Hyperbolic geometry of gene expression.
Patterns of gene expressions play a key role in determining cell state. Although correlations in gene expressions have been well documented, most of the current methods treat them as independent variables. One way to take into account gene correlations is to find a low-dimensional curved geometry that describes variation in the data. Here we develop such a method and find that gene expression across multiple cell types exhibits a low-dimensional hyperbolic structure. When more genes are taken into account, hyperbolic effects become stronger but representation remains low dimensional. The size of the hyperbolic map, which indicates the hierarchical depth of the data, was the largest for human cells, the smallest for mouse embryonic cells, and intermediate in differentiated cells from different mouse organs. We also describe how hyperbolic metric can be incorporated into the t-SNE method to improve visualizations compared with leading methods.


Width of spared neurovascular bundle after robot-assisted laparoscopic prostatectomy in patients with prostate cancer: is it a reliable factor for predicting postoperative sexual outcome?
To investigate the relationship between the width of spared neurovascular bundle (NVB) measured during robot-assisted laparoscopic prostatectomy and postoperative sexual outcomes. Patients with localized prostate cancer with erectile hardness score ≥2 (N = 105) who underwent NVB-sparing robot-assisted laparoscopic prostatectomy were included. Patients were divided into three groups [first (Q1) vs. second and third (Q2-3) vs. fourth (Q4) quartile] according to width of spared NVB measured with a flexible ruler after prostate removal. Preoperative and postoperative sexual function was evaluated according to erectile hardness score and Expanded Prostate Cancer Index Composite questionnaires. The proportion of patients with postoperative erectile hardness score ≥2 at postoperative 6 months was as follows: 38.9% (Q1), 48.6% (Q2-3), and 83.3% (Q4) (P = 0.016). The preoperative/postoperative 6-month sexual function score was 40.7/16.9 (Q1), 48.1/19.0 (Q2-3), and 51.2/28.1 (Q4). Postoperative sexual function was significantly associated with preoperative sexual function in Q4 (P = 0.006) and Q2-3 (P = 0.030) but not in Q1. On multivariate analysis, the width of spared NVB was a significant predictor for postoperative 6-month erectile hardness score ≥2. Limitation includes selection bias and short follow-up duration. Not only the performance but also the degree and quality of NVB sparing thought to be important for postoperative sexual function. Measurement of the width of NVB during surgery could be an easy intraoperative method for assessing the quality of NVB sparing.


Phialophora verrucosa infection in a BMT patient.
Phialophora is a dematiaceous fungus isolated from soil and wood. Human infections including chromoblastomycosis, mycotic keratitis, cutaneous infections, and prosthetic valve endocarditis have been reported. We report a case of fatal hemorrhage due to Phialophora verrucosa in a patient with prolonged neutropenia undergoing autologous bone marrow transplant (BMT) for acute myelogenous leukemia (AML). Bacterial infections complicated induction and consolidation chemotherapies. Liposomal amphotericin B (LAMB) was given from day +33 to day +72 for febrile neutropenia. Death occurred on day +74 due to tracheal hemorrhage. Autopsy revealed granulation tissue on the posterior wall of the trachea with fungal hyphae on histopathology; the tissue grew Phialophora verrucosa. In vitro susceptibility studies revealed a minimum inhibitory concentration to AmB of 0.1 microg/ml. This represents the first reported case of invasive P. verrucosa in a BMT patient leading to fatal hemorrhage, despite large cumulative doses of LAMB to which the organism remained susceptible.


Ten-year follow-up of kidney transplantation from hepatitis B surface antigen-positive donors.
Hepatitis B surface antigen positivity (HBsAg(+)) was believed to be an exclusion for kidney donation. However, in the presence of an organ shortage, allocation of kidneys from HBsAg(+) donors to recipients with anti-HBsAb(+) might be allowed. We examined the 10-year outcomes of kidney transplants (KT) from HBsAg(+) donors to natural or vaccine-induced anti-HBsAb(+) recipients (Group 1). Hepatitis B hyperimmune globulin (HBIG) and lamivudine were not used at any time. We compared the 10-year outcomes of patients who had HBsAg(+) prior to KT and received kidneys from HBsAg(-) donors (Group 2). The endpoint was patient survival determined by Kaplan-Meier and Cox proportional hazard methods. A total of 41 patients were transplanted from 1991-1997. There were 14 Group 1 patients and 27 Group 2 patients. Anti-HBsAb titer ranged from 10 to >1000 mIU/mL. Actuarial 10-year patient survivals were 92.8% and 62.5% for Group 1 and Group 2. Only 1 patient in Group 1 died; this case was due to an acute myocardial infarction. Eleven deaths occurred among Group 2; they were due to chronic active hepatitis (n = 5), hepatoma (n = 3), acute fibrosing cholestatic hepatitis (n = 1), and stroke (n = 2). More than 2 times elevated ALT occurred among 45% of Group 2 but none in Group 1. No patients in Group 1 had positive HBsAg and HBV DNA at last follow-up. Four patients in Group 2 displayed seroconversion to positive HBeAg after KT. Secondary analysis examining the impact of KT on patient life expectancy (from the start of dialysis until last follow-up) used Cox regression, revealing that KT was significantly associated with an increased risk for death within 12 months after transplantation (RR = 30, P = .005) but a decreased risk for death thereafter (RR = .03, P = .005) for Group 2. However, KT did not have significant impact on the risk for death within the first year for Group 1 (P = .61). Our results showed that the 10-year survival of KT from HBsAg(+) donors to recipients with anti-HBsAb(+) was good. This was not associated with evidence of active liver disease. The presence of HBsAg(+) in donors thus should not be considered an exclusion for kidney donation for anti-HBsAb(+) recipients.


Genome-wide studies reveal that Lin28 enhances the translation of genes important for growth and survival of human embryonic stem cells.
Lin28 inhibits the expression of let-7 microRNAs but also exhibits let-7-independent functions. Using immunoprecipitation and deep sequencing, we show here that Lin28 preferentially associates with a small subset of cellular mRNAs. Of particular interest are those for ribosomal proteins and metabolic enzymes, the expression levels of which are known to be coupled to cell growth and survival. Polysome profiling and reporter analyses suggest that Lin28 stimulates the translation of many or most of these targets. Moreover, Lin28-responsive elements were found within the coding regions of all target genes tested. Finally, a mutant Lin28 that still binds RNA but fails to interact with RNA helicase A (RHA), acts as a dominant-negative inhibitor of Lin28-dependent stimulation of translation. We suggest that Lin28, working in concert with RHA, enhances the translation of genes important for the growth and survival of human embryonic stem cells.


[Purification and characterization of peroxidase from Phellinus igniarius (author's transl)].
A Peroxidase (EC 22.214.171.124) of the basidiomycet Phellinus igniarius was derived from mycel and a medium containing glucose and extract of yeast by using various methods of preparation. The enzyme resists extreme conditions (pH, temperature salt concentration). Its optimum pH for activities is in the acid range. Two isoenzymes were found. The molecular weight, isoelectric point, Michaelis-Menten constant, indolacetic acid oxidase activity and spectral and analytical properties of this peroxidase were determined. It is assumed that the enzyme has an intracellular as well as an extracellular field of activity.


Treatment of mixed Oesophagostomum and hookworm infection: effect of albendazole, pyrantel pamoate, levamisole and thiabendazole.
Oesophagostomum bifurcum has recently been recognized as a common parasite of man in northern Togo and in Ghana. In a preliminary trial several anthelmintics were evaluated in the treatment of mixed Oesophagostomum and hookworm infections. Diagnosis was based on faecal culture, since the eggs of Oesophagostomum and hookworm cannot be distinguished morphologically. Of the anthelmintics tested, albendazole was most effective against both parasites. Pyrantel pamoate, 2 x 10 mg/kg, was effective against Oesophagostomum but not against hookworm. The cure rates for both parasites were moderate with thiabendazole and poor with levamisole.


Can molar incisor hypomineralization cause dental fear and anxiety or influence the oral health-related quality of life in children and adolescents?-a systematic review.
Molar Incisor Hypomineralization (MIH) are first molars with developmental enamel defects and are common findings in many child populations. The porous nature of MIH enamel and the presence of post-eruptive enamel breakdown leads to the presence of hypersensitivity and pain, which is often the patient's main complaint and can result in dental fear and affect the quality of life. The present review aims to summarise the evidence for the ability of MIH to cause problems, such as dental fear and anxiety (DFA) and to summarise the evidence for a possibly negative impact on the oral health-related quality of life (OHRQoL) of MIH affected children and adolescents, in a systematic review. Two searches, (1) MIH AND dental anxiety and (2) MIH AND Quality of life, were performed in MEDLINE/PubMed and Scopus. Selection demands were fulfilling the MIH diagnosis criteria using validated instruments and questionnaires for assessing DFA and OHRQoL, respectively. After removing duplicates and articles not fulfilling the selection demands, 6 studies concerning MIH and DFA and 8 studies concerning MIH and OHRQoL remained. Children and adolescents with diagnosed MIH did not seem to suffer from increased dental fear and anxiety, but indicated an impaired oral health-related quality of life.


Review article: freedom to lead a life we have reason to value? A spotlight on health inequity in the Asia Pacific region.
The Asia Pacific region is home to more than 60% of the world's population. Life expectancy at birth differs between countries by as much as 27 years. This article suggests that asymmetric economic growth, unplanned urbanization, marked environmental change, unequal improvements in daily living conditions, and the unequal distribution and access to quality health care have contributed to health inequities in the Asia Pacific region. Contextually specific evidence and action are needed. This requires ongoing monitoring of health inequities and systematic evaluation of societal changes and their impact on health inequities. It requires better understanding of how to translate theoretical and empirical demonstrations of the social and environmental impact on health inequities into evidence-informed policies and programs, in diverse geopolitical, socioeconomic, and sociocultural contexts across the Asia Pacific region and the range of associated complex policy processes. A spotlight is needed on health inequities and their causes else the status quo will persist.


Vertebral Artery Tortuosity and Morphometric Characteristics of Patients with Recurrent Cervical Artery Dissection.
Cervical Artery Dissection is an important cause of stroke in the young. Data on incidence and associations of recurrence in patients with cervical artery dissection are lacking. Increased Vertebral Artery Tortuosity Index has been reported in patients with cervical artery dissection and associated with earlier age of arterial dissection in patients with connective tissue disease. To test the hypothesis that increased vertebral artery tortuosity is associated with recurrent cervical artery dissection. We reviewed data from a single-center registry of cervical artery dissection patients enrolled between 2011-2021. CT angiography was reviewed for neck length, vertebral artery dominance, and vertebral artery tortuosity index. Incidence rate of recurrent dissection was calculated using Poisson regression. Differences between groups were analyzed using the Kruskal-Wallis rank sum test and Fisher's exact test. The cohort included 155 patients: women (56%), mean (SD) age 42 (±10) years, and 116 single and 39 multiple artery dissections. Eleven (7.1%) had a recurrence with an incidence rate (95% CI) of 1.91 (1.06, 3.44) per 100 person-years. Vertebral artery tortuosity did not differ significantly between single and recurrent groups (median (IQR) 46.81 (40.85, 53.91) vs 44.97 (40.68, 50.62) p = 0.388). Morphometric characteristics of height, neck length, and BMI were not associated with recurrence. There was no difference in vertebral artery tortuosity by dissection location (carotid vs vertebral). In this single center cohort of patients with cervical artery dissection, there was no difference in VTI between single and recurrent groups.


Traumatic vertebra and endplate fractures promote adjacent disc degeneration: evidence from a clinical MR follow-up study.
The integrity of endplate is important for maintaining the health of adjacent disc and trabeculae. Yet, pathological impacts of traumatic vertebra and endplate fractures were less studied using clinical approaches. This study aims to investigate their effects on the development of adjacent disc degeneration, segmental kyphosis, Modic changes (MCs), and high-intensity zones (HIZs). Magnetic resonance (MR) images of patients with acute traumatic vertebral compression fractures (T11-L5) were studied. On MR images, endplate fractures were evaluated as present or absent. Disc signal, height, bulging area, sagittal Cobb angle, MCs, and HIZs were measured on baseline and follow-up MR images to study the changes of the disc in relation to vertebra fractures and endplate fractures. Ninety-seven patients were followed up for 15.4 ± 14.0 months. There were 123 fractured vertebrae, including 79 (64.2%) with endplate fractures and 44 (35.8%) without. Both the adjacent and control discs decreased in signal and height over time (p < 0.001), and the disc adjacent to vertebral fractures had greater signal and height loss than the control disc (p < 0.05). In the presence of endplate fractures, the adjacent discs had greater signal decrease in follow-up (p < 0.05), as compared to those without endplate fractures. Sagittal Cobb angle significantly increased in segments with endplate fractures (p < 0.05). Vertebra fractures were associated with new occurrence of MCs in the fractured vertebra (p < 0.001) but not HIZs in the adjacent disc. Traumatic vertebral fractures were associated with accelerated adjacent disc degeneration, which appears to be further promoted by concomitant endplate fractures. Endplate fractures were associated with progression of segmental kyphosis.


Effects of enhanced parasympathetic tone on atrioventricular nodal conduction during atrioventricular nodal reentrant tachycardia.
The effects of various physiologic and pharmacologic stimuli on the anterograde slow pathway in patients with atrioventricular nodal reentrant tachycardia are well characterized. We sought to further characterize the nature of anterograde and retrograde conduction during tachycardia and to define the differential input of the parasympathetic nervous system to these pathways. A custom-made neck suction collar was placed to stimulate the carotid body baroreceptors during supraventricular tachycardia. Neck suction at -60 mm Hg was applied and changes in tachycardia cycle length, AH, and ventriculoatrial intervals were measured in 20 patients. These measurements were repeated after intravenous administration of 10 mg of edrophonium to enhance vagal tone. We observed a 15 +/- 6 ms increase in tachycardia cycle length from baseline (p <0.0001) and a 14 +/- 6 ms increase in AH interval (p <0.0001), but no change in the VA interval with neck suction alone. The tachycardia cycle length prolonged 26 +/- 55 ms (p <0.0001) with edrophonium and an additional 12 +/- 43 ms (p <0.001) with neck suction after edrophonium. There was no change in the VA interval before or after edrophonium during neck suction. There were 10 tachycardia terminations in 8 patients during anterograde slow pathway block during neck suction, with tachycardia cycle length prolongation and mean AH prolongation before termination of 45 +/- 37 ms (vs 15 +/- 7 ms increase in AH interval without tachycardia termination, p = 0.10). There were 12 tachycardia terminations in 4 patients with retrograde block during neck suction, only after edrophonium, without any preceding change in tachycardia cycle length during 11 episodes. We conclude that anterograde slow pathway demonstrates gradual conduction slowing with parasympathetic enhancement, whereas retrograde fast pathway responds with abrupt block.


The CNN Hip Accelerometer Posture (CHAP) Method for Classifying Sitting Patterns from Hip Accelerometers: A Validation Study.
Sitting patterns predict several healthy aging outcomes. These patterns can potentially be measured using hip-worn accelerometers, but current methods are limited by an inability to detect postural transitions. To overcome these limitations, we developed the Convolutional Neural Network Hip Accelerometer Posture (CHAP) classification method. CHAP was developed on 709 older adults who wore an ActiGraph GT3X+ accelerometer on the hip, with ground-truth sit/stand labels derived from concurrently worn thigh-worn activPAL inclinometers for up to 7 d. The CHAP method was compared with traditional cut-point methods of sitting pattern classification as well as a previous machine-learned algorithm (two-level behavior classification). For minute-level sitting versus nonsitting classification, CHAP performed better (93% agreement with activPAL) than did other methods (74%-83% agreement). CHAP also outperformed other methods in its sensitivity to detecting sit-to-stand transitions: cut-point (73%), TLBC (26%), and CHAP (83%). CHAP's positive predictive value of capturing sit-to-stand transitions was also superior to other methods: cut-point (30%), TLBC (71%), and CHAP (83%). Day-level sitting pattern metrics, such as mean sitting bout duration, derived from CHAP did not differ significantly from activPAL, whereas other methods did: activPAL (15.4 min of mean sitting bout duration), CHAP (15.7 min), cut-point (9.4 min), and TLBC (49.4 min). CHAP was the most accurate method for classifying sit-to-stand transitions and sitting patterns from free-living hip-worn accelerometer data in older adults. This promotes enhanced analysis of older adult movement data, resulting in more accurate measures of sitting patterns and opening the door for large-scale cohort studies into the effects of sitting patterns on healthy aging outcomes.


Hydroxytyrosol encapsulated in biocompatible water-in-oil microemulsions: How the structure affects in vitro absorption.
Over the last years, the incorporation of natural antioxidants in food and pharmaceutical formulations has gained attention, delaying or preventing oxidation phenomena in the final products. In order to take full advantage of their properties, protection in special microenvironments is of great importance. The unique features of the natural phenolic compound hydroxytyrosol (HT) - including antioxidant, anti-inflammatory, antiproliferative and cardioprotective properties - have been studied to clarify its mechanism of action. In the present study novel biocompatible water-in-oil (W/O) microemulsions were developed as hosts for HT and subsequently examined for their absorption profile following their oral uptake. The absorption of HT in solution was compared with the encapsulated one in vitro, using a coculture model (Caco-2/TC7 and HT29-MTX cell lines). The systems were structurally characterized by means of Dynamic Light Scattering (DLS) and Electron Paramagnetic Resonance (EPR) techniques. The diameter of the micelles remained unaltered after the incorporation of 678 ppm of HT but the interfacial properties were slightly affected, indicating the involvement of the HT molecules in the surfactant monolayer. EPR was used towards a lipophilic stable free radial, namely galvinoxyl, indicating a high scavenging activity of the systems and encapsulated HT. Finally, after the biocompatibility study of the microemulsions the intestinal absorption of the encapsulated HT was compared with its aqueous solution in vitro. The higher the surfactants' concentration in the system the lower the HT concentration that penetrated the constructed epithelium, indicating the involvement of the amphiphiles in the antioxidant's absorption and its entrapment in the mucus layer.


Application of a preoperative pain management mode based on instant messaging software in elderly hip fracture patients: a randomized controlled trial.
Preoperative analgesia of hip fracture in elderly patients is important, but it is also lacking. In particular, nerve block was not provided in time. In order to provide more effective analgesia, we designed a multimodal pain management mode based on instant messaging software. From May to September 2022, a total of 100 patients with unilateral hip fracture aged over 65 were randomly divided into the test group and the control group. Finally, 44 patients in each group completed the result analysis. A new pain management mode was used in the test group. This mode focuses on the full information exchange between medical personnel in different departments, early fascia iliaca compartment block (FICB), and closed-loop pain management. Outcomes include the time when FICB is completed for the first time; The number of cases of FICB completed by emergency doctors; Patients' pain score, pain duration. The time for patients in the test group to complete FICB for the first time was 3.0 [1.925-3.475] h, which was less than the time for patients in the control group (4.0 [3.300-5.275] h). The difference was statistically significant (P < 0.001). Compared with 16 patients in the control group, 24 patients in the test group completed FICB by emergency doctors, and there was no statistical difference between the two groups (P = 0.087). The test group was superior to the control group in the highest NRS score (4.00 [3.00-4.00] vs 5.00 [4.00-5.75]), the duration of the highest NRS score (20.00 [20.00-25.00] mins vs 40.00 [30.00-48.75] mins), and the NRS > 3 time (35.00 [20.00-45.00] mins vs 72.50 [60.00-45.00] mins). The analgesic satisfaction of patients in the test group (5.00 [4.00-5.00]) was also significantly higher than that of the control group (3.00 [3.00-4.00]). The above four indexes were different between the two groups (P < 0.001). Using instant messaging software, the new model of pain management can enable patients to receive FICB as soon as possible and improve the timeliness and effectiveness of analgesia. Chinese Clinical Registry Center, ChiCTR2200059013, 23/04/2022.


Genetic control of body weight by the human brain proteome.
Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with body weight but the biological relevance of most remains unexplored. Given the critical role of the brain in body weight regulation, we set out to determine whether genetic variants linked with body mass index (BMI) could be mapped to brain proteins. Using genetic colocalization, we mapped 25 loci from the largest BMI GWAS (n = 806,834) to brain protein concentrations obtained from publicly available datasets. We also performed a proteome-wide Mendelian randomization on 696 brain proteins followed by genetic colocalization and identified 35 additional brain proteins. Only a minority of these proteins (<30%) had a colocalization signal with cortex gene expression levels, highlighting the value of moving beyond gene expression levels and examining brain protein levels. In conclusion, we identified 60 unique proteins expressed in the brain that may be critical regulators of body weight in humans.


A comparison of two sedative premedications for minor oral surgery under local anaesthesia.
Two commonly used drug combinations were studied as premedications before surgical 3rd molar removal under local anaesthesia. The study was randomized, crossover and double-blind in 12 patients. Our routine premedication for lengthy operations, consisting of diazepam 10 mg p.o. plus i.m. scopolamine 0.006 mg/kg and morphine 0.2 mg/kg, was compared with a combination of diazepam 10 mg p.o. plus metoprolol 50 mg p.o. The latter combination was expected to cause fewer central nervous system side effects and be more suitable for out-patient surgery. Drug levels in blood, physiological and biochemical indicators of operation-related stress, CNS side effects, and the patients' subjective preferences were monitored. Both combinations were equally accepted by the patients, but the diazepam/scopolamine/morphine combination caused clearly more side effects after discharge than diazepam/metoprolol. The operation-related haemodynamic changes and plasma catecholamine responses were similar after both premedications.


The role of omentectomy in the surgical treatment of uterine serous carcinoma.
The aims of this study were to assess the role of omentectomy in the staging of uterine serous carcinoma (USC) and to evaluate its impact on patient outcomes. Patients diagnosed with USC at the First Affiliated Hospital of Sun Yat-sen University of China were retrospectively reviewed. The clinicopathological characteristics and survival data of 187 patients were analyzed. Risk factors for omental metastasis were evaluated. Kaplan-Meier survival curves were used to compare survival status and the presence of omental metastasis. We found that 35 of 187 patients (18.7%) had omental metastases. Omental metastasis was significantly associated with adnexal involvement (40.0% vs 19.1%, P = 0.008, OR 2.828, 95% CI 1.286-6.218). Multivariate analysis showed that in addition to lymph node metastases and suboptimal surgery, omental metastasis in USC remained an independent predictor of decreased PFS and OS (PFS, HR 1.48, 95% CI 1.14-4.63, P = 0.024; OS, HR 1.39, 95% CI 1.04-3.60, P = 0.043). The incidence of omental metastasis is not low in patients with USC. Visual assessment and omental biopsy may be insufficient for recognizing occult metastases. Omentectomy should be part of the staging surgery in USC patients because it provides additional information about survival. Prospective studies are needed to confirm these results.


Multi-tissue DNA methylation age: Molecular relationships and perspectives for advancing biomarker utility.
The multi-tissue DNA methylation estimator of chronological age (DNAm-age) has been associated with a wide range of exposures and health outcomes. Still, it is unclear how DNAm-age can have such broad relationships and how it can be best utilized as a biomarker. Understanding DNAm-age's molecular relationships is a promising approach to address this critical knowledge gap. In this review, we discuss the existing literature regarding DNAm-age's molecular relationships in six major categories: animal model systems, cancer processes, cellular aging processes, immune system processes, metabolic processes, and nucleic acid processes. We also present perspectives regarding the future of DNAm-age research, including the need to translate a greater number of ongoing research efforts to experimental and animal model systems.


ACGME 2011 Duty Hours Restrictions and Their Effects on Surgical Residency Training and Patients Outcomes: A Systematic Review.
The ACGME instituted the 2011 residency duty-hour restrictions (DHR) to increase resident well-being and patient safety. However, its eventual remodeling came after patient care was deemed unaffected. We aimed to identify the effects of the ACGME 2011-DHR on (1) patient outcomes, (2) surgical resident case volume, and (3) surgical resident quality of life. Literature search using Google Scholar, PubMed, Cochrane, and Embase for publications between 2010 and 2020, on the 2011-DHR effects on resident and patient outcomes. Studies containing the number of cases performed during training, quality of life, and surgical patients' outcomes were included. Fifteen studies met inclusion criteria. There was no difference in complication rates for surgical patients post 2011-DHR (p = 0.561). 2011-DHR caused surgical caseload shifts from interns to senior residents reflected by decreased operative cases for interns (p = 0.005) with significantly more total cases performed by chief residents (p = 0.0006). Pre-2011-DHR had more work flexibility that led to higher resident well-being (p = 0.01). Only 25% of residents approved of the 2011-DHR while 87% felt these restrictions would have adverse effects. Current literature supports that the 2011-DHR did not improve patient outcomes, decreased surgical experience for junior residents and shifted clinical responsibilities to senior residents. System wide regulations such as the 2011-DHR may unintentionally create professional and personal life imbalance and introduce stress over resident inability to perform clinical responsibilities. Future systemic interventions to address resident well-being should be made with caution and not solely limited to the number of hours they work in a single week or in a single shift.


Comparative analysis of peptidylarginine deiminase-2 expression in canine, feline and human mammary tumours.
The peptidylarginine deiminase (PAD) enzyme family converts arginine residues in proteins to citrulline. In the canine mammary gland, PAD2 expression is first detected in epithelial cells in oestrus and becomes more widely expressed during dioestrus. PAD2 appears to modify nuclear histones, suggesting a role for the enzyme in chromatin remodelling and gene regulation. Recent evidence suggests that PAD2 plays a role in gene regulation in primary human breast epithelial cells. PAD2 may therefore be involved in gene regulation as it relates to mammary development, the oestrus cycle and potentially to neoplasia. The aim of the present study was to determine whether PAD2 expression was increased or decreased in mammary carcinoma compared with normal mammary tissue. A human mammary tissue microarray and archival surgical biopsy tissues from canine and feline mammary tumours were used to demonstrate differential expression of PAD2 in mammary carcinoma that appeared to be consistent across species. Normal human and canine mammary epithelium showed strong cytoplasmic and nuclear expression of PAD2, but there was reduced PAD2 expression in mammary carcinomas from both species. Feline mammary carcinomas had complete loss of nuclear PAD2 expression. Loss of nuclear PAD2 expression may therefore represent a marker of progression towards more aggressive neoplasia.


Reliability and validity of shoulder tightness measurement in patients with stiff shoulders.
The purposes of this study were (1) to examine intratester and intertester reliability of measurement of anterior and posterior shoulder tightness in patients with stiff shoulders (SS), and (2) to assess construct validity by determining the relations between shoulder tightness, shoulder range of motion (ROM), and self-report measures of functional limitation. Anterior and posterior shoulder tightness were measured by two testers in below-chest abduction and cross-chest adduction tests with an inclinometer, respectively, in 16 patients with SS. Both the intratester and intertester reliability for shoulder tightness measurements were good (intratester ICC=0.84 and 0.91; intertester ICC=0.82 and 0.89). The limit of intra-tester and inter-tester agreement (mean, -0.3+/-4.4 degrees ) was acceptable as compared to the standard deviations of the measurements (range, 6.2-7.4 degrees ). Significant relationships between internal rotation and posterior shoulder tightness (R2=0.448, P=0.002), external rotation and anterior shoulder tightness (R2=0.499, P=0.003), and functional disabilities and posterior shoulder tightness (R2=0.432, P=0.006) were found. Significant correlations between shoulder internal rotation and cross-chest adduction, shoulder external rotation and below-chest abduction were observed, indicating that internal and external rotations might be related to posterior and anterior shoulder stiffness. The study also revealed significant relationship between functional disabilities and cross-chest adduction. Below-chest abduction and cross-chest adduction were found to provide reliable data. The construct validity of the abduction and adduction tests is supported by the relationship among these measurements, shoulder ROM, and functional disabilities in patients with SS.


A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations.
To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia (PA). Randomized, double-blind, placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month. Two geriatric hospitals in the North Western Health Care Network, Melbourne, Australia. Thirty-one inpatients with serum vitamin B12 levels between 100 and 150 pmol/L, without PA, other malabsorption disorders, or progressive neurological or terminal illness. The mean age was 81.4 years. After informed consent, a medical and drug history was taken and the Mini-Mental State Examination (MMSE) completed. A dietitian made assessment of oral cobalamin intake. Blood was taken for serum vitamin B12, serum and red cell folate assay, full blood examination, fasting serum gastrin, parietal and intrinsic factor antibodies, fasting serum homocysteine, and creatinine. Patients were then randomized to receive 10 microg oral cyanocobalamin, 50 microg oral cyanocobalamin, or placebo treatment for 1 month, after which the investigations and clinical examinations were repeated. Percentage change in the level of vitamin B12, homocysteine, folate, and red cell parameters and absolute changes in MMSE were calculated and compared between groups. The groups were compared on the number of responders who improved their level of B12 by 20%. Chi-square calculations on changes in serum vitamin B12 concentration were also performed. Mean serum vitamin B12 +/- standard deviation improved by 51.7 +/- 47.1% in the 50-microg group, 40.2 +/- 34.4% in the 10-microg group, and 11.7 +/- 24.5% in the placebo group. The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group (P=.044). The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group (P=.186). Eight of 10 subjects in each treatment group were classified as responders, compared with two of 11 in the placebo group (P=.004). Homocysteine levels fell in patients receiving cyanocobalamin, but this fall failed to reach statistical significance. There were no significant changes in the other parameters measured. Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12. This result has implications for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12.


Functionalized graphene with Co-ZIF adsorbed borate ions as an effective flame retardant and smoke suppression agent for epoxy resin.
In order to reduce the fire risk of epoxy resin (EP), functionalized reduced graphene oxide (RGO) with Co-ZIF (zeolitic imidazolate frameworks-67) adsorbed borate ions (ZIF-67/RGO-B) was prepared. The results of transmission electron microscopy (TEM) showed that ZIF-67 was grown on the surface of RGO triumphantly. In addition, the structure of ZIF-67/RGO-B was not significantly changed compared with ZIF-67/RGO. Subsequently, ZIF-67/RGO-B was added into EP by a simple blending method. The combustion results showed that the heat and smoke production of EP composites were obviously reduced. In particular, compared with pure EP, the peak heat release rate (pHRR), the total heat release (THR) and the maximum value of smoke density (Ds,max) of the composite with 2 wt% ZIF-67/RGO-B were reduced by 65.1%, 41.1% and 66.0%, respectively. The main mechanism of ZIF-67/RGO-B for reducing the fire risk of EP was analyzed according to the results of the char analysis. This work provided a new type of modified RGO for reducing the fire hazard of EP.


Regulation of gene expression through a transcriptional repressor that senses acyl-chain length in membrane phospholipids.
Membrane phospholipids typically contain fatty acids (FAs) of 16 and 18 carbon atoms. This particular chain length is evolutionarily highly conserved and presumably provides maximum stability and dynamic properties to biological membranes in response to nutritional or environmental cues. Here, we show that the relative proportion of C16 versus C18 FAs is regulated by the activity of acetyl-CoA carboxylase (Acc1), the first and rate-limiting enzyme of FA de novo synthesis. Acc1 activity is attenuated by AMPK/Snf1-dependent phosphorylation, which is required to maintain an appropriate acyl-chain length distribution. Moreover, we find that the transcriptional repressor Opi1 preferentially binds to C16 over C18 phosphatidic acid (PA) species: thus, C16-chain containing PA sequesters Opi1 more effectively to the ER, enabling AMPK/Snf1 control of PA acyl-chain length to determine the degree of derepression of Opi1 target genes. These findings reveal an unexpected regulatory link between the major energy-sensing kinase, membrane lipid composition, and transcription.


Investigation of response factor ruggedness for the determination of drug impurities using high-performance liquid chromatography with ultraviolet detection.
Quantification of impurities in drug substances and dosage forms using HPLC assays with UV detection is often done by comparison to a standard of the drug itself. Depending on the spectra of the compounds involved, small changes in wavelength may cause response factors to vary from day to day and instrument to instrument. Lack of assay ruggedness with respect to wavelength can lead to poor reproducibility of results. Response factor ruggedness was investigated for potential impurities in LY297802 tartrate, a potent muscarinic agonist. The UV responses of some impurities at 280 nm, the analytical detection wavelength, differ from that of the parent and change significantly with small shifts in wavelength. The ruggedness of response factors was examined on a single detector and among several different detectors. Results varied significantly among the different detectors. The UV spectra of the impurities could be used to predict the effect of wavelength on ruggedness of response. A wavelength system suitability sample is proposed as a way to overcome variability due to small differences in detector wavelength.


Brain correlates underlying creative thinking: EEG alpha activity in professional vs. novice dancers.
Neuroscientific research on creativity has revealed valuable insights into possible brain correlates underlying this complex mental ability domain. However, most of the studies investigated brain activity during the performance of comparatively simple (verbal) type of tasks and the majority of studies focused on samples of the normal population. In this study we investigate EEG activity in professional dancers (n=15) who have attained a high level of expertise in this domain. This group was compared with a group of novices (n=17) who have only basic experience in dancing and completed no comprehensive training in this field. The EEG was recorded during performance of two different dancing imagery tasks which differed with respect to creative demands. In the first task participants were instructed to mentally perform a dance which should be as unique and original as possible (improvisation dance). In the waltz task they were asked to imagine dancing the waltz, a standard dance which involves a sequence of monotonous steps (lower creative demands). In addition, brain activity was also measured during performance of the Alternative Uses test. We observed evidence that during the generation of alternative uses professional dancers show stronger alpha synchronization in posterior parietal brain regions than novice dancers. During improvisation dance, professional dancers exhibited more right-hemispheric alpha synchronization than the group of novices did, while during imagining dancing the waltz no significant group differences emerged. The findings complement and extend existing findings on the relationship between EEG alpha activity and creative thinking.


Impact of Urbanisation Intensity on Bird Diversity in River Wetlands around Chaohu Lake, China.
Urbanisation is known to result in 'urban stream syndrome', which poses a huge threat to the river health. Birds, which are an important part of the river ecosystem, are sensitive to environmental changes in the basin. The ratio of the impervious surface area is a macroscopic indicator of urbanisation intensity in river basins. In this study, we combined the results of a year-round field survey of seven river wetlands around Chaohu Lake (China) with satellite remote sensing image data from the same period. The species richness at sections of the lake entrance was higher than in the middle sections of the river, and the Shannon-Wiener index during autumn was higher than that during winter. The waterbird diversity index declined exponentially with increases in the intensity of urbanisation. The changes in the land use patterns around river wetlands associated with urbanisation resulted in the loss of food resources and habitats. Therefore, the intensity of urbanisation was an important driving factor that leads to changes in the bird community structure of river wetlands, so it had a significant impact on the diversity of river wetland birds in all four seasons combined with a variety of influencing factors. Our research could be a guide for urban landscape planning and bird diversity protection. For example, the results suggested that it is necessary to identify river wetlands as an important part of the urban ecosystem, reduced building area, increased vegetation coverage, and retained slope protection and river beach land.


A triple combination 'nano' dry powder inhaler for tuberculosis: in vitro and in vivo pulmonary characterization.
Inhalation route of drug delivery is the most favorable for pulmonary infections wherein direct drug delivery is desired to the lungs. Tuberculosis is one such infection suffering from poor therapeutic efficacy because of low patient compliance due to high drug dosing and lengthy treatment protocols. The current research work was undertaken to develop a dry powder inhaler (DPI) for administration of three first-line antitubercular antibiotics directly to the lungs to improve the treatment rates. Nanoformulations of isoniazid, pyrazinamide, and rifampicin were prepared, spray-dried to obtain a dry powder system, and blended with inhalation grade lactose to develop the DPI. The DPI was evaluated for its flow properties, pulmonary deposition, dissolution profile, and stability. The DPI possessed excellent flow properties with a fine particle fraction of 45% and a mass median aerodynamic diameter of approximately 5 µm indicating satisfactory lung deposition. In vitro drug release exhibited a sustained release of the formulations. In vivo studies showed a prolonged deposition in the lung at elevated concentrations compared to oral therapy. Stability studies proved that the formulation remained stable at accelerated and long-term stability conditions. The DPI could complement the existing oral therapy in enhancing the therapeutic efficacy in patients.


The effect of temperature and excitation energy on Raman scattering in bulkHfS2.
Raman scattering (RS) in bulk hafnium disulfide (HfS2) is investigated as a function of temperature (5 K - 350 K) with polarization resolution and excitation of several laser energies. An unexpected temperature dependence of the energies of the main Raman-active (A1gand Eg) modes with the temperature-induced blueshift in the low-temperature limit is observed. The low-temperature quenching of a modeω1(134 cm-1) and the emergence of a new mode at approx. 184 cm-1, labeledZ, is reported. The optical anisotropy of the RS inHfS2is also reported, which is highly susceptible to the excitation energy. The apparent quenching of the A1gmode atT = 5 K and of the Egmode atT= 300 K in the RS spectrum excited with 3.06 eV excitation is also observed. We discuss the results in the context of possible resonant character of light-phonon interactions. Analyzed is also a possible effect of the iodine molecules intercalated in the van der Waals gaps between neighboringHfS2layers, which inevitably result from the growth procedure.


Cellular Function of TRIM E3 Ubiquitin Ligases in Health and Disease.
The field of the Tripartite Motif (TRIM) family has progressively attracted increasing interest during the last two decades [...].


Combatting Compassion Fatigue With Mindfulness.
The purpose of this project was to implement an evidence-based, mindfulness therapeutic intervention, to help reduce compassion fatigue and to improve faculty attrition rates in an urban school setting. Implementation of the mindfulness intervention included an educational didactic workshop, basic exercises in mindfulness, a take-home manual, and the development of a mindfulness web portal to promote sustainability of the project. Outcomes were measured using Stamm's Professional Quality of Life Scale V (ProQOL-V Scale), in addition to a descriptive analysis of demographics and a postprogram satisfaction survey. Scores obtained from the ProQOL-V Scale confirmed the presence of compassion fatigue. Posttesting showed program satisfaction with a high interest in implementing mindfulness activities. Self-repor ted improvements were noted in mood/emotion following the workshop, and attrition rate decreased by 10%. It appears that mindfulness training is a feasible intervention to implement with individuals experiencing the effects of stress and compassion fatigue. More research is needed to extend these preliminary findings into the realm of nursing both clinically and academically.


Use of High-Refractive Index Hydrogels and Tissue Clearing for Large Biological Sample Imaging.
Recent advances in tissue clearing and light sheet fluorescence microscopy have improved insights into and understanding of tissue morphology and disease pathology by imaging large samples without the requirement of histological sectioning. However, sample handling and conservation of sample integrity during lengthy staining and acquisition protocols remains a challenge. This study overcomes these challenges with acrylamide hydrogels synthesised to match the refractive index of solutions typically utilised in aqueous tissue clearing protocols. These hydrogels have a high-water content (82.0 ± 3.7% by weight). The gels are stable over time and FITC-IgG readily permeated into and effluxed out of them. Whilst the gels deformed and/or swelled over time in some commonly used solutions, this was overcome by using a previously described custom refractive index matched solution. To validate their use, CUBIC cleared mouse tissues and whole embryos were embedded in hydrogels, stained using fluorescent small molecule dyes, labels and antibodies and successfully imaged using light sheet fluorescence microscopy. In conclusion, the high water content, high refractive index hydrogels described in this study have broad applicability to research that delves into pathophysiological processes by stabilising and protecting large and fragile samples.


Evaluation and management of the older adult with chronic kidney disease.
Chronic kidney disease (CKD) has a high prevalence in the elderly population. Almost half of the population reaches moderate impairment (CKD 3) by 65 years of age. This article describes CKD staging in the geriatric population and several common clinical presentations of renal disease. Diagnosis and treatment regimens of CKD are discussed. Geriatric patients are at an increased risk for renal dysfunction from many causes. Some causes are inherent with aging, such as gross structural and cellular changes, decrease in physiologic function, and lowered vascular compensatory reserve. Exposures, including medications and diagnostic testing, are contributors to acute kidney injury.


Intra-specific variation in strategic ejaculation according to level of polyandry in Callosobruchus chinensis.
Optimal sperm allocation should differ according to the level of polyandry within a population, because the risk of sperm competition depends on the re-mating frequency of females. We compared the number of sperm ejaculated by males into the female reproductive organ between strains with different levels of polyandry in the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae) when males were reared in different larval densities in a bean. The results showed that males derived from a population with a higher level of polyandry increased ejaculatory expenditure when they were reared under higher larval densities. We discuss the evolutionary correlation of ejaculatory expenditure to the level of polyandry.


[Correlation between the synthesis of extracellular proteases and the synthesis of the red pigment prodigiosin in Serratia marcescens].
A correlation has been established between synthesis of exocellular protease and synthesis of a red pigment prodigiosine by Serratia marcescens. Chloramphenicol, an inhibitor of protein synthesis, inhibits also synthesis of the pigment. Leucine, an inductor of synthesis of the exocellular protease by Serratia marcescens VI, induces also synthesis of the pigment. A mixture of 18 natural amino acids, asparagine and ammonium ions represses both synthesis of the enzyme and the pigment.


[Development of a method for the quantitative assessment of the microorganism sensitivity to antibiotics by using discs. A study of the patterns of doxycycline diffusion from discs into the nutrient agar].
Doxycycline concentrations provided by the antibiotic diffusion from paper discs into sterile agarized medium and the medium plated with staphylococci and Coli bacteria were studied at different distances from the disc center. Infection of the nutrient medium with the test cultures had no effect on the antibiotic diffusion rate. A linear relation between the logarithm of the antibiotic concentration in the agar and distance from the disc centre were found. Probably it is possible to determine the MIC of the antibiotic with respect to various microorganisms by the value of the radius of the growth inhibition zone around the disc using diagrams expressing such a relation.


Local signalling in dermomyotomal cell type specification.
The development and differentiation of the avian myotome was studied after removal of the neural tube, including neural crest, and after replacement of dorsal half-somites by ventral half-somites. Results show that in the absence of neural tissue myoblast differentiation within the somites does not take place. Ventral half-somites are able to undergo muscle differentiation if they were grafted in place of dorsal half somites. It is suggested that local signals must be responsible for the dorsalisation of the newly formed somite including myoblast differentiation. Neural crest cells are discussed as possible sources of these signals.


N-Doped Carbon Nanotubes Derived from Graphene Oxide with Embedment of FeCo Nanoparticles as Bifunctional Air Electrode for Rechargeable Liquid and Flexible All-Solid-State Zinc-Air Batteries.
This work reports a novel approach for the synthesis of FeCo alloy nanoparticles (NPs) embedded in the N,P-codoped carbon coated nitrogen-doped carbon nanotubes (NPC/FeCo@NCNTs). Specifically, the synthesis of NCNT is achieved by the calcination of graphene oxide-coated polystyrene spheres with Fe3+, Co2+ and melamine adsorbed, during which graphene oxide is transformed into carbon nanotubes and simultaneously nitrogen is doped into the graphitic structure. The NPC/FeCo@NCNT is demonstrated to be an efficient and durable bifunctional catalyst for oxygen evolution (OER) and oxygen reduction reaction (ORR). It only needs an overpotential of 339.5 mV to deliver 10 mA cm-2 for OER and an onset potential of 0.92 V to drive ORR. Its bifunctional catalytic activities outperform those of the composite catalyst Pt/C + RuO2 and most bifunctional catalysts reported. The experimental results and density functional theory calculations have demonstrated that the interplay between FeCo NPs and NCNT and the presence of N,P-codoped carbon structure play important roles in increasing the catalytic activities of the NPC/FeCo@NCNT. More impressively, the NPC/FeCo@NCNT can be used as the air-electrode catalyst, improving the performance of rechargeable liquid and flexible all-solid-state zinc-air batteries.


Intracellular GTP level determines cell's fate toward differentiation and apoptosis.
Since the adequate supply of guanine nucleotides is vital for cellular activities, limitation of their syntheses would certainly result in modulation of cellular fate toward differentiation and apoptosis. The aim of this study was to set a correlation between the intracellular level of GTP and the induction of relevant signaling pathways involved in the cell's fate toward life or death. In that regard, we measured the GTP level among human leukemia K562 cells exposed to mycophenolic acid (MPA) or 3-hydrogenkwadaphnin (3-HK) as two potent inosine monophosphate dehydrogenase inhibitors. Our results supported the maturation of the cells when the intracellular GTP level was reduced by almost 30-40%. Under these conditions, 3-HK and/or MPA caused up-regulation of PKCα and PI3K/AKT pathways. Furthermore, co-treatment of cells with hypoxanthine plus 3-HK or MPA, which caused a reduction of about 60% in the intracellular GTP levels, led to apoptosis and activation of mitochondrial pathways through inverse regulation of Bcl-2/Bax expression and activation of caspase-3. Moreover, our results demonstrated that attenuation of GTP by almost 60% augmented the intracellular ROS and nuclear localization of p21 and subsequently led to cell death. These results suggest that two different threshold levels of GTP are needed for induction of differentiation and/or ROS-associated apoptosis.


Can microorganisms convert antimony trioxide or potassium antimonyl tartrate to methylated stibines?
No evidence could be found for the production, in culture, of methylated antimony compounds from water-insoluble or soluble antimony derivatives by the aerobes, Scopulariopsis brevicaulis or Bacillus sp. or by anaerobes associated with cot mattress materials. The study does not support the hypothesis that volatile organoantimony compounds are a cause of cot deaths. Anaerobic cultures from a polluted pond generated trimethylstibine from potassium antimonyl tartrate.


Immunobiology of Acinetobacter baumannii and genospecies 3.
Five representative, taxonomically and serologically defined clinical isolates of Acinetobacter baumannii and genospecies 3, and A. baumannii strain ATCC 19606 were examined for immunogenicity in rabbits following experimental bacteremia. All rabbits seroconverted as determined with the aid of the tube O-agglutination, indirect hemagglutination, and enzyme-linked immunosorbent assay (ELISA) procedures. Immunoblots detected over twenty immunogenic, proteinase-K-degradable polypeptide antigens in trichloroacetic acid extracts, outer membrane protein fractions, and mechanically disrupted (type MM2 mixer drill) cell preparations. Sodium periodate-susceptible phenol-water and phenol-chloroform-light petroleum lipopolysaccharide (LPS) extracts proved to be immunogenic for the rabbits as well. Convalescent sera from two patients with documented bacteremia due to genospecies 3, serovar 4, likewise revealed numerous anti-polypeptide and anti-LPS antibodies comprising the immunoglobulin G (IgG) and the IgM class.


The conformational plasticity of protein kinases.
Protein kinases operate in a large number of distinct signaling pathways, where the tight regulation of their catalytic activity is crucial to the development and maintenance of eukaryotic organisms. The catalytic domains of different kinases adopt strikingly similar structures when they are active. By contrast, crystal structures of inactive kinases have revealed a remarkable plasticity in the kinase domain that allows the adoption of distinct conformations in response to interactions with specific regulatory domains or proteins.


An analytical study of the role of various factors causing red tide outbreaks of trichodesmium as deduced from field and laboratory observation.
The marine blue green alga Trichodesmium sp is found in red-tide outbreaks in sub-tropical areas in the Pacific and Indian Oceans, the Arabian Seas and the equatorial currents of the Gulf of Mexico. Giberellic acid stimulated the growth of Trichodesmium cultures to a greater extent than in the diatom Melosira sulcata. While increasing either the nitrate or phosphate above the normal levels in the culture medium did not greatly stimulate the growth of this organism, Trichodesmium did thrive in nitrogen impoverished waters by nitrogen fixation. The relevance of these findings to the hydrological factors which favour red-tide outbreaks is discussed.


The Natural History of Cervical Intraepithelial Neoplasia Grades 1, 2, and 3: A Systematic Review and Meta-analysis.
The aim of the study was to obtain an updated overview of regression, persistence, and progression rates of conservatively managed cervical intraepithelial neoplasia grade 1 (CIN 1)/CIN 2/CIN 3. Data sources were MEDLINE, Embase, and Cochrane (January 1, 1973-April 14, 2020). Two reviewers extracted data and assessed risk of bias. To estimate outcome rates, we pooled proportions of the individual study results using random-effects meta-analysis, resulting in point estimates and corresponding 95% CIs. Heterogeneity was quantified by the I2 and τ2 measures. Eighty-nine studies were included, 63 studies on CIN 1 (n = 6,080-8,767), 42 on CIN 2 (n = 2,909-3,830), and 7 on CIN 3 (n = 245-351). The overall regression, persistence, and progression to CIN 2 or worse and CIN 3 or worse rates for women with conservatively managed CIN 1 were 60% (95% CI = 55-65, I2 = 92%), 25% (95% CI = 20-30, I2 = 94%), 11% (95% CI = 8-13, I2 = 89%), and 2% (95% CI = 1-3, I2 = 82%), respectively. The overall regression, persistence, and progression rates for CIN 2 were 55% (95% CI = 50-60, I2 = 85%), 23% (95% CI = 19-28, I2 = 83%), and 19% (95% CI = 15-23, I2 = 88%), respectively. Finally, for CIN 3, these were 28% (95% CI = 17-41, I2 = 68%), 67% (95% CI = 36-91, I2 = 84%), and 2% (95% CI = 0-25, I2 = 95%), respectively. Cervical intraepithelial neoplasia grade 2 regression was significantly higher in women 30 years or younger and high-risk human papillomavirus-negative women (66%, 95% CI = 62-70, I2 = 76%; 94%, 95% CI = 84-99, I2 = 60%). Only 2/7,180 (0.03%) and 10/3,037 (0.3%) of the CIN 1 and CIN 2 cases progressed to cervical cancer. Most CIN 1/CIN 2 will regress spontaneously in less than 24 months, with the highest rates in high-risk human papillomavirus-negative and young women, whereas progression to cancer is less than 0.5%. Conservative management should be considered, especially in fertile women and with expected high compliance. Given the heterogeneity in regression rates of high-grade histology, this should be classified as CIN 2 or CIN 3 to guide management.


Low-Ammonium Environment Increases the Nutrient Exchange between Diatom-Diazotroph Association Cells and Facilitates Photosynthesis and N2 Fixation-a Mechanistic Modeling Analysis.
Diatom-diazotroph associations (DDAs) are one of the most important symbiotic dinitrogen (N2) fixing groups in the oligotrophic ocean. Despite their capability to fix N2, ammonium (NH4+) remains a key nitrogen (N) source for DDAs, and the effect of NH4+ on their metabolism remains elusive. Here, we developed a coarse-grained, cellular model of the DDA with NH4+ uptake and quantified how the level of extracellular NH4+ influences metabolism and nutrient exchange within the symbiosis. The model shows that, under a fixed growth rate, an increased NH4+ concentration may lower the required level of N2 fixation and photosynthesis, and decrease carbon (C) and N exchange. A low-NH4+ environment leads to more C and N in nutrient exchange and more fixed N2 to support a higher growth rate. With higher growth rates, nutrient exchange and metabolism increased. Our study shows a strong effect of NH4+ on metabolic processes within DDAs, and thus highlights the importance of in situ measurement of NH4+ concentrations.


Highlights from Faraday Discussion 228: time resolved imaging of photo-induced dynamics.
of recent Faraday Discussions meeting (2021, vol. 228) on time resolved imaging of photo-induced dynamics. The meeting, originally scheduled to take place at IIT Bombay, took place online.


Immunological analysis of v-myc gene products using antibodies against a myc-specific synthetic peptide.
Rabbit antisera were prepared against a synthetic peptide corresponding to the carboxyterminal amino acid sequences of the transforming protein p110gag-myc of avian oncovirus MC29. Analysis of immunoprecipitates formed with these sera (anti-mycC) demonstrated that the gag-myc hybrid proteins encoded by the avian leukemia viruses MC29, CMII, and OK10 were recognized by the anti-peptide sera, but not the gag or pol precursor proteins of helper viruses or the MH2-encoded p100gag-mil protein. In cells transformed by OK10 or MH2, putative v-myc proteins of 60K (OK10) and 59/61K (MH2) were also precipitated by anti-mycC. In addition, the anti-peptide sera reacted specifically with the gag-myc proteins encoded by three partially transformation-defective mutants of MC29, td10A, td10C, and td10H, and by MC29 variant HBI.


Continuous dynamic monitoring of pressure and flow patterns during assisted ventilation.
A system for continuous, dynamic monitoring of children requiring ventilatory assistance has been developed and used in a critical care setting. Breath by breath airway pressure changes are measured on a specially adapted meter with high-and low-pressure limit alarms, and are displayed graphically on a bedside oscilloscope. This system has proved to be beneficial in detecting ventilator system malfunction; in adjusting ventilator settings, such as inspiratory/expiratory ratios, end-expiratory pressure, and phase duration and flow ratios; in assessing compliance of a child requiring ventilatory assistance and his capability for spontaneous breathing; and in the early recognition of potentially harmful problems attendant upon assisted ventilation. The system provides additional educational benefit for the I.C.U. personnel, who become more knowledgeable regarding ventilatory problems, and more apt to discover them promptly. The simplicity of the system, compatibility with other I.C.U. monitoring equipment, capability for continuous, dynamic monitoring, and broad scope recommended it for infants and children requiring assisted ventilation.


The 5'UTR-specific mutation in VEEV TC-83 genome has a strong effect on RNA replication and subgenomic RNA synthesis, but not on translation of the encoded proteins.
Venezuelan equine encephalitis virus (VEEV) is one of the most pathogenic members of the Alphavirus genus in the Togaviridae family. Viruses in the VEEV serocomplex continuously circulate in the Central and South America. The only currently available attenuated strain VEEV TC-83 is being used only for vaccination of at-risk laboratory workers and military personnel. Its attenuated phenotype was shown to rely only on two point mutations, one of which, G3A, was found in the 5' untranslated region (5'UTR) of the viral genome. Our data demonstrate that the G3A mutation strongly affects the secondary structure of VEEV 5'UTR, but has only a minor effect on translation. The indicated mutation increases replication of the viral genome, downregulates transcription of the subgenomic RNA, and, thus, affects the ratio of genomic and subgenomic RNA synthesis. These findings and the previously reported G3A-induced, higher sensitivity of VEEV TC-83 to IFN-alpha/beta suggest a plausible explanation for its attenuated phenotype.


Health literacy dimensions as predictors of self-care agency among nursing students.
Self-care agency refers to the individuals' ability to recognize their needs to identify and perform self-care actions. However, the literature regarding the predictors of self-care agency among nursing students is limited. More specifically, the association between the dimensions of health literacy and self-care agency is lacking. This study was conducted to investigate whether nursing students' health literacy predicts self-care agency. A cross-sectional design was used. A total of 178 nursing students participated in this study. The participants completed the Health Literacy Questionnaire and the Appraisal of Self-Care Agency Scale-Revised. Bivariate correlations and multiple linear regression (Enter method) analyses were performed. Bivariate correlations revealed that the nine Health Literacy Questionnaire scales had moderate, statistically significant correlations with self-care agency (Pearson's r = 0.31 to 0.46, p < .01). Multiple linear regression analysis showed that the model was statistically significant: F(9, 168) = 8.19, p < .001. The adjusted R2 was 0.268, meaning that the model explained 26.8 % of the outcome variance (self-care agency). The following scales (i.e., dimensions) of health literacy predicted more than a quarter of nursing students' self-care agency: "Actively managing my health," "Social support for health," "Navigating the healthcare system," and "Ability to find good health information".


Exercise ameliorates aberrant synaptic plasticity without enhancing adult-born cell survival in the hippocampus of serotonin transporter knockout mice.
Deficits in hippocampal cellular and synaptic plasticity are frequently associated with cognitive and mood disorders, and indeed common mechanisms of antidepressants are thought to involve neuroplastic processes. Here, we investigate hippocampal adult-born cell survival and synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in serotonin transporter (5-HTT) knockout (KO) mice. From 8 weeks of age, mice either continued in standard-housing conditions or were given access to voluntary running wheels for 1 month. Electrophysiology was performed on hippocampal slices to measure LTP and LTD, and immunohistochemistry was used to assess cell proliferation and subsequent survival in the dentate gyrus. The results revealed a reduced LTP in 5-HTT KO mice that was restored to wild-type (WT) levels after chronic exercise. While LTD appeared normal in 5-HTT KO, exercise decreased the magnitude of LTD in both WT and 5-HTT KO mice. Furthermore, although 5-HTT KO mice had normal hippocampal adult-born cell survival, they did not benefit from the pro-proliferative effects of exercise observed in WT animals. Taken together, these findings suggest that reduced 5-HTT expression is associated with significant alterations to functional neuroplasticity. Interestingly, 5-HTT appeared necessary for exercise-induced augmentation of adult-born hippocampal cell survival, yet exercise corrected the LTP impairment displayed by 5-HTT KO mice. Together, our findings further highlight the salience of serotonergic signalling in mediating the neurophysiological benefits of exercise.


30-day readmission following weight loss surgery: can psychological factors predict nonspecific indications for readmission?
Thirty-day readmissions occur in 5% or more of bariatric surgery patients. Some readmissions relate directly to surgical risks, whereas others relate to more nonspecific complaints or nonadherence and may reflect risks outside of the surgical procedure. To investigate whether presurgical psychosocial factors are related to readmission. Tertiary/quaternary academic referral center. Bariatric surgery patients readmitted within 30 days of surgery during 2012-2015 were identified (n = 102). Patients were matched (2:1) on body mass index, age, sex, and race to 204 nonreadmitted patients. Psychiatric variables and psychological testing (Minnesota Multiphasic Personality Inventory-2-Restructured Form) at intake were compared between the 2 groups. Among those readmitted, the indication for readmission was investigated. Those with specific complications (n = 61) were delineated from those with nonspecific indications (n = 33). Those with nonspecific readmissions were younger and more likely to be female. These patients were also less likely to be in outpatient psychiatric care than nonreadmitted patients. Significant differences were found on the Uncommon Virtues scale of the Minnesota Multiphasic Personality Inventory-2-Restructured Form, which reflects a tendency to underreport disinhibited behaviors. Those with nonspecific readmissions had significantly higher underreporting scores compared to those with specific indications or those not readmitted. Readmitted patients, particularly those with nonspecific indications, were more likely to presurgically present themselves in an overly positive manner. The tendency to underreport may affect the team's ability to identify risk factors that could be ameliorated before surgery. Readmitted patients were also less likely to be receiving mental health care. Such ongoing treatment may increase monitoring and/or adherence after surgery.


Prevalence of under and over weight in children with neurodisability, using body composition measures.
We aimed to compare rates of under and overweight in children with different neurodevelopmental disorders (NDD) by measuring weight, height/length, arm-to-leg bioelectrical impedance (BIA) and subscapular and triceps skinfolds in 146 children aged 4-16 years attending special schools. Z scores were calculated and skinfolds and lean mass Z scores were further adjusted for height. Underweight was found in 9% (14) children (body mass index (BMI) < 2nd) but only 3% (4) had skinfolds <5th centile. Overweight was much commoner, with 41% (58) children having BMI > 95th and 20% (14) had skinfolds >95th centile. Children with cerebral palsy were very short with low BMI and lean mass, but only 8% (3) had skinfolds <5th centile. The children with Down syndrome were also very short and once adjusted for height, half had skinfolds >95th centile. We conclude that overweight and raised body fat is now common in children with NDD, even when the BMI is low.


A new method to study shape recovery of red blood cells using multiple optical trapping.
In this new method for studying the shape recovery of deformed red blood cells, three optical traps ("optical tweezers") induce a parachute-shaped red cell deformation, which is comparable to the deformation in small capillaries. The shape recovery is recorded, and a relaxation time is obtained for each individual red blood cell. The sensitivity of this technique for the detection of differences in relaxation times is demonstrated on subpopulations of density-separated red blood cells: "young" cells have shorter (162 ms) and "old" cells have longer (353 ms) relaxation times compared with the total population (271 ms). The relaxation time is remarkably shorter (114 ms) when the plasma surrounding the cells is replaced by a phosphate-buffered saline solution. The main advantages of this technique are the relatively short measuring and preparation time and the physiological type of deformation and shape recovery in which all relevant cell properties play a role. Therefore, especially when automated further, the technique may be a powerful tool for the study of (sub)populations of pathological red blood cells.


Remarks on q-space MR propagator in partially restricted, axially-symmetric, and isotropic environments.
The problem of reconstruction of an apparent propagator from a series of diffusion-attenuated magnetic resonance (MR) signals is revisited. In nonimaging acquisitions, the inverse Fourier transform of the MR signal attenuation is consistent with the notion of an ensemble average propagator. However, in image acquisitions where one is interested in quantifying a displacement distribution in every voxel of the image, the propagator derived in the traditional way may lead to a counter-intuitive profile when it is nonsymmetric, which could be a problem in partially restricted environments. By exploiting the reciprocity of the diffusion propagator, an alternative is introduced, which implies a forward Fourier transform of the MR signal attenuations yielding a propagator reflected around the origin. Two simple problems were considered as examples. In the case of diffusion in the proximity of a restricting barrier, the reflected propagator yields a more meaningful result, whereas in the case of curving fibers, the original propagator is more intuitive. In the final section of the article, two more one-dimensional transformations are introduced, which enable the reconstruction of two- and three-dimensional propagators in, respectively, axially symmetric and isotropic environments - in both cases, from one-dimensional q-space MR data.


[Trabecular meshwork and elastin].
Evidence that elastic fibers with elastin exists in the trabecular meshwork (TM) and play an important role in aqueous outflow resistance is presented. The elastic fibers consist of abundant microfibrillar components containing glycoproteins and amorphous components containing elastin. If TM tissues are digested with elastase, the cells composing trabecular sheets and Schlemm's canal are separated with a decrease of elastin and come in contact with each other with reproduction of elastin. When the anterior segments of eyes are perfused with elastase, the intraocular pressure drops with a decrease of outflow resistance. A large quantity of elastin exists in fine fibrils lying underneath the trabecular wall of Schlemm's canal in primary open angle glaucoma (POAG) eyes, in pseudoexfoliation (PE) materials of PE glaucoma eyes and in basement membrane and fine fibril-like materials of steroid glaucoma eyes. In congenital and juvenile glaucoma eyes, however, instead of elastin, fibronectin localizes in basement membrane and fine fibril-like materials. When TM tissues respond to steroid hormone, the tissues synthesize and secret microfibrils and elastin, components of the elastic fibers. Elastin gene expresses in human TM. Orally administered elastase is transferred in aqueous humor and digests elastin in TM. Therefore it is possible that such a drug decreases the outflow resistance of glaucoma eyes.


A new colorimetric method for the estimation of glycosylated hemoglobin.
A new colorimetric method, based on the phenol sulphuric acid reaction of carbohydrates, is described for the determination of glycosylated hemoglobin. Hemolyzates were treated with 1 mol/l oxalic acid in 2 mol/l Hcl for 4 h at 100 degrees C, the protein was precipitated with trichloroacetic acid, and the free sugars and hydroxymethyl furfural in the protein free supernatant were treated with phenol and sulphuric acid to form the color. The new method is compared to the thiobarbituric acid method and the ion-exchange chromatographic method for the estimation of glycosylated hemoglobin in normals and diabetics. The increase in glycosylated hemoglobin in diabetic patients as estimated by the phenol-sulphuric acid method was more significant (P less than 0.001) than the increase observed by the thiobarbituric acid method (P less than 0.01). The correlation between the phenol-sulphuric acid method and the column method was better (r = 0.91) than the correlation between the thiobarbituric acid method and the column method (r = 0.84). No significant correlation between fasting and postprandial blood sugar level and glycosylated hemoglobin level as determined by the two colorimetric methods was observed in diabetic patients.


Transcriptional regulation of Treg homeostasis and functional specification.
CD4+Foxp3+ regulatory T (Treg) cells are key players in keeping excessive inflammation in check. Mounting evidence has shown that Treg cells exert much more diverse functions in both immunological and non-immunological processes. The development, maintenance and functional specification of Treg cells are regulated by multilayered factors, including antigens and TCR signaling, cytokines, epigenetic modifiers and transcription factors (TFs). In the review, we will focus on TFs by summarizing their unique and redundant roles in Treg cells under physiological and pathophysiological conditions. We will also discuss the recent advances of Treg trajectories between lymphoid organs and non-lymphoid tissues. This review will provide an updated view of the newly identified TFs and new functions of known TFs in Treg biology.


[Predict response to decitabine in patients with myelodysplastic syndrome and related neoplasms].
Objective: To identify clinical and molecular signatures for predicting response to decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and related neoplasms. Methods: The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment. Results: Of 109 MDS and related neoplasms patients, there were 70 males and 39 females, the median age was 61 years old (ranges: 17-85 years old) . According to the international prognostic scoring system (IPSS) , 46 cases were included in the relatively low risk group (low risk and intermediate-1 risk) , 63 in the relative high risk group (intermediate-2 and high risk) . There were 21 cases with complex karyotype, 17 chromosome 7 abnormality and 17 monosomal karyotype. The median courses of DAC treatment was 4 (2-11) . A total of 74 patients achieved response (67.9%) and 30 (27.5%) achieved complete response (CR) . Univariate analysis found that CR was higher in patients with high risk of IPSS, complex karyotypes, monosomal karyotypes, chromosome 7 abnormality, and platelet doubling after one cycle of DAC treatment. Patients with TP53 gene mutation were more likely to receive CR, 10 of 15 patients with TP53 mutations achieved CR. (66.7%) , which was significantly higher than that of the patients without TP53 gene mutation (21.3%) (P=0.001) . Multivariate analysis showed that TP53 gene mutation, platelet doubling after one cycle of DAC treatment and the complex karyotype were independent prognostic factors for CR. Of them, TP53 gene mutation is the strongest predictor (OR=4.39, 95%CI, 1.20-16.06, P=0.026) . Conclusion: TP53 mutation, platelet doubling after one cycle of DAC treatment and complex karyotypes could predict CR to DAC.


Determinants of eating behaviour in Black, Asian and Minority Ethnic (BAME) university students when living at and away from home: With a focus on the influence of food enculturation and food acculturation.
For some students, university, can be a period of increased autonomy in food choice and for black, Asian and minority ethnic (BAME) and international students, the addition of culture may be a governing factor. This study aimed to examine the extent of dietary acculturation and dietary enculturation on the influence of student's food choices using a phenomenological approach. Sixty participants (forty-one home students and nineteen international students) recruited by purposive sampling, were included in the study. Data collection involved self-administered multiple choice and short answer questionnaires and semi structured interviews. The results were analysed using thematic analysis. When living away from home, six major themes influenced the eating behaviour of the studied population: social environment, individual factors, physical environment, university life, enculturation and acculturation. When at home, five major themes were influential: social environment, individual factors, physical environment, enculturation and acculturation. The main findings suggest dietary enculturation is a factor which influences the dietary behaviour of both international students and BAME home students.


A trial of folate supplementation in children with homozygous sickle cell disease.
A double blind controlled trial of supplementation with folic acid has been performed in 117 children with homozygous sickle cell (SS) disease aged 6 months to 4 years over a 1 year period. No megaloblastic change was observed in either group. At the end of the study period the folate supplemented group showed no significant differences in haemoglobin, growth characteristics, or in the proportion of children affected by major or minor infections, acute splenic sequestration, dactylitis or episodes of bone or abdominal pain. However, the folate supplemented group showed a significantly lower mean cell volume and the placebo group contained a significant excess of children experiencing multiple episodes of dactylitis. The results are compatible with mild folate deficiency in some patients in the placebo group but the absence of striking effects on haematology or growth suggest that the policy of regular folate supplementation in children with SS disease should be critically reviewed.


A practical approach to restoring occlusion for edentulous patients. Part II: Arranging the functional and rational mold combination.
A practical approach to restoring the edentulous patient to full occlusion is no easy task. It requires the dentist to establish a philosophy of occlusion, select an occlusal concept to be used with the philosophy, and then choose an occlusal scheme to satisfy the concept and fulfill the philosophy. Several combinations of molds can be used in this manner. Of the three presented, the Trubyte functional/rational combination was found most acceptable. The requirements and techniques in the use of this combination were described.


Microfracture in Linear, Isolated, Narrow, Engaging Hill-Sachs Lesion.
Treatment of Hill-Sachs lesions is still controversial despite the frequent incidence in patients with recurrent shoulder dislocation. We report the use of arthroscopic microfracture for the treatment of recurrent shoulder dislocation with a linear, isolated, narrow, engaging Hill-Sachs lesion. Arthroscopic microfracture can be an alternative treatment option to obtain healing of defects and avoid external rotation limitation in young, active patients with recurrent dislocation with linear, isolated, narrow, engaging lesions.


Unusual angiographic manifestations of craniopharyngioma: a case report.
A craniopharyngioma with two unusual manifestations, a dense capsular stain and occlusion of the internal carotid artery, is reported. Neither of these findings appear to have been reported previously. Explanations for these unusual phenomena are offered.


Bacteriocholorophyll a cation radical in solution and in reaction centers of Rhodopseudomonas sphaeroides. Resonance Raman scattering.
Resonance Raman spectra of the pi-cation of bacterio-chlorophyll a in solution at 30 K are reported and discussed. Outer (formula: see text) bonds of the pyrroles and the methine bridges are weakened by the ionization, while (formula: see text) and Mg-N bonds remain essentially unaffected. Resonance Raman spectra of reaction centers suggest that the positive charge on P-870+ should be localized on a single bacteriochlorophyll molecule by the lifetime of the scattering process (approximately 10(-13)s).


Purification and properties of the ubiquitin-conjugating enzymes Cdc34 and Ubc13.Mms2.
A prerequisite for structure/function studies on the ubiquitin-conjugating enzymes (Ubc) Cdc34 and Ubc13.Mms2 has been the ability to express and purify recombinant derivatives of each. This chapter describes the methods used in the expression and purification of these proteins from Escherichia coli, including variations of these protocols used to generate (35)S, (15)N, (13)C/(15)N, and seleno-L-methionine derivatives. Assays used to measure the Ub thiolester and Ub conjugation activities of these Ubcs are also described.


Microbial metabolism of C1 and C2 compounds. The role of acetate during growth of Pseudomonas AM1 on C1 compounds, ethanol and beta-hydroxybutyrate.
Pseudomonas AM1 grows on beta-hydroxybutyrate and methanol at similar rates. beta-Hydroxybutyrate is not metabolized by way of the glyoxylate bypass, but is assimilated by the novel route (with acetate as an intermediate) that operates during growth of this organism on ethanol. Evidence from short-term labelling experiments indicates that acetate, which is a possible intermediate in the assimilation of C(1) compounds, is rapidly metabolized to glycine during growth of Pseudomonas AM1 on methanol.


Structural analysis of the gene encoding rat cholesterol alpha-hydroxylase, the key enzyme for bile acid biosynthesis.
The gene encoding cholesterol 7 alpha-hydroxylase (P450VIIA) was isolated from rat genomic DNA. The gene spanned about 11 kilobases and contained six exons. Blotting analysis of genomic DNA and complete matching of restriction maps of several isolated genomic clones indicated that there appeared to be only one gene in the rat genome. The putative transcription initiation site was present 61 base pairs upstream from the ATG codon. The typical TATA sequence and CCAAT promoter element were found at 24 and 47 base pairs upstream from the transcription initiation site, respectively. Alignment of several P450 proteins showed that the cholesterol 7 alpha-hydroxylase gene shared location of introns with none of the other P450 genes except for intron 5, which was in the same position as intron 10 of the gene encoding P450IVA1. The alignment also indicated that the distal helix of cholesterol 7 alpha-hydroxylase contained an asparagine in place of the well conserved threonine that is postulated to be involved in the O2 binding site. Unusual residues, Asn-126 and Thr-442, were also found at the sites where all other P450s have positively charged amino acids, which are considered to be involved in interaction with heme propionate. These replacements may be related to the unique function and unusual lability of the hydroxylase. Analysis of evolutionary distance between the cholesterol 7 alpha-hydroxylase gene and other known P450 genes indicated that yeast P450LIA is most closely related to P450VIIA. This finding suggests that the cholesterol 7 alpha-hydroxylase gene is an evolutionarily old P450 gene.


Erratum regarding previously published articles.
[This corrects the article DOI: 10.1016/j.metop.2021.100149.][This corrects the article DOI: 10.1016/j.metop.2022.100202.][This corrects the article DOI: 10.1016/j.metop.2021.100160.][This corrects the article DOI: 10.1016/j.metop.2021.100136.][This corrects the article DOI: 10.1016/j.metop.2022.100203.][This corrects the article DOI: 10.1016/j.metop.2022.100182.].


A robust and efficient alluvial filtration method for the clarification of adeno-associated viruses from crude cell lysates.
Adeno-associated virus (AAV) based vectors have recently been gaining importance as DNA delivery systems. Efficient downstream processing of AAV remains a major challenge as serotypes differ in physicochemical properties, making it difficult to design uniform purification processes. Clarification of AAV is an especially critical step. Harvesting of AAV, like other viruses, often requires cell lysis, resulting in a difficult-to-filter cell lysate. In this study, we evaluated the applicability of diatomaceous earth (DE) as a filter aid for clarification of AAV crude cell lysates. DE filtration proved to be a viable clarification method for AAV2, AAV5 and AAV8. Based on a design of experiment approach, the DE concentration was identified as the main factor influencing AAV particle loss. The loss of AAV during DE filtration was limited to < 2% by maintaining the DE quantity below 0.181 mg DE/1010 AAV. Use of DE reduced manual handling time 3-fold and increased the filter capacity 3.5-fold compared to filtration combined with a prior centrifugation step. Moreover, we showed that the DE type had only a minor influence on the filtration performance. This study demonstrated that filtration with DE as a filter aid is an efficient clarification method for different AAV serotypes.


The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children.
Obesity is known to be associated with many diseases in the long and short terms. Elevated oxidative stress contributes to the development of such obesity-related diseases as dyslipidemia, diabetes mellitus and hypertension. Levels of the endogenous antioxidants paraoxonase and arylesterase have been shown to decrease in such diseases. The purpose of this study was to investigate whether or not changes in lifestyle and metformin therapy would affect serum paraoxonase and arylesterase levels. The study was performed with 25 overweight, 26 obese and 25 morbidly obese patients aged 6-15 years as well as 27 healthy children. Serum paraoxonase (PON1) and arylesterase (ARE) activity levels and total cholesterol, triglyceride, low-density protein, high-density protein, very low-density protein, glucose, aspartate amino transferase and alanine amino transferase levels were measured. Enrolled patients were assessed at initial presentation and again at 6 months. No procedure was performed in the control group, while the overweight, obese and morbidly obese groups were recommended diet and exercise and given metformin therapy (insulin-resistant subjects only). Serum PON1 activity levels in patients with metabolic syndrome were significantly lower than those in individuals without metabolic syndrome (p<0.05), while lipid concentrations were significantly higher (p<0.05). Metabolic syndrome patients had higher serum glucose, total cholesterol, low-density protein, very low-density protein and triglyceride values compared to those of the control group but significantly lower high-density protein values (p<0.05). No difference was determined between the groups in terms of PON1 and ARE levels following diet and exercise and metformin therapy. Measurement of PON1 and ARE enzyme levels may be useful in monitoring the effectiveness of treatment aimed at reducing oxidative stress in obese children.


Going digital as a result of COVID-19: Insights from students' and teachers' impressions in a Swedish university.
During the past two years, the entire world has been coping with the consequences of the COVID-19 pandemics. The need for physical distancing, forced an accelerated digital transformation of the education sector. The emergency remote education (ERE) has been manifested differently across diverse countries in the world. In this paper, we bring a case study about students' and teachers' impressions and experiences regarding the changes that have happened due to pandemic conditions in university courses in informatics at a Swedish university. This research is conducted through a mix of quantitative and qualitative empirical data. These data have been collected through the students surveys, course logs, as well as teachers and ICT pedagogue interviews. The collected data have been analyzed through the technology-mediated learning (TML) theoretical framework. Based on the thematic analysis on the collected data, we have identified three main themes: a) Preparedness, b) Challenges with ERE and c) Opportunities with ERE. As a result, through analyzing data in the light of the ERE experiences that encompasses the educational process, affordance, and beliefs, knowledge, and practices, we provide a set of lessons-learned experiences and indicate the possible lines of actions when it comes to the learning design in the constrained pandemic situations.


Mutagenicity of nitrosamines formed from nitrosation of spermidine.
5 nitrosamines formed from the nitrosation of spermidine were investigated for mutagenicity using various strains of Salmonella typhimurium in the presence and absence of S9 mix. Using the plate incorporation method, 3-butenyl-(2-propenyl)-N-nitrosamine, 3-hydroxybutyl (2-hydroxypropyl)-N-nitrosamine, 4-hyroxybutyl-(2-hydroxypropyl)-N-nitrosamine, 4 hydroxybutyl-(3-hydroxypropyl)-N-nitrosamine, and in the liquid test 3-hydroxybutyl-(3-hydroxypropyl)-N-nitrosamine were mutagenic in the absence of S9 mix.


Thioredoxin and hematologic malignancies.
Thioredoxin (Trx) is an inflammation-inducible small oxidoreductase protein ubiquitously expressed in all organisms. Trx acts both intracellularly and extracellularly and is involved in a wide range of physiological cellular responses. Inside the cell, Trx alleviates oxidative stress by scavenging reactive oxygen species (ROS), regulates a variety of redox-sensitive signaling pathways as well as ROS-independent genes, and exerts cytoprotective effects. Outside the cell, Trx acts as growth factors or cytokines and promotes cell growth and many other cellular responses. Trx is also implicated in tumorigenesis. Trx is a proto-oncogene and is overexpressed in many cancers and correlates with poor prognosis. Trx stimulates cancer cell survival, promotes tumor angiogenesis, and inhibits both spontaneous apoptosis and drug-induced apoptosis. Inhibitors targeting Trx pathway provide a promising therapeutic strategy for cancer prevention and intervention. More recently, data from our laboratory demonstrate an important role of Trx in expanding long-term repopulating hematopoietic stem cells. In this chapter, we first provide an overview of Trx including its isoforms, compartmentation, and functions. We then discuss the roles of Trx in hematologic malignancies. Finally, we summarize the most recent findings from our lab on the use of Trx to enhance hematopoietic reconstitution following hematopoietic stem cell transplantation.


Implementation of competence committees during the transition to CBME in Canada: A national fidelity-focused evaluation.
This study evaluated the fidelity of competence committee (CC) implementation in Canadian postgraduate specialist training programs during the transition to competency-based medical education (CBME). A national survey of CC chairs was distributed to all CBME training programs in November 2019. Survey questions were derived from guiding documents published by the Royal College of Physicians and Surgeons of Canada reflecting intended processes and design. Response rate was 39% (113/293) with representation from all eligible disciplines. Committee size ranged from 3 to 20 members, 42% of programs included external members, and 20% included a resident representative. Most programs (72%) reported that a primary review and synthesis of resident assessment data occurs prior to the meeting, with some data reviewed collectively during meetings. When determining entrustable professional activity (EPA) achievement, most programs followed the national specialty guidelines closely with some exceptions (53%). Documented concerns about professionalism, EPA narrative comments, and EPA entrustment scores were most highly weighted when determining resident progress decisions. Heterogeneity in CC implementation likely reflects local adaptations, but may also explain some of the variable challenges faced by programs during the transition to CBME. Our results offer educational leaders important fidelity data that can help inform the larger evaluation and transformation of CBME.


Control of Rous sarcoma virus RNA translation and packaging by the 5' and 3' untranslated sequences.
A cytopathic mutant of Rous sarcoma virus-PrB was isolated and shown to have two large deletions, which result in the junction of Gag sequences in P27 to the 5' end of Env, and in the loss of the Src gene. This replication-defective (rd) and transformation-defective (td) mutant can replicate in the presence of its helper, which is also td, but the viral particles produced are poorly infectious. Most of the virions do not contain viral RNA, and the mutant RNA accumulates in infected cells, where it is poorly translated and packaged. Molecular clones of the mutant, of its helper and of a PrBtd strain were obtained in lambda-EMBL3, characterized, shown to be biologically active by transfection assays and sequenced. Nucleotide sequence comparisons indicate that the strong ribosome-binding site of Rous sarcoma virus RNA, responsible for the efficient RNA translation in vivo and in vitro, is mutated in PrB-(HM) mutant RNA; this causes the inhibition of RNA translation, as demonstrated by translation competition experiments using virus RNA made in vitro that carries the original or the mutated ribosome-binding site. In addition, an insertion present at the 3' end of both the mutant and the helper RNA, but absent in PrBtd RNA, is probably responsible for the inhibition of RNA packaging. Finally, these data are discussed in the light of a model of a 5'----3' Rous sarcoma virus RNA structure leading to a circular RNA molecule, which has implications in RNA translation, packaging and reverse transcription.


Evaluation of UBE3A antibodies in mice and human cerebral organoids.
UBE3A is an E3 ubiquitin ligase encoded by the neurally imprinted UBE3A gene. The abundance and subcellular distribution of UBE3A has been the topic of many previous studies as its dosage and localization has been linked to neurodevelopmental disorders including Autism, Dup15q syndrome, and Angelman syndrome. While commercially available antibodies have been widely employed to determine UBE3A localization, an extensive analysis and comparison of the performance of different UBE3A antibodies has not been conducted. Here we evaluated the specificities of seven commercial UBE3A antibodies in two of the major experimental models used in UBE3A research, mouse and human pluripotent stem cell-derived neural cells and tissues. We tested these antibodies in their two most common assays, immunofluorescence and western blot. In addition, we also assessed the ability of these antibodies to capture dynamic spatiotemporal changes of UBE3A by utilizing human cerebral organoid models. Our results reveal that among the seven antibodies tested, three antibodies demonstrated substantial nonspecific immunoreactivity. While four antibodies show specific localization patterns in both mouse brain sections and human cerebral organoids, these antibodies varied significantly in background signals and staining patterns in undifferentiated human pluripotent stem cells.