Surgical approach to uterine myomatosis in patients with infertility: open, laparoscopic, and robotic surgery; results according to the quantity of fibroids.
To compare approaches to myomectomy (laparotomic, laparoscopic, and robotic). To show the relationship between the number of fibroids and the reproduction diagnosis. Observational, analytical, retrospective, and cross-sectional study; where the surgical approach used, was evaluated in terms of surgical bleeding, time, number and weight of fibroids and reproductive results. 69 patients were treated through different approaches and divided into 3 groups. The differences found among groups were in favor of laparotomic myomectomy in terms of the number (p=0.000) and weight of fibroids (p=0.004). Robotic surgery was also longer (p=0.000). In the analysis of the influence of the number of fibroids to achieve pregnancy, the result was in favor of the minimally invasive routes, after surgery, both in the group of < 6 fibroids (p=0.017), and that of > 6 fibroids (p=0.001), without differences in the time from surgery to pregnancy (p=0.979). The surgical approach decision should consider the number and size of resected fibroids, surgical time, and reproductive diagnosis. The minimally invasive route should be offered whenever possible due to its better outcome on achieving pregnancy, without forgetting the benefits of laparotomy, while also accrediting the recently introduced robotic-assisted approach.


Platelets in liver disease, cancer and regeneration.
Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.


PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice.
Macrophages play an important role in the pathogenesis of COPD. Macrophage polarization towards the M2 phenotype has been observed in the lung tissues of COPD patients and cigarette smokers. The molecular basis of this process remains unclear, and it has not been completely illuminated in animal models of emphysema. In our study, we combined cigarette smoke (CS) exposure with intraperitoneal injection of cigarette smoke extract (CSE) to build an emphysema model. We found by immunohistochemical staining and flow cytometry that the expression level of CD206 and the ratio of M2 to M1 macrophages was increased in emphysematous mice. We also demonstrated that decreased protein level for phosphatase and tensin homology deleted on chromosome ten (PTEN) and increased total protein levels for phosphorylation -protein kinase B (p-AKT) in the lung tissue of emphysematous mice and in CSE-treated RAW264.7 cells. In both bone marrow-derived macrophages (BMDMs) from emphysematous mice and CSE-treated RAW264.7 cells, we observed by RT-PCR that the mRNA levels of M2 macrophage-related markers and cytokines were increased. Furthermore, M1 macrophage-related markers and cytokines were decreased. Meanwhile we treated BMDMs from emphysematous mice and CSE-treated RAW264.7 cells with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor (LY294002), we observed a reduction in RNA levels of M2 macrophage-related markers and cytokines. In conclusion, we confirmed that macrophage M2 polarization was induced in emphysematous mice generated by CS exposure combined with intraperitoneal injection of CSE. We also showed that M2 polarization was mediated through PTEN/PI3k/AKT pathway activation.


Dendrimers and nanotubes: a fruitful association.
Dendrimers and nanotubes (particularly carbon nanotubes (CNTs)) are two types of nano-objects which have met independently a large success within the scientific community. Surprisingly, their association has been poorly studied up to now, despite some original properties recently reported and that will be emphasized in this tutorial review. One can name as a few, the elaboration of single-walled carbon nanotubes from dendrimers, CNTs functionalised with dendrimers displaying field effect transistor properties and/or used as biosensors, and modified biological properties (either enhanced biocompatibility or enhanced antimicrobial activity). However, not all the nanotubes are carbon nanotubes, and original properties were also reported for dendrimers associated with non-CNTs, such as the elaboration of specific nano-filters and of highly efficient and reusable catalysts. Furthermore, non-CNTs constituted of dendrimers, particularly those obtained by layer-by-layer deposition of positively and negatively charged dendrimers associated with quantum dots display an excellent detection limit for DNA hybridization (10 fM).


[The effectiveness of cardiac contractility modulation in patients with chronic heart failure and atrial fibrillation: results of the 12-month follow-up].
To evaluate the efficacy, safety and effect on the prognosis of cardiac contractility modulation (CCM) in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction and atrial fibrillation compared with the group of only optimal drug therapy (ODT) of the 12-month follow-up. Patients (n=200) were sequentially included in two groups: group 1 patients with CHF who are on ODT in combination with implanted CCM devices (n=100), group 2 comparison patients with CHF who receive only ODT (n=100). Initially and after 12 months, 12-channel electrocardiography (ECG), transthoracic echocardiography, daily ECG-monitoring, determination of the level of NT-proBNP, a six-minute walk test and an assessment of the quality of life according to the Minnesota Questionnaire were performed. In the CCM therapy group, a significant clinical improvement was revealed, which was expressed in the form of a decrease in functional class CHF by NYHA (New York Heart Association), an increase in the distance of a six-minute walk test and an improvement in the quality of life according to Minnesota Questionnaire, as well as an improvement in left ventricle contractile function compared to the ODT group. The absence of a proarrhythmogenic effect of the CCM was shown. There was a significant decrease in the frequency of the readmission due to CHF and the probability of achieving the combined endpoint in the CCM therapy group compared with only ODT. The use of CCM in patients with CHF and atrial fibrillation is an effective and safe method of therapy that leads to the development of reverse remodeling of the myocardium, improves the clinical status of patients and reduces the frequency of readmission due to decompensation of CHF.


Double-chambered right ventricle: surgical experience and anatomical considerations.
Fourteen patients with double-chambered right ventricle underwent surgical treatment and repair of associated anomalies. The anomalous muscle band was isolated in 5 cases, associated with membranous ventricular septal defect in 7, with discrete sub-aortic stenosis in one and with double outlet right ventricle in one. All patients survived. The obstructing muscular band was a hypertrophic structure identifiable either with a displaced moderator band, still related to the anterior papillary muscle, or with a giant septoparietal band, inserting to the anterior free wall and occasionally present in normal hearts. According to this interpretation, referring the obstructive band to the septomarginal complex, double-chambered right ventricle should not be regarded strictly as a truncoconal malformation.


[Study on the tribochemistry of antiwear additive BA1 by FTIRM].
This paper studied the tribochemistry of antiwear additive BA1 by FTIR microscope technique. We observed the changes of physical properties, interpreted the infrared spectra of the products in the track and concluded the chemical mechanism through the change of BA1 concentration, load and rubbing time. The results shows that the BA1 was decomposed, oxided and a thin film was produced when rubbed. This film makes the rubbing efficiency less.


Local Action of Increased Pressure Induces Hyperpolarization Electrical Signals and Influences Photosynthetic Light Reactions in Wheat Plants.
Long-distance electrical signals caused by the local action of stressors influence numerous physiological processes in plants including photosynthesis and increase their tolerance to the action of adverse factors. Depolarization electrical signals were mainly investigated; however, we earlier showed that hyperpolarization electrical signals (HESs) can be caused by moderate stressors (e.g., local moderate heating) and induce photosynthetic inactivation. We hypothesized that HESs are related to stressor-induced increases in the hydrostatic pressure in the zone of action of the stressor and following the propagation of a hydraulic wave. In the current work, we tested this hypothesis through the direct investigation of electrical signals induced by the local action of artificially increased pressure and an analysis of the subsequent photosynthetic changes in the nonirritated parts of plants. The electrical signals and parameters of photosynthetic light reactions were investigated in wheat plants. The local action of the increased pressure was induced by the action of weights on the wheat leaf. Extracellular electrodes were used for electrical signal measurements. Pulse-amplitude-modulation fluorescent imaging was used for measurements of the quantum yield of photosystem II and nonphotochemical quenching of chlorophyll fluorescence in wheat leaves. It was shown that the local action of pressure on wheat leaf induced electrical signals near the irritated zone: HESs were caused by low pressure (10 kPa) and depolarization signals were induced by high pressure (100 kPa). The local action of moderate pressure (50 kPa) induced weak electrical signals near the irritated zone; however, HESs were observed with increasing distance from this zone. It was also shown that the local action of this moderate pressure induced the photosynthetic inactivation (decreasing the quantum yield of photosystem II and increasing the nonphotochemical quenching of chlorophyll fluorescence) in the nonirritated parts of the wheat leaves. Thus, our results show that the local action of the increased pressure and, probably, subsequent propagation of the hydraulic wave induce electrical signals (including HESs) and photosynthetic inactivation in nonirritated parts of plants that are similar to ones caused by the local action of moderate stressors (e.g., moderate heating). This means that both HESs and depolarization electrical signals can have a hydraulic mechanism of propagation.


Interdependence between the Social and Material Convoy: Links between Volunteering, Widowhood, and Housing Transitions.
Relocation in older adulthood may occur due to triggering events, such as widowhood. Guided by Kahn and Antonucci's convoy model, this study explores the influence of volunteering on decision to relocate following the death of a spouse. Using three waves of data from the Health and Retirement Study (2006, 2008, and 2010), 5,146 community-dwelling married older individuals who were 65 years or older in 2008 were included. Findings from two multinomial logistic regression models showed that widows and widowers who were not volunteering in 2008 were more likely to move out of area in 2010 than their married counterparts, whereas the relationship between widowhood and relocation was not detected among those involved in volunteering. This article emphasizes the interdependency of social relationships and residences, a fundamental of one's material convoy, for older adults. Volunteering experiences may not only affect instrumental and emotional support after the loss of a key anchor in one's social convoy, but may also facilitate a widowed older adult to age in place rather than relocate.


Italian consensus and recommendations on diagnosis and treatment of low-grade gliomas. An intersociety (SINch/AINO/SIN) document.
In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.


A case of intravascular lymphoma presenting as myelopathy diagnosed with a skin biopsy.
Intravascular lymphoma (IVL) is a rare subtype of non-Hodgkin lymphoma with exclusively or predominantly intravascular proliferation. Without therapeutic intervention, the neurologic involvement is rapidly progressive and inevitably fatal. Most of the IVL patients have prominent or exclusive manifestations in the nervous system and there are several reports of patients presenting with spinal symptoms. A 68-year-old male patient admitted with the complaints of progressive paraparesis. T2-weighted magnetic resonance imaging (MRI) of the spinal cord showed hyperintense lesions in the thoracic cord. A diagnosis of myelitis of unknown etiology was assumed, and steroid pulse therapy was administered, which temporarily improved the patient's symptoms. However, the paraparesis recurred, and other symptoms, such as vertigo, psychosis, and seizures, developed 1-month after the initial treatment. Multiple high-intensity lesions were detected in the bilateral subcortical white matter on DW MRI. Based on the patient's clinical course, IVL was suspected; however, obtaining histological confirmation was not possible, as no Gd-enhanced brain or spinal lesions were identified and repeated cerebrospinal fluid examinations were negative for tumor cells. Therefore, a random skin biopsy was performed, and IVL was diagnosed. Obtaining a comparatively favorable outcome was possible owing to the subsequent administration of R-CHOP chemotherapy. IVL should be included in the differential diagnosis of atypical case of presumed myelitis. An early diagnosis and chemotherapy is crucial for improving the patient's outcome. When obtaining a diagnosis based on tissues other than skin is difficult, a random skin biopsy should be considered in patients with suspected IVL.


Using Monte Carlo methods to commission electron beams: a feasibility study.
The purpose of this study was to investigate the feasibility of using Monte Carlo methods to assist in the commissioning of electron beams for a medical linear accelerator. The EGS4/BEAM code system was used to model an installed linear accelerator at this institution. Following an initial tuning of the input parameters, dosimetry data normally measured during the machine commissioning was calculated using the Monte Carlo code. All commissioning data was calculated for 6- and 12-MeV electron beams, and a subset of the commissioning data was calculated for the 20-MeV electron beams. On central axis, calculated percentage depth dose, cross-beam profiles, cone-insert ratios, and air-gap factors were generally within 2% of Dmax or 1 mm of the measured commissioning data; however, calculated open-cone ratios were not within 2%, in most cases. Calculated off-axis dose profiles for small fields were generally within the 2% (1-mm) criteria; however, calculated dose profiles for larger (open cone) fields frequently failed the 2% (1-mm) criteria. The remaining discrepancies between Monte Carlo calculations and measurement could be due to flaws in the Monte Carlo code, inaccuracies in the simulation geometry, the approximation of the initial source configuration, or a combination of the above. Although agreement between Monte Carlo calculated and measured doses was impressive and similar to previously published comparisons, our results did not prove our hypothesis that Monte Carlo calculations can generate electron commissioning data that is accurate within 2% of Dmax or 0.1 cm over the entire range of clinical treatment parameters. Although we believe that this hypothesis can be proved, it remains a challenge for the medical physics community. We intend to pursue this further by developing systematic methods for isolating causes of these differences.


Adaptation of the egg of the desert beetle, Microdera punctipennis (Coleoptera: Tenebrionidae), to arid environment.
Microdera punctipennis Kaszab (Coleoptera: Tenebrionidae) is an endemic species in Guerbantonggut desert in China. To explore the ways that M. punctipennis egg adapts to dry desert environment, morphological characteristics of the egg was investigated along with the egg of the nondesert beetle Tenebrio molitor (Coleoptera: Tenebrionidae). Water loss rate and survival rate of these eggs under different dry treatments (relative humidity0, 10, and 20%) were measured to evaluate the desiccation resistance of the eggs at different developmental stages (day 0, 2, and 5 eggs). Our results showed that the 50-egg weight in T. molitor was heavier than M. punctipennis, while the 50-first-instar larva weight in T. molitor was almost the same as in M. punctipennis. The water loss rate of M. punctipennis egg under dry conditions was significantly lower than T. molitor, and the egg survival rate was significantly higher than T. molitor. The estimated developmental threshold temperature of M. punctipennis egg was 18.30°C, and the critical thermal maximum of M. punctipennis egg is above 39°C. These features partly account for the adaptability of M. punctipennis to desert environment in egg stage.


Cytidine deaminase 435C>T polymorphism relates to gemcitabine-platinum efficacy and hematological toxicity in Chinese non-small-cell lung cancer patients.
CDA 435C>T is reported as a functional SNP but there is no relevant research on the efficacy/hematological toxicity of gemcitabine-platinum treatment in Chinese non-small-cell lung cancer (NSCLC) patients. In this study, 63 patients who received radical resection (stage IB or IIIA) and 100 advanced NSCLC (stage IIIB or IV) patients have been collected, and all were treated with gemcitabine-platinum regimens from February of 2017 to February 2019. CDA 435C>T polymorphisms have been detected by PCR and direct sequencing. CT scan results and blood routine examinations have been collected to evaluate the efficacy and hematological toxicity. Then the relationships have been analyzed about CDA 435C>T. We found that T allele carriers have better therapy response (p<0.05). Patients carrying CDA 435C/T or T/T genotypes are statistically associated with a better efficacy (p<0.05) but are more prone to leukopenia (p<0.05). Although there is no difference in grade III-IV hematologic toxicity of 163 patients (p>0.05), in the case of 100 stage IIIB-IV patients, the CDA 435C/T and T/T have an increased risk (p<0.05). Regarding the CDA 435C>T polymorphism in the Chinese population, in patients with the mutant T allele, gemcitabine is more effective, but they are more prone to suffering from hematological toxicity, especially the late-stage patients.


Use of a Phase Reference for Field Mapping with Amplitude Images at Low Field
We present a method to obtain MRI amplitude images that can picture the magnetic field due to arbitrary shaped magnetized objects. The method employees the gradient recalled echo sequence and two sets of data obtained in separate experiments, one of which provides a phase reference image making it possible to eliminate the effect of the B0 field inhomogeneities. The final magnitude images have a good signal-to-noise even at low fields, and provide qualitative as well as quantitative information about the magnetic field produced by the ferromagnetic object. As an example the method is applied to study the field produced by a small metal piece in a 500-G scanner, and the experimental results are compared with numerical simulations. Copyright 1998 Academic Press.


Potential role of abnormal ion transport in the pathogenesis of chronic sinusitis.
To create well-differentiated cultures of normal and chronic sinusitis paranasal sinus epithelial cells and to compare their electrophysiologic properties. In vitro investigation using primary sinus epithelial cells, initially cultured on plastic tissue culture dishes. Cells were characterized by means of immunocytochemical analysis and then passaged to air-liquid interface culture conditions. The morphologic features of air-liquid interface cultures were assessed using light and electron microscopy. Epithelial Na(+) channel, Na(+)-K(+)-2Cl(-) cotransporter, cystic fibrosis transmembrane conductance regulator, and Ca(2+)-activated Cl(-) channel function were investigated in Ussing chambers. Specimens were obtained from 15 patients undergoing transsphenoidal pituitary procedures, tumor removal, or trauma repair and from 9 patients with chronic sinusitis. After culture at an air-liquid interface for 21 days, the epithelium was pseudostratified and contained basal, mucous secretory, and ciliated cells. There were no detectable morphologic differences between normal and chronic sinusitis cells. In cultures of normal cells, median basal short circuit current was 4.7 microA/cm(2), and Na(+) transport, defined as the amiloride hydrochloride-sensitive component, was approximately 20% of the total. Basal and amiloride-sensitive short circuit currents were greater in cultures of chronic sinusitis cells. Basal short circuit currents in both types of cultures were insensitive to the Cl(-) transport inhibitor bumetanide, but all responded to forskolin or uridine triphosphate. After amiloride pretreatment, forskolin and uridine triphosphate responses were greater in chronic sinusitis cells. We established methods for well-differentiated sinus epithelial cultures. The cells exhibited Na(+) absorption and Cl(-) secretion, and elevated rates of ion transport may be pathophysiologically relevant in chronic sinusitis.


[Characteristics and numerical simulation of surface albedo in temperate desert steppe in Inner Mongolia].
Based on the meteorological and biological observation data from the temperate desert steppe ecosystem research station in Sunitezuoqi of Inner Mongolia during growth season (from May 1st to October 15th, 2008), the diurnal and seasonal characteristics of surface albedo in the steppe were analyzed, with related model constructed. In the steppe, the diurnal variation of surface albedo was mainly affected by solar altitude, being higher just after sunrise and before sunset and lower in midday. During growth season, the surface albedo was from 0.20 to 0.34, with an average of 0.25, and was higher in May, decreased in June, kept relatively stable from July to September, and increased in October. This seasonal variation was related to the phenology of canopy leaf, and affected by precipitation process. Soil water content (SWC) and leaf area index (LAI) were the key factors affecting the surface albedo. A model for the surface albedo responding to SWC and LAI was developed, which showed a good performance in consistent between simulated and observed surface albedo.


Campylobacter jejuni outer membrane proteins are antigenic for humans.
All Campylobacter jejuni strains have a major outer membrane protein (OMP) that migrates between a molecular weight of 41,000 (41K) and 45K and represents more than 50% of protein present, plus several more minor bands. Using 125I-radiolabeled C. jejuni cells in a radioimmunoprecipitation procedure to assess whether the OMPs were antigenic, we studied serum from rabbits immunized with C. jejuni cells, from humans convalescent after C. jejuni infection, and from appropriate controls. In this assay, the major OMP was the major antigen for both homologously and heterologously immunized rabbits and infected humans but not for controls. Minor bands at 29K and 50K were also antigenic. We tested human and animal sera in a Western blot procedure using anti-immunoglobulin A (IgA), anti-IgG, or anti-IgM conjugates. Homologous and heterologous immune rabbit serum, but not control serum, recognized a large number of membrane proteins between 15K and 91K, including the major OMP. Both Campylobacter spp.-infected and healthy humans showed IgA, IgG, and IgM responses to the major OMP, although the response was more pronounced in the former group. Sera from infected humans recognized several minor bands to a significantly greater extent than control sera did. Our data suggest that there is antigenic similarity between the OMPs of different C. jejuni strains and that some of these OMPs recognized by infected animals and humans have vaccinogenic potential.


Prostaglandins mediate suppression of lymphocyte proliferation and cytokine synthesis in acute Trypanosoma cruzi infection.
Suppression of host lymphoproliferative responses to mitogens and Ag is characteristically seen during acute infection with the protozoan parasite Trypanosoma cruzi. We investigated the reciprocal regulation of prostaglandins (PG), TNF-alpha, and nitric oxide (NO) production and their effects on cytokine production and lymphoproliferative responses to parasite Ag and to Con A by spleen cells (SC) from T.-cruzi-infected mice. Large amounts of PGE2, TNF-alpha, and NO were produced during infection. TNF-alpha stimulated PG and NO synthesis, while both mediators inhibited TNF-alpha synthesis. Blocking PG also reduced NO synthesis indicating that PG stimulate NO production. Treatment with indomethacin or NMLA stimulated lymphoproliferation on days 6 and 22 of infection; on day 14, when suppression of proliferation and NO production was maximal, combined inhibition of NO and PG production restored parasite Ag specific and Con A proliferative responses. Blocking PG or NO production increased IL-2, IFN-gamma, and TNF-alpha, but not IL-12 production by SC; IL-10 levels were not reduced. Indomethacin-treated infected mice had higher mortality compared to untreated infected animals. The data indicate that PG, together with NO and TNF-alpha, participate in a complex circuit that controls lymphoproliferative and cytokine responses in T. cruzi infection.


Metformin and trametinib have synergistic effects on cell viability and tumor growth in NRAS mutant cancer.
Attempts to directly block the mutant neuroblastoma rat sarcoma oncogene (NRAS) protein, a driving mutation in many cancer types, have been unsuccessful. Current treatments focus on inhibition of different components of NRAS' two main downstream cascades: PI3K/AKT/mTOR and MAPK. Here we test a novel dual therapy combination of metformin and trametinib on a panel of 16 NRAS mutant cell lines, including melanoma cells, melanoma cells with acquired trametinib resistance, lung cancer and neuroblastoma cells. We show that both of the main downstream cascades of NRAS can be blocked by this combination: metformin indirectly inhibits the PI3K/AKT/mTOR pathway and trametinib directly impedes the MAPK pathway. This dual therapy synergistically reduced cell viability in vitro and xenograft tumor growth in vivo. We conclude that metformin and trametinib combinations are effective in preclinical models and may be a possible option for treatment of NRAS mutant cancers.


Obstruction of a Codman-Hakim programmable valve by a migrating pressure control cam.
Although the Codman-Hakim programmable valve is popular, several problems arising from its design have been described. The authors report an additional cause of shunt obstruction in the system. A 6-year-old girl who had received a ventriculoperitoneal shunt with the Codman-Hakim programmable valve system presented with worsening consciousness. The valve proved hard to flush, and emergency revision of the valve was performed. Examination of the extracted valve revealed that the pressure control cam had migrated into the outlet of the valve, thus causing the obstruction. A crack in the plastic housing surrounding the cam suggesting a past impact to the system was also revealed. These factors should thus be kept in mind as potential sources of obstruction of the valve system, especially in patients susceptible to episodes of head impact.


Buspirone hydrochloride: a unique new anxiolytic agent. Pharmacokinetics, clinical pharmacology, abuse potential and clinical efficacy.
Buspirone is the first of a new class of anxioselective agents, the azaspirodecanediones. It achieves peak serum concentrations within one hour and has a serum half-life of 2 to 5 hours. Animal studies have suggested antianxiety activity and the absence of abuse potential. Buspirone is both a dopamine agonist and antagonist, and appears to interact with numerous neurochemical systems in the brain, but not with gamma-aminobutyric acid or at benzodiazepine receptors. Buspirone increases prolactin and growth hormone levels under experimental conditions. In healthy subjects, it has much less effect on psychomotor performance and electroencephalographic results than diazepam. Buspirone offsets some of the impairment due to alcohol when the agents are combined. The drug has anxiolytic properties comparable to those of diazepam, with less sedating effects. It had no abuse potential in tests with casual drug users.


Low density lipoprotein-apheresis decreases oxidized low density lipoproteins and monocyte adhesion to endothelial cells.
The mutual interaction between monocytes and low density lipoprotein (LDL) in atherogenesis prompted a test of the hypothesis that LDL-apheresis could reduce the adhesive properties of monocytes to endothelium; and therefore interfere with a key mechanism in atheroma formation. Five patients affected by heterozygous familial hypercholesterolemia were studied. All patients received LDL-apheresis treatment with selective adsorption of LDL-cholesterol on dextran-sulphate columns. Low density lipoprotein particles were isolated by sequential preparative ultracentrifugation and subfractionated by ion exchange high performance liquid chromatography. Thiobarbituric acid reacting products of lipid peroxidation were measured fluorometrically. Vitamin E was estimated by high performance liquid chromatographic technique. Monocytes were isolated from patients blood before and 1 day after LDL-apheresis by Percoll gradient. The blood samples for monocyte adhesion were drawn from control subjects for 2 consecutive days. The adhesion of monocytes to an endothelial monolayer was evaluated by assaying the peroxidase content of the adherent monocytes. Low density lipoprotein-apheresis reduced total cholesterol (-65%; p < 0.01), LDL-cholesterol (-75%; p < 0.01), triglycerides (-51%; p < 0.05), and fibrinogen (-28%; p < 0.01). With LDL-apheresis treatment, a reduction of 54% in oxidized LDLs was observed; vitamin E concentration significantly increased in LDLs (+ 14.2%; p < 0.05). The monocyte adhesion decreased by approximately 61% after apheresis; the variation became statistically significant (-65%; p < 0.01) when endothelial cells were stimulated by lipopolysaccaride.


Calcium Nanoparticles Impregnated With Benzenedicarboxylic Acid: A New Approach to Alleviate Combined Stress of DDT and Cadmium in Brassica alboglabra by Modulating Bioacummulation, Antioxidative Machinery and Osmoregulators.
At present, the alleviation of stress caused by climate change and environmental contaminants is a crucial issue. Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant (POP) and an organochlorine, which causes significant health problems in humans. The stress caused by cadmium (Cd) and the toxicity of DDT have direct effects on the growth and yield of crop plants. Ultimately, the greater uptake and accumulation of DDT by edible plants affects human health by contaminating the food chain. The possible solution to this challenging situation is to limit the passive absorption of POPs into the plants. Calcium (Ca) is an essential life component mandatory for plant growth and survival. This study used impregnated Ca (BdCa) of benzenedicarboxylic acid (Bd) to relieve abiotic stress in plants of Brassica alboglabra. BdCa mitigated the deleterious effects of Cd and reduced DDT bioaccumulation. By increasing the removal efficacy (RE) up to 256.14%, BdCa greatly decreased pollutant uptake (Cd 82.37% and DDT 93.64%) and supported photosynthetic machinery (86.22%) and antioxidant enzyme defenses (264.73%), in applied plants. Exogenously applied Bd also successfully improved the antioxidant system and the physiochemical parameters of plants. However, impregnation with Ca further enhanced plant tolerance to stress. This novel study revealed that the combined application of Ca and Bd could effectively relieve individual and combined Cd stress and DDT toxicity in B. alboglabra.


Predictors of anxiety in multiple sclerosis.
The aims of this study were to (1) identify the predictors of symptoms of anxiety, and (2) evaluate the differential association of somatic and nonsomatic symptoms of depression on anxiety over time in persons with multiple sclerosis (MS). Participants were 513 persons with MS who previously enrolled in a study exploring the experience of living with MS and completed a 4-month follow-up survey. The main outcome measure used was the Hospital Anxiety and Depression Scale-Anxiety. Demographic, disease-associated variables (time since onset of MS, Expanded Disability Status Scale Mobility, pain, and fatigue), and Time 1 psychological variables were entered into a hierarchical regression model to examine predictors at baseline for anxiety symptoms at Time 2. A large portion of the sample was White (92%), female (82%), and had relapsing-remitting MS (57%). After adjusting for demographic and disease related variables, anxiety (β <.001), employment (β = .07), and nonsomatic depressive symptoms (β = .10) at baseline significantly predicted anxiety at Time 2, ps < .05. Interactions revealed significant effects for time since onset of MS and somatic symptoms as well as time since onset and nonsomatic symptoms, ps < .05. Nonsomatic symptoms were more linked to anxiety early in the disease and somatic symptoms were more prominently linked to anxiety later in the disease. Findings suggest that nonsomatic symptoms of depression and employment predict anxiety in MS. The relationship between different aspects of depression and anxiety may change over the course of the disease.


Hypnotic activity of brotizolam: a study in general practice.
A double-blind, crossover study was carried out in general practice on the hypnotic activity of 0.25 mg brotizolam in patients aged between 18 and 70 years complaining of insomnia (11 men, 28 women). Patients reported that they slept better, that they awoke less frequently and that they slept longer with brotizolam than with placebo. Overall the patients preferred brotizolam to placebo, and subjective assessments of well-being after brotizolam did not differ from those after placebo. Brotizolam was well tolerated and there were no incidents of note.


Glass-forming property of the system diethyl sulphoxide/water and its cryoprotective action on Escherichia coli survival.
In this work the thermal properties of diethyl sulphoxide (Et2SO), as well as its cryoprotective ability are studied and related to other well-known cryoprotectant substances, like dimethyl sulphoxide (Me2SO). We have investigated the thermal properties of Et2SO/water systems using Differential Scanning Calorimetry at a very low heating/cooling rate (2 degrees C/min). Liquid/solid or glassy/crystalline transitions have been observed only for the solutions with content of Et2SO ranging from 5 up to 40% w/w and/or greater than 85%. In the 45-75% w/w Et2SO range we have found a noticeable glass-forming tendency and a great stability of the amorphous state to the reheating. In samples with Et2SO content ranging from 80 to 85%, we observed a great stability of the glass forming by cooling, but a lesser stability to the subsequent reheating. The glass-forming tendency of these solutions is discussed in terms of existing competitive interactions between molecules of Et2SO, on the one hand, and Et2SO and water molecules, on the other hand. The results are well explainable on the basis of the model structure of water/Et2SO solutions, deduced by Raman and infrared studies [J. Mol. Struct. 665 (2003) 285-292]. The cryoprotective ability of Et2SO on Escherichia coli survival has been also investigated, and a comparison among Et2SO and other widely used cryoprotectants, like Me2SO and glycerol has been done. Survival of E. coli, determined after freezing-thawing process, was maximal at 45% w/w Et2SO (more than 85% viability). It should be noted that at the same concentration the survival is only about 35% in the presence of Me2SO and not more than 15% in the presence of glycerol. These features are well consisted with the glass-forming properties of Et2SO.


Effects of remifentanil on hemodynamics, liver function and ICAM-1 expression in liver cancer patients undergoing surgery.
The objective of the present study was to investigate the effects of remifentanil on hemodynamics, liver function, and expression of intercellular adhesion molecule-1 (ICAM-1) in patients with liver cancer undergoing surgery. A total of 60 patients who underwent liver cancer resection in The First People's Hospital of Xiangyang, Hubei University of Medicine from January 2014 to January 2016 were selected, including 33 males and 27 females, with an average age of 54.12±4.77 years. Patients were randomly divided into the control group and experimental group (n=30 each). The control group and experimental group were anesthetized with propofol/isoflurane and remifentanil/propofol, respectively. In addition to general parameters, the following parameters were analyzed: mean systolic blood pressure and mean diastolic blood pressure were obtained before treatment, during anesthesia induction and intubation, during blockade of traction reflexes in surgery, and before extubation at the end of surgery. The recovery time from anesthesia withdrawal to spontaneous breathing, time of eye opening, time of extubation, and level of consciousness were recorded. Liver expression of ICAM-1 was measured with SABC staining, and the expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were recorded on the first, third, fifth, and seventh day after surgery. According to hemodynamic parameters, patients in the experimental group experienced a more stable condition than patients in the control group (P<0.05). In addition, the recovery time of the experimental group was shorter than that of the control group (P<0.05). Markers of liver function (AST, ALT and TBIL) of the two groups after surgery were higher than those before surgery, and the increases of the experimental group were significantly lower than those of the control group. ICAM-1 expression in the experimental group was significantly lower than in the control group (P<0.05). In conclusion, anesthesia with remifentanil better maintained the stability of hemodynamics, played a protective role against hepatic ischemia-reperfusion injury, and reduced ICAM-1 expression.


Plasticity-related genes in brain development and amygdala-dependent learning.
Learning about motivationally important stimuli involves plasticity in the amygdala, a temporal lobe structure. Amygdala-dependent learning involves a growing number of plasticity-related signaling pathways also implicated in brain development, suggesting that learning-related signaling in juveniles may simultaneously influence development. Here, we review the pleiotropic functions in nervous system development and amygdala-dependent learning of a signaling pathway that includes brain-derived neurotrophic factor (BDNF), extracellular signaling-related kinases (ERKs) and cyclic AMP-response element binding protein (CREB). Using these canonical, plasticity-related genes as an example, we discuss the intersection of learning-related and developmental plasticity in the immature amygdala, when aversive and appetitive learning may influence the developmental trajectory of amygdala function. We propose that learning-dependent activation of BDNF, ERK and CREB signaling in the immature amygdala exaggerates and accelerates neural development, promoting amygdala excitability and environmental sensitivity later in life.


[Dynamics of psychogenic depressive disorders occasioned by the birth of a sick child into a family].
In order to study the time-course of depressive neurosis, the author followed up 51 women living under the conditions of a prolonged psychotraumatic situation (the presence in the family of a child with infantile cerebral paralysis). Two variants of depressive disturbances formation closely associated with the premorbid characteristics of the patients' personality have been identified. It was shown that with passing years the neurotic disturbances led to a clinically homogeneous neurotic development of depressive nature. The author outlines the mechanism of the time-course of the given type of borderline disturbances, proceding from neurotic depressive reactions to depressive neurosis and further to a specific development of the personality.


Early contingent negative variation (CNV) shows a small symmetrical negativity in a somatosensory paradigm.
The influence of sensory modulation on the early stage of information processing was investigated with a somatosensory contingent negative variation (CNV) paradigm. Whether or not even a somatosensory input as well as auditory or visual stimulus to one hemisphere elicits the symmetrical "early CNV" was also examined. Eleven normal individuals (3 males, 8 females) performed a conventional CNV paradigm with a click sound as the warning stimulus (WS) and a red light flash as the imperative stimulus (IS). Nine individuals (5 males, 4 females) did the somatosensory CNV paradigm with paired electrical stimuli as WS and IS. The subjects were instructed to press a button in response to IS as fast as possible. The early CNV amplitude was smaller and P300 latency was longer in somatosensory paradigm than conventional paradigm. In addition, the latency of P100 in a somatosensory paradigm was longer than that of N100 in a conventional paradigm. These findings suggest that the initiation of early detection, reflected by P100, the initiation of cognition, reflected by P300, and orienting response, reflected by early CNV, are delayed in a somatosensory CNV paradigm. Furthermore, all event-related potentials (ERPs) evoked by somatosensory stimuli showed a bilateral symmetry.


Fluoride resistance and adherence of selected strains of Streptococcus mutans to smooth surfaces after exposure to fluoride.
The fluoride resistance and smooth surface adherence characteristics of Streptococcus mutans were examined using tooth model and radioactive cell assays. Resistance to 600 ppmF by S. mutans isolated from the plaque of radiation-induced xerostomia patients receiving daily topical applications of a caries preventive 1% NaF gel was transient. Resistance induced in vitro in two strains of S. mutans by exposure to gradually increasing levels of NaF was apparently permanent. Smooth surface adherence by both fluoride-sensitive and -resistant strains of S. mutans 6715 in a tooth model system was slightly diminished by 1% NaF gel. Fluoride-resistant strains retained 89 to 93% of their adherence capability in 600 ppmF, as determined by the cell radiolabeling assay.


Identification of MicroRNAs in Zebrafish Spermatozoa.
MicroRNAs (miRNAs) participate in almost all biological processes. Plenty of evidences show that some testis- or spermatozoa-specific miRNAs play crucial roles in the process of gonad and germ cell development. In this study, the spermatozoa miRNA profiles were investigated through a combination of illumina deep sequencing and bioinformatics analysis in zebrafish. Deep sequencing of small RNAs yielded 11,820,680 clean reads. By mapping to the zebrafish genome, we identified 400 novel and 204 known miRNAs that could be grouped into 104 families. Furthermore, we selected the six highest expressions of known miRNAs to detect their expression patterns in different tissues by stem-loop quantitative real-time polymerase chain reaction. We found that among the six miRNAs, dre-miR-202-5p displayed specific and high expression in zebrafish spermatozoa and testis. Fluorescence in situ hybridization analysis indicated that dre-miR-202-5p was predominantly expressed in all kind of germ cells at different spermatogenetic stages, including spermatogonia and spermatozoa, but barely expressed in the germ cells in the ovary. This sex-biased expression pattern suggests that dre-miR-202-5p might be related to spermatogenesis and the functioning of spermatozoa. The identification of miRNAs in zebrafish spermatozoa and germ cells offers new insights into the spermatogenesis and spermatozoa in the teleost and other vertebrates.


Teaching Research Skills to Student Pharmacists in One Semester: An Applied Research Elective.
Objectives. To implement and assess the effectiveness of a 15-week applied research elective that introduced students to secondary database analysis in clinical pharmacy. Design. In small groups, students learned, planned, developed and completed a secondary database study to answer an original research question. During one semester, they completed a basic research proposal and Institutional Review Board application, created and analyzed a National Health and Nutrition Examination Survey (NHANES) sample dataset, and reported the results in an abstract and poster presentation. Assessment. All deliverables resulted in high grades. Mean scores on a survey conducted following completion of the course revealed that students strongly agreed or agreed that they had high levels of confidence about performing research-related tasks. Eight student groups delivered poster presentations at professional conferences. Conclusions. Within one semester, student pharmacists with no or little research experience completed original research projects that contributed to pharmacy practice knowledge. They felt highly confident doing research-related tasks, and successfully disseminated their studies beyond the classroom.


A phase I study of fever-range whole body hyperthermia (FR-WBH) in patients with advanced solid tumours: correlation with mouse models.
Various studies in animal tumour models have revealed the potential of fever-range whole body hyperthermia (FR-WBH) to be used in cancer therapy. To determine the safety of FR-WBH treatment in the clinic, patients with advanced solid tumours were heated in the outpatient setting to 39-39.5 degrees C for 3 or 6h, or 39.5-40 degrees C for 6h using the Heckel-HT 2000 apparatus. These WBH treatments were well tolerated, with no significant adverse events related to cardiac, hepatic, renal or pulmonary systems. In the majority of patients, flow cytometric analysis of peripheral blood leukocyte populations indicated that there were transient decreases in the number of circulating T lymphocytes and a concomitant decrease in the number of L-selectin positive lymphocytes in the peripheral blood. These findings closely mimic the affects seen previously in pre-clinical murine studies in which this same fever-like treatment was shown to inhibit tumour growth. These studies have established the safety of this treatment and will allow for future clinical trials where application of FR-WBH treatment can be combined with other anti-cancer therapies, including immunotherapy and chemotherapy.


Measurement of bone marrow lesions by MR imaging in knee osteoarthritis using quantitative segmentation methods--a reliability and sensitivity to change analysis.
Longitudinal assessment of bone marrow lesions (BMLs) in knee osteoarthritis (KOA) by MRI is usually performed using semi-quantitative grading methods. Quantitative segmentation methods may be more sensitive to detect change over time. The purpose of this study was to evaluate and compare the validity and sensitivity to detect changes of two quantitative MR segmentation methods for measuring BMLs in KOA, one computer assisted (CAS) and one manual (MS) method. Twenty-two patients with KOA confined to the medial femoro-tibial compartment obtained MRI at baseline and follow-up (median 334 days in between). STIR, T1 and fat saturated T1 post-contrast sequences were obtained using a 1.5 T system. The 44 sagittal STIR sequences were assessed independently by two readers for quantification of BML. The signal intensities (SIs) of the normal bone marrow in the lateral femoral condyles and tibial plateaus were used as threshold values. The volume of bone marrow with SIs exceeding the threshold values (BML) was measured in the medial femoral condyle and tibial plateau and related to the total volume of the condyles/plateaus.The 95% limits of agreement at baseline were used to determine the sensitivity to change. The mean threshold values of CAS and MS were almost identical but the absolute and relative BML volumes differed being 1319 mm3/10% and 1828 mm3/15% in the femur and 941 mm3/7% and 2097 mm3/18% in the tibia using CAS and MS, respectively. The BML volumes obtained by CAS and MS were significantly correlated but the tissue changes measured were different. The volume of voxels exceeding the threshold values was measured by CAS whereas MS included intervening voxels with normal SI.The 95% limits of agreement were narrower by CAS than by MS; a significant change of relative BML by CAS was outside the limits of -2.0%-4.7% whereas the limits by MS were -6.9%-8.2%. The BML changed significantly in 13 knees using CAS and in 10 knees by MS. CAS was a reliable method for measuring BML and more sensitive to detect changes over time than MS. The BML volumes measured by the two methods differed but were significantly correlated.


Antigens of the basement membrane and the peritumoral stroma in human colonic adenocarcinomas: an immunofluorescence study.
Twenty colonic adenocarcinomas were studied by immunofluorescence with antisera against components of the basement membrane: type IV collagen, laminin and heparan sulfate-rich proteoglycan, as well as antisera against antigens of the connective tissue: type-III collagen, fibronectin and hyaluronectin. Marked alterations of the basement membranes were consistently observed on staining with each one of the first three antisera. In contrast, staining of the normal components of connective tissue was in most cases as intense as in normal colonic mucosa. Hyaluronectin, a marker of peritumoral stroma, was found to be present in 12 out 15 tumors studied.


Effect of a MAST Exercise Program on Anthropometric Parameters, Physical Fitness, and Serum Lipid Levels in Obese Postmenopausal Women.
The purpose of this study was to examine an influence of a mixed aerobic and strength training program (MAST) on anthropometry, serum lipid levels, physical performance, and functional fitness in obese postmenopausal women. The MAST sessions were held three times per week, and the exercise program lasted for 10 weeks. The exercise group demonstrated a statistically significant improvement in maximal oxygen uptake, a waist/hip ratio, and strength of the upper and lower body. An increase in LDL-C levels was observed in the control group. A 10-week MAST program encompassing Nordic-walking as an aerobic component, and strength exercises, induces positive changes in functional fitness, HDL-C, LDL-C and a waist/hip ratio in obese postmenopausal women. The observed changes implicate an increase in a health-related quality of life among the women administered to the physical exercise program.


Genetics of Type 2 Diabetes in U.S. Hispanic/Latino Individuals: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in U.S. Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2,499 T2D case subjects and 5,247 control subjects from six Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance levels. Conditional analysis on known index single nucleotide polymorphisms (SNPs) indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (odds ratio 1.49 [95% CI 1.27-1.75]). This association was consistent across Hispanic/Latino background groups and replicated in the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium. Among 80 previously known index SNPs at T2D loci, 66 SNPs showed consistency with the reported direction of associations and 14 SNPs significantly generalized to the HCHS/SOL. A genetic risk score based on these 80 index SNPs was significantly associated with T2D (odds ratio 1.07 [1.06-1.09] per risk allele), with a stronger effect observed in nonobese than in obese individuals. Our study identified a novel independent signal suggesting an African ancestry-specific allele at KCNQ1 for T2D. Associations between previously identified loci and T2D were generally shown in a large cohort of U.S. Hispanics/Latinos.


Model fidelity of group antenatal and postnatal care: a process analysis of the first implementation of this innovative service model by the Preterm Birth Initiative-Rwanda.
Background: For a large trial of the effect of group antenatal care on perinatal outcomes in Rwanda, a Technical Working Group customized the group care model for implementation in this context. This process analysis aimed to understand the degree of fidelity with which the group antenatal care model was implemented during the trial period. Methods: We used two discreet questionnaires to collect data from two groups about the fidelity with which the group antenatal care model was implemented during this trial period. Group care facilitators recorded descriptive data about each visit and self-assessed process fidelity with a series of yes/no checkboxes. Master Trainers assessed process fidelity with an 11-item tool using a 5-point scale of 0 (worst) to 4 (best). Results: We analyzed 2763 questionnaires completed by group care facilitators that documented discreet group visits among pregnant and postnatal women and 140 questionnaires completed by Master Trainers during supervision visits. Data recorded by both groups was available for 84 group care visits, and we compared these assessments by visit. Approximately 80% of all group visits were provided as intended, with respect to both objective measures (e.g. group size) and process fidelity. We did not find reliable correlations between conceptually-related items scored by Master Trainers and self-assessment data reported by group visit facilitators. Conclusions: We recommend both the continued participation of expert observers at new and existing group care sites and ongoing self-assessment by group care facilitators. Finally, we present two abbreviated assessment tools developed by a Rwanda-specific Technical Working Group that reviewed these research results.


Continuous glucose monitoring.
Real-time continuous glucose monitoring (RT-CGM) has the potential to revolutionise the care and treatment of individuals with type 1 diabetes (T1D). During the past three years, several devices to measure the interstitial fluid intermittently or continuously have been developed and approved as an adjunct to blood glucose monitoring for use in individuals with T1D. Original studies using these earlier devices showed promise in lowering HbA1c in selected individuals with suboptimal control (1). The first randomised controlled trial with a subcutaneous continuous sensor demonstrated a significant decrease in HbA1c in adult and paediatric patients with poor metabolic control using the RT-CGM device continuously for 3 months compared with the self-monitoring of blood glucose (SMBG) control group (2). Recent randomised controlled trials clearly demonstrated that RT-CGM can significantly reduce HbA1c. Additionally, retrospective use of CGM data can positively affect metabolic control in both type 1 and type 2 diabetes.


[Reversion of atracurium and vecuronium residual nondepolarising neuromuscular blockade with low doses of neostigmine].
To assess the effectiveness of low doses of neostigmine in the reversion of residual non-polarising neuromuscular blockade (RNMB). The work involved one hundred and nineteen adult patients, ASA I-III, anaesthetised with fentanyl, thiopental, O2-N2O-isoflurane and atracurium (n=62) or vecuronium (n=57). RNMB was monitored with continuous electromyography of adductor pollicis with TOF stimulation. When TOF-Ratio (TR) < 75%, neostigmine 0.035, 0.03, 0.025 or 0.02 mg/kg (and atropine 0.0175, 0.015, 0.0125 or 0.01 mg/kg) were administrated based on the degree of NMB (0-1, 2, 3 or 4) to TOF stimulation respectively, registering the time to achieve TR > 75% and secondary effects. Both groups were homogeneous. Twenty-five point eight percent (25.8%) (group A) and 21.1% (group V) presented TR>75% at the end of surgery, while 11.3% and 19.2% showed TR < 75% with 0-1 responses, 6.5% and 11.5% 2 responses, 4.8% and 7.6% 3 responses, and 51.6% and 50% 4 responses to TOF stimulation in groups A or V respectively. All patients who received neostigmine presented TR > 75% in 10.5+/-7 (group A) and 10.3+/-6.4 min. (group V). A predominance of secondary effects in the atracurium group was observed (p=0.027), basically due to excessive salivation, nausea and vomiting. There were no cases of RNMB. The reversion of the residual neuromuscular blockade of atracurium or vecuronium with low doses of neostigmine and atropine adjusted to the degree of RNMB is effective even in deep blockades, reducing the risk of secondary effects.


Clinical assessment of vascular calcification.
Cardiovascular calcification poses an increased risk for cardiovascular events in advanced phases of chronic kidney disease. This evidence has brought many investigators to focus their attention on the importance of detection of calcification and avoidance of further development of it with appropriate therapeutic choices. Physicians can use a variety of noninvasive imaging tools to identify cardiovascular calcification, some with merely qualitative and others with both qualitative and quantitative capabilities. Plain x-rays and ultrasonography can be used to identify macroscopic calcification of aorta and peripheral arteries, echocardiography is helpful for assessment of valvular calcification, and computed tomography technologies constitute the gold standard for quantification of cardiovascular calcification. The latter is also useful to monitor calcification progression and to assess the effect of different therapeutic strategies directed at modifying calcification progression. In this article, we review the clinical significance of vascular calcification and some of the evidence surrounding the most commonly employed noninvasive imaging techniques.


Inflammatory bowel disease in liver transplanted patients.
Most common hepatobiliary manifestation of inflammatory bowel disease (IBD) are primary sclerosing cholangitis (PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation (LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Anti-tumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.


Adrenergic control of glycemia in the paraventricular nucleus of the hypothalamus in pigeons.
The effects of local injections of adrenaline into the paraventricular nucleus (PVN) and into other anterior hypothalamic areas on blood glucose levels were investigated in conscious pigeons (Columba livia). Adrenaline evoked a reliable and potent increase in blood glucose levels when injected into the PVN; no glycemic change was observed after vehicle injections into the PVN or after adrenaline injections into the 3rd ventricle or hypothalamic structures adjacent to the PVN. Local pretreatment with propranolol, but not with phentolamine, abolished the adrenaline-induced hyperglycemia. The present results indicate that adrenergically mediated circuits into the avian PVN play an important role in central mechanisms of energy balance that may be equivalent to those observed in mammalian species.


Speech-language pathology in Malta: meeting local needs in a global perspective.
Education in logopaedics and patterns of service delivery for the communication-disordered have expanded over the past decade in the Maltese Islands to address local needs, culture and circumstances. This paper provides an overview of the expansion of trained staff, caseloads and mode of service delivery. Various strategies are reported as having been adopted by the relatively underresourced training establishment to ensure the preparation and maintenance of competent and accountable practitioners, as recommended by the International Association of Logopedics and Phoniatrics. The success in training is perceived as being the result of the collaborative approach adopted with local service providers and expatriate colleagues. Strategic plans to strengthen the profession and service provision are also discussed.


Innovations in access to care: a patient-centered approach.
To receive health care, patients with nonemergent problems must gain access to a complex, interdependent ambulatory care system currently structured around the conventional office appointment model. The system does not effectively accommodate diverse patient needs and preferences, contributing to both overuse and underuse of health care resources. A patient-centered access model would help patients secure appropriate and preferred medical assistance when and where it is needed. Characteristics of patient-centered access include availability, appropriateness, preference, and timeliness. One or more of these characteristics often is missing in patients' health care experiences. The goal of this paper is to present patient-centered access as an integrated concept and philosophy to provide context for evaluating specific access initiatives. On the basis of an assessment of existing literature, 3 organizing principles of patient-centered access are proposed and discussed: work at the high end of expertise; align care with need and preference; and serve when service is needed. Patient-centered access warrants serious consideration, given the stakes involved for patients, providers, and payers. Few concepts support all 6 of the Institute of Medicine's aims for the 21st century: safety, effectiveness, patient-centeredness, timeliness, efficiency, and equitability. Patient-centered access is such a concept.


Normal reference values of Southwick's anteroposterior angle in prepubertal and pubertal normal adolescents.
Measurement of the Southwick's anteroposterior (AP) angle (shaft epiphysis proximal femoral AP angle) is not only a useful tool for planning the surgical treatment of deformities caused by slipped capital femoral epiphysis, but seems to be also important for recognizing the risk of epiphysiolysis development in obese patients (increased AP angle) or to confirm the diagnosis of slipped capital femoral epiphysis (decreased AP angle). To establish normal reference values of the Southwick's AP angle, we studied 97 normal nonobese adolescents (42 females, 55 males), with ages ranging between 8 and 16 years. The mean (SD) AP angle was 151.2 (5.0), ranging from 140 to 164. The limits for the first (p25) and third (p75) quartiles were 148 and 155, respectively. No difference was observed in the AP angle in males when compared with females. The AP angle was evaluated according to sex, chronological age, bone age, weight, height, and pubertal stage of development. We observed an inverse correlation of the AP angle with chronological age (r=-0.57) and bone age (r=-0.52). A weak inverse correlation was also found with stature (r=-0.33). Only a tendency toward an inverse correlation with weight (r=-0.27) or body mass index (r=-0.26) was observed. No significant correlation with the pubertal stage was found. When chronological and bone ages were divided into intervals, a significant reduction of the AP angle was observed only in patients older than 14 years compared with those younger than 10 years of age. In this study, we propose that the AP angle should be considered to be normal if it varies between 148 and 155. We conclude that the normal AP angle does not depend on sex; however, it tends to decrease with stature, and chronological and bone ages. In the normal weight range also, the AP angle decreases, contrasting with our previous findings in obese adolescents, in which the AP angle increases with the severity of obesity.


Living better or living longer? Perceptions of patients and health care professionals in oncology.
Cancer can influence the views of patients on treatment goals and make them different from those of health care professionals (HCPs). It is crucial to understand patient expectations regarding cancer treatment. We performed a cross-sectional survey of patients with cancer and HCPs to evaluate their perceptions about treatment priorities and to analyse variables that might influence their opinions. To identify treatment choices, we interviewed all participants using a structured questionnaire with fictitious case vignettes. We enrolled a total of 230 participants, including 144 patients and 86 HCPs (35 nurses, 21 physicians, 30 others). Treatment priority between survival time (28.5% for patients vs. 8.1% for HCP) and quality of life (45.8% vs. 87.2%) differed significantly, with the remaining participants stating they were uncertain or unwilling to respond, or providing invalid responses (P < 0.01). In logistic regression, prioritising survival time was more frequent in patients, adjusting for age and gender (odds ratio (OR) = 3.95; P < 0.01). The view that the physician alone should be responsible for treatment choices was more frequent among patients than HCPs (18.8 vs. 5.8%; P = 0.01). In Brazil, our results suggest that survival time is more important for patients with cancer than for HCPs, whereas quality of life is more important for HCPs than for patients with cancer, who place great emphasis on physicians as decision-makers. Given that Brazilian patients often rely on physicians for decisions, the potential impact of different priorities between survival time and quality of life when patients and HCPs are compared is unknown.


Reptation and constraint release dynamics in bidisperse polymer melts.
Bidisperse melts of linear, entangled polymer chains were studied using dissipative particle dynamics. The entanglement constraints were mimicked with our newly developed slip-spring approach. The compositions cover blends with short matrix chains, slightly above the molecular entanglement weight as well as blends were both chain lengths exhibit distinct entangled dynamics at various weight fractions. The Struglinsky-Graessley parameter Gr, which is the ratio between the relaxation time of the long chains due to pure reptation and the relaxation time of the tube caused by constraint release, ranges between values high above and below unity. We compare our slip-spring model with simulations that use conventional generic polymer models where bond crossings are prevented by excluded-volume interactions and find fairly good agreement in terms of the mean squared displacement. However, the slip-spring approach requires only a fraction of the computational time, making large scale systems feasible. The dynamical interference of the two different chain lengths is discussed in terms of reptation and constraint release dynamics. For bidisperse melt compositions with Gr < 1.0 the relaxation time of the long chain component is not affected by constraint release. However, for compositions where constraint release is supposed to contribute significantly to the relaxation mechanism (Gr > 1.0), we find strong evidence that the long chains reptate inside a dilated tube whose diameter increases with an exponent of 1/2 towards lower weight fraction of the long chains. Furthermore we observe a linear relation between the relaxation time and weight fraction. Therefore, based on the relaxation times, our results support the validity of the tube dilation model as proposed by Doi et al. [Macromolecules 20, 1900-1906 (1987)].


Introducing a procedure for predicting and reducing tire/road noise using a fast-computing hybrid model.
Prediction and reduction of tire noise are some of the main concerns of tire designers nowadays. Due to tire noise's sophisticated nature, low-noise tire design is like a maze path improbable to achieve without a scientific understanding of the underlying causes. This paper develops a knowledge-based hybrid model, incoherent summation of sounds generated and amplified by texture impact, tread impact, air-pumping, Helmholtz resonance, pipe resonance, horn effect, and air cavity resonance. The required data have been carried out by measuring C1 radial tires' noise levels in a semi-anechoic chamber. The developed model [with about a 1.7 dB(A) error on total noise prediction] presents mechanisms' contributions to the overall sound. The model is substituted with a fast-computing statistical model employing data generated based on Taguchi design. Machine learning methods are implemented for this aim, and the support vector machine provides the most accurate model. The proposed fast-computing hybrid model, developed based on a scientific description of underlying mechanisms, is applicable for noise reduction. The model's sensitivity to 21 tire parameters is analyzed, leading to valuable tips on lower tire noise. The results show the critical role of tread pattern characteristics, especially groove angle, in tire noise.


Results of cemented femoral revisions for periprosthetic femoral fractures in the elderly.
The treatment goals of Vancouver type B2 periprosthetic femoral fractures in elderly patients with a limited life expectancy are early weight bearing without compromising the fracture healing. Thirty-one patients with a mean age of 82 years were treated with a long cemented stem with additional allograft or plate fixation, followed by immediate full weight bearing. Seven major complications occurred within the first 3 months postoperatively. Forty-three percent of patients had died within the first year with their implant in place. Sixteen patients had survived more than 1 year. None of the implants had to be revised at a mean follow-up of 46 months. The results of this series suggest that this technique can provide acceptable results and offers the advantages of reduced cost and early weight bearing.


Outcomes of percutaneous endoscopic gastrostomy tube placement using a T-fastener gastropexy device in head and neck and esophageal cancer patients.
Percutaneous endoscopic gastrostomy (PEG) tube placement by the pull technique in head, neck, and esophageal cancer patients has a high complication rate, particularly in infections, and a small risk of tumor implantation. The T-fastener gastropexy technique uses a transabdominal approach to place the PEG device. The objective of this study was to review the clinical outcomes and complications related to endoscopic PEG placement with the T-fastener gastropexy technique in patients with head, neck, and esophageal cancers. This study was a retrospective review of all patients with head, neck, and esophageal cancers with PEG placement from January 1998 to June 2008. Clinical data including patient's age, gender, type and stage of cancer, date of PEG placement and removal, and reason for PEG removal was recorded. The study group consisted of a total of 356 patients of which 244 were male and 112 were female with a mean age of 63.3 years. There were 276 patients with head and neck cancer, 75 patients with esophageal cancer, and 5 with gastro-esophageal junction cancer. Staging data was available for 326 patients of which 56 (17.1%) had early stage disease (stage 1 and 2) and 270 patients (82.9%) had late stage (3 and 4) disease. None of these patients received antibiotic prophylaxis prior to PEG placement. Cellulitis around the PEG site occurred in 8.4% of cases and an abscess in 3.7% of cases. Only 4 (1.2%) infectious complications were within the first 30 days of PEG placement, and there were no intraoperative deaths or cases of tumor implantation. In the authors' experience, the T-fastener gastropexy technique for PEG placement in head, neck, and esophageal cancer patients carried a low overall complication rate and compared favorably with the results of pull method reported in the literature.


Architecture of a federated query engine for heterogeneous resources.
The Federated Utah Research and Translational Health e-Repository (FURTHeR) is a Utah statewide informatics platform for the new Center for Clinical and Translational Science at the University of Utah. We have been working on one of FURTHeR's key components, a federated query engine for heterogeneous resources, that we believe has the potential to meet some of the fundamental needs of translational science to access and integrate diverse biomedical data and promote discovery of new knowledge. The architecture of the federated query engine for heterogeneous resources is described and demonstrated.


Overexpression of Hsp104 by Causing Dissolution of the Prion Seeds Cures the Yeast [PSI+] Prion.
The yeast Sup35 protein misfolds into the infectious [PSI+] prion, which is then propagated by the severing activity of the molecular chaperone, Hsp104. Unlike other yeast prions, this prion is unique in that it is efficiently cured by the overexpression as well as the inactivation of Hsp104. However, it is controversial whether curing by overexpression is due to the dissolution of the prion seeds by the trimming activity of Hsp104 or the asymmetric segregation of the prion seeds between mother and daughter cells which requires cell division. To answer this question, we conducted experiments and found no difference in the extent of curing between mother and daughter cells when half of the cells were cured by Hsp104 overexpression in one generation. Furthermore, curing was not affected by the lack of Sir2 expression, which was reported to be required for asymmetric segregation of the [PSI+] seeds. More importantly, when either hydroxyurea or ethanol were used to inhibit cell division, the extent of curing by Hsp104 overexpression was not significantly reduced. Therefore, the curing of [PSI+] by Hsp104 overexpression is not due to asymmetric segregation of the prion seeds, but rather their dissolution by Hsp104.


IFN-gamma alters the response of Borrelia burgdorferi-activated endothelium to favor chronic inflammation.
Borrelia burgdorferi, the agent of Lyme disease, promotes proinflammatory changes in the endothelium that lead to the recruitment of leukocytes. The host immune response to infection results in increased levels of IFN-gamma in the serum and lesions of Lyme disease patients that correlate with greater severity of disease. Therefore, the effect of IFN-gamma on the gene expression profile of primary human endothelial cells exposed to B. burgdorferi was determined. B. burgdorferi and IFN-gamma synergistically augmented the expression of 34 genes, 7 of which encode chemokines. Six of these (CCL7, CCL8, CX3CL1, CXCL9, CXCL10, and CXCL11) attract T lymphocytes, and one (CXCL2) is specific for neutrophils. Synergistic production of the attractants for T cells was confirmed at the protein level. IL-1beta, TNF-alpha, and LPS also cooperated with IFN-gamma to induce synergistic production of CXCL10 by the endothelium, indicating that IFN-gamma potentiates inflammation in concert with a variety of mediators. An in vitro model of the blood vessel wall revealed that an increased number of human T lymphocytes traversed the endothelium exposed to B. burgdorferi and IFN-gamma, as compared with unstimulated endothelial monolayers. In contrast, addition of IFN-gamma diminished the migration of neutrophils across the B. burgdorferi-activated endothelium. IFN-gamma thus alters gene expression by endothelia exposed to B. burgdorferi in a manner that promotes recruitment of T cells and suppresses that of neutrophils. This modulation may facilitate the development of chronic inflammatory lesions in Lyme disease.


(un) Disciplining the nurse writer: doctoral nursing students' perspective on writing capacity.
In this article, we offer a perspective into how Canadian doctoral nursing students' writing capacity is mentored and, as a result, we argue is disciplined. We do this by sharing our own disciplinary and interdisciplinary experiences of writing with, for and about nurses. We locate our experiences within a broader discourse that suggests doctoral (nursing) students be prepared as stewards of the (nursing) discipline. We draw attention to tensions and effects of writing within (nursing) disciplinary boundaries. We argue that traditional approaches to developing nurses' writing capacity in doctoral programs both shepherds and excludes emerging scholarly voices, and we present some examples to illustrate this dual role. We ask our nurse colleagues to consider for whom nurses write, offering an argument that nurses' writing must ultimately improve patient care and thus would benefit from multiple voices in writing.


Parents' beliefs, perceptions and practices: Influence on child school readiness in Western Sydney, Australia.
Beliefs, practices and perceptions of early child development informing school readiness were examined for parents of preschool-aged children living in one multicultural suburb in Western Sydney, Australia. Survey data (N = 87) and semi-structured interviews (N = 52) with parents were collected in public spaces (e.g., parks, libraries, church halls and community centres) in mid-2019. Participants, primarily migrants of South Asian background, believed children learn through practical activities, prioritising academic and social development, with less focus on emotional development and communication skills. Parents' approached school readiness through the engagement of children in shared activities that maintained traditional cultural practices while simultaneously seeking to create community connection. Raising awareness of and engagement in both formal (e.g., early education services) and informal services (e.g., playgroups, library groups) could provide migrant and refugee parents with supportive networks in their local communities. Offering subsidies for attendance at early childhood programmes may reduce costs and encourage attendance, particularly for outdoor activities, helping to establish support networks for parents and children before starting primary school. These connections may provide families with a pathway for the identification and access of other local services and supports for their children. Programmes could also offer a platform for raising parental awareness of a holistic approach to child development and its importance for school success. Incorporating multicultural activities into early childhood programmes and settings could further assist parents in maintaining traditional cultural ties while creating essential local community connections.


[Abdominocruroplasties: technique. An approach to abdominal and crural surgery].
The abdomino-cruroplasty is the result of a combination of an abdominoplasty (or "mini-lift" as described by French authors) and a reduction plasty of the thighs. Our prime objective is the one-stage correction of the cutaneous and fatty excess of both the abdomen and the thighs with a single scar hidden in the skin folds; we also obtain an equilibration of "up" and "down" forces to avoid deformation of the pubic region. The technical points are explained.


Susceptibility of Florida Aedes aegypti and Aedes albopictus to dengue viruses from Puerto Rico.
Locally acquired dengue cases in the continental U.S. are rare. However, outbreaks of dengue-1 during 2009, 2010, and 2013 in Florida and dengue-1 and -2 in Texas suggest vulnerability to transmission. Travel and commerce between Puerto Rico and the U.S. mainland is common, which may pose a risk for traveler-imported dengue cases. Mosquitoes were collected in Florida and used to evaluate their susceptibility to dengue viruses (DENV) from Puerto Rico. Aedes aegypti and Ae. albopictus were susceptible to virus infection with DENV-1 and -2. No significant differences were observed in rates of midgut infection or dissemination between Ae. aegypti or Ae. albopictus for DENV-1 (6-14%). Aedes aegypti was significantly more susceptible to midgut infection with DENV-2 than Ae. albopictus (Ae. aegypti, ∼28%; Ae. albopictus, ∼9%). The dissemination rate with dengue-2 virus for Ae. aegypti (23%) was greater than Ae. albopictus (0%), suggesting that Ae. albopictus is not likely to be an important transmitter of the DENV-2 isolate from Puerto Rico. These results are discussed in light of Florida's vulnerability to DENV transmission.


Surgical treatment of 21 patients with spinal metastases of differentiated thyroid cancer.
Differentiated thyroid cancer (DTC) is a common primary cancer for spinal metastases (SM). The treatments for DTC spinal metastases (SM) have evolved from simple surgery and radiotherapy to a multidisciplinary comprehensive therapeutic strategy of combined spinal surgery, general surgery, radiotherapy, nuclear medicine and endocrinology. The purpose of this study was to discuss the efficacy and prognosis associated with different surgical treatments of SM patients with DTC. A total of 21 consecutive patients with SM of DTC that were treated between 1999 and 2013 were studied. Biopsy was routinely performed to achieve the pathological diagnosis before treatment. Three patients underwent total spondylectomy intralesionally or piecemeally, and 18 had curettage. Postoperative recurrence and survival times were analyzed by the Kaplan-Meier methods. Nineteen patients (90%) had an average of 42.7 months (range, 7-170 months) follow-up. The median visual analogue scale for pain reduced from 5 points to 1 point (P < 0.01), and the median Karnofsky performance score increased from 70 to 90 points after surgery (P < 0.01). Seventeen patients with neurological deficits attained improvements after surgeries, of at least one level according to the Frankel classification (P < 0.01). Eight patients with curettage had recurrence. Four patients died of DTC, 12 patients lived with disease, and three patients were disease-free. No significant effects on postoperative recurrence or survival were observed between surgery combined with conservative treatment, total spondylectomy, the number of bone metastases and visceral metastasis. DTC-SM have a relatively favorable prognosis, and curettage and stabilization can effectively relieve the pain and improve the quality of life and neurological status of the patients. For patients with Tomita scores of ≤3, total spondylectomy may have better clinical outcomes. Comprehensive therapeutic strategies including surgery, radioiodine, external beam radiation therapy and embolization should be considered for most patients.


Diagnosis and management of a young woman with acute isolated lateral sinus thrombosis.
Isolated lateral sinus thrombosis (LST) was mentioned in the past as a complication of middle ear infection. In the recent years, it was not frequently studied. Our patient, a 23-year-old woman who was taking an oral contraceptive pill, displayed 24 hours of migraine, such as headache; her systemic examinations were normal. She underwent neuroimaging examinations in the first 36 hours of admission. Native head computed tomography (CT) revealed hyperdensities along the left tentorium, involving the left lateral sinus (LS). Cranial magnetic resonance imaging (MRI) showed hypointense signal on MRI T2*SW (susceptibility-weighted) in the region of the left LS. MR venography noted the absence of flow-related signal within the left LS. The clinical symptoms, signs and neuroimaging results formulated the diagnosis of left isolated LS thrombosis. Laboratory data demonstrated an elevated D-dimer and homozygosity for the factor V Leiden mutation. She was immediately started on anticoagulation in the form of low-molecular-weight Heparin; then, she was treated with Warfarin for an indefinite duration. The headaches resolved within two days and her neurological examination was also normal. A second MR venography achieved after two weeks demonstrated complete recanalization of the venous sinuses. We did not observe any LST recurrence, deep vein thrombosis or pulmonary embolism during one year of follow-up. The early initialization of anticoagulation produced a favorable evolution. An acute isolated left LST could be identified in her case on the head CT combined with MRI and MR venography.


Scattering and transport properties of the three classical Wigner-Dyson ensembles at the Anderson transition.
An extensive numerical analysis of the scattering and transport properties of the power-law banded random matrix model (PBRM) at criticality in the presence of orthogonal, unitary, and symplectic symmetries is presented. Our results show a good agreement with existing analytical expressions in the metallic regime and with heuristic relations widely used in studies of the PBRM model in the presence of orthogonal and unitary symmetries. Moreover, our results confirm that the multifractal behavior of disordered systems at criticality can be probed by measuring scattering and transport properties, which is of paramount importance from the experimental point of view. Thus, a full picture of the scattering and transport properties of the PBRM model at criticality corresponding to the three classical Wigner-Dyson ensembles is provided.


Evolution of Neuropeptide Precursors in Polyneoptera (Insecta).
Neuropeptides are among the structurally most diverse signaling molecules and participate in intercellular information transfer from neurotransmission to intrinsic or extrinsic neuromodulation. Many of the peptidergic systems have a very ancient origin that can be traced back to the early evolution of the Metazoa. In recent years, new insights into the evolution of these peptidergic systems resulted from the increasing availability of genome and transcriptome data which facilitated the investigation of the complete neuropeptide precursor sequences. Here we used a comprehensive transcriptome dataset of about 200 species from the 1KITE initiative to study the evolution of single-copy neuropeptide precursors in Polyneoptera. This group comprises well-known orders such as cockroaches, termites, locusts, and stick insects. Due to their phylogenetic position within the insects and the large number of old lineages, these insects are ideal candidates for studying the evolution of insect neuropeptides and their precursors. Our analyses include the orthologs of 21 single-copy neuropeptide precursors, namely ACP, allatotropin, AST-CC, AST-CCC, CCAP, CCHamide-1 and 2, CNMamide, corazonin, CRF-DH, CT-DH, elevenin, HanSolin, NPF-1 and 2, MS, proctolin, RFLamide, SIFamide, sNPF, and trissin. Based on the sequences obtained, the degree of sequence conservation between and within the different polyneopteran lineages is discussed. Furthermore, the data are used to postulate the individual neuropeptide sequences that were present at the time of the insect emergence more than 400 million years ago. The data confirm that the extent of sequence conservation across Polyneoptera is remarkably different between the different neuropeptides. Furthermore, the average evolutionary distance for the single-copy neuropeptides differs significantly between the polyneopteran orders. Nonetheless, the single-copy neuropeptide precursors of the Polyneoptera show a relatively high degree of sequence conservation. Basic features of these precursors in this very heterogeneous insect group are explained here in detail for the first time.


Metastable phosphorus neutral monoradical: a key intermediate in the bicyclic cage formation.
A key intermediate in the formation of a bicyclic cage formed between a biradical (LCP)2 (L = carbene) and an unsaturated substrate via a [2 + 2] cycloaddition reaction has been isolated and fully characterized including by X-ray diffraction analysis. The isolation of this intermediate proves that this cycloaddition reaction proceeds stepwise which is preferred over a concerted mechanism.


Men who work at age 70 or older.
The federal policy on older workers has shifted from the encouragement of early withdrawal from the labor force to the encouragement of continuous participation in the labor force. In this light, it is instructive to investigate the backgrounds of elderly people who work at age 70 or older. This article presents the findings of a study, using data from the 1993 Asset and Health Dynamics of the Oldest Old Study, that investigated the effects of health, economic conditions (net worth, employer-provided pensions, and supplemental medical insurance coverage), education, and spouse's work status on the probability of working among men aged 70 or older. The study addressed the probability of working, the probability of working fulltime and of working part-time, and the probability of being self-employed and of being employed by others. Implications for policy are discussed.


Chemo-immunotherapy induces tumor regression in a mouse model of spontaneous mammary carcinogenesis.
Tumor-specific immune tolerance represents an obstacle for the development of effective anti-tumor immune responses through cancer vaccines. We here evaluated the efficacy of chemo-immunotherapy in breaking tumor-specific immune tolerance in an almost incurable mouse model of spontaneous carcinogenesis.Transgenic HER-2/neu mice bearing large mammary tumors received the adoptive transfer of splenocytes and serum isolated from immune donors, with or without pre-conditioning with cyclophosphamide. Treatment efficacy was assessed by monitoring tumor growth by manual inspection and by magnetic resonance imaging. The same chemo-immunotherapy protocol was tested on tumor-free HER-2/neu mice, to evaluate the effects on tumor emergence.Our data show that chemo-immunotherapy hampered carcinogenesis and caused the regression of large mammary tumor lesions in tumor-bearing HER-2/neu mice. The complete eradication of a significant number of tumor lesions occurred only in mice receiving cyclophosphamide shortly before immunotherapy, and was associated with increased serum anti HER-2/p185 antibodies and tumor leukocyte infiltration. The same protocol significantly delayed the appearance of mammary tumors when administered to tumor-free HER-2/neu mice, indicating that this chemo-immunotherapy approach acted through the elicitation of an effective anti-tumor immune response. Overall, our data support the immune-modulatory role of chemotherapy in overcoming cancer immune tolerance when administered at lymphodepleting non-myeloablative doses shortly before transfer of antigen-specific immune cells and immunoglobulins. These findings open new perspectives on combining immune-modulatory chemotherapy and immunotherapy to overcome immune tolerance in cancer patients.


[Partial lipodystrophy, hypocomplementemia and glomerulonephritis].
Renal involvement is found in 20 to 50% of cases of Partial lipodystrophy (PLD). We report 8 cases of PLD of which 6 had a glomerular nephropathy and 2 had no renal disease but all had persistent hypocomplementemia and 5 had circulating nephritic factor (C3NeF). The analysis of these cases and of all the cases reported in the literature shows the specificity of the glomerular involvement. Membranoproliferative glomerulonephritis (MPGN) with dense intramembranous deposits is a constant finding in PLD with renal involvement. This variety of MPGN is well known for being associated with persistent hypocomplementemia. However, the presence of hypocomplementemia and C3NeF in patients with PLD but without nephritis raises the question of the interrelationship between alternative pathway complement activation and the development of MPGN with or without lipodystrophy. There is no valid explanation in the present state of knowledge for the association of partial lipodystrophy hypocomplementemia, and MPGN. From the answer to this problem should emerge a better understanding of the role of complement in renal disease and in particular in the unusual form of glomerular injury seen in MPGN.


Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation.
Recent epidemiological studies have found an alarming trend of increased cancer incidence in adults younger than 50 years of age and projected a substantial rise in cancer incidence over the next 10 years in this age group. This trend was exemplified in the incidence of non-cardia gastric cancer and its disproportionate impact on non-Hispanic white females under the age of 50. The trend is concurrent with the increasing incidence of autoimmune diseases in industrialized countries, suggesting a causal link between the two. While autoimmunity has been suspected to be a risk factor for some cancers, the exact mechanisms underlying the connection between autoimmunity and cancer remain unclear and are often controversial. The link has been attributed to several mediators such as immune suppression, infection, diet, environment, or, perhaps most plausibly, chronic inflammation because of its well-recognized role in tumorigenesis. In that regard, autoimmune conditions are common causes of chronic inflammation and may trigger repetitive cycles of antigen-specific cell damage, tissue regeneration, and wound healing. Illustrating the connection between autoimmune diseases and cancer are patients who have an increased risk of cancer development associated with genetically predisposed insufficiency of cytotoxic T lymphocyte-associated protein 4 (CTLA4), a prototypical immune checkpoint against autoimmunity and one of the main targets of cancer immune therapy. The tumorigenic process triggered by CTLA4 insufficiency has been shown in a mouse model to be dependent on the type 2 cytokines interleukin-4 (IL4) and interleukin-13 (IL13). In this type 2 inflammatory milieu, crosstalk with type 2 immune cells may initiate epigenetic reprogramming of epithelial cells, leading to a metaplastic differentiation and eventually malignant transformation even in the absence of classical oncogenic mutations. Those findings complement a large body of evidence for type 1, type 3, or other inflammatory mediators in inflammatory tumorigenesis. This review addresses the potential of autoimmunity as a causal factor for tumorigenesis, the underlying inflammatory mechanisms that may vary depending on host-environment variations, and implications to cancer prevention and immunotherapy.