of this study was to develop a risk stratification model of pre-examination risk factors to enable targeted sedation during colonoscopy. Between October 2011 and January 2012, consecutive outpatients who were willing to start colonoscopy without sedation at 11 Norwegian centers were prospectively recruited. Patients recorded pain on a validated 4-point scale (none, slight, moderate, or severe pain). Potential risk factors for a painful procedure (defined as moderate or severe pain) were evaluated using multivariate logistic regression analyses, and the area under the receiver operating characteristics curve (AUROC) was calculated to assess the discriminatory ability of the derived model. A total of 1198 patients (635 men and 563 women) were included. Seven independent, pre-procedural risk factors for patient pain were identified: female sex, age < 40 years, previous abdominal surgery, abdominal pain as indication for colonoscopy, anticipation of pain, previous painful colonoscopy, and a history of diverticulitis. In patients with 0, 1, 2, or ≥ 3 risk factors, a painful colonoscopy was experienced by 35 %, 43 %, 52 %, and 63 % of women and 18 %, 24 %, 35 %, and 63 % of men, respectively. The model showed modest discrimination abilities (AUROC = 0.69). Female sex was a strong risk factor for pain during colonoscopy, and sedation or analgesia should be considered for all women prior to colonoscopy. For male patients, the presence of multiple risk factors should encourage the endoscopist to offer sedation.


An ultrastuctural study of hair fiber damage and restoration following treatment with permanent hair dye.
Hair fibers are comprised of non-nucleated keratinocytes and are biologically dead. Clinical damage to the hair shaft occurs with the application of hair dye. Whether this damage can be repaired and the time frame involved is of interest and may help to determine the optimal interval between repeat applications. Ultrastructural changes of hair shafts after application of permanent hair dye were observed sequentially in a 26-year-old woman. The dye contained p-phenylenediamine, m-aminophenol, resorcin and hydrogen peroxide as an oxidizer. Scanning and transmission electron microscopy was performed immediately before application of the hair dye and again at 30 min, 1 h, 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks. The hair showed cuticular swelling with focal degeneration. In some places there was exposure of the hair cortex due to extensive cuticular detachment. There were many holes of various size in the endocuticle, small focal lacunae along the intercellular space and an ill-defined A-layer especially beneath the area of cuticular detachment. The exocuticle appeared normal. The findings were most dramatic in the 6 h and 1 day specimens and tended to improve gradually thereafter. The 8 week specimen showed near complete restoration of the hair cuticle and return to the precoloring state. Hair returns to its precoloring state and this requires 8 weeks.


Inflammation enhances mu-opioid receptor transcription and expression in mice intestine.
Opioid receptors (ORs) and their mRNA are present in the central and peripheral nervous systems of mammals and in different peripheral tissues, including the gut. Using a model of croton oil-induced (CO) intestinal inflammation in mice, we have shown a 6-fold increase in the potency of the antitransit and antisecretory effects of mu-OR agonists, mediated by peripheral ORs. We postulate that the enhanced effects are mediated by an increase in the expression of intestinal OR. We used jejunum (stripped of the mucosal layer) from mice with CO-induced intestinal inflammation and, as control subjects, saline-treated animals (SS). We evaluated the quantity of mu-OR mRNA determined by a competitive reverse-transcriptase polymerase chain reaction; the levels of mu-OR protein by Western blot immunoassay, and the localization and number of cells expressing mu-OR using immunohistochemistry. The results show a significant increase of mu-OR mRNA (7.7-fold) and receptor protein (3-fold) during intestinal inflammation. Inflammation also induced a 64.3% increase in the number of neurons expressing mu-OR immunoreactivity in the myenteric plexus but not in the submucosal plexus. Our results show that intestinal inflammation enhances the transcription and translation of mu-OR mRNA, thus explaining the increased potency of mu-opioids during inflammation.


Bone turnover, calcium homeostasis, and vitamin D status in Danish vegans.
A vegan diet has been associated with increased bone fracture risk, but the physiology linking nutritional exposure to bone metabolism has only been partially elucidated. This study investigated whether a vegan diet is associated with increased bone turnover and altered calcium homeostasis due to insufficient intake of calcium and vitamin D. Fractionated and total 25-hydroxyvitamin D (25(OH)-D), parathyroid hormone (PTH), calcium, and four bone turnover markers (osteocalcin, N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptide of type I collagen (CTX)) were measured in serum from 78 vegans and 77 omnivores. When adjusting for seasonality and constitutional covariates (age, sex, and body fat percentage) vegans had higher concentrations of PINP (32 [95% CI: 7, 64]%, P = 0.01) and BAP (58 [95% CI: 27, 97]%, P < 0.001) compared to omnivores, whereas CTX (30 [95% CI: -1, 72]%, P = 0.06) and osteocalcin (21.8 [95% CI: -9.3, 63.7]%, P = 0.2) concentrations did not differ between the two groups. Vegans had higher serum PTH concentration (38 [95% CI: 19, 60]%; P < 0.001) and lower 25(OH)-D serum concentration (-33 [95% CI: -45, -19]%; P < 0.001), but similar serum calcium concentration (-1 [95% CI: -3, 1]%, P = 0.18 compared to omnivores. Vegans have higher levels of circulating bone turnover markers compared to omnivores, which may in the long-term lead to poorer bone health. Differences in dietary habits including intake of vitamin D and calcium may, at least partly, explain the observed differences.


Emotional health outcomes are influenced by sexual minority identity and HIV serostatus.
For people living with HIV (PLWH) and sexual minorities (SM), the intersection of identities can compound experiences like stigma and discrimination resulting in poor emotional health. We investigated the separate and interactive associations of HIV serostatus and sexual identity with emotional health. Our dataset included 371 participants. Emotional health was assessed by the NIH Toolbox emotion battery which yields negative affect, social satisfaction, and psychological well-being. Regressions were conducted for each composite, with HIV serostatus, sexual identity, and their interaction as independent variables along with covariates. The HIV serostatus x SM identity interaction was statistically significant in the regression of Negative Affect (p = .01): heterosexuals living with HIV had worse Negative Affect compared to heterosexual HIV-persons (p = .01). The interaction terms were for social satisfaction and psychological well-being were not significant. However, among PLWH, sexual minorities reported better Social Satisfaction (p = .03) and marginally better psychological well-being (p = .07) compared to heterosexuals.


Latamoxef and the newborn.
Thirty one preterm neonates who had clinical, radiological, or bacteriological evidence of infection and who would normally have received gentamicin and penicillin were treated with latamoxef (Moxalactam) 100 mg/kg/day. All were examined prospectively for clinical improvement and possible side effects. Biochemical and haematological values were monitored and pharmacokinetic variables determined. Thirty babies improved during treatment; latamoxef was effective in eradicating the infecting organisms in 7 of 9, including three babies infected with Lancefield group B streptococci. High serum concentrations of latamoxef were achieved after either intravenous or intramuscular administration and accumulation did not occur. Treatment had no effect on renal or hepatic function nor did it result in increased serum values of non-protein bound bilirubin. Clotting studies, where performed, were normal and no babies had bloody stools. Two disulfiram-like reactions were recorded. Latamoxef proved a safe and efficacious alternative to gentamicin with penicillin in the initial treatment of neonates with clinical evidence of infection.


[Prophylactic cranial irradiation in non-small cell lung cancer].
Prophylactic cranial irradiation (PCI) has become part of the standard treatment in patients with small cell lung cancer (SCLC) in complete remission. Not only does it decrease the risk of brain recurrence by almost 50%, it has a significant positive effect on survival (5.4 percent increase at 3 years). As the prognosis of patients with locally advanced non-small cell lung cancer (NSCLC) has improved with combined modality treatment, brain metastases have also become an important cause of failure (10 to 30%, approaching 50% in certain studies as in SCLC). Survival after treatment of brain metastases is poor and impact on quality of life of patients is important. As in SCLC, 4 randomised evaluating PCI in NSCLC have been carried out in the seventies and early eighties. If 3 out of 4 trials have shown a significant decrease of brain metastases, none of them demonstrated any impact on survival. Thus PCI cannot be recommended as standard treatment in NSCLC, however new trials would be needed.


The incidence of spondyloarthritis in Slovenia.
Epidemiological studies of spondyloarthritides (SpA) are rare and data for our country are lacking. We aimed to determine the incidence of SpA in a well-defined region in Slovenia.We performed a retrospective chart review of adults diagnosed with SpA between January 2014 and December 2016 at an integrated secondary/tertiary medical center, which provides rheumatology services to almost a half of the adult national population, that is, 700,000 adults. Potential cases were ascertained by searching the electronic medical records for ICD-10 codes M02, M07, M13, M45, M 46.1, K50, K51, and L40. SpA cases were stratified as axial and peripheral SpA and then the annual incidence rates of SpA overall and both subsets were estimated.During the 3-year period we identified 302 SpA cases (55.0% males, median [interquartile range] age 46.7 [35.0-57.5] years). 98 (32.5%) of them had predominantly axial SpA and the remainder peripheral SpA. The estimated annual incidence rate per 100,000 adults in our region was 14.3 (95% confidence interval [CI] 12.8-16.0) for SpA overall, 4.6 (95% CI 3.8-5.6) for axial SpA, and 9.6 (95% CI 8.4-11.1) for peripheral SpA.The estimated annual incidence rate of 14.3 cases per 100,000 adults in SpA overall was comparable to that of rheumatoid arthritis in our population. The peripheral SpA was twice as common as axial SpA.


Should I stay or should I go? Eukaryotic translation initiation factors 1 and 1A control start codon recognition.
Start codon selection is a key step in translation initiation as it sets the reading frame for decoding. Two eukaryotic initiation factors, eIF1 and eIF1A, are key actors in this process. Recent work has elucidated many details of the mechanisms these factors use to control start site selection. eIF1 prevents the irreversible GTP hydrolysis that commits the ribosome to initiation at a particular codon. eIF1A both promotes and inhibits commitment through the competing influences of its two unstructured termini. Both factors perform their tasks through a variety of interactions with other components of the initiation machinery, in many cases mediated by the unstructured regions of the two proteins.


[Criteria of genetic predisposition to hereditary non polyposis colorectal cancers].
Clinical and histological characteristics of non polypoid colorectal cancers with an hereditary predisposition are presented. The various known genetic syndromes (hereditary non polyposis colorectal cancers, Lynch syndrome type I and type II, Torre-Muir's syndrome, hereditary flat adenoma syndrome) are discussed to find a possible correlation between this nosological classification and their molecular substratum. The main problem today, is to correctly define the population of hereditary predisposed patients to colon cancer, in order to seek and identify the major responsible gene. Any physician, specialist or not, should be encouraged to give the details of the cancer familial context of his patients, in order to aid the oncologist geneticist in his task.


[A case of primary osteogenic sarcoma of the kidney].
Extraosseous osteogenic sarcoma can occur anywhere in the body, but it is exceedingly rare to find this malignancy in renal tissue. A review of the literature revealed only 16 cases which appeared to be clearly identifiable as malignant extraosseous bone-forming sarcoma of the kidney and our report presents 17th case. The patient was a 67-year-old oriental woman. In March 1994, abdominal plain radiographs showed several dense calcifications in the left flank at another hospital. In May 1995, a huge tumor appeared in the left upper quadrant, so she was admitted to department of Internal Medicine of our institute for further examination. As the subsequent abdominal CT scan showed a huge renal tumor with accompanying calcifications, she was transferred to department of Urology. We diagnosed this tumor to be a huge renal cell carcinoma featuring calcifications and performed left nephrectomy. Microscopically, this tumor demonstrated predominantly osteoblast-like tumor cells coupled with osteoid and bone formation. Its histological appearance was compatible with that of osteogenic sarcoma. Bone scan and skeletal radiograph presents to evidence of malignancy, which led to our diagnosis of primary osteogenic sarcoma of the left kidney. Two months after nephrectomy, we found a large palpable recurrent mass in the left upper quadrant of the abdomen. Although two courses of cisplatin were then administered, her condition deteriorated until death on October 25, 1995, about four months after nephrectomy.


MicroRNA‑27a‑3p regulates the proliferation and chemotaxis of pulmonary macrophages in non‑small cell lung carcinoma tissues through CXCL2.
The present study aimed to investigate microRNA (miRNA)-27a-3p expression in the pulmonary macrophages and peripheral blood of patients with early non-small cell lung carcinoma (NSCLC) and its regulatory effect on the infiltration of pulmonary macrophages into cancer tissues and invasion of NSCLC cells. Blood specimens were withdrawn from 36 patients with NSCLC and 29 healthy subjects. NSCLC tissues and cancer-adjacent tissues were both obtained from patients with NSCLC; furthermore, certain tissue samples were used to extract macrophages. The levels of miRNA-27a-3p and C-X-C motif ligand chemokine 2 (CXCL2) mRNA were detected by reverse transcription-quantitative PCR and the levels of CXCL2 protein were measured by ELISA and western blot analysis. A dual-luciferase reporter assay was performed to determine the interactions between miRNA and mRNA. An MTT assay was employed to examine the viability of transfected cells and macrophages and a Transwell assay was performed to assess chemotaxis. The differential expression of miRNA-27a-3p in NSCLC tissues, pulmonary macrophages and peripheral blood indicated that miRNA-27a-3p exerted different roles in these specimens. CXCL2 was upregulated in NSCLC tissues at both transcriptional and translational levels. In addition, the untranslated region of CXCL2 was confirmed to be directly targeted by miRNA-27a-3p prior to its transcriptional activation. Furthermore, miRNA-27a-3p regulated CXCL2 expression, thereby affecting the proliferation of human pulmonary macrophages. The present study highlights that miRNA-27a-3p expression in the pulmonary macrophages and peripheral blood of patients with NSCLC is downregulated, while its target gene CXCL2 is upregulated. miRNA-27a-3p may regulate the viability and chemotaxis of macrophages in tumor tissues of patients with NSCLC through CXCL2 and is expected to become a genetic marker of this disease.


Factors Associated with Utilization of HIV Testing Services among Adolescents Aged 10-19 Years in Lira District, Northern Uganda: A Cross-Sectional Study.
HIV testing remains a problem among adolescents in low- and middle-income countries, and yet, HIV testing is a cornerstone in the fight against HIV. However, there is scanty literature on the utilization of HIV testing services by adolescents especially in rural settings. This study is aimed at determining the uptake of HIV testing services and associated factors among adolescents aged 10-19 years in Lira District, Northern Uganda. This was a cross-sectional study done among 277 randomly selected adolescents aged 10-19 years attending outpatient clinics in Pentecostal Assembly of God (PAG) Mission Hospital, Ngetta Health Center III, and Boroboro Health Center III. Data were collected using an interviewer-administered structured questionnaire. Data collected included sociodemographic characteristics, history of test and receipt of HIV results in the last three months, and facility-related factors affecting uptake of HIV testing services. Data analysis consisted of descriptive statistics, cross-tabulations, and logistic regression at a 95% level of significance in SPSS version 25. The uptake of HIV testing services was 43% (119/277) among the study participants. Adolescents who had completed primary education (aOR: 5.47; 95% CI: 1.07-28.15; p = 0.042), are employed (aOR: 2.77; 95% CI: 1.16-6.60; p = 0.022), had used a condom in the last sexual intercourse (aOR: 4.46; 95% CI: 1.78-11.15; p = 0.001), and are involved in HIV testing outreaches (cOR: 10.86; 95% CI: 3.81-30.93; p ≤ 0.001) were more likely to uptake HIV testing services compared to those who had tertiary education, are unemployed, had never used a condom, and are not involved in HIV testing outreaches. Utilization of HIV testing services by adolescents aged 10-19 in Lira District, Northern Uganda, is generally low. The Ministry of Health should strengthen HIV testing services targeting adolescents to increase uptake of HIV testing services.


Ku70 or Ku80 deficiencies in the fungus Botrytis cinerea facilitate targeting of genes that are hard to knock out in a wild-type context.
The filamentous ascomycete Botrytis cinerea is one of the most studied models for understanding the necrotrophic behaviour of phytopathogenic fungi. The genomes of two strains of B. cinerea have been sequenced (B05.10 and T4), which may contribute to elucidating the virulence polymorphism in this fungus. In this study, both strains were genetically modified in order to construct recipient strains designed to target genes that are hard to knock out. Deletions of BcKu70 gene in B05.10 strain and BcKu80 gene in T4 strain both affected the nonhomologous end-joining (NHEJ) DNA repair mechanism. NHEJ is responsible for the ectopic integration of gene replacement cassettes during fungal transformation and leads to a lower frequency of homologous recombination (HR). Ku deficiencies in B. cinerea did not disturb in vitro or in planta growth, but clearly improved HR efficiency for the putative sesquiterpene cyclase-encoding gene Cnd15, which was hard to knock out in a wild-type strain.


Deoxygenative [1,2]-hydride shift rearrangements in nucleoside and sugar chemistry: analogy with the [1,2]-electron shift in the deoxygenation of ribonucleotides by ribonucleotide reductases.
A variant of the semipinacol rearrangement that was observed in our laboratory has been applied to the synthesis of several furanose and pyranose derivatives. The process consists of an "orchestrated" [1,2]-hydride shift with departure of a leaving group from the opposite face. Transient formation of a C=O group is followed by rapid transfer of a hydride-equivalent from the same face from which the leaving group departed, which results in double inversion of stereochemistry at the two vicinal carbon atoms. Treatment of 2'-O- and 3'-O-tosyladenosine with lithium triethylborohydride in DMSO/THF gave the respective 2'- and 3'-deoxynucleoside analogues with beta-D-threo configurations. Identical treatment of 5'-O-TPS-2'-O-tosyladenosine gave 9-(5-O-TPS-2-deoxy-beta-D-threo-pentofuranosyl)adenine. The same [1,2]-hydride shift and stereochemistry with the 5'-OH and 5'-O-TPS compounds demonstrated the absence of remote hydroxyl-group participation. Application of this process to other nucleoside 2'-O-tosyl derivatives gave the 2'-deoxy-threo compounds in good yields. The reaction-rate order was OTs approximately Br >> Cl for 2'-O-tosyladenosine, 2'-bromo-2'-deoxyadenosine, and 2'-chloro-2'-deoxyadenosine (all with beta-d-ribo configurations). Analogous results were obtained with mannopyranoside derivatives with either 4,6-O-benzylidene protection or a free OH group at C4. Deuterium labeling clearly defined the stereochemical course as a cis-vicinal [1,2]-hydride shift on the face opposite to the original cis OH and OTs groups followed by hydride transfer from the face opposite to the [1,2]-hydride shift. Synthetic and mechanistic considerations are discussed.


Current evidence in the management of poststroke hemiplegic shoulder pain: a review.
Hemiplegic shoulder pain is a common, complex, and distressing complication, which is related to stroke and occurs in the paralytic side of the patient. It not only presents in the early stage but also can persist into the chronic stage of stroke. The incidence of this complication varies from 12% to 58%, and the most common period of occurrence is at 8-10 weeks poststroke. The multifactorial etiology and underlying mechanisms make it intractable. It is difficult to get a clear description of the percentage of patients receiving adequate pain relief because of a large number of treatments and different results found in interventional studies performed in subjects in different stages of stroke. This review summarizes the incidence, temporal presentation, and etiology of hemiplegic shoulder pain and the current advances in its management and analyzes the reliability and validity of the studies. It suggests careful and regular assessment, and an integrated care model is necessary in practice.