phyBWT2: phylogeny reconstruction via eBWT positional clustering.
Molecular phylogenetics studies the evolutionary relationships among the individuals of a population through their biological sequences. It may provide insights about the origin and the evolution of viral diseases, or highlight complex evolutionary trajectories. A key task is inferring phylogenetic trees from any type of sequencing data, including raw short reads. Yet, several tools require pre-processed input data e.g. from complex computational pipelines based on de novo assembly or from mappings against a reference genome. As sequencing technologies keep becoming cheaper, this puts increasing pressure on designing methods that perform analysis directly on their outputs. From this viewpoint, there is a growing interest in alignment-, assembly-, and reference-free methods that could work on several data including raw reads data. We present phyBWT2, a newly improved version of phyBWT (Guerrini et al. in 22nd International Workshop on Algorithms in Bioinformatics (WABI) 242:23-12319, 2022). Both of them directly reconstruct phylogenetic trees bypassing both the alignment against a reference genome and de novo assembly. They exploit the combinatorial properties of the extended Burrows-Wheeler Transform (eBWT) and the corresponding eBWT positional clustering framework to detect relevant blocks of the longest shared substrings of varying length (unlike the k-mer-based approaches that need to fix the length k a priori). As a result, they provide novel alignment-, assembly-, and reference-free methods that build partition trees without relying on the pairwise comparison of sequences, thus avoiding to use a distance matrix to infer phylogeny. In addition, phyBWT2 outperforms phyBWT in terms of running time, as the former reconstructs phylogenetic trees step-by-step by considering multiple partitions, instead of just one partition at a time, as previously done by the latter. Based on the results of the experiments on sequencing data, we conclude that our method can produce trees of quality comparable to the benchmark phylogeny by handling datasets of different types (short reads, contigs, or entire genomes). Overall, the experiments confirm the effectiveness of phyBWT2 that improves the performance of its previous version phyBWT, while preserving the accuracy of the results.


How Iranian Medical Trainees Approach their Responsibilities in Clinical Settings; A Grounded Theory Research.
It seems we are now experiencing "responsibility problems" among medical trainees (MTs) and some of those recently graduated from medical schools in Iran. Training responsible professionals have always been one of the main concerns of medical educators. Nevertheless, there is a dearth of research in the literature on "responsibility" especially from the medical education point of view. Therefore, the present study was carried out with the aim of presenting a theoretical based framework for understanding how MTs approach their responsibilities in educational settings. This qualitative study was conducted at Shiraz University of Medical Sciences (SUMS) using the grounded theory methodology. 15 MTs and 10 clinical experts and professional nurses were purposefully chosen as participants. Data was analyzed using the methodology suggested by Corbin and Strauss, 1998. "Try to find acceptance toward expectations", "try to be committed to meet the expectations" and "try to cope with unacceptable expectations" were three main categories extracted based on the research data. Abstractly, the main objective for using these processes was "to preserve the integrity of student identity" which was the core category of this research too. Moreover, it was also found that practically, "responsibility" is considerably influenced by lots of positive and negative contextual and intervening conditions. "Acceptance" was the most decisive variable highly effective in MTs' responsibility. Therefore, investigating the "process of acceptance" regarding the involved contextual and intervening conditions might help medical educators correctly identify and effectively control negative factors and reinforce the constructive ones that affect the concept of responsibility in MTs.


Encapsulation of chimeric protein rSAG1/2 into poly(lactide-co-glycolide) microparticles induces long-term protective immunity against Toxoplasma gondii in mice.
In the present study, the poly(lactide-co-glycolide) (PLG) polymer was used as an adjuvant to encapsulate the chimeric protein rSAG1/2 for preparing a microparticle vaccine against Toxoplasma gondii. The resulting PLG-encapsulated rSAG1/2 (PLG-rSAG1/2) microparticles, 1.27-1.65μm in diameter, showed 72-83% entrapment efficiency. The amount of released rSAG1/2 protein from microparticles gradually increased over a long 56-day period and the protein still retained its antigenicity. Intraperitoneal immunization with the microparticles in BALB/c mice elicited significant long-term (10weeks) humoral and cell-mediated immune responses, accompanied by secretion of a large amount of IFN-γ, to achieve strong protection (83%) against a lethal subcutaneous tachyzoite challenge. In conclusion, we have successfully encapsulated rSAG1/2 with the PLG polymer to produce stable microparticles that can effectively induce not only long-term immunity but also high protection against T. gondii. These crucial data would be advantageous for developing long-term Toxoplasma vaccines for future use in humans and animals.


Role of citicoline and choline in the treatment of post-stroke depression: an exploratory study.
To compare selective serotonin reuptake inhibitors (SSRIs) and nootropic drugs in the reduction of anxiety and depressive symptoms in post-stroke patients. This retrospective cohort study included patients diagnosed with post-stroke depression that were treated with either SSRIs or nootropic drugs (i.e. citicoline or choline alphoscerate). Depression and anxiety were assessed using the Hamilton Rating Scales. Statistical associations between the use of nootropic drugs and mood disorder improvements were determined by measuring assessment scores at 6-months. A total of 44 post-stroke patients with depression (aged 45-75 years) were enrolled in the study: 20 were treated with SSRIs and 24 received nootropic drugs. From baseline to follow-up, the SSRI group showed a large effect size with regard depression (success rate difference [SRD] 0.57; 95% confidence interval [CI] 0.21, 0.79) and anxiety (SRD 0.49; 95% CI 0.14, 0.74), whereas the nootropic group showed a small effect size for depression (SRD 0.16; 95% CI -0.17, 0.46) and a small effect size for anxiety (SRD 0.36; 95% CI -0.03, 0.62). The administration of nootropic drugs could be a valid therapeutic strategy to manage post-stroke patients suffering from mild-moderate anxiety or anxious-depressive syndrome, but this requires further research.


Monitoring of polycyclic aromatic hydrocarbons in seafoods from Lake Timsah.
Concentrations of polycyclic aromatic hydrpcarvons (PAHs) in some seafoods caught from Lake Timsah were determined. The tested samples were tilapia fish (Oreochromis aureus), crabs (Portuns pelagicus), bivalves (Venerupis decussata), clams (Strombus tricornis) and gastropods (Munes Sp.). Where these seafoods are locally and favorite consumed foods in the area around the lake (Ismailia governorate). Results showed that crabs contained significantly higher concentrations of both total and carcinogenic PAHs ranging from 1318.6 to 3767.4 and 1230.3 to 3442.2 microg kg(-1), respectively. Meanwhile, clams contained significantly lower levels with mean value of 28.4 microg kg(-1) for total and 24.4 microg kg(-1) for carcinogenic PAHs. The most frequently detected PAHs in the tested samples were indeno(1,2,3-cd)pyrene followed by benzo(a)pyrene, dibenzo(a,h)anthracene, and benzo(b)fluoranthene which are characterized as carcinogenic compounds.


Double-edged effects of elevating temperature on the aging of exogenous arsenic in flooded paddy soils.
Temperature variation can have a significant impact on arsenic (As) bioavailability in paddy soils. However, details regarding the transformation of exogenous As during the aging process in paddy soils at various temperatures remain unclear. This work investigated the effects of temperature on the As extractability and As species transformation of three paddy soils spiked with exogenous arsenate at 60 mg kg-1 under flooded aging and explored the related chemical and microbial mechanisms. The results showed that 0.05 M NH4H2PO4-extractable As decreased over time during flooded aging for 192 days, and it decreased by approximately one-third at 35 °C compared with 15 °C and 25 °C at the same aging time, indicating that higher temperatures facilitated the decrease in As extractability. As(V) reduction mainly occurred at 35 °C because the abundance and As(V)-reducing capacity of the predominant indigenous bacteria, the Bacillus sp strains, and the abundance of the arrA gene were significantly higher than those at 15 °C and 25 °C. The reduction of As(V) to As(III) and aging occurred simultaneously. The kinetic models were established, and the rate constants of the reduction and aging processes were obtained. Soil properties significantly affected the aging and reduction processes of extractable As(V). Our study indicated that elevating temperature had dual effects on the environmental risk of As in the flooded aging process. The previous definition of "aging" based on cationic metals needs to be updated according to the transformation characteristics of As species in flooded conditions. Our results addressed the necessity of impeding the reduction of As(V) in paddy soils under global warming.


Genetic polymorphisms influence gene expression of human periodontal ligament fibroblasts in the early phases of orthodontic tooth movement.
Genetic polymorphisms could be involved in the individual rate of OTM (orthodontic tooth movement) corresponding to the clinical phenomenon of "slow movers" and "fast movers". This study evaluated, if genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6 are associated with the expression of RANKL, OPG, COX2 and IL6 by human periodontal ligament (hPDL) fibroblasts during OTM. Primary hPDL fibroblasts from periodontal connective tissue of teeth extracted from 57 human subjects for medical reasons were collected, isolated, cultivated and characterized. To simulate orthodontic forces in PDL pressure areas, a physiological compressive force of 2 g/cm2 was applied to the hPDL fibroblasts under cell culture conditions at 70% confluency for 48 h, using a glass disc. Thereafter we analysed relative expression of RANKL, OPG, COX2 and IL6 by RT-qPCR. We also performed genotyping analysis of seven genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6. Relative gene expression was compared among the genotypes. The genotype TT in polymorphism rs9594738 (RANKL) had a higher RANKL expression in the recessive model (p = 0.021; TT vs. CT + CC). For polymorphism rs9594738 (RANKL), in the recessive model, TT was associated with a higher RANKL/OPG expression ratio (p = 0.013; TT vs. CT + CC). In the dominant model, GG genotype in rs5275 (COX2) was associated with a lower gene expression of COX2 (p = 0.04; GG vs. AA + AG). Genetic polymorphisms in genes associated with OTM affect the relative force-induced upregulation of these genes in hPDL fibroblasts.


A staged procedure for the treatment of chronic patellar tendon ruptures after total knee arthroplasty.
The management of extensor mechanism lesions after total knee replacement is still associated with an unacceptably high complication rate, especially in its chronic setting. In this study, we report on 4 patients with chronic (> 3 months) patellar tendon rupture after knee arthroplasty, who were treated with a novel procedure of staged patella advancement prior to reconstruction with autografts. Initially, a unilateral frame was applied connecting the patella with the tibial shaft. The construct allowed for gradual distal advancement of the patella based on the Ilizarov principles. After achieving the desired patella height, the frame was removed, and the patellar tendon was reconstructed with hamstrings. All four patients experienced a significant improvement in extensor lag by a mean of 38.0°, while Knee society scores increased by a mean of 38.5 units. No substantial loss in active knee flexion was observed. Our findings suggest that our technique yields favorable outcomes in patients with patellar tendon disruption in the setting of a total knee arthroplasty.


A simple nutrition screening tool to identify nutritional deterioration in long stay paediatric inpatients: The paediatric nutrition rescreening tool (PNRT).
Children with extended hospital stays are at risk of nutritional deterioration making regular nutrition screening throughout their admission an integral part of the nutrition care pathway. The purpose of this study was to design and validate a simple, quick and universal weekly rescreening tool to identify hospital acquired nutritional deterioration during a child's hospital stay. A prospective, longitudinal sample of children aged 0-16 years admitted to a paediatric tertiary hospital with a length of stay ≥7 days were included in the study. Agreement between nutritional deterioration markers of reduction in weight (kg), body mass index (kg/m2), energy intake (kcal/day) and protein intake (g/day) over a 7-day period and two proposed rescreening questions was determined using sensitivity, specificity, area under the curve and positive and negative predictive values. Sixty-one children were included in the study with 224 full 7-day datasets. The sensitivity and specificity of the rescreening question 'Has the child had reduced nutritional intake in the last 7 days' for identifying children with a ≥25% reduction in energy intake over the previous 7-day period were 61.9% (95% CI 41.1-82.7) and 82.2% (95% CI 76.9-87.5) respectively. The sensitivity of 'Has the child lost weight or had poor weight gain' at detecting weight loss was 71.4% (95% CI 54.7-88.2) and specificity 87.8% (95% CI 83.1-92.5). The paediatric nutrition rescreening questions provide a valid and simple tool to detect nutritional deterioration in long stay paediatric patients and should be an integral part of the nutrition care process.


Dietary Intake in Association with All-Cause Mortality and Colorectal Cancer Mortality among Colorectal Cancer Survivors: A Systematic Review and Meta-Analysis of Prospective Studies.
We carried out a systematic review and meta-analysis to determine the effects of both prediagnostic and postdiagnostic dietary intake on all-cause mortality and CRC-specific mortality among CRC survivors. An extensive search of PubMed and Embase was conducted to identify eligible studies. We applied a random-effects model to estimate the pooled relative risks (RRs)/hazard ratios (HRs) and their 95% confidence intervals (CIs). As a result, a total of 45 studies were included in the final analysis. Pooled effect sizes from at least three study populations showed that whole grains and calcium were inversely associated with all-cause mortality, with RRs/HRs (95% CIs) of 0.83 (0.69-0.99) and 0.84 (0.73-0.97), respectively. In contrast, a positive association between an unhealthy dietary pattern and both all-cause mortality (RR/HR = 1.47, 95% CI = 1.05-2.05) and CRC-specific mortality (RR/HR = 1.52, 95% CI = 1.13-2.06) was observed among CRC survivors. In the subgroup analysis by CRC diagnosis, prediagnostic and postdiagnostic dietary intake such as carbohydrates, proteins, lipids, and fiber were observed to have different effects on all-cause mortality. Overall, an unhealthy dietary pattern increased the risks of both all-cause mortality and CRC-specific mortality. The role of prediagnostic and postdiagnostic intake of dietary elements such as macronutrients and fatty acids could be different in the risk of all-cause mortality.


[Malama project in the Region of Murcia (Spain): environment and breastfeeding].
To identify protective factors and risk factors for the initiation and length of breastfeeding and full breastfeeding, in the Region of Murcia (Spain). The Malama study (Medio Ambiente y Lactancia Materna) is a follow up study from birth up to years of 1,000 mother-child pairs. A description of breastfeeding practices are presented here, the survival curve of breastfeeding and a Cox regression model of the pilot study that includes 101 mother-child pairs and 6 months of follow-up. After six months the prevalence of breastfeeding was 35 %. The mean duration of full breastfeeding was 63 days (median 45 days) with six months prevalence of 8 %. Hazard ratios (HR) for full breastfeeding were, to be a smoker (1.89; 95 % CI: 1.18-3.02), older than 35 years of age (2.04; 95 % CI: 1.22-3.42), caesarean birth (1.63; 95 % CI: 1.00-2.66). As well as those previously mentioned risks for breastfeeding, there were also hazard ratios for primary school education or less (1.63; 95 % CI: 0.98-2.82); to have breastfed an earlier child for at least 16 weeks (0.33; 95 % CI: 0.13-0.79), and to be the first birth (0.50; 95 % CI: 0.27-0.95). The length of both breastfeeding and full breastfeeding increased with the length of the maternal leave (0.96; 95 % CI: 0.94-0.99). Pregestational occupational exposure to endocrine disruptors did not seem to interfere with the duration of breastfeeding. In order to improve quality and duration of breastfeeding programmes, paediatric research and training on breastfeeding practice should be encouraged, to reduce unnecessary caesarean sections, promote tobacco cessation, focus human and economic resources to women with less education, and include legal mechanisms to ensure longer maternal leave.


Low expression of Aldo-keto reductase 1B10 is a novel independent prognostic indicator for nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is one of the most common human head and neck cancers with high incidence in Southern China, Southeast Asia and North Africa. Because of its nonspecific symptoms, the early diagnosis of NPC is very difficult. The 5-year survival rate is not ideal in spite of great innovations in radiation and chemotherapy treatments. Highly sensitive and specific prognostic biomarkers are eager for NPC clinical diagnosis. To find specific target molecules is very important for individualized treatment. Aldo-keto reductase B10 (AKR1B10) is closely related to tumorigenesis and tumor development, and however, its expression level in NPC tissues is not clear. AKR1B10 expression levels were validated in benign, para-cancerous nasopharyngeal and NPC tissues by immunohistochemical evaluation. AKR1B10 was positively expressed in 42 (82.4 %) of 51 benign specimens, and 235 (98.7 %) of 238 para-carcinoma specimens. This percentage was significantly higher than 44.5 % (133/299) in nasopharyngeal carcinoma tissue (p < 0.01). AKR1B10 mRNA quantitative levels detected by real-time quantitative RT-PCR in 90 NPC tissue samples (0.10 ± 0.21) were significantly lower than that in 15 benign tissue samples (1.03 ± 1.12) (p < 0.01). AKR1B10 expression levels in NPC were correlated negatively with T-classification, lymph node metastasis (p < 0.05). We established nasopharyngeal cancer monoclonal cells CNE-2/AKR1B10 with AKR1B10 stable expression and CNE-2/vector cells without AKR1B10 expression by using a modified lentivirus-mediated method, and found that AKR1B10 inhibited the proliferation of CNE-2/AKR1B10 cells by using MTT assay and flow cytometry, and cell migration by in vitro scratch test. Taken together, our data suggest that low expression of AKR1B10 is an independent prognostic indicator in nasopharyngeal carcinoma, and that AKR1B10 may be involved in regulating the proliferation and migration of nasopharyngeal cancer cells.


Multiple urethral anomalies: anterior urethral diverticulum, posterior urethral valves, and distal hypospadias.
We report an infant with antenatally detected bilateral hydroureteronephrosis and a penile cyst who was eventually diagnosed with an anterior urethral diverticulum (AUD), subcoronal hypospadias, and posterior urethral valves (PUV) after birth. To our knowledge, there are no reports where all three anomalies have been found to coexist. As per urethral catheterisation was difficult, cystoscopy-guided catheterisation was performed. On retracting the complete foreskin, a subcoronal hypospadias was identified. The AUD was resected partially, and during a cystoscopy for completion of AUD resection, a dilated anterior urethra was found collapsed, and thin PUV were identified and divided. He remains well at nine months with an improving renal cortical thickness. The vesicoureteric reflux had resolved.


A second Candida albicans resistance gene (Carg2) regulates tissue damage, but not fungal clearance, in sub-lethal murine systemic infection.
The severity of systemic infection with the yeast Candida albicans has been shown to be under complex genetic control. C57/L mice carry an allele that is associated with an increase in tissue destruction when compared with C57Bl/6 mice; however, the gene affects only the severity of tissue lesions, and does not influence the magnitude of the fungal burden in either kidney or brain. Studies in [C57/LxC57Bl/6]F1 hybrid mice, and [C57/LxC57Bl/6]F1xC57/L backcross mice, demonstrated that the gene behaves as a simple Mendelian co-dominant.


Particulate matter concentrations and characterization in urban subway system-case study Tehran, Iran.
The present work aims to evaluate the indoor and outdoor air quality in the stations of the Tehran subway system. In this study, the particulate sampling of the four Tehran subway stations was conducted in March-July 2018 during different seasons to determine indoor and outdoor PM10 and PM2.5 concentrations and elemental composition. The samples were analyzed to determine 11 elements such as Pb(Lead), Cd(Cadmium), Ni(Nickel), Co(Cobalt), Mn(Manganese), Zn(Zink), Fe(Iron), Cu(Copper), As(Arsenic), Al(Aluminum) and Cr(Chromium) qualitatively. The experimental results indicated that the average concentrations of both PM10 and PM2.5 in indoor stations (platforms) were approximately 2-5 times higher than those in the outdoors (ambient air). In addition, PM10 and PM2.5 concentrations exceeded the daily-standard values (US-EPA; PM10 = 50 µg.m-3, PM2.5 = 25 µg.m-3) in 100% indoor measurements and 84% outdoor measurements. Moreover, the average indoor PM10 and PM2.5 concentrations in weekday values were 1.4 and 1.5 times higher than those measured on weekends, which may be related to the lower frequency of trains. Further, indoor and outdoor correlation of PM10 concentrations (Pearson r = 0.6) was more than that of PM2.5 concentrations (Pearson r = 0.2), indicating the additional sources for PM2.5 in indoor stations. Additionally, the average PM2.5 / PM10 ratio was 0.52 for indoor measurements and 0.34 for outdoors, indicating that PM10 particles were the dominant particle type in both sampling areas and passengers in indoor stations exposed to higher PM2.5 concentrations than those in outdoor stations. Finally, based on elemental analysis, Fe was the most enriched element in indoor and outdoor PM10 and PM2.5 samples. The concentration of Fe ranged from 16 to 81 µg.m-3 in indoor stations and 0.6 to 2.5 µg.m-3 in outdoors. Other enriched elements were Al, Cu, Zn, and Mn, respectively.


Editor's Choice - PRINciples of optimal antithrombotiC therapy and coagulation managEment during elective fenestrated and branched EndovaScular aortic repairS (PRINCE2SS): An International Expert Based Delphi Consensus Study.
Management of antithrombotic therapy in patients undergoing elective fenestrated branched endovascular aortic repair (F-BEVAR) is not standardised, nor are there any recommendations from current guidelines. By designing an international expert based Delphi consensus, the study aimed to create recommendations on the pre-, intra-, and post-operative management of antithrombotic therapy in patients scheduled for elective F-BEVAR in high volume centres. Eight facilitators created appropriate statements regarding the study topic that were voted on, using a four point Likert scale, by a selected panel of international experts using a three round modified Delphi consensus process. Based on the experts' responses, only those statements reaching Grade A (full agreement ≥ 75%) or B (overall agreement ≥ 80% and full disagreement < 5%) were included in the final document. The round answers' consistency was graded using Cohen's k, the intraclass correlation coefficient, and, in case of double re-submission, the Fleiss k. Sixty-seven experts were included in the final analysis and voted the initial 43 statements related to pre- (n = 15), intra- (n = 10), and post-operative (n = 18) management of antithrombotic drugs. At the end of the process, six statements (13%) were rejected, 20 statements (44%) received a Grade B consensus, and 18 statements (40%) reached a Grade A consensus. Most statements (27; 71%) exhibited very high or high consistency grades, and 11 (29%) a fair or poor grading. The intra-operative statements mostly concentrated on threshold for and monitoring of proper heparinisation. The pre- and post-operative statements mainly focused on indications for dual antiplatelet therapy and its management, considering the possible need for cerebrospinal fluid drainage. Based on the elevated strength and high consistency of this international expert based Delphi consensus, most of the statements might guide current clinical management of antithrombotic therapy for elective F-BEVAR. Future studies are needed to clarify the debated issues.


Comment on Xu et al. Isolation and Identification of a Novel Phlebovirus, Hedi Virus, from Sandflies Collected in China. Viruses 2021, 13, 772.
The article from Xu et al. [...].


A framework for the automatic generation of surface topologies for abdominal aortic aneurysm models.
Patient-specific abdominal aortic aneurysms (AAAs) are characterized by local curvature changes, which we assess using a feature-based approach on topologies representative of the AAA outer wall surface. The application of image segmentation methods yields 3D reconstructed surface polygons that contain low-quality elements, unrealistic sharp corners, and surface irregularities. To optimize the quality of the surface topology, an iterative algorithm was developed to perform interpolation of the AAA geometry, topology refinement, and smoothing. Triangular surface topologies are generated based on a Delaunay triangulation algorithm, which is adapted for AAA segmented masks. The boundary of the AAA wall is represented using a signed distance function prior to triangulation. The irregularities on the surface are minimized by an interpolation scheme and the initial coarse triangulation is refined by forcing nodes into equilibrium positions. A surface smoothing algorithm based on a low-pass filter is applied to remove sharp corners. The optimal number of iterations needed for polygon refinement and smoothing is determined by imposing a minimum average element quality index with no significant AAA sac volume change. This framework automatically generates high-quality triangular surface topologies that can be used to characterize local curvature changes of the AAA wall.


Human os penis.
We report a case of human penile ossification with roentgenologic and histologic confirmation. The English literature is reviewed, and the pathogenesis of such a rare lesion is presented. Penile ossification appears to be an acquired metaplastic process occurring in an area of fibrosis.


Good outcome after an 8-year radial head resection on a Monteggia fracture in a young patient: A case report and literature review.
Monteggia fractures are proximal ulna fractures that involve radial caput displacement. Radial caput excision or resection is only suggested in situations of Monteggia lesions with radial caput fractures. Radial head resection should be avoided because the radial head is the principal stabilizer of the elbow and forearm. In this case report, we present a case of radial head resection at a young age after Monteggia reconstruction. A 26-year-old female came to the orthopaedic clinic for removal implant control after eight years postoperatively, patient had motorcycle accident at 2015 and performed ORIF Monteggia fracture with radial head resection. The patient also showed good alignment of the antebrachi, and there were no limitations in performing supination, pronation, and flexion of elbow and wrist movements. There were also no complications related to the radial head resection from the x-ray examination. After eight years postoperatively of ORIF Monteggia reconstruction with radial head resection showed a good outcome and improved quality of life for this patient. There was improvement in DASH and MEPS scores. Patients with radial head resection at a young age after Monteggia reconstruction had good results and should be considered.


Modeling the Progression of Epithelial Leak Caused by Overdistension.
Mechanical ventilation is necessary for treatment of the acute respiratory distress syndrome but leads to overdistension of the open regions of the lung and produces further damage. Although we know that the excessive stresses and strains disrupt the alveolar epithelium, we know little about the relationship between epithelial strain and epithelial leak. We have developed a computational model of an epithelial monolayer to simulate leak progression due to overdistension and to explain previous experimental findings in mice with ventilator-induced lung injury. We found a nonlinear threshold-type relationship between leak area and increasing stretch force. After the force required to initiate the leak was reached, the leak area increased at a constant rate with further increases in force. Furthermore, this rate was slower than the rate of increase in force, especially at end-expiration. Parameter manipulation changed only the leak-initiating force; leak area growth followed the same trend once this force was surpassed. These results suggest that there is a particular force (analogous to ventilation tidal volume) that must not be exceeded to avoid damage and that changing cell physical properties adjusts this threshold. This is relevant for the development of new ventilator strategies that avoid inducing further injury to the lung.


A thousand pericardial valves in aortic position: risk factors for postoperative acute renal function impairment in elderly.
Postoperative renal dysfunction after aortic valve replacement is a serious complication. To minimize its occurrence, risk factors have to be identified, and if possible eliminated. Of 1000 consecutive patients, who underwent AVR, a file study was performed chi(2)nd logistic regression analysis were performed to study the effect of 24 preoperative, 7 peroperative and 7 postoperative factors on the occurrence of 30-day postoperative worsening of renal function. Fifty-three patients had a 30-day postoperative decrease of renal function. Nine of these patients died, which is significantly more than the mortality without this complication (P<0.0001). In those nine patients, another complication (postoperative heart failure, thromboembolism or respiratory failure) was present. Thirteen factors were significant in an univariate analysis: preoperative renal dysfunction (P<0.001), age>80 (P<0.001), atrial fibrillation (P<0.001) , preoperative pulmonary edema (P=0.001), conduction defect (P=0.002), diabetes (P=0.006), myocardial infarction (P=0.006), postoperative heart failure (P=0.007), cross clamp time >75 min (P=0.015), previous coronary artery bypass grafting (CABG) (P=0.018), concomitant CABG (P=0.031), ejection fraction <50% (P=0.033) and CVA (P=0.035). Four factors were identified as independent predictors in a multivariate analysis: renal dysfunction (P<0.001, Odds ratio [OR] 5.5; 95% confidence interval [CI] 2.9-10.4), preoperative atrial fibrillation (P=0.010, OR=2.3, 95% CI=1.2-4.2), age>80 (P=0.014, OR=2.2, 95% CI=1.2-4.1) and myocardial infarction (P=0.022, OR=2.2, 95% CI=1.1-4.4). Few factors are liable for therapeutic intervention, especially in elderly and patients with comorbidity. In patients with risk factors, shortening of cross clamping time or installation of minimal extracorporeal circulation might be beneficial.


Comparison of in vitro and in vivo systems for propagation of Rift Valley fever virus from clinical specimens.
Several cell cultures and animals were compared for their relative sensitivity as primary isolation systems for Rift Valley fever virus (RVFV) and to determine if virulence characteristics of the isolates were altered in these systems. Eleven human sera from known cases of Rift Valley fever (RVF) were obtained from the 1987 epidemic in Mauritania and served as the source of virus for these studies. Sera were inoculated directly into cell cultures (Vero, C6/36 and DBS-FRhL-2) and animals (ICR suckling mice, Lak:LVG(SYR) hamsters and WF rats) concurrently. The cell lines provided a quick method to propagate, quantitate and identify these specimens without prior adaption. The isolates were highly virulent for suckling mice and hamsters, but not for WF rats, even after cell culture passage, which indicated that the Mauritanian isolates more closely resembled those strains from sub-Saharan Africa than those from the 1977-78 Egyptian epidemic.


Genome-informed contributions to malaria therapies: feeding somewhere down the (pipe)line.
Whole-genome sequences of Plasmodium spp. have helped redefine malaria research, including initiatives that seek to develop drugs, vaccines, and other antimalarial therapies. The problems caused by malaria were brought to the public's attention once more on World Malaria Day (April 25). Unfortunately, the current impact of genome-informed research is not as great as might have been hoped, and the reasons for this and continuing challenges are discussed.


Relationship of hemolysis buffer structure, pH and ionic strength to spontaneous contour smoothing of isolated erythrocyte membranes.
Isolated human erythrocyte membranes crenate when suspended in isotonic medium, but can use MgATP to reduce their net positive curvature, yielding smooth discs and cup forms that eventually undergo endocytosis. An earlier report from this laboratory (Patel, V.P. and Fairbanks, G. (1981) J. Cell Biol. 88, 430-440), has described a phenomenon of ATP-independent shape change in which ghosts prepared by hemolysis and washing in synthetic zwitterionic buffers crenated at 0 degree C, but underwent conversion to smooth discs and cups when warmed in the absence of MgATP. We have further explored the effect of the hemolysis condition on the requirement for ATP in ghost shape change. 25 hemolysis buffers were applied at 10 mM (pH 7.4, 0 degree C). Eight anionic buffers with relatively high ionic strength (e.g., phosphate and diethylmalonic acid (DMA] yielded ghosts requiring ATP for shape change, while two cationic buffers (Bistris and imidazole) and ten synthetic zwitterionic buffers (e.g., Tricine and Hepes) with lower ionic strength produced ghosts that smoothed spontaneously at 30 degrees C. Hemolysis at intermediate ionic strength yielded mixed populations in which spontaneous smoothing was expressed in all-or-none fashion. Maximal ATP-independent shape change was induced by hemolysis at pH 7.3-7.7, while ATP was required after hemolysis at pH less than or equal to 7.1 even when the ionic strength at hemolysis was low. Ghosts requiring ATP could be converted to ATP independence by washing at low ionic strength, but ATP independence could not be reversed readily by washing at high ionic strength. Exposure to low ionic strength at pH greater than 7.1 presumably changes membrane organization in a way that alters the temperature dependence of tensions within the bilayer or skeleton of the composite membrane.


Are There Any Differences in the Clinical and Economic Outcomes Between US Cancer Patients Receiving Appropriate or Inappropriate Venous Thromboembolism Prophylaxis?
Prophylaxis is often underused and inappropriately prescribed. This study compares the efficacy and cost of appropriate and partial prophylaxis in cancer patients at risk for VTE.


Prolonged Cardiogenic Shock Due to Hydrogen Sulfide Intoxication Requiring Long-Term Venoarterial Extracorporeal Membrane Support.
We describe a case of severe biventricular failure and cardiovascular collapse following exposure to the manure gas hydrogen sulfide. Initial tests indicated uncoupling of cellular bioenergetics in addition to myocardial damage. Cardiopulmonary support with venoarterial extracorporeal membrane oxygenation was initiated, and the patient could be successfully weaned from support after 28 days. (Level of Difficulty: Advanced.).


Population dynamics and growth patterns for a cohort of northern red oak (Quercus rubra) seedlings.
I studied the survival and development of a 1986 cohort of northern red oak (Quercus rubra L.) seedlings growing under a variety of overstory and microsite conditions in a northern hardwood forest dominated by northern red oak, red maple (Acer rubrum L.) paper birch (Betula papyrifera Marsh.), and scattered white pine (Pinus strobus L.). Fifty naturally regenerating seedlings of oak were randomly selected in each of three canopy classes: no overstory, partial overstory, and complete overstory. Growth and mortality were measured for six years. Seedling height growth decreased with overstory density, with less growth evident with even a partial overstory. Seedling survival also declined with overstory density and depended on microtopography to a lesser extent. After six years, 92% of the seedlings survived in the open, compared to 54% under the partial overstory, and 36% under the complete overstory. The open environment, in which woody and herbaceous regrowth formed a low canopy reducing light intensities to about 50% of full sunlight, provided a favorable site for the growth and survival of northern red oak.


Transmitter receptors reveal segregation of cortical areas in the human superior parietal cortex: relations to visual and somatosensory regions.
Regional distributions of ligand binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABA(A), GABA(B); cholinergic: muscarinic M2, nicotinic; adrenergic: alpha1, alpha2; serotonergic: 5-HT1A, 5-HT2; dopaminergic: D1) were studied in human postmortem brains by means of quantitative receptor autoradiography. Binding site densities were measured in the superior parietal lobule (SPL) (areas 5L, 5M, 5Ci, and different locations within Brodmann's area (BA) 7), somatosensory (BA 2), and visual cortical areas (BA 17, and different locations within BAs 18 and 19). Similarities of receptor distribution between cortical areas were analyzed by cluster analysis, uni- and multivariate statistics of mean receptor densities (averaged over all cortical layers), and profiles representing the laminar distribution patterns of receptors. A considerable heterogeneity of regional receptor densities and laminar patterns between the sites was found in the SPL and the visual cortex. The most prominent regional differences were found for M2 receptors. In the SPL, rostrocaudally oriented changes of receptor densities were more pronounced than those in mediolateral direction. The receptor distribution in the rostral SPL was more similar to that of the somatosensory cortex, whereas caudal SPL resembled the receptor patterns of the dorsolateral extrastriate visual areas. These results suggest a segregation of the different SPL areas based on receptor distribution features typical for somatosensory or visual areas, which fits to the dual functional role of this cortical region, i.e., the involvement of the human SPL in visuomotor and somatosensory motor transformations.


Rapid and selective removal of preservative from ophthalmic formulations during eyedrops instillation.
About 70% of eyedrops contain benzalkonium chloride (BAK) as a preservative to prevent the growth of microorganisms. While preservatives are mandated to maintain sterility, many patients exhibit irritation and toxicity to such compounds. We propose to mitigate the ocular toxicity in the ocular formulations without compromising sterility by designing a device that can be incorporated into an eyedrops bottle to selectively remove the preservatives during the process of drop instillation. Here, we specifically focus on macroporous poly(2-hydroxyethyl methacrylate) (pHEMA) gel due to its excellent biocompatibility and high partition coefficient for BAK. In addition to specific selectivity for BAK, the device also requires high hydraulic permeability to allow drop dispensing without excessive pressure drop. The pHEMA monolith can remove nearly 100% of contained BAK from a 25 ml, 0.012% BAK solution with negligible uptake of the hydrophilic drugs such as timolol and dorzolamide. The filter, however, had to be pre-equilibrated with hydrophobic drugs to reach a high separation of BAK without reducing the concentration of the active drug. The average hydraulic permeability of the filter was 0.025 Darcy, which is about 5-fold lower than the ideal value. Incorporation of a pHEMA macroporous gel into an eyedrops bottle can virtually eliminate the exposure of the eyes to the preservatives without compromising the sterility. Our novel design can eliminate the preservative induced toxicity from eyedrops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases such as glaucoma and dry eyes.


Personalized multimodal prehabilitation reduces cardiopulmonary complications after pancreatoduodenectomy: results of a propensity score matching analysis.
The purpose of prehabilitation is to improve postoperative outcomes by increasing patients' resilience against the stress of surgery. This study investigates the effect of personalized multimodal prehabilitation on patients undergoing pancreatoduodenectomy. Included patients were screened for six modifiable risk factors: (1) low physical fitness, (2) malnutrition, (3) low mental resilience, (4) anemia and hyperglycemia, (5) frailty, and (6) substance abuse. Interventions were performed as needed. Using 1:1 propensity score matching (PSM), patients were compared to a historical cohort. From 120 patients, 77 (64.2%) performed a cardiopulmonary exercise test to assess their physical fitness and provide them with a preoperative training advice. Furthermore, 88 (73.3%) patients received nutritional support, 15 (12.5%) mental support, 17 (14.2%) iron supplementation to correct for iron deficiency, 18 (15%) regulation support for hyperglycemia, 14 (11.7%) a comprehensive geriatric assessment, and 19 (15.8%) substance abuse support. Of all patients, 63% required ≥2 prehabilitation interventions. Fewer cardiopulmonary complications were observed in the prehabilitation cohort (9.2% versus 23.3%; p = 0.002). In surgical outcomes and length of stay no differences were observed. Our prehabilitation program is effective in detecting risk factors in patients; most patients required multiple interventions. Consequently, a reduction in cardiopulmonary complications was observed.


Reducing stigma and discrimination against older people with mental disorders: a technical consensus statement.
This technical consensus statement is jointly produced by the Old Age Psychiatry section of the World Psychiatric Association and the World Health Organization, with the collaboration of several NGOs and the participation of experts from different Regions. It is intended to be a tool for (i) promoting debate at all levels on the stigmatisation of older people with mental disorders; (ii) outlining the nature, causes and consequences of this stigmatisation; and (iii) promoting and suggesting policies, programmes and actions to combat this stigmatisation.


Congenital ichthyosis and endodermal sinus tumor of the ovary in a ten-year-old child.
Acquired ichthyosis is very likely to be associated with a malignancy, especially with Hodgkins disease. The association of congenital ichthyosis with malignant tumors has been so far reported only in two instances. Herein we report on a third case. Due to the small number of cases, no conclusion can be drawn about the correlations between the two diseases.


Mental Health in Mothers of Autistic Children with a Medical Home: The Potentially Mechanistic Roles of Coping and Social Support.
Mothers of autistic children often report poor mental health outcomes. One established risk factor for these outcomes is the child having a medical home. This study examined possible mediating variables (coping, social support) in this relationship in 988 mothers of autistic children from the 2017/2018 National Survey of Children's Health (NSCH). The results of the multiple mediation model suggest the relationship between having a medical home and maternal mental health is largely explained by indirect associations with coping and social support. These findings suggest that clinical interventions for coping and social support provided by the medical home for mothers of autistic children may improve maternal mental health outcomes over and above implementation of a medical home.


The two homologous domains of human angiotensin I-converting enzyme interact differently with competitive inhibitors.
The endothelial angiotensin I-converting enzyme (ACE; EC 220.127.116.11) has recently been shown to contain two large homologous domains (called here the N and C domains), each being a zinc-dependent dipeptidyl carboxypeptidase. To further characterize the two active sites of ACE, we have investigated their interaction with four competitive ACE inhibitors, which are all potent antihypertensive drugs. The binding of [3H] trandolaprilat to the two active sites was examined using the wild-type ACE and four ACE mutants each containing only one intact domain, the other domain being either deleted or inactivated by point mutation of the zinc-coordinating histidines. In contrast with all the previous studies, which suggested the presence of a single high affinity inhibitor binding site in ACE, the present study shows that both the N and C domains of ACE contain a high affinity inhibitor binding site (KD = 3 and 1 X 10(-10) M, respectively, at pH 7.5, 4 degrees C, and 100 mM NaCl). Chloride stabilizes the enzyme-inhibitor complex for each domain primarily by slowing its dissociation rate, as the k-1 values of the N and C domains are markedly decreased (about 30- and 1100-fold, respectively) by 300 mM NaCl. At high chloride concentrations, the chloride effect is much greater for the C domain than for the N domain resulting in a higher affinity of this inhibitor for the C domain. In addition, the inhibitory potency of captopril (C), enalaprilat (E), and lisinopril (L) for each domain was assayed by hydrolysis of Hip-His-Leu. Their Ki values for the two domains are all within the nanomolar range, indicating that they are all highly potent inhibitors for both domains. However, their relative potencies are different for the C domain (L greater than E greater than C) and the N domain (C greater than E greater than L). The different inhibitor binding properties of the two domains observed in the present study provide strong evidence for the presence of structural differences between the two active sites of ACE.


A virtual training program for improving cultural competence among academic nurse educators.
Everyday, nursing students interact with culturally diverse clients. Nursing education recognizes that cultural competence is a necessary outcome of nursing programs. Nurse educators expect all nursing students to provide culturally congruent care to multicultural clients. Therefore, nurse educators must be culturally competent in order to prepare culturally competent nursing students for clinical practice. This study aimed to evaluate the effect of virtual training program on the cultural competence of academic nurse educators. This randomized controlled study included nurse educators working in six nursing schools affiliated with medical universities of Kerman province in southeastern Iran. Sixty-nine nurse educators were randomly assigned to the intervention (n = 35) and control (n = 34) groups. The training program consisted of three 2-hour sessions for a month. Cultural Diversity Questionnaire for Nurse Educators Revised (CDQNE-R) was used to evaluate the cultural competence of educators before and one month after the virtual training program. Both the intervention (3.29 ± 0.58) and control (3.24 ± 0.58) groups demonstrated a similar level of cultural competence before the training program (t = 0.05, p = 0.95). After the training, the intervention group showed a significant increase in cultural competence (3.80 ± 0.7) compared to the control group (3.23 ± 0.67). This improvement resulted in culturally competent participants becoming culturally proficient, as evidenced by a large effect size (t = -4.76, p = 0.001). The virtual training program had a positive impact on the cultural competence of nurse educators. Given the importance of cultural competence in nursing education, continuing education programs that focus on strengthening the cultural competence of nurse educators should be prioritized. The experiences gained from implementing virtual training programs can serve as a valuable resource for nurse educators seeking to enhance their cultural competence.


Five-year changes of social activity and incident long-term care needs among depressed older adults: A 15-year follow up.
To examine the effects of changes in individual/multiple social activities between 65 and 70 years of age on incident long-term care (LTC) needs between 70 and 80 in older adults with depressive symptoms. Participants were recruited from the New Integrated Suburban Seniority Investigation Project, an ongoing prospective cohort study. A total of 525 older adults with depressive symptoms were included. The validated 15-item Geriatric Depression Scale was used to assess depressive symptoms. A self-report questionnaire was used to measure social activities (social-related, learning, and personal). LTC needs was defined according to Japan's Long-term Care Insurance System. A competing risk model and a Laplace regression model were used to estimate the hazard ratios of LTC needs incidence and the 25th percentile difference in LTC-needs-free survival time and their 95% confidence intervals. Out of 4314 person-years of mild LTC needs, 108 individuals developed it. Participants who increased their frequency of learning activities have a lower risk of developing mild LTC needs. Increasing the frequency could also prolong LTC-needs-free survival time by approximately 2.61 years. Out of 4535 person-years for severe LTC needs, 54 individuals developed it. Participants with a continuous regular frequency of learning activities had a lower risk of developing severe LTC needs. However, the association between this frequency and LTC-needs-free survival time for severe LTC needs was insignificant in the multivariable models. Increased frequency of learning activities reduced the risk of LTC needs among older adults with depressive symptoms and prolonged their LTC-needs-free survival time.


An integrative atlas of chicken long non-coding genes and their annotations across 25 tissues.
Long non-coding RNAs (LNC) regulate numerous biological processes. In contrast to human, the identification of LNC in farm species, like chicken, is still lacunar. We propose a catalogue of 52,075 chicken genes enriched in LNC ( http://www.fragencode.org/ ), built from the Ensembl reference extended using novel LNC modelled here from 364 RNA-seq and LNC from four public databases. The Ensembl reference grew from 4,643 to 30,084 LNC, of which 59% and 41% with expression ≥ 0.5 and ≥ 1 TPM respectively. Characterization of these LNC relatively to the closest protein coding genes (PCG) revealed that 79% of LNC are in intergenic regions, as in other species. Expression analysis across 25 tissues revealed an enrichment of co-expressed LNC:PCG pairs, suggesting co-regulation and/or co-function. As expected LNC were more tissue-specific than PCG (25% vs. 10%). Similarly to human, 16% of chicken LNC hosted one or more miRNA. We highlighted a new chicken LNC, hosting miR155, conserved in human, highly expressed in immune tissues like miR155, and correlated with immunity-related PCG in both species. Among LNC:PCG pairs tissue-specific in the same tissue, we revealed an enrichment of divergent pairs with the PCG coding transcription factors, as for example LHX5, HXD3 and TBX4, in both human and chicken.


Intraoperative lactic acid concentration during liver transplantation and cutoff values to predict early mortality: a retrospective analysis of 3,338 cases.
We aimed to explore the distribution of intraoperative lactic acid (LA) level during liver transplantation (LT) and determine the optimal cutoff values to predict post-LT 30-day and 90-day mortality. Intraoperative LA data from 3,338 patients were collected between 2008 to 2019 and all-cause mortalities within 30 and 90 days were retrospectively reviewed. Of the three LA levels measured during preanhepatic, anhepatic, and neohepatic phase of LT, the peak LA level was selected to explore the distribution and predict early post-LT mortality. To determine the best cutoff values of LA, we used a classification and regression tree algorithm and maximally selected rank statistics with the smallest P value. The median intraoperative LA level was 4.4 mmol/L (range: 0.5-34.7, interquartile range: 3.0-6.2 mmol/L). Of the 3,338 patients, 1,884 (56.4%) had LA levels > 4.0 mmol/L and 188 (5.6%) had LA levels > 10 mmol/L. Patients with LA levels > 16.7 mmol/L and 13.5-16.7 mmol/L showed significantly higher 30-day mortality rates of 58.3% and 21.2%, respectively. For the prediction of the 90-day mortality, 8.4 mmol/L of intraoperative LA was the best cutoff value. Approximately 6% of the LT recipients showed intraoperative hyperlactatemia of > 10 mmol/L during LT, and those with LA > 8.4 mmol/L were associated with significantly higher early post-LT mortality.


[Physical occupational activity and colonic carcinoma mortality in Swiss men 1979-1982].
Colorectal cancers are the second most frequent cause of cancer death among men. To our knowledge, approximately six studies have been able to show an inverse relationship between occupational physical activity and colon cancer mortality. Information drawn from the mortality statistics for the years 1979-1982 was used to study this hypothetical association among Swiss men aged 15-79. At-risk-populations were calculated based on 1980 national census data on occupation of all Swiss men. Estimates of occupational physical activity (OPA) were based on job titles of death certificates and were "blindly" classified into three groups of low, moderate and high OPA by three independent experts. Among the cohort of 1.86 million men, 1995 deaths of colon cancer and 1066 deaths of rectal cancer occurred during the four study years. The standardized mortality ratio showed a significant, graded and inverse relationship between OPA and mortality from colon cancer but not from rectal cancer. The estimated relative risk for colon cancer of the physically inactive, as compared to those active, was 1.3 to 1.4, slightly influenced by minor differences in the way of classification of OPA. For several reasons this estimate of excess risk is probably on the low side. The subgroup of men with jobs with very high OPA showed no further reduction in risk of colon cancer, which suggests that other etiologic factors, such as diet, may play an important role. As sedentary lifestyle and colon cancer are both frequent in central Europe the hypothesized protective effect of habitual physical activity against colon cancer would seem important, especially from the public health point of view.


CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.
Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations.


Improving otoscopy education and diagnostic accuracy: A prospective interventional study.
To assess and improve otoscopy examination skills across various medical specialities who perform otoscopy during their professional practice. A pre-intervention survey was created using www.surveymonkey.com, which included several preliminary questions to clarify the participant's speciality and training level, followed by 25 individual otoscopy images. The participants were given 12 possible diagnoses for each otoscopy image and asked to choose the single best answer. After completing the survey, participants were asked to watch an otoscopy teaching session. This teaching session was created with multidisciplinary feedback, and the content included a demonstration video and a didactic lecture. Finally, a post-intervention survey was circulated four weeks later to the same cohort of doctors to assess improvement. A total of 79 pre-intervention surveys were collected with an average score of 53% (range 20-100%). The spectrum of medical specialities that completed the pre-intervention survey included paediatrics, ear, nose, and throat (ENT), emergency medicine, and general practice. The largest cohort of surveys came from senior house officers (SHO). In addition, 78.5% of responses were completed by doctors who had not worked in ENT before. After completing the otoscopy teaching session and at least four weeks after the initial survey, 23 post-intervention surveys were completed with an average score of 66% (range 32-100%), a 13% improvement. The results of the pre-intervention survey show that many doctors have difficulty diagnosing ear conditions. The implementation of a 25-min teaching session achieved a 13% improvement in the otoscopy knowledge of doctors across a variety of specialities.


Apoplectic intracerebral hemorrhage: an unusual complication of cerebral radiation necrosis.
A patient with apoplectic intracerebral hemorrhage from delayed cerebral radionecrosis is reported. The histological changes of abnormal telangiectatic vessels account for the unusual clinical presentation. The pathogenesis and treatment of radionecrosis are discussed, and massive hemorrhage as a complication is emphasized.


Pattern of follicular development during the estrous cycle of aged rats.
The pattern of follicular development during the estrous cycles of aged rats was examined and compared with that of mature rats. In both, preovulatory follicles are derived from a select group of small pre-Graafian follicles which begin to develop at estrus and reach the preovulatory size by the morning of proestrus, but the rate of growth, as judged by an increase in the percentage of granulosa cells incorporating 3H-thymidine, is accelerated in the follicles of aged rats. A second mechanism, which accounts for preovulatory follicles in aged rats, involves the rescue from atresia of pre-Graafian and preovulatory follicles. The existence of this mechanism is supported by the observation that at metestrus in aged rats virtually all follicles, regardless of their state of atresia, possess a high percentage of granulosa cells incorporating 3H-thymidine, indicating that the follicles are growing rapidly. However, some of these rapidly growing follicles show signs of atresia such as pyknotic nuclei within their granulosa cell layers. Since follicles in the initial stage of atresia contain defective oocytes (Peluso et al. 1979b), their rescue and development into preovulatory follicles would result in the ovulation of defective oocytes, a fact which accounts in part of the lower fertility in these older animals.


Sleep, Dietary, and Exercise Behavioral Clusters Among Truck Drivers With Obesity: Implications for Interventions.
The objectives of the study were to describe a sample of truck drivers, identify clusters of drivers with similar patterns in behaviors affecting energy balance (sleep, diet, and exercise), and test for cluster differences in health safety, and psychosocial factors. Participants' (n = 452, body mass index M = 37.2, 86.4% male) self-reported behaviors were dichotomized prior to hierarchical cluster analysis, which identified groups with similar behavior covariation. Cluster differences were tested with generalized estimating equations. Five behavioral clusters were identified that differed significantly in age, smoking status, diabetes prevalence, lost work days, stress, and social support, but not in body mass index. Cluster 2, characterized by the best sleep quality, had significantly lower lost workdays and stress than other clusters. Weight management interventions for drivers should explicitly address sleep, and may be maximally effective after establishing socially supportive work environments that reduce stress exposures.


Circumferential abdominoplasty.
In Italy, 34.2% of the population has a BMI higher than 25, and another 9.8% of the population has a BMI higher than 30. In Italy, there are 4 million and 700,000 obese people. Bariatric surgery has evolved as a very effective therapy for morbid obesity. After such dramatic weight loss, patients are usually left with redundant skin and unwieldy subcutaneous tissue. The circumferential truncal excess cannot be corrected by a regular abdominoplasty alone. In this group of patients, lateral excess can actually be over accentuated by a traditional abdominoplasty. In our institution, we are used performing abdominoplasty according to Pascal-Le Louarn's surgical technique. In our cases, the adoption of this technique has been successful with a high rate of very satisfied patients, no major complications and few minor complications primarily in the smoker patients. The charts of 41 consecutive circumferential abdominoplasty were reviewed. The preoperative markings, the surgical technique, the post-operative course, and the complications are described. The average operative time was 220 min. The average lipoaspirate was 1,600 cc. The mean weight loss during the surgery was 3.4 kg. There were 18 immediate complications, including 11 seromas, and 7 partial wound dehiscences. There were 26 late complications, including 8 hypertrophic scars and 18 local hypoestesia. All seromas were resolved within 3 weeks. All patients were satisfied. Circumferential abdominoplasty performed with Pascal-Le Louarn's surgical technique is an effective, appropriate, and safe method to treat patients with lipodistrophy of the trunk following massive weight loss.


Right ectopic paraesophageal parathyroid adenoma with refractory hypercalcemia in pregnancy: A case report and review of the literature.
Ectopic parathyroid adenoma is rare during pregnancy but poses multiple challenges in treatment. It presents as primary hyperparathyroidism which leads to symptoms and complications of hypercalcemia in both the mother and fetus. A 38-year-old Sudanese female presented with diffuse bone pain and polyuria. Laboratory investigations revealed elevated serum calcium and parathyroid hormone. Ultrasound of the neck did not show any abnormal lesion, however 99mTc-sestamibi scan showed a right sided parathyroid adenoma, and an earlier CT scan showed the adenoma to be in an ectopic paraesophageal position. Focused surgical neck exploration was done, and the ectopic parathyroid adenoma was excised. Preoperative localization of the ectopic parathyroid adenoma allows for a focused surgical procedure. Ultrasound is the safest during pregnancy, but 99mTc-sestamibi and CT scan may be necessary if ultrasound or initial bilateral neck exploration do not detect any adenoma. Mild elevations in maternal serum calcium can have detrimental effects on the fetus which suggests that a surgical approach may be necessary in the majority of cases. Ectopic parathyroid adenoma is rare during pregnancy and is detrimental to both the mother and fetus. Preoperative localization allows for a focused surgery which is a definitive treatment and can safely be performed during the 2nd trimester of pregnancy.


Factors Associated with Japanese Nurses' Support on End-of-life Decision-making: A Cross-sectional Study.
This study aimed to clarify the factors associated with Japanese nurses' end-of-life decision-making support. Cross-sectional study. An online survey was conducted among 278 nurses. Significantly associated factors included visiting nursing, nursing experience duration, female sex, workshop participation, and time spent on end-of-life care. Visiting nursing was the most significant factor associated with nurses' end-of-lifedecision-making support. Consideration should be given to the curriculum in basic nursing education related to visiting nursing. It shouldinclude end-of-life care as well as resources for end-of-life decision-making to increase the number of patients who die in their preferred setting.


Increased frequency of coxsackie B virus IgM in women with spontaneous abortion.
IgM antibodies to Coxsackie B virus serotypes 1-5 (CBV 1-5) were studied by radioimmunoassay (RIA) of blood samples from women who had undergone a spontaneous abortion or given birth to a stillborn child. Results were compared with those of controls comprising healthy pregnant women who had not suffered such experiences. Among 48 women with abortions, 16 (33%) had CBV-IgM, while among the controls only three of 37 (8%) had these antibodies, a statistically significant difference (P less than 0.025). Among 21 women with a stillborn child, 11 (52%) were CBV-IgM positive, while the corresponding proportion in their controls was four of 18 (22%), a difference which is not statistically significant. It is concluded that CBV may be an important causative agent in spontaneous abortions and possibly also in stillbirths.


Perfusion method for harvesting bone marrow cells from dogs.
To compare composition and colony formation of bone marrow mononuclear cells (BMMCs) harvested from dogs by means of a new perfusion method and the conventional aspiration method. 7 healthy adult Beagles. BMMCs were collected from the humeri and femurs of Beagles via perfusion and aspiration methods. Flow cytometric analysis was performed to quantify the presence of contaminant cells from the peripheral blood and the percentage of CD34+ progenitor cells in the BMMCs. A CFU assay was conducted to determine the number of progenitor cells in the BMMCs. The perfusion method was safely performed in all 7 dogs. Flow cytometric analysis revealed that the percentages of contaminant CD3+CD4+, CD3+CD8+, and CD21 + lymphocytes in BMMCs obtained via perfusion were significantly lower than percentages obtained via aspiration. The percentage of CD34+ cells obtained via perfusion was significantly higher than that obtained via aspiration. In addition, perfusion yielded a significantly higher CFU count than did aspiration. The perfusion method used in this study can minimize the contamination of bone marrow samples with peripheral blood and was a more efficient means for collecting canine bone marrow progenitor cells than the conventional aspiration method. Therefore, the perfusion method can be more suitable than aspiration for harvesting bone marrow cells for transplantation in dogs.


Myocardial protection properties of parishins from the roots of Gastrodia elata Bl.
Parishins, important constituents of Gastrodia elata (G. elata), are known to exhibit a number of biological and pharmacological properties. However, their role and mechanisms of action in myocardial ischemia are unknown. The present study investigated the potential protective effects and mechanisms of parishins extracted from G. elata on hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes. The results demonstrated that parishins had significant protective effects on myocardial cells with parishins J and B providing greater cardioprotection through down-regulation of the level of cleaved-caspase-3 and cytochrome c in the cytoplasm and Bax, and up-regulation of cytochrome c in the mitochondria and Bcl-2 than induced by the positive control gastrodin. Additional study of the mechanisms of action indicated that the myocardial protection provided by parishin J was due to inhibition of JNK1 phosphorylation levels, down-regulation of c-jun and ATF-2 phosphorylation levels, a decrease in the phosphorylation of 14-3-3 and an increase in its binding to Bax. Therefore, parishin J was revealed to be a promising candidate as a novel treatment for myocardial protection.


The influence of compression on the healing of experimental tibial fractures.
Experimental studies of the effects of various mechanical conditions and stimuli on bone healing have disclosed an improvement potential in bone fracture mineralization and biomechanical properties. We therefore evaluated the effect of a clinically practicable application of a mechanical compressive interfragmentary stimulus on the healing of experimental tibial diaphyseal fractures. Sixty Male rats received a standardized tibial shaft osteotomy stabilized with a unilateral external fixator with a zero interfragmentary distance, and then randomly assigned to the compression (N=20), control (N=20) or distraction (N=20) group. From days 4 to day 14, the external fixator was either tightened (compression group) or loosened (distraction group) once daily to gradually induce a total axial displacement of the external fixator pin clamps of 1.25 mm. Evaluation at 30 and 60 days post-osteotomy included radiography, dual-energy X-ray absorptiometry (DXA), quantitative CT and mechanical testing. All fractures healed radiographically with sparse callus. At 60 days, the compression and control groups exhibited significantly less amount of mineralized callus in terms of DXA measured callus area and bone mineral content (BMC) compared to the distraction group. These groups also demonstrated a smaller volume of low-mineralized bone tissue (callus) and a larger volume of highly mineralized bone tissue (cortical bone) measured by QCT than in the distraction group. Both mechanical strength and stiffness was significantly higher in the compression and control groups than in the distraction group at 60 days. Compression did not enhance fracture healing in terms of mineralization, bending strength, or stiffness at the time of union, compared with the control condition. The compression and control groups exhibited improved healing in terms of mechanical strength and stiffness and a more mature callus mineralization compared with the distraction group.


Systematic differences in treatment effect estimates between propensity score methods and logistic regression.
In medical research both propensity score methods and logistic regression analysis are used to estimate treatment effects in observational studies. From literature reviews it has been concluded that treatment effect estimates from both methods are quite similar. With this study we will show that there are systematic differences which can be substantial. We used a simulated population with a known marginal treatment effect and applied a propensity score method and logistic regression analysis to adjust for confounding. The adjusted treatment effect in logistic regression is in general further away from the true marginal treatment effect than the adjusted effect in propensity score methods. The difference is systematic and dependent on the incidence proportion, the number of prognostic factors and the magnitude of the treatment effect. For instance, a substantial difference of 20% is found when the treatment effect is 2.0, the incidence proportion is 0.20 and there are more than 11 prognostic factors. Propensity score methods give in general treatment effect estimates that are closer to the true marginal treatment effect than a logistic regression model in which all confounders are modelled.


Dielectric behavior of Fe3N@C composites with green synthesis and their remarkable electromagnetic wave absorption performance.
Fe3N has been considered as a new generation of ideal ferromagnetic materials with the virtues of high saturated magnetization and high resistance to oxidation. However, a facile and eco-friendly fabrication of Fe3N still needs to be investigated. Herein, the gelatin derived from fish skin was chosen as the raw material of carbon and the amino acid inherent in fish skin can act as a nitrogen source for the generation of Fe3N. Besides, the influence of graphitization degree to dielectric behavior of composites was further investigated. In this work, the composites fabricated by 0.8 mmol Fe(NO3)3 exhibited optimal absorption performance with the minimum reflection loss of -77.6 dB at 2.2 mm. Besides, the absorption bandwidth was detected as 7.76 GHz (covering from 10.24 to 18 GHz) at the matching thickness of 2.7 mm. According to the analysis of dielectric constant, the degree of graphitization affects the dielectric behavior mainly in determining the orientation speed of the dipole and the conductive loss. This work provides a new thought for the investigation of the electromagnetic absorption mechanism of composite.


Expression of HLA-DR and urokinase-type plasminogen activator in stage IV gastric cancer.
BACKGROUND: Some patients with stage IV gastric cancer have a long survival. Host immune response and proteolytic activity in the primary tumor may be associated with outcome in these patients. The purpose of this study was to assess prognostic factors in patients with stage IV far advanced gastric cancer.METHODS: Findings in 26 patients who underwent resection of stage IV gastric cancer were retrospectively analyzed for clinicopathological variables, and for the immunohistochemical expression of human leukocyte antigen (HLA)-DR as an index of host immune response and for expression of urokinase type-plasminogen activator (u-PA) as an index of proteolytic activity in the tumor.RESULTS: Of the 13 clinicopathological and immunohistochemical variables tested by univariate analysis surgical curability, lymph node metastasis, HLA-DR expression, and u-PA expression had a significant influence on survival after surgery. Multivariate analysis showed that surgical curability, HLA-DR expression, and u-PA expression independently influenced survival. Patients positive for HLA-DR expression [HLA-DR (+)] and regative for u-PA expression [u-PA (-)] had the best survival: 25-month median survival and 25% 5-year survival rate. Patients who were HLA-DR (+) and u-PA (+), or HLA-DR (-) and u-PA (-) had a median survival of 10 months, a 1-year survival rate of 46.2%, and a 2-year survival rate of 7.7%. HLA-DR (-) and u-PA (+) patients had the worst survival: 4.5-month median survival and 0% 1-year survival.CONCLUSIONS: These findings suggest that host immune response and proteolytic activity in the primary tumor may determine malignant potential, and that the combination of positive-HLA-DR and negative-u-PA expression in cancer cells may be a predictor of prolonged survival in stage IV gastric cancer patients.


Preparing anti-SARS-CoV-2 agent EIDD-2801 by a practical and scalable approach, and quick evaluation via machine learning.
EIDD-2801 is an orally bioavailable prodrug, which will be applied for emergency use authorization from the U.S. Food and Drug Administration for the treatment of COVID-19. To investigate the optimal parameters, EIDD-2801 was optimized via a four-step synthesis with high purity of 99.9%. The hydroxylamination procedure was telescoped in a one-pot and the final step was precisely controlled on reagents, temperature and reaction time. Compared to the original route, the yield of the new route was enhanced from 17% to 58% without column chromatography. The optimized synthesis has been successfully determinated on a decagram scale: the first step at 200 g and the final step at 20 g. Besides, the relationship between yield and temperature, time, and reagents in the deprotection step was investigated via Shapley value explanation and machine learning approach-decision tree method. The results revealed that reagents have the greatest impact on yield estimation, followed by the temperature.


Intracranial hemorrhage in newly diagnosed non-promyelocytic acute myeloid leukemia patients admitted for intensive induction chemotherapy.
Intracranial hemorrhage (ICH) in acute myeloid leukemia (AML) patients is a major concern due to the increased risk of mortality. Few studies have examined ICH specifically in newly diagnosed AML patients receiving intensive induction chemotherapy (IC) and prophylactic platelet transfusions during thrombocytopenia <10/nL. This retrospective cohort study included 423 newly diagnosed AML patients without acute promyelocytic leukemia who underwent IC between 2007 and 2019. We assessed risk factors, clinical features, and outcomes of ICH. 17 of 423 patients (4%) suffered ICH during hospital stay, and 4 patients (24%) died directly because of ICH despite routine prophylactic platelet transfusions. Patients with ICH had a negatively impacted overall survival (median OS, 20.1 vs. 104.8 months) and were more likely not to continue with curative treatment. Main risk factors were female gender, severe thrombocytopenia, and decreased fibrinogen. Patients with subsequent ICH also had laboratory signs of liver dysfunction. Intracranial hemorrhage remains a potentially deadly complication with notable incidence despite prophylactic platelet substitution, suggesting that additional prophylactic interventions may be required to further reduce the frequency of ICH in high-risk patients. Unrecognized genetic factors may simultaneously predispose to AML and platelet dysfunction with ICH.


Maternal administration of superoxide dismutase and catalase in phenytoin teratogenicity.
Embryonic bioactivation and formation of reactive oxygen species (ROS) are implicated in the mechanism of phenytoin teratogenicity. This in vivo study in pregnant CD-1 mice evaluated whether maternal administration of the antioxidative enzymes superoxide dismutase (SOD) and/or catalase conjugated with polyethylene glycol (PEG) could reduce phenytoin teratogenicity. Initial studies showed that pretreatment with PEG-SOD alone (0.5-20 KU/kg i.p. 4 or 8 h before phenytoin) actually increased the teratogenicity of phenytoin (65 mg/kg i.p. on gestational days [GD] 11 and 12, or 12 and 13) (p < .05), and appeared to increase embryonic protein oxidation. Combined pretreatment with PEG-SOD and PEG-catalase (10 KU/kg 8 or 12 h before phenytoin) was not embryo-protective, nor was PEG-catalase alone, although PEG-catalase alone reduced phenytoin-initiated protein oxidation in maternal liver (p < .05). However, time-response studies with PEG-catalase (10 KU/kg) on GDs 11, or 11 and 12, showed maximal 50-100% increases in embryonic activity sustained for 8-24 h after maternal injection (p < .05), and dose-response studies (10-50 KU/kg) at 8 h showed maximal respective 4-fold and 2-fold increases in maternal and embryonic activities with a 50 KU/kg dose (p < .05). In controls, embryonic catalase activity was about 4% of that in maternal liver, although with catalase treatment, enhanced embryonic activity was about 2% of enhanced maternal activity (p < .05). PEG-catalase pretreatment (10-50 KU/kg 8 h before phenytoin) also produced a dose-dependent inhibition of phenytoin teratogenicity, with maximal decreases in fetal cleft palates, resorptions and postpartum lethality at a 50 KU/kg dose (p < .05). This is the first evidence that maternal administration of PEG-catalase can substantially enhance embryonic activity, and that in vivo phenytoin teratogenicity can be modulated by antioxidative enzymes. Both the SOD-mediated enhancement of phenytoin teratogenicity, and the inhibition of phenytoin teratogenicity by catalase, indicate a critical role for ROS in the teratologic mechanism, and the teratologic importance of antioxidative balance.


Recruitment of a cytoplasmic chaperone relay by the A2A adenosine receptor.
The adenosine A2A receptor is a prototypical rhodopsin-like G protein-coupled receptor but has several unique structural features, in particular a long C terminus (of >120 residues) devoid of a palmitoylation site. It is known to interact with several accessory proteins other than those canonically involved in signaling. However, it is evident that many more proteins must interact with the A2A receptor, if the trafficking trajectory of the receptor is taken into account from its site of synthesis in the endoplasmic reticulum (ER) to its disposal by the lysosome. Affinity-tagged versions of the A2A receptor were expressed in HEK293 cells to identify interacting partners residing in the ER by a proteomics approach based on tandem affinity purification. The receptor-protein complexes were purified in quantities sufficient for analysis by mass spectrometry. We identified molecular chaperones (heat-shock proteins HSP90α and HSP70-1A) that interact with and retain partially folded A2A receptor prior to ER exit. Complex formation between the A2A receptor and HSP90α (but not HSP90β) and HSP70-1A was confirmed by co-affinity precipitation. HSP90 inhibitors also enhanced surface expression of the receptor in PC12 cells, which endogenously express the A2A receptor. Finally, proteins of the HSP relay machinery (e.g. HOP/HSC70-HSP90 organizing protein and P23/HSP90 co-chaperone) were recovered in complexes with the A2A receptor. These observations are consistent with the proposed chaperone/coat protein complex II exchange model. This posits that cytosolic HSP proteins are sequentially recruited to folding intermediates of the A2A receptor. Release of HSP90 is required prior to recruitment of coat protein complex II components. This prevents premature ER export of partially folded receptors.


Performance trade-offs and individual quality in decathletes.
Many constraints of organismal design at the cell and organ level, including muscle fiber types, musculoskeletal gearing and control-surface geometry, are believed to cause performance trade-offs at the whole-organism level. Contrary to this expectation, positive correlations between diverse athletic performances are frequently found in vertebrates. Recently, it has been proposed that trade-offs between athletic performances in humans are masked by variation in individual quality and that underlying trade-offs are revealed by adjusting the correlations to 'control' quality. We argue that quality is made up of both intrinsic components, due to the causal mapping between morpho-physiological traits and performance, and extrinsic components, due to variation in training intensity, diet and pathogens. Only the extrinsic component should be controlled. We also show that previous methods to estimate 'quality-free' correlations perform poorly. We show that Wright's factor analysis recovers the correct quality-free correlation matrix and use this method to estimate quality-free correlations among the 10 events of the decathlon using a dataset of male college athletes. We found positive correlations between all decathlon events, which supports an axis that segregates 'good athletes' from 'bad athletes'. Estimates of quality-free correlations are mostly very small (<0.1), suggesting large, quality-free independence between events. Because quality must include both intrinsic and extrinsic components, the physiological significance of these adjusted correlations remains obscure. Regardless, the underlying architecture of the functional systems and the physiological explanation of both the un-adjusted and adjusted correlations remain to be discovered.


Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1.
Precise positioning of dendritic branches is a critical step in the establishment of neuronal circuitry. However, there is limited knowledge on how environmental cues translate into dendrite initiation or branching at a specific position. Here, through a combination of mutation, RNAi, and imaging experiments, we found that a Dscam-Dock-Pak1 hierarchical interaction defines the stereotypical dendrite growth site in the Drosophila aCC motoneuron. This interaction localizes the Cdc42 effector Pak1 to the plasma membrane at the dendrite initiation site before the activation of Cdc42. Ectopic expression of membrane-anchored Pak1 overrides this spatial specification of dendritogenesis, confirming its function in guiding Cdc42 signaling. We further discovered that Dscam1 localization in aCC occurs through an inter-neuronal contact that involves Dscam1 in the partner MP1 neuron. These findings elucidate a mechanism by which Dscam1 controls neuronal morphogenesis through spatial regulation of Cdc42 signaling and, subsequently, cytoskeletal remodeling.


The screening of chemicals for juvenoid-related endocrine activity using the water flea Daphnia magna.
U.S. Environmental Protection Agency is charged with developing a screening and testing paradigm for detecting endocrine toxicity of chemicals that are subject to regulation under the Food Quality Protection and the Safe Drinking Water Acts. In this study, we developed and evaluated a screening assay that could be employed to detect juvenoid-related endocrine-modulating activity in an invertebrate species. Juvenoid activity, anti-juvenoid activity, and juvenoid potentiator activity of chemicals was assessed using the water flea Daphnia magna. Male sex determination is under the regulatory control of juvenoid hormone, presumably methyl farnesoate, and this endpoint was used to detect juvenoid modulating activity of chemicals. Eighteen chemicals were evaluated for juvenoid agonist activity. Positive responses were detected with the juvenoid hormones methyl farnesoate and juvenile hormone III along with the insect growth regulating insecticides pyriproxyfen, fenoxycarb, and methoprene. Weak juvenoid activity also was detected with the cyclodiene insecticide dieldrin. Assays performed repetitively with compounds that gave either strong positive, weak positive, or negative response were 100% consistent indicating that the assay is not prone to false positive or negative responses. Five candidate chemicals were evaluated for anti-juvenoid activity and none registered positive. Four chemicals (all trans-retinoic acid, methoprene, kinoprene, bisphenol A) also were evaluated for their ability to potentiate the activity of methyl farnesoate. All registered positive. Results demonstrate that an in vivo assay with a crustacean species customarily employed in toxicity testing can be used to effectively screen chemicals for juvenoid-modulating activity.


LC/MS with a particle beam interface in forensic toxicology.
Many instruments are used in forensic toxicology to screen biologic samples for drugs and other compounds. Many of these screening instruments (and others) are used to confirm positive screening tests. The focus of this article is the use of a high pressure liquid chromatograph/mass spectrometer (HPLC/MS) for screening forensic postmortem and human performance DWI cases. This screening procedure involves an HPLC with a particle beam interfaced to a mass spectrometer detector and a photodiode array detector. Drugs such as the antidepressants, drugs of abuse, over-the-counter cold and pain preparations, anticonvulsants, benzodiazepines, and some medications that are not available in the United States are selected at therapeutic and subtherapeutic levels. Limits of detection and extraction efficiencies are presented for many compounds. Several cases are discussed showing different drug combinations.


Correlations among perceptual-motor ability, self-concept and reading achievement in early elementary grades.
This study investigated the correlation among measures of perceptual-motor abilities, self-concept, and reading achievement and determined whether perceptual-motor ability and self-concept can predict reading achievement in the early elementary grades. A total of 105 boys and 108 girls from the first, and second and third grades were tested on the stabilometer, a modified Minnesota Manual Dexterity Test, a tapping test, the Primary Self-concept Inventory, and the Science Research Associates Assessment Survey. Intercorrelations across grade levels tended to be low and nonsignificant. The multiple regression procedures yielded no strong predictions of reading achievement. These findings tended to confirm the specificity of perceptual-motor ability, self-concept, and reading achievement.


Endothelial monocyte-activating polypeptide-II (EMAP-II): a novel inducer of lymphocyte apoptosis.
The novel, proinflammatory cytokine endothelial monocyte-activating polypeptide-II (EMAP-II) was first found in tumor cell supernatants. EMAP-II is closely related or identical to the p43 auxiliary protein of the multisynthase complex, which is involved in protein synthesis. In vitro, EMAP-II induces procoagulant activity, increased expression of E- and P-selectins and tumor necrosis factor receptor-1, and ultimately, programmed cell death (apoptosis) in cultured endothelial cells. EMAP-II is also chemotactic for monocytes and neutrophils. However, the role of the p43/EMAP-II cytokine form in tumors is not understood. We hypothesized an immune-regulatory role within neoplastic tissues and investigated its effects on lymphocytes. EMAP-II causes a dose-dependent inhibition of proliferation and apoptosis in Jurkat T cells and mitogen-activated peripheral blood mononuclear cells. Coculture with DLD-1 colorectal cancer cells or media conditioned by these cells induces apoptosis in Jurkat cells, which is partially reversed by antibodies against EMAP-II. Our data suggest that EMAP-II constitutes a component of a novel, immunosuppressive pathway in solid tumors, which is not normally expressed outside the cell but in tumors, may be subject to abnormal processing and released from tumor cells.


The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies.
Common pediatric solid cancers fail to respond to standard immuno-oncology agents relying on preexisting adaptive antitumor immune responses. The adoptive transfer of tumor-antigen specific T cells, such as CAR-gene modified T cells, is an attractive strategy, but its efficacy has been limited. Evidence is accumulating that local barriers in the tumor microenvironment prevent the infiltration of T cells and impede therapeutic immune responses. A thorough understanding of the components of the functional compartment of the tumor microenvironment and their interaction could inform effective combination therapies and novel engineered therapeutics, driving immunotherapy towards its full potential in pediatric patients. This review summarizes current knowledge on the cellular composition and significance of the tumor microenvironment in common extracranial solid cancers of childhood and adolescence, such as embryonal tumors and bone and soft tissue sarcomas, with a focus on myeloid cell populations that are often present in abundance in these tumors. Strategies to (co)target immunosuppressive myeloid cell populations with pharmacological anticancer agents and with selective antagonists are presented, as well as novel concepts aiming to employ myeloid cells to cooperate with antitumor T cell responses.


Management and risk factor control of coronary artery disease in elderly versus nonelderly: a multicenter registry.
Coronary artery disease (CAD) is a leading cause of death in elderly because aging is the important non-modifiable risk factors of atherosclerosis and also a predictor of poor outcomes. Underuse of guideline directed therapy may contribute to suboptimal risk factor control and worse outcomes in the elderly. We aimed to explore the management of CAD, risk factors control as well as goal attainment in elderly compared to nonelderly CAD patients. The CORE-Thailand is an ongoing multicenter, prospective, observational registry of patients with high atherosclerotic risk in Thailand. The data of 4120 CAD patients enrolled in this cohort was analyzed comparing between the elderly (age ≥ 65 years) vs. nonelderly (age < 65 years). There were 2172 elderly and 1948 nonelderly patients. The elderly CAD patients had higher prevalence of hypertension, dyslipidemia, atrial fibrillation and chronic kidney disease. The proportion of patients who received coronary revascularization was not different between the elderly and nonelderly CAD patients. Antiplatelets were prescribed less in the elderly while statin was prescribed in the similar proportion. Goal attainments of risk factor control of glycemic control, low density lipoprotein cholesterol, and smoking cessation except the blood pressure goal were higher in the elderly CAD patients. The CORE-Thailand registry showed the equity in the treatment of CAD between elderly and non-elderly. Elderly CAD patients had higher rate of goal attainment in risk factor control except blood pressure goal. The effects of goal attainment on cardiovascular outcomes will be demonstrated from ongoing cohort.


A novel signal-off photoelectrochemical biosensor for M.SssI MTase activity assay based on GQDs@ZIF-8 polyhedra as signal quencher.
DNA methylation catalyzed by M.SssI methyltransferases (MTase) has important roles in gene expression and other cellular activities, and relates to some diseases, especially cancers. Therefore, it is important to develop a sensitive sensing platform for M.SssI MTase activity assay. Here, taking zeolitic imidazolate framework-8 (ZIF-8) polyhedra as the carriers of graphene quantum dots (GQDs), GQDs-embedded ZIF-8 polyhedra (denoted as GQDs@ZIF-8 polyhedra) were successfully prepared and used as the multi-functional signal quencher to construct a novel signal-off photoelectrochemical (PEC) biosensor for M.SssI MTase activity assay. Firstly, the indium tin oxide (ITO) slice was modified with TiO2, poly(diallyldimethylammonium chloride) and CdTe quantum dots (QDs). The obtained electrode was used as the photoelectrode and labeled as ITO/TiO2/CdTe QDs. Then, single-stranded DNA (S1) was anchored on the photoelectrode surface via S-Cd bond. After hybridization between S1 and biotinylated single-stranded DNA (S2), the streptavidin (SA)-labeled GQDs@ZIF-8 polyhedra were introduced to the modified electrode via the specific reaction between biotin and SA. As the signal quencher, GQDs@ZIF-8 polyhedra could not only inhibit the photocurrent signal of the ITO/TiO2/CdTe QDs electrode due to the steric hindrance effect, but also act as peroxidase mimetics to catalyze precipitation reaction of 4-chloro-1-naphthol, resulting in the evident depression of the photocurrent signal. For the specially designed S1/S2 double-strand DNA, the decreased photocurrent was quantitatively correlated with the M.SssI MTase activity (linear response range, 0.005-150 U mL-1; detection limit, 0.004 U mL-1). The developed GQDs@ZIF-8 polyhedra and related PEC biosensor may have potential applications in clinical research and disease diagnosis.


5-{4'-[(5-Benzyl-2H-tetra-zol-2-yl)meth-yl]biphenyl-2-yl}-1H-tetra-zole monohydrate.
In the title compound, C22H18N8·H2O, the dihedral angle between the tetra-zole rings is 69.58 (1)° while the terminal phenyl ring makes dihedral angles of 26.98 (8) and 39.75 (8)° with the other benzene rings. The rings of the biphenyl unit subtend a dihedral angle of 55.23 (8)°. In the crystal, the solvent water mol-ecule is linked to the main mol-ecule via an N-H⋯O hydrogen bond. In addition, C-H⋯N and O-H⋯N hydrogen bonds link the components into chains along [010]. The crystal structure also features C-H⋯π and π-π inter-actions, with centroid-centroid distances of 3.6556 (9) and 3.826 (1) Å.


Randomized, controlled, double-blinded field trial to assess Leishmania vaccine effectiveness as immunotherapy for canine leishmaniosis.
Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009-1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185-8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.