Reactivation of Epstein-Barr virus-specific cytotoxic T cells by in vitro stimulation with the autologous lymphoblastoid cell line.
Unfractionated mononuclear (UM) cells and T cells freshly prepared from the blood of adult donors were co-cultivated in microtest plate wells with progressively lower numbers of cells from the autologous EB-virus-transformed B-cell line. The fresh cells present in co-cultures from EB virus antibody-negative (seronegative) donors regularly facilitated autologous cell line outgrowth, monitored after 4 weeks, whereas outgrowth was markedly inhibited in the corresponding co-cultures from seropositive donors. Larger-scale co-cultures, set up at a ratio of 80-100 fresh UM cells to one autologous virus-transformed B cell, were harvested after 8 to 12 days and the T-cell subpopulation was examined for cytotoxicity both by growth inhibition and by chromium release assays. Cytotoxic T cells were generated exclusively in seropositive donor co-cultures and were strongly active against the autologous virus-transformed cell line without affecting either autologous uninfected B cells or any of a range of EB virus genome-negative target cell lines chosen as sensitive indicators of non-specific cytotoxicity. Recognition of allogeneic EB-virus-transformed cells was restricted to those whose HLA-A and/or B and/or B and/or C antigen expression matched that of the effector cells themselves;; moreover target cell lysis was specifically inhibited in the presence of monoclonal antibodies binding to these HLA antigens. The results indicate that EB-virus-specific HLA-restricted memory T cells, present in the blood of previously-infected individuals, can be reactivated in vitro using the established autologous virus-transformed cell line as a stimulus. THe reactivated cytotoxic cells appear to recognize a virus-induced lymphocyte-detected membrane antigen, LYD-MA, analogous to that first invoked to explain the cytotoxic response to primary EB virus infection observed during infectious monoucleosis.


Public health leadership "Transformation of dreams to reality".
This oration examines the multifaceted nature and skills of leadership in the field of public health from the eyes of public health practitioner. Through diverse examples from personal and professional experiences, the oration debunks common misconceptions surrounding leadership and underscores its capacity to motivate and steer individuals or groups towards a shared vision. It challenges the notion that leaders must possess all-encompassing knowledge, instead emphasizing the significance of traits such as courage, confidence, strategic thinking, and collaboration. Moreover, the oration also delves into the question of whether leadership is an innate quality or one that can be acquired through experience and training, recognizing that while some individuals exhibit inherent leadership qualities, others develop them over time. Throughout the article, the author shares his personal and professional journey in public health leadership, recounting formative experiences ranging from serving as a class representative to working in rural areas and marginalized communities. These encounters at various levels, encompassing departmental, institutional, national, and international, enabled the author to apply leadership attributes such as empathy, effective communication, teamwork, and change management to affect positive transformations in healthcare utilisation. The article summarises the fact that leadership is a continuous (not abstract) variable which is present in everyone, albeit, in different proportions and that, it can be acquired by persistence and perseverance.


Scanning electron microscope and intragingival microorganisms in periodontal diseases.
During the past two decades there has been an increased understanding of bacterial invasion as a pathogenic mechanism of periodontal diseases. Scanning Electron Microscope (SEM) has played a key role in supporting the idea that bacterial invasion may be another pathogenic mechanism in periodontal disease. This has been due to the fact that SEM has a larger depth of focus and better resolving power than the Light Microscope (LM) and also allows for observation of rather large areas of tissue showing in depth the surface of the sample. This review deals with information obtained by using SEM as the fundamental method in studying and specifically identifying microorganisms within gingival tissues. New methodology using correlative microscopy for rapidly identifying invasive bacteria of periodontal tissues is discussed.


Screening for breast cancer.
Strong evidence supports the value of breast cancer screening with mammography, and high-quality mammography screening can be considered a major public health achievement. As noted earlier in the discussion about the evaluation of service screening, the group of women who did not participate in mammographic screening in the decades after screening had been introduced had essentially unchanged or only minor improvements in mortality compared with the pattern before the introduction of screening, despite widespread use of adjuvant chemotherapy or hormonal therapy. Breast cancer should be treated in its preclinical phase if we are to save the lives of women with this disease, and a considerable body of evidence outlines best practices that, with broader adherence, would result in greater breast cancer mortality reductions than have been observed to date.


Human epididymis protein 4 as a new diagnostic biomarker for rheumatoid arthritis-associated interstitial lung disease.
This study aimed to evaluate the role of human epididymis protein 4 (HE4) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. HE4 levels in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) samples were determined via electrochemiluminescence immunoassays in 102 RA patients (46 patients with ILD and 56 patients without ILD) and 51 healthy controls (HCs). Serum HE4 levels were significantly higher in RA-ILD patients (141.8±65.92 pmol/l) than those in the RA-no ILD patients (82.67±26.17 pmol/l) and healthy controls (35.72±7.6 pmol/l) (p<0.0001). Consistent with serum HE4 levels, BALF HE4 levels were significantly higher in RA-ILD patients (637.6±154.9 pmol/l) than those in the RA-no ILD patients (427.3±111.2 pmol/l) and healthy controls (206.9±30.46 pmol/l) (p<0.0001). In RA-ILD patients, HE4 levels were positively correlated with HRCT (high-resolution computed tomography) fibrosis scores, whereas a significant inverse relationship was found between HE4 levels and lung function parameters (such as, diffusion capacity of the lung for carbon monoxide (DLCO)). The logistic regression analysis showed that high levels of BALF HE4 (≥595 pmol/l) were associated with RA-ILD (odds ratio [OR] =8.09; 95% confidence interval [CI] =1.317-49.682; p=0.024). Serum and BALF HE4 levels were elevated in RA-ILD patients and strongly associated with the severity of ILD, thus supporting their potential clinical value as a new diagnostic aid for patients with RA-ILD.


Anticipated synchronization in coupled inertial ratchets with time-delayed feedback: a numerical study.
We investigate anticipated synchronization between two periodically driven deterministic, dissipative inertial ratchets that are able to exhibit directed transport with a finite velocity. The two ratchets interact through a unidirectional delay coupling, one is acting as a master system while the other one represents the slave system. Each of the two dissipative deterministic ratchets is driven externally by a common periodic force. The delay coupling involves two parameters, the coupling strength and the (positive-valued) delay time. We study the synchronization features for the unbounded, current carrying trajectories of the master and the slave, respectively, for four different strengths of the driving amplitude. These in turn characterize differing phase space dynamics of the transporting ratchet dynamics, regular, intermittent and a chaotic transport regime. We find that the slave ratchet can respond in exactly the same way as the master will respond in the future, thereby anticipating the nonlinear directed transport.


[The effect of Kuka mineral water on blood coagulability and fibrinolysis in patients with chronic pyelonephritis].
Chronic pyelonephritis (CP) is now ranking first among renal disorders, its incidence still tends to grow. Despite an impressive antibacterial armory, the efficacy of CP treatment remains low. In search of more effective and tolerable methods, the author directed his attention to CP balneotherapy. In addition to well-known health resorts where CP is successfully treated, Zheleznovodsk and Truskavets, a less known place is mentioned. It is the spa Kuka in the Transbaikal region. Mineral water Kukinskaya or Kuka (pH 6.18) comprises carbon dioxide, hydrocarbon-calcium and magnesium hydrocarbonates. The spa treatment was given to 65 CP patients. They underwent a general examination and evaluation of hemostasis. It was found that oral treatment with Kukinskaya mineral water produced a positive action on the blood coagulability and fibrinolysis. After the crenotherapy the pain persisted in 11.8%, leukocyturia in 9.9%, nephrogenic hypertension in 16.4% of the patients only. This proves the method effective for CP.


Structure and electrochromism of two-dimensional octahedral molecular sieve h'-WO3.
Octahedral molecular sieves (OMS) are built of transition metal-oxygen octahedra that delimit sub-nanoscale cavities. Compared to other microporous solids, OMS exhibit larger versatility in properties, provided by various redox states and magnetic behaviors of transition metals. Hence, OMS offer opportunities in electrochemical energy harnessing devices, including batteries, electrochemical capacitors and electrochromic systems, provided two conditions are met: fast exchange of ions in the micropores and stability upon exchange. Here we unveil a novel OMS hexagonal polymorph of tungsten oxide called h'-WO3, built of (WO6)6 tunnel cavities. h'-WO3 is prepared by a one-step soft chemistry aqueous route leading to the hydrogen bronze h'-H0.07WO3. Gentle heating results in h'-WO3 with framework retention. The material exhibits an unusual combination of 1-dimensional crystal structure and 2-dimensional nanostructure that enhances and fastens proton (de)insertion for stable electrochromic devices. This discovery paves the way to a new family of mixed valence functional materials with tunable behaviors.


Characterization of architecture signals in proteins.
A quantitative, property-based approach to protein sequence analysis is presented, grounded in Fourier analysis and signal-processing methodologies. The resulting tools are applied to four protein structure families. We demonstrate the existence of architecture-specific, large amplitude periodicities in amino acid properties encoded in the sequences of proteins. These signals, whose statistical significance we establish, occur at well-defined wavenumbers, but are expressed in different physical properties in the various proteins which fold to a common architecture. This result explains the long-known convergence of unrelated sequences to a common fold. It is further suggested that these results provide a physical basis for the experimental observation that unrelated sequences that adopt similar architectures fold with similar rates.


Rumination Mediates the Relationship between Infant Temperament and Adolescent Depressive Symptoms.
This study examined prospective associations between negative emotionality, rumination, and depressive symptoms in a community sample of 301 youths (158 females) followed longitudinally from birth to adolescence. Mothers reported on youths' negative emotionality (NE) at age 1, and youths self-reported rumination at age 13 and depressive symptoms at ages 13 and 15. Linear regression analyses indicated that greater NE in infancy was associated with more depressive symptoms at age 15, even after controlling for child gender and depressive symptoms at age 13. Moreover, analyses indicated that rumination significantly mediated the association between infancy NE and age 15 depressive symptoms in the full sample. When analyzed separately by gender, however, rumination mediated the relationship between NE and depressive symptoms for girls but not for boys. The results confirm and extend previous findings on the association between affective and cognitive vulnerability factors in predicting depressive symptoms and the gender difference in depression in adolescence, and suggest that clinical interventions designed to reduce negative emotionality may be useful supplements to traditional cognitive interventions for reducing cognitive vulnerability to depression.


Association of Pelvic and Para-Aortic Lymphadenectomy With Survival in Stage I Endometrioid Endometrial Cancer: Matched Cohort Analyses From the National Cancer Database.
To estimate whether pelvic and para-aortic lymphadenectomy was associated with increased survival in stage I endometrioid endometrial cancer. We performed matched cohort analyses of women with stage I endometrioid endometrial cancer who underwent hysterectomy with no lymphadenectomy, pelvic lymphadenectomy, or combined pelvic and para-aortic lymphadenectomy. Cox proportional hazards survival analyses were performed with inverse probability weights. Hazard ratios (HRs) were covariate and propensity score adjusted. Covariates included cancer center type, age, race, Hispanic ethnicity, insurance type, community median income quartile, comorbidity score, history of prior cancer, depth of myometrial invasion, tumor grade, tumor size, lymphovascular space invasion, cytology status, surgical margin status, hospital volume, and use of adjuvant radiotherapy or chemotherapy. Additional analyses included subset analyses by grade, sensitivity analyses with imputation of missing data, and testing for sensitivity to possible unmeasured confounding. Median (interquartile range [IQR]) lymph node counts were 0, 10 (5-15), and 20 (15-27) nodes in the no lymphadenectomy, pelvic, and combined pelvic and para-aortic lymphadenectomy-matched cohorts, respectively. Matched cohorts were well balanced. Two analyses were performed: no lymphadenectomy (n = 7,487) versus pelvic lymphadenectomy (n = 7,487), and pelvic lymphadenectomy (n = 7,060) versus combined pelvic and para-aortic lymphadenectomy (n = 7,060). Performance of pelvic lymphadenectomy was associated with increased survival compared with no lymphadenectomy (5-year survival [95% CI], 91.4% [90.2% to 92.6%] v 87.3% [85.9% to 88.8%]; HR, 0.71 [95% CI, 0.64 to 0.78]; P < .001). Addition of para-aortic lymphadenectomy was associated with increased survival compared with pelvic lymphadenectomy alone (5-year survival [95% CI], 91.0% [89.8% to 92.2%] v 89.8% [88.4% to 91.1%]; HR, 0.85 [95% CI, 0.77 to 0.95]; P = .003). Associations were robust to sensitivity analyses. Lymphadenectomy was associated with increased survival in stage I endometrioid endometrial cancer. An adequately powered randomized trial is needed.


Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency.
The lysosomal catabolism of sulfatide requires arylsulfatase A and a specific sphingolipid activator protein, SAP-1. While most patients with metachromatic leukodystrophy have mutations in the gene for arylsulfatase A, some patients have deficient SAP-1, as determined by immunological techniques. We now describe the molecular findings in a patient who died at 22 years of age with SAP-1 deficiency. The DNA polymerase chain reaction was used to amplify regions of cDNA which were subcloned in M13 phage DNA and sequenced by the dideoxy chain-termination method. The patient was found to have a 33-base-pair insertion between nucleotides 777 and 778 (numbered from the A of the ATG initiation codon). No other changes were found in the coding sequence of the cDNA from this patient. At the site of the insertion some normal people have an additional 9 base pairs, which correspond to the last 9 nucleotides at the 3' end of the insertion. The cDNAs from the second-cousin parents were amplified and sequenced, and in both two alleles were identified, one with the 33-base-pair insertion and one with no insertion. Two brothers were found to have only the normal alleles and a sister was found to have the 33-base-pair insertion and a normal allele. The findings confirm studies performed on leukocyte extracts demonstrating normal antigen levels in the two brothers and a lower level in the sister. The presence of 11 additional amino acids in the coding region of mature SAP-1 in this patient causes significant changes in the hydropathy profile compatible with the previous findings at the protein level.


Callous-unemotional traits and antisocial behavior among adolescents: the role of self-serving cognitions.
Self-serving cognitions and callous-unemotional traits play important roles in adolescent antisocial behavior. The objective of this study was to cross-sectionally explore the mediating role of self-serving cognitions in the relationship between callous-unemotional traits and antisocial behavior. A sample of 972 high-school students completed self-report questionnaires assessing callous-unemotional traits, self-serving cognitive distortions and antisocial behavior. Two competing models exploring indirect effects accounting for the relationships between self-serving cognitive distortions, callous-unemotional traits and antisocial behaviors were tested. Both models revealed significant indirect effects, suggesting both pathways are possible. Gender was found to moderate these models. These findings suggest the importance of targeting self-serving cognitions in therapeutic interventions and increase our understanding of the role of self-serving cognitions in antisocial behavior.


Spraying Zinc Sulfate to Reveal the Mechanism through the Glutathione Metabolic Pathway Regulates the Cadmium Tolerance of Seashore Paspalum (Paspalum vaginatum Swartz).
Cadmium (Cd) is considered to be one of the most toxic metals, causing serious harm to plants' growth and humans' health. Therefore, it is necessary to study simple, practical, and environmentally friendly methods to reduce its toxicity. Until now, people have applied zinc sulfate to improve the Cd tolerance of plants. However, related studies have mainly focused on physiological and biochemical aspects, with a lack of in-depth molecular mechanism research. In this study, we sprayed high (40 mM) and low (2.5 mM) concentrations of zinc sulfate on seashore paspalum (Paspalum vaginatum Swartz) plants under 0.5 mM Cd stress. Transcriptome sequencing and physiological indicators were used to reveal the mechanism of Cd tolerance. Compared with the control treatment, we found that zinc sulfate decreased the content of Cd2+ by 57.03-73.39%, and that the transfer coefficient of Cd decreased by 58.91-75.25% in different parts of plants. In addition, our results indicate that the antioxidant capacity of plants was improved, with marked increases in the glutathione content and the activity levels of glutathione reductase (GR), glutathione S-transferase (GST), and other enzymes. Transcriptome sequencing showed that the differentially expressed genes in both the 0.5 Zn and 40 Zn treatments were mainly genes encoding GST. This study suggests that genes encoding GST in the glutathione pathway may play an important role in regulating the Cd tolerance of seashore paspalum. Furthermore, the present study provides a theoretical reference for the regulation mechanism caused by zinc sulfate spraying to improve plants' Cd tolerance.


Interleukin 17A gene polymorphism rs2275913 is associated with osteitis after the Bacillus Calmette-Guérin vaccination.
Interleukin-17 (IL-17) appears to promote the host's defence against mycobacterial infections. This study evaluated the association between IL17A gene polymorphism and the risk of Bacillus Calmette-Guérin (BCG) osteitis after newborn vaccination and between IL17A gene polymorphism and IL-17A concentrations in serum. IL17A rs2275913 gene polymorphisms and serum IL-17A concentrations were studied in 132 adults aged 21-49 years from across Finland, who had BCG osteitis in infancy after a newborn BCG vaccination. The subjects were recruited in 2007-2008, and their whole-blood samples were sent to the National Institute for Health and Welfare, Turku, Finland. Their genotypes and minor allele frequencies were compared with 405 population-based unvaccinated controls aged two to three months from a prospective birth cohort study. The genotypes and allele frequencies of IL17A rs2275913 differed significantly between the former BCG osteitis patients and controls. The genotype was variant in 75.8% of cases and 64.0% of controls (p = 0.012), and the minor allele frequency was 50.0% in the cases and 41.6% of the controls (p = 0.009). Serum IL-17 concentrations did not differ significantly between the cases with wild or variant genotypes. IL17A rs2275913 gene polymorphism was associated with a risk of BCG osteitis after vaccination.


NFAT targets signaling molecules to gene promoters in pancreatic β-cells.
Nuclear factor of activated T cells (NFAT) is activated by calcineurin in response to calcium signals derived by metabolic and inflammatory stress to regulate genes in pancreatic islets. Here, we show that NFAT targets MAPKs, histone acetyltransferase p300, and histone deacetylases (HDACs) to gene promoters to differentially regulate insulin and TNF-α genes. NFAT and ERK associated with the insulin gene promoter in response to glucagon-like peptide 1, whereas NFAT formed complexes with p38 MAPK (p38) and Jun N-terminal kinase (JNK) upon promoters of the TNF-α gene in response to IL-1β. Translocation of NFAT and MAPKs to gene promoters was calcineurin/NFAT dependent, and complex stability required MAPK activity. Knocking down NFATc2 expression, eliminating NFAT DNA binding sites, or interfering with NFAT nuclear import prevented association of MAPKs with gene promoters. Inhibiting p38 and JNK activity increased NFAT-ERK association with promoters, which repressed TNF-α and enhanced insulin gene expression. Moreover, inhibiting p38 and JNK induced a switch from NFAT-p38/JNK-histone acetyltransferase p300 to NFAT-ERK-HDAC3 complex formation upon the TNF-α promoter, which resulted in gene repression. Histone acetyltransferase/HDAC exchange was reversed on the insulin gene by p38/JNK inhibition in the presence of glucagon-like peptide 1, which enhanced gene expression. Overall, these data indicate that NFAT directs signaling enzymes to gene promoters in islets, which contribute to protein-DNA complex stability and promoter regulation. Furthermore, the data suggest that TNF-α can be repressed and insulin production can be enhanced by selectively targeting signaling components of NFAT-MAPK transcriptional/signaling complex formation in pancreatic β-cells. These findings have therapeutic potential for suppressing islet inflammation while preserving islet function in diabetes and islet transplantation.


Acute appendicitis complicated with necrotizing fasciitis in a patient with adult-onset Still's disease: A case report.
Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown etiology characterized by evanescent salmon-pink rash, spiking fever, arthralgia/ arthritis, and lymphadenopathy. AOSD sometimes was fatal when it is complicated by macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH). Nonetheless, the literature provides no recommendations for treatment of AOSD patients with severe sepsis. A previously healthy 65-year-old man with history of AOSD was referred to our hospital for persistent right lower quadrant abdominal pain for 2 days. One week later, an abdominal wall abscess and hematoma developed by extravasation from the inferior epigastric vessels, complicated by necrotizing fasciitis of the right thigh and groin region. To our best knowledge, this case was the first reported case of a perforated appendix complicated with necrotizing fasciitis in a patient with AOSD. The patient was diagnosed as acute appendicitis complicated with necrotizing fasciitis and abdominal wall abscess. This case received intravenous tigecycline injection and daily 10 mg prednisolone initially, and shifted to daily intravenous hydrocortisone 200 mg for suspected MAS or HLH. This patient underwent surgical intervention and debridement for necrotizing fasciitis. The patient's symptoms progressed worse rapidly. He died from cytomegalovirus viremia and bacterial necrotizing fasciitis complicated by septic shock. (1) The steroid dose was difficult to titrate when AOSD complicated by sepsis. The differential diagnosis from MAS/HLH with bacterial/viral infection related severe sepsis was difficult but critical for decision making from clinicians and rheumatologists. (2) The conservative treatment with antibiotics for perforated appendix is safe but has a higher failure rate in immunocomprised patients such as systemic lupus erythematosus and AOSD. Early surgical intervention might contribute to better outcome. (3) The abdominal wall abscess can be spread from intra-abdominal lesion through the inferior epigastric vessels which were as weak points of abdominal wall. Imaging examinations contribute to acute diagnosis and help surgeons perform surgical interventions to prevent morbidity and mortality.


A Brazilian Portuguese cross-cultural adaptation of the modified JOA scale for myelopathy.
To develop a version of the modified Japanese Orthopaedic Association (mJOA) scale that had been translated into Portuguese and cross-culturally adapted for the Brazilian population. The well-established process of forward-backward translation was employed along with cross-cultural adaptation. Three bilingual translators (English and native Portuguese) performed the forward translation of the mJOA scale from English to Portuguese based on iterative discussions used to reach a consensus translation. The translated version of the mJOA scale was then back-translated into English by a native English-speaking translator unaware of the concepts involved with the mJOA scale. The original mJOA scale and the back-translated version were compared by a native North American neurosurgeon, and as they were considered equivalent, the final version of the mJOA scale that had been translated into Portuguese and cross-culturally adapted was defined. To facilitate global and cross-cultural comparisons of the severity of cervical myelopathy, this study presents a version of the mJOA scale that was translated into Portuguese and cross-culturally adapted for the Brazilian population.


Quantitative and qualitative characteristics of blood cells in black-shouldered, Brahminy, and black kites.
Black-shouldered kites (BSK, Elanus caeruleus), Brahminy kites (BrK, Haliastur indus), and black kites (BK, Milvus migrans govinda) are medium-sized hawks found in Thailand, and little is known about the hematology of these three kite species. This study reports basic hematologic values and describes the light microscopic, cytochemical, and ultrastructural characteristics of blood cells in these kites. Blood samples were collected from 113 healthy kites (50 BSKs, 53 BrKs, and 10 BKs) from January 2012 to December 2017. Complete blood cell counts, cytochemical staining (Sudan black B, peroxidase [PO], periodic acid-Schiff, α-naphthyl acetate esterase, and β-glucuronidase), and transmission electron microscopy were performed using standard methods. Hematology, morphometry, and cytochemical staining patterns of blood cells were tabulated. BSK erythrocytes were smaller than BrK and BK erythrocytes. Heterophils, the largest granulocytes, were the most prevalent leukocytes in all kites. Cytochemical reactions in blood cells from these three kite species were the same, except that heterophils from BrKs were the only cells positive for PO. The ultrastructure of heterophil and eosinophil granules from the BSKs were similar in their homogeneous electron densities but differed in shape. The eosinophil granules from BrKs and BKs revealed heterogeneous electron densities with central pallor in some granules. Basophils had different granular electron densities, and some granules were electron-lucent. The 23 baseline hematologic values and morphologic, cytochemical, and ultrastructural characteristics of all blood cell types in this study provide reference data for future kite healthcare.


Quantum walks on the N-cycle subject to decoherence on the coin degree of freedom.
For a discrete time quantum walk (QW) on the N-cycle, allowing for decoherence on the coin, we derive a number of results, including an explicit formula for the position probability distribution. For a QW of this type, we show that the mixing behavior tends, in the long run, to a uniform distribution regardless of the initial state of the system and irrespective of the parity of the number of nodes N. These results confirm the findings of previous authors who arrived at similar conclusions through extensive numerical simulations. In particular, we infer that the mixing time M(epsilon) for the time-averaged probability distribution is of order no greater than O(N2/).


High-dose versus low-dose tranexamic acid for paediatric craniosynostosis surgery: a double-blind randomised controlled non-inferiority trial.
Tranexamic acid (TXA) reduces blood loss and transfusion in paediatric craniosynostosis surgery. The hypothesis is that low-dose TXA, determined by pharmacokinetic modelling, is non-inferior to high-dose TXA in decreasing blood loss and transfusion in children. Children undergoing craniosynostosis surgery were enrolled in a two-centre, prospective, double-blind, randomised, non-inferiority controlled trial to receive high TXA (50 mg kg-1 followed by 5 mg kg-1 h-1) or low TXA (10 mg kg-1 followed by 5 mg kg-1 h-1). Primary outcome was blood loss. Low dose was determined to be non-inferior to high dose if the 95% confidence interval (CI) for the mean difference in blood loss was above the non-inferiority margin of -20 ml kg-1. Secondary outcomes were transfusion, TXA plasma concentrations, and biological markers of fibrinolysis and inflammation. Sixty-eight children were included. Values were non-inferior regarding blood loss (39.4 [4.4] vs 40.3 [6.2] ml kg-1 [difference=0.9; 95% CI: -14.2, 15.9]) and blood transfusion (21.3 [1.6] vs 23.6 [1.5] ml kg-1 [difference=2.3; 95% CI: -2.1, 6.7]) between high-dose (n=32) and low-dose (n=34) groups, respectively. The TXA plasma concentrations during surgery averaged 50.2 (8.0) and 29.6 (7.6) μg ml-1. There was no difference in fibrinolytic and inflammatory biological marker concentrations. No adverse events were observed. Tranexamic acid 10 mg kg-1 followed by 5 mg kg-1 h-1 is not less effective than a higher dose of 50 mg kg-1 and 5 mg kg-1 h-1 in reducing blood loss and transfusion in paediatric craniosynostosis surgery. NCT02188576.


Changes in the adrenergic effects and membrane activity of the circular muscle of rat uterus during late pregnancy and postpartum.
Circular muscle strips of rat uterus were obtained in the morning on Days 21 and 22 of pregnancy, and on the first postpartum day. Changes in the effects of noradrenaline and isoprenaline due to pregnant stage and incubation period in vitro were investigated, taking the contractile response and membrane activity as indicators. Plateau potential was dominant in Day 21 and postpartum preparations, and spike potential on Day 22. Noradrenaline (3 X 10(-7), 10(-6) M) caused excitation in Day 21 and postpartum preparations, whereas it caused inhibition in Day 22 preparations during early exposure to Krebs solution. When contractile potentiation was caused, plateau potential was prolonged, and when contractile depression was caused the plateau potential was suppressed. By incubation in vitro with Krebs solution, a transformation of the effect of noradrenaline from excitation to inhibition was caused in Day 21 preparations, and from strong to weak inhibition in Day 22 preparations. Isoprenaline of 3 X 10(-10) M concentration markedly depressed the contractile response in Day 22 preparations, whereas 10(-8) M isoprenaline was not enough to suppress the spontaneous contractions in postpartum preparations.


[The case of a patient with peritoneal metastasis from cholangiocarcinoma who responded to adoptive immunotherapy and cetuximab].
A 59-year-old female patient underwent pancreaticoduodenectomy because of bile duct cancer 4 years before the first consultation at our clinic. Because the resected bile duct margin was positive, radiation therapy was administered to the hepatic hilum, 5-fluorouraci(l 5-FU) was continuously infused, and S-1 was administered as adjuvant therapy. Three years later, cancer of the uterine body was diagnosed. At the time of hysterectomy, nodules were observed in the Douglas pouch. Biopsy confirmed the presence of peritoneal metastasis from cholangiocarcinoma (hospital A). At the time of the first consultation, ascites was observed. Symptoms improved after the administration of bevacizumab( Bmab) and gemcitabine (GEM), but recurred after 7 months. The patient was admitted to hospital B because of impaired gastrointestinal passage and massive ascites. OK-432-combined adoptive immunotherapy, in which lymphocytes from the removed ascites were cultured and transferred into the abdominal cavity after OK-432 treatment, was performed. Examination of the specimen resected in hospital A indicated that it was strongly positive for epidermal growth factor receptor (EGFR), and hence, cetuximab( Cmab) was administered both at admission and after discharge. Cmab alone was continued and the tumor marker levels normalized. The patient is currently healthy at 7 years after the onset of peritoneal recurrence (5.5 years after the initiation of Cmab therapy).


Superinduction of the human interferon-beta promoter.
Superinduction, that is induction with simultaneous blocking of mRNA translation, enhances the induction of interferon-beta in response to virus or double-stranded RNA in human fibroblasts. Expression of the cloned IFN-beta gene upon transfer into heterologous cells reflects the endogeneous interferon expression with respect to induction or superinduction indicating the involvement of cellular mediators in this mode of gene regulation. Expression from gene hybrids in mouse Mo57/2 cells reveals that 5' flanking DNA sequences from the human IFN-beta gene are responsible for induction and superinduction. Superinduction of the human IFN-beta promoter is demonstrated in several rodent and primate cell lines. In addition, expression from promoter mutants in mouse cells indicates that DNA sequences responsible for induction and superinduction are identical.


Teacher's Autonomy Support and Engagement in Math: Multiple Mediating Roles of Self-efficacy, Intrinsic Value, and Boredom.
Previous studies have highlighted the impacts of environmental factors (teacher's autonomy support) and individual factors (self-efficacy, intrinsic value, and boredom) on academic engagement. This study aimed to investigate these variables and examine the relations among them. Three structural equation models tested the multiple mediational roles of self-efficacy, intrinsic value, and boredom in the relation between teacher's autonomy support and behavioral, emotional, and cognitive engagement, respectively, in math. A total of 637 Chinese middle school students (313 males, 324 females; mean age = 14.82) voluntarily participated in this study. Results revealed that self-efficacy, intrinsic value, and boredom played important and mediating roles between perceived teacher's autonomy support and student engagement. Specifically, these three individual variables partly mediated the relations between perceived teacher's autonomy support and behavioral and cognitive engagement, while fully mediating the relation between perceived teacher's autonomy support and emotional engagement. These findings complement and extend the understanding of factors affecting students' engagement in math.


Prepatent detection of Fasciola gigantica infection in bovine calves using metacercarial antigen.
Metacercarial antigen of Fasciola gigantica was evaluated for early immunodiagnosis of experimental bovine fasciolosis using ELISA and Western blot. In ELISA, the experimental F. gigantica infection was detected as early as 2 weeks post-infection (WPI). The gradual increasing trend of antibody level was observed from 2 to 7 WPI, followed by a plateau, which was maintained up to 14 WPI. In Western blot, sera from experimentally infected calves recognized one distinct polypeptide of 21 kDa in fractionated metacercarial antigen as early as 10th day post infection. From 2 WPI, more polypeptide bands were reacting. Recognition of these protein bands persisted till the end of the experiment (14 WPI). Cattle sera collected from the field showed 34.5% seroprevalence of fasciolosis by ELISA using MAg. Comparative immunoblot studies of metacercarial antigen with anti-Gigantocotyle explanatum and anti-Paramphistomum epiclitum sera revealed that 21 and 25 kDa polypeptides of metacercarial antigen did not cross-react with any of these sera and appear to be unique to F. gigantica and having the desirable qualities of early and specific immunodiagnosis.


[Clinical, diagnostic and therapeutic aspects of congenital anophthalmos].
This study was aimed at elucidating the diagnostic potentialities of computer-aided tomography (CAT) in congenital micro- and anophthalmia. Twenty-five young patients with various clinical manifestation of this abnormality were examined. Used in complex with the traditional diagnostic methods, CAT played the key role. It permitted imaging the entire complex of changes in the orbit and its contents, which helped choose adequate therapeutic measures. Surgical treatment was proven to be little effective or useless at all in cases with a more than 4 cm3 deficit of the orbital volume on the involved side; contrary to this, early staged fitting with prostheses is effective and creates favorable conditions for subsequent surgical correction in a less than 4 cm3 deficit of the volume.


An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92.
The Eastern Cooperative Oncology Group conducted a Phase I trial to determine the maximally tolerated doses of combination therapy with alpha interferon (IFN-alpha) and all-trans-retinoic acid (tRA). Fifty patients with incurable malignancies received IFN-alpha administered subcutaneously three times weekly, and tRA administered by mouth at bedtime. Doses were escalated between patient groups, starting at tRA dose level of 45 mg/m2 and 3 million units of IFN-alpha. Major, dose-limiting toxicities were attributable to either the tRA (rash, chelitis) or IFN (constitutional symptoms), and were observed only at tRA dose levels of 224 mg/m2 and 291 mg/m2, or 6 million units of IFN-alpha. The maximally tolerated dose level of 172.5 mg/m2 of tRA and 3 million units of IFN-alpha was well-tolerated, with no grade 3 or 4 toxicities attributable to therapy. One patient at the third dose level (75 mg/m2 of tRA and 3 million units of IFN-alpha) developed acute hepatic and renal failure and a metabolic encephalopathy of unclear etiology. We conclude that tRA and IFN-alpha may be safely administered together at the maximally tolerated dose of tRA as a single agent without unexpected side effects. The recommended doses of IFN-alpha and tRA for Phase II trials are 3 million units of IFN-alpha and 172.5 mg/m2 of tRA.


Fabrication of two-dimensional nanosheets via water freezing expansion exfoliation.
Layered materials, if exfoliated effectively, will exhibit several unique properties, offering great potential for diverse applications. To this end, in this study, we develop a novel, universal, and environmentally friendly method named as 'water freezing expansion exfoliation' for producing two-dimensional nanosheets. This method exploits the expansion in the volume of water upon freezing. When the water freezing expansion condition is reproduced in layered materials, the layers exfoliate to overcome the van der Waals force between them. The expansion process is performed by repeated cycling between 4 °C and -20 °C to effectively exfoliate layered materials of graphite, hexagonal boron nitride (h-BN), MoS2 and WS2. Systematic characterization of the samples thus obtained using electron microscopy and optical studies substantiate the formation of thin flakes (graphene, h-BN, MoS2, and WS2 nanosheets). The method demonstrated in this study is cost-effective and does not demand sophisticated equipment and stringent high temperature conditions. Given this general applicability, this method holds great promise for exfoliating layered materials that are sensitive to elevated temperature.


Computational FEM Model, Phantom and Ex Vivo Swine Breast Validation of an Optimized Double-Slot Microcoaxial Antenna Designed for Minimally Invasive Breast Tumor Ablation: Theoretical and Experimental Comparison of Temperature, Size of Lesion, and SWR, Preliminary Data.
Malignant neoplasms are one of the principal world health concerns and breast cancer is the most common type of cancer in women. Advances in cancer detection technologies allow treating it in early stages; however, it is necessary to develop treatments which carry fewer complications and aesthetic repercussions. This work presents a feasibility study for the use of microwave ablation as a novel technique for breast cancer treatment. A microwave applicator design is also being proposed for this purpose. The coupling of the designed antenna was predicted with computer simulation. The standing wave ratio obtained through simulation was 1.87 and the result of experimental validation was 1.04. The optimized antenna has an optimal coupling (SWR = 1.04) so ablation temperatures can be achieved in a relatively short time using low power. Varying the time and power, the heating pattern can be changed to treat different tumors. However, as some discrepancies are still present, a deeper study of the dielectric properties and their variation with temperature is required.


A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice.
The purpose of this double-blind, multicenter trial was to compare the efficacy and safety of sertraline (50-150 mg/day) with those of citalopram (20-60 mg/day) in patients with major depression in general practice during 24 weeks of treatment. The patients were assessed using the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales. Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale. Altogether 400 patients were randomized into the study. A total of 308 patients completed the 24-week study in accordance with the protocol. A significant reduction in the total Montgomery-Asberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks, with no statistically significant differences between the drugs. In the intention to treat-last observation carried forward analysis 76% responded to treatment in the sertraline and 81% in the citalopram group. The final mean doses were 82 mg/day (64% higher than baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in the citalopram group. The response rate in completers in accordance with protocol was 90% in the sertraline group and 93% in the citalopram group. The side-effects were those usually seen, and both sertraline and citalopram were considered to be well tolerated. It was concluded that patients with major depression in general practice respond well to 24 weeks of treatment with sertraline or citalopram. With regard to efficacy, no statistically significant differences were found between the drugs.


Aggregation of Mod5 is affected by tRNA binding with implications for tRNA gene-mediated silencing.
Mod5 is a multifunctional protein that modifies a subset of tRNAs in the cytoplasm and is also required for an RNA-mediated form of transcriptional silencing. Previous in vivo studies have shown that the nuclear silencing function of Mod5 does not require that the causative tRNA gene encode a Mod5 substrate, although Mod5 is still required. However, previous data have not directly tested whether Mod5 can directly bind substrate and nonsubstrate RNAs. We herein demonstrate that Mod5 directly binds to both substrate and nonsubstrate RNAs, including a highly structured, non-tRNA sequence (5S-rRNA), consistent with previous in vivo data. Furthermore, we show that some RNAs drastically change the aggregation behavior of Mod5 with implications for tRNA gene-mediated silencing.


The impact of waiting time and comorbid conditions on the survival benefit of kidney transplantation.
Longer waiting times may limit the survival benefit of kidney transplantation in older patients or those with a high burden of comorbid disease. We performed a longitudinal study of mortality among 63,783 transplant candidates who started dialysis between April 1995 and December 2000. We determined the relative risk (RR) of death and increase in life expectancy among subjects who received a first deceased donor transplant after different waiting times compared to subjects who had equivalent waiting times but remained on dialysis. Transplant recipients had a lower long-term RR of death and the risk reduction was greatest in recipients with longer waiting times (RR of death 12 months after transplantation for recipients with waiting times of 0, 1, 2, 3 years was 0.49, 0.43, 0.38, 0.34, P = 0.0006). The average increase in life expectancy in transplant recipients was 9.8 years and was lower in older recipients and recipients with comorbid conditions. Increased waiting times from 1 to 3 years only moderately decreased the overall survival benefit of transplantation from 7.1 to 5.6 years, and all subjects derived a survival benefit from transplantation with waiting times up to 3 years. These findings do not support limiting access to transplantation for otherwise suitable candidates on the basis of longer anticipated waiting times.


[Description of a case of acute neurological toxicity after DTIC-adriamycin-vincristine therapy (author's transl)].
A case of acute neurological toxicity was observed in a patient with a retroperitoneal fibromyxosarcoma treated with DTIC (NSC-45382), Adriamycin and Vincristine. The neurological symptoms started one hour after drug administration and rapidly declined with symptomatic therapy: no EEG and scintigraphic changes were detectable. The case is discussed in relation to central nervous system complications reported by other authors, following administration of DTIC and Adriamycin.


A systematic scoping review evaluating sugar-sweetened beverage taxation from a systems perspective.
Systems thinking can reveal surprising, counterintuitive or unintended reactions to population health interventions (PHIs), yet this lens has rarely been applied to sugar-sweetened beverage (SSB) taxation. Using a systematic scoping review approach, we identified 329 papers concerning SSB taxation, of which 45 considered influences and impacts of SSB taxation jointly, involving methodological approaches that may prove promising for operationalizing a systems informed approach to PHI evaluation. Influences and impacts concerning SSB taxation may be cyclically linked, and studies that consider both enable us to identify implications beyond a predicted linear effect. Only three studies explicitly used systems thinking informed methods. Finally, we developed an illustrative, feedback-oriented conceptual framework, emphasizing the processes that could result in an SSB tax being increased, maintained, eroded or repealed over time. Such a framework could be used to synthesize evidence from non-systems informed evaluations, leading to novel research questions and further policy development.


Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth.
We have investigated the neurite growth-stimulating properties of euxanthone, a xanthone derivative isolated from the Chinese medicinal plant Polygala caudata. Euxanthone was shown to exert a marked stimulatory action on neurite outgrowth from chick embryo dorsal root ganglia explanted in collagen gels, in the absence of added neurotrophins. It was also shown to promote cell survival in explanted chick embryo ganglia, and to stimulate neurite outgrowth from isolated adult rat primary sensory neurons in vitro. The further finding that euxanthone stimulates neurite outgrowth from explants of chick embryo retina and ventral spinal cord suggests an action on signaling pathways downstream of neuronal receptors for specific neurotrophic factors. Consistent with this, euxanthone did not promote neurite outgrowth from non-transfected PC12 cells, or from PC12 cells transfected with TrkB or TrkC, under conditions in which these cells extended neurites in response to, respectively, the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3. Western blot analysis of euxanthone-stimulated dorsal root ganglion explants showed that expression of phospho-mitogen-activated protein (MAP) kinase was up-regulated after 1 h of euxanthone-treatment. Inhibition of the MAP kinase pathway using PD98059, a specific inhibitor of MAP kinase kinase, blocked all euxanthone-stimulated neurite outgrowth. However, analysis of phospho-Akt expression indicated that the phosphatidylinositol-3 kinase-Akt pathway, another major signaling pathway engaged by neurotrophins, is not significantly activated by euxanthone. These results suggest that euxanthone promotes neurite outgrowth by selectively activating the MAP kinase pathway.


Structure-activity of three phospholipid analogues towards inhibition of phospholipase A2 in macrophages.
At concentrations 1-20 microns in culture medium of rat peritoneal macrophages which were stimulated with ionophore A23187, the phospholipid analogues 1-decyl-2-octyl-glycerophosphocholine and 1-dodecyl-2-octanamido-2-deoxy glycerophosphocholine were found more potent inhibitors than 1-octyl-2-deoxy glycerophosphocholine to lower the phospholipase A2 activities. The inhibitory effect was measured by [3H] eicosatetraenoic acid ([3H]20:4) release in macrophages and extracellular fluids and synthesis of [3H] eicosanoids after incubation of macrophages with traces of the molecular species of lecithin 1-octadecanoyl-2-[3H] eicosatetraenoyl glycerophosphocholine. The three phospholipid analogues developed higher inhibitory effects than mepacrine, dexamethasone or bromophenacyl bromide, at corresponding concentrations in medium.


Delayed aortic rupture following perforating trauma.
The immediate death rate for aortic rupture caused by pointed and sharp-edged instruments is very high; however, delayed aortic rupture following the trauma is rarely reported. A patient who had an upper abdominal stab wound was sent to our hospital, and an emergency exploratory laparotomy was performed. No traumatic aortic rupture was found at that time. However, on the fifth day after surgery, aortic rupture occurred, and a large retroperitoneal hematoma was formed. The patient eventually died. Aortic rupture was confirmed by a second emergency exploratory laparotomy and the autopsy. The information from exploratory laparotomies, post-operative observations and treatments, medical imaging reports, and reasons for delayed aortic rupture, as well as the underlying pathophysiological processes, are discussed in this case report.


Fibromyalgia and nutrition, what do we know?
Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.


Individual and familial predictors of impairment in childhood anxiety disorders.
To determine which correlates of childhood anxiety disorders are predictive of impaired functioning as judged by clinicians. Seventy-four families of children with anxiety disorders attending a hospital outpatient clinic completed questionnaires measuring child symptoms of anxiety and depression, maternal psychopathology, maternal ratings of child psychopathology, and developmental and environmental difficulties. Clinicians completed the Global Assessment of Functioning (GAF) for each child, and correlations between it and the other measures were ascertained. Maternal ratings of child conduct problems, child symptoms of depression, maternal phobic anxiety, developmental difficulties, and psychosocial adversity were significantly correlated with GAF. Results of a multiple regression analysis revealed that these variables accounted for 25% of the variance in GAF scores. The first four variables were significant predictors of impairment in children with phobic disorders. Psychosocial adversity was the only significant predictor of impairment in children with generalized anxiety disorder. In addition to child depression and developmental or psychosocial adversity, impairment in childhood anxiety disorders appears to be related to parental anxiety and behavior management difficulties, particularly in phobic disorders. Addressing the latter factors may enhance treatment efficacy.


Multiple facets of laticifer cells.
In the latex-bearing plants, the laticiferous system is the tubing structure that contains the latex and is constituted of living cells (laticifers). While laticifers are present only in a small percentage of the flowering plant species, they represent a type of specialized tissue within the plant where a myriad of metabolites are synthesized, some of them of considerable commercial importance. In this mini-review we synopsize the present knowledge about laticifer cells and discuss about their particular features as well as some evolutionary and ecophysiological cues and the potential exploitation of the knowledge generated around this peculiar type of plant cell. We illustrate some of these questions with the experience in Euphorbia lathyris laticifers and latex.


Premature ventricular complexes: therapeutic dilemmas and decisions.
Adult subjects with high-grade VEA have an increased risk of sudden death. In all likelihood, the risk reflects a predisposition to VF with concomitant but possibly independently caused VEA. Among patients sustaining acute myocardial infarction, the severity of VEA late after infarction appears to depend primarily on the extent of underlying coronary artery disease and the extent of tissue damage sustained, as does the likelihood of sudden death. It is not yet clear whether suppression of one manifestation of severe coronary artery disease, namely VEA, confers protection against more serious manifestations - particularly sudden death. Although increased mortality among patients with and without overt coronary artery disease is associated with high-grade VEA and although the absolute frequency of PVCs is strongly correlated with severity defined with conventional classification schemes, frequent, unifocal PVCs in the absence of high-grade VEA appear to carry only a small associated risk of sudden death [56]. Furthermore, even though early PVCs may be particularly hazardous soon after the onset of acute myocardial infarction, they do not appear to be malignant during the hospital phase or among ambulatory patients with or without coronary artery disease. The temptation to suppress even low-grade VEA is strong because even a single PVC can initiate VF in the ischemic heart, and it is of course possible that suppression could prevent a single PVC from occurring after the onset of ischemia and initiating VF. However, suppression of PVCs, even if successful in an ambulatory patient, will not necessarily suppress VEA initiated by a new bout of ischemia. Accordingly, based on currently available information, low-grade VEA does not require treatment in our view in ambulatory patients without specific indications.


Influence of peas (Pisum sativum) as a dietary ingredient and flavomycin supplementation on the performance and intestinal microflora of broiler chicks.
1. Two experiments were carried out to study the effects of diets containing various concentrations of pea meal (Pisum sativum L.), with or without flavomycin supplementation, on the performance and intestinal microflora of broiler chicks. 2. During the 7 to 28-d period, chicks fed on diets containing 300, 600 and 800 g pea meal/kg consumed more food and gained more weight than chicks receiving a maize-isolated soyabean protein control diet. The addition of flavomycin to the diets had similar effects on the performance of both the control and the pea groups. 3. Pea diets, with and without supplemental flavomycin, had little influence on the composition of intestinal microflora. The counts of enterococci in the small intestine and Clostridium perfringens and coliforms in the caeca of pea-fed chicks exceeded those of control chicks.


Memory cytolytic T-lymphocytes: induction, regulation and implications for vaccine design.
The design of vaccines that protect against intracellular infections or cancer remains a challenge. In many cases, immunity depends on the development of antigen-specific memory CD8+ T-cells that can express cytokines and kill antigen-bearing cells when they encounter the pathogen or tumor. Here, the authors review current understanding of the signals and cells that lead to memory CD8+ T-cell differentiation, the relationship between the primary CD8+ T-cell response and the memory response and the regulation of memory CD8+ T-cell survival and function. The implications of this new knowledge for vaccine design are discussed, and recent progress in the development of lipidated peptide vaccines as a promising approach for vaccination against intracellular infections and cancer is reviewed.


A transistor based air flow transducer for thermohygrometric control of neonatal ventilatory applications.
An air flow transducer for controlling heated humidifiers used in neonatal artificial ventilation, suitable for in-line application in monopatient breathing circuits, is described here. The sensor is built with two nominally identical bipolar junction transistors, with different packages, as hot elements operated at a regulated constant voltage. The operation principle is based on the differential convective heat power exchanged with the fluid stream due to the different thermal conductivities of the transistors' packages. The underlying theory is described in mathematical terms and the theoretical model is validated with experimental data in the mass flow rate range from 4 to 215 mg s(-1). The nonlinear behavior allows sensitivities from -5 mV/(mg s(-1)) at flow rates in the range of 4-130 mg s(-1) to -2 mV/(mg s(-1)) at higher flow rates up to 215 mg s(-1). The linear range extends from 40 to 130 mg s(-1), with constant sensitivity equal to -5 mV/(mg s(-1)). The differential nature of the output allows to obtain repeatabilities in the order of 2% for fluid temperatures between 20 and 25 degrees C and of about 6% if the fluid temperature lies in the range of 15-35 degrees C. The relatively long time constant, in the order of 20+/-5 s, makes the sensor suitable for average flow rate measurements. Using the sensor's output as a control variable of a heated humidifier for artificial ventilation, the relative humidity of gases varies by only 20% in the flow rate range of the sensor (from 95% to 75%), whereas the same parameter shows a variation of about 40% (from 100% to 60%) with the same humidifier without flow control.


Use of National Institute for Health and Care Excellence head injury guidelines among patients with delayed presentation after head trauma can lead to missed traumatic brain injury: a 5-year institutional review.
In 2014, traumatic brain injury (TBI) caused 3 million ER visits, hospitalizations, and deaths in the US. The National Institute for Health and Care Excellence (NICE) guidelines, initially generated using data from patients presenting within 24 h of head trauma, are used to determine the need for head computed tomography (CT) scan in patients after 24 h. The authors wanted to determine the proportion of CT scans for head trauma performed at our center in late presenters (>24 h after head trauma), the incidence of intracranial pathology in early (24 h) versus late (>24 h) presenters, and the sensitivity of the NICE guidelines for TBI in these two subpopulations. A retrospective chart review was conducted at a tertiary care center in Karachi. All people (>16) who had a head CT for head trauma from 2010 to 2015 were included. Age, sex, primary diagnosis, comorbid disorders, mechanism-of-injury, duration (in hours) from head trauma to presentation, site, and extent of injury (injury severity scale), hospital stay, number and details of surgical procedures, CT scan findings, other injuries, and mortality were recorded. Means were compared using the Independent Sample t-test, while categorical variables were compared using χ2. Multivariate logistic regression analyses were used to identify TBI predictors. The authors found 2009 eligible patients; seven were excluded due to incomplete medical records. The final statistical analysis comprised 2002 head trauma patients. Overall, 52% of early and late presenters had severe injuries, and 2.3% died. 32.2% of patients with head trauma had CT after 24 h. Early presenters were 46.7% traumatized, while late presenters were 63%. The NICE guidelines were 93% sensitive for early presenters and 83% for late presenters with traumatic intracranial injury. Patients coming to the emergency department after 24 h of head trauma are a large proportion of the overall head trauma population. The NICE guidelines for late-presenting head injuries are less sensitive and may overlook intracranial injuries if imaging is not performed.


Mechanism of catabolite repression of tryptophanase synthesis in Escherichia coli.
Repression of tryptophanase (tryptophan indole-lyase) by glucose and its non-metabolizable analogue methyl alpha-glucoside has been studied employing a series of isogenic strains of Escherichia coli lacking cyclic AMP phosphodiesterase and altered for two of the proteins of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), Enzyme I and Enzyme IIAGlc. Basal activity of tryptophanase was depressed mildly by inclusion of glucose in the growth medium, but inducible tryptophanase synthesis was subject to strong glucose repression in the parental strain, which exhibited normal PTS enzyme activities. Methyl alpha-glucoside was without effect in this strain. Loss of Enzyme I decreased sensitivity to repression by glucose but enhanced sensitivity to repression by methyl alpha-glucoside. Loss of Enzyme IIAGlc activity largely abolished repression by methyl alpha-glucoside but had a less severe effect on glucose repression. The repressive effects of both sugars were fully reversed by inclusion of cyclic AMP in the growth medium. Tryptophan uptake under the same conditions was inhibited weakly by glucose and more strongly by methyl alpha-glucoside in the parental strain. Inhibition by both sugars was alleviated by partial loss of Enzyme I. Inhibition by methyl alpha-glucoside appeared to be largely due to energy competition and was not responsible for repression of tryptophanase synthesis. Measurement of net production of cyclic AMP as well as intracellular concentrations of cyclic AMP revealed a good correlation with intensity of repression. The results suggest that while basal tryptophanase synthesis is relatively insensitive to catabolite repression, inducible synthesis is subject to strong repression by two distinct mechanisms, one dependent on enzyme IIAGlc of the PTS and the other independent of this protein. Both mechanisms are attributable to depressed rates of cyclic AMP synthesis. No evidence for a cyclic-AMP-independent mechanism of catabolite repression was obtained.


Epstein-Barr virus (EBV)-associated epithelial and non-epithelial lesions of the oral cavity.
Epstein-Barr virus (EBV) is known to be associated with the development of malignant lymphoma and lymphoproliferative disorders (LPDs) in immunocompromised patients. EBV, a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, as well as various pathological types of lymphoid malignancy. Furthermore, EBV is associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC), salivary gland tumor, gastric carcinoma and breast carcinoma. In terms of oral disease, there have been several reports of EBV-related oral squamous cell carcinoma (OSCC) worldwide. However, the role of EBV in tumorigenesis of human oral epithelial or lymphoid tissue is unclear. This review summarizes EBV-related epithelial and non-epithelial tumors or tumor-like lesions of the oral cavity. In addition, we describe EBV latent genes and their expression in normal epithelium, inflamed gingiva, epithelial dysplasia and SCC, as well as considering LPDs (MTX- and age-related) and DLBCLs of the oral cavity.


Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance.
The rise of antibiotic resistance necessitates the search for new platforms for drug development. Prodrugs are common tools for overcoming drawbacks typically associated with drug formulation and delivery, with ester prodrugs providing a classic strategy for masking polar alcohol and carboxylic acid functionalities and improving cell permeability. Ester prodrugs are normally designed to have simple ester groups, as they are expected to be cleaved and reactivated by a wide spectrum of cellular esterases. However, a number of pathogenic and commensal microbial esterases have been found to possess significant substrate specificity and can play an unexpected role in drug metabolism. Ester protection can also introduce antimicrobial properties into previously nontoxic drugs through alterations in cell permeability or solubility. Finally, mutation to microbial esterases is a novel mechanism for the development of antibiotic resistance. In this review, we highlight the important pathogenic and xenobiotic functions of microbial esterases and discuss the development and application of ester prodrugs for targeting microbial infections and combating antibiotic resistance. Esterases are often overlooked as therapeutic targets. Yet, with the growing need to develop new antibiotics, a thorough understanding of the specificity and function of microbial esterases and their combined action with ester prodrug antibiotics will support the design of future therapeutics.


Effects of very small doses of urine on acceleration and delay of sexual maturation in female house mice.
Four types of chemosignal donors were used: adult intact males, grouped adult intact females, pregnant females and lactating females. A daily dose of 0.001 ml urine was sufficient to produce the same degree of acceleration or delay known to occur with whole urine from each donor type. With 0.00001 ml the age of puberty did not differ from that of water-treated controls for any of the treatments. With the intermediate, 0.0001 ml/day dose, the results were variable, depending upon the donor type. The results indicate that for young mice daily exposure to extremely small quantities of urine can influence the physiological events accelerating or delaying puberty.


Accumulation of altered aspartyl residues in erythrocyte proteins from patients with Down's syndrome.
Spontaneous protein deamidation of labile Asn residues, generating L-isoaspartates and D-aspartates, is associated with cell aging and is enhanced by an oxidative microenvironment; to minimize the damage, the isoaspartate residues can be 'repaired' by a specific L-isoaspartate (D-aspartate) protein O-methyltransferase (PIMT). As both premature aging and chronic oxidative stress are typical features of Down's syndrome (DS), we tested the hypothesis that deamidated proteins may build up in trisomic patients. Blood samples were obtained from children with karyotypically confirmed full trisomy 21 and from age-matched healthy controls. Using recombinant PIMT as a probe, we demonstrated a dramatic rise of L-isoaspartates in erythrocyte membrane proteins from DS patients. The content of D-aspartate was also significantly increased. The integrity of the repair system was checked by evaluating methionine transport, PIMT specific activity, and intracellular concentrations of adenosylmethionine and adenosylhomocysteine. The overall methylation pathway was directly monitored by incubating fresh red blood cells with methyl-labeled methionine; a three-fold increase of protein methyl esters was detected in trisomic children. Deamidated species include ankyrin, band 4.1, band 4.2 and the integral membrane protein band 3; ankyrin and band 4.1 were significantly hypermethylated in DS. When DS red blood cells were subjected to oxidative treatment in vitro, the increase of protein deamidation paralleled lipid peroxidation and free radical generation. We observed a similar pattern in Epstein-Barr virus B-lymphocytes from trisomic patients. In conclusion, our findings support the hypothesis that protein instability at asparagine sites is a biochemical feature of DS, presumably depending upon the oxidative microenvironment. The possible pathophysiological implications are discussed.


Seasonal variation in vitamin D levels in the Canterbury, New Zealand population in relation to available UV radiation.
The optimal plasma 25-hydroxyvitamin D (25(OH)D) concentration is probably >75 nmol/L but in temperate regions lower levels are common. Few studies report the intensity of solar ultraviolet (UV) radiation when 25(OH)D is measured. We measured plasma 25(OH)D and incident solar UVB radiation in Christchurch and modelled the relationship between them. 25(OH)D, total calcium (CaT), ionised calcium (CaI) and parathyroid hormone (PTH) were measured in healthy volunteers (119 female, 82 male; median age 45 years, range 18 to 83) between February and July 2004. Vitamin D-weighted UV energy measurements (dUV) for Christchurch were from the National Institute of Water and Atmospheric Research (NIWA) UV Atlas. In February 2004, 88% of 25(OH)D levels were below 75 nmol/L, increasing to 100% in June and July. Severe deficiency (<12.5 nmol/L) was found in 1.5% of subjects. From February to July, 25(OH)D and CaI fell and CaT rose (p<0.001,<0.01, and <0.001). There was a hyperbolic relationship between PTH and 25OHD while CaT and CaI correlated negatively with PTH (r=-0.30 and -0.33; both p<0.001). Monthly mean dUV intensity ranged from 10 kJ m-2 day-1 in Dec 2003 to 0.5 kJ m-2 day-1 in June 2004. Compartmental modelling estimated that a Christchurch person made 1200 IU/day of vitamin D in mid-summer but only 60 IU/day in midwinter. Daily supplements of 1450 or 2600 IU vitamin D3 are predicted to raise the annual minimum mean plasma 25(OH)D to 75 or 100 nmol/L respectively. Most Christchurch people are vitamin D deficient most of the time and a daily supplement of 2600 IU vitamin D3 would correct this.


Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA.
Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine-glycine-glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA forms an intramolecular G quadruplex structure, which is bound with high affinity and specificity by the FMRP RGG box. We determined that hydrophobic interactions are important in the FMRP RGG box-MAP1B RNA association, with minor contributions from electrostatic interactions. Our findings that at low protein:RNA ratios the RNA G quadruplex structure is slightly stabilized, whereas at high ratios is unfolded, suggest a mechanism by which the FMRP concentration variation in response to a neurotransmitter stimulation event could act as a regulatory switch for the protein function, from translation repressor to translation activator.


Donor-derived Transmission of Hepatitis A Virus Following Kidney Transplantation: Clinical Course of Two Cases From One Donor.
Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.


Investigation on influence of Wurster coating process parameters for the development of delayed release minitablets of Naproxen.
The present work aims at studying process parameters affecting coating of minitablets (3 mm in diameter) through Wurster coating process. Minitablets of Naproxen with high drug loading were manufactured using 3 mm multi-tip punches. The release profile of core pellets (published) and minitablets was compared with that of marketed formulation. The core formulation of minitablets was found to show similarity in dissolution profile with marketed formulation and hence was further carried forward for functional coating over it. Wurster processing was implemented to pursue functional coating over core formulation. Different process parameters were screened and control strategy was applied for factors significantly affecting the process. Modified Plackett Burman Design was applied for studying important factors. Based on the significant factors and minimum level of coating required for functionalization, optimized process was executed. Final coated batch was evaluated for coating thickness, surface morphology, and drug release study.


Distribution of orthodontic services in Norway.
There is a lack of studies that have evaluated how different ways of organizing and financing orthodontic services perform with respect to access to care, and the cost of care. In Norway, orthodontic services for children and adolescents are partly financed by the state, and the size of the state subsidy depends on the severity of the malocclusion. Orthodontists have the freedom to establish a practice where they wish. The aim of this study was to examine whether there are inequalities with respect to access to orthodontic services in Norway, and to study the development of costs of the services from 2004 to 2007. Data on mean waiting time for starting treatment and working hours in practice were collected using a questionnaire that was sent to all the orthodontists in the country (n = 165). The response rate was 74%. The number of patients who received treatment according to different criteria of need was recorded from data in each practice. Information about the development of costs for orthodontic treatment was obtained from the National Insurance Administration. In almost all the areas, waiting time for starting treatment was within clinically acceptable limits, and there were only small differences in supply of orthodontic treatment in different areas. Patients with the greatest need were given priority over patients with the least need, which is in line with the aims of the authorities. In 2007 the reimbursements for orthodontic treatment from the National Insurance Administration amounted to Euro 48 million. In deflated prices this was virtually the same amount as in 2004. Our results show that the combination of public funding and freedom to establish a practice ensures that services are available for the individuals who are most in need of treatment. The authorities also have control over costs. The experiences from the orthodontic services in Norway are useful for policymakers in other countries. In particular, an important finding is that an orthodontic service where the state subsidy depends on the severity of the malocclusion can secure both equal access to the services and contain costs.


Isolation and characterization of novel mutations in the pSC101 origin that increase copy number.
pSC101 is a narrow host range, low-copy plasmid commonly used for genetically manipulating Escherichia coli. As a byproduct of a genetic screen for a more sensitive lactam biosensor, we identified multiple novel mutations that increase the copy number of plasmids with the pSC101 origin. All mutations identified in this study occurred on plasmids which also contained at least one mutation localized to the RepA protein encoded within the origin. Homology modelling predicts that many of these mutations occur within the dimerization interface of RepA. Mutant RepA resulted in plasmid copy numbers between ~31 and ~113 copies/cell, relative to ~5 copies/cell in wild-type pSC101 plasmids. Combining the mutations that were predicted to disrupt multiple contacts on the dimerization interface resulted in copy numbers of ~500 copies/cell, while also attenuating growth in host strains. Fluorescent protein production expressed from an arabinose-inducible promoter on mutant origin derived plasmids did correlate with copy number. Plasmids harboring RepA with one of two mutations, E83K and N99D, resulted in fluorescent protein production similar to that from p15a- (~20 copies/cell) and ColE1- (~31 copies/cell) based plasmids, respectively. The mutant copy number variants retained compatibility with p15a, pBBR, and ColE1 origins of replication. These pSC101 variants may be useful in future metabolic engineering efforts that require medium or high-copy vectors compatible with p15a- and ColE1-based plasmids.


An earthworm-like microrobot for colonoscopy.
Miniature robotics for colonoscopy has become a hot research topic with the development of minimally invasive surgery (MIS). In this paper, a novel microrobot for colonoscopy that operates based on a simulation of the squirming motion of the earthworm is described. The robot uses a unique driving unit called a linear electromagnetic driver. The prototype measures 9.5 mm in diameter and 120 mm in length. It is driven by a linear direct current (DC) motor designed and manufactured by the authors. This paper describes the prototype, locomotion principle, and control system in detail. It then describes two models that were built to study the robot's ability to move in the viscoelastic colon environment. A slepe model of motion was developed and some mathematical evaluations of locomotion conditions were conducted. Experiments to test the creeping ability of the prototype on a slope were performed to verify these expressions. From the viscoelastic model relative to acting force between the robot and the colon, a transcendent equation about locomotive efficiency of the critical squirm step was deduced and solved to instruct the design of the robot. Last, in vitro experiments in the fresh colon of a pig were performed. The results show that this kind of microrobot can propel itself freely and reliably in the soft viscoelastic colon. Finally, future areas of research are noted.


MicroRNA-182 prevents vascular smooth muscle cell dedifferentiation via FGF9/PDGFRβ signaling.
The abnormal phenotypic transformation of vascular smooth muscle cells (SMCs) causes various proliferative vascular diseases. MicroRNAs (miRNAs or miRs) have been established to play important roles in SMC biology and phenotypic modulation. This study revealed that the expression of miR‑182 was markedly altered during rat vascular SMC phenotypic transformation in vitro. We aimed to investigate the role of miR‑182 in the vascular SMC phenotypic switch and to determine the potential molecular mechanisms involved. The expression of miR‑182 gene was significantly downregulated in cultured SMCs during dedifferentiation from a contractile to a synthetic phenotype. Conversely, the upregulation of miR‑182 increased the expression of SMC-specific contractile genes, such as α-smooth muscle actin, smooth muscle 22α and calponin. Additionally, miR‑182 overexpression potently inhibited SMC proliferation and migration under both basal conditions and under platelet-derived growth factor-BB stimulation. Furthermore, we identified fibroblast growth factor 9 (FGF9) as the target gene of miR‑182 for the phenotypic modulation of SMCs mediated through platelet-derived growth factor receptor β (PDGFRβ) signaling. These data suggest that miR‑182 may be a novel SMC phenotypic marker and a modulator that may be used to prevent SMC dedifferentiation via FGF9/PDGFRβ signaling.


Effect of topical zinc oxide on bacterial growth and inflammation in full-thickness skin wounds in normal and diabetic rats.
The effects of topical zinc oxide on bacterial growth and inflammation were studied in full-thickness excised cutaneous wounds in normal rats and in hyperglycemic alloxan-diabetic rats. Two concentrations of zinc oxide in a gauze compress (15 or 60 mg/g) were applied to the wounds of the normal rats, but only the higher concentration was used for the diabetic rats. The polymorphonuclear leukocyte count, the alkaline phosphatase activity and bacterial counts in the granulation tissue were recorded on postoperative day 4. In the normal rats there was no significant intergroup difference in polymorphonuclear leukocyte density, though alkaline phosphatase activity was significantly depressed in those treated with the higher zinc oxide concentration. Bacterial growth in granulation tissue decreased at both zinc oxide concentrations. None of these effects was found in the diabetic rats. The results indicate that hyperglycemic diabetic rats respond differently to local zinc oxide treatment than do normal rats, and that the antibacterial activity of zinc oxide in vivo is not solely due to a direct toxic effect on the bacteria.


Activin signalling and response to a morphogen gradient.
Using combinations of amphibian embryo tissues, it is shown that the selection of genes expressed by a cell is determined by its distance from a source of activin, a peptide growth factor contained in vegetal cells and able to induce other cells to form mesoderm. This long-range signal spreads over at least 10 cell diameters in a few hours. It does so by passive diffusion, because it can by-pass cells that do not themselves respond to the signal nor synthesize protein. These results provide direct support for the operation of a morphogen concentration gradient in vertebrate development.


Liver X receptor α inhibits osteosarcoma cell proliferation through up-regulation of FoxO1.
Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. We analyzed liver X receptor α (LXRα) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent noncancerous tissues. Moreover, we investigated LXRα's potential role in regulating cell proliferation in Saos-2 and U2OS cells. We found that activation of LXRα, a member of nuclear receptor, was able to inhibit cell proliferation in Saos-2 and U2OS cells. At the molecular level, our results further revealed that expression of tumor suppressor gene, FoxO1, was up-regulated by LXRα activation. LXRα activates FoxO1 transcription through a direct binding on its promoter region. LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment.


[Hyperbaric oxygen therapy in the treatment of wounds, in plastic and reconstructive surgery].
After recalling the mechanism of action of hyperbaric oxygen (HBO) on healing processes, the authors review the principal indications for this technique in plastic and reconstructive surgery, such as crush injuries and acute post-traumatic ischemia of the limbs, skin flaps and skin grafts, when there is a risk of their not taking, and burns. They stress the importance of strict, stratified therapeutic protocols with control of the hyperoxygenation induced by HBO. In the authors' experience, transcutaneous measurements of the partial pressure of oxygen under the hyperbaric atmosphere is a very useful method with a predictive value to determine the indications for treatment with HBO and to monitor its effects.


Cooked color of precooked ground beef patties manufactured with mature bull trimmings.
Lean (80%) ground beef was formulated with 0, 25, 50, 75, or 100% mature bull trimmings, formed into patties, cooked to 71 °C in an air-impingement oven, and stored at -20 °C until reheating to 71 °C either in a microwave oven or on a gas-fired chargrill. Instrumental color of raw patties was not (P ≥ .080) affected by levels of bull trim. After initial cooking, internal cooked redness values were not affected (P ≥ .202) by the proportion of bull trim; however, the internal reheated patty redness increased (greater a* values and lesser HA; P ≤ .001) with increasing proportions of bull trimmings. Formulating ground beef with high levels (>50%) of mature, bull trimmings had minimal effects on raw ground beef color, but patties formulated with the highest proportions of bull trimmings appeared undercooked even after cooking twice to 71 °C.


Ocean acidification affects coral growth by reducing skeletal density.
Ocean acidification (OA) is considered an important threat to coral reef ecosystems, because it reduces the availability of carbonate ions that reef-building corals need to produce their skeletons. However, while theory predicts that coral calcification rates decline as carbonate ion concentrations decrease, this prediction is not consistently borne out in laboratory manipulation experiments or in studies of corals inhabiting naturally low-pH reefs today. The skeletal growth of corals consists of two distinct processes: extension (upward growth) and densification (lateral thickening). Here, we show that skeletal density is directly sensitive to changes in seawater carbonate ion concentration and thus, to OA, whereas extension is not. We present a numerical model of Porites skeletal growth that links skeletal density with the external seawater environment via its influence on the chemistry of coral calcifying fluid. We validate the model using existing coral skeletal datasets from six Porites species collected across five reef sites and use this framework to project the impact of 21st century OA on Porites skeletal density across the global tropics. Our model predicts that OA alone will drive up to 20.3 ± 5.4% decline in the skeletal density of reef-building Porites corals.


Predictors of mammographic density among women with a strong family history of breast cancer.
Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.


[Renal oncocytoma: report of 5 cases].
Renal oncocytoma is a rare, benign tumour, which is rarely diagnosed preoperatively. The authors report 5 cases of renal oncocytoma operated over a 10-year period. Based on a review of the literature, the various complementary investigations allowing a preoperative diagnosis and the indications for conservative surgery are discussed and analysed.


Multi-echo fMRI: A review of applications in fMRI denoising and analysis of BOLD signals.
In recent years the field of fMRI research has enjoyed expanded technical abilities related to resolution, as well as use across many fields of brain research. At the same time, the field has also dealt with uncertainty related to many known and unknown effects of artifact in fMRI data. In this review we discuss an emerging fMRI technology, called multi-echo (ME)-fMRI, which focuses on improving the fidelity and interpretability of fMRI. Where the essential problem of standard single-echo fMRI is the indeterminacy of sources of signals, whether BOLD or artifact, this is not the case for ME-fMRI. By acquiring multiple echo images per slice, the ME approach allows T2* decay to be modeled at every voxel at every time point. Since BOLD signals arise by changes in T2* over time, an fMRI experiment sampling the T2* signal decay can be analyzed to distinguish BOLD from artifact signal constituents. While the ME approach has a long history of use in theoretical and validation studies, modern MRI systems enable whole-brain multi-echo fMRI at high resolution. This review covers recent multi-echo fMRI acquisition methods, and the analysis steps for this data to make fMRI at once more principled, straightforward, and powerful. After a brief overview of history and theory, T2* modeling and applications will be discussed. These applications include T2* mapping and combining echoes from ME data to increase BOLD contrast and mitigate dropout artifacts. Next, the modeling of fMRI signal changes to detect signal origins in BOLD-related T2* versus artifact-related S0 changes will be reviewed. A focus is on the use of ME-fMRI data to extract and classify components from spatial ICA, called multi-echo ICA (ME-ICA). After describing how ME-fMRI and ME-ICA lead to a general model for analysis of fMRI signals, applications in animal and human imaging will be discussed. Applications include removing motion artifacts in resting state data at subject and group level. New imaging methods such as multi-band multi-echo fMRI and imaging at 7T are demonstrated throughout the review, and a practical analysis pipeline is described. The review culminates with evidence from recent studies of major boosts in statistical power from using multi-echo fMRI for detecting activation and connectivity in healthy individuals and patients with neuropsychiatric disease. In conclusion, the review shows evidence that the multi-echo approach expands the range of experiments that is practicable using fMRI. These findings suggest a compelling future role of the multi-echo approach in subject-level and clinical fMRI.


Comparison of two devices to simulate vision with intraocular lenses.
The simulation of vision with intraocular lenses (IOLs) prior to the clinical validation is of great interest for manufacturers as well as clinicians. We have tested the influence of different IOLs on the perception of contrast using different devices. A Rassow telescope and the VirtIOL have been used to assess the contrast sensitivity function (CSF) through monfocal IOL (CT Asphina 409 MP, IOL 1), multifocal IOL (AT LISA tri 839 MP, IOL 2) and extended-depth-of-focus-IOL (TECNIS Symfony ZXR00, IOL3) in 21 participants, aged between 22 and 29 years. Contrast sensitivity (CS) was tested at various spatial frequencies (3-30 cycles per degree), using the Tuebingen contrast sensitivity test. All tested IOL reduced the CS when compared to measurements with a trial lens correction of refractive errors. The analysis of the area under the curve of the contrast sensitivity function (AUC-CSF) revealed a significant reduction compared to the trial lens correction in case the Rassow telescope was used (IOL 1: P=0.008; IOL2: P<0.001; IOL3: P<0.001) and the same was true for the VirtIOL device for IOL2 and IOL3 (IOL2: P<0.001; IOL3: P<0.001), but not for IOL1 (P=0.192). Interdevice analysis of the AUC-CSF revealed significant differences for IOL1 and IOL2 (IOL1: P=0.025; IOL2: P<0.001), while no difference was found for IOL3 (P=0.092). Bland-Altman analysis as well as intraclass correlations coefficients indicated only weak interdevice agreement for the tested IOL. The assessment of the interdevice analysis for the Rassow telescope and the VirtIOL device revealed only a minor agreement between the two devices. In order to investigate vision with IOLs prior to a clinical validation, the use of the VirtIOL device is recommended.


Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression of prostate cancer in vivo.
Recently, lysine-specific demethylase 1 (LSD1) was identified as the first histone demethylase. LSD1 interacted with androgen receptor (AR) and promoted androgen-dependent transcription of target genes, such as PSA, by ligand-induced demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9). Meanwhile, the phenomenon of epithelial-mesenchymal transition (EMT) had received considerable attention in tumor recurrence and metastasis. This study examined the effect of Pargyline (an inhibitor of LSD1) on the process of EMT in vitro and in vivo. SCID mice were injected subcutaneously with LNCap cells. Pargyline was given intraperitoneally or not after castration (implemented with Bilateral orchidectomy), then PSA levels in serum and tumor were determined to assess time to androgen-independent progression. The results showed that LSD1 expression was up-regulated when PCa progressed to Castration Resistant Prostate Cancer (CRPC). Pargyline reduced LNCap cells migration and invasion ability, and inhibited the process of EMT by up-regulating expression of E-cadherin, and down-regulating expressions of N-cadherin and Vimentin in vitro and in vivo. Although, Pargyline did not change the level of AR, it reduced PSA expression both in vitro and in vivo. Furthermore, Pargyline delayed prostate cancer transition from androgen-dependent to androgen-independent state (CRPC). These findings indicated that inhibition of LSD1 might be a promise adjunctive therapy with androgen deprivation therapy (ADT) for locally advanced or metastatic prostate cancer.