Finite element analysis and computed tomography based structural rigidity analysis of rat tibia with simulated lytic defects.
Finite element analysis (FEA), CT based structural rigidity analysis (CTRA) and mechanical testing is performed to assess the compressive failure load of rat tibia with simulated lytic defects. Twenty rat tibia were randomly assigned to four equal groups (n=5). Three of the groups included a simulated defect at various locations: anterior bone surface (Group 1), posterior bone surface (Group 2) and through bone defect (Group 3). The fourth group was a control group with no defect (Group 4). Microcomputed tomography was used to assess bone structural rigidity properties and to provide 3D model data for generation of the finite element models for each specimen. Compressive failure load calculated using CT derived rigidity parameters (FCTRA) was well correlated to failure load recorded in mechanical testing (R(2)=0.96). The relationships between mechanical testing failure load and the axial rigidity (R(2)=0.61), bending rigidity (R(2)=0.71) and FEA calculated failure loads, considering bone as an elastic isotropic (R(2)=0.75) and elastic transversely isotropic (R(2)=0.90) are also well correlated. CTRA stress, calculated adjacent to the defect, were also shown to be well correlated with yield stresses calculated using the minimum density at the weakest cross section (R(2)=0.72). No statistically significant relationship between apparent density and mechanical testing failure load was found (P=0.37). In summary, the results of this study indicate that CTRA analysis of bone strength correlates well with both FEA and results obtained from compression experiments. In addition there exist a good correlation between structural rigidity parameters and experimental failure loads. In contrast, there was no correlation between average bone density and failure load.


Computed tomographic diagnosis of left superior vena cava and absence of the azygos vein: case report.
The radiologic findings on plain chest films and contrast-enhanced computed tomography (CCT) of the thorax in a case of isolated persistence of the left superior vena cava associated with absence of the right azygos vein are described. Chest x-rays allowed a presumptive diagnosis of the vascular anomaly. Confirmation of this anomaly was achieved by CT.


Reproducibility and minimal detectable change of three-dimensional kinematic analysis of reaching tasks in people with hemiparesis after stroke.
Three-dimensional kinematic analysis of reaching has emerged as an evaluative measure of upper-extremity motor performance in people after stroke. However, the psychometric properties supporting the use of kinematic data for evaluating longitudinal change in motor performance have not been established. The objective of this study was to determine, in a test-retest reliability manner, the reproducibility and minimal detectable change for reaching kinematics in people after stroke. Fourteen participants with hemiparesis after stroke performed forward reaching tasks on 2 occasions 37.3 (SD=9.8) days apart. At each session, participants performed 4 forward reaching tasks produced by the combination of 2 target heights (low and high [109 and 153 cm from the floor, respectively]) and 2 instructed movement speeds (self-selected and as fast as possible). Two analytical methods were used to calculate kinematic parameters. Relative reliability (intraclass correlation coefficient) ranged from .04 to .99, and absolute reliability (standard error of measurement) ranged from 2.7% to 76.8%, depending on the kinematic variable, the demands of the motor task (target height and movement speed), and the analytical method. Bland-Altman analysis, a statistical method used to assess the repeatability of a method, revealed few systematic errors between sessions. The minimal detectable change ranged from 7.4% to 98.9%. Depending on the demands of the motor task and the analytical method, most kinematic outcome measures (such as peak hand velocity, endpoint error, reach extent, maximum shoulder flexion range of motion, and minimum elbow extension range of motion) are reliable measures of motor performance in people after stroke. However, because of the magnitude of within-subject measurement error, some variables (such as peak hand velocity, time to peak hand velocity, and movement time) must change considerably (>50%) to indicate a real change in individual participants. The results of our reliability analysis, which are based on our cohort of participants with hemiparesis after stroke and our specific paradigm, may not be generalizable to different subpopulations of people with hemiparesis after stroke or to the myriad movement tasks and kinematic variables used for the assessment of reaching performance in people after stroke.


Learning curve of tympanoplasty type I.
To determine the time required to train a surgeon to skillfully perform tympanoplasty type I. From July 1, 2001 to December 31, 2006, 75 patients who underwent tympanoplasty type I were enrolled in this study. All of the procedures were performed by two surgeons trained in the same tertiary referral center. We stratified the patients into groups according to the surgeon level at the time of their surgery. We analyzed the operation time and surgical outcomes of these patients. The average operation time of resident physicians was 116.36 min, which was significantly longer (p<0.0001) than that of the attending physicians (average 83.11 min). There was no statistical difference in surgical success rate and post-operative complication between the resident year and attending year groups. We stratified the patients according to surgeon years, from year 3 to year 7. The operation time of the 4th and the 5th year surgeons was not statistically different from that of 3rd year surgeons. However, the operation time of the 6th and 7th year surgeons was statistically shorter than that of 3rd year surgeons. There was no difference on surgical success rate and complications among all year groups. A surgeon's years of experience could make the difference in terms of speed of operation. It takes 5 years for surgeons to reach a plateau in learning curve on the speed of performing tympanoplasty type I. We therefore conclude that it takes 5 years to train a surgeon for tympanoplasty type I.


[The 2021 Activity Report of the Tissue Transplantation and Biotechnology Section of the German Ophthalmological Society].
The Section on Tissue Transplantation and Biotechnology of the German Ophthalmologic Society presented its 11th annual report for the year 2021. The number of corneal samples has still risen in comparison to former years. Nevertheless, there is still a need for import of transplants from abroad. Therefore, the transplant bottleneck has not yet been eliminated.


Sickle cell anemia and trait in southern India: further studies.
Population surveys and family studies among 568 members of nine ethnic groups in southern India identified 15 homozygotes for sickle hemoglobin (HbS)who had mild clinical and hematological manifestations with high levels of fetal hemoglobin (mean=20%, range 8-36%) in a heterogeneous red cell distribution. In one family, the heterozygous mother had a hemoglobin pattern consistent with a form of the heterocellular hereditary persistence of fetal hemoglobin. Sickle cell trait was found in 153(27%) of those studied. Chromatographic quantitation of the hemoglobin fractions in these heterozygotes showed a trimodal distribution of the proportion of HB Sexplicable by a genetic model postulating the presence of genotypes with two (-alpha/-alpha), three (-alpha/alpha alpha) and four (alpha alpha/alpha alpha) active alpha-globin genes. Globin synthesis studies in four heterozygotes believed to have two active alpha-globin genes demonstrated an alpha/non-alpha total activity ratio (0.57) consistent with this model.


The association of skin diseases with human herpesvirus 8 infection in HIV carriers.
The seroprevalence to Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 (HHV-8) was surveyed in human immunodeficiency virus type 1 (HIV-1) carriers with or without skin diseases, and also in HIV-1 negative individuals in Thailand. Using an immunofluorescence assay, the seropositive rates to lytic antigens of HHV-8 in HIV-1 carriers with or without skin diseases were 25% and 7.4%, respectively, but none of HIV-1 negative individuals had antibody. The seroprevalence to HHV-8 antigens was high in HIV positive individuals with low CD4/CD8 ratio, suggesting that HHV-8 is reactivated during the immunosuppressive state. Several polypeptides with apparent molecular weights of 34-38,000 and 40,000, which were specific to HHV-8, were identified by the immunoprecipitation test using the seropositive sera. Our results suggested that HHV-8 co-existed with HIV in HIV-1 carriers and the existence of HHV-8 may be associated with clinical features in the skin.


Potentiation of mitomycin C, 6-mercaptopurine, bleomycin, cis-diamminedichloroplatinum and 5-fluorouracil by mycotrienins and mycotrienols.
Mycotrienins I and II and mycotrienols I and II are ansamycin antibiotics containing a triene structure, isolated from Streptomyces rishiriensis. An amphotericin B-resistant clone (AMBR-1) derived from cultured Chinese hamster V79 cells was cross-resistant to mycotrienins I and II, but not to mycotrienol I or II. These four ansamycin antibiotics were found to potentiate significantly the action of some anti-cancer agents including 5-fluorouracil, cis-diamminedichloroplatinum, bleomycin, mitomycin C and 6-mercaptopurine against cultured V79 cells. The action of adriamycin was not potentiated. These four ansamycin antibiotics showed a synergism spectrum similar to that of smaller polyene antibiotics.


Mussel-inspired cellulose nanofiber/poly(vinyl alcohol) hydrogels with robustness, self-adhesion and antimicrobial activity for strain sensors.
Flexible strain sensors have attracted substantial attention given their application in human-computer interaction and personal health monitoring. Due to the inherent disadvantages of conventional hydrogels, the manufacture of hydrogel strain sensors with high tensile strength, excellent adhesion, self-healing and antimicrobial properties in vitro, and conductive stability is still a challenge. Herein, a conductive hydrogel consisting of polydopamine-coated cellulose nanofibers (CNF@PDA), carbon nanotubes (CNT), and polyvinyl alcohol (PVA) was developed. The CNTs in PVA/CNF@PDA/CNT hydrogels were uniformly dispersed in the presence of CNF@PDA by hydrogen bonding, resulting in a nearly threefold increase in conductivity (0.4 S/m) over hydrogels without PDA. The hydrogel exhibited satisfactory tensile properties (tensile stress up to 0.79 MPa), good fatigue resistance, self-recovery and excellent antimicrobial activity in vitro. It showed excellent adhesion, especially the adhesion strength of pigskin was increased to 27 kPa. In addition, the hydrogel was used as a strain sensor, exhibiting excellent strain sensitivity (strain coefficient = 2.29), fast response (150 ms), and great durability (over 1000 cycles). The fabricated strain sensors can detect both large and subtle human movements (e.g., wrist bending and vocalization) with stable and repeatable electrical signals, indicating potential applications in personal health monitoring.


Superior colliculus lesions preferentially disrupt multisensory orientation.
The general involvement of the superior colliculus (SC) in orientation behavior and the striking parallels between the multisensory responses of SC neurons and overt orientation behaviors have led to assumptions that these neural and behavioral changes are directly linked. However, deactivation of two areas of cortex which also contain multisensory neurons, the anterior ectosylvian sulcus and rostral lateral suprasylvian sulcus have been shown to eliminate multisensory orientation behaviors, suggesting that this behavior may not involve the SC. To determine whether the SC contributes to this behavior, cats were tested in a multisensory (i.e. visual-auditory) orientation task before and after excitotoxic lesions of the SC. For unilateral SC lesions, modality-specific (i.e. visual or auditory) orientation behaviors had returned to pre-lesion levels after several weeks of recovery. In contrast, the enhancements and depressions in behavior normally seen with multisensory stimuli were severely compromised in the contralesional hemifield. No recovery of these behaviors was observed within the 6 month testing period. Immunohistochemical labeling of the SC revealed a preferential loss of parvalbumin-immunoreactive pyramidal neurons in the intermediate layers, a presumptive multisensory population that targets premotor areas of the brainstem and spinal cord. These results highlight the importance of the SC for multisensory behaviors, and suggest that the multisensory orientation deficits produced by cortical lesions are a result of the loss of cortical influences on multisensory SC neurons.


Dissection of the interferon gamma-MHC class II signal transduction pathway reveals that type I and type II interferon systems share common signalling component(s).
We have used a herpes virus thymidine kinase (HSV-TK) based metabolic selection system to isolate mutants defective in the interferon gamma mediated induction of the MHC class II promoter. All the mutations act in trans and result in no detectable induction of MHC and invariant chain (Ii) gene expression. Scatchard analysis indicates that the mutants have a normal number of surface IFN gamma receptors with the same affinity constant. The mutants fall into two broad categories. One class of mutants is still able to induce MHC class I, IRF-1, 9-27, 1-8 and GBP genes by IFN gamma. A second class of mutants is defective for the IFN gamma induction of all the genes tested; surprisingly, the IFN alpha/beta induction of MHC class I, 9-27, ISG54 and ISG15 genes is also defective in these mutants, although different members of this class can be discriminated by the response of the GBP and IRF-1 genes to type I interferons. These data demonstrate that the signalling pathways of both type I and type II interferon systems share common signal transduction component(s). These mutants will be useful for the study of IFN gamma regulation of class II genes and Ii chain, and to elucidate molecular components of type I and type II interferon signal transduction.


Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2).
Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries have re-ignited interest in the role of neuroinflammation in the pathogenesis of neurodegenerative diseases. TREM2 is highly expressed in microglia, the resident immune cells of the central nervous system. Along with its adaptor protein, DAP12, TREM2 regulates inflammatory cytokine release and phagocytosis of apoptotic neurons. Here, we report apolipoprotein E (apoE) as a novel ligand for TREM2. Using a biochemical assay, we demonstrated high-affinity binding of apoE to human TREM2. The functional significance of this binding was highlighted by increased phagocytosis of apoE-bound apoptotic N2a cells by primary microglia in a manner that depends on TREM2 expression. Moreover, when the AD-associated TREM2-R47H mutant was used in biochemical assays, apoE binding was vastly reduced. Our data demonstrate that apoE-TREM2 interaction in microglia plays critical roles in modulating phagocytosis of apoE-bound apoptotic neurons and establish a critical link between two proteins whose genes are strongly linked to the risk for AD.


Unraveling the impact of 27-hydroxycholesterol in autoimmune diseases: Exploring promising therapeutic approaches.
The role of 27-hydroxycholesterol (27-OHC) in autoimmune diseases has become a subject of intense research in recent years. This oxysterol, derived from cholesterol, has been identified as a significant player in modulating immune responses and inflammation. Its involvement in autoimmune pathogenesis has drawn attention to its potential as a therapeutic target for managing autoimmune disorders effectively. 27-OHC, an oxysterol derived from cholesterol, has emerged as a key player in modulating immune responses and inflammatory processes. It exerts its effects through various mechanisms, including activation of nuclear receptors, interaction with immune cells, and modulation of neuroinflammation. Additionally, 27-OHC has been implicated in the dysregulation of lipid metabolism, neurotoxicity, and blood-brain barrier (BBB) disruption. Understanding the intricate interplay between 27-OHC and autoimmune diseases, particularly neurodegenerative disorders, holds promise for developing targeted therapeutic strategies. Additionally, emerging evidence suggests that 27-OHC may interact with specific receptors and transcription factors, thus influencing gene expression and cellular processes in autoimmune disorders. Understanding the intricate mechanisms by which 27-OHC influences immune dysregulation and tissue damage in autoimmune diseases is crucial for developing targeted therapeutic interventions. Further investigations into the molecular pathways and signaling networks involving 27-OHC are warranted to unravel its full potential as a therapeutic target in autoimmune diseases, thereby offering new avenues for disease intervention and management.


Transfer of sensitivity to tumor promoters by transfection of DNA from sensitive into insensitive mouse JB6 epidermal cells.
Sensitivity to promotion of transformation by tumor promoters in mouse epidermal JB6 cells appears to have a genetic basis since the phenotypes of both promotable and nonpromotable JB6 cells derived from a common parent line are stable. Hybridization of promotable (P(+)) and nonpromotable (P(-)) cells previously indicated that promotability appears to behave as a dominant trait. These results suggest that it should be possible to find DNA sequences which specify sensitivity to promotion of anchorage independence by 12-o-tetradecanoyl-phorbol-13-acetate (TPA). Cellular DNA isolated from one of two P(+) lines, JB6 Cl 41 or JB6 Cl 22, was CaPO(4) precipitated and used to transfect the P(-) cell line JB6 Cl 30. At 7 days posttransfection, the cells were suspended in agar with or without TPA at 1.6 x 10(-8) M and assayed 10 days later for TPA-dependent colony formation. Untreated or Cl 30 DNA-treated P(-) JB6 Cl 30 cells yielded 40 to 50 colonies per 10(5) cells. In contrast, transfection of Cl 30 cells with "P(+) DNA" derived from either Cl 41 or Cl 22 yielded 200 to 500 TPA-induced colonies per 10(5) cells, or a five- to eightfold enhancement of promotability. The enhanced promotability obtained after transfection with P(+) DNA was stable, as judged by the retention of promotability for at least eight passages in cell lines derived from TPA-induced agar colonies. Other transfectants showed irreversible transformation by TPA, as observed in the parental P(+) lines. When NIH 3T3 cells instead of the putative preneoplastic JB6 Cl 30 cells were used as recipients for transfection of P(+) DNA, no evidence for acquisition of promotability was obtained. P(-) JB6 Cl 25, like Cl 30, also permitted expression of transfected P(+) DNA. These results suggest that sensitivity to phorbol ester promotion of transformation in JB6 cells is determined by DNA sequence(s) present in the P(+) DNA and requires recipient cells of the appropriate phenotype for expression.


Transcatheter Aortic Valve Implantation by Intercostal Access: Initial Experience with a No-Touch Technique.
Transcatheter aortic valve implantation (TAVI) is now a well-established therapeutic option in an elderly high-risk patient cohort with aortic valve disease. Although most commonly performed via a transfemoral route, alternative approaches for TAVI are constantly being improved. Instead of the classical mini-sternotomy, it is possible to achieve a transaortic access via a right anterior mini-thoracotomy in the second intercostal space. We describe our experience with this sternum- and rib-sparing technique in comparison to the classical transaortic approach. Our retrospective study includes 173 patients who were treated in our institution between January 2017 and April 2020 with transaortic TAVI via either upper mini-sternotomy or intercostal thoracotomy. The primary endpoint was 30-day mortality, and secondary endpoints were defined as major postoperative complications that included admission to the intensive care unit and overall hospital stay, according to the Valve Academic Research Consortium 3. Eighty-two patients were treated with TAo-TAVI by upper mini-sternotomy, while 91 patients received the intercostal approach. Both groups were comparable in age (mean age: 82 years) and in the proportion of female patients. The intercostal group had a higher rate of peripheral artery disease (41% vs. 22%, p = 0.008) and coronary artery disease (71% vs. 40%, p < 0.001) with a history of percutaneous coronary intervention or coronary artery bypass grafting, resulting in significantly higher preinterventional risk evaluation (EuroScore II 8% in the intercostal vs. 4% in the TAo group, p = 0.005). Successful device implantation and a reduction of the transvalvular gradient were achieved in all cases with a significantly lower rate of trace to mild paravalvular leakage in the intercostal group (12% vs. 33%, p < 0.001). The intercostal group required significantly fewer blood transfusions (0 vs. 2 units, p = 0.001) and tended to require less reoperation (7% vs. 15%, p = 0.084). Hospital stays (9 vs. 12 d, p = 0.011) were also shorter in the intercostal group. Short- and long-term survival in the follow-up showed comparable results between the two approaches (30-day, 6-month- and 2-year mortality: 7%, 23% and 36% in the intercostal vs. 9%, 26% and 33% in the TAo group) with acute kidney injury (AKI) and reintubation being independent risk factors for mortality. Transaortic TAVI via an intercostal access offers a safe and effective treatment of aortic valve stenosis.


Etched castings as an adjunct to mouth preparation for removable partial dentures.
Electrochemically etched nonprecious metal castings have been bonded to etched enamel for use in mouth preparation procedures for removable partial denture placement. The castings have been in service and subject to loading by the dentures for 26 to 42 months. To date, bond strengths have been sufficient to support function of both castings and removable partial dentures clinically. None of the castings has failed in its bond. Evidence that the technique may be a valuable adjunct is building in the field of prosthodontics. Use may be far reaching as dentists apply the concept to a wide variety of patient requirements in dental treatment. As more commercial dental laboratories acquire the capability to etch metals, cost should be minimized. Application is not time-consuming. Some steps are technique-sensitive, however, and short cuts are not well tolerated. This is especially true of cementation procedures where moisture or contamination of the field may lead to failure of the bond. It should be noted that each nonprecious metal is different from other metals in its composition, and therefore, results and techniques reported in this study can only be cited for the metal used. In addition, the acid used for etching one alloy may not be effective on another alloy. Finally, it is important that all castings be checked under a binocular microscope to ensure that proper etching did occur. Underetching and overetching both lead to a weakened bond and potential failure.


Guillain-Barré syndrome associated with Epstein-Barr virus in a cytomegalovirus-negative patient.
Epstein-Barr virus and cytomegalovirus have both been associated with Guillain-Barré syndrome after antibody investigations in several patients. In the teenage female patient in this present report, Guillain-Barré syndrome following infectious mononucleosis was associated with sero-conversion against Epstein-Barr virus but not cytomegalovirus. The findings are consistent with the hypothesis that Epstein-Barr virus might be an etiological agent for the Guillain-Barré syndrome and that infection with cytomegalovirus is not a requisite for the syndrome.


Function of a bovine papillomavirus type 1 exonic splicing suppressor requires a suboptimal upstream 3' splice site.
Alternative splicing is an important mechanism for the regulation of bovine papillomavirus type 1 (BPV-1) gene expression during the virus life cycle. Previous studies in our laboratory have identified two purine-rich exonic splicing enhancers (ESEs), SE1 and SE2, located between two alternative 3' splice sites at nucleotide (nt) 3225 and nt 3605. Further analysis of BPV-1 late-pre-mRNA splicing in vitro revealed a 48-nt pyrimidine-rich region immediately downstream of SE1 that inhibits utilization of the nt 3225 3' splice site. This inhibitory element, which we named an exonic splicing suppressor (ESS), has a U-rich 5' end, a C-rich central part, and an AG-rich 3' end (Z. M. Zheng, P. He, and C. C. Baker, J. Virol. 70:4691-4699, 1996). The present study utilized in vitro splicing of both homologous and heterologous pre-mRNAs to further characterize the ESS. The BPV-1 ESS was inserted downstream of the 3' splice site in the BPV-1 late pre-mRNA, Rous sarcoma virus src pre-mRNA, human immunodeficiency virus tat-rev pre-mRNA, and Drosophila dsx pre-mRNA, all containing a suboptimal 3' splice site, and in the human beta-globin pre-mRNA, which contains a constitutive 3' splice site. These studies demonstrated that suppression of splicing by the BPV-1 ESS requires an upstream suboptimal 3' splice site but not an upstream ESE. Furthermore, the ESS functions when located either upstream or downstream of BPV-1 SE1. Mutational analyses demonstrated that the function of the ESS is sequence dependent and that only the C-rich region of the ESS is essential for suppression of splicing in all the pre-mRNAs tested.


Impact of Dental Health Education on "Specific Learning Needs" Children.
This article compares and evaluates the effect of dental health education through schoolteachers and dental health professionals to "specific learning needs" children attending special school. A total of 71 "specific learning needs" children attending special school participated in the study. The baseline oral hygiene index-simplified (OHI-S) for all the participants was recorded. The training of schoolteachers was done using audiovisual and verbal methods on dental health facts and how to provide instructions on oral hygiene measures for reinforcing to the students. The students were randomly divided into three groups: Group 1 - No further dental health education by the schoolteachers or by the dental professionals was given to these students after the initial oral health education. Group 2 - In this group, the trained teachers taught students about the importance of oral health and demonstrated them brushing technique at intervals of 15 days, 1 month and 3 months. Group 3 - The dental professionals imparted dental health education and also demonstrated brushing techniques to these students at intervals of 15 days, 1 month and 3 months. Six months following the intervention a second examination was done to find out the OHI-S scores. Data analysis were done with Statistical Packages for the Social Sciences (SPSS) version 16 using one-way analysis of variance (ANOVA) statistical test. Group 2 demonstrated significant decline in OHI-S scores after intervention and all the three groups showed a statistically significant difference between the baseline OHI-S score and the scores after 6 months. Schoolteachers can be utilized for reinforcing dental health education among "specific learning needs" children effectively. How to cite this article: Relwani AH, Kiran S, Bhatt R, Patel M. Impact of Dental Health Education on "Specific Learning Needs" Children. Int J Clin Pediatr Dent 2016;9(1):31-34.


The effect of probiotic supplementation on episiotomy wound healing among primiparous women: a triple-blind randomized clinical trial.
Probiotics increase the defense power of immune system and accelerate the wound healing process by anti-inflammatory mechanisms at the wound site. The present study aimed at evaluating the effect of Lactobacillus casei oral supplementation on episiotomy wound healing among primiparous women. This triple-blind randomized clinical trial was performed on 74 primiparous women delivered in Alzahra Hospital, Tabriz, Iran. Participants with mediolateral episiotomy (incision length equal to and less than 5 cm) were randomly assigned to the probiotic and placebo groups. The probiotic group received Lactobacillus casei 431 with 1.5 * 109 colony-forming unit /capsule once a day from the day after birth to 14 days. Wound healing as a primary outcome was measured by Redness, Edema, Ecchymosis, Discharge, Approximation and pain as a secondary outcome by the Visual Analogue Scale before discharge, 5 ± 1 and 15 ± 1 days after birth. The data were analyzed using independent t-test and repeated measures one way analysis of variance. The mean (standard deviation: SD) score of wound healing in the probiotic group altered from 4.91(1.86) before discharge to 1.55 (0.99) during 5 ± 1 days after birth and reached to 0.95 (0.27) during 15 ± 1 days after birth. Further, the mean (SD) score of wound healing in the placebo group altered from 4.62 (1.99) before discharge to 2.80 (1.20) during 5 ± 1 days after birth and reached to 1.45(0.71) during 15 ± 1 days after birth (adjusted mean difference: -0.50, confidence interval 95%: -0.96 to -0.05, P = 0.03). Lactobacillus casei oral supplementation is effective in healing episiotomy wounds. It is suggested to evaluate the effect of topical use of Lactobacillus casei on episiotomy repair and pain in further studies. Iranian Registry of Clinical Trials (IRCT): IRCT20170506033834N7. Date of registration: 11/08/2021.


Global genomic signature reveals the evolution of fall armyworm in the Eastern hemisphere.
The major plant pest fall armyworm (FAW), Spodoptera frugiperda, is native to the Americas and has colonized Africa and Asia within the Eastern hemisphere since 2016, causing severe damage to multiple agricultural crop species. However, the genetic origin of these invasive populations requires more in-depth exploration. We analysed genetic variation across the genomes of 280 FAW individuals from both the Eastern hemisphere and the Americas. The global range-wide genetic structure of FAW shows that the FAW in America has experienced deep differentiation, largely consistent with the Z-chromosomal Tpi haplotypes commonly used to differentiate 'corn-strain' and 'rice-strain' populations. The invasive populations from Africa and Asia are different from the American ones and have a relatively homogeneous population structure, consistent with the common origin and recent spreading from Africa to Asia. Our analyses suggest that north- and central American 'corn-strain' FAW are the most likely sources of the invasion into the Eastern hemisphere. Furthermore, evidence based on genomic, transcriptomic and mitochondrial haplotype network analyses indicates an earlier, independent introduction of FAW into Africa, with subsequent migration into the recent invasive population.


New, miniaturized breath analyser for applications on Earth and in space.
The present article deals with the development and application of an innovative breath analyser for metabolic stress testing and cardio respiratory measurements. The system is based on new, miniaturized ceramic gas sensors, which have the unique ability to measure simultaneously oxygen and carbon dioxide concentrations as well as flow rates. The small size of just a few millimetres allows the operation of the sensor directly in a breathing mask, minimizing dead space and breath resistance. Due to these properties and the fast response time of the measurement, it will be possible to perform a breath-by-breath analysis, in both stationary and mobile mode, with low environmental and psychological influences of the experimental circumstances to the tested person. The current development status and the most interesting technical data, experimental results, and benefits of the new breath analyser are described in the article.


Dissociated brain organization for two-digit addition and subtraction: an fMRI investigation.
The present study compared the patterns of brain activation elicited by two-digit addition and subtraction problems. Thirty-two Chinese undergraduates of the same educational background and of similar age were asked to assess whether arithmetic operations were true or false during functional magnetic resonance imaging. Results showed that both complex addition and subtraction were supported by the broad neural system that involved regions within the inferior parietal lobule, the precuneus, and the inferior occipital gyrus, as well as some subcortical structures. Nevertheless, complex problems involving addition elicited more activation mainly in the bilateral medial frontal gyrus, whereas problems involving subtraction had more activation in the precentral gyrus and the thalamus in the right hemisphere, as well as the inferior parietal lobule in the left hemisphere. This pattern of dissociated activation suggests that partially separate neuronal networks might support these different operations. It also suggests that complex addition has a greater reliance on the fronto-parietal cortical circuit and subtraction on the parieto-subcortical circuit.


Maternal exposure to ambient air pollution mixture and premature rupture of membranes: Evidence from a large cohort in Southern California (2008-2018).
There is minimal evidence of relationships between maternal air pollution exposure and spontaneous premature rupture of membranes (SPROM), a critical obstetrical problem that can significantly increase maternal and fetal mortality and morbidity. No prior study has explored the PROM risk related to specific components of particulate matter with aerodynamic diameters of ≤ 2.5 µm (PM2.5). We examined associations between maternal exposure to nitrogen dioxide (NO2), ozone (O3), PM2.5, PM10, and PM2.5 constituents and SPROM. A large retrospective cohort study was conducted and included 427,870 singleton live births from Kaiser Permanente Southern California during 2008-2018. Monthly averages of NO2, O3 (8-h daily maximum), PM2.5, and PM10 were measured using empirical Bayesian kriging based on measurements from monitoring stations. Data on PM2.5 sulfate, nitrate, ammonium, organic matter, and black carbon were obtained from a fine-resolution model. A discrete time approach with pooled logistic regressions was used to estimate associations throughout the pregnancy and based on trimesters and gestational months. The quantile-based g-computation models were fitted to examine the effects of 1) the air pollution mixture of four pollutants of interest and 2) the mixture of PM2.5 components. There were 37,857 SPROM cases (8.8%) in our study population. We observed relationships between SPROM and maternal exposure to NO2, O3, and PM2.5. PM2.5 sulfate, nitrate, ammonium, and organic matter were associated with higher SPROM risks in the single-pollutant model. Mixture analyses demonstrated that the overall effects of the air pollution mixture and PM2.5 mixture in this study were mainly driven by O3 and PM2.5 nitrate, respectively. Underweight mothers had a significantly higher risk of SPROM associated with NO2. Our findings add to the literature on associations between air pollution exposure and SPROM. This is the first study reporting the impact of PM2.5 constituents on SPROM.


[An experimental study of antisense TGF-beta 1 inhibiting keloid fibroblast proliferation in vitro].
To study the effect of antisense TGF-beta 1 on keloid fibroblast proliferation in vitro. The antisense TGF-beta 1 was transfected into the keloid fibroblast by liposome. The cell count technique was used to test the effect of antisense TGF-beta 1 on keloid fibroblast proliferation in vitro. Cell apoptosis was tested by FCM. Antisense TGF-beta 1 can inhibit the proliferation of keloid fibroblast in vitro; Antisense TGF-beta 1 can increase the apoptosis ratio of keloid fibroblast in vitro. Antisense TGF-beta 1 can induce keloid fibroblast apoptosis and inhibit keloid fibroblast proliferation in vitro, which may contribute to the inhibition of keloid formation in vivo.


Decision making under deep uncertainty for pandemic policy planning.
Policymakers around the world were generally unprepared for the global COVID-19 pandemic. As a result, the virus has led to millions of cases and hundreds of thousands of deaths. Theoretically, the number of cases and deaths did not have to happen (as demonstrated by the results in a few countries). In this pandemic, as in other great disasters, policymakers are confronted with what policy analysts call Decision Making under Deep Uncertainty (DMDU). Deep uncertainty requires policies that are not based on 'predict and act' but on 'prepare, monitor, and adapt', enabling policy adaptations over time as events occur and knowledge is gained. We discuss the potential of a DMDU-approach for pandemic decisionmaking.


[Parotid tumors: a diagnostic and therapeutic protocol in 81 surgical cases].
In the last five years we cured 81 patients divided in two groups: the first was managed inordinately, the second according to a diagnostic and therapeutic protocol. The first 23 patients were differently evaluated, before surgery, by means of traditional sialography, US, CT, CT sialography, MR, larger bore needles and FNAB. Neoplasm enucleations, atipic resections, superficial and total conservative parotidectomies were performed. The following 58 patients were evaluated and cured according to a diagnostic and therapeutic protocol. Diagnostic and therapeutic time were shortened, patients endurance improved and cost lowered. We think that many diagnostic procedures are useless and delay operation that, if possible, must be performed according to principles of radical extirpation.


Are There Contraindications for Uniportal Video-Assisted Thoracic Surgery?
Allowing oneself to indulge in illusory superiority when it comes to uniportal video-assisted thoracic surgery (VATS) can harm patients and the specialty. It is important for every VATS surgeon to remain vigilant. One must be clear about the absolute and relative contraindications for VATS: those conditions that should deter from even attempting a uniportal approach. Once the operation is started, one must also bear in mind those situations that should prompt one to convert. Only by first safeguarding patients in this way can the aspiring uniportal VATS surgeon go on to safely master the approach and explore its benefits.


A simplified one stage modification of portoazygos disconnection for massive variceal hemorrhage.
A one stage, complete abdominal portoazygos disconnection procedure is a safe and efficient method for the treatment of acute variceal bleeding. This method was performed upon five patients who were bleeding due to severe cirrhosis of the liver, with no operative mortality. No recurrence of bleeding occurred during a follow-up study of one to four years.


First insight into the effect of single oral dose therapy with artemisinin-naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection.
Praziquantel is the current drug of choice against schistosomiasis. The dependency on praziquantel exclusively is problematic, given the spread of the disease and the threat of drug resistance. This study investigates an alternative antischistosomal drug using the compound naphthoquine phosphate tablet, which is a novel single oral dose antimalarial drug, containing a combination of naphthoquine phosphate and artemisinin. In the present study, the therapeutic efficacies of different artemisinin-naphthoquine phosphate combination-dosing protocols were evaluated in experimentally infected mice harbouring juvenile or adult stages of Schistosoma mansoni (Egyptian strain). The study shows that the oral administration of artemisinin-naphthoquine phosphate combination in a single dose of 400 mg/kg on day 7 p.i. resulted in a significant worm burden reduction of 95.07%. When used at a dose of 600 mg/kg on day 21 p.i., all female worms were killed before depositing eggs, resulting in complete absence of eggs in hepatic and intestinal tissues. The same dose given on day 42 p.i. reduced total and female worm burdens by 93.36% and 94.17%, respectively. In addition, artemisinin-naphthoquine phosphate combination induced significant reductions of 80.18% and 76.73% in the hepatic and intestinal tissue egg loads, respectively. Artemisinin-naphthoquine phosphate combination also induced significant alterations in the oogram pattern with elevated levels of dead eggs. Antipathological activities were evident in the amelioration of hepatic granulomata. Our findings hold promise for the development of a novel antischistosomal drug using an artemisinin-naphthoquine phosphate combination. Further in vitro and in vivo studies should be launched to elucidate the possible mechanism/s of action and to study the effect of artemisinin-naphthoquine phosphate combination on other human schistosomes.


Assessing the learning needs of physical medicine and rehabilitation residents to develop a geriatric medicine and rehabilitation curriculum.
Older adults with functional impairment are cared for by physiatrists in rehabilitation, but physiatrist training in geriatric-related competencies remains suboptimal. To develop a geriatric rehabilitation (GR) curriculum and explore opportunities for improvement, a needs assessment of stakeholders was conducted to understand physical medicine and rehabilitation (PMR) residents' comfort levels and learning needs in geriatrics. A mixed-methods design was employed. PMR residents (n = 18) and practicing physiatrists (n = 40) completed a questionnaire; and PMR residents, physiatrists and key informants (n = 9; n = 4; n = 6) participated in focus groups and semi-structured interviews to explore geriatric experiences of trainees and educational needs in geriatrics and rehabilitation. Data were qualitatively analyzed using constructivist-grounded theory. Residents and physiatrists highlighted similar topics as areas of low comfort in knowledge. Interviews prioritized critical geriatric topics (gait assessment, falls, cognitive impairment, movement disorders, and polypharmacy) and highlighted disposition planning and end-of-life care as areas needing further curriculum support. Challenges in delivering geriatric education were also identified. What emerged from the needs assessment was a series of critical geriatric educational priorities for the development of a GR curriculum for physiatry trainees - arising at an opportune time given the shift toward competency-based residency education.


The Reach and Accuracy of Information on Autism on TikTok.
Although social media platforms have made information about autism more accessible to the general public, concerns have been raised about the unfiltered nature of the content they host. In the current study, we examined the reach and accuracy of videos providing informational content about autism on TikTok, a popular social media platform. We examined engagement indicators (including views and "likes") for the TikTok videos associated with the #Autism hashtag. Two coders independently fact-checked informational content of the most viewed videos from the #Autism hashtag videos and coded it as either accurate, inaccurate or 'overgeneralization' based on the consistency of the information in the videos with current knowledge on autism. Videos associated with the "#Autism" hashtag accrued 11.5 billion views collectively. An examination of the top 133 videos providing informational content on autism, which totaled 198.7 million views and 25.2 million likes, showed that 27% of the videos were classified as accurate, while 41% were classified as inaccurate and 32% as overgeneralized. There were no significant differences in engagement between accurate and inaccurate/overgeneralized videos. Videos created by healthcare professionals were more likely to include accurate information. The informational content about autism made available on TikTok reaches a wide number of people. Most of the information provided, however, appears to be misaligned with current knowledge. It is important for healthcare providers and other professionals to be aware of the autism-related content being shared on TikTok so that they can better engage with the large community of TikTok users.


Immunophenotypic characterization and clinical outcome in cats with lymphocytosis.
Lymphocytosis is relatively common in cats, but few studies describe lymphocyte populations or the clinical course associated with different immunophenotypic expansions. We hypothesized that cats frequently develop non-neoplastic lymphocytosis and that different neoplastic immunophenotypes have variable prognoses. We aimed to characterize the lymphocyte expansions in a large population of cats with lymphocytosis and to assess clinical presentation and outcome in a subset. Three cohorts of cats older than 1 year with lymphocytosis (>6000/μL) were examined to define immunophenotypic categories (n = 146), evaluate outcome (n = 94), and determine prevalence of immunophenotypes (n = 350). Retrospective study of cats with blood submitted for flow cytometry. Medical records (n = 94) were reviewed for clinical data, treatment, and survival information. Five major immunophenotypic categories were identified: B cell, heterogeneous (≥2 lineages expanded), CD4+ T cell, CD4-CD8- (double negative [DN]) T cell, and CD5-low-expressing T cell. B-cell and heterogeneous phenotypes were more consistent with a non-neoplastic process, having polyclonal antigen receptor gene rearrangements, younger age at presentation, lower lymphocyte counts, and prolonged survival. The neoplastic phenotypes, CD4+ T cell, DN T cell, and CD5 low T cell, had different median survival times (752 days [n = 37], 271 days [n = 7], 27.5 days [n = 12], respectively). Among CD4+ T-cell cases, cats with abdominal lymphadenopathy, intestinal involvement, or both and females had shorter survival. Among 350 cats with lymphocytosis, CD4+ T-cell lymphocytosis was most common, followed by heterogeneous and B-cell phenotypes. Neoplastic CD4+ T-cell lymphocytosis is common in cats and has a prolonged clinical course compared to aberrant T-cell phenotypes. Cats with heterogeneous and B-cell lymphocyte expansions commonly have non-neoplastic disease.


Pharmacokinetics under the COVID-19 storm.
The storm-like nature of the health crises caused by COVID-19 has led to unconventional clinical trial practices such as the relaxation of exclusion criteria. The question remains: how can we conduct diverse trials without exposing subgroups of populations to potentially harmful drug exposure levels? The aim of this study was to build a knowledge base of the effect of intrinsic/extrinsic factors on the disposition of several repurposed COVID-19 drugs. Physiologically based pharmacokinetic (PBPK) models were used to study the change in the pharmacokinetics (PK) of drugs repurposed for COVID-19 in geriatric patients, different race groups, organ impairment and drug-drug interactions (DDIs) risks. These models were also used to predict epithelial lining fluid (ELF) exposure, which is relevant for COVID-19 patients under elevated cytokine levels. The simulated PK profiles suggest no dose adjustments are required based on age and race for COVID-19 drugs, but dose adjustments may be warranted for COVID-19 patients also exhibiting hepatic/renal impairment. PBPK model simulations suggest ELF exposure to attain a target concentration was adequate for most drugs, except for hydroxychloroquine, azithromycin, atazanavir and lopinavir/ritonavir. We demonstrate that systematically collated data on absorption, distribution, metabolism and excretion, human PK parameters, DDIs and organ impairment can be used to verify simulated plasma and lung tissue exposure for drugs repurposed for COVID-19, justifying broader patient recruitment criteria. In addition, the PBPK model developed was used to study the effect of age and ethnicity on the PK of repurposed drugs, and to assess the correlation between lung exposure and relevant potency values from in vitro studies for SARS-CoV-2.


[Experience with the treatment of longitudinal oblique and spiral fractures of the leg by Goetze's percutaneous cerclage].
After the short review of the literary data in respect of Goetze's percutaneous cerclage 25 cases are presented: in all cases satisfactory functional results have been obtained. With proper use this method is useful for the treatment of long oblique and spiral fractures of the leg, if suitable technical equipment is available.


Immunohistochemical localisation of PDE5 in Leydig and myoid cells of prepuberal and adult rat testis.
Expression of phosphodiesterase 5 (PDE5) in the rat testis at several pre and postnatal developmental stages was investigated by immunohistochemistry. The enzyme was localised in vascular smooth muscle cells, as well as in Leydig and peritubular cells. The latter were identified as myoid, based on their immunoreactivity to desmin and alpha-smooth muscle actin. The presence of PDE5 in myoid cells was confirmed by Western blot analysis and immunohistochemistry performed on highly purified cell fractions, obtained from 16-day-old rats. The expression of PDE5 in these somatic cells of rat testis is discussed in view of the roles played by cGMP signal transduction pathways in the mammalian male reproductive function.


Chronic progressive external ophthalmoplegia in a heredo-ataxia: neurogenic or myogenic? A clinical, neuropathological and submicroscopic study.
A patient with Friedreich's disease and chronic progressive external ophthalmoplegia is descirbed. An investigation was performed into the nature of the ocular motor disorders, which appeared clinically to be supranuclear. The EMG of the ocular muscles suggested myopathy. A specimen of ocular muscle was obtained by biopsy and examined with the light microscope and-for the first time-under the electron microscope. Signs of mitochondrial myopathy were found alongside neurogenic features. Postmortem examination of the central nervous system confirmed the diagnosis of Friedreich's disease with lesions of the motor cells in the anterior horn of the spinal cord. No evidence was found for a supranuclear or inernuclear origin of the ocular palsies, but 20-30 per cent of the neutrons in the nuclei III and IV were atrophic. Lesions of the non-medullated motor nerve fibres were also visible under the electron microscope. That the origin of the c. p. e. o. in this heredo-ataxia is neurogenic-nuclear is postulated on the grounds of the neuropathological and electronmicroscopic findings. Resemblances to the microscopic and submicroscopic and submicroscopic appearance of many types of "ocular myopathy" and "ophthalmoplegia-plus" throw doubt upon the myogenic character of these conditions. Possibly chronic, slowly progressive atrophy in the nuclear areas of the ocular motor nerves must in these cases also be held responsible for the c. p. e. o. Perhaps Moebius's Kern-Schwund theory may be revived after 85 years.


Engaging stakeholders in the use of an interactive simulation tool to support decision-making about the implementation of colorectal cancer screening interventions.
We aimed to understand how an interactive, web-based simulation tool can be optimized to support decision-making about the implementation of evidence-based interventions (EBIs) for improving colorectal cancer (CRC) screening. Interviews were conducted with decision-makers, including health administrators, advocates, and researchers, with a strong foundation in CRC prevention. Following a demonstration of the microsimulation modeling tool, participants reflected on the tool's potential impact for informing the selection and implementation of strategies for improving CRC screening and outcomes. The interviews assessed participants' preferences regarding the tool's design and content, comprehension of the model results, and recommendations for improving the tool. Seventeen decision-makers completed interviews. Themes regarding the tool's utility included building a case for EBI implementation, selecting EBIs to adopt, setting implementation goals, and understanding the evidence base. Reported barriers to guiding EBI implementation included the tool being too research-focused, contextual differences between the simulated and local contexts, and lack of specificity regarding the design of simulated EBIs. Recommendations to address these challenges included making the data more actionable, allowing users to enter their own model inputs, and providing a how-to guide for implementing the simulated EBIs. Diverse decision-makers found the simulation tool to be most useful for supporting early implementation phases, especially deciding which EBI(s) to implement. To increase the tool's utility, providing detailed guidance on how to implement the selected EBIs, and the extent to which users can expect similar CRC screening gains in their contexts, should be prioritized.


Relapse and Risk-taking among Iranian Methamphetamine Abusers Undergoing Matrix Treatment Model.
This study investigated the correlation between risk-taking and relapse among methamphetamine (MA) abusers undergoing the Matrix Model of treatment. This cross-sectional study was conducted on male patients who were stimulant drug abusers undergoing the matrix treatment in the National Center for Addiction Research. A sampling was done using the availability method including 92 male patients. Demographic questionnaires and drug abuse related questionnaire were completed for each patient. Then, Bart's balloon risk-taking test was administered to the patients. Participants had a mean age ± standard deviation (SD) of 27.59 ± 6.60 years with an age range of 17-29 years. Unemployment, unmarried status, criminal offense, and also addiction family history increased the probability of relapse. In addition, a greater adjusted score of the risk-taking test increased the odds of relapse by more than 97%. The simultaneous abuse of opium and stimulants compared to the abuse of stimulants only, revealed no statistically significant differences for relapse. Patients with higher risk-taking behavior had a more probability of relapse. This finding indirectly implies the usefulness of Bart's risk-taking test in assessing risk-taking behavior in stimulant drug abusers.


Impact of the Casimir-Polder potential and Johnson noise on Bose-Einstein condensate stability near surfaces.
We investigate the stability of magnetically trapped atomic Bose-Einstein condensates and thermal clouds near the transition temperature at small distances 0.5 microm< or =d< or =10 microm from a microfabricated silicon chip. For a 2 microm thick copper film, the trap lifetime is limited by Johnson noise induced currents and falls below 1 s at a distance of 4 microm. A dielectric surface does not adversely affect the sample until the attractive Casimir-Polder potential significantly reduces the trap depth.


What is 'Alzheimer's Disease'? The 'Auguste D' Case Re-opened.
What is Alzheimer's: an organic, neuropathological psychiatric disease, caused by plaques and tangles in aging brains or/and an existential condition affecting the minds of aging persons experiencing disconnection from meaning-bearing networks of social relations? Reviewing current research and revisiting Alzheimer's original case of 'Auguste D' this paper offers an historical-sociological genealogy that raises fundamental questions of causality, and even of the ontological status of Alzheimer's and the dementia reputed to it as a disease entity. Drawing on Kuhn's notion of 'science as usual' and Foucault's notion of the discursive formation of 'regimes of truth', our analysis seeks to understand how a sole medical focus on either bio-markers of neurological disease or genetic association was accomplished in the absence of sufficient and robust evidence. To counter the exclusion of psychosocial considerations, this paper offers two original hypotheses on the iconic case of 'Auguste D', taking into account the social milieu in which she lived and the specific circumstances of her life. It goes on to suggest the way in which the contemporary socio-cultural context may have dementiagenic tendencies. This research supports Gaines and Whitehouse's argument that research into the phenomenon and symptoms of Alzheimer's should focus on extracorporal and psychosocial factors.


Dual Protein Localization to the Envelope and Thylakoid Membranes Within the Chloroplast.
The chloroplast houses various metabolic processes essential for plant viability. This organelle originated from an ancestral cyanobacterium via endosymbiosis and maintains the three membranes of its progenitor. Among them, the outer envelope membrane functions mainly in communication with cytoplasmic components while the inner envelope membrane houses selective transport of various metabolites and the biosynthesis of several compounds, including membrane lipids. These two envelope membranes also play essential roles in import of nuclear-encoded proteins and in organelle division. The third membrane, the internal membrane system known as the thylakoid, houses photosynthetic electron transport and chemiosmotic phosphorylation. The inner envelope and thylakoid membranes share similar lipid composition. Specific targeting pathways determine their defined proteomes and, thus, their distinct functions. Nonetheless, several proteins have been shown to exist in both the envelope and thylakoid membranes. These proteins include those that play roles in protein transport, tetrapyrrole biosynthesis, membrane dynamics, or transport of nucleotides or inorganic phosphate. In this review, we summarize the current knowledge about proteins localized to both the envelope and thylakoid membranes in the chloroplast, discussing their roles in each membrane and potential mechanisms of their dual localization. Addressing the unanswered questions about these dual-localized proteins should help advance our understanding of chloroplast development, protein transport, and metabolic regulation.


DNA transfection of Escherichia coli by electroporation.
Electroporation was applied to transfection and transformation of Escherichia coli. Efficient transfer of DNA was achieved by a single voltage pulse at 2.5 kV (initial electric field strength = 6.25 kV/cm), with a 25 microF capacitor. As the recipient for transfecting DNA in the electroporation, spheroplasts, EDTA-treated cells and osmotically shocked bacteria were inferior to intact E. coli. Various parameters affecting the transfection efficiency were defined including growth phase of recipient cells, concentrations of DNA and cells, temperature and additions. In most strains tested, electroporation was far more efficient than Ca2+-dependent transfection (transformation). Various aspects of the electroporation-mediated DNA uptake are discussed.


Intra-peritoneal injection of polyclonal anti-interferon alpha antibodies cross the blood brain barrier and neutralize interferon alpha.
The central nervous system (CNS) is known to be an immunologically privileged organ in the body largely because the blood brain barrier (BBB) prevents the flow of large molecules, proteins, and cells from crossing into the CNS from the periphery. These restrictive properties of the BBB have made it difficult to treat CNS diseases. In this study, mice were infected intracranially (i.c.) with Sindbis virus (SV) and then treated either i.c. or intraperitoneally (i.p.) with neutralizing antibodies against interferon alpha (IFNalpha). SV infected control mice received i.p. saline. Antibodies against mouse IFNalpha were detected in the brain tissue of mice that received i.p. and i.c. injections of the antibody. ELISA analysis showed that both i.c. and i.p. antibody treated mice had significantly decreased levels of IFNalpha in the brain tissue. Also, mice that received IFNalpha neutralizing antibodies showed decreased presence of protein kinase R (PKR) measured by immunohistochemical densitometry, indicating the antibody successfully inhibited IFNalpha. The data shows that antibodies are capable of crossing the BBB and inhibiting IFNalpha, indicating that it is possible to target molecules of interest in the CNS with peripheral antibody treatment.


Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study.
Leptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia. A matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted. Genotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy-Weinberg equilibrium (P > 0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR = 6.44; 95%CI (3.98-10.40); P < 0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR = 3.48; 95%CI (1.15-10.54); P = 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR = 14.19; 95%CI (1.77-113.76); P = 0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR = 0.14; 95%CI (0.09-0.23); P < 0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR = 6.70; 95%CI (4.16-11.05); P < 0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D' = 1, r2 = 0.012). Our data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.


Anti-synthetase syndrome-associated interstitial lung disease possibly caused by atezolizumab in a patient with lung adenocarcinoma: a case report.
Anti-aminoacyl-tRNA synthetase (ARS) antibody-positive patients present with a variety of symptoms, including interstitial lung disease (ILD), which is termed anti-synthetase syndrome (ASS). But it is rare that ASS-ILD is considered an immune-related adverse event after the use of immune checkpoint inhibitors (ICIs). A 47-year-old male with advanced lung adenocarcinoma was treated with platinum and ICI combination immunotherapy and was followed up as an outpatient. Nine months after the start of treatment, he developed a fever and cough, and imaging findings showed lung consolidations in the bilateral lower lung fields. The patient was positive for anti- ARS antibodies and was considered to have developed ASS-ILD due to ICIs remitted with steroid therapy. The patient was found to be positive for anti-ARS antibodies before ICI administration, and the antibody titer was elevated compared to that before ICI administration. The examination of anti-ARS antibodies pior to the administration of ICIs may be useful in predicting the development of ASS-ILD.


Structure-based design of nitrosoureas containing tyrosine derivatives as potential antimelanoma agents.
Two new nitrosoureas (TNUs), containing tyrosine derivatives as carriers of nitrosourea cytotoxic group have been synthesised. The physicochemical properties such as half-life time (tau(0.5)), alkylating and carbamoylating activities were determined. The nitrosoureas showed a higher inhibiting effect on the DOPA-oxidase activity of mushroom tyrosinase than that of the antitumour drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). In vitro cytotoxic effects of newly synthesised tyrosine containing nitrosoureas have been studied and compared to those of CCNU. A higher cytotoxicity to B16 melanoma cells than to YAC-1 and to lymphocytes was demonstrated for the tyrosine containing nitrosoureas in comparison with CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea derivatives as potential antimelanomic drugs might be developed.


Screening, prevention and socioeconomic costs associated with the treatment of colorectal cancer.
Colorectal cancer (CRC), the third most prevalent cancer worldwide, imposes a significant economic and humanistic burden on patients and society. One study conservatively estimated the annual expenditures for colorectal cancer to be approximately dollars US 5.3 billion in 2000, including both direct and indirect costs. However, other investigators estimated inpatient costs alone incurred in the US in 1994 to be around dollars US 5.14 billion. Therefore, the economic burden of colorectal cancer in the US could be projected to be somewhere in the range of dollars US 5.5-6.5 billion by considering that inpatient costs approximate 80% of total direct costs. No worldwide data have been published, but assuming that the US represents 25-40% of total expenditures in oncology, as seen for breast and lung cancers, a rough estimate for colorectal cancer would be in the range of dollars US 14-22 billion. Screening helps increase patient survival by diagnosing colorectal cancer early. The ideal method among the four tests most used (faecal occult blood test, flexible sigmoidoscopy, colonoscopy and double contrast barium enema) has not been identified. Economic studies of colorectal cancer screening are complex because of the many variables involved, as well as the fact that the outcomes must be followed for many years, and the lack of consensus on screening guidelines. Intuitively, modelling colorectal cancer is one way to overcome these hurdles; published modelling studies predict colorectal cancer screening programs to be within the threshold of dollars US 40000 per life-year saved. The faecal occult blood test appears to be the only clearly effective test, both from a clinical and an economic viewpoint. Important limitations are the invasiveness and inconvenience of the screening procedures, except faecal occult blood test. Patients' comfort and satisfaction are essential in improving compliance with screening recommendations, which appears to be low even in the US (35% of the general population aged over 40 years and 60% of the high-risk population), the country with the highest awareness and compliance in the world. Since colorectal cancer is generally a disease of the elderly, its economic burden is expected to grow in the near future, mainly due to population aging. Potential avenues to pursue in order to contain or reduce the economic burden of colorectal cancer would be the design and implementation of efficient screening programmes, the improvement of patient awareness and compliance with screening guidelines, the development of appropriate prevention programs (i.e. primary and secondary), and earlier diagnosis.


Differential uptake of nitrogen forms by two herbs in the Gurbantunggut desert, Central Asia.
Understanding how plants adjust their requirements for different N forms can help elucidate plant coexistence strategies in N-limited desert ecosystems. To understand the mechanisms involved, we investigated whether two desert herbs can directly absorb dissolved organic nitrogen (N) and tested whether the patterns changed over different growth stages. Two dominant herbaceous species, Astragalus arpilobus and Arnebia decumbens, from the southern edge of the Gurbantunggut desert, China, were selected. Short-term (24 h) 15 N-labelled tracer (15 N-NO3 , 15 N-NH4 , 2-13 C-15 N-Glycine) treatments were conducted at two soil depths (0-5 cm and 5-15 cm) in the season of rapid growth (June) and in the peak biomass season (July). Enrichment in 13 C and 15 N was assessed in the two species receiving glycine. The ratio 13 C:15 N was 0.21-1.39 at the 24-h harvest, suggesting that approximately 10.5-69.5% of glycine had been absorbed. The amount of absorbed 15 N was significantly affected by species, month, soil depth and N form. The two species absorbed most 15 N from the 0-5 cm soil layer, and the absorption rate in July was higher than that in June. The absorption of 15 N-NO3 and 15 N-NH4 was significantly higher than that of 2-13 C-15 N-Glycine. The results indicate that these herbs could use amino acids in the N-deficient desert ecosystem. The two co-existing species used different forms of inorganic N for their requirements and maintained a specific preference throughout various growth stages.


Apathy predicts hedonic but not craving response to cocaine.
Cocaine-induced craving has been implicated in the maintenance of ongoing cocaine use and is presumed to be mediated by enhanced synaptic availability of monoamines, including dopamine. Apathy is a neuropsychiatric syndrome that is associated with hypodopaminergic functioning and is neurobiologically distinct from depression. Apathy has been observed to be prevalent during the initial phases of abstinence in cocaine-dependent individuals. In the current report, we sought to investigate the relationship between apathy, depression, and craving in response to an acute intravenous administration of cocaine. To this end, sixteen non-treatment seeking volunteers were evaluated. Following acute administration of cocaine (40 mg, IV), patients with low apathy scores exhibited increased craving, whereas patients with high apathy scores exhibited decreased craving. In addition, patients with high apathy scores exhibited increased ratings of the subjective measure of "High", suggesting that high apathy predicts a greater hedonic response in dependence. Self-reported ratings of depression did not account for the observed differences. The data reveal that cocaine-induced craving is not ubiquitous, and may not play a critical role in the maintenance of cocaine dependence. Overall, the findings suggest that apathy predicts hedonic but not craving response to cocaine.


A Spanish matrix sentence test for assessing speech reception thresholds in noise.
To develop, optimize, and evaluate a new Spanish sentence test in noise. The test comprises a basic matrix of ten names, verbs, numerals, nouns, and adjectives. From this matrix, test lists of ten sentences with an equal syntactical structure can be formed at random, with each list containing the whole speech material. The speech material represents the phoneme distribution of the Spanish language. The test was optimized for measuring speech reception thresholds (SRTs) in noise by adjusting the presentation levels of the individual words. Subsequently, the test was evaluated by independent measurements investigating the training effects, the comparability of test lists, open-set vs. closed-set test format, and performance of listeners of different Spanish varieties. In total, 68 normal-hearing native Spanish-speaking listeners. SRTs measured using an adaptive procedure were 6.2 ± 0.8 dB SNR for the open-set and 7.2 ± 0.7 dB SNR for the closed-set test format. The residual training effect was less than 1 dB after using two double-lists before data collection. No significant differences were found for listeners of different Spanish varieties indicating that the test is applicable to Spanish as well as Latin American listeners. Test lists can be used interchangeably.


Sister chromatid exchanges in human leukocyte chromosomes: spontaneous and induced frequencies in early- and late-proliferating cells in vitro.
Human leukocyte cultures were pulse-treated with the trifunctional alkylating mutagen trenimon in a final concentration of 10(-7) M for 15--20 h after culture start, i.e., in the G1 phase of the cell cycle. At 24 h after culture start bromodeoxyuridine (BUdR) was added to the trenimon-treated cultures and to several untreated cultures running in parallel. The series treated with BUdR only and the series treated with BUdR+trenimon were each used to prepare two cultures at different culture times. Mitoses were collected during consecutive intervals of 12 h from 30 h up to 102 h after culture initiation by colcemid. For all preparation times (42 h, 54 h, 66 h, 78 h, 90 h, and 102 h) the frequencies of first, second, and third and further mitoses were determined in the BUdR- and in the BUdR+trenimon-treated series. In the trenimon-treated series a clear cell cycle delay was detected as compared with the normal distribution of different types of mitoses found in series treated with BUdR only. Spontaneous and trenimon-induced sister chromatid exchange (SCE) frequencies were determined in second mitoses occurring at 66 h, 78 h, 90 h, and 102 h after culture start. For all these preparation times about six SCE per metaphase were consistently found in BUdR-treated, and about 19 SCE per metaphase in BUdR+-trenimon-treated series, indicating a homogeneous sensitivity of early- and late-proliferating cells with respect to the induction of SCE.


Roles of CSF2 as a modulator of inflammation during retinal degeneration.
Colony-stimulating factor 2 (CSF2) is a potent cytokine that stimulates myeloid cells, such as dendritic cells and macrophages. We have been analyzing the roles of microglia in retinal degeneration through the modulation of inflammation in the eye, and examined the roles of CSF2 in this process. Both subunits of the CSF2 receptor are expressed in microglia, but no evidence suggesting the involvement of CSF2 in inflammation in the degenerating eye has been reported. We found that Csf2 transcripts were induced in the early phase of in vitro mouse adult retina culture, used as degeneration models, suggesting that CSF2 induction is one of the earliest events occurring in the pathology of retinal degeneration. The administration of CSF2 into the retina after systemic NaIO3 treatment increased the number of microglia. To examine the roles of CSF2 in retinal inflammation, we overexpressed CSF2 in retinal explants. Induction of CSF2 activated microglia and Müller glia, and the layer structure of the retina was severely perturbed. CC motif chemokine ligand 2 (Ccl2) and C-X-C motif chemokine ligand 10 (Cxcl10), both of which are expressed in activated microglia, were strongly induced by the expression of CSF2 in the retina. The addition of CSF2 to primary retinal microglia and the microglial cell lines MG5 and BV2 showed statistically significant increase in Ccl2 and Il1b transcripts. Furthermore, CSF2 induced proliferation, migration, and phagocytosis in MG5 and/or BV2. The effects of CSF2 on microglia were mild, suggesting that CSF2 induced strong inflammation in the context of the retinal environment.


Menstrual exacerbation of schizophrenia symptoms.
To better understand premenstrual exacerbations of schizophrenia in women and weigh treatment options. A PubMed literature search was conducted, using the search terms 'schizophrenia', 'psychosis', 'menstrual exacerbation', 'hormones' and assessing relevance to premenstrual exacerbation of schizophrenia symptoms. Exacerbations are usually distinguishable from periodic or menstrual psychosis, a relatively rare condition. Controversy continues about whether low estrogen periods of the month lead to an increase in schizophrenia symptoms among women of reproductive age or whether some women suffer from both schizophrenia and premenstrual dysphoric disorder (PMDD). No treatment trials of specific interventions have been conducted so that physicians must decide on a case-by-case basis whether to raise antipsychotic doses premenstrually, try estrogens or estrogen/progesterone combinations or selective estrogen receptor modulators, or target PMDD symptoms. Clinicians need to be aware of premenstrual symptom aggravation in a large minority of women with schizophrenia. Treatment strategies will depend on the nature of the symptoms that are exacerbated. Optimal treatment needs to be adjusted to the individual woman.


Nitric oxide induces antioxidant machinery, PSII functioning and artemisinin biosynthesis in Artemisia annua under cadmium stress.
Soil contamination by heavy metals poses a significant environmental challenge, as the practical implementation of existing remediation technologies in the field has encountered numerous obstacles. This has necessitated the requirement of finding alternate solutions to reduce the harm caused to plants. In this study, nitric oxide (NO) was investigated for its potential to reduce cadmium (Cd) toxicity in A. annua plants. Although NO plays a vital role in the growth and development of plants, information on its role in reducing abiotic stress in plants is limited. A. annua plants were exposed to 20 and 40 mg/kg Cd regardless of the addition of exogenous sodium nitroprusside (SNP), a NO donor, at 200 µM concentration. Results showed that SNP treatment improved plant growth, photosynthesis, chlorophyll fluorescence, pigment content, and artemisinin production while reducing Cd accumulation and improving membrane stability in A. annua during Cd stress. The results demonstrated that NO can effectively reverse Cd-induced damage in A. annua by modulating the antioxidant system, maintaining redox homeostasis, and improving photosynthetic performance and different fluorescence parameters such as Fv/Fm, ФPSII, and ETR. The supplementation of SNP caused a substantial improvement in chloroplast ultrastructure, stomatal behavior, and different attributes relate to glandular secretory trichomes, which in turn increased artemisinin production; 14.11 % in plants exposed to Cd stress of 20 mg/kg. Our findings highlight that NO could be useful in mediating the repair of Cd-induced damage to A. annua, and suggest that it may play a critical role in plant signaling networks, improving plant adaptability to Cd stress. The results have important implications for developing new strategies to mitigate the negative impacts of environmental contaminants on plant health, and ultimately, the ecosystem.


Transcriptome profile of liver at different physiological stages reveals potential mode for lipid metabolism in laying hens.
Liver is an important metabolic organ that plays a critical role in lipid synthesis, degradation, and transport; however, the molecular regulatory mechanisms of lipid metabolism remain unclear in chicken. In this study, RNA-Seq technology was used to investigate differences in expression profiles of hepatic lipid metabolism-related genes and associated pathways between juvenile and laying hens. The study aimed to broaden the understanding of liver lipid metabolism in chicken, and thereby to help improve laying performance in the poultry industry. RNA-Seq analysis was carried out on total RNA harvested from the liver of juvenile (n = 3) and laying (n = 3) hens. Compared with juvenile hens, 2567 differentially expressed genes (1082 up-regulated and 1485 down-regulated) with P ≤ 0.05 were obtained in laying hens, and 960 of these genes were significantly differentially expressed (SDE) at a false discovery rate (FDR) of ≤0.05 and fold-change ≥2 or ≤0.5. In addition, most of the 198 SDE novel genes (91 up-regulated and 107 down-regulated) were discovered highly expressed, and 332 SDE isoforms were identified. Gene ontology (GO) enrichment and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the SDE genes were most enrichment in steroid biosynthesis, PPAR signaling pathway, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, three amino acid pathways, and pyruvate metabolism (P ≤ 0.05). The top significantly enriched GO terms among the SDE genes included lipid biosynthesis, cholesterol and sterol metabolic, and oxidation reduction, indicating that principal lipogenesis occurred in the liver of laying hens. This study suggests that the majority of changes at the transcriptome level in laying hen liver were closely related to fat metabolism. Some of the SDE uncharacterized novel genes and alternative splicing isoforms that were detected might also take part in lipid metabolism, although this needs further investigation. This study provides valuable information about the expression profiles of mRNAs from chicken liver, and in-depth functional investigations of these mRNAs could provide new insights into the molecular networks of lipid metabolism in chicken liver.


Size, volume and weight of the stomach in patients with morbid obesity compared to controls.
There is no mention in surgical literature regarding anatomic measurements of the stomach in patients with morbid obesity. We investigated by a prospective study the length of the lesser and greater curvature, the volume or total capacity and the weight of the stomach in morbidly obese patients compared to controls. 30 patients with different degrees of morbid obesity were compared to 20 controls. Measurements included length of both curvatures of the stomach, weight and total volume of saline needed to distend the stomach. Patients with morbid obesity were submitted to resectional gastric bypass. The stomach of controls was obtained from autopsy material during the first day after death. The length of the lesser curvature, total gastric capacity and weight of the stomach of morbidly obese patients were similar to control subjects. The length of greater curvature was significantly less in patients with morbid obesity. No significant differences were found in anatomic measurements of the stomach between control subjects and patients with morbid obesity.


Developmental patterns of intestinal disaccharidases in human amniotic fluid.
A close relationship exists between relative disaccharidase activities (maltase, sucrase, trehalase, palatinase, turanase, lactase, and cellobiase) in amniotic fluid and corresponding jejunal mucosa of five human fetuses (16 to 21 weeks of gestation) suggesting that these intestinal enzymes pass into amniotic fluid. Serial determination of disaccharidase activities in amniotic fluid samples collected between 10 and 42 weeks of gestation showed maximum mean activities at 14 to 17 weeks of gestation and a rapid drop to less than 12 per cent maximum values at about 22 weeks. This drop is probably caused by combined effects of decreased extrusion rate of intestinal disaccharidases and increased reabsorption of the enzymes in swallowed amniotic fluid with fetal development.


A water-soluble fluorescent organic nano-photosensitizer for the ratiometric detection of mitochondrial G-quadruplexes with photodynamic therapy potential.
We report a water-soluble AIEgen (TPAL) that can self-assemble into fluorescent organic nanoparticles for the ratiometric detection of mitochondrial DNA (mtDNA) parallel G-quadruplexes (G4s) with high selectivity, a low detection limit and photodynamic therapy (PDT) potential.


Changes in lifestyle after hypertension diagnosis in Canada.
Lifestyle modification should be an important part of therapy when hypertension is first diagnosed, with or without starting antihypertensive medication. The objective of the present study was to determine the extent to which recently diagnosed hypertensive Canadians modify their lifestyles and to examine how lifestyle modification relates to antihypertensive medication use. The longitudinal National Population Health Survey in Canada was conducted between 1994 and 2002, including five interview cycles at two-year intervals. During this time, 1281 persons reported hypertension in one cycle but not in the previous cycle, and were considered to be new hypertensive patients. Information collected included body mass index, smoking, alcohol consumption, physical inactivity and medication use. The main lifestyle modification associated with newly diagnosed hypertensive patients was smoking cessation, with a 18.6% relative risk reduction (RRR). A smaller change was seen in decreasing physical inactivity (RRR 6.2%). Persons not taking antihypertensive medication were not more likely to make lifestyle improvements. Paradoxically, new hypertensive patients showed increased numbers in the obese category (RRR -9.6%). Weight gain was especially marked among antihypertensive medication users and largest in female beta-blocker users (RRR -36.6%). If confirmed, this needs to be considered when prescribing to overweight people. In general, a greater effort is required to manage hypertension by lifestyle risk modification with or without antihypertensive medication.


[Possibility of using enriched glial and neuronal cell fractions to study transport of neurotransmitter amino acids in old age].
Calculated on a protein basis the yield of neuronal and glial cell-enriched fractions obtained from the brain of aged and adult rats was found to be equal. In aged animals the high affinity uptake of 14C-GABA by neuronal fractions is reduced by 27.34% while that of glial fractions by 11.87%. At 0 degrees both age groups studied the uptake of 14C-GABA is greatly inhibited--by 66% in neurones and 92% in glia. The conclusion is drawn that glial cells are changed much less with age than neurones and thus their role as modulators of neuronal function increases with age.


Utilization of dry matter and bioelements in larvae of Neodiprion sertifer Geoffr. (Hym., Diprionidae) feeding on Scots pine (Pinus sylvestris L.).
In the laboratory the consumption (C), egestion (F), assimilation (A) and assimilation efficiency (A/C) of dry matter and of the bioelements C, N, P, K, Ca, Mg, S and Na were studied weekly during the whole feeding stage. The larvae were reared in clusters of 10 individuals (on average 3.5 ♂♂ and 6.5 ♀♀), fed one-year-old needles. The average values of (C), (F) and (A) were 2,950, 2,530 and 414 mg dw per cluster, respectively, implying a dry matter assimilation efficiency of only 14.0%. The mean production of tissue (P) per cluster amounted to 250 mg dw. The concentration of bioelements in faeces (in order as above) was 51.2, 0.80, 0.08, 0.36, 0.41, 0.11, 0.10 and 0.02% of dw, and in larval tissue 57.5, 7.60, 0.64, 0.85, 0.24, 0.22, 0.24 and 0.06% of dw, respectively. The concentration of N and P in larval tissue was 5.8 and 4.9 times higher than in food, that of K, Mg, S and Na about twice, that of C and Ca about equal or less. The assimilation efficiency of the bioelements was estimated at 14.5, 59.3, 47.4, 20.9, 4.6, 12.5, 13.8 and 44.4%, and the energetics (C), (F), (A), (P) and (R=A-P) at 61,900, 53,600, 8,320, 6,710 and 1,610 J per cluster, respectively. It is argued that in N. sertifer the high consumption rate, low efficiency of dry matter assimilation and low nitrogen accumulation, in all attained at a low maintenance cost, are adaptations to a food low in nitrogen content (1.3% of dw). The study is part of an investigation on the interaction between insect consumption and pine growth, performed within the Swedish Coniferous Forest Project.


Substance P increases production of proinflammatory cytokines and formation of osteoclasts in dental pulp fibroblasts in patients with severe orthodontic root resorption.
The objective of this study was to determine the extent to which substance P (SP) increases proinflammatory cytokine production and osteoclast formation of human dental pulp fibroblasts (HDPF) in patients with severe orthodontically induced inflammatory root resorption (OIIRR). HDPF were obtained from 5 patients with severe apical root resorption after orthodontic treatment. The levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha were determined after 24 hours by using ELISA kits. Furthermore, culture supernatants were added to cultured human osteoclasts, and osteoclast formation was observed after tartrate-resistant acid phosphatase (TRAP) staining and the formation of resorption cavities. Stimulation with SP increased the levels of IL-1beta, IL-6, and TNF-alpha, in a time- and concentration-dependent manner, although the increase was greater in the severe root resorption (SRR) group than in the nonresorption (NR) group (P < 0.001, 3-way repeated measures ANOVA). As for osteoclast formation, the numbers of TRAP-positive multinucleate cells and resorptive pits were significantly increased in the SRR group compared with the NR group (P < 0.001, 2-way repeated measures ANOVA). These results suggest that HDPF stimulated with SP might be deeply involved in the progress of inflammation in pulp tissue and the incidence of SRR during orthodontic treatment.


Inhibition of type A monoamine oxidase by coptisine in mouse brain.
The inhibitory effects of coptisine, a protoberberine isoquinoline alkaloid, on type A and type B monoamine oxidase (MAO-A and MAO-B) activities in mouse brain were investigated. Coptisine showed an inhibitory effect on MAO-A activity in a concentration-dependent manner using a substrate kynuramine, but coptisine did not inhibit MAO-B activity. Coptisine exhibited 54.3% inhibition of MAO-A activity at 2 microM. The values of Km and Vmax of MAO-A were 151.9 +/- 0.6 microM and 0.40 +/- 0.03 nmol/min/mg protein, respectively (n=5). Coptisine competitively inhibited MAO-A activity with kynuramine. The Ki value of coptisine was 3.3 microM. The inhibition of MAO-A by coptisine was found to be reversible by dialysis of the incubation mixture. These results suggest that coptisine is a potent reversible inhibitor of MAO-A, and that coptisine functions to regulate the catecholamine content.


Coronary Revascularization in Patients With Cancer.
The treatment of coronary artery disease (CAD) in cancer patients is an evolving landscape. Recent data emphasizes the importance of aggressive management of cardiovascular risk factors and diseases in improving cardiovascular health in this unique group of patients regardless of cancer type or stage. Novel cancer therapeutics such as immune therapies and proteasome inhibitors have been associated with CAD. Recent stent technologies may safely allow for shorter duration (< 6 months) of dual antiplatelet therapy post-percutaneous coronary interventions. Intracoronary imaging may be useful in the decision making process in terms of stent positioning and healing. Large registry studies have partially filled a gap left by the lack of randomized controlled trials in the treatment of CAD in cancer patients. Cardio-oncology is gaining traction as a major sub-specialty in the cardiology field given the release of the first European Society of Cardiology - Cardio-oncology guidelines in 2022.


Effectiveness of in vitro fertilization with preimplantation genetic screening: a reanalysis of United States assisted reproductive technology data 2011-2012.
To assess effectiveness of preimplantation genetic screening (PGS) in fresh IVF cycles. Reanalysis of retrospective US national data. Not applicable. A total of 5,471 fresh autologous IVF cycles with PGS and 97,069 cycles without PGS, reported in 2011-2012 to the Centers for Disease Control and Prevention. Not applicable. Cycles that reached ET, miscarriage rates, live birth rates per cycle and per transfer. More PGS than non-PGS cycles reached ET (64.2% vs. 62.3%), suggesting favorable patient selection bias for patients using PGS. Nevertheless, live births rates per cycle start (25.2% vs. 28.8%) and per ET (39.3% vs. 46.2%) were significantly better in non-PGS cycles, whereas miscarriage rates were similar (13.7% vs. 13.9%). With a maternal age >37 years significantly more cycles in the PGS group reached ET (53.1% vs. 41.9%), suggesting a significant selection bias for more favorable patients in the PGS population. This bias rather than the PGS procedure may partially explain the observed improved live birth rate per cycle (17.7% vs. 12.7%) and lower miscarriage rate (16.8% vs. 26.0%) in the older PGS group. Overall, PGS decreased chances of live birth in association with IVF. National improvements in live birth and miscarriage rates reported with PGS in older women are likely the consequence of favorable patient selection biases.


Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma.
Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite improvements in surgical, radiation and chemotherapy treatments, the overall survival of UM and prognosis remain poor. In the present study, we hypothesized that Sirtuin 1 and 2 (SIRT1/2), class III histone deacetylases (HDACs), were critical in controlling the destiny of bulk tumor cells and cancer stem cells (CSCs) of UM. We testified this hypothesis in four lines of UM cells (92.1, Mel 270, Omm 1 and Omm 2.3). Our results showed that inhibition of SIRT1/2 by Tenovin-6 induced apoptosis in UM cells by activating the expression of tumor suppressor genes such as p53 and elevating reactive oxygen species (ROS). Tenovin-6 inhibited the growth of UM cells. Tenovin-6 and vinblastine was synergistic in inducing apoptosis of UM cell line 92.1 and Mel 270. Furthermore, Tenovin-6 eliminated cancer stem cells in 92.1 and Mel 270 cells. In conclusion, our findings suggest that Tenovin-6 may be a promising agent to kill UM bulk tumor cells and CSCs.


Clonidine.
Clonidine has provided a nonaddicting solution to an ancient problem, opiate withdrawal without opiates. Gold and colleagues' initial demonstration that this alpha 2 adrenergic agonist could be used to detoxify opiate addicts provided the first nonaddicting treatment for opiate dependency. This discovery has also led to research investigating the utility of clonidine for a number of other neuropsychiatric conditions as well. Clonidine has been studied for use in neonatal narcotic addiction, alcohol detoxification, akathisia, mania, narcolepsy, attention deficit disorder, panic disorder, and alcohol amnestic disorder. Additionally, the clinical application of clonidine was based upon a large body of preclinical research and has opened up other avenues of investigation for non-addictive treatment of opiate dependency.


Weight cycling and the risk of type 2 diabetes in the EPIC-Germany cohort.
Studies on weight cycling and the risk of type 2 diabetes have revealed inconsistent results, possibly due to differences in the definition of weight fluctuations. Here, we investigated whether weight cycling during adulthood is related to diabetes risk in a large cohort study, using a complementary approach to define patterns of weight development. Weight cycling, weight loss and weight gain were defined (1) a priori, using distinct categories, and (2) by functional principal component analysis (FPCA) to capture weight patterns in greater detail. Associations of weight cycling, weight loss and weight gain with the risk of type 2 diabetes were evaluated by Cox regression models. A priori defined weight cycling was associated with increased diabetes risk, compared with stable weight (HR 1.36 [95% CI 1.09, 1.68]). No significant association between FPCA-derived weight cycling and risk of diabetes was observed after adjustment for concurrent weight patterns (HR 1.19 [95% CI 0.89, 1.60]). Subgroup analyses showed that FPCA-derived weight cycling during net weight gain was associated with a higher risk of diabetes (HR 1.68 [95% CI 1.14, 2.48]). A priori defined weight gain (HR 2.08 [95% CI 1.60, 2.70]) was more clearly related to the risk of diabetes than FPCA-derived weight gain (HR 1.20 [95% CI 0.95, 1.51]), while no significant associations were observed for weight loss. Overall, weight cycling may not be an independent risk factor for type 2 diabetes when accounting for concurrent patterns of weight development. However, weight cycling may pose a stronger risk of diabetes than non-cycling during net weight gain.


The effect of a quality improvement programme reducing blood culture contamination on the detection of bloodstream infection in an emergency department.
Contaminated blood cultures (BC) generate avoidable costs and prolong hospital stays. To measure our hospital's performance against the recommended standard of <3% BC contamination, we performed a prospective study. We prospectively determined the frequency of contaminated and genuinely positive BC hospital-wide over seven months. Overall, 73 of 1,829 blood cultures reviewed were contaminated (4.0%). However, distribution of contamination was not uniform. Finding a consistently higher incidence of contamination (11.7%) in our emergency department (ED) than elsewhere in the hospital (2.5%), we adopted a collaborative quality improvement strategy targeted to the ED. A combination of education, modified BC packs and regular feedback of BC results was associated with a significant reduction in contamination (7.4%, p=0.01) over the next six months. Our data suggests that contaminated BC were more likely to have been taken during regular day time hours (odds ratio (OR) 2.7, p=0.012), rather than overnight and were not associated with influxes of new junior medical staff. We found no evidence that the incidence of true bloodstream infection (12.8%) diagnosed by our ED was adversely affected by our intervention (10.7%, p=0.35). Using a simple and inexpensive collaborative intervention we reduced BC contamination without adversely affecting the detection of genuine BSI.