Facile Transformation of Murine and Human Primary Dendritic Cells into Robust and Modular Artificial Antigen-Presenting Systems by Intracellular Hydrogelation.
The growing enthusiasm for cancer immunotherapies and adoptive cell therapies has prompted increasing interest in biomaterials development mimicking natural antigen-presenting cells (APCs) for T-cell expansion. In contrast to conventional bottom-up approaches aimed at layering synthetic substrates with T-cell activation cues, transformation of live dendritic cells (DCs) into artificial APCs (aAPCs) is demonstrated herein using a facile and minimally disruptive hydrogelation technique. Through direct intracellular permeation of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel monomer and UV-activated radical polymerization, intracellular hydrogelation is rapidly accomplished on DCs with minimal influence on cellular morphology and surface antigen display, yielding highly robust and modular cell-gel hybrid constructs amenable to peptide antigen exchange, storable by freezing and lyophilization, and functionalizable with cytokine-releasing carriers for T-cell modulation. The DC-derived aAPCs are shown to induce prolonged T-cell expansion and improve anticancer efficacy of adoptive T-cell therapy in mice compared to nonexpanded control T cells, and the gelation technique is further demonstrated to stabilize primary DCs derived from human donors. The work presents a versatile approach for generating a new class of cell-mimicking biomaterials and opens new venues for immunological interrogation and immunoengineering.


[Category-specific deficits in semantic dementia: links between perception and semantic knowledge].
The nature of knowledge and its relationship with the perceptual processes are among the most central issues in the study of human cognition. Should knowledge be abstract, then semantic memory and perception should be relatively independent. On the contrary, if knowledge is sensory-dependent, then memory and perception should be very close. The first view is supported by the multiple system approach of memory, whereas the second view is supported by the single-store memory theories. One way to study these links is through the category-specific impairment and the sensory-functional theory (SFT). Category-specific impairment is generally observed for living items compared to artefacts. The SFT explains this deficit by defining living items as essentially based on perception. In the abstract view of knowledge, a living deficit should be related to a deficit in processing sensory knowledge. On the opposite, the sensory-dependent view states that this deficit results from perception impairment. This article focuses on the relations between knowledge and perception in semantic dementia (SD). SD is characterized by a progressive loss of semantic knowledge, making it particularly interesting to study. This article first focuses on the SFT, to explain the category-specific impairment. The issue of perceptual processing in SD is then reviewed from the lowest level (senses) to the highest level of perception (multimodal integration). The data demonstrated normal perception for these patients. However, visual integration appeared to be impaired for existing knowledge. This result is discussed in relation with a possible involvement of the anterior temporal lobes. These regions are known to be the most vulnerable in SD. Recently these regions have also been shown to be involved in the multimodal integration. Taken together, these data suggest that perception and knowledge could be linked and partially explained by the SFT. Finally, the data support the sensory-dependent approaches of memory.


Usefulness of an early diagnosis for the favorable prognosis of fibrocartilaginous embolism diagnosed by magnetic resonance imaging in 10 small- to middle-sized dogs.
Fibrocartilaginous embolism (FCE), a disorder of rapid onset featured by nonprogressive paralysis and paresis of four legs, shows clinical symptoms very similar to those of other disorders, e.g., disk herniation. We examined 10 animals diagnosed with FCE based on clinical symptoms and magnetic resonance imaging (MRI) findings in a retrospective study to examine the relationship between onset-to-diagnosis/treatment initiation time and prognosis of FCE. Statistical procedures, including Fisher's exact probability test, were conducted. All animals in a group, in which the diagnosis was made and treatment was initiated after an elapse of <15 days after onset, showed improved symptoms; the group showed a positive correlation (r = 0.76) between "onset-to-symptom improvement time" and "onset-to-diagnosis/treatment initiation time". Furthermore, the mean onset-to-diagnosis/ treatment initiation times were 2.67 days and 10.25 days in groups without and with sequelae, respectively; the time was significantly (P < 0.02) shorter in the group without sequelae. A significant difference was found between the groups in early diagnosis and treatment initiation. Our study indicates that the early precise diagnosis for acutely developed paralysis and paresis of four legs through testings including MRI, as well as the early onset of their treatment are important to obtain a favorable prognosis.


Outcomes of male patients with Alport syndrome undergoing renal replacement therapy.
Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases. Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival. Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls. These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure.


Hardware assessment using the multi-module, multi-resolution system (M3R): a signal-detection study.
The multi-module, multi-resolution system (M3R) is used for hardware assessment in objective, task-based signal detection studies in projection data. A phantom capable of generating multiple realizations of a random textured background is introduced. Measured backgrounds from this phantom are used along with simulated lumpy and uniform backgrounds to investigate signal-to-noise ratio as a function of exposure time. Results are shown to agree with theoretical predictions, exhibiting a power-law like dependence previously seen for studies performed either in simulation or without an imaging system, and help validate the use of simulated lumpy backgrounds in observer studies. A second study looks at signal-detection performance, measured by AUC (area under the receiver operating characteristic curve), in lumpy backgrounds for 20 M3R aperture combinations as a function of lump size and signal size. Observer performance reveals an improvement in AUC for certain ranges of signal and lump combinations through the use of multiplexed, multiple-pinhole apertures, indicating a need for task-specific aperture optimization. The channelized Hotelling observer is used with Laguerre-Gauss channels for both observer studies. Methods for selection of number of channels and channel width are discussed.


Resident cardiac stem cells.
Regardless of erroneous claims by a minority of reports, adult cardiomyocytes are terminally differentiated cells which do not re-enter the cell-cycle under any known physiological or pathological circumstances. However, it has recently been shown that the adult heart has a robust myocardial regenerative potential, which challenges the accepted notions of cardiac cellular biology. The source of this regenerative potential is constituted by resident cardiac stem cells (CSCs). These CSCs, through both cell transplantation and in situ activation, have the capacity to regenerate significant segmental and diffuse myocyte losts, restoring anatomical integrity and ventricular function. Thus, CSC identification has started a brand new discipline of cardiac biology that could profoundly changed the outlook of cardiac physiology and the potential for treatment of cardiac failure. Nonetheless, the dawn of this new era should not be set back by premature attempts at clinical application before having accumulated the required scientifically reproducible data.


T'ai Chi exercise in patients with chronic heart failure.
To review the physiological and psychosocial effects of a 12-week T'ai Chi program (TC) in patients with heart failure (HF) as previously reported in a clinical trial. We randomized 30 patients with chronic HF (left ventricular ejection fraction < or =40%) to receive TC plus usual care (n = 15), or usual care alone (wait-list control, n = 15). Outcome measures included quality of life, exercise capacity, B-type natriuretic peptide, catecholamine levels, heart rate variability, and sleep stability. The mean age (+/-SD) of patients was 64 +/- 13 years, mean baseline ejection fraction (+/-SD) was 23 +/- 7%, and median New York Heart Association Class was 2 (range 1-4). At 12 weeks, patients who participated in TC showed improved quality of life (mean change -17 +/- 11 vs. 8 +/- 15, Minnesota Living with HF Questionnaire, p = 0.001), increased exercise capacity (mean change 85 +/- 46 vs. -51 +/-58 m, 6-min walk, p = 0.001), and decreased B-type natriuretic peptide (mean change -48 +/- 104 vs. 90 +/- 333 pg/ml, p = 0.03) compared to the control group. Those who participated in TC also showed improvement in sleep stability (increase in high-frequency coupling +0.05 +/- 0.10 vs. -0.06 +/- 0.09 proportion of estimated total sleep time, p = 0.04; reduction in low-frequency coupling -0.09 +/- 0.09 vs. +0.13 +/- 0.13 proportion of estimated total sleep time, p < 0.01), compared to the control group. TC may enhance quality of life, exercise capacity, and sleep stability in patients with chronic HF.


Sequential assembly of centromeric proteins in male mouse meiosis.
The assembly of the mitotic centromere has been extensively studied in recent years, revealing the sequence and regulation of protein loading to this chromosome domain. However, few studies have analyzed centromere assembly during mammalian meiosis. This study specifically targets this approach on mouse spermatocytes. We have found that during prophase I, the proteins of the chromosomal passenger complex Borealin, INCENP, and Aurora-B load sequentially to the inner centromere before Shugoshin 2 and MCAK. The last proteins to be assembled are the outer kinetochore proteins BubR1 and CENP-E. All these proteins are not detected at the centromere during anaphase/telophase I and are then reloaded during interkinesis. The loading sequence of the analyzed proteins is similar during prophase I and interkinesis. These findings demonstrate that the interkinesis stage, regularly overlooked, is essential for centromere and kinetochore maturation and reorganization previous to the second meiotic division. We also demonstrate that Shugoshin 2 is necessary for the loading of MCAK at the inner centromere, but is dispensable for the loading of the outer kinetochore proteins BubR1 and CENP-E.


Persistence and safety assessment of novel probiotic strain Lactobacillus plantarum 1 strain Lp86 and Lp36 in Salmonella typhi infected mice.
The species of Lactic acid bacteria are known to confer beneficial effects on the host by inhabiting in their gastrointestinal tract (GIT). They succeed in surviving the harsh conditions of the GIT by exhibiting strong tolerance against gastric acids, digestive enzymes and bile simultaneously antagonizing the pathogens by production of antimicrobials. This study has been conducted to elaborate these probiotic characteristics in vivo for which mice were intragastrically given a probiotic approved dose of 1011cfu/ml for 4 days to assess the persistence of two probiotic candidates Lactobacillus plantarum Lp36 and Lactobacillus plantarum Lp86. The fecal count of the test probiotic candidates were seen to persist well in the GIT for 15 days with a count ranging between 104-108cfu/ mg of feces (p>0.01). The safety assessment of L. plantarum Lp36 in healthy and S. typhi in infected mice showed an increase in cell count from (day zero of inoculation) 106cfu/100mg of feces to108cfu/100mg (p>0.01) which was maintained till day six, suggesting the persistence in the GIT. The sections of the mice intestinal lining under scanning electron microscope revealed the adherence of Lp36 and Lp86 to the intestinal epithelia. The mice did not show any adverse effect on its health. These findings make our strains promising probiotic candidates to be used to promote health benefits after further assessments.


INTERNAL LIMITING MEMBRANE PEELING VERSUS INVERTED FLAP TECHNIQUE FOR TREATMENT OF FULL-THICKNESS MACULAR HOLES: A COMPARATIVE STUDY IN A LARGE SERIES OF PATIENTS.
The inverted flap (IF) technique has recently been introduced in macular hole (MH) surgery. The IF technique has shown an increase of the success rate in the case of large MHs and in MHs associated with high myopia. This study reports the anatomical and functional results in a large series of patients affected by MH treated using pars plana vitrectomy and gas tamponade combined with internal limiting membrane (ILM) peeling or IF. This is a retrospective, consecutive, nonrandomized comparative study of patients affected by idiopathic or myopic MH treated using small-gauge pars plana vitrectomy (25- or 23-gauge) between January 2011 and May 2016. The patients were divided into two groups according to the ILM removal technique (complete removal vs. IF). A subgroup analysis was performed according to the MH diameter (MH < 400 µm and MH ≥ 400 µm), axial length (AL < 26 mm and AL ≥ 26 mm), and the presence of chorioretinal atrophy in the macular area (present or absent). We included 620 eyes of 570 patients affected by an MH, 300 patients underwent pars plana vitrectomy and ILM peeling and 320 patients underwent pars plana vitrectomy and IF. Overall, 84.94% of the patients had complete anatomical success characterized by MH closure after the operation. In particular, among the patients who underwent only ILM peeling the closure rate was 78.75%; among the patients who underwent the IF technique, it was 91.93% (P = 0.001); and among the patients affected by full-thickness MH ≥400 µm, success was achieved in 95.6% of the cases in the IF group and in 78.6% in the ILM peeling group (P = 0.001); among the patients with an axial length ≥26 mm, success was achieved in 88.4% of the cases in the IF group and in 38.9% in the ILM peeling group (P = 0.001). Average preoperative best-corrected visual acuity was 0.77 (SD = 0.32) logarithm of the minimum angle of resolution (20/118 Snellen) in the peeling group and 0.74 (SD = 0.33) logarithm of the minimum angle of resolution (20/110 Snellen) in the IF group (P = 0.31). Mean postoperative best-corrected visual acuity was 0.52 (SD = 0.42) logarithm of the minimum angle of resolution (20/66 Snellen) in the peeling group and 0.43 (SD = 0.31) logarithm of the minimum angle of resolution (20/53 Snellen) in the IF group (P = 0.003). Vitrectomy associated with the inverted ILM flap technique seems to be effective surgery for idiopathic and myopic large MHs, improving both functional and anatomical outcomes.


Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors.
Oncocytic tumors are a distinctive class of proliferative lesions composed of cells with a striking degree of mitochondrial hyperplasia that are particularly frequent in the thyroid gland. To understand whether specific mitochondrial DNA (mtDNA) mutations are associated with the accumulation of mitochondria, we sequenced the entire mtDNA in 50 oncocytic lesions (45 thyroid tumors of epithelial cell derivation and 5 mitochondrion-rich breast tumors) and 52 control cases (21 nononcocytic thyroid tumors, 15 breast carcinomas, and 16 gliomas) by using recently developed technology that allows specific and reliable amplification of the whole mtDNA with quick mutation scanning. Thirteen oncocytic lesions (26%) presented disruptive mutations (nonsense or frameshift), whereas only two samples (3.8%) presented such mutations in the nononcocytic control group. In one case with multiple thyroid nodules analyzed separately, a disruptive mutation was found in the only nodule with oncocytic features. In one of the five mitochondrion-rich breast tumors, a disruptive mutation was identified. All disruptive mutations were found in complex I subunit genes, and the association between these mutations and the oncocytic phenotype was statistically significant (P=0.001). To study the pathogenicity of these mitochondrial mutations, primary cultures from oncocytic tumors and corresponding normal tissues were established. Electron microscopy and biochemical and molecular analyses showed that primary cultures derived from tumors bearing disruptive mutations failed to maintain the mutations and the oncocytic phenotype. We conclude that disruptive mutations in complex I subunits are markers of thyroid oncocytic tumors.


Relativistic Effects on NMR Parameters of Halogen-Bonded Complexes.
Relativistic effects are found to be important for the estimation of NMR parameters in halogen-bonded complexes, mainly when they involve the heavier elements, iodine and astatine. A detailed study of 60 binary complexes formed between dihalogen molecules (XY with X, Y = F, Cl, Br, I and At) and four Lewis bases (NH3, H2O, PH3 and SH2) was carried out at the MP2/aug-cc-pVTZ/aug-cc-pVTZ-PP computational level to show the extent of these effects. The NMR parameters (shielding and nuclear quadrupolar coupling constants) were computed using the relativistic Hamiltonian ZORA and compared to the values obtained with a non-relativistic Hamiltonian. The results show a mixture of the importance of the relativistic corrections as both the size of the halogen atom and the proximity of this atom to the basic site of the Lewis base increase.


Psychotic bipolar disorders: dimensionally similar to or categorically different from schizophrenia?
For over a century, clinicians have struggled with how to conceptualize the primary psychoses, which include psychotic mood disorders and schizophrenia. Indeed, the nature of the relationship between mood disorders and schizophrenia is an area of ongoing controversy. Psychotic bipolar disorders have characteristics such as phenomenology, biology, therapeutic response, and brain imaging findings, suggesting both commonalities with and dissociations from schizophrenia. Taken together, these characteristics are in some instances most consistent with a dimensional view, with psychotic bipolar disorders being intermediate between non-psychotic bipolar disorders and schizophrenia spectrum disorders. However, in other instances, a categorical approach appears useful. Although more research is clearly necessary to address the dimensional versus categorical controversy, it is feasible that at least in the interim, a mixed dimensional/categorical approach could provide additional insights into pathophysiology and management options, which would not be available utilizing only one of these models.


Kinship in the SRP RNA family.
The signal recognition particle (SRP) is a ribonucleoprotein complex which participates in the targeting of protein to cellular membranes. The RNA component of the SRP has been found in all domains of life, but the size of the molecule and the number of RNA secondary structure elements vary considerably between the different phylogenetic groups. We continued our efforts to identify new SRP RNAs, compare their sequences, discover new secondary structure elements, conserved motifs, and other properties. We found additional proof for the variability in the apical loop of helix 8, and we identified several bacteria which lack all of their SRP components. Based on the distribution of SRP RNA features within the taxonomy, we suggest seven alignment groups: Bacteria with a small (4.5S) SRP RNA, Bacteria with a large (6S) SRP RNA, Archaea, Fungi (Ascomycota), Metazoa group, Protozoa group, and Plants. The proposed divisions improve the prediction of more distantly related SRP RNAs and provide a more inclusive representation of the SRP RNA family. Updates of the Rfam SRP RNA sequence collection are expected to benefit from the suggested groupings.


Effect of tachycardia heart failure on the restitution of left ventricular function in closed-chest dogs.
Cardiac mechanical restitution and relaxation restitution are thought to be physiological correlates of the recovery kinetics of Ca2+ release mechanisms and sequestration capacity of the sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca2+ handling, we sought to delineate changes in mechanical and relaxation restitution produced by heart failure. Six dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions and after tachycardia heart failure (THF) produced by rapid LV pacing for 3 to 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at graded extrasystolic intervals (ESIs). Mechanical response was assessed from single-beat elastance. Relaxation was assessed from the time constant of isovolumic relaxation (tau), the average rate of pressure fall during isovolumic relaxation (Ravg), and peak negative dP/dt, the first derivative of LV pressure. Normalized mechanical and relaxation responses plotted against ESI produced monoexponential curves of mechanical and relaxation restitution. THF depressed baseline contractile and relaxation parameters compared with control (end-systolic elastance, 4.7 +/- 0.4 versus 7.1 +/- 0.5 mm Hg/mL, P < .005; tau, 34.8 +/- 2.2 versus 26.7 +/- 1.2 ms, P < .05; all values mean +/- SEM). THF slowed mechanical restitution and delayed development of peak contractile response, with the time constant of mechanical restitution increasing from 61.8 +/- 6.9 to 100.2 +/- 9.6 ms, P < .01. THF abolished the biphasic behavior of relaxation restitution, and this relation was approximated by a single monoexponential function. There was no difference in the time constants of the first phase of relaxation restitution at control and after THF (TCR1, normalized 1/Ravg, 44.3 +/- 5.6 versus 42.0 +/- 8.5 ms, P = NS; TCR1, normalized (dP/dtmin)-1, 42.2 +/- 6.3 versus 36.7 +/- 4.3 ms, P = NS). These results indicate that THF alters the recovery kinetics of SR Ca2+ release to a significantly greater extent than those of SR Ca2+ sequestration and that the abnormal time course of Ca2+ availability to the myofilaments is the rate-limiting step in the recovery of cardiac function after a depolarization.


Cryopreservation and transplantation of spermatogonia and testicular tissue for preservation of male fertility.
The existence of spermatogonial stem cells in the testis offers clinically relevant options for preservation and restoration of male fertility. New approaches based on male germ cell transplantation and testicular tissue grafting can be applied to generate a limited number of sperm cells and could therefore be considered important new avenues for restoration of fertility in oncological patients. We have developed approaches to infuse germ cells into rodent and primate testes and shown that germ cell transplantation is a procedure for restoration of spermatogenesis in the testis that might be adaptable to primates. As a promising alternative, grafting of testicular tissue has been used to produce fertile sperm. The rapid progress in the development of novel experimental strategies to generate sperm by transplantation of spermatogonial stem cells or by grafting of testicular tissue should stimulate oncologists to consider the cryopreservation of testicular tissue. This review introduces the reader to the physiology of spermatogonial stem cells and summarizes the current and potential future options for fertility preservation in male oncological patients.


Never Too Old? Occurrence of Medulloblastoma in the Elderly beyond the 70th Year of Life.
The occurrence of medulloblastoma (MB) in the elderly is an absolutely rare event. Concerning this issue we report on two MB patients beyond the 70th year of life. Two patients older than 70 years presented with a mass in the posterior fossa without evidence of a preexisting malignant tumor. After careful radiological work-up the suspected diagnosis was metastasis of an unknown primary tumor. Both patients underwent surgery and histopathological analysis revealed MB in both cases (classical MB and desmoplastic type). The two cases presented here represent also one classical MB and one additional desmoplastic MB. To our knowledge we report for the first time that there are different molecular subtypes of MB in the elderly patients that seem to be consistent with those subtypes mainly occurring in young adults. Unfortunately the patients died within one week after surgery due to respiratory insufficiency and an unclear cause. The presented cases show that MB can occur in the elderly. Although this constellation is absolutely rare, MB should be considered in the differential diagnosis, especially when a primary tumor is not known or detected.


Towards an arthritis flare-responsive drug delivery system.
Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent dye demonstrates flare-dependent disassembly measured as loss of fluorescence. Moreover, a single dose of TA-loaded hydrogel but not the equivalent dose of locally injected free TA reduces arthritis activity in the injected paw. Together, our data suggest flare-responsive hydrogel as a promising next-generation drug delivery approach for the treatment of IA.


Empirical mode decomposition of digital mammograms for the statistical based characterization of architectural distortion.
Among the different and common mammographic signs of the early-stage breast cancer, the architectural distortion is the most difficult to be identified. In this paper, we propose a new multiscale statistical texture analysis to characterize the presence of architectural distortion by distinguishing between textural patterns of architectural distortion and normal breast parenchyma. The proposed approach, firstly, applies the bidimensional empirical mode decomposition algorithm to decompose each mammographic region of interest into a set of adaptive and data-driven two-dimensional intrinsic mode functions (IMF) layers that capture details or high-frequency oscillations of the input image. Then, a model-based approach is applied to IMF histograms to acquire the first order statistics. The normalized entropy measure is also computed from each IMF and used as a complementary textural feature for the recognition of architectural distortion patterns. For evaluating the proposed AD characterization approach, we used a mammographic dataset of 187 true positive regions (i.e. depicting architectural distortion) and 887 true negative (normal parenchyma) regions, extracted from the DDSM database. Using the proposed multiscale textural features and the nonlinear support vector machine classifier, the best classification performance, in terms of the area under the receiver operating characteristic curve (or Az value), achieved was 0.88.


Revised model for evaluating visiting health care services in rural and remote settings.
Visiting health care services were developed to improve access to essential health care in rural and remote areas. Evaluating these services requires a robust framework. The objective of this study was to assess the confirmability and credibility of a model of 7 principles for effective visiting health care services. Three iterative online survey rounds administered between July and December 2020. A heterogeneous panel of 13 experts in rural and remote health care participated, including managers of health care services, senior clinical staff in rural and remote regions and research academics specialising in rural infrastructure. The model was appraised using the Delphi method involving iterative online survey rounds to facilitate anonymous and structured discussion between panel members. Findings indicate consensus between panel members and support for a revised model. The revised model includes 4 modifications: (a) proposal of a new principle titled Feasibility, (b) restructure of 2 existing principles, (c) refined shape of the model to more accurately reflect the nature of service delivery and (d) detailed definitions of each principle. This study presents a credible, revised version of the model of 7 principles for effective visiting services. This will enhance the quality of the health workforce across geographically large countries, like Australia, enabling organisations to more effectively and consistently evaluate the impact of their service on rural and remote communities.


Protein Kinase CK2α', More than a Backup of CK2α.
The serine/threonine protein kinase CK2 is implicated in the regulation of fundamental processes in eukaryotic cells. CK2 consists of two catalytic α or α' isoforms and two regulatory CK2β subunits. These three proteins exist in a free form, bound to other cellular proteins, as tetrameric holoenzymes composed of CK2α2/β2, CK2αα'/β2, or CK2α'2/β2 as well as in higher molecular forms of the tetramers. The catalytic domains of CK2α and CK2α' share a 90% identity. As CK2α contains a unique C-terminal sequence. Both proteins function as protein kinases. These properties raised the question of whether both isoforms are just backups of each other or whether they are regulated differently and may then function in an isoform-specific manner. The present review provides observations that the regulation of both CK2α isoforms is partly different concerning the subcellular localization, post-translational modifications, and aggregation. Up to now, there are only a few isoform-specific cellular binding partners. The expression of both CK2α isoforms seems to vary in different cell lines, in tissues, in the cell cycle, and with differentiation. There are different reports about the expression and the functions of the CK2α isoforms in tumor cells and tissues. In many cases, a cell-type-specific expression and function is known, which raises the question about cell-specific regulators of both isoforms. Another future challenge is the identification or design of CK2α'-specific inhibitors.


Bereavement From COVID-19, Gender, and Reports of Depression Among Older Adults in Europe.
The coronavirus disease 2019 (COVID-19) pandemic has left older adults around the world bereaved by the sudden death of relatives and friends. We examine if COVID-19 bereavement corresponds with older adults' reporting depression in 27 countries and test for variations by gender and country context. We analyze the Survey of Health, Ageing and Retirement in Europe COVID-19 data collected between June and August 2020 from 51,383 older adults (age 50-104) living in 27 countries, of whom 1,363 reported the death of a relative or friend from COVID-19. We estimate pooled multilevel logit regression models to examine if COVID-19 bereavement is associated with self-reported depression and worsening depression, and we test whether national COVID-19 mortality rates moderate these associations. COVID-19 bereavement is associated with significantly higher probabilities of both reporting depression and reporting worsened depression among older adults. Net of one's own personal loss, living in a country with the highest COVID-19 mortality rate is associated with women's reports of worsened depression but not men's. However, the country's COVID-19 mortality rate does not moderate associations between COVID-19 bereavement and depression. COVID-19 deaths have lingering mental health implications for surviving older adults. Even as the collective toll of the crisis is apparent, bereaved older adults are in particular need of mental health support.


Automated landmark extraction for orthodontic measurement of faces using the 3-camera photogrammetry methodology.
To set up a three-dimensional photogrammetric scanning system for precise landmark measurements, without any physical contact, using a low-cost and noninvasive digital photogrammetric solution, for supporting several necessity in clinical orthodontics and/or surgery diagnosis. Thirty coded targets were directly applied onto the subject's face on the soft tissue landmarks, and then, 3 simultaneous photos were acquired using photogrammetry, at room light conditions. For comparison, a dummy head was digitized both with a photogrammetric technique and with the laser scanner Minolta Vivid 910i (Konica Minolta, Tokyo, Japan). The precise measurement of the landmarks is ranged between 0.017 and 0.029 mm. The system automatically measures spatial position of face landmarks, from which distances and angles can be obtained. The facial measurements were compared with those done using laser scanning and manual caliper. The adopted method gives higher precision than the others (0.022-mm mean value on points and 0.038-mm mean value on linear distances on a dummy head), is simple, and can be used easily as a standard routine. The study demonstrated the validity of photogrammetry for accurate digitization of human face landmarks. This research points out the potential of this low-cost photogrammetry approach for medical digitization.


Task interest and actual performance: the moderating effects of assigned and adopted purpose goals.
This research examined whether and which purpose goals moderate the relationship between task interest and actual performance and whether assigned goals have different effects (Study 1) than adopted goals (Study 2). Two studies were conducted using a full 2 X 2 design of the performance-mastery and approach-avoidance distinctions, plus control conditions. In the control conditions, that is, in a neutral purpose goal context, the expected positive relationship between initial task interest and actual performance was found. In a purpose goal context, this link held only for a congruent mastery-approach goal (either assigned or adopted). The gain in task interest found in a neutral purpose context was observed in the purpose goal conditions only when participants attained their purpose goals. It was concluded that having an incongruent purpose goal may undermine the positive effect of prior task interest on actual performance as well as on subsequent task interest.


Targeting AKT with Oridonin Inhibits Growth of Esophageal Squamous Cell Carcinoma In Vitro and Patient-Derived Xenografts In Vivo.
Overexpression or activation of AKT is very well known to control cell growth, survival, and gene expression in solid tumors. Oridonin, an inflammatory medical and diterpenoid compound isolated from Rabdosia rubescens, has exhibited various pharmacologic and physiologic properties, including antitumor, antibacterial, and anti-inflammatory effects. In this study, we demonstrated that oridonin is an inhibitor of AKT and suppresses proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo The role of AKT in ESCC was studied using immuno-histochemical analysis of a tumor microarray, the effect of AKT knockdown on cell growth, and treatment of cells with MK-2206, an AKT inhibitor. Oridonin blocked AKT kinase activity and interacted with the ATP-binding pocket of AKT. It inhibited growth of KYSE70, KYSE410, and KYSE450 esophageal cancer cells in a time- and concentration-dependent manner. Oridonin induced arrest of cells in the G2-M cell-cycle phase, stimulated apoptosis, and increased expression of apoptotic biomarkers, including cleaved PARP, caspase-3, caspase-7, and Bims in ESCC cell lines. Mechanistically, we found that oridonin diminished the phosphorylation and activation of AKT signaling. Furthermore, a combination of oridonin and 5-fluorouracil or cisplatin (clinical chemotherapeutic agents) enhanced the inhibition of ESCC cell growth. The effects of oridonin were verified in patient-derived xenograft tumors expressing high levels of AKT. In summary, our results indicate that oridonin acts as an AKT inhibitor to suppress the growth of ESCC by attenuating AKT signaling. Mol Cancer Ther; 17(7); 1540-53. ©2018 AACR.


Construction and selection of recombinant plasmids containing full-length complementary DNAs corresponding to rat insulins I and II.
We have used a synthetic deoxydecanucleotide to generate an insulin-specific cDNA probe suitable for selecting transformants that contain nearly full-length cDNAs corresponding to the mRNAs coding for rat insulins I and II. Double-stranded cDNA was synthesized from x-ray-induced rat insulinoma poly(A)-RNA, inserted in pBR322 plasmid DNA by the homopolymeric tailing technique, and cloned in Escherichia coli chi 1776. Colony hybridization with oligonucleotide-primed cDNA yielded 16 positive clones of which 7 corresponded to rat insulin I mRNA and 9 to rat insulin II mRNA. Restriction endonuclease maps of representative clones of each group indicated that these contained the complete coding sequences, as was confirmed by nucleotide sequence analysis of the 5' region of the cloned DNA for rat insulin II. Nucleotide sequence analysis also established the amino acid sequence of the prepeptide of rat preproinsulin II. Comparison of the amino acid sequence of the prepeptides of rat preproinsulin I and II shows that three conservative amino acid substitutions have occurred in this region of the molecule.


Atomistic Assessment of Solute-Solute Interactions during Grain Boundary Segregation.
Grain boundary solute segregation is becoming increasingly common as a means of stabilizing nanocrystalline alloys. Thermodynamic models for grain boundary segregation have recently revealed the need for spectral information, i.e., the full distribution of environments available at the grain boundary during segregation, in order to capture the essential physics of the problem for complex systems like nanocrystalline materials. However, there has been only one proposed method of extending spectral segregation models beyond the dilute limit, and it is based on simple, fitted parameters that are not atomistically informed. In this work, we present a physically motived atomistic method to measure the full distribution of solute-solute interaction energies at the grain boundaries in a polycrystalline environment. We then cast the results into a simple thermodynamic model, analyze the Al(Mg) system as a case study, and demonstrate strong agreement with physically rigorous hybrid Monte Carlo/molecular statics simulations. This approach provides a means of rapidly measuring key interactions for non-dilute grain boundary segregation for any system with an interatomic potential.


pH, healing rate and symptom relief in acid-related diseases.
Suppression of gastric acid secretion is widely used and logical for the treatment of acid-related diseases. Healing of duodenal ulcer, gastric ulcer and gastroesophageal reflux disease is correlated significantly with the degree and the duration of suppression of intragastric acidity over 24 hours and with the length of the treatment. To date, proton pump inhibitors are the most effective agents among the currently available antisecretory drugs in offering the highest healing rate and fastest resolution of symptoms. Combinations of an antisecretory drug with one or more antimicrobial agents accelerate healing of peptic ulcers.


Investigating the validity of the DN4 in a consecutive population of patients with chronic pain.
Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients' pain was classified by two independent (pain-)physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive (physical-) examination by the physician is still obligate.


Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens.
Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically achievable concentration of 2.5 µg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.


Specialty Space: Breast Care Centers.
As background, breast care centers around the world vary in interior design based on geographical location and the trends of the healthcare design process at the time of construction. However, at the forefront of healthcare interior design is the evidence-based design (EBD) process and the Universal Design (UD) guidelines. The Center for Health Design states that the EBD process differs from the linear design process, in that EBD uses relevant evidence to educate and guide the design decisions. The objective of this study was to support future EBD and UD use in the development of patient areas in breast care center interior design. The methods for this study incorporated an extensive review of the literature, examples of eight breast care centers around the world, observations, an interview, and a staff survey concerning the interior design of a local breast care center. The results revealed that using the EBD process and UD, to develop guidelines for patient areas in breast care centers' interior design, directors could use guidelines to evaluate existing breast care centers or preconstruction for new breast care centers. This study concluded with design guidelines for patient areas in breast care center interior design. The recommended guidelines targeted the following features: robes (vs. hospital gowns), spa-like atmosphere, monochromatic color scheme, use of wood and stone, private check-in areas, wayfinding, room temperature comfort, seating comfort, seating style choices including bariatric, personal items storage, access to natural light, indirect artificial lighting, living plants, views of nature, flooring comfort, and wheelchair accessibility.


Cluster analysis of visual cortical responses evoked by moving lines.
The cortical evoked responses to a bar of light (line) moving in 8 different directions across the visual field of 6 unanaesthetized, immobilized cats were compared in 18 experimental sessions. The shape of the response is unique for each direction. This is particularly apparent during the first 350 msec of the response. Cluster analysis of the evoked potentials reveals that the recognition of the direction of the moving line is probably less distinct when the line moves in a downward direction. This finding is more pronounced in the left hemisphere. The results of the cluster analysis indicate that the technique may be a useful tool in the analysis and classification of large numbers of evoked potentials. Furthermore, such clustering may eventually reveal some of the physiological mechanisms that contribute to the shape of the evoked response.


ECG Quiz: A Murmur in an Asymptomatic Athlete.
A 35-year-old, active duty Army officer presented for a screening physical exam before entering special training for HALO (High Altitude Low Opening) parachute qualification. This training involves jumping from aircraft at extreme altitudes with deployment of the parachute at relatively low altitudes (free fall). At the time of this evaluation he was assigned to a special operations airborne unit on active jump status. Careful review of his recent exercise history revealed a gradual decrease in endurance over the past several years, which he felt was due to decreased training intensity. His exercise consisted of running 3 to 4 miles four times a week and physical fitness training with his military unit three times a week. He continued to achieve high scores on the Army Physical Readiness Test.


Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada.
The novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3%-28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4%-96.3%) and 95.8% (95% CrI: 95.5%-96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.


Blinding trachoma: prevention with the safe strategy.
Trachoma, the second leading cause of blindness worldwide, differentially affects the poorest communities, which may have the least access to resources. With the establishment of the Global Elimination of Blinding Trachoma by 2020 (GET 2020) goal, the World Health Organization has set an ambitious target for country programs. The currently recommended surgery for trichiasis/entropion, antibiotics for active disease, facial cleanliness, and environmental change to reduce transmission (SAFE) strategy targets all key elements believed to be necessary for a short- and long-term intervention program. This report reviews the need for a multi-faceted strategy, and the evidence supporting the elements of SAFE. Concerns about the implementation are discussed. Additional research is suggested that will enhance the implementation of the SAFE strategy. In the current climate of significant political and social momentum for trachoma control, the SAFE strategy is a safe bet to accomplish the elimination of blinding trachoma.


Randomized phase III trial of pegfilgrastim versus filgrastim after autologus peripheral blood stem cell transplantation.
Nonrandomized trials suggest that pegfilgrastim, a pegylated granulocyte colony-stimulating factor, could be used in lieu of filgrastim after autologus peripheral blood stem cell transplantation. This phase III, randomized, double-blinded, placebo-controlled trial compared the efficacy, costs, and safety of single-dose pegfilgrastim (single 6 mg dose) versus daily filgrastim (5 microg/kg/day) for this indication. Seventy-eight patients, matched for age, sex, underlying disease, stage, and CD34/kg transplant dose were enrolled. Cytokines were started on day +1 posttransplant and continued to an absolute neutrophil count (ANC) of 5x10(9)/L for 3 days or 10x10(9)/L for 1 day. The median time to neutrophil engraftment (ANC >1.5x10(9)/L for 3 days or 5x10(9)/L for 1 day) was the same in both groups (12 days). No differences in platelet engraftment (11 versus 13 days), number of platelet transfusions (5 versus 4), percent with positive cultures for bacterial pathogens (23% versus 15%), days of fever (1 versus 2), deaths prior to engraftment (1 versus 1), or duration of hospital stay (19 versus 19 days) were seen between the pegfilgrastim and filgrastim groups, respectively. Using the average wholesale price for doses used in this trial, there was a per-patient savings of $961 for the pegfilgrastim group (P < .001). This phase III study failed to demonstrate a difference in time to neutrophil engraftment or any clinical sequelae between pegfilgrastim and filgrastim when given post-APBSCT, with pegfilgrastim achieving a cost savings over filgrastim.


Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.
Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.


Computation by Convective Logic Gates and Thermal Communication.
We demonstrate a novel computational architecture based on fluid convection logic gates and heat flux-mediated information flows. Our previous work demonstrated that Boolean logic operations can be performed by thermally driven convection flows. In this work, we use numerical simulations to demonstrate a different , but universal Boolean logic operation (NOR), performed by simpler convective gates. The gates in the present work do not rely on obstacle flows or periodic boundary conditions, a significant improvement in terms of experimental realizability. Conductive heat transfer links can be used to connect the convective gates, and we demonstrate this with the example of binary half addition. These simulated circuits could be constructed in an experimental setting with modern, 2-dimensional fluidics equipment, such as a thin layer of fluid between acrylic plates. The presented approach thus introduces a new realm of unconventional, thermal fluid-based computation.


Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex.
Legionella pneumophila is an opportunistic pathogen that causes the potentially fatal pneumonia Legionnaires' Disease. This infection and subsequent pathology require the Dot/Icm Type IV Secretion System (T4SS) to deliver effector proteins into host cells. Compared to prototypical T4SSs, the Dot/Icm assembly is much larger, containing ~27 different components including a core complex reported to be composed of five proteins: DotC, DotD, DotF, DotG, and DotH. Using single particle cryo-electron microscopy (cryo-EM), we report reconstructions of the core complex of the Dot/Icm T4SS that includes a symmetry mismatch between distinct structural features of the outer membrane cap (OMC) and periplasmic ring (PR). We present models of known core complex proteins, DotC, DotD, and DotH, and two structurally similar proteins within the core complex, DotK and Lpg0657. This analysis reveals the stoichiometry and contact interfaces between the key proteins of the Dot/Icm T4SS core complex and provides a framework for understanding a complex molecular machine.


Accuracy of the Masimo SET® LNCS neo peripheral pulse oximeter in cyanotic congenital heart disease.
Introduction Non-invasive peripheral pulse oximeters are routinely used to measure oxyhaemoglobin saturation (SpO2) in cyanotic congenital heart disease. These probes are calibrated in healthy adult volunteers between arterial saturations of ~75 and 100%, using the gold standard of co-oximetry on arterial blood samples. There are little data to attest their accuracy in cyanotic congenital heart disease. Aims We aimed to assess the accuracy of a commonly used probe in children with cyanotic congenital heart disease. Children with cyanotic congenital heart disease admitted to the Paediatric Intensive Care Unit with an arterial line in situ were included to our study. Prospective simultaneous recordings of SpO2, measured by the Masimo SET® LNCS Neo peripheral probe, and co-oximeter saturations (SaO2) measured by arterial blood gas analysis were recorded. A total of 527 paired measurements of SpO2 and SaO2 (using an ABL800 FLEX analyser) in 25 children were obtained. The mean bias of the pulse oximeter for all SaO2 readings was +4.7±13.8%. The wide standard deviation indicates poor precision. This mean bias increased to +7.0±13.7% at SaO2 recordings <75%. The accuracy root mean square of the recordings was 3.30% across all saturation levels, and this increased to 4.98% at SaO2 <75%. The performance of the Masimo SET® LNCS Neo pulse oximeter is poor when arterial oxyhaemoglobin saturations are below 75%. It tends to overestimate saturations in children with cyanotic congenital heart disease. This may have serious implications for clinical decisions.


Age-varying associations between coping and depressive symptoms throughout adolescence and emerging adulthood.
The objective of the current study was to apply the novel technique of time-varying effect modeling to examine age-varying associations between specific coping strategies and depressive symptoms across adolescence and emerging adulthood (ages 14-24). The participants were drawn from a community sample and followed across 4 years of high school and once 5 years postgraduation (N = 1,251, 53% female, 58% non-Hispanic White). Coping and depressive symptom questionnaires were administered across all data collection time points. Time-varying effect modeling used all available data (N = 5,651 measurement occasions) and adjusted for gender. Venting emotions and denial were associated with more depressive symptoms at a similar magnitude across adolescence and emerging adulthood. A positive association between problem solving oriented strategies (planning, active coping) and depressive symptoms was not observed until age 17.5, after which the magnitude of the association strengthened. More frequent instrumental and emotional support seeking were linked to fewer depressive symptoms between ages 18.8 and 23.6. More frequent use of humor was associated with greater depressive symptoms from ages 14.0 to 14.6, but with fewer depressive symptoms from ages 16.8 to 18.8. The findings illuminate when and how associations between specific coping strategies and depressive symptoms may emerge and change across developmental age, generating both theoretical and clinical implications.


Ethics and law for the radiologic technologist.
Radiologic technologists face daily decisions based on both ethics and law. Ethics has a long history in medicine and includes biomedical, professional and personal ethics. Health care professionals also must be aware of administrative, constitutional, civil and criminal law. They are subject to both criminal and civil penalties for misconduct in the course of carrying out professional duties.


Population Attributable Fraction of Gas Stoves and Childhood Asthma in the United States.
Indoor gas stove use for cooking is associated with an increased risk of current asthma among children and is prevalent in 35% of households in the United States (US). The population-level implications of gas cooking are largely unrecognized. We quantified the population attributable fraction (PAF) for gas stove use and current childhood asthma in the US. Effect sizes previously reported by meta-analyses for current asthma (Odds Ratio = 1.34, 95% Confidence Interval (CI) = 1.12−1.57) were utilized in the PAF estimations. The proportion of children (<18 years old) exposed to gas stoves was obtained from the American Housing Survey for the US, and states with available data (n = 9). We found that 12.7% (95% CI = 6.3−19.3%) of current childhood asthma in the US is attributable to gas stove use. The proportion of childhood asthma that could be theoretically prevented if gas stove use was not present (e.g., state-specific PAFs) varied by state (Illinois = 21.1%; California = 20.1%; New York = 18.8%; Massachusetts = 15.4%; Pennsylvania = 13.5%). Our results quantify the US public health burden attributed to gas stove use and childhood asthma. Further research is needed to quantify the burden experienced at the county levels, as well as the impacts of implementing mitigation strategies through intervention studies.


The Association Between Vaginal Microbiota Dysbiosis, Bacterial Vaginosis, and Aerobic Vaginitis, and Adverse Pregnancy Outcomes of Women Living in Sub-Saharan Africa: A Systematic Review.
Background: Previous studies have described the association between dysbiosis of the vaginal microbiota (VMB) and related dysbiotic conditions, such as bacterial vaginosis (BV) and aerobic vaginitis (AV), and various adverse pregnancy outcomes. There is limited overview of this association from countries in sub-Saharan Africa (SSA), which bear a disproportionally high burden of both vaginal dysbiotic conditions and adverse pregnancy outcomes. This systematic review assesses the evidence on the association between VMB dysbiosis, BV, and AV, and late adverse pregnancy outcomes in women living in SSA. Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis Statement (PRISMA) guidelines were followed. Three databases [PubMed, Embase (Ovid), and Cochrane] were used to retrieve observational and intervention studies conducted in SSA that associated VMB dysbiosis, BV, or AV and preterm birth/labor/delivery, preterm rupture of membranes (PROM), low birthweight, small for gestational age, intrauterine growth restriction, intrauterine infection, intrauterine (fetal) death, stillbirth, perinatal death, or perinatal mortality. Results: Twelve studies out of 693 search records from five SSA countries were included. One study identified a positive association between VMB dysbiosis and low birthweight. Despite considerable differences in study design and outcome reporting, studies reported an association between BV and preterm birth (7/9), low birthweight (2/6), PROM (2/4), intrauterine infections (1/1), and small for gestational age (1/1). None of the retrieved studies found an association between BV and pregnancy loss (5/5) or intrauterine growth retardation (1/1). At least two studies support the association between BV and PROM, low birthweight, and preterm birth in Nigerian pregnant women. No reports were identified investigating the association between AV and late adverse pregnancy outcomes in SSA. Conclusion: Two of the included studies from SSA support the association between BV and PROM. The remaining studies show discrepancies in supporting an association between BV and preterm birth or low birthweight. None of the studies found an association between BV and pregnancy loss. As for the role of VMB dysbiosis, BV, and AV during pregnancy among SSA women, additional research is needed. These results provide useful evidence for prevention efforts to decrease vaginal dysbiosis and its contribution to adverse pregnancy outcomes in SSA.


Ischemic stroke. Clinical strategies based on mechanisms and risk factors.
Ischemic stroke is a common disorder associated with significant morbidity and mortality. Results of several pivotal clinical trials completed within the last decade have helped refine stroke prevention and treatment strategies. Endarterectomy for symptomatic carotid artery stenosis, anticoagulation in atrial fibrillation, and IV t-PA treatment of hyperacute ischemic stroke may reduce the burden of stroke. Ongoing studies are addressing newly recognized risk factors, such as aortic arch and intracranial atherosclerosis, as well as neuroprotective agents and locally delivered thrombolytics. Successful patient management requires a targeted clinical approach based on vascular localization and risk factor assessment.


Psychometric assessment of the Emotional Reactions Instrument-Korean (ERI-K) to measure Korean children's emotional reaction to hospitalization.
The purpose of this study was to test psychometric properties of the Emotional Reactions Instrument-Korean (ERI-K). A convenience sample of 170 hospitalized Korean children was recruited. Each child was asked to describe how she or he felt during hospitalization, through the ERI-K and the Facial Affective Scale. Surprisingly, children reported lower levels of negative emotions and physical discomfort and a moderate level of positive emotion (Happy, Good). Internal consistency reliability of .88 for the 14-item scale provides strong support for reliability. Construct validity was supported by item-to-total correlations ranging between .42 and .65. Exploratory factor analysis identified two factors that explained 54% of the variance. Further testing of the ERI-K is recommended to provide additional evidence of psychometric adequacy across Korean populations.


Public perceptions of snakes and snakebite management: implications for conservation and human health in southern Nepal.
Venomous snakebite and its effects are a source of fear for people living in southern Nepal. As a result, people have developed a negative attitude towards snakes, which can lead to human-snake conflicts that result in killing of snakes. Attempting to kill snakes increases the risk of snakebite, and actual killing of snakes contributes to loss of biodiversity. Currently, snake populations in southern Nepal are thought to be declining, but more research is needed to evaluate the conservation status of snakes. Therefore, we assessed attitudes, knowledge, and awareness of snakes and snakebite by Chitwan National Park's (CNP) buffer zone (BZ) inhabitants in an effort to better understand challenges to snake conservation and snakebite management. The results of this study have the potential to promote biodiversity conservation and increase human health in southern Nepal and beyond. We carried out face-to-face interviews of 150 randomly selected CNP BZ inhabitants, adopting a cross-sectional mixed research design and structured and semi-structured questionnaires from January-February 2013. Results indicated that 43 % of respondents disliked snakes, 49 % would exterminate all venomous snakes, and 86 % feared snakes. Farmers were the most negative and teachers were the most ambivalent towards snakes. Respondents were generally unable to identify different snake species, and were almost completely unaware of the need of conserve snakes and how to prevent snakebites. Belief in a snake god, and the ability of snakes to absorb poisonous gases from the atmosphere were among many superstitions that appeared to predispose negativity towards snakes of BZ residents. People with predisposed negativity towards snakes were not proponents of snake conservation. Fear, negativity, ambivalence towards, and ignorance about, snakes and the need for snake conservation were strong indicators of the propensity to harm or kill snakes. It seems that if wanton killing of snakes continues, local snake populations will decline, and rare and endangered snake species may even become locally extirpated. Moreover, inappropriate perception and knowledge about snakes and snakebites may put BZ people at increased risk of venomous snakebite. Therefore, intensive, pragmatic educational efforts focused on natural history and ecology of snakes and prevention of snakebite should be undertaken in communities and at schools and universities.


[Analysis on the epidemiological features of human brucellosis in northern and southern areas of China, 2015-2016].
Objective: To analyze the epidemiological characteristics of human brucellosis in northern and southern areas of China, and to develop national strategies for brucellosis prevention and control. Methods: Individual data on human brucellosis was collected from the National Notifiable Infectious Disease Reporting Information System to describe the situation of brucellosis in China during 2015-2016. Epidemiological features of the disease in northern and southern areas of China were analyzed. Results: A total of 104 125 cases were reported in mainland China during 2015-2016, with an average incidence rate as 3.81/100 000. The overall incidence rate from the northern provinces was 7.77/100 000 in 2016, a 18.6% decrease from 2015 (9.55/100 000), whereas the incidence rate in the southern provinces was 0.27/100 000 in 2016, with an increase of 28.6% than 0.21/100 000 in 2015. 90.0% of the newly infected counties mainly distributed in southern China. As for the locations of reporting cases, most of them were in the same counties in the northern areas (52.3%) while most cases in the southern areas (59.6%) were imported from other counties. The median age of the cases was 48 (IQR: 38-58) years, with male-to-female ratios as 2.7∶1 in the north and 2.2∶1 in the south. Majority of the cases were occupation-related, from both the northern (86.8%) and southern (62.7%) areas. Human brucellosis occurred every month throughout the year but with an obvious seasonal increase between March and July. Conclusions: Different epidemiological features of human brucellosis appeared in both northern and southern areas of China. The disease was seen endemic in the northern and dispersal in the southern provinces. Appropriate strategies for brucellosis prevention and control should be developed, according to the different epidemiological characteristics in the northern or southern areas.


Creating a paper-based personal health record for HIV-infected persons.
A personal health record (PHR) contains information that a client believes is important to his/her health status; it can be either paper or Internet-based. The purposes of this action research were to determine the length of time an expert HIV nurse clinician needed to create a comprehensive PHR and to determine how hard it was for the patient to understand different components of a PHR. The average respondent (N = 9) was older, female, completed high school, African American, diagnosed with AIDS, and taking HIV medications for 11 years. The HIV nurse expert spent an average of 79 minutes preparing the PHR. Clients had the greatest difficulty understanding laboratory tests, medications, medical history, and immunizations. PHRs are evolving through the consumer-empowerment movement, technology, and a growing awareness of the consequences of medical errors. Nurses need to assist clients to create and use the PHR as an important tool in self-care management.


Genomics and pharmacogenomics of brain disorders.
CNS disorders are the third major problem of health in developed countries, with approximately 10% of direct costs associated with a pharmacological treatment of doubtful cost-effectiveness. There is an alarming abuse of psychotropic drugs worldwide and only 20-30% of patients with CNS disorders appropriately respond to conventional drugs. The pathogenesis of most CNS disorders is the result of the interplay of genetic and epigenetic factors with environmental factors leading to post-transcriptional changes and proteomic and metabolomic dysfunctions. It is estimated that genetics accounts for 20% to 95% of variability in drug disposition and pharmacodynamics, and about 25-60% of the Western population is defective in genes responsible for drug metabolism. In the European population only 25% of subjects are pure extensive metabolizers for the trigenic cluster integrated by the CYP2D6, CYP2C19 and CYP2C9 genes. About 50% of adverse drug events in CNS disorders might be attributed to pharmacogenomic factors. The rationale for practical pharmacogenomics and personalized therapeutics based on individual genomic profiles implies the management of different types of genes and their products including (i) genes associated with the mechanism of action of psychotropic drugs (neurotransmitters, receptors, transporters), (ii) genes encoding enzymes responsible for drug metabolism (phase I, phase II reactions), (iii) disease-specific genes associated with a particular pathogenic cascade, and (iv) pleiotropic genes with multilocative effects in metabolomic networks. The incorporation of genomic medicine procedures and pharmacogenomics into clinical practice, together with educational programs for the correct use of medication, must help to optimize therapeutics in CNS disorders.


Effects of different imaging models on least-squares image reconstruction accuracy in photoacoustic tomography.
In the classic formulation of photoacoustic tomography (PAT), two distinct descriptions of the imaging model have been employed for developing reconstruction algorithms. We demonstrate that the numerical and statistical properties of unweighted least-squares reconstruction algorithms associated with each imaging model are generally very different. Specifically, some PAT reconstruction algorithms, including many of the iterative algorithms previously explored, do not work directly with the raw measured pressure wavefields, but rather with an integrated data function that is obtained by temporally integrating the photoacoustic wavefield. The integration modifies the statistical distribution of the data, introducing statistical correlations among samples. This change is highly significant for iterative algorithms, many of which explicitly or implicitly seek to minimize a statistical cost function. In this work, we demonstrate that iterative reconstruction by least-squares minimization yields better resolution-noise tradeoffs when working with the raw pressure data than with the integrated data commonly employed. In addition, we demonstrate that the raw-data based approach is less sensitive to certain deterministic errors, such as dc offset errors.


Inductive transfer learning for molecular activity prediction: Next-Gen QSAR Models with MolPMoFiT.
Deep neural networks can directly learn from chemical structures without extensive, user-driven selection of descriptors in order to predict molecular properties/activities with high reliability. But these approaches typically require large training sets to learn the endpoint-specific structural features and ensure reasonable prediction accuracy. Even though large datasets are becoming the new normal in drug discovery, especially when it comes to high-throughput screening or metabolomics datasets, one should also consider smaller datasets with challenging endpoints to model and forecast. Thus, it would be highly relevant to better utilize the tremendous compendium of unlabeled compounds from publicly-available datasets for improving the model performances for the user's particular series of compounds. In this study, we propose the Molecular Prediction Model Fine-Tuning (MolPMoFiT) approach, an effective transfer learning method based on self-supervised pre-training + task-specific fine-tuning for QSPR/QSAR modeling. A large-scale molecular structure prediction model is pre-trained using one million unlabeled molecules from ChEMBL in a self-supervised learning manner, and can then be fine-tuned on various QSPR/QSAR tasks for smaller chemical datasets with specific endpoints. Herein, the method is evaluated on four benchmark datasets (lipophilicity, FreeSolv, HIV, and blood-brain barrier penetration). The results showed the method can achieve strong performances for all four datasets compared to other state-of-the-art machine learning modeling techniques reported in the literature so far.


Improvement in vision: a new goal for treatment of hereditary retinal degenerations.
Introduction: Inherited retinal degenerations (IRDs) have long been considered untreatable and incurable. Recently, one form of early-onset autosomal recessive IRD, Leber congenital amaurosis (LCA) caused by mutations in RPE65 (retinal pigment epithelium-specific protein 65 kDa) gene, has responded with some improvement of vision to gene augmentation therapy and oral retinoid administration. This early success now requires refinement of such therapeutics to fully realize the impact of these major scientific and clinical advances. Areas covered: Progress toward human therapy for RPE65-LCA is detailed from the understanding of molecular mechanisms to preclinical proof-of-concept research to clinical trials. Unexpected positive and complicating results in the patients receiving treatment are explained. Logical next steps to advance the clinical value of the therapeutics are suggested. Expert opinion: The first molecularly based early-phase therapies for an IRD are remarkably successful in that vision has improved and adverse events are mainly associated with surgical delivery to the subretinal space. Yet, there are features of the gene augmentation therapeutic response, such as slowed kinetics of night vision, lack of foveal cone function improvement and relentlessly progressive retinal degeneration despite therapy, that still require research attention.


[The impact of the orthopedic surgeons' attire on patient preferences].
The formal appearance of health care professionals may influence their trustworthiness. To determine the effect of the orthopedic surgeon's attire on patients' perceptions of credibility and reliability of professionals. In a cross-sectional design, 351 patients (mean age 43 ± 17 years, 62% males) from the Department of Orthopedics and Traumatology of a Chilean regional hospital in southem of Chile were chosen to complete a questionnaire of attire preferences, in which five photographs with male and female orthopedic surgeons appeared (executive, formal attire, informal attire, scrubs and casual clothing). The influence of attire in the perception of physicians' trustworthiness to resolve medical situations was analyzed. Forty four percent of patients had no physician gender predilection (p = 0.32). Forty three percent of male and 38% of female patients preferred the use of formal attire. In situations of credibility or confidence, all patients chose mostly the use of white coats with formal attire by professionals. The probability of choosing an orthopedic surgeon with a formal attire was significantly higher among patients who considered the attire and appearance of the professional to be very important (Odds ratio = 3.74; p < 0.01). Patients prefer orthopedic surgeons wearing white coats and formal attire, which improves credibility of these professionals to correctly solve medical situations.


A role for plant science in underpinning the objective of global nutritional security?
The challenges of achieving global food security have become more demanding as scientists have realized that not only calorie content but also food composition and colonic microbial content impact our health and well-being, dramatically. The ways that the nutrients we consume affect our health are highly complex due to the diversity of what we eat, the varying digestibility of what we eat, the changing composition and functioning of each individual's gut microbiota, the differences in absorption and bioavailability of the nutrients we eat, the differences in responses between individuals to what they eat and the multi-fold mechanisms of action that nutrients have on our health. It has been accepted for more than 50 years that diets rich in plants, particularly fruit and vegetables, protect health, and yet such diets have declined, with lower fruit and vegetable content and much more cheap, sugary, oily, processed foods, over the same period. These dietary shifts have had a marked impact on the incidence of chronic diseases: obesity, metabolic diseases, type 2 diabetes and cardiovascular diseases. Greater support for research into the ways that plant-based foods impact health will be essential for changing dietary patterns to protect health and to achieve global nutritional security.


Familial aggregation of adolescent personality disorders.
A family study of DSM-III-R personality disorders was conducted in the families of 66 clinically referred adolescents to examine the validity of personality disorder diagnoses in adolescents. Semistructured interviews of Axis I and II disorders, including the Structured Clinical Interview for DSM-III-R Personality Disorders, were used to directly interview 66 clinically referred adolescents and their adult first-degree family members, combining family study and family history data. The relatives of adolescents with avoidant personality disorder had an increased prevalence of avoidant and cluster A (schizoid, schizotypal, and paranoid) personality disorders. The relatives of adolescents with borderline personality disorder demonstrated increased rates of borderline and avoidant personality disorders, even after adjusting for comorbidity. The results of this study support the validity of Axis II diagnoses, particularly avoidant and borderline disorders, in adolescents.


Individual determinants of primary healthcare utilisation in Gaza Strip, Palestine.
To examine the extent to which primary care patients are using the primary healthcare (PHC) services in Gaza Strip, Palestine, and to determine the factors that are associated with the use of these services. Using Andersen's behavioural model, the authors interviewed 956 PHC attendees. Patients were questioned about predisposing factors: age, sex, marital status, education, work status, household size, life events (psychological and financial), perceived living conditions and health locus of control. Enabling factors included urbanisation and household income. Need factors included self-rated health. Healthy lifestyle was measured by two variables: smoking and physical activity. Outcome factors were measured by patients' satisfaction with PHC. The study revealed that the majority of interviewed patients (64.7%) reported high use (>3 times per 6 months) of PHC within the 6-month period before the interview. The main factors found to be associated with high use of PHC were older age, married and divorced/widowed status, perceived bad living conditions, not working, high level of income, poorly rated health status and current smoking habit. Gazean primary care patients are high users of PHC services. The increased use of these services is associated with the basic predisposing, enabling and needs factors and with the unique bad living conditions. Tobacco use was another aspect associated with high use of PHC. Effective health management, based on promoting a healthy lifestyle, is needed. The findings of this study can be used to improve health service planning and guide decision-makers towards healthcare resource allocation according to healthcare needs.


Non-catalytic facile synthesis of superhard phase of boron carbide (B13C2) nanoflakes and nanoparticles.
Boron Carbide is one the hardest and lightest material that is also relatively easier to synthesis as compared to other superhard ceramics like cubic boron nitride and diamond. However, the brittle nature of monolithic advanced ceramics material hinders its use in various engineering applications. Thus, strategies that can toughen the material are of fundamental and technological importance. One approach is to use nanostructure materials as building blocks, and organize them into a complex hierarchical structure, which could potentially enhance its mechanical properties to exceed that of the monolithic form. In this paper, we demonstrated a simple approach to synthesize one- and two-dimension nanostructure boron carbide by simply changing the mixing ratio of the initial compound to influence the saturation condition of the process at a relatively low temperature of 1500 degrees C with no catalyst involved in the growing process. Characterization of the resulting nano-structures shows B13C2, which is a superhard phase of boron carbide as its hardness is almost twice as hard as the commonly known B4C. Using ab-initio density functional theory study on the elastic properties of both B12C3 and B13C2, the high hardness of B13C2 is consistent to our calculation results, where bulk modulus of B13C2 is higher than that of B4C. High resolution transmission electron microscopy of the nanoflakes also reveals high density of twinning defects which could potentially inhibit the crack propagation, leading to toughening of the materials.


Myocellular limitations of human performance and their modification through genome-dependent responses at altitude.
Human muscle operates along a continuum of power output, which is set through bioenergetic and anatomical principles. In turn, environmental and intrinsic factors during contractile work exert pronounced control over muscle performance by instructing muscle remodelling. This phenotypic control is specifically indicated with intense exercise at altitude, when extra strain is put on energy supply and the temperature-dependent mechanical efficiency of contraction. While it is classically thought that chronic exposure to hypoxia is maladaptive, repeated short episodes of reduced oxygenation alone or in combination with intense endurance work is now understood to preserve exercise performance when atmospheric oxygen levels are low. Endurance training at moderate altitude exploits the temperature-dependent malleability of energy supply that may maximize metabolic flux at altitude. The contribution of genomic mechanisms is important to the plasticity of metabolic pathways in exercised muscle. This is highlighted by the association of distinct gene polymorphisms in master governors of mitochondrial and vascular growth with exercise phenotypes. Feedforward control of human locomoter muscle by exercise involves the transient upregulation of transcript expression for metabolic processes. The response of the mitochondrial transcriptome to intense exercise is graded with respect to mitochondrial content and deoxygenation during muscle work and reflects exercise-induced mitochondrial biogenesis. This supports the notion that genome-mediated muscle malleability is under feedback control by design constraints of the pathway of oxygen. Thus, activity-dependent and genetic mechanisms contribute to the interindividual difference in the metabolic bottlenecks in athletes performing in exceptional environmental conditions.


Dietary lipids and cancer.
Cancer is one of the main causes of death in Western countries. Among the factors that contribute to the appearance of this disease, diet has a fundamental role, and specifically fats are the main component related to the increase in the incidence of cancerous diseases, particularly breast, colon-rectal, and prostate cancer. From dietary lipids, much attention has been given to the beneficial effects of fish oil, rich in polyunsaturated fatty acids n-3 serie, as well as of olive oil, rich in monounsaturated fatty acids--primarily oleic acid. On the contrary, a negative effect has been reported for polyunsaturated fatty acids n-6 serie and for saturated fatty acids. Nutrition constitutes an important aspect of the life of cancer patients. Currently, nutritional formulas are being designed with supplements of polyunsaturated n-3 fatty acids and other components such as arginine, RNA, lysine, etc., with the aim of ameliorating the effects of this pathology. The results demonstrate the lower morbility and therefore improved quality of life, a decline in mortality, and a reduction in related costs.


A facile strategy for the modification of polyethylene substrates with non-fouling, bioactive poly(poly(ethylene glycol) methacrylate) brushes.
This manuscript reports a facile strategy for the modification of polyethylene, a widely used biomaterial, with a thin non-biofouling coating that can act as a platform to introduce biochemical cues to control and direct, e.g., cell adhesion and proliferation. The non-biofouling coating is produced, following a two-step strategy involving photobromination of the polyethylene substrate followed by surface-initiated ATRP of poly(ethylene glycol) methacrylate. The resulting coatings, which are referred to as polymer brushes, are robust and withstand prolonged exposure to aqueous ethanol and phosphate buffered saline and also do not show any signs of detachment or degradation in the in vivo studies over a period of 10 d. Functionalization of these polymer brush coatings with extracellular matrix derived peptide sequences, promotes adhesion and spreading of endothelial cells.


The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep.
The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of -56.4% (52.3-60.5%, 95% confidence interval) and for lys-bradykinin -52.8% (46.5-59.1%). The ED50 values were 0.69 (0.51-1.32) and 1.46 (1.19-2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses (greater than 1.9 pmoles) of both kinins. Intravenous indomethacin (5 mg.kg-1) increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4 microns at 0.35 ml.min-1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.


EHealth Literacy in UK Teenagers and Young Adults: Exploration of Predictors and Factor Structure of the eHealth Literacy Scale (eHEALS).
Increasingly, teenagers and young adults (TYAs) seek out health information online; however, it is not clear whether they possess electronic health (eHealth) literacy, defined as "the ability to select, appraise, and utilize good quality health information from the internet." A number of factors are included in the Lily model proposed by Norman and Skinner underpinning the development of eHealth literacy. It is important to understand which elements may influence the development of eHealth literacy in young people, as the current generation will continue to "Google it" when faced with a health problem throughout their lives. The objectives of this study are to explore potential factors influencing young people's eHealth literacy and explore the underlying constructs of the eHealth Literacy Scale (eHEALS) in a population of UK university students. A total of 188 undergraduate psychology students from a large UK University were recruited as an opportunity sample. Of these, 88.8% (167/188) of participants were female with a mean age of 20.13 (SD 2.16) years and the majority were White British (159/188, 84.6%). Employing a cross-sectional design TYAs completed the following measures exploring eHealth literacy (eHEALS): Irrational Health Belief Scale; Newest Vital Sign (NVS), a measure of functional health literacy; Need for Cognition Scale, a preference for effortful cognitive activity; and General Self-Efficacy (GSE) Scale, exploring personal agency and confidence. The eHEALS was also subject to exploratory factor analysis (EFA), for which in addition to the total variance explained, the scree plot, eigenvalues, and factor loadings were assessed to verify the structure. eHEALS and GSE were significantly positively correlated (r=0.28, P<.001) and hierarchical linear modeling revealed GSE as the significant predictor of scores on the eHEALS (F1,186=16.16, P<.001, R2=0.08), accounting for 8.0% of the variance. Other notable relationships were GSE and need for cognition (NFC) were also positively correlated (r=0.33, P<.001), and NFC and irrational health beliefs were significantly negatively correlated (r=-.14, P=.03). Using Spearman correlations, GSE and NVS (rs=0.14, P=.04) and NFC and NVS (rs=0.19, P=.003) were positively correlated. An EFA revealed the scale to be stable and identified a 2-factor structure related to information acquisition and information application. This is the first study in the UK to explore relationships between these key variables and verify the structure of the eHEALS in a TYA population in the UK. The findings that self-efficacy has a major influence firmly consolidate its status as fundamental to the development of eHealth literacy. Future studies will explore the influence of body image and the development of eHealth literacy in more diverse TYA populations.


Hypoxia-mimetic agents inhibit proliferation and alter the morphology of human umbilical cord-derived mesenchymal stem cells.
The therapeutic efficacy of human mesenchymal stem cells (hMSCs) for the treatment of hypoxic-ischemic diseases is closely related to level of hypoxia in the damaged tissues. To elucidate the potential therapeutic applications and limitations of hMSCs derived from human umbilical cords, the effects of hypoxia on the morphology and proliferation of hMSCs were analyzed. After treatment with DFO and CoCl₂, hMSCs were elongated, and adjacent cells were no longer in close contact. In addition, vacuole-like structures were observed within the cytoplasm; the rough endoplasmic reticulum expanded, and expanded ridges were observed in mitochondria. In addition, DFO and CoCl₂ treatments for 48 h significantly inhibited hMSCs proliferation in a concentration-dependent manner (P < 0.05). This treatment also increased the number of cells in G0/G1 phase and decreased those in G2/S/M phase. The hypoxia-mimetic agents, DFO and CoCl₂, alter umbilical cord-derived hMSCs morphology and inhibit their proliferation through influencing the cell cycle.


Properties of the inactive ribosomal components in rat liver and hepatoma.
1. The relative concentrations of the inactive ribosomal components were compared in normal and regenerating rat liver and in two transplantable rat hepatomas (hepatomas 7800 and 5123D). 2. The size of the ribosomal-subunit pools in normal liver was not significantly affected by partial hepatectomy or neoplasia although, as shown previously, significant changes do occur in the monomer pool. 3. Further, the subunit pools in both liver and hepatoma were not significantly influenced by several treatments that caused dramatic changes in the size of the ribosomal monomer (and dimer) pools. 4. The high concentration of inactive monomers and dimers in the hepatomas appears to arise from limitations at the translational level, since they can be incorporated into pre-existing polyribosomes under the influence of cycloheximide.


[Determination on of C/EBP in human liver cancer, normal adult liver and various diseased liver tissues].
C/EBP, a heat-stable DNA-binding protein, play a very important role in establishing and maintaining the differentiation state of liver cells as a transcription factor enriched in the liver. In order to identify its distribution, localization and function, immunocytochemical examination (ABC method) was done by using anti-C/EBP polypeptide antibodies 1103#, 425# in 20 normal human adult liver tissues, 5 neonatal liver tissues, 6 hepatitis tissues, 25 liver cirrhosis tissues, 80 hepatocellular carcinoma tissues (40 cases with associated surrounding non-tumor hepatic tissues) and 26 cholangiocarcinoma tissues (15 cases with associated surrounding non-tumor tissues). The results showed that C/EBP expression was restricted to terminally differentiated liver cells, and was very low or undetectable in poorly differentiated liver cells, such as liver tumor cells. Its expression also correlated with the grading of hepatocellular carcinoma. Besides, positive C/EBP stain could be found in all regenerating bile ductules. The C/EBP has a diffuse distribution which could be detected both in nuclei and in cytoplasm, but more abundant in cytoplasm. The results are in accordance with the concept that C/EBP plays an important role in establishing and maintaining the differentiation state of liver cells.


Reverse neurocutaneous vs propeller perforator flaps in diabetic foot reconstruction.
Introduction Reverse neurocutaneous and propeller perforator flaps are both used to reconstruct diabetic distal lower limb defects. Our study aims to compare outcomes between these two groups of flaps with an emphasis on indications and complication rates. Method A retrospective analysis was conducted, reviewing data from 54 diabetic patients who underwent reconstruction of acute or chronic wounds of the foot and ankle between 2005-2018. Thirty-four patients (Group A) had a reverse neurocutaneous flap (NCF): nineteen sural and fifteen lateral supramalleolar flaps. Twenty patients (Group B) had a propeller flap (PF) based on peroneal (n = 13) or posterior tibial artery perforators (n = 7). All patients had a preoperative Doppler examination to identify the nutrient artery of the flap. In both groups, we recorded patients' demographics, characteristics of the defect, postoperative complications and time to heal. Follow-up ranged from 6 to 59 months. Student's t-test and chi-squared test were used for statistical analysis. Results Mean patients' age was 59.1 and 50.8 years for Group A and B, respectively. Defects were located at the Achilles zone (n = 16), posterior heel (n = 14), foot dorsum (n = 9), lateral and medial malleolar areas (n = 8), anterior ankle (n = 5) and lateral foot (n = 2). Mean size of the defect was 42.8 cm2 in Group A and 23 cm2 in Group B. Uneventful healing was recorded in 20/34 neurocutaneous flaps and in 12/20 propeller flaps; complications included two complete flap losses (one NCF, one PF), seventeen distal flap necroses (10 NCFs, 7 PFs), fifteen delayed wound healing events over the donor or recipient site (12 NCFs, 3 PFs). Secondary surgeries were required in 15 NCF and 8 PF patients. Mean healing time was 48.1 and 40.7 days for Group A and B, respectively. All patients, except one NCF case, which resulted in leg amputation, returned to previous levels of ambulation. Conclusion Reverse neurocutaneous and propeller flaps may provide stable reconstruction of diabetic lower limb defects; neurocutaneous flaps are specially indicated for larger and more distally located defects, although they might be associated with longer healing time and additional revision surgeries. Propeller flaps were more frequently used in younger patients for smaller and more proximally located defects.