Relation of quantitative coronary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography.
To assess the relation of quantitative measures of coronary stenoses to the development of exercise-induced regional wall motion abnormalities, 34 patients with isolated, single vessel coronary artery lesions and normal wall motion at rest underwent exercise echocardiography and quantitative angiography on the same day. Although all 11 patients with a visually estimated stenosis greater than or equal to 75% had an ischemic response and 10 (91%) of 11 patients with a less than or equal to 25% visually estimated stenosis had a normal response by exercise echocardiography, among 12 patients with a visually estimated stenosis of 50%, 6 (50%) had an ischemic response and 6 (50%) had a normal exercise echocardiogram. Quantitative measurements of stenosis severity distinguished patients with ischemic (group 1) from normal (group 2) exercise echocardiographic responses as follows: minimal luminal diameter (mm), group 1 1.0 +/- 0.4 versus group 2 1.7 +/- 0.4, p less than 0.0001; minimal cross-sectional area (mm2), group 1 0.9 +/- 0.6 versus group 2 2.5 +/- 1.1, p less than 0.0001; percent diameter stenosis, group 1 68.3 +/- 14.2 versus group 2 42.2 +/- 12.1, p less than 0.0001; and percent area stenosis, group 1 87.5 +/- 7.8 versus group 2 64.8 +/- 15.9, p less than 0.0001. These data validate the utility of exercise echocardiography by demonstrating that 1) coronary stenosis severity measured by quantitative angiography is closely related to wall motion abnormalities detected by exercise echocardiography, and 2) exercise echocardiography can be used as a noninvasive means to assess the physiologic significance of coronary artery lesions.


Small bowel obstruction by the silicone tube of the gastric band.
A wide range of operations are used today for morbid obesity. Adjustable gastric banding (AGB) is one of the most widespread. Numerous complications after AGB are known, namely gastric perforation, band slippage, penetration of the band into stomach, port disconnection, port-site infection, etc. The authors present a case of small bowel obstruction caused by the intra-abdominal silicone tube of the gastric band in a woman with AGB performed 9 years before, with a very good result and considerable weight loss. She was operated as an emergency, and part of the terminal ileum was found incarcerated around and between the silicone tube and the anterior abdominal wall. Bowel resection for intestinal necrosis, with terminal ileostomy, was performed, followed 1 month later by an end-to-end ileo-ileal anastomosis. The patient recovered without sequelae.


m6A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension.
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling induced by human pulmonary arterial smooth muscle cell (HPASMC) proliferation, migration, and apoptosis resistance. m6A (N6-methyladenosine) is the most prevalent RNA posttranscriptional modification in eukaryotic cells. However, its role in PAH remains elusive. We designed this study to investigate whether m6A modification and its effector proteins play a role in pulmonary vascular resistance. Lung samples were used to profile m6A concentrations in control subjects and patients with PAH. Bioinformatics analysis, real-time PCR, immunohistochemistry, and Western blotting were used to determine the role of m6A effectors in PAH. The biological effects of GRAP modified by m6A were investigated using in vitro and in vivo models. Furthermore, RIP-PCR was used to assess the writers and readers of GRAP. In this study, we revealed that m6A-modified GRAP mRNA was upregulated in PAH lung samples, cHx/Su-induced mouse models, and hypoxia-stimulated HPASMCs; however, GRAP mRNA and protein were abnormally downregulated. Functionally, overexpression of GRAP drastically alleviated the proliferative and invasive ability of PAH HPASMCs through inhibition of the Ras/ERK signaling pathway in vitro and in vivo. In addition, METTL14 (methyltransferase-like 14) and the m6A binding protein YTHDF2 were significantly increased in PAH. Moreover, we found that m6A-modified GRAP mRNA was recognized by YTHDF2 to mediate the degradation. GRAP expression was consistently negatively correlated with METTL14 and YTHDF2 in vivo and in vitro. Taken together, for the first time, our findings highlight the function and therapeutic target value of GRAP and extend our understanding of the importance of RNA epigenetics in PAH.


Preparation of a new construct of human histone deacetylase 8 for the crystallization of enzyme-inhibitor complexes.
The metal-dependent histone deacetylases (HDACs) are critical regulatory enzymes that modulate myriad cellular processes. Implicated in cancer, neurodegenerative diseases, and other clinical disorders, various HDAC isozymes serve as validated drug targets. However, structural similarities among the HDAC isozymes challenge efforts in targeting a single isozyme for therapeutic intervention with an inhibitor. X-ray crystallography remains the premiere technique for studying the chemistry of isozyme-selective inhibition. While crystal structures of many HDAC-inhibitor complexes have been determined, especially with the class I isozyme HDAC8, the study of complexes with large inhibitors is complicated by flexible regions of the protein structure that can hinder crystallization. Here, we outline an approach for the identification of regions in HDAC8 that may hinder crystallization. We also describe protocols for the design and preparation of a truncated HDAC8 construct, HDAC8374, that enabled the successful crystallization and structure determination of the HDAC8-Trapoxin A complex at 1.24Å resolution.


Analysis of mitogen-activated protein kinase activation.
The biological functions of mast cells are regulated by several protein kinases, including the tyrosine kinases Fyn, Lyn, Syk, and FAK and the serine/threonine kinases Akt and PKC alpha/beta. The mitogen-activated protein kinases extracellular signal-regulated kinases, JNK, and p38MAPK also play a significant role in the regulation of mast cell biological function. This chapter will detail recent advances in determining mitogen-activated protein kinase activation in single cells. These methods are applicable to studies of signal transduction in mast cells.


Modulation of basal ganglia neurotransmission by the classical antipsychotic fluphenazine is due in part to the blockade of dopamine D1-receptors.
Classical antipsychotics, such as fluphenazine, influence neurotransmission by blocking both dopamine D1- and D2-receptors which in turn results in widespread adaptive changes in the neurochemistry of the basal ganglia. The purpose of the present study was to determine the role of D1-receptors in mediating some of these neurochemical events, including changes in D1- and D2-receptor binding, and the expression of preproenkephalin and glutamic acid decarboxylase mRNAs. For these experiments, rats were given a depot injection of fluphenazine decanoate or injected twice daily for 21 days with the D1-receptor antagonist SCH-23390. An additional group received both fluphenazine and SCH-23390 and controls were given saline. Fluphenazine administration decreased D2-receptor binding throughout the basal ganglia while SCH-23390 was without effect. In contrast to the uniform reduction in D2-receptor binding, fluphenazine altered D1-receptor binding in a region-dependent manner. Region-dependent changes were also observed in animals given SCH-23390 which increased binding in the entopeduncular nucleus and posterior caudate-putamen without affecting other brain regions. Both fluphenazine and SCH-23390 significantly enhanced preproenkephalin and glutamic acid decarboxylase (GAD) mRNA expression in the anterior striatum. Fluphenazine also increased GAD mRNA levels in the entopeduncular nucleus. Together, these results indicate that the attenuation of D1-receptor-mediated neurotransmission modulates a number of clinically relevant neurochemical processes in the basal ganglia.


A Stunt of Sustainability: Artificial Humic Substances Can Generate and Stabilize Single Fe0 Species on Mineral Surfaces.
Iron species are omnipresent in fertile soils and contribute to biological and geological redox processes. Here, we show by advanced electron microscopy techniques that an important, but previously not considered iron species, single atom Fe0 stabilized on clay mineral surfaces, is contained in soils when humic substances are present. As the concentration of neutral iron atoms is highest under frost logged soil conditions, their formation can be attributed to the action of a then reductive microbiome. The Fe0 /Fe2+ couple is with -0.04 V standard potential highly suited for natural environmental remediation and detoxification, and its occurrence can help to explain the sustained auto-detoxification of black soils.


Analyzing the diffusion and duration of antibodies to SARS-CoV-2 during the natural infection and comparison with vaccination.
To monitor SARS-CoV-2 diffusion, we measured anti-Spike S1/S2 IgGs in the serum of nearly 4000 workers employed in several healthcare facilities for one year. We found that the antibody response persists at least over 8 months in symptomatic subjects, particularly in individuals with anosmia/dysgeusia. Moreover, analyzing a smaller cohort (124 healthcare employees of which 57 had a previous history of SARS-CoV-2 exposure) vaccinated with two doses of Comirnaty vaccine, we observed that in symptomatic subjects previously exposed to SARS-CoV-2 one dose vaccine was sufficient to stimulate very high levels of antibodies, suggesting that these subjects should take only one dose of vaccine.


Instructions to Prospective Authors by Indian Biomedical Journals: An Opportunity to Promote Responsible Conduct of Research.
Journals provide instructions to prospective authors to facilitate the process of manuscript publication. The information provided under such instructions could be a potential opportunity to promote responsible conduct of research (RCR). We analyzed 74 Indian biomedical journals for the type of information provided in the "instructions to authors" section and adherence to the International Committee of Medical Journal Editors (ICMJE) recommendations. Among the 71 journals that had an "instructions to authors" section, 53 journals adhered to ICMJE recommendations. We discuss sections of the ICMJE recommendations detailed by Indian biomedical journals under the "instructions to authors" section and emphasize components that require greater exposure.


Three cases of non-surgical treatment of stent loss during percutaneous coronary intervention.
Percutaneous coronary intervention with stenting is widely used for ischemic heart disease. Because stent loss, which occurs rarely during the procedure, might have dire consequences, such as bleeding, stent embolism, acute myocardial infarction, emergency coronary artery bypass graft, and death, appropriate treatment is needed as soon as stent loss occurs. We report three cases of stent loss which were successfully treated with three different non-surgical methods.


HTLV-I infection in patients with autoimmune thyroiditis (Hashimoto's thyroiditis).
To investigate the possible relationship of HTLV-I virus infection to autoimmune thyroid disease, we examined, firstly, the frequency of HTLV-I seropositivity among patients with Hashimoto's thyroiditis and, secondly, the frequency of Hashimoto's thyroiditis in patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Of 144 patients with Hashimoto's thyroiditis in the Tokushima and Kochi Prefectures, Japan, 9 (6.3%) were positive for serum HTLV-I virus antibody 2 of whom were confirmed histologically to have Hashimoto's thyroiditis. This percentage is significantly higher (P < 0.01) than the estimated prevalence (2.2%) of HTLV-I carriers among the general population in this region. Of 9 patients with HAM/TSP, 3 (33.3%), including 2 biopsy-proven cases, had evidence of Hashimoto's thyroiditis. This proportion is apparently much higher than the prevalence (1.7%) of Hashimoto's thyroiditis in the general population. These findings suggest that HTLV-I virus may be related to the development of Hashimoto's thyroiditis.


Hybrid operation for arteriovenous malformations with associated multiple intracranial aneurysms and subarachnoid hemorrhage: Case report.
The hybrid surgical concept for the treatment of brain arteriovenous malformations (AVMs) with associated intracranial aneurysms (IAs) is still not widely practiced. Concomitant occurrence of AVMs with IAs is common. Subarachnoid hemorrhage (SAH) as a result of AVM or IA rupture is often associated with these dual pathological phenomena. We present a case of concomitant occurrence of AVMs and IAs that was successfully treated using the hybrid operation concept. A 62-year-old man presented with sudden onset of severe headache, dizziness, nausea, and vomiting for 4 hours. Computed tomography revealed SAH and a hematoma in the right frontal lobe. A computed tomographic angiogram also revealed a right frontal AVM with 3 IAs. We used a hybrid operating room to successfully treat both AVMs and IAs. Two years of follow-up showed that the patients were well and performed their daily duties. The hybrid operating room is an innovative, safe, and effective method for the treatment of AVMs with associated IAs, particularly high-grade AVMs and IAs with hemorrhage or SAH. Patients with concomitant AVMs and IAs have the highest chance of hemorrhage compared with those with AVM or IAs alone.


In situ freezing of the rat urinary bladder: DNA adduct formation in the bladder epithelium demonstrated by 32P-postlabeling assay.
In situ freezing of the urinary bladder has been demonstrated to exert tumor-initiating potential in two-stage urinary bladder carcinogenesis in the rat. In the present experiment, DNA modification was examined after in situ freezing of the whole urinary bladder performed by pinching with frozen forceps at -15 degrees C or -30 degrees C for 2 s. The 32P-postlabeling analysis revealed at least 2 DNA adducts in the epithelial cells of the urinary bladder collected 3 days after freezing. Single-strand breaks of DNA were also found by means of the alkaline elution assay in the bladder epithelium collected 10 min after freezing. Thus, the previously demonstrated tumor-initiating activity of in situ freezing in urinary bladder carcinogenesis was revealed to be associated with substantial DNA damage and adduct formation.


Neurobiochemical aspects of maprotiline (Ludiomil) action.
In the first part of the paper a short review of the neurobiochemical effects of the antidepressant drug maprotiline is given. Its most obvious effect is the inhibition of noradrenaline uptake in peripheral and central neurones. The peculiarity of this action consists in its high degree of selectivity, as no inhibition of serotonin uptake could be demonstrated in vivo. In the second part, the results of new experiments are described. These show that serotonin uptake is not diminished in rat mid-brain synaptosomes even after treatment with very high doses of maprotiline (600 mg/kg p.o.). In addition, the influence of the antidepressant on noradrenaline and serotnin uptake was studied in rat cerebral cortex, cerebellum, hypothalamus and pons-medulla. Dopamine and serotonin uptake were measured in the corpus striatum. Again, only the uptake of noradrenaline was found to be inhibited. There was not even a slight tendency towards inhibition of serotonin uptake. This high degree of selectivity distinguishes maprotiline from the tricyclic antidepressants and thus makes it an intersting 'extreme-type' uptake inhibitor.


The influence of luteinizing hormone-releasing hormone (LHRH) on the process of protein and/or peptide secretion characterized by the formation of granular vesicles in mammalian pinealocytes. Comparative in vitro study.
In the present study, the effect of LHRH on the process of protein and/or peptide secretion characterized by the formation of granular vesicles has been studied by means of an in vitro system in the pinealocytes of three different species of rodents. LHRH has a strong influence on the activity of this process. However, this effect varies with the presence of noradrenaline (NA) in the medium and is not identical in the individual species studied. In the rat and mouse, for example, LHRH induces an increase in the number of granular vesicles when the pinealocytes are cultured in a NA-free medium, while, in contrast, in the hamster this stimulatory effect is found exclusively in the presence of NA. Moreover, in the pinealocytes of the mouse, in the presence of NA, LHRH shows an inhibitory effect on protein secretion. These results clearly demonstrate that LHRH, at least under the present in vitro conditions, acts on the synthetic activity of the pineal gland, and demonstrates the importance of pineal protein and/or peptide "hormones" in pineal endocrinology.


Effectiveness of Evidence-Based Asthma Interventions.
Researchers often struggle with the gap between efficacy and effectiveness in clinical research. To bridge this gap, the Community Healthcare for Asthma Management and Prevention of Symptoms (CHAMPS) study adapted an efficacious, randomized controlled trial that resulted in evidence-based asthma interventions in community health centers. Children (aged 5-12 years; N = 590) with moderate to severe asthma were enrolled from 3 intervention and 3 geographically/capacity-matched control sites in high-risk, low-income communities located in Arizona, Michigan, and Puerto Rico. The asthma intervention was tailored to the participant's allergen sensitivity and exposure, and it comprised 4 visits over the course of 1 year. Study visits were documented and monitored prospectively via electronic data capture. Asthma symptoms and health care utilization were evaluated at baseline, and at 6 and 12 months. A total of 314 intervention children and 276 control children were enrolled in the study. Allergen sensitivity testing (96%) and home environmental assessments (89%) were performed on the majority of intervention children. Overall study activity completion (eg, intervention visits, clinical assessments) was 70%. Overall and individual site participant symptom days in the previous 4 weeks were significantly reduced compared with control findings (control, change of -2.28; intervention, change of -3.27; difference, -0.99; P < .001), and this result was consistent with changes found in the rigorous evidence-based interventions. Evidence-based interventions can be successfully adapted into primary care settings that serve impoverished, high-risk populations, reducing the morbidity of asthma in these high-need populations.


Effect οf οxygen availability and pH οn adaptive acid tolerance response of immobilized Listeria monocytogenes in structured growth media.
The aim of the present study was to evaluate the effect of oxygen availability (aerobic, hypoxic and anoxic conditions) and sub-optimal pH (6.2 and 5.5) in a structured medium (10% w/V gelatin) on the growth of two immobilized L. monocytogenes strains (C5, 6179) at 10 °C and their subsequent acid resistance (pH 2.0, e.g., gastric acidity). Anaerobic conditions resulted in lower bacterial population (P < 0.05) (7.8-8.2 log CFU/mL) at the end of storage than aerobic and hypoxic environment (8.5-9.0 log CFU/mL), a phenomenon that was intensified at lower pH (5.5), where no significant growth was observed for anaerobically grown cultures. Prolonged habituation of L. monocytogenes (15 days) at both pH increased its acid tolerance resulting in max. 10 times higher t4D (appx. 60 min). The combined effect though of oxygen availability and suboptimal pH on L. monocytogenes acid resistance was found to vary with the strain. Anoxically grown cultures at pH 5.5 exhibited the lowest tolerance towards lethal acid stress, with countable survivors occurring only until 20 min of exposure at pH 2.0. Elucidating the role of oxygen limiting conditions, often encountered in structured foods, on acid resistance of L. monocytogenes, would assist in assessing the capacity of L. monocytogenes originated from different food-related niches to withstand gastric acidity and possibly initiate infection.


Management of orbitozygomatic fractures.
Management of orbitozygomatic fractures forms part of the scope of practice of many oral and maxillofacial surgeons. As aspects of management vary among surgeons who treat such injuries, this confidential study was undertaken to examine some of the protocols of Australian and New Zealand oral and maxillofacial surgeons. Eighty-one per cent of the respondents treated orbitozygomaticfractures and on average, each treated approximately 24 cases per year. Also, about one in five cases required orbital floor exploration.Further, the preferred imaging baseline was computed tomography plus plain X-rays, while the preferred implant materials for orbital floor reconstruction were autologous bone and resorbable membrane. The incidence of postoperative retrobulbar haemorrhage was estimated at approximately 1:1000. Most oral and maxillofacial surgeons treat orbitozygomatic injuries as part of their surgical scope.


Activating transcription factor 6 plays protective and pathological roles in steatosis due to endoplasmic reticulum stress in zebrafish.
Many etiologies of fatty liver disease (FLD) are associated with the hyperactivation of one of the three pathways composing the unfolded protein response (UPR), which is a harbinger of endoplasmic reticulum (ER) stress. The UPR is mediated by pathways initiated by PRKR-like endoplasmic reticulum kinase, inositol-requiring 1A/X box binding protein 1, and activating transcription factor 6 (ATF6), and each of these pathways has been implicated to have a protective or pathological role in FLD. We used zebrafish with FLD and hepatic ER stress to explore the relationship between Atf6 and steatosis. A mutation of the foie gras (foigr) gene caused FLD and hepatic ER stress. The prolonged treatment of wild-type larvae with tunicamycin (TN), which caused chronic ER stress, phenocopied foigr. In contrast, acute exposure to a high dose of TN robustly activated the UPR but was less effective at inducing steatosis. The sterol regulatory element binding protein transcription factors were not required for steatosis in any of these models. Instead, depleting larvae of active Atf6 either through a membrane-bound transcription factor peptidase site 1 mutation or an atf6 morpholino injection protected them against steatosis caused by chronic ER stress, but exacerbated steatosis caused by acute TN treatment. ER stress causes FLD. A loss of Atf6 prevents steatosis caused by chronic ER stress but can also potentiate steatosis caused by acute ER stress. This demonstrates that Atf6 can play both protective and pathological roles in FLD.


Anti-Müllerian hormone, testosterone and free androgen index following the dose-adjusted unilateral diathermy in women with polycystic ovary syndrome.
The aim of this study was to investigate changes of anti-Müllerian hormone, testosterone and free androgen index after two diathermy methods. We have also aimed at evaluating prognostic value of these parameters for an ovulatory response. This prospective, comparative study included ninety-six women with polycystic ovary syndrome unresponsive to clomiphene citrate. Patients were assigned to two groups; the first group underwent unilateral laparoscopic ovarian drilling with thermal doses adjusted to ovarian volume: median of 720J (IQR), while the second group underwent bilateral drilling with fixed doses of 1200J. Anti-Müllerian hormone (AMH), testosterone (T), free androgen index (FAI)and luteinizing hormone (LH) were measured at baseline, at 1st and 6th month of follow up. AMH, T and LH levels significantly decreased (P<0.001, P≤0.024, P<0.001) after diathermy in both responders and nonresponders from either treatment group. On contrary, FAI levels (P<0.001) significantly changed only in responders, irrespective of the treatment. In 1st and 6th month of follow up median levels of AMH, T and FAI among responders from different treatment groups were equivalent, whereas the responders in bilateral group had higher LH levels in the 1st month of follow up (P=0.003). Nonresponders differed between treatment groups only in AMH level which was decreased in unilateral group throughout the follow up (P≤0.021). The baseline value of T (semi-standardized coefficient, β=-0.28) and value of T in the 1st month (β=-0.72) after the diathermy were significant and consistent indicator of the response to therapy within 6months and the ovulation response in the 1st month. The value of T is the strongest and consistent indicator of ovulatory response after diathermy. www.ClinicalTrials.gov , NCT01833949.


The functional health needs of older persons in custody: A rapid review.
The number of older persons in custody is increasing and older incarcerated individuals have higher functional healthcare needs and higher healthcare costs. Consideration of available measures and interventions to address functional decline, are therefore imperative given the importance of disability to healthcare spending. To identify the existing literature describing the functional health needs of older incarcerated individuals. This rapid review synthesized existing literature on the functional health of older incarcerated individuals. Three electronic databases and two correctional service health-related journals were searched. Bibliographic searches of seminal articles and key authors were conducted for thoroughness. Fifteen articles were retained in the final analysis. The methods of the included studies were heterogenous. Consideration of basic self-care (activities of daily living) and functional mobility were the primary ways of capturing functional health. The concept of 'Prison ADLs' emerged and measured the unique aspects of correction-specific functional activities. This review identified the existing literature on how the functional health of older incarcerated persons is operationalized and measured, and how it is considered within this unique context. The concept of 'Prison ADLs' provides insight into the functional experiences of this population. Additionally, performance across PADLs typically declines before abilities across traditional ADLs.


Inadequate cytoplasmatic calcium signals in alveolar macrophages after cardiac surgery.
Patients undergoing cardiac surgery have an elevated risk for pulmonary complications. A dysfunction of alveolar macrophages (AM) might promote postoperative infections. Therefore intracellular calcium [Ca(2+)](i) as an important second messenger in cellular signaling was assessed in AM. Twelve patients undergoing elective coronary artery bypass graft surgery (CABG) were enrolled in this clinical trial. After anesthesia induction and 2 h after cardiopulomary bypass (CPB) declamping, the bronchoalveolar lavage (BAL) fluid was collected preoperatively from the right middle lobe and postoperatively from the left lingula of the lung. Cell subpopulations and [Ca(2+)](i) signals were assessed via flow cytometry. To express the changes of [Ca(2+)](i) signals the Fluo4/FuraRed-Ratio was used. After surgery the [Ca(2+)](i) baseline in unstimulated AMs were significantly reduced (p < 0.001). A significant signal reduction after fMLP (p = 0.021) and C5a (p = 0.028) stimulation was found in FSC high AMs after surgery, even though all populations showed a trend of less responsiveness. We suggest that the reduced [Ca(2+)](i) signaling in postoperative AMs is caused by a reduced coupling to membrane channels. These preliminary data suggest an inadequate [Ca(2+)](i) signal of AM after surgery, which may contribute to a local immune dysfunction in the lung.


One-pot synthesis of magnetite nanorods/graphene composites and its catalytic activity toward electrochemical detection of dopamine.
Magnetite (Fe3O4) nanorods anchored over reduced graphene oxide (rGO) were synthesized through a one-pot synthesis method, where the reduction of GO and in-situ generation of Fe3O4 nanorods occurred concurrently. The average head and tail diameter of Fe3O4 nanorods anchored over the rGO matrix are found to be 32 and 11 nm, respectively, and morphology, structure and diameter of bare Fe3O4 nanorods were not altered even after the composite formation with rGO. The increased structural disorders and decrement in the sp(2) domains stimulated the high electrical conductivity and extended catalytic active sites for the prepared rGO/Fe3O4 nanocomposite. The constructed rGO/Fe3O4/GCE sensor exhibited excellent electrocatalytic activity toward the electrooxidation of dopamine (DA) with a quick response time of 6s, a wide linear range between 0.01 and 100.55 µM, high sensitivity of 3.15 µA µM(-1) cm(-2) and a lower detection limit of 7 nM. Furthermore, the fabricated sensor exhibited a practical applicability in the quantification of DA in urine samples with an excellent recovery rate. The excellent electroanalytical performances and straight-forward, surfactant and template free preparation method construct the rGO/Fe3O4 composite as an extremely promising material for the diagnosis of DA related diseases in biomedical applications.


Daily Variations of Corneal White-to-White Diameter Measured with Different Methods.
A precise determination of the corneal diameter is essential for the diagnosis of various ocular diseases, cataract and refractive surgery as well as for the selection and fitting of contact lenses. The aim of this study was to investigate the agreement between two automatic and one manual method for corneal diameter determination and to evaluate possible diurnal variations in corneal diameter. Horizontal white-to-white corneal diameter of 20 volunteers was measured at three different fixed times of a day with three methods: Scheimpflug method (Pentacam HR, Oculus), placido based topography (Keratograph 5M, Oculus) and manual method using an image analysis software at a slitlamp (BQ900, Haag-Streit). The two-factorial analysis of variance could not show a significant effect of the different instruments (p = 0.117), the different time points (p = 0.506) and the interaction between instrument and time point (p = 0.182). Very good repeatability (intraclass correlation coefficient ICC, quartile coefficient of dispersion QCD) was found for all three devices. However, manual slitlamp measurements showed a higher QCD than the automatic measurements with the Keratograph 5M and the Pentacam HR at all measurement times. The manual and automated methods used in the study to determine corneal diameter showed good agreement and repeatability. No significant diurnal variations of corneal diameter were observed during the period of time studied.


[Comparation of Toxoplasma gondii separated from HIV-positive people and RH strain GRA6 gene].
To comparatively analyze Toxoplasma gondii separated from HIV-positive people and RH strain GRA6 gene. By using the nested PCR, the amplification of Dali HIV-positive blood samples and RH strains of Toxoplasma GRA6 genome was performed. The GRA6 gene amplification positive product was selected and the electrophoresis imaging was performed by being digested with the Mse I endonuclease, and the gene sequences were measured and analyzed. The GRA6 gene fragment (800 bp) was successfully amplified, and about 600 bp and 200 bp bands were got by Mse I. The sequencing results showed that T. gondii GRA6 gene positive samples had 2 nucleotide variation compared with T. gondii strain RH, namely 447 base pair at C becoming G, and 623 base pair at G becoming T. At 146 bp and 690 bp, the Mse I restriction sites (TTAA) were found. The preliminary judgment shows that the Dali HIV-positive T. gondii genotype is consistent with RH strain, belonging to genotype I.


Effects of thyroxine on the ontogeny of the vitellogenic response in Pleurodeles waltli of both sexes.
In the newt, Pleurodeles waltli, vitellogenin synthesis can be induced by oestrogen prior to metamorphosis and well before vitellogenin synthesis is normally observed in females. Vitellogenin indicubility has been shown to occur during normal development at stage 53 in both sexes. Immersion of young larvae in thyroxine at concentrations that did not result in early morphological metamorphosis led to a precocious acquisition of liver responsiveness to oestrogen. Treatment of larvae with thiourea greatly diminished the ability of oestradiol to induce vitellogenin synthesis, although it did not abolish the hormonal response.


Positive dromotropic effect of dibutyryl cyclic adenosine 3',5'-monophosphate on the atrioventricular node.
The effect of atrioventricular (A-V) conduction of N6-2'-0-dibutyryl cyclic 3',5'-adenosine monophosphate (dibutyryl cyclic AMP) was investigated in comparison with those of norepinephrine, cyclic 3',5'-adenosine monophosphate (cyclic AMP), adenosine-5'-monophosphate (5'-AMP), and adenosine by the use of the isolated, blood-perfused A-V node preparation of the dog. Single injections of dibutyryl cyclic AMP (3-300 micronmol) and norepinephrine (0.1-1 nmol) into the posterior septal artery of the preparation (the upper part of the A-V node is mainly perfused through this artery) produced a dose-dependent decrease in the A-V conduction time. The time to the peak effect and the duration of the effect of dibutyryl cyclic AMP were much longer than with norepinephrine. The positive dromotropic effect of dibutyryl cyclic AMP was resistant to the beta-adrenoceptor blocking action of propranolol. Unlike dibutyryl cyclic AMP, cyclic AMP (above 30 nmol), 5'-AMP and adenosine (above 1 nmol) injected into the posterior septal artery prolonged the A-V conduction time in a dose-dependent manner. The results indicate that dibutyryl cyclic AMP has a mode of action on A-V nodal cells which differs distinctly from that of either norepinephrine or cyclic AMP, 5'-AMP, and adenosine.


Identification of Crucial Residues in α-Conotoxin EI Inhibiting Muscle Nicotinic Acetylcholine Receptor.
α-Conotoxins (α-CTxs) are small disulfide-rich peptides from venom of Conus species that target nicotinic acetylcholine receptors (nAChRs). The muscle-type nAChRs have been recognized as a potential target for several diseases, such as myogenic disorders, muscle dystrophies, and myasthenia gravis. EI, an α4/7-CTx, mainly blocks α1β1δε nAChRs and has an extra N-terminal extension of three amino acids. In this study, the alanine scanning (Ala-scan) mutagenesis was applied in order to identify key residues of EI for binding with mouse α1β1δε nAChR. The Ala-substituted analogues were tested for their abilities of modulating muscle and neuronal nAChRs in Xenopus laevis oocytes using two-electrode voltage clamp (TEVC) recordings. Electrophysiological results indicated that the vital residues for functional activity of EI were His-7, Pro-8, Met-12, and Pro-15. These changes exhibited a significant decrease in potency of EI against mouse α1β1δε nAChR. Interestingly, replacing the critical serine (Ser) at position 13 with an alanine (Ala) residue resulted in a 2-fold increase in potency at the α1β1δε nAChR, and showed loss of activity on α3β2 and α3β4 nAChRs. Selectivity and potency of [S13A] EI was improved compared with wild-type EI (WT EI). In addition, the structure-activity relationship (SAR) of EI revealed that the "Arg1-Asn2-Hyp3" residues at the N-terminus conferred potency at the muscle-type nAChRs, and the deletion analogue △1-3 EI caused a total loss of activity at the α1β1δε nAChR. Circular dichroism (CD) spectroscopy studies demonstrated that activity loss of truncated analogue △1-3 EI for α1β1δε nAChR is attributed to disturbance of the secondary structure. In this report, an Ala-scan mutagenesis strategy is presented to identify crucial residues that are significantly affecting potency of E1 for mouse α1β1δε nAChR. It may also be important in remodeling of some novel ligands for inhibiting muscle-type nAChRs.


Concentration dependent antioxidative and apoptotic effects of sulforaphane on bovine granulosa cells in vitro.
Sulforaphane (SFN) has received a great deal of research attention because of its ability to induce the production of a battery of antioxidant enzymes in certain concentrations through the activation of the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, which may effectively neutralize reactive oxygen species (ROS) induced oxidative stress. This study was conducted to investigate the potential of different concentrations of SFN in inducing antioxidative and apoptotic effects in granulosa cells (GCs). For this purpose, bovine GCs were collected from preovulatory antral follicles and cultured with different concentrations of SFN (0-80 μM) and based on phenotypic evaluation three concentrations were selected: 2 μM (low), 10 μM (medium), and 20 μM (high) for further investigations. The results showed that there was a dramatic loss of cell viability and higher cytotoxic effects of SFN on GCs at higher concentrations (>15 μM). The expression of NRF2 increased significantly (p < 0.05) with fold change ranged 3-8 in SFN treated GCs, whereas Kelch Like ECH Associated Protein 1 (KEAP1) expression was either downregulated or similar as control group under the same conditions. Moreover, the relative expression of the genes (PRDX1, CAT, TXN1and SOD1) downstream to NRF2 activation was found to be highly expressed (fold change ranged from 2 to 5, p < 0.05) in SFN treated GCs compared to the untreated control. In addition, ROS accumulation was higher in GCs treated with 20 μM SFN which in turn results in a higher accumulation of lipid droplets. Compared to control, no changes in the mitochondrial activity was observed at 2 and 10 μM SFN concentrations; however, significantly lower mitochondrial activity was found at high concentration (20 μM). The results of this study clearly showed that 10 μM SFN concentration played a crucial role in activating Nrf2 pathway without inducing apoptotic characteristics and this concentration may have beneficial effects in boosting the production of phase II antioxidant enzymes in GCs. However, at high concentration (20 μM), SFN may generate excessive ROS that causes mitochondrial dysfunction and induces cellular stress and eventually leads to apoptosis. These data strongly suggest a concentration dependent antioxidative and apoptotic effects of SFN on GCs.


Hyperspectral image-based analysis of thermal damage for ex-vivo bovine liver utilizing radiofrequency ablation.
Thermal ablation is the predominant methodology to treat liver tumors for segregating patients who are not permitted to have surgical intervention. However, noticing or predicting the size of the thermal strategies is a challenging endeavor. We aim to analyze the effects of ablation district volume following radiofrequency ablation (RFA) of ex-vivo liver exploiting a custom Hyperspectral Imaging (HSI) system. RFA was conducted on the ex-vivo bovine liver at focal and peripheral blood vessel sites and observed by Custom HSI system, which has been designed to assess the exactness and proficiency using visible and near-infrared wavelengths region for tissue thermal effect. The experiment comprised up to ten trials with RFA. The experiment was carried out in two stages to assess the percentage of the thermal effect on the investigated sample superficially and for the side penetration effect. Measuring the diffuse reflectance (Ŗd) of the sample to identify the spectral reflectance shift which could differentiate between normal and ablated tissue exploiting the designed cross-correlation algorithm for monitoring of thermal ablation. Determination of the diffuse reflection (Ŗd) spectral signature responses from normal, thermal effected, and thermal ablation regions of the investigated liver sample. Where the ideal wavelength range at (600-640 nm) could discriminate between these different regions. Then, exploited the converted RGB image of the HS liver tissue after RFA for more validations which shows that the optimum wavelength for differentiation at (530-560 nm and 600-640 nm). Finally, applying statistical analysis to validate our results presenting that wavelength 600 nm had the highest standard deviation (δ) to differentiate between various thermally affected regions regarding the normal tissue and wavelength 640 nm shows the highest (δ) to differentiate between the ablated and normal regions. The designed and implemented medical imaging system incorporated the hyperspectral camera capabilities with the associate cross-correlation algorithm that could successfully distinguish between the ablated and thermally affected regions to assist the surgery during the tumor therapy.


Allylpolyalkoxybenzene Inhibitors of Galactonolactone Oxidase from Trypanosoma cruzi.
Inhibition of biosynthetic pathways of compounds essential for Trypanosoma cruzi is considered as one of the possible action mechanisms of drugs against Chagas disease. Here, we investigated the inhibition of galactonolactone oxidase from T. cruzi (TcGAL), which catalyzes the final step in the synthesis of vitamin C, an antioxidant that T. cruzi is unable to assimilate from outside and must synthesize itself, and identified allylbenzenes from plant sources as a new class of TcGAL inhibitors. Natural APABs (apiol, dillapiol, etc.) inhibited TcGAL with IC50 = 20-130 µM. The non-competitive mechanism of TcGAL inhibition by apiol was established. Conjugation of APABs with triphenylphosphonium, which ensures selective delivery of biologically active substances to the mitochondria, increased the efficiency and/or the maximum percentage of TcGAL inhibition compared to nonmodified APABs.


A comparison of independent living outcomes following traumatic brain injury and spinal cord injury.
This study compares independent living outcomes in persons with traumatic brain injury (TBI) and spinal cord injury (SCI). Both injuries represent life-altering events that are known to have a negative impact on independent living and are predominantly experienced by members of the same demographic group. However, the types of resultant impairments and disabilities experienced by the two populations differ substantially. The TBI participants were recruited consecutively from Canada's largest tertiary care trauma centre and followed prospectively for four years. The SCI participants were recruited via a mailed survey to members of a provincial branch of the Canadian Paraplegic Association. Independent living outcomes were measured using DeJong and Hughes' (1982) classification system of productivity status, the Reintegration to Normal Living Index, and questions on assistance from environmental supports in the form of wheelchair use and paid/unpaid personal assistance. The TBI group was found to be significantly more productive, have higher levels of satisfaction with their current experience of community integration, and use fewer environmental supports than their SCI counterparts (P<or=0.0001). Methodological and demographic differences between the samples are discussed in relation to the results. The results suggest that various aspects of independent living in these two defined groups (TBI and SCI) although highly related require specific attention and that clinicians and researchers working with TBI and SCI might benefit from further collaborative efforts.


N4-acetylcytidine modification of lncRNA CTC-490G23.2 promotes cancer metastasis through interacting with PTBP1 to increase CD44 alternative splicing.
Although N4-acetylcytidine (ac4C) modification affects the stability and translation of mRNA, it is unknown whether it exists in noncoding RNAs, and its biological function is unclear. Here, nucleotide-resolution method for profiling CTC-490G23.2 ac4C sites and gain- and loss-of-function experiments revealed that N-acetyltransferase 10 (NAT10) is responsible for ac4C modification of long noncoding RNAs (lncRNAs). NAT10-mediated ac4C modification leads to the stabilization and overexpression of lncRNA CTC-490G23.2 in primary esophageal squamous cell carcinoma (ESCC) and its further upregulation in metastatic tissues. CTC-490G23.2 significantly promotes cancer invasion and metastasis in vitro and in vivo. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the binding of CD44 pre-mRNA to polypyrimidine tract-binding protein 1 (PTBP1), resulting in a oncogenic splicing switch from the standard isoform CD44s to the variant isoform CD44v(8-10). CD44v(8-10), but not CD44s, binds to and increases the protein stability of vimentin. Expression levels of CTC-490G23.2 and CD44v(8-10) can predict poor prognosis in cancer patients. Furthermore, the antisense oligonucleotide (ASO)/SV40-LAH4-L1 peptide self-assembled nanocomplexes targeting CTC490G23.2 exerts a significantly suppressive effect on cancer metastasis. The outcome of this study will provide new mechanistic insight into the ac4C modification of lncRNAs and useful clues for the development of novel systemic therapies and prognostic biomarkers.


[Morphological characteristics of the changes in the prosencephalon of guinea pigs exposed to general vibrations].
After 7 or 30 days of exposure to general vibration (frequency: 40 Hz, amplitude: 1 mm) for 3 hours per day, the prosencephalon of guinea pigs exhibited a wide range of morphological changes, including congestion, haemorrhages, the presence of the heterochromic neurons and perivascular spaces as well as diffuse spongiosis. In contrast, after 14 days' exposure to general vibration of the same parameters, diffuse spongiosis of the prosencephalon was found in all the animals under examination. Hypothalamus, cerebral cortex and periventricular gray matter were unaffected by spongiosis in most of the animals. The nerve fibre sheats were unchanged in all cases.


H1- and H2-receptors for histamine in the ileum of the guinea pig.
Clark's equation used in its inverted form (double reciprocal plots) was shown to be valid regarding the interaction of histamine with its receptors in the guinea-pig ileum. Burimamide, a typical H2-receptor antagonist potentiated the stimulating effect of small concentrations of histamine (10(-6) M) on the intestinal smooth muscle, probably, by blocking H2-receptors which may show the opposite effect. The calculated parameters of affinity (pKn) remained constant under different conditions. A linear correlation between length of the preparation and maximal contractions has been found.


Splanchnic and extrasplanchnic arterial hemodynamics in patients with cirrhosis.
This study was designed to assess the contribution of splanchnic and extrasplanchnic vascular hemodynamics to the hyperdynamic circulation in patients with cirrhosis. Cardiac index and flow volume index and pulsatility index (PI) of superior mesenteric artery (SMA) and femoral artery (FA) were measured with Doppler ultrasonography in 40 controls and 86 patients with cirrhosis (Child-Pugh grade A=41, grade B=30, and grade C=15). Mean arterial pressure was also recorded to calculate systemic vascular resistance index. Systemic vascular resistance index was significantly lower in each Child-Pugh group than in controls. SMA blood flow index was significantly higher in each Child-Pugh group than in controls and the increase in SMA blood flow index paralleled the degree of liver dysfunction. SMA-PI was significantly lower in each Child-Pugh group than in controls and the decrease in SMA-PI paralleled the degree of liver dysfunction. FA blood flow index was slightly higher in Child-Pugh grade A patients and significantly higher in grade B patients than in controls, whereas grade C patients had normal FA blood flow index. FA-PI was significantly lower in grade A and grade B patients than in controls, whereas grade C patients had normal FA-PI. When all patients were examined together, SMA-PI significantly correlated with systemic vascular resistance index (r=0.69, p<0.01). In contrast, FA-PI did not significantly correlate with systemic vascular resistance index (r=0.15, p=0.18). Splanchnic arterial vasodilatation plays an important role in the pathogenesis of decreased systemic vascular resistance seen in patients with cirrhosis.


Influence of clomiphene citrate in vivo on subsequent steroid formation and gonadotropic responsiveness in vitro of isolated human follicular cells.
Granulosa and thecal cells from human preovulatory follicles, extirpated from the ovaries of women undergoing sterilization by minilaparotomy, were incubated for 2 hours in the presence or in the absence of human gonadotropin (hCG). The follicles were obtained from 16 women, 8 of whom had previously been treated with clomiphene citrate (CC) to induce follicular maturation. The tissue contents of cyclic AMP (cAMP) and the content of progesterone (P), testosterone (T) and estradiol-17 beta (E2) in the incubation medium were measured. Granulosa and thecal cells from control and CC-induced follicles all responded to hCG in vitro with increased formation of cAMP. Both granulosa and thecal cells from CC-induced follicles produced larger amounts of P in vitro than cells from spontaneously matured follicles. There were no other differences in the patterns of steroid formation or reactivity to hCG between the cells from the two types of follicle. It is concluded that CC treatment in vivo induces the growth and maturation of preovulatory follicles with apparently normal biochemical characteristics, as far as the content of and capacity to form cyclic AMP, progesterone, testosterone and estradiol-17 beta are concerned.


Standoff detection of bacterial spores by field deployable coherent Raman spectroscopy.
Vibrational spectroscopies offer great potential for standoff detection of chemical and biological warfare agents, avoiding contamination to the operator and equipment. Among them, particularly promising is Coherent anti-Stokes Raman scattering (CARS) spectroscopy, using synchronized pump/Stokes laser pulses to set up a vibrational coherence of target molecules at a laser focus, which is read by further interaction with a probe pulse, resulting in the emission of a coherent beam detectable at a distance. CARS has previously demonstrated the capability to detect bacterial spores based on the Raman spectrum of the characteristic molecule calcium dipicolinate (CaDPA); however, a complex and bulky laser technology, which is only suitable for a laboratory environment, was employed. Here we develop a broadband CARS setup based on a compact, industrial grade ytterbium laser system. We demonstrate high signal-to-noise ratio detection of Bacillus atrophaeus spores at a concentration of 105 cfu/mm2, at a standoff distance of 1 m, and an acquisition time of 1 s. Our system, which combines chemical specificity and sensitivity along with improved ruggedness and portability, paves the way to a new generation of instruments for real-world standoff detection of chemical and biological threats.


Ramadan during pregnancy and neonatal health-Fasting, dietary composition and sleep patterns.
Large shares of pregnant Muslims worldwide observe the Ramadan fast. Previous research showed that Ramadan during pregnancy is associated with adverse offspring health outcomes lasting throughout the life-course. Evidence on effects on birth outcomes is inconclusive, however, and previous research did not consider the role of dietary composition and sleep patterns during Ramadan. This study systematically documents maternal lifestyle during Ramadan and assesses if diet and sleep adaptations to Ramadan, independent of and in addition to maternal fasting, are associated with neonatal health outcomes. This study reports a survey of 326 Muslims who delivered their baby in Mainz, Germany, linked to maternal & infant hospital records. Participants reported on fasting, dietary composition and sleep schedules while pregnant during Ramadan. Fasting during pregnancy was associated with reduced birthweight, in particular for fasting during the first trimester (-352ˑ92g, 95% CI: -537ˑ38; -168ˑ46). Neither dietary composition nor altered sleep were directly associated with birthweight. However, dietary composition during Ramadan outside of fasting hours seems to moderate the fasting-birthweight association, which disappeared for women switching to high-fat diets. The finding that dietary intake during Ramadan potentially moderates the fasting-birthweight association is of high relevance to pregnant Muslims who wish to fast and their healthcare professionals, since dietary choices outside of fasting hours are often relatively easily modifiable. This is the first study to include information on maternal diet and sleep during Ramadan, and additional research is needed to assess the roles of specific (macro)nutrients and food groups.


Source contribution analysis of nutrient pollution in a P-rich watershed: Implications for integrated water quality management.
It is still a great challenge to address nutrient pollution issues caused by various point sources and non-point sources on the watershed scale. Source contribution analysis based on watershed modeling can help watershed managers identify major pollution sources, propose effective management plans and make smart decisions. This study demonstrated a technical procedure for addressing watershed-scale water pollution problems in an agriculture-dominated watershed, using the Dengsha River Watershed (DRW) in Dalian, China as an example. The SWAT model was improved by considering the constraints of soil nutrient concentration, i.e., nitrogen (N) and phosphorus (P), when modeling the nutrient uptake by a typical crop, corn. Then the modified SWAT model was used to quantify the contributions of all known pollution sources to the N and P pollution in the DRW. The results showed that crop production and trans-administrative wastewater discharge were the two dominant sources of nutrient pollution. This study further examined the responses of nutrient loss and crop yield to different fertilizer application schemes. The results showed that N fertilizer was the limiting factor for crop yield and that excessive levels of P were stored in the agricultural soils of the DRW. An N fertilizer application rate of approximately 40% of the current rate was suggested to balance water quality and environmental protection with crop production. The long-term impact of legacy P was investigated with a 100-year future simulation that showed the crop growth could maintain for 12 years even after P fertilization ceased. Our study highlights the need to consider source attribution, fertilizer application and legacy P impacts in agriculture-dominated watersheds. The analysis framework used in this study can provide a scientifically sound procedure for formulating adaptive and sustainable nutrient management strategies in other study areas.


In Vitro Comparison of Internal and Marginal Adaptation between Printed and Milled Onlays.
Nowadays, milling is still the gold standard for fabricating indirect restorations, but to overcome its disadvantages, there are alternatives, such as 3D printing. This study aimed to compare the gaps between the prepared tooth and milled and printed onlays fabricated with the same CAD design. It also aimed to determine the gap reproducibility across onlays fabricated by 3D printing and milling. A resin tooth was prepared for an onlay. After scanning the preparation, an onlay was designed with proprietary dental software. Next, 22 onlays were milled in a graphene-reinforced PMMA disc (Group 1), and 22 onlays were 3D-printed with a hybrid composite material (Group 2). After that, all fabricated restorations were scanned and superimposed on the scanned prepared resin tooth. Subsequently, a specific software was used to measure the margin, central, and intaglio-located gap between the milled or printed restoration and the preparation. Finally, measurements were compared with a multifactor analysis of variance. The results demonstrated that printed onlays (Group 2) adapted better to the prepared tooth than the milled ones (Group 1) (p < 0.05). The comparison of standard deviations showed the better gap reproducibility of printed onlays (p < 0.05). This study concluded that the printed onlays adapted significantly better to the prepared tooth than the milled onlays. Printed onlays also showed significantly better gap reproducibility.


Discovery of nonpeptide 3,4-dihydroquinazoline-4-carboxamides as potent and selective sst2 agonists.
Nonpeptide sst2 agonists can provide a new treatment option for patients with acromegaly, carcinoid tumors, and neuroendocrine tumors. Our medicinal chemistry efforts have led to the discovery of novel 3,4-dihydroquinazoline-4-carboxamides as sst2 agonists. This class of molecules exhibits excellent human sst2 potency and selectivity against sst1, sst3, sst4 and sst5 receptors. Leading compound 3-(3-chloro-5-methylphenyl)-6-(3-fluoro-2-hydroxyphenyl)-N,7-dimethyl-N-{[(2S)-pyrrolidin-2-yl]methyl}-3,4-dihydroquinazoline-4-carboxamide (28) showed no inhibition of major CYP450 enzymes (2C9, 2C19, 2D6 and 3A4) and weak inhibition of the hERG channel.


Taking the Temperature of Distance Learners: Does University Climate Influence Perceptions of Belonging in a Distance Education Environment?
This study aimed to gain an understanding of how students' perceptions of belonging are impacted by their observations of the cultural/racial climate and diversity and inclusion in a distance education environment. Studies have evaluated students' perceptions of belonging and racial climate in a physical environment; there is a gap in understanding those perceptions within a distance education environment. In 2019, an online survey was administered to distance learning students from four academic programs at a national university that provides education services in all 50 states. Results of a multiple linear regression analysis showed that students' perceptions of university inclusion and diversity efforts, experiences related to language barriers, and advisors played a significant role in students' perceptions of belonging, F(4, 205) = 52.96, p < .000, with an R2 of .51. Supporting an equitable distance learning environment should be a paramount objective for universities.


Sustainable decontamination of heavy metal in wastewater and soil with novel rectangular wave asymmetrical alternative current electrochemistry.
A new concept of removal and recovery of heavy metals and simultaneous regeneration and reuse of ethylenediamine-tetraacetic acid (EDTA) in soil washing effluent containing metal-EDTA complexes is proposed, which is used to remediate heavy metal contaminated soil. To achieve this goal, soil washing approach coupled with rectangular wave asymmetrical alternative current electrochemistry (RW-ACE) equipped with amidoxime-functionalized electrodes (Ami-CF) is employed. With high hydrophilicity and strong binding affinity, Ami-CF could specifically compete for heavy metals over EDTA under electric field. RW-ACE system is found successfully to achieve the non-destructive decomplexation of heavy metal-EDTA, and then regenerate EDTA for highly recycling, which saves as high as 98.9 % EDTA consumption compared with conventional washing method. Moreover, more than 90% of heavy metals are recovered and deposited on the electrode with a majority of them existed as zero-valence state as evidenced by XPS. The RW-ACE method is universal for various heavy metals such as Cu2+, Zn2+, Cd2+, and Pb2+ in an authentic contaminated soil, and the loss of soil nutrient is very limited. Along with long-term assessment and operation cost estimation, the RW-ACE method is a sustainable remediation approach for the heavy metal polluted wastewater and soils, and easily scaled up for field practice.


Recommendations for Using PowerPoint 2016/2020 to Create Individualized Matching to Sample Sessions on the iPad.
A recent tutorial by Cummings and Saunders (Behavior Analysis in Practice, 12, 483-490, 2019) described methods to arrange match-to-sample tasks using PowerPoint on laptops with touch screens. Similar paradigms may be used on tablet-based systems such as the iPad. Because iPads may be commonly used by behavior-analytic practitioners, modifications to the procedures described by Cummings and Saunders (2019) may facilitate the successful use of these systems in treatment programs. Here we describe additional procedures and settings that may increase practitioners' success when using match-to-sample instructional arrangements on the iPad.


Injuries after Forklift Trucks Accidents - Injury Patterns, Therapy and Outcome in the Context of the Statutory Accident Insurance.
The use of forklift trucks during work has a high accident potential. The aim of this study is to describe injury patterns, treatment and outcome after forklift truck accidents in the context of the employers' liability insurance association. Retrospective data collection of all cases between 2004 and 2019. Excluded were patients < 18 years, without follow-up or with definitive external treatment. Trauma mechanism, injury patterns and distribution, treatment, complications, time of incapacity for work, return to work and impairment of earning capacity were recorded. Of 109 patients with 110 injuries, 52.7% showed isolated injuries and 47.3% combined injuries, which affected the lower extremity in 95 cases. There were fractures in 85.5%, including 32.7% in open form. The mean length of stay was 29.1 days (range 1 - 129); an indication for surgery was seen in 80.9%. Surgical treatment required an average of 3 interventions, with significantly more operations for soft tissue closure than for the fractures (p ≤ 0.023). Amputations were necessary in 8 cases; complications occurred in 29.1%. Return to work was possible in 90%, after a mean period of incapacity for work of 33.6 weeks. A total of 40% showed a pensionable impairment of earning capacity. Accidents with forklift trucks result in complex lower extremities injuries with the need of multi-stage treatment and show relatively high complication rates. A return to work is often possible after a long period of convalescence, and a pensionable impairment of earning capacity often persists.


Electro-optics of confined systems.
Confinement in microenvironments occurs in many natural systems and technological applications. However, little is known about the behaviour of the immersed nanoparticles. In this work we show that their diffusion, electro-orientation and electric field induced polarization can be determined through electric birefringence experiments. We analyze aqueous dispersions of silver nanowires and clay particles confined inside microdroplets. We have observed that confinement reduces the amount of particles that can be oriented by the external electric field. However, the polarizability of the oriented particles is not affected by the presence of the oil/water boundary, and it is the same as in unbounded media, which agrees with the fact that the electric polarization and related phenomena are short-ranged.


CuO/Cu-MOF nanocomposite for highly sensitive detection of nitric oxide released from living cells using an electrochemical microfluidic device.
The integration of large surface area and high catalytic profiles of Cu-MOF and CuO nanoparticles is described toward electrochemical sensing of nitric oxide (NO) in a microfluidic platform. The CuO/Cu-MOF nanocomposite was prepared through hydrothermal method, and its formation was confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). The CuO/Cu-MOF nanostructured modified Au electrodes enabled electrocatalytic NO oxidation at 0.6 V vs. reference electrode, demonstrating linear response over a broad concentration range of 0.03-1 μM and 1-500 μM with a detection limit of 7.8 nM. The interference effect of organic molecules and common ions was negligible, and the sensing system demonstrated excellent stability. Finally, an electrochemical microfluidic NO sensor was developed to detect of NO released from cancer cells, which were stimulated by L-arginine. Furthermore, in the presence of Fe3+, the stressed cells produced more NO. This work offers considerable potential for its practical applications in clinical diagnostics through determination of chemical symptoms in microliter-volume biological samples. Electrochemical microfluidic NO sensor was developed for detection of NO released from cancer cells. This miniaturized device consumes less materials and provides the basis for greener analytical chemistry.


Effect of free gingival graft before implant placement on peri-implant health and soft tissue changes: a randomized controlled trial.
To evaluate the clinical outcome and changes in posterior buccal soft tissue following implant restoration in groups with and without a free gingival graft (FGG) before implant placement. Twenty-six individuals who required implant restoration and displayed lack of keratinized mucosa (KM) were recruited and assigned to the FGG group (with FGG before implant placement) or Control group (without FGG before implant placement) randomly. A screw-retained conventional implant restoration was performed for each patient. Peri-implant soft tissue was captured by an intraoral scanner and analyzed by an image processing software. Clinical parameters (plaque index, gingival index, probing depth, and bleeding on probing) were assessed at baseline and 1, 3, 6, and 12 months. Buccal soft tissue changes (mucosal margin, soft tissue thickness, and width of keratinized mucosa) on the buccal side of implant site were assessed at 1, 3, 6, and 12 months. Two-way ANOVA and Bonferroni test were used to analyze significant difference between groups at each time point (α = 0.05). The clinical parameters were lower in the FGG group than that in the Control group, although there were no significant differences between the two groups (P > 0.05). Peri-implant soft tissue collapsed and the changes (mucosal margin and soft tissue thickness) were significantly greater in the Control group than the FGG group (P < 0.05). Width of KM was larger in the FGG group than the Control group, although there was no significant difference between the two groups (P > 0.05). Minimal peri-implant soft tissue changes occurred in two groups. Performing FGG before implant placement is a viable procedure to maintain peri-implant soft tissue but might not affect peri-implant health during 12 months follow-up. However, small sample size must be considered. Trial registration This study was retrospectively registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000037954; Date of registration: 6 September 2020).


An algebraic characterization of self-generating chemical reaction networks using semigroup models.
The ability of a chemical reaction network to generate itself by catalyzed reactions from constantly present environmental food sources is considered a fundamental property in origin-of-life research. Based on Kaufmann's autocatalytic sets, Hordijk and Steel have constructed the versatile formalism of catalytic reaction systems (CRS) to model and to analyze such self-generating networks, which they named reflexively autocatalytic and food-generated. Recently, it was established that the subsequent and simultaenous catalytic functions of the chemicals of a CRS give rise to an algebraic structure, termed a semigroup model. The semigroup model allows to naturally consider the function of any subset of chemicals on the whole CRS. This gives rise to a generative dynamics by iteratively applying the function of a subset to the externally supplied food set. The fixed point of this dynamics yields the maximal self-generating set of chemicals. Moreover, the set of all functionally closed self-generating sets of chemicals is discussed and a structure theorem for this set is proven. It is also shown that a CRS which contains self-generating sets of chemicals cannot have a nilpotent semigroup model and thus a useful link to the combinatorial theory of finite semigroups is established. The main technical tool introduced and utilized in this work is the representation of the semigroup elements as decorated rooted trees, allowing to translate the generation of chemicals from a given set of resources into the semigroup language.


[Vascular complications following renal transplantation: diagnostic evaluation].
Vascular complications after renal transplantation are the most frequent type of complication following urological complications. They may affect the function of the transplant. Early vascular complications include renal artery or vein thrombosis, lesions to the iliac vessels and cortical necrosis. Delayed complications mainly include renal artery stenosis, arteriovenous fistula, and rarely false aneurysm. Doppler sonography, sometimes with the use of intravenous contrast, is the imaging modality of choice in the acute setting or routine follow-up. MRI may be performed for additional morphological and functional evaluation while CT may provide additional evaluation of the arterial supply. Angiography is performed prior to endovascular treatment.


Psychometric validation of the neuropathic pain symptom inventory for its use in Spanish.
Clinical instruments are required for the assessment of neuropathic pain (NP). The primary aim of this study was to perform a complete psychometric validation of the Neuropathic Pain Symptom Inventory (NPSI) in Spanish patients. A linguistically validated version in Spanish of the NPSI and other clinical instruments for NP were administered on two occasions separated by at least one month to 548 patients suffering from chronic NP. The authors evaluated the responsiveness, the construct validity, and the internal structure of the NPSI by means of, respectively, receiver operating characteristic (ROC) curves analysis and calculation of reliable change indices, a multitrait-multimethod (MTMM) design, and primary component analysis. Internal consistency and test-retest reliability were evaluated, respectively, by calculating several Cronbach's alpha coefficients and intraclass correlation coefficients of some scores selected appropriately. The areas under the ROC curves were greater than 0.85. The MTMM design found convergent-discriminant correlations correctly aligned for all NPSI subscores in the first assessment, and for all but paresthesia/dysesthesia subscores in the second assessment. The five components of the NPSI described by its authors were confirmed on one occasion, but the "electric shocks" and "stabbing" items did not associate consistently, as in the original version, the first time the NPSI was administered. All reliability coefficients were above 0.70. The Spanish NPSI has good concurrent and construct validity and is reliable for a wide range of patients with NP. One exception to the original structure was found affecting one item, presumably relating to a cultural feature.


Polydisperse low-density lipoproteins in hyperalphalipoproteinemic chronic alcohol drinkers in association with marked reduction of cholesteryl ester transfer protein activity.
Long-term heavy alcohol intake is well known to increase serum high-density lipoprotein (HDL) cholesterol concentrations. Epidemiologic studies have shown that the protective effect of alcohol intake against coronary heart disease (CHD) is observed in moderate alcohol drinkers, but not in heavy ones. To clarify whether heavy alcohol intake may cause abnormalities in lipoprotein metabolism, we analyzed the plasma lipoproteins in eight male chronic heavy alcohol drinkers with marked hyperalphalipoproteinemia. Although their serum HDL cholesterol levels were remarkably high, ranging from 2.67 to 3.58 mmol/L, three patients had CHD and corneal arcus was present in seven patients. Cholesteryl ester transfer protein (CETP) activity was reduced in all subjects (7.3% +/- 4.2%/10 microL/18 h in alcohol drinkers v 20.5% +/- 2.4%/10 microL/18 h in control; mean +/- SD, P < .001). The CETP mass levels were also markedly reduced in these subjects. The analysis of low-density lipoprotein (LDL) on nondenaturing polyacrylamide gradient gel electrophoresis revealed that four subjects with severely low CETP activity (< 25% of control) had polydisperse LDLs, similar to those observed in genetic CETP deficiency. The other four subjects with approximately half the normal CETP activity had homogeneous but smaller-sized LDLs, as compared with control subjects. Particle size of HDL was larger than that of normal control HDL in all subjects. After cessation of alcohol intake, plasma HDL cholesterol levels were decreased and LDLs became more homogeneous and normal in size, in parallel with elevation of CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Targeting SLP76:ITK interaction separates GVHD from GVL in allo-HSCT.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematological malignancies, due to graft-versus-leukemia (GVL) activity mediated by alloreactive donor T cells. However, graft-versus-host disease (GVHD) is also mediated by these cells. Here, we assessed the effect of attenuating TCR-mediated SLP76:ITK interaction in GVL vs. GVHD effects after allo-HSCT. CD8+ and CD4+ donor T cells from mice expressing a Y145F mutation in SLP-76 did not cause GVHD but preserved GVL effects against B-ALL cells. SLP76Y145FKI CD8+ and CD4+ donor T cells also showed less inflammatory cytokine production and migration to GVHD target organs. We developed a novel peptide to specifically inhibit SLP76:ITK interactions, resulting in decreased phosphorylation of PLCγ1 and ERK, decreased cytokine production in human T cells, and separation of GVHD from GVL effects. Altogether, our data suggest that inhibiting SLP76:ITK interaction could be a therapeutic strategy to separate GVHD from GVL effects after allo-HSCT treatment.


An association study of 43 SNPs in 16 candidate genes with atorvastatin response.
Variation in individual response to statin therapy has been widely studied for a potential genetic component. Multiple genes have been identified as potential modulators of statin response, but few study findings have replicated. To further examine these associations, 2735 individuals on statin therapy, half on atorvastatin and the other half divided among fluvastatin, lovastatin, pravastatin and simvastatin were genotyped for 43 SNPs in 16 genes that have been implicated in statin response. Associations with low-density lipoprotein cholesterol (LDL-C) lowering, total cholesterol lowering, HDL-C elevation and triglyceride lowering were examined. The only significant associations with LDL-C lowering were found with apoE2 in which carriers of the rare allele who took atorvastatin lowered their LDL-C by 3.5% more than those homozygous for the common allele and with rs2032582 (S893A in ABCB1) in which the two groups of homozygotes differed by 3% in LDL-C lowering. These genetic effects were smaller than those observed with the demographic variables of age and gender. The magnitude of all the differences found is sufficiently small that genetic data from these genes should not influence clinical decisions on statin administration.


Steroid 21-hydroxylase activity in equine ovarian follicles evidenced by isotope dilution-mass spectrometry.
Steroid 21-hydroxylase activity of the microsome-enriched fraction of follicular linings from equine ovaries has been demonstrated by gas chromatography-mass spectrometry. The 21-hydroxylated metabolites were quantified by isotope dilution with deuterated analogues. The two most abundant potential substrates for follicular steroid 21-hydroxylase, progesterone (P) and 17-hydroxyprogesterone (17OHP), were converted respectively to 11-deoxycorticosterone (DOC) and 11-deoxycortisol with corresponding apparent specific activities of 308 and 24 pmol/mg protein/h and apparent Km values of 1.1 and 6.4 microM. Competitive inhibition of the P-to-DOC conversion was exerted by 17OHP and pregnenolone. Hence, the ovarian follicle of the mare is an extraadrenal site of preferential DOC biosynthesis by an enzyme having steroid 21-hydroxylase activity.


Ruptured versus stable plaques in human coronary arteries.
To derive a model for the identification of left anterior descending (LAD) coronary artery stenoses predisposed to plaque rupture and thrombosis. Coronary angiograms of 186 consecutive patients (original sample) with an anterior ST elevation myocardial infarction (STEMI) and a recanalized LAD were reconstructed in the three-dimensional space. Culprit lesions were compared with 293 stable LAD coronary stenoses on the same patients. A model for predicting stenoses with a high probability of thrombosis was derived and validated in 50 subsequent patients with STEMI, and 50 patients with stable lesions (validation sample). The majority of culprit lesions occurred between 20 and 40 mm from the LAD ostium, whereas the majority of stable lesions were found in a distance of more than 60 mm (P<0.001). Culprit lesions were statistically significantly longer than stable ones (23.2 ± 10.4 mm vs. 14.7 ± 7.2 mm; P<0.001). Bifurcations on culprit lesions were significantly more frequent (86.6%) compared with stable lesions (41.3%, P<0.001). Lesion angulation was significantly sharper in culprit lesions, which were symmetrical whereas stable lesions resided in the inner vessel wall in respect to the local vessel curvature. A simple additive tool was developed by using these parameters in a multiple regression model. The discriminating ability of the proposed index was high in both the original [area under the receiver operating characteristic curve: 0.88 (95% confidence interval: 0.85-0.91)] and validation sample [area under the receiver operating characteristic curve: 0.69 (95% confidence interval: 0.59-0.78)]. Specific anatomic characteristics of LAD segments associated with STEMI can be identified on coronary angiograms and assist the risk stratification of coronary stenoses.


COVID-19-related mortality in cancer patients in an Irish setting.
The COVID-19 pandemic has impacted significantly on healthcare across the globe. It has been reported to have higher incidence and be associated with worse outcomes in patients with cancer. To examine the characteristics of patients with cancer who were diagnosed with COVID-19 and to identify factors which may predict a poorer outcome. Patients attending oncology services in Beaumont Hospital who were diagnosed with COVID-19 between March and May 2020 were included. Demographics and outcomes were determined by chart review. Twenty-seven patients were included in the study. The median age was 62; 59% were male. Ten patients (37%) died all of whom had metastatic or incurable locally advanced disease. Patients with lung cancer had a higher rate of COVID-19 and poorer outcomes. Those with a performance status (PS) ≥ 3 were more likely to die than those with PS ≤ 2. Compared to those who recovered, patients who died had a higher number of organs affected by cancer and a higher mean Palliative Prognostic Score. Patients attending oncology services during the initial phase of the COVID-19 pandemic had an increased rate of SARS-CoV-2 infection and a higher mortality rate than the general population. Those who died had more advanced cancer as demonstrated by poorer performance status, a greater burden of metastatic disease and a higher Palliative Prognostic Score.


Metastatic colorectal cancer: Advances in the folate-fluoropyrimidine chemotherapy backbone.
Notwithstanding recent treatment advances in metastatic colorectal cancer (mCRC), chemotherapy with a combination of a fluoropyrimidine and a folate agent, often 5-fluorouracil (5-FU) and leucovorin, remains the backbone of treatment regimens for the majority of patients with mCRC. This is despite a recent focus on molecular-targeted treatments and patient stratification according to mutational status or expression levels of specific genes. Intracellular folate concentration was discovered to be pivotal in the cytotoxic efficacy of 5-FU, paving the way to the current standard combination therapy approach. Subsequent discovery that systemic chemotherapy agents, such as irinotecan and oxaliplatin, can further increase the efficacy of 5-FU-based treatments led to the development of several combination chemotherapy regimens, including FOLFOX, FOLFIRI and FOLFOXIRI. Subsequent efforts to optimise 5-FU-based treatments have focused on 5-FU analogues, initially capecitabine and the combination drug tegafur/gimeracil/oteracil (S-1) and then TAS-102, which has recently been evaluated in phase 3 clinical trials for refractory colorectal cancer. Further approaches taken to improve the efficacy of 5-FU chemotherapy regimens have focused on optimising the route and dosing schedules and regulating folate metabolism. Pharmacokinetic variability caused by the requirement for metabolic conversion of leucovorin has been central to recent research, and the development of agents such as arfolitixorin which bypass the need for metabolic conversion remains promising for future therapeutic candidates. In this review, we summarise the evidence leading to the current treatment regimens employing 5-FU and leucovorin, focusing on recent approaches taken to optimise and refine treatments to improve clinical outcomes in patients with mCRC.


Spontaneous rupture of the iliac vein.
A spontaneous rupture of the left iliac vein is described. A 2 cm tear on the anterior surface of the left iliac vein was discovered at emergency laparotomy on a patient who was suspected of having a huge intraabdominal hemorrhage. Prodromal symptoms, cause, and treatment are discussed. The nine previously reported cases are reviewed. This case represents the seventh successful repair of an idiopathic rupture of an iliac vein.


Actovegin®: a biological drug for more than 5 decades.
Actovegin(®) is a biological drug manufactured from a natural source: it is a calf blood hemodialysate. Its therapeutic benefits stem from a variety of pharmacodynamic actions that can be summarized to a common goal, i.e. the enhancement of cellular metabolism; this results from an insulin-like activity mediated by Inositol-phospho-oligosaccharides. Actovegin(®) results in beneficial effects in several pathophysiological clinical settings including malfunction of the blood circulation and trophic disturbances in the brain, impairment of peripheral blood circulation and associated diseases, dermal transplants and acute and chronic wounds. Here, we give an overview of the pharmacodynamic actions of calf-blood hemidialysate and its beneficial effects in a variety of clinical settings.


Timing Strategy of Preoperative Aspirin and Its Impact on Early Outcomes in Patients Undergoing Coronary Artery Bypass Grafting: A Propensity Score Matching Analysis.
Data are lacking regarding optimal discontinuation time of preoperative aspirin before coronary artery bypass grafting (CABG). We aimed at assessing the impact of aspirin discontinuation according to time intervals before CABG and its influence on early postoperative outcomes. In this retrospective study, we enrolled 652 patients who underwent primary isolated nonemergent CABG between October 2014 and December 2017. Patients were assigned into groups according to the time interval between the last aspirin dose administration and the time of surgery. The first group comprised patients who were given aspirin ≤24-h before CABG (n = 304), whereas the second group consisted of patients who took aspirin between 24 and 48 h before CABG (n = 348). Efficacy endpoints included 30-d mortality rate, incidence of major adverse cardiac and cerebral events (MACCE) and composite rates of 30-d mortality/MACCE. Propensity score matching was used for final comparison. Overall, multivariate analysis showed that aspirin administration ≤24 h before CABG was associated with reduced 30-d mortality rate and MACCE by 75% and 57%, respectively. Before as well as after propensity score matching, multivariate analysis showed that aspirin administration ≤24-h before CABG was associated with reduced composite rates of 30-d mortality rate and MACCE by 55% and 59%, respectively. Subgroup analysis stratified by the type of surgery showed that aspirin administration ≤24-h significantly reduced composite rates of 30-d mortality/MACCE in patients after off-pump CABG. Preoperative administration of aspirin ≤24-h before CABG is associated with the reduction of postoperative mortality as well as MACCE. The evidence also suggests that aspirin administration ≤24-h is strongly associated with reduced composite rates of 30-d mortality/MACCE in patients submitted to off-pump CABG.


Treatment of posttransplant lymphoproliferative disorder with poor prognostic features in children and young adults: Short-course EPOCH regimens are safe and effective.
No guidelines exist for which intensive chemotherapy regimen is best in pediatric or young adult patients with high-risk posttransplant lymphoproliferative disorder (PTLD). We retrospectively reviewed patients with PTLD who received interval-compressed short-course etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (SC-EPOCH) regimens at our institution. Eight patients were included with median age of 12 years. All patients achieved a complete response with a manageable toxicity profile. Two patients developed second, clonally unrelated, EBV-positive PTLD and one patient had recurrence at 6 months off therapy. No graft rejection occurred during therapy. All eight patients are alive with median follow-up of 29 months.


Particulate matter exposure during pregnancy and infancy and risks of autism spectrum disorder in children: A systematic review and meta-analysis.
This meta-analysis aimed to clarify the relationship between particulate matter (PM) and autism spectrum disorder (ASD) in detail. A systematic literature search was performed using eight databases before April 9, 2022. The estimated effects were combined separately according to the PM type. Subgroup analyses were conducted in terms of the study design type, study location, exposure window, birth year, and sex. PM2.5 was associated with an increased risk of ASD, while PM10 was not. PMc, PM1, and diesel particulate matter (DPM) were also associated with an increased risk of ASD. Specifically, a 10 μg/m3 increase in PM2.5 was associated with a 1.337-fold increased risk of ASD in children, and a 10 μg/m3 increase in PMc and PM1 may increase the risk of ASD by 1.062 and 3.643 times, respectively. PM2.5 exposure may increase the risk of ASD in boys. Exposure to PMc might increase the risk of ASD in children born after the year 2000. The combined results of different PM differed between studies with continuous and non-continuous data for different study design type, study location, and birth year. The sensitive window for PM2.5 exposure to increase the risk of ASD may be from the first, second, and third trimesters to the first year of the postnatal period. Exposure to PMc during pregnancy was significantly associated with ASD. Exposure to PM2.5 may increase the risk of ASD in boys. Exposure to PM2.5 during the first, second, and third trimesters and postnatally increased the risk of ASD.


Second primary malignancies of the head and neck in children.
Second malignant neoplasms are not uncommon in children, especially following multimodality therapy. The incidence of second cancers may approach 12% at 20 years following the initial cancer. Diligent surveillance is mandatory over a patient's lifetime to minimize morbidity and mortality from second malignant neoplasms.


Analysis of hemorrhagic risk factors during deep brain stimulation surgery for movement disorders: comparison of the circumferential paired and multiple electrode insertion methods.
The most serious complication of deep brain stimulation (DBS) surgery is intracranial hemorrhage. The authors have assessed risk factors for hemorrhage in DBS surgery and compared two types of microelectrode insertion technique on hemorrhagic risk. A total of 171 DBS procedures were performed on 110 patients (58 females, 52 males) by the same neurosurgeon at a single center between May 2005 and May 2010. We used two microelectrode insertion methods: multiple microelectrode insertion (MMI) and circumferential paired microelectrode insertion (CPMI). We analyzed the correlation between bleeding rates and gender, age, hypertension, target location, simultaneous bilateral procedure and electrode insertion method. Of the 171 DBS procedures, 138 were on 85 patients with Parkinson's disease, 16 were in 15 patients with essential tremor and 17 were on ten patients with dystonia. There were nine postoperative hemorrhagic events (5.26%), of which three were symptomatic (1.75%), and one permanent neurological deficit event (0.58%). Compared with the bleeding rate in the MMI method (9/106, 8.5%), there was no instance of bleeding with the CPMI method (0/65, 0%) (p = 0.04). In other factors, the correlation with hemorrhage was not found. Use of the CPMI method significantly decreased the rate of bleeding. This new surgical technique seems to be safe and accurate and may be recommended as another surgical option.


Towards intelligent packaging: BCP-EVOH@ optode for milk freshness measurement.
Intelligent packaging represents an emerging trend in the food industry, especially for highly perishable foods like milk and dairy products. Despite the apparent simplicity, miniaturized BCP-EVOH@ sensor, made of bromocresol purple (BCP) covalently bound to ethylene-vinyl alcohol (EVOH) copolymer, meets the goal of milk freshness monitoring during chilled storage, allowing both naked-eye evaluation and chemometric-assisted spoilage modelling and measurements.


Effects of tamoxifen versus raloxifene on retinal capillary endothelial cell proliferation.
Endothelial cell proliferation in angiogenesis is active in conditions such as cancers and diabetic retinopathy. Tamoxifen (T) and raloxifene (R) have been compared in numerous studies as a prophylaxis for breast cancer, and T is used to treat breast cancer. T, unlike R, has been linked to an increase in uterine cancers, thrombo-embolic events, and cataract. The purpose of our study was to evaluate the efficacies of T and R in reducing estrogen-induced retinal capillary endothelial cell proliferation. Rhesus monkey retinal capillary endothelial cells (ATCC RF/6A) were used to assay cell proliferation when treated with 0.0, 0.1, 1.0, and 10.0 nM 17 β estradiol (E2) for 24 and 48 h. Viable cells were counted using a Neubauer hemocytometer with a trypan blue exclusion method to determine the number of viable cells. Cell counts were also performed using 1.0 nM E2 with 0.01, 0.1, 1.0, and 10.0 nM concentrations of either T or R. Cell medium, collected at 24 h, was evaluated for vascular endothelial growth factor and pigment epithelium-derived factor. Viable cells were significantly greater in cultures treated with 1.0 or 10.0 nM E2, compared to cells treated with 0.0 or 0.1 nM E2 both at 24 and 48 h. Viable cell counts were reduced significantly in cultures treated with 0.1, 1.0, or 10.0 nM T or R in addition to the 1.0 nM E2. Cell counts were not significantly different when comparing equal concentrations of T and R, that is, 1.0 nM E2+1 nM T or R. Vascular endothelial growth factor and pigment epithelium-derived factor protein/10,000 cells was reduced by 1.0 nM E2, but returned to higher levels with the introduction of T and R to growth media. T and R showed similar potency in inhibiting estrogen-induced retinal capillary endothelial cell proliferation. Considering drug safety profiles, our results, when extended to animals and humans, suggest that R is preferable to T in treating angiogenic retinal diseases. Further studies on the signaling mechanism of estrogen-induced endothelial cell proliferation may lead to new treatment strategies in the treatment of ocular angiogenic diseases.


The long-term prognosis of the primary glomerulonephritides. A morphological and clinical analysis of 1747 cases.
Long-term studies of all types of primary glomerulonephritis (GN) taking into consideration the major morphological and clinical findings revealed the following: 1) Endocapillary GN, post-streptococcal type has a very good prognosis when only glomerulitis is present. The prognosis is significantly worse if either interstitial inflammation with fibrosis or nephrotic syndrome (NS) is present at the time of the biopsy. 2) The prognosis of the various types of mesangioproliferative GN (IgA nephritis, non-IgA nephritis, and immunohistologically negative GN) is very good if there is only glomerulitis. The prognosis is worse for all three types when the renal cortical interstitium exhibits inflammation with fibrosis at the time of the biopsy, and is worst of all when both interstitial fibrosis (IF) and the signs of acute renal failure (ARF) are present. Of this group, the type in which there are negative immunohistological findings exhibits the best prognosis. No difference in prognosis is found between IgA nephritis and non-IgA nephritis. 3) Minimal changes GN with NS has a very good prognosis when the interstitium is not involved. The presence of interstitial inflammation and fibrosis worsens the prognosis significantly. 4) Focal sclerosing GN has a much poorer prognosis than minimal changes GN with NS, even when there is glomerulitis only (5- and 10-year renal survival rates (RSRs) of 90% and 67%, respectively). If interstitial inflammation and fibrosis are present, the prognosis is significantly worse (5- and 10-year RSRs of 84% and 55%, respectively). The prognosis is worst when both ARF and IF are present at the time of the biopsy (5- and 10-year RSRs of 56% and 46%, respectively). From the clinical side, the prognosis is significantly worse if, at the time of the biopsy, NS is present or the serum creatinine concentration is elevated to more than 1.3 mg%. 5) Chronic membranous GN has a better prognosis than focal sclerosing GN if glomerulitis only is present (5-year RSR, 88%; 10-year RSR, 77%). If the renal cortical interstitium is also involved (in the form of IF), the prognosis is significantly worse (5-year RSR, 65%; 10-year RSR, 38%). The prognosis in this disease, too, is worst when both ARF and IF are present at the time of the biopsy (5-year RSR, 38%; 10-year RSR, 25%). 6) Membranoproliferative GN has a worse prognosis than any of the types of GN so far mentioned (5-year RSR, 51%; 10-year RSR, 32%).(ABSTRACT TRUNCATED AT 400 WORDS)


Pathophysiology of Tumor Cell Release into the Circulation and Characterization of CTC.
The traditional model of metastatic progression postulates that the ability to form distant metastases is driven by random mutations in cells of the primary tumor.


Identification and biochemical characterization of Leishmania strains isolated in Peru, Mexico, and Spain.
Eight Leishmania promastigotes were isolated from different geographical areas: three (LP1, LP2, and LP3) from the provincial department La Libertad and the fourth (LP4) from the department of Cajamarca (northern Peru); another three (LM1, LM2, and LM3) in the province of Campeche (Mexico); and the last (LS1) from a clinical case of a dog in Madrid (Spain). The isolates were characterized by carbohydrate cell-surface residues using agglutinations with four purified lectins, by isoenzyme analysis using different isoenzymes, by analysis of kinetoplast DNA (kDNA) restriction fragment length polymorphism using four different restriction endonucleases and by the final metabolite patterns after in vitro culture. These isolates were compared with four reference strains and typified as: Leishmania (Leishmania) donovani, two strains of L. (L.) infantum, and one species of L. (Viania) peruviana. According to our results and the statistical study, the Peruvian isolates represent three different strains: one would be L. (V.) peruviana, another the strain isolated in Cajamarca (LP4) and the third would include the three strains from the department of La Libertad (LP1, LP2, and LP3), these latter three isolates being phylogenetically closer to the reference strain L. (L.) donovani. Meanwhile, the three isolates from Mexico form a group with close phylogenetic relationships to each other. The isolate from Spain belongs to the species L. (L.) infantum. Thus, a close correlation was drawn between the identity of each strain and its geographical origin.


Clinical characteristics and unlicensed applications of licensed psychotropic drugs within a regional tertiary service for patients with affective disorders.
Referral to tertiary services is recommended when patients with mood and anxiety disorders have not responded to multiple treatments in primary or secondary care. Within specialist services, some patients undergo treatment with licensed psychotropic medications outside the narrow terms of their market authorization ('unlicensed applications'). We examined the demographic and clinical characteristics of patients referred to a regional specialist service to determine the extent of and factors associated with recommendations for unlicensed ('off label') prescriptions. Retrospective examination of demographic and clinical characteristics and treatment recommendations in patients seen within a 5-year period. Patients were allocated to three broad diagnostic clusters (unipolar depressive disorders, bipolar disorder, anxiety disorders), and two groups (with or without comorbid disorders). We compared patients in whom all treatment recommendations were for licensed applications with patients in whom at least one treatment was for an unlicensed application, across a range of variables reflecting illness 'burden' (duration, inpatient treatment, electroconvulsive therapy, nonfatal self-harm, psychosis). From 177 new referrals, 148 patients (91 females, 57 males) could be placed within one of the three clusters. Many patients with bipolar disorder had not undergone treatment with lithium or formal psychological interventions in secondary care. Treatment recommendations involving unlicensed applications of medications were common (approximately 50%) in all clusters, but there were no significant differences in measures of illness burden between groups of patients, categorized according to licensed or unlicensed prescriptions. Retrospective examination of notes recorded for other purposes, within a single service, in which treatment recommendations might reflect idiosyncratic practice is a limitation of our findings. Also, examined variables could not provide a comprehensive indication of illness severity or functional impairment. Our findings confirm that 'off label' prescribing is common in psychiatric practice. Treatment decisions relating to unlicensed applications appear to be influenced by factors other than overall illness burden.