Modulation of cyclins and p53 in mesangial cell proliferation and apoptosis during Habu nephritis.
Mesangial cell (MC) proliferation and apoptosis are the main pathological changes observed in mesangial proliferative nephritis. In this study, we explored the role of cyclins and p53 in modulating MC proliferation and apoptosis in a mouse model of Habu nephritis. The Habu nephritis group was prepared by injection of Habu toxin. Mesangiolysis and mesangial expansion were determined by periodic acid-Schiff (PAS) reagent staining. Immunohistochemical analysis of PCNA and KI67, and TUNEL staining were used to detect cell proliferation and apoptosis, respectively. Expression levels of cyclins and p53 were examined by Western blotting. PAS staining showed that mesangial dissolution appeared on days 1 and 3, and mesangial proliferation with extracellular matrix accumulation was apparent by days 7 and 14. Both PCNA and KI67 immunohistochemical analysis showed that MC proliferation began on day 3, peaked on day 3 and 7, and recovered by day 14. TUNEL staining results showed that MC apoptosis began to increase on day 1, continued to rise on day 7, and peaked on day 14. Western blot analysis showed that cyclin D1 was upregulated on day 1, cyclins A2 and E were upregulated on days 3 and 7, and p53 was upregulated on days 3, 7 and 14. There was no change in the expression levels of Bax or p21. We explored the tendency for MC proliferation and apoptosis during the process of Habu nephritis and found that cyclins and p53 may modulate the disease pathology. This will help us determine the molecular pathogenesis of MC proliferation and provide new targets for disease intervention.


Estimating the error of CT-based measurements of aortic lumen volume used in endovascular planning.
Planning of endovascular sealing of abdominal aortic aneurysms requires measurement of the aortic lumen volume. The aim of this study was to investigate mathematically the effect of intra- and inter-observer variability error, as well as cardiac cycle-related variability, on these measurements. Mean (±2SD) intra- and inter-observer error in lumen measurements and mean (+2SD) cardiac cycle-related variability were obtained from published literature and added to the measurement of the flow lumen volume of a 57 mm abdominal aortic aneurysm to calculate average and extreme error possibilities. The aneurysm volume was measured at 165 ml. The calculated possible mean measurement error due to cardiac cycle variation, intra- and inter-observer variability was +11.0%, resulting in a potential measurement of 183.1 ml. The calculated extreme errors were +24.3% (if 2SD of all errors were added to the mean) and +3.5% (if 2SD of all errors, except cardiac cycle, were subtracted from the mean), resulting in potential measurements of 170.8 ml and 205.1 ml, respectively. When considering the errors combined, the proportion of patients who may have volume measurement errors of up to ±2.5 ml, ±2.6 to ±5.0 ml and ±5.1 to ±7.5 ml were 18%, 17% and 15%, respectively. Measurement of CT-based aortic lumen volumes in abdominal aortic aneurysms is imprecise. This has practical implications for the planning and the performance of complex endovascular therapies.


Biofilm distribution on tympanostomy tubes: An ex vivo descriptive study.
Tympanostomy tube (TT) insertion is a common procedure in children with otitis media with effusion. Post-TT otorrhea (PTTO) is a frequent post-operative complication. Biofilms are involved in chronic PTTO cases. To describe and qualitatively analyze the geometry and sites prone to biofilms on removed TTs, relatively to their position in the ear, past medical/surgical history and PTTO presence. Biofilms presence and topographic distribution on TTs were ex vivo evaluated by using scanning electron microscope, confocal microscope and stereo-microscope. Forty-eight TTs from 30 children were analyzed. Indications for removal were: 71% due to retained TTs (average time from insertion: 24.4 ± 15.1 months), 23% due to chronic PTTO, and 6% due to TT obstruction/dysfunction. Different types of bacterial biofilms were detected on all TTs, regardless the time from their insertion nor their types. Biofilms were observed more on the perpendicular junction and on the internal lumen, and more biofilm colonies were detected on the medial part, facing the middle ear mucosa. TTs removed from children with PTTO exhibited more biofilm colonies when compared to their peers. Of the 16 children who underwent adenoidectomy concomitantly with TT insertion, 10 (62%) children were sent for TT removal due to retained TTs, and 6 (38%) children due to chronic PTTO (p = 0.03). Descriptive analysis of biofilm topographic distribution demonstrated adhesions on specific TT areas: perpendicular junctions and the internal lumen. Such "prone zones" may be the future target areas for changes in TT geometry or can be specifically coated with anti-biofilm materials.


Patent mining on soil pollution remediation technology from the perspective of technological trajectory.
Recent years have seen a marked growth in soil environmental problems, however, the research & development (R&D) direction of soil pollution remediation technology (SPRT) for addressing related challenges to the global ecosystem is still unclear. Patent is the most effective carrier of technological information. Therefore, this study investigates the status and future direction of SPRT through the analysis and mining of 14,475 patents from 1971 to 2020. In 2006-2020, 14,435 SPRT patents (79% of the total) were published, which is in the development stage. By measuring the proportion of high-value patents, determined by the ratio of the number of patent families containing two or more patents (PF2) to that containing at least one patent (PF1), we found that United States (PF2/PF1 = 0.711), Japan (PF2/PF1 = 0.500), and South Korea (PF2/PF1 = 0.431) hold a monopoly. International patent organizations serve as a bridge for technology transfer. Patent CN101947539-A measured by structural hole index (Effective size = 98.194, Efficiency = 0.926) has the most significant technological influence. Therefore, in order to accomplish the technological transition and improve the soil remediation capacity, more attention should be paid to the microbial-assisted phytoremediation technology related to inorganic pollutants, hyperaccumulators and stabilizers. Additionally, patents CN102834190-A (Effective size = 23.930, Efficiency = 0.855, Constraint = 0.141, Hierarchy = 0.089) and CN105855289 (Effective size = 21.453, Efficiency = 0.795 Constraint = 0.149, Hierarchy = 0.086) are both at the location of structural holes. So, more research should be carried out on green and cost-effective solutions for reducing organic pollutants in soil remediation. The current study identifies opportunities for innovations and breakthroughs in SPRT and offers relevant information on technological development prospects.


An exploration of the association between premorbid weight status on patient and caregiver factors at pre and post-treatment among youth with anorexia nervosa/atypical anorexia nervosa.
Patients with atypical anorexia nervosa (AAN) or anorexia nervosa (AN) with premorbid history of higher weight (PHW; median BMI ≥ 85th %ile) may report greater eating disorder (ED) pathology, anxiety, and depression, than patients with premorbid history of lower weight (PLW; mBMI <85th %ile). Less is known about caregiver attitudes or treatment outcome related to premorbid weight history. The current study examined associations between premorbid weight history and patient/caregiver factors at presentation, during treatment, and end of treatment among adolescents (N = 138) diagnosed with AN/AAN and their caregivers who received interdisciplinary ED treatment. The sample comprised adolescents with PHW (n = 58, 40.6 %) or PLW (n = 82, 59.4 %). Adolescents with PHW did not differ with regard to patient- or caregiver-reported ED symptoms, comorbid psychopathology, rates of treatment completion, and attainment of estimated body weight compared to PLW (ps > .05). Adolescents with PHW (vs. PLW) were more likely to be diagnosed with AAN (67.9 %, p < .001), identify as cisgender male (p < .001) and to have lost more weight prior to presentation (p < .001). Perceived caregiver burden was lower among adolescents with PHW vs. PLW (p < .001). Further research should expand on this preliminary study exploring associations between premorbid weight history on patient and caregiver factors at treatment presentation and conclusion to enhance the efficacy of evidence-based treatment across the weight-spectrum.


Adverse drugs reactions (ADR) suspected through phone triage and assessed by medically staffed ambulances: A pilot study.
Prompt and definitive diagnosis of adverse drug reactions (ADRs) is a challenge for health care providers. There is a global burden of ADRs worldwide associated with a negative impact on the patient's health, in parallel with increasing costs for the community. This study aims to determine the annual incidence of ADRs in the cohort of patients requiring immediate intervention of the French prehospital emergency medical service (PEMS). The definitive diagnosis of ADR was provided by the follow-up of the entire course of hospitalization from PEMS presentation to final discharge in each suspected case. A retrospective study examining the incidence of ADR at the Paris PEMS was performed in 2015. From January the 1st to December the 31st, 2015, 485 cases of suspected ADR were selected. Twenty-eight patients could not be identified at the hospital and were considered as lost to follow-up. For the 457 cases with the final diagnosis and outcome available, 359 had a definitive and new diagnosis of ADR, 9 were related to substance of abuse and alcohol, 14 were duplicates and 75 were excluded by drug causality was ruled out. Long-term follow-up was performed for 359 cases. Among them, 22 patients (6.1%) died of an ADR. Twenty-five severe ADRs were notified for children ages 2 to 16 with a cluster of 9 cases (36%) resulting from an accidental outbreak of poisonings with alimemazine in a classroom. No fatality was reported among children suffering from an ADR. The collaboration between PEMS and in hospital Pharmacovigilance Centre is feasible from the PEMS report to the long-term follow-up. The definition of a clinical pattern for some drugs is needed to allow the medical team to anticipate the clinical outcome of the involved patient and therefore adapting the patient's support as soon as possible.


Hepatitis C Treatment Initiation Among US Medicaid Enrollees.
Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection is highly effective but remains underused. Understanding disparities in the delivery of DAAs is important for HCV elimination planning and designing interventions to promote equitable treatment. To examine variations in the receipt of DAA in the 6 months following a new HCV diagnosis. This retrospective cohort study used national Medicaid claims from 2017 to 2019 from 50 states, Washington DC, and Puerto Rico. Individuals aged 18 to 64 years with a new diagnosis of HCV in 2018 were included. A new diagnosis was defined as a claim for an HCV RNA test followed by an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis code, after a 1-year lookback period. Outcome was receipt of a DAA prescription within 6 months of diagnosis. Logistic regression was used to examine demographic factors and ICD-10-identified comorbidities associated with treatment initiation. Among 87 652 individuals, 43 078 (49%) were females, 12 355 (14%) were age 18 to 29 years, 35 181 (40%) age 30 to 49, 51 282 (46%) were non-Hispanic White, and 48 840 (49%) had an injection drug use diagnosis. Of these individuals, 17 927 (20%) received DAAs within 6 months of their first HCV diagnosis. In the regression analyses, male sex was associated with increased treatment initiation (OR, 1.24; 95% CI, 1.16-1.33). Being age 18 to 29 years (OR, 0.65; 95% CI, 0.50-0.85) and injection drug use (OR, 0.84; 95% CI, 0.75-0.94) were associated with decreased treatment initiation. After adjustment for state fixed effects, Asian race (OR, 0.50; 95% CI, 0.40-0.64), American Indian or Alaska Native race (OR, 0.68; 95% CI, 0.55-0.84), and Hispanic ethnicity (OR, 0.81; 95% CI, 0.71-0.93) were associated with decreased treatment initiation. Adjustment for state Medicaid policy did not attenuate the racial or ethnic disparities. In this retrospective cohort study, HCV treatment initiation was low among Medicaid beneficiaries and varied by demographic characteristics and comorbidities. Interventions are needed to increase HCV treatment uptake among Medicaid beneficiaries and to address disparities in treatment among key populations, including younger individuals, females, individuals from minoritized racial and ethnic groups, and people who inject drugs.


[Mastication rehabilitation via dysgnathia surgery and simultaneous implantation].
Within the last 2 years 26 endosseous implants have been used in combination with orthognathic surgery in the maxilla and mandible. The results show, that endosseous implants can be used simultaneously with orthognathic surgery. This helps to treat dysfunctions often seen in partially edentulous patients that undergo orthognathic surgery and at the same time reduce the risk of relapse by achieving stable occlusion.


What is and what is not positive body image? Conceptual foundations and construct definition.
A decade ago, research on positive body image as a unique construct was relatively nonexistent, and now this area is flourishing. How and why did positive body image scholarship emerge? What is known about this contemporary construct? This article situates and contextualizes positive body image within Cash's scholarship, eating disorder prevention efforts, feminist influences, strength-based disciplines within psychology, and Buddhism. Extracting insights from quantitative and qualitative research, this article demonstrates that positive body image is (a) distinct from negative body image; (b) multifaceted (including body appreciation, body acceptance/love, conceptualizing beauty broadly, adaptive investment in appearance, inner positivity, interpreting information in a body-protective manner); (c) holistic; (d) stable and malleable; (e) protective; (f) linked to self-perceived body acceptance by others; and (g) shaped by social identities. Complementing what positive body image is, this article further details what positive body image is not to provide a more nuanced understanding of this construct.


Redox-sensitive fluorescent biosensors detect Sinorhizobium meliloti intracellular redox changes under free-living and symbiotic lifestyles.
Reactive oxygen species such as hydrogen peroxide (H2O2) are key signaling molecules that control the setup and functioning of Rhizobium-legume symbiosis. This interaction results in the formation of a new organ, the root nodule, in which bacteria enter the host cells and differentiate into nitrogen (N2)-fixing bacteroids. The interaction between Sinorhizobium meliloti and Medicago truncatula is a genetic model to study N2-fixing symbiosis. In previous work, S. meliloti mutants impaired in the antioxidant defense, showed altered symbiotic properties, emphasizing the importance of redox-based regulation in the bacterial partner. However, direct measurements of S. meliloti intracellular redox state have never been performed. Here, we measured dynamic changes of intracellular H2O2 and glutathione redox potential by expressing roGFP2-Orp1 and Grx1-roGFP2 biosensors in S. meliloti. Kinetic analyses of redox changes under free-living conditions showed that these biosensors are suitable to monitor the bacterial redox state in real-time, after H2O2 challenge and in different genetic backgrounds. In planta, flow cytometry and confocal imaging experiments allowed the determination of sensor oxidation state in nodule bacteria. These cellular studies establish the existence of an oxidative shift in the redox status of S. meliloti during bacteroid differentiation. Our findings open up new possibilities for in vivo studies of redox dynamics during N2-fixing symbiosis.


Autoimmune response to Chlamydia trachomatis infection and in vitro fertilization outcome.
This observational study was conducted in 235 patients undergoing IVF who had a cervical swab positive for Chlamydia trachomatis and who underwent antibiotic treatment until a negative cervical swab before IVF attempt. After oocyte retrieval, follicular fluids of 109 patients out of 228 still showed the presence of IgA antichlamydia antibodies and a significantly lower pregnancy and implantation rate; therefore we conclude that patients should undergo IVF procedure after serum antichlamydia IgA tests negative.


Anti-diarrhoeal activity of aqueous extract of Ocimum kilimandscharicum.
Ocimum kilimandscharicum Baker ex Güerke, commonly referred to as Kapur Tulsi, is a medicinal herb that belongs to the family of Lamiaceae. It is traditionally popular for its gastroprotective effects, including its use as a digestive and anti-diarrhoeal. The present study aims to prove the anti-diarrhoeal activity of aqueous extract of leaves of Ocimum kilimandscharicum in animal models. The aqueous extract was tested at three different dose levels (100, 200 and 400mg/kg, p.o. in rats and the corresponding doses in mice) against castor-oil induced diarrhoea model and castor oil induced enteropooling assay in rats; and charcoal meal test/intestinal motility test in mice. The parameters observed were the onset of defecation, cumulative faecal weight and consistency of faeces in the castor oil induced diarrhoea model; the weight of intestinal content in castor oil induced enteropooling assay; and the distance travelled by charcoal in the intestinal motility test. A significant delay in the onset of defecation (p<0.05), reduction in the cumulative faecal weight (p<0.001), along with a change in the faecal consistency from watery to solid form was observed at the dose of 200mg/kg in the castor oil-induced diarrhoea model. Similarly, the extract at the doses of 100mg/kg (p<0.01) and 200mg/kg (p<0.001) significantly decreased the weight of intestinal content in castor oil induced enteropooling assay. In the charcoal meal test the extract at the dose of 280mg/kg (corresponding to 200mg/kg in rats) significantly (p<0.01) reduced the distance travelled by charcoal. The aqueous extract of leaves of Ocimum kilimandscharicum showed anti-diarrhoeal activity, which may be due to its anti-motility and anti-secretory effects, which thus proved the traditional claims.


Recovery effect of phenylpropanoid glycosides from Magnolia obovata fruit on alloxan-induced pancreatic islet damage in zebrafish (Danio rerio).
Investigation of phytochemicals from Magnolia obovata fruit led to the isolation of three novel phenylpropanoid glycosides: obovatoside A-C (1-3) and two known phenylpropanoids, syringin (4) and pavonisol (5). The structures of 1-5 were determined by NMR, HRMS, IR and CD spectroscopic analyses. All compounds were evaluated for their effects on recovery from alloxan-induced pancreatic islet damage in zebrafish. All compounds increased the size of the injured pancreatic islet from 0.60- to 1.14-fold. Compounds 1 and 3-5 significantly increased glucose absorption in zebrafish.


Investigation of syphilis immunology and Treponema pallidum subsp. pallidum biology to improve clinical management and design a broadly protective vaccine: study protocol.
The syphilis epidemic continues to cause substantial morbidity and mortality worldwide, particularly in low- and middle-income countries, despite several recent disease control initiatives. Though our understanding of the pathogenesis of this disease and the biology of the syphilis agent, Treponema pallidum subsp. pallidum has improved over the last two decades, further research is necessary to improve clinical diagnosis and disease management protocols. Additionally, such research efforts could contribute to the identification of possible targets for the development of an effective vaccine to stem syphilis spread. This study will recruit two cohorts of participants with active syphilis infection, one with de novo infection, one with repeat infection. Whole blood specimens will be collected from each study participant at baseline, 4, 12, 24, 36, and 48 weeks, to track specific markers of their immunological response, as well as to compare humoral reactivity to Treponema pallidum antigens between the two groups. Additionally, we will use serum specimens to look for unique cytokine patterns in participants with early syphilis. Oral and blood samples, as well as samples from any syphilitic lesions present, will also be collected to sequence any Treponema pallidum DNA found. By furthering our understanding of syphilis pathogenesis and human host immune response to Treponema pallidum, we will provide important data that will help in development of new point-of-care tests that could better identify active infection, leading to improved syphilis diagnosis and management. Findings could also contribute to vaccine development efforts.


Extrahypothalamic corticotropin-releasing hormone mediates (-)-nicotine-induced elevation of plasma corticosterone in rats.
(-)-Nicotine activates the hypothalamic-pituitary-adrenal axis via an activation of the brainstem catecholaminergic neurons in rats. The present study was undertaken to clarify the mechanisms involved in the (-)-nicotine-induced activation of brainstem catecholaminergic neurons in anesthetized rats. Physostigmine (a cholinesterase inhibitor) (0.31 and 0.77 micromol/animal, i.p.) dose-dependently elevated plasma corticosterone in the presence of scopolamine (a muscarinic receptor antagonist) (2.3 micromol/animal, i.p.). (-)-Nicotine (250 and 500 nmol/animal, i.c.v.) dose-dependently elevated plasma corticosterone with concomitant noradrenaline release in the hypothalamic paraventricular nucleus. The (-)-nicotine (500 nmol/animal, i.c.v.)-induced elevation of corticosterone was abolished by phentolamine (an alpha-adrenoceptor antagonist) (0.66 micromol/animal, i.c.v.), and attenuated by (+/-)-sotalol (a beta-adrenoceptor antagonist) (0.97 micromol/animal, i.c.v.). The (-)-nicotine-induced increases of plasma corticosterone and hypothalamic noradrenaline release were abolished either by hexamethonium (a nicotinic acetylcholine receptor antagonist) (1.8 micromol/animal, i.c.v.), CP-154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) (a selective CRF-1 receptor antagonist) (1.3 micromol/animal, i.c.v.) or indomethacin (a cyclooxygenase inhibitor) (1.2 micromol/animal, i.c.v.). These results suggest that (-)-nicotine elevates plasma corticosterone by CRF-1 receptor- and prostaglandin-mediated noradrenaline release in the paraventricular nucleus in rats.


Effects of water stress on gas exchange and water relations of a succulent epiphyte, Kalanchoë uniflora.
Measurements of gas exchange, xylem tension and nocturnal malate synthesis were conducted with well-watered and droughted plants of Kalanchoë uniflora. Corresponding results were obtained with plants grown in 9 h and 12 h photoperiods. In well-watered plants, 50 to 90% of total CO2-uptake occurred during the light period. Nocturnal CO2-uptake and malate synthesis were higher and respiration rate was lower in old leaves (leaf pairs 6 to 10) compared to young leaves (leaf pairs 1 to 5). Within four days of drought distinct physiological changes occurred. Gas exchange during the light period decreased and CO2-uptake during the dark period increased. Nocturnal malate synthesis significantly increased in young leaves.Respiration rate decreased during periods of drought, this decrease being more pronounced in young leaves compared to old leaves. Restriction of gas exchange during the light period resulted in a decrease of transpiration ratio from more than 100 to about 20. The difference between osmotic pressure and xylem tension decreased in young leaves, indicating a reduction in bulk leaf turgor-pressure.We conclude that both the CAM-enhancement in young leaves and the decrease of respiration rate are responsible for the increase of nocturnal CO2-uptake during water stress. During short drought periods, which frequently occur in humid habitats, the observed physiological changes result in a marked reduction of water loss while net CO2-uptake is maintained. This might be relevant for plant growth in the natural habitat.


Bone formation in organ cultures of bone marrow.
Bone formation in organ cultures of intact marrow fragments from mouse is described. Marrow explants were cultured on the top surface of a millipore filter at a gas-liquid interface. Observations with both light- and electron microscopes demonstrated the formation of a well-organised trabecular matrix lined with osteoblast-like cells. The tissue and cells were positive for alkaline-phosphatase activity. Large amounts of thick, well-banded collagen fibrils and matrix vesicles typical of those found in bone were present. The tissue became mineralised in the presence of 10 mM Na-beta-glycerophosphate; in its absence a similar trabecular matrix developed but mineralisation did not take place.


Hemisynthetic trifluralin analogues incorporated in liposomes for the treatment of leishmanial infections.
Leishmaniasis, a vector-borne parasitic disease caused by Leishmania protozoa, is one of the most neglected tropical diseases in terms of drug discovery and development. Current treatment is based on a limited number of chemotherapeutic agents all of which present either/or resistance issues, severe toxicities and adverse reactions associated with extended treatment regimens, and high cost of therapy. Dinitroanilines are a new class of drugs with proven in vitro antileishmanial activity. In previous work a liposomal formulation of one dinitroaniline (TFL) was found to be active against Leishmania parasites in a murine model of visceral leishmaniasis (VL) and in the treatment of experimental canine leishmaniasis. In this study we have investigated the use of dinitroaniline analogues (TFL-A) associated to liposomes, as means to further improve TFL antileishmanial activity. The potential of the liposomal formulations was assessed in vitro against Leishmania infantum promastigotes and intracellular amastigotes and in vivo in a murine model of zoonotic VL. Free and liposomal TFL-A were active in vitro against Leishmania parasites, and they also exhibited reduced cytotoxicity and haemolytic activity. Treatment of infected mice with liposomal TFL-A reduced the amastigote loads in the spleen up to 97%, compared with the loads for untreated controls. These findings illustrate that chemical synthesis of new molecules associated with the use of Nano Drug Delivery Systems that naturally target the diseased organs could be a promising strategy for effective management of VL.


Novel markers in pediatric-type follicular lymphoma.
The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)-associated markers stathmin and LLT-1 were positive in most of the cases (12/13 and 12/13, respectively). Interestingly, FOXP-1 was uniformly positive in PTFL (12/13 cases) in contrast to reactive GCs in FH, where only a few isolated positive cells were observed. FISH revealed no evidence of BCL2, BCL6, or MYC rearrangements in the examined cases. By PCR, clonal immunoglobulin gene rearrangements were detected in 100% of the tested PTFL cases. Our study confirmed the unique morphological and immunophenotypic features of PTFL and suggests that FOXP-1 can represent a novel useful diagnostic marker in the differential diagnosis between PTFL and FH.


Retraction statement: The pattern of neurological manifestations of tuberculosis among adult Sudanese patients attending multi-neurological centers and hospitals in Sudan: A hospital-based cross-sectional study.
[This retracts the article DOI: 10.1002/hsr2.1068.].


Ameloblastic Fibrosarcoma of the Mandible: A Case Report and a Review of the Literature.
Odontogenic sarcomas and their subtypes are very rare tumors. The authors' objectives were to report an additional case of ameloblastic fibrosarcoma, review the clinicopathologic features, discuss their treatment approach, and complete a thorough review of the literature.


Diethyl 2-(triphenyl-meth-yl)malonate.
In the title compound, C(26)H(26)O(4), steric crowding of the Ph(3)C- group with the -CH(CO(2)Et)(2) unit leads to a long C-C bond [1.585 (2) Å]. One of the two ethyl groups is disordered over two sites in a 60:40 ratio.


AttSec: protein secondary structure prediction by capturing local patterns from attention map.
Protein secondary structures that link simple 1D sequences to complex 3D structures can be used as good features for describing the local properties of protein, but also can serve as key features for predicting the complex 3D structures of protein. Thus, it is very important to accurately predict the secondary structure of the protein, which contains a local structural property assigned by the pattern of hydrogen bonds formed between amino acids. In this study, we accurately predict protein secondary structure by capturing the local patterns of protein. For this objective, we present a novel prediction model, AttSec, based on transformer architecture. In particular, AttSec extracts self-attention maps corresponding to pairwise features between amino acid embeddings and passes them through 2D convolution blocks to capture local patterns. In addition, instead of using additional evolutionary information, it uses protein embedding as an input, which is generated by a language model. For the ProteinNet DSSP8 dataset, our model showed 11.8% better performance on the entire evaluation datasets compared with other no-evolutionary-information-based models. For the NetSurfP-2.0 DSSP8 dataset, it showed 1.2% better performance on average. There was an average performance improvement of 9.0% for the ProteinNet DSSP3 dataset and an average of 0.7% for the NetSurfP-2.0 DSSP3 dataset. We accurately predict protein secondary structure by capturing the local patterns of protein. For this objective, we present a novel prediction model, AttSec, based on transformer architecture. Although there was no dramatic accuracy improvement compared with other models, the improvement on DSSP8 was greater than that on DSSP3. This result implies that using our proposed pairwise feature could have a remarkable effect for several challenging tasks that require finely subdivided classification. Github package URL is https://github.com/youjin-DDAI/AttSec .


[Sturge--Weber-Klippel--Trenaunay syndrome (case report)].
Sturge-Weber syndrome is characterized by capillary malformations in the face, associated with leptomeningeal and choroidal venous malformations. Klippel-Trenaunay syndrome consists of the triad: capillary malformation of one leg, ipsilateral hypertrophy and varicose veins. We report the case of a 23-year-old male patient who presented a complex congenital neurocutaneous syndrome with vascular malformations involving the brain, face and limbs and associated with epilepsia and leptomeningeal calcifications. The patient fulfilled the diagnostic criteria of both vascular phacomatosis syndromes. Similar descriptions of dual or overlapping syndromes have been published. Many show that there is no clear distinction between Klippel-Trenaunay syndrome and Sturge-Weber syndrome. There is a clinical and biological overlap. The complexity of the disease phenotypes shows that a classification based on an eponymous category does not enable resolution of the nosological problems. Some authors suggest that these vascular malformations are best described in anatomical/histological or functional terms. We report a new observation that illustrates these difficulties.


Neurosensory function of the inferior alveolar nerve after bilateral sagittal ramus osteotomy: a retrospective study of 68 patients.
The aim of the present study was to report the incidence of neurosensory dysfunction in the lower lip and chin after bilateral sagittal split osteotomy at four postoperative time points, and the relation of impairment to factors connected with the operation. Sixty-eight patients who had undergone the procedure (at 136 operated sites) were reviewed, and neurosensory recovery was studied at 2, 6, 18 and finally 30 months postoperatively. A change in neurosensory recovery was seen over this period of time. Two months postoperatively, 84 sites had reduced sensitivity (62%). The incidence of disorder decreased to 52 sites (38%) at 6 months, 43 sites (32%) at 1.5 years and 32 sites (24%) at the final 2.5-year check up. The patient age at the time of surgery, the type of osteosynthesis and the perioperative position of the inferior alveolar nerve were variables that influenced the neurosensory outcome. In conclusion, this retrospective study shows that the most important factors influencing postoperative nerve function are patient age, fixation method and the perioperative position of the inferior alveolar nerve.


Ecological theory in practice: illustrations from a community-based intervention to promote the health of recent mothers.
We present a qualitative case study where we used four principles of ecological theory from community psychology as a template to assess the dynamics about how a preventive community intervention was transacted in eight communities in Victoria, Australia. The principles were cycling of resources, interdependence, adaptation, and succession. Ecological thinking focuses on key resources in communities. That is, the people, events, and settings that are the foundations of thinking about communities as systems. The data set consists of field diaries kept by and serial interviews with nine community development workers over a 2-year period. We found that the analysis highlighted a process-oriented way of representing the intervention, one that sees beyond the intervention's technical components (or packaged elements) to the complexities of the cultural and political change processes occurring beneath. The value of this is the attention focussed on likely project sustainability.


Negative regulation of gamma-globin gene expression by cyclic AMP-dependent pathway in erythroid cells.
Fetal hemoglobin inducers such as hemin, butyrate, and hydroxyurea stimulate gamma-globin gene expression by activating the cyclic GMP (cGMP)-dependent pathway. Although cGMP activates the cyclic AMP (cAMP)-dependent pathway by suppressing cGMP-inhibited phosphodiesterase 3 (PDE3), the effects of the cAMP-dependent pathway on gamma-globin gene expression are unknown. The cAMP-dependent pathway was activated in K562 cells using the adenylate cyclase activator forskolin. Expression of gamma-globin mRNA was examined by primer extension, and transcriptional activity of the gamma-globin gene promoter was determined by reporter gene assays. PDE3 was expressed in K562 cells at a high level. The cAMP-dependent pathway was found to be activated in K562 cells in which the cGMP-dependent pathway was activated by hemin. Activation of the cAMP-dependent pathway by forskolin inhibited hemin-induced expression of gamma-globin mRNA and decreased transcriptional activity of the gamma-globin gene promoter. The levels of phosphorylation of mitogen-activated protein kinases (MAPKs) were not affected by the cAMP-dependent pathway. These results suggested that the cAMP-dependent pathway, which is independent of MAPK pathways, plays a negative role in gamma-globin gene expression in K562 cells. cAMP and cGMP may have differential roles in the regulation of gamma-globin gene expression in erythroid cells.


Effect of glucagon on vagally induced gastric acid secretion in humans.
The effect of a physiologically relevant dose of pancreatic glucagon, 85 pmol/kg/hr, or saline on gastric acid secretion induced by modified sham feeding (chew and spit), was studied in 10 healthy volunteers. Gastric pH was held constant (pH 5.5) by intragastric titration. Glucagon infusion inhibited gastric acid secretion significantly, from 19.6 +/- 1.5 mmol H+ per hour during saline, to 10.4 +/- 1.4 mmol H+ per hour. Blood glucose increased during glucagon infusion and remained constant during saline infusion. Serum gastrin concentrations increased significantly by sham feeding, during saline as well as glucagon infusion, and no difference between the gastrin response during saline or glucagon infusion was found. Thus glucagon, in a physiologic dose, reduces vagally mediated acid secretion by a gastrin-independent mechanism.


Neutrophilic granulocyte percentage is associated with anxiety in Chinese hospitalized heart failure patients.
In patients with heart failure, anxiety disorder is common and associated with adverse prognosis. This study intended to find more confounding factors of Chinese heart failure patients. We enrolled 284 hospitalized heart failure patients, whose New York Heart Association (NYHA) classed as II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. All the patients were scaled in Hamilton Rating Scale for Anxiety (14-items) (HAM-A14). Ordinal logistic regression analysis was performed to examine the association of correlated factors with anxiety disorder. There were 184 patients had anxiety accounting for 64.8% of all 284 hospitalized heart failure patients. The neutrophilic granulocyte percentage, urea nitrogen, total bilirubin and brain natriuretic peptide were positively associated with HAM-A14 score, meanwhile, the hemoglobin, red blood cells counts, albumin and LVEF were negatively associated with HAM-A14 score (All P < 0.05). After the adjustments of sex, hemoglobin, urea nitrogen, total bilirubin, albumin and brain natriuretic peptide, the neutrophilic granulocyte percentage was significantly associated with anxiety (OR = 43.265, P = 0.012). The neutrophilic granulocyte percentage was 0.616 ± 0.111, 0.640 ± 0.102, 0.681 ± 0.106 and 0.683 ± 0.113 in heart failure patients with no anxiety, possible anxiety, confirmed anxiety and obvious anxiety, respectively. Neutrophilic granulocyte percentage as well as the traditional risk factors such as sex, urea nitrogen and brain natriuretic peptide is associated with anxiety in hospitalized heart failure patients.


Unconventional electronic phase transition in SnBi2Te4: role of anomalous thermal expansion.
We propose SnBi2Te4to be a novel topological quantum material exhibiting temperature (T) mediated transitions between rich electronic phases. Our combined theoretical and experimental results suggest that SnBi2Te4goes from a low-Tsemimetallic phase to a high-T(room temperature) insulating phase via an intermediate metallic phase. Single crystals of SnBi2Te4are characterized by various experimental probes including synchrotron based x-ray diffraction, magnetoresistance, Hall effect, Seebeck coefficient and magnetization. X-ray diffraction data confirms an anomalous thermal expansion of the unit cell volume below ∼100 K, which significantly affects the bulk band structure and hence the transport properties. Simulated surface states are found to be topologically robust with varyingT. This indirectly supports the experimentally observed paramagnetic singularity in the entireT-range. The proposed coexistence of such rich phases is a rare occurrence, yet it facilitates a fertile ground to tune them in a material driven by structural changes.


The association between vitamin C and vitamin E supplement use before hematopoietic stem cell transplant and outcomes to two years.
To examine the prevalence of supplement use in persons before receiving hematopoietic stem cell transplant (HSCT) and the association of select supplements with outcomes. This observational cohort study included a questionnaire on supplement use before HSCT. Nonrelapse mortality, recurrence/relapse, and mortality or relapse (the inverse of disease-free survival) were followed to two years. Subjects/Setting Persons receiving HSCT at the Fred Hutchinson Cancer Research Center between September 1994 and December 1997 were eligible (N=1,182). Statistical Analyses Performed Descriptive statistics and univariate and Cox regression analyses were conducted. Sixty-six percent of patients used supplements (31% vitamin C, 19% vitamin E, and 20% herbs or others preparations). Vitamin C at > or =500 mg/day was inversely associated with recurrence among persons with breast cancer (RR=0.11; 95% CI, 0.02-0.89; P=.03). However, among persons with acute leukemia, vitamin C at > or =500 mg/day was positively associated with nonrelapse mortality (RR=2.25; 95% CI, 1.33-3.83; P=.01) and mortality or relapse (RR=1.63; 95% CI, 1.09-2.44; P=.01), respectively. Vitamin E at > or =400 IU/day was positively associated with mortality or relapse (RR=1.77; 95% CI, 1.06 -2.96; P=.02). Applications/Conclusions Though this work was observational, the results suggest supplemental vitamin C before therapy may be beneficial in persons with breast cancer but both vitamin C and vitamin E may increase risk in persons with acute leukemia receiving HSCT. Practitioners should document supplement use in subjects receiving therapy for cancer.


Reorganization of functional brain maps after exercise training: Importance of cerebellar-thalamic-cortical pathway.
Exercise training (ET) causes functional and morphologic changes in normal and injured brain. While studies have examined effects of short-term (same day) training on functional brain activation, less work has evaluated effects of long-term training, in particular treadmill running. An improved understanding is relevant as changes in neural reorganization typically require days to weeks, and treadmill training is a component of many neurorehabilitation programs. Adult, male rats (n=10) trained to run for 40 min/day, 5 days/week on a Rotarod treadmill at 11.5 cm/s, while control animals (n=10) walked for 1 min/day at 1.2 cm/s. Six weeks later, [(14)C]-iodoantipyrine was injected intravenously during treadmill walking. Regional cerebral blood flow-related tissue radioactivity was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping. Exercised compared to nonexercised rats demonstrated increased influence of the cerebellar-thalamic-cortical (CbTC) circuit, with relative increases in perfusion in deep cerebellar nuclei (medial, interposed, lateral), thalamus (ventrolateral, midline, intralaminar), and paravermis, but with decreases in the vermis. In the basal ganglia-thalamic-cortical circuit, significant decreases were noted in sensorimotor cortex and striatum, with associated increases in the globus pallidus. Additional significant changes were noted in the ventral pallidum, superior colliculus, dentate gyrus (increases), and red nucleus (decreases). Following ET, the new dynamic equilibrium of the brain is characterized by increases in the efficiency of neural processing (sensorimotor cortex, striatum, vermis) and an increased influence of the CbTC circuit. Cerebral regions demonstrating changes in neural activation may point to alternate circuits, which may be mobilized during neurorehabilitation.


Dihydrocapsaicin induces translational repression and stress granule through HRI-eIF2α phosphorylation axis.
Stress granules (SGs) are cytoplasmic biomolecular condensates that are formed against a variety of stress conditions when translation initiation is perturbed. SGs form through the weak protein-protein, protein-RNA, and RNA-RNA interactions, as well as through the intrinsically disordered domains and post-translation modifications within RNA binding proteins (RBPs). SGs are known to contribute to cell survivability by minimizing the stress-induced damage to the cells by delaying the activation of apoptosis. Here, we find that dihydrocapsaicin (DHC), an analogue of capsaicin, is a SG inducer that promotes polysome disassembly and reduces global protein translation via phosphorylation of eIF2α. DHC-mediated SG assembly is controlled by the phosphorylation of eIF2α at serine 51 position and is controlled by all four eIF2α stress kinases (i.e., HRI, PKR, PERK, and GCN2) with HRI showing maximal effect. We demonstrate that DHC is a bonafide compound that induces SG assembly, disassembles polysome, phosphorylates eIF2α in an HRI dependent manner, and thereby arrest global translation. Together, our results suggest that DHC is a novel SG inducer and an alternate to sodium arsenite to study SG dynamics.


Caveolin-1, transforming growth factor-beta receptor internalization, and the pathogenesis of systemic sclerosis.
To review the scientific literature supporting the participation of caveolin-1 in the pathogenesis of tissue fibrosis and the notion that modulation of the caveolin-1 pathway may represent a novel treatment for systemic sclerosis and other fibrotic diseases. Caveolin-1 plays an important role in the regulation of transforming growth factor-beta (TGF-beta) signaling owing to its participation in TGF-beta receptor internalization. TGF-beta receptor internalized through caveolin-1 lipid rafts undergoes rapid degradation, effectively decreasing TGF-beta signaling. Studies have shown that caveolin-1 knockdown in vitro markedly increased collagen gene expression in normal human lung fibroblasts. Caveolin-1 was reduced in affected systemic sclerosis lungs and skin and in idiopathic pulmonary fibrosis lung tissues and fibroblasts. Increasing caveolin-1 expression markedly improved bleomycin-induced pulmonary fibrosis. Restoration of caveolin bioavailability employing penetratin, a cell-permeable peptide carrier for a bioactive caveolin-1 fragment, abrogated TGF-beta activation of cultured human dermal fibroblasts. Systemic administration of penetratin-caveolin-1 peptide to mice with bleomycin-induced lung fibrosis reduced fibrosis. Caveolin-1 plays an important role in the regulation of TGF-beta signaling and participates in the pathogenesis of systemic sclerosis and idiopathic pulmonary fibrosis. Restoration of caveolin function employing active caveolin-1 fragments coupled to cell-permeable carrier peptides may represent a novel approach for their treatment.


Boosting the resolution of multidimensional NMR spectra by complete removal of proton spin multiplicities.
Over decades multidimensional NMR spectroscopy has become an indispensable tool for structure elucidation of natural products, peptides and medium sized to large proteins. Heteronuclear single quantum coherence (HSQC) spectroscopy is one of the work horses in that field often used to map structural connectivity between protons and carbons or other hetero nuclei. In overcrowded HSQC spectra, proton multiplet structures of cross peaks set a limit to the power of resolution and make a straightforward assignment difficult. In this work, we provide a solution to improve these penalties by completely removing the proton spin multiplet structure of HSQC cross peaks. Previously reported sideband artefacts are diminished leading to HSQC spectra with singlet responses for all types of proton multiplicities. For sideband suppression, the idea of restricted random delay (RRD) in chunk interrupted data acquisition is introduced and exemplified. The problem of irreducible residual doublet splitting of diastereotopic CH2 groups is simply solved by using a phase sensitive JRES approach in conjunction with echo processing and real time broadband homodecoupling (BBHD) HSQC, applied as a 3D experiment. Advantages and limitations of the method is presented and discussed.


Changes in plasma alpha-1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation.
The binding of drugs to plasma proteins is an important consideration in drug development. We have reported that the dose of adenosine, lidocaine, and magnesium (ALM) fluid therapy for resuscitation from hemorrhagic shock is nearly 3-times higher for pigs than rats. Since lidocaine strongly binds to serum alpha-1-acid glycoprotein (AGP), the aim of the study was to investigate the effect of hemorrhagic shock on levels of AGP in rats and pigs. Healthy adult male Sprague-Dawley rats and female crossbred pigs (n = 33 each) underwent tail vein and peripheral ear vein blood sampling, respectively, to collect plasma for AGP measurements. Rats (n = 17) and pigs (n = 16) underwent surgical instrumentation and uncontrolled hemorrhage via liver resection, and were treated with 3% NaCl ± ALM IV bolus followed 60 min later by 4 h 0.9% NaCl ± ALM IV drip. Rats were monitored for 72 h with blood samples taken post-surgery, and at 5.25, 24, and 72 h. Pigs were monitored for 6 h with blood samples taken post-surgery, and at 60 min and 6 h. Plasma AGP was measured with rat- and pig-specific enzyme-linked immunosorbent assay kits. Baseline AGP levels in rats were 3.91 μg/mL and significantly 83-fold lower than in pigs (325 μg/mL). Surgical instrumentation was associated with ~10-fold increases in AGP in rats and a 21% fall in pigs. AGP levels remained elevated in rats after hemorrhage and resuscitation (28-29 μg/mL). In contrast, no significant differences in plasma AGP were found in ALM- or Saline-treated pigs over the monitoring period. We conclude that the trauma of surgery alone was associated with significant increases in AGP in rats, compared to a contrasting decrease in pigs. Higher levels of plasma AGP in pigs prior to hemorrhagic shock is consistent with the higher ALM doses required to resuscitate pigs compared with rats.


The number of nucleolar silver-stained granules of active nucleolus organizer regions in mitotic and interphase cells of rat Yoshida and Zajdela ascitic tumors.
To provide more information on the number of silver-stained granules (SSGs) of active mitotic nucleolus organizer regions (NORs) as well as interphase nucleoli, rat Yoshida ascitic sarcoma and Zajdela ascitic hepatoma cells were studied by means of standardized one-step and two-step silver-staining procedures. The number of SSGs of mitotic active NORs was relatively constant and corresponded to the number of active NORs of animals bearing the tumors investigated. Some anaphases and telophases were "asymmetric", i.e. chromosomal figures (future nuclei) in one and the same cell contained different number of SSGs (active NORs). The incidence of such asymetric anaphases and telophases was higher in aneuploid (hypoploid) Zajdela hepatoma than in euploid (diploid) Yoshida sarcoma cells. In the interphase, the number of SSGs was low in small or large cells with distinct chromocenters or chromosomes condensation presumably representing postmitotic and premitotic cells. In contrast, the highest number of SSGs was noted in nucleoli of large cells which were usually characterized by a fine chromatin structure.


Feasibility, acceptability, and preliminary efficacy of a handcycling high-intensity interval training program for individuals with spinal cord injury.
Pilot nonrandomized clinical trial. To examine the feasibility, acceptability, and preliminary efficacy of performing handcycling high-intensity interval training (HIIT) for 6 weeks in wheelchair users with spinal cord injury. Participant's home. Participants completed pre- and postgraded exercise stress tests, exercise surveys and 6 weeks of handcycling HIIT. The HIIT program consisted of two weekly, 25 min supervised at-home sessions (2-3 min warm-up, then ten intervals of cycling with a ratio of 1 min work at 90% peak power output (PPO) to 1 min recovery at 0-20% PPO, then 2-3 min cool down). Real-time power output and heart rate were recorded via sensors and a bike computer. The sensor data were analyzed to evaluate training efficacy. Seven of the ten enrolled participants (70%) completed the study. All but one completed the required 12 sessions. The participants met at least 1 of the HIIT target intensity criteria in 76 out of 89 total sessions (85.4%) performed. Participants expressed a high level of enjoyment on the Physical Activity Enjoyment Scale, mean (SD) = 114.8 (11.3), and satisfaction with the overall experience. Five of the seven participants (71%) who completed the study felt an increase in endurance, function, and health. Objective physiological changes showed mixed results. Six weeks of handcycling HIIT appears to be safe, feasible and acceptable. A longer HIIT work interval may be needed to elicit significant physiological responses. Future investigation of the feasibility and efficacy of differing HIIT parameters is needed.


The national child odontology registry (SCOR): a valuable resource for odontological and public health research.
Since 1972 The National Child Odontology Registry has collected data on the oral health of most of all Danish children and adolescents. However, comprehensive information on the registry has not previously been available, making it difficult to approach and use the registry for research purposes. By combining historical documentation and simple descriptive statistics we provide an overview of major events in the timeline of The National Child Odontology Registry and discuss how they impact the available data. We provide a broad overview of the dental variables in the registry, and how the registration criteria for some of the core dental variables (gingivitis, periodontitis, and dental caries) have changed over time. We then provide examples of how aggregate variables for the core dental diseases, allowing for comparison across registration criteria, can be created. Most of the Danish population born during or after 1965 have a least one entry in the National Child Odontology Registry, with 68% having entries spanning their entire childhood and adolescence. The prevalence of gingivitis and periodontitis seem to increase significantly in the years immediately following changes in how registration criteria for these variables, raising questions as to whether these diseases are generally underreported, or subject to overreporting in the years following the registration changes. The mandatory ages of registration instituted in 2003, do not appear to have had a strong impact on the ages at which registrations are made. For variables not directly comparable across datasets due to changes in registration criteria aggregate variables of measurements can be computed in most cases. The National Child Odontology Registry provides a unique opportunity to study the impact of childhood oral health on life trajectories, but using the registry is not without issues, and we strongly recommend consulting with experts in the field of odontology to ensure the best use of available data.


Low-Temperature Spark Plasma Sintering of ZrW2-xMoxO₈ Exhibiting Controllable Negative Thermal Expansion.
Molybdenum-doped zirconium tungstate (ZrW2-xMoxO₈) has been widely studied because of its large isotropic coefficient of negative thermal expansion (NTE). However, low density and poor sinterability limit its production and application. In this study, relative density greater than 90% single-phase ZrW2-xMoxO₈ (0.0 ≤ x ≤ 1.0) sintered bodies were fabricated by spark plasma sintering (500⁻600 °C for 10 min) using ZrW2-xMoxO₇(OH)₂·2H₂O precursor powders as the starting material. High-temperature X-ray diffraction and thermomechanical analysis were used to investigate the change in the order⁻disorder phase transition temperature of the sintered materials; it gradually dropped from 170 °C at x = 0.0 to 78 °C at x = 0.5, and then to below room temperature at x ≥ 0.7. In addition, all sintered bodies exhibited NTE behavior. The NTE coefficient was controllable by changing the x value as follows: from -7.85 × 10-6 °C-1 (x = 0) to -9.01 × 10-6 °C-1 (x = 0.6) and from -3.22 × 10-6 °C-1 (x = 0) to -2.50 × 10-6 °C-1 (x = 1.0) before and after the phase transition, respectively. Rietveld structure refinement results indicate that the change in the NTE coefficient can be straightforwardly traced to the thermodynamic instability of the terminal oxygen atoms, which only have one coordination.


Coincident chromosomal disomy in meiotic dyads from triploid yeast.
Among meiotic asci produced by triploid (3N) Saccharomyces cerevisiae are cases in which exactly two of the four ascospores proliferate into colonies. Given the unique asymmetry problems inherent in distributing three chromosome homologues in meiosis, these ascospore dyads are of special interest. We have tested 40 of these dyads (80 ascospores) for their chromosome content by ascertaining whether they have inherited one or two copies of each of the sixteen yeast chromosomes from the parental triploid. Overall, then, ascospores in these dyads can be either haploid (N) or disomic (N + 1) for each chromosome. The principal results of this analysis include: (1) Coincident disomy (inheritance of two copies of a given chromosome in both members of an ascospore dyad) was detected for 15 of the 16 yeast chromosomes, and at least once in every dyad. (2) Coincident disomy increased as a function of the mean number of disomic chromosomes per spore in each dyad, but this increase differed functionally from that expected if coincident disomy in the two ascospores were a simple, meiotically independent, concomitant of multiple disomy. We conclude from these results that: (1) The ascospore dyads, as the two proliferating spores of single meioses from the triploid, represent meiotic sisters. That is, they stem from the same half of the first meiotic division. (2) Multiply-disomic meiotic segregants of yeast triploids proliferate at the expense of their multiple disomy, as cells in spore colonies experience repeated and independent disomic chromosome losses (N + 1----N).(ABSTRACT TRUNCATED AT 250 WORDS)


Investigating a Proposed Model of Social Competence in Children With Traumatic Brain Injuries.
The goal of the current study was to test a proposed model of social competence for children who have suffered a traumatic brain injury (TBI). We hypothesized that both peer and teacher reports of social behavior would mediate the relation between intraindividual characteristics (e.g., executive function) and peer acceptance. Participants were 52 children with TBI (M age = 10.29; M time after injury: 2.46 years). Severity of TBI ranged from complicated mild to severe. Classroom and laboratory measures were used to assess executive function, social behavior, and peer acceptance. Analyses revealed that peer reports of social behavior were a better mediator than teacher reports of the associations between executive function, social behaviors, and peer acceptance. The results underscore the importance of including peer reports of social behavior when developing interventions designed to improve the social, emotional, and behavioral outcomes of children with TBI.


Automatic assessment of dairy cows' rumen function over time and links to feed changes and milk production.
A 3-dimensional (3D) vision-based system was previously designed to automatically estimate the rumen motility of individual cows. This longitudinal study aimed to explore the associations between 3D vision-based rumen function assessment and dairy cow feed changes and milk production on a commercial farm. The 3D vision system was attached to an automatic milking robot to estimate the ruminal contraction frequency and rumen fill in 42 lactating cows during each milking event for 66 d. Additionally, we collected data on milk production, milk composition, general health, and changes in feeding practices. The 3D vision system showed that half the cows displayed a drastic decrease in the estimated rumen fill when all cows began grazing. The grazing and decreased rumen fill were also associated with herd-level milk fat depression. Over the 66 d, one cow was detected with reduced milk production and suspected rumen dysfunction by the farmer. The 3D vision system, however, identified this cow as having sudden decreases in estimated ruminal contraction frequency and rumen fill 4 d before detection by the farmer. In this longitudinal study, the 3D vision-based rumen function assessment system showed potential as a useful management-supporting tool for dairy farmers. The system, however, requires further validation with more cows of various breeds and ages. We suggest validating the 3D vision system with rumen boluses, quantified adjustments in feeding practices, more cases with ruminal dysfunction, and systematic health assessments for future studies.


Introduction to "Immunotherapies for Multiple Myeloma".
Multiple myeloma (MM) is the second most common hematological cancer after diffuse large B-cell lymphoma, accounting for about 10% of all blood cancers [...].


Biophysical analysis of the putative acetyltransferase SACOL2570 from methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of a myriad of insidious and intractable infections in humans, especially in patients with compromised immune systems and children. Here, we report the apo- and CoA-bound crystal structures of a member of the galactoside acetyltransferase superfamily from methicillin-resistant S. aureus SACOL2570 which was recently shown to be down regulated in S. aureus grown in the presence of fusidic acid, an antibiotic used to treat MRSA infections. SACOL2570 forms a homotrimer in solution, as confirmed by small-angle X-ray scattering and dynamic light scattering. The protein subunit consists of an N-terminal alpha-helical domain connected to a C-terminal LβH domain. CoA binds in the active site formed by the residues from adjacent LβH domains. After determination of CoA-bound structure, molecular dynamics simulations were performed to model the binding of AcCoA. Binding of both AcCoA and CoA to SACOL2570 was verified by isothermal titration calorimetry. SACOL2570 most likely acts as an acetyltransferase, using AcCoA as an acetyl group donor and an as-yet-undetermined chemical moiety as an acceptor. SACOL2570 was recently used as a scaffold for mutations that lead the generation of cage-like assemblies, and has the potential to be used for the generation of more complex nanostructures.


(Phenyl-iodos-yl)benzene tosyl-ate dihydrate.
The structure of the title salt (systematic name: oxodiphenyl-λ5-iodanylium 4-methyl-benzene-sulfonate dihydrate), C12H10IO+·C7H7O3S-·2H2O, at 150 K, has monoclinic (P21/c) symmetry. The mol-ecular structure features an angular (phenyl-iodos-yl)benzene cation, the geometry of which was hitherto undescribed in the literature: in the cation, both I-C bonds are approximately normal to the I=O bond, forming a C-I-C angle of 95.36 (4)°. The crystal structure displays O-H⋯O, O-H⋯I and O-H⋯S hydrogen bonding.


Nucleotide sequence of the putative replicase gene of the sour cherry strain of plum pox potyvirus.
The complete nucleotide sequence of the NIb coding region of the sour cherry strain of plum pox potyvirus (PPV-SoC) has been determined. It consists of 1554 nucleotides and encodes a putative replicase protein of 518 amino acids. Sequence identity scores between NIb of PPV-SoC and other isolates of PPV are significantly low (c. 78%). Many of the nucleotide substitutions, however, are silent. PPV-SoC differs from isolates of PPV-D, PPV-M and PPV-E1 Amar at multiple amino acid positions that are conserved between the other isolates. The NIb sequence extends the PPV-SoC sequence presently available to 2781 nt from the 3' end (approximately 28% of the genome).


Incorporation of Chiral Frustrated Lewis Pair into Metal-Organic Framework with Tailored Microenvironment for Heterogeneous Enantio- and Chemoselective Hydrogenation.
The development of efficient heterogeneous catalysts with multiselectivity (e.g., enantio- and chemoselectivity) has long been sought after but with limited progress being made so far. To achieve enantio- and chemoselectivity in a heterogeneous system, as inspired by enzymes, we illustrate herein an approach of creating an enzyme-mimic region (EMR) within the nanospace of a metal-organic framework (MOF) as exemplified in the context of incorporating a chiral frustrated Lewis pair (CFLP) into a MOF with a tailored pore environment. Due to the high density of the EMR featuring the active site of CFLP and auxiliary sites of the hydroxyl group/open metal site within the vicinity of CFLP, the resultant EMR@MOF demonstrated excellent catalysis performance in heterogeneous hydrogenation of α,β-unsaturated imines to afford chiral β-unsaturated amines with high yields and high enantio- and chemoselectivity. The role of the hydroxyl group/open metal site in regulating chemoselectivity was proved by the observation of a catalyst-substrate interaction experimentally, which was also rationalized by computational results. This work not only contributes a MOF as a new platform for multiselective catalysis but also opens a promising avenue to develop heterogeneous catalysts with multiselectivity for challenging yet important transformations.


The advantages of live/real time three-dimensional transesophageal echocardiography during assessments of pulmonary stenosis.
This report sought to compare live/real-time three-dimensional transesophageal echocardiography (3D-TEE) with two-dimensional transesophageal echocardiography (2D-TEE) and to determine whether there are advantages to using 3D-TEE on patients with pulmonary stenosis (PS). Sixteen consecutive adult patients (50 % male and 50 % female; mean age 33 ± 13.4 years) with PS and indications of TEE were prospectively enrolled in this study. Following this, initial 2D-TEE and 3D-TEE examinations were performed, and 3D-TEE images were analyzed using an off-line Q-lab software system. Finally, the 2D-TEE and 3D-TEE findings were compared. In the present study, 3D-TEE allowed us to obtain the en face views of pulmonary valves (PVs) in all but one patient. While this patient was without a PV due to a previous tetralogy of Fallot operation, we could detect the type of PV in the other 15 (93.7 %) patients by using 3D-TEE. Due to poor image quality, the most stenotic area was not measurable in only one (6.2 %) of the patients. In eight (50 %) of the patients, severity and localization of stenosis were more precisely determined with 3DTEE than with 2D-TEE. The PVs' maximal annulus dimensions were found to be significantly larger when they were measured using 3D modalities. This study provides evidence of the incremental value of using 3D-TEE rather than 2D-TEE during assessments of PS, specifically in cases where special conditions (pregnancy, pulmonary regurgitation, and concomitant atrial septal defects) cause recordings of the transvalvular peak gradient to be inaccurate. Therefore, 3D-TEE should be used as a complementary imaging tool to 2D-TEE during routine echocardiographic examinations.


Tissue characterization of uterine myometrium using the ultrasound gray-level histogram width.
The purpose of this study was to clarify the usefulness of the gray-level histogram width for tissue characterization of the uterine myometrium. Thirty-five patients with uterine fibroids, 5 patients with adenomyosis, and 9 patients with extensive myometrial invasion by endometrial carcinoma were studied. The gray-level histogram width was determined by transvaginal ultrasonography. The Mann-Whitney U test was used for statistical analysis. Receiver operating characteristic curves were generated for use in tissue characterization. Significant differences in the gray-level histogram width were found between normal myometrium (54.2% ± 4.2%) and carcinoma (58.2% ± 3.9%), normal myometrium and fibroid (64.3% ± 5.2%), and carcinoma and fibroid. However, it was difficult to identify adenomyosis. The cutoff values to distinguish normal myometrium from carcinoma, normal myometrium from fibroid, and carcinoma from fibroid are 56, 58, and 64, respectively. The gray-level histogram width is useful for tissue characterization of the uterine myometrium.


Effects of dyslipidemia on E antigen seroconversion of patients with chronic hepatitis B treated by nucleoside (acid) analogs.
The prevalence of dyslipidemia in China is increasing annually. Current studies suggest that dyslipidemia affects the antiviral efficacy of hepatitis C virus (HCV) therapies, while recent studies suggest that serum lipids influence the response rates of chronic hepatitis B (CHB) patients receiving PEGylated interferon-alpha (Peg IFN-α) treatment. However, the role of dyslipidemia in the efficacy of nucleoside (acid) analogues (NAs) in CHB patients remains unclear. From January 2010 to December 2013, data from 179 treatment-naive patients with CHB who were hepatitis B e antigen (HBeAg)-positive and had visited the first affiliated hospital of Wenzhou Medical University were assessed. Of these patients, 68 were assigned to the dyslipidemia group (diagnosed with CHB complicated with dyslipidemia) and 111 to the normolipidemic group. The following 3 treatment strategies were performed for all CHB patients over a 5-year period: lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy, telbivudine (LdT) monotherapy, and entecavir (ETV) monotherapy. Serum assessments, blood biochemistry, HBV serological markers, HBV DNA before treatment and HBeAg serological conversion and virological responses at different timepoints after treatment were compared between the two groups. Measurement data were compared by τ tests and enumeration data by χ2 tests. Correlation analysis was performed using binary logistic regression analysis. The rates of HBeAg seroconversion in the dyslipidemia group at years 1, 2, 3, and 4 were 10.3, 13.2, 17.6, and 22.1%, respectively, which were not significantly lower than those of the normolipidemic group (11.7, 16.2, 18.0 and 33.3%; χ2 = 0.085, 0.293, 0.004, and 2.601, respectively; Ρ > 0.05). However, the rates of HBeAg seroconversion in the dyslipidemia group were significantly lower than those in the normolipidemic group at year 5 (27.9% vs. 43.2%, χ2 = 4.216, Ρ < 0.05). Univariate logistic regression analysis revealed significant differences in group, gender, PTA, ALT, AST, CR, and LDL-C between groups with and without seroconversion. Multivariate regression analysis demonstrated that dyslipidemia (OR = 1.993, Ρ = 0.038) and male gender (OR = 2.317, Ρ = 0.029) were risk factors associated with HBeAg seroconversion. During antiviral therapy, dyslipidemia affects HBeAg seroconversion in CHB patients treated with NAs, but does not affect the virological response.


Geographic variation and evolution in the life cycle of the witch-hazel leaf gall aphid, Hormaphis hamamelidis.
Two divergent life cycles associated with different elevations and latitudes have been documented for the witch-hazel leaf gall aphid, Hormaphis hamamelidis. At low elevation in northern Virginia, the aphid had seven distinct generations alternating between the primary host, witchhazel (Hamamelis virginiana), and a secondary host, river birch (Betula nigra). These findings confirm the original published life cycle description for the same locality. A second, abbreviated life cycle consisting of only three generations restricted to witch-hazel was discovered at high elevation (1000 m) in north central and northwestern Virginia. Aphids of both life cycles were sympatric at a middle elevation site. The life cycles and morphology suggest that the two forms are separate species. Although monoecious life cycles on primary hosts in aphids generally are thought to be ancestral to complex host-alternating ones, it is certainly possible that monoecious cycles are sometimes secondarily derived from complex cycles. By constructing a preliminary phylogeny of the described species in the tribe Hormaphidini, we propose that the abbreviated life cycle is derived from the complex one in the case of these witchhazel gall aphids. Our findings are discussed in the context of current theory regarding the evolutionary stability of complex life cycles.


Proximal dislocation of a sutureless Perceval valve after the second aortic valve replacement.
Sutureless aortic valve replacement is a widely used technique that facilitates short cross-clamping time and has excellent hemodynamic outcomes. However, it is associated with paravalvular leakage or migration risk. We report a surgical case using a sutureless aortic valve replacement in a 74-year-old male patient with a history of previous aortic valve replacement. He underwent redo aortic valve replacement with the Perceval valve (Corcym Canada Corp, Vancouver, Canada), which got dislocated with moderate-to-severe aortic paravalvular leakage at 3 months after implantation. Our observations suggested that redo aortic valve replacement using a sutureless aortic valve can cause valve dislocation as it might be difficult to clearly remove calcification and excess tissue and implant the valve to crimp on the annulus precisely. This report also highlights the challenges of performing repeat aortic valve replacement after explanting the Perceval valve, which includes the aortotomy height and annulus identification. Although the Perceval valve can help improve patient prognosis, careful implantation and thorough follow-up examinations are warranted.


Theileria annulata induced brisket oedema in a bull and its successful treatment.
In the present case, jugular vein engorgement and oedema of the brisket region which mimic the signs of pseudopericarditis due to theileriosis in a bull was reported. An adult Ongole crossbred bull with history of weakness, anorexia and oedema at brisket region was referred to Teaching Veterinary Clinical Complex, College of Veterinary Science, Proddatur. Physical examination revealed the presence of ticks over the body, right and left prescapular lymphadenopathy and oedema at brisket region. Blood examination revealed the presence of piroplasms in erythrocytes, schizont in lymphocytes, anaemia and lymphopenia. Bull was treated with injection buparvaquone along with supportive medications. By the 3rd week of therapy improvement was noticed by disappearance of brisket oedema and recurrence was not noticed during the 8 months of observation.


Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia.
Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are two well-characterized members of the silent information regulator 2 (Sir2) family of proteins. Both Sirt1 and Sirt3 have been shown to play vital roles in resistance to cellular stress, but the interaction between these two sirtuins has not been fully determined. In this study, we investigated the role of Sirt1-Sirt3 axis in blood-brain barrier (BBB) permeability after ischemia in vitro. Human brain microvascular endothelial cells and astrocytes were co-cultured to model the BBB in vitro and oxygen and glucose deprivation (OGD) was performed to mimic ischemia. The results of transepithelial electrical resistance (TEER) showed that suppression of Sirt1 via siRNA or salermide significantly decreased BBB permeability, whereas Sirt3 knockdown increased BBB permeability. In addition, Sirt1 was shown to regulate Sirt3 expression after OGD through inhibiting the AMPK-PGC1 pathway. Application of the AMPK inhibitor compound C partially prevented the effects of Sirt1-Sirt3 axis on BBB permeability after OGD. The results of flow cytometry and cytochrome c release demonstrated that Sirt1 and Sirt3 exert opposite effects on OGD-induced apoptosis. Furthermore, suppression of Sirt1 was shown to attenuate mitochondrial reactive oxygen species (ROS) generation, which contribute to the Sirt1-Sirt3 axis-induced regulation of BBB permeability and cell damage. In summary, these findings demonstrate that the Sirt1-Sirt3 axis might act as an important modulator in BBB physiology, and could be a therapeutic target for ischemic stroke via regulating mitochondrial ROS generation.


Left and right ventricular function after streptokinase reperfusion: assessment by gated blood pool scans.
Twenty-three patients with acute anterior or inferior myocardial infarction (AMI, IMI) were investigated by gated blood pool scans at a mean 4.9 h after reperfusion and 10 days later. Eighteen (78%) successful reperfusion cases were divided into two groups; reperfusion in less than 4 h (Rp less than 4 h, n = 9) and reperfusion in more than 4 h (Rp greater than 4 h, n = 9) from the onset of chest pain. As control group, gated blood pool scans were also performed in the early hours following infarction in an additional 42 patients who received conventional treatments. Rp less than 4 h demonstrated significant improvement of mean LVEF in AMI (from 39.5 +/- 3.3 to 50.3 +/- 3.1%, p less than 0.01) and IMI (from 54.6 +/- 4.3 to 60.4 +/- 5.8%, p less than 0.01). Improvement of initially abnormal segments was noticed in 68% of AMI and 65% of IMI by quantitative wall motion analysis, while Rp greater than 4 h showed only slight improvement of LVEF and regional wall motion compared to Rp less than 4 h. On the other hand, the control group showed no significant change in left ventricular performance and regional wall motion. In patients with AMI, RVEF remained within normal range. In IMI, whether reperfused or not, the RVEF showed moderate improvement. In conclusion, these studies indicated that the time of reperfusion and location of infarction may influence functional recovery after streptokinase reperfusion.


The Interaction Between Gender and Diabetes Mellitus in the Coronary Heart Disease Risk.
Cardiovascular disease (CVD) despite the advances in medical management keeps on as the primary cause of morbidity and mortality for both genders in Western societies. Sex differences though modify the clinical picture as well as the effectiveness of treatment. In this literature review article we searched publications in Englishlanguage on MEDLINE and the Cochrane Database from the beginning of the databases to January 2016. Among the specific key words and phrases we used were Diabetes Mellitus; Gender; Coronary artery disease; Stroke and Cardiovascular disease. Various studies have found that diabetic women have increased risk of coronary heart disease than their male counterparts; however, further research into this field has questioned this finding and there is much controversy among many researchers. Women have a different risk factor profile, are usually treated less effectively than men, and have a variance in the levels of sex hormones throughout their life which complicate the study and understanding of the mechanisms involved in insulin resistance, diabetes mellitus and cardiovascular risk profile. The connection between diabetes mellitus and cardiovascular disease is variable according to gender and further studies are needed to elucidate the lenient differentiations in gender specific hormones, risk factor profile, and therapeutic implications between genders.


Serum 25-hydroxyvitamin D is associated with reduced verbal episodic memory in healthy, middle-aged and older adults.
There is increasing evidence supporting an association of higher serum vitamin D concentration with better cognitive performance in older individuals. However, to date, consideration of the putative association between vitamin D and cognition has been based principally on studies investigating clinical participant samples manifesting vitamin D deficiency, particularly in older people. Moreover, relationships between vitamin D and cognition are typically not considered in the context of counter-regulatory calcium-modulating hormones or calcium homeostasis. Serum vitamin D/bioactive (ionised) calcium/parathyroid hormone homeostasis was considered in the context of cognitive performance in healthy, middle-aged and older individuals. A cross-sectional sample of 179 participants between the ages of 47-84 years was recruited for this study (114 females, 65 males). Participants provided fasting blood samples for analysis of serum 25-hydroxyvitamin D levels, ionised calcium (iCa) and parathyroid hormone (PTH) and completed cognitive measures of verbal episodic learning and memory. Serum 25-hydroxyvitamin D concentrations were negatively associated (with and without covariates of age, gender, depression and NART scores, iCa, and PTH) with measures of verbal episodic learning and memory, in particular with trial 5 of the Rey Auditory Verbal Learning Test (RAVLT) and long-delay free recall on the RAVLT. Overall, the findings from this study suggest an association between higher vitamin D status and poorer performance on verbal episodic memory in middle-aged and older individuals with normal vitamin D-calcium-PTH homeostasis. Despite requiring replication in other participant samples, this is a potentially important finding as it indicates that it may not be beneficial from a cognitive perspective to provide vitamin D supplements in individuals with already adequate vitamin D status.


Selective Laser Sintering 3-Dimensional Printing as a Single Step Process to Prepare Amorphous Solid Dispersion Dosage Forms for Improved Solubility and Dissolution Rate.
This study reports the development of ritonavir-copovidone amorphous solid dispersions (ASDs) and dosage forms thereof using selective laser sintering (SLS) 3-dimensional (3-D) printing in a single step, circumventing the post-processing steps required in common techniques employed to make ASDs. For this study, different drug loads of ritonavir with copovidone were processed at varying processing conditions to understand the impact, range, and correlation of these parameters for successful ASD formation. Further, ASDs characterized using conventional and advanced solid-state techniques including wide-angle X-ray scattering (WAXS), solid-state nuclear magnetic resonance (ssNMR), revealed the full conversion of the crystalline drug to its amorphous form as a function of laser-assisted selective fusion in a layer-by-layer manner. It was observed that an optimum combination of the powder flow properties, surface temperature, chamber temperature, laser speed, and hatch spacing was crucial for successful ASD formation, any deviations resulted in print failures or only partial amorphous conversion. Moreover, a 21-fold increase in solubility was demonstrated by the SLS 3-D printed tablets. The results confirmed that SLS 3-D printing can be used as a single-step platform for creating ASD-based pharmaceutical dosage forms with a solubility advantage.


Decadal variability in the occurrence of wintertime haze in central eastern China tied to the Pacific Decadal Oscillation.
Haze is a serious issue in China with increasing concerns, and understanding the factors driving decadal-scale variations in haze occurrence is relevant for government policymaking. Using a comprehensive observational haze dataset, we demonstrate notable decadal fluctuations in the number of haze days (HD) during winter in central eastern China, showing a decline since the mid-1980s. The leading mode of the wintertime HD features an increasing trend for 1959-2012 in eastern China, highly correlated with China's gross domestic product (GDP) that represents increasing trend of pollutant emissions, and to a lesser extent meteorological factors. The second mode shows decadal variations in central eastern China associated with Pacific Decadal Oscillation (PDO). Observations and numerical simulations suggest that Mongolia High and corresponding descending motion tend to be enhanced (weakened) in central eastern China during the positive (negative) phase of PDO. With PDO shifting towards a negative phase, the weakened Mongolia High and ascending anomalies make the air unstable and conduce to the spread of pollutants, leading to the decline in the wintertime HD over central eastern China since the mid-1980s. Based on above physical mechanisms, a linear model based on PDO and GDP metrics provided a good fit to the observed HD.


Carborane Substituents Promote Direct Electrophilic Insertion over Reduction-Metalation Reactions.
Two-electron reduction of 1,1'-bis(o-carborane) followed by reaction with [Ru(η-mes)Cl2 ]2 affords [8-(1'-1',2'-closo-C2 B10 H11 )-4-(η-mes)-4,1,8-closo-RuC2 B10 H11 ]. Subsequent two-electron reduction of this species and treatment with [Ru(η-arene)Cl2 ]2 results in the 14-vertex/12-vertex species [1-(η-mes)-9-(1'-1',2'-closo-C2 B10 H11 )-13-(η-arene)-1,13,2,9-closo-Ru2 C2 B10 H11 ] by direct electrophilic insertion, promoted by the carborane substituent in the 13-vertex/12-vertex precursor. When arene=mesitylene (mes), the diruthenium species is fluxional in solution at room temperature in a process that makes the metal-ligand fragments equivalent. A unique mechanism for this fluxionality is proposed and is shown to be fully consistent with the observed fluxionality or nonfluxionality of a series of previously reported 14-vertex dicobaltacarboranes.


Onset of alopecia areata after Epstein-Barr virus infectious mononucleosis.
The pathogenesis of alopecia areata (AA) is incompletely known. A positive family history in some points to a genetic predisposition, and discordance of the disease in identical twins suggests environmental triggers exist. We sought to determine whether the Epstein-Barr virus (EBV) is a possible environmental trigger for AA. We queried the National AA Registry for all patients who self-reported sudden onset of AA with concurrent EBV mononucleosis. Among the 6256 individuals registered between December 2001 and August 2007, 1586 patients reported an environmental trigger-including 12 individuals who had an EBV infection within 6 months before the onset of AA. This study relies on self-reported data, and not all medical records confirming EBV infections were available for review. The association between EBV and AA is worthy of further investigation.


Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles.
A single chain polypeptide containing the low density lipoprotein receptor (LDLR) ligand Seq-1 with blood-brain barrier (BBB) crossing activity has been successfully modified by conventional genetic engineering to self-assemble into stable protein-only nanoparticles of 30nm. The nanoparticulate presentation dramatically enhances in vitro, LDLR-dependent cell penetrability compared to the parental monomeric version, but the assembled protein does not show any enhanced brain targeting upon systemic administration. While the presentation of protein drugs in form of nanoparticles is in general advantageous regarding correct biodistribution, this principle might not apply to brain targeting that is hampered by particular bio-physical barriers. Irrespective of this fact, which is highly relevant to the nanomedicine of central nervous system, engineering the cationic character of defined protein stretches is revealed here as a promising and generic approach to promote the controlled oligomerization of biologically active protein species as still functional, regular nanoparticles.


Iatrogenic pseudoaneurysm rupture of the middle cerebral artery after an intracranial pressure monitor placement: a case report and literature review.
Thalamic hemorrhage (TH) is a devastating disease with a high mortality rate; however, no specific form of therapy has been proven to reduce mortality. Patients with hemorrhagic stroke undergo intracranial pressure (ICP) monitoring. However, cases involving pseudoaneurysms caused by ICP monitoring in patients with intracerebral hemorrhage have not been reported previously. Here, we report a case of pseudoaneurysm caused by an ICP monitor that was fitted due to hypertensive cerebral hemorrhage.


[mTOR/p70s6k signaling pathway is involved in megakaryocyte polyploidization].
To investigate the mechanisms of megakaryocyte polyploid cell cycle control. The expression and phosphorylation of mTOR/p70s6k pathway proteins was detected by western blot. Double-labeling techniques were used to investigate in which of the phase of the polyploid cell cycle S6K1 at Thr421/Ser424 are phosphorylated. Nocodazole induced a relatively synchronized polyploidization in Dami cells. The expression of mTOR and the phosphorylation of mTOR at Ser2448 increased when Dami cells begin to progress from G1 to S-phase in cell cycle. Analysis of flow cytometry showed that phosphorylation of S6K1 at Thr421/Ser424 increased at G2/M-phase. mTOR/S6K1 pathway is involved in megakaryocyte polyploid cell cycle control.


A self-checking treatment couch coordinate calculation system in radiotherapy.
Traditionally, the treatment couch coordinates (TCCs) for patients undergoing radiotherapy can only be determined at the time of treatment, placing pressure on the treating therapists and leaving several pathways for errors such as wrong-site treatment or wrong treatment table shift from a reference point. The purpose of this work is to propose an accurate, robust, and streamlined system that calculates TCC in advance. The proposed system combines the advantages of two different calculation methods that use an indexed immobilization device. The first method uses an array of reference ball bearings (BBs) embedded in the CT scanner's couch-top. To obtain the patient-specific TCC, the spatial offset of the treatment planning isocenter from the reference BB is used. The second method performs a calculation using the one-to-one mapping relationship between the CT scanner's DICOM (Digital Imaging and Communications in Medicine) coordinate system and the TCC system. Both methods use a reference point in the CT coordinate system to correlate a point in the TCC system to perform the coordinate transfer between the two systems. Both methods were used to calculate the TCC and the results were checked against each other, creating an integrated workflow via automated self-checking. The accuracy of the calculation system was retrospectively evaluated with 275 patients, where the actual treatment position determined with cone-beam CT was used as a reference. An efficient workflow transparent to the therapists at both CT simulation and treatment was created. It works with any indexed immobilization device and can be universally applied to all treatment sites. The two methods had comparable accuracy, with 95% of the calculations within 3 mm. The inter-fraction variation was within ± 1.0 cm for 95% of the coordinates across all the treatment sites. A robust, accurate, and streamlined system was implemented to calculate TCCs in advance. It eases the pressure on the treating therapists, reduces patient setup time, and enhances the patient safety by preventing setup errors.


Sex differences in suicidal ideation in a community sample from China.
In a large sample of over 4,000 Chinese residents in the Wuling and Sino-Vietnamese border regions of China, females had a higher incidence of ever wishing that they were dead. This sex difference was found regardless of marital status, age, and occupation.


Patch enlargement of the aortic valve ring by extending the aortic incision into the anterior mitral leaflet. New operative technique.
This communication describes a new surgical procedure of enlarging the narrow aortic valve ring by extending the aortic incision through the fibrous origin of the aortic leaflet of the mitral valve into this leaflet. A fusiform patch is sutured to the V-shaped defect in the aortic leaflet of the mitral valve and in the aortic anulus. This procedure permits the replacement of the aortic valve by a suitable prosthesis. Between June of 1976 and February of 1978, eight patients underwent this surgical procedure. At the time of operation the patients were between 8 and 50 years old. The estimated enlargement of the aortic root ranged from 10 to 25 mm. The operative technique is described, peculiarities of this method are discussed, and the results are reported. Six to 27 months following operation, the clinical condition of six patients is good. Four patients show no impairment of mitral valve function. In one case, preoperatively diagnosed mitral incompetence persists. In another patient the pericardial patch broke from the aortic leaflet of the mitral valve, so that the valve had to be replaced on the fourth postoperative day. One patient died of myocardial necrosis because of insufficient myocardial protection during operation. One child with acute aortic insufficiency caused by staphylococcal endocarditis and congestive heart failure died of septicemia 3 months postoperatively. Mitral incompetence was not detectable in this child.


Distribution, parabrachial region projection, and coexistence of neuropeptide and catecholamine cells of the nucleus of the solitary tract in the pigeon.
The chemical nature of the cells of the nucleus of the solitary tract (NTS) that project to the parabrachial nucleus (PB) was investigated in the pigeon by the use of fluorescent bead retrograde tracer and immunofluorescence for the detection of substance P (SP), leucine-enkephalin (LENK), cholecystokinin (CCK), neurotensin (NT), somatostatin (SS), and tyrosine hydroxylase (TH). Cells immunoreactive for CCK were located in subnuclei lateralis dorsalis pars anterior (LDa) and medialis superficialis pars posterior, and caudal NTS (cNTS); 22-26.5% of these cells were double-labeled bilaterally. Immunoreactive SP cells were found in ventral NTS subnuclei; 24-25% of these cells were double-labeled bilaterally. Cells immunoreactive for LENK and NT were concentrated in the anterior NTS; 5.5-7.5% of the LENK cells were double-labeled bilaterally, while 11% (ipsilateral) and 21% (contralateral) of the NT immunoreactive cells were double-labeled. Many SS immunoreactive cells were found in peripherally located subnuclei; 5.5-6.5% of these cells were double-labeled bilaterally. Catecholamine cells were distributed in LDa, peripheral subnuclei, and cNTS; 23% of these cells were double-labeled ipsilaterally and 8.5% contralaterally. A two-color double-labeling immunofluorescence technique revealed many cells immunoreactive for both NT and LENK, only a rare cell immunoreactive for both SS and SP, and no cells immunoreactive for both TH and SP. Cells immunoreactive for SP, CCK, NT, and TH are major contributors to NTS projections to PB. The confinement of these substances to specific NTS subnuclei, which receive visceral sensory information from specific organs, may contribute to the chemical encoding of ascending visceral information.


Deep Phenotyping and Prediction of Long-term Cardiovascular Disease: Optimized by Machine Learning.
Prediction of cardiovascular disease (CVD) is important in clinical practice. Machine learning (ML) may offer an improved alternative to current CVD risk stratification in individual patients. We aim to identify important predictors and compare ML models with traditional models according to their prediction performance in a large long-term follow-up cohort. The Atherosclerosis Risk in Communities (ARIC) study was designed to study the progression of subclinical disease to cardiovascular events over a 25-year follow-up period. All phenotypic variables at visit 1 were obtained. All-cause death, CVD, and coronary heart disease were the outcomes for analysis. The ML framework involved variable selection using the random survival forest (RSF) method, model building, and 5-fold cross-validation. Model performance was evaluated by discrimination using the Harrell concordance index (C-index), accuracy using the Brier score (BS), and interpretability using the number of variables in the model. Of the 14,842 participants in ARIC, the average age was 54.2 years, with 45.2% male and 26.2% Black participants. Thirty-eight unique variables were selected in the RSF top 20 importance ranking of all 6 outcomes. Aging, hypertension, glucose metabolism, renal function, coagulation, adiposity, and sodium retention dominated the predictions of all outcomes. The ML models outperformed the regression models and established risk scores with a higher C-index, lower BS, and varied interpretability. The ML framework is useful for identifying important predictors of CVD and for developing models with robust performance compared with existing risk models.


Synergistic Effect of a Physiological Ratio of Estradiol and Testosterone in the Treatment of Early-stage Atherosclerosis.
Clinical trials and epidemiological data suggest that estrogen replacement therapy (ERT) fails to reduce cardiovascular events in postmenopausal women with coronary heart disease (CHD). The high concentration of estrogen supplementation may increase the risk of thrombosis and result in testosterone deficiency, which is considered the main reason for failure. Thus, we hypothesized that a physiologic dosage of estradiol combined with testosterone may become a new therapeutic strategy in postmenopausal women with CHD. We used human umbilical vein endothelial cells (HUVECs) and female C57BL/6 mice as the experimental subjects. With the HUVECs, we found an appropriate E2/T ratio of 5:1 (5×10(-8) mol/L estradiol and 10(-8) mol/L testosterone), which has a significant anti-apoptotic effect on HUVECs by inducing a C-reactive protein. In the in vivo study, we verified the beneficial effects of the defined appropriate E2/T ratio in mice with early stage atherosclerosis. We found that replacement therapy with the defined appropriate E2/T ratio had beneficial effects of reducing the lipid lesions, reducing the formation of foam cells, reducing endothelial injury, modulating the coagulation system function and inhibiting inflammation and was significantly more effective than either estradiol or testosterone supplementation alone. The present study demonstrated that estradiol and testosterone have a synergistic effect on early stage atherosclerosis, and replacement therapy with the defined appropriate E2/T ratio can significantly suppress the development of atherosclerosis through reducing the lipid lesions, reducing the formation of foam cells, reducing endothelial injury, modulating the coagulation system function and inhibiting inflammation.