Perspectives on parity violation in chiral molecules: theory, spectroscopic experiment and biomolecular homochirality.
The reflection (or 'mirror') symmetry of space is among the fundamental symmetries of physics. It is connected to the conservation law for the quantum number parity and a fundamental 'non-observable' property of space (as defined by an absolute 'left-handed' or 'right-handed' coordinate system). The discovery of the violation of this symmetry - the non-conservation of parity or 'parity violation' - in 1956/1957 had an important influence on the further development of physics. In chemistry the mirror symmetry of space is connected to the existence of enantiomers as isomers of chiral ('handed') molecules. These isomers would relate to each other as idealized left or right hand or as image and mirror image and would be energetically exactly equivalent with perfect space inversion symmetry. Parity violation results in an extremely small 'parity violating' energy difference between the ground states of the enantiomers which can be theoretically calculated to be about 100 aeV to 1 feV (equivalent to 10-11 to 10-10 J mol-1), depending on the molecule, but which has not yet been detected experimentally. Its detection remains one of the great challenges of current physical-chemical stereochemistry, with implications also for fundamental problems in physics. In biochemistry and molecular biology one finds a related fundamental question unanswered for more than 100 years: the evolution of 'homochirality', which is the practically exclusive preference of one chiral, enantiomeric form as building blocks in the biopolymers of all known forms of life (the l-amino acids in proteins and d-sugars in DNA, not the reverse d-amino acids or l-sugars). In astrobiology the spectroscopic detection of homochirality could be used as strong evidence for the existence of extraterrestrial life, if any. After a brief conceptual and historical introduction we review the development, current status, and progress along these three lines of research: theory, spectroscopic experiment and the outlook towards an understanding of the evolution of biomolecular homochirality.


Using mathematical modelling to inform on the ability of stormwater ponds to improve the water quality of urban runoff.
This paper concerns the mathematical modelling of flow and solute transport through stormwater ponds. The model is based on appropriate lumped system conservation equations that are solved using standard numerical techniques. The model was used to route a first flush pollution scenario through a cylindrical pond for 16 combinations of elevation and diameter of a submerged pipe outlet, in conjunction with a high level weir. Higher pipe elevations and smaller pipe diameters created larger pond volumes and hence led to greater dilution of the pollutant. In contrast, lower pipe elevations created larger storage volumes, leading to better flow attenuation. Interestingly, larger pipe diameters improved peak flow attenuation, even though the storage used decreased.


Endovascular Options for the Ascending Aorta and Aortic Arch: A Scoping Review.
The gold standard for aneurysmal repair of the ascending aorta and the aortic arch has been open surgery with an established track record of good results in suitable patients. In recent years, with innovations in the endovascular field alternative endovascular solutions for pathologies of the aortic arch and ascending aorta became available. At first reserved only for highly selected patients unfit for open surgery, endovascular aortic arch repair is now being offered to patients with suitable anatomy in high-volume referral centers after discussion in an interdisciplinary team. The present scoping review aims at providing an overview on indications, available devices, technical aspects, and feasibility studies of endovascular arch repair both in elective and emergent situations, including also experiences and considerations from our center.


Effects of PGE2 and PGF2 alpha on the simulation by noradrenaline and oxytocin of human cervical muscle activity at term.
Cervical specimens were obtained by needle biopsy in connection with caesarean section at term pregnancy. The preparations were superfused in an organ chamber and contractions were registered isometrically. Prostaglandin (PG) E2 and F2 alpha inhibited spontaneous contractions. The stimulatory action of noradrenaline was not influenced by PGF2 alpha but was reduced by PGE2 whereas both PGs abolished the excitatory effect of oxytocin.


Characteristics of mentally disordered offenders referred for low secure forensic rehabilitation.
In the light of recognition of an increased need for secure mental health provision both at a local and national level, a 12-bed low secure forensic rehabilitation unit, Hillis Lodge, was opened in Birmingham in 2001. The aim of this study was to investigate characteristics of patients referred to this service. A retrospective case note survey was undertaken of all referrals to Hillis Lodge between August 2000 and April 2004. A comparison was then made between the accepted group and those not accepted for admission to identify characteristics that may be associated with admission to a low secure forensic unit. For the referred sample, mean age was 38 years (range 23-65 years, SD = 9.17) and in 86.4% of cases the primary diagnosis was schizophrenia. Those accepted were more likely to be detained under Part III sections of the Mental Health Act 1983 and have a greater number of previous convictions. By identifying need in this particular patient sample, this study has helped to inform the assessment process and treatment programmes in a low secure forensic rehabilitation service.


The "extent of information desired"-scale in psychiatric in-patients: a behavioural approach.
The purpose of this study was to investigate the "extent of information desired" (EID)-scale through a behavioural approach. Standardised interviews consisting of the EID-scale and four (half) open questions were conducted in a convenience sample of psychiatric in-patients and information seeking behaviour was measured. At the same time, socially desirable behaviour was assessed by means of Marlowe-Crowne social desirability (MCSD). 39 patients were interviewed. The behavioural approach yielded mixed results, but there was no correlation between EID- and MCSD-scores. From the calculated correlations information seeking behaviour is perceived as socially undesirable, whereas EID-scores seem unaffected by social desirability. It is difficult to define independent variables which would reflect information seeking behaviour. The ones we used might have been confounded. We found a correlation between the EID-scale used and the information seeking behaviour, without a strong correlation with social desirability. The EID-scale used may predict patients' desire for information within a well-defined clinical context. The step to validation requires more robustness of the research model and a better profiling of patients.


Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus.
A diverse T cell repertoire is essential for a vigorous immune response to new infections, and decreasing repertoire diversity has been implicated in the age-associated decline in CD8 T cell immunity. In this study, using the well-characterized mouse influenza virus model, we show that although comparable numbers of CD8 T cells are elicited in the lung and lung airways of young and aged mice after de novo infection, a majority of aged mice exhibit profound shifts in epitope immunodominance and restricted diversity in the TCR repertoire of responding cells. A preferential decline in reactivity to viral epitopes with a low naive precursor frequency was observed, in some cases leading to "holes" in the T cell repertoire. These effects were also seen in young thymectomized mice, consistent with the role of the thymus in maintaining naive repertoire diversity. Furthermore, a decline in repertoire diversity generally correlated with impaired responses to heterosubtypic challenge. This study formally demonstrates in a mouse infection model that naturally occurring contraction of the naive T cell repertoire can result in impaired CD8 T cell responses to known immunodominant epitopes and decline in heterosubtypic immunity. These observations have important implications for the design of vaccine strategies for the elderly.


Proposed alternative revision strategy for broken S1 pedicle screw: radiological study, review of the literature, and case reports.
There have been many reports outlining differing methods for managing a broken S1 screw. To the authors' best knowledge, the technique used in the present study has not been described previously. It involves insertion of a second pedicle screw without removing the broken screw shaft. Radiological study, literature review, and two case reports of the surgical technique. To report a proposed new surgical technique for management of broken S1 pedicle screws. Computed tomography (CT) scans of 50 patients with a total of 100 S1 pedicles were analyzed. There were 25 male and 25 female patients with an average age of 51 years ranging from 36 to 68 years. The cephalad-caudal length, medial-lateral width, and cross-sectional area of the S1 pedicle were measured and compared with the diameter of a pedicle screw to illustrate the possibility of inserting a second screw in S1 pedicle without removal of the broken screw shaft. Two case reports of the proposed technique are presented. The left and right S1 pedicle cross-sectional area in female measured 456.00 ± 4.00 and 457.00 ± 3.00 mm(2), respectively. The left and right S1 pedicle cross-section area in male measured 638.00 ± 2.00 and 639.00 ± 1.00 mm(2), respectively. There were statistically significant differences when comparing male and female S1 pedicle length, width, and cross-sectional area (p<.05). At 2-year follow-up, the two case reports of the proposed technique showed resolution of low back pain and radicular pain. Plain radiograph and CT scan showed posterolateral fusion mass and hardware in good position with no evidence of screw loosening. The S1 pedicle dimensions measured on CT scan reviewed in the present study showed that it may be anatomically feasible to place a second screw through the S1 pedicle without the removal of the broken screw shaft. This treatment method will reduce the complications associated with other described revision strategies for broken S1 screws.


Diffusion Tensor Imaging for Quantitative Assessment of Anterior Cruciate Ligament Injury Grades and Graft.
As the need for quantitative assessment of anterior cruciate ligament (ACL) injuries and ACL graft increases, diffusion tensor imaging (DTI) becomes a more valuable measuring tool. However, DTI changes in differing injury grades of ACL and longitudinal graft remain unclear. To investigate the diagnostic performance of DTI in quantitatively assessing ACL injury severity and the development of ACL grafts within 6 months of surgery. A cohort study. Thirty-five patients diagnosed with grades I-IV ACL injuries and 20 volunteers as controls were recruited. T1 -weighted, T2 -weighted, proton density (PD)-weighted, and DTI at 3.0T MRI. ACL injury grades in arthroscopic images and DTI quantitative data were evaluated from July 2016 to July 2018. Chi-square test, analysis of variance, Spearman correlation analysis, and receiver operator characteristic (ROC) curves. Both fractional anisotropy (FA) (r = -0.898, P < 0.05) and apparent diffusion coefficient (ADC) (r = 0.851, P < 0.05) were significantly correlated with the severity of ACL injuries. The area under the curve (AUC) values for differentiation between low- and high-grade ACL injuries with FA and ADC were 0.973 and 0.963, respectively. Although there were no significant differences in FA (P > 0.05) and ADC (P > 0.05) between grades I and II ACL injuries or in ADC (P > 0.05) between grades III and IV, there were significant differences in FA and ADC between two grades (P < 0.05). There were significant differences in FA (P < 0.05) and ADC (P < 0.05) between normal ACL and 3-month graft postoperation, as well as in ADC values between 3-month and 6-month graft postoperation (P < 0.05). DTI could be used to quantitatively evaluate the ACL injury grades and the development of ACL grafts. The diagnostic efficiency of FA values was higher than that of ADC values. 1 TECHNICAL EFFICACY: Stage 3.


Mutation of bcl-x gene in non-Hodgkin's lymphoma.
The bcl-x gene product has two forms, bcl-xl and bcl-xs. The bcl-xl form, similar to bcl-2, inhibits apoptosis. Reverse transcriptase-polymerase chain reaction/single-stranded conformation polymorphism (RT-PCR-SSCP) gel analysis was used to screen for mutations of the bcl-xl transcript of 50 non-Hodgkin's lymphoma (NHL) cases. One missense mutation in a patient with diffuse large B-cell lymphoma was found. Sequence analysis of this case showed that AGC (Ser) was mutated to GGC (Gly) in codon 154. An examination of mutation and/or polymorphism in born marrow samples of this case and 50 normal controls by the RT-PCR-SSCP method could not detect bandshifts. Mutation of the bcl-x gene in NHL has not been reported previously. There is a possibility that mutation of the bcl-x gene play a role in the tumorigenesis of NHL.


In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges.
The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo-electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines.


Functional genomics evidence unearths new moonlighting roles of outer ring coat nucleoporins.
There is growing evidence for the involvement of Y-complex nucleoporins (Y-Nups) in cellular processes beyond the inner core of nuclear pores of eukaryotes. To comprehensively assess the range of possible functions of Y-Nups, we delimit their structural and functional properties by high-specificity sequence profiles and tissue-specific expression patterns. Our analysis establishes the presence of Y-Nups across eukaryotes with novel composite domain architectures, supporting new moonlighting functions in DNA repair, RNA processing, signaling and mitotic control. Y-Nups associated with a select subset of the discovered domains are found to be under tight coordinated regulation across diverse human and mouse cell types and tissues, strongly implying that they function in conjunction with the nuclear pore. Collectively, our results unearth an expanded network of Y-Nup interactions, thus supporting the emerging view of the Y-complex as a dynamic protein assembly with diverse functional roles in the cell.


Bismuth-based therapies for the first step eradication of Helicobacter pylori.
Combination of a proton pump inhibitor, amoxicillin, and clarithromycin, which have been recommended as a primary treatment for Helicobacter pylori (H. pylori) infection, provides eradication in approximately 50% of cases of H. pylori infection in Turkey. There is no effective eradication regimen for H. pylori in our country. We aimed to compare bismuth- based triple and quadruple treatments for eradication of H. pylori. Eighty-two patients were enrolled into the study between October 2002 and August 2003. The patients were randomly assigned into two groups. One group received ranitidine bismuth citrate 2x400 mg, metronidazole 3x500 mg and tetracycline 2x1000 mg for 14 days (RMT group) and the other group pantoprazole 2x40 mg, bismuth subcitrate 4x300mg, amoxicillin 2x1000 mg and clarithromycin 2x500 mg for 14 days (PBAC group). The eradication was assessed four weeks after completion of the treatment, and the patients underwent endoscopy and were asked whether there were changes in their symptoms. When H. pylori was negative on both histological examination and urease test, the disease was considered eradicated. H. pylori was eradicated in 26 of 42 patients in the RMT group (61.9%) and in 22 of 40 patients in the PBAC group (55%). In total, eradication was achieved in 48 out of 82 patients (58.5%). There was no significant difference in eradication between the groups. Neither regimen (RMT or PBAC) was effective in eradicating H. pylori infection in our area. Further investigations are needed.


The Risk Perception COVID-19 Scale (RP-COVID19-S): Initial Validation and Its Relationship with Gender and Age in a Cuban Population Sample.
Risk perception about COVID-19 constitutes an important variable contributing to promotion of personal protection practices. The aims of this study were to exploring the factorial structure of the risk perception COVID-19 scale (RP-COVID19-S) in a sample of Cuban adults and to identify its relationship with variables such as gender and age. A cross-sectional web-based survey design was conducted. The sample comprised 394 Cuban participants. Categorical Principal Component Analysis (CATPCA) was used to explore internal factorial structure of the scale. Logistic regression was modeling to identify variables independently associated with RP about COVID-19. CATPCA allowed identifying a three-dimensional factorial structure into the scale: knowledge and beliefs, emotional reactions and behavioral dissonance, and motivations for change. The odds of a woman with middle RP compared to low RP was 2.17 times more than for a man. Also, the odds of a woman with high knowledge and beliefs compared to low knowledge and beliefs were 1.96 times more than for a man. The odds of a person in older group, with middle risk perception compared with low level, was 5.0 (global risk perception), 3.33 (knowledge and beliefs), and 3.13 (emotional reactions and behavioral dissonance) times more than for a person in younger group, respectively. The Risk Perception to COVD-19 Scale (RP-COVID-19-S) showed satisfactory psychometric properties to evaluated risk perception related to COVID-19 in Cuban population sample. Middle level of global risk perception was found in the sample. High level of risk perception about COVID-19 was found on participants older than 42 years old and in woman.


Accurate prediction of nuclear receptors with conjoint triad feature.
Nuclear receptors (NRs) form a large family of ligand-inducible transcription factors that regulate gene expressions involved in numerous physiological phenomena, such as embryogenesis, homeostasis, cell growth and death. These nuclear receptors-related pathways are important targets of marketed drugs. Therefore, the design of a reliable computational model for predicting NRs from amino acid sequence has now been a significant biomedical problem. Conjoint triad feature (CTF) mainly considers neighbor relationships in protein sequences by encoding each protein sequence using the triad (continuous three amino acids) frequency distribution extracted from a 7-letter reduced alphabet. In addition, chaos game representation (CGR) can investigate the patterns hidden in protein sequences and visually reveal previously unknown structure. In this paper, three methods, CTF, CGR, amino acid composition (AAC), are applied to formulate the protein samples. By considering different combinations of three methods, we study seven groups of features, and each group is evaluated by the 10-fold cross-validation test. Meanwhile, a new non-redundant dataset containing 474 NR sequences and 500 non-NR sequences is built based on the latest NucleaRDB database. Comparing the results of numerical experiments, the group of combined features with CTF and AAC gets the best result with the accuracy of 96.30% for identifying NRs from non-NRs. Moreover, if it is classified as a NR, it will be further put into the second level, which will classify a NR into one of the eight main subfamilies. At the second level, the group of combined features with CTF and AAC also gets the best accuracy of 94.73%. Subsequently, the proposed predictor is compared with two existing methods, and the comparisons show that the accuracies of two levels significantly increase to 98.79% (NR-2L: 92.56 %; iNR-PhysChem: 98.18%; the first level) and 93.71% (NR-2L: 88.68%; iNR-PhysChem: 92.45%; the second level) with the introduction of our CTF-based method. Finally, each component of CTF features is analyzed via the statistical significant test, and a simplified model only with the resulting top-50 significant features achieves accuracy of 95.28%. The experimental results demonstrate that our CTF-based method is an effective way for predicting nuclear receptor proteins. Furthermore, the top-50 significant features obtained from the statistical significant test are considered as the "intrinsic features" in predicting NRs based on the analysis of relative importance.


Pacemaker syndrome with DDD pacing.
DDD pacing may be associated with certain problems similar to those of the pacemaker syndrome. In the absence of mechanical dysfunction, pacemaker-mediated tachycardias have occurred in the presence of VA conduction. The correction of this problem is found in more versatile programming capability. In addition, certain phenomena relating to intraatrial conduction times and the optimal AV delay are discussed.


Stroke-related stigma among West Africans: Patterns and predictors.
Disability-adjusted life-years lost after stroke in Low & Middle-Income Countries (LMICs) is almost seven times those lost in High-income countries. Although individuals living with chronic neurological and mental disorders are prone to stigma, there is a striking paucity of literature on stroke-related stigma particularly from LMICs. To assess the prevalence, severity, determinants and psycho-social consequences of stigma among LMIC stroke survivors. Between November 2015 and February 2016, we conducted a cross-sectional survey of 200 consecutive stroke survivors attending a neurology clinic in a tertiary medical center in Ghana. The validated 8-Item Stigma Scale for Chronic Illness (SSCI-8) questionnaire was administered to study participants to assess internalized and enacted domains of stigma at the personal dimension with further adaptation to capture family and community stigma experienced by stroke participants. Responses on the SSCI-8 were scored from 1 to 5 for each item, where 1=never, 2=rarely, 3=sometimes, 4=often and 5=always with a score range of 8-40. Demographic and clinical data on stroke type and severity as well as depression and Health-Related Quality of Life indicators were also collected. Predictors of stroke-related stigma were assessed using Linear Models (GLM) via Proc GENMOD in SAS 9.4. 105 (52.5%) subjects recruited were males and the mean±SD age of stroke survivors in this survey was 62.0±14.4years. Mean SSCI-8 score was highest for personal stigma (13.7±5.7), which was significantly higher than family stigma (11.9±4.6; p=0.0005) and social/community stigma (11.4±4.4; p<0.0001). Approximately 80% of the cohort reported experiencing mild-to-moderate degrees of stigma. A graded increase in scores on the Geriatric Depression Scale and Centre for Epidemiological Studies-Depression scale was observed across the three categories. Living in an urban setting was associated with higher SSCI-8 scores. Moreover, stroke subjects with more severe post-stroke residual symptom deficits reported a significantly higher frequency of stigma. Four out of five stroke survivors in this Ghanaian cohort reported experiencing some form of stigma. Stigmatized individuals were also more likely to be depressed and have lower levels of quality of life. Further studies are required to assess the consequences of stigma from stroke in LMIC.


CRISPR/Cas9 genome editing in wheat: enhancing quality and productivity for global food security-a review.
Wheat (Triticum aestivum L.) is an important cereal crop that is grown all over the world for food and industrial purposes. Wheat is essential to the human diet due to its rich content of necessary amino acids, minerals, vitamins, and calories. Various wheat breeding techniques have been utilized to improve its quality, productivity, and resistance to biotic and abiotic stress impairing production. However, these techniques are expensive, demanding, and time-consuming. Additionally, these techniques need multiple generations to provide the desired results, and the improved traits could be lost over time. To overcome these challenges, researchers have developed various genome editing tools to improve the quality and quantity of cereal crops, including wheat. Genome editing technologies evolve quickly. Nowadays, single or multiple mutations can be enabled and targeted at specific loci in the plant genome, allowing controlled removal of undesirable features or insertion of advantageous ones. Clustered, regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) is a powerful genome editing tool that can be effectively used for precise genome editing of wheat and other crops. This review aims to provide a comprehensive understanding of this technology's potential applications to enhance wheat's quality and productivity. It will first explore the function of CRISPR/Cas9 in preserving the adaptive immunity of prokaryotic organisms, followed by a discussion of its current applications in wheat breeding.


Isolation of single stranded DNA from purified hepatitis A-virus.
Hepatitis A-virus was purified from human stools by three purification steps. Virus was identified by radioimmunoassay and purity monitored with immune electron microscopy. Virus particles, serologically and morphologically identical, banded in CsCl in two density ranges at 1.31-1.34 g/cm3 and at 1.41-1.43 g/cm3. Virions of density 1.31-1.34 g/cm3 were shown to contain single-stranded DNA of different size classes. Class I 1.33 kb, class II 4.61 kb in addition a small amount of molecules was detected with lengths up to 15 kb.


ADAM proteases: ligand processing and modulation of the Notch pathway.
ADAM metalloproteases play important roles in development and disease. One of the key functions of ADAMs is the proteolytic processing of Notch receptors and their ligands. ADAM-mediated cleavage of Notch represents the first step in regulated intramembrane proteolysis of the receptor, leading to activation of the Notch pathway. Recent reports indicate that the transmembrane Notch ligands also undergo ADAM-mediated processing in cultured cells and in vivo. The proteolytic processing of Notch ligands modulates the strength and duration of Notch signals, leads to generation of soluble intracellular domains of the ligands, and may support a bi-directional signaling between cells.


Lymphatic mapping and sentinel lymph node biopsy.
Malignant melanoma--cancer of the pigment cells--has the highest mortality rate of all skin cancers. With early detection and treatment, however, malignant melanoma is highly curable. Recently, diagnostic modalities for nodal involvement have been perfected, reducing the morbidity of elective lymph node dissections and rendering them unnecessary in many cases. Total lymphadenectomy procedures are being replaced by intraoperative lymphatic mapping and sentinel lymph node biopsy using gamma detector probes. This article reviews lymphatic drainage from the primary site to possible lymph node basins and selective lymph node dissection using lymphoscintigraphy and intraoperative mapping as guides. This article also includes a case study, beginning with a diagnosis of malignant melanoma and following a successful postoperative course.


Epithelial-myoepithelial carcinoma originating from minor salivary gland in the inferior turbinate: A case report and literature review.
Epithelial-myoepithelial carcinoma (EMC) is a rare tumor that occurs mainly in the major salivary glands. Cases occurring in the nasal cavity are rarely reported. The patient was a 48-year-old woman with a postoperative pathological diagnosis of EMC. The patient recovered well after surgery. We consulted and summarized all previous cases of nasal EMC. We also discuss the clinical presentation, treatment, and prognosis of EMC of the nasal cavity and paranasal sinuses.


The effects of resistance exercise training on arterial stiffness in metabolic syndrome.
Arterial stiffness is a strong independent risk factor for cardiovascular disease and is elevated in individuals with metabolic syndrome (MetS). Resistance training is a popular form of exercise that has beneficial effects on muscle mass, strength, balance and glucose control. However, it is unknown whether resistance exercise training (RT) can lower arterial stiffness in patients with MetS. Thus, the aim of this study was to examine whether a progressive RT program would improve arterial stiffness in MetS. A total of 57 subjects (28 healthy sedentary subjects; 29 MetS) were evaluated for arterial structure and function, including pulse wave velocity (cfPWV: arterial stiffness), before and after an 8-week period of RT or continuation of sedentary lifestyle. We found that 8 weeks of progressive RT increased skeletal muscle strength in both Con and MetS, but did not change arterial stiffness in either MetS (cfPWV; Pre 7.9 ± 0.4 m/s vs. Post 7.7 ± 0.4 m/s) or healthy controls (cfPWV; Pre 6.9 ± 0.3 m/s vs. Post 7.0 ± 0.3 m/s). However, when cfPWV is considered as a continuous variable, high baseline measures of cfPWV tended to show a decrease in cfPWV following RT. Eight weeks of progressive RT did not decrease the group mean values of arterial stiffness in individuals with MetS or healthy controls.


Pitch synchronous changes of the anterior cricothyroid gap by using ultrasonography.
The purpose of this study was to describe changes of the anterior cricothyroid space during respiration and phonation by using ultrasonography. Furthermore, to assess and correlate laryngeal dimensions in a large cohort of voice healthy men. Epidemiological study. Ultrasound examinations of the laryngeal skeleton, as well as of the cricothyroid space were performed in 64 voice healthy, elderly male subjects. This was done during respiration, phonation in midrange, and high phonation. We could not find any significant correlation concerning lengths of the cricothyroid space when correlated with voice range, highest or lowest frequency. General anthropometric parameters such as body height, weight, or body mass index did not show any considerable correlation with dimensions of the laryngeal skeleton. Functionally orientated surgery of the larynx requires exact knowledge of the anatomy and landmarks of the laryngeal skeleton. Topographic relations and dimensions between the thyroid and cricoid cartilages play an important role in cricoid approximation.


Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST): Development and Validation of a Prognostic Model in Untreated Adolescent Idiopathic Scoliosis Using the Simplified Skeletal Maturity System.
Prognostic study and validation using prospective clinical trial data. To derive and validate a model predicting curve progression to ≥45° before skeletal maturity in untreated patients with adolescent idiopathic scoliosis (AIS). Studies have linked the natural history of AIS with characteristics such as sex, skeletal maturity, curve magnitude, and pattern. The Simplified Skeletal Maturity Scoring System may be of particular prognostic utility for the study of curve progression. The reliability of the system has been addressed; however, its value as a prognostic marker for the outcomes of AIS has not. The BrAIST trial followed a sample of untreated AIS patients from enrollment to skeletal maturity, providing a rare source of prospective data for prognostic modeling. The development sample included 115 untreated BrAIST participants. Logistic regression was used to predict curve progression to ≥45° (or surgery) before skeletal maturity. Predictors included the Cobb angle, age, sex, curve type, triradiate cartilage, and skeletal maturity stage (SMS). Internal and external validity was evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n = 152). Indices of discrimination and calibration were estimated. A risk classification was created and the accuracy evaluated via the positive (PPV) and negative predictive values (NPV). The final model included the SMS, Cobb angle, and curve type. The model demonstrated strong discrimination (c-statistics 0.89-0.91) and calibration in all data sets. The classification system resulted in PPVs of 0.71-0.72 and NPVs of 0.85-0.93. This study provides the first rigorously validated model predicting a short-term outcome of untreated AIS. The resultant estimates can serve two important functions: 1) setting benchmarks for comparative effectiveness studies and 2) most importantly, providing clinicians and families with individual risk estimates to guide treatment decisions. Level 1, prognostic.


Association between 21-gene-assay and detection of disseminated tumor cells in patients with early breast cancer: results from the IRMA trial.
Disseminated tumor cells (DTCs) in the bone marrow (BM) are known to be of prognostic value for patients with early breast cancer (EBC). In addition to histopathological features, multigene expression assays, such as the commercially available 21-gene Breast Recurrence Score® assay, have been validated for evaluating prognosis and making decisions concerning adjuvant treatment in EBC. In a previous retrospective study from our group, the 21-gene assay was shown to be associated with DTC-detection. A secondary endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC. DTC-status and RS result were assessed in patients with ER-positive/HER2-negative EBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. Patients with a high RS result (≥ 26) were more frequently DTC-positive (22.6%) than patients with a low RS result (8.6%, p = 0.034). The odds for DTC-positivity increased with rising RS values (p = 0.047). We therefore confirm that a high genomic risk is associated with tumor cell dissemination into the BM. Further trials are needed to investigate whether therapeutic decisions could be further individualized by combining DTC-status and prognostic gene signature testing.


Leukotriene B4 in the immune system.
Leukotriene (LT) B4 is a biologically active molecule derived from arachidonic acid via the 5-lipoxygenase pathway. It mediates certain inflammatory and immunological reactions. The role of LTB4 in the immune system has been questioned since lymphocytes have been regarded to lack the enzymes involved in LTB4 formation. This review focuses on the recently described biosynthesis of LTB4 in B-lymphocytes and the effects of this compound on lymphocyte functions.


5-HT1A and D-2 receptor affinity of o-methoxyphenylpiperazine derivatives with terminal benzamide fragment on N-4 alkyl chain. 2.
The synthesis of some o-methoxyphenylpiperazines with a benzamide moiety on N-4 alkyl chain was accomplished and their affinity for dopamine and serotonin receptor subtypes was assayed by in vitro receptor binding. The results show that several derivatives had a good affinity both on D-2 and 5-HT1A receptors, the IC50s ranging from 10(-7) to 10(-8) M.


Nerve regulation of class I and class II-asymmetric forms of acetylcholinesterase in rat skeletal muscles.
Two classes of collagen-tailed, asymmetric forms (A-forms) of acetylcholinesterase (AChE) have been described in skeletal muscles of vertebrates. They are distinguished by their different solubilization requirements: class I A-forms are solubilized in the presence of high salt, whereas class II A-forms require in addition a chelating agent for solubilization. We report here that class II A-forms are less sensitive to nerve section than are class I A-forms. The latter form decreases faster and to a lower level of activity after denervation. The decay of both AChE classes is more rapidly in short-stump nerves than in long ones. The effect of nerve section on class II A-forms appears to be dependent on the particular muscle group being studied. Both classes of A-forms reappear after muscle reinnervation, but the class I A-forms recovered earlier. More interestingly, both classes of A-forms increase in normally innervated skeletal muscles after contralateral nerve injury. In this case, however, the class II A-forms change first. Muscular disuse induced by contralateral tenotomy is also followed by a rise in class II A-forms. Our results, showing differences in response and flexibility in the changes of the two classes of A-forms in several experimental conditions, represent a relevant contribution to the understanding of the regulation and functional role of the asymmetric forms of AChE in vertebrate skeletal muscles.


Refining nursing practice through workplace learning: A grounded theory.
To examine how experienced registered nurses in direct patient care learn within the constantly changing contemporary healthcare environment. The key objectives were to examine educational interactions amongst workplace, nurse and nursing practice, with a focus on the influence of context. Registered nurses must maintain competence throughout their careers. The related ongoing learning is triggered by external demands and nurses' internal motivation. Experienced nurses, poised to retire, have worked through the recent tumultuous changes in health care and therefore provide insight into how they sustained excellent patient care. The methodology for this study was a grounded theory informed by symbolic interactionism. EQUATOR guidelines for qualitative research (COREQ) applied. Data collection entailed semi-structured interviews with experienced nurses across diverse settings and participant observation on two acute care units. Analysis of data was conducted using three-level coding, constant comparison, theoretical sampling and extensive memoing. Refining nursing practice begins during nursing education and early employment. Getting grounded involves establishing key capabilities, specifically becoming self-aware, setting high standards, cultivating healthy apprehension and seeing the whole patient picture. Three catalysts for workplace learning are mentor-guides, workplace camaraderie and a highly functional workplace team. Refining nursing practice includes both formal and informal learning; however, significant nursing expertise is developed through puzzling and enquiring, an iterative process of learning while nursing. Facilitating the development of capabilities for nurses' workplace learning during nursing education and early work experiences contributes to excellent patient care. Healthcare organisations need to value and support the unique contributions of mentor-guides in the clinical setting and promote individuals' development of expertise by nurturing camaraderie and developing highly functional workplace teams. Attending to the processes and catalysts for nurses' workplace learning will contribute to excellent patient care.


A rice quantitative trait locus for salt tolerance encodes a sodium transporter.
Many important agronomic traits in crop plants, including stress tolerance, are complex traits controlled by quantitative trait loci (QTLs). Isolation of these QTLs holds great promise to improve world agriculture but is a challenging task. We previously mapped a rice QTL, SKC1, that maintained K(+) homeostasis in the salt-tolerant variety under salt stress, consistent with the earlier finding that K(+) homeostasis is important in salt tolerance. To understand the molecular basis of this QTL, we isolated the SKC1 gene by map-based cloning and found that it encoded a member of HKT-type transporters. SKC1 is preferentially expressed in the parenchyma cells surrounding the xylem vessels. Voltage-clamp analysis showed that SKC1 protein functions as a Na(+)-selective transporter. Physiological analysis suggested that SKC1 is involved in regulating K(+)/Na(+) homeostasis under salt stress, providing a potential tool for improving salt tolerance in crops.


Safety assessment for Tris(2,4-di-tert-butylphenyl) phosphite (Irgafos 168) used as an antioxidant and stabilizer in food contact applications.
During and after fabrication of polymeric food contact articles (FCA), polymers undergo oxidation by thermal decomposition processes initiated by oxygen, heat, light, shear, and catalyst residues. To reduce degradation of the polymer, a commonly used secondary antioxidant (AO), Irgafos 168 (I-168), may be included. Use of I-168 in polymeric FCAs presents a potential concern for neurotoxicity due to its phosphate-containing degradation species, I-168ate. As a result, we evaluated dietary exposure and oral toxicity data for I-168 and its degradants when used as an AO in FCAs. Our exposure assessment included extensive review of the U.S. food-contact regulatory history of I-168 resulting in a combined cumulative estimated daily intake (CEDI) of 0.09 mg/kg bw/day for I-168 and I-168ate when used as an AO in FCAs. Our comprehensive literature review of toxicological data and supporting structure activity relationship (SAR) analysis of I-168 reactivity against acetylcholinesterase diminished concern for potential neurotoxic effects of I-168 and its degradants. An acceptable daily intake (ADI) value of 1 mg/kg bw/day for I-168 was derived from a two-year rodent combined chronic toxicity/carcinogenicity study, which is higher than the CEDI and supports the safety of current authorized food contact use levels of I-168.


Correlates of HIV/STD testing and willingness to test among rural-to-urban migrants in China.
This study investigates socio-demographic, behavioral, psychological, and structural factors associated with self-reported HIV/STD testing and willingness to test among 1,938 Chinese migrants. Overall, 6% and 14% of participants had ever been tested for HIV and STD, respectively. The results of multivariate analyses indicate that working at entertainment sectors, engaging in commercial sex, and utilization of health care were positively associated with both HIV and STD testing. Younger age, selling blood, perceived peer sexual risk involvement, and satisfaction with life were associated with HIV testing only. Female gender, early sexual debut, multiple sexual partners, and perceived vulnerability to HIV/STD were associated with STD testing only. Male gender, having premarital sex, perceived higher severity of and vulnerability to HIV/STD, and utilization of health care were associated with willingness to be tested for both HIV and STD. Interventions designed to raise the perception of vulnerability to HIV/STD and to improve access to and utilization of health care may be effective in encouraging more HIV testing in this vulnerable population.


Is a local sample internationally representative? Reproducibility of four cognitive tests in family dogs across testing sites and breeds.
A fundamental precept of the scientific method is reproducibility of methods and results, and there is growing concern over the failure to reproduce significant results. Family dogs have become a favoured species in comparative cognition research, but they may be subject to cognitive differences arising from genetic (breeding lines) or cultural differences (e.g. preferred training methods). Such variation is of concern as it affects the validity and generalisability of experimental results. Despite its importance, this problem has not been specifically addressed to date. Therefore, we aimed to test the influence of three factors on reproducibility: testing site (proximal environment), breed and sex (phenotype). The same experimenter tested cognitive performance by more than 200 dogs in four experiments. Additionally, dogs' performance was tested in an obedience task administered by the owner. Breed of dog and testing site were found to influence the level of performance only mildly, and only in a means-end experiment and the obedience task. Our findings demonstrate that by applying the same test protocols on sufficiently large samples, the reported phenomena in these cognitive tests can be reproduced, but slight differences in performance levels can occur between different samples. Accordingly, we recommend the utilisation of well-described protocols supported by video examples of the whole experimental procedure. Findings should focus on the main outcome variables of the experiments, rather than speculating about the general importance of small or secondary performance outcomes which are more susceptible to random or local noise.


The continued value of central histopathological review of testicular tumours.
Central histopathological review of testicular tumours prior to definitive treatment can have an important impact on patient management. This study was designed to assess the continued value of central review in the light of increasing subspecialization and increased numbers of consultant histopathologists. The original and review reports of 291 testicular cancer specimens from 1998 to 2002 were analysed, looking particularly at major diagnosis, vascular invasion and the tumour elements within non-seminomatous germ cell tumours (NSGCT). When a diagnosis was altered any effect on subsequent patient management was assessed. There was a discrepancy in tumour type in 11 cases (4%) compared with 6% in 1992-1997. The commonest change was from seminoma to NSGCT or combined germ cell tumour (5/11). There was also diagnostic difficulty with spermatocytic seminoma (3/11). The clinical management of all 11 cases was influenced as a result of the review diagnosis. Discrepancies in vascular invasion were noted in 13 of the 126 NSGCTs (10%) compared with 20% in 1992-1997. Differences in NSGCT tumour elements, though clinically less important, were frequent in both groups. There continues to be a small number of significant and clinically important errors identified following central histopathological review of testicular tumours. This study highlights the value of central review and supports its continued practice in the management of testicular tumours.


Contrast enhanced reflux sonography in children: a comparison to standard radiological imaging.
The diagnosis of vesicoureteral reflux is routinely performed by voiding cystourethrography. Especially in the course of conservative treatment, the radiation dose might increase during the years. With the development of ultrasound echo enhancing agents we assessed their diagnostic efficacy for evaluation of vesicoureteral reflux to replace voiding cystourethrography with radiation-free ultrasound. A total of 104 children with a mean age of 5.4 years were examined using echo enhancing ultrasound after informed consent was obtained. For control purposes, all children underwent standard voiding cystourethrography as well. The diagnosis of vesicoureteral reflux was positive when microbubbles appeared in the ureter or renal pelvis. The sonographic findings were correlated with those obtained by standard voiding cystourethrography. Of the 208 ureter and renal units investigated vesicoureteral reflux was detected in 76 (37%) by both technologies. Diagnosis was made sonographically in 5 units and by voiding cystourethrography in 3. All reflux grades (I to V) could be identified. The specificity and sensitivity of the contrast reflux ultrasound were significantly high. The long contrast time of up to 30 minutes combined with the high contrast effect resulted in convincing images with high levels of diagnostic confidence. Our results clearly demonstrate that the diagnostic accuracy of vesicoureteral reflux by contrast enhanced ultrasound is statistically significant compared to standard radiological voiding cystourethrography. Therefore, this methodology represents an exceptional approach to reduce the number of children being exposed to ionizing radiation especially during conservative followup.


Direct extraction and detection of malachite green from marine sediments by magnetic nano-sized imprinted polymer coupled with spectrophotometric analysis.
This research describes the application of magnetic molecularly imprinted nano-sized polymers (MMIPs) for the selective extraction and fast detection of malachite green (MG) from marine sediment samples followed by UV-Vis spectrophotometry. The novel material was prepared by surface imprinting using methacrylic acid as the functional monomer for fixing the template molecules. The polymers obtained at each step were thoroughly studied by transmission electron microscopy, FTIR spectroscopy and thermogravimetric analysis. Simultaneously, the adsorption performances of the resulting nanoparticles were analysed in detail and an excellent affinity with the MG was revealed. Further, the main parameters of magnetic molecular imprinted solid-phase extraction (MMIP-SPE) were screened via multivariate optimization methods. The magnetic nanoparticles were used as special adsorbents to directly extract MG from crude marine sediment extracts. The developed method exhibits satisfactory recoveries from the spiked samples, ranging from 80.40 to 92.96% with an RSD of less than 5.18% (n = 3).


Synthesis of paeonol ester derivatives and their insecticidal, nematicidal, and anti-oomycete activities.
Paeonol is extracted and isolated as a rich and sustainable natural bioresource from the root bark of Paeonia suffruticosa, the derivatives of which exhibit numerous biological activities. It is well known that ester compounds play a very important role in pest control, such as organophosphorus, carbamate and pyrethroid pesticides. To discover biorational natural product-based pesticides, three series of (60) paeonol ester derivatives (7a-t, 8g,p, 9g,p, 10g-j,n-u, 11g,u, 12g,u, 13a-p, 14b,c, and 15b,c) were prepared by structural modification of paeonol, and their structures were well characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 nuclear magnetic resonance (13 C-NMR), high-resolution mass spectrometry (HRMS), and melting point. Furthermore, we assessed the compounds as insecticidal, nematicidal, and anti-oomycete agents against three serious agricultural pests, Mythimna separata, Heterodera glycines, and Phytophthora capsici. Among all tested compounds: (i) compound 8p showed more significant insecticidal activity than toosendanin, and the final mortality rates of 8p and toosendanin against M. separata (1 mg mL-1 ) were 70.4%, and 51.9%, respectively; (ii) compound 7a exhibited more promising nematicidal activity than paeonol, and the median lethal concentration (LC50 ) values of 7a and 1 against H. glycines were 15.47 and 50.80 mg L-1 , respectively; (iii) compounds 7n and 13m displayed more significant anti-oomycete activity compared to zoxamide against Phytophthora capsici, and the median effective concentration (EC50 ) values of 7n, 13m, and zoxamide were 23.72, 24.51, and 26.87 mg L-1 , respectively; and the protective effect of the compounds against Phytophthora capsici in vivo further confirmed the effectiveness of the agents. This study suggested that the introduction of a nitro at the C5 or C3 position of paeonol could improve its bioactivity against M. separata, H. glycines, and Phytophthora capsici. © 2022 Society of Chemical Industry.


Appropriateness of antibiotic use in community hospitals in rural Newfoundland and Labrador.
Surveillance of the appropriateness of antimicrobial prescribing can identify targets for quality improvement in antimicrobial stewardship. Our objective was to measure antibiotic prescription prevalence, indication, and appropriateness at three rural community hospitals in a 1-day point prevalence study. Inpatient antibiotic prescriptions given at three community hospitals on April 24, 2019 were provided by the hospital pharmacies. These prescriptions were analyzed using the Australian National Antimicrobial Prescribing Survey (NAPS) tool. Prescriptions were assessed by an infectious diseases physician and analyzed per prescription. Eighty prescriptions given to 58 inpatients were included. Antibiotic treatment prevalence was 58/120 beds (48.3%), and overall appropriateness was 37/80 prescriptions (46.3%). The most prescribed antibiotics were ceftriaxone (17 [21.3%]; 47.1% appropriate), piperacillin-tazobactam (10 [12.5%]; 10.0% appropriate), and moxifloxacin (9 [11.3%]; 0% appropriate). The most common indications were respiratory tract infections (36 [45.0%]; 36.1% appropriate), skin and soft tissue infections (14 [17.5%]; 78.6% appropriate), and urinary tract infections (9 [11.3%]; 11.1% appropriate). Of the 80 prescriptions, 50 (62.5%) documented an indication, and 71 (88.8%) documented a stop or review date. We observed a high treatment prevalence and low appropriateness. Overall appropriateness was lower than in urban hospitals.


Postoperative Analgesic Effectiveness of Quadratus Lumborum Block for Cesarean Delivery under Spinal Anesthesia.
Spinal morphine is the mainstay of postcesarean analgesia. Quadratus lumborum block has recently been proposed as an adjunct or alternative to spinal morphine. The authors evaluated the analgesic effectiveness of quadratus lumborum block in cesarean delivery with and without spinal morphine. Randomized trials evaluating quadratus lumborum block benefits in elective cesarean delivery under spinal anesthesia were sought. Three comparisons were considered: spinal morphine versus spinal morphine and quadratus lumborum block; spinal morphine versus quadratus lumborum block; and no block or spinal morphine versus quadratus lumborum block. The two coprimary outcomes were postoperative (1) 24-h cumulative oral morphine equivalent consumption and (2) pain at 4 to 6 h. Secondary outcomes included area under the curve pain, time to analgesic request, block complications, and opioid-related side effects. Twelve trials (924 patients) were analyzed. The mean differences (95% CIs) in 24-h morphine consumption and pain at 4 to 6 h for spinal morphine versus spinal morphine and quadratus lumborum block comparison were 0 mg (-2 to 1) and -0.1 cm (-0.7 to 0.4), respectively, indicating no benefit. For spinal morphine versus quadratus lumborum block, these differences were 7 mg (-2 to 15) and 0.6 cm (-0.7 to 1.8), respectively, also indicating no benefit. In contrast, for no block or spinal morphine versus quadratus lumborum block, improvements of -18 mg (-28 to -7) and -1.5 cm (-2.4 to -0.6) were observed, respectively, with quadratus lumborum block. Finally, for no block or spinal morphine versus quadratus lumborum block, quadratus lumborum block improved area under the 48-h pain curve by -4.4 cm · h (-5.0 to -3.8), exceeding the clinically important threshold (3.96 cm · h), but no differences were observed in the other comparisons. Moderate quality evidence suggests that quadratus lumborum block does not enhance analgesic outcomes when combined with or compared with spinal morphine. However, the block improves postcesarean analgesia in the absence of spinal morphine. The clinical utility of this block seems limited to situations in which spinal morphine is not used.


The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa.
Anorexia nervosa (AN) is characterized by subnormal estrogen and dehydroepiandrosterone (DHEA) levels. We sought to determine whether the combination of DHEA + estrogen/progestin is superior to placebo in preserving skeletal health over 18 months in AN. Females with AN, aged 13 to 27 years, were recruited for participation in this double-blind, placebo-controlled, randomized trial. Ninety-four subjects were randomized, of whom 80 completed baseline assessments and received either study drug (oral micronized DHEA 50 mg + 20 µg ethinyl estradiol/0.1 mg levonorgestrel combined oral contraceptive pill [COC] daily; n = 43) or placebo (n = 37). Serial measurements of areal bone mineral density (aBMD), bone turnover markers, and serum hormone concentrations were obtained. Sixty subjects completed the 18-month trial. Spinal and whole-body aBMD z scores were preserved in the DHEA + COC group, but decreased in the placebo group (comparing trends, P = .008 and P = .001, respectively). Bone turnover markers initially declined in subjects receiving DHEA + COC and then returned to baseline. No differences in body composition, adverse effects of therapy, or alterations in biochemical safety parameters were observed. Combined therapy with DHEA + COC appears to be safe and effective for preventing bone loss in young women with AN, whereas placebo led to decreases in aBMD. Dehydroepiandrosterone + COC may be safely used to preserve bone mass as efforts to reverse the nutritional, psychological, and other hormonal components of AN are implemented.


Author Correction: Re-examination of the relationship between marine virus and microbial cell abundances.
The original publication of this Article included analysis of virus and microbial cell abundances and virus-to-microbial cell ratios. Data in the Article came from 25 studies intended to be exclusively from marine sites. However, 3 of the studies included in the original unified dataset were erroneously classified as marine sites during compilation. The records with mis-recorded longitude and latitude values were, in fact, taken from inland, freshwater sources. The three inland, freshwater datasets are ELA, TROUT and SWAT. The data from these three studies represent 163 of the 5,671 records in the original publication. In the updated version of the Article, all analyses have been recalculated using the same statistical analysis pipeline released via GitHub as part of the original publication. Removal of the three studies reduces the unified dataset to 5,508 records. Analyses involving all grouped datasets have been updated with changes noted in each figure. All key results remain qualitatively unchanged. All data and scripts used in this correction have been made available as a new, updated GitHub release to reflect the updated dataset and figures.


The characteristics of posttraumatic syringomyelia.
Retrospective cross-sectional study. To investigate the characteristics of posttraumatic symptomatic syringomyelia after spinal cord injury (SCI). Swiss Paraplegic Centre, Nottwil, Switzerland. The patient database was screened for patients diagnosed with posttraumatic syringomyelia. Syrinx characteristics were determined on T2-weighted magnetic resonance images. Binary logistic regression analysis was used to investigate the effects of age, injury level, injury severity and syrinx location on early syrinx formation, syrinx length and syrinx extending cranial to the lesion. The data of 138 patients were analyzed. The majority of the patients (78.3%) suffered from motor and sensory complete SCI (American Spinal Injury Association Impairment Scale (AIS) A). Syringomyelia was diagnosed a median 15.0 years after SCI at a median age of 42 years. The cervical spine was involved in >57% of the patients, and syringomyelia extended over a median seven vertebral levels. Complete SCI (P=0.035) and age (P=0.001) were significant predictors of early syrinx formation. Syringomyelia occurred significantly earlier in older (>30 years) patients (P⩽0.002) and those with complete SCI (P=0.027) compared with younger patients (⩽30 years) and those with incomplete SCI (AIS B-D), respectively. Age, injury level, injury severity (AIS A) and syrinx location did not have any significant (P>0.9) effect on syrinx extending cranially or syrinx length. Posttraumatic syringomyelia mainly occurs in patients with complete SCI (AIS A) and involves the cervical spine in 6 of the 10 patients. Patients with complete SCI and those age >30 years have an increased risk of syrinx formation within 5 years after injury.


Synthesis of Quinazolin-2,4,6-triamine Derivatives as Non-purine Xanthine Oxidase Inhibitors and Exploration of Their Toxicological Potential.
In this work, a new set of quinazolin-2,4,6-triamine derivatives were synthesized to explore their potential biological activity as xanthine oxidase (XO) inhibitors, superoxide scavengers and screening of their toxicological profile. Among all the synthesized compounds, B1 exhibited better inhibitory activity against bovine xanthine oxidase (bXO) than allopurinol (IC50 =1.56 μM and IC50 =6.99 μM, respectively). As superoxide scavengers, B1, B2 and B13 exhibited a better effect than allopurinol (97.3 %, 82.1 %, 87.4 % and 69.4 %, respectively). Regarding the toxicological profile, B1 was less cytotoxic than methotrexate on HCT-15 cancer cells. Apoptosis results obtained in cells of female and male mice, showed that B1 and B2 presented a similar behaviour to CrO3 (positive control) with respect to the average frequency to induce apoptosis; while B13 apoptosis induced effect was similar to DMSO and control group. Finally, B1, B2, B13 did not induce genotoxicity in a micronuclei murine model compared to CrO3 .


Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency.
Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency.


Nanostructured Materials for Drug Delivery and Tissue Engineering Applications.
Nanotechnology and nanostructured materials for drug delivery and tissue engineering applications are relatively new field that is constantly advancing and expanding. The materials used are at the nanoscale level. Recently, great discoveries and applications have been made (Agents for use in chemotherapy, biological agents and immunotherapy agents) in the treatment of diseases in various areas. Tissue engineering is based on the regeneration and repair of damaged organs and tissues by developing biological substitutes that restore, maintain or improve the function of tissues and organs. Cells isolated from patients are used to seed 3D nanoparticles that can be synthetic or natural biomaterials. For the development of new tissue in tissue engineering, it is necessary to meet the conditions for connecting cells. This paper will present the ways of connecting cells and creating new tissues. Some recent discoveries and advances in the field of nanomedicine and the application of nanotechnology in drug delivery will be presented. Furthermore, the improvement of the effectiveness of new and old drugs based on the application of nanotechnology will be shown.


Physiological role of growth hormone in adult life.
Some historical background on the physiological effects of pituitary gland extract and later of purified hGH in experimental animals is given, and the regulatory role of hGH in the human adult is reviewed. The effects of hGH on carbohydrate, protein and lipid metabolism are complex and closely linked to the action of other hormones, particularly insulin.


Neutron and X-ray diffraction structural analysis of phosphatidylinositol bilayers.
Phosphatidylinositol (PI) bilayers, squeezed together by applied osmotic pressures, were studied by both neutron diffraction and X-ray diffraction. The lamellar repeat period for PI bilayers decreased from 9.5 nm at an applied pressure of 1.1.10(6) dyn/cm2 (1.1 atm) to 5.4 nm at an applied pressure of 1.6.10(7) dyn/cm2 (16 atm). Further increases in applied pressure, up to 2.7.10(9) dyn/cm2 (2700 atm) reduced the repeat period by only about 0.3 nm, to 5.1 nm. Thus, a plot of applied pressure versus repeat period shows a sharp upward break for repeat periods less than about 5.4 nm. For repeat periods of less than 5.4 nm, analysis of neutron-scattering density profiles and electron-density profiles indicates that the structure of the PI bilayers changes as the bilayers are dehydrated, even though there are only small changes in the repeat period. These structural changes are most likely due to removal of water from the headgroup regions of the bilayer. D2O/H2O exchange experiments show that, at an applied pressure of 2.8.10(7) dyn/cm2, water is located between adjacent PI headgroups in the plane of the bilayer. We conclude that, although electrostatics provide the dominant long-range repulsive interaction, hydration repulsion and steric hindrance between PI headgroups from apposing bilayers provide the major barriers for the close approach of adjacent PI bilayers for repeat periods less than 5.4 nm. This structural analysis also indicates that the phosphoinositol group extends from the plane of the bilayer into the fluid space between adjacent bilayers. This extended orientation for the headgroup is consistent with electrophoretic measurements on PI vesicles.


Codon preference and primary sequence structure in protein-coding regions.
The stochastic complexity of a data base of 365 protein-coding regions is analysed. When the primary sequence is modeled as a spatially homogeneous Markov source, the fit to observed codon preference is very poor. The situation improves substantially when a non-homogeneous model is used. Some implications for the estimation of species phylogeny and substitution rates are discussed.


CXC chemokine KC fails to induce neutrophil infiltration and neoangiogenesis in a mouse model of myocardial infarction.
Chemokines and neutrophils, known as important players in the inflammatory cascade, also contribute to heart tissue recovery and scar formation after myocardial infarction (MI). The objective of this study was to determine the importance of ELR-containing CXC chemokine KC in neutrophil infiltration and neoangiogenesis, in a mouse model of chronic MI. MI was induced in mice divided in four groups: control (untreated), anti-KC "later" (anti-KC antibody injections started 4 days after MI and then delivered every 72 hours for 3 weeks, to inhibit angiogenesis), anti-KC "earlier" (anti-KC antibody injections 1 day before and 1 day after MI, to block neutrophil infiltration), anti-KC (anti-KC antibody injections 1 day before and 1 day after MI, and then every 72 hours for 3 weeks). The efficiency of the anti-KC treatment was determined by the measurement of KC serum concentration and immunofluorescence staining, in each of the four groups. Surprisingly, we did not find any difference in neutrophil infiltration in the infarcted area between untreated and treated animals. Moreover, the heart function, infarct size, and neoangiogenesis were not different between the four groups. As expected, a comparable anti-CXCR2 treatment of mice before and after MI was able to significantly reduce neutrophil infiltration into the infarcted area and angiogenesis, but also to reduce the infarction size after long or "later" treatment. The major finding of our study is that KC, a potent neutrophil chemoattractant and an established angiogenic factor, failed to interfere in the post-infarction inflammatory response, in wound healing and scar formation after MI. Therefore, these aspects need to be carefully taken into account when devising therapeutic strategies for myocardial infarction and ischemic cardiomyopathy.


Gastric myoelectrical and neurohormonal changes associated with nausea during tilt-induced syncope.
Nausea is a common prodromal symptom of neurally mediated syncope, but the biological factors linking nausea with syncope have not been studied. We aimed to characterize nausea during tilt-induced syncope by exploring related changes in gastric myoelectrical activity and plasma epinephrine, norepinephrine, and vasopressin concentrations across study phases of recumbency, tilt, syncope, and recovery. Electrogastrographic and plasma hormone changes were compared between patients with tilt-induced syncope and nausea (n = 18) and control subjects (n = 6) without symptoms or hemodynamic changes during tilt-table testing. Over a 4-minute period preceding syncope, sequential electrogastrography epochs demonstrated an increase over time in bradygastria (P = .003) and tachygastria (P = .014) power ratios, while the dominant frequency (P < .001) and the percent normogastria (P = .004) decreased. Syncope led to significant differences between cases and controls in electrogastrographic power ratios in each frequency range: bradygastria (P = .001), tachygastria (P = .005), and normogastria (P = .03). Nausea always followed electrogastrographic changes, and nausea resolution always preceded electrogastrographic normalization. Plasma vasopressin (676.5 ± 122.8 vs 91.2 ± 15.3 pg/mL, P = .012) and epinephrine (434 ± 91.3 vs 48.7 ± 2.5 pg/mL, P = .03), but not norepinephrine (P > .05), also differed with syncope between cases and controls. The nausea related to tilt-induced syncope is temporally associated with changes in gastric myoelectrical activity and increases in plasma vasopressin and epinephrine. The biological mechanisms that induce syncope are physiologically distinct from other experimental models of nausea such as illusory self-motion, yet nausea with syncope appears to have similarly associated electrogastrographic and hormone changes. Thus, tilt-induced syncope could serve as an informative experimental model for nausea research.


Spermicidal contraceptives and poor reproductive outcomes: the epidemiologic evidence against an association.
The first widely publicized report of an association between spermicidal contraception and congenital malformations and spontaneous abortion had considerable impact on obstetric practice. A large number of more recent epidemiologic studies have generally failed to support the earlier finding, and it is concluded that no such association has been demonstrated. The available evidence precludes the need for additional regulation of spermicidal contraception.


A case report of SARS-CoV-2 confirmed in saliva specimens up to 37 days after onset: Proposal of saliva specimens for COVID-19 diagnosis and virus monitoring.
We present the case of a 71-year-old man who, despite becoming asymptomatic after having some mild symptoms of COVID-19, had SARS-CoV-2 RNA detected for 37 days after onset, from his concentrated and purified saliva specimens using sugar chain-immobilized gold nanoparticles. It was suggested that the early morning saliva specimens were more likely to show positive results than those obtained later in the day.


Forskolin inhibits tension development in detergent-treated cardiac muscle fibers.
In detergent-treated cardiac muscle fibers, forskolin, a potent activator of adenylate cyclases, inhibits tension development elicited with submaximal [Ca2+] and increases incorporation of 32P into troponin-I. A similar reduced tension development has been observed after treatment with cAMP or the catalytic subunit of the cAMP-dependent protein kinase. It is concluded that these fibers still contain much of the enzyme cascade involved in evoking a contractile response to beta-adrenergic stimulation.


COVID-19 preparedness among public and healthcare providers in the initial days of nationwide lockdown in India: A rapid electronic survey.
The COVID-19 Pandemic has been raging across continents in recent months. Public health measures are crucial in preventing COVID-19. The Government of India declared a nationwide lockdown on 24 March, 2020. The objective of this study is to assess preparedness among general public and healthcare providers against COVID-19 by way of adopting public health measures at the very beginning of the nationwide lockdown in India. A rapid cross sectional electronic survey was conducted across the country between 25 and 27 March, 2020. Participants were general public and healthcare providers. Online questionnaire was generated in Google Forms. This included precautionary measures such as staying home, hand hygiene, wearing masks, cough hygiene and advisory against face touching. The web link to the form was shared through WhatsApp. Descriptive data analysis was done using Epi Info software (version-7). A total of 226 persons (general public = 183; healthcare providers [HCPs] = 43) participated in the study. During the lockdown, HCPs spent more time outside than the general public (p = 0.009). Only 47% of the participants claimed to practise frequent hand washing and majority (72%; n = 163) did not wear masks while outdoors. Almost a half (45%) of the participants touched their face frequently and very few (8%) participants covered their mouth or nose while coughing or sneezing. There was no significant difference between HCPs and general public in frequent hand washing (p = 0.456), wearing masks (p = 0.255), face touching (p = 0.632) or covering mouth/nose while coughing or sneezing (p = 0.428). There is lack of preparedness among general public and healthcare providers against COVID-19 at the beginning of the nationwide lockdown in India.


Rapidly destructive osteoarthritis can mimic infection.
The intraoperative appearance of rapidly destructive osteoarthritis and septic arthritis can be similar. Three patients at our institution demonstrated preoperative or intraoperative findings potentially consistent with infection during primary total hip arthroplasty; however, none of these patients were found to have an actual infection. One of these patients underwent an unnecessary 2-stage total hip arthroplasty secondary to the intraoperative appearance of their joint fluid. We advocate performing an infection workup preoperatively when patients present with rapid degenerative changes of their hip joint to diminish the uncertainty of proceeding with arthroplasty.


Clinical Characteristics, Treatment, and Survival Outcome of Ependymoma in Infants.
Treatment modalities of ependymoma in infants remain controversial. Postoperative adjuvant radiotherapy could prolong overall survival but has the potential to affect nervous system development in infants. The role of adjuvant chemotherapy in prolonging overall survival for infants with ependymoma is still unclear. Therefore we designed this study to explore the effect of treatment modalities on survival time of infants with ependymoma. We studied 72 infants with ependymoma from the Surveillance, Epidemiology, and End Results database in this retrospective analysis. Univariate and multivariate Cox proportional hazard models were adopted to determine hazard ratios and compare overall survival. Among 72 infants with ependymoma, 35 were male (48.6%) and 37 were female (51.4%). The 5-year overall survival of all patients was 67%. Forty-six infants (63.9%) received gross total resection, 20 (27.8%) received subtotal resection, and 6 (8.3%) did not receive surgical resection or only autopsy. Twenty-one infants (29.2%) received radiotherapy, and 45 (62.5%) received chemotherapy. Multivariate analysis revealed that patients accepted surgical resection (No vs. gross total resection, P < 0.001; No vs. subtotal resection, P = 0.026) and chemotherapy (No vs. Yes, P = 0.024) are the independent prognostic factors for overall survival. Treatment modality is associated with survival time in infants with ependymoma. The extent of resection and chemotherapy were independent prognostic factors for infants with ependymoma.


Compliance with standard precautions among operating room nurses in South Korea.
Standard precautions are widely adopted to prevent the transmission of bloodborne pathogens among health care workers. There is no system to monitor compliance with standard precautions among health care workers, and few studies have been done to identify the level of compliance with standard precautions among health care workers in South Korea. This study aimed to determine the level of compliance with and education on standard precautions among operating room nurses in South Korea. A cross-sectional survey was done with 158 operating room scrub nurses from 7 general hospitals that each had 500 beds or more in Busan, South Korea, from April to May 2006. Data were collected using self-administered questionnaires on compliance with double gloving, using protective eyewear, and no recapping of needles. Twelve percent (19/158) of the participants always used double gloving, 2% (3/158) always used protective eyewear, and 10% (15/158) always practiced not recapping used needles. All hospitals investigated in the study had regular educational programs lasting less than 1 hour on the control of hospital infection for new employees. Only 1 hospital has provided on the job training on the infection control for current operating room nurses. Operating room nurses in this study rarely complied with standard precautions, especially with using protective eyewear. Training on a more regular basis should be established to increase the compliance with standard precautions among operating room nurses in South Korea.


Autopsy case of Rosai-Dorfman disease presenting as fibrinous pericarditis.
Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis that is characterized histopathologically by accumulation of CD68-positive, S100-positive, and CD1a-negative histiocytes. Cardiac involvement of RDD is rare. We report here an autopsy case of cardiac involvement of RDD presenting as fibrinous pericarditis. A 14-year-old Japanese boy complained of loss of appetite and breathing difficulty when lying down. He was found dead on his back in his bedroom. One year before his death, he was diagnosed with RDD after skin biopsy. At autopsy, the deceased was 153 cm in height and weighed 38 kg with systemic edema. He had flat pigmented light-brown spots, as well as many pale reddish-brown papules on the abdomen and both thighs. Cervical and mediastinal lymphadenopathy was observed. A large amount of pleural and ascitic fluid was observed. The spleen weighed 381.9 g and showed splenomegaly. The heart weighed 620 g and showed acute fibrinous pericarditis with adhesion. Abundant fibrin was observed on the epicardial surface. The infiltrating cells were CD68-positive, S100-positive, and CD1a-negative histiocytes. The skin and spleen showed histiocytic involvement. Systemic edema, large amounts of pleural and ascitic fluid, a high brain natriuretic peptide level in blood, and hemosiderin-laden macrophages in the lungs suggested chronic heart failure. We speculate that the cause of death was extranodal cardiac involvement of RDD with chronic heart failure. This case highlights the need for forensic pathologists to perform a complete autopsy to determine the cause of sudden death when cardiac involvement of RDD is present.


Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis.
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent due to its selective killing on cancer cells while sparing the normal cells. Nevertheless, breast adenocarcinoma cells can develop TRAIL resistance. Therefore, this project investigated the anti-cancer effects of the combination of epigenetic drugs zebularine and trichostatin A (ZT) with TRAIL (TZT) on the human breast adenocarcinoma cells. This treatment regimen was compared with the natural anti-cancer compound curcumin (Cur) and standard chemotherapeutic drug doxorubicin (Dox). As compared to TRAIL treatment, TZT treatment hampered the cell viability of human breast adenocarcinoma cells MDA-MB-231 significantly but not MCF-7 and immortalized non-cancerous human breast epithelial cells MCF10A. Unlike TZT, Cur and Dox treatments reduced cell viability in both human breast adenocarcinoma and epithelial cells significantly. Nevertheless, there were no changes in cell cycle in both TRAIL and TZT treatments in breast adenocarcinoma and normal epithelial cells. Intriguingly, Cur and Dox treatment generally induced G2/M arrest in MDA-MB-231, MCF-7 and MCF10A but Cur induced S phase arrest in MCF10A. The features of apoptosis such as morphological changes, apoptotic activity and the expression of cleaved poly (ADP) ribose polymerase (PARP) protein were more prominent in TRAIL and TZT-treated MDA-MB-231 as compared to MCF10A at 24 h post-treatment. Compared to TZT treatment, Cur and Dox treatments exhibited lesser apoptotic features in MDA-MB-231. Collectively, the sensitization using Zeb and TSA to augment TRAIL-induced apoptosis might be an alternative therapy towards human breast adenocarcinoma cells, without harming the normal human breast epithelial cells.


Endorsing sustainable development in BRICS: The role of technological innovation, renewable energy consumption, and natural resources in limiting carbon emission.
This research aimed to examine the complex interaction between technological innovation, renewable energy consumption, natural resources, and carbon dioxide (CO2) emissions of BRICS (i.e., Brazil, Russia, India, China, and South Africa) countries from 1990 to 2019, to accomplish the Paris Climate Conference (COP-21) objective of reducing CO2 emissions to promote environmental sustainability. The long-run empirical estimations derived from the CS-ARDL technique, which considered other estimation issues like cross-sectional dependency and slope heterogeneity, indicated that technological innovation, renewable energy consumption, and natural resources increase environmental sustainability by limiting CO2 emissions, in the short-run and long-run. The technological innovation-related activities have a CO2 mitigating effect as shown by the negative coefficients which ranges between -0.05 and -0.14. This shows that they increase environmental sustainability and aid in achieving Sustainable Development Goals (SDGs) 13. Similarly, renewable energy and natural resources decrease CO2 emissions as shown by the coefficient of renewable energy (-0.31 to -0.81) and natural resources (-0.01 to 0.95); thereby increasing ecological quality by limiting CO2 emissions. Furthermore, the interaction of technological innovation with natural resource rent and renewable energy consumption also aids in mitigating CO2 emissions and increases environmental health. Finally, panel causality analysis revealed a significant causality from all explanatory variables to CO2 emissions. Based on the results, significant policy suggestions are provided, such as improving energy effectiveness, investing in energy technologies, and increasing renewable energy consumption to stimulate technological innovation to achieve the target of a net-zero‑carbon economy.


An ARL1 mutation affected autophagic cell death in yeast, causing a defect in central vacuole formation.
When the cdc28 strain of Saccharomyces cerevisiae is incubated at restrictive temperatures, the yeasts digest themselves in 7 days by activating autophagic machinery. In parallel, the cell-proliferative activity decreases progressively after about 48 h. We have previously referred to this phenomenon as autophagic death. In the present study, we isolated and characterized a recessive mutant strain, dlp2, which delays the progression toward autophagic death. The cdc28 dlp2 cells contain many small vesicles instead of the large central vacuoles that are usually found in parental cdc28 cells. We showed that the dlp2 phenotype results from the presence of a single mutation in the gene ARL1 (ADP-ribosylation factor-like protein 1). Morphological and biochemical analyses of cdc28 dlp2 suggested that a defect in central vacuole formation is caused by aberrant membrane trafficking, although the protein-sorting to vacuoles is not affected. After a shift to a restrictive temperature, the components of the cytoplasm and nucleus of cdc28 dlp2 were condensed, with an accompanying formation of vesicles in the periphery (epiplasm) of the cells rather than an activation of the autophagic machinery. Introducing this ARL1 mutation into the normal ARL1 locus of the wild-type W303 strain again inhibited the progression of apoptotic cell death due to a defect in vacuole formation, which in this case was induced by the proapoptotic protein Bax. Thus, the ARL1 gene plays an important role in the formation of central vacuoles and in the progression of programmed cell death induced by cell-cycle arrest or Bax. These results suggested the presence of a programmed-cell death machinery in yeast that is similar to that related to the Type II cell death of mammalian cells characterized by autophagocytosis.


Structural Basis of GABAB Receptor Regulation and Signaling.
GABAB receptors (GBRs), the G protein-coupled receptors for the inhibitory neurotransmitter γ-aminobutyric acid (GABA), activate Go/i-type G proteins that regulate adenylyl cyclase, Ca2+ channels, and K+ channels. GBR signaling to enzymes and ion channels influences neuronal activity, plasticity processes, and network activity throughout the brain. GBRs are obligatory heterodimers composed of GB1a or GB1b subunits with a GB2 subunit. Heterodimeric GB1a/2 and GB1b/2 receptors represent functional units that associate in a modular fashion with regulatory, trafficking, and effector proteins to generate receptors with distinct physiological functions. This review summarizes current knowledge on the structure, organization, and functions of multi-protein GBR complexes.


Juvenile myelomonocytic leukemia: a report from the 2nd International JMML Symposium.
Juvenile myelomonocytic leukemia (JMML) is an aggressive childhood myeloproliferative disorder characterized by the overproduction of myelomonocytic cells. JMML incidence approaches 1.2/million persons in the United States (Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975-1995). Although rare, JMML is innately informative as the molecular genetics of this disease implicates hyperactive Ras as an essential initiating event. Given that Ras is one of the most frequently mutated oncogenes in human cancer, findings from this disease are applicable to more genetically diverse and complex adult leukemias. The JMML Foundation (www.jmmlfoundation.org) was founded by parent advocates dedicated to finding a cure for this disease. They work to bring investigators together in a collaborative manner. This article summarizes key presentations from The Second International JMML Symposium, on 7-8 December 2007 in Atlanta, GA. A list of all participants is in Supplementary Table.


β-1,4-Galactosyltransferase I involved in Schwann cells proliferation and apoptosis induced by tumor necrosis factor-alpha via the activation of MAP kinases signal pathways.
β-1,4-galactosyltransferase-I (β-1,4-GalT-I) plays a critical role in the initiation and maintenance of peripheral nervous system inflammatory reaction. However, the exact function of β-1,4-GalT-I in the regulation of SCs proliferation and apoptosis remains unclear. In this study, we found that low concentration of tumor necrosis factor-alpha (TNF-α) induced SCs proliferation, while high concentration of TNF-α induced SCs apoptosis. Meanwhile, the expressions of β-1,4-GalT-I, TNFR1, and TNFR2 were changed following. When β-1,4-GalT I overexpression, low concentration of TNF-α-induced SCs proliferation was partially repressed. Concurrently, the activity of ERK1/2 was decreased. While knocking down β-1,4-GalT I expression, high concentration of TNF-α-induced SCs apoptosis was partially rescued. Consistent with this, the activity of P38 and JNK were decreased. We also found anti-TNFR2 antibody suppressed low concentration of TNF-α-induced SCs proliferation, while anti-TNFR1 antibody inhibited high concentration of TNF-α-induced SCs apoptosis. Thus, present data show that β-1,4-GalT I may play an important role in SCs proliferation and apoptosis induced by TNF-α via different signal pathways and TNFR.


Discovery of pathogen-regulated small RNAs in plants.
Small RNAs have emerged as one of the most important regulators for gene expression in eukaryotes. Small RNA-mediated gene silencing has been shown to play an essential role in antiviral defense in both plant and animal systems (Li and Ding, 2005; Voinnet, 2005; Wang et al., 2006). These viral RNA-generated small interfering RNAs (siRNAs) are extragenomic in origin. Studies from our lab and others suggest that host-endogenous small RNAs also play an important role in plant defense in response to other pathogens besides viruses (Katiyar-Agarwal et al., 2006; Navarro et al., 2006). The methods described here provide an opportunity to identify many more novel pathogen-regulated small RNAs in plants, which will help in understanding the regulatory mechanism of plant immunity. Here, we introduce the approaches of powerful high-throughput parallel sequencing and hybridization-based technologies for the discovery and detection of pathogen-regulated small RNAs. We mainly compare and discuss the methods of low-molecular-weight (LMW) RNA extraction from pathogen-infected tissue and strategies for detecting endogenous small RNAs by Northern blot analysis.


Gonadotropin-Releasing Hormone Receptor Expression in Human Spinal Cord.
The expression of the gonadotrophin-releasing hormone receptor expression on pituitary gonadotrophs in humans is well characterized. In nervous system they have also been found in hippocampi and cerebral cortex. However, gonadotrophin-releasing hormone receptor expression in human spinal cord has not been reported. This study was to analyze the gonadotrophin-releasing hormone receptor expression in human spinal cord by immunohistochemistry, mRNAs by reverse transcriptase polymerase chain reaction, cDNA cloning and Western blot. The results show immunoreactive material to gonadotrophin-releasing hormone receptor in motoneurons of the spinal cord. Further, the study revealed that spinal cord expressed the gonadotrophin-releasing hormone receptor mRNA. The amplicon sequence corresponds to 100% of identity to GenBank. In Western blot, a band of 37 kDa were found in extracts of spinal cord and placenta as a control. In conclusion, human spinal cord expresses gonadotrophin-releasing hormone receptor analyzed through immunohistochemistry, the expression of its mRNA, cloning its cDNA and Western blot analysis. The presence of gonadotrophin-releasing hormone receptor in the spinal cord suggests the possibility of an extrapituitary functional role independent of reproductive system.


Flight patterns of foraging bees relative to density of artificial flowers and distribution of nectar.
Flight patterns of honeybees (Apis mellifera ligustica) were quantified as the bees foraged among artificial 'flowers' for sugar solution ('nectar'). Bees exhibited considerable directionality on successive flights which minimized repeat visits to flowers and they usually made short flights to nearby flowers, thus minimizing flight time. The change in direction on successive flights between flowers were independent of the number of immediately preceding consecutive rewarding visits but decreased as the number of non-rewarding visits increased. Flight distances were short after visits to rewarding flowers but increased as the number of immediately preceding non-rewarding visits increased. The bees' rate of caloric intake (calories/time) was highest at the floral arrays having the highest density, and it was greater at arrays with clumped nectar-distributions than at those with randomly distributed nectar. These findings are explained in terms of the observed flight patterns.


Experience of King Abdullah Medical City in Placement of Inferior Vena Cava Filter Prior to Bariatric Surgery in Extremely High-Risk Patients for Thromboembolic Events.
Bariatric surgery is used to treat morbid obese patients. Venous thromboembolism (VTE) is considered to be one of the leading causes of postoperative morbidity and mortality. Therefore, inferior vena cava filter (IVCF) is used to minimize the risk of VTE in high-risk patients. Medical information was collected for the preoperative, operative and postoperative stages for all patients underwent bariatric surgery at KAMC from March 2013 to July 2017. Five cases with IVCF were included in this study. Age ranged from 35 to 66 years old; 4 (80%) were female. Preoperative body mass index ranged from 42 to 64 kg/m2. Postoperative findings were reported. IVCF seems to be beneficial for patients undergoing bariatric surgery.


Recurrent and novel GLB1 mutations in India.
GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India.


The IL-1β signalling pathway and its role in regulating pro-inflammatory and pro-labour mediators in human primary myometrial cells.
Interleukin (IL)-1β plays a central role in the processes of human labour and delivery. The adaptor proteins involved in the IL-1β signalling pathway in human myometrium are not known. This study sought to determine the role of the adaptor proteins myeloid differentiation primary response 88 (MyD88), tumour necrosis factor receptor-associated factor 6 (TRAF6), IL-1 receptor-associated kinase 4 (IRAK4) and transforming growth factor beta-activated kinase 1 (TAK1) in IL-1β-induced formation of pro-inflammatory and pro-labour mediators in human myometrium. Human primary myometrial cells were transfected with siRNA against MyD88 (siMYD88), TRAF6 (siTRAF6), IRAK4 (siIRAK4) or TAK1 (siTAK1), treated with IL-1β, and assayed for the mRNA expression and or secretion of pro-inflammatory and pro-labour mediators. Transfection of primary myometrial cells with siMYD88, siTRAF6, siIRAK4 and siTAK1 significantly decreased IL-1β-induced IL-1α, IL-6, growth-regulated alpha protein (GRO-α), IL-8, monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 mRNA expression and release of IL-6, GRO-α, IL-8, MCP-1, ICAM-1 and prostaglandin PGF2α. The expression and secretion of the extracellular matrix remodelling enzyme matrix metalloproteinase (MMP)-9 was significantly lower with siMYD88 and siTRAF6. Finally, IL-1β-induced nuclear factor κB (NF-κB) transcriptional activity was significantly attenuated by transfection with siMyD88, siTRAF6 and siIRAK4; there was no effect of siTAK1 transfection on NF-κB transcriptional activity. Collectively, these findings suggest that MyD88, TRAF6, IRAK4 and TAK1 are involved in IL-1β signalling in human myometrium. Further studies are required to determine if inhibition of these proteins can prevent preterm birth.


Indomethacin tocolysis and white matter injury in preterm infants.
This study aims to clarify the relationship between indomethacin tocolysis and neonatal white matter injury (WMI) in preterm infants. We conducted a retrospective review of preterm infants born at 24-32 weeks who had sufficient cranial ultrasound examinations (CUS) to determine the incidence and severity of abnormalities. Infants with normal CUS were compared on univariate and multivariate analyses with infants with the different forms of WMI. On multivariate logistic regression analysis, indomethacin tocolysis was significantly correlated with periventricular echogenicity (PVE; OR 2.84 95% CI 1.41-5.7, p = 0.003), but not with periventricular leucomalacia (PVL; OR 1.83 95% CI0.6-5.6, p = 0.29). Indomethacin was not related to increased risk for periventricular-intraventricular hemorrhage or periventricular hemorrhagic infarction. These findings suggest caution in the use of indomethacin as a tocolytic therapy.