[A therapeutic approach: the "Maxillo Family"].
For patients with severe facial injuries, global management from trauma to "cure", is the leitmotif in the department of maxillofacial surgery of Besançon. The progressive development of therapy groups led to the creation of the "Maxillo Family" which is more or less modelled after well known "Gueules Cassées" French Association. We also created the "Journal of Maxillo" in which every injured patient can write his own story. This seems to be a very good therapeutic approach not only from the patients' point of view but also for practitioners and nurses. The testimony of a young woman victim of a dramatic accident with severe facial injury illustrates the interesting aspects of this therapeutic approach.


Gas-liquid chromatographic determination of strychnine in grain baits.
A simple and rapid gas-liquid chromatographic procedure, using a 6' times 1/4'' glass column packed with 5% SE-30 on Chromosorb W (DMCS) and a flame ionization detector, is described. Grain baits containing strychnine alkaloid are ground, mixed, and extracted by shaking with chloroform containing an internal standard, 1,3,5-triphenylbenzene. Without further cleanup, extract filtrates are injected directly into a gas chromatograph. Peak height ratios are used for quantitation of strychnine. The analysis of commercial samples shows that the method compares well with a commonly employed ultraviolet spectrophotometric method; good precision, with recoveries ranging from 89.9 to 91.7%, is obtained in the analysis of prepared samples. The method is sensitive to 2 mug strychnine.


Detection of Legionella Pneumophila in Urine and Serum Specimens of Neutropenic Febrile Patients with Haematological Malignancies.
Background: Legionella pneumophila (L. pneumophila) is a gram-negative bacterium which causes Legionnaires' disease as well as Pontiac fever. The Legionella infections in patients suffering from neutropenia- as a common complication of cancer chemotherapy- can distribute rapidly. We aimed to detect of L. pneumophila in haematological malignancy suffering patients with neutropenic fever by targeting the (macrophage infectivity potentiator) mip gene. Subjects andMethods: Serum and urine specimens were obtained from 80 patients and presence of mip gene of L. pneumophila in specimens was investigated by PCR. Results: The L. pneumophila infection was detected in 21 (26.2%) and 38 (47.5%) of urine and serum specimens, respectively. Conclusion: Our findings indicated that the relative high prevalence of L. pneumophila in the studied patients group which show the necessity of considering this microorganism in future studies from detection and treatment point of view in cancer patients.


Retroperitoneal laparoscopic liposuction for large adrenal myelolipomas: a report of nine cases.
Removing relatively large adrenal myelolipomas using retroperitoneal laparoscopy is difficult and carries risk of intraoperative injury to adjacent organs and vessels. We aimed to introduce a new method of retroperitoneal laparoscopic liposuction with suction units for resection of large adrenal myelolipomas. From June 2005 to October 2011, 8 patients (nine lesions, including bilateral lesions in 1 patient) with adrenal myelolipoma more than 8 cm in maximum diameter underwent retroperitoneal laparoscopic liposuction with suction units. Patients included 3 males and 5 females with a mean age of 47 years (range, 35-62 years). Tumor resection was performed after deflation and shrinkage of tumor. The mean maximum diameter was 10.5 cm, ranging from 8 to 14 cm. Five tumors were located on the right side, two were on the left side, and one was bilateral. Adrenal computed tomography was done in each patient preoperatively. Round or oval masses were found in dense fat in the adrenal area, and all cases were diagnosed as adrenal myelolipoma. Five patients had backache or abdominal discomfort; three patients had no symptoms. The mean operation time was 75 minutes, and the mean intraoperative blood loss was 30 mL. The mean postoperative length of stay was 3 days. No significant intraoperative or postoperative complications occurred. The follow-up length ranged from 8 to 77 months. No tumor recurrence was observed. Retroperitoneal laparoscopic liposuction with suction units is safe and effective for resection of relatively large adrenal myelolipomas. Deflation and shrinkage of the tumor make the operation safer and easier without affecting its pathological diagnosis.


Multimodal MRI study of the relationship between plaque characteristics and hypoperfusion in patients with transient ischemic attack.
Transient ischemic attack is a significant risk factor for acute cerebral infarction. Previous studies have demonstrated that hypoperfusion in patients with transient ischemic attack was associated with the recurrence of transient ischemic attack, stroke, and persistent worsening of neurological symptoms. Moreover, transient ischemic attack patients classified as high-risk group according to the ABCD2 score have a higher incidence of stroke. Therefore, the objective of this study was to investigate the plaque characteristics of transient ischemic attack patients with concomitant cerebral hypoperfusion using multimodal MRI, as well as hemodynamic changes in the high-risk group with transient ischemic attack patients. A total of 151 patients with transient ischemic attack were prospectively recruited for this study. All enrolled patients underwent multimodal MRI, including DWI, TOF-MRA, HR-VWI, and DSC-PWI. Finally, 56 patients met the inclusion criteria. Based on DSC-PWI images, patients were divided into two groups: hypoperfusion (n = 41) and non-hypoperfusion (n = 15). Clinical baseline characteristics and plaque characteristics were analyzed between the two groups. Furthermore, within the hypoperfusion group, patients were further classified into low-risk (n = 11) and high-risk (n = 30) subgroups based on the ABCD2 score. Hemodynamic differences between these subgroups were also analyzed. Compared with the non-hypoperfusion group, the hypoperfusion group had a significantly higher prevalence of hypertension (68.3% vs. 33.3%, p = 0.019) and hyperhomocysteinemia (65.9% vs. 33.3%, p = 0.029). Moreover, the hypoperfusion group exhibited more significant luminal stenosis degree [41.79 ±31.36 vs. 17.62±13.62, p = 0.006] and greater NWI (57.1%±20.47% vs. 40.21%± 21.56%, p = 0.009) compared to the non-hypoperfusion group. In addition, the high-risk group identified by the ABCD2 score had a higher rMTT [117.6(109.31-128.14) vs. 108.36(100.67-119.92), p = 0.037]. Transient ischemic attack patients with hypoperfusion exhibited a higher prevalence of hypertension and hyperhomocysteinemia, as well as higher luminal stenosis degree, and greater NWI. Furthermore, Transient ischemic attack patients in the high-risk group demonstrated higher MTT.


[Influence of perinatal factors on the latter evolution of function of the nervous system in the low weight newborn infant (author's transl)].
Psychomotor follow up study of a group of low weight newborn infants, with ages in between seven months and three years. The most important perinatal data registered in the records of each baby were studied in relation with the neurological examination and electroencephalogram. The incidence of pathological perinatal factors were studied in relation with latter development, as well as with the group incidence of neuroevolutive and electroencephalogram abnormalities. The great interest of this type of study as well as the convenience of been undertaken by a real paediatrical and neurological team, so to be able to obtain best results, and improve our knowledges on this subject, remarking the importance of perinatal factors and the possible influence of these, on latter neurological maturation of the infant, as well as the ned of establishing a correct ethiological diagnosis of certain type of subnormalities and their prevention is commented.


A role for two-component signaling elements in the Arabidopsis growth recovery response to ethylene.
Previous studies indicate that the ability of Arabidopsis seedlings to recover normal growth following an ethylene treatment involves histidine kinase activity of the ethylene receptors. As histidine kinases can function as inputs for a two-component signaling system, we examined loss-of-function mutants involving two-component signaling elements. We find that mutants of phosphotransfer proteins and type-B response regulators exhibit a defect in their ethylene growth recovery response similar to that found with the loss-of-function ethylene receptor mutant etr1-7. The ability of two-component signaling elements to regulate the growth recovery response to ethylene functions independently from their well-characterized role in cytokinin signaling, based on the analysis of cytokinin receptor mutants as well as following chemical inhibition of cytokinin biosynthesis. Histidine kinase activity of the receptor ETR1 also facilitates growth recovery in the ethylene hypersensitive response, which is characterized by a transient decrease in growth rate when seedlings are treated continuously with a low dose of ethylene; however, this response was found to operate independently of the type-B response regulators. These results indicate that histidine kinase activity of the ethylene receptor ETR1 performs two independent functions: (a) regulating the growth recovery to ethylene through a two-component signaling system involving phosphotransfer proteins and type-B response regulators and (b) regulating the hypersensitive response to ethylene in a type-B response regulator independent manner.


Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides.
Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in the deterioration of joint cartilage and bone. Toll-like receptor 4 (TLR4) has been pinpointed as a key factor in RA-related inflammation. While Toll-like receptor antagonizing peptide 2 (TAP2) holds potential as an anti-inflammatory agent, its in vivo degradation rate hinders its efficacy. We engineered depots of TAP2 encapsulated in click-crosslinked hyaluronic acid (TAP2+Cx-HA) for intra-articular administration, aiming to enhance the effectiveness of TAP2 as an anti-inflammatory agent within the joint cavity. Our data demonstrated that FI-TAP2+Cx-HA achieves a longer retention time in the joint cavity compared to FI-TAP2 alone. Mechanistically, we found that TAP2 interacts with TLR4 on the cell membranes of inflammatory cells, thereby inhibiting the nuclear translocation of NF-κB and maintaining it in an inactive cytoplasmic state. In a rat model of RA, the TAP2+Cx-HA formulation effectively downregulated the inflammatory cytokines TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This led to a more rapid restoration of cartilage thickness, increased deposition of glycosaminoglycans, and new bone tissue formation in the regenerated cartilage, in comparison to a single TAP2 treatment after a six-week period. Our results suggest that TAP2+Cx-HA could serve as a potent intra-articular treatment for RA, offering both symptomatic relief and promoting cartilage regeneration. This innovative delivery system holds significant promise for improving the management of RA and other inflammatory joint conditions. STATEMENT OF SIGNIFICANCE: In this study, we developed a therapy by creating toll-like receptor 4 (TLR4)-antagonizing peptide (TAP2)-loaded click-crosslinked hyaluronic acid (TAP2+Cx-HA) depots for direct intra-articular injection. Our study demonstrates that FI-TAP2+Cx-HA exhibits a more than threefold longer lifetime in the joint cavity compared to FI-TAP2 alone. Furthermore, we found that TAP2 binds to TLR4 and masks the nuclear localization signals of NF-κB, leading to its sequestration in an inactive state in the cytoplasm. In a rat model of RA, TAP2+Cx-HA effectively suppresses inflammatory molecules, specifically TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This resulted in faster regeneration of cartilage thickness, increased glycosaminoglycan deposits in the regenerated cartilage, and a twofold increase in new bone tissue formation compared to a single TAP2 treatment.


Functional microdomains in G-protein-coupled receptors. The conserved arginine-cage motif in the gonadotropin-releasing hormone receptor.
An Arg present in the third transmembrane domain of all rhodopsin-like G-protein-coupled receptors is required for efficient signal transduction. Mutation of this Arg in the gonadotropin-releasing hormone receptor to Gln, His, or Lys abolished or severely impaired agonist-stimulated inositol phosphate generation, consistent with Arg having a role in receptor activation. To investigate the contribution of the surrounding structural domain in the actions of the conserved Arg, an integrated microdomain modeling and mutagenesis approach has been utilized. Two conserved residues that constrain the Arg side chain to a limited number of conformations have been identified. In the inactive wild-type receptor, the Arg side chain is proposed to form an ionic interaction with Asp3.49(138). Experimental results for the Asp3. 49(138) --> Asn mutant receptor show a modestly enhanced receptor efficiency, consistent with the hypothesis that weakening the Asp3. 49(138)-Arg3.50(139) interaction by protonation of the Asp or by the mutation to Asn favors activation. With activation, the Asp3. 49(138)-Arg3.50(139) ionic bond would break, and the unrestrained Arg would be prevented from orienting itself toward the water phase by a steric clash with Ile3.54(143). The mutation Ile3.54(143) --> Ala, which eliminates this clash in simulations, causes a marked reduction in measured receptor signaling efficiency, implying that solvation of Arg3.50(139) prevents it from functioning in the activation of the receptor. These data are consistent with residues Asp3.49(138) and Ile3.54(143) forming a structural motif, which helps position Arg in its appropriate inactive and active receptor conformations.


Percutanous dilatational tracheotomy in the ICU: a Norwegian survey focusing on perceived risk and safety attitudes.
Despite its popularity, serious complications do occur with percutaneous dilatational tracheotomy in the ICU. The associated risks in daily practice are probably underestimated and may reflect system flaws in training and team function. This study was performed to obtain an impression of risk perception and safety culture in connection with percutaneous dilatational tracheotomy in Norwegian ICUs. The Medical Director or intensivist on-call in the 30 ICUs participating in the Norwegian Intensive Care Registry was telephone interviewed using a semi-structured questionnaire. Data on the practice of tracheotomy and a qualitative assessment of complications experienced during the last 2 years were collected. In the second part, percutaneous dilatational tracheotomy operators in two ICUs were questioned about their perception of risk with percutaneous dilatational tracheotomy and asked to assess their own abilities as percutaneous dilatational tracheotomy operators and the training they had undergone. Of the 30 ICUs, 23 used percutaneous dilatational tracheotomy. The majority reported knowledge of severe complications like bleeding, hypoxia and tube dislodgment. Percutaneous dilatational tracheotomy-related deaths were also reported. Operators rated themselves relatively low and indicated the absence of any organized training. They acknowledged the known hazards related to percutaneous dilatational tracheotomy and suggested measures like fibreoptic guidance during the percutaneous dilatational tracheotomy and fewer operators with more experience as well as better team training, to improve patient safety. Based on the frequent reporting of serious complications and the suggested safety precautions, we conclude that the percutaneous dilatational tracheotomy is considered a high-risk procedure and that there is still room for improving the safety of this much used ICU procedure.


Early epidural blood patch in spontaneous intracranial hypotension.
Thirty patients with a typical orthostatic headache were treated by early lumbar epidural blood patch (EBP) without previously performing lumbar puncture or identifying a CSF leak and with or without typical MRI changes. A complete cure was obtained in 77% of patients after one (57%) or two (20%) EBPs. Spontaneous intracranial hypotension with typical orthostatic headache can be diagnosed without lumbar puncture and can be cured by early EBP in a majority of patients.


Sulbactam combined with tigecycline improves outcomes in patients with severe multidrug-resistant Acinetobacter baumannii pneumonia.
The purpose of this study was to review the treatment plan of patients with multidrug-resistant Acinetobacter baumannii (MDR-AB) pneumonia and analyze the factors associated with patient deaths and the medication regimen. We collected 1,823 qualified respiratory specimens that were culture-positive for MDR-AB. 166 patients confirmed to have hospital-acquired MDR-AB pneumonia were selected as the research subjects. The differing clinical characteristics and treatment interventions between the surviving group and death group within 28 days were analyzed. The mortality rate was high for those aged > 75 years (p = 0.001). Patients who underwent invasive catheter placement (p < 0.001) and mechanical ventilation (p = 0.046) had a higher mortality rate. Combination therapy with tigecycline can reduce the mortality rate (p < 0.001) of MDR-AB pneumonia in patients with carbapenem-resistant AB(CRAB). Combination therapy with sulbactam was shown to reduce the mortality rate (p < 0.001), and high-dose sulbactam (> 3 g/day) might be better than low-dose sulbactam (≤ 3 g/day). Reducing the time of invasive catheter placement and mechanical ventilation in patients in the intensive care unit (ICU), antimicrobial treatment, combined with tigecycline and sulbactam, might help reduce the mortality rate in patients with severe MDR-AB hospital-acquired pneumonia.


Five-plex isotope dimethyl labeling for quantitative proteomics.
Stable isotope dimethyl labeling, a widely used method for quantitative proteomics, was extended to five channels for the first time. Comprehensive proteome and phosphoproteome quantification validated the high quantification accuracy and throughput of this five-plex method.


Precursor T-cell acute lymphoblastic leukemia/lymphoma involving the uterine cervix, myometrium, endometrium, and appendix.
This report presents a case of precursor T-cell acute lymphoblastic leukemia/lymphoma (ALL) involving the uterine cervix, myometrium, endometrium, and appendix. The patient was a 38-year-old woman with a history of ALL who had been in remission for 4 years following chemotherapy. The malignant lymphoid infiltrate was characterized by blasts, showing scant cytoplasm, irregular hyperchromatic nuclei, and occasional prominent nucleoli. They were immunoreactive for CD45RB, CD3, CD43, CD34, and focally for TdT. Curiously, the blasts replaced the endometrial stroma and spared the associated epithelium. The patient was again treated with chemotherapy but her disease did not respond. She succumbed to her disease approximately 10 months after her initial evaluation for symptoms related to ALL relapse. Precursor T-cell ALL most commonly presents as a mediastinal mass in adolescent males. Although any organ may be affected, involvement of the female reproductive organs is rare. This case shows some of the varied manifestations of precursor T-cell ALL and highlights the necessity of considering the female reproductive tract as a possible location of relapsing disease.


Development of a Supportive Parenting App to Improve Parent and Infant Outcomes in the Perinatal Period: Development Study.
The transition to parenthood can be challenging, and parents are vulnerable to psychological disorders during the perinatal period. This may have adverse long-term consequences on a child's development. Given the rise in technology and parents' preferences for mobile health apps, a supportive mobile health intervention is optimal. However, there is a lack of a theoretical framework and technology-based perinatal educational intervention for couples with healthy infants. The aim of this study is to describe the Supportive Parenting App (SPA) development procedure and highlight the challenges and lessons learned. The SPA development procedure was guided by the information systems research framework, which emphasizes a nonlinear, iterative, and user-centered process involving 3 research cycles-the relevance cycle, design cycle, and rigor cycle. Treatment fidelity was ensured, and team cohesiveness was maintained using strategies from the Tuckman model of team development. In the relevance cycle, end-user requirements were identified through focus groups and interviews. In the rigor cycle, the user engagement pyramid and well-established theories (social cognitive theory proposed by Bandura and attachment theory proposed by Bowlby) were used to inform and justify the features of the artifact. In the design cycle, the admin portal was developed using Microsoft Visual Studio 2017, whereas the SPA, which ran on both iOS and Android, was developed using hybrid development tools. The SPA featured knowledge-based content, informational videos and audio clips, a discussion forum, chat groups, and a frequently asked questions and expert advice section. The intervention underwent iterative testing by a small group of new parents and research team members. Qualitative feedback was obtained for further app enhancements before official implementation. Testing revealed user and technological issues, such as web browser and app incompatibility, a lack of notifications for both administrators and users, and limited search engine capability. The information systems research framework documented the technical details of the SPA but did not take into consideration the interpersonal and real-life challenges. Ineffective communication between the health care research team and the app developers, limited resources, and the COVID-19 pandemic were the main challenges faced during content development. Quick adaptability, team cohesion, and hindsight budgeting are crucial for intervention development. Although the effectiveness of the SPA in improving parental and infant outcomes is currently unknown, this detailed intervention development study highlights the key aspects that need to be considered for future app development.


Copy Number Gain at Xq28 in a Child with Global Developmental Delay Associated with a Variant Form of Hoyeraal-Hreidarsson Syndrome.
We report the case of a child from Central Brazil with global developmental delay (GDD), syndromic features, and absence of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, with a rearrangement at Xq28 harboring the DKC1 gene. GTC-banding revealed a male karyotype (46,XY) with no visible numerical or structural alterations. Chromosomal microarray analysis (CMA) showed a 0.36-Mb gain at Xq28 of maternal origin, encompassing 22 genes, including DKC1. Rearrangements and mutations involving this gene have been associated with dyskeratosis congenita, X-linked (OMIM 305000) and Hoyeraal-Hreidarsson syndrome. CMA was a powerful and efficient approach to identify a gain at Xq28 harboring the DKC1 gene in our patient with GDD syndromic features and no cutaneous alterations, suggesting that this variant is associated with the Hoyeraal-Hreidarsson syndrome.


Production of high-starch, low-glucose potatoes through over-expression of the metabolic regulator SnRK1.
Transgenic potato (Solanum tuberosum cv. Prairie) lines were produced over-expressing a sucrose non-fermenting-1-related protein kinase-1 gene (SnRK1) under the control of a patatin (tuber-specific) promoter. SnRK1 activity in the tubers of three independent transgenic lines was increased by 55%-167% compared with that in the wild-type. Glucose levels were decreased, at 17%-56% of the levels of the wild-type, and the starch content showed an increase of 23%-30%. Sucrose and fructose levels in the tubers of the transgenic plants did not show a significant change. Northern analyses of genes encoding sucrose synthase and ADP-glucose pyrophosphorylase, two key enzymes involved in the biosynthetic pathway from sucrose to starch, showed that the expression of both was increased in tubers of the transgenic lines compared with the wild-type. In contrast, the expression of genes encoding two other enzymes of carbohydrate metabolism, alpha-amylase and sucrose phosphate synthase, showed no change. The activity of sucrose synthase and ADP-glucose pyrophosphorylase was also increased, by approximately 20%-60% and three- to five-fold, respectively, whereas the activity of hexokinase was unchanged. The results are consistent with a role for SnRK1 in regulating carbon flux through the storage pathway to starch biosynthesis. They emphasize the importance of SnRK1 in the regulation of carbohydrate metabolism and resource partitioning, and indicate a specific role for SnRK1 in the control of starch accumulation in potato tubers.


Use of industrial hygiene and safety professionals: a survey of South Carolina manufacturing plants.
There has been considerable debate about manpower adequacy in industrial hygiene and safety, but little indication as to which industries make use of these professionals and to what extent. This paper presents the results of a survey of manufacturing industry in South Carolina, which suggest that plants not only make less use of the services of industrial hygiene and safety engineers than might seem desirable, but have only a limited perception of the need.


Seroprevalance of anti-SARS-CoV-2 antibodies in the IgG class in hospitalized children in the north-eastern part of Poland in 2021.
In children, SARS-CoV-2 infection may manifest with symptoms of fever, cough, muscle pain, diarrhea or waste smell and taste. However, in most cases it is mild or asymptomatic. Determination of the level of anti-SARS CoV-2 IgG antibodies in children enables to assess retrospectively the incidence of the SARS-CoV-2 infection among children. The aim of the research was to analyze the results of anti-SARS-CoV-2 antibodies in the IgG class contained in children hospitalized in north-eastern Poland in 2021. The material for the study was venous blood collected once from children hospitalized in Children's University Hospital in Białystok in 2021. The results obtained from 615 children aged from 1 month to 11 years were analyzed. Determination of the level of antibodies was performed using the automated SARS-COV-2 IgG II test on the VIDAS® analyzer. The analysis of the results of the anti-SARS-CoV-2 IgG value showed that half of children (52%, n=319) had contact with SARS-CoV-2 virus of which approximately 15% (n=47) had documented infection with this virus. There was no difference in the frequency of infections among boys and girls, antibodies were detected in 51% and 53%, respectively. The highest percentage of positive results was observed in children aged 7 to 10 years, 62% (91/147). The least children with a positive result were in the group below 1 year of age, 24% (4/17). High values of the antibody index (>15.00) were most often found among younger children, aged 1-2 years. The presented results showed that infection with the SARS-CoV-2 virus does not depend on the sex of children but the value of anti-SARS-CoV-2 IgG antibodies decreased with the age of the child.


Imaging evaluation of nonobstetric conditions during pregnancy: what every radiologist should know.
In recent decades, there has been a significant increase in the number of imaging examinations performed on pregnant patients. That increase has occurred across the various modalities, including ultrasound, computed tomography, and magnetic resonance imaging. However, little is known about the risks that these examinations generate for the mother and fetus, related to the use of ionizing radiation or the use of contrast media. When pregnant patients are submitted to imaging studies, the principles of protection established by the International Commission on Radiological Protection should always be respected, to avoid injury to the pregnant woman and the fetus. The potential deleterious effects on the fetus must be weighed against the damage caused by not performing an examination that is clearly indicated, given that a delayed or missed diagnosis can be even more harmful to the health of the mother and of the fetus itself. The purpose of this review article is to address concerns regarding the safety of imaging methods used during pregnancy, as well as to identify typical clinical situations that require decisions to be made about the indication and optimal planning of imaging examinations.


Sintering behaviour of 45S5 bioactive glass.
In this study, we report on the effect of Bioglass structural transformations on its sintering behaviour. While heating up to 1000 degrees C, five successive transformations occur: glass transition, glass-in-glass phase separation, two crystallization processes and a second glass transition. The sintering of the material exhibits two main shrinkage stages associated with the two glass transitions at 550 and 850 degrees C. At 580 degrees C, the glass-in-glass phase separation induces a decrease in the sintering rate immediately followed by the major crystalline phase crystallization (Na(2)CaSi(2)O(6)) between 600 and 700 degrees C, from the surface to the bulk of the particles. A complete inhibition of sintering takes place followed by a minor shrinkage effect due to crystallization. A plateau is then observed until the second glass transition temperature is reached. A modification of Frenkel's model allows the determination of the glass-in-glass phase separation kinetics and the identification of the structural transformations effects on sintering behaviour.


Effect of Hyperhomocysteinemia on Clinical Outcome and Hemorrhagic Transformation After Thrombolysis in Ischemic Stroke Patients.
Background and Purpose: Hyperhomocysteinemia (Hhcy) is a well-known risk factor for ischemic stroke. However, the role of Hhcy in the clinical outcome of ischemic stroke has not been fully elucidated. In addition, previous studies have found that Hhcy was implicated in the disruption of the blood-brain barrier, which may increase the risk of hemorrhagic transformation (HT) after thrombolysis. Thus, the aim of this study was to investigate the effect of Hhcy on the clinical outcome and HT after thrombolysis in ischemic stroke patients. Methods: Patients who were diagnosed with ischemic stroke and received intravenous thrombolytic therapy between January 2016 and September 2018 were included in this study. Multivariate logistic regression analysis was used to assess the association between Hhcy, clinical outcome, and HT after thrombolysis. Furthermore, the potential interaction between Hhcy and hypertension on the clinical outcome and HT after thrombolysis was also assessed. Results: Of 568 patients, 455 (80.1%) had Hhcy, 66 (11.6%) had HT, and 219 (38.6%) had poor outcome. Patients with Hhcy had a higher incidence of poor outcome than the patients with non-Hhcy (40.9 vs. 29.2%, p = 0.022). However, there was no significant difference in the incidence of HT (11.9 vs. 10.6%, p = 0.711) between patients with Hhcy and non-Hhcy. After adjustment for major covariates, multivariate logistic regression analysis disclosed that Hhcy was independently associated with increased risk of poor outcome (OR = 1.760; 95% CI: 1.069-2.896) but was not associated with the risk of HT (OR = 1.017; 95% CI: 0.495-2.087). In addition, we found no significant interaction between Hhcy and hypertension on the clinical outcome (p = 0.513) or HT (p = 0.170) after thrombolysis. Conclusion: We found that Hhcy was an independent risk factor for poor outcome, but not an independent risk factor for HT after thrombolysis in ischemic stroke patients. In addition, there was no significant interaction of Hhcy and hypertension on the clinical outcome or HT after thrombolysis.


[Asylum seekers and refugees in the emergency department].
This cross-sectional study describes the health problems and the health care of asylum seekers and refugees from the point of view of accident & emergency (A & E) physicians at the major hospital in St. Gallen, Switzerland. The physicians filled in a detailed questionnaire and documented all consultations of asylum seekers/refugees and of a control group of patients during eleven weeks (2 x 98 consultations). 76% of these asylum seekers/refugees originated from former Yugoslavia. The distribution of the main ICD-coded diagnoses did not differ between asylum seekers/refugees and the control group after correction for age. In comparison with the asylum seekers and refugees attending GPs, injuries were much more common in the A & E department attenders (37% vs. 8%). Asylum seekers/refugees and the patients in the control group did not differ in respect to being classified as an emergency case (58% vs. 65%). There were also no differences in hospitalisation rates (29% vs. 36%). Asylum seekers/refugees who were registered with a GP attended the A & E department more often during the night than during the day compared to patients who were not registered with a GP. Consultations which have been classified as emergencies occurred more frequently during the day than at night time. The time of residence in Switzerland was negatively associated with the registration with a GP and with being classified as an emergency case. A lack of experience in caring for asylum seekers and refugees and of specific training in this field has been the major complaint by the A & E physicians. Asylum seekers should be introduced to the tasks and functions of the various sectors of the national health care system as early as possible. Registration with a GP in the community should be promoted.


Development of a proxy for past surface UV-B irradiation: a thermally assisted hydrolysis and methylation py-GC/MS method for the analysis of pollen and spores.
A method was developed for the analysis of the UV-absorbing sporopollenin monomers p-coumaric acid and ferulic acid in very low numbers of pollen. This enables the analysis of pollen or spores from cultured plants, from herbarium collections, and from sediment, soil, and peat cores. The method involves thermally assisted hydrolysis and methylation using tetramethylammonium hydroxide combined with gas chromatography and mass spectrometry. Pyrolysis, gas chromatographic, and mass spectrometric conditions were optimized for the analysis of minimal amounts of pollen. The method has a detection limit of approximately 60 fresh pollen of Alnus glutinosa and a relative standard deviation of approximately 10% between 100 and 600 pollen.


Impact of a Multimodal and Combination Therapy on Self-Regulation and Internal Coherence in German Breast Cancer Survivors With Chronic Cancer-Related Fatigue: A Mixed-Method Comprehensive Cohort Design Study.
Background: Recent studies have proved the relevance of salutogenetic variables for fatigue management in breast cancer survivors with cancer-related fatigue (CRF). This comprehensive cohort design study is the first to examine the impact of 2 multimodal therapies, multimodal therapy (MT) and combined therapy (CT), compared with standard aerobic training (AT) on salutogenetic variables (self-regulation and internal coherence) and distress in breast cancer survivors with CRF. Methods: A total of 105 patients started the therapies and n = 84 completed the Self-regulation Scale, the Internal Coherence Scale, the Cancer Fatigue Scale, and the Hospital Anxiety and Depression Scale at baseline, 10 weeks after treatment (T1) and n = 81 after 6 months (T2). Patient satisfaction and qualitative feedback regarding therapy quality was assessed at T1. A general linear model including allocation type, therapy arm (MT/CT/AT), and bias-adjusting propensity scores tested the superiority of both multimodal therapies versus AT for all questionnaires at T1 and T2. Results: MT and CT were superior to AT to improve self-regulation and patients' satisfaction at T1. Additionally, CT showed superiority for self-regulation at T2 (all P < .05). Compared with AT, internal coherence was significantly higher for patients in the MT arms at T2, respectively (all P < .01). Pearson's correlations between self-regulation, internal coherence, and CRF improved from baseline to T2 (Mean r = -0.60). Qualitative feedback confirmed patients' benefits in several health-related categories. Conclusions: Self-regulation and internal coherence are manipulable variables with relevant CRF associations. They can be positively affected by multimodal therapies. Alongside patients' satisfaction and qualitative feedback they help refine treatment.


Magnetic and Structural Studies of Sc Containing Ruthenate Double Perovskites A2ScRuO6 (A = Ba, Sr).
Ruthenium-containing double perovskites A2ScRuO6 have been synthesized as polycrystalline powders and structurally characterized using a combination of synchrotron X-ray and neutron powder diffraction methods. When A = Ba, a hexagonal 6L perovskite structure is obtained if the synthesis is conducted at ambient pressure and a rock-salt ordered cubic structure is obtained if the sample is quenched from high pressures. The Sr oxide Sr2ScRuO6 is obtained with a rock-salt ordered corner sharing topology. Heat capacity and bulk magnetic susceptibility measurements show that the three oxides are antiferromagnets. Cubic Ba2ScRuO6 undergoes a metal-insulator transition near 270 K and hexagonal Ba2ScRuO6 is a semiconductor with an activation energy of 0.207 eV. The magnetic structures of the two rock-salt ordered double perovskites were established using powder neutron diffraction and are described by k = (0,0,1) and k = (0,0,0) for the Ba and Sr oxides, respectively, corresponding to type I antiferromagnetic structures, with ferromagnetic layers stacked antiferromagnetically. The ambient-pressure hexagonal polymorph of Ba2ScRuO6 has partial Sc-Ru ordering at both the face-sharing B2O9 dimer and corner-sharing BO6 sites. The magnetic structure is described by k = (1/2,0,0) with the basis vector belonging to the irreducible representation Γ3.


Late recurrent post-transplant primary biliary cirrhosis in British Columbia.
Late recurrent primary biliary cirrhosis (PBC) following orthotopic liver transplant remains a controversial topic. The first documented case of recurrence occurring in 16 patients transplanted for PBC and followed at the authors' institution for longer than one year is presented. A 54-year-old man transplanted for PBC developed a cholestatic pattern of enzyme elevation on post-transplant day (PTD) 1305. Repeat antimitochondrial antibody was strongly positive (1:300 to 1:400). A liver biopsy revealed severe bile duct damage, lymphocytic cholangitis, focal periductal noncaseating granuloma and minimal endotheliitis. Recurrent PBC was diagnosed. At the time of orthotopic liver transplant this patient received induction immunosuppression with OKT3 crossed over to cyclosporine (CsA), azathioprine (AZA) and prednisone. AZA was discontinued early and maintenance CsA tapered to a target trough level of 150 to 200 ng/mL by PTD 365. Prednisone was withdrawn by PTD 664. CsA levels during PTDs 1225 to 1305 (before elevation of hepatobiliary enzymes) were below target at 114 to 166 ng/mL. Of the 16 patients, all but three were maintained on CsA, AZA and prednisone. One was on CsA (trough levels on target) and AZA; the other two, including the patient with recurrent PBC, were on CsA only. The trough CsA level of the patient without recurrent PBC has been within the target range. The authors speculate that the underlying defect in immunoregulation in PBC persists post-transplant and that in the patient without recurrent PBC this defect was unmasked by lowered maintenance immunosuppression--allowing recurrence of PBC in a previously stable liver allograft.


Gastrointestinal lymphoma.
Primary gastrointestinal lymphoma comprises a group of distinctive clinicopathological entities, most of which are not included in current lymph node-based lymphoma classifications. They may be of B- or T-cell type, with primary gastrointestinal Hodgkin's disease being extremely uncommon. Most low grade B-cell gastrointestinal lymphomas are of mucosa-associated lymphoid tissue (MALT) type, so called because they recapitulate the features of MALT rather than those of lymph nodes. Paradoxically, however, most MALT lymphomas arise in the stomach, which normally contains no organized lymphoid tissue. These gastric MALT lymphomas appear to arise in MALT acquired as a reaction to infection of the stomach by Helicobacter pylori and their growth can be influenced by eradication of this organism from the stomach. Low grade MALT lymphomas, which usually have a very favorable clinical course, may undergo high grade transformation; high grade tumours also may arise de novo and these probably also belong to the MALT group. Immunoproliferative small intestinal disease (IPSID) is a special form of MALT lymphoma with a restricted geographic distribution, which is characterized by synthesis of alpha heavy-chain immunoglobulin. Other gastrointestinal B-cell lymphomas include mantle cell lymphoma, which presents as lymphomatous polyposis, and Burkitt's or Burkitt-like lymphoma. Enteropathy (celiac disease)-associated T-cell lymphoma (EATL) is the most common primary gastrointestinal T-cell lymphoma. This is a clinically aggressive tumor that arises from the intraepithelial T-cell population, which is increased in celiac disease.


The era of genomics: impact on sepsis clinical trial design.
This article aims to address the predictable impact of genetics on the design of clinical trials in the field of critical care medicine, with emphasis on the pathophysiology of sepsis and its treatment. Published articles reporting studies on sepsis and septic shock or assessing the influence of genetics and pharmacogenomics in the treatment of critical illnesses. Because most common diseases including sepsis have been shown to be influenced by inherited differences in our genes, completion of the Human Genome Project and the concomitant publication of the human single nucleotide polymorphism map both contribute to change our approach to medicine. Advances in genotyping techniques and bioinformatics enabling detection of single nucleotide polymorphisms have caused an explosion in pharmacogenomics-the research dealing with the interactions of an individual's genotype and the outcome of a drug therapy. Pharmacogenomics will undoubtedly be used to improve future health care and clinical research in different ways. Whereas treatment allocation has been based mainly on phenotype, genetic characterization will help researchers to identify suitable subjects for clinical trials, to facilitate interpretation of the results of clinical trials, and to identify novel targets for future drugs or new markets for current products. As interindividual variability in drug response is a substantial clinical problem, the second major objective of pharmacogenomic research is to decrease adverse responses to therapy through determination of adequate therapeutic targets and genetic polymorphisms that alter drug specificity and toxicity. Ultimately, genetic information will be used to select the most effective therapeutic agent and the optimal dosage to elicit the expected drug response for a given individual. Implementation of genetic criteria for stratification of patient populations and individual assessment of treatment risks and benefits emerges as a major challenge to the pharmaceutical industry. In the future, technologies such as gene chip array will enhance genetic medicine and provide novel insights into a patient's susceptibility to disease, enabling a better assessment of prognostic risk factors, quicker diagnosis, and accurate prediction of individual responsiveness to drugs. The predictable consequences of such an approach on the prevention and treatment of diseases could revolutionize medicine.


Value of pelvic ultrasound combined with pituitary MRI in diagnosis of central precocious puberty in girls.
This study aimed to investigate the value of pelvic ultrasound combined with pituitary magnetic resonance imaging (MRI) based on an artificial intelligence algorithm in the diagnosis of girls with central precocious puberty (CPP), providing reference for the prevention and control of CPP in girls. 75 girls with CPP and 75 normal girls in Nantong First People's Hospital were studied. Pelvic ultrasound parameters were compared between the two groups based on an artificial intelligence algorithm. Pituitary MRI parameters were analyzed, and pituitary function parameters were explored. The results showed that the diagnostic sensitivity, specificity, and accuracy of the convolutional neural network (CNN) algorithm were 72.3%, 74.6%, and 78.3%, respectively. The sensitivity, specificity, and accuracy of CNN algorithm were significantly higher (p<0.05). The long diameter, anteroposterior diameter, and transverse diameter of the uterus in the precocious puberty (PP) group were significantly larger than those in the normal group (NG). The ovarian long diameter, ovarian anteroposterior diameter, and ovarian transverse diameter in PP group were significantly larger than those in NG. Uterine volume and ovarian volume in PP group were clearly higher than those in NG. The largest follicle diameter was clearly larger in PP patients than in NG patients. The coronal height, coronal width, sagittal height, and sagittal anteroposterior diameter of PP group were clearly higher than those of NG (p<0.05). The sagittal cross-sectional area of pituitary MRI morphology in PP group was significantly greater than that in NG. The pituitary MRI morphology pituitary volume was 272.68 mm in PP group and 191.37 mm in NG, and the pituitary volume was clearly larger in PP group than in NG. The pituitary function parameters estradiol (E2), luteinizing hormone (LH) peak, follicle-stimulating hormone (FSH) peak, and LH peak/FSH peak were greater in PP group than in NG. In summary, the uterine size and ovarian size of girls and the pituitary function index in PP group were larger. Pelvic ultrasound and pituitary MRI indexes can better diagnose CPP and can be widely used in clinical practice with positive diagnostic value.


Systematic studies of the interactions between a model polyphenol compound and microbial β-glucosidases.
Lignin is a major obstacle for cost-effective conversion of cellulose into fermentable sugars. Non-productive adsorption onto insoluble lignin fragments and interactions with soluble phenols are important inhibition mechanisms of cellulases, including β-glucosidases. Here, we examined the inhibitory effect of tannic acid (TAN), a model polyphenolic compound, on β-glucosidases from the bacterium Thermotoga petrophila (TpBGL1 and TpBGL3) and archaeon Pyrococcus furiosus (PfBGL1). The results revealed that the inhibition effects on β-glucosidases were TAN concentration-dependent. TpBGL1 and TpBGL3 were more tolerant to the presence of TAN when compared with PfBGL1, while TpBGL1 was less inhibited when compared with TpBGL3. In an attempt to better understand the inhibitory effect, the interaction between TAN and β-glucosidases were analyzed by isothermal titration calorimetry (ITC). Furthermore, the exposed hydrophobic surface areas in β-glucosidases were analyzed using a fluorescent probe and compared with the results of inhibition and ITC. The binding constants determined by ITC for the interactions between TAN and β-glucosidases presented the same order of magnitude. However, the number of binding sites and exposed hydrophobic surface areas varied for the β-glucosidases studied. The binding between TAN and β-glucosidases were driven by enthalpic effects and with an unfavorable negative change in entropy upon binding. Furthermore, the data suggest that there is a high correlation between exposed hydrophobic surface areas and the number of binding sites on the inhibition of microbial β-glucosidases by TAN. These studies can be useful for biotechnological applications.


A semi-localized elastic net for surface reconstruction of objects from multislice images.
The traveling salesman problem (TSP) is a prototypical problem of combinatorial optimization and, as such, it has received considerable attention from neural-network researchers seeking quick, heuristic solutions. An early stage in many computer vision tasks is the extraction of object shape from an image consisting of noisy candidate edge points. Since the desired shape will often be a closed contour, this problem can be viewed as a version of the TSP in which we wish to link only a subset of the points/cities (i.e. the "noisefree" ones). None of the extant neural techniques for solving the TSP can deal directly with this case. In this paper, we present a simple but effective modification to the (analog) elastic net of Durbin and Willshaw which shifts emphasis from global to local behavior during convergence, so allowing the net to ignore some image points. Unlike the original elastic net, this semi-localized version is shown to tolerate considerable amounts of noise. As an example practical application, we describe the extraction of "pseudo-3D" human lung outlines from multiple preprocessed magnetic resonance images of the torso. An effectiveness measure (ideally zero) quantifies the difference between the extracted shape and some idealized shape exemplar. Our method produces average effectiveness scores of 0.06 for lung shapes extracted from initial semi-automatic segmentations which define the noisefree case. This deteriorates to 0.1 when extraction is from a noisy edge-point image obtained fully-automatically using a feedforward neural network.


Valproic acid regulates Ang II-induced pericyte-myofibroblast trans-differentiation via MAPK/ERK pathway.
Myocardial fibrosis (MF) plays an important part in cardiovascular diseases. The main cytological characteristics of MF is the increased number of myofibroblasts, which have multiple sources such as EMT, EndMT, myeloid progenitors, monocytes, and fibrocytes. Recent data showed that pericytes may represent a major source of myofibroblasts in kidney fibrosis. Valproic acid (VPA) is a kind of short-chain fatty acid. It was reported in recent studies that VPA regulates gene expression and influences various signal pathways. HDACs inhibitors can hinder the growth of tumor cells and differentiation of stem cells. And little is known about the effects of HDACs inhibitors on myofibroblasts transdiffererntiaton. This study focused on the role of HDACs in pericyte-myofibroblast trans-differentiation and how HDACs inhibitor VPA influenced proliferation, migration, viability and myofibroblast trans-differentiation of pericytes for the first time. Rat cardiac fibrosis model was induced by Ang II. Immunohistochemistry was employed to examine cardiac fibrosis and flow cytometry was used to analyze whether inflammatory cells involve VPA-induced trans-differentiation. Pericytes proliferation, migration and differentiation to myofibroblasts were performed to examine the role of VPA on pericyte trans-differentiation. Immunoblot and qPCR were applied to identify the signal transduction involving in VPA-induced trans-differentiation. In vivo study showed that HDAC inhibitor VPA blocks cardiac fibrosis, and inflammation inhibition was not involved in this process. VPA treatment inhibited Ang II pericyte proliferation, migration and transdifferentiation to myofibroblast. Furthermore, the inhibition of α-SMA expression by VPA was related to reduce phosphorylation of ERK, and a pharmacological inhibitor of MEK suppressed Ang II-induced α-SMA expression. HDAC4 knockdown resulted in inhibiting Ang II-mediated α-SMA expression as well as the phosphorylation of ERK. Moreover, the inhibitors of protein phosphatase 2A and 1 (PP2A and PP1) restored the Ang II-stimulated α-SMA expression from the inhibitory effect of VPA. Together, the current data indicate that the differentiation of pericytes to myofibroblasts is HDAC4 dependent and requires phosphorylation of ERK.


Adult oral health-related quality of life instruments: A systematic review.
To identify the existing OHRQoL instruments for adults, describe their scope (generic or specific), theoretical background, validation type and cross-cultural adaptation. A systematic search was conducted, and articles presenting validation of OHRQoL instruments in adults were included. Data were collected about the validation type: external validation (correlations/associations); or internal validation (factor analysis/principal components analysis, item response theory); and cross-cultural adaptation. Of 3730 references identified, 326 were included reporting 392 studies. Forty-two original instruments were found among 74 different versions, 40 generic and 34 condition-specific. Locker's theoretical framework was the predominant model. The oral health impact profile (OHIP) presented 20 versions, with OHIP-14 being the most frequent (26.8%), followed by geriatric oral assessment index (GOHAI) (14.0%), OHIP-49 (11.7%) and oral impacts on daily performances (OIDP) (9.7%). Most studies focused on external validation (65.3%), while internal validation was reported in 24.8% (n = 26) of OHIP-14 studies, 50.9% (n = 28) of GOHAI and 21.1% (n = 8) of OIDP studies. Most internal validation studies were conducted in English-speaking countries (n = 33), and cross-cultural adaptation was mostly in non-English-speaking European countries (n = 40). Many generic and condition-specific instruments were found, but few have gone through a rigorous internal validation process or have undergone cross-cultural adaptation. This, in turn, makes it difficult for researchers to choose an appropriate measure based on known psychometric properties. OHIP-14, OIDP and GOHAI seem to be the most widely validated instruments. Equalizing measurement properties for comparability are challenging due to theoretical heterogeneity. Future studies should assess psychometric properties, explore the factorial structure and work towards a consensus on critical issues.


Neural processing of emotional overinvolvement in borderline personality disorder.
Patients with borderline personality disorder (BPD) fare better clinically if their families are rated as being high in emotional overinvolvement, which is characterized by marked emotionality, anxious concern, and protective behavior. This is not true of patients with disorders such as schizophrenia or major depression. We used functional magnetic resonance imaging methods to explore the link between emotional overinvolvement (EOI) and better clinical outcome in BPD. Specifically, we tested the hypothesis that, unlike healthy controls or people with other psychiatric problems, people with BPD process EOI as an approach-related stimulus. Participants with BPD (n = 13) and dysthymia (n = 10) (DSM-IV criteria for both) and healthy controls (n = 11) were imaged using a high field strength (3T) scanner while they listened to a standardized auditory stimulus consisting of either 4 neutral or 4 EOI comments. Participants also rated their mood before and after exposure to the comments. All participants reported increased negative mood after hearing EOI and rated the EOI comments as negative stimuli. However, after subtracting activation to neutral comments, participants with BPD showed higher activation in left prefrontal regions during EOI compared to the other groups. Increased left prefrontal activation during EOI was also correlated with clinical measures indicative of borderline pathology. Participants with dysthymia showed increased amygdala activation during EOI. This was not true for the healthy controls or participants with BPD. For people with BPD, EOI may be activating neural circuitry implicated in the processing of approach-related stimuli. Increased left prefrontal activation to EOI may be a vulnerability marker for BPD. These findings may also help explain why BPD patients do better clinically in high EOI family environments.


Models in researching cardiovascular morphogenesis.
Several types of "models" are used in modern biological and biomedical research and teaching. This article attempts to provide a brief explanation of the termini model organism, theoretic and mathematic model, three-dimensional (3D) model, and 4D model, and an overview about the generation and the fields of applications of these types of models. It will then focus on the application of theoretic and mathematic models, 3D models, 4D models, and simulation for researching cardiovascular morphogenesis.


Chromium(0)-promoted [6pi + 2pi] cycloadditions of allenes with cycloheptatriene.
Photoinitiated [6pi + 2pi] cycloadditions of allenes with (eta(6)-cycloheptatriene)tricarbonylchromium(0) (1) are described. An example of asymmetric induction obtained by reaction of 1 with a chiral 1,3-disubstituted allene is also reported.


Idiopathic mast cell activation syndrome is more often suspected than diagnosed-A prospective real-life study.
Idiopathic mast cell activation syndrome (MCAS) is characterized by three diagnostic criteria: (1) episodic mast cell (MC)-driven signs/symptoms of at least two organ systems in the absence of clonal MC expansion and definite triggers, (2) episodic increase in tryptase, and (3) response to MC-targeted treatment. Many patients believe they have MCAS, but how often this is the case remains unknown. We prospectively investigated patients with suspected MCAS (n = 100) for the diagnostic criteria including baseline tryptase, KIT D816V mutation, and patient-reported outcome measures (PROMs) over the course of 12 weeks. Comorbid depression and anxiety were explored with the Hospital Anxiety and Depression Scale (HADS). In 53% of our patients (80% females), suspicion of MCAS was based on self-evaluation. In total, patients reported 87 different symptoms, mostly fatigue (n = 57), musculoskeletal pain/weakness (n = 49), and abdominal pain (n = 43), with overall high disease activity and impact. Two of 79 patients had increased tryptase (by >20% +2 ng/ml) following an episode. Only 5%, with any of the PROMs used, showed complete response to MC-targeted treatment. Depression and anxiety disorders were frequent comorbidities (n = 23 each), and 65 patients had pathological HADS values, which were linked to high disease impact and poor symptom control. Mast cell activation syndrome was confirmed in only 2% of patients, which implies that it is not MC activation that drives signs and symptoms in most patients with suspected MCAS. There is a high need for comprehensive research efforts aimed at the identification of the true underlying pathomechanism(s) in patients with suspected MCAS.


The bacteriology of acute maxillary sinusitis.
Sinus secretions obtained by antral aspiration from 347 patients with acute maxillary sinusitis were examined bacteriologically. Special attention was paid to the method by which anaerobic bacteria could be recovered. On the total, 485 sinus secretion samples were examined, of these 336 were aspirates, 149 yields of injection-aspirations. Aerobic bacteria were cultured from 263 aspirates and from 100 injection-aspiration samples. Only anaerobes were recovered from 6 sinuses. Bacterial culture was negative in 115 sinuses (24%). The most common pathogens isolated were Haemophilus influenzae (50.5%), Streptococcus pneumoniae (18.5%), Streptococcus pyogenes (5%) and Branhamella catarrhalis (1.5%). A true anaerobic infection was considered to be present in only 7 sinuses (1.5%) indicating that anaerobes are not a significant cause of acute maxillary sinusitis. According to this study the most common pathogen in acute maxillary sinusitis in young adults is H. influenzae. From this follows that in such patients aminopenicillins may be a more appropriate choice than conventional penicillin in the antimicrobial treatment of acute maxillary sinusitis.


Evolving neoantigen profiles in colorectal cancers with DNA repair defects.
Neoantigens that arise as a consequence of tumor-specific mutations can be recognized by T lymphocytes leading to effective immune surveillance. In colorectal cancer (CRC) and other tumor types, a high number of neoantigens is associated with patient response to immune therapies. The molecular processes governing the generation of neoantigens and their turnover in cancer cells are poorly understood. We exploited CRC as a model system to understand how alterations in DNA repair pathways modulate neoantigen profiles over time. We performed whole exome sequencing (WES) and RNA sequencing (RNAseq) in CRC cell lines, in vitro and in vivo, and in CRC patient-derived xenografts (PDXs) to track longitudinally genomic profiles, clonal evolution, mutational signatures, and predicted neoantigens. The majority of CRC models showed remarkably stable mutational and neoantigen profiles; however, those carrying defects in DNA repair genes continuously diversified. Rapidly evolving and evolutionary stable CRCs displayed characteristic genomic signatures and transcriptional profiles. Downregulation of molecules implicated in antigen presentation occurred selectively in highly mutated and rapidly evolving CRC. These results indicate that CRCs carrying alterations in DNA repair pathways display dynamic neoantigen patterns that fluctuate over time. We define CRC subsets characterized by slow and fast evolvability and link this phenotype to downregulation of antigen-presenting cellular mechanisms. Longitudinal monitoring of the neoantigen landscape could be relevant in the context of precision medicine.


A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia.
Romiplostim and eltrombopag, the first thrombopoietic receptor-agonists with demonstrated efficacy against immune thrombocytopenia in prospective controlled studies, were recently authorized in most countries for adults with chronic immune thrombocytopenia. So far, no data are available about the potential contribution of switching from romiplostim to eltrombopag or vice versa in terms of efficacy or tolerance. Efficacies and tolerance profiles were evaluated for 46 patients who sequentially received both drugs, switching from one to the other. The reasons for switching were: lack of efficacy for 23 patients, platelet-count fluctuations for 11, side effects for 4, and 8 patients' preferences. For 50-80% of the patients, switching from romiplostim to eltrombopag or eltrombopag to romiplostim effectively impacted the platelet count, with fluctuations disappearing in 54% and side effects resolved in 100%. In 80% of the patients, the 2 thrombopoietic receptor-agonists achieved similar response patterns. Our results confirmed that switching from one thrombopoietic receptor-agonist to the other could be beneficial in clinical practice for patients with severe chronic immune thrombopenia who failed to respond or experienced adverse events to the first. (Clinical Trials.gov identifier: NCT01618734).


Effects of sepiolite and biochar on the photosynthetic and antioxidant systems of pakchoi under Cd and atrazine stress.
Sepiolite and biochar effectively immobilize Cd and atrazine in vegetable soils. This study further investigated the effects of sepiolite and biochar on the photosynthetic and antioxidative defence systems of pakchoi under Cd and atrazine stress. The results showed that after adding sepiolite and biochar to contaminated soil, the chlorophyll content was restored and the photosynthetic rate increased, whereas the soluble sugar content of pakchoi decreased. In the antioxidant system of the plants, the activities of peroxidase, ascorbate peroxidase, and superoxide dismutase decreased, while the activity of catalase increased. The content of malondialdehyde, glutathione, and O2·- increased, but the content of H2O2 decreased. In general, remediation materials reduced the bioavailability of Cd and atrazine, reduced the stress on pakchoi, and restored and improved the rate of photosynthesis and function of antioxidants.


Identification of transcription start sites of trans-spliced genes: uncovering unusual operon arrangements.
In Caenorhabditis elegans, the transcripts of many genes are trans-spliced to an SL1 spliced leader, a process that removes the RNA extending from the transcription start site to the trans-splice site, thereby making it difficult to determine the position of the promoter. Here we use RT-PCR to identify promoters of trans-spliced genes. Many genes in C. elegans are organized in operons where genes are closely clustered, typically separated by only ~100 nucleotides, and transcribed by an upstream promoter. The transcripts of downstream genes are trans-spliced to an SL2 spliced leader. The polycistronic precursor RNA is processed into individual transcripts by 3' end formation and trans-splicing. Although the SL2 spliced leader does not appear to be used for other gene arrangements, there is a relatively small number of genes whose transcripts are processed by SL2 but are not close to another gene in the same orientation. Although these genes do not appear to be members of classical C. elegans operons, we investigated whether these might represent unusual operons with long spacing or a different, nonoperon mechanism for specifying SL2 trans-splicing. We show transcription of the entire region between the SL2 trans-spliced gene and the next upstream gene, sometimes several kilobases distant, suggesting that these represent exceptional operons. We also report a second type of atypical "alternative" operon, in which 3' end formation and trans-splicing by SL2 occur within an intron. In this case, the processing sometimes results in a single transcript, and sometimes in two separate mRNAs.


Palliative care needs at different phases in the illness trajectory: a survey study in patients with cancer.
Despite the growing consensus on the benefits of initiating palliative care early in the disease trajectory, it remains unclear at what point palliative care needs emerge. This study investigates quality of life and unmet palliative care needs at three phases in the cancer trajectory, curative, life-prolonging and most advanced (prognosis <6 months/no further disease-modifying treatment). We collected self-reported data from 620 patients with cancer in the University Hospital of Ghent, Belgium. They completed a questionnaire on quality of life (using the EORTC QLQ-C30) and unmet care needs within the domains of palliative care. We used European reference values of the EORTC QLQ-C30 to compare the mean scores with a norm group. The groups further on in the cancer trajectory reported statistically and clinically poorer functioning compared with earlier phases, also when controlled for the effects of sex, age or type of cancer. Higher symptom burdens for fatigue, pain, dyspnoea and appetite loss were found in groups further into the trajectory, p < .001. Patients in the curative phase experienced physical symptoms and had clinically worse functioning than a European reference group. This paper demonstrates the ongoing need for oncologists to address the broader palliative care needs of patients from diagnosis onwards.


Relationship between Retinal Inner Nuclear Layer Thickness and Severity of Visual Field Loss in Glaucoma.
Glaucoma is a disease characterized by pathologic changes in inner retinal layers, which are comprised of retinal ganglion cells (RGCs). As retinal ganglion cells (RGCs) cross over other retinal neurons that are connected by synapses, it is meaningful to investigate the outer retinal changes in glaucoma. We evaluated the association between thicknesses of segmented retinal layers in macular region and severity of visual field loss in open-angle glaucoma (OAG). This study involved 103 glaucomatous eyes. Retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) thicknesses were measured at the macular level using the Spectral-domain optical coherence tomography with segmentation software. The functional losses were measured using 24-2 standard automated perimetry. Macular structure losses were positively correlated with functional loss for RNFL, GCL, and IPL (R = 0.550, 0.637, and 0.649, respectively, P < 0.001) and negatively correlated with INL (R = -0.295, P = 0.041). By multivariate regression analysis, INL thickness was significantly associated with visual field mean deviation (dB) and optic disc hemorrhage. These finding carefully suggest reactive responses of neuronal or glial cells located in the INL occur during glaucoma progression.


Airway inflammation and occupational asthma.
Airway inflammation due to exposure to a wide variety of agents encountered in the workplace is a major cause of occupational asthma. This article reviews major examples of occupational asthma linked to airway inflammation, including their epidemiology, pathophysiology, and clinical course.


An intuitive approach to measuring protein surface curvature.
A natural way to measure protein surface curvature is to generate the least squares fitted (LSF) sphere to a surface patch and use the radius as the curvature measure. While the concept is simple, the sphere-fitting problem is not trivial and known means of protein surface curvature measurement use alternative schemes that are arguably less straightforward to interpret. We have developed an approach to solve the LSF sphere problem by turning the sphere-fitting problem into a solvable plane-fitting problem using a transformation known as geometric inversion. The approach works on any arbitrary surface patch, and returns a radius of curvature that has direct physical interpretation. Additionally, it is flexible in its ability to find the curvature of an arbitrary surface patch, and the "resolution" can be adjusted to highlight atomic features or larger features such as peptide binding sites. We include examples of applying the method to visualization of peptide recognition pockets and protein conformational change, as well as a comparison with a commonly used solid-angle curvature method showing that the LSF method produces more pronounced curvature results.


[Value of MDM2, CDK4 and SATB2 immunohistochemistry in histologic diagnosis of low-grade osteosarcoma].
To investigate the value of combined application of MDM2, CDK4 and SATB2 immunohistochemistry in pathological diagnosis of low-grade osteosarcoma. Forty-seven cases of low grade osteosarcoma, including low grade central osteosarcoma (n=20) and parosteal osteosarcoma (n=27), were selected from Shanghai Jiaotong University Affiliated the Sixth People's Hospital. The clinical, radiography and histopathology were reviewed. The sensitivity and specificity of MDM2, CDK4 and SATB2 immunohistochemistry in the diagnosis of low-grade osteosarcoma were assessed along with an evaluation of their expressions in fibrous dysplasia, desmoplastic fibroma, low-grade fibrosarcoma and other fibrous tumors. Low-grade osteosarcoma had protracted clinical course, occurring mostly in elder adults and mainly involving long bones. Radiographic studies showed that low-grade central osteosarcoma had a mainly malignant lytic presentation, however about 5/18 of tumors overlapping with intermediate and benign bone diseases, while parosteal osteosarcoma was characterized by a densely sclerotic malignant appearance. Histologically, low-grade osteosarcomas were characterized by well-differentiated spindle tumor cells, various mature tumor bones and an aggressive growth pattern. The positive expression rates of MDM2 and CDK4 in low-grade osteosarcoma were 74.5% and 55.3%, respectively. Eighty-three percent of low-grade osteosarcoma expressed one or both markers. Low-grade osteosarcoma and fibrous dysplasia were both positive for SATB2, while desmoplastic fibroma, low-grade fibrosacoma and other fibrous tumors were negative for SATB2. Accurate diagnosis of low-grade osteosarcoma should be based on combination of clinical presentation, imaging and histopathology, with immunohistochemistry as a diagnostic adjunct. Positive immunostaining for CDK4 and/or MDM2 supports the diagnosis of low-grade osteosarcoma, but the negative one does not rule out such lesion. The negative expression of SATB2 is helpful to exclude fibrous tumors originating from bone with the exception of fibrous dysplasia.


The Role of Nrf2 in Liver Disease: Novel Molecular Mechanisms and Therapeutic Approaches.
Oxidative stress and inflammation are the most important pathogenic events in the development and progression of liver diseases. Nuclear erythroid 2-related factor 2 (Nrf2) is the master regulator of the cellular protection via induction of anti-inflammatory, antioxidant, and cyto-protective genes expression. Multiple studies have shown that activation or suppression of this transcriptional factor significantly affect progression of liver diseases. Comprehensive understanding the roles of Nrf2 activation/expression and the outcomes of its activators/inhibitors are indispensable for defining the mechanisms and therapeutic strategies against liver diseases. In this current review, we discussed recent advances in the function and principal mechanisms by regulating Nrf2 in liver diseases, including acute liver failure, hepatic ischemia-reperfusion injury (IRI), alcoholic liver disease (ALD), viral hepatitis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC).


Mesenchymal stromal cell infusion to treat steroid-refractory acute GvHD III/IV after hematopoietic stem cell transplantation.
Acute GvHD (aGvHD) is a life-threatening complication of hematopoietic stem cell transplantation. Frontline therapy for aGvHD consists of corticosteroid administration. However, ∼25% of the patients have a steroid-refractory disease, a sign of poor prognosis. An alternative therapy for steroid-refractory aGvHD is infusion of mesenchymal stromal cells (MSCs). Herein, we report the results of 46 patients treated with MSC infusion as salvage therapy for steroid-refractory aGvHD III/IV (78% grade IV). Patients received a median cumulative dose of MSCs of 6.81 × 106/kg (range, 0.98-29.78 × 106/kg) in a median of 3 infusions (range, 1-7). Median time between the onset of aGvHD and the first MSC infusion was 25.5 days (range, 6-153). Of the patients, 50% (23/46) presented clinical improvement. Of these, 3 patients (13%) had complete response, 14 (61%) had partial response and 6 (26%) had transient partial response. The estimated probability of survival at 2s year was 17.4%. Only 2 patients (4.3%) presented acute transient side effects (nausea/vomiting and blurred vision) during cell infusion. No patient had late or severe side effects because of MSC infusion. These results suggest that this therapeutic modality is safe and should be considered for steroid-refractory aGvHD, especially in countries where other second-line agents are less available.


Percutaneous radiofrequency ablation: minimally invasive therapy for renal tumors.
Currently, up to 60% of renal tumors are detected incidentally by abdominal imaging. Most of these tumors are small and localized to the kidney. Owing to the shift to lower stage at diagnosis, radical nephrectomy has fallen out of favor and has been replaced by nephron-sparing surgery. Currently, partial nephrectomy is the treatment of choice for patients with small renal tumors. As the trend towards less invasive therapy continues, laparoscopic and percutaneous ablation techniques have gained popularity for the treatment of renal tumors in patients who are high-risk surgical candidates, or have a solitary kidney, limited renal function or multifocal disease. Percutaneous radiofrequency ablation is a safe, minimally invasive treatment option for those patients.


Application of oral implants to the general dental practice.
The use of dental implants has become a management strategy for replacing missing teeth. As new implant surface technologies develop and prosthetic options increase, the field of dental implantology continues to change. General dentists con sidering the use of this treatment modality in their practices should understand the vital role treatment planning plays in achieving predictable outcomes. This article reviews specific issues the general dentist typically faces when considering patients for single-tooth, partially-edentulous-arch and full-arch tooth replacement using dental implants. The author analyzes patient-based assessments, as well as diagnostic criteria and steps, to help practitioners predict patient-specific issues that may signal complications. He also discusses approaches for resolving complications. The article emphasizes the importance of careful evaluation in predicting patient-specific issues that can lead to gingival recession and suggests approaches to manage these situations. Dental implants have become an increasingly common treatment option for missing dentition. Because innovations in implant surfaces continue to promote faster bone growth with better predictability, general dentists should be aware of the importance of treatment planning, assessment and teamwork in achieving successful outcomes.


Immunoaffinity column cleanup with liquid chromatography using post-column bromination for aflatoxins in medicinal herbs and plant extracts.
A new and accurate method to quantitate aflatoxins in medicinal herbs is developed. This method consists of extraction of the sample with MeOH-H2O (70:30) followed by clean-up of the extracts with immunoaffinity columns and, finally, high-performance liquid chromatographic determination with fluorescence detection. Aflatoxins B1 and G1 are determined as their bromine derivatives, produced in an online post-column derivatization system. The overall average recoveries for three different medicinal herbs spiked at levels of 1.3 and 2.6 ng/g of total aflatoxins range from 93% to 97%. The detection limit is 0.15 ng/g for both G2 and B2 and 0.20 ng/g for both G1 and B1, based on a signal-to-noise ratio of 3:1 and a precision (within-laboratory relative standard deviation) ranging from 0.8% to 1.4%. The use of immunoaffinity columns provides excellent clean-up of these particular extracts, which are generally difficult to analyze. The method is applied successfully to 96 samples of natural drugs.


17 Beta-estradiol increases endothelial nitric oxide synthase mRNA copy number in cerebral blood vessels: quantification by real-time polymerase chain reaction.
The enzyme endothelial nitric oxide synthase (eNOS) plays a critical role in the maintenance of vascular tone. The mechanism by which estrogen increases eNOS function remains controversial. We demonstrate here using real-time polymerase chain reaction (PCR) and immunoblot analysis that in vivo estrogen treatment leads to a 100% increase in eNOS messenger RNA (mRNA) copy number and increases eNOS protein levels by 47% in mouse cerebral blood vessels. These data suggest that estrogen can modulate eNOS at the transcriptional level in blood vessels in vivo.


A field evaluation of the impact of transfer efficiency on worker exposure during spray painting.
This paper presents a mathematical model to predict breathing-zone overspray concentrations produced during spray painting as a function of the overspray generation rate, ventilation and work practices. The overspray generation rate required an estimate of the spray gun transfer efficiency, which was provided by a previously developed mathematical model. These models were evaluated in the field under two different scenarios: first in a controlled environment that approximated the assumptions of models, and then under actual spray painting conditions. Results from the first test showed the model overestimated transfer efficiency, but the measured exposures and predicted exposures were not significantly different. During actual spray painting operations, all task exposures were within a factor of three of the model predictions, and there was no statistical difference between the measured and predicted values. The predicted average exposure of each worker was within the 95% confidence interval. The overall mean exposure was within one standard error of the model prediction. The current study expands on the original exposure model by including a transfer efficiency model to provide a better estimate of the overspray generation rate. The theoretical foundation between exposure and its primary determinants is established, and this knowledge can be applied to design and can evaluate optimal control interventions. Also, the general methodology presented here for developing an exposure model is applicable to operations other than spray painting.


Simultaneous indocyanine green and fluorescein angiography using a confocal scanning laser ophthalmoscope.
Fluorescein and indocyanine green (ICG) angiography are both useful in the diagnosis and treatment of many retinal diseases. In some cases, both tests must be performed for diagnosis and treatment; however, performing both is time-consuming and may require multiple injections. We designed a compact digital confocal scanning laser ophthalmoscope to perform true simultaneous fluorescein and ICG angiography. We report our experience using the instrument to perform 169 angiograms in 117 patients. There were no unexpected adverse effects from mixing the dyes and administering them in 1 injection. An entire examination, including fundus photography, fluorescein angiography, and ICG angiography, could be performed in 45 minutes. It was possible to study differences in fluorescein patterns by comparing identically timed frames and to find cases in which ICG or fluorescein was optimal in visualizing retinal and subretinal structures. Confocal optical sections in the depth (z) dimension allowed viewing in different planes. It was possible to overlay ICG and fluorescein images or compare them side-by-side using a linked cursor. Digital transmission of the images was also performed. Simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently. The availability of simultaneous angiography will allow critical determination of the relative advantages and disadvantages of both types of angiography.


Molecular identification and functional analysis of a maize (Zea mays) DUR3 homolog that transports urea with high affinity.
Successful molecular cloning and functional characterization of a high-affinity urea permease ZmDUR3 provide convincing evidence of ZmDUR3 roles in root urea acquisition and internal urea-N-remobilization of maize plants. Urea occurs ubiquitously in both soils and plants. Being a major form of nitrogen fertilizer, large applications of urea assist cereals in approaching their genetic yield potential, but due to the low nitrogen-use efficiency of crops, this practice poses a severe threat to the environment through their hypertrophication. To date, except for paddy rice, little is known about the biological basis for urea movement in dryland crops. Here, we report the molecular and physiological characterization of a maize urea transporter, ZmDUR3. We show using gene prediction, PCR-based cloning and yeast complementation, that a functional full-length cDNA encoding a 731 amino acids-containing protein with putative 15 transmembrane α-helixes for ZmDUR3 was successfully cloned. Root-influx studies using (15)N-urea demonstrated ZmDUR3 catalyzes urea transport with a K m at ~9 µM when expressed in the Arabidopsis dur3-mutant. qPCR analysis revealed that ZmDUR3 mRNA in roots was significantly upregulated by nitrogen depletion and repressed by reprovision of nitrogen after nitrogen starvation, indicating that ZmDUR3 is a nitrogen-responsive gene and relevant to plant nitrogen nutrition. Moreover, detection of higher urea levels in senescent leaves and obvious occurrence of ZmDUR3 transcripts in phloem-cells of mature/aged leaves strongly implies a role for ZmDUR3 in urea vascular loading. Significantly, expression of ZmDUR3 complemented atdur3-mutant of Arabidopsis, improving plant growth on low urea and increasing urea acquisition. As it also targets to the plasma membrane, our data suggest that ZmDUR3 functions as an active urea permease playing physiological roles in effective urea uptake and nitrogen remobilization in maize.


[Pseudocontinent colostomy - a manometric study].
The intraluminal pressure in terminal segment of colon has been studied at 42 patients undergone an exterpation of rectum and taken out pseudocontinent colostomy onto a front part of the abdomen. Schmidt's pattern smooth muscle muff, modified in the Clinic Surgery and Coloproctology at MU--Varna, has been transplanted around the colon, taken out as continent colostomy. The intraluminal pressure in the terminal segment of colon has been identified with an index of resistance on the side the smooth muscle muff against the spontaneous evacuation of the colon content. The pressure has been registrated at rest and after the mechanical dillatation of muscle muff. The pressure at the check group of 20 patients with taken out continent colostomy has been investigated manometrically. The basal intraluminal pressure at the patients with a transplanted smooth muscle muff has been 30 +/- 2.9 mmHg at the end of the first postoperative month, as it has been sustained permanent (29.7 +/- 3.0 mmHg) up to the second postoperative jear (0.001). The pressure has been increased up to the mean value of 42 +/- 2.5 mmHg, as it has been sustained at this level for a period of 120 sec. The basal intraluminal pressure at the patients with transplanted smooth muscle muff has been more then four times higher in comparison with the pressure in c. sigmoideum, which has been a prerequisite for stopping of the spontaneous evacuation. A conclusion has been done that the index of resistance in the terminal segment of colon has been depended on a functional potential of the smooth muscle muff directly. The transplanted muff has been an anatomic structure manifested a functional activity in terms of isolation.


The physiology of parathyroid hormone-related protein: an emerging role as a developmental factor.
Parathyroid hormone-related protein (PTHrP) is the agent responsible for humoral hypercalcemia of malignancy. Its pathogenic role in this syndrome is well established and attention has focused in recent years on the elucidation of the roles played by PTHrP in normal developmental and adult physiology. This review focuses on studies of the past two years: (a) elucidation of the posttranslational processing pattern of PTHrP, the mechanisms of action of the various secretory forms of PTHrP, the role of PTHrP as an intracrine regulator of cell growth and cell death; (b) the emergence of PTHrP as a critical developmental factor in the mammary gland, epidermis, and the skeleton; and (c) the advances in understanding of the roles of PTHrP in the regulation of pancreatic islet mass, vascular smooth muscle tone and proliferation, and materno-fetal calcium transfer across the placenta.


Increased insulin sensitivity and decreased body weight in female rats after postnatal corticosterone exposure.
Glucocorticoids are important for normal brain development. Elevation or removal of these hormones can permanently modify the structure and function of the fetal brain. The purpose of this study was to examine the effects of postnatal corticosterone exposure of female pups on metabolic, endocrine and anthropometric variables in adulthood. Female pups were given subcutaneous injections of corticosterone (5 mg/kg, CORT) or vehicle 3 and 5 days after birth. From 6 weeks of age, the CORT rats weighed significantly less than did controls, with diminished fat depots, decreased serum levels of leptin and reduced food intake. Adult CORT rats showed increased insulin sensitivity, measured by hyperinsulinemic, euglycemic clamp (5 mU/kg/min), as compared with controls. CORT rats had lower basal corticosterone levels and lower corticosterone levels 15 and 90 min after exposure to stress. The results indicate that postnatal exposure to corticosterone leads to increased insulin sensitivity, low body weight with diminished fat depots, leptin and food intake. This suggests that postnatal exposure to corticosterone induces specific programming, with consequences in adult life.


Brain Gray Matter MRI Morphometry for Neuroprognostication After Cardiac Arrest.
We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting. Prospective cohort study. Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy). High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest. None. Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem. These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.


Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins.
Splicing factor 1 (SF1) recognizes the branch point sequence (BPS) at the 3' splice site during the formation of early complex E, thereby pre-bulging the BPS adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the BPS. The 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65) interacts with SF1 and was shown to recruit the U2 snRNP to the spliceosome. Co-immunoprecipitation experiments of SF1-interacting proteins from HeLa cell extracts shown here are consistent with the presence of SF1 in early splicing complexes. Surprisingly almost all U2 snRNP proteins were found associated with SF1. Yeast two-hybrid screens identified two SURP domain-containing U2 snRNP proteins as partners of SF1. A short, evolutionarily conserved region of SF1 interacts with the SURP domains, stressing their role in protein-protein interactions. A reduction of A complex formation in SF1-depleted extracts could be rescued with recombinant SF1 containing the SURP-interaction domain, but only partial rescue was observed with SF1 lacking this sequence. Thus, SF1 can initially recruit the U2 snRNP to the spliceosome during E complex formation, whereas U2AF65 may stabilize the association of the U2 snRNP with the spliceosome at later times. In addition, these findings may have implications for alternative splicing decisions.


Tandem Repeats in Proteins: Prediction Algorithms and Biological Role.
Tandem repetitions in protein sequence and structure is a fascinating subject of research which has been a focus of study since the late 1990s. In this survey, we give an overview on the multi-faceted aspects of research on protein tandem repeats (PTR for short), including prediction algorithms, databases, early classification efforts, mechanisms of PTR formation and evolution, and synthetic PTR design. We also touch on the rather open issue of the relationship between PTR and flexibility (or disorder) in proteins. Detection of PTR either from protein sequence or structure data is challenging due to inherent high (biological) signal-to-noise ratio that is a key feature of this problem. As early in silico analytic tools have been key enablers for starting this field of study, we expect that current and future algorithmic and statistical breakthroughs will have a high impact on the investigations of the biological role of PTR.


Making Room at the Table for Obstetrics, Midwifery, and a Culture of Normalcy Within Maternity Care.
The principle of avoiding the worst possible outcomes guided the enormous successes of modern obstetrics in reducing the morbidity and mortality of childbirth. The challenges of improving the quality of childbirth today has prompted health care providers, policymakers, and patients to ask whether this principle is in fact preventing us from supporting the normal processes of childbirth, resulting in undue intervention and potentially causing harm. In this commentary, we suggest that recognizing the strengths of the medical model of childbirth does not preclude looking outside of it to meet the maternity care needs of the majority of healthy, low-risk women. Obstetricians have the good fortune to have a partner in their work among midwives, who hail from a long tradition of incorporating a perspective of "normalcy" in the care of childbearing women. Given the many evidence-based practices demonstrating the strengths of midwifery to actualize patient-centered, low-intervention birth, we advocate for the explicit establishment of professional standards for team-based physician-midwife care. More than merely introducing midwives into a physician-dominated setting, this means elevating the contributions of midwives and meaningfully incorporating a culture of normalcy to standardize practices such as intermittent auscultation, continuous birth support, nonpharmacologic pain management, and positional flexibility in labor. The literature suggests that a woman's health care provider is the most powerful determinant of her birth outcomes; striking the balance between averting poor outcomes and normalcy compels us to make room at the table for both obstetricians and midwives.


Intuiting a Monsoonal Ethnography in Three Bay of Bengal Cities.
This visual essay offers an exploration of monsoonal materiality and agency in the urban environments of three cities situated around the Bay of Bengal: Chennai, Dhaka and Yangon. The text and images emerge from Monsoon Assemblages, a research project exploring intersections between changing monsoon climates and rapid urbanization in South Asia. Multi-modal, more-than-human ethnography has been employed during the course of research to explore how the lively materiality of the monsoon is entangled within urban lived environments. The essay outlines the process of intuiting a monsoonal ethnography and conveys the power of immersive field experience. By collecting and curating an assemblage of visual material and fieldnotes, this piece seeks to evoke the materiality and agency of the monsoon, itself a complex assemblage that manifests in different ways in different places. The juxtaposition of image and text conveys the generative and multifaceted agency of the monsoon and the urban environments it becomes enmeshed within.


Colchicine reduced pericardial effusion due to postcardiac injury syndrome following cardiac resynchronization therapy implantation.
We present a case of postcardiac injury syndrome with pericardial effusion following cardiac resynchronization therapy implantation which was treated by only colchicine. Although treatment using colchicine is not as common as NSAIDs or steroids, colchicine seems to be an effective and safe treatment option for the syndrome.


Cavity quantum-electrodynamical time-dependent density functional theory within Gaussian atomic basis. II. Analytic energy gradient.
Following the formulation of cavity quantum-electrodynamical time-dependent density functional theory (cQED-TDDFT) models [Flick et al., ACS Photonics 6, 2757-2778 (2019) and Yang et al., J. Chem. Phys. 155, 064107 (2021)], here, we report the derivation and implementation of the analytic energy gradient for polaritonic states of a single photochrome within the cQED-TDDFT models. Such gradient evaluation is also applicable to a complex of explicitly specified photochromes or, with proper scaling, a set of parallel-oriented, identical-geometry, and non-interacting molecules in the microcavity.


A Comparison of Transvaginal Removal and Repair of Uterine Defect for Type II Cesarean Scar Pregnancy and Uterine Artery Embolization Combined With Curettage.
Background: There is no consensus on a standardized therapy for type II cesarean scar pregnancy (CSP II). The objective of the present study was to evaluate the efficacy and safety and compare costs associated with transvaginal removal and repair (TRR) of uterine defect for CSP II to those of uterine artery embolization (UAE) and curettage. Methods: We conducted a retrospective study that included 87 patients diagnosed with CSP II and treated by performing UAE in combination with curettage and hysteroscopy (n = 53), or TRR (n = 34). Clinical data and outcomes were analyzed. Results: UAE and TRR groups exhibited similar success rates. The TRR group had significantly lower complication rates (30.19 vs. 8.82%, P < 0.05) and lower total costs (13,765.89 ± 2,029.12 vs. 9,063.82 ± 954.67, P < 0.05) than the UAE group. The anterior myometrium of the lower uterine segment was relatively thicker after performing TRR, and no patient suffered from recurrent CSP II. The proportion of patients in the TRR group who had full-term delivery without uterine rupture was 88.24% (30/34), while four patients failed to pregnancy. Conclusion: TRR is a safe and effective treatment method for patients with CSP II and presents a highly cost-effective outcome, especially for patients with future fertility desire.