Electrically produced artificial ventilation.
The induction of inspiration by delivering a burst of short-duration stimuli to body-surface electrodes is over a century old. The authors have used the term electroventilation to describe the technique. Inspiration can be produced with stimuli applied to electrodes placed bilaterally at the base of the neck, over the phrenic nerve motor points. Transchest electrodes placed anterior to the axillae can be used to stimulate the long thoracic and phrenic nerves. Paraxiphoid electrodes can be used to stimulate the phrenic nerves as they enter the diaphragm. With any of these electrode placements, inspired volumes in excess of spontaneous tidal volumes can be achieved in man, baboon, and dog. Of major importance is the need to use short-duration (less than 10-microseconds) pulses in the train of stimuli that produces contraction of the inspiratory muscles. The duration of inspiration is determined by the duration of the train, which is typically 0.5-1 s. The use of short-duration pulses minimizes the risk of producing cardiac arrhythmias and results in very little sensation at the skin.


Antioxidant activity of extracts obtained from residues of different oilseeds.
Residues of the oil-extracting process of oilseeds contain bioactive substances such as phenolic compounds, which could be used as natural antioxidants for the protection of fats and oils against oxidative deterioration. Thus, the extraction of such constituents from residual material can be considered to contribute to the added value of these residues, which could justify their isolation. In the present work the fat-free residues of eight different oilseeds whose oils are usable for nutritional applications, and also as renewable resources, were extracted with 70% methanol, 70% acetone, water, and ethyl acetate/water, respectively. The resulting extracts were investigated regarding their content of total phenolic compounds by the Folin-Ciocalteau assay, sinapine, flavanoids, and the UV-absorption spectra. Further, the antioxidant activity of the extracts was characterized by the DPPH method, the beta-carotene-linoleic acid assay, and ESR investigations. The fat-free residues of the different oilseeds contained considerable amounts of extractable substances. The yields decreased with decreasing polarity of the solvent in the order water, 70% methanol, 70% acetone, and ethyl acetate. The ratio of total phenolic compounds to the extractable compounds ranged from 3 to 19%. There was no significant correlation between the amount of total extractable compounds and the total phenolic compounds (p < 0.001). All extracts showed remarkable antioxidant activities determined with the different methods. The effects depended strongly on the solvent used for the extraction as well as on the extracted residue. A correlation between the methods used for the characterization of the antioxidant activity and the composition of the residues could not be shown.


A novel overlap syndrome: systemic sclerosis associated with antiphospholipid syndrome--a case series.
Antiphospholipid syndrome (APS) can be either primary or secondary to autoimmune diseases, malignancies, infectious diseases, or drug-induced conditions. The aim of this study was to describe a novel overlap syndrome of APS and systemic sclerosis (SSc) in a case series. A retrospective review of medical files of hospitalized patients who were followed in two rheumatology clinics in Israel for the diagnosis of SSc and APS was sought. A MEDLINE search was performed for reports of APS/SSc overlap syndrome. Five patients with the overlap syndrome of APS and SSc were retrieved. The diagnosis of both diseases was confirmed by the American College of Rheumatology classification criteria. Four patients were women and of an older age group (42-68 years old). Three patients had primary APS, and in two patients APS was secondary to SSc. Two of the five patients died. The interval between APS and SSc was < 1-18 years. APS/SSc overlap syndrome is described for the first time as a case series. The patients may be older, with an interval of up to 18 years between diseases. The APS patients did not suffer from SLE. The overlap syndrome was characterized in certain instances with severe disease and two patients died. With relevant clinical manifestations, APS should be sought in SSc patients and treated appropriately.


Developments in internal monitoring techniques.
In an effort to increase accuracy and speed, improve detection limits and reduce uncertainties in internal dosimetry, laboratories have developed improved or new internal monitoring techniques in both in vivo measurements and bioassay analyses. Most of these techniques have not yet entered routine monitoring programmes. This paper intends to summarise these new techniques, show their potential improvements compared to the currently employed monitoring routines and discuss the main aspects of the EC-funded IDEA project, which aims at a comprehensive assessment of these techniques and the enhancements necessary to bring them to broader acceptance in the routine monitoring community.


Genetic Heterogeneity in Colorectal Cancer and its Clinical Implications.
Despite the recent advances in the development of complementary diagnostic exams and modern targeted therapies, colorectal cancer remains a major cause of morbidity and mortality worldwide. In this context, a lot of research has been conducted in the last years to find new markers of poor prognosis. The existence of a complex tumour architecture formed by multiple subclones genetically heterogeneous has been increasingly considered in recent studies as an element of particular importance. This feature seems to influence factors as relevant as the representativeness of tumour biopsies for genetic diagnosis and the efficacy of targeted therapies.There is growing evidence suggesting a relation between genetic heterogeneity and the patientsâ prognosis. The widespread use of next-generation sequencing techniques will allow a better understanding of the true degree of genetic heterogeneity in colorectal tumours, its causes and impact on the course of the disease. In this review we intend to analyse the recent findings related to the genetic heterogeneity of colorectal cancer, as well as its major clinical implications.


A computer-based instrumentation system for measurement of breath-by-breath oxygen consumption and carbon dioxide production.
Improvements are implemented (Version 4) in a Computer-Based Respiratory Measurement System (CBRMS) identified as Version 3. The programming language has been changed from Pascal to C. A Gateway 2000 desktop computer with 486 DX2/50MHz CPU and a plug-in data I/O board (KEITHLEY METRABYTE/ASYST/DAC's DAS-HRES 16-bit Analog and Digital I/O board) replaces an HP 9836 system used in Version 3. The breath-by-breath system consists of a mass spectrometer for measuring fractional concentrations of oxygen and carbon dioxide and the accommodation of a turbine or pneumotachometer for measuring inspiratory and expiratory flows. The temperature of the inspiratory and expiratory gases can be monitored if temperature corrections are necessary for the flow measurement device. These signals are presented to the PC via the data acquisition module. To compare the two Versions, ten significant respiratory parameters were investigated and compared for physiological resting states and steady states obtained during an exercise forcing. Both graphical and statistical (analysis of variance, regression, and correlation) tests were carried out on the data. The results from the two versions compared well for all ten parameters. Also, no evidence of a statistically significant difference was found between the resting and steady-state results of the present CBRMS (Version 4) and the previous CBRMS (Version 3). This evidence suggests that Version 3 (Pascal) has been successfully converted to Version 4 (C). Implementation of the CBRMS in C on a PC has several advantages.(ABSTRACT TRUNCATED AT 250 WORDS)


Abortion legalized: challenges ahead.
To see whether advocacy for abortion law and comprehensive abortion care (CAC) sites after legalization of abortion in Nepal is adequate among educated people (above school leaving certificate). 150 participants were assigned randomly who agreed to be in the survey and were given structured questionnaires to find out their perception of abortion and CAC sites. Majority know abortion is legalized and majority have positive attitude about legalization of abortion, however majority are not aware of abortion service in CAC sites and none knew the cost of abortion service. Proper and adequate advocacy of the new abortion law and CAC service is essential.


The proto-oncoprotein SYT interacts with SYT-interacting protein/co-activator activator (SIP/CoAA), a human nuclear receptor co-activator with similarity to EWS and TLS/FUS family of proteins.
The proto-oncoprotein SYT is involved in the unique translocation t(X;18) found in synovial sarcoma SYT-SSX fusions. SYT has a conserved N-terminal domain (SNH domain) that interacts with the human paralog of Drosophila Brahma (hBRM) and Brahma-related gene 1 (BRG1) chromatin remodeling proteins and a C-terminal transactivating sequence rich in glutamine, proline, glycine, and tyrosine (QPGY domain). Here we reported the isolation of the ribonucleoprotein SYT-interacting protein/co-activator activator (SIP/CoAA), which specifically binds the QPGY domain of SYT and also the SYT-SSX2 translocation fusion. SIP/CoAA is a general nuclear co-activator and an RNA splicing modulator that contains two RNA recognition motifs and multiple hexapeptide repeats. We showed that the region consisting of the hexapeptide motif (YQ domain) is similar to the hexapeptide repeat domain found in EWS and in TLS/FUS family proteins. The YQ domain also resembles the QPGY region of SYT itself and like all these other domains acts as a transcriptional activator in reporter assays. Most interestingly, the last 84 amino acids adjacent to YQ down-modulate by 25-fold the YQ transactivation of the reporter gene, and both domains are important for SIP/CoAA binding to SYT. In addition, SYT acts together with SIP/CoAA in stimulating estrogen and glucocorticoid receptor-dependent transcriptional activation. Activation is hormone-dependent and requires functional hBRM and/or BRG1. The stimulation is strongly reduced if the N-terminal region of hBRM/BRG1 (amino acids 1-211) is deleted. This region encompasses the SNF11 binding domain (amino acids 156-211), which interacts specifically with SYT in vivo and in vitro.


Single agent lenalidomide in newly diagnosed multiple myeloma: a retrospective analysis.
Recently, lenalidomide and low dose dexamethasone were found to result in superior overall survival compared to lenalidomide and high dose dexamethasone. The immune suppressive effects of dexamethasone can antagonize lenalidomide immunomodulatory activity and may explain this observation. We conducted a retrospective analysis to evaluate the single agent activity of lenalidomide in newly diagnosed myeloma. Records of patients with newly diagnosed symptomatic multiple myeloma treated with single agent lenalidomide at H. Lee Moffitt Cancer Center and Roswell Park Cancer Institute were reviewed. Data were collected on disease characteristics, demographics, and treatment outcomes. Responses were assessed as per the International Myeloma Working Group criteria. From March 2007 to July 2009, 17 patients with newly diagnosed multiple myeloma were treated with single agent lenalidomide at both institutions. The median age was 70 years (range 46-84 years). Lenalidomide was generally well tolerated and no grade 4 hematologic toxicities were noted. The overall response rate (> or =partial remission) to lenalidomide alone was 47% at a median follow-up of 7 months (range 1-26). This experience suggests that lenalidomide alone can induce an anti-myeloma effect in previously untreated patients who are considered poor candidates for concurrent dexamethasone.


Endocannabinoid-dependent disinhibition of orexinergic neurons: Electrophysiological evidence in leptin-knockout obese mice.
In the ob/ob mouse model of obesity, chronic absence of leptin causes a significant increase of orexin (OX) production by hypothalamic neurons and excessive food intake. The altered OX level is linked to a dramatic increase of the inhibitory innervation of OX producing neurons (OX neurons) and the over expression of the endocannabinoid 2-arachidonoylglycerol (2-AG) by OX neurons of ob/ob mice. Little is known about the function of the excitatory synapses of OX neurons in ob/ob mice, and their modulation by 2-AG. In the present study, we fill this gap and provide the first evidence of the overall level of activation of OX neurons in the ob/ob mice. We performed in vitro whole-cell patch-clamp recordings on OX neurons located in the perifornical area of the lateral hypothalamus in acute brain slices of wt and ob/ob mice. We identified OX neurons on the basis of their electrophysiological membrane properties, with 96% of concordance with immunohistochemisty. We found that OX neurons of ob/ob mice are innervated by less efficient and fewer excitatory synapses than wt mice. Consequently, ob/ob OX neurons show more negative resting membrane potential and lower action potential firing frequency than wt. The bath application of the cannabinoid type-1 receptor agonist WIN55,212-2, depresses both the excitatory and the inhibitory synapses in ob/ob animals, but only the excitatory synapses in wt animals. Finally, the physiologic release of 2-AG induces a prevalent depression of inhibition (disinhibition) of OX neurons in ob/ob animals but not in wt. In ob/ob mice, chronic absence of leptin induces a 2-AG mediated functional disinhibition of OX neurons. This helps explain the increase of OX production and, consequently, the excessive food intake of ob/ob mice.


Osteology of the coronoid process with clinical correlation to coronoid fractures in terrible triad injuries.
Terrible triad complex elbow fracture-dislocations are represented by elbow dislocations associated with fractures of the coronoid and radial head. Published literature has focused on classifying coronoid fractures by their radiographic morphology on plain x-ray images and computed tomography imaging. No study has specifically related native coronoid osteology to in situ fracture morphology. We identified 3 distinct bony regions of the coronoid, (medial, intermediate, and lateral ridges) with correlation to common fracture patterns associated with terrible triad injuries. Coronoid osteology in 8 fresh frozen cadaveric elbows was examined, and three distinct ridges were identified and dimensions measured. The measurements were compared with retrospective intraoperative measurements taken of coronoid fracture fragments being stabilized during terrible triad injury repair. Classification of native coronoid process anatomy into functional ridges (medial, intermediate, lateral) may improve our understanding of coronoid fracture patterns in unstable terrible triad injuries. Basic Science, Anatomic Study, Cadaver and In Vivo.


Discovery of N-(Naphtho[1,2-b]Furan-5-Yl) Benzenesulfonamides as Novel Selective Inhibitors of Triple-Negative Breast Cancer (TNBC).
Any type of breast cancer not expressing genes of the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) is referred to as triple-negative breast cancer (TNBC). Accordingly, TNBCs do not respond to hormonal therapies or medicines targeting the ER, PR, or HER2. Systemic chemotherapy is therefore the only treatment option available today and prognoses remain poor. We report the discovery and characterization of N-(naphtho[1,2-b]furan-5-yl)benzenesulfonamides as selective inhibitors of TNBCs. These inhibitors were identified by virtual screening and inhibited different TNBC cell lines with IC50 values of 2-3 μM. The compounds did not inhibit normal (i.e. MCF-7 and MCF-10A) cells in vitro, indicating their selectivity against TNBC cells. Considering the selectivity of these inhibitors for TNBC, these compounds and analogs can serve as a promising starting point for further research on effective TNBC inhibitors.


[Epithelial cyst in the central nervous system--characteristic expression of cytokeratin].
Twenty one cases of epithelial cysts in the central nervous system including six colloid cysts of the third ventricle, eight Rathke's cleft cysts in the sella, two enterogenous cysts in the posterior fossa, two epithelial cysts in the spinal canal and three neuroectodermal cysts in the cerebrum were examined immunohistochemically for expression of intermediate filamentous proteins-simple type, stratified type and skin type cytokeratins and GFAP. Colloid cysts of the third ventricle. Rathke's cleft cysts in the sella and epithelial cysts in the spinal canal expressed complexed type cytokeratins while enterogenous cysts and neuroectodermal cysts showed only simple type cytokeratins. In addition, several Rathke's cleft cysts demonstrated skin type differentiation and expressed GFAP in occasional lining cells. The characteristic composition and distribution of cytokeratins in various kinds of epithelial cysts in the central nervous system are demonstrated and discussed with regards to their origins.


Influence of 12-week jogging on body fat and serum lipids.
This study examined the influence of different levels of distance running on percent body fat and serum lipids in untrained male University students (n = 40) with a mean age of 24.1 years. Subjects were assigned randomly to four groups (n = 10) in each group): Group 1 (control), Group 2 (1.6 km joggers), Group 3 (3.2 km joggers) and Group 4 (4.8 km joggers). Subjects in the exercise groups jogged the prescribed distances three times a week for 12 weeks at about 85 percent of maximal heart rate. Percent body fat, serum cholesterol and triglyceride levels were estimated before and after the training programme. In comparison with control group, exercise groups showed statistically significant (p less than .05) decrease of body fat values (1.6 km joggers 6%; 3.2 km joggers 5.33%; 3.2 km joggers 11%; 4.8 km joggers 9.42%). However, Newman-Keul's post hoc analysis showed a significant (p less than .05) reduction in serum triglyceride only in 3.2 km joggers. This was attributed to the high pre-training level of serum triglyceride in the group. Cholesterol values showed insignificant changes. It was concluded that moderate physical activities of different intensities have lowering effects on body fat and serum lipids.


Clinical leadership training in integrated primary care networks: a qualitative evaluation.
To explore how a clinical leadership training programme contributes to successful implementation of integrated dementia care in local primary care networks. A qualitative design was used in local primary care networks in the Netherlands. Twenty-six primary care professionals, nurses (n=22), general practitioners (n=2) and occupational therapists (n=2) followed a 2-year practice-based educational programme including individual coaching and interactive group training. Embedded leadership training created opportunities for direct application of acquired leadership skills. Reports of coaching sessions and transcripts of semi-structured interviews with 20 leadership trainees, 8 network members and a focus group interview with 9 leadership trainees were thematically analysed. They identified 50 learning goals, mostly associated with personal leadership competences. These professionals perceived some improvement in their leadership behaviour and preferred a duo-network leadership arrangement. Individual coaching sessions and group training sessions were perceived as fruitful support. Coaching sessions were found to facilitate learning processes regarding personal competencies, collaboration issues and role clarification. Group meetings were appreciated for exercises on transformational leadership behaviour and exchange of experiences. Network leaders and members observed improved quality of care and mentioned continuity of leadership, perseverance of leaders and a sufficient time period to bring about change as important facilitating factors. Clinical leadership training to stimulate integrated primary care is promising as it was positively valued and contributed to improved perceived leadership competencies. Network leaders and members experienced improved quality of care when at least continuity in leadership was warranted.


Comparison between old and young men for responses to fast velocity maximal lengthening contractions of the elbow flexors.
Controversy exists concerning the susceptibility of elderly individuals to eccentric exercise-induced muscle damage. This study investigated the hypothesis that muscle damage induced by fast maximal lengthening contractions would be greater for old than young men. Ten old (64 +/- 4 years) and young (25 +/- 6 years) men performed 30 maximal voluntary lengthening contractions of the elbow flexors at an angular velocity of 210 degrees s(-1). Prior to exercise, no significant differences were evident between groups for criterion measures. A significant (P < 0.05) group x time interaction was found only for isometric strength and muscle soreness with the old group showing significantly slower recovery of strength and less development of soreness compared with the young group. These results did not support the hypothesis that old men would be more susceptible to muscle damage, but confirmed a previous study reporting that recovery of muscle strength was slower for old than young individuals.


X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children-A Case Report.
Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling.


Delay and Packet-Drop Tolerant Multistage Distributed Average Tracking in Mean Square.
This article studies the distributed average tracking (DAT) problem pertaining to a discrete-time linear time-invariant multiagent network, which is subject to, concurrently, input delays, random packet drops, and reference noise. The problem amounts to an integrated design of delay and a packet-drop-tolerant algorithm and determining the ultimate upper bound of the tracking error between agents' states and the average of the reference signals. The investigation is driven by the goal of devising a practically more attainable average tracking algorithm, thereby extending the existing work in the literature, which largely ignored the aforementioned uncertainties. For this purpose, a blend of techniques from Kalman filtering, multistage consensus filtering, and predictive control is employed, which gives rise to a simple yet comepelling DAT algorithm that is robust to the initialization error and allows the tradeoff between communication/computation cost and stationary-state tracking error. Due to the inherent coupling among different control components, convergence analysis is significantly challenging. Nevertheless, it is revealed that the allowable values of the algorithm parameters rely upon the maximal degree of an expected network, while the convergence speed depends upon the second smallest eigenvalue of the same network's topology. The effectiveness of the theoretical results is verified by a numerical example.


Testicular tumor ultrasound characteristics and association with histopathology.
This study was undertaken to develop knowledge of ultrasound characteristics of germ cell testicular neoplasms, associate these characteristics with histopathologic tumor types, and lay a foundation for study of ultrasound findings in benign versus malignant testicular lesions. The medical records and ultrasound images of 107 patients with testicular tumor were reviewed. Demographic and clinical characteristics and ultrasound findings of patients with seminoma were compared to those of patients with non-seminoma. 55 patients had seminoma (1 bilateral) and 52 non-seminoma. Ultrasound images of seminoma were more often hypoechoic, homogeneous, and lobulated than those of non-seminoma (p < 0.001). Images of non-seminoma were more often heterogeneous and cystic (p < 0.001). There was no difference in tumor size, multiplicity, presence of calcium or lesion margination. Testicular microlithiasis was more common in seminoma (p < 0.02). Careful analysis of ultrasound images can permit an educated assessment of testicular tumor histopathology.


Prebypass muscle relaxant: to the patient or the pump?
The objective of this study was to assess the difference in muscular relaxation, produced by administration of the prebypass relaxant dose to the patient or in the bypass circuit. This prospective study was conducted on 100 patients scheduled to undergo elective coronary artery bypass grafting. All patients received 2 mg of vecuronium as prebypass relaxant, with neuromuscular junction monitoring using an accelograph. The patients in Group A (n=50) received the prebypass relaxant dose directly through the central venous cannula during heparinisation while group B patients (n=50) received it into the bypass circuit after initiation of bypass. Further doses of the relaxant were administered, if the train of four ratio was more than 10% at anytime after 5 min of bypass. The train of four ratio before heparinisation was similar in both groups, 12+/-6% in Group A and 13+/-5% in Group B, but after the prebypass relaxant dose, it was 1+/-2% in Group A and 15+/-3% in Group B (P<0.05). On bypass, in Group A it was 3+/-2%, 5+/-2%, 6+/-3% and 6+/-3% at 1, 5, 10 and 15 min at normothermia, while in Group B it was 29+/-6%, (P<0.01) at 1 min, 19+/-7%, (P<0.05) at 5 min, 13+/-6% at 10 min and 3+/-2% at 15 min. Additional doses of relaxant on bypass were required in 48 patients in Group B and none in Group A (P<0.01). It is concluded that the degree of muscle relaxation is significantly more profound when the prebypass relaxant dose is given to the patient directly before initiating the bypass, than when it is added to the bypass circuit after initiating the bypass. Time taken is longer and dose needed is larger, to produce the same effect.


Diabetes mellitus and alcohol.
Alcohol influences glucose metabolism in several ways in diabetic patients as well as in non-diabetic patients. Since alcohol inhibits both gluconeogenesis and glycogenolysis, its acute intake without food may provoke hypoglycaemia, especially in cases of depleted glycogen stores and in combination with sulphonylurea. Consumed with a meal including carbohydrates, it is the preferred fuel, which may initially lead to somewhat higher blood glucose levels and hence an insulin response in type 2 diabetic patients. Depending on the nature of the carbohydrates in the meal, this may be followed by reactive hypoglycaemia. Moderate consumption of alcohol is associated with a reduced risk of atherosclerotic disorders. Diabetic patients benefit from this favourable effect as much as non-diabetic patients. Apart from effects on lipid metabolism, haemostatic balance and blood pressure, alcohol improves insulin sensitivity. This improvement of insulin sensitivity may also be responsible for the lower incidence of type 2 diabetes mellitus reported to be associated with light-to-moderate drinking. In case of moderate and sensible use, risks of disturbances in glycaemic control, weight and blood pressure are limited. Excessive intake of alcohol, however, may not only cause loss of metabolic control, but also annihilate the favourable effects on the cardiovascular system.


Invasion of HEp-2 cells by Shigella spp. isolated from acute pediatric diarrhea.
Aim: Shigella infection is an important global health problem in developing countries where hygiene is poor and hence shigellosis is a main cause of diarrhoea-associated mortality and morbidity, particularly in children under the age of five. The bacterial entry into colon and rectal epithelial cells has been named 'bacterium-directed phagocytosis'. This term highlights that the bacteria actively stimulate their own uptake into non-professional phagocytes. The aim of this study was to demonstrate the invasion of HEp-2 cells by Shigella spp. isolated from acute pediatric diarrhea in Tehran, Iran. Methods: Three-hundred and ten non-duplicative diarrheal stool samples were collected from the children admitted to Children's Medical Center in Tehran, Iran. Samples were cultured and suspected colonies were identified by routine microbiological and biochemical tests. The invasion of the two isolated Shigella spp. to HEp-2 cells was studied. Results: Of 310 stool samples, 16 (5.2%) Shigella spp. were isolated, including seven (43.7%) S. sonnei and nine (56.3%) S. flexneri. Four (44.4%) S. sonnei and seven (42.8%) S. flexneri showed invasive phenotype to HEp-2. Conclusion: Shigella sonnei and S. flexneri are reported as the most prevalent Shigella spp. in nature which infect humans. Invasion of various cell lines gives the chance of survival to Shigella spp. This ability causes more virulent infections in the host. Despite costly and time consuming cell culture techniques, the current method described in this paper is reliable for detecting invasive behavior of Shigella spp. Results have also shown that not all the Shigella spp. are able to invade intestinal epithelial cells.


Altered expression of vascular endothelial growth factor, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and Soluble Fms-like Tyrosine Kinase-1 in peripheral blood mononuclear cells from normal and preeclamptic pregnancies.
Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. It complicates around 2%-10% pregnancies worldwide due to imbalance between proangiogenic and anti-angiogenic factors, leading to incomplete placentation, ischemia, and endothelial dysfunction. The study was aimed to analyze the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors, i.e., VEGF receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), and soluble Fms-like tyrosine kinase-1 (sFlt-1) from maternal peripheral blood mononuclear cells (PBMCs) of PE patients. This was a cross-sectional comparative study comprising 18 normotensive and 18 PE patients; the patients were further divided as early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP). The expression level of VEGF, its receptors (VEGFR-1 and VEGFR-2), and sFlt-1 was investigated using real-time polymerase chain reaction. There was a significant change in the mRNA expression with a decrease in VEGF, VEGFR-1, and VEGFR-2 and an increase in sFlt-1 in PBMCs of PE and normal pregnancies (P < 0.001). sFlt-1 mRNA expression was increased by 2.95-fold in the PE group with an inverse correlation with expression of VEGFR-2 (Spearman's rho = 0.68). Based on these findings, we conclude that PE is associated with decrease in the mRNA expression of VEGF, VEGFR-1, and VEGFR-2 as compared to an increase in sFlt-1 in PBMCs.


Potential of biosorbent developed from fruit peel of Trewia nudiflora for removal of hexavalent chromium from synthetic and industrial effluent: Analyzing phytotoxicity in germinating Vigna seeds.
Chromium (VI) removal efficiency of a biosorbent prepared from fruit peel of Trewia nudiflora plant was studied. The effect of pH, sorbent dose, initial metal concentration and temperature was studied with synthetic Cr⁺⁶ solution in batch mode. About 278 mg/g of Cr⁺⁶ sorption was obtained at 293 K at an optimum pH of 2.0 and biosorbent dose of 0.75 g/L. Equilibrium sorption data with varying initial concentration of Cr⁺⁶ (22-248 mg/L) at three different temperatures (293-313 K) were analyzed by various isotherms. Biosorption kinetics and thermodynamics were described using standard model equations. Encouraging results were obtained by the application of the biosorptive treatment for removal of Cr⁺⁶ from wastewater collected from common effluent treatment plant of tannery industry. In addition, C⁺⁶r desorption behavior was studied on different systems. Biosorbent was characterized by FESEM, FT-IR and XRD, etc. Effect of the biosorptive treatement with respect to the phytotoxicity of Cr⁺⁶ was analyzed by studying the seed germination behavior and enzyme activity of a pulse seed (Vigna radiata L.). Different concentrations of Cr⁺⁶ solution in both synthetic medium, as well as, in tannery effluent was employed and the results were compared with that of biosorbent treated medium. The study showed that due to efficient removal of Cr⁺⁶ from aqueous phase, considerable enhancement of seed germination, as well as, increase in root length was obtained for the biosorbent treated solutions which were close to that of the control values. Significant decrease (P < 0.01) in POD activity was observed in seeds irrigated with biosorbent treated wastewater compared to untreated wastewater. The study showed that the novel biosorbent prepared might be utilized for abatement of heavy metal toxicity, i.e., Cr⁺⁶ from industrial effluent.


OH radical initiated oxidation of 1,3-butadiene: isomeric selective study of the dominant addition channel.
We report the first isomeric selective kinetic study of the dominant isomeric pathway in the OH initiated oxidation of 1,3-butadiene in the presence of O(2) and NO using the laser photolysis-laser induced fluorescence (LP-LIF) technique. The photodissociation of the precursor 2-iodo-but-3-en-1-ol results exclusively in the dominant OH-butadiene addition product, permitting important insight into the OH initiated oxidation mechanism. On the basis of analysis of the time dependent OH/OD signals, we have determined a rate constant for O2 addition to the hydroxyalkyl radical of 7.0(-3.0)(+7.0) x 10(-13) cm(3) s(-1), and we find a value of 1.5(-0.6)(+1.0) x 10(-11) cm(3) s(-1) for the overall reaction rate constant of the hydroxy peroxy radical with NO. We also report the first clear experimental evidence of the (E) form of the delta-hydroxyalkoxy channel through isotopic labeling experiments and provide an upper bound of 13 +/- 5% to its branching ratio. This species provides a mechanistic pathway for the formation of 4-hydroxy-2-butenal, which has been identified as a first generation end product. This isomeric selective kinetic study, together with a previous study on the minor channel of the 1,3-butadiene oxidation, yields a comprehensive picture of butadiene oxidation under high NOx conditions relevant to most regions in the continental US.


A simple LC-MS/MS method using HILIC chromatography for the determination of fosfomycin in plasma and urine: application to a pilot pharmacokinetic study in humans.
A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, using hydrophilic interaction liquid chromatography (HILIC) chromatography for the analysis of fosfomycin in human plasma and urine, has been developed and validated. The plasma method uses a simple protein precipitation using a low volume sample (10 μL) and is suitable for the concentration range of 1 to 2000 μg/mL. The urine method involves a simple dilution of 10 μL of sample and is suitable for a concentration range of 0.1 to 10 mg/mL. The plasma and urine results, reported, respectively, are for recovery (68, 72%), inter-assay precision (≤9.1%, ≤8.1%) and accuracy (range -7.2 to 3.3%, -1.9 to 1.6%), LLOQ precision (4.7%, 3.1%) and accuracy (1.7% and 1.2%), and includes investigations into the linearity, stability and matrix effects. The method was used in a pilot pharmacokinetic study of a critically ill patient receiving i.v. fosfomycin, which measured a maximum and minimum plasma concentration of 222 μg/mL and 172 μg/mL, respectively, after the initial dose, and a maximum and minimum plasma concentration of 868 μg/mL and 591μg/mL, respectively, after the fifth dose. The urine concentration was 2.03 mg/mL after the initial dose and 0.29 mg/mL after the fifth dose.


Clinical manifestations. Failure to thrive in the elderly.
1. Failure to thrive (FTT) is a diagnosis used with increasing frequency in the acute care setting. The purpose of this study was to determine how the diagnosis of FTT was being applied to the geriatric population. 2. FTT was used in the study population to describe the general deterioration seen in patients with chronic or incurable illnesses. Many patients were near the terminal stage. The diagnosis was not used specifically for the geriatric population; there was a lack of specificity in the diagnosis and treatment of FTT. 3. Common complaints of patients diagnosed as FTT included ADL changes, weight loss, and anorexia. Nursing care can significantly contribute to the management of symptoms and the prevention of complications.


Transport properties of glass-forming liquids suggest that dynamic crossover temperature is as important as the glass transition temperature.
It is becoming common practice to partition glass-forming liquids into two classes based on the dependence of the shear viscosity η on temperature T. In an Arrhenius plot, ln η vs 1/T, a strong liquid shows linear behavior whereas a fragile liquid exhibits an upward curvature [super-Arrhenius (SA) behavior], a situation customarily described by using the Vogel-Fulcher-Tammann law. Here we analyze existing data of the transport coefficients of 84 glass-forming liquids. We show the data are consistent, on decreasing temperature, with the onset of a well-defined dynamical crossover η(×), where η(×) has the same value, η(×) ≈ 10(3) Poise, for all 84 liquids. The crossover temperature, T(×), located well above the calorimetric glass transition temperature T(g), marks significant variations in the system thermodynamics, evidenced by the change of the SA-like T dependence above T(×) to Arrhenius behavior below T(×). We also show that below T(×) the familiar Stokes-Einstein relation D/T ∼ η(-1) breaks down and is replaced by a fractional form D/T ∼ η(-ζ), with ζ ≈ 0.85.


Highly homogenous tri-acylated S-LPS acts as a novel clinically applicable vaccine against Shigella flexneri 2a infection.
Shigellosis, a major cause of diarrhea worldwide, exhibits high morbidity and mortality in children. Specificity of Shigella immunity is determined by the structure of the main protective O-antigen polysaccharide component incorporated into the lipopolysaccharide (LPS) molecule. Endotoxicity, however, precludes LPS clinical use. Thus, there is still no vaccine against the most prevalent shigellosis species (serotype S. flexneri 2a), despite ongoing efforts focused on inducing serotype-specific immunity. As LPS is highly heterogenous, we hypothesized that more homogenous pools of LPS might be less toxic. We developed a method to generate a homogenous S. flexneri 2a LPS subfraction, Ac3-S-LPS, containing long chain O-specific polysaccharide (S-LPS) and mainly tri-acylated lipid A, with no penta- and hexa-acylated, and rare tetra-acylated lipid A. Ac3-S-LPS had dramatically reduced pyrogenicity and protected guinea pigs from shigellosis. In volunteers, 50 µg of injected Ac3-S-LPS vaccine was safe, with low pyrogenicity, no severe and few minor adverse events, and did not induce pro-inflammatory cytokines. In spite of the profound lipid A modification, the vaccine induced a prevalence of IgG and IgA antibodies. Thus, we have developed the first safe immunogenic LPS-based vaccine candidate for human administration. Homogenous underacetylated LPSs may also be useful for treating other LPS-driven human diseases. Clinical trial registry: http://grls.rosminzdrav.ru/.


Intramolecular Conjugate Ene Reaction of γ-Difluoromethyl- and γ-Trifluoromethyl-α,β-Unsaturated γ-Butyrolactones.
A general synthetic strategy to cis-fused bicyclic γ-butyrolactones via the retro-Diels-Alder reaction/intramolecular conjugate ene cascade (RDA/ICE) reaction under the flash-vacuum pyrolysis of maleic anhydride adducts is developed. The reaction gave high yields of products with high stereoselectivity. The existence of the difluoromethyl or trifluoromethyl group at the γ-position of the in situ-generated homoalkenyl- or homoalkynyl-α,β-unsaturated γ-butyrolactones was found to accelerate the rate of the intramolecular conjugate ene reaction leading to γ-difluoromethylated and γ-trifluoromethylated cis-fused bicyclic γ-butyrolactones.


The influence of maxillary gingival exposure on dental attractiveness ratings.
This study examined the influence of maxillary gingival display on the attractiveness ratings awarded by lay people. One hundred and twenty university students (94 females, 26 males) were shown seven photographs of a male and seven photographs of a female subject, each with varying levels of gingival display ranging from -2 to +4 mm. Attractiveness ratings were recorded on a 10-point numerical scale for each of the photographs. The photographs where the full height of the incisors were revealed and no gingival tissue was visible (0 mm of gingiva) were rated as the most attractive. Gingival display of more than 2 mm was rated as progressively less attractive. Linear regression analysis revealed that those students who had received orthodontic treatment rated the photographs representing the female student as more attractive than those representing the male (P < 0.05).


Ultrafast laser waveguide writing: Lithium niobate and the role of circular polarization and picosecond pulse width.
For the first time to our knowledge, ultrafast laser writing has generated room-temperature stable guided-wave optics in bulk lithium niobate for the telecommunication spectrum. Among a seven-dimensional parameter space for waveguide optimization, two frequently overlooked parameters, pulse duration and polarization, were found to be key in overcoming undesired nonlinear optical responses imposed by this material. Single-mode waveguides were best formed with circularly polarized light having a relatively long pulse duration of approximately 1.0 ps. The waveguides were highly polarization dependent and guided in both telecommunication bands near 1300 and 1550 nm, exhibiting losses as low as 0.7 dB/cm.


Long-term survival of Borrelia burgdorferi lacking the hibernation promotion factor homolog in the unfed tick vector.
Borrelia burgdorferi, a causative agent of Lyme borreliosis, is a zoonotic pathogen that survives in nutrient-limited environments within a tick, prior to transmission to its mammalian host. Survival under these prolonged nutrient-limited conditions is thought to be similar to survival during stationary phase, which is characterized by growth cessation and decreased protein production. Multiple ribosome-associated proteins are implicated in stationary-phase survival of Escherichia coli. These proteins include hibernation-promoting factor (HPF), which dimerizes ribosomes and prevents translation of mRNA. Bioinformatic analyses indicate that B. burgdorferi harbors an hpf homolog, the bb0449 gene. BB0449 protein secondary structure modeling also predicted HPF-like structure and function. However, BB0449 protein was not localized in the ribosome-associated protein fraction of in vitro-grown B. burgdorferi. In wild-type B. burgdorferi, bb0449 transcript and BB0449 protein levels are low during various growth phases. These results are inconsistent with patterns of synthesis of HPF-like proteins in other bacterial species. In addition, two independently derived bb0449 mutants successfully completed the mouse-tick infectious cycle, indicating that bb0449 is not required for prolonged survival in the nutrient-limited environment in the unfed tick or any other stage of infection by B. burgdorferi. We suggest either that BB0449 is associated with ribosomes under specific conditions not yet identified or that BB0449 of B. burgdorferi has a function other than ribosome conformation modulation.


Neurogenic inflammation, vascular permeability, and mast cells. II. Additional evidence indicating that mast cells are not involved in neurogenic inflammation.
Activation of cutaneous sensory nerves induces vasodilatation and vascular permeability, i.e., neurogenic inflammation. We examined the histology and possible mast cell involvement in cutaneous neurogenic inflammation induced by electrical nerve stimulation (ENS). Three lines of evidence indicated that mast cells were not involved in rodent cutaneous neurogenic inflammation induced by electrical stimulation of the saphenous nerve. 1) Most mast cells (86.5% of all mast cells in the dorsal skin of the paw) were found in the deep dermis, whereas vessels developing increased vascular permeability after nerve stimulation (visualized with the supravital dye Monastral blue B, a macro-molecular tracer) were localized predominantly in the superficial dermis. By contrast, i.v. substance P, which also causes increased cutaneous vascular permeability, predominantly caused deeper vessels to leak. As analyzed by electron microscopy, the vessels that developed permeability in response to nerve stimulation, and were thereby stained with Monastral blue B, were found to be exclusively postcapillary venules. 2) Disodium cromoglycate (DSCG), a mast cell stabilizing compound, inhibited the cutaneous vascular permeability induced by intradermal injections of anti-IgE in a dose-dependent manner. By contrast, vascular permeability induced by ENS was not influenced by disodium cromoglycate treatment. 3) ENS and i.v. substance P both induced cutaneous vascular permeability in mast cell-deficient W/Wv mice, despite the fact that their skin contained only 4.7% of the mast cells present in their normal +/+ litter mates. The magnitude of ENS-induced vascular permeability responses in W/Wv mice were similar to control +/+ and BALB/c mice. This study supports our earlier observations suggesting that mast cell activation is not essential for the initial, vascular permeability phase of neurogenic inflammation in rodent skin.


[Medical nutrition therapy in elderly patients with diabetes].
An important factor in medical nutritional therapy for elderly patients with diabetes is optimization of energy intake and macronutrient composition, with consideration of the food source and quality of nutrient. In addition, malnutrition and vitamin deficiency should be carefully considered. A dietary pattern that includes a high intake of vegetables, legumes, seaweed, and fish and a low intake of refined grains, sweets, sugar-sweetened beverages, and alcohol is favorable for diabetic patients. Particular attention should be paid to the excessive intake of sweets and fruits. Furthermore, the type and degree of physical function, cognitive function, lifestyle, social factors, medication, and hospitalization vary among elderly individuals. Therefore, individualized medical nutritional therapy that takes into account all these factors is essential.


Expression and purification of human farnesoid X receptor-ligand binding domain as soluble form using a dual cistronic expression vector.
In this study, we show the expression and purification of the human recombinant farnesoid X receptor (FXR)- ligand binding domain (LBD) protein in E. coli using a double cistronic vector, pACYCDuet-1, as a soluble form. We describe here the expression and characterization of a biologically active FXR-LBD(248-476). When expressed in the influence of bacterial promoters (P(T7) and P(Tac)) of the single cistronic expression vectors, the human recombinant FXR-LBD(248-476) was found to be totally insoluble. However, by using a double cistronic expression vector, we were able to obtain the human recombinant FXR-LBD(248-476) in a soluble form. To allow for biological activities, we have subcloned into the pACYCDuet-1 vector, expressed in E. coli cells at some optimized conditions, and purified and characterized the human recombinant active FXR-LBD(248-476) proteins using the fluorescence polarization assay. This suggests that the expression of FXR-LBD in a double cistronic vector improves its solubility and probably assists its correct folding for the biologically active form of the proteins. We suggest that this may represent a new approach to high expression of other nuclear receptors and may be useful as well for other classes of heterodimeric protein partners.


Spin canting in the 3D anionic dicyanamide structure (SPh(3))Mn(dca)(3) (Ph = phenyl, dca = dicyanamide).
Through use of the SPh(3)(+) (Ph = phenyl, C(6)H(5)) cation as a molecular template, a new three-dimensional Mn(dca)(3)(-) [dca = dicyanamide, N(CN)(2)(-)] anionic structure has been crystallized. At room temperature, (SPh(3))Mn(dca)(3) (1) crystallizes in the monoclinic space group P2(1)/c, with a = 11.7079(5) A, b = 12.8554(5) A, c = 16.8605(6) A, beta = 100.666(2) degrees, and V = 2493.8(3) A(3). Magnetic susceptibility measurements indicate that this salt exhibits a spin canted long range antiferromagnetically ordered ground state below 2.5 K.


Do dietary antioxidants alleviate the cost of immune activation? An experiment with greenfinches.
Reactive oxygen and nitrogen species produced by metabolism and immune defenses can cause extensive damage to biomolecules. To counteract this damage, organisms rely on exogenous and endogenous antioxidants, although their relative importance in maintaining redox balance is unclear. We supplemented captive greenfinches with dietary antioxidants--carotenoids and vitamin E--and injected them with an inflammatory agent, phytohemagglutinin. Compared to controls, immune-challenged birds circulated more lipid peroxidation products but also increased total plasma antioxidativity. Carotenoid (but not vitamin E) supplementation generally reduced lipid peroxidation, but this did not compensate for the effects of immune activation. Levels of an endogenous antioxidant--uric acid--strongly contributed to plasma antioxidativity. We found no evidence that dietary antioxidants are immunostimulatory. These results demonstrate the antioxidant function of carotenoids in birds and show that simultaneous assessment of oxidative stress-driven damage, antioxidant barrier, and individual antioxidants is critical for explaining the potential costs of immune system activation.


Wearable magnetic field sensors for flexible electronics.
Highly flexible bismuth Hall sensors on polymeric foils are fabricated, and the key optimization steps that are required to boost their sensitivity to the bulk value are identified. The sensor can be bent around the wrist or positioned on the finger to realize an interactive pointing device for wearable electronics. Furthermore, this technology is of great interest for the rapidly developing market of -eMobility, for optimization of eMotors and magnetic bearings.


Sublethal Effects of Diamide Insecticides on Development and Flight Performance of Chloridea virescens (Lepidoptera: Noctuidae): Implications for Bt Soybean Refuge Area Management.
High-dose and refuge are the most important strategies for delaying resistance evolution in Bt crops. Insecticide sprays in refuge areas could be necessary and may limit refuge effectiveness. Here, we evaluated the sublethal effects of two diamide insecticides (chlorantraniliprole and flubendiamide) on Chloridea virescens life history traits and flight performance. Sublethal concentrations of chlorantraniliprole and flubendiamide increased larval and pre-pupal development times and decreased larval weight; flubendiamide increased pupal development times. Chlorantraniliprole increased adult male longevity and reduced female fertility, while flubendiamide reduced fecundity. Overall life table parameters were negatively impacted by both treatments. Males exposed to either insecticide showed significant reductions in flight duration and distance for unsustained flights (<30 min). The duration and distance of the first flights were reduced when exposed to chlorantraniliprole. Sustained flights (>30 min) were generally unaffected by insecticide exposure and both sexes flew >6400 m in a single flight. The sublethal effects of flubendiamide and chlorantraniliprole on C. virescens' population dynamics could lead to generation asynchrony and provide insufficient susceptible moths when sprayed on refuge crops. However, the distance and duration of flight may still be sufficient to ensure mixing of potentially resistant and susceptible populations from refuge plots.


Maternal and Infant Secretory Immunoglobulin A across the Peripartum Period.
Salivary secretory immunoglobulin A (sIgA) concentrations change over early infancy. The primary immunoglobulin in breast milk is sIgA, however, no study has examined the role of maternal sIgA in relation to infant salivary sIgA. This study aimed to examine within-source associations and mean level changes of maternal and infant sIgA across the first 6 months of life, to examine the interrelations between maternal and infant sIgA across the first 6 months of life, and to determine the association between breastfeeding and infant sIgA. Participants were a convenience sample of 51 mother-infant dyads. Salivary sIgA was collected from the mother in the third trimester. Infant and maternal salivary and maternal breast milk sIgA was collected at approximately 1, 3, and 6 months postpartum. Maternal salivary sIgA showed no mean level change across the visits, and levels were moderately associated over time. Breast milk sIgA was moderately associated over time; infant salivary sIgA was weakly associated over time. Both breast milk and infant sIgA levels decreased from 1 to 3 months postpartum. Maternal salivary sIgA was not related to infant or breast milk sIgA. Breastfed infants had lower levels of salivary sIgA. Likewise, higher concentrations of breast milk sIgA were related to lower concentrations of infant sIgA. Maternal salivary sIgA is highly stable over the peripartum period, whereas breast milk and infant salivary sIgA was variable. Infant secretory IgA development does not depend positively on maternal salivary or breast milk sIgA.


High-potency hybrid compounds related to insulin and amphioxus insulin-like peptide.
We describe the synthesis and biological evaluation of five two-chain, insulin-like compounds structurally related both to insulin and to a putative insulin like peptide (ILP) whose sequence was deduced from a cDNA cloned from Branchiostoma californiensis (amphioxus), a primitive vertebrate [Chan, S. J., Cao, Q.-P., & Steiner, D. F. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 9319-9323]. The present compounds feature an A-chain corresponding to the A-domain of the putative amphioxus ILP A-domain, except that amino acid substitutions have been made at positions A2, A3, A5, and/or A8, linked via disulfide bonds to the B-chain of bovine insulin. Amphioxus ILP [2 Ile] A/insulin B, amphioxus ILP [2 Ile, 8 His] A/insulin B, amphioxus ILP [2 Ile, 5 Gln, 8 His] A/insulin B, and amphioxus ILP [2 Ile, 3 Ile, 5 Gln, 8 His] A/insulin B all display insulin-like metabolic activity and growth-promoting activity (mitogenesis) equal to or greater than that of natural insulin. Amphioxus ILP [8 His] A/insulin B shows activity in these assays greater than that of its parent compound, but not as high as compounds featuring Ile rather than Leu at position A2. In contrast, the parent compound of the present analogues, i.e., amphioxus ILP A/insulin B, displays potencies ranging from 4.0 to 9.8% relative to insulin in insulin receptor binding and lipogenesis assays, respectively. This parent compound displayed activity in growth factor assays too low for exact quantitation [Chu, Y.-C., Hu, S. Q., Zong, L., Burke, G. T., Gammeltoft, S., Chan, S. J., Steiner, D. F., & Katsoyannis, P. G. (1994) Biochemistry (in press)].(ABSTRACT TRUNCATED AT 250 WORDS)


A novel reusable PAni-PVA-Amylase film: activity and analysis.
Alpha-amylase was immobilized onto polyaniline-polyvinyl alcohol (PAni-PVA) film by cross linking with glutaraldehyde. The activity yield and immobilization efficiency was calculated as 13.58% and 30.60% respectively. The PAni-PVA-Amylase films were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and amylase activity assay. The immobilized α-amylase had its optimum activity at pH 7.0 and 25°C. The immobilization of α-amylase onto the PAni-PVA films protected the enzyme from Fe(2+) inhibition. The PAni-PVA-Amylase films could be used effectively for 30 cycles with 60% retention of the activity.


Development and Preliminary Validation of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).
Patient-reported outcome (PRO) measures developed and validated on patients with the currently defined phenotypes of chronic rhinosinusitis (CRS) are needed to support clinical trials in CRS. This study developed and examined the initial reliability and validity of the CRS-PRO, a new PRO measure of CRS. Instrument development was performed through structured interviews and focus groups with clinical experts and 45 patients with CRS meeting current definitions of disease, 21 patients with CRS without nasal polyps (CRSsNP), and 24 patients with CRS with nasal polyps (CRSwNP) to identify items important to patients. Then another 50 patients (32 with CRSsNP and 18 with CRSwNP) with stable CRS symptoms were enrolled to evaluate the reliability of the instrument. Each patient completed the CRS-PRO, Sinonasal Outcome Test-22 (SNOT-22), and 4 Patient-Reported Outcome Measurement Information System short forms at the baseline visit and then at least 7 days later. After the development process, 21 items were identified from the conceptual domains of physical symptoms, sensory impairment, psychosocial effects, and life impact. Using the responses of the 50 patients with CRS, 21 draft items were further refined to 12 items by eliminating conceptually similar or highly correlated items or those with low mean symptom severity. The 12-item questionnaire was shown to have excellent internal consistency (Cronbach α, 0.86) and test-retest reliability with a high intraclass correlation coefficient (0.89) and Pearson's correlation (r = 0.82, P < .0001). The 12-item CRS-PRO correlated highly with the longer SNOT-22 (r = 0.83, P < .0001) demonstrating its concurrent validity. We also demonstrated validity and reliability in a separate analysis for patients with CRSsNP and CRSwNP. The CRS-PRO is a concise, valid, and reliable measure that was developed with extensive input from patients with CRS with current disease definitions.


[Progestin-induced mammary adenocarcinomas in BALB/c mice. Progression from hormone-dependent to autonomous tumors].
We have developed an experimental model in which the administration of progestins induces mammary tumors in female virgin BALB/c mice. In this paper we review the morphological and biological features of progestin-induced tumors, such as estrogen receptor (ER) and progesterone receptor (PR) patterns of expression, hormone dependence and epidermal growth factor receptors (EGF-R) we also examine our data concerning the systemic effects of medroxyprogesterone acetate (MPA) as regards its stimulating EGF synthesis in salivary glands and its subsequent increase in serum. This growth factor seems to play an important role in the induction of mammary tumors. Direct MPA proliferative effects mediated by PR were demonstrated using primary cultures of progestin-dependent (PD) mammary tumors. Antiprogestins inhibited cell growth beyond control values, suggesting that PR are involved in cell proliferation even in the absence of the ligand. Progesterone-independent (PI) tumors expressing high levels of PR and ER are also inhibited by estrogen or antiprogestin treatment, suggesting that PR are involved in the control of autonomous tumor growth. Estrogen-resistant variants may be selected which may revert to an estrogen-sensitive phenotype after several transplants in untreated mice. The similarities between the tumors obtained with this model and human breast cancer as regards morphological features, evolution and the regulation of growth control converts this model into a useful tool to explore the mechanisms related with acquisition of hormone independence and autonomous tumor growth.


Association mapping reveals novel genes and genomic regions controlling grain size architecture in mini core accessions of Indian National Genebank wheat germplasm collection.
Wheat (Triticum aestivum L.) is a staple food crop for the global human population, and thus wheat breeders are consistently working to enhance its yield worldwide. In this study, we utilized a sub-set of Indian wheat mini core germplasm to underpin the genetic architecture for seed shape-associated traits. The wheat mini core subset (125 accessions) was genotyped using 35K SNP array and evaluated for grain shape traits such as grain length (GL), grain width (GW), grain length, width ratio (GLWR), and thousand grain weight (TGW) across the seven different environments (E1, E2, E3, E4, E5, E5, E6, and E7). Marker-trait associations were determined using a multi-locus random-SNP-effect Mixed Linear Model (mrMLM) program. A total of 160 non-redundant quantitative trait nucleotides (QTNs) were identified for four grain shape traits using two or more GWAS models. Among these 160 QTNs, 27, 36, 38, and 35 QTNs were associated for GL, GW, GLWR, and TGW respectively while 24 QTNs were associated with more than one trait. Of these 160 QTNs, 73 were detected in two or more environments and were considered reliable QTLs for the respective traits. A total of 135 associated QTNs were annotated and located within the genes, including ABC transporter, Cytochrome450, Thioredoxin_M-type, and hypothetical proteins. Furthermore, the expression pattern of annotated QTNs demonstrated that only 122 were differentially expressed, suggesting these could potentially be related to seed development. The genomic regions/candidate genes for grain size traits identified in the present study represent valuable genomic resources that can potentially be utilized in the markers-assisted breeding programs to develop high-yielding varieties.


Restoration of cell-mediated immune responses with transfer factor.
Five anergic patients with chronic mucocutaneous candidiasis were given transfer factor from donors with positive delayed reactions to Candida. In each recipient, the delayed skin reactions of the transfer factor donors appeared in the recipients and no recipient developed reactivities not possessed by the donor. Prior to injection of transfer factor, in vitro stimulation of the patients' lymphocytes with antigens did not result in MIF production, however, after transfer factor this response was positive. Therapy with transfer factor alone did not have therapeutic benefit, however, in 2 patients treatment with amphotericin-B followed by transfer factor has produced cutaneous remissions of 18 months.


[Health economic evaluation reporting guideline and application status].
Using the guidelines of health economic evaluation reporting is conducive to regulating the contents of this reporting, improving the quality of studies into health economics evaluation. This article summarized the history of the guidelines and specified the instrument used to study " Quality of Health Economic Studies (QHES)" and the checklist about Consolidated Health Economics Evaluation Reporting Standards (CHEERS)-the two specific evaluation contents in this guideline, the article also introduced its present application status of the guideline and its pros and cons. The checklist of CHEERS emphasized the evaluation of this report, while QHES instrument focused on quantitative evaluation on the quality of economic studies. Despite different emphasis, the two guides are actually mutually complemented.


Vitamin D metabolism by alveolar immune cells in tuberculosis: correlation with calcium metabolism and clinical manifestations.
The aim of this study was to investigate the relationship between the pulmonary vitamin D metabolism in tuberculosis and the calcium metabolism abnormalities and other clinical characteristics of the disease. The metabolism of 25-hydroxyvitamin D3 (25(OH)D3) by alveolar immune cells recovered by bronchoalveolar lavage (BAL) was evaluated in parallel to the results of calcium metabolism, 25(OH) D and 1,25 dihydroxyvitamin D (1,25(OH)2D) plasma levels and other clinical parameters obtained in 14 tuberculosis patients. Whilst predominant metabolites produced by lavage cells in patients and controls were 5(E)--and 5(Z) -19-nor-10-oxo-25(OH)D3, 1,25(OH)2D3 was produced by cells from all tuberculosis patients but not by cells from controls. Calcium metabolism abnormalities were observed in only some patients, but the production of 1,25 (OH)2D3 by lavage cells was found to correlate both with 1,25(OH)2D levels (r = 0.67) and post-load urinary calcium excretion (r = 0.59). 1,25(OH)2D3 production by lavage cells was increased in patients of black origin, and those presenting with hilar adenopathy without pulmonary infiltrates, and was correlated with the number of lymphocytes recovered by lavage (r = 0.87). We conclude that 1,25(OH)2D3 production by alveolar immune cells makes a major contribution to the abnormalities in calcium metabolism seen in tuberculosis patients, and may be partly dependent on the clinical characteristics evaluated here.


The effect of catalytic converter legislation on suicide rates in Grampian and Scotland 1980-2003.
To examine the effect of catalytic converter legislation on suicide rates in Grampian and Scotland since its implementation in 1993. (1) Population study in Grampian and Scotland using national population and mortality statistics for 1980 to 2003. (2) Retrospective, controlled cohort study of individualswho had unsuccessfully attempted suicide by motor had unsuccessfully attempted suicide by motor vehicle exhaust gassing to examine the theory of method substitution. method substitution. There was a significant fall in suicides by motor vehicle exhaust gas inhalation in Scotland and Grampian following the introduction of compulsory catalytic converter legislation. However, in the same time period, there was a significant increase in numbers of suicides by hanging and total suicide rates in Scotland. There was a non-significant trend in a small sample of patients from a local hyperbaric unit for an increased rate of subsequent completed suicide between those who had previously attempted suicide by motor vehicle exhaust gas inhalation and controls. Catalytic converter legislation has resulted in a decrease in the number of suicides by motor vehicle exhaust gas inhalation. Overall suicide rates have not decreased. There is evidence to suggest that those who would have previously committed suicide by motor vehicle exhaust gas inhalation find alternative methods of suicide, so called 'method substitution'. Initiatives to reduce suicide rates should be directed at those means that are used by impulsive suicide attempters, as other, determined individuals, will commit suicide by another method.


[Continuous glucose monitoring system, as a valuable tool in the care of children and adolescents with diabetes mellitus].
Good metabolic control of diabetic patients is mainly based on the results of self measured blood glucose levels. Important excursions of blood glucose may, however, be hidden in the usual case of 4-5 daily determinations. The aim of this paper was to give detailed information about this new diagnostic tool and to report the first Hungarian pediatric experiences with continuous glucose monitoring. Continuous glucose monitoring system (Mini-Med) is able to monitor the changes of tissue glucose levels for up to 72 hours by measuring glucose concentration via a s.c. canula every 5 minutes. In its present form the results of continuous glucose monitoring cannot be observed real time by the patient, it provides useful information retrospectively mainly for the doctor. The sensor detected unexpectedly high fluctuation of glucose levels in several patients. It was possible to distinguish between nighttime hypoglycaemia (Somogyi-effect) or dawn phenomenon-induced morning hyperglycaemiae by the use of continuous glucose monitoring. Fever may influence peripheral circulation representing a limitation in the use (or evaluation) of continuous tissue glucose monitoring. The authors found good correlation between continuous glucose monitoring and self blood glucose monitoring results. The best correlation was observed in the low blood glucose range. The continuous glucose monitoring results provide useful information for the diabetologist in order to modify insulin treatment. Continuous glucose monitoring-based changes in insulin treatment are reported to result in better long term metabolic control. Continuous glucose monitoring in the near future will obviously play a primary role in insulin pump therapy where it will provide glucose result for the pump.


Mineralization of humic acids (HAs) by a solar photo-Fenton reaction mediated by ferrioxalate complexes: commercial HAs vs extracted from leachates.
The mineralization of bio-recalcitrant humic acids (HAs) by a solar photo-Fenton (SPF) process was investigated in aqueous system, in order to understand its abatement in real high-HA content matrices, such as sanitary landfill leachates. SPF reactions were performed in tubular photoreactors with CPCs at lab-scale (simulated solar light) and pilot-scale (natural sunlight). Considering the experimental conditions selected for this work, the formation of insoluble HA-Fe3+ complexes was observed. Thus, to avoid HA precipitation, oxalic acid (Ox) was added, since Fe3+-Ox complexes present a higher stability constant. The effect of different process variables on the performance of SPF reaction mediated by ferrioxalate complexes (SPFF) was assessed with excess of H2O2 (50-250 mg L-1), at lab-scale: (i) pH (2.8-4.0); (ii) initial iron concentration (20-60 mg Fe3+ L-1); (iii) iron-oxalate molar ratio (Fe3+-Ox of 1:3 and 1:6); (iv) temperature (20-40 °C); (v) UV irradiance (21-58 WUV m-2); and (vi) commercial-HA concentration (50-200 mg C L-1). At the best lab conditions (40 mg Fe3+ L-1, pH 2.8, 30 °C, 1.6 Fe3+-Ox molar ratio, 41 WUV m-2), commercial HAs' mineralization profile was also compared with HAs extracted from a sanitary landfill leachate, achieving 88 and 91% of dissolved organic carbon removal, respectively, after 3-h irradiation (8.7 kJUV L-1). Both reactions followed the same trend, although a 2.1-fold increase in the reaction rate was observed for the leachate-HA experiment, due to its lower humification degree. At pilot-scale, under natural sunlight, 95% HA mineralization was obtained, consuming 42 mM of H2O2 and 5.9 kJUV L-1 of accumulated UV energy. However, a pre-oxidation during 2.8 kJUV L-1 (12 mM H2O2) was enough to obtain a biodegradability index of 89%, showing the strong feasibility to couple the SPFF process to a downstream biological oxidation, with low chemicals and energetic demands. Graphical abstract .


[Treatment of diabetes mellitus during Ramadan].
In the treatment of patients with diabetes mellitus it is fundamental that the therapeutic schemes are adapted to each's patient characteristics such as age, associated diseases and diabetes complications. This therapeutic individualization must also include lifestyles and socio-cultural and religious factors as the celebration of Ramadan. Although Muslin diabetics are theoretically free from Ramadan, they commonly wish to fast in practice. It is therefore needed a right approach of the patient during this period. In this Review, we analyze the prevalence of diabetes among different ethnicities, the possible complications of the disease in relation to fasting's pathophysiology, and the studies performed to rightly manage type 1 and 2 diabetic patients during Ramadan. It is necessary to adapt the therapeutic scheme both for patients treated with dietetic measures or oral drugs and for patients receiving insulin. It is also important the involvement of health professionals in the advice, orientation and adaptation of the therapeutic regimen of Muslin people with diabetes.


Nurse manager exemplar: a journey out of the glass house.
Our interdisciplinary patient care planning process began with team members convening in a closed room "talking" about the patient. The patient, family, physician, and even the staff nurse at times were unable to attend. No medical record was available for use. This article discusses the vital role of the nurse manager in the evolution of Health Care Team Rounds and the impact of the behaviorally based competencies on the process. When all is said and done, this is why we are here. This is our work!


[Methodical aspects of pneumatic segment plethysmography. II. The problem of cuff width and cuff-pressure].
Pneumatic segment-plethysmography was used to investiage the influence of different cuff-widths and cuff-pressures on arterial inflow to the calf. It was demonstrated that 1. using consistently 80 Torr for the small respectively 50 Torr for the wide cuff no significant difference for small suprapatellar thigh-circumferences was found. On the contrary for large suprapatellar thigh-circumferences there was a statistically significant difference of the arterial inflow; 2. using both cuffs for all thigh-circumferences, a confirmity of arterial inflow was found if a coupling-factor was individually calculated in each case from upper arm- and thigh-pressure; 3. the arterial inflow to the calf did not differ at pressures of 42 Torr and 50 Torr, whereas at 70 Torr arterial inflow was significantly diminished.


Bioproduction, structure elucidation and in vitro antiproliferative effect of eumelanin pigment from Streptomyces parvus BSB49.
In this study, the structure of the purified extracellular eumelanin pigment isolated from Streptomyces spp. was elucidated by detailed analysis via two different spectroscopic techniques (FT-IR and NMR). In vitro antiproliferative effects of eumelanin were evaluated on HeLa cell line. These experiments were carried out with the evaluation of the parameters including cell viability, cell index, and mitotic index. With the cell viability and cell index, IC50 concentration of eumelanin was determined as 10 μM. This result showed that the IC50 concentration of eumelanin decreased the values of cell viability, cell index and mitotic index. These changes are statistically significant (p < 0.01). The ability of the dissolved eumelanin (250 μg mL-1) to scavenge free radicals was determined via DPPH and ABTS and was shown to be about 87.73% and 75.2%, respectively, compared with standard antioxidants. It was observed that dry weights of eumelanin yield among the selected strains ranged from 160 to 240 mg L-1. The strain with the highest production potential was selected for 16S rDNA sequence analysis and, accordingly, the selected strain BSB49 was identified as Streptomyces parvus and the sequence analysis results were deposited in NCBI under accession number MK894155.


Validity and reliability of diastolic pulse contour analysis (windkessel model) in humans.
The present study assessed (1) the impact of the measurement site (lower versus upper extremity) on the corresponding compliance variables and (2) the overall reliability of diastolic pulse contour (Windkessel-derived) analysis in normal and hypertensive subjects. Arterial tonograms were recorded in the supine position from the radial and posterior tibial arteries in 20 normotensive (116+/-12/68+/-8 mm Hg) and 27 essential hypertensive subjects (160+/-16/94+/-14 mm Hg). Ensemble-averaged data for each subject were fitted to a first-order lumped-parameter model (basic Windkessel) to compute whole-body arterial compliance (C(A)) and to a third-order lumped-parameter model (modified Windkessel) to compute proximal compliance (C(1)) and distal compliance (C(2)). Despite high-fidelity waveforms in each subject, the first-order Windkessel model did not yield interpretable (positive) values for C(A) in 50% of normotensives and 41% of hypertensives, whereas the third-order model failed to yield interpretable C(1) or C(2) results in 15% of normotensives and 41% of hypertensives. No between-site correlations were found for the first-order time constant, 2 of the 3 third-order model curve-fitting constants, or C(A), C(1), or C(2) (P>0.50). Mean values for all 3 compliance variables were higher for the leg than the arm (P<0.05 each). We conclude that differences in Windkessel-derived compliance values in the arm and leg invalidate whole-body model assumptions and suggest a strong influence of regional circulatory properties. The validity and utility of Windkessel-derived variables is further diminished by the absence of between-site correlations and the common occurrence of uninterpretable values in hypertensive subjects.


Development of a simple, practice-based tool to assess quality of paediatric emergency care delivery in resource-limited settings: identifying critical actions via a Delphi study.
Provision of timely, high-quality care for the initial management of critically ill children in African hospitals remains a challenge. Monitoring the completion of critical actions during resuscitations can inform efforts to reduce variability and improve outcomes. We sought to develop a practice-based tool based on contextually relevant actions identified via a Delphi process. Our goal was to develop a tool that could identify gaps in care, facilitate identification of training and standardised assessment to support quality improvement efforts. Six sentinel conditions were selected based on disease epidemiology and mortality at rural and urban African emergency departments. Potential critical actions were identified through focused literature review. These actions were evaluated within a three-round modified Delphi process. A set of logistical filters was applied to the candidate list to derive a practice-based tool. Attendees at an international emergency medicine conference comprised an expert panel of 25 participants, with 84% working primarily in African settings. Consensus rounds allowing novel responses were conducted via online and in-person surveys. The expert panel generated 199 actions that apply to six conditions in emergently ill children. Application of appropriateness criteria refined this to 92 candidate actions across the following seven categories: core skills, active seizure, altered mental status, diarrhoeal illness, febrile illness, respiratory distress and polytrauma. From these, we identified 28 actions for inclusion in a practice-based tool contextually relevant to the initial management of critically ill children in Africa. A group consensus process identified critical actions for severely ill children with select sentinel conditions in emergency paediatric care in an African setting. Absence of these actions during resuscitation might reflect modifiable gaps in quality of care. The resulting practice-based tool is context relevant and can serve as a foundation for training and quality improvement efforts in African hospitals and emergency departments.


Serum fetuin-A and recurrent urolithiasis in young adults.
Recurrence of urolithiasis is frequent. There are no reliable markers able to indicate recurrent stone former patients. Fetuin-A inhibits hydroxyapatite crystals formation and expansion. This study aims at evaluating whether serum fetuin-A may predict recurrent urolithiasis in young adults. This is a multicentre study. Young adults patients with recurrent urolithiasis attending 3 urology clinics were enrolled from July 2011 to December 2012. Inclusion criteria were: age 18-40 years, presence of more than one kidney stone. Exclusion criteria were: diabetes mellitus, metabolic disorders, obesity, hypertension, cardiovascular disease, infection diseases. Controls were participants without history of urolithiasis and currently undetected stones. Routine biochemistry, serum concentration of oxalate, fetuin-A, and parathyroid hormone (PTH) were assessed; 24/h urinary excretion of creatinine, uric acid, calcium, sodium, phosphorus, potassium, magnesium, glucose, oxalate, amylase, and protein was measured. Kidney ultrasonography and plain X-ray examination was performed. The total cohort was represented by 120 young adults participants (90 patients, and 30 controls). Clinical characteristics were not different between patients and controls. No significant differences were found in serum concentrations as well as in 24/h urinary excretion of recorded variables. No significant difference was found in serum concentration of fetuin-A (median 35.1 ± 18.62 SD Vs 35.12 ± 14.12, μg/ml; p = 0,908). The data of present study do not substantiate the hypothesis that serum fetuin-A may be a reliable predictor of recurrent urolithiasis in young adults.


Late diagnosis of severe colchicine intoxication.
A 4-year-old Turkish girl was referred to our hospital with the findings of encephalopathy and pancytopenia. She had a history of severe abdominal cramps and gastrointestinal bleeding. A confused state, muscle pain and weakness, erythema-bullous and erythema-nodosum-like skin lesions, and alopecia were observed at her hospitalization. All of these symptoms resolved on follow-up. On laboratory investigation severe thrombocytopenia and leukopenia, mild anemia, a moderate increase in aspartate aminotransferase and alanine aminotransferase levels were detected. After reevaluating her medical history, it was learned that she had accidentally taken 1.3 to 1.5 mg/kg of colchicine 3 to 4 days before her first hospitalization. The possibility of misdiagnosis of colchicine intoxication should be borne in mind, and pediatricians must be aware of its toxic effects, especially in areas where patients with familial Mediterranean fever are present.


Hypouricemic and arthritis relapse-reducing effects of compound tufuling oral-liquid in intercritical and chronic gout: A double-blind, placebo-controlled, multicenter randomized trial.
In the double-blind, randomized, controlled trial, we aimed to evaluate the effects of compound tufuling oral liquid (CoTOL) on serum uric acid (sUA) levels and recurrence of acute gouty arthritis in intercritical and chronic gout treatment. A total of 210 patients with gout were screened from 8 hospitals to observe the sUA and acute gouty arthritis recurrence rate-reducing effects of CoTOL in intercritical and chronic gout during a 12-week treatment. We treated 139 and 71 patients with CoTOL and the placebo, respectively, and evaluated their sUA levels, acute gouty arthritis recurrence rate, and adverse events at week 0, 6, and 12. Twenty-five and 12 patients in the treatment and control groups, respectively, had interrupted treatments, whereas 114 and 59 cases, respectively, completed their treatments. At the end of the 12-week treatment, the average decrease in sUA was 74.26 (95% confidence interval [CI]: 56.74-91.77 μmol/L) and 28.81 μmol/L (95% CI: 4.91-52.71 μmol/L) in the treatment and control groups, respectively (P = 0.004). The average decrease rate of sUA was 12.76% (95% CI: 9.82%-15.70%) and 4.57% (95% CI: 0.42%-8.71%) in the treatment and control groups, respectively (P = 0.004), and the gouty arthritis recurrence rate of the treatment group was lower than that of the control group (from week 6 to 12, 21.93% and 50.88% in the treatment and control group, respectively, P < 0.001; from baseline to week 12, 38.5% and 63.16%, respectively, P = 0.003). Severe adverse events were not observed in either groups, and fewer leucopenia incidences were observed in the treatment group than those in the control group (3/139 vs. 7/71, respectively, P = 0.033). CoTOL reduced sUA levels and effectively prevented acute arthritis recurrence in intercritical and chronic gout without serious adverse events.


Foot Involvement as the First Manifestation in Rheumatoid Arthritis Patients in Lahore.
Objective The objective of this study was to determine the involvement of the foot as the first manifestation in rheumatoid arthritis (RA). Methods This study was conducted on 100 patients who presented to the outpatient department of the Rheumatology Department at Fatima Memorial Hospital and College of Medicine and Dentistry in Lahore, Pakistan. The period of this cross-sectional study was three months - from October 2017 to December 2017. One hundred patients aged more than 16 years, who were diagnosed as cases of RA with foot involvement, and with a disease duration of less than two years (to minimize recall bias), were enrolled for the study. Results Out of the 100 patients, 20% were male and 80% were female. The mean age of the study population was 41.16 ± 12.343 years. Foot Involvement as the first manifestation was noted in 29 (29%) of the cases. The pattern of foot involvement shows a 59% forefoot involvement, 27% hindfoot involvement, and 14% midfoot involvement. Walking difficulty was most common in forefoot involvement (71.42% of cases), followed by hindfoot involvement (20% of cases), and least common in midfoot involvement (8.57% of cases) (p=0.0001). Conclusion Foot involvement as the first manifestation is quite common in RA and should not be ignored, especially in patients with large joint involvement sparing the hands.


Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017: part 2 - categorical bivariate analysis and attributable fractions.
As the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco. SEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including "All (non-skin) Cancer") from National Cancer Institute in US states 2001-2017. Drug exposures taken from the National Survey of Drug Use and Health 2003-2017, response rate 74.1%. Federal seizure data provided cannabinoid exposure. US Census Bureau furnished income and ethnicity. Exposure dichotomized as highest v. lowest exposure quintiles. Data processed in R. Nineteen thousand eight hundred seventy-seven age-standardized cancer rates were returned. Based on these rates and state populations this equated to 51,623,922 cancer cases over an aggregated population 2003-2017 of 124,896,418,350. Fifteen cancers displayed elevated E-Values in the highest compared to the lowest quintiles of cannabidiol exposure, namely (in order): prostate, melanoma, Kaposi sarcoma, ovarian, bladder, colorectal, stomach, Hodgkins, esophagus, Non-Hodgkins lymphoma, All cancer, brain, lung, CLL and breast. Eleven cancers were elevated in the highest THC exposure quintile: melanoma, thyroid, liver, AML, ALL, pancreas, myeloma, CML, breast, oropharynx and stomach. Twelve cancers were elevated in the highest tobacco quintile confirming extant knowledge and study methodology. For cannabidiol RR declined from 1.397 (95%C.I. 1.392, 1.402), AFE declined from 28.40% (28.14, 28.66%), PAR declined from 15.3% (15.1, 15.5%) and minimum E-Values declined from 2.13. For THC RR declined from 2.166 (95%C.I. 2.153, 2.180), AFE declined from 53.8% (53.5, 54.1%); PAR declined from 36.1% (35.9, 36.4%) and minimum E-Values declined from 3.72. For tobacco, THC and cannabidiol based on AFE this implies an excess of 93,860, 91,677 and 48,510 cases; based on PAR data imply an excess of 36,450, 55,780 and 14,819 cases. Data implicate 23/28 cancers as being linked with THC or cannabidiol exposure with epidemiologically-causal relationships comparable to those for tobacco. AFE-attributable cases for cannabinoids (91,677 and 48,510) compare with PAR-attributable cases for tobacco (36,450). Cannabinoids constitute an important multivalent community carcinogen.


Palladium-catalyzed direct regioselective ortho-phosphonation of aromatic azo compounds with dialkyl phosphites.
An efficient palladium-catalyzed regioselective C-P bond formation of azo compounds through C-H bond functionalization using dialkyl phosphites as phosphorus source under mild conditions was developed. A series of both symmetrical and unsymmetrical azoarenes were successfully phosphonylated through this procedure with tolerance of a broad range of functional groups.


Functional thyrotropin receptor attenuates malignant phenotype of follicular thyroid cancer cells.
Thyrotropin (TSH) is a thyroid-specific growth factor inducing differentiated function and growth of thyrocytes in vitro. In thyroid cancer, loss of TSH-receptor (TSHR) expression is a sign of de-differentiation and is believed to contribute to the malignant phenotype. The present studies aimed to determine the in vitro and in vivo effects of functioning TSHR in the follicular thyroid cancer cell line HTC, a subclone of FTC133 cells, lacking endogenous expression of TSHR, and HTCtshr+ cells transfected with human TSHR-cDNA. HTCtshr+ cells grew faster in vitro (doubling time 1.15 vs 1.56 d, p < 0.05) and TSH caused a dose-dependent growth response. Adhesion to and invasion through reconstituted basement membrane were reduced in HTCtshr+ cells, but when stimulated with TSH increased to levels comparable to naïve HTC cells. In vivo, tumor latency was 11 d for naïve HTC as compared to 21 d for HTCtshr+ xenografts. Smaller tumor volumes were registered for HTCtshr+ cells (250 +/- 217 vs 869 +/- 427 mm3, p < 0.05). Angiogenesis, as determined by vascular surface density (VSD) of experimental tumors, was enhanced in naïve HTC tumors (VSD 0.87 +/- 0.1 microm-1 vs 0.55 +/- 0.2 microm-1 in HTCtshr+, p < 0.05). VEGF secretion was more pronounced in naïve HTC cells stimulated with EGF, than in HTCtshr+ cells stimulated with either TSH or EGF. In conclusion, regained expression of functional TSHR in the follicular thyroid cancer cell line HTC alters in vitro features commonly associated with the malignant phenotype. Smaller tumors and reduced angiogenesis of xenotransplanted HTC cells with functioning TSHR suggest a less aggressive in vivo phenotype. The present data highlight the pivotal role of TSHR to affect transformed thyrocytes in vitro and in vivo. They also suggest a role for EGF as a modulator of angiogenesis in thyrocytes devoid of TSHR.


The effects of different exercise training modalities on plasma proenkephalin Peptide F in women.
Due to the important interactions of proenkephalin fragments (e.g., proenkephalin [107-140] Peptide F) to enhance activation of immune cells and potentially combat pain associated with exercise-induced muscle tissue damage, we examined the differential plasma responses of Peptide F to different exercise training programs. Participants were tested pre-training (T1), and after 8 weeks (T2) of training. Fifty-nine healthy women were matched and then randomly assigned to one of four groups: heavy resistance strength training (STR, n=18), high intensity endurance training (END, n=14), combined strength and endurance training (CMB, n=17), or control (CON, n=10). Blood was collected using a cannula inserted into a superficial vein in the antecubital fossa with samples collected at rest and immediately after an acute bout of 6 X 10 RM in a squat resistance exercise before training and after training. Prior to any training, no significant differences were observed for any of the groups before or after acute exercise. With training, significant (P≤0.95) elevations were observed with acute exercise in each of the exercise training groups and this effect was significantly greater in the CMB group. These data indicate that in untrained women exercise training will not change resting of plasma Peptide F concentrations unless both forms of exercise are performed but will result in significant increases in the immediate post-exercise responses. Such findings appear to indicate adrenal medullary adaptations opioid production significantly altered with exercise training.


Phase diagram of a binary mixture in a closed cavity.
Normally, the phase diagram is reported as a property of the binary mixture. We show that the phase diagram (that is, the zones of thermodynamic stability of the states of the binary mixture) is also affected by the size of the container. We investigate the thermodynamic stability of the binary mixture in a closed cavity, and identify the zone in parameters where the binary mixture is heterogeneous in equilibrium (the zone of spinodal decomposition), the zone where the mixture is always homogeneous in equilibrium, and the zone where the transition between these two states is possible (the metastable nucleation zone). In addition, we investigate the properties of the smallest single droplet that may be in equilibrium in the closed cavity (for the given average concentration, all smaller droplets would always dissolve). We show that the size of such droplets depends on the cavity's size, as ∼L^{1/2}.


Role of eosinophils and neutrophils in innate and adaptive protective immunity to larval strongyloides stercoralis in mice.
The goal of this study was to determine the roles of eosinophils and neutrophils in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. The experimental approach used was to treat mice with an anti-CCR3 monoclonal antibody to eliminate eosinophils or to use CXCR2-/- mice, which have a severe neutrophil recruitment defect, and then determine the effect of the reduction or elimination of the particular cell type on larval killing. It was determined that eosinophils killed the S. stercoralis larvae in naïve mice, whereas these cells were not required for the accelerated killing of larvae in immunized mice. Experiments using CXCR2-/- mice demonstrated that the reduction in recruitment of neutrophils resulted in significantly reduced innate and adaptive protective immunity. Protective antibody developed in the immunized CXCR2-/- mice, thereby demonstrating that neutrophils were not required for the induction of the adaptive protective immune response. Moreover, transfer of neutrophil-enriched cell populations recovered from either wild-type or CXCR2-/- mice into diffusion chambers containing larvae demonstrated that larval killing occurred with both cell populations when the diffusion chambers were implanted in immunized wild-type mice. Thus, the defect in the CXCR2-/- mice was a defect in the recruitment of the neutrophils and not a defect in the ability of these cells to kill larvae. This study therefore demonstrated that both eosinophils and neutrophils are required in the protective innate immune response, whereas only neutrophils are necessary for the protective adaptive immune response to larval S. stercoralis in mice.


The association of adenocarcinoma and hemosputum in pulmonary malignancies.
Hemosputum was considered one of the popular symptoms of patients with centrally located carcinoma of the lung, especially squamous cell or small cell type. Recent studies reported a relative increase in adenocarcinoma compared with squamous cell carcinoma, especially in developed countries. The main purpose of this study was to determine the trend of histological type associated with the occurrence of hemosputum in patients with pulmonary malignancy. Retrospectively, the data from 1,050 patients with pulmonary malignancy who underwent bronchoendoscopic examination at our institution between May 1993 and May 2000 were analyzed. One hundred and forty-nine out of 1,050 patients had hemosputum. There were 66 patients with adenocarcinoma, 55 with squamous cell carcinoma, 15 with small cell carcinoma, 5 with large cell carcinoma, 3 with other cell type carcinoma and 5 with metastatic carcinoma. On bronchoendoscopic examination, abnormal findings in the segmental or more proximal bronchi were found in 82 patients, including 36 with squamous cell carcinoma, 31 with adenocarcinoma, 12 with small cell carcinoma, 2 with large cell carcinoma and 1 with metastatic carcinoma. On the other hand, 67 patients were diagnosed with pulmonary malignancy in the subsegmental or more distal area, including 35 with adenocarcinoma, 19 with squamous cell carcinoma, 3 with small cell carcinoma, 3 with large cell carcinoma, 3 with other cell type carcinoma and 4 with metastatic carcinoma. The most frequent histological type of malignancy with hemosputum was adenocarcinoma. The number of abnormalities in the peripheral region with hemosputum showed a progressive increase. The number of adenocarcinoma with hemosputum was increased in both central and peripheral regions.