Periodical, neurological-functional assessment for cervical cord injury.
The residual, reversible potentials of neurological-functional recovery in patients paralysed due to a cervical cord injury were periodically checked according to the various assessment methods from the initial period of 72 hours after injury to the final follow-up of 7 years. In our series, the data on the neurological changes were a little different from those reported in the literature. In the complete paralysis group, only 2 of the 30 patients showed slight functional recovery of less than 1 grade in the Frankel classification with descent of the cord lesion level. Twenty three patients showed descent of a half to one segment from the initial cord lesion level. The remaining 5 patients deteriorated because of ascent of a half to two segments from the initial cord lesion level. All patients with complete paralysis remained essentially unchanged. In the incomplete group, 58 of the 70 patients had significant recovery of more than 1 grade in the Frankel classification. The grade of neurological recovery was different in each patient. Patients with a central cord lesion showed remarkably better recovery of the cord function than those with other types of cord lesions. Nineteen of the 49 patients with a central cord lesion regained independent walking ability with or without aid. Neurological recovery in the incomplete paralysis group might be expected until approximately 6 months after injury. The early appearance of signs of recovery was an indication of better results. There was no difference in the neurological recovery between patients who had been realigned surgically and those who have been realigned non-surgically. Our neurological-functional assessment method reflecting the sectional and logitudinal cord level function and expressing more detailed information was demonstrated. Magnetic resonance imaging (MRI) was used to assess residual cord function. The area of abnormal signal intensity almost corresponded to the cord level diagnosed neurologically.


Mortality patterns in long-term survivors of childhood or adolescent central nervous system tumour in Sweden.
A growing number of young patients with central nervous system (CNS) tumour survived for more than five years. However, these long-term survivors might be at risk of multiple late effects thus leading to a higher risk of late mortality. We aimed to explore the risk of late mortality and the pattern of mortality among long-term survivors of childhood or adolescent CNS tumour. We identified 5-year survivors with childhood or adolescent CNS tumour before age 20 years through the Swedish Cancer Registry. Five controls were randomly matched for each patient to generate the reference group. We retrieved information about death via Cause of Death Register. We calculated the absolute excess risk (AER) of death and the hazard ratio (HR) of death using Cox proportional hazard model. Long-term survivors with CNS tumour suffered a significant higher risk of overall mortality (HR 6.56, 95% CI 5.71-7.53; AER 5.89, 95% CI 5.03-6.87). The mortality rate declined with the increasing survival time, but it was still higher even after 30 years of follow-up. Malignant neoplasms contributed mostly to late mortality with an AER of 3.75 (95% CI 2.95-4.75). Female survivors, survivors diagnosed at a younger age and survivors with medulloblastoma were particularly strongly associated with a higher risk of death. Long-term survivors of childhood and adolescent CNS tumours are at a higher risk of late mortality, and the risk of death is affected by gender, age at diagnosis and types of CNS tumour.


Experience with more than 100 total artificial heart implants.
The SynCardia Total Artificial Heart (SynCardia Systems Inc, Tucson, Ariz) has been used as a bridge to cardiac transplantation in 930 patients worldwide and in 101 patients in our program. Our experience with SynCardia Total Artificial Heart implantation documents its indications, safety, and efficacy. Data regarding preoperative condition, mortality, and morbidity have been reviewed and analyzed. From January 1993 to December 2009, 101 patients had bridge to transplant procedures with the SynCardia Total Artificial Heart. Ninety-one percent of cases were Interagency Registry for Mechanically Assisted Circulatory Support profile 1, and the remaining 9% of cases were failing medical therapy on multiple inotropic medications. The mean support time was 87 days (median, 53 days; range, 1-441 days). Pump outputs during support were 7 to 9 L/min. Adverse events included strokes in 7.9% of cases and take-back for hemorrhage in 24.7% of cases. Survival to transplantation was 68.3%. Causes of death of 32 patients on device support included multiple organ failure (13), pulmonary failure (6), and neurologic injury (4). Survival after transplantation at 1, 5, and 10 years was 76.8%, 60.5%, and 41.2%, respectively. The longest-term survivor is currently alive 16.4 years postimplantation. These patients were not candidates for left ventricular assist device therapy and were expected to die. The SynCardia Total Artificial Heart offers a real alternative for survival with a reasonable complication rate in appropriate candidates who otherwise might have been assigned to hospice care.


Prognostic use of human leukocyte antigen genotyping for rheumatoid arthritis susceptibility, disease course, and clinical stratification.
HLA markers of the class II region are important for determination of the predisposition to RA, clinical manifestations, and rate of progression of joint destruction in this autoimmune disease. Furthermore, evidence emerges indicating that HLA markers also have an impact on treatment outcome in RA. Currently, several immunopathogenetic models of HLA-dependent influences in RA are under debate. These models insufficiently explain the graded influence of HLA-DR and HLA-DQ on manifestation and joint destruction, however. Currently, there is not enough evidence to unequivocally identify a primary susceptibility locus or to pinpoint the HLA-dependent mechanism in RA. Overall, the influence of HLA class II markers on disease susceptibility is rather restricted, and, in turn, their utility in establishing the diagnosis of RA is of limited use. Although relative risks are higher for the association of particular genotypes with extra-articular forms of RA, HLA genotyping may not contribute to prognostication in individual patients but may aid in disease stratification. In contrast, HLA genotyping in early RA, particularly when combined with the determination of RFs and determination of the presence of bony erosions, is of value to identify patients at risk for poor outcome. In turn, these patients may benefit from early aggressive therapy, and HLA genotyping should be useful to aid in risk stratification in patients and thus helpful for the choice of treatment. Lastly, disease and risk stratification based on HLA markers along with the elucidation of HLA-dependent mechanisms may facilitate the development of specific immunotherapy modalities.


Anti-HER2 scFv Expression in Escherichia coli SHuffle®T7 Express Cells: Effects on Solubility and Biological Activity.
Breast cancer is the second most commonly diagnosed cancer, worldwide. Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer is correlated with poor prognosis. HER2-targeting monoclonal antibodies resulted in longer survival of HER2+ breast cancer. Single-chain variable fragment (scFv) demonstrates improved penetrability into tumors. Due to the presence of two disulfide bond, scFv expression in reducing bacterial cytoplasm may cause formation of inclusion bodies. Disulfide bond can be formed properly in cytoplasm of SHuffle® strain as it is trxB-, gor-, and overexpresses cytoplasmic DsbC chaperone. In this study, the anti-HER2 scFv was successfully expressed and purified in BL21 (DE3) and SHuffle® cells. Here, significant higher soluble anti-HER2 scFv was produced in SHuffle® than in BL21 strain. The specific binding of anti-HER2 scFv to HER2 was shown by flow cytometry analysis and ELISA. Moreover, it was demonstrated that the anti-HER2 scFv produced in SHuffle® binds to HER2 at higher level as compared to that expressed in BL21 cells. Furthermore, competitive ELISA-based study suggested that anti-HER2 scFv recognizes the same epitope of HER2 receptor as the trastuzumab antibody. Our findings indicated that correct disulfide bond formation in SHuffle® strain can result in enhanced solubility and higher biological activity level of anti-HER2 scFv.


Use of a diffusion model for mono- and bicomponent anion-exchange of two isoenzymes of glucoamylase from Aspergillus niger in a fixed bed.
The adsorption of glucoamylases I and II (GA I and GA II, respectively) from Aspergillus niger on the anion exchanger DEAE-Toyopearl 650 was studied in fixed-bed experiments, and the effect of temperature, flowrate, inlet concentration, bed length, and particle size on the process was characterized. The anion exchanger showed a higher adsorption capacity for the more active isoenzyme GA I in all experimental conditions studied. A mathematical model accounting for external and pore diffusion and nonlinear equilibrium isotherm (for GA I) was used to fit the experimental breakthrough curves, showing very accurate fittings in all of the operating conditions. The values of the pore diffusion coefficient at 15, 20, and 25 degrees C were, respectively, 1.25 x 10(-)(11), 1.46 x 10(-)(11) and 1.83 x 10(-)(11) (for GA I) and 1.82 x 10(-)(11), 2.44 x 10(-)(11) and 2.73 x 10(-)(11) (for GA II) m(2)/s. Bicomponent adsorption experiments showed no significant interference effects between GA I and GA II, and so the mathematical model was again used to fit these experiments, yielding very satisfactory results.


Dopamine receptors in Parkinson's disease.
1. Parkinson's disease is associated with profound decreases in striatal dopamine concentrations. 2. There are significant increases in the densities of striatal D1 and D2 receptors as part of the compensatory mechanism. 3. Levodopa therapy induces a down-regulation of both D1 and D2 receptors to normal densities. 4. Positron emission tomography detects striatal changes in early Parkinson's disease or toxin-induced parkinsonism.


Evaluation of immunoreactivity with monoclonal antibody NCRC 11 in breast carcinoma.
Immunocytochemical staining with monoclonal antibody NCRC 11 of formalin fixed paraffin embedded tumour tissue has been studied in 444 cases of primary breast cancer with a minimum follow period of 6 years. The relationship between extent of staining, assessed on a four point scale, and patient survival has been confirmed. There are significant relationships between staining and both histological grade and oestrogen receptor status. No association has been shown between staining and lymph node stage or tumour size. Simplification of staining assessment by modification to two staining groups still allows significant separation of patients into prognostic groups and incorporation into an existing prognostic index.


Recurrent abdominal pain in children: a long term follow-up.
A long-term follow-up study (minimum of 10 years) of 16 children admitted for recurrent abdominal pain revealed that in 50% of the sample the disturbance disappeared completely, persisted in 25% and in the remaining 25% other painful symptoms developed. The variables that characterized the poor outcome group were: belonging to a "painful family", many surgical procedures, low educational level and social class and a low score in the Q3 factor of the Sixteen Personality Factor Questionnaire (spare capacity to control emotions).


Memory B cell diversity: insights for optimized vaccine design.
The overarching logos of mammalian memory B cells (MBCs) is to cache the potential for enhanced antibody production upon secondary exposure to cognate antigenic determinants. However, substantial phenotypic diversity has been identified across MBCs, hinting at the existence of unique origins or subfunctions within this compartment. Herein, we discuss recent advancements in human circulatory MBC subphenotyping as driven by high-throughput cell surface marker analysis and other approaches, as well as speculated and substantiated subfunctions. With this in mind, we hypothesize that the relative induction of specific circulatory MBC subsets might be used as a biomarker for optimally durable vaccines and inform vaccination strategies to subvert antigenic imprinting in the context of highly mutable pathogens such as influenza virus or SARS-CoV-2.


Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor.
Proliferative diabetic retinopathy results from excess blood vessel growth into the vitreous fluid of the eye. Retinal angiogenesis is regulated by expression of vascular endothelial growth factor (VEGF), and many studies have shown that VEGF is critically involved in proliferative diabetic retinopathy. VEGF is alternatively spliced to form the angiogenic (VEGF(xxx)) and potentially anti-angiogenic (VEGF(xxx)b) family of isoforms. The VEGF(xxx)b family is found in normal tissues, but down-regulated in renal and prostate cancer. Previous studies on endogenous expression of VEGF in the eye have not distinguished between the two families of isoforms. We measured VEGF(xxx)b isoform expression in normal human eye tissue (lens, sclera, retina and iris) and vitreous fluid using enzyme-linked immunosorbent assay and Western blotting with a VEGF(xxx)b-specific antibody. VEGF(xxx)b protein was expressed in lens, sclera, retina, iris and vitreous fluid. Multiple isoforms were seen, including VEGF(165)b, VEGF(121)b, VEGF(145)b, VEGF(183)b and VEGF(189)b. In non-diabetic patients, 64+/-7% of the VEGF in the vitreous was VEGF(xxx)b (n=18), whereas in diabetic patients only 12.5+/-3.6% of total VEGF was VEGF(xxx)b. Since VEGF(xxx)b inhibits VEGF(xxx)-induced angiogenesis in a one-to-one stoichiometric manner, these results show that in the eye of diabetic patients VEGF splicing was switched from an anti-angiogenic to a pro-angiogenic environment. This occurred through changes to the ratio of VEGF(xxx):VEGF(xxx)b. Alterations to splicing, and through that to the balance of VEGF isoforms, could therefore be a potential therapeutic strategy for diabetic retinopathy.


Circulating ciRS-7 as a potential non-invasive biomarker for epithelial ovarian cancer: An investigative study.
Ovarian cancer (OC) is the most common malignant neoplasm of the female reproductive system in developed countries. Early detection, diagnosis and prognosis are particularly important to OC. The potential of circulating circular RNAs (circRNAs) as non-invasive biomarkers of various tumors has been especially described in recent years. The aim of this study was to explore the diagnostic and prognostic value of circulating cirRS-7 in patients with epithelial ovarian cancer (EOC). Pre- and postoperative plasma samples from 111 EOC patients (47 cases with FIGO stage IA-IIB and 64 cases with FIGO stage IIB-IV) and healthy female volunteers was collected. Circulating ciRS-7 and hsa-miR-7-5p was analyzed using reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of circulating cirRS-7 as biomarker was estimated by the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) and Kaplan-Meier analysis. The preoperative expression levels of circulating ciRS-7 were increased in plasma of EOC FIGO stage I-IV patients than in the healthy controls (p < 0.001). However, the expression levels of ciRS-7 in the postoperative period were significantly lower in EOC FIGO stage IIA-IIA patients than healthy controls and EOC FIGO stage IIB-IV patients (p < 0.05, p < 0.001). The AUC of ciRS-7 for diagnosing EOC FIGO stage I-IV patients in pre-and postoperative periods was 0.90, 0.92, 0.84, 0.88, 0.58 and 0.86, respectively. Higher circulating ciRS-7 expression is associated with lymph node invasion, FIGO stage, distant metastasis, and worse overall survival (OS) of patients. Moreover, multivariate Cox analysis showed that higher circulating ciRS-7 was an independent predictor of OS in EOC FIGO stage IIB-IV patients. In addition, in plasma of EOC patients, ciRS-7 negatively correlated with has-miR-7-5p in pre-and postoperative periods (p < 0.001). Circulating ciRS-7 levels in plasma can be considered a potential candidate biomarker for diagnosing EOC patients. Dysregulation of ciRS-7 may participate in the molecular mechanism of EOC through hsa-miR-7-5p sponging.


Occupational blood and body fluid exposure of university health care workers.
Occupational exposure to bloodborne pathogens caused by percutaneous injuries or mucosal contamination is common in hospital settings. Reports of exposures to human blood and body fluids from Padua university health care workers since 2004 to 2006 and compliance with follow-up after injury according to the patients' source were analyzed. The injury reports were 497. The residents in surgery and anesthesiology were significantly more injured than others, and the compliance with follow-up was low: from 26.3% (hepatitis B virus) to 40% (hepatitis C virus) with a positive source, less than 30% with a negative source, as far as 40% with an unknown source. No seroconversion was observed in subjects completing the follow-up. We suspect underestimation of injury reports and low compliance with the follow-up requests that health care workers adhere to the protocols and follow the standard procedures to prevent exposures to bloodborne pathogens.


Canadian Support for IVF Access and Use.
Apply Weiner's attribution-affect-action (AAA) model to the context of societal support for access to assisted reproductive technology (ART). Five hundred and fifty-four Canadians were randomly assigned to 1 of 4 vignette conditions describing reproductively challenged women differentiated by the root cause of their need for ART. Following this, participants completed an online questionnaire measuring the components of the AAA model. The overall expected relationships among the AAA framework variables were found. Participants were least willing to support access to ART for women perceived as relatively more responsible for their fertility issues and who elicited lower levels of sympathy, whereas participants were most willing to support access for women viewed as less responsible and who elicited more sympathy. Additionally, participants were most supportive of general access to ART and least supportive when asked to offer personal funds to assist the women with access. These findings have potential implications for Canadian health care policy decisions on funding fertility treatments through the universal health care system. Further research on this issue, as well as the development and testing of interventions aimed at addressing beliefs around equitable and inclusive access to ART, are warranted.


Nuclear cardiology and CVD in the developing world: Are we applying our scarce resources appropriately? Why is our mortality rate so high?
While mortality rates from cardiovascular diseases have progressively decreased in developed nations, this has not been observed to the same extent in the developing world. Nuclear Cardiology utilization remains low or non-existent for most of those living in the low-to-middle-income countries. How much of the decline in mortality observed in the developed world has to do with advanced cardiac imaging? Are we applying our scarce resources appropriately for myocardial perfusion imaging? Are myocardial revascularizations being guided by appropriate use criteria? Is more imaging necessary to reduce the mortality rates further in the developing world?


Oncologic outcomes of pre- versus post-operative radiation in Resectable soft tissue sarcoma: a systematic review and meta-analysis.
Postoperative radiation therapy for soft tissue sarcomas demonstrated good local recurrence-free survival rates and survival outcomes. However, the results remained controversial. This study aimed to evaluate the role of preoperative and postoperative radiation therapy for the treatment of resectable soft tissue sarcomas. The electronic database PubMed, MEDLINE, Cochrane Library, and EMBASE were performed from inception till 30 November, 2019. The effect of preoperative versus postoperative radiation therapy on resectable soft tissue sarcomas was compared and then assessed. A total of 15 studies with 12,813 patients were included, and most of these had acceptable quality scores. Of these, 10 studies reported data on local recurrence. The pooled results indicated no significant differences between preoperative radiotherapy and postoperative radiotherapy groups for local recurrence, with a risk ratio (RR) and 95% confidence interval (CI) of 0.84 (95%CI = 0.58-1.21). No difference was observed in the overall survival and distant metastasis between the two groups. According to the pooled results, preoperative radiotherapy group showed a significant risk for complications (RR = 2.11, 95%CI = 1.36-3.27). The postoperative radiation therapy does not increase the local recurrence, overall survival, and distant metastasis, but might result in lowering complications.


Salivary levels of mutans streptococci and Lactobacilli among Palestinian school children in East Jerusalem.
The aim of the present study was to investigate the distribution of oral cariogenic bacteria among 12-year-old Palestinian children attending schools in East Jerusalem. Salivary levels of mutans streptococci (MS) and Lactobacilli (LB) were examined by semi-quantitative commercial kits and then correlated to social-demographic parameters. Overall, 52.1 % of the examined children presented the highest possible ranking score categories for MS bacteria, with only 5.4 % in the lowest category. Only 12.6 % of the school children presented the highest LB score, while 25 % had the lowest ranking score. Salivary MS levels in children attending private schools were lower than those of children in government schools and United Nations Relief and Works Agency (UNRWA) schools. Conversely, levels of LB were lowest in children attending UNRWA schools compared to government and private schools. Girls had significantly higher amounts of MS and LB than boys (p = 0.001). Lower MS levels were significantly related to the following socioeconomic variables: higher father's education level (p = 0.037), higher mother's education level (p = 0.063), mother's employment status (p = 0.012), and lower home density (p = 0.001). For LB, the only significant socioeconomic variable was higher father's employment level, which was related to lower LB level (p = 0.025). Levels of MS and LB were found to be strongly related with socioeconomic status among Palestinian children in East Jerusalem. The relatively high prevalence of cariogenic bacteria suggests that oral care prevention and treatment demands special attention from the health care institutions and authorities.


Oncological and cosmetic outcomes of oncoplastic breast conserving surgery.
Breast-conserving surgery and radiotherapy is firmly established as a good and safe option for most women with early breast cancer. The important outcome measures of breast conservation are survival, local recurrence, cosmesis and patient satisfaction. Partial breast reconstructive techniques may improve cosmesis and patient satisfaction without compromising the oncological outcomes. A search of the Medline and Pubmed databases of studies on breast conserving surgery where partial breast reconstructive techniques were employed. The keywords used were breast conserving surgery, oncoplastic breast surgery, partial breast reconstruction and reduction mammoplasty. The oncological and cosmetic outcomes of these studies were analysed. Studies on partial breast reconstructive techniques often lack oncological outcomes and long-term results are not available. On intermediate follow-up (up to 4.5 years) local recurrence rates vary from 0 to 1.8% per year. Cosmetic failure rates vary from 0 to 18%. To date, detailed studies are small and outcome measures vary. Breast surgeons should be aware of the range of surgical techniques that may enhance the aesthetic results of breast-conserving surgery as well as expand the indications for its use. There is a need for routine assessment of oncological and cosmetic outcomes and long-term results of partial breast reconstructive techniques in relation to these outcomes are awaited.


Sucralfate does not ameliorate acute radiation proctitis: randomised study and meta-analysis.
During pelvic radiotherapy, many patients develop radiation-induced gastrointestinal symptoms, which may interfere with treatment. Prophylaxis during radiotherapy should ideally prevent acute reaction and the development of delayed injury. Sucralfate, an aluminium sucrose octasulphate, has been used for acute and delayed radiation side-effects. However, conflicting results have been published. We report here a prospective, randomised, placebo-controlled study of prophylactic sucralfate during pelvic radiotherapy. In addition, a meta-analysis of available data from the literature has been carried out. Fifty-one patients with localised pelvic tumours scheduled for curative conformal pelvic radiotherapy (total dose 64-70 Gy over 6.5-7 weeks in 2 Gy daily fractions) were included. Peroral sucralfate 2 g three times daily, or identically appearing placebo tablets, was given during the course of radiotherapy. Symptom registration, endoscopy and biopsies were carried out immediately before radiotherapy, 2 weeks and 6 weeks into the treatment course, and 2 weeks after completing radiotherapy. Mucosal cup forceps biopsies were obtained through a rigid proctoscope. Graded endoscopic appearance and quantitative histology were registered. On the basis of previously published negative reports, an unplanned interim analysis of 44 evaluable patients showed significantly increased diarrhoea in the sucralfate group and the trial was stopped. No difference was seen in other symptoms, endoscopic appearance or histology. A meta-analysis comprising five published studies showed no statistically significant beneficial effect of sucralfate on acute symptoms. Sucralfate cannot be recommended for prophylaxis of acute radiation proctopathy and may even worsen the symptoms.


Application of magnetization transfer at 3.0 T in three-dimensional time-of-flight magnetic resonance angiography of the intracranial arteries.
To apply magnetization transfer (MT) at 3.0 T in three-dimensional time-of-flight magnetic resonance angiography of the intracranial arteries. This study was performed on phantoms and seven volunteers to determine the effects of MT at 3.0 T. By using a modulated MT approach and an altered phase encode order, the specific absorption rate (SAR) was kept below 3 W/kg over any 8-second time period. For a 20-degree flip angle and 36 msec repetition time, the background suppression at 3.0 T was improved with MT by 52 +/- 5% for white matter and 40 +/- 8% for grey matter, making the distal intracranial vasculature significantly more discernible. MT at 3.0 T can significantly improve background suppression in 3D time-of-flight magnetic resonance angiography (MRA) of the intracranial arteries without exceeding SAR guidelines.


Anaerobes in specific infectious and noninfectious diseases: new developments.
With the buildup of new research data, newer associations between anaerobic bacteria and diseases/conditions were evaluated. The aim of the mini-review was to draw attention and to encourage further multidisciplinary studies of the associations. We considered microbiome-disease correlations such as a decrease of fecal Faecalibacterium prausnitzii abundance in inflammatory bowel disease (IBD) and IBD recurrence, suggesting that F. prausnitzii could be a good biomarker for IBD. A link of subgingival Porphyromonas gingivalis with cardiovascular diseases was reported. Decreased Roseburia abundance was observed in the gut of Alzheimer's and Parkinson's disease patients. Akkermansia muciniphila was found to improve adipose/glucose metabolism, however, its intestinal abundance was observed in neurodegenerative diseases as well. Severe Clostridioides difficile infections have been reported in neonates and young children. Carcinogenic potential of anaerobes has been suggested. Fusobacterium nucleatum was implicated in the development of oral and colorectal cancer, Porphyromonas gingivalis and Tannerella forsythia were linked to esophageal cancer and Cutibacterium acnes subsp. defendens was associated with prostate cancer. However, there are some controversies about the results. In a Swedish longitudinal study, neither P. gingivalis nor T. forsythia exhibited oncogenic potential. The present data can enrich knowledge of anaerobic bacteria and their multifaceted significance for health and disease and can draw future research directions. However, more studies on large numbers of patients over prolonged periods are needed, taking into account the possible changes in the microbiota over time.


Development and evaluation of a biorelevant medium simulating porcine gastrointestinal fluids.
Simulated human intestinal media, have proved to be a useful biopharmaceutics tool as a dissolution media for predicting in vivo dissolution and pharmacokinetic profile in humans. During drug product development preclinical animal models are also required to assess drug product performance, and there is a need to develop species specific intestinal media to similarly predict in vivo pharmacokinetic profiles in each preclinical model. Pigs, are increasingly being used in preclinical drug development, however to date there is a lack of quantitative information about the composition of porcine gastrointestinal (GI) fluids. As a result, a porcine biorelevant medium has not yet been developed, which is essential to improve interpretation and forecast of preclinical results using biorelevant in vitro dissolution studies. GI fluid samples, were collected from landrace pigs, and characterized. Fasted State Simulated Intestinal Fluid of pigs (FaSSIFp) was developed based on the physiological composition of the GI fluids in terms of pH, buffer capacity, osmolality, surface tension, as well as the bile salt, phospholipid and free fatty acid content. This study demonstrated that FaSSIFp was superior at predicting the solubility of the six model drugs in porcine intestinal fluids (PIF). A markedly high correlation (r2 0.98) was observed between the solubility obtained in PIF and FaSSIFp, whereas poor correlation (r2 0.12) was found for the solubility of the model drugs between human FaSSIF and PIF. This confirms that species specific biorelevant intestinal media are crucial to provide more accurate predictions of pharmacokinetic studies in preclinical models. Additionally, the availability of a species specific intestinal medium offers the potential to improve in vitro-in silico approaches to predict in vivo absorption and to reduce the overall number of animals needed in oral drug product development testing.


Corticospinal tracts by diffusion tensor tractography in patients with arteriovenous malformations.
To visualize the corticospinal tract (CST) in patients with arteriovenous malformations (AVMs) by using diffusion tensor tractography (DTT) and to confirm the clinical reliability of DTT in patients with AVMs. We performed DTT in 24 patients who had their AVMs near the CST. Tracts and AVMs were shown simultaneously, providing information on their spatial relationships. We also counted numbers of voxels in the DTT-CST at the level of the AVM. DTT was visualized in 23 patients. In all 9 patients with hemiparesis, their DTT-CSTs were involved in the AVM or its surrounding lesion. Their volume of DTT-CST at the affected side was significantly decreased when compared with the contralateral side (P = 0.0469). All 14 patients whose DTT-CSTs were free from lesion had no hemiparesis. DTT was safe and clinically applicable in patients with AVMs. DTT is recommended when an AVM is located near the corticospinal tract.


Patterns, predictors, and outcomes of frailty trajectories in community-dwelling older adults: Results from the FREEDOM Cohort Study.
To identify subgroups of people with distinct frailty trajectories, identify baseline characteristics associated with these trajectories, and determine their coincident clinical outcomes. This study examined the longitudinal database from the FREEDOM Cohort Study. All 497 participants of the FREEDOM (French Acronym for "FRagilitéEtEvaluation àDOMicile" / In English "Frailty and Evaluation at Home") cohort requested a comprehensive geriatric assessment. Community-dwelling subjects over 75 years, or over 65 years with at least two comorbidities were included. Frailty was assessed using Fried's criteria, depression using the Geriatric Depression Scale (GDS) and cognitive function using the Mini Mental State Examination (MMSE) questionnaire. Frailty trajectories were modelled using k-means algorithms. Predictive factors were determined by multivariate logistic regression. Clinical outcomes included incident cognitive deficit, falls and hospitalization. The trajectory models allowed determine four frailty trajectories: "robust stable" (Trajectory A, 26.8%), "pre-frail worsening to frailty" (Trajectory B, 35.8%), "frail improving to less frailty" (Trajectory C, 23.3%), and "frail worsening to more frailty" (Trajectory D, 14.1%). Trajectory B was associated with age (OR 1.2 (95CI, 1.05 - 1.17)), potential cognitive deficit/dementia (OR 2.01 (95CI, 1.01- 4.05)) and depressive symptoms (OR 2.36 (95CI, 1.36 - 4.12)). Hypertension was distinguishing factor between" trajectory B vs. C and D. Depressive symptoms were two time more associated with D (OR 10.51) vs. C (OR 4.55). The incidence of clinical outcomes was significantly increased in poor frailty trajectories. This study allowed to determine frailty trajectories among older subjects requested a comprehensive geriatric assessment. The more significant predictive factors associated with poor frailty trajectory were advanced in age, potential cognitive deficit/dementia, depressive symptoms and hypertension. This emphasizes the need for adequate measures to controlled hypertension, depressive symptoms and to maintain or improve cognition in older adults.


Signaling pathways regulating protein synthesis during ageing.
Ageing in many organisms, including humans, is accompanied by marked alterations in both general and specific protein synthesis. Protein synthesis is normally under tight control by a broad array of regulatory factors, which facilitate appropriate rates of mRNA translation. Are the wide changes in protein synthesis simply a corollary of the ageing process or do they have a causative role in senescent decline? The jury is still out on this important question. Nevertheless, recent studies reveal an intimate interface between mechanisms that govern the translation of mRNA and molecular pathways implicated in ageing. In our manuscript we consider these links, which potentially underlie age-associated changes in protein synthesis.


The Transcription Factor Tox2 Drives T Follicular Helper Cell Development via Regulating Chromatin Accessibility.
T follicular helper (Tfh) cells provide essential help to B cells in germinal center (GC) reactions. Bcl6 is the obligatory lineage transcription factor in Tfh cells. Here, we examined the molecular pathways that induce Bcl6 gene expression and underscore Bcl6-dependent function during Tfh cell commitment. Integration of genome-wide Bcl6 occupancy in Tfh cells and differential gene expression analyses suggested an important role for the transcription factor Tox2 in Tfh cell differentiation. Ectopic expression of Tox2 was sufficient to drive Bcl6 expression and Tfh development. In genome-wide ChIP-seq analyses, Tox2-bound loci associated with Tfh cell differentiation and function, including Bcl6. Tox2 binding was associated with increased chromatin accessibility at these sites, as measured by ATAC-seq. Tox2-/- mice exhibited defective Tfh differentiation, and inhibition of both Tox2 and the related transcription factor Tox abolished Tfh differentiation. Thus, a Tox2-Bcl6 axis establishes a transcriptional feed-forward loop that promotes the Tfh program.


Depressive symptoms and risk for malnutrition among hospitalized elderly people.
To explore the association between depressive symptoms and risk for malnutrition in hospitalized elderly people. 195 hospitalized medical patients older than 65 years of age were studied in a cross-sectional design. Depression was assessed by 30-item Geriatric Depression Scale (GDS), nutritional status was evaluated by the Mini-Nutritional Assessment (MNA). Eating and digestive problems were assessed using selected items of Nutrition Risk Index (NRI), cognitive and functional status by Folstein and Barthel indices respectively; demographic data, diagnoses and medications were obtained from medical records. The prevalence of depression in the studied population was 28%. MNA scores were significantly lower among depressed patients as compared with non-depressed (22.86 vs. 24.96, p < 0.001), indicating a higher risk for undernutrition among depressed persons. After controlling for age, cognitive status, functional ability, and number of illnesses, undernutrition was significantly associated with depression (OR = 2.23; 95% CI: 1.04-4.8). Nutritional risk is associated with depression in aged inpatients. Close case management of the elderly hospitalized patients that include assessment and treatment for both disorders may be beneficial.


Thermochemical stabilities, electronic structures, and optical properties of C56X10 (X = H, F, and Cl) fullerene compounds.
Stimulated by the recent isolation and characterization of C₅₆Cl₁₀ chlorofullerene (Tan et al., J Am Chem Soc 2008, 130, 15240), we perform a systematic study on the geometrical structures, thermochemistry, and electronic and optical properties of C₅₆X₁₀ (X = H, F, and Cl) on the basis of density functional theory (DFT). Compared with pristine C₅₆, the equatorial carbon atoms in C₅₆X₁₀ are saturated by X atoms and change to sp³ hybridization to release the large local strains. The addition reactions C₅₆ + 5X₂ --> C₅₆X₁₀ are highly exothermic, and the optimal temperature for synthesizing C₅₆X₁₀ should be ranged between 500 and 1000 K. By combining 10 X atoms at the abutting pentagon vertexes and active sites, C₅₆Cl₁₀ molecules exhibit large energy gaps between the highest occupied and lowest unoccupied molecular orbitals (from 2.84 to 3.00 eV), showing high chemical stabilities. The C₅₆F₁₀ and C₅₆Cl₁₀ could be excellent electron acceptors for potential photonic/photovoltaic applications in consequence of their large vertical electron affinities. The density of states is also calculated, which suggest that the frontier molecular orbitals of C₅₆X₁₀ are mainly from the carbon orbitals of two separate annulene subunits, and the contributions derived from X atoms are secondary. In addition, the ultraviolet-visible spectra and second-order hyperpolarizabilities of C₅₆X₁₀ are calculated by means of time-dependent DFT and finite field approach, respectively. Both the average static linear polarizability <α> and second-order hyperpolarizability <γ> of these compounds are larger than those of C₆₀ due to lower symmetric structures and high delocalization of π electron density on the two separate annulene subunits.


Carboxymethylcellulose obtained by ethanol/water organosolv process under acid conditions.
Sugar cane bagasse pulps were obtained by ethanol/water organosolv process under acid and alkaline conditions. The best condition of acid pulping for the sugarcane bagasse was 0.02 mol/L sulfuric acid at 160 degrees C, for 1 h, whereas the best condition for alkaline pulping was 5% sodium hydroxide (base pulp) at 160 degrees C, for 3 h. For the residual lignin removal, the acid and alkaline pulps were submitted to a chemical bleaching using sodium chlorite. Pulps under acid and alkaline conditions bleached with sodium chlorite presented viscosities of 3.6 and 7.8 mPa x s, respectively, and mu-kappa numbers of 1.1 and 2.4, respectively. The pulp under acid condition, bleached with sodium chlorite was used to obtain carboxymethylcellulose (CMC). CMC yield was 35% (pulp based), showing mass gain after the carboxymethylation reaction corresponding to 23.6% of substitution or 0.70 groups -CH(2) COONa per unit of glucose residue. The infrared spectra showed the CMC characteristic bands and by the infrared technique it was possible to obtain a substitution degree (0.63), similar to the substitution degree calculated by mass gain (0.70).


t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activating NF-κB-p65.
Although sEH inhibitors are well studied in inflammatory and cardiovascular diseases, their effects on gliomas are unclear. In this study, we investigated the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87 human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell line. Our results showed that t-AUCB efficiently inhibited sEH activities in all three cell lines (the inhibition rate was more than 80% in each) and suppressed U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth inhibition on HepG2. We detected high levels of phosphorylated NF-κB-p65 (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-κB inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-κB-p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation level. We propose to further test this promising reagent for its anti-glioma activity in clinical relevant orthotopic brain glioma models.


Hemophagocytic Lymphohistiocytosis Masquerading as Acute Liver Failure: A Single Center Experience.
Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening disorder of extreme inflammation and unregulated immune response which require prompt recognition and early introduction of definitive therapy. HLH can present with wide range of hepatic dysfunction ranging from mild elevation of transaminases to liver failure. This study is carried out to describe the clinical and laboratory presentation of HLH. Patients who were diagnosed with HLH between January 2013 and December 2015 were retrospectively included in this study. Six patients were diagnosed as secondary HLH with median age of 28.5 years at diagnosis. All patients were presented with history of deep jaundice and high grade fever with pancytopenia and splenomegaly. Underlying diagnosis was viral infections in 4 and probable viral infection in remaining two. Bone marrow hemophagocytosis was present in 3 cases. Three patients were treated with corticosteroids only and one each with corticosteroids with cyclosporine or intravenous immunoglobulin (IVIG) and HLH treatment protocol. One patient died due to acute respiratory distress syndrome (ARDS); another patient died in follow-up due to respiratory failure due to pneumonia. HLH is rare and potentially life-threatening cause of prolonged fever, jaundice and pancytopenia. Early diagnosis and initiation of specific therapy can improve clinical outcome.


Life and death beneath macrophyte canopies: effects of understory kelps on growth rates and survival of marine, benthic suspension feeders.
Experiments conducted on rocky bottoms at 7-11 m depth in the San Juan Archipelago, Washington assessed effects of canopies of understory kelps on growth of benthic suspension feeders, determined the mechanisms responsible for effects, and assessed the influence of kelp canopies on survivorship of benthic fauna. Kelp canopics influenced growth rates of diverse suspension feeders. At several sites the musselMytilus edulis, the barnacleBalanus glandula, and the serpulid polychaetePseudochitinopoma occidentalis grew faster on the bottom beneath kelp canopies than on nearby exposed substrata. The cheilostome bryozoanMembranipora membranacea showed a mixed response to kelp canopies, growing faster in exposed regions at one site, but faster beneath canopies at another. There were no differences in growth of 2 other species (the cheilostome bryozoanCheilopora praelonga and the spongeMyxilla incrustans) between kelp and no-kelp treatments; however, some processes influenced by plant canopies affected their growth. Specific mechanisms responsible for kelp effects on growth were assessed in a series of field experiments usingPseudochitinopoma, Membranipora, Cheilopora andMyxilla. Particulate deposition on the bottom, which is more intense beneath canopies, negatively affected growth of all 4 species. Kelps also reduced rates of flow and prevented devented development of microalgal turfs beneath the canopy.Pseudochitinopoma grew faster in the weaker flows below canopies and bothCheilopora andMyxilla grew faster where there were no microalgal turfs. These other effects of kelp canopies were at least as important to growth (in the cases ofCheilopora andMyxilla) or more important to growth (in the case ofPseudochitinopoma) than were the general, deleterious effects of higher sedimentation beneath canopies.The lower growth rates caused by higher sedimentation beneath kelp canopies did not result in higher rates of animal mortality. Surprisingly, kelp canopies typically did not influence mortality due to predation. For 7 of 12 taxa, mortality rates did not differ between kelp-covered and exposed treatments. Significantly higher mortality occurred outside canopies for only 4 of 12 taxa, and for at least 2 of these 4 differences probably were not related to predation.Mytilus, a species rare at these depths, exhibited higher mortality beneath kelp canopies due to predation by crabs. Other macrophytes in fresh and salt water, as well as some benthic animals that create complex, 3-dimensional habitats, should influence benthic organisms and assemblages in ways analogous to the kelps acting through their effects on flow, particle transport, and shading.


In vivo short-term assays of repair and replication of rat liver DNA.
A short-term in vivo method for assay of repair and replication of rat liver DNA has been developed, by which possible hepatocarcinogens could be identified in a few days. F344 rats were treated orally with two genotoxic hepatocarcinogens, dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2AAF), or a nongenotoxic hepatocarcinogen, carbon tetrachloride (CCl4). Then at suitable times after treatment, their hepatocytes were isolated by a two-step collagenase perfusion technique in situ and incubated with [3H]dThd with or without hydroxyurea, which inhibits DNA replication. Their nuclear DNA was then extracted and the incorporation of [3H]dThd into nuclear DNA was determined in a liquid scintillation counter. Unscheduled DNA synthesis (DNA repair), induced by DMN at doses of 2.5-10 mg/kg body weight and by 2AAF at doses of 12.5-50 mg/kg body weight, could be detected 2 h and 4 h after their administration as an increase of DNA synthesis of up to 5.8-fold and 6.0-fold, respectively, in the presence of hydroxyurea. Replicative DNA synthesis, induced by CCl4 at a dose of 200 mg/kg body weight, could be detected 48 h after its administration as a 23-fold increase of DNA synthesis in the absence of hydroxyurea and was inhibited approximately 97%-99% by hydroxyurea. Replicative DNA synthesis induced by 2AAF at a dose of 25 mg/kg body weight 16 h after its administration could be detected as a 6.8-fold increase of DNA synthesis in the absence of hydroxyurea. These results show that unscheduled and replicative DNA synthesis can be clearly distinguished by simultaneous measurements of the incorporation of [3H]dThd into nuclear DNA in the presence and absence of hydroxyurea.


Antibiofilm efficacy of Leuconostoc mesenteroides J.27-derived postbiotic and food-grade essential oils against Vibrio parahaemolyticus, Pseudomonas aeruginosa, and Escherichia coli alone and in combination, and their application as a green preservative in the seafood industry.
Foodborne pathogen-mediated biofilms in food processing environments are severe threats to human lives. In the interest of human and environmental safety, natural substances with antimicrobial properties and generally regarded as safe (GRAS) status are the futuristic disinfectants of the food industry. In this study, the efficacy of bioactive, soluble products (metabolic by-products) from lactic acid bacteria (LAB) and plant-derived essential oils (EO) were investigated as biocidal agents. The postbiotic produced by kimchi-derived Leuconostoc mesenteroides J.27 isolate was analyzed for its metabolic components to reveal its antimicrobial potential against three pathogenic microorganisms (Vibrio parahaemolyticus, Pseudomonas aeruginosa, and Escherichia coli). Additionally, the efficacy of food-grade EO (eugenol and thymol, respectively) was also assessed in our study. Determination of the minimum inhibitory concentration (MIC) of postbiotic and EO against three tested pathogens revealed that the sub-MIC (0.5 MIC) of postbiotic and EO could efficiently inhibit the biofilm formation on both seafood (squid) and seafood-processing surfaces (rubber and low-density polyethylene plastic). Moreover, the polymerase chain reaction (PCR) analysis confirmed that the LAB J.27 isolate possesses bacteriocin- and enzyme-coding genes. The residual antibacterial activity of the produced postbiotic was maintained over a diverse pH range (pH 1-6) but was entirely abolished at neutral or higher pH values. However, the activity was unaffected by exposure to high temperatures (100 and 121 °C) and storage (30 days). Notably, the leakage of intracellular metabolites, damage to DNA, and the down-regulation of biofilm-associated gene expression in the pathogens increased significantly (p > 0.05) following the combination treatment of postbiotic with thymol compared to postbiotic with eugenol. Nonetheless, all in vitro results indicated the prospective use of combining Leu. mesenteroides J.27-derived postbiotic with both EO as a "green preservative" in the seafood industry to inhibit the formation of pathogenic microbial biofilms.


Post-resection mucosal margin shrinkage in oral cancer: quantification and significance.
The importance of tumor free margins in outcome of cancer surgery is well known. Often the pathological margins are reported to be significantly smaller than the in situ margins. This discrepancy is due to margin shrinkage the quantum of which has not been studied in patients with oral cancers. To quantify the shrinkage of mucosal margin following excision for carcinoma of the oral tongue and buccal mucosa. Mucosal margins were measured prior to resection and half an hour after excision in 27 patients with carcinoma of the tongue and buccal mucosa. The mean margin shrinkage was assessed and the variables affecting the quantum of shrinkage analyzed. The mean shrinkage from the in situ to the post resection margin status was 22.7% (P < 0.0001). The mean shrinkage of the tongue margins was 23.5%, compared to 21.2% for buccal mucosa margins. The mean shrinkage in T1/T2 tumors (25.6%) was significantly more than in T3/T4 (9.2%, P < 0.011). There is significant shrinkage of mucosal margins after surgery. Hence this should be considered and appropriate margins should be taken at initial resection to prevent the agony of post-operative positive surgical margins.


Alterations of sensory perceptions in healthy elderly subjects during fasting and refeeding. A pilot study.
Sensory perception losses may contribute to age-related malnutrition by affecting food selection and consumption. To determine the effects of a 36-hour fast followed by a 6-hour refeeding period on sensory perceptions in 7 healthy elderly subjects (65-80 years of age) and 6 healthy young subjects (18-35 years of age). Self-perceived hunger and olfactory ratings were recorded on visual analogue scales in response to three different classes of odorant stimuli (salt, sweet and sour). Odorant stimuli were administered three times during the study, twice during the fasting period (12 and 24 h fasted) and once at the end of the re-nutrition period. A significant difference was found between the two groups for the self-perceived hunger ratings in response to the sour stimuli. A significant difference was observed between the two groups for olfactory ratings as regards the salt and sour odorant stimuli. Among the metabolic changes associated with fasting and refeeding, blood glucose was significantly related (r(2) = 0.97, p = 0.001) to the perception of hunger in the control group subjects, but no such relationship was found for the elderly subjects (r(2) = 0.16, p = NS). (1) Self-perceived hunger and olfactory ratings are specifically affected in healthy elderly. (2) Nutritional status can modulate sensory perceptions in elderly and young during the transition from fasting to refeeding.


PEGylation of HPMA-based block copolymers enhances tumor accumulation in vivo: a quantitative study using radiolabeling and positron emission tomography.
This paper reports the body distribution of block copolymers (made by controlled radical polymerization) with N-(2-hydroxypropyl)methacrylamide (HPMA) as hydrophilic block and lauryl methacrylate (LMA) as hydrophobic block. They form micellar aggregates in aqueous solution. For this study the hydrophilic/hydrophobic balance was varied by incorporation of differing amounts of poly(ethylene glycol) (PEG) side chains into the hydrophilic block, while keeping the degree of polymerization of both blocks constant. PEGylation reduced the size of the micellar aggregates (Rh=113 to 38 nm) and led to a minimum size of 7% PEG side chains. Polymers were labeled with the positron emitter (18)F, which enables to monitor their biodistribution pattern for up to 4h with high spatial resolution. These block copolymers were investigated in Sprague-Dawley rats bearing the Walker 256 mammary carcinoma in vivo. Organ/tumor uptake was quantified by ex vivo biodistribution as well as small animal positron emission tomography (PET). All polymers showed renal clearance with time. Their uptake in liver and spleen decreased with size of the aggregates. This made PEGylated polymers--which form smaller aggregates--attractive as they show a higher blood pool concentration. Within the studied polymers, the block copolymer of 7% PEGylation exhibited the most favorable organ distribution pattern, showing highest blood-circulation level as well as lowest hepatic and splenic uptake. Most remarkably, the in vivo results revealed a continuous increase in tumor accumulation with PEGylation (independent of the blood pool concentration)--starting from lowest tumor uptake for the pure block copolymer to highest enrichment with 11% PEG side chains. These findings emphasize the need for reliable (non-invasive) in vivo techniques revealing overall polymer distribution and helping to identify drug carrier systems for efficient therapy.


Sleep onset latency is related with reduced bone mineral density in elderly people with insomnia: a retrospective study.
Inconsistent outcome about association between insufficient sleep and bone mineral density (BMD) has been reported. The present study aimed to determine whether BMD was associated with score of Pittsburgh Sleep Quality Index (PSQI). A total of 410 patients (mean age 81.6±5.9 years) attending our hospital for evaluation of sleep were retrospectively studied. Dual-Energy X-ray Absorptiometry was used to measure BMD and T-score at femoral neck and lumbar spines over L2-L4 regions. Subjective sleep status was evaluated by the PSQI questionnaires. The Mann-Whitney U test and chi-square analysis were used to compare continuous variables and categorical variables, respectively. Spearman correlation test was conducted to find the relationship between BMD and other clinical factors. Multinomial logistic regressions analysis was performed to analyze independent factors predicting BMD. Majority of the participants with osteoporosis (OP) were female and had lower body mass index (BMI) and higher sleep onset latency score. Spearman correlation test showed that gender, BMI, score of total PSQI, and sleep onset latency were significantly related to BMD and T-score in femoral neck and lumbar region L2-L4. Finally, multinomial logistic regression analysis demonstrated that gender and age were independent factors for OP and osteopenia and that after adjustment for gender, age, and BMI, sleep onset latency of <15 minutes (OR: 0.38; 95% CI: 0.15-0.96; P=0.04) and 16-30 minutes (OR: 0.37; 95% CI: 0.17-0.79; P=0.01) were less likely to have reduced BMD. There was a significant association between BMD and sleep onset latency, suggesting that, in elderly patients with sleep problem, BMD measurement and intervention for OP might be valuable.


Intravascular ultrasound estimation of arterial stenosis.
The evaluation of the degree of reduction in the cross-sectional area of an artery has important pathophysiologic and therapeutic implications. Currently, no technique can easily provide this information. In this in vitro study we evaluated the potential of a new imaging technique, intravascular high frequency ultrasound angioscopy, in the estimation of percentage of cross-sectional area stenosis of an artery. To do this, we compared intravascular high frequency ultrasound to previously-validated external high frequency ultrasound and to anatomic estimation of arterial stenosis. Using a prototype intraluminal imaging catheter with a 20 MHz ultrasound transducer at its tip, we imaged 20 arterial segments of various size (15 to 90 mm2 lumen area by anatomy) in the control state and after experimental stenosis. These arterial segments were also imaged by external high frequency ultrasound. Lumen areas were measured from calibrated ultrasound images in the control state and after stenosis, and percentage of cross-sectional area stenosis was calculated. These data were compared to the percentage of area stenosis derived from calibrated anatomic photographs of the arteries taken in the control state and after stenosis. Both intravascular ultrasound angioscopy and external high frequency ultrasound yielded high-resolution, two-dimensional, circumferential images of the arteries. Alterations in vessel area and shape were apparent after creation of stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of phosphorus nutrition on growth and metabolism of Duo grass (Duo festulolium).
Use of suitable plants that can extract and concentrate excess P from contaminated soil serves as an attractive method of phytoremediation. Plants vary in their potential to assimilate different organic and inorganic P-substrates. In this study, the response of Duo grass (Duo festulolium) to variable rates of soil-applied potassium dihydrogen phosphate (KH(2)PO(4)) on biomass yield and P uptake were studied. Duo grown for 5 weeks in soil with 2.5, 5 and 7.5 g KH(2)PO(4) kg(-1) soil showed a significantly higher biomass and shoot P content of 8.3, 11.4 and 12.3g P kg(-1) dry weight respectively compared to plants that received no soil added P. Also, the ability of Duo to metabolize different forms of P-substrates was determined by growing them in sterile Hoagland's agar media with different organic and inorganic P-substrates, viz. KH(2)PO(4), glucose-1-phosphate (G1P), inositiol hexaphosphate (IHP), adenosine triphosphate (ATP) and adenosine monophosphate (AMP) for 2 weeks. Plants on agar media with different P-substrates also showed enhanced biomass yield and shoot P relative to no P control and the P uptake was in the order of ATP>KH(2)PO(4)>G1P>IHP=AMP>no P control. The activities of both phytase (E.C.18.104.22.168) and acid phosphatases (E.C.220.127.116.11) were higher in all the P received plants than the control. Duo grass is capable of extracting P from the soil and also from the agar media and thus it can serve as possible candidate for phytoextraction of high P-soil.


Persistence of DNA from canine parvovirus modified-live virus in canine tissues.
Canine parvovirus (CPV-2) modified-live virus vaccine strain can replicate in lymphoid tissues and intestinal mucosa after administration, being shed through canine faeces. Detection of vaccine strains has been reported in the bloodstream and faeces, potentially interfering with molecular diagnostic tests. The persistence of these strains in canine tissues has not yet been described. With this aim, canine tissues were tested during a molecular survey to screen for the presence of canine enteric viruses. Tissue samples from 165 dead dogs were tested by a conventional PCR assay. Positive samples and five commercial vaccines were subjected to sequence analysis. Vaccinal strains were detected and virus load was measured by using a set of real-time PCR assays using minor-groove binder (MGB) probes. Seventy-five dogs (45.4%) tested positive for CPV-2. Strains from 70 dogs were characterised as field variants. The presence of CPV sequences of vaccine origin was observed in the spleen, intestine, and mesenteric lymph nodes of five young dogs. Vaccinal strains were detected from 12 to 24 days after the last vaccine administration. Viral loads comprised between 6.3 × 102 and 9.95 × 104 DNA copies/10 µl of template. This study confirms that CPV vaccinal strains can be detected in canine tissues after vaccination, so post-mortem diagnosis of CPV infection needs further molecular analyses to assess the viral type (vaccine or field strains). The present study updates the current information on the persistence of CPV vaccine strains in canine tissues and their possible interference with molecular assays.


Accessory cells provide more than one signal for lectin mitogen-stimulated proliferation of human lymphocytes.
A culture system was developed in which human peripheral blood mononuclear cells (PBMC) depleted of Ia-expressing cells did not proliferate in response to the lectin mitogen phytohemagglutinin (PHA). These cells were able to respond to mitogen if purified autologous accessory cells were added back to the culture, thus showing an absolute requirement for Ia-expressing accessory cells in mitogen-driven T-cell proliferation. The identity of these accessory cells was shown to be not only monocytes but also Ia-expressing B cells and possibly other unidentified Ia-bearing cell types. Human interleukin-1 (IL-1) in the lectin mitogen-unresponsive culture system was found unable to reconstitute normal human T-cell proliferation. This suggests that those cells with Ia surface antigen acting as accessory cells must deliver more than an IL-1 signal for T-cell proliferation. The phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was tested for its ability to replace necessary Ia-expressing accessory cells. TPA was able to replace accessory cells in culture, thus mimicking the Ia-expressing accessory cells and all their delivered signals in the triggering of human lymphocytes.


StackCBPred: A stacking based prediction of protein-carbohydrate binding sites from sequence.
Carbohydrate-binding proteins play vital roles in many important biological processes. The study of these protein-carbohydrate interactions, at residue level, is useful in treating many critical diseases. Analyzing the local sequential environments of the binding and non-binding regions to predict the protein-carbohydrate binding sites is one of the challenging problems in molecular and computational biology. Existing experimental methods for identifying protein-carbohydrate binding sites are laborious and expensive. Thus, prediction of such binding sites, directly from sequences, using computational methods, can be useful to fast annotate the binding sites and guide the experimental process. Because the number of carbohydrate-binding residues is significantly lower than the number of non-carbohydrate-binding residues, most of the methods developed for the prediction of protein-carbohydrate binding sites are biased towards over predicting the negative class (or non-carbohydrate-binding). Here, we propose a balanced predictor, called StackCBPred, which utilizes features, extracted from evolution-driven sequence profile, called the position-specific scoring matrix (PSSM) and several predicted structural properties of amino acids to effectively train a Stacking-based machine learning method for the accurate prediction of protein-carbohydrate binding sites (https://bmll.cs.uno.edu/).


The binding of Chlamydia trachomatis and zinc to McCoy cells (mouse fibroblasts).
Zinc was found to have profoundly different effects upon the infection of McCoy cells (mouse fibroblasts) by two strains of Chlamydia trachomatis dependent upon the time and concentration of zinc exposure. Radiolabeled zinc-65 became McCoy cell-associated in a manner independent of incubation temperature, but highly dependent on incubation time and zinc concentration. This effect was maximal after 30 to 60 minutes of incubation. Correspondingly, incubation of a chlamydia inoculant with McCoy cells and supplemental zinc (10(-5) to 10(-4) M) for 1 h was associated with significantly (approximately twofold) more binding of the chlamydia to the McCoy cells compared with control media (8 X 10(-6) M Zn). More prolonged incubation of the chlamydia and McCoy cells with supplemental zinc was associated with significantly fewer chlamydia inclusions. Concentrations of 5 X 10(-4) M zinc or higher were also found to be toxic to the McCoy cells after 48 h of incubation. Brief exposure to supplemental zinc may augment infection of cells by chlamydia: however, more prolonged exposure to the same concentrations of zinc lessens cellular infection by chlamydia.


The Adolescent Cannabis Check-Up: feasibility of a brief intervention for young cannabis users.
In this study, we assessed the feasibility and effectiveness of the Adolescent Cannabis Check-Up (ACCU), a brief intervention for young cannabis users. For this initial feasibility study, we used an uncontrolled pre-test/post-test design. Participants were cannabis users aged between 14 and 19 years (n = 73) and concerned parents (n = 69). The intervention comprised an individual assessment session followed 1 week later by a session of personalized feedback delivered in a motivational interviewing style. An optional third session that focused on skills and strategies for making behavioral change was offered. Of the entire sample of cannabis users, 78% reported voluntarily reducing or stopping their cannabis use during the 90 days to follow-up and 16.7% reported total abstinence during this time. In addition, significant reductions were found on measures of both quantity and frequency of use and dependence. These reductions were maintained at 6-month follow-up. Clearly, these preliminary findings must be interpreted with caution given the study design and absence of a control group. The ACCU was, however, able to attract and retain young cannabis users who were not necessarily interested in change. The approach was acceptable to young people and associated with reductions in cannabis use. It appears to be a model that warrants further research in early and brief interventions for this population.


Rhinocerebral zygomycosis: an increasingly frequent challenge: update and favorable outcomes in two cases.
Zygomycosis or mucormycosis is an increasingly frequent life-threatening infection caused by opportunistic fungal organisms of the class Zygomycetes. The pathognomonic feature is the presence of invasive aseptate mycelia that are larger than other filamentous fungi with the hyphae exhibiting right angle and haphazard branching. Usually classified as rhinocerebral, disseminated, and cutaneous types, this classification serves as important predictor of pathogenesis and outcome. These occur mostly in immunosuppressed patients including individuals with diabetes (43% exhibit the rhino-cerebral form) and patients with organ transplants and hematologic malignancies. Without early aggressive treatment, the disease follows a dismal and fatal course. The prognosis has not shown any appreciable change in the past 40 years with a stagnant mortality rate of 44%. We present 2 cases of rhinocerebral zygomycosis (RCZ), in a 58-year-old male and a 63-year-old female; both were poorly controlled diabetic patients with maxillary lesions suggestive of osteomyelitis. The patients were leading a near normal life with minimal discomfort or signs and symptoms of underlying mycosis. Most of the health care professionals treating these patients often overlooked the disease or recommended inadequate therapy. Despite long delays and inadequate initial therapy these patients survived with little outward morbidity. The prognosis for this condition may therefore be considered less dire than previously thought.


Anti-tick monoclonal antibody applied by artificial capillary feeding in Rhipicephalus (Boophilus) microplus females.
The tick Rhipicephalus microplus is an ectoparasite harmful to livestock, a vector of disease agents that affects meat and milk production. However, resistance to acaricides reflects the need for alternative tick control methods, among which vaccines have gained increasing relevance. In this scenario, monoclonal antibodies can be used to identify and characterize antigens that can be used as vaccine immunogens. Capillary tube artificial feeding of partially engorged R. microplus females with monoclonal antibodies against proteins from the gut of tick were used to test the effects of immunoglobulins in the physiology of the parasite. The results of artificial feeding showed that female ticks over 25mg and under 60 mg in weight performed better in the artificial feeding process, with a 94-168% weight increase after 24h of feeding. Results showed that artificial feeding of ticks proved to be a viable technique to study the effects of antibodies or drugs in the physiology of the parasite. One monoclonal antibody (BrBm2) induced decreased oviposition. Moreover, the antigen recognized by BrBm2 was identified as a 27-kDa protein and immunolabeled on digestive vesicles membranes of digestive cells of partially and fully engorged females.


Intraoperative Parathormone Monitoring Mitigates Age-Related Variability in Targeted Parathyroidectomy for Patients with Primary Hyperparathyroidism.
Preoperative parathyroid localization studies, namely, sestamibi (MIBI) and surgeon-performed ultrasound (SUS), are commonly used for targeted parathyroidectomy (PTX) with intraoperative parathormone monitoring (IPM) in patients with primary hyperparathyroidism (pHPT). This study examined age-related variability in abnormal parathyroid gland localization for targeted PTX and the value of IPM across age groups. A retrospective review examined prospectively collected data of 833 patients who underwent targeted PTX guided by IPM. The patients were stratified into three age groups as follows: younger [<47 years; mean -1 standard deviation (SD)], typical (47-73 years), and older (>73 years; mean +1 SD) based on an age distribution curve for pHPT. The accuracy, sensitivity, and positive predictive value (PPV) for MIBI, SUS, and IPM were analyzed and compared among age groups. Operative success was defined as eucalcemia for 6 months or longer after PTX, and operative failure was defined as elevated calcium and PTH levels within 6 months after PTX. Of the 833 patients, the youngest group had the highest accuracy and sensitivity for MIBI, SUS, and IPM compared with the older groups (p < 0.05). The accuracy and sensitivity of MIBI and SUS also decreased significantly with increased age (p < 0.05). Within all three age groups, IPM was consistently more accurate and sensitive than SUS or MIBI (p < 0.05). Age can significantly affect the accuracy and sensitivity of MIBI and SUS in targeted PTX for patients with pHPT. Across all age groups, IPM remains more accurate than preoperative localization studies. For the elderly, in whom multiglandular disease appears increased, surgeons should have a lower threshold for conversion to bilateral neck exploration.


Allergy Testing - An Overview.
Childhood allergies pose huge economic burden and adverse effects on quality of life. Serum IgE has been considered a surrogate allergy marker for decades. Availability of several over-the-counter allergy tests add to confusion of partially trained caregivers. The present review focuses on current status of allergy testing in Indian scenario. Various in-vitro and in-vivo diagnostic modalities are available for allergy detection. Skin prick tests are useful for aero-allergies whereas oral challenge tests are best for identifying suspected food allergies. An allergy test should be individualized based on clinical features, diagnostic efficacy, and cost-benefit analysis.


Effects of intravenous chemotherapy after TURBT for high-risk nonmuscle invasive bladder cancer: results of a retrospective study.
This study compared the efficacy and safety of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for high-risk nonmuscle invasive bladder cancer (HRNMIBC) patients after transurethral resection of the bladder tumor (TURBT) surgery. A retrospective analysis was performed on 349 HRNMIBC cases admitted to TangDu hospital between January 2014 and June 2019. After TURBT, 262 patients received intravesical chemotherapy alone, whereas 87 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. The recurrence rate and progression rate were assessed by Chi-square test, the prognostic factors for tumor recurrence were predicted by univariable and multivariable Cox hazards analyses, recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. In this study, the recurrence rate was 24.7% (19/77) in the intravenous chemotherapy combined group and 41.6% (102/245) in the intravesical chemotherapy group, while the progression rate was 6.5% (5/77) and 14.3% (35/245) in the two groups respectively. The two groups differed significantly in recurrence rate (p = 0.007) while the progression rate did not show a significant difference (p = 0.071). Multivariable analyses revealed that additional intravenous chemotherapy treatment was an independent prognostic factor for tumor recurrence in the cohort (hazard ratio [HR], 0.495, 95% confidence interval [CI], 0.275-0.892, p = 0.019). Kaplan-Meier curves showed significant differences in RFS and PFS between the two groups, with a log-rank P value of p < 0.005 and p = 0.045, respectively. Grade 3/4 toxicity was reported in 2 of 77 patients in the intravenous chemotherapy combined group, including nausea/vomiting 1.3% (1/77) and hypoleukemia 1.3% (1/77). Intravenous chemotherapy of gemcitabine and cisplatin combined with intravesical chemotherapy after TURBT can effectively reduce the postoperative recurrence rate, most toxicities were minor and reversible, and it may be considered as a new choice for HRNMIBC patients.


Dietary galactooligosaccharide affects intestinal microbiota, stress resistance, and performance of Caspian roach (Rutilus rutilus) fry.
The aim of this study was to assess the effects of galactooligosaccharide (GOS), on the growth performance, stress resistance and intestinal microbiota of Caspian roach (Rutilus rutilus) fry. Specimens (1.36 ± 0.03 g) were fed either a basal control diet (0% GOS, non-supplemented) or the basal diet supplemented with 1% and 2% of GOS. After 7 weeks of the feeding trials, growth factors (final weight, weight gain, specific growth rate, condition factor and food conversion ratio) as well as body composition, resistance to salinity stress and autochthonous intestinal microbiota were assessed. Results demonstrated that at the end of the trial growth factors (final weight, weight gain, SGR, FCR) were significantly higher in 2% GOS fed fish (P < 0.05). In addition, supplementation of GOS significantly increased both survival rate (P < 0.05), and resistance to a salinity stress challenge of prebiotic fed groups (P < 0.05). However, body composition and the total autochthonous intestinal heterotrophic bacteria counts remained unaffected in different treatments (P > 0.05). Nevertheless, autochthonous lactic acid bacteria levels were significantly elevated in fish fed 2% dietary GOS (P < 0.05). These results confirm that GOS improves growth performance, stress resistance and modulates intestinal microbiota by increasing lactic acid bacteria of Caspian roach fry, a very important fish species in the Caspian Sea.


Meta-analysis of associations of genetic polymorphisms with cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are among the most hazardous complications of aneurysmal subarachnoid hemorrhage (aSAH). Genetic factors are thought to play a significant role in the development of both complications. To perform a comprehensive meta-analysis of studies that study the association between different genetic polymorphisms and development of DCI and/or CV. We searched MEDLINE and Science Direct databases on May 29, 2021, using iterations of the keywords "subarachnoid hemorrhage", "vasospasm", "delayed cerebral ischemia", and "gene". After duplicates were removed, the two reviewers screened the titles of the articles and abstracts independently. A random-effect model was used to calculate the relative risk with 95% CI; a fixed-effect model was additionally explored. We pooled data from 16 articles that reported an association between eNOS, apolipoprotein E4 (ApoE4), haptoglobin (Hp), or ryanodine-1 (RYR-1) and CV, DCI, or both. Presence of Hp 2-2 was associated both with CV (RR 2.10, 95% CI 1.33-3.31, p = 0.0014) and DCI (RR 1.57, 95%CI 1.06-2.34, p = 0.026). ApoE4 allele had a borderline association with CV (RR 1.48, 95%CI 0.99-2.21, p = 0.054). Our meta-analysis supports the association between the presence of the Hp2-2 allele and the occurrence of CV and DCI after aSAH. Further studies investigating this association are needed to reinforce this finding.


Inclusion and equity in education: Current policy reform in Nova Scotia, Canada.
This article aims to explore the context of inclusive education policy in Canada, and to highlight the particular case of inclusive education policy reform in the province of Nova Scotia. As with most other provinces and territories, inclusive education policy in Nova Scotia has broadened to include a lens of equity, with a focus on not only students with special education needs, but all students - particularly those most often marginalized by and within Canadian school systems. The article reflects on the first phase of the developmental evaluation process which took place prior to full implementation of the policy. Four interconnected key themes emerge: 1) the shifting roles and identities for educators and specialized staff; 2) the changing roles of classroom teachers; 3) the importance of support to ensure effective universal and differentiated classroom practices; and 4) the professional learning of school staff. Although situated within the Nova Scotian and the national Canadian context, the discussion and implications can readily be applied to international systems engaged in developing and implementing broad inclusive education policy.


Energy budgets for populations of long-lived arthropod predators (Chilopoda: Lithobiidae) in an old beech forest.
Energy budgets are derived for two chilopod populations-Lithobius mutabilis L. Koch and L. curtipes C.L. Koch (Chilopoda, Lithobiidae)-in a 125-year-old beech stand in the Solling, Northern West Germany. Lithobiids were sampled from February 1972 to July 1975 by monthly quadrat samples (12 samples of 625 cm2 each) which were extracted in an apparatus slightly modified after Kempson (Kempson et al. 1963; Weidemann 1971). Regression equations are set up relating fresh weight to width of the cephalic shield and dry weight to fresh weight. The calorific content is estimated by use of literature data. Oxygen consumption is estimated from laboratory measurements in a Warburg apparatus. The values have been corrected for temperature fluctuations in the field and should be increased by a factor of about 1.75 to account for the higher activity of lithobiids in the field. Energy balances for average individuals of L. mutabilis and L. curtipes are presented. An average individual of L. mutabilis produces in the course of its life about 0.42 kJ, respires 0.92 kJ (laboratory value) or 1.6 kJ when increased activity in the field (f.a.) is taken into account. An average individual of L. curtipes produces about 0.18 kJ and respires 0.40 kJ, or 0.7 kJ (f.a.). Production, respiration, and assimilation of the populations are estimated by multiplying the energetic values obtained for the different instars of the average individual with the number of instars occurring per year (average individual method). Population biomass and respiration is obtained by a "direct method". By means of regression equations fresh weight, dry weight, energy content, and oxygen consumption of each animal extracted were determined and from this the population energy budget established.The values for the L. mutabilis population are: abundance 55 individuals m-2, biomass 2.9 kJ m-2, production 2.55 kJ m-2, respiration 5.5 kJ m-2 or 9.6 kJ m-2 (f.a.), and assimilation 8.0 kJ m-2 or 12.2 kJ m-2 (f.a.). The values for the L. curtipes population are: abundance 39 individuals m-2, biomass 0.9 kJ m-2, production 1.1 kJ m-2, respiration 2.3 kJ m-2 or 4.0 kJ m-2 (f.a.), assimilation 3.3 kJ m-2 or 5.1 kJ m-2 (f.a.). The fit of the values obtained for production and respiration to the regression equations of McNeill and Lawton (1970), Shorthouse (1971), and Humphreys (1979) is discussed. It is argued that the production values given for two lithobiid populations by Wignarajah (1968), which were used by McNeill and Lawton and Humphreys for their regression equations, are severely underestimated. Regarding the relationship between biomass and production, the values show fairly good agreement with regression equations between production: biomass ratio and life length, but not with equations relating production: biomass ratio and body weight. Both chilopod species together contribute about 17%-27% to total assimilation by predatory macroarthropods in the system studied. Total consumption of the L. mutabilis population is estimated as 35.5 kJ m-2, of the L. curtipes population as 14.8 kJ m-2. This is about 3%-4% of mean annual production of total soil fauna.


Limitations of a TCP model incorporating population heterogeneity.
The variation between individuals in their dose-response characteristics complicates attempts to extract estimates of radiobiological parameters (e.g. alpha, beta, etc) from fits to clinical dose-response data. The use of 'population' dose-response models that explicitly account for this variability is necessary to avoid obtaining skewed parameter estimates. In this work, we evaluated an example of a 'population' tumour control probability (TCP) model in terms of its ability to provide reliable parameter estimates. This was accomplished by performing fits of this population model to 'pseudo' data sets, which were generated with Monte Carlo techniques and based on preset values for the various radiobiological parameters. The fitting exercises illustrated considerable correlations between the model parameters. Especially significant was the large correlation observed between the parameter mu=alpha/sigmaalpha used to characterize the level of population heterogeneity in radiosensitivity and the alpha/beta parameter typically used to describe the response to fractionation. The results imply that fits to clinical data may not be able to distinguish between tumours exhibiting a high degree of heterogeneity and a strong beta-mechanism and those containing little heterogeneity and having a weak beta-mechanism. One implication is that basing the design of optimal fractionation regimes on such fitting results may be error-prone. If in vitro assays are to be used to independently determine biologically reasonable ranges for parameter values, an accurate knowledge of the relationship between in vitro and in vivo dose-response characteristics is required.


Performance improvement of keV Neutrons-based PGNAA setups.
The performance of keV neutrons based Prompt Gamma Ray Neutron Activation Analysis (PGNAA) setups have been observed to improve by enclosing its neutron source inside the moderator. The keV neutrons were produced via (7)Li(p,n) reaction and (3)H(p,n) reactions. For the two PGNAA setups, the maximum intensity of the prompt gamma-ray yield was observed for a 5cm long moderator with the neutron source positioned at a distance of 0.5cm from the moderator-end facing the sample. Due to enclosing the source inside the moderator, the prompt gamma-ray yield from the (7)Li(p,n) reaction and (3)H(p,n) reaction based PGNAA setups have increased by a factor of three as compared to that achieved from these setups with the source outside the moderator. This study provides a theoretical basis for the measurement of performance of (7)Li(p,n) reaction and the (3)H(p,n) reaction based PGNAA setups.


The cross-cultural adaptation and reliability of the online Hebrew version of the extended Nordic Musculoskeletal Questionnaire.
The Nordic Musculoskeletal Questionnaire assesses musculoskeletal (NMQ) symptoms in occupational environments. Physiotherapists are known to work with their bodies, and hence prone to occupational musculoskeletal injuries. To date, there is no Hebrew version of the extended version of the NMQ (NMQ-E). To cross-culturally adapt the NMQ-E into Hebrew and evaluate the intra-rater reliability of the online Hebrew version (HNMQ-E) in a population of physiotherapists. After cross-cultural adaptation, test-retest reliability over a week was assessed with 65 participants who had no change in their health status over the past week. Statistical analysis included the calculation of Cohen's kappa coefficient (κ), observed proportions of agreement, and intraclass correlations. Intra-rater reliability for the prevalence of pain was moderate to substantial (κ = 0.51-0.80), and highly variable agreement for questions about pain consequences (κ = 0.20-0.94). Observed proportions of agreement were higher than 0.78 for all the items. The mean completion time of the survey was 6:30 ± 3:37. The online version of the HNMQ-E has been found to be reliable and practical. Future studies on the properties of the HNMQ-E should investigate more general working populations.


Synthesis and characterization of G5 PAMAM dendrimer containing daunorubicin for targeting cancer cells.
A multifunctional dendritic nanodevice containing folate (FA) as the targeting molecule and daunorubicin (DNR) as the chemotherapeutic drug has been designed and synthesized. The primary amino groups on the surface of the generation 5 poly(amidoamine) dendrimer (G5 dendrimer) were acetylated partially. FA and DNR were conjugated to the remaining primary amino groups on the G5 dendrimer through amide and ester linkage, respectively, to generate the difunctional dendritic device. The synthetic approach of G5 PAMAM dendrimer containing daunorubicin and folic acid would be useful for targeting the overexpressed membrance-associated folate receptors of KB human carcinoma cell line and discreating them effectively.


Physiological determinants of growth rate in response to phosphorus supply in wild and cultivated Hordeum species.
Under favorable nutrition, accessions of the weedy barleygrass (Hordeum leporinum and H. glaucum) had a higher relative growth rate (RGR) than did accessions of cultivated barley (H. vulgare) or its wild progenitor (H. spontaneum). RGR was not positively correlated with the presumed level of soil fertility at the collection site of an accession either within or among species. RGR was reduced more strongly by low-P supply in the progenitor than in the crop or weed, indicating that selection of cultivars to grow in fertile soils had not reduced their potential to grow effectively under low-P conditions. Seed and embryo masses were more important than RGR in determining plant size. Relative differences among assessions in plant size declined with time, because (1) accessions with small seeds had a higher RGR, and (2) RGR of large-seeded accessions declined with time. Absolute growth rate correlated positively with leaf area and negatively with photosynthetic rate per unit leaf area. Under favorable nutrition, maximum photosynthetic rate correlated negatively with leaf length and therefore was higher in the weeds than in the crop or progenitor accessions. P absorption potential did not differ consistently among species but generally increased in response to P stress. Cultivars produced a few tall tillers, whereas weeds and progenitors produced many small tillers. The cultivar had a larger proportion of reproductive tillers, allocated a larger proportion of biomass to grain, and produced larger grains than did the weedy accession. By contrast, the weed began maturing seeds sooner, produced more reproductive tillers, and produced more grains per car and per plant than did the cultivar. The study suggests two major conclusions: (1) A low RGR is not an adaptation to low P supply in annual Hordeum species. (2) Seed size is the major determinant of early plant size between accessions in these Hordeum species under favorable nutrition. However, large seed size indirectly results in a low RGR because of the inverse relationship between plant size and RGR and results in a low photosynthetic rate because of the inverse relationship between leaf size and photosynthesis.


Stapedial electromyograms recorded by electrocochleography.
The stapedial reflex (SR) can be obtained by the impedance method only when the middle ear is intact. In order to examine the function of the stapedius muscle in diseased ears, the recording of the stapedial electromyogram by an electrocochleographic (ECoG) method was considered. The SR was recorded simultaneously by the impedance method in ten normal subjects for comparison. The outputs of ECoG were averaged by a signal processor up to 200 times under a longer sweep time, and a large biphasic wave with a latency of about 11 ms was obtained on the ECoG records. The amplitude increase of the biphasic wave caused by raising the intensity of the acoustic stimulation paralleled that of the SR. This means that the biphasic wave obtained by ECoG with a latency of about 11 ms originated from the stapedius muscle.


Extended reality veterinary medicine case studies for diagnostic veterinary imaging instruction: Assessing student perceptions and examination performance.
Educational technologies in veterinary medicine aim to train veterinarians faster and improve clinical outcomes. COVID-19 pandemic, shifted face-to-face teaching to online, thus, the need to provide effective education remotely was exacerbated. Among recent technology advances for veterinary medical education, extended reality (XR) is a promising teaching tool. This study aimed to develop a case resolution approach for radiographic anatomy studies using XR technology and assess students' achievement of differential diagnostic skills. Learning objectives based on Bloom's taxonomy keywords were used to develop four clinical cases (3 dogs/1 cat) of spinal injuries utilizing CT scans and XR models and presented to 22 third-year veterinary medicine students. Quantitative assessment (ASMT) of 7 questions probing 'memorization', 'understanding and application', 'analysis' and 'evaluation' was given before and after contact with XR technology as well as qualitative feedback via a survey. Mean ASMT scores increased during case resolution (pre 51.6% (±37%)/post 60.1% (± 34%); p < 0.01), but without significant difference between cases (Kruskal-Wallis H = 2.18, NS). Learning objectives were examined for six questions (Q1-Q6) across cases (C1-4): Memorization improved sequentially (Q1, 2 8/8), while Understanding and Application (Q3,4) showed the greatest improvement (26.7%-76.9%). Evaluation and Analysis (Q5,6) was somewhat mixed, improving (5/8), no change (3/8) and declining (1/8).Positive student perceptions suggest that case studies' online delivery was well received stimulating learning in diagnostic imaging and anatomy while developing visual-spatial skills that aid understanding cross-sectional images. Therefore, XR technology could be a useful approach to complement radiological instruction in veterinary medicine.


Immunoregulatory effects of alpha-interferon. Effects on in-vitro antibody synthesis by lymphocytes from patients with rheumatoid arthritis.
The immunosuppressive effects of alpha-interferon (IFN) on the in-vitro synthesis of specific anti-influenza virus antibody by lymphocytes from 20 healthy donors were compared with those from 12 patients with rheumatoid arthritis. No differences were observed between the two groups. IFN suppressed the induction of in-vitro antibody synthesis by lymphocytes from rheumatoid donors but did not affect antibody synthesis once this had been initiated. Furthermore, the IFN-mediated suppression of antibody synthesised by rheumatoid lymphocytes could also be reversed by B cell helper supernatant. These findings make it unlikely that alpha-IFN affects established B cell responses characteristic of the rheumatic diseases.


The effect of PD-1 expression on tumor-associated macrophage in T cell lymphoma.
Our study aimed to explore the programmed death 1 (PD-1) expression on tumor-associated macrophage (TAM) in T cell non-Hodgkin lymphoma (T-NHL) and its relationship with lymphoma prognosis. The effect of PD-1 expression on the function of macrophages was also studied. Multispectral image quantitative analysis was applied for detecting PD-1 expression on macrophages in T cell lymphoma tissues. The Kaplan-Meier analysis was performed to evaluate the value of PD-1 expression of TAM in predicting the overall survival of T-NHL. PD-1 overexpression THP-1-derived macrophage was constructed and was cocultured with Jurkat cells to explore the effect of PD-1 on macrophage function. In 17 T cell lymphoma cases, the 1-year overall survival rate was significantly lower in patients with higher PD-1 expression on TAMs (0.25 vs 0.86, p < 0.05). After co-cultured with Jurkat cells, classically activated (M1)-related markers on PD-1 overexpressed macrophages were significantly lower than those on controls, while the expressions of alternatively activated (M2) related markers were similar. The PD-1 overexpressed macrophages showed inhibited phagocytosis (4.42% vs 40.7%, p < 0.001) and increased IL-10 secretion (144.48 pg/ml vs 32.32 pg/ml, p < 0.001). High PD-1 expression on TAMs in T-NHL may predict poor prognosis. The PD-1 overexpression of macrophages significantly inhibited polarization of M1 macrophages and phagocytosis, and more IL-10 was excreted. These changes may enhance the pro-tumor effects of tumor microenvironment.


Comparisons between in vitro whole cell imaging and in vivo zebrafish-based approaches for identifying potential human hepatotoxicants earlier in pharmaceutical development.
Drug-induced liver injury (DILI) is a major cause of attrition during both the early and later stages of the drug development and marketing process. Reducing or eliminating drug-induced severe liver injury, especially those that lead to liver transplants or death, would be tremendously beneficial for patients. Therefore, developing new pharmaceuticals that have the highest margins and attributes of hepatic safety would be a great accomplishment. Given the current low productivity of pharmaceutical companies and the high costs of bringing new medicines to market, any early screening assay(s) to identify and eliminate pharmaceuticals with the potential to cause severe liver injury in humans would be of economic value as well. The present review discusses the background, proof-of-concept, and validation studies associated with high-content screening (HCS) by two major pharmaceutical companies (Pfizer Inc and Jansen Pharmaceutical Companies of Johnson & Johnson) for detecting compounds with the potential to cause human DILI. These HCS assays use fluorescent-based markers of cell injury in either human hepatocytes or HepG2 cells. In collaboration with Evotec, an independent contract lab, these two companies also independently evaluated larval zebrafish as an early-stage in vivo screen for hepatotoxicity in independently conducted, blinded assessments. Details about this model species, the need for bioanalysis, and, specifically, the outcome of the phenotypic-based zebrafish screens are presented. Comparing outcomes in zebrafish against both HCS assays suggests an enhanced detection for hepatotoxicants of most DILI concern when used in combination with each other, based on the U.S. Food and Drug Administration DILI classification list.


Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo.
The accumulation of p53 protein following whole body irradiation of adult mice was studied using a new polyclonal antibody to mouse p53. While dramatic accumulation of the protein was apparent in splenocytes, thymocytes and osteocytes no p53 protein accumulation was detected in the hepatocytes of the irradiated mouse. Thus, the upstream initiating signals that control the induction of p53 are controlled in a tissue specific manner. While massive apoptosis accompanies p53 induction in thymocytes and splenocytes it is not seen in the osteocytes. Thus the downstream consequences of p53 induction are also tightly controlled. These results have profound significance for an understanding of the role of the p53 tumour suppression pathway in different tissues.