The glucagon-like peptide 1 receptor agonist liraglutide attenuates placental ischemia-induced hypertension.
Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic perturbations of nitric oxide function, reflective of generalized endothelial dysfunction. Therapies that target the nitric oxide pathway have shown promise in both clinical and preclinical studies of preeclampsia. The glucagon-like peptide 1 agonists have been shown to increase nitric oxide and lower blood pressure in patients with diabetes, in part, through activation of nitric oxide synthase (NOS). Therefore, we hypothesized that a direct acting glucagon-like peptide 1 receptor agonist would improve stigmata of the preeclampsia syndrome. Using the reduced uterine perfusion pressure rat model, we found that treatment with liraglutide significantly lowered blood pressure, improved renal function, and upregulated NOS3 protein expression in the mesenteric arterial bed. However, there were adverse effects on pup growth that were likely related to diminished food intake in the dams. Collectively, these data support the premise that the use of drugs that improve NOS abundance, including the glucagon-like peptide 1 agonists, is a rational therapeutic approach to the treatment of preeclampsia, but suggest cautious and careful study of their safety before potential clinical use in humans.NEW & NOTEWORTHY Drugs that target the glucagon-like peptide-1 pathway such as liraglutide are already used clinically, and it has been shown to promote endothelial nitric oxide synthase (NOS3) expression. We demonstrate that liraglutide, a glucagon-like peptide 1 receptor (GLP-1R) agonist, lowers blood pressure, improves renal function, and upregulates NOS3 in a rat model of placental ischemia. These data suggest that drugs that target the nitric oxide system, including GLP-1R agonists, are a potential therapeutic option for preeclampsia.


Inflammatory biomarkers and emotional approach coping in men with prostate cancer.
Emotion-regulating coping is associated with improvements in psychological and physical health outcomes. Yet in the context of prostate cancer-related stressors, limited research has characterized associations of emotion-regulating coping processes (emotional expression, emotional processing) and inflammatory processes that are related to disease risk. This investigation examined the relation of Emotional Approach Coping (EAC) with markers of inflammation to test the hypothesis that higher EAC scores at study entry (T1) would be associated with lower proinflammatory markers four months later (T2), specifically sTNF-RII, CRP, and IL-6. Forty-one men (M age=66.62 years; SD=9.62) who had undergone radical prostatectomy or radiation therapy for localized prostate cancer within two years completed questionnaires, including assessments of EAC, at T1, and provided blood samples for immune assessments at T2. When controlling for relevant biobehavioral controls, emotional processing predicted lower IL-6 (B=-.66, p<.01), sTNF-RII (B=-.43, p<.05), and CRP (B=-.43, p<.10), whereas emotional expression was significantly associated with higher levels of sTNF-RII (B=.55, p<.05). Associations of emotional expression and IL-6 (B=.38, p<.10), and CRP (B=.44, p<.10) approached significance. Probing interactions of emotional processing and expression (though only approaching significance) suggested that expression of emotion is associated with higher inflammation (CRP and sTNF-RII) only in the context of low emotional processing. Attempts at emotion regulation via emotional processing appear to modulate inflammatory processes. Understanding, making meaning of, and working through emotional experience may be a promising target of intervention to reduce inflammation with potential effects on psychological and cancer outcomes in men with prostate cancer.


Recognition of paediatric otopathology by General Practitioners.
General Practitioners (GPs) are required to diagnose a number of common ear pathologies on a regular basis. In particular, otitis media with effusion (OME) can be well managed in primary care if a reliable diagnosis can be made. We set out to assess the confidence and ability of GPs to diagnose otopathology, as well as the access that they had to tympanometry and pneumatic otoscopy to assist in making their diagnoses. Twenty GPs were shown a series of forty slides, half with OME and half with normal tympanic membranes; they were then asked to state whether each image represented an ear with OME or not. The same GPs were then shown 20 slides, half of which were ears with a common pathology and half were normal; the participants were asked to state whether the slide was of a normal ear or make a diagnosis of the pathology. Access to equipment and previous training were assessed via a short questionnaire. The median score for the correct diagnosis of OME was 53% (range 30-67.5%), only slightly higher than chance. The participants correctly identified that an ear was abnormal for a mean of 80% of the time (range 65-95%), but were only able to make a correct diagnosis of the pathology for a mean of 41% of the ears (range 20-80%). No participant had access to pneumatic otoscopy or tympanometry in their practices. GPs have difficulty in correctly diagnosing OME from otoscopy alone, but are able to determine the presence of other otopathology. They were less able to diagnose specific abnormalities.


Persistently high urine glucose levels caused by familial renal glycosuria.
Glycosuria generally occurs when the threshold for glucose reabsorption by the proximal renal tubule is exceeded or when reabsorption of filtered glucose is impaired. Although the discovery of glycosuria in a child will prompt screening for diabetes mellitus, it is also a sign of a rare tubulopathy called "familial renal glycosuria" (OMIM #233100). This tubulopathy is linked to a defect in the sodium-glucose co-transporter 2, encoded by the SLC5A2 gene. Here, we describe and discuss two pediatric cases in whom familial renal glycosuria was discovered fortuitously after the observation of persistently high urine glucose levels in the absence of hyperglycemia.


Robust extraction of P300 using constrained ICA for BCI applications.
P300 is a positive event-related potential used by P300-brain computer interfaces (BCIs) as a means of communication with external devices. One of the main requirements of any P300-based BCI is accuracy and time efficiency for P300 extraction and detection. Among many attempted techniques, independent component analysis (ICA) is currently the most popular P300 extraction technique. However, since ICA extracts multiple independent components (ICs), its use requires careful selection of ICs containing P300 responses, which limits the number of channels available for computational efficiency. Here, we propose a novel procedure for P300 extraction and detection using constrained independent component analysis (cICA) through which we can directly extract only P300-relevant ICs. We tested our procedure on two standard datasets collected from healthy and disabled subjects. We tested our procedure on these datasets and compared their respective performances with a conventional ICA-based procedure. Our results demonstrate that the cICA-based method was more reliable and less computationally expensive, and was able to achieve 97 and 91.6% accuracy in P300 detection from healthy and disabled subjects, respectively. In recognizing target characters and images, our approach achieved 95 and 90.25% success in healthy and disabled individuals, whereas use of ICA only achieved 83 and 72.25%, respectively. In terms of information transfer rate, our results indicate that the ICA-based procedure optimally performs with a limited number of channels (typically three), but with a higher number of available channels (>3), its performance deteriorates and the cICA-based one performs better.


Plant nitrogen and fluctuations of insect populations: A test with the cinnabar moth-tansy ragwort system.
Nine populations of cinnabar moth, introduced to North America as biological control agents of tansy ragwort, were studied for 4 to 6 years. We tested the hypothesis that good quality of the food plant, measured as percent protein, would destabilize the moth populations. A positive correlation occurred between the percent nitrogen in the plants and the coefficient of variation of moth population density. Moths tended to be larger and produce more eggs in areas with food plants of better quality. Larval survival was also correlated with the quality of the food and the fluctuation of the population density. Food plants with high nitrogen levels increase larval survival and moth fecundity and allow the moth populations to periodically overexploit their food supply, thus accentuating population fluctuations. This finding is discussed in relation to other studies of cinnabar moth.


[Modulation of norepinephrinergic control of hypothalamus preoptic areas on hibernation bouts in ground squirrels (Citellus dauricus)].
In our previous work, it was shown that hibernation could be enhanced by injection of 6-hydroxydopamine (6-OHDA, 200 micrograms) into the lateral cerebral ventricle of ground squirrels by destructing norepinephrine (NE) nerve terminals in brain areas including hypothalamus, cerebral cortex, hippocampus and periaqueductal gray matter of middle brain. In order to identify the specific area contributing for the modulation of NE system on hibernation, small doses of 6-OHDA (4 micrograms) were microinjected bilaterally into medial preoptic hypothalamus (MPA), lateral preoptic hypothalamus (LPA) and ventromedial hypothalamic nucleus (VMH). The results showed: (1) Depletion of NE on MPA may facilitate hibernation. (2) Little effect was seen by microinjection of 6-OHDA into LPA. (3) The effect of 6-OHDA on VMH was similar to that on MPA, through the mechanism remains to be investigated.


Low-power multilevel resistive switching inβ-Ga2O3based RRAM devices.
In this study, multilevel switching at low-power in Ti/TiN/Ga2O3/Ti/Pt resistive random-access memory (RRAM) devices has been systematically studied. The fabricated RRAM device exhibits an excellent non-overlapping window between set and reset voltages of ∼1.1 V with a maximumRoff/Ronratio of ∼103. Moreover, to the best of our knowledge, the multi-bit storage capability of these RRAM devices with a reasonably highRoff/Ronratio is experimentally demonstrated, for the first time, for lower compliance currents at 10μA, 20μA and 50μA. The multi-bit resistive switching behavior of the Ga2O3RRAM device at a low compliance current paves the way for low-power and high-density data storage applications.


Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion.
Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.


Glucose depletion hyperpolarizes guinea pig hippocampal neurons by an increase in potassium conductance.
Superfusion of guinea pig hippocampal brain slices with a glucose-free solution induced a membrane hyperpolarization and an increase in input conductance of neurons in the CA3 region. Under voltage clamp, glucose depletion induced an outward current with a reversal potential near the K+ equilibrium potential. The action of glucose depletion was different from the effect of ouabain, indicating that low-glucose-induced changes in the membrane conductance are primarily due to alterations in cell metabolism rather than due only to an inhibition of the Na+/K+ pump.


Loneliness in Older Indian Dyads.
Loneliness has been recognised as a major public health concern in older adults in developed nations, with little focus on low- and middle-income countries such as India. While the protective nature of social relationships on loneliness has been explored in the context of marriage, typically these benefits are examined in individual spouses rather than within the marital dyad. A sample of 398 opposite-sex married Indian couples (mean age 54.8 years) was obtained from the pilot wave of the Longitudinal Aging Study in India (LASI) conducted in 2010. These cross-sectional data were analysed using the Actor-Partner Interdependence Model, with one's own and one's partner's cognitive function, functional limitations, depressive symptoms, employment status and contact with friends included as predictors of loneliness. There were no gender differences in the pattern of associations. Depression was positively associated with loneliness with actor and partner effects being significant. One's partner being employed was associated with less loneliness. The sample showed low levels of depression, loneliness, and reduced functionality; however, depression still predicted one's own and one's partner's loneliness. Future work using longitudinal data could examine the role of employment in loneliness, particularly within the context of gender roles.


Anatomical variations in the harvest of anterolateral thigh flap perforators: a cadaveric and clinical study.
The anterolateral thigh (ALT) flap has become increasingly popular due to its versatility and minimal donor site morbidity. Its major limitation has been uncertainty in predicting perforator anatomy, with the occasional absence of suitable perforators and high variability in their size and course. The variability of this anatomy has not been adequately explored previously. A cadaveric study was undertaken, in which 19 thighs (from 10 fresh cadavers) underwent contrast injection and angiographic imaging. Anatomical variations of the vasculature were recorded. A clinical study of 44 patients undergoing ALT flap reconstruction was also undertaken. Perforator anatomy was described in the first 32 patients, and the subsequent 12 patients underwent computed tomography angiography with a view to predicting individual anatomy and improving operative outcome. Cadaver angiography was able to highlight and classify the variations in arterial anatomy, with four patterns observed and marked variability between cases. In 32 patients undergoing ALT flaps without preoperative CT angiography (CTA), five patients (16%) did not have any suitable perforators from the descending branch of the lateral circumflex femoral artery. By selecting the limb of choice with preoperative CTA, the incidence of flap unsuitability was reduced to 0%. Comparing CTA with Doppler, CTA was more accurate (sensitivity 100%) and provided more information. The perforators supplying the ALT flap show significant variability in location and course, with the potential for unsuitable perforators limiting flap success. Preoperative CTA can demonstrate the vascular anatomy and can aid perforator selection and operative success.


Choice and control for people ageing with intellectual disability in group homes.
Many people ageing with intellectual disabilities (ID) age in place in group homes. Participation is a central concept in support and service to people with ID, but age is often a determining factor for participation among this group. Choice and control are dimensions of participation. The aim of this article is to explore how choice and control in the everyday life of people ageing with ID is expressed and performed in the group home's semi-private spaces. Participant observations and interviews with residents and staff were conducted in four different group homes in Sweden that had older residents. Four categories were found that can be understood as aspects of choice and control in the group home's semi-private spaces in the everyday life of people ageing with ID. These categories included aspects such as space and object, time and routines, privacy, and a person-centred approach. People ageing with ID are vulnerable when it comes to maintaining choice and control in various situations in the home's semi-private spaces. It is argued that occupational therapists should include this occupational arena in their evaluations and interventions for people ageing with ID.


Low-Titre GAD Antibody-Associated Late-Onset Cerebellar Ataxia with a Significant Clinical Response to Intravenous Immunoglobulin Treatment.
Antiglutamic acid decarboxylase antibody-associated cerebellar ataxia (GAD-Abs CA) is a rare, but increasingly detected, autoimmune neurological disorder characterized by the clinical presence of a cerebellar syndrome concomitant with positive GAD-Abs levels in serum and cerebrospinal fluid (CSF). It represents 3% of all immune-mediated sporadic CAs. Low-titre GAD-Abs CA is an even rarer subtype of GAD-Abs CA. We report on a 68-year-old woman with a 3-year history of progressive gait ataxia. In addition to the modified Rankin Scale (mRS), we used two other objective scales to evaluate CA severity, i.e. the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for Assessment and Rating of Ataxia (SARA). Series of CT and MRI showed atrophy of the cerebellum. Except for the glycated haemoglobin (HbA1c) levels, all other routine laboratory examinations were within normal limits. Autoimmune laboratory examinations showed positive (25.8 U/mL) serum GAD-Abs levels. The GAD antibody index was <1.0. The CSF analysis showed no oligoclonal immunoglobulin bands. Intravenous immunoglobulin (IVIg) therapy was started and significant improvement was observed. The diagnosis of low-titre GAD-Abs CA was established.


Bioactivity-guided isolation of trypanocidal coumarins and dihydro-pyranochromones from selected Apiaceae plant species.
Bioactivity-guided isolation of natural products from plant matrices is widely used in drug discovery. Here, this strategy was applied to identify trypanocidal coumarins effective against the parasite Trypanosoma cruzi, the etiologic agent of Chagas disease (American trypanosomiasis). Previously, phylogenetic relationships of trypanocidal activity revealed a coumarin-associated antichagasic hotspot in the Apiaceae. In continuation, a total of 35 ethyl acetate extracts of different Apiaceae species were profiled for selective cytotoxicity against T. cruzi epimastigotes over host CHO-K1 and RAW264.7 cells at 10 μg/mL. A flow cytometry-based T. cruzi trypomastigote cellular infection assay was employed to measure toxicity against the intracellular amastigote stage. Among the tested extracts, Seseli andronakii aerial parts, Portenschlagiella ramosissima and Angelica archangelica subsp. litoralis roots exhibited selective trypanocidal activity and were subjected to bioactivity-guided fractionation and isolation by countercurrent chromatography. The khellactone ester isosamidin isolated from the aerial parts of S. andronakii emerged as a selective trypanocidal molecule (selectivity index ∼9) and inhibited amastigote replication in CHO-K1 cells, though it was significantly less potent than benznidazole. The khellactone ester praeruptorin B and the linear dihydropyranochromones 3'-O-acetylhamaudol and ledebouriellol isolated from the roots of P. ramosissima were more potent and efficiently inhibited the intracellular amastigote replication at < 10 μM. The furanocoumarins imperatorin, isoimperatorin and phellopterin from A. archangelica inhibited T. cruzi replication in host cells only in combination, indicative of superadditive effects, while alloimperatorin was more active in fractions. Our study reports preliminary structure-activity relationships of trypanocidal coumarins and shows that pyranocoumarins and dihydropyranochromones are potential chemical scaffolds for antichagasic drug discovery.


Splenic function following experimental dearterialization injury in the suckling rat.
An experimental splenic dearterilization injury was created in 1-wk-old rats to study the effect of vascular trauma on splenic function. Splenic weight significantly decreased 1 wk following injury but returned to control values within a month. Total splenic nuclear activity diminished initially but increased to above control values 1 mo after injury, and finally returned to normal at 2 mo. Survival rate after an intraperitoneal challenge with pneumococcus in groups 1 wk following total splenectomy and partial dearterlization was not significantly different than controls. This study confirmed the clinical impression that vascular injury to the spleen causes only a transient impariment of splenic size and function and provides further incentive to perform splenorrhaphy following splenic trauma.


Effects of intra-hippocampal injections of the NK2 receptor antagonist saredutant on the elevated plus maze, and the mouse defense test battery.
Intracerebroventricular (i.c.v.) or intraperitoneal (IP) administration of saredutant (SR48968), an NK2 receptor antagonist, produces anxiolytic-like effects in rodents in a number of animal models of anxiety. NK2 binding sites are present in several limbic structures in rats, including the hippocampus, thalamus, septum and prefrontal cortex, suggesting involvement in the modulation of emotional processes. The current study investigated the behavioral effects of saredutant infused into the ventral hippocampus (VH), a structure associated with cognitive and emotional processes, to clarify the neural substrate underlying the anxiolytic-like effect of the compound. Saredutant (10, 100 or 500 pmol/0.2 μL) was injected bilaterally into the VH of male CD-1 mice tested in the elevated plus-maze and mouse defense test battery (MDTB). Results from the EPM showed that microinjections of 10 pmol/0.2 μL of saredutant increased entries and time spent in the open arms and enhanced end-arm exploration. In the MDTB, saredutant (500 pmol/0.2 μL) decreased vocalizations and increased escape attempts in mice confronted with a rat. Taken together, these results suggest that hippocampal tachykinin mechanisms are involved in the modulation of anxiety and defensive behaviors.


[Overcoming the difficulty of recruiting young people. Keys to obtaining qualitative data in a study of sexualities].
Sexuality is a central aspect of young's lives. It is a task of public health to understand how they are constructed with all their diversity, and to give satisfactory answers in the field of sexual health. The characteristics of qualitative research (flexible, open and reflective) provide the opportunity to design studies that are accepted and adapted to the realities of young people, especially in a sensitive field. The aim of this note is to provide clues for the recruitment of young people. In our case, the knowledge of key informants regarding the study population and the research context was essential, both to choose an approach and recruitment strategy and to adapt the data collection techniques. Finally, we used individual interviews and triangular groups opportunistically in waiting rooms of sexual health care services specialized in young people, where there was already a predisposition to talk about sexuality.


Development of a home-based auditory training to improve speech recognition on the telephone for patients with cochlear implants: A randomised trial.
Speech recognition on the telephone poses a challenge for patients with cochlear implants (CIs) due to a reduced bandwidth of transmission. This trial evaluates a home-based auditory training with telephone-specific filtered speech material to improve sentence recognition. Randomised controlled parallel double-blind. One tertiary referral centre. A total of 20 postlingually deafened patients with CIs. Primary outcome measure was sentence recognition assessed by a modified version of the Oldenburg Sentence Test filtered to the telephone bandwidth of 0.3-3.4 kHz. Additionally, pure tone thresholds, recognition of monosyllables and subjective hearing benefit were acquired at two separate visits before and after a home-based training period of 10-14 weeks. For training, patients received a CD with speech material, either unmodified for the unfiltered training group or filtered to the telephone bandwidth in the filtered group. Patients in the unfiltered training group achieved an average sentence recognition score of 70.0%±13.6% (mean±SD) before and 73.6%±16.5% after training. Patients in the filtered training group achieved 70.7%±13.8% and 78.9%±7.0%, a statistically significant difference (P=.034, t10 =2.292; two-way RM ANOVA/Bonferroni). An increase in the recognition of monosyllabic words was noted in both groups. The subjective benefit was positive for filtered and negative for unfiltered training. Auditory training with specifically filtered speech material provided an improvement in sentence recognition on the telephone compared to training with unfiltered material.


Microwave-assisted efficient synthesis of pyrazole-fibrate derivatives as stimulators of glucose uptake in skeletal muscle cells.
The design and synthesis of a series of pyrazolo[3,4-d]pyrimidinones containing fibrate side chains have been accomplished by utilizing the concept of molecular hybridization. All the synthesized compounds were evaluated for the glucose uptake stimulatory effect in L6 rat skeletal muscle cells. Four compounds (3f, 3g, 3j and 3q) were found to show significant stimulation of glucose uptake. Further these four compounds have been examined for their Glut4 translocation stimulatory effect in L6-Glut4myc myotubes. Compound 3q was found to exert maximum increase in GLUT4myc translocation.


High-dimensional super-resolution imaging reveals heterogeneity and dynamics of subcellular lipid membranes.
Lipid membranes are found in most intracellular organelles, and their heterogeneities play an essential role in regulating the organelles' biochemical functionalities. Here we report a Spectrum and Polarization Optical Tomography (SPOT) technique to study the subcellular lipidomics in live cells. Simply using one dye that universally stains the lipid membranes, SPOT can simultaneously resolve the membrane morphology, polarity, and phase from the three optical-dimensions of intensity, spectrum, and polarization, respectively. These high-throughput optical properties reveal lipid heterogeneities of ten subcellular compartments, at different developmental stages, and even within the same organelle. Furthermore, we obtain real-time monitoring of the multi-organelle interactive activities of cell division and successfully reveal their sophisticated lipid dynamics during the plasma membrane separation, tunneling nanotubules formation, and mitochondrial cristae dissociation. This work suggests research frontiers in correlating single-cell super-resolution lipidomics with multiplexed imaging of organelle interactome.


Location of the femoral head in developmental dysplasia of the hip: three-dimensional evaluation by means of magnetic resonance image.
By using magnetic resonance imaging, we analyzed the position of the femoral head in 21 hips of 21 infants with developmental dislocation. The femoral head changed its location according to the hip position. In type A dislocation, the head was anterior to the acetabulum when the hip was extended, and it was posterior when the hip was flexed. There was wide contact area between the femoral head and the acetabulum in any hip position. In type B, the head was on the rim of the acetabulum when the hip was extended. When the hip was flexed, the head was on the posterior rim of the acetabulum, and there was no contact between the femoral head and acetabular cartilage. Some heads slipped into the socket with a click phenomenon when the hip was flexed/abducted. In type C dislocation, the head was on the edge of the acetabulum when the hip was extended. When the hip was flexed, the head moved posteriorly, and it was completely out of the socket.


Magnetic resonance imaging of the brain and spine.
The efficacy of magnetic resonance imaging (MRI) in the diagnosis of diseases of the central nervous system is reviewed. MRI, computed tomography (CT) and certain radionuclide studies are compared in the evaluation of intracranial tumours, cerebral vascular disease, multiple sclerosis and other white matter diseases, dementia, head injury, infection, epilepsy, spinal lesions and in paediatric central nervous system disorders. The measurement of cerebrospinal fluid volumes and dynamics by MRI is discussed. MRI most clearly has advantages where CT is degraded by bone hardening and streak artefacts (spine, skull base, posterior and temporal fossa, sella and parasellar regions) and in diseases in which the X-ray attenuation of the suspected lesion differs little from normal parenchyma (paediatric brain disorders, demyelination and dysmyelination, early oedema associated with infarction, infection or low-grade infiltrating neoplasm, subacute and chronic haemorrhage and lesions in the spinal subarachnoid space and cord). Elsewhere MRI and CT should be seen as complementary rather than competitive methods of imaging. In spite of an absence of information about the contribution of MRI to management decisions and a lack of rigorous, prospective controlled trials, MRI will play an increasing role in the diagnosis of diseases of the central nervous system.


Use of deodorized yellow mustard powder to control Escherichia coli O157:H7 in dry cured Westphalian ham.
Dry cured (uncooked) hams with low water activity and pH ≥5.6 seem a likely food vehicle for Escherichia coli O157:H7. In previous work, isothiocyanates produced from mustard glucosinolates by bacterial myrosinase-like activity converted deodorized mustard into a potent antimicrobial in dry sausage. In this study its value in controlling E. coli O157:H7 survival in Westphalian ham was investigated. Hams were inoculated with a 7.5 log cfu g(-1) cocktail of E. coli O157:H7, 4% or 6% (w/w) deodorized yellow mustard powder was surface applied and monitored 80 d for pathogen survival. In one trial to accelerate formation of isothiocyanate, a Staphylococcus (S.) carnosus meat starter culture was added to hams at 45 d (after salt equilibration). At 21 d, E. coli O157:H7 was reduced by 3 log cfu g(-1) on hams treated with mustard powder compared to only a 1 log cfu g(-1) reduction in the control. By 45 d, mustard powder caused a reduction of >5 log cfu g(-1)E. coli O157:H7, whereas it took 80 d for numbers in control hams to be similarly reduced. Although the commercial process used caused a 5 log cfu g(-1) reduction of E. coli O157:H7 in 80 d, 4% or 6% deodorized mustard accelerated this reduction and the S. carnosus starter culture may have contributed to the maintenance of this effect.


Beyond isolation: preferred rates of oscillation, from fireflies to epilepsy.
The observed light synchronism that comes naturally to a variety of oscillatory systems includes not only fireflies flashing in unison (1), but a number of other organisms and cells that have a preferred rate of oscillation. The observed motion of analogous phenomena such as these and brain cells that emit electric signals in rhythm (beneficial or detrimental) indicated by the frequency tracings of an electroencephalogram may contain many unexpected symmetries. In the investigation of these symmetries light could reveal itself to be the critical interface.


Novel antibacterial agents for skin and skin structure infections.
With the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multidrug-resistant gram-positive infections remains important. With treatment options limited, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives. This review focuses on agents newly introduced and those presently in clinical development for the treatment of skin and skin structure infections. Linezolid, quinupristin-dalfopristin, and daptomycin have been approved by the Food and Drug Administration for the treatment of skin and skin structure infections. Two newer compounds, oritavancin and dalbavancin, are in clinical development for this indication. In addition, the quinolones moxifloxacin and gatifloxacin recently were approved for cutaneous infections. At the conclusion of this learning activity, participants should be familiar with the modes of action, clinical indications, dosage regimens, and contraindications and cautions for several novel antibacterial agents for skin and skin structure infections.


COVID-19 During Pregnancy and Puerperium - A Review by the Austrian Society of Gynaecology and Obstetrics (OEGGG).
After the first case of COVID-19 pneumonia was reported in Wuhan, Hubei Province, China, in December 2019, the infection quickly spread to the rest of China and then to the wider world. The available information on pregnant women infected with COVID-19 is now significantly greater. There are now several case series and systematic reviews of cohorts, some of which include more than 100 cases. This review evaluates the scientific literature available until May 1, 2020 and discusses common questions about COVID-19 in the context of pregnancy and the postpartum period.


Predictors of caregiver adherence to administration of amodiaquine during delivery of seasonal malaria chemoprevention in Nigeria, Burkina Faso, Chad, and Togo.
Malaria is the leading cause of morbidity and mortality among infants and children under-five in sub-Saharan Africa. In the Sahel, seasonal malaria chemoprevention (SMC) is delivered door-to-door in monthly cycles. In each cycle, children are administered sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) on Day 1 by community distributors, and AQ on Day 2 and Day 3 by caregivers. Non-adherence to AQ administration by caregivers has implications for emergence of antimalarial resistance. Predictors of non-adherence to administration of AQ on Day 2 and Day 3 among caregivers of children aged 3-59 months who had received Day 1 SP and AQ during the last 2020 SMC cycle (n = 12,730) were analysed using data from SMC coverage surveys in Nigeria, Burkina Faso and Togo, and fitting multivariate random-effects logistic regression models. Previous adverse reaction to SMC medicines by eligible children (OR: 0.29, 95% CI 0.24-0.36, p < 0.001), awareness of the importance of administering Day 2 and Day 3 AQ (OR: 2.19, 95% CI 1.69-2.82, p < 0.001), caregiver age, and home visits to caregivers delivered by the Lead Mothers intervention in Nigeria (OR: 2.50, 95% CI 1.93-2.24, p < 0.001), were significantly associated with caregiver adherence to Day 2 and Day 3 AQ administration. Increasing caregivers' knowledge of SMC and interventions such as Lead Mothers have the potential to improve full adherence to AQ administration.


Acetylcholinesterase levels in nasal turbinate congestion.
In a previous communication, one of the authors discussed prolonged congestion of the turbinates following nasal surgery. The clinical factors responsible were allergy or the traumatic effects of nasal packing on the turbinates. A study of turbinate function was done to find the factor responsible for this congestion. Biopsies of an inferior turbinate were obtained preoperatively and two weeks after surgery. The specimens were examined for the level of acetylcholinesterase by histochemical assay and were also studied by examining sections histologically. In the majority of cases, the level of acetylcholinesterase fell with the appearance of congestion and rose when the turbinates returned to normal. These results suggest a connection between turbinate congestion and levels of tissue acetylcholinesterase in the presence of inflammation or allergy.


Synovial fluid lipoproteins: review of current concepts and new directions.
Recent developments in plasma lipoprotein and apolipoprotein research have been striking, but few studies have focused on the analysis of lipoproteins in synovial fluid (SF). SF contains small amounts of lipoproteins and apolipoproteins. The lipid concentration of normal human SF is extremely low and is in sharp contrast to the concentrations found in plasma. Little is known about the lipids in pathological SF, but studies have noted increased cholesterol and lipoprotein content in rheumatoid arthritis (RA) SF ranging from 40% to 60% of the total plasma lipoproteins. Recently apolipoproteins AI, B and E have also been found to be in increased amounts in RA SF. Several theories have been proposed to account for the increased presence of SF lipids in RA. Animal and human studies indicate the SF cholesterol, lipoproteins, and apolipoproteins may aggravate the inflammatory reaction within the synovial space. Research suggests an immunologic role for plasma lipoproteins on lymphocyte and monocytes in the blood and lymph. SF lipoproteins and apolipoproteins should be studied to define their actions within the synovial space.


Peripheral administration of palmitoylated prolactin-releasing peptide induces Fos expression in hypothalamic neurons involved in energy homeostasis in NMRI male mice.
Energy homeostasis is the result of a balance between energy intake and expenditure, and the hypothalamus plays a key role in the regulation of these processes. The hypothalamic prolactin-releasing peptide (PrRP) is involved in food intake regulation and energy homeostasis, although only its lipidized analogs exert central anorexigenic effects after peripheral administration. The aim of the present study was to delineate the extent of the Fos expression as a marker of neuronal activation within the hypothalamic structures involved in food intake regulation after peripherally administered palmitoylated PrRP31 (palm-PrRP31) and to determine whether the anorexigenic effect of peripherally administered palm-PrRP31 influence the activity of hypocretin (HCRT) and oxytocin (OXY) neurons, i.e., the neuropeptides crucially involved in the regulation of energy homeostasis. The data confirmed an anorexigenic effect of palm-PrRP31 treatment (5mg/kg, s.c.) in mice. In the palm-PrRP31-treated animals, a significant increase in Fos expression was observed in the hypothalamic paraventricular (PVN), dorsomedial (DMN), and arcuate (Arc) nuclei and in the neurons of the nucleus of the solitary tract (NTS). Moreover, significant Fos expression was observed in the lateral hypothalamic area (LHA) HCRT neurons and PVN OXY neurons after palm-PrRP31 administration. The present findings may indicate that palm-PrRP31 may be involved in energy homeostasis via the activation of several hypothalamic structures. Fos activation of the hypothalamic OXY and HCRT neurons in the PVN and LHA emphasizes the importance of the areas mentioned in the central action of palm-PrRP31.


The Social Neuroscience of Interpersonal Emotions.
In our daily lives, we constantly engage in reciprocal interactions with other individuals and represent ourselves in the context of our surrounding social world. Within social interactions, humans often experience interpersonal emotions such as embarrassment, shame, guilt, or pride. How interpersonal emotions are processed on the neural systems level is of major interest for social neuroscience research. While the configuration of laboratory settings in general is constraining for emotion research, recent neuroimaging investigations came up with new approaches to implement socially interactive and immersive scenarios for the real-life investigation of interpersonal emotions. These studies could show that among other brain regions the so-called mentalizing network, which is typically involved when we represent and make sense of others' states of mind, is associated with interpersonal emotions. The anterior insula/anterior cingulate cortex network at the same time processes one's own bodily arousal during such interpersonal emotional experiences. Current research aimed to explore how we make sense of others' emotional states during social interactions and investigates the modulating factors of our emotional experiences during social interactions. Understanding how interpersonal emotions are processed on the neural systems level may yield significant implications for neuropsychiatric disorders that affect social behavior such as social anxiety disorders or autism.


Caveolin-1 Expression Together with VEGF can be a Predictor for Lung Metastasis and Poor Prognosis in Osteosarcoma.
Caveolin-1, the major protein component of caveolae, plays vital functions in tumorigenesis and metastasis. Previous evidence demonstrated the positive role of Caveolin-1 in the regulation of endothelial cell differentiation and the involvement of Caveolin-1 in vascular endothelial growth factor (VEGF) mediated angiogenesis. The correlation of Caveolin-1 expression and angiogenesis is not yet elucidated in osteosarcoma. This study aimed to investigate the expression levels of Caveolin-1 and VEGF in osteosarcoma and their associations with clinicopathological data. This study included 66 formalin-fixed and paraffin embedded osteosarcoma tissue samples. The expression levels of Caveolin-1 and VEGF were assessed by immunohistochemistry. Then associations with clinicopathological variables and the correlation between both markers were evaluated statistically. We also investigated the expression of Caveolin-1 and VEGF values in gene microarrays of osteosarcoma patients and cell lines by using GEO data sets on https://www.ncbi.nlm.nih.gov. Caveolin-1 and VEGF were expressed in 19.6% and 77.3%, respectively. Caveolin-1 expression was associated positively with osteoblastic histological subtype (P < 0.0001). VEGF expression showed positive association with patient age, histological grade and clinical stage (P = 0.031, P = 0.024 and P < 0.001; respectively). An inverse correlation between Caveolin-1 and VEGF expressions in osteosarcoma was found (r = 0.2 P = 0.04). In silico analysis of Caveolin-1 and VEGF expression supported our results. Our results suggest that Caveolin-1 may act as a tumor suppressor in osteosarcoma. Down-regulation of Caveolin-1 can be used as an indicator for poor prognosis in osteosarcoma patients. Meanwhile, overexpression of VEGF is a predictor of pulmonary metastasis and poor prognosis.


Comparison study of autonomous activity in bladders from normal and paraplegic rats.
To identify differences in the pattern of pressure generated by isolated bladders from normal and paraplegic rats. Nine female Wister rats were made paraplegic by spinal cord transsection at the vertebral level T8-T9 and sacrificed between D21 and D28. A further group (n = 9) was used as a control group. Each bladder was excised and placed in an organ bath where intravesical pressures were measured. Pressure changes were divided in two well-defined groups: macro-transients and spikes. The effects of intravesical volume load and muscarinic (M) agonists were studied. We demonstrated a higher frequency, a longer duration, and a higher variance of duration in macro-transients in the neurogenic group. Intravesical volume load influenced the amplitude and frequency of macro-transients in both groups similarly. The effects of the muscarinic (M(2))-selective agonist arecaïdine were different in neurogenic bladder; the effects of the non-selective muscarinic (M)-agonist carbachol were similar in both groups. We showed that the pattern of autonomous activity was significantly different between normal and neurogenic rat bladders. We also found evidence for alterations in the muscarinic response of isolated neurogenic rat bladders. This model offers an exciting new research tool to evaluate the detrusor activity in neurogenic and normal conditions.


Creatine kinase values in amyotrophic lateral sclerosis.
Serum creatine kinase (CK1) values were recorded while or soon after the diagnosis of amyotrophic lateral sclerosis (ALS) was established in 140 of 217 (65%) consecutive patients seen in the Motor Neuron Disease Clinic at this center during a 5-year period. Second creatine kinase (CK2) determinations were recorded on 48 of 140 (34%) ALS patients later in the course of the disease. The mean CK1 and CK2 values (unit, times the upper limit of normal) were 1.22 (range, 0.1 to 3.0; median, 0.80) and 1.34 (range, 0.1-9.2; median, 0.80) (P=0.11, r=0.92, mean difference=28.2%). Of the 140 ALS patients, 58 (41%) (male:female ratio: 2.9:1.0) had elevated CK1 values ranging from 1.03 to 13.0 (mean, 2.21; median, 1.67). Twelve patients (8.6%) had CK1 values greater than 3.0. Mean CK1 values were significantly greater (P=0.001) in male (mean, 1.56) versus female (mean, 0.80) ALS patients, and significantly greater (P=0.009) in limb-onset (mean, 1.34) versus bulbar-onset (mean, 0.80) disease. CK1 values correlated poorly with and were not predictive of age of onset or survival.


Rat thalamic α₄β₂ neuronal nicotinic acetylcholine receptor occupancy assay using LC-MS/MS.
In vivo brain receptor occupancy has been the key assay in driving preclinical drug discovery program and there is a need to hasten this screening step. Radiolabeled methods, which are time consuming and expensive, are most widely employed to measure receptor occupancy. Thus we sought to develop and validate an alternative novel approach for measuring rat brain α₄β₂ neuronal nicotinic acetylcholine receptor occupancy using high performance liquid chromatography combined with tandem mass spectrometric detector (LC-MS/MS). Tracer optimization studies like in vivo dose and time dependent brain regional distribution; saturation binding and blocking study with nicotine and atropine were carried out for ZW-104 in rats. Assay validity was tested by pretreatment with potent α₄β₂ ligands; TC-1734, cytisine, ABT-089, ABT-594 and A-366833. Receptor occupancy along with plasma and brain exposure levels of α₄β₂ ligand was measured in the same set of animals. The regional distribution of ZW-104 in rat was found to be, thalamus>frontal cortex>striatum>hippocampus>cerebellum, and is in accordance with the distribution and regional densities of α₄β₂ nAChRs measured using [¹⁸F]ZW-104 in mice and baboons. Pretreatment with nicotine and α₄β₂ ligands dose dependently reduced the binding of ZW-104 in the thalamus. Non-nicotinic antagonist atropine did not alter the binding of ZW-104 in the thalamus, indicating the tracer specificity. The ED₅₀ values calculated for occupancy were found to be 3.01, 0.83, 14.81, 0.001 and 0.11 mg/kg for TC-1734, cytisine, ABT-089, ABT-594, and A-366833, respectively. These findings demonstrate that non-radiolabeled ZW-104 is suitable for determining the α₄β₂ receptor occupancy in rat brain. The LC-MS/MS based receptor occupancy assay is a rapid method and allows the generation of occupancy data along with the brain and plasma concentration in the same group of animals.


Clinicopathologic factors influence accurate endosonographic assessment for early gastric cancer.
EUS has become a valuable tool for the selection of patients who are suitable for EMR of early gastric cancer (EGC). The aim of this study was to evaluate the various clinicopathologic factors affecting the diagnostic accuracy of EUS in EGC. A retrospective, single-center study. A total of 206 patients suspected of EGC endoscopically who underwent EUS examination and curative treatment for EGC at Severance Hospital, Seoul, Korea, from October 2001 to May 2005 were included. We reviewed the medical records of 206 patients and compared preoperative EUS staging with final histopathologic staging of the resected specimen according to the clinicopathologic parameters. The diagnostic accuracy of EUS for predicting tumor invasion depth was significantly affected by the histopathologic differentiation and the size of tumor. The differentiated cell types were associated with higher diagnostic accuracy in predicting the tumor invasion. Lesions located in the mid one third of the stomach larger than 3 cm had significantly higher probability of overstaging. Poorly differentiated histologic diagnosis had a significantly higher probability of understaging. There was no significant factor associated with the endosonographic prediction of lymph node metastasis. EGC with undifferentiated histopathologic features or large tumor size is more frequently associated with an incorrect diagnosis in tumor invasion depth by EUS. EGC with a size larger than 3 cm and poorly differentiated histologic diagnosis should be cautiously considered in the decision on treatment modality by pretreatment EUS staging.


Effect of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: A meta-analysis of placebo-controlled randomized trials.
Our aim was to study the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on the risk of any cardiovascular event in adults with overweight or obesity and without diabetes. We conducted a random-effects meta-analysis of placebo-controlled randomized controlled trials. Nine trials were eligible and, in total, 11 430 patients were included, of which 7702 (67%) were submitted to treatment with GLP-1 RA. During follow-up, 673 participants receiving GLP-1 RA treatment (8.7%) and 416 participants receiving placebo (11.2%) had a cardiovascular event. Treatment with GLP-1 RA versus placebo resulted in a reduction in the risk of any cardiovascular event (RR = 0.81, CI 0.70-0.92; p = .001). In overweight or obese adults without diabetes, treatment with GLP-1 RA reduced the risk of cardiovascular events. Our findings support the use of GLP-1 RA for reducing the cardiovascular risk of these patients.


Angiotensin-converting enzyme 2 deficiency accelerates and angiotensin 1-7 restores age-related muscle weakness in mice.
A pharmacologic strategy for age-related muscle weakness is desired to improve mortality and disability in the elderly. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II into angiotensin 1-7, a peptide known to protect against acute and chronic skeletal muscle injury in rodents. Since physiological aging induces muscle weakness via mechanisms distinct from other muscle disorders, the role of ACE2-angiotensin 1-7 in age-related muscle weakness remains undetermined. Here, we investigated whether deletion of ACE2 alters the development of muscle weakness by aging and whether angiotensin 1-7 reverses muscle weakness in older mice. After periodic measurement of grip strength and running distance in male ACE2KO and wild-type mice until 24 months of age, we infused angiotensin 1-7 or vehicle for 4 weeks, and measured grip strength, and excised tissues. Tissues were also excised from younger (3-month-old) and middle-aged (15-month-old) mice. Microarray analysis of RNA was performed using tibialis anterior (TA) muscles from middle-aged mice, and some genes were further tested using RT-PCR. Grip strength of ACE2KO mice was reduced at 6 months and was persistently lower than that of wild-type mice (p < 0.01 at 6, 12, 18, and 24-month-old). Running distance of ACE2KO mice was shorter than that of wild-type mice only at 24 months of age [371 ± 26 vs. 479 ± 24 (m), p < 0.01]. Angiotensin 1-7 improved grip strength in both types of older mice, with larger effects observed in ACE2KO mice (% increase, 3.8 ± 1.5 and 13.3 ± 3.1 in wild type and ACE2KO mice, respectively). Older, but not middle-aged ACE2KO mice had higher oxygen consumption assessed by a metabolic cage than age-matched wild-type mice. Angiotensin 1-7 infusion modestly increased oxygen consumption in older mice. There was no difference in a wheel-running activity or glucose tolerance between ACE2KO and wild-type mice and between mice with vehicle and angiotensin 1-7 infusion. Analysis of TA muscles revealed that p16INK4a, a senescence-associated gene, and central nuclei of myofibers increased in middle-aged, but not younger ACE2KO mice. p16INK4a and central nuclei increased in TA muscles of older wild-type mice, but the differences between ACE2KO and wild-type mice remained significant (p < 0.01). Angiotensin 1-7 did not alter the expression of p16INK4a or central nuclei in TA muscles of both types of mice. Muscle ACE2 expression of wild-type mice was the lowest at middle age (2.6 times lower than younger age, p < 0.05). Deletion of ACE2 induced the early manifestation of muscle weakness with signatures of muscle senescence. Angiotensin 1-7 improved muscle function in older mice, supporting future application of the peptide or its analogues in the treatment of muscle weakness in the elderly population.


Decreased plasma levels of neureglin-1 in drug naïve patients and chronic patients with schizophrenia.
Although the neuregulin-1 (NRG1) gene is one of the susceptibility genes for schizophrenia and various other psychiatric diseases, it remains unclear how individual psychiatric diseases affect the expression of the NRG1 protein in patients. A previous study reported a schizophrenia-linked decrease in serum NRG1 levels. The present study aimed to replicate this initial finding and to assess its disease specificity for schizophrenia. We collected plasma samples from drug-naïve patients with first-episode schizophrenia (n=80), patients with chronic schizophrenia (n=86), patients with bipolar I disorder (n=60), patients with bipolar II disorder (n=60) and patients with major depressive disorder (n=60), we measured the plasma levels of NRG1β1 and compared the levels with those of age- and sex-matched healthy volunteers (n=82). One-way ANOVA and post hoc analyses detected specific NRG1β1 decreases in the participants with first-episode and chronic schizophrenia but not in those with bipolar I disorder, bipolar II disorder or major depressive disorder. The mean plasma levels of NRG1β1 immunoreactivity were 4.27±0.71 ng/mL in the participants with first-episode schizophrenia, 4.08±0.64 ng/mL in the participants with chronic schizophrenia and 7.21±0.91 ng/mL in the healthy controls. Although we analyzed the pathological correlations of NRG1β1 immunoreactivity in terms of the clinical parameters of the sample, we observed only weak positive correlations with the age of the participants with chronic schizophrenia and the disease onset times of the participants with bipolar II disorder. We failed to identify correlations between other clinical parameters and plasma NRG1β1 immunoreactivity among all patient subjects. These findings suggest that NRG1 may serve as a relatively specific disease marker for schizophrenia. However, the pathological role of this decrease must be explored further.


Effect of oral slow-release terbutaline on early morning dyspnoea.
Eight male patients with partly reversible airflow obstruction, who had a diurnal variation in peak expiratory flow rate (PEFR) of more than 20% were treated with placebo and slow-release terbutaline tablets (5 mg at 08.00 hours and 10 mg at 20.00 hours) for 8 days. On Day 8 of each period, PEFR and serum terbutaline were measured at 4 and 2-h intervals, respectively. PEFR on the terbutaline day showed a significant increase at 08.00, 12.00, 24.00, 04.00 and 08.00 hours as compared to the placebo day. Slow-release terbutaline prevented early morning dyspnoea. The serum concentration was 3.3 ng/ml during the day and 3.5 ng/ml during the night. During terbutaline therapy the patients reported fewer complaints than during the placebo period. It was concluded that slow-release terbutaline tablets are suitable for twice daily treatment.


The mechanism of hyperlipidaemia in the nephrotic syndrome.
The mechanism of hyperlipidaemia in the nephrotic syndrome has not been fully established. We propose that it results from hypoalbuminaemia due to inhibition of the reaction catalysed by lecithin cholesterol acyltransferase converting cholesterol of high density lipoproteins to cholesterol esters and to an inhibition of high density lipoprotein particle formation from very low density lipoproteins due to reduced activity of lipoprotein lipase.


SEMA3G functions as a novel prognostic biomarker associated with Wnt pathway in clear cell renal cell carcinoma.
Renal cell cancer (RCC) is one of the most common cancer, and the incidence of clear cell renal cell cancer rank at the first among multiple subtypes of RCC. Tumor heterogeneity and limited therapies expedite researches and studies on prognostic biomarkers and molecular mechanism. SEMA3G mediates various bimolecular processes but few studies have assessed the influence of SEMA3G on ccRCC. The expression of SEMA3G at mRNA level in ccRCC was analyzed using 4 TCGA datasets. The expression at protein level was verified by immunohistochemistry and western blot. Biological pathway was explored by GSEA and western blot. At both mRNA and protein level, SEMA3G expressed significantly lower in ccRCC tissues compared with normal renal tissues, and the expression was highly associated with clinical stage and pathological grade. Low expression of SEMA3G indicated a poorer overall survival and disease specific survival. Transwell and wound-healing assays showed that overexpressed SEMA3G inhibited the cell motility of renal cancer cells. Upregulated SEMA3G suppressed the invasion and proliferation of both 769-P and 786-O cells. Wnt signaling pathway was tested to work in the interfering of SEMA3G on tumorigenesis and progression of ccRCC. The results provide novel insight into the role of SEMA3G in ccRCC, suggesting the prognostic value and potential suppressor role of SEMA3G.


Application of the wholebrain calculation interactive framework to map whole-brain neural connectivity networks.
The aim of this work was to develop a simple and feasible method of mapping the neural network topology of the mouse brain. Wild-type C57BL/6 J mice (n = 10) aged 8-10 weeks were injected with the cholera toxin subunit B (CTB) tracer in the anterior (NAcCA) and posterior (NAcCP) parts of the nucleus accumbens (NAc) core and in the medial (NAcSM) and lateral (NAcSL) parts of the NAc shell. The labeled neurons were reconstructed using the WholeBrain Calculation Interactive Framework. The NAcCA receives neuronal projections from the olfactory areas (OLF) and isocortex; the thalamus and isocortex project more fibers to the NAcSL, and the hypothalamus send more fiber projections to the NAcSM. Cell resolution can be automatically annotated, analyzed, and visualized using the WholeBrain Calculation Interactive Framework, making large-scale mapping of mouse brains at cellular and subcellular resolutions easier and more accurate.


Characteristics and outcomes of patients with hyperthyroidism attending a hospital endocrine clinic-A retrospective study.
A study looking at the distribution, management and outcomes of patients referred to a secondary care endocrine clinic with a diagnosis of hyperthyroidism. Retrospective longitudinal study of 442 patients referred over a 15-year period (2002-2017) with a diagnosis of hyperthyroidism to a secondary care endocrine clinic. Information on demographics, diagnosis, treatments and outcomes was recorded as patients attended for clinic visits. Patients were initially treated with 1-2 courses of thionamides and subsequently referred for radioiodine or surgery in cases of relapse. Patients (75% female, age range 17-91 years) were treated with thionamides for an average of 295 days. As expected, the majority of patients had Graves Disease (GD) (80%), followed by those with multinodular goitre (MNG) (8.6%), amiodarone-induced hyperthyroidism (6.7%) and toxic nodule (3.7%). Drug-induced remission rates were best seen in patients with GD (43%), and side effects necessitating change in treatment were relatively low (2.5%). In 121 patients who received radioiodine, hypothyroidism occurred in 50% of patients and was commoner in patients with GD (65%) than in those with MNG (22%) and toxic nodule (6.3%). This study is only one of a few reporting on the characteristics of patients with hyperthyroidism attending a typical secondary care endocrine clinic. Whilst we appreciate its limitations, we encourage similar methods of collecting valuable real world data to facilitate conduction of specialist peer review visits in other similar clinic settings.


Validation of the Hsp150 polypeptide carrier and HSP150 promoter in expression of rat alpha2,3-sialyltransferase in yeasts.
Heterologous glycoproteins usually do not fold properly in yeast cells and fail to leave the endoplasmic reticulum. Here we show that the Hsp150Delta polypeptide carrier promoted proper folding and secretion of the catalytic ectodomain of rat alpha2,3-sialyltransferase (ST3Ne) in Pichia pastoris. The efficiency of the Hsp150Delta carrier in P. pastoris and Saccharomyces cerevisiae was at least as high as that of the MFalpha carrier. Most of Hsp150Delta-ST3Ne and MFalpha-ST3Ne remained noncovalently attached to the cell wall via the ST3Ne portion. The strength of the HSP150 promoter was found to be comparable to that of the GAL1 promoter.


A Pattern of Care Report on the Management of Patients with Squamous Cell Carcinoma of the Anus-A Study by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gastrointestinal Tumors Study Group.
Background and objectives: The diagnosis and therapy of squamous cell carcinoma of the anus may vary significantly in daily clinical practice, even if international guidelines are available. Materials and Methods: We conducted a pattern of care survey to assess the management of patients with anal cancer in Italy (38 questions). We analyzed 58 questionnaires. Results: Most of the respondents work in public and/or university hospitals (75.8%) in northern Italy (65.5%). The majority (88.0%) treat less than 20 patients/year. Common examinations for diagnosis and staging are anorectal endoscopy (84.5%), computed tomography scan (86.2%) and pelvic magnetic resonance imaging (MRI) (96.5%). The most frequently prescribed dose to primary tumor is 50-54 Gy (46.5-58.6%) for early stage disease and 54-59.4 Gy (62.1-32.8%) for locally advanced cases. Elective volumes are prescribed around 45 Gy (94.8%). Most participants use volumetric intensity modulated radiotherapy (89.7%) and a simultaneous integrated boost (84.5%). Concurrent radiotherapy, 5-fluorouracil and mitomycin is considered the standard of care (70.6%). Capecitabine is less frequently used (34.4%). Induction chemotherapy is an option for extensive localized disease (65.5%). Consolidation chemotherapy is rarely used (18.9%). A response evaluation is conducted at 26-30 weeks (63.9%) with a pelvic MRI (91.4%). Follow-up is generally run by the multidisciplinary tumor board (62.1%). Conclusions: Differences were observed for radiotherapy dose prescription, calling for a consensus to harmonize treatment strategies.


Spontaneous arterial thrombosis in a patient with human immunodeficiency virus infection: successful treatment with pharmacomechanical thrombectomy.
Patients with human immunodeficiency virus (HIV) have various coagulation abnormalities as well as increased risk for development of clinical thrombosis and subsequent embolic events. We report acute lower leg ischemia caused by spontaneous atheroembolism with no identifiable source in a young patient with HIV infection. Treatment included percutaneous mechanical thrombectomy and thrombolysis, which reversed the arterial ischemia. Physicians should be aware of thromboembolic disease as a possible complication of HIV.


Analysis of creatine, creatinine, creatine-d3 and creatinine-d3 in urine, plasma, and red blood cells by HPLC and GC-MS to follow the fate of ingested creatine-d3.
Creatine, which is increasingly being used as an oral supplement, is naturally present in the body. Studies on the fate of a particular dose of creatine require that the creatine be labeled, and for studies in humans the use of a stable isotopic label is desirable. The concentrations of total creatine and total creatinine were determined using HPLC. Creatine and creatinine were then separated using cation exchange chromatography and each fraction was derivatized with trifluoroacetic anhydride and the ratio of the deuterated:undeuterated species determined using GC-MS. Ratios of creatine:creatine-d(3), and creatinine:creatinine-d(3), and the concentrations of each of these species, were able to be determined in urine, plasma and red blood cells. Thus, the uptake of labeled creatine into plasma and red blood cells and its excretion in urine could be followed for a subject who ingested creatine-d(3). Creatine-d(3) was found in the plasma and red blood cells 10 min after ingestion, while creatine-d(3) and creatinine-d(3) were found in the urine collected after the first hour.


An evaluation of pharmacists' expectations towards pharmacogenomics.
Given their expertise in pharmacotherapy, pharmacists are well positioned to play a leading role in the implementation of pharmacogenomics in clinical practice. However, little is known about the opinions of pharmacists towards pharmacogenomics or their willingness to integrate this new field in their practice. We conducted a survey of 284 pharmacists practicing in the province of Québec (Canada) to describe the opinions, expectations and concerns of pharmacists toward pharmacogenomics. Pharmacists were very hopeful regarding the potential role of pharmacogenomics. Moreover, more than 95% of responders would be willing to recommend pharmacogenomic testing. Nevertheless, only 7.7% of pharmacists currently felt comfortable advising patients based on pharmacogenomic test results. Accordingly, the majority of responders (96.6%) indicated that they would like to undertake continuing education related to pharmacogenomics. Pharmacists are extremely hopeful towards pharmacogenomic testing. Furthermore, a vast majority is willing to integrate these tests as part of their clinical practice. Proper education will be required if the integration of pharmacogenomics in patient care is to be optimal.


Source of lung surfactant phospholipids: comparison of palmitate and acetate as precursors.
The phospholipids and the fatty acid compositions of major phospholipids in rat lung parenchyma, microsomes, lamellar bodies and alveolar wash were quantified. Adult rats were injected simultaneously with [3H]palmitate and [14C]acetate into the femoral vein. The appearance of labeled phosphatidylcholine (PC), desaturated phosphatidylcholine (DSPC) and phosphatidylglycerol (PG) in each lung fraction was measured during short periods of time (5 min to 2 hr) after isotope administration. Relatively more PC, DSPC and PG labeled with acetate radioactivity in lung microsomes entered lamellar body and alveolar wash fractions than those labeled with palmitate radioactivity. However, there was no difference between palmitate and acetate labeled phospholipids in the transport from microsomes to lamellar bodies by phospholipid exchange proteins. On the other hand, prior injection of colchicine resulted in decrease in the transport of PC from microsomes to alveolar space to a relatively greater extent in the acetate radioactivity than in the palmitate radioactivity.


Infectious complications of burns casualties during the Yom-Kippur War.
During the October 1973 military conflict, 41 burned patients hospitalized at the Sheba Medical Center were closely followed up. All the patients who had burns occupying 20% or more of the body surface developed wound infections. Pseudomonas aeruginosa was the major pathogen isolated. Most infections occurred during the second week following the injury. Serial cultures revealed that only the isolation of Proteus species and P. aeruginosa from wounds could predict an infection caused by those microorganisms. During treatment with gentamicin and carbenicillin a marked increase in carbenicillin-resistant P. aeruginosa and gentamicin-resistant Klebsiella strains was noted. Cross-infections with carbenicillin-resistant P. aeruginosa was not a major cause in the development of resistant strains.


A novel method for the component identification of human blood products: Mass spectrometric analysis of human fibrinogen digested after SDS-PAGE in-gel digestion.
Human fibrinogen, as a blood product of special origin, is relatively simple to prepare and purify. Therefore, completely isolating and removing the relevant impurity proteins is difficult. Further, which impurity protein components are present is not clear. In this study, human fibrinogen products from seven enterprises were collected from the market, and the presence of impurity proteins was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Subsequently, the major 12 impurity proteins were identified and screened by in-gel enzymolysis mass spectrometry, and 7 major impurity proteins with different peptide coverage were identified by enzyme-linked immunosorbent assay, in agreement with the mass spectrometry results. The seven major impurity proteins included fibronectin, plasminogen, F-XIII, F-VIII, complement factor H, cystatin-A, and α-2-macroglobulin. The final test results were in the range of undetectable to 50.94 µg/mL, with correspondingly low levels of impurity proteins between different companies and a manageable risk. Moreover, we found that these impurity proteins existed in the form of polymers, which might also be an important cause of adverse reactions. This study established a protein identification technique applicable to fibrinogen products, which provided new ideas for studying the protein composition of blood products. In addition, it provided a new means of testing for companies to monitor the flow of proteomic fractions and improve the purification yield and product quality. It laid the foundation for reducing the risk of clinical adverse reactions.


Metal debris from bony resection in knee arthroplasty--is it an issue?
Metal particles are generated during bone preparation in knee arthroplasty. These particles may produce third-body wear, or may have a role in osteolysis. Knowledge of their characteristics may help in the development of methods to reduce the amount of metal debris during bone cutting procedures. We performed bony resection of the distal femur and proximal tibia on 15 pig knees, simulating a total knee arthroplasty (TKA). Metal debris was collected from the saw blades, cutting blocks and bone surfaces and cleaned for microanalysis. The average loss of metal from the saw blades was 1.13 mg. The average volume of a wear particle was 3.4 x 10(-16) m(3). From this, it was estimated that approximately 500,000 particles are released from the saw blade alone. Material analysis of the particles indicated that the majority originated from the metallic cutting guides, suggesting that many millions of wear particles would be generated during the surgical procedure. Two particle shapes predominated: platelet shape and ploughed shape. Wear particles are produced during resection for a TKA. These may enter the artificial articulation and cause accelerated wear and macrophage activation. Redesign of cutting blocks and saw blades may reduce the amount of debris produced during surgery.


Chemotherapy induces Notch1-dependent MRP1 up-regulation, inhibition of which sensitizes breast cancer cells to chemotherapy.
Multi-drug Resistance associated Protein-1 (MRP1) can export chemotherapeutics from cancer cells and is implicated in chemoresistance, particularly as is it known to be up-regulated by chemotherapeutics. Our aims in this study were to determine whether activation of Notch signalling is responsible for chemotherapy-induced MRP1 expression Notch in breast cancers, and whether this pathway can be manipulated with an inhibitor of Notch activity. MRP1 and Notch1 were investigated in 29 patients treated with neoadjuvant chemotherapy (NAC) for breast cancer, using immunohistochemistry on matched biopsy (pre-NAC) and surgical samples (post-NAC). Breast epithelial cell cultures (T47D, HB2) were treated with doxorubicin in the presence and absence of functional Notch1, and qPCR, siRNA, Western blots, ELISAs and flow-cytometry were used to establish interactions. In clinical samples, Notch1 was activated by neoadjuvant chemotherapy (Wilcoxon signed-rank p < 0.0001) and this correlated with induction of MRP1 expression (rho = 0.6 p = 0.0008). In breast cell lines, doxorubicin induced MRP1 expression and function (non-linear regression p < 0.004). In the breast cancer line T47D, doxorubicin activated Notch1 and, critically, inhibition of Notch1 activation with the γ-secretase inhibitor DAPT abolished the doxorubicin-induced increase in MRP1 expression and function (t-test p < 0.05), resulting in enhanced cellular retention of doxorubicin and increased doxorubicin-induced apoptosis (t-test p = 0.0002). In HB2 cells, an immortal but non-cancer derived breast cell line, Notch1-independent MRP1 induction was noted and DAPT did not enhance doxorubicin-induced apoptosis. Notch inhibitors may have potential in sensitizing breast cancer cells to chemotherapeutics and therefore in tackling chemoresistance.


Why did the copepod Calanus sinicus increase during the 1990s in the Yellow Sea?
Recent field and retrospective data were combined to investigate variations from 1984 to 1998 in the spring abundance of dominant copepods in the Yellow Sea. A calanoid copepod, Calanus sinicus, was chosen to assess the long-term changes in abundance associated with temperature, salinity, chlorophyll-a and predator abundance. Average anomalies of sea surface temperature (SST), salinity, and the abundance of C. sinicus were positive in the 1990s and negative in the 1980s. The average abundances of C. sinicus in the study area in the 1990s were also significantly higher than those in the 1980s (p<0.01). Catches of the anchovy Engraulis japonicus, a predator of C. sinicus, showed a decreasing trend during the study period. The higher abundances of C. sinicus in the 1990s may have been affected by an increase in water temperature and a decrease in predators, without distinctive changes in chlorophyll-a concentrations during the study period.


Time Trends in Adolescent School Absences and Associated Bullying Involvement Between 2000 and 2019: A Nationwide Study.
Education is a central determinant of adolescent health. School absences and bullying involvement jeopardize wellbeing, mental health, and educational attainment. We analyzed time trends in school absenteeism over two decades and examined the association of absenteeism with bullying involvement.We analyzed data from the nationwide School Health Promotion study, with self-reported data from Finnish middle school students in grades 8 and 9 (ages 14-17, N = 1 000 970). Questionnaires assessed frequency of illness absences (IA), truancy, frequency of bullying victimization, bullying perpetration, and involvement in both bullying perpetration and victimization. Frequent school absences were defined as occurring on more than 3 days during the prior month (2000-2015), or at least weekly (2017-2019).Frequent IA increased from 12% to 2000 to 22% in 2015. In 2017-2019, frequent IA was reported by 3.5%. Frequent truancy declined from 9% to 2000 to 4% in 2015, and remained at 4% during 2017-2019. Bully victimization was reported at least weekly by 6.9%, perpetration by 5.4% and victimization-perpetration by 1.9% of participants in total. In a logistic regression model, every type of bullying involvement increased odds for both IA and truancy.Since bullying involvement was associated with both IA and truancy, particular concern should be raised for adolescents involved in bullying, and for their social and educational functioning. The concurrent increase in IA and decrease in truancy may reflect destigmatization of mental health problems or other changes in reporting absenteeism.


Characteristic changes of pediatric maxillofacial fractures in China during the past 20 years.
The changes in the characteristics of maxillofacial fractures in pediatric patients during the past 20 years in China were investigated in an attempt to find valuable insight into the future prevention of such fractures. In this retrospective study, all pediatric patients age 0 to 12 years treated for maxillofacial fractures at our hospital between January 1987 and December 2006 were included. The epidemiologic information, including patient's gender, age, etiology, fracture type, and fracture site were divided chronologically into two 10-year periods: period 1 (January 1987 to December 1996) and period 2 (January 1997 to December 2006). Both periods were compared and analyzed. The characteristics of pediatric maxillofacial fractures in our data remained relatively consistent during the past 20 years. The only confirmed significant difference was the change in proportion of maxillofacial fractures in patients 0 to 2 years of age. The characteristics of maxillofacial fractures can be influenced by social and economic factors; however, they are also associated with the subjects' social role in each particular age group. In China, the key to reducing occurrences of pediatric facial fractures is to prevent accidental falls in children as much as possible.


Students' Perspective on Active Learning in Nutrition Education.
To analyze the perception of nutrition undergraduates about the use of active methodologies as teaching-learning tools for the Nutrition Education course. Quali-quantitative cross-sectional research with application of a structured questionnaire and subsequent use of focus groups. Fifty-three sixth and eighth semester nutrition students, taking or having taken the course of Nutrition Education, with mean age (SD) of 23.6 (±5.02) years; 84% were females, and 54% were sixth semester students. Ten students (8 females) participated in the qualitative phase of the research. The use of active learning (AL) in the Nutrition Education course in a university with a traditional teaching method. Descriptive statistics was performed using absolute and relative frequencies, whereas qualitative analysis was based on categorical content analysis. Participants reported not knowing the meaning of AL, but they believed that these methodologies were useful for their learning process and different from what they had experienced in the traditional method. In the above-mentioned course, AL improved students' skills, which should be developed throughout their degree program, and familiarized them with methods that can be replicated in their professional life, be it in an academic career or in other fields.


Proofreaders' decreased Stroop interference.
12 professional proofreaders and 12 control subjects performed a Stroop color-word task. The control subjects showed significantly more Stroop interference than did the proofreaders. It appears that a career in proofreading makes it easier for subjects to ignore the meaning of word stimuli.


[Evaluation of the association between benign prostatic hyperplasia and sexual disorders].
The aim of this study was to determine the incidence of sexual dysfunction in patients with benign prostatic hyperplasia (BPH). During the last 6 months 88 patients (mean age 65 years, range 55-78) suffering from BPH, without other chronic disease, were studied. Andrological evaluation enabled us to find erectile dysfunction in 52% of patients, ejaculation problems in 41% and decrease of libido in 54%. Due to the great impact of these disturbances in patients' quality of life, we believe that clinical and therapeutic approach in BPH patients should be global, with both urological and andrological assessment.


Reducing GABA receptors.
A number of important drugs act on GABA(A) receptors, pentameric GABA-gated chloride channels assembled from among 19 known subunits. In trying to discover the roles in the brain of the subunits and their combinations, with the goal of developing more selective drugs, one tool has been to reduce expression of the subunits and examine the functional consequences. After briefly examining the properties of GABA(A) receptors, this review surveys the means available for receptor subunit reduction, and some of the observations to which their application has led. The methods discussed include radiation-induced deletion, gene knockout, knock-in mutations, antisense, ribozymes, RNA interference, dominant negative constructs, and transcriptional regulation, e.g., via decoy oligonucleotides.


Immunosuppressant material in human seminal fluid. Inhibition of blast transformation and of NK activity by seminal fluid patients of a male infertility clinic.
Human seminal plasma from normal or patients with abnormal parameters of the ejaculates contains an inhibitory material that expresses potent in vitro inhibitory activity on PHA-M-induced blast transformation and NK activity. Using the test of inhibition of NK activity, the semen samples from individuals with higher concentrations of fructose had higher inhibitory activity. The results described herein suggest that inhibitory activity for blast transformation may be present in the prostatic fluid while the NK inhibition aspects are correlated with the vesicle-marker (fructose). Inhibition of the immune responses by human seminal plasma of the effector functions indicates the interesting implication that soluble factors may indirectly protect against or promote human autoimmune infertility disease.


The association between passive social network usage and depression/negative emotions with envy as a mediator.
This study aimed to investigate the relationships between passive social network usage (PSNU) and depression/negative emotions over time with the mediating role of envy among Vietnamese adolescents. First, it revealed that PSNU had a simultaneous effect on depression/negative emotions as well as at different time points, indicating that social network site behaviors can predict psychological states over time (explained by the social comparison theory). Second, the autoregressive effect also confirmed a potential reciprocal relationship between PSNU and depression, whereas PSNU appeared to have an impact on negative emotions but not the other way around. Specifically, depression at Time 1 was positively associated with PSNU at Time 2, whereas negative emotions did not exhibit a similar pattern (explained by the cognitive dissonance theory). The different associations were interpreted as depression having cognitive elements, while negative emotions were thought to be purely emotional states. The results demonstrated that behavior may potentially have a long-lasting effect on mental health (both negative emotions and depression), while it was depression, rather than negative emotions, that had a long-term effect on behaviors. Third, envy played a mediating role that connected the changes of PSNU and depression/negative emotions. The implications and limitations of these findings are discussed.


Precise nanoscale temperature mapping in operational microelectronic devices by use of a phase change material.
The microelectronics industry is pushing the fundamental limit on the physical size of individual elements to produce faster and more powerful integrated chips. These chips have nanoscale features that dissipate power resulting in nanoscale hotspots leading to device failures. To understand the reliability impact of the hotspots, the device needs to be tested under the actual operating conditions. Therefore, the development of high-resolution thermometry techniques is required to understand the heat dissipation processes during the device operation. Recently, several thermometry techniques have been proposed, such as radiation thermometry, thermocouple based contact thermometry, scanning thermal microscopy, scanning transmission electron microscopy and transition based threshold thermometers. However, most of these techniques have limitations including the need for extensive calibration, perturbation of the actual device temperature, low throughput, and the use of ultra-high vacuum. Here, we present a facile technique, which uses a thin film contact thermometer based on the phase change material [Formula: see text], to precisely map thermal contours from the nanoscale to the microscale. [Formula: see text] undergoes a crystalline transition at [Formula: see text] with large changes in its electric conductivity, optical reflectivity and density. Using this approach, we map the surface temperature of a nanowire and an embedded micro-heater on the same chip where the scales of the temperature contours differ by three orders of magnitude. The spatial resolution can be as high as 20 nanometers thanks to the continuous nature of the thin film.


Increased prevalence of fracture and hypoglycaemia in young adults with concomitant type 1 diabetes mellitus and coeliac disease.
Both Type 1 diabetes mellitus (T1DM) and coeliac disease (CD) are independently associated with reduced bone mineral density (BMD) and increased fracture risk. Whilst poorer glycaemic control and increased microvascular complications have been described, the literature examining bone health and fractures in adults with concomitant T1DM and CD (T1DM + CD) is limited. To evaluate fracture prevalence and explore associations with glycaemic control, hypoglycaemia and microvascular disease in T1DM + CD compared with T1DM alone. We conducted a retrospective cross-sectional study of young adults with T1DM, who attended diabetes clinics at a large tertiary referral centre between August 2016 and February 2017. Clinical information, radiological and biochemistry results were extracted from medical records. Patients with comorbid chronic kidney disease, glucocorticoid use, hypogonadism and untreated hyperthyroidism were excluded. A total of 346 patients with T1DM alone (median age 23 years) and 49 patients with T1DM + CD (median age 24 years) were included. Median age, gender distribution, BMI, haemoglobin A1c, daily insulin dose and serum 25-hydroxyvitamin D levels were similar between groups. Higher adjusted fracture risk was observed in T1DM + CD compared with T1DM (12.2% vs 3.5%; OR 3.50, 95% CI 1.01-12.12, P = .01), yet BMD was only measured in 6% of patients. The adjusted risk of hypoglycaemia ≥2/week was greater for T1DM + CD (55% vs 38%, OR 3.28, 95% CI 1.61-6.69, P = .001); however, this was not independently associated with fractures. Replete vitamin D (≥ 50 nmol/L) was associated with less hypoglycaemia (OR 0.48, 95% CI 0.29-0.80; P = .005), but not with fractures. Coeliac disease status was independently associated with increased fracture prevalence in young adults with T1DM. Recurrent hypoglycaemia was also increased in T1DM + CD, although hypoglycaemia was not independently associated with fractures. Prospective studies are required to determine the long-term impacts of CD on bone health and glycaemic control in patients with T1DM.


An electronic open field.
An electronic open field made with inexpensive, off-the-shelf materials is described. Its automatic operation frees the researcher from tedious and time consuming direct observations in experiments measuring exploratory behavior, goal preference, etc. Its numeric output can be read from the display or interfaced to printers, recorders, computers, etc. As an example of its operation, experimental results measuring sexual motivation (proceptivity) of female rats are reported.


Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities.
Wnt signaling is a highly conserved signaling pathway that plays a critical role in controlling embryonic and organ development, as well as cancer progression. Genome-wide sequencing and gene expression profile analyses have demonstrated that Wnt signaling is involved mainly in the processes of breast cancer proliferation and metastasis. The most recent studies have indicated that Wnt signaling is also crucial in breast cancer immune microenvironment regulation, stemness maintenance, therapeutic resistance, phenotype shaping, etc. Wnt/β-Catenin, Wnt-planar cell polarity (PCP), and Wnt-Ca2+ signaling are three well-established Wnt signaling pathways that share overlapping components and play different roles in breast cancer progression. In this review, we summarize the main findings concerning the relationship between Wnt signaling and breast cancer and provide an overview of existing mechanisms, challenges, and potential opportunities for advancing the therapy and diagnosis of breast cancer.


Impact of training on rating competence in cognitive therapy.
This naturalistic study examines the impact of a training package on the inter-rater reliability scores of a scale devised to measure competence in cognitive therapy (CT). The study was conducted at the Newcastle Cognitive and Behavioural Therapies Centre, where trainees are routinely required to submit videotapes of their therapeutic work for marking independently by two supervisors. This process was used as vehicle for the present work, whereby the trainees' videos were assessed in terms of their competence using a recently revised rating scale (CTS-R). The inter-rater reliability of the supervisors' ratings was assessed both before and after the administration of a teaching package designed to improve the reliability in the use of the CTS-R. The results showed an improvement in the inter-rater agreement of five out of 12 items of the scale. The overall agreement also improved significantly following training.


Children with chronic organ failure possibly ending in organ transplantation: a survey in an Italian region of 5,000,000 inhabitants.
The Italian Piedmont region sponsored in 2005 a population-based registry to assess the epidemiology of childhood chronic organ failure involving kidneys, liver, heart or lungs. Patients in chronic organ failure who were younger than 18 years were selected, and entered the registry when accomplishing the standard failure criteria for each organ. The cases were reported by the general paediatricians of the region and integrated with the data gathered by the Children University Hospital, a tertiary care centre. In Piedmont (647,727 inhabitants < 18 years), a total of 146 children (217 cases per million of paediatric population) were found to be affected by chronic organ failure (mean age 10 years; range 0-17). The organ failure involved kidneys in 68 subjects (48%), liver in 24 (17%), heart in 21 (15%) and lungs in 28 (20%), and was severe in 32 subjects (6 on transplantation waiting list). The most represented disease leading to chronic renal failure was renal hypodysplasia (79%). Chronic liver failure was mostly caused by biliary atresia (30%), autoimmune hepatitis (25%) and Wilson's disease (21%). Dilated cardiomyopathy (62%) and surgically treated congenital cardiopathy were the two leading causes of chronic heart failure. The most represented disease leading to chronic lung failure was cystic fibrosis (89%). This is the first report of the literature focusing on the epidemiology of chronic organ failure in children encompassing a region of 4,000,000 inhabitants. This clinical condition is rare, but medically and socially very demanding not only in childhood but the life along, as most of these patients will need solid organ transplantation decades later.


Hemispheric asymmetry non-linear analysis of EEG during emotional responses from idiopathic Parkinson's disease patients.
Recent studies show right hemisphere has a unique contribution to emotion processing. The present study investigated EEG using non-linear measures during emotional processing in PD patients with respect to motor symptom asymmetry (i.e., most affected body side). We recorded 14-channel wireless EEGs from 20 PD patients and 10 healthy age-matched controls (HC) by eliciting emotions such as happiness, sadness, fear, anger, surprise and disgust. PD patients were divided into two groups, based on most affected body side and unilateral motor symptom severity: left side-affected (LPD, n = 10) or right side-affected PD patients (RPD, n = 10). Nonlinear analysis of these emotional EEGs were performed by using approximate entropy, correlation dimension, detrended fluctuation analysis, fractal dimension, higher order spectra, hurst exponent (HE), largest Lyapunov exponent and sample entropy. The extracted features were ranked using analysis of variance based on F value. The ranked features were then fed into classifiers namely fuzzy K-nearest neighbor and support vector machine to obtain optimal performance using minimum number of features. From the experimental results, we found that (a) classification performance across all frequency bands performed well in recognizing emotional states of LPD, RPD, and HC; (b) the emotion-specific features were mainly related to higher frequency bands; and (c) predominantly LPD patients (inferred right-hemisphere pathology) were more impaired in emotion processing compared to RPD, as showed by a poorer classification performance. The results suggest that asymmetric neuronal degeneration in PD patients may contribute to the impairment of emotional communication.


Exploring the Psychosocial Needs of Adolescents Whose Parent Is Diagnosed With Breast Cancer.
Cancer has a major impact on the individual patient and their family, especially children. However, little is known about the needs of adolescents (10-19 years) whose parent is diagnosed with cancer, especially breast cancer. Insights into psychosocial needs are important to develop appropriate guidance and support for these adolescents. The aim of this study is to explore the psychosocial needs of adolescents whose parent is diagnosed with breast cancer to improve the support for these adolescents. This is an exploratory, qualitative study. In-depth interviews were conducted, and an interview guide was designed with the following topics: experiences, needs, and support. Participants were selected purposively and approached via the parent(s) after consultation. Interviews were audiotaped, transcribed, and thematically analyzed by using the software program NVivo. Fourteen adolescents (12-19 years) were interviewed, which resulted in five themes: distraction, support, being able to talk about it, information, and continuing a normal life. Adolescents whose parent is diagnosed with breast cancer need the best possible preservation of their normal lives. It is important for them to be able to share their story and find support from someone close to them. The route to the adolescent is always through the parent. Healthcare professionals can discuss the well-being of the adolescent during regular consultation with the parent. If there are concerns, healthcare professionals can advise the parent about the possible needs of the adolescent and could coach the parent in supporting the adolescent to discuss their needs.


[Diagnostic image (241). A woman with malaise, periodic fever and extreme fatigue].
A 51-year-old white woman with extreme fatigue, fever episodes, weight loss, leucocytosis and increased erythrocyte sedimentation rate showed diffuse high uptake of 18F-fluorodeoxyglucose in the entire aortic wall, which is characteristic of giant cell large-vessel arteritis, such as Takayasu disease.


Oocyte efficiency: does live birth rate differ when analyzing cryopreserved and fresh oocytes on a per-oocyte basis?
To compare the efficiency of oocyte cryopreservation (OC) and IVF using the metric "live births per mature oocyte retrieved." Retrospective analysis. University-based fertility center. Forty women who underwent OC with thaw attempt between 2004 and 2010; 25 autologous and 15 donor-oocyte treatments were included. One thousand nine hundred eight women underwent their first, fresh conventional IVF treatment between 2004 and 2010; 1,392 used autologous oocytes, and 516 used donor oocytes. Autologous and donor-oocyte cycles were analyzed separately. All oocytes were obtained from women <age 40 years old. None. Live-birth rate per mature oocyte retrieved (primary outcome), live-birth rate per ET, and blastocyst formation rate. When OC/thaw cycles were compared with fresh IVF attempts, there was no significant difference in live-birth rate per mature oocyte retrieved (2.7% vs. 4.2%, respectively) or live-birth rate per ET (45.8% vs. 51.9%). Significantly more oocytes were harvested in the OC versus fresh IVF cycles (21 vs. 16); however, fewer blastocysts developed (3.9 vs. 6.3). Thus, we noted an age-independent approximate twofold decrease in blastocyst formation in the OC group. Our data suggest that while assisted reproductive technology remains an inefficient process, OC may be approaching fresh IVF when live birth is the primary consideration. However, OC may negatively impact the potential for blastocyst formation.


Structure-activity relationship of three new piperazine derivates with anxiolytic-like and antidepressant-like effects.
Anxiety and depression are common mental disorders affecting millions of people worldwide. Unsatisfactory clinical outcomes with the use of the available pharmacological interventions among some patients demand newer drugs with proven efficacy, safety, and tolerability profile. In this study, the LQFM211, LQFM213, and LQFM214 were designed from the piperazine scaffold and administered orally in mice. These mice were later evaluated in the open field, elevated plus maze, and forced swimming tests to assess the exploratory, anxiolytic, and antidepressant-like activities, respectively. The mechanism of action of these new derivatives was evaluated using flumazenil (benzodiazepine antagonist) and WAY100635 (5-HT1A receptor antagonist). Unlike LQFM214, the LQFM211 and LQFM213 elicited anxiolytic and antidepressant-like effects. The blockade of the effect of LQFM213 by WAY100635 suggests the involvement of the serotonergic pathway.