Use of the levonorgestrel-releasing intrauterine system: an Austrian perspective.
Approximately 12 million women worldwide use the levonorgestrel-releasing intrauterine system (IUS), with approximately 180,000 users of this IUS currently reported in Austria. A patient satisfaction study of 591 women in Austria revealed a high number of 'very satisfied' (79%) and 'satisfied' (19%) patients. Reliability, comfort, excellent compatibility and less severe, shorter and less painful monthly periods were the most frequently named advantages of the levonorgestrel-releasing IUS. Medication-induced cervical priming before insertion can be carried out on a routine or selective basis (for example in nullipara, in women who have undergone cervical conisation or in women who have previously experienced painful insertion). There is, at present, no evidence of an increased rate of breast cancer through use of the levonorgestrel-releasing IUS. A directly comparative study with oral contraceptives in young nullipara showed excellent results for the levonorgestrel-releasing IUS, with no perforations, inflammation or pregnancies.


Targeting KRAS Mutant in Non-Small Cell Lung Cancer: Novel Insights Into Therapeutic Strategies.
Although KRAS-activating mutations represent the most common oncogenic driver in non-small cell lung cancer (NSCLC), various attempts to inhibit KRAS failed in the past decade. KRAS mutations are associated with a poor prognosis and a poor response to standard therapeutic regimen. The recent development of new therapeutic agents (i.e., adagrasib, sotorasib) that target specifically KRAS G12C in its GDP-bound state has evidenced an unprecedented success in the treatment of this subgroup of patients. Despite providing pre-clinical and clinical efficacy, several mechanisms of acquired resistance to KRAS G12C inhibitors have been reported. In this setting, combined therapeutic strategies including inhibition of either SHP2, SOS1 or downstream effectors of KRAS G12C seem particularly interesting to overcome acquired resistance. In this review, we will discuss the novel therapeutic strategies targeting KRAS G12C and promising approaches of combined therapy to overcome acquired resistance to KRAS G12C inhibitors.


[Surgical treatment of middle cerebral artery aneurysms].
A review of 413 cases of middle cerebral artery aneurysms out of the means of 1621 cases which were operated upon by one of the authors (J. Suzuki), is made with regard to their surgical management. At operation, the patient is placed in the supine position with the head fixed neutral and chin slightly up. Small craniotomy is performed by means of a small semi-circular skin incision just behind the hair line. After exposure of the internal carotid artery, the arachnoid overlying the Sylvian fissure is cut distally in order to expose the middle cerebral artery. The most important principle for aneurysm surgery is to secure the afferent artery prior to aneurysm exposure. In our approach, the M1 portion runs horizontally so that we can secure the parent artery after evacuation of liquor at the chiasma and then dissect the aneurysm. We usually put the temporary clips on the afferent and efferent arteries of aneurysm, that is the M1 and M2's during dissection of the aneurysm. In order to prolong the time of temporary arterial occlusion, 20% mannitol solution is administered intravenously just prior to dural incision under normotensive and normothermic anesthesia. Under such condition, it is possible to occlude the middle cerebral artery for 40 minutes. On the treatment of aneurysm, it is important to expose the whole aneurysm. If only neck portion is exposed and treated, kinking or stenosis of the parent artery can occur due to adhesion, and a second aneurysm or small artery hidden behind can easily overlooked. Therefore, exposure of the entire aneurysm is necessary. Subsequently, ligation should be carried out, then neck clipping performed.(ABSTRACT TRUNCATED AT 250 WORDS)


Predicting the minimal energy costs of human walking.
Preferred stride frequency (PSF) of human walking has been shown to be predictable as the resonant frequency of a force-drive harmonic oscillator (FDHO). The purpose of this study was to determine whether walking at the PSF and FDHO leads to minimal metabolic and mechanical costs. Subjects walked on a level treadmill at the PSF, FDHO, and frequencies above and below. Effects of stride length (SL) and speed (S) were assessed by two conditions, one in which SL was constant and the other in which S was constant. The predictability of PSF from resonance was replicated. Walking at the PSF and FDHO frequencies resulted in metabolic costs which were not significantly different (P greater than 0.05). A U-shaped oxygen consumption curve was observed with the minimum at the PSF and FDHO conditions when S was constant. A two-component curve in which a breakpoint was observed was found in the SL constant condition. A significant increase in metabolic cost was observed above the PSF/FDHO (P less than 0.01). Internal work (power) values were not significantly different between walking frequencies for the S constant condition. In the SL constant condition, internal work values showed linear increases as frequency increased. It was concluded that PSF of walking arises from the interface of the resonance properties of the limbs as oscillators and the tendency of biological systems to self-optimize.


Mitochondrial changes in adenocarcinoma of the pancreas.
The aim of our study was to analyse the mitochondrial ultrastructure in primary ductal adenocarcinomas of the pancreas and to compare it with normal pancreatic cells. 52 samples of adenocarcinoma of the pancreas obtained by surgical resection or by endosonographic biopsy were examined. Compared to normal mitochondrial ultrastructure in non-tumorous cells, the mitochondria in cancer cells had a dense matrix and condensed configuration or with lucent-swelling matrix associated with disarrangement and distortion of cristae and partial or total cristolysis. Functionally, these structural alterations presume the presence of hypoxia-tolerant and hypoxia-sensitive cancer cells.


Treatment effects of GnRH agonist on the binding of estrogen and progesterone, and the histological findings of uterine leiomyomas.
The changes in the histology and steroid hormone binding capacity of the uterine leiomyomas treated with; GnRH agonists (GnRHa buserelin acetate in, 900 micrograms/day for 16 weeks) were investigated. The occurrence of hyaline degeneration in the myometrium was significantly higher in the GnRHa-treated group than in the control group, and the grade of hyaline degeneration was more advanced in the GnRHa group. After the GnRHa treatment, the Bmax of the estrogen receptor increased significantly in the leiomyomas and myometrium. The Bmax of progesterone receptors in the myometrium decreased significantly and the reduction rates of leiomyomas (% of the initial volumes) measured by MRI correlated (r = 0.775) with the Bmax of progesterone receptors. In summary, GnRHa caused hyaline degeneration of the uterine leiomyomas which were responsible for the shrinkage. The shrunk leiomyomas have the potential for regrowth in response to estrogen as they still have high concentrations of the estrogen receptors.


The use of caged adenine nucleotides and caged phosphate in intact skeletal muscle fibres of the mouse.
The effects of 1-(2-nitrophenyl)ethyl ester of ATP (NPE-caged ATP), NPE-caged ADP, NPE-caged phosphate (Pi) and desoxybenzoinyl phosphate (desyl-caged Pi) on mouse skeletal muscle function were studied. All these caged compounds, when microinjected into intact single mouse muscle fibres, reduced the myoplasmic calcium during a tetanus (tetanic [Ca2+]i) and reduced force. Flash photolysis partially reversed this reduction of tetanic [Ca2+]i and force. In fibres fatigued by repeated tetani, flash photolysis of NPE-caged ATP, ADP and Pi, also caused a transient recovery of tetanic [Ca2+]i, and force. Because photolytic release of ATP, ADP and Pi produced comparable effects it seems that the mechanism of action is the reduction in concentration of the caged compound rather than the release of the biologically active molecule. Experiments on mechanically skinned rat skeletal muscle fibres with intact T-tubular/sarcoplasmic reticulum coupling showed that 1 mM NPE-caged ATP had no effect on depolarization-induced force. This result suggests that the depressant effects of the NPE-caged compounds are neither on voltage-activated Ca2+ release from the sarcoplasmic reticulum nor on myofibrillar function. Thus all the caged compounds tested inhibit excitation-contraction coupling in muscle by an unknown mechanism and this limits their value as sources of biologically important molecules. This inhibitory effect was smallest for desyl-caged Pi and under conditions of maximal activation photolytic release of Pi caused a direct inhibition of the contractile proteins. This inhibition amounted to a 1% reduction of maximum force with an increase of [Pi] of about 0.3 mM. The mean rate of force decline under these conditions was 55 s-1, which reflects the rate of cross-bridge cycling during a maximal tetanus.


Size-dependent patterns in depolarization maps from turbid medium and tissue.
Mueller matrix measurements on turbid media can be used to quantify its polarization properties in terms of retardance, diattenuation, and depolarization. In particular, the depolarizing ability of such media, which is represented by the depolarization index, has been shown to be a useful diagnostic parameter. However, being a single valued metric, its dependence on a host of tissue optical parameters makes it difficult to interpret. In this paper, we show that a map of depolarization as a function of input polarization state parameters can be used to infer information about the size of scatterer and order of birefringent and depolarizing layers in turbid medium. The experiments carried out on different mice organ tissues indicate that the depolarization characteristics of tissue are closely represented by depolarization properties of intralipid. We also observed that these maps do not vary in the presence of absorption.


Characterization of Wall Paintings of the Harem Court in the Alhambra Monumental Ensemble: Advantages and Limitations of In Situ Analysis.
Non-invasive techniques (X-ray fluorescence, XRF, and Raman spectroscopy) were used for the study of the Hispano Muslim wall paintings. Principal component analysis (PCA) was performed on the semi-quantitative XRF results directly provided by the in-built factory calibrations with minimum user manipulation. The results obtained were satisfactory and highlighted differences and similarities among the measurement points. In this way, it was possible to differentiate the decorations carried out on gypsum plasterwork and the wall paintings over lime plaster. The color palette, revealed by combining the results from XRF and Raman spectroscopies, comprised the pigments hematite, lapis lazuli, cinnabar (in poor conservation state), and possibly, carbon. Evidence of past interventions was also provided by PCA on XRF data, which detected the presence of Pb, Ba, and Zn in some areas. Furthermore, the preparation layers have been studied in detail on cross-sections of two microsamples. Several layers of lime plaster with a compact microstructure have been observed. The characteristic of the pictorial layer and the identification of calcium oxalate point to the use of a secco-technique. The main alteration identified was a gypsum surface layer covering the painting and signs of plaster deterioration due to gypsum migration to more internal areas. Finally, the comparison with the observations made by restorers in previous interventions on these paintings revealed the importance of the representativeness gained with the in situ study, which enabled the analysis of a high number of areas.


Ovarian serous carcinoma: relationship of p53 and bcl-2 with tumor angiogenesis and VEGF expression.
The aim of the study was to assess the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in ovarian serous carcinoma and to examine their relation with apoptosis.Paraffin-embedded specimens of 41 cases of ovarian serous carcinomas were evaluated by immunohistochemistry for VEGF, p53, and bcl-2 expression. MVD was assessed with CD31 staining. We investigated the association of tumor angiogenesis (MVD and VEGF) with clinicopathologic factors, p53 overexpression, and bcl-2 expression.There was a significant correlation between high MVD and suboptimal debulking and advanced stage disease. A significant negative correlation was expressed between bcl-2 and VEGF expression. In univariate analysis, only stage had a significant impact on disease-free survival.The results of this study suggest that higher degree of angiogenesis is associated with suboptimal debulking and advanced-stage disease. Expression of VEGF had negative association with VEGF expression.


Identification of a group of cellular cofactors that stimulate the binding of RNA polymerase II and TRP-185 to human immunodeficiency virus 1 TAR RNA.
A double-stranded RNA structure transcribed from the HIV-1 long terminal repeat known as TAR is critical for increasing gene expression in response to the transactivator protein Tat. Two cellular factors, RNA polymerase II and TRP-185, bind specifically to TAR RNA, but require the presence of cellular proteins known as cofactors which by themselves are unable to bind to TAR RNA. In an attempt to determine the mechanism by which these cofactors stimulate binding to TAR RNA, we purified these factors from HeLa nuclear extract and amino acid microsequence analysis performed. Three proteins were identified in the cofactor fraction including two previously described proteins, elongation factor 1alpha (EF-1alpha) and the polypyrimidine tract-binding protein (PTB), and a novel protein designated the stimulator of TAR RNA-binding proteins (SRB). SRB has a high degree of homology with a variety of cellular proteins known as chaperonins. Recombinant EF-1alpha, PTB, and SRB produced from vaccinia expression vectors stimulated the binding of RNA polymerase II and TRP-185 to TAR RNA in gel retardation analysis. These studies define a group of cellular factors that function in concert to stimulate the binding of TRP-185 and RNA polymerase II to HIV-1 TAR RNA.


Sexual satisfaction among Korean-American couples in the Midwestern United States.
One hundred couples composed of American husbands and Korean wives from the midwestern United States were surveyed with respect to sexual satisfaction. Though the responses of spouses were correlated highly, husbands were more satisfied with the quality of the sexual relationship than were wives. As found previously with more general populations, self-esteem and higher levels of positive regard, communication, and cohesion were related to higher sexual satisfaction for both husbands and wives. For wives, higher socioeconomic status and younger age were related to higher sexual satisfaction, as was the husband's being a current or retired member of the US military. Cultural factors were also important; conflicts over sexual practices related to cultural differences, though limited to about 10% of the subjects, were related to sexual satisfaction for both husbands and wives. Wives' English proficiency was related slightly to sexual satisfaction, but not husbands' proficiency in Korean. For husbands only, marital conflict over cultural differences and rejection by relatives and friends were related negatively to sexual satisfaction. Clinical implications of the results are discussed.


Polybrominated diphenyl ethers (PBDEs) in mussels from cultures and natural population.
Polybrominated diphenyl ether (PBDE) mass fractions were determined in mussel samples collected from 6 locations around Thermaikos Gulf in north Greece. PBDEs were present in all sampling sites and the average total (ΣPBDEs) ranged from 17.7 to 32.3ng/g l.w., characterising Thermaikos as low polluted, a fact further supported by congener ratios and literature comparison. Distribution was even among stations with one exception. Congener profiles exhibited predominance of penta-/octa-BDEs as well as BDE-209. Statistical analysis showed significant difference in pollution levels between the two types of mussel cultures. No variations were observed for mussel bunch position or between cultures and natural population. Congener correlation analysis suggested different pollution sources between higher and lower brominated congeners as well as different metabolic/degradation processes. Bioaccumulation factors indicated that an increase in congener bromination degree leads to bioaccumulation capacity reduction. Consumption of mussels from Thermaikos gulf area poses no threat for public health concerning PBDEs.


Hydroxyproline interference during the gas chromatographic analysis of D/L aspartic acid in human dentine.
The proportion of D- to L-enantiomers of aspartic acid in metabolically isolated proteins has been used by forensic scientists to estimate age at death. We have demonstrated the interference of a derivative of hydroxyproline (N-TFA isopropyl Hyp ester) with the N-TFA isopropyl L-Aspartic (Asp) acid ester during gas chromatography of amino acids. This has serious implications for the accurate quantification of the D- to L-Asp ratio extracted from collagenous proteins. Having demonstrated the potential for this co-elution in amino acid standards, acid-soluble dentine proteins and non-mineralised collagen, we argue that this problem can be overcome either by high resolution separation or by analysis of the (Hyp-poor) non-collagenous protein fraction.


Neural substrates of memory: from synapse to system.
One of the fundamental challenges of modern neuroscience is to understand how memories are acquired, stored, and retrieved by the brain. In the broadest terms, attempts to dissect memory can be broken down into four experimental disciplines: (1) identification of molecular components, (2) ex vivo and in vivo cellular analysis of neuronal function, (3) theoretical modeling approaches of neural systems, and (4) organismal-level behavioral analyses. Our objective here is to offer a conceptually unifying perspective and to discuss this perspective in relation to an experiment analysis of memory in Drosophila.


The role of the adrenal gland in ethanol-induced triglyceride mobilization.
The effect of a large ethanol (ETOH) dose (4.8 g/kg) on triglyceride (TG) levels of plasma, brain and liver was studied in the rat. TG levels were measured in fasted male rats treated with ETOH or after ETOH and tetraethylammonium treatment in intact rats. The levels of TG were also measured after treatment with ETOH and dexamethasone (DXM) in adrenalectomized rats. Plasma TG levels significantly increased in the nonadrenalectomized and adrenalectomized rats by one- and twofold respectively. Brain TG levels increased significantly when intact animals were placed under either stress or when they were treated with ETOH and stress simultaneously. The adrenalectomized rats showed a similar response when they were treated with ETOH and DXM simultaneously. The liver TG levels were significantly different from control in all treated animals. The ETOH-treated adrenalectomized rats' TG levels were significantly less than control. This study suggests that stress and the adrenal gland play important roles in ETOH-induced TG levels in the rat.


Successful treatment via chemotherapy and surgical resection of a femoral hemangiopericytoma with pulmonary metastasis.
Hemangiopericytoma (HPC) is a soft-tissue neoplasm composed of proliferating capillary pericytes. It has variable and unpredictable malignancy and most commonly occurs in the fifth or sixth decade of life. Diagnosis is based on the histological aspect. HPC is exceedingly rare in childhood. In both adults and children, curative surgery is the most important predictor of survival. The place of chemotherapy in the treatment of HPC is not well established. We describe a case of adult-type metastatic HPC of the thigh in a 13-year-old boy. The response to neoadjuvant chemotherapy was excellent, and local control of this initially unresectable tumor was achieved without radiation therapy or mutilating surgery. The child is alive and well and has had 8 years of follow-up after treatment.


Ultrasensitive detection of plant hormone abscisic acid-based surface-enhanced Raman spectroscopy aptamer sensor.
Abscisic acid (ABA), as the most common plant hormone in the growth of wheat, can greatly affect the yield when its levels deviate from normal. Therefore, highly sensitive and selective detection of this hormone is greatly needed. In this work, we developed an aptamer sensor based on surface-enhanced Raman spectroscopy (SERS) and applied it for the high sensitivity detection of ABA. Biotin-modified ABA aptamer complement chains were modified on ferrosoferric oxide magnetic nanoparticles (Fe3O4MNPs) and acted as capture probes, and sulfhydryl aptamer (SH-Apt)-modified silver-coated gold nanospheres (Au@Ag NPs) were used as signal probes. Through the recognition of the ABA aptamer and its complementary chains, an aptamer sensor based on SERS was constructed. As SERS internal standard molecules of 4-mercaptobenzoic acid (4-MBA) were encapsulated between the gold core and silver shell of the signal probes; the constructed aptamer sensor generated a strong SERS signal of 4-MBA after magnetic separation. When there were ABA molecules in the detection system, with the preferential binding of ABA aptamer and ABA molecule, the signal probes were released from the capture probes, after magnetic separation, leading to a linear decrease in SERS intensity of 4-MBA. Thus, the detection response was linear over a logarithmic concentration range, with an ultra-low detection limit of 0.67 fM. In addition, the practical use of this assay method was demonstrated in ABA detection from fresh wheat leaves, with a relative error (RE) of 5.43-8.94% when compared with results from enzyme-linked immunosorbent assay (ELISA). The low RE value proves that the aptamer sensor will be a promising method for ABA detection.


Rad18-dependent SUMOylation of human specialized DNA polymerase eta is required to prevent under-replicated DNA.
Translesion polymerase eta (polη) was characterized for its ability to replicate ultraviolet-induced DNA lesions that stall replicative polymerases, a process promoted by Rad18-dependent PCNA mono-ubiquitination. Recent findings have shown that polη also acts at intrinsically difficult to replicate sequences. However, the molecular mechanisms that regulate its access to these loci remain elusive. Here, we uncover that polη travels with replication forks during unchallenged S phase and this requires its SUMOylation on K163. Abrogation of polη SUMOylation results in replication defects in response to mild replication stress, leading to chromosome fragments in mitosis and damage transmission to daughter cells. Rad18 plays a pivotal role, independently of its ubiquitin ligase activity, acting as a molecular bridge between polη and the PIAS1 SUMO ligase to promote polη SUMOylation. Our results provide the first evidence that SUMOylation represents a new way to target polη to replication forks, independent of the Rad18-mediated PCNA ubiquitination, thereby preventing under-replicated DNA.


Prevalence and Phylogenetic Analysis of Microsporidium Enterocytozoon bieneusi in Diarrheal Patients.
Enterocytozoon bieneusi can cause severe diarrhea in children and adults. However, in China, there are scant studies on E. bieneusi in diarrheal children and adults, with the exception of prevalence and genotyping data in a small number of cities including Hubei, Shanghai, and Heilongjiang. In this study, 196 fecal samples (n = 132 in Chongqing, n = 44 in Shandong, n = 20 in Hubei) were collected, including 91 from children and 105 from adults. Through microscopic examination, 19 positive samples (11 from children and 8 from adults) were detected. Using PCR examination, the internal transcriptional spacer (ITS) region was utilized by nested PCR to detect and characterize E. bieneusi. Twenty positive samples were detected, including 14 from children (≤11 years of age) and 6 from adults. According to the sequence analysis of ITS data, one known zoonotic (D) and seven novel (CQH5-11) genotypes were identified. This is the first molecular epidemiological study of E. bieneusi in diarrheal patients in different regions of China. Therefore, this study can provide useful information for the molecular epidemiology and control of E. bieneusi infection in humans in the future.


Sunlike White Light-Emitting Diodes Based on Rare-Earth-Free Luminescent Materials.
Solid-state lighting (SSL) sources based on light-emitting diodes represent the new generation of highly efficient illumination systems that significantly impact energy-saving. The development of white light-emitting diodes (WLEDs) with a combination of high color rendering index (CRI) and high deep-red color rendering R9 is an important challenge in the field of solid-state lighting. On the other hand, most WLEDs use rare-earth inorganic luminescent materials. The annual demand for rare-earth metals has doubled to 125,000 tons in 15 years, and the demand is projected to reach 315,000 tons in 2030. The explosion in demand for these materials, combined with a monopolistic supply source, represents a real risk for the development of WLEDs in the next few years. Luminescent organic materials are a relevant and promising alternative. Here, we report a WLED with a very high CRI of 95.7 and R9 of 78.7, obtained using a combination of a blue LED chip (excitation source) and two organic luminescent dyes (Coumarin 6 and Lumogen Red) acting as spectral converters in a multilayer remote phosphor configuration. To the best of our knowledge, this is the first rare-earth-free WLED with such high values of CRI and R9.


Spinal arteriovenous malformation associated with spinal metameric syndrome: a treatable cause of long-term paraplegia?
Cutaneomeningospinal angiomatosis, or Cobb syndrome, is a rare metameric developmental disorder presenting as an extradural-intradural vascular malformation that involves bone, muscle, skin, spinal cord, and nerve roots. A 14-year-old girl with a red nevus involving the T6-9 dermatomes on the left side of her back presented with a 5-year history of bowel and bladder incontinence, paraplegia, and lower-extremity sensory loss. Magnetic resonance imaging demonstrated a hemangioma in the T-8 and T-9 vertebral bodies and a spinal cord AVM nidus extending from T-6 to T-9. The AVM was successfully embolized and the patient regained lower-extremity strength, ambulation, and normal sphincter functions after 5 years of having been wheelchair bound. The authors report the restoration of ambulation after endovascular embolization of a large spinal AVM in a patient with long-standing paraplegia due to Cobb syndrome.


Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides that Restore Trafficking and Activity of ΔF508-CFTR.
Cystic fibrosis (CF) is a loss-of-function disease caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, a chloride ion channel that localizes to the apical plasma membrane of epithelial cells. The most common form of the disease results from the deletion of phenylalanine-508 (ΔF508), leading to the accumulation of CFTR in the endoplasmic reticulum with a concomitant loss of chloride flux. We discovered that cyclic tetrapeptides, such as 11, 14, and 15, are able to correct the trafficking defect and restore cell surface activity of ΔF508-CFTR. Although this class of cyclic tetrapeptides is known to contain inhibitors of certain histone deacetylase (HDAC) isoforms, their HDAC inhibitory potencies did not directly correlate with their ability to rescue ΔF508-CFTR. In full HDAC profiling, 15 strongly inhibited HDACs 1, 2, 3, 10 and 11, but not HDACs 4-9. Although 15 had less potent IC(50) values than reference agent vorinostat (2) in HDAC profiling, it was markedly more potent than 2 in rescuing ΔF508-CFTR. We suggest that specific HDACs can have a differential influence on correcting ΔF508-CFTR, which may reflect both deacetylase and protein scaffolding actions.


Current steering detection scheme of three terminal antenna-coupled terahertz field effect transistor detectors.
An antenna-coupled field effect transistor (FET) as a plasma wave terahertz detector is used with the current steering to record separately the gate-source and gate-drain photoresponses and their phase sensitive combination. This method is based on the observation that the plasmon-terminal coupling is cut off in saturation, resulting in only one-sided sensitivity. A polarimetric example is presented with intensity and polarization angle reconstruction using a single three-terminal antenna-coupled Si-metal-oxide semiconductor FET (MOSFET). The technique is applicable to various detection schemes and technologies (high electron mobility transistors and GaAs-, GaN-, and Si-MOSFETs), and other application possibilities are discussed.


[Decision-making support in Intensive Care to facilitate organ donation : Position paper of the Ethics Section and the Organ Donation and Transplantation Section of the German Interdisciplinary Association of Critical Care and Emergency Medicine (DIVI) in collaboration with the Ethics Section of the German Society of Medical Intensive Care Medicine and Emergency Medicine (DGIIN)].
Injuries, especially traumatic brain injury, or specific illnesses and their respective sequelae can result in the demise of the patients afflicted despite all efforts of modern intensive care medicine. If in principle organ donation is an option after a patient's death, intensive therapeutic measures are regularly required in order to maintain the homeostasis of the organs. These measures, however, cannot benefit the patient afflicted anymore-which in turn might lead to an ethical conflict between dignified palliative care for him/her and expanded intensive treatment to facilitate organ donation for others, especially if the patient has opted for the limitation of life-sustaining therapies in an advance directive. The Ethics Section and the Organ Donation and Transplantation Section of the German Interdisciplinary Association of Critical Care and Emergency Medicine (DIVI) have convened several meetings and a telephone conference and have arrived at a decision-making aid as to the extent of treatment for potential organ donors. This instrument focusses first on the assessment of five individual dimensions regarding organ donation, namely the certitude of a complete and irreversible loss of all brain function, the patient's wishes as to organ donation, his or her wishes as to limiting life-sustaining therapies, the intensity of expanded intensive treatment for organ protection and the odds of its successful attainment. Then, the combination of the individual assessments, as graphically shown in a {Netzdiagramm}, will allow for a judgement as to whether a continuation or possibly an expansion of intensive care measures is ethically justified, questionable or even inappropriate. The aid described can help mitigate ethical conflicts as to the extent of intensive care treatment for moribund patients, when organ donation is a medically sound option. NOTE: Gerald Neitzke und Annette Rogge contributed equally to this paper and should be considered co-first authors.


Exercise does not induce major changes in plasma muscle enzymes, creatinine, glucose and total proteins concentrations in untrained beagle dogs.
Changes in plasma creatinine (Pl-Creat), glucose, total proteins (Pl-TP), creatine kinase (Pl-CK), lactate dehydrogenase, aspartate aminotransferase and packed cell volume were evaluated in untrained Beagle dogs before, during and after a 60 min race at an average speed of 9 km/h. There was no major effect of exercise on those parameters except, when phases are compared, a slight increase of Pl-TP during exercise (max. + 6.4%), a moderate but after exercise (delayed increase of Pl-CK max. + 245%) and a slight decrease of Pl-Creat after exercise (max. -9.6%). It was therefore concluded that strenuous exercise in sedentary dogs did not induce major variations in any of routine plasma variables measured and would not lead to clinically relevant misinterpretation. However, for Pl-CK, the interpretation of repeated measures may be misleading if two samples are collected in the same animal before and after exercise.


[The descendants questionnaire: a method for examining rural exodus in the areas of departure].
The authors examine the rural exodus in the Cameroon "through the use of a Descendants Questionnaire which is used to record the present place of residence of emigrant children as declared by their fathers. The methodology adopted for this exercise, though it raises certain specific problems, has made possible the recording of concrete conditions prevalent in the areas of departure of migrants." The project reported here began in 1981 and is continuing today. Copies of the questionnaire and the coding sheet are included in appendixes. (SUMMARY IN ENG)


One year in review 2021: axial spondyloarthritis.
Axial spondyloarthritides (axSpA) are a group of systemic inflammatory rheumatic diseases with a broad spectrum of clinical manifestations and typical imaging features, rarely accompanied by laboratory abnormalities. They can be classified into a so-called non-radiographic form (nr-axSpA), unlike the radiographic one, because magnetic resonance imaging may show specific inflammatory lesions when conventional radiology is not able to highlight them. Inflammatory involvement of the axial skeleton tends to associate typically with new bone formation and peripheral joints may also be affected. Patients with axSpA are at higher risk of developing some typical extraarticular manifestations, particularly, acute anterior uveitis, psoriasis and inflammatory bowel disease. In this paper we review the literature on axSpA of 2019 and 2020 (Medline search of articles published from 1st January 2019 to 31st December 2020).


Differential sensitivity of the caudal and rostral nucleus accumbens to the rewarding effects of a H1-histaminergic receptor blocker as measured with place-preference and self-stimulation behavior.
A recent series of studies in rats has demonstrated positively reinforcing and memory enhancing effects following lesions of the nucleus tuberomammillaris, which is the only known source of neuronal histamine. The aim of the present experiments was to assess whether inhibition of histaminergic neurotransmission in the ventral striatum has positively reinforcing effects. In Experiment 1 rats with chronically-implanted cannulae were injected with the H1 receptor blocker d-( + )-chlorpheniramine at doses of 0.1, 1.0 and 10.0 microg into the rostral or caudal parts of the nucleus accumbens, a brain region known to be involved in reward-related processes. Immediately after the treatment the animals were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. During the drug-free test for conditioned place preference, when a choice among the four quadrants was provided, those rats injected with 10.0 microg chlorpheniramine in the caudal nucleus accumbens spent more time in the treatment corral, indicative of a positively rewarding drug action. In Experiment 2 the question was posed whether injection of chlorpheniramine into the nucleus accumbens influences electrical self-stimulation of the lateral hypothalamus. For this purpose rats were chronically implanted with two bipolar electrodes aimed at the lateral-hypothalami and with two additional guide cannulae aimed either at the rostral or caudal nucleus accumbens. After having established reliable self-stimulation behavior at one of the two electrode sites the animals were allowed to self-stimulate for one hour (baseline). Then they were unilaterally injected with 10.0 microg chlorpheniramine or vehicle and allowed to self-stimulate for another hour (test). On the next day the same procedure took place, except for the difference that the animals received an injection aimed at the hemisphere not treated so far. Animals treated with chlorpheniramine in the caudal and in the rostral nucleus accumbens displayed higher rates of ipsihemispheric self-stimulation behavior. Moreover, the animals treated with the H1 receptor blocker in the caudal nucleus accumbens displayed higher rates of ipsihemispheric self-stimulation than those having received an injection in the rostral pole. Upon completion of this part of the experiment all animals received an additional intraperitoneal treatment with chlorpheniramine (20 mg/kg) or vehicle, respectively, and were tested in the same way described above. This treatment also resulted in an amplification of intracranial self-stimulation behavior. These results support the hypothesis that histaminergic neurotransmission is involved in the inhibitory control of a central system subserving reward-related processes. The present data also further highlight the nucleus accumbens as functionally heterogenous along its rostrocaudal axis, with the caudal-shell subregion being more sensitive to antihistaminic induced reward than the rostral entity.


Synthesis and processing of lysosomal alpha-fucosidase in cultured human fibroblasts.
The lysosomal enzyme alpha-L-fucosidase from human skin fibroblasts is synthesized as a 53 kDa glycosylated precursor which is then proteolytically processed to a 50 kDa mature form. This was confirmed by pulse-chase labeling studies with chase times up to 72 h. In fibroblasts treated with 1-deoxymannojirimycin to prevent trimming of high mannose oligosaccharides, endoglycosidase H (endo H) treatment completely deglycosylated and reduced the size of immunoprecipitated alpha-fucosidase by 4-5 kDa, suggesting the presence of two oligosaccharide units. Endoglycosidase H and endo F studies on untreated alpha-fucosidase suggested the presence of one complex-type and one high mannose-type unit, and that the final processing from 53 to 50 kDa did not involve the removal of carbohydrate. Processing was inhibited by the thiol proteinase inhibitor Ep-459, but not by Ep-475 or leupeptin. Since Ep-459 treatment increased both alpha-fucosidase activity (3-fold) and the amount of immunoprecipitable alpha-fucosidase protein in normal human skin fibroblasts, this suggests a role for cysteine-like proteinases either directly or indirectly in lysosomal hydrolase processing and turnover. Subcellular fractionation studies revealed that the proteolytic processing of the 53 kDa precursor to the 50 kDa mature form occurred in the lysosome, or some other dense organelle.


Why was the perinatal mortality rate higher in Denmark than in Sweden? The development in the 1970s and 1980s.
The purpose of this article is to identify factors explaining why the perinatal mortality rate ceased to fall in Denmark during the 1980s, while it continued to do so in Sweden, and to study the ability of known risk factors to predict this development. My analysis is based on routinely collected published data on all births, where I have studied the levels and changes in known risk factors for perinatal deaths in the two countries. The results of the study are: The proportion of low birth weight infants and the mothers' age and parity did not differ or change in a way that explains the higher perinatal mortality rate in Denmark during the 1980s. The weight specific perinatal mortality rate was the same in the two countries, with the exception of very low birth weight babies, i.e. below 1,500 grammes, where the perinatal mortality rate was higher in Denmark; this difference increased during the 1980s. The proportion of very low birth weight infants increased in Denmark from the 1970s to the 1980s while it remained stable in Sweden. The Danish increase in the proportion of low birth weight infants can be due to changed registration practices with more very small infants being registered in the 1980s. Among the factors studied registration practices, smoking and neonatal care seemed to be able to explain part of the differences between the two countries. The relative risk of perinatal death associated with the mothers' age and parity varied depending on the size of the groups at risk: the more women in high age and parity groups the lower the relative risk, which indicates that a selection as well as a causal effect was present. A conclusion is that the changes in relative risk over time associated with age and parity should lead to a closer investigation of the characteristics actually associated with an increased risk in order not to treat all old and multiparous women as patients at risk.


[Effect of corticosteroids on the action of sympathomimetics].
Corticosteroids restore the bronchial responsiveness to beta-adrenergic stimulants in man. This has been shown both in severe asthmatic patients and in normal subjects, rendered insensitive by artificial means. On the contrary, in patients with bronchial asthma who have airways reactive to beta-adrenergic stimulants, the combination of corticosteroids and sympathicomimetics results in an additive effect of their bronchodilating capacity. Animal models, both in vivo and in vitro, show the same type of interaction between corticosteroids and beta-adrenergic stimulants. The mechanism by which corticosteroids restore the bronchial sensitivity to beta-adrenergic stimulation is not completely understood. Several mechanisms may be involved such as increased agonist binding, decreased receptor turn-over, increased uncoupling between receptor and adenylcyclase, decreased extraneuronal uptake, decreased COMT-activity. The relevance of the influence of corticosteroids on the metabolism of membrane phospholipids remains highly speculative.


Randomized, Evaluator-Blinded Study Comparing Safety and Effect of Two Hyaluronic Acid Gels for Lips Enhancement.
Hyaluronic acid (HA) fillers may differ in terms of gel characteristics and ease of use and it is of interest whether this might affect safety and duration of effect. To compare the long-term safety and effect of 2 HA fillers produced by 2 different technologies for lip enhancement. Subjects with very thin to moderately thick lips were randomized and treated with HA-RK (N = 31) or HA-JV (N = 29) to improve lip fullness by ≥ 1 grade on a 5-point scale, using a maximum of 3 mL of product. A smaller volume of HA-RK compared with HA-JV was required to improve lip fullness by ≥ 1 grade (mean: 1.54 mL vs 1.94 mL, p < .001). Despite the smaller volume, lip fullness and global aesthetic improvement were comparably sustained in both groups. At 6 months, 60.0% versus 57.7% of subjects (HA-RK vs HA-JV) had improved lip fullness. At 12 months, 71.4% versus 76.0% had aesthetic improvement (blinded evaluations) and 85.7% versus 86.2% felt more attractive. Both products were well tolerated. Both products achieved durable improvement in lip fullness and aesthetic appearance. A significantly smaller amount of HA-RK was required compared with HA-JV to achieve optimal treatment effect.


Molecular Identification and Genotyping of Babesia canis in Dogs from Meshkin Shahr County, Northwestern Iran.
Canine babesiosis is one of the mainly worldwide-distributed tick-borne haemoprotozoan parasitic diseases in dogs. A total of 43 blood samples were randomly collected from naturally infected dogs in seven villages from different geographical areas of Meshkin Shahr, Ardabil Province, Iran. The presence of Babesia species detected with standard methods including parasitological and gene sequencing techniques targeting the 18S rRNA gene. Our results revealed that four dogs 9.3% (4/43) including one female and three male dogs were infected with Babesia. All four Babesia-infected dogs were confirmed B. canis by the molecular-based method. Sequence alignments comparison of the B. canis genotypes A and B, it was revealed that all B. canis isolates belonged to genotype B. This study provides essential data for subsequently define the critical importance of the molecular studies in management and prevention of the canine babesiosis in Iran.


Identification and functional characterization of ASK/Dbf4, a novel cell survival gene in cutaneous melanoma with prognostic relevance.
Malignant melanoma is one of the most aggressive and invasive metastatic tumors derived from melanocytes that have undergone malignant transformation by acquisition of genetic and epigenetic alterations. Oligonucleotide microarray-based screening of distinct stages in the tumor progression model of cutaneous melanoma identified ASK/Dbf4, as a novel determinant for melanoma development. Quantitative real-time polymerase chain reaction-based confirmation of ASK/Dbf4 on a series of benign nevi, dysplastic nevi, primary cutaneous melanomas and cutaneous melanoma metastases; and a number of other controls using normal human melanocytes as calibrator not only revealed a melanoma-specific over-expression but also revealed that higher ASK/Dbf4-expressing melanomas were associated with lower relapse-free survival. Additionally, we also confirmed the observed over-expression of ASK/Dbf4 in melanoma using western blot analysis and immunohistochemistry. As ASK/Dbf4 is known to be a cyclin-like regulatory subunit of mammalian Cdc7 from the studies in yeast, the present study investigated its role in melanoma cells. In keeping with its expected role, our data suggest that up-regulated ASK/Dbf4 is localized in the nucleus and binds to human Cdc7 to form Cdc7-ASK/Dbf4 complexes in several analyzed melanoma cell lines. Further, we demonstrate that small interfering RNA-mediated depletion of ASK/Dbf4 retarded melanoma cell survival and proliferation. In summary, we report the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggest that up-regulation of ASK/Dbf4 is a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma.


New method for the estimation of platelet ascorbic acid.
Present techniques for the estimation of platelet ascorbic acid allow interference by other substances in the sample. A new and more specific method of analysis is presented. The proposed method owes its increased specificity to resolution of the extract by thin-layer chromatography. By this means ascorbic acid is separated from other reducing substances present. The separated ascorbic acid is eluted from the thin layer and estimated by a new and very sensitive procedure: ascorbic acid is made to react with ferric chloride and the ferrous ions so formed are estimated spectrophotometrically by the coloured derivative which they form with tripyridyl-Striazine. Results obtained with normal blood platelets were consistently lower than simultaneous determinations by the dinitrophenylhydrazine (DNPH) method.


Acari ectoparasites of bats from Minas Gerais, Brazil.
Ectoparasites were recovered from Brazilian bats captured from April to November 1997 at or near Parque Estadual do Rio Doce, State of Minas Gerais, southeastern Brazil. Sixty bats were collected, representing three families and 13 species. Five Acari families were recorded: Myobiidae, Trombiculidae, Labidocarpidae, Macronyssidae, and Spinturnicidae. The macronyssid Radfordiella desmodi Radovsky (71 specimens) and the spinturnicid Periglichrus iheringi Oudemans (45 specimens) were the most abundant mite species. They were mainly recorded on Desmodus rotundus (Geoffroy) and Artibeus litratus (Ofers), respectively. Among trombiculid chiggers, the genus Colicus Brennan (55 specimens) was predominant and found mainly on Carollia perspicillata (L.). The current study presents new data about host-parasite relationships and increases the understanding of geographical distribution for some mite and chigger species.


Toxic element profiles in selected medicinal plants growing on serpentines in Bulgaria.
Populations of medicinal plants growing on serpentines and their respective soils were analyzed for Fe, Ni, Mn, Cr, Co, Cd, Cu, Zn, and Pb using inductively coupled plasma atomic emission spectrometry. Aqua regia extraction and 0.43 M acetic acid extraction were used for the quantification of pseudototal and bioavailable fractions, respectively, of elements in soil and nitric acid digestion for determination of total element content in plants. Screening was performed to (1) document levels of toxic metals in herbs extensively used in preparation of products and standardized extracts, (2) compare accumulation abilities of ferns and seed plants, and (3) estimate correlations between metal content in plants and their soils. The toxic element content of plants varied from site to site on a large scale. The concentrations of Fe and Ni were elevated while those of Cu, Zn, and Pb were close to average values usually found in plants. The highest concentrations for almost all elements were measured in both Teucrium species. Specific differences in metal accumulation between ferns and seed plants were not recorded. The investigated species are not hyperaccumulators but can accumulate toxic elements, in some cases exceeding permissible levels proposed by the World Health Organization and European Pharmacopoeia. The harvesting of medicinal plants from serpentines could be hazardous to humans.


[Risk factors in the Glenn bidirectional shunt as an intermediate procedure before Fontan correction].
The bidirectional Glenn shunt is the most common palliation before the Fontan repair, especially in high-risk patients. We studied the influence of certain risk factors in bidirectional Glenn results, with and without an additional source of pulmonary blood flow. Between 1993 and 1998 twenty patients (6-53 months of age) underwent a bidirectional Glenn shunt as the intermediate repair for the Fontan procedure. Diagnoses were: 7 cases of double inlet single ventricle, 4 of tricuspid atresia, 3 of unbalanced AV septal defect, 4 of mitral atresia, 1 hypoplastic left heart syndrome and 1 TGA with hypoplasia of the right ventricle. 17 patients had undergone previous operations. Mean preoperative arterial oxygen saturation was 78.5%. In 6 patients an auxiliary source of pulmonary blood flow was added. Hospital mortality was 15%. In 4 patients the bidirectional Glenn failed. By univariate analysis low weight, preoperative functional status and high pulmonary pressure were factors associated with early death. In bidirectional Glenn failure only the duration of ventilatory support was significant. By multivariate analysis, preoperative functional status and pulmonary pressure were significant. Mean postoperative arterial oxygen saturation at a mean follow-up of 10 months was 84%. Bidirectional Glenn shunt is an effective and low-risk palliation for patients with univentricular hearts. Only low weight and high pulmonary pressure were significant in hospital mortality, and we advise the association of an additional source of pulmonary blood flow in these patients at the start. Early extubation provides correct performance of the shunt.


Knowledge and utilization of electrocardiogram among resident doctors in family medicine in Nigeria.
Electrocardiogram (ECG) is a simple, readily affordable, and noninvasive tool for the evaluation of cardiac disorders. There is a dearth of information on the utility of ECG in general practice in Nigeria. We assessed the knowledge and utilization of ECG among family medicine residents in Nigeria. A cross-sectional evaluation was conducted between November 2011 and May 2012 in four family medicine training centers in Nigeria. A self-administered questionnaire was used to obtain information from the resident doctors regarding their ECG requests, preferred source of interpretation, most common ECG diagnosis, and update of ECG knowledge. Only 61 out of 120 questionnaires (50.8%) were returned. The respondents were mostly between 31 and 40 years (54.7%) and were predominantly males (73.8%) and senior residents (65.6%). Fifty-four (88.3%) respondents made <5 ECG requests/week, and the most common indication was hypertension (50%). ECG interpretation was either self-reported (41%), by a cardiologist (26.5%), or automated reports (21.3%). Self-reporting of ECG was more common among senior residents (P < 0.01). Left ventricular hypertrophy was the most common ECG diagnosis (55.8%). About 69% of respondents did not update their knowledge of ECG. Most respondents (50%) reported basic interpretation as the aspect of ECG for which further learning was desired. Teaching ECG to resident doctors in the update courses of the postgraduate medical colleges and continuing medical education (CME) activities was adjudged the best way to improve knowledge/utility (61.1%). The attitude to and utility of ECG among family medicine residents in Nigeria is poor. Improved knowledge, attitude, and utilization of ECG through curriculum revision, hands-on tutorials, and CMEs are highly recommended.


Updates in hyperkalemia: Outcomes and therapeutic strategies.
Hyperkalemia is a frequent clinical abnormality in patients with chronic kidney disease, and it is associated with higher risk of mortality and malignant arrhythmias. Severe hyperkalemia is a medical emergency, which requires immediate therapies, followed by interventions aimed at preventing its recurrence. Current treatment paradigms for chronic hyperkalemia management are focused on eliminating predisposing factors, such as high potassium intake in diets or supplements, and the use of medications known to raise potassium level. Among the latter, inhibitors of the renin-angiotensin aldosterone system are some of the most commonly involved medications, and their discontinuation is often the first step taken by clinicians to prevent the recurrence of hyperkalemia. While this strategy is usually successful, it also deprives patients of the recognized benefits of this class, such as their renoprotective effects. The development of novel potassium binders has ushered in a new era of hyperkalemia management, with a focus on chronic therapy while maintaining the use of beneficial, but hyperkalemia-inducing medications such as renin-angiotensin aldosterone system inhibitors. This review article examines the incidence and clinical consequences of hyperkalemia, and its various treatment options, with special emphasis on novel therapeutic agents and the potential benefits of their application.


Methanogenic activity inhibition by increasing the linear alkylbenzene sulfonate (LAS) concentration.
The effect of the initial concentration of linear alkylbenzene sulfonate (LAS) on specific methanogenic activity (SMA) was investigated in this work. Six anaerobic flasks reactors with 1 L of total volume were inoculated with anaerobic sludge (2 g VSS L(-1)). The reactors were assayed for 42 days, and fed with volatile fatty acids, nutrients, and LAS. The initial LAS concentrations were 0, 10, 30, 50, 75, and 100 mg L(-1) for the treatment flasks T1 (control), T2, T3, T4, T5, and T6, respectively. When compared with T1, T2 exhibited a 30% reduction in maximum SMA and total methane production (TMP). In treatment T3 through T6, the reductions were 44-97% (T3-T6) for SMA, and 30-90% (T3-T6) for TMP. Total LAS removal increased following the increase in the initial LAS concentration (from 36% at T1 to 76% at T6), primarily due to the high degree of sludge adsorption. LAS biodegradation also occurred (32% in all treatments), although this was most likely associated with the formation of non-methane intermediates. Greater removal by adsorption was observed in long-chain homologues, when compared to short-chain homologues (C13 > C10), whereas the opposite occurred for biodegradation (C10 > C13). The C13 homologue was adsorbed to a great extent (in mass) in T4, T5 and T6, and may also have inhibited methane formation in these treatments.


Prevalence of Congenital Cutaneous Anomalies in 1000 Newborns and a Review of the Literature.
There are limited reports studying on congenital cutaneous anomalies in newborns, particularly in Turkey. Some of congenital cutaneous anomalies serve as an important clue for accompanying syndromes or other medical conditions. This study aimed to determine the prevalence of congenital cutaneous anomalies in newborns and to discuss their clinical significance with a brief review of literature. A total of 1,000 newborns were examined by a dermatologist in a hospital-based, cross-sectional, prospective study between October 2011 and April 2012. We observed 11 different congenital cutaneous anomalies in 48 newborns of 1,000 (4.8%). The most commonly seen anomalies were sacral dimple, accessory nipple, acrochordon, hypospadias, open spinal dysraphism, and accessory tragus. None of the newborns with cutaneous anomalies had any association. Although congenital cutaneous anomalies are rare in newborns, clinicians should be aware of them as they may be in association with syndromes and other medical conditions. It is also important to give appropriately provided information to avoid parents concerns.


Decision support system for breast cancer detection using mammograms.
Mammograms are by far one of the most preferred methods of screening for breast cancer. Early detection of breast cancer can improve survival rates to a greater extent. Although the analysis and diagnosis of breast cancer are done by experienced radiologists, there is always the possibility of human error. Interobserver and intraobserver errors occur frequently in the analysis of medical images, given the high variability between every patient. Also, the sensitivity of mammographic screening varies with image quality and expertise of the radiologist. So, there is no golden standard for the screening process. To offset this variability and to standardize the diagnostic procedures, efforts are being made to develop automated techniques for diagnosis and grading of breast cancer images. This article presents a classification pipeline to improve the accuracy of differentiation between normal, benign, and malignant mammograms. Several features based on higher-order spectra, local binary pattern, Laws' texture energy, and discrete wavelet transform were extracted from mammograms. Feature selection techniques based on sequential forward, backward, plus-l-takeaway-r, individual, and branch-and-bound selections using the Mahalanobis distance criterion were used to rank the features and find classification accuracies for combination of several features based on the ranking. Six classifiers were used, namely, decision tree classifier, fisher classifier, linear discriminant classifier, nearest mean classifier, Parzen classifier, and support vector machine classifier. We evaluated our proposed methodology with 300 mammograms obtained from the Digital Database for Screening Mammography and 300 mammograms from the Singapore Anti-Tuberculosis Association CommHealth database. Sensitivity, specificity, and accuracy values were used to compare the performances of the classifiers. Our results show that the decision tree classifier demonstrated an excellent performance compared to other classifiers with classification accuracy, sensitivity, and specificity of 91% for the Digital Database for Screening Mammography database and 96.8% for the Singapore Anti-Tuberculosis Association CommHealth database.


Effects of dietary macronutrient distribution on vascular integrity in obesity and metabolic syndrome.
Metabolic syndrome is a condition characterized by a clustering of risk factors for cardiovascular disease. Emerging data suggest vascular integrity is disrupted in metabolic syndrome. Vascular integrity may be determined using several measurements, including pulse wave velocity, augmentation index, and flow-mediated dilation. Arterial stiffness has become an important clinical indicator of cardiovascular disease risk. Several circulating inflammatory peptides also impact vascular integrity. The present review examines the efficacy of nutritional interventions aimed at improving vascular integrity and reducing levels of associated inflammatory peptides in individuals with metabolic syndrome, with a specific focus on the effect of dietary macronutrient redistribution on these factors.


Complete Genome Sequencing and Comparative Genomics of Three Potential Probiotic Strains, Lacticaseibacillus casei FBL6, Lacticaseibacillus chiayiensis FBL7, and Lacticaseibacillus zeae FBL8.
Lacticaseibacillus casei, Lacticaseibacillus chiayiensis, and Lacticaseibacillus zeae are very closely related Lacticaseibacillus species. L. casei has long been proposed as a probiotic, whereas studies on functional characterization for L. chiayiensis and L. zeae are some compared to L. casei. In this study, L. casei FBL6, L. chiayiensis FBL7, and L. zeae FBL8 were isolated from raw milk, and their probiotic properties were investigated. Genomic analysis demonstrated the role of L. chiayiensis and L. zeae as probiotic candidates. The three strains were tolerant to acid and bile salt, with inhibitory action against pathogenic bacterial strains and capacity of antioxidants. Complete genome sequences of the three strains were analyzed to highlight the probiotic properties at the genetic level, which results in the discovery of genes corresponding to phenotypic characterization. Moreover, genes known to confer probiotic characteristics were identified, including genes related to biosynthesis, defense machinery, adhesion, and stress adaptation. The comparative genomic analysis with other available genomes revealed 256, 214, and 32 unique genes for FBL6, FBL7, and FBL8, respectively. These genomes contained individual genes encoding proteins that are putatively involved in carbohydrate transport and metabolism, prokaryotic immune system for antiviral defense, and physiological control processes. In particular, L. casei FBL6 had a bacteriocin gene cluster that was not present in other genomes of L. casei, resulting in this strain may exhibit a wide range of antimicrobial activity compared to other L. casei strains. Our data can help us understand the probiotic functionalities of the three strains and suggest that L. chiayiensis and L. zeae species, which are closely related to L. casei, can also be considered as novel potential probiotic candidate strains.


Effects of repeated short versus single long episodes of focal ischemia on somatosensory evoked potentials and development of cerebral infarction in cats.
The effects of repeated short episodes of focal ischemia at 30-minute intervals or a single equivalent long episode of focal ischemia on neuronal function and development of cerebral infarction were compared using somatosensory evoked potential (SEP) recording and 2,3,5-triphenyltetrazolium chloride staining in a cat model. Seventeen cats underwent transorbital occlusion of the middle cerebral artery (MCA), using one of three procedures: sham-operation; single 1-hour occlusion of the MCA, followed by 3 hours of recirculation; or three 20-minute occlusions of the MCA at 30-minute intervals, followed by 3 hours of recirculation. Two of six cats in the single long-term occlusion group showed recovery of SEP, whereas all six cats in the repeated short-term occlusion group showed recovery of SEP at 3 hours after recirculation. All six cats in the single long-term occlusion group had cerebral infarction of various sizes, but only one cat in the repeated short-term occlusion group developed infarction. Repeated short episodes of focal ischemia are relatively less damaging than a single equivalent long episode of focal ischemia, even if the reperfusion interval is extended to 30 minutes.


Ondansetron blocks nifedipine-induced analgesia in rats.
The serotonergic system is involved in pain transmission and the 5-hydroxytryptamine (5-HT3) receptor subtype mediates some of these effects at the spinal level. Therefore, we explored the effects of the serotonergic system on nifedipine-induced analgesia by using the 5-HT3 receptor antagonist ondansetron. Male Sprague-Dawley rats were pretreated with ondansetron (1 mg/ kg intraperitoneally) or normal saline. After 15 min, rats received injections of nifedipine (15 mg/kg intraperitoneally) or dimethylsulfoxide (DMSO), solvent for nifedipine, as a control. Nociception was assessed by tail-flick method. Rats treated with nifedipine alone had an increase in tail-flick latency of 122%, as measured by the area under the curve, compared to rats treated with DMSO alone. Pretreatment with ondansetron, however completely blocked the analgesic effect of nifedipine, with tail-flick latency remaining at baseline throughout the measurement period. These results indicate that the 5-HT3 receptor plays an important role in the analgesic response to nifedipine and that medications that block this receptor may decrease the analgesic effectiveness of this type of therapy.


Gnathostomiasis: import from Laos.
Gnathostomiasis is a nematode infestation endemic in Southeast Asia, which can involve multiple organs including the liver, eyes, gastrointestinal tract and CNS. The most common manifestation is recurrent migratory subcutaneous swellings which can appear anywhere on the body and are accompanied by pruritus and systemic symptoms such as low-grade fever, loss of appetite and nausea. The diagnosis is based on the clinical picture, history of travel, peripheral blood eosinophilia and the determination of agent-specific antibody levels. The standard treatment is albendazole. We present a 37-year-old Laotian woman, who had lived in Germany for 17 years, but developed recurrent swelling of the cheek following a visit to Laos. Because of the typical clinical findings, the history of a visit to Laos, and the presence of specific anti-Gnathostoma antibodies on Western blot, the diagnosis of cutaneous gnathostomiasis was made.


Observing Pain in Individuals with Cognitive Impairment: A Pilot Comparison Attempt across Countries and across Different Types of Cognitive Impairment.
Facial expression is a key aspect in observational scales developed to improve pain assessment in individuals with cognitive impairments. Although these scales are used internationally in individuals with different types of cognitive impairments, it is not known whether observing facial expressions of pain might differ between regions or between different types of cognitive impairments. In a pilot study, facial responses to standardized experimental pressure pain were assessed among individuals with different types of cognitive impairments (dementia, mild cognitive impairment, Huntington's disease, and intellectual disability) from different countries (Denmark, Germany, Italy, Israel, and Spain) and were analyzed using facial descriptors from the PAIC scale (Pain Assessment in Impaired Cognition). We found high inter-rater reliability between observers from different countries. Moreover, facial responses to pain did not differ between individuals with dementia from different countries (Denmark, Germany, and Spain). However, the type of cognitive impairment had a significant impact; with individuals with intellectual disability (all being from Israel) showing the strongest facial responses. Our pilot data suggest that the country of origin does not strongly affect how pain is facially expressed or how facial responses are being scored. However, the type of cognitive impairment showed a clear effect in our pilot study, with elevated facial responses in individuals with intellectual disability.


Sensitivity and specificity of food specific IgE and IgG determinations for the diagnosis of food allergy.
Among the methods currently used to demonstrate a sensitization to foods, the measurement of food specific IgE antibodies (sIgE) is the most practical but not the most accurate. The "sensitivity" of food sIgE determinations is, for example, suboptimal with unstable allergens in fruits and vegetables that are involved in the (birch) pollen-related immediate oral allergy syndromes. In this particular syndrome the history is often conclusive and can be substantiated by skin prick tests with fresh foods. The "sensitivity" of sIgE tests is much better when sIgE are directed to stable plant or animal food allergens which often cause non-immediate generalized reactions. Foods, usually, contain many different (glyco)proteinic allergens of which some are stable and others not. The "sensitivity" of the sIgE test with a particular food, therefore, varies according to the type of allergen that is recognized by the patient. The "specificity" of sIgE tests with foods is affected by the existence of homologous food allergens which induce cross-reactive IgE that may or may not be clinically relevant. While variable, clinical cross-reactivity is more common among botanically-related fruits, among different nuts, among mammalian foods and among seafood than among cereals, grains and legumes. The "specificity" of food sIgE tests is much better when sIgE are directed to unique non-cross-reactive food allergens. Unfortunately, neither the presence of food sIgE nor its level are predictive of clinical reactivity. The identification of individual allergens in foods and the characterization of the relevant IgE binding sites in these allergens might lead to the development of tests that only measure sIgE to clinical relevant food allergens.


VEGFR2 translocates to the nucleus to regulate its own transcription.
Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is the major mediator of the angiogenic effects of VEGF. In addition to its well known role as a membrane receptor that activates multiple signaling pathways, VEGFR2 also has a nuclear localization. However, what VEGFR2 does in the nucleus is still unknown. In the present report we show that, in endothelial cells, nuclear VEGFR2 interacts with several nuclear proteins, including the Sp1, a transcription factor that has been implicated in the regulation of genes needed for angiogenesis. By in vivo chromatin immunoprecipitation (ChIP) assays, we found that VEGFR2 binds to the Sp1-responsive region of the VEGFR2 proximal promoter. These results were confirmed by EMSA assays, using the same region of the VEGFR2 promoter. Importantly, we show that the VEGFR2 DNA binding is directly linked to the transcriptional activation of the VEGFR2 promoter. By reporter assays, we found that the region between -300/-116 relative to the transcription start site is essential to confer VEGFR2-dependent transcriptional activity. It was previously described that nuclear translocation of the VEGFR2 is dependent on its activation by VEGF. In agreement, we observed that the binding of VEGFR2 to DNA requires VEGF activation, being blocked by Bevacizumab and Sunitinib, two anti-angiogenic agents that inhibit VEGFR2 activation. Our findings demonstrate a new mechanism by which VEGFR2 activates its own promoter that could be involved in amplifying the angiogenic response.


Management of a large dentigerous cyst occurring in a six-year-old boy.
A case of dentigerous cyst in a six-year-old healthy Brazilian boy, who had a diagnostic hypothesis of ameloblastoma and keratocyst because of the extension and radiographic appearance is presented. The importance of a previous incisional biopsy and consequent conservative treatment is discussed.


Characterization of resting functional MRI activity alterations across epileptic foci and networks.
Brain network alterations have been studied extensively in patients with mesial temporal lobe epilepsy (mTLE) and other focal epilepsies using resting-state functional magnetic resonance imaging (fMRI). However, little has been done to characterize the basic fMRI signal alterations caused by focal epilepsy. Here, we characterize how mTLE affects the fMRI signal in epileptic foci and networks. Resting-state fMRI and diffusion MRI were collected from 47 unilateral mTLE patients and 96 healthy controls. FMRI activity, quantified by amplitude of low-frequency fluctuations, was increased in the epileptic focus and connected regions in mTLE. Evidence for spread of this epileptic fMRI activity was found through linear relationships of regional activity across subjects, the association of these relationships with functional connectivity, and increased activity along white matter tracts. These fMRI activity increases were found to be dependent on the epileptic focus, where the activity was related to disease severity, suggesting the focus to be the origin of these pathological alterations. Furthermore, we found fMRI activity decreases in the default mode network of right mTLE patients with different properties than the activity increases found in the epileptic focus. This work provides insights into basic fMRI signal alterations and their potential spread across networks in focal epilepsy.


EGCG Prevents the Onset of an Inflammatory and Cancer-Associated Adipocyte-like Phenotype in Adipose-Derived Mesenchymal Stem/Stromal Cells in Response to the Triple-Negative Breast Cancer Secretome.
Triple-negative breast cancer (TNBC) cells secretome induces a pro-inflammatory microenvironment within the adipose tissue, which hosts both mature adipocytes and adipose-derived mesenchymal stem/stromal cells (ADMSC). The subsequent acquisition of a cancer-associated adipocyte (CAA)-like phenotype is, however, unknown in ADMSC. While epidemiological studies suggest that consuming a polyphenol-rich diet reduces the incidence of some obesity-related cancers, the chemopreventive impact of green tea-derived epigallocatechin-3-gallate (EGCG) against the cues that trigger the CAA phenotype remain undocumented in ADMSC. Human ADMSC were exposed to human TNBC-derived MDA-MB-231 conditioned media (TNBC cells secretome) supplemented or not with EGCG. Differential gene expression was assessed through RNA-Seq analysis and confirmed by RT-qPCR. Protein expression levels and the activation status of signal transduction pathways mediators were determined by Western blotting. ADMSC chemotaxis was assessed by a real-time cell migration assay. The TNBC cells secretome induced in ADMSC the expression of the CAA cytokines CCL2, CCL5, IL-1β, and IL-6, and of immunomodulators COX2, HIF-1α, VEGFα, and PD-L1. The epithelial-to-mesenchymal biomarker Snail was found to control the CAA phenotype. EGCG inhibited the induction of CAA genes and the activation status of Smad2 and NF-κB. The induced chemotactic response was also inhibited by EGCG. The induction of an inflammatory and CAA-like phenotype in ADMSC can be triggered by the TNBC cells secretome, while still efficiently prevented by diet-derived polyphenols.


Topographic organization and neurochemical identity of dorsal raphe neurons that project to the trigeminal somatosensory pathway in the rat.
The primary goals of this study were to: 1) examine the distribution of neurons within the dorsal raphe (DR) nucleus that project to cortical and subcortical sites along the trigeminal somatosensory pathway in rat; 2) determine the extent to which different regions within this ascending sensory system receive collateral projections from the same DR neuron; and 3) identify the putative transmitters contained within these DR projection neurons. Long-Evans hooded rats received pressure injections of various combinations of retrograde fluorescent tracers; into the whisker-related regions of the primary somatosensory cortex (barrel field cortex [BC]), ventral posterior medial thalamus (VPM), and principal nucleus of the trigeminal complex (PrV). The distribution of retrogradely labeled neurons within the DR was examined by fluorescence microscopy. The major finding was that cortically projecting neurons were located within the midline regions of the rostral portion of the DR, whereas cells projecting to subcortical trigeminal somatosensory structures were distributed bilaterally in the lateral wing regions of the DR as well as in the midline portions of the nucleus. Single neurons that send axon collaterals to multiple cortical and subcortical trigeminal somatosensory targets were observed in the dorsomedian and ventromedian regions of the DR. DR neurons that projected to cortical and subcortical sites contained serotonin but not tyrosine hydroxylase, the marker enzyme for catecholamine transmitters. Taken together, these findings provide further evidence of neurochemical specificity and functional anatomical organization within the DR efferent projection system.


Responses of increasingly complex intestinal epithelium in vitro models to bacterial toll-like receptor agonists.
The intestine fulfills roles in the uptake of nutrients and water regulation and acts as a gatekeeper for the intestinal microbiome. For the latter, the intestinal gut barrier system is able to respond to a broad range of bacterial antigens, generally through Toll-like receptor (TLR) signaling pathways. To test the capacity of various in vitro intestinal models, we studied IL-8 secretion, as a marker of pro-inflammatory response through the TLR pathway, in a Caco-2 monoculture, Caco-2/HT29-MTX di-culture, Caco-2/HT29-MTX/HMVEC-d tri-culture and in a HT29-p monoculture in response to exposure to various TLR agonists. Twenty-one-day-old differentiated cells in Transwells were exposed to Pam3CSK4 (TLR1/2), lipopolysaccharide (TLR4), single-stranded RNA (TLR7/8), Poly(i:C) (TLR3) and flagellin (TLR5) for 24 h. In all systems IL-8 secretion was increased in response to flagellin exposure, with HT29-p cells also responding to Poly(I:C) exposure. All other agonists did not induce an IL-8 response in the tested in vitro models, indicating that the specific TLRs are either not present or not functional in these models. This highlights the need for careful selection of in vitro models when studying intestinal immune responses and the need for improved in vitro models that better recapitulate intestinal immune responses.


How different is California? A comparison of U.S. physician organizations.
Data from a national study of medical groups and independent practice associations are used to examine the extent to which California physician organizations are different from physician organizations in the rest of the United States. California physician organizations are different in many ways: most notably, they are more likely to have external incentives to improve quality and more likely to use recommended care management processes for treating patients with chronic illnesses. The implications of these differences for policy and practice are discussed.


Host specificity and phylogeny of Trichostrongylidae of domestic ruminants in the Guinea savannah of the Adamawa plateau in Cameroon.
Gastro-intestinal tracts were examined from thirteen Gudali zebu cattle, ten goats and ten sheep from the Adamawa highland in Northern Cameroon. A total of 28,325 adult helminths were recovered from the abomasa, small and large intestines. Five trichostrongylid genera were identified by their morphology: Haemonchus, Trichostrongylus and Oesophagostomum were predominant in both cattle and small ruminants, whilst Cooperia was only found in cattle both in the abomasum and small intestines. The molecular species identification and the inference of their phylogenetic relationships was based on the analysis of the hypervariable region I of the small subunit 18S rDNA (SSU) and the Second Internal Transcribed Spacer (ITS-2) of 408 adult trichostrongylid worms, which were PCR-amplified, sequenced, and compared with available database entries. Consistent with earlier findings, the SSU was invariable within the Haemonchus and Trichostrongylus genera, confirming the prior classification based on the morphology of the worms, but the ITS-2 was highly inter- and intraspecifically variable and thus allowed to distinguish individual species and to study the haplotype diversity within the different species. In cattle, we report for the first time in Cameroon co-infection with two species of Haemonchus (H. placei and H. similis), together with two species of Cooperia (C. punctata and C. pectinata) and one species of Trichostrongylus (T. axei). In goats and sheep, we found one highly polymorphic clade of Haemonchus contortus and two Trichostrongylus species (T. axei and T. colubriformis). When compared with other Trichostrongylidae from different regions of the world and wildlife, the analysis of haplotypes did not indicate any host and geographical isolation, but a very high haplotype diversity among H. contortus. These findings illustrate the complexity of trichostrongylid populations in domestic ruminants and suggest grazing overlap between domestic and wildlife hosts.


Imaging Fast-Acting Drug Effects in Humans Using 1H-MRS.
Proton magnetic spectroscopy (1H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmacological treatment, chronic drug use, and alcohol dependence. In contrast, the capacity of 1H-MRS to evaluate the biochemical changes in the minutes to hours following drug consumption, which contribute to fast-acting drug-induced changes in perception, mood, cognition, and behavior, is largely unexplored. This Viewpoint highlights the utility of 1H-MRS imaging for revealing neural mechanisms of rapid drug action in the human brain, with implications for phasic, in vivo changes in biosynthetic and catabolic pathways after drug exposure. Drawing from examples of psychostimulant drug effects, neuromodulatory input and drug-induced mood, we present strategies to optimize 1H-MRS for noninvasively imaging fast-acting drug effects and other rapid phenomena within the living human brain. These approaches could provide powerful tools for both basic research and drug development.


[Analysis of Component Spectral Characteristics of PM10-Bound PAHs and the Influence of Weather Conditions During Spring in Xiamen].
In order to study pollution status and distribution characteristics of PAHs in PM10 during the spring in city and suburban Xiamen. A total of 18 PAHs were analyzed in the aerosol samples collected in daytime and nighttime during 11th to 21st of April, 2013 in city and suburban Xiamen. Results showed diurnal variation of Σ PAHs in suburban was weaker than that in city. In the city, the concentration of PAHs during daytimes was higher than that during nighttimes, close to 1.83 times, and it is still under the national environmental standards. In different times and space scales, PAHs were a bimodal distribution, the components of PAHs gave the priority to low and middle rings in urban and suburban during daytimes and nighttimes. PAHs with high molecular weight decreased gradually by the increase of particle size, and the proportion of low molecular weight PAHs increased gradually in the meantime. In the city, the change of size distribution among 2-4 rings PAHs in PM10 during days and nights was bigger than these among 5-7 rings. The main sources of PAHs were estimated by DR, the main contributions included gasoline and diesel combustion, the smelting furnace exhaust emissions. During sampling periods, the relationship between the concentration of PAHs, temperature and WD is negative, PAHs had a positive correlation with the visibility and WS in suburban. And in urban, the relationship with temperature during the day was negative, and with an opposite correlation between other meteorological elements.


Results of a multi-media multiple behavior obesity prevention program for adolescents.
This study reports on effectiveness trial outcomes of Health in Motion, a computer tailored multiple behavior intervention for adolescents. Using school as level of assignment, students (n=1800) from eight high schools in four states (RI, TN, MA, and NY) were stratified and randomly assigned to no treatment or a multi-media intervention for physical activity, fruit and vegetable consumption, and limited TV viewing between 2006 and 2007. Intervention effects on continuous outcomes, on movement to action and maintenance stages, and on stability within action and maintenance stages were evaluated using random effects modeling. Effects were most pronounced for fruit and vegetable consumption and for total risks across all time points and for each behavior immediately post intervention. Co-variation of behavior change occurred within the treatment group, where individuals progressing to action or maintenance for one behavior were 1.4-4.2 times more likely to make similar progress on another behavior. Health in Motion is an innovative, multiple behavior obesity prevention intervention relevant for all adolescents that relies solely on interactive technology to deliver tailored feedback. The outcomes of the effectiveness trial demonstrate both an ability to initiate behavior change across multiple energy balance behaviors simultaneously and feasibility for ease of dissemination.


[Factors associated with investment in an office medicine project by general practice residents].
To identify thefactors associated with investment in an office medicine project by French general practice (GP) residents. We conducted a national survey using a web-based self-administered questionnaire and analyzed the data collected by multiple logistic regressions. The dependent variable was "an office medicine project" The explanatory variables were both individual (socio-demographic and linked to training trajectories) and contextual (related to the available training programmes and the regional medical demography). The response rate was 48.5%. Out of the 1,695 residents of the study sample, 315 (18.6%) already had a project to setup an office practice during their third cycle ofmedical studies. The main factors associated with this project were (p < 0.05): to receive strong academic support, to live in a rural or semi-rural area, to work as a GP locum, to perform residency training in the same city as the medical training and to perform residency training in a region with a high percentage of GPs 55years and older. This study showed that a project to setup an office practice was influenced by both individual and contextualfactors. Special attention should be paid to the means and content of training to ensure better supportfor residents, which could make office general practice more attractive.


Cisplatin-Rich Polyoxazoline-Poly(aspartic acid) Supramolecular Nanoparticles.
Cisplatin-rich supramolecular nanoparticles are constructed through the supramolecular inclusion interaction between the admantyl (Ad)-terminated poly(aspartic acid) (Ad-P(Asp)) and the β-cyclodextrin (β-CD)-terminated poly(2-methyl-2-oxazoline). In the formation of the nanoparticles, the β-CD/admantane inclusion complex integrates poly(2-methyl-2-oxazoline) and poly(aspartic acid) chains to form pseudoblock copolymers, followed by the coordination between carboxyl groups in P(Asp) block and cisplatin. This coordination interaction drives the formation of nanoparticle and enables cisplatin incorporated into the nanoparticles. The spherical cisplatin-rich supramolecular nanoparticles have 53% cisplatin-loading content, good stability, and effective inhibition of the cell proliferation when it is tested in H22 cancer cells. Near-infrared fluorescence imaging of tumor bearing mice reveals that the cisplatin-rich nanoparticles can target the tumor in vivo effectively.


Germination of Phaseolus vulgaris: IV. Patterns of Protein Synthesis in Excised Axes.
Soluble proteins from excised Phaseolus vulgaris axes incubated for 1 hour in (3)H or (14)C- amino acid mixtures at different times during the period leading up to initiation of cell elongation were compared by acrylamide gel electrophoresis. Differences in electrophoretic patterns were found when proteins from axes incubated during the 1st hour of imbibition were compared with proteins from axes incubated during the hour when cell elongation was initiated. These differences greatly diminished by the 2nd hour of imbibition which suggests that they were due primarily to incomplete axis imbibition. A 5-hour actinomycin D treatment which reduced amino acid incorporation by 40% in the 5th hour had no apparent effect on the electrophoretic pattern during that hour.


The attribution of navigational- and goal-directed agency in dogs (Canis familiaris) and human toddlers (Homo sapiens).
Both human infants and nonhuman primates can recognize unfamiliar entities as instrumental agents ascribing to them goals and efficiency of goal-pursuit. This competence relies on movement cues indicating distal sensitivity to the environment and choice of efficient goal-approach. Although dogs' evolved sensitivity to social cues allow them to recognize humans as communicative agents, it remains unclear whether they have also evolved a basic concept of instrumental agency. We used a preferential object-choice procedure to test whether adult pet dogs and human toddlers can identify unfamiliar entities as agents based on different types of movement cues that specify different levels of agency. In the navigational agency condition, dogs preferentially chose an object that modified its pathway to avoid collision with obstacles over another object showing no evidence of distal sensitivity (regularly bumping into obstacles). However, in the goal-efficiency condition where neither object collided with obstacles as it navigated toward a distal target, but only 1 of them exhibited efficient goal-approach as well, toddlers, but not dogs, showed a preference toward the efficient goal-directed agent. These findings indicate that dogs possess a limited concept of environmentally sensitive navigational agency that they attribute to self-propelled entities capable of modifying their movement to avoid colliding with obstacles. Toddlers, in contrast, demonstrated clear sensitivity to cues of efficient variability of goal-approach as the basis for differentiating, attributing, and showing preference for goal-directed instrumental agency. (PsycINFO Database Record


Concepts, contexts and expert systems.
This paper describes problems identified in our attempts to develop an expert system for management of urinary tract infections. We found three aspects which we believe are important to consider when developing such systems. The objective of our future work will be to evaluate the impact of these problems on expert system development and usage.


Myeloid-Derived Suppressive Cells Promote B cell-Mediated Immunosuppression via Transfer of PD-L1 in Glioblastoma.
The potent immunosuppression induced by glioblastoma (GBM) is one of the primary obstacles to finding effective immunotherapies. One hallmark of the GBM-associated immunosuppressive landscape is the massive infiltration of myeloid-derived suppressor cells (MDSC) and, to a lesser extent, regulatory T cells (Treg) within the tumor microenvironment. Here, we showed that regulatory B cells (Breg) are a prominent feature of the GBM microenvironment in both preclinical models and clinical samples. Forty percent of GBM patients (n = 60) scored positive for B-cell tumor infiltration. Human and mouse GBM-associated Bregs were characterized by immunosuppressive activity toward activated CD8+ T cells, the overexpression of inhibitory molecules PD-L1 and CD155, and production of immunosuppressive cytokines TGFβ and IL10. Local delivery of B cell-depleting anti-CD20 immunotherapy improved overall survival of animals (IgG vs. anti-CD20 mean survival: 18.5 vs. 33 days, P = 0.0001), suggesting a potential role of Bregs in GBM progression. We unveiled that GBM-associated MDSCs promoted regulatory B-cell function by delivering microvesicles transporting membrane-bound PD-L1, able to be up-taken by tumoral B cells. The transfer of functional PD-L1 via microvesicles conferred Bregs the potential to suppress CD8+ T-cell activation and acquisition of an effector phenotype. This work uncovered the role of B cells in GBM physiopathology and provides a mechanism by which the GBM microenvironment controls B cell-mediated immunosuppression.See related Spotlight on p. 1902.


[Atrial fibrillation concomitant with valvular heart disease].
Patients with valvular heart disease frequently have atrial fibrillation(AF) due to elevated pressure and dilatation of the left and right atria and pulmonary veins. Guidelines for valvular heart disease and AF recommend that surgical treatment for the valvular heart disease should be performed concomitantly with AF surgery. The Full-Maze procedure has evolved into the gold standard of treatment for medically refractory AF. In addition to the pulmonary vein isolation, the right and left atrial incisions of the Full-Maze procedure are designed to block potential macroreentrant pathways. According to the mechanisms of AF with valvular heart disease, the Full-Maze procedure is more effective for the patients than the pulmonary vein isolation alone.


Is There Sufficient Training of Health Care Staff on Noise Reduction in Neonatal Intensive Care Units? a Pilot Study From Neonoise Project.
Evidence indicates that exposure to high levels of noise adversely affects human health, and these effects are dependent upon various factors. In hospitals, there are many sources of noise, and high levels exert an impact on patients and staff, increasing both recovery time and stress, respectively. The goal of this pilot study was to develop, implement, and evaluate the effectiveness of a training program (TP) on noise reduction in a neonatal intensive care unit (NICU) by comparing the noise levels before and after the implementation of the program. In total, 79 health professionals participated in the study. The measurements of sound pressure levels took into account the layout of the unit and locations of the main sources of noise. General results indicated that LAeq levels before implementation of the training program were often excessive, ranging from 48.7 ± 2.94 dBA to 71.7 ± 4.74 dBA, exceeding international guidelines. Similarly, following implementation of the training program, noise levels remained unchanged (54.5 ± 0.49 dBA to 63.9 ± 4.37 dBA), despite a decrease in some locations. There was no significant difference before and after the implementation of TP. However, a significant difference was found for Lp,Cpeak, before and after training staff, suggesting greater care by health care professionals performing their tasks. Even recognizing that a TP is quite important to change behaviors, this needs to be considered in a broader context to effectively control noise in the NICU.


Plant defensins and defensin-like peptides - biological activities and biotechnological applications.
Plant defensins are cationic peptides that are ubiquitous within the plant kingdom and belong to a large superfamily of antimicrobial peptides found in several organisms collectively called defensins. The primary structure of these peptides includes 45 to 54 amino acid residues with considerable sequence variation. At the level of three-dimensional structure, they are small and globular, composed of three anti-parallel β-sheets and one α-helix, which is highly conserved among these peptides. The three-dimensional structure is stabilized by four disulfide bridges formed by eight strictly conserved Cys residues. Two of these bridges compose the Cys-stabilized α-helix β-strand motif, which is found in other peptides with biological activities. Plant defensins present numerous biological activities, such as inhibiting protein synthesis, ion channel function and α-amylase and trypsin activity; impairing microbial, root hair and parasitic plant growth; mediating abiotic stress and Zn tolerance; altering ascorbic acid redox state; stimulating sweet taste sensation; serving as epigenetic factors; affecting self-incompatibility; and promoting male reproductive development. Some of these biological activities, such as microbial growth inhibition and sweet taste induction, coupled with a scaffold that provides these peptides with incredible physicochemical resistance to harsh environments and the potential for simple amino acid substitution, raise the opportunity to improve the function of defensins or introduce new activities, endowing these peptides with great biotechnological and medical significance. This review will cover the biological activities and roles of plant defensins and will focus on their application in the field of biotechnology.


Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease.
Huntington's disease (HD) is a progressive neurodegenerative disorder with no effective treatment. Geldanamycin is a benzoquinone ansamycin that binds to the heat shock protein Hsp90 and activates a heat shock response in mammalian cells. In this study, we show by using a filter retardation assay and immunofluorescence microscopy that treatment of mammalian cells with geldanamycin at nanomolar concentrations induces the expression of Hsp40, Hsp70 and Hsp90 and inhibits HD exon 1 protein aggregation in a dose-dependent manner. Similar results were obtained by overexpression of Hsp70 and Hsp40 in a separate cell culture model of HD. This is the first demonstration that huntingtin protein aggregation in cells can be suppressed by chemical compounds activating a specific heat shock response. These findings may provide the basis for the development of a novel pharmacotherapy for HD and related glutamine repeat disorders.


A Concise Review on Recent Developments of Machine Learning for the Prediction of Vibrational Spectra.
Machine learning has become more and more popular in computational chemistry, as well as in the important field of spectroscopy. In this concise review, we walk the reader through a short summary of machine learning algorithms and a comprehensive discussion on the connection between machine learning methods and vibrational spectroscopy, particularly for the case of infrared and Raman spectroscopy. We also briefly discuss state-of-the-art molecular representations which serve as meaningful inputs for machine learning to predict vibrational spectra. In addition, this review provides an overview of the transferability and best practices of machine learning in the prediction of vibrational spectra as well as possible future research directions.