Hemodynamic effects of brefanolol and propranolol assessed by noninvasive methods in patients with arterial hypertension.
In a placebo-controlled, randomized, cross-over study, 16 patients (10 males, 6 females; 50.6 +/- 10.4 years; body weight of 74.5 +/- 8.9 kg; mean +/- SD) with arterial hypertension (WHO stages I and II) were administered single oral doses of placebo, 80 mg of propranolol, as well as 50 and 100 mg of brefanolol (a beta-adrenergic blocking agent with vasodilating properties) in order to determine the resulting hemodynamic effects. Blood pressure, heart rate, and various hemodynamic parameters were assessed noninvasively by mechano- and impedance cardiography as well as by venous occlusion plethysmography before and 2, 4, 6, 10, and 24 h after drug administration. Treatment with propranolol resulted in the typical hemodynamic changes induced by a beta-adrenergic blocking agent characterized by a significant reduction in blood pressure, heart rate, cardiac output, stroke volume, and an increase in total peripheral resistance. A dose of 100 mg of brefanolol also led to comparable hemodynamic effects. Similar significant decreases in blood pressure, heart rate, and cardiac output also occurred with 50 mg of brefanolol, but stroke volume and reactive hyperemia increased. Thus, in this phase of drug development, dose titration with 50 and 100 mg of brefanolol indicates that the lower dose gives rise to a more balanced relationship between its beta-adrenergic blocking and vasodilating properties.


Ground state selection under pressure in the quantum pyrochlore magnet Yb2Ti2O7.
A quantum spin liquid is a state of matter characterized by quantum entanglement and the absence of any broken symmetry. In condensed matter, the frustrated rare-earth pyrochlore magnets Ho2Ti2O7 and Dy2Ti2O7, so-called spin ices, exhibit a classical spin liquid state with fractionalized thermal excitations (magnetic monopoles). Evidence for a quantum spin ice, in which the magnetic monopoles become long range entangled and an emergent quantum electrodynamics arises, seems within reach. The magnetic properties of the quantum spin ice candidate Yb2Ti2O7 have eluded a global understanding and even the presence or absence of static magnetic order at low temperatures is controversial. Here we show that sensitivity to pressure is the missing key to the low temperature behaviour of Yb2Ti2O7. By combining neutron diffraction and muon spin relaxation on a stoichiometric sample under pressure, we evidence a magnetic transition from a disordered, non-magnetic, ground state to a splayed ferromagnetic ground state.


Reproductive health in SLE.
Oral contraceptives containing oestrogens and hormone replacement therapy are generally not prescribed for women with systemic lupus erythematosus (SLE). The concern regarding oestrogens is based on the greater incidence of SLE in women, abnormalities of oestrogen metabolism, murine models of lupus, several anecdotes of patients having disease flares while receiving hormones, and one retrospective study in patients with pre-existing renal disease. For healthy women and those with SLE, there are clinical settings in which exogenous oestrogens provide benefit. For pre-menopausal women, these include provision of safe and effective birth control, protection against bone loss, and the consideration of oral contraceptives to preserve fertility in patients taking cyclophosphamide. For post-menopausal women, these include treatment of hot flushes and vaginal dryness, prevention of osteoporosis and, more controversial, prevention of atherosclerosis. Other exogenous hormones (clomiphene citrate, gonadotropins, gonadotropin-releasing hormones) may be used to elevate levels of endogenous oestrogen and stimulate ovulation in patients with diminished fertility. This chapter focuses on three broad categories: birth control, assisted reproduction and hormone replacement.


The effect of chorionic villus sampling on the fraction of cell-free fetal DNA in maternal plasma.
This study aims to assess whether the fraction of cell-free fetal DNA (cffDNA) is different at 24 h or 7 days after chorionic villus sampling (CVS), compared to subjects that do not undergo CVS. Pregnant women undergoing CVS for genetic testing and matched subjects undergoing first trimester combined screening alone were enrolled between 11(0/7) and 13(6/7) weeks gestation. The fractions of cffDNA were compared before the procedure, 24 h after and 7 days after between CVS patients and ultrasound-only patients. Forty-five women underwent CVS and 45 had ultrasound alone. The women undergoing CVS were, on average, older (36.8 years versus 28.5 years, p=0.001) and had a higher baseline fraction of cffDNA than women in the comparison group (11.4% versus 9.8%, p=0.033). Both groups had a decrease in the mean fraction of cffDNA after 24 h. After 7 days, the trend of the mean fraction of cffDNA continued to decline in the CVS group but began to trend toward an increase in the ultrasound only group. CVS does not significantly increase the fraction of cell free fetal (placental) DNA in the maternal plasma. A downward trend in cffDNA in maternal plasma is seen at 24 h and 7 days following CVS compared to baseline.


Diversity of Sarcosaprophagous Calyptratae (Diptera) on Sandy Beaches Exposed to Increasing Levels of Urbanization in Brazil.
Sandy beaches are among the most impacted ecosystems worldwide, and the effects of urbanization on the biodiversity of these habitats are largely unknown, particularly in Brazil. We investigated the composition and structure of assemblages of sarcosaprophagous insects (Diptera: Calliphoridae, Sarcophagidae, and Muscidae) on six sandy beaches exposed to differential levels of human impact in Pernambuco State, Brazil. In total, 20,672 adults of 40 species were collected, of which 70% were Calliphoridae. Sarcophagidae had the highest diversity with 26 species of nine genera. A strong overlap in the composition of the assemblages across the six beaches was observed, with only a few species being restricted to one type of beach. The flesh flies Dexosarcophaga carvalhoi (Lopes), Peckia intermutans (Walker), and Titanogrypa larvicida (Lopes) occurred exclusively in beaches under low anthropogenic impact. Species with strong medical and veterinary importance such as Synthesiomyia nudiseta (Wulp) occurred even in beaches under low human presence. The invasive species Chrysomya albiceps (Wiedemann) and Chrysomya megacephala (F.) (Calliphoridae) were dominant in all beaches, which exposes the vulnerability of sandy beaches to exotic species. Our data imply that sarcosaprophagous flies can be used as early biological indicators to suggest urbanization in coastal environments.


Autologous pericranium grafts for large orbital implants.
Insufficient orbital volume in an anophthalmic socket is a major problem for the placement of an ocular prosthesis. This study reports the outcomes of the use of autologous pericranium graft in association with a large primary or secondary orbital implant in patients with a contracted socket and large orbital volume deficit. This was a retrospective single-institution study. Participants were 13 patients with contracted socket, volume deficit, and insufficient conjunctiva to cover the new implant divided into two groups, A (n = 3) and B (n = 10), according to the baseline condition of the socket. Surgery was primary evisceration (group A only) and placement of a large orbital implant followed by an autologous pericranium graft over the implant (groups A and B). Mean follow-up duration for the patient series was 9.5 months (range 9-24). Complete epithelialization of the pericranium graft was recorded at 47.3 days of follow-up (range 33-67). No cases of implant exposure or shrinkage were noted during follow-up. Main postoperative complications were conjunctival granuloma (five patients, 38.5%), conjunctival seroma (one patient, 7.7%). All patients were satisfied with the aesthetic outcome. Autologous pericranial graft was effective in reconstructing the contracted socket so that the anophthalmic socket could accommodate a larger or secondary orbital implant. The efficacy of this procedure needs to be confirmed in a larger patient series.


Variations in the diagnostic process among urologists in one region recorded using an interactive computer program.
To analyse how male cases suffering from lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are handled within a well-defined health-care region in Scandinavia, an interactive computer program containing 20 cases suffering from LUTS due to BPH was used for recording the diagnostic process and the treatment decisions; 37 out of a total of 50 urologists practicing within a small health region participated. The diagnostic process varied considerably due to a varying choice of diagnostic tests and the large differences in interpreting the qualities described by the tests. The probability that a patient would be offered a treatment within the region was analysed. For many patients the probability that a treatment was chosen was in the vicinity of 50%. No treatment probability was correlated to the symptom score of the patients. While the probability that a transurethral prostatic resection would be offered to the patients within the region was correlated significantly to urodynamic variables, residual urine and to cystoscopy findings, the probability that transurethral microwave or finasteride therapy would be offered was not correlated to any of the described qualities. The costs of the diagnostic process in all the patients incurred by each of the urologists varied by up to 500%. It was estimated that approximately 40% of the costs involved diagnostic tests that did not influence the decision to offer or not to offer treatment. In conclusion, the enormous variations in the handling of the cases recorded in the study stress the need that a management formula should be used in the handling of patients with LUTS.


Structure and evolution of ENTH and VHS/ENTH-like domains in tepsin.
Tepsin is currently the only accessory trafficking protein identified in adaptor-related protein 4 (AP4)-coated vesicles originating at the trans-Golgi network (TGN). The molecular basis for interactions between AP4 subunits and motifs in the tepsin C-terminus have been characterized, but the biological role of tepsin remains unknown. We determined X-ray crystal structures of the tepsin epsin N-terminal homology (ENTH) and VHS/ENTH-like domains. Our data reveal unexpected structural features that suggest key functional differences between these and similar domains in other trafficking proteins. The tepsin ENTH domain lacks helix0, helix8 and a lipid binding pocket found in epsin1/2/3. These results explain why tepsin requires AP4 for its membrane recruitment and further suggest ENTH domains cannot be defined solely as lipid binding modules. The VHS domain lacks helix8 and thus contains fewer helices than other VHS domains. Structural data explain biochemical and biophysical evidence that tepsin VHS does not mediate known VHS functions, including recognition of dileucine-based cargo motifs or ubiquitin. Structural comparisons indicate the domains are very similar to each other, and phylogenetic analysis reveals their evolutionary pattern within the domain superfamily. Phylogenetics and comparative genomics further show tepsin within a monophyletic clade that diverged away from epsins early in evolutionary history (~1500 million years ago). Together, these data provide the first detailed molecular view of tepsin and suggest tepsin structure and function diverged away from other epsins. More broadly, these data highlight the challenges inherent in classifying and understanding protein function based only on sequence and structure.


Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.
The study aimed to use network pharmacology research and in vitro experiments to investigate the material basis and molecular mechanisms of silybin in the treatment of papillary thyroid carcinoma. Papillary thyroid cancer (PTC) has a decent prognosis; however, recurrence and metastasis are the leading causes of death in patients with PTC. A key research focus in thyroid cancer treatment is the inhibition of PTC proliferation, invasion, and migration. Silybin, the major active element in the traditional Chinese herb silymarin, has been used to treat a range of diseases, including cancer, but no study has been undertaken to determine whether it can help prevent PTC. In this study, we attempted to determine through network pharmacology and in vitro experiments if silybin inhibits the development of papillary thyroid cancer by inhibiting cell cycle and invasive migration. To predict the probable targets and underlying mechanisms of silybin against PTC, a network pharmacology research was performed. In vitro experiments were conducted to further evaluate silybin's anti-cancer properties and priority targets against PTC. The datasets revealed a total of 489 silybin targets acting on PTC, and functional enrichment analysis suggested that the target genes were enriched in functions and pathways related to PTC development, invasion, migration, and immunotherapy. By constructing these target PPI networks, the seven hub genes, fibronectin 1 (FN1), tissue inhibitor of metalloproteinases 1 (TIMP1), N-cadherin (CDH2), collagen type III alpha 1 chain (COL3A1), cyclin D1 (CCND1), AP-1 transcription factor subunit (JUN), and hepatocyte growth factor receptor (MET) were found. These hub genes were determined to be highly linked to a worse clinicopathological form, a higher risk of metastatic recurrence, and a worse prognosis of PTC. The common immunological checkpoint gene expression levels were positively correlated with the expression levels of the hub genes. Silybin decreased the proliferative and metastatic capacity of PTC cells, according to in vitro investigations. When PTC was treated with silybin, the FN1/AKT signaling pathway was blocked, CCND1 expression was reduced, and CDH2, Vimentin, Snail, Slug and PD-L1 expressions were dramatically reduced, while E-cadherin expression was significantly elevated. These findings provide preliminary evidence that silybin inhibits PTC cell proliferation, metastasis, and invasion by altering the FN1/AKT signaling pathway and inhibiting the EMT process. Silybin can reverse immunosuppression in papillary thyroid cancer by affecting immunological checkpoint gene expression levels. These studies provide a theoretical and experimental scientific basis for the potential anticancer effects of silybin on PTC.


Fluctuation in seed abundance has contrasting effects on the fate of seeds from two rapidly germinating tree species in an Asian tropical forest.
The seed predator satiation hypothesis states that high seed abundance can satiate seed predators or seed dispersers, thus promoting seed survival. However, for rapidly germinating seeds in tropical forests, high seed abundance may limit dispersal as the seeds usually remain under parent trees for long periods, which may lead to high mortality due to rodent predation or fungal infestations. By tracking 2 species of rapidly germinating seeds (Pittosporopsis kerrii, family Icacinaceae; Camellia kissi, family Theaceae), which depend on dispersal by scatter-hoarding rodents, we investigated the effects of seed abundance at the community level on predation and seed dispersal in the tropical forest of Xishuangbanna Prefecture, Southwest China. We found that high seed abundance at the community level was associated with delayed and reduced seed removal, decreased dispersal distance and increased pre-dispersal seed survival for both plant species. High seed abundance was also associated with reduced seed caching of C. kissi, but it showed little effect on seed caching of P. kerrii. However, post-dispersal seed survival for the 2 plant species followed the reverse pattern. High seed abundance in the community was associated with higher post-dispersal survival of P. kerrii seeds, but with lower post-dispersal survival of C. kissi seeds. Our results suggest that different plant species derive benefit from fluctuations in seed production in different ways.


Physical and chemical quality characteristics and antioxidant properties of strawberry cultivars (Fragaria × ananassa Duch.) in Greece: assessment of their sensory impact.
There are many factors determining the strawberry organoleptic profile and they are difficult to define. In this study, the sensory, physical, and chemical quality characteristics, the antioxidant properties as examined using ferric reducing antioxidant power (FRAP) and 1-diphenyl-2-picrylhydrazyl (DPPH) assays, the lactone concentration, and the FaFAD1 expression of ripe strawberries (cv. Camarosa, Florida Fortuna, and Sabrina) from Greece were evaluated and their interrelationships were investigated. 'Camarosa' had the highest antioxidant capacity and polyphenol content, although significant intra-cultivar variations of sugars, solid soluble content/titratable acidity (SSC/TA), red color intensity, sweetness, and hardness were recorded. In 'Sabrina' there was a constant lactone presence and FaFAD1 expression; it also had the lowest ascorbic acid content, the highest pH, SSC/TA index, firmness, and sweetness. 'Fortuna' showed the lowest sweetness and aroma indices, whereas 'Camarosa' had intermediate ones. Overall, firmness was correlated with hardness, while pH and SSC/TA index correlated with juiciness and sweetness. Both γ-decalactone and γ-dodecalactone concentrations were correlated with FaFAD1 expression and pH, but they did not solely determine the aroma sensory perception. In total, FRAP values were positively correlated with ascorbic acid and polyphenol content, and negatively with pH. Significant inter- and intra-cultivar variation was recorded, revealing the impact of the genotype and underlining the effect of microenvironmental and cultivation conditions on quality and sensory perception. © 2018 Society of Chemical Industry.


Influence of porcelain veneering on the marginal fit of Digident and Lava CAD/CAM zirconia ceramic crowns.
Marginal fit is a very important factor considering the restoration's long-term success. However, adding porcelain to copings can cause distortion and lead to an inadequate fit which exposes more luting material to the oral environment and causes secondary caries. The purpose of this study was to compare the marginal fit of 2 different all-ceramic crown systems before and after porcelain veneering. This study was also intended to verify the marginal fit of crowns originated from green machining of partially sintered blocks of zirconia (Lava CAD/CAM system) and that of crowns obtained through machining of fully sintered blocks of zirconia (Digident CAD/CAM system). 20 crowns were made per each system and the marginal fit was evaluated through a light microscope with image processing (Accura 2000) at 50 points that were randomly selected. Each crown was measured twice: the first measurement was done after obtaining a 0.5 mm coping and the second measurement was done after porcelain veneering. The means and standard deviations were calculated and statistical inferences among the 2 groups were made using independent t-test and within the same group through paired t-test. The means and standard deviations of the marginal fit were 61.52 ± 2.88 µm for the Digident CAD/CAM zirconia ceramic crowns before porcelain veneering and 83.15 ± 3.51 µm after porcelain veneering. Lava CAD/CAM zirconia ceramic crowns showed means and standard deviations of 62.22 ± 1.78 µm before porcelain veneering and 82.03 ± 1.85 µm after porcelain veneering. Both groups showed significant differences when analyzing the marginal gaps before and after porcelain veneering within each group. However, no significant differences were found when comparing the marginal gaps of each group before porcelain veneering and after porcelain veneering as well. The 2 all-ceramic crown systems showed marginal gaps that were within a reported clinically acceptable range of marginal discrepancy.


Computer assisted axial tomography in cerebrovascular lesions.
Computer assisted axial tomography was performed in 32 patients with clinically possible cerebrovascular lesions. Decreased absorption as a sign of infarction was found in 15, increased absorption as a sign of hemorrhage in 7 cases. In another 7 cases, diagnosed as hemorrhagic infarction, a simultaneous occurrence of increased and decreased absorption appeared. Increased absorption might also depend on compression effect of edema. In three cases no abnormal attenuation could be demonstrated. Infarctions could be observed years after the onset of the symptoms; intracerebral hemorrhages regressed slowly.


Olfactory neurogenesis and its role in fear memory modulation.
Olfaction is a critical sense that allows animals to navigate and understand their environment. In mammals, the critical brain structure to receive and process olfactory information is the olfactory bulb, a structure characterized by a laminated pattern with different types of neurons, some of which project to distant telencephalic structures, like the piriform cortex, the amygdala, and the hippocampal formation. Therefore, the olfactory bulb is the first structure of a complex cognitive network that relates olfaction to different types of memory, including episodic memories. The olfactory bulb continuously adds inhibitory newborn neurons throughout life; these cells locate both in the granule and glomerular layers and integrate into the olfactory circuits, inhibiting projection neurons. However, the roles of these cells modulating olfactory memories are unclear, particularly their role in fear memories. We consider that olfactory neurogenesis might modulate olfactory fear memories by a plastic process occurring in the olfactory bulb.


The Intersection of Type 2 Myocardial Infarction and Heart Failure.
Background Type 2 myocardial infarction (T2MI) is common and associated with high cardiovascular event rates. However, the relationship between T2MI and heart failure (HF) is uncertain. Methods and Results We identified patients with T2MI at a large tertiary hospital between October 2017 and May 2018. Patient characteristics, causes of T2MI, and subsequent HF hospitalizations were determined by physician chart review. We identified 359 patients with T2MI over the study period; 184 patients had a history of HF. Among patients with ejection fraction (EF) assessment (N=180), the majority had preserved EF (N=107; 59.4%), followed by reduced EF (N=54; 30.0%), and mid-range EF (N=19; 10.6%). Acute HF was the most common cause of T2MI (20.9%). Of those whose T2MI was precipitated by HF (N=75), the mean EF was 53.0±16.8% and 16 (21.3%) were de novo diagnoses of HF. Among patients with T2MI who were discharged alive with available follow-up (N=289), 5.5% were hospitalized with acute HF within 30 days, 17.3% within 180 days, and 22.1% within 1 year. In subgroup analyses, among patients with T2MI with prevalent or new HF (N=161), the rate of HF hospitalization at 1 year was 34.2%, considerably higher than those with T2MI and no HF diagnosis at discharge (7.0%; N=9/128). Conclusions Index presentations of HF or worsening chronic HF represent the most common causes of T2MI. ≈1 in 5 patients with T2MI will be readmitted for HF within 1 year of their event. Strategies to prevent HF events after a T2MI are needed.


The use of health foods, spices and other botanicals in the Sikh community in London.
Attitudes and practice concerning complementary and alternative medicine (CAM) are currently an area of considerable interest. However, little is known about the overall importance of such practices, for example, in immigrant communities such as the Sikh (Punjabi) British. The use of CAM in immigrants belonging to the Sikh religion in London was studied. The primary objective was to analyse the extent to which traditional medicine is used and understood by this population. Traditional Sikh medicine is important to this group of informants and a total of 42 species were recorded and identified tentatively. The most frequently mentioned species were Allium cepa (onion -- gunda), Allium sativum (garlic -- lasan, thon), Capsicum frutescens (cayenne pepper -- lalmirch), Cinnamomum verum (cinnamom--dhal chini), Citrus limon (lemon -- nimbu), Foeniculum vulgare (fennel -- saunf), Elettaria cardamomum (cardamom -- elaichi) and Zingiber officinale (ginger -- adrak). The study also highlights the rapid change this tradition is undergoing in a diaspora situation. In depth studies on the use of CAM among other immigrant communities and among ethnic groups are urgent and may help to manage better the treatment of minor ailments as well as chronic diseases. Specifically, more research on traditional and herbal remedies amongst the numerous ethnic groups in urban Britain and how this impacts on the use of biomedicine (e.g. as it is provided by the NHS) is essential.


[Cerebral salt wasting syndrome (CSWS) - rare case from a surgical department].
Cerebral salt wasting syndrome (CSWS) is one of several possible causes of the development of hyponatraemia in patients with severe cranial trauma associated with intracranial bleeding and brain oedema. Other possible causes of post-traumatic hyponatraemia include the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The authors present the case of a twenty-five-year-old polytraumatized female patient who was treated in our department and who was diagnosed with cerebral salt wasting syndrome. In patients with severe cranial trauma and subsequent hyponatraemia, CSWS should be considered. It is crucial to distinguish between CSWS and SIADH as wrongly selected treatment can have serious or even fatal impacts for a gravely injured patient.


Minimally-invasive treatment of three- and four-part fractures of the proximal humerus in elderly patients.
The surgical treatment of three- and four-part fractures of the proximal humerus in osteoporotic bone is difficult and there is no consensus as to which technique leads to the best outcome in elderly patients. Between 1998 and 2004 we treated 76 patients aged over 70 years with three- or four-part fractures by percutaneous reduction and internal fixation using the Humerusblock. A displacement of the tuberosity of > 5 mm and an angulation of > 30 degrees of the head fragment were the indications for surgery. Of the patients 50 (51 fractures) were available for follow-up after a mean of 33.8 months (5.8 to 81). The absolute, age-related and side-related Constant scores were recorded. Of the 51 fractures, 46 (90.2%) healed primarily. Re-displacement of fragments or migration of Kirschner wires was seen in five cases. Necrosis of the humeral head developed in four patients. In three patients a secondary arthroplasty had to be performed, in two because of re-displacement and in one for necrosis of the head. There was one case of deep infection which required a further operation and one of delayed healing. The mean Constant score of the patients with a three-part fracture was 61.2 points (35 to 87) which was 84.9% of the score for the non-injured arm. In four-part fractures it was 49.5 points (18 to 87) or 68.5% of the score for the non-injured arm. The Humerusblock technique can provide a comfortable and mobile shoulder in elderly patients and is a satisfactory alternative to replacement and traditional techniques of internal fixation.


Onychomycosis in Rome, Italy.
This report presents the results of a study conducted between 1985 and 1994 on onychomycosis observed in the city of Rome. Six thousand six hundred and eighty eight patients were examined during this period. Among them 1,762 (26.3%) were affected by fungal nail infections. Because the etiologic agents could not be isolated in 105 cases (6%), the results refer to 1,657 subjects (24.8% of the total), presenting with positive microscopic and cultural examinations. Thirty eight patients (2.3%) had onychomycosis of both their hands and feet. From an etiological point of view, 59.1% of the nail infections were caused by yeasts, 23.2% were infected with dermatophytes and 17.6% by non-dermatophytic fungi. The etiology of onychomycosis of the hands differed from that of the feet. Yeasts were primarily responsible for onychomycosis of the hands (86.2%), while dermatophytes caused tinea unguium peduum (48%). Fungal fingernail infections by Candida spp. were the most common (50.3%), followed by those of the feet by dermatophytes (20%). Candida albicans was responsible for 70.6% of the hand infections but for only 15.9% of those of the feet. Trichophyton rubrum and T mentagrophytes were the most common dermatophytes, mainly causing toenail infections (23.4% and 21%, respectively), while Aspergillus spp., Scopulariopsis brevicaulis, Acremonium spp. and Aspergillus niger were the most common non-dermatophytes observed. With regard to sex, the fungal nail infections were more widespread in women (72.1%) and in subjects of both sexes over the age of 50.


Mask- and distractor-triggered inhibitory processes in the priming of motor responses: an EEG study.
Masked stimuli presented near the threshold of conscious awareness may act as primes, affecting responses to subsequent targets. With arrows as primes and targets, the prime-mask-target sequence has been shown to evoke triphasic lateralized readiness potentials (LRP) with two phases of imbalance between hemispheres preceding the target-related contralateral preponderance of negativity: first a negative, then a positive preponderance contralateral to prime direction. The present article provides evidence that the second wave is related to mask presentation and reflects inhibitory processing independent of reductions in prime visibility, even being evoked by nonmasking distractors that leave the prime fully accessible for consciousness. Of all hypotheses put forward to account for inverse effects in masked priming, this finding is most compatible with the mask-triggered inhibition hypothesis suggested by P. Jaśkowski (2007).


Deception methods in psychology: have they changed in 23 years?
To learn whether criticism and regulation of research practices have been followed by a reduction of deception or use of more acceptable approaches to deception, the contents of all 1969, 1978, 1986, and 1992 issues of the Journal of Personality and Social Psychology were examined. Deception research was coded according to type of (non)informing (e.g., false informing, consent to deception, no informing), possible harmfulness of deception employed (e.g., powerfulness of induction, morality of the behavior induced, privacy of behavior), method of deception (e.g., bogus device or role, false purpose of study, false feedback), and debriefing employed. Use of confederates has been partly replaced by uses of computers. "Consent" with false informing declined after 1969, then rose in 1992. Changes in the topics studied (e.g., attribution, socialization, personality) largely accounted for the decline in deception in 1978 and 1986. More attention needs to be given to ways of respecting subjects' autonomy, to appropriate debriefing and desensitizing, and to selecting the most valid and least objectionable deception methods.


Towards the pharmacotherapy of eating disorders.
The purpose of this review is to discuss pharmacological options for the treatment of patients with eating disorders. Sequentially described are pharmacotherapy studies of anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). The quantity of drug trials performed with AN patients has been very limited. While the majority of studies have failed to show medication efficacy for the acute treatment of AN, there is data which suggests that fluoxetine hydrochloride may play a role in preventing relapse during maintenance therapy. Atypical antipsychotics, most often olanzapine, have shown promise in a number of uncontrolled studies. BN has been most extensively studied, with the majority of pharmacological trials focusing on antidepressants. Fluoxetine, at a dose of 60 mg/day, is FDA-approved for the treatment of BN. Psychotherapy, particularly cognitive behavioural therapy (CBT) is of well-established utility in BN and data suggests that the combination of an antidepressant plus CBT is superior to either treatment alone. Recently, there has been interest in the 5-HT3 antagonist, ondansetron, and the anticonvulsant, topiramate. BED investigators have focused largely on antidepressants, which may reduce symptoms of depression and augment psychotherapy. While sibutramine and topiramate have both been associated with weight loss in controlled trials, the former appears to be fairly well-tolerated and the latter appears to be responsible for the emergence of significant cognitive and peripheral nervous system side effects in some patients. Further pharmacological research with eating disorder patients is needed, particularly in the areas of AN and BED. Also, pharmacological augmentation strategies for those not responding to primary therapies should be explored.


Epidemiology of time-loss injuries in international fencing: a prospective, 5-year analysis of Fédération Internationale d'Escrime competitions.
The study aimed to determine the risk of time-loss injuries in international fencing and to characterise their type, location, severity and mechanism. Variations in risk associated with sex and discipline categories are also examined. Data on participation and withdrawal due to injury from 809 competitions comprising the major events of the 2010-2014 seasons (inclusive) for the Fédération Internationale d'Escrime were compiled from official results. Athletes who withdrew due to injury sustained in each competition were contacted individually to obtain follow-up information including time lost from fencing participation (practice/competition) and sequelae. A total of 176 injuries were recorded from 637 776 athlete exposures (AEs) in 85 686 participants (men=47 869; women=37 817) over the study period, for an overall incidence of 0.28/1000 AEs (95% CI 0.24 to 0.32). Men had significantly greater risk than women (RR=1.42, 95% CI 1.05 to 1.94); épée had a significantly lower risk than foil or sabre (RR=0.52, 95% CI 0.35 to 0.76; RR=0.47, 95% CI 0.32 to 0.69, respectively). The majority of injuries were sprains (40.8%) and strains (20.1%), which occurred in the lower extremities (72.4%); ankle sprains were the most common specific injury (25.3%). Intrinsic effort of the fencer (non-contact injury) was the most common mechanism related to a time-loss injury (47.1% of cases). The overall median time loss was 4 weeks; 32.1% of the injuries involved 2 weeks or less away from fencing participation. The data indicate that the risk of time-loss injury in international fencing is very low and primarily involves sprains and strains in the lower extremity.


Responses evoked by a vestibular implant providing chronic stimulation.
Patients with bilateral vestibular loss experience dehabilitating visual, perceptual, and postural difficulties, and an implantable vestibular prosthesis that could improve these symptoms would be of great benefit to these patients. In previous work, we have shown that a one-dimensional, unilateral canal prosthesis can improve the vestibulooccular reflex (VOR) in canal-plugged squirrel monkeys. In addition to the VOR, the potential effects of a vestibular prosthesis on more complex, highly integrative behaviors, such as the perception of head orientation and posture have remained unclear. We tested a one-dimensional, unilateral prosthesis in a rhesus monkey with bilateral vestibular loss and found that chronic electrical stimulation partially restored the compensatory VOR and also that percepts of head orientation relative to gravity were improved. However, the one-dimensional prosthetic stimulation had no clear effect on postural stability during quiet stance, but sway evoked by head-turns was modestly reduced. These results suggest that not only can the implementation of a vestibular prosthesis provide partial restitution of VOR but may also improve perception and posture in the presence of bilateral vestibular hypofunction (BVH). In this review, we provide an overview of our previous and current work directed towards the eventual clinical implementation of an implantable vestibular prosthesis.


The terminal membrane C5b-9 complex of human complement. Evidence for the existence of multiple protease-resistant polypeptides that form the trans-membrane complement channel.
C5b-9(m) complexes were incorporated into lecithin liposomes and subjected to proteolysis in the presence of DTT to remove the externally oriented annulus. Liposomes were recovered that selectively carried the membrane-bound, thin-walled cylindrical portion of the C5b-9(m) complex. The presence of DTT during proteolysis enhanced peptide bond cleavage in the C5b-9(m) complex. All C5-C9 components were degraded to lower m.w. fragments. A protease-resistant, but hydrophilic 85 to 86,000-dalton polypeptide derivative of C5, possibly representing the C5 beta-chain, was recovered in the fluid phase. This component is not intimately associated with the target lipid bilayer. Immunochemical analyses yielded evidence for the existence of minor C5-C9 antigenic determinants on the membrane-bound C5b-9(m) residue. SDS polyacrylamide gel electrophoreses of liposomes carrying the C5b-9(m) residues revealed the persistence of at least six major polypeptides of approximately m.w. 50,000, 45,000, 40,000, 38,000, 20,000, and 16,000. The data are interpreted to indicate that multiple protease-resistant polypeptide chains derived from several terminal C components participate in formation of the trans-membrane C channel.


A Comparison of Characteristics and Food Insecurity Coping Strategies between International and Domestic Postsecondary Students Using a Food Bank Located on a University Campus.
We compared food insecurity status, coping strategies, demographic characteristics, and self-rated health of international and domestic postsecondary students requesting emergency food hampers from a campus food bank (CFB). We collected data from a cross-sectional convenience sample of domestic and international students who accessed the CFB at the University of Alberta. Food insecurity was prevalent (international students: n = 26/27 (96.2%), domestic students: n = 31/31 (100%)). Compared with their domestic peers, international students were less likely to rate their mental health negatively (14.8% vs 38.7%, P = 0.04). The primary income source was government loans (54.8%) for domestic students and research assistantships (33.3%) for international students. To cope with not having enough money for food, the majority of both student groups delayed bill payments or buying university supplies, applied for loans or bursaries, purchased food on credit, or worked more. International students were less likely to ask friends or relatives for food (48.1% vs 77.4%, P = 0.02). Domestic and international students mostly used similar coping strategies to address food insecurity; however, they paid for their education using different income sources. Distinct strategies for international and domestic students are required to allow more students to cover their educational and living expenses.


Design and Development of Nanostructured Co Delivery of Artemisinin and Chrysin for Targeting hTERT Gene Expression in Breast Cancer Cell Line: Possible Clinical Application in Cancer Treatment.
Breast cancer is one of the most significant causes of female cancer death worldwide. To explore the possibility of a novel chemo-preventive strategy for improving breast cancer treatment, the anticancer effects of two natural compounds, Artemisinin (Art) and Chrysin (Chr), against T47D breast cancer cells were investigated. For this purpose, Art and Chr were co-encapsulated in PEGylated PLGA nanoparticles (NPs) and the synthesized NPs were characterized by FE-SEM, FTIR, and DLS and then, MTT assay was used to assess and compare the cytotoxicity of various concentrations of the chemotheruptic molecules in pure and nanoformulated forms as well as in alone and combination state after 48 h exposure time. Drug release study was performed using the dialysis method. Also, the mRNA levels of hTERT genes expression were studied by quantitative real-time PCR. The results showed that pure and formulations drugs exhibited dose-dependent cytotoxicity against T47D cells and especially, Art/Chr-PLGA/PEG NPs had a more synergistic anti-proliferative effect and significantly arrested the growth of cancer cells than the other groups. Moreover, Real-time PCR results revealed that Art, Chr and combination of Art-Chr in pure and encapsulated forms inhibited hTERT gene expression. It was found that Art/Chr-PLGA/PEG NPs relative to pure combination could further decline hTERT expression in all concentrations. Our study demonstrated that Art/Chr-PLGA/PEG NPs based combinational therapy holds promising potential for the treatment of breast cancer.


Driven by Ambitions: The Nurse Practitioner's Role Transition in Dutch Hospital Care.
Insight into nurse practitioners' (NPs') role transition can help NP students and new graduates in taking on new responsibilities in a changing and demanding healthcare context. The aim of the research was to explore the role transition from nurse to NP using the components of Meleis's Framework of Transitions. A qualitative descriptive design was used. Individual interviews (n = 9) and two focus group discussions (n = 12) were held with NPs. Data were analyzed with the directed content analysis method. The Framework component transitions' nature was characterized by changes in the healthcare system, combined with professional and educational role changes. Transition conditions showed that the respondents felt distressed after they became accountable for a patient's care and well-being. Although the respondents were authorized to do medical procedures, they initially lacked nursing role models and NP protocols. Process indicators showed ongoing transition; the respondents were still developing clinical competencies and confidence in patient care while relying on earlier acquired nursing competencies. Outcome indicators showed that the respondents found themselves successful in the medical extension of two different nursing roles: continuity of medical care for hospitalized patients in acute and intensive care settings, and being responsible for continuity of care for chronic patients in outpatient clinics. Role transition was characterized by coping with feelings of distress at the cost of time and effort. The respondents' strategies to adapt to new expectations, combined with organizational support, determined the outcomes as well as the start of new transitions. NPs' role transition in hospital care implies a dynamic ongoing process that needs to be supported, with the ultimate goal to improve patient outcomes.


Isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells.
Bone marrow mesenchymal stem cells (MSCs) are adult pluripotent cells that are considered to be an important resource for human cell-based therapies. Understanding the clinical potential of MSCs may require their use in preclinical large-animal models, such as pigs. The objectives of the present study were 1) to establish porcine MSC (pMSC) cultures; 2) to optimize in vitro pMSC culture conditions, 3) to investigate whether pMSCs are amenable to genetic manipulation, and 4) to determine pMSC reprogramming potential using somatic cell nuclear transfer (SCNT). The pMSCs isolated from bone marrow grew, attached to plastic with a fibroblast-like morphology, and expressed the mesenchymal surface marker THY1 but not the hematopoietic marker ITGAM. Furthermore, pMSCs underwent lipogenic, chondrogenic, and osteogenic differentiation when exposed to specific inducing conditions. The pMSCs grew well in a variety of media, and proliferative capacity was enhanced by culture under low oxygen atmosphere. Transient transduction of pMSCs and isogenic skin fibroblasts (SFs) with a human adenovirus carrying the gene for green fluorescent protein (GFP; Ad5-F35eGFP) resulted in more pMSCs expressing GFP compared with SFs. Cell lines with stable genetic modifications and extended expression of transgene were obtained when pMSCs were transfected with a plasmid containing the GFP gene. Infection of pMSC and SF cell lines by an adeno-associated virus resulted in approximately 12% transgenic cells, which formed transgenic clonal lines after propagation as single cells. The pMSCs can be expanded in vitro and used as nuclear donors to produce SCNT embryos. Thus, pMSCs are an attractive cell type for large-animal autologous and allogenic cell therapy models and for SCNT transgenesis.


Whole genome analysis unveils genetic diversity and potential virulence determinants in Vibrio parahaemolyticus associated with disease outbreak among cultured Litopenaeus vannamei (Pacific white shrimp) in India.
Vibrio parahaemolyticus has caused widespread mortality in Indian shrimp aquaculture in recent years. However, there are insufficient genome data for the isolates from Indian shrimp vibriosis to analyze genetic diversity and track the acquisition of genetic features that could be involved in virulence and fitness. In this study, we have performed genome analysis of V. parahaemolyticus isolated from moribund shrimps collected from shrimp farms along coastal Karnataka, India, for better understanding of their diversity and virulence. Five newly sequenced genomes of V. parahaemolyticus along with 40 genomes retrieved from NCBI were subjected to comparative genome analysis. The sequenced genomes had an overall genome size of 5.2 Mb. MLST analysis and core genome phylogenomic analysis revealed considerable genetic diversity among the isolates obtained from the moribund shrimps. Interestingly, none of the V. parahaemolyticus isolates possessed the classical features (PirAB) of the strains associated with Acute Hepatopancreatic Necrosis Disease (AHPND). This study also revealed the presence of multiple virulence attributes, including ZOT, ACE and RTX toxins, secretion systems, and mobile genetic elements. The findings of this study provide insights into the possible transition of an environmental V. parahaemolyticus to emerge as pathogens of aquaculture species by increasing its virulence and host adaptation. Future studies focusing on continuous genomic surveillance of V. parahaemolyticus are required to study the evolution and transmission of new variants in shrimp aquaculture, as well as to design and implement biosecurity programs to prevent disease outbreaks.


Neuroanatomical correlates of the Benton Facial Recognition Test and Judgment of Line Orientation Test.
Two of the most successful and widely used tests developed by Arthur Benton and colleagues are the Facial Recognition Test (FRT) and Judgment of Line Orientation Test (JLO), which probe visuoperceptual and visuospatial functions typically associated with right hemisphere structures, especially parietal, occipitoparietal, and occipitotemporal structures. Taking advantage of a large database of focal lesion patients (the Iowa Neurological Patient Registry), we used a new lesion-deficit mapping technique to investigate the neuroanatomical correlates of FRT and JLO performance. For the FRT, there were 201 patients with relevant data; of these, 38 were impaired on the FRT, and failure was most strongly associated with lesions in the right posterior-inferior parietal and right ventral occipitotemporal (fusiform gyrus) areas. For the JLO, there were 181 patients with relevant data; of these, 23 were impaired on the JLO, and failure was most strongly associated with lesions in the right posterior parietal region. These findings put new empirical teeth in the localizing value of the FRT and JLO tests, and they extend and sharpen previous work that had pointed to right posterior structures as being important for FRT and JLO performance


Hearing Loss in the Elderly: Is the Hearing Handicap Inventory for the Elderly - Screening Version Effective in Diagnosis When Compared to the Audiometric Test?
Introduction Hearing losses inherent to the natural process of aging represent today a major public health issue, despite the little attention that their adequate care still receives. Early recognition and proper management of these shortcomings can significantly improve hearing, as well as the patient's general quality of life, reducing the overall impact of this important and prevalent condition of the aging process. Objective The aim of this research was to evaluate the accuracy of the Hearing Handicap Inventory for the Elderly - Screening Version (HHIE-S) in the diagnosis of hearing loss in the elderly when compared with the audiometric test. Methods Through a cross-sectional study, our target population was composed of 138 individuals, aged over 60 and with any otorhinolaryngological complaints, recruited at the Clinic of Otorhinolaryngology and Speech Therapy of the Faculdade de Medicina de Marília (Famema), in the city of Marília, SP, Brazil. Patients already in the process of auditory rehabilitation were excluded, as well as those who did not demonstrate the minimum level of oral understanding necessary to allow the interview. Results The prevalence of hearing loss according to the questionnaire was of 76.1%, while audiometry showed 79.7%. We found the diagnostic accuracy of the instrument to be of 86.2%, with a sensitivity of 89.1% and a specificity of 75.0%, regardless of gender. Conclusion Thereby, we conclude that the standardized questionnaire under rating is suitable for the screening of hearing loss in the elderly, given its high accuracy and user-friendly quality.


Concentration Measurement of Amino Acid in Aqueous Solution by Quantitative 1H NMR Spectroscopy with Internal Standard Method.
We describe a procedure to determine concentrations of amino acid standard solutions by quantitative NMR spectroscopy using an internal standard. The measurement samples were prepared by solvent exchange to remove any intense solvent signal in the 1H NMR spectra. The method was demonstrated on valine aqueous solutions of different concentrations. The accuracy of the measured concentrations that fell well within the range of the expanded uncertainty is also discussed. All of the results are in good agreement with the preparation values. We believe that this approach should be useful to determine the concentrations of standard solutions whose solute components are difficult to weigh because of extremely small amount or hygroscopicity.


TopoICSim: a new semantic similarity measure based on gene ontology.
The Gene Ontology (GO) is a dynamic, controlled vocabulary that describes the cellular function of genes and proteins according to tree major categories: biological process, molecular function and cellular component. It has become widely used in many bioinformatics applications for annotating genes and measuring their semantic similarity, rather than their sequence similarity. Generally speaking, semantic similarity measures involve the GO tree topology, information content of GO terms, or a combination of both. Here we present a new semantic similarity measure called TopoICSim (Topological Information Content Similarity) which uses information on the specific paths between GO terms based on the topology of the GO tree, and the distribution of information content along these paths. The TopoICSim algorithm was evaluated on two human benchmark datasets based on KEGG pathways and Pfam domains grouped as clans, using GO terms from either the biological process or molecular function. The performance of the TopoICSim measure compared favorably to five existing methods. Furthermore, the TopoICSim similarity was also tested on gene/protein sets defined by correlated gene expression, using three human datasets, and showed improved performance compared to two previously published similarity measures. Finally we used an online benchmarking resource which evaluates any similarity measure against a set of 11 similarity measures in three tests, using gene/protein sets based on sequence similarity, Pfam domains, and enzyme classifications. The results for TopoICSim showed improved performance relative to most of the measures included in the benchmarking, and in particular a very robust performance throughout the different tests. The TopoICSim similarity measure provides a competitive method with robust performance for quantification of semantic similarity between genes and proteins based on GO annotations. An R script for TopoICSim is available at http://bigr.medisin.ntnu.no/tools/TopoICSim.R .


Association of Very Early Treatment Initiation With the Risk of Long-term Disability in Patients With a First Demyelinating Event.
Early treatment is associated with better long-term outcomes in patients with a first demyelinating event and early multiple sclerosis (MS). However, magnetic resonance (MR) findings are not usually integrated to construct propensity scores (PSs) when evaluating outcomes. We assessed the association of receiving very early treatment with the risk of long-term disability including an MR score (MRS) in patients with a first demyelinating event. We included 580 patients with a first demyelinating event prospectively collected between 1994 and 2021, who received at least 1 disease-modifying drug (DMD). Patients were classified into tertiles according to the cohort's distribution of the time from the first demyelinating event to the first DMD: first tertile (FT) or very early treatment (6 months; n = 194), second tertile (6.1-16 months, n = 192), and third tertile (TT) (16.1 months, n = 194). A 5-point MRS was built according to the sum of the following indicators: ≥9 brain lesions (1 point); ≥1 infratentorial lesion (1 point); ≥1 spinal cord (SC) lesion (1 point); ≥1 contrast-enhancing (CE) brain lesion (1 point); and ≥1 CE SC lesion (1 point). PS based on covariates and the MRS was computed for each of the outcomes. Inverse PS-weighted Cox and linear regression models assessed the risk of different outcomes between tertile groups. Finally, to confirm the role of MR in treatment decision, we studied the time elapsed from the first demyelinating event to treatment initiation according to the MRS in all patients with radiologic available information, renamed as raw-MRS. Very early treatment decreased the risk of reaching Expanded Disability Status Scale 3.0 (hazard ratio [HR] 0.55, 95% CI 0.32-0.97), secondary progressive MS (HR 0.40, 95% CI 0.19-0.85), and sustained disease progression at 12 months after treatment initiation (HR 0.50, 95% CI 0.29-0.84), when compared with patients from the TT group. Patients from the FT group had a lower disability progression rate (β estimate -0.009, 95% CI -0.016 to -0.002) and a lower severe disability measured by the Patient-Determined Disease Step (β estimate -0.52, 95% CI -0.91 to -0.13) than the TT group. Finally, there was a 62.4% reduction in the median time between the first demyelinating event and the first-ever treatment initiation from patients displaying a raw-MRS 1 to patients with a raw-MRS 5. Using PS models with and without MRS, we showed that treatment initiation at very early stages is associated with a reduction in the risk of long-term disability accrual in patients with a first demyelinating event. This study provides Class III evidence that earlier treatment of patients with MS presenting with a first demyelinating event is associated with improved clinical outcomes.


The prognosis of severe lupus nephritis based on the Modification of Diet in Renal Disease (MDRD) study estimated glomerular filtration rate.
The level of renal function at biopsy is predictive of outcome in patients with severe lupus nephritis (SLN). While renal function has been based on serum creatinine (SCr) alone, measuring the estimated glomerular filtration rate (eGFR) utilizing the Modification of Diet in Renal Disease (MDRD) Study equation has been found to be more accurate. The MDRD eGFR (ml/min/1.73 m(2)) at biopsy was calculated in 86 patients with SLN and patients were categorized based on eGFR: ≥60 (33 pts), 59-30 (33 pts) and <30 (20 pts). An eGFR was <60 in 18% of patients with a normal SCr. After 120 ± 65 months of follow-up, attainment of a complete remission (76% versus 30% versus 10%, p < 0.0001) and patient survival without end-stage renal disease (ESRD; 10 year survival: 85% versus 45% versus 14%, p < 0.0001 overall) was highest in patients with an eGFR ≥60 and lowest in those with an eGFR <30. The long-term prognosis for patients with severe lupus nephritis and an eGFR ≥60 was extremely good. Since the prognosis for patients with an eGFR <60 was poor even in those patients with a normal SCr, renal function is more accurately determined by the MDRD eGFR.


The kallikrein-kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity.
The therapeutic use of angiotensin converting enzyme (ACE) inhibitors, at a large scale, in arterial hypertension has showed that these molecules can exert beneficial effects on insulin sensitivity and may reduce the occurrence of type 2 diabetes mellitus. One hypothesis explaining these effects of ACE inhibitors may relate to their capacity to interfere with bradykinin (BK) metabolism and action. BK may participate in the regulation of substrate utilization by several tissues by improving blood flow and substrate delivery to the tissues and also by promoting translocation of glucose transporters. Moreover, BK has been shown to increase phosphorylation of insulin receptor and its cell substrates. BK also appears to improve the release of insulin. Furthermore, insulin may activate the kallikrein-kinin system, which consequently may increase its metabolic effects. However, in experimental diabetes mellitus, BK can participate to the inflammatory reaction leading to Langerhans islets destruction. In diabetes, whereas tissue kallikrein mRNA levels were reduced in several organs, an overexpression of kinin receptors, an increase in plasma levels of kininogens and kallikrein and an activation of the kinin system have all been reported. Lastly, kinins may be involved in the development of diabetic nephropathy. Reduction of kinin metabolism by ACE inhibitors might be involved in the beneficial effects exerted by these compounds in diabetic kidney functions.


Sequential cyclic changes of hair roots revealed by dermoscopy demonstrate a progressive mechanism of diffuse alopecia areata over time.
Diffuse alopecia areata (DAA) often leads to a complete hair shedding within a few months. To explore features and mechanisms underlying DAA. Scalp and hair root dermoscopy were conducted on 23 DAA patients throughout the disease process, 20 patchy Alopecia areata patients, 23 acute telogen effluvium (ATE) patients and 10 normal controls. Histopathology was also evaluated. We found almost all hair roots were anagen in early stage DAA in 18 patients (18/23, 78.3%) within the first 4-8 weeks after hair loss onset. Anagen effluvium (~4 weeks) was followed by catagen (~4 weeks) and then telogen/exogen (~8 weeks) effluvium with overlap. Hair root and proximal hair shaft depigmentation was more prominent in later DAA disease stages. Black dots, exclamation mark hairs and inconsistent thickness of hair shafts were found more often in early than later DAA (Ps < 0.01). Early DAA histopathology revealed more prominent inflammation and hair follicle regression than that observed in the later stages. Patchy alopecia areata patients showed mixed anagen, catagen and telogen hair roots while ATE patients showed increased exogen and mildly decreased hair root pigmentation. Sequential cyclic staging of shed hairs in DAA indicates the insult may be hair-cycle specific. We suggest that DAA is initially an anagen effluvium disease involving an intense inflammatory insult, later progressing to a brief catagen effluvium, and then to telogen effluvium with premature exogen, in later stages of DAA.


Pulmonary embolism following 2-octyl-cyanoacrylate/lipiodol injection for obliteration of gastric varices: an imaging perspective.
Bleeding from esophageal and gastric varices remains a significant cause of morbidity and mortality for patients with liver cirrhosis. Currently, therapeutic strategies for gastric variceal bleeding include transjugular intrahepatic portosystemic shunt, cyanoacrylate sclerotherapy and hepatic transplantation. Though relatively safe and efficacious, endoscopic sclerotherapy using cyanoacrylate has known complications including infection, bleeding, and distal embolization. This case report describes a patient who became febrile and tachycardic following sclerotherapy and subsequently had an abnormal chest radiograph that prompted further evaluation for pulmonary embolization of the sclerosant. The focuses of this report are the computed tomographic and radiographic findings associated with 2-octyl-cyanoacrylate/lipiodol pulmonary embolization.


Radiation effects in the rat spinal cord: evaluation with apparent diffusion coefficient versus T2 at serial MR imaging.
To prospectively determine whether apparent diffusion coefficients (ADCs) are more sensitive to radiation-induced changes in the rat spinal cord than T2 relaxation times. The study was approved by the institutional ethical committee on animal welfare. One centimeter of the thoracolumbar spinal cord of six rats was irradiated with 36 Gy. For 3-6 months after irradiation, five 7.0-T magnetic resonance (MR) imaging measurements were performed in each rat until motor impairment developed. Six age-matched rats were examined as controls. Measurements were performed by using diffusion-weighted imaging with five b values and a spin-echo sequence with 20 echoes. ADC and T2 values were calculated, and the spatiotemporal evolution of the radiation-induced lesions was determined semiautomatically. The final MR measurements were compared with the histologic findings. Shortly before the neurologic signs appeared, the first radiation effects manifested as well-circumscribed white matter (WM) lesions with a low longitudinal ADC and normal or high T2. WM lesions with high T2 correlated with confluent necrosis at histologic analysis, whereas WM lesions with normal T2 correlated with focal necrosis and demyelination. In the gray matter (GM), lesions with diffusely high T2 were present and were attributed to edema. T2 changes in the GM preceded T2 and ADC changes in the WM. In the WM, longitudinal ADC was more sensitive for the detection of radiation damage than T2, but in the GM, T2 was more sensitive.


Cytotoxicity and DNA binding characteristics of dextran-conjugated doxorubicins.
The antitumor antibiotic doxorubicin was conjugated with polymeric dextrans of various molecular weights and the cytotoxicity of the conjugates against human carcinoma KB-3-1 cells and its multidrug-resistant subclone KB-V-1 cells was measured by tetrazolium salt MTT assay. The conjugates were much less toxic to the KB-3-1 cells than the free doxorubicin but exhibited similar toxicity to the KB-V-1 cells. The conjugate-DNA interactions were monitored in real-time using an optical biosensor based on evanescent wave detection to obtain the association (ka) and dissociation (kd) rate constants as well as the equilibrium binding constants (KA) of the bindings. Both ka and kd values for the conjugates are more than three magnitudes smaller than those for free doxorubicin, while the KA values of the conjugate-DNA complexes are only about 10 times smaller than that of the free doxorubicin-DNA complex. The results indicate that the cytotoxicity and the DNA-binding kinetics of doxorubicin may be modified with dextran conjugation. The KA values obtained from the biosensor measurements were in close agreement with those determined in solution by fluorescent titration method, verifying the utility of the label-free biosensing measurements as an efficient method for studying ligand-DNA interactions.


Lysophosphatidyl choline and cataracts in uveitis.
In aqueous humor from rabbits with uveitis or after anterior chamber paracentesis, the levels of lysophosphatidyl choline (LPC) were 10.2mug/ml and 14.7mug/ml, respectively. These LPC levels induce early cataractous changes in the rabbit lens in culture. Analysis of the fatty acid composition of LPC showed that saturated fatty acids were more predominant in secondary aqueous humor than in primary aqueous humor. In vitro, natural LPC induced more pronounced gains in sodium ions and water by the lens than similar concentrations of synthetic L-alpha-lysopalmitoyl phosphatidyl choline. In contrast to prostaglandin E, the levels of LPC in aqueous humor of rabbits with uveitis are cataractogenic. Thus, LPC or its precursors, rather than prostaglandins, are involved in the production of cataracts in uveitis.


Sebaceous carcinoma of the right arm.
Sebaceous carcinoma is an uncommon cutaneous neoplasm that is often misdiagnosed as a benign lesion, but has an aggressive clinical behavior, including a rate of distant metastasis of up to 60%. In this paper, we describe a case of sebaceous carcinoma in the right arm of a 67-year-old woman. The relevant histopathology and appropriate diagnostic and treatment approach is discussed.


Upper gastrointestinal endoscopy in emergency setting for patients receiving oral anticoagulants - practice updates.
Anticoagulants are frequently used medications in diverse cardiovascular diseases. Their uses highly increase the risk of bleeding from upper and lower gastrointestinal sources, whether there is a classic vitamin K antagonist or a novel oral anticoagulant. Their interruption can promote procoagulation status with different thromboembolic accidents. Discontinuation of oral anticoagulants before the elective procedures is standardized but there are no guidelines for managing bleeding lesions of upper gastrointestinal tract concomitant with anticoagulation. Also, because some of the anticoagulants are new comers, there is no specific antidote, and so their anticoagulation effect cannot be antagonized fast in order to reduce the bleeding. Therefore, the endoscopic hemostasis must be definitive and efficient. This is a short review of the current management for the bleeding lesions of the upper gastrointestinal tract in patients taking oral anticoagulants.


Comparative analysis of therapeutically important indole compounds in in vitro cultures of Hypericum perforatum cultivars by HPLC and TLC analysis coupled with densitometric detection.
Five indole compounds (5-hydroxy-L-tryptophan, L-tryptophan, indole-3-acetic acid, melatonin, serotonin) and hypericin were identified and quantified in methanolic extracts of shoot cultures of three Hypericum perforatum cultivars (Helos, Elixir, Topas) growing on two variants of Murashige -Skoog medium differing in concentrations of growth regulators (naphthalene-l-acetic acid and 6-benzylaminopurine). Extracts of the aboveground parts of field-grown plants (Hyperici herba) were also analyzed by HPLC and TLC analysis coupled with densitometric detection. Determination of four compounds was based on our assay described earlier. The methods of determination of 5-hydroxy-L-tryptophan and hypericin were developed and validated in this study. The composition and contents of the metabolites under study differed between the cultivars cultured in vitro and between medium variants containing diverse contents of growth regulators. The contents of individual indole compounds in the biomass from in vitro cultures ranged from 39.6 to 343.2 mg/100 g dry mass. 5-Hydroxy-L- tryptophan was the dominating metabolite (from 78.2 to 343.2 mg/100 g dry mass). Extracts from shoots of the cultivar Helos also contained high contents of serotonin (319.9 and 197.4 mg/100 g dry mass). The contents of indole compounds in Hyperici herba were also diverse (from 7.1 to 55.3 mg/100 g dry mass). 5-Hydroxy-L-tryptophan was the dominating metabolite as well. Hypericin content ofHyperici herba, equaling 12.2 mg/100 g dry mass was from 3.3 to 10 times higher than in extracts from shoots cultured in vitro. The present report is the first analysis of endogenous accumulation of indole compounds in Hyperici herba which involves, apart from melatonin, four other compounds.


Hepatitis A outbreak associated with kava drinking.
Hepatitis A is caused by the hepatitis A virus (HAV), with transmission occurring through the faecal-oral route. In May 2013, a case of hepatitis A infection was reported to a Western Australian regional public health unit, with infection acquired in Fiji. Following this, 2 further cases were linked to the index case by kava drinking and 1 further case was a household contact of a secondary case. This outbreak highlights that the preparation of kava drink and/or the use of a common drinking vessel could be a vehicle for the transmission of HAV.


[Clinical treatment of infective endocarditis with vegetations in pregnant women and the outcomes of gestation].
To investigate the clinical treatment of infective endocarditis with vegetations in pregnant women and the outcomes of the gestation. Nine cases of pregnant women diagnosed as infective endocarditis with vegetations in Beijing Anzhen Hospital, Capital Medical University from January 2001 to October 2015 were enrolled in retrospective analysis. Consultations were held by doctors from department of obstetrics, anesthesiology, cardiology, cardial surgery and extracorporeal circulation to decide the individualized treatment plan for the 9 cases of pregnant women after admissions. Clinical treatments including general treatment, anti-infection treatment, cardiac surgery, and termination of pregnancy surgery were completed through collaboration among related departments. The clinical characters, therapeutic regimens, maternal and neonatal outcomes of the 9 cases were analyzed. (1) Clinical characters: the ages of the 9 cases of pregnant women were from 25 to 36 years old. The onset gestational ages were from 19 to 36 weeks. fever, cough, sputum and progressive anemia were the main symptoms. Patients had cyanosis of lips, could not lie on the back or even be orthopnea, when heart failure happened. Heart murmur was audible and splenomegaly was touched in physical examination. Blood cultures were positive. Basic heart disease types: 7 cases of congenital heart diseases included 2 cases of aortic insufficiency, 1 case of mitral insufficiency, 1 case of patent ductus arteriosus, 1 case of right ventricular outflow tract stenosis and 2 cases of ventricular septal defect.Two cases of rheumatic heart diseases included 1 case of mitral stenosis, 1 case of mitral stenosis after artificial disc changed and jammed. According to endocardial vegetations attached position there were 3 cases of mitral valve vegetations, 2 cases of pulmonary valve vegetations, 3 cases of aortic vegetations and 1 case of right ventricular outflow tract neoplasm. Preoperative heart function classification: 1 case of level Ⅱ, 3 cases of level Ⅲ, 5 cases of level Ⅳ. (2) TREATMENTS: general treatment included oxygen uptake, rest in bed, cardiac strengthen and diuretic therapy, etc. Combined and adequate antibiotics were applied in anti-infection treatment according to drug sensitive test. Nine cases of pregnant women were all performed surgical treatment of heart diseases and removal of the endocardial vegetations. Caesarean sections were performed for 2 cases in second trimester and for 7 cases in last trimester. Cardiac surgery and caesarean section were operated in 6 cases at the same time among 22-34 weeks of pregnancy. Cardiac surgery were respectively operated in 2 cases 11 days and 32 days after the caesarean section at 33, 37 weeks of pregnancy. While Cardiac surgery was operated (at 26 weeks of pregnancy) before the caesarean section (at 37 weeks of pregnancy) in another 1 case. (3) Maternal and neonatal outcomes: 7 cases of pregnant women were rescued successfully, while 2 cases of pregnant women were death. Postoperative heart function classification: 1 case of level Ⅰ, 2 cases of level Ⅱ, 4 cases of level Ⅲ and 2 cases of level Ⅵ. Neonatal survivals were 6 cases including 2case of full-term infants, 4 cases of preterm infants. Stillbirth or neonatal death were 3 cases, which included 2 cases performed caesarean section in second trimester and 1 case of very low weight infant who was given up treatment by family because of severe asphyxia. Followed up periods were from 1 to 7 years with an average time of (2.0±1.6) years. Infants and young children grew and developed well during the period of follow up. The risk is extremely high of pregnancy with infective endocarditis with vegetations. But there is still a way to save the maternal and neonatal life by using a multidisciplinary collaboration formulation and implementation of individualized treatment plan and selecting the appropriate time for heart surgery and the termination of pregnancy.


Hematopoietic stem and progenitor cell responses to low radiation doses - implications for leukemia risk.
Studies of the responses of hematopoietic stem and progenitor cells (HSPCs) to low doses of ionizing radiation formed an important aspect of the RISK-IR project ( www.risk-ir.eu ). A brief overview of these studies is presented here. The findings confirm the sensitivity of HSPCs to radiation even at low doses, and illustrate the substantial impact that differentiation state has upon cell sensitivity. The work provides mechanistic support for epidemiological findings of leukemia risk at dose levels used in diagnostic CT imaging, and further suggests that low-dose irradiation may facilitate bone marrow transplantation, a finding that could lead to refinements in clinical practice.


[Effects of injecting adenosine A1 receptor agonist into baihui (GV20) on the cerebral cortex in ischemia/reperfusion injury model rats].
To investigate the effects of injecting adenosine A1 receptor agonist (CCPA) into Baihui (GV20) on the cerebral cortex induced by the ischemia/reperfusion of middle cerebral artery occlusion (MCAO) in rats. Twenty-four SD rats were randomly divided into four groups, i. e., the sham-operation group, the model group, the DMSO group, and the CCPA group. The MCAO model was established by thread embolism method. At the moment of ischemia/reperfusion, the rats in DMSO group and the CCPA group were injected with DMSO (20 microL) and CCPA (0.1 mmol) 20 microL into Baihui respectively. The rats' behavior, the histomorphology of ischemic penumbra in the cerebral cortex, the expressions of Bcl-2 protein, and the apoptosis rate of neurocytes were assessed. Compared with the model group and the DMSO group, the rats' behavior were markedly improved in the CCPA group (P<0.05). No obvious karyopyknosis and cytoplasm empty dye of neurons appeared. The Bcl-2 expressions in rats' cerebral cortex obviously increased (P<0.01). The apoptosis number of neurons obviously decreased (P<0.01). Injecting CCPA into Bahui improved the rats' behavior and histomorphology in the ischemic penumbra, elevated the expressions of Bcl-2 protein, and reduced the neurons apoptosis rate in the ischemic penumbra. It alleviated the cerebral ischemia-reperfusion injury. Therefore, it could be taken as a new treatment method.


[Psychological support of cancer patients in the oncological consultation].
Due to its life threatening character, a cancer diagnosis represents an existential rupture, disturbing an individual's life trajectory perceived beforehand as a continuum. As a consequence, a patient's physical, psychological, social and spiritual equilibrium may be disturbed, calling for a support by clinicians, which surpasses biomedical treatment. A key element of support relies on patient-centered communication, which not only demands technical skills, but also a reflective approach on interpersonal factors which shape the relationship, on the choice and the idealized representation of the clinician's profession as well as its limits. This article summarizes main aspects of patient-physician communication and our experience as teachers of the so-called Communication Skills Training. It provides a review on research in progress in this field and finally indicates other elements of support, which contribute to the << narrative reconstruction >> of the patient facing the rupture induced by cancer.


Nasopharyngeal carcinoma in children.
Ten children with lymphoepithelioma of the nasopharynx were reviewed. Six had regional spread at presentation and four developed distant metastases. Seven patients are alive, six free of disease. The 5-year survival rate was 62.5% of this series. Five patients presented later with endocrine abnormalities probably related to the radiotherapy; these endocrine problems were minimal and responded to therapy.


Maturation of collagen Ketoimine cross-links by an alternative mechanism to pyridinoline formation in cartilage.
The tensile strength of fibrillar collagens depends on stable intermolecular cross-links formed through the lysyl oxidase mechanism. Such cross-links based on hydroxylysine aldehydes are particularly important in cartilage, bone, and other skeletal tissues. In adult cartilages, the mature cross-linking structures are trivalent pyridinolines, which form spontaneously from the initial divalent ketoimines. We examined whether this was the complete story or whether other ketoimine maturation products also form, as the latter are known to disappear almost completely from mature tissues. Denatured, insoluble, bovine articular cartilage collagen was digested with trypsin, and cross-linked peptides were isolated by copper chelation chromatography, which selects for their histidine-containing sequence motifs. The results showed that in addition to the naturally fluorescent pyridinoline peptides, a second set of cross-linked peptides was recoverable at a high yield from mature articular cartilage. Sequencing and mass spectral analysis identified their origin from the same molecular sites as the initial ketoimine cross-links, but the latter peptides did not fluoresce and were nonreducible with NaBH(4). On the basis of their mass spectra, they were identical to their precursor ketoimine cross-linked peptides, but the cross-linking residue had an M+188 adduct. Considering the properties of an analogous adduct of identical added mass on a glycated lysine-containing peptide from type II collagen, we predicted that similar dihydroxyimidazolidine structures would form from their ketoimine groups by spontaneous oxidation and free arginine addition. We proposed the trivial name arginoline for the ketoimine cross-link derivative. Mature bovine articular cartilage contains about equimolar amounts of arginoline and hydroxylysyl pyridinoline based on peptide yields.


Suggested revision of NEMA standards.
The purpose of the NEMA Standards is to "eliminate misunderstandings between the manufacturer and the purchaser and to assist the purchaser in selecting the proper product for its particular need" (NEMA Bylaw Art. V, Sec. 1). The sections on count-rate performance, however, have caused considerable misunderstanding of NEMA specifications by salespersons and users, many of whom fail to distinguish between input and observed count rates and between intrinsic and system (extrinsic) performance. The "maximum count rate" is shown to be an unreliable index of camera performance at useful count rates, and is misconstrued by some users to mean the maximum clinically useful count rate. The sections on count-rate performance can be made more meaningful to users by substituting "observed count rate" for "input count rate," by deleting the section on "maximum count rate," and by adding a section on system count-rate performance.


Chronic episodic diarrhoea associated with apparent intestinal colonisation by the yeasts Saccharomyces cerevisiae and Candida famata in a German shepherd dog.
A 3-year-old German shepherd dog was presented with a history of lifelong episodic diarrhoea. An adverse reaction to food was considered the most likely cause of the diarrhoea. The dog had received prolonged antibiotic therapy for most of its life as well as receiving probiotics containing the yeast Saccharomyces cerevisiae (syn. S. boulardi) for a year before referral. The probiotic was discontinued 2 months before to referral. Examination and culture of faecal samples identified yeast-like organisms, S. cerevisiae and Candida famata. S. cerevisiae has been isolated from humans in association with predisposing conditions such as prolonged sojourns in hospital, immunosuppression, broad-spectrum antibiotic therapy and prosthetic devices, but is regarded as non-pathogenic in humans and is rarely associated with disease in animals. C. famata has been isolated from animals, humans and the environment, but is regarded as a very rare pathogen. No evidence of immunosuppression was found in the dog. The presence of yeasts in the faecal isolates and the history of prolonged use of antibiotics and probiotics with a concurrent adverse reaction to food, suggest that conditions may have occurred within the bowel that made it possible for the yeasts to colonise parts of it. This has apparently not been reported before.


A preliminary study on the functional analysis of peripheral blood lymphocytes from ovarian cancer patients developing HAMA after immunoscintigraphy.
In the follow-up of ovarian cancer patients, rising levels of the tumor-associated antigen CA 125 are an indication for immunoscintigraphy. Human anti-mouse antibodies (HAMA) are frequently found after immunoscintigraphy with murine MAb directed against CA 125. Since we observed that patients developing high HAMA-levels in serum remained free of tumor or had stable disease, we examined the cytotoxic activity of peripheral blood lymphocytes (PBL) by a fluorescence-based assay. Our results demonstrate that PBLs of patients with high anti-idiotypic antibodies show an increased cytotoxic activity (by a factor of 4) compared to those of patients with low HAMA levels. The clinical course of the patients after the first injection of murine monoclonal antibody was observed over a period of 1 to 3 years. Improvement or deterioration of patients' clinical condition corresponded with the results obtained by functional analysis. Further investigations concerning the course of cytotoxic activity in HAMA-positive patients will have to clarify HAMA's role in the immune response.


The Tub alpha 3 gene from Zea mays: structure and expression in dividing plant tissues.
A gene (Tub alpha 3) coding for an alpha-Tub, expressed in dividing tissues, has been cloned from Zea mays. The deduced amino acid (aa) sequence, 450 aa long, is very similar to the other plant alpha-Tub (85-89% homology) so far reported, and in particular to the other two aa sequences (alpha 1-Tub and alpha 2-Tub) already published from the same species (93% homology). The genomic structure is also very similar, having three introns located at the same positions as in the Tub alpha 1 and Tub alpha 2 genes, one of them placed at the same position in the homologous genes from Arabidopsis thaliana. Nevertheless, the noncoding sequences are very different from the two other maize genomic sequences. In particular, no homology has been found either in the 5' upstream or in the 3'-untranslated sequences. Using specific 3' probes, it has been possible to detect the mRNA coded by this gene in many of the plant organs measured, but its highest abundance is observed in the organs rich in dividing cells, a pattern correlated with that of the histone H4-encoding gene. A cDNA clone has been identified in maize coleoptiles and sequenced, confirming the expression of the Tub alpha 3 in this organ. No preferential accumulation in any organ of the plant was found, in contrast with what was observed in the Tub alpha 1 and Tub alpha 2 genes already described. The Tub alpha gene family seems to consist in maize by at least two groups of homologous sequences, each one including a maximum of two or three coding units.


An F41-K88-related genetic determinant of bovine septicemic Escherichia coli mediates expression of CS31A fimbriae and adherence to epithelial cells.
A genetic determinant related to that encoding the F41 fimbrial adhesin was cloned from a bovine septicemic isolate of Escherichia coli. This determinant was found to mediate expression of morphologically distinct fimbriae in E. coli HB101. The gene encoding the fimbrial subunit protein was identified, and the nucleotide sequence was determined. Homology with the amino-terminal amino acid sequence of CS31A (J. Girardeau, M. Der Vartanian, J. Ollier, and M. Contrepois, Infect. Immun. 56:2180-2188, 1988) was observed, suggesting that this determinant encodes expression of the CS31A fimbrial antigen. The CS31A subunit gene was found to share extensive homology in its signal sequence to the subunit genes encoding the F41 and K88 adhesins. No apparent homology between the mature F41 and CS31A subunits was identified. However, substantial relatedness to the K88 fimbrial subunit was observed. Analysis of the protein products encoded by the CS31A, F41, and K88 determinants in maxicells established that despite extensive genetic similarities between the determinants, each encodes a distinct profile of proteins. E. coli HB101 harboring the cloned CS31A determinant was found to adhere to epithelial cells in a tissue culture assay, suggesting a role for CS31A in adherence. A CS31A-specific DNA hybridization probe detected homologous sequences among enterotoxigenic as well as septicemic E. coli isolates from calves.


Cystatin C: A Promising Marker of Renal Function in Patients with Systemic Lupus Erythematosus?
Cystatin C has a higher correlation with glomerular filtration rate and a more significant clinical prognosis than creatinine. We sought to determine whether it is a marker of renal function different from creatinine (cystatin C potentially superior to creatinine), in patients with systemic lupus erythematosus. 37 patients with systemic lupus erythematosus were evaluated. Serum cystatin C was determined by nephelometry and creatinine by modified Jaffe method. We compared five formulas: Chronic Kidney Disease â Epidemiology Collaboration cystiatin; Chronic Kidney Disease â Epidemiology Collaboration creatinine-cystatin; Cockcroft-Gault; Modification of Diet in Renal Disease and Chronic Kidney Disease â Epidemiology Collaboration creatinine, using the latter as a reference. We analyzed the influence of clinical and laboratory factors in cystatin C variation, using multivariate linear regression. Cystatin C was singly elevated in ten participants, versus none isolated creatinine elevation, and this difference was significant (p = 0.002). There was a difference between the estimated glomerular filtration rate by Chronic Kidney Disease â Epidemiology Collaboration cystatin and by Chronic Kidney Disease â Epidemiology Collaboration creatinine (-6.0541 mL/min/1.73 m², p = 0.07), more pronounced for lower glomerular filtration rate. Consequently, Chronic Kidney Disease â Epidemiology Collaboration cystatin reclassified 4 patients as having chronic kidney disease de novo and 1 patient as not having chronic kidney disease (p = 0.375). Cystatin C was only significantly influenced by age (p < 0.001). Several reports showed cystatin C as a better marker to define chronic kidney disease, allowing more accurate classification and risk stratification, compared with creatinine. In this study, Cystatin C revealed as a promisor marker of renal function in patient with lupus, mainly in patients with lower glomerular filtration rates. The correlation between age and cystatin C seems to be a confounding factor, as glomerular filtration rate physiologically declines with ageing. Cystatin C was potentially superior to creatinine and in this study and cystatin C seems to detect changes in glomerular filtration rate earlier than creatinine and may be a better screening method for chronic kidney disease in systemic lupus erythematosus.


The prognostic value of immunohistochemical estrogen receptor analysis in paraffin-embedded and frozen sections versus that of steroid-binding assays.
Estrogen receptors (ER) were independently analyzed using dextran-coated charcoal assays (ER-DCC) and immunohistochemical assays in frozen (ER-ICA) and paraffin-embedded tissue (ER-PAR) from 130 human breast cancer specimens drawn from postmenopausal high-risk patients registered in the Danish Breast Cancer Cooperative Group. ER was best detected with the ER-DCC assay followed by the ER-ICA (relative sensitivity 87%) and the ER-PAR assays (relative sensitivity 71%). The semiquantified staining features of the immunohistochemical assays were statistically significantly correlated with each other and with ER-DCC. Analysis of disease-free interval (DFI) and overall survival (OS) showed that all assays allowed statistically significant discrimination between a high risk and a low risk group, although the sensitivity differences tended to be reflected as small differences in clinical discriminatory power. The patient groups were then stratified according to adjuvant treatment [radiotherapy (RT) versus radiotherapy and tamoxifen (RT + TAM)]. The survival advantage was tied primarily to the receptor status itself in the steroid-binding assays, but was linked to both the receptor status and the adjuvant treatment in the immunohistochemical assays. Thus, the relative risks in terms of DFI and OS were of the same relative magnitude in the RT and RT + TAM groups for ER-DCC assays using a cut-off level of 10 fmol/mg cytosol protein, while there were large differences in the relative risks between RT and RT + TAM groups for ER-ICA and ER-PAR assays. We conclude that an ER assay in fresh tissue should be given first priority, but if there is no fresh tissue, an ER assay in paraffin-embedded tissue offers a reasonably good alternative as a prognosticator and an equivalent alternative as a predictor of the response to endocrine treatment.


Post-operative nausea and vomiting (PONV) after thyroid surgery: a prospective, randomized study comparing totally intravenous versus inhalational anesthetics.
The incidence of postoperative nausea and vomiting (PONV) after thyroidectomy and the association of Propofol versus Sevoflurane use for anesthesia maintenance were investigated during a randomized, prospective study. One hundred and ninety-eight patients underwent thyroidectomy receiving either Sevoflurane (0.5-1.3% end-tidal) or Propofol (50-200 mg/kg/min) for anesthesia maintenance. All patients received Propofol for induction of anesthesia, Succinylcholine or Vecuronium, Nitrous Oxide, and Fentanyl. Prophylactic antiemetics were not administered. The combined incidence of PONV was 54.4 per cent over the 24-hour postoperative evaluation period. PONV was more common in patients receiving Sevoflurane than Propofol for maintenance of anesthesia (64.6% vs 43.8%). In women (n = 117), the incidence of PONV resulted higher when receiving inhalational Sevoflurane than Propofol for maintenance (70.6% vs 42.4%). However, in men (n = 81), there was no significant difference in PONV between anesthetic regimens (47.4% with Sevoflurane vs 49.6% with Propofol). Patients undergoing thyroid surgery are at high risk for the development of PONV. Propofol for maintenance of anesthesia, although more expensive than Sevoflurane, may reduce the rate of PONV.


Osteopontin--a possible anchor of osteoclasts to bone.
A key event in bone resorption is the binding of osteoclasts to the mineral matrix of bone surfaces. A candidate for mediating this binding is osteopontin, a major cell- and hydroxyapatite-binding protein synthesized by osteoblasts. In support of this hypothesis is the fact that the synthesis of osteopontin is stimulated by calcitriol (1,25-dihydroxy-vitamin(D3), a substance that induces bone resorption. The present study demonstrates that osteopontin is highly enriched at regions of the bone surface where osteoclasts are anchored. Furthermore, the vitronectin receptor, which has known specificity for osteopontin, is shown preferentially localized at the corresponding area of the osteoclast plasma membrane. The results thus support the hypothesis that osteoclasts when resorbing bone are anchored by osteopontin bound both to the mineral of bone matrix and to a vitronectin receptor on the osteoclast plasma membrane.


SheddomeDB 2023: A Revision of an Ectodomain Shedding Database Based on a Comprehensive Literature Review and Online Resources.
Ectodomain shedding of membrane proteins is a proteolytic event involved in several biological phenomena, including inflammation, development, diseases, and cancer progression. Though ectodomain shedding is a post-translational modification that plays an important role in cellular regulation, this biological phenomenon is seriously underannotated in public protein databases. Given the importance of the shedding events, we conducted a comprehensive literature review for membrane protein shedding and constructed the database, SheddomeDB in 2017. In response to user feedback, novel shedding findings, more associated biomedical events, and the advance in web technology, we revised SheddomeDB to a new version, SheddomeDB 2023. The revised SheddomeDB 2023 includes 481 protein entries across seven species; all the content was manually verified and curated. The content of SheddomeDB 2023 mainly came from a comprehensive literature survey by our newly developed semiautomated screening tool. We also integrated verified and updated cleavage and secretome information from other databases into the revision. In addition, SheddomeDB 2023 features a graphical presentation of cleavage information and a user-friendly interface for searching and browsing entries in the database. This revised comprehensive database of ectodomain shedding is expected to benefit biomedical researchers across different disciplines.


Structure, dynamics, and regulation of TRF1-TIN2-mediated trans- and cis-interactions on telomeric DNA.
TIN2 is a core component of the shelterin complex linking double-stranded telomeric DNA-binding proteins (TRF1 and TRF2) and single-strand overhang-binding proteins (TPP1-POT1). In vivo, the large majority of TRF1 and TRF2 exist in complexes containing TIN2 but lacking TPP1/POT1; however, the role of TRF1-TIN2 interactions in mediating interactions with telomeric DNA is unclear. Here, we investigated DNA molecular structures promoted by TRF1-TIN2 interaction using atomic force microscopy (AFM), total internal reflection fluorescence microscopy (TIRFM), and the DNA tightrope assay. We demonstrate that the short (TIN2S) and long (TIN2L) isoforms of TIN2 facilitate TRF1-mediated DNA compaction (cis-interactions) and DNA-DNA bridging (trans-interactions) in a telomeric sequence- and length-dependent manner. On the short telomeric DNA substrate (six TTAGGG repeats), the majority of TRF1-mediated telomeric DNA-DNA bridging events are transient with a lifetime of ~1.95 s. On longer DNA substrates (270 TTAGGG repeats), TIN2 forms multiprotein complexes with TRF1 and stabilizes TRF1-mediated DNA-DNA bridging events that last on the order of minutes. Preincubation of TRF1 with its regulator protein Tankyrase 1 and the cofactor NAD+ significantly reduced TRF1-TIN2 mediated DNA-DNA bridging, whereas TIN2 protected the disassembly of TRF1-TIN2 mediated DNA-DNA bridging upon Tankyrase 1 addition. Furthermore, we showed that TPP1 inhibits TRF1-TIN2L-mediated DNA-DNA bridging. Our study, together with previous findings, supports a molecular model in which protein assemblies at telomeres are heterogeneous with distinct subcomplexes and full shelterin complexes playing distinct roles in telomere protection and elongation.


Changes on indigenous microbiota, colour, bioactive compounds and antioxidant activity of pasteurised pomegranate juice.
Juices prepared from arils of 'Mollar' pomegranates were analysed for naturally occurring microorganisms, CIE Lab colour parameters, total phenols, anthocyanins and punicalagins, ellagic acid content and antioxidant capacity before and after low-, mild- and high-temperature pasteurisations (LTPs, MTPs and HTPs): 65, 80 and 90 °C for 30 or 60s. Mean aerobic plate count (APC), yeast and mold count (YMC), and lactic acid bacteria (LAB) for fresh juices were 5.7, 5.36 and 4.0 log CFU/mL, respectively. MTPs and HTPs were sufficiently effective to decrease APCs to nil or negligible levels. An increase in CIE a values and decrease in CIE b values were the characteristic colour changes in heat-treated juices. The effect of pasteurisations showed that total phenols, punicalagins and ellagic acid were not much affected by thermal processing. Total anthocyanin content and antioxidant capacity were substantially and significantly influenced by the heat treatment applied. A linear relationship was observed between Trolox equivalent antioxidant capacity (TEAC) values and total anthocyanins, suggesting that they contributed strongly to the antioxidant capacity of pomegranate juice.


Relationship between Urinary Alzheimer-Associated Neuronal Thread Protein and Apolipoprotein Epsilon 4 Allele in the Cognitively Normal Population.
We investigated the relationship between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) levels and apolipoprotein epsilon 4 (ApoE ɛ4) alleles, as well as other factors that cause cognitive decline, in the cognitively normal population. We recruited 329 cognitively normal right-handed Han Chinese subjects who completed ApoE gene testing and urinary AD7c-NTP testing. There was no significant difference in urinary AD7c-NTP levels between the normal control and subjective cognitive decline groups. Urinary AD7c-NTP levels were significantly higher in subjects with ApoE ɛ3/4 and 4/4 [0.6074 (0.6541) ng/mL] than in subjects without ApoE ɛ4 [0.4368 (0.3392) ng/mL and 0.5287 (0.3656) ng/mL], and urinary AD7c-NTP levels positively correlated with ApoE genotype grade (r = 0.165, p = 0.003). There were significant differences in urinary AD7c-NTP levels between subjects with and without a history of coronary heart disease or diabetes. Urinary AD7c-NTP levels were not related to years of education, nature of work, family history of dementia, a history of hypertension, stroke, anemia, or thyroid dysfunction. Urinary AD7c-NTP levels were positively correlated with ApoE grade in the cognitively normal population. The relationship between risk factors of cognitive decline and urinary AD7c-NTP levels provides a new way for us to understand AD and urinary AD7c-NTP.