[Dependence and necessities of non-covered services for the elderly in a health sector of Zaragoza].
Dependency to carry out the activities of daily living (ADL) and home care needs of older adults depend upon factors which are not well understood. Caregiving is mainly provided by the family. The aim of this study is to estimate the prevalence of ADL dependence and associated factors among older adults and to identify associated factors with unmet home care needs in people over age 75 in Zaragoza (Spain). A cross-sectional study was conducted on a representative sample of the community dwelling population over age, 75 in one Health Care District in Saragossa in 1998 (n = 351). Data were collected during a personal interview. ADL dependency was assessed by the Katz index. Home care needs were assessed using prevalent norms for desired frequency of care. Sources of informal care, socio-demographic characteristics, self-rated health and depression (Yesavage Geriatric Depression Scale) were considered independent variables. Logistic regression was used to identify factors associated with both ADL dependency and unmet home care needs. Prevalence of ADL dependence is 37.3%. The variables predicting ADL dependence are the perception of poor health, depression, being a female and being over 85 years of age. The prevalence of unmet care needs among ADL dependent individuals is 22.1%. Sources of help are limited to the families. Being a woman and living alone are the stronger risk factors for unmet needs. A high percentage of older adults are dependent. Informal support is insufficient and confined to the family. The social and health care system in Spain should provide to the family, emotional, financial and social support and special care for disabled people living alone and with limited material resources.


Bone Vertebrae Metastases With Spinal Cord Compression: A Rare Event in Wilms Tumor.
Bone metastases and intraspinal spread are rare events in Wilms tumor. We report 2 cases of Wilms tumor with vertebral metastases associated with spinal cord compression; 1 case was reported during diagnosis and the other at relapse. Both children benefited from emergency surgical decompression followed by intensive multimodality therapy, resulting in long-term disease-free remission.


Primary and Secondary Stability of Extrashort (4-mm) Implants in the Edentulous Mandible: Preliminary Results of a Prospective Clinical Trial.
To compare the primary and secondary stability of conventional (≥ 8-mm) and extrashort (4-mm) implants in edentulous patients using different methods of assessment. Patients underwent implant surgery and were randomly allocated into two groups: test, with two conventional implants in the anterior region and two extrashort (4-mm) implants in the posterior region; and control, with two conventional (≥ 8-mm) implants in the anterior region only. Primary stability (S1-implant placement) was assessed by insertion torque, implant stability quotient (ISQ, Osstell), and damping capacity (PTV, Periotest), while secondary stability (S221-21 days after S1; and S2clip-at prosthetic loading, ± 3 months after S1) was evaluated by ISQ and PTV. The statistical significance level was set at P < .05. Fifty conventional implants and 24 extrashort implants were placed in 25 patients. The overall survival rate was 97.3%. There was no statistically significant difference between the insertion torque of conventional and extrashort implants (P > .05). PTV values were significantly lower for conventional implants only at S2clip (P = .041). ISQ values were significantly greater for conventional implants at S1 (P = .004), whereas at S221 and S2clip, no differences were found (P = .413 and P = .490, respectively). Damping capacity showed no significant differences between S1-S2M21 and S1-S2clip. ISQ values showed a significant increase of stability between S1-S2clip, for conventional (P = .022) and extrashort (P = .005) implants, which was different from that observed between S1-S221. There was a moderate negative correlation between the PTV and ISQ variables (r = 0.5) of extrashort implants, and between the PTV and insertion torque (r = -0.3) of conventional implants. For extrashort implants, there was a null correlation between ISQ and torque (r = 0.0). There was a moderately positive correlation between ISQ and torque (r = 0.3) in the conventional implant group. The results suggest that extrashort and conventional implants present similar primary and secondary stability values and may similarly influence restorative protocols.


Urinary incontinence triggered by stretching exercises.
A 47-year-old female patient who experienced urinary urgency after having stretching exercises of her legs is presented. Stretching of the legs are thought to be responsible for conus medullaris tethering which in turn causes urinary complaints. What is interesting in this case is that her complaints about urinary urgency stopped as she quit stretching exercise movements of her legs. There are some examples of such cases in the literature. The urinary urgency after stretching exercises warned us to investigate this patient in regard to tethered conus medullaris. Tethering of the conus medullaris can be temporary and can cause reversible functional disorders of the bladder. Incontinence at any age should be evaluated cautiously as it could be a sign of an underlying important developmental failure.


Molecular basis for multimerization in the activation of the epidermal growth factor receptor.
The epidermal growth factor receptor (EGFR) is activated by dimerization, but activation also generates higher-order multimers, whose nature and function are poorly understood. We have characterized ligand-induced dimerization and multimerization of EGFR using single-molecule analysis, and show that multimerization can be blocked by mutations in a specific region of Domain IV of the extracellular module. These mutations reduce autophosphorylation of the C-terminal tail of EGFR and attenuate phosphorylation of phosphatidyl inositol 3-kinase, which is recruited by EGFR. The catalytic activity of EGFR is switched on through allosteric activation of one kinase domain by another, and we show that if this is restricted to dimers, then sites in the tail that are proximal to the kinase domain are phosphorylated in only one subunit. We propose a structural model for EGFR multimerization through self-association of ligand-bound dimers, in which the majority of kinase domains are activated cooperatively, thereby boosting tail phosphorylation.


The Role of Social Capital in African Americans' Attempts to Reduce and Quit Cocaine Use.
Research examining substance users' recovery has focused on individual-level outcomes while paying limited attention to the contexts within which individuals are embedded, and the social processes involved in recovery. This paper examines factors underlying African American cocaine users' decisions to reduce or quit cocaine use and uses practice theory to understand how lifestyle changes and shifts in social networks facilitate access to the capital needed to change cocaine use patterns. The study, an in-depth analysis of substance-use life history interviews carried out from 2010 to 2012, included 51 currently not-in-treatment African American cocaine users in the Arkansas Mississippi Delta region. A blended inductive and deductive approach to data analysis was used to examine the socio-cultural and economic processes shaping cocaine use and recovery. The majority of participants reported at least one lifetime attempt to reduce or quit cocaine use; motivations to reduce use or quit included desires to meet social role expectations, being tired of using, and incarceration. Abstinence-supporting networks, participation in conventional activities, and religious and spiritual practices afforded access to capital, facilitating cocaine use reduction and sobriety. Interventions designed to increase connection to and support from nondrug using family and friends with access to recovery capital (e.g., employment, faith community, and education) might be ideal methods to reduce substance use among minorities in low-income, resource-poor communities.


The effect of mastic mouthwash on halitosis and oral hygiene in orthodontic patients: a randomized clinical trial.
The aim of this trial was to investigate the effect of mastic mouthwash on halitosis using as a proxy the levels of the Volatile Sulfur Compounds (VSCs), and the effect on plaque and gingival indices in adolescents undergoing orthodontic treatment with fixed conventional labial appliances. The study was a double-blinded, placebo-controlled, parallel-group, randomized clinical trial. Thirty patients with fixed orthodontic appliances were randomly allocated at a 1:1 ratio, to either the mastic-mouthwash or the placebo-mouthwash group. Eligibility criteria included ages between 13 and 18, active orthodontic treatment with fixed appliances, good general health, and total initial VSCs levels above 150 ppb. The primary outcome was the objective hydrogen sulfide (H2S) level, measured with the Oral ChromaTM device. The secondary outcomes were (1.) the methyl-mercaptan (CH3SH) and (2.) dimethyl sulfide [(CH3)2S] levels, measured with the same device, (3.) the subjective perception of the own malodour via questionnaires, and (4.) the oral hygiene assessed with the use of the Modified Silness and Löe Plaque Index (PI-M) and the Silness and Löe Gingival Index (GI) at baseline (T0) and after 2 weeks (T1). Stratified randomization by gender was used, and allocation was concealed with opaque numbered sealed envelopes. H2S level dropped from 221.00 ppb (T0) to 125.00 ppb (T1), and the difference between treatment groups was statistically significant in favour of the mastic group (coef: 72.34, 95% CI: 8.48, 136.27, P = 0.03). The levels of the other VSCs, the subjective measurements of oral malodour, and the oral hygiene indices did not differ between treatment arms. The objective organoleptic assessment by a calibrated examiner was not performed. Mastic mouthwashes could be an alternative treatment for adolescent patients suffering from halitosis during orthodontic treatment with fixed appliances. The trial was registered at ClinicalTrials.gov (identifier: NCT05647369).


Regulatory T cells and T-cell-derived IL-10 interfere with effective anti-cytomegalovirus immune response.
Cytomegalovirus (CMV) establishes lifelong chronic infection in its host with mostly asymptomatic or only mild disease, but under immunosuppressive conditions the virus can reactivate and infection can cause life-threatening disease. CMV has evolved several mechanisms to escape from host's immunity, allowing persistence of the virus. Until now, it remains elusive whether regulatory T cells (Tregs) have an impact on insufficient host immune response against the virus in this context. In the present study, we provide evidence that CD4(+)Foxp3(+) naturally occurring Tregs (nTregs) as well as CD4(+)Foxp3(-)IL-10(+)-induced Tregs (iTregs) interfere with an effective anti-mouse CMV (mCMV) immune response. Depletion of Foxp3(+) Tregs by using DEREG mice resulted in enhanced T-cell activation as measured by the expression of CD62L, granzyme B and interferon (IFN)-γ and was associated with reduced viral titers in salivary glands, the organ where mCMV mainly persists. Moreover, we identified CD4(+)Foxp3(-) T cells to produce elevated levels of the immunosuppressive cytokine IL-10 at early time points during mCMV infection. Analysis of T-cell activation and viral replication in mCMV-infected IL-10(flox/flox) × CD4-cre mice and IL-10(flox/flox) × FIC mice revealed that T-cell-specific inactivation of IL-10, but not Foxp3(+) Treg-specific IL-10 ablation alone, resulted in elevated IFN-γ production by T cells associated with a significant decrease in viral loads in salivary glands. Thus, our data illustrate a crucial role for CD4(+)Foxp3(+) nTregs as well as IL-10-producing CD4(+)Foxp3(-) iTregs in the regulation of appropriate T-cell responses and viral clearance during mCMV infection.


[Kitchen and schizophrenia: a crossroad activity of an ecological, occupational and neuropsychological assessment].
In this exploratory study, the authors examine the various occupational and neuropsychological assessments used to analyze deficits qualitatively and quantitatively in patients with schizophrenia. Considering that it is necessary to further explore their repercussion on the performance of activity of daily living (ADL) and domestic activities (DA), they thus attempt to verify if the distinction between two levels of functional autonomy could translate at the cognitive and clinical levels in (25) 23 patients included in a program destined to young adults (schizophrenia spectrum DSM-IV criteria) in Montréal. These patients had the opportunity, within the clinical program, to submit to neuropsychological evaluations as well as evaluations offered by the occupational therapy service thanks to a tool frequently used by occupational therapists entitled Assessment of Motor and Process Skills (AMPS). The objective of this article is to conjugate two possible perspectives, drawn from two different disciplines, on a very current human activity such as "preparing meals" in people suffering from schizophrenia and which functioning of daily life is disturbed.


The use of enamel matrix derivative in the treatment of periodontal defects: a literature review and meta-analysis.
Periodontal disease results in the loss of the attachment apparatus. In the last three decades, an increasing effort has been placed on seeking procedures and materials to promote the regeneration of this tissue. The aim of this paper is to evaluate the effect of enamel matrix derivative (EMD) during regenerative procedures. In addition, a meta-analysis is presented regarding the clinical results during regeneration with EMD, to gain evidence as to what can be accomplished following treatment of intrabony defects with EMD in terms of probing depth reduction, clinical attachment level gain, defect fill (using re-entry studies), and radiographic parameters. The review includes in vitro and in vivo studies as well as human case reports, clinical comparative trials, and histologic findings. In addition, a meta-analysis is presented regarding the regenerative clinical results. For this purpose, we used 28 studies-including 955 intrabony defects treated with EMD that presented baseline and final data on probing depth, clinical attachment level (CAL) gain, or bone gain-to calculate weighted mean changes in the different parameters. The selected studies were pooled from the MEDLINE database at the end of May, 2003. The meta-analysis of intrabony defects treated with EMD resulted in a mean initial probing depth of 7.94 +/- 0.05 mm that was reduced to 3.63 +/- 0.04 mm (p = 0.000). The mean clinical attachment level changed from 9.4 +/- 0.06 mm to 5.82 +/- 0.07 mm (p = 0.000). These results were significantly better than the results obtained for either open-flap debridement (OFD) or guided tissue regeneration (GTR). In contrast, histologically, GTR is more predictable than EMD in terms of bone and cementum formation. No advantage was found for combining EMD and GTR. Xenograft, or EMD and xenograft, yielded inferior results compared with EMD alone, but a limited number of studies evaluated this issue. Promising results were noted for the combination of allograft materials and EMD. EMD seems to be safe, was able to regenerate lost periodontal tissues in previously diseased sites based on clinical parameters, and was better than OFD or GTR. Its combination with allograft materials may be of additional benefit but still needs to be further investigated.


Telemonitoring and self-management in the control of hypertension (TASMINH2): a randomised controlled trial.
Control of blood pressure is a key component of cardiovascular disease prevention, but is difficult to achieve and until recently has been the sole preserve of health professionals. This study assessed whether self-management by people with poorly controlled hypertension resulted in better blood pressure control compared with usual care. This randomised controlled trial was undertaken in 24 general practices in the UK. Patients aged 35-85 years were eligible for enrolment if they had blood pressure more than 140/90 mm Hg despite antihypertensive treatment and were willing to self-manage their hypertension. Participants were randomly assigned in a 1:1 ratio to self-management, consisting of self-monitoring of blood pressure and self-titration of antihypertensive drugs, combined with telemonitoring of home blood pressure measurements or to usual care. Randomisation was done by use of a central web-based system and was stratified by general practice with minimisation for sex, baseline systolic blood pressure, and presence or absence of diabetes or chronic kidney disease. Neither participants nor investigators were masked to group assignment. The primary endpoint was change in mean systolic blood pressure between baseline and each follow-up point (6 months and 12 months). All randomised patients who attended follow-up visits at 6 months and 12 months and had complete data for the primary outcome were included in the analysis, without imputation for missing data. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN17585681. 527 participants were randomly assigned to self-management (n=263) or control (n=264), of whom 480 (91%; self-management, n=234; control, n=246) were included in the primary analysis. Mean systolic blood pressure decreased by 12.9 mm Hg (95% CI 10.4-15.5) from baseline to 6 months in the self-management group and by 9.2 mm Hg (6.7-11.8) in the control group (difference between groups 3.7 mm Hg, 0.8-6.6; p=0.013). From baseline to 12 months, systolic blood pressure decreased by 17.6 mm Hg (14.9-20.3) in the self-management group and by 12.2 mm Hg (9.5-14.9) in the control group (difference between groups 5.4 mm Hg, 2.4-8.5; p=0.0004). Frequency of most side-effects did not differ between groups, apart from leg swelling (self-management, 74 patients [32%]; control, 55 patients [22%]; p=0.022). Self-management of hypertension in combination with telemonitoring of blood pressure measurements represents an important new addition to control of hypertension in primary care. Department of Health Policy Research Programme, National Coordinating Centre for Research Capacity Development, and Midlands Research Practices Consortium.


"Lacking warmth": Alexithymia trait is related to warm-specific thermal somatosensory processing.
Alexithymia is a personality trait involving deficits in emotional processing. The personality construct has been extensively validated, but the underlying neural and physiological systems remain controversial. One theory suggests that low-level somatosensory mechanisms act as somatic markers of emotion, underpinning cognitive and affective impairments in alexithymia. In two separate samples (total N=100), we used an established Quantitative Sensory Testing (QST) battery to probe multiple neurophysiological submodalities of somatosensation, and investigated their associations with the widely-used Toronto Alexithymia Scale (TAS-20). Experiment one found reduced sensitivity to warmth in people with higher alexithymia scores, compared to individuals with lower scores, without deficits in other somatosensory submodalities. Experiment two replicated this result in a new group of participants using a full-sample correlation between threshold for warm detection and TAS-20 scores. We discuss the relations between low-level thermoceptive function and cognitive processing of emotion.


Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity.
Caloric restriction (CR), a reduction of food intake while avoiding malnutrition, can delay the onset of cancer and age-related diseases in several species, including mice. In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. In addition, longitudinal telomere length measurements in peripheral blood leukocytes from individual mice showed that CR resulted in maintenance and/or elongation telomeres in a percentage of WT mice, a situation that mimics telomere dynamics in TgTERT cohorts. These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing "health span" and extending mouse longevity.


Osseous microarchitecture of the scaphoid: Cadaveric study of regional variations and clinical implications.
Bone strength and structure are closely associated with fracture and screw fixation, however osseous micro architecture on scaphoid has not been clearly addressed. We conducted histomorphometric study of the scaphoid using micro CT to find regional variations and differences in the scaphoid to provide better understanding of fracture mechanism and suggest optimal screw position. We divided scaphoid into eight regions and collected regional data from eleven different cadaveric scaphoids. A computer program was used to measure parameters, which includes mean subchondral bone thickness, bone mineral density for bone density parameters, and tissue mineral density, trabecular thickness, trabecular spacing, trabecular number and bone volume fraction for bone quality parameters. All bone strength parameters were measured the maximum value in the regions where scaphoid articulates with radius. Articular regions presented higher bone strength parameters and thicker subchondral bone. The minimum value of trabecular number was in midcarpal side of waist portion. There was trend of higher subchondral bone thickness in the scaphoid which articulates with capitate and radius. This histomorphometric study showed regional variation of the scaphoid in terms of bone density and quality parameters. Waist portion presented thick subchondral and trabecular bone for high cross section moment of inertia against bending. Three point bending for scaphoid fracture and vertical screw placement are suggested based on these variations.


Cardiac Disorders and Pathophysiology of Sarcomeric Proteins.
The sarcomeric proteins represent the structural building blocks of heart muscle, which are essential for contraction and relaxation. During recent years, it has become evident that posttranslational modifications of sarcomeric proteins, in particular phosphorylation, tune cardiac pump function at rest and during exercise. This delicate, orchestrated interaction is also influenced by mutations, predominantly in sarcomeric proteins, which cause hypertrophic or dilated cardiomyopathy. In this review, we follow a bottom-up approach starting from a description of the basic components of cardiac muscle at the molecular level up to the various forms of cardiac disorders at the organ level. An overview is given of sarcomere changes in acquired and inherited forms of cardiac disease and the underlying disease mechanisms with particular reference to human tissue. A distinction will be made between the primary defect and maladaptive/adaptive secondary changes. Techniques used to unravel functional consequences of disease-induced protein changes are described, and an overview of current and future treatments targeted at sarcomeric proteins is given. The current evidence presented suggests that sarcomeres not only form the basis of cardiac muscle function but also represent a therapeutic target to combat cardiac disease.


Trends in hip dysplasia control: analysis of radiographs submitted to the Orthopedic Foundation for Animals, 1974 to 1984.
From 1974 through 1984, the Orthopedic Foundation for Animals evaluated 143,218 radiographic submissions representing 151 breeds of dogs. All breeds from which there were 35 or more evaluations had some frequency of dysplasia. Seventy breeds, each with over 100 submissions, were tabulated and ranked according to frequency of hip dysplasia. Frequency of dysplasia varied from 0.6% in the Borzoi to 46.9% in the Saint Bernard. These data were compared with data obtained earlier (1966 to 1973) on evaluations in 38 breeds for changes in frequency. There was significant (P less than 0.05) reduction in frequency of dysplasia in 27 breeds, a significant (P less than 0.05) increase in frequency in only 1 breed (German Shorthaired Pointer), and no significant change in frequency in 10 breeds. The median significant decrease was 22.4%, and the range was from 3.1% in the Chesapeake Bay Retriever to 48.7% in the Keeshond. The reduction in frequency of hip dysplasia demonstrated the value of a control program. There were 5 breeds with a significant (P less than 0.05) decrease in frequency of dysplasia that had over 5,000 evaluations from 1974 to 1984. The decreases in frequency were independent of changes in American Kennel Club registrations for these breeds (a dramatic decline in registrations for the German Shepherd Dog and Old English Sheepdog, and a dramatic increase for the Rottweiler, Golden Retriever, and Labrador Retriever). Frequency regressed linearly in the German Shepherd Dog and Old English Sheepdog, but regressed nonlinearly in the other 3 breeds. The percentage reduction in frequency from the base frequency (1966 to 1973) for these breeds was 17.5% for the German Shepherd Dog, 23.1% for the Old English Sheepdog, 9.1% for the Rottweiler, 10.1% for the Golden Retriever, and 6.8% for the Labrador Retriever.


A Novel Virtual Reality Assessment of Functional Cognition: Validation Study.
Cognitive deficits are present in several neuropsychiatric disorders, including Alzheimer disease, schizophrenia, and depression. Assessments used to measure cognition in these disorders are time-consuming, burdensome, and have low ecological validity. To address these limitations, we developed a novel virtual reality shopping task-VStore. This study aims to establish the construct validity of VStore in relation to the established computerized cognitive battery, Cogstate, and explore its sensitivity to age-related cognitive decline. A total of 142 healthy volunteers aged 20-79 years participated in the study. The main VStore outcomes included verbal recall of 12 grocery items, time to collect items, time to select items on a self-checkout machine, time to make the payment, time to order coffee, and total completion time. Construct validity was examined through a series of backward elimination regression models to establish which Cogstate tasks, measuring attention, processing speed, verbal and visual learning, working memory, executive function, and paired associate learning, in addition to age and technological familiarity, best predicted VStore performance. In addition, 2 ridge regression and 2 logistic regression models supplemented with receiver operating characteristic curves were built, with VStore outcomes in the first model and Cogstate outcomes in the second model entered as predictors of age and age cohorts, respectively. Overall VStore performance, as indexed by the total time spent completing the task, was best explained by Cogstate tasks measuring attention, working memory, paired associate learning, and age and technological familiarity, accounting for 47% of the variance. In addition, with λ=5.16, the ridge regression model selected 5 parameters for VStore when predicting age (mean squared error 185.80, SE 19.34), and with λ=9.49 for Cogstate, the model selected all 8 tasks (mean squared error 226.80, SE 23.48). Finally, VStore was found to be highly sensitive (87%) and specific (91.7%) to age cohorts, with 94.6% of the area under the receiver operating characteristic curve. Our findings suggest that VStore is a promising assessment that engages standard cognitive domains and is sensitive to age-related cognitive decline.


Characterization of wheat - Psathyrostachys huashanica small segment translocation line with enhanced kernels per spike and stripe rust resistance.
Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs), a distant wild relative of common wheat, possesses rich potentially valuable traits, such as disease resistance and more spikelets and kernels per spike, that could be useful for wheat genetic improvement. Development of wheat - P. huashanica translocation lines will facilitate its practical utilization in wheat breeding. In the present study, a wheat - P. huashanica small segmental translocation line, K-13-835-3, was isolated and characterized from the BC1F5 population of a cross between wheat - P. huashanica amphiploid PHW-SA and wheat cultivar CN16. Cytological studies showed that the mean chromosome configuration of K-13-835-3 at meiosis was 2n = 42 = 0.10 I + 19.43 II (ring) + 1.52 II (rod). GISH analyses indicated that chromosome composition of K-13-835-3 included 40 wheat chromosomes and a pair of wheat - P. huashanica translocation chromosomes. FISH results demonstrated that the small segment from an unidentified P. huashanica chromosome was translocated into wheat chromosome arm 5DS, proximal to the centromere region of 5DS. Compared with the cultivar wheat parent CN16, K-13-835-3 was highly resistant to stripe rust pathogens prevalent in China. Furthermore, spikelets and kernels per spike in K-13-835-3 were significantly higher than those of CN16 in two growing seasons. These results suggest that the desirable genes from P. huashanica were successfully transferred into CN16 background. This translocation line could be used as novel germplasm for high-yield and, eventually, resistant cultivar breeding.


Neural mechanisms in body fluid homeostasis.
Under steady-state conditions, urinary sodium excretion matches dietary sodium intake. Because extracellular fluid osmolality is tightly regulated, the quantity of sodium in the extracellular fluid determines the volume of this compartment. The left atrial volume receptor mechanism is an example of a neural mechanism of volume regulation. The left atrial mechanoreceptor, which functions as a sensor in the low-pressure vascular system, is located in the left atrial wall, which has a well-defined compliance relating intravascular volume to filling pressure. The left atrial mechanoreceptor responds to changes in wall left atrial tension by discharging into afferent vagal fibers. These fibers have suitable central nervous system representation whose related efferent neurohumoral mechanisms regulate thirst, renal excretion of water and sodium, and redistribution of the extracellular fluid volume. Efferent renal sympathetic nerve activity undergoes appropriate changes to facilitate renal sodium excretion during sodium surfeit and to facilitate renal sodium conservation during sodium deficit. By interacting with other important determinants of renal sodium excretion (e.g., renal arterial pressure), changes in efferent renal sympathetic nerve activity can significantly modulate the final renal sodium excretion response with important consequences in pathophysiological states (e.g., hypertension, edema-forming states).


A CCAAT/enhancer binding protein beta isoform, liver-enriched inhibitory protein, regulates commitment of osteoblasts and adipocytes.
Although both osteoblasts and adipocytes have a common origin, i.e., mesenchymal cells, the molecular mechanisms that define the direction of two different lineages are presently unknown. In this study, we investigated the role of a transcription factor, CCAAT/enhancer binding protein beta (C/EBPbeta), and its isoform in the regulation of balance between osteoblast and adipocyte differentiation. We found that C/EBPbeta, which is induced along with osteoblast differentiation, promotes the differentiation of mesenchymal cells into an osteoblast lineage in cooperation with Runx2, an essential transcription factor for osteogenesis. Surprisingly, an isoform of C/EBPbeta, liver-enriched inhibitory protein (LIP), which lacks the transcriptional activation domain, stimulates transcriptional activity and the osteogenic action of Runx2, although LIP inhibits adipogenesis in a dominant-negative fashion. Furthermore, LIP physically associates with Runx2 and binds to the C/EBP binding element present in the osteocalcin gene promoter. These data indicate that LIP functions as a coactivator for Runx2 and preferentially promotes the osteoblast differentiation of mesenchymal cells. Thus, identification of a novel role of the C/EBPbeta isoform provides insight into the molecular basis of the regulation of osteoblast and adipocyte commitment.


Detection of SERS active labelled DNA based on surface affinity to silver nanoparticles.
Developments in specific DNA detection assays have been shown to be increasingly beneficial for molecular diagnostics and biological research. Many approaches use optical spectroscopy as an assay detection method and, owing to the sensitivity and molecular specificity offered, surface enhanced Raman scattering (SERS) spectroscopy has become a competitively exploited technique. This study utilises SERS to demonstrate differences in affinity of dye labelled DNA through differences in electrostatic interactions with silver nanoparticles. Results show clear differences in the SERS intensity obtained from single stranded DNA, double stranded DNA and a free dye label and demonstrate surface attraction is driven through electrostatic charges on the nucleotides and not the SERS dye. It has been further demonstrated that, through optimisation of experimental conditions and careful consideration of sequence composition, a DNA detection method with increased sample discrimination at lower DNA concentrations can be achieved.


Chrysotile-induced cell transformation and transcriptional changes of c-myc oncogene in human embryo lung cells.
It has been verified that asbestos induce neoplastic transformation of several rodent cell lines in vitro. Very little information is available, however, on asbestos-induced human cell line transformation and oncogene activation in the development of asbestos-induced cell transformation. This study was designed to investigate the induction of cell transformation and transcriptional changes of the c-myc oncogene by chrysotile asbestos fibers (CAF) in human embryo lung (HEL) cells. Surface-modified CAF soaked in aluminium citrate (AC), rare earth compounds (REC) or sodium selenite (SS) solutions were used to observe the effects of surface modification on chrysotile-induced cell transformation and transcriptional changes in the c-myc oncogene. The results showed that the natural CAF caused dose-dependent increases in transformed foci, along with increased transcription of the c-myc oncogene in HEL cells, while the pretreated CAF induced fewer transformed foci and less c-myc oncogene transcription than the natural CAF. The percent inhibition of equivalent AC, REC and SS were 38.9%, 50.0%, 33.3% (for transformation focus), 81.6%, 69.5%, 89.9% (for c-myc oncogene transcription), respectively. These results indicated that CAF may induce cell transformation and transcriptional changes and that the carcinogenicity of CAF might be reduced by pretreatment of CAF with the above-mentioned compounds.


Comparison of accelerated diagnostic pathways for acute chest pain risk stratification.
The History Electrocardiogram Age Risk factor Troponin (HEART) Pathway and Emergency Department Assessment of Chest pain Score (EDACS) are validated accelerated diagnostic pathways designed to risk stratify patients presenting to the emergency department with chest pain. Data from large multisite prospective studies comparing these accelerated diagnostic pathways are limited. The HEART Pathway Implementation is a prospective three-site cohort study, which accrued adults with symptoms concerning for acute coronary syndrome. Physicians completed electronic health record HEART Pathway and EDACS risk assessments on participants. Major adverse cardiac events (death, myocardial infarction and coronary revascularisation) at 30 days were determined using electronic health record, insurance claims and death index data. Test characteristics for detection of major adverse cardiac events were calculated for both accelerated diagnostic pathways and McNemar's tests were used for comparisons. 5799 patients presenting to the emergency department were accrued, of which HEART Pathway and EDACS assessments were completed on 4399. Major adverse cardiac events at 30 days occurred in 449/4399 (10.2%). The HEART Pathway identified 38.4% (95% CI 37.0% to 39.9%) of patients as low-risk compared with 58.1% (95% CI 56.6% to 59.6%) identified as low-risk by EDACS (p<0.001). Major adverse cardiac events occurred in 0.4% (95% CI 0.2% to 0.9%) of patients classified as low-risk by the HEART Pathway compared with 1.0% (95% CI 0.7% to 1.5%) of patients identified as low-risk by EDACS (p<0.001). Thus, the HEART Pathway had a negative predictive value of 99.6% (95% CI 99.1% to 99.8%) for major adverse cardiac events compared with a negative predictive value of 99.0% (95% CI 98.5% to 99.3%) for EDACS. EDACS identifies a larger proportion of patients as low-risk than the HEART Pathway, but has a higher missed major adverse cardiac events rate at 30 days. Physicians will need to consider their risk tolerance when deciding whether to adopt the HEART Pathway or EDACS accelerated diagnostic pathway. NCT02056964.


The mechanism of the reaction between glutathione and 1-menaphthyl sulphate catalysed by a glutathione S-transferase from rat liver.
1. The glutathione S-transferase that catalyses the reaction of 1-menaphthyl (naphth-1-ylmethyl) sulphate with GSH was purified 76-fold from rat liver. 2. The properties of the purified enzyme were studied by gel filtration and isoelectric focusing. 3. The initial-velocity pattern in the absence of products and the product-inhibition pattern have been determined. These are consistent with an Ordered Bi Bi mechanism in which the GSH adds to the enzyme before 1-menaphthyl sulphate and the products are released in the order SO(4) (2-) followed by S-(1-menaphthyl)glutathione. 4. Dead-end-inhibition studies with p-aminobenzoic acid, which has been shown to be competitive with GSH and non-competitive with 1-menaphthyl sulphate, support the suggestion that an Ordered Bi Bi mechanism is operative. 5. Values were determined for some of the dissociation and Michaelis constants for the reaction of the substrates and products with the enzyme. 6. It appears that S-(1-menaphthyl)glutathione activates the enzyme when the concentration of GSH is saturating and that of 1-menaphthyl sulphate is low (of the order of its Michaelis constant).


Comparison of two techniques used for the recovery of third-stage strongylid nematode larvae from herbage.
A laboratory trial to determine the efficacy of two methods in recovering known numbers of third-stage (L3) strongylid nematode larvae from herbage was carried out. Herbage samples consisting almost entirely of star grass (Cynodon aethiopicus) that had no L3 nematode parasitic larvae were collected at Onderstepoort, South Africa. Two hundred grams samples were placed in fibreglass fly gauze bags and seeded with third-stage strongylid nematode larvae at 11 different levels of herbage infectivity ranging from 50 to 8000 L3/kg. Eight replicates were prepared for each of the 11 levels of herbage infectivity. Four of these were processed using a modified automatic Speed Queen heavy-duty washing machine at a regular normal cycle, followed by isolation of larvae through centrifugation-flotation in saturated sugar solution. Larvae in the other four samples were recovered after soaking the herbage in water overnight and the larvae isolated with the Baermann technique of the washing. There was a strong correlation between the number of larvae recovered using both methods and the number of larvae in the seeded samples, indicating that the two methods give a good indication of changes in the numbers of larvae on pasture if applied in epidemiological studies. The washing machine method recovered higher numbers of larvae than the soaking and Baermann method at all levels of pasture seeding, probably because the machine washed the samples more thoroughly and a sugar centrifugation-flotation step was used. Larval suspensions obtained using the washing machine method were therefore cleaner and thus easier to examine under the microscope. In contrast, the soaking and Baermann method may be more suitable in field-work, especially in places where resources and equipment are scarce, as it is less costly in equipment and less labour intensive. Neither method recovered all the larvae from the seeded samples. The recovery rates for the washing machine method ranged from 18 to 41% while those for the soaking and Baermann method ranged from 0 to 27%. Practical application of the two methods to estimate the number of nematode larvae on pastures without applying a correction factor would therefore result in a significant underestimation. This study provides a model, which can be applied in various laboratories to determine the larval recovery rates for techniques being used and the application of a correction factor when estimating the actual numbers of larvae on pasture.


LINE-1 hypermethylation in peripheral blood of cutaneous melanoma patients is associated with metastasis.
Aberrant DNA methylation pattern is a well-known epigenetic marker of cancer cells. Recently, aberrant methylation was also reported in the peripheral blood of cancer patients and it could potentially serve as a biomarker for cancer risk. We investigated the methylation pattern of LINE-1 and other repetitive DNA elements in peripheral blood of cutaneous melanoma patients in order to search for an association with clinical characteristics. The patient cohort was composed by 69 unrelated melanoma patients, 28 of whom were hereditary cases (with or without CDKN2A mutations) and 41 were isolated (sporadic) melanoma cases. Methylation of LINE-1 was evaluated by pyrosequencing, whereas additional repetitive DNA sequences were assessed using Illumina 450K methylation microarray. Melanoma patients exhibited a higher, albeit heterogeneous, LINE-1 methylation level compared with controls. Hereditary melanoma patients carrying CDKN2A mutations showed a hypermethylated pattern of both LINE-1 and repetitive DNA elements compared with other patients. In particular, the methylation level at one specific CpG of LINE-1 was found to be correlated with the occurrence of metastasis. Our data suggest that LINE-1 hypermethylation in peripheral blood of melanoma patients is a potential epigenetic biomarker for metastasis occurrence.


Update on Descemet membrane endothelial keratoplasty.
To provide an update on new perspectives on Descemet membrane endothelial keratoplasty (DMEK). Preloaded DMEK grafts allow optimization of DMEK surgery time and reduce costs of the procedure, which is allowing the procedure to become more easily performed as reflected in the increasing number of cases. The surgical technique in the United States differs from the technique in Europe, but outcomes have been similar. Hemi-DMEK and quarter-DMEK have shown similar outcomes to conventional DMEK with respect to corneal transparency and visual acuity. Three-year follow-up of hemi-DMEK has also shown stability in endothelial cell count while maintaining corneal transparency. DMEK is becoming more accepted as the procedure of choice for treating endothelial failure. However, challenges with the surgical technique have limited wider implementation of this lamellar corneal transplantation. Preloaded DMEK provides one solution for the surgical challenges associated with the procedure while also reducing costs. Variations in the surgical technique for DMEK, including hemi-DMEK and quarter-DMEK, allow for central corneal clarity similar to traditional DMEK, but both result in lower endothelial cell density (ECD).


Temporal and spatial variations in nutrient stoichiometry and regulation of phytoplankton biomass in Hong Kong waters: influence of the Pearl River outflow and sewage inputs.
In 2001, the Hong Kong government implemented the Harbor Area Treatment Scheme (HATS) under which 70% of the sewage that had been formerly discharged into Victoria Harbor is now collected and sent to Stonecutters Island Sewage Works where it receives chemically enhanced primary treatment (CEPT), and is then discharged into waters west of the Harbor. The relocation of the sewage discharge will possibly change the nutrient dynamics and phytoplankton biomass in this area. Therefore, there is a need to examine the factors that regulate phytoplankton growth in Hong Kong waters in order to understand future impacts. Based on a historic nutrient data set (1986-2001), a comparison of ambient nutrient ratios with the Redfield ratio (N:P:Si=16:1:16) showed clear spatial variations in the factors that regulate phytoplankton biomass along a west (estuary) to east (coastal/oceanic) transect through Hong Kong waters. Algal biomass was constrained by a combination of low light conditions, a rapid change in salinity, and strong turbulent mixing in western waters throughout the year. Potential stoichiometric Si limitation (up to 94% of the cases in winter) occurred in Victoria Harbor due to the contribution of sewage effluent with high N and P enrichment all year, except for summer when the frequency of stoichiometric Si limitation (48%) was the same as P, owing to the influence of the high Si in the Pearl River discharge. In the eastern waters, potential N limitation and N and P co-limitation occurred in autumn and winter respectively, because of the dominance of coastal/oceanic water with low nutrients and low N:P ratios. In contrast, potential Si limitation occurred in spring and a switch to potential N, P and Si limitation occurred in eastern waters in summer. In southern waters, there was a shift from P limitation (80%) in summer due to the influence of the N-rich Pearl River discharge, to N limitation (68%) in autumn, and to N and P co-limitation in winter due to the dominance of N-poor oceanic water from the oligotrophic South China Sea. Our results show clear temporal and spatial variations in the nutrient stoichiometry which indicates potential regulation of phytoplankton biomass in HK waters due to the combination of the seasonal exchange of the Pearl River discharge and oceanic water, sewage effluent inputs, and strong hydrodynamic mixing from SW monsoon winds in summer and the NE monsoon winds in winter.


Photocaged dicarbonyl probe provides spatiotemporal control over protein glycation.
Protein glycation is a disease associated, non-enzymatic, posttranslational modification generated by endogenous dicarbonyl metabolites. Currently, there is a lack of chemical tools capable of studying protein adducts caused by this class of reactive species. Here, we report a chemical biology platform, termed T-DiP (targetable-dicarbonyl precursor), that releases a physiologically relevant dose of bio-orthogonally functionalized dicarbonyl probe upon irradiation with 365 nm light. This approach enables protein glycation to be controlled with spatiotemporal precision within live cells and expands the chemical toolbox needed to elucidate the roles of glycated proteins across various pathologies.


Belief in just deserts regarding individuals infected with COVID-19 in Japan and its associations with demographic factors and infection-related and socio-psychological characteristics: a cross-sectional study.
Prejudice related to the coronavirus disease 2019 (COVID-19) is a social issue worldwide. A possible psychological factor that promotes prejudice is the belief in just deserts (BJD) regarding individuals infected with COVID-19 (i.e., the belief that the infected individual deserves to be infected). The BJD is based on the belief in immanent justice. It is reportedly higher in Japan than in other countries. Therefore, we conducted a cross-sectional study to investigate the BJD among Japanese individuals and clarify its associations with demographic factors or infection-related and socio-psychological characteristics. To this end, we conducted an online questionnaire survey in Japan from August 7-8, 2020, with 1,207 respondents aged 20-69 years. We performed screening to exclude inappropriate responses. We investigated the association between the BJD and demographic factors such as gender and age. We also investigated the association between the BJD and infection-related and socio-psychological characteristics, including risk perception of COVID-19 infection and human rights restrictions (i.e., the degree of agreement with government restrictions on individuals' behavior during emergencies). Among the surveyed items, human rights restrictions showed a strong association with BJD, followed by risk perception of COVID-19 infection. Men had a slightly higher BJD than women. Our study is significant in that it is the first to investigate the items associated with the BJD, thereby providing foundational information for revising individual perceptions of justice related to COVID-19 and solving prejudice-related issues.


Early extubation failure in very low birth weight infants: Clinical outcomes and predictive factors.
To identify the clinical outcomes and the potential predictive factors of early extubation failure (EEF) in very low birth weight (VLBW) infants. A retrospective study of VLBW infants admitted to the neonatal intensive care unit (NICU) over fifteen years. Neonates were intubated and mechanically ventilated on the first day of life, and early extubated within the first 3 days. EEF was defined as the need for re-intubation within 3 days of the first extubation. A composite outcome of mortality or any major morbidity (grade 3-4 intraventricular hemorrhage or periventricular leukomalacia; stage 3-4 retinopathy of prematurity, moderate-severe bronchopulmonary dysplasia or stage 2-3 necrotizing enterocolitis) was assessed. In total, 394 infants were extubated early. Of those, 347 (88%) had early extubation success (EES), whereas 47 (12%) had EEF. Incidence of the composite outcome was significantly higher in the EEF group than the EES group, even after adjusting for confounding factors. Logistic regression indicated that birth weight < 1000 g (p < 0.01), administration of≥2 doses of surfactant (p < 0.01) and administration of≥2 inotropic agents (p < 0.01) were all significantly associated with EEF. The area under the curve (AUC) for the combination of these three factors (AUC = 0.77) indicated significantly higher predictive value (p < 0.01) for EEF in VLBW infants, compared with individual factors (AUC = 0.59 for≥2 inotropic agents, AUC = 0.64 for birth weight≤1000 g and AUC = 0.66 for≥2 doses of surfactant). EEF is associated with poor clinical outcomes in VLBW infants. The combination of birth weight and the requirement for surfactants and inotropic agents can predict EEF.


Identity signaling, identity reception, and the evolution of social recognition in a Neotropical frog.
Animals recognize familiar individuals to perform a variety of important social behaviors. Social recognition is often mediated by communication between signalers who produce signals that contain identity information and receivers who categorize these signals based on previous experience. We tested two hypotheses about adaptations in signalers and receivers that enable the evolution of social recognition using two species of closely related territorial poison frogs. Male golden rocket frogs (Anomaloglossus beebei) recognize the advertisement calls of conspecific territory neighbors and display a "dear enemy effect" by responding less aggressively to neighbors than strangers, whereas male Kai rocket frogs (Anomaloglossus kaiei) do not. Our results did not support the identity signaling hypothesis: both species produced advertisement calls that contain similar amounts of identity information. Our results did support the identity reception hypothesis: both species exhibited habituation of aggression to playbacks simulating the arrival of a new neighbor, but only golden rocket frogs showed renewed aggression when they subsequently heard calls from a different male. These results suggest that an ancestral mechanism of plasticity in aggression common among frogs has been modified through natural selection to be specific to calls of individual males in golden rocket frogs, enabling a social recognition system.


Cryo-Electrospinning Generates Highly Porous Fiber Scaffolds Which Improves Trabecular Meshwork Cell Infiltration.
Human trabecular meshwork is a sieve-like tissue with large pores, which plays a vital role in aqueous humor outflow. Dysfunction of this tissue can occur, which leads to glaucoma and permanent vision loss. Replacement of trabecular meshwork with a tissue-engineered device is the ultimate objective. This study aimed to create a biomimetic structure of trabecular meshwork using electrospinning. Conventional electrospinning was compared to cryogenic electrospinning, the latter being an adaptation of conventional electrospinning whereby dry ice is incorporated in the fiber collector system. The dry ice causes ice crystals to form in-between the fibers, increasing the inter-fiber spacing, which is retained following sublimation. Structural characterization demonstrated cryo-scaffolds to have closer recapitulation of the trabecular meshwork, in terms of pore size, porosity, and thickness. The attachment of a healthy, human trabecular meshwork cell line (NTM5) to the scaffold was not influenced by the fabrication method. The main objective was to assess cell infiltration. Cryo-scaffolds supported cell penetration deep within their structure after seven days, whereas cells remained on the outer surface for conventional scaffolds. This study demonstrates the suitability of cryogenic electrospinning for the close recapitulation of trabecular meshwork and its potential as a 3D in vitro model and, in time, a tissue-engineered device.


[Role of the RIG-I-like receptors in antiviral response].
The innate nonspecific immunity is the first line of defense against viral infection. Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are two main receptor families detecting viral nucleic acid. So far, three RLR family members were characterized: RIG-I, MDA5 and LGP2. RLR constitute a family of cytoplasmic helicases, which recognized intracellular single-stranded and double-stranded RNA that is introduced to cytosol during viral infection and replication. In this work we review the current knowledge about the mechanisms of viral recognition by RIG-I-like receptors and their signaling pathways for the activation of type I interferons and pro-inflammatory cytokines synthesis.


Glycated hemoglobin levels are mostly dependent on nonglycemic parameters in 9398 Finnish men without diabetes.
Determinants of the variance in glycated hemoglobin (HbA1c) among individuals without type 2 diabetes remain largely unknown. We investigated the determinants of HbA1c, fasting plasma glucose, and 2-hour glucose in an oral glucose tolerance test and the associations of these glycemic markers with insulin sensitivity and insulin secretion in Finnish men without type 2 diabetes. The design and setting were the cross-sectional population-based Metabolic Syndrome in Men study including 10 197 Finnish men, aged 45-70 years, and randomly selected from the population register of Kuopio, Eastern Finland. Participants were a total of 9398 men without type 2 diabetes or with newly diagnosed type 2 diabetes at baseline (mean age 57 ± 7 y; body mass index 27.0 ± 4.0 kg/m(2), mean ± SD) in the Metabolic Syndrome in Men study cohort. The intervention included an oral glucose tolerance test. Glycemic and nonglycemic determinants of the variance in HbA1c among participants without type 2 diabetes and the association of HbA1c with insulin secretion and insulin sensitivity were measured. Age, fasting plasma glucose, and high-sensitivity C-reactive protein were the strongest determinants of HbA1c, explaining 12% of the variance in HbA1c levels in participants without type 2 diabetes. Disposition index (insulin secretion) and the Matsuda insulin sensitivity index (insulin sensitivity) explained only less than 2% of the variance in HbA1c in the participants without type 2 diabetes. The variance in HbA1c among men without type 2 diabetes was largely determined by nonglycemic factors and only weakly by impaired insulin sensitivity and insulin secretion.


Phenotypic mixing of retroviruses in mitogen-stimulated lymphocytes: analysis of xenotropic and defective endogenous mouse viruses.
In addition to the known induction of xenotropic endogenous virus in B-mitogen-stimulated murine lymphocyte cultures, distinguishable defective viruses were also induced in different mouse strains (NFS/N, 129, BALB/c). AKR cells produced xenotropic virus and also, in contrast to BALB/c, ecotropic virus. The drug bromodeoxyuridine appeared to have differential effects on virus expression, amplifying xenotropic virus induction but inhibiting the spontaneous production of the ecotropic virus in AKR cultures and of the defective virus in NFS/N cells. Infecting stimulated BALB/c or AKR cultures with Friend leukaemia virus resulted in the production of ecotropic-xenotropic pseudotype viruses, indicating that the infecting ecotropic virus replicates in the cells in which xenotropic virus is induced. No pseudotypes or recombinants were observed following infection of spleen cells releasing defective viruses. Friend leukaemia virus and xenotropic virus with an ecotropic envelope replicated equally well in stimulated lymphocytes from the different strains examined. Taken together, these findings indicate that the non-infectious viruses are encoded by defective proviruses, rather than resulting from faulty, host cell-controlled, virus maturation.


[IgG subclasses: placental transfer in the full-term neonate and their evolution during the first 3 months of life].
The authors studied the placental transfer of IgG subclasses in 43 newborns (NB) and their mothers. All the observations included low-risk pregnancies and full-term deliveries. The values expressed in arithmetric mean +/- standard deviation (means +/- SD), and referred in mg %, showed the following results: maternal Ig Gtotal 1,183 +/- 237 versus (vs.) NBG 1,179 +/- 187; maternal Ig G1 792 +/- 230 vs. NB 822 +/- 124; maternal Ig G2 138 +/- 77 vs. NB 209 +/- 70; maternal Ig G3 48 +/- 33 vs. NB 95 +/- 30, and maternal Ig G4 10 +/- 8 vs. NB 4.9 +/- 2. The relation between the average levels of maternal and cord serum was 1, 1.5, 1.9 and 0.48 for Ig G1, Ig G2, Ig G3 and Ig G4, respectively. It was also proved a maximum decrease in the levels of the subclasses in the first three months for the Ig G3, a percentage being noticed in the third month, in relation to the NB level, of 18, 29, 1.9 and 19% for Ig G1, Ig G2, Ig G3 and Ig G4, respectively. After primovaccination, a response was produced and it affected the 4 subclasses: Ig G1 845 mg %, Ig G2 229 mg %, Ig G3 38 mg % and Ig G4 7.44 mg %, with an increment in relation to prevaccination values of 5.5, 3.7, 20.7 and 12.4, respectively. The authors concluded by showing reference patterns in the active placental transfer of Ig G subclasses in normal full-term newborns.


Expression of bovine rotavirus VP8 and preparation of IgY antibodies against recombinant VP8.
Group A rotavirus is the leading cause of acute gastroenteritis in cattle and swine. Although, vaccination against this virus is an effective strategy for prevention, additional strategy to control disease is necessary. Egg yolk immunoglobulin (IgY)-based passive immunization could be a better option in preventing this disease. Bovine rotavirus (BRV) is group A rotavirus and possesses a genome of 11 segments of double-stranded RNA. The outer layer of capsid is composed of two proteins (VP7 and VP4), which induce virus neutralizing antibodies. Trypsin cleavage of VP4 produces VP8 (28 kDa) and VP5 (60 kDa) fragments. Since a number of studies have demonstrated the induction of neutralizing antibodies using VP8 subunit vaccines, we have produced IgY against the recombinant VP8. The cDNA spanning the VP8 subunit was amplified from bovine rotavirus-infected cells and cloned into pET21d(+) expression vector to generate recombinant VP8. The resulting carboxy-terminal His-tagged VP8 proteins were expressed in Escherichia coli strain BL21(DE3) by isopropyl β-D-1-thiogalactopyranoside (IPTG) induction. The recombinant proteins were purified using Ni-NTA agarose beads, and the purified protein was used as the immunizing agent to produce polyclonal antibodies in chicken. The resulting polyclonal antisera specifically recognized VP8 in Western blot assay and were able to neutralize BRV replication in cell cultures. These results demonstrate that IgY can be used in immunological assays and, in addition, in passive immunization of newborn calves against BRV.


Adjustable computerized stereotaxic brain atlas for transmission and emission tomography.
A computerized brain atlas adjustable to the patient's anatomy would serve serveral purposes. It could be used in stereotaxic surgery. Even more important would be its use in medical imaging to identify various brain structures, such as the basal ganglia and their nuclei, as well as individual cortical gyri. This atlas could be used for additional mapping of nonvisible structures in images obtained with methods having a high spatial resolution, such as computed tomography and nuclear magnetic resonance. Anatomic information obtained in this way might then be transferred to images of low resolution, such as those obtained in positron emission tomography or single-photon emission computed tomography, in order to select anatomically correct regions of interest. The methods used in the construction of such an atlas are briefly described. An attempt to implement such an atlas based on digitized photographs of brain slices is described.


Nitric oxide mechanism of protection in ischemia and reperfusion injury.
In 1992 nitric oxide (NO) was declared molecule of the year by Science magazine, and ever since research on this molecule continues to increase. Following this award, NO was shown to be a mediator/protector of ischemia and reperfusion injury in many organs, such as the heart, liver, lungs, and kidneys. Controversy has existed concerning the actual protective effects of NO. However, literature from the past 15 years seems to reinforce the consensus that NO is indeed protective. Some of the protective actions of NO in ischemia and reperfusion are due to its potential as an antioxidant and anti-inflammatory agent, along with its beneficial effects on cell signaling and inhibition of nuclear proteins, such as NF-kappa B and AP-1. New therapeutic potentials for this drug are also continuously emerging. Exogenous NO and endogenous NO may both play protective roles during ischemia and reperfusion injury. Sodium nitroprusside and nitroglycerin have been used clinically with much success; though only recently have they been tested and proven effective in attenuating some of the injuries associated with ischemia and reperfusion. NO inhalation has, in the past, mostly been used for its pulmonary effects, but has also recently been shown to be protective in other organs. The potential of NO in the treatment of ischemic disease is only just being realized. Elucidation of the mechanism by which NO exerts its protective effects needs further investigation. Therefore, this paper will focus on the mechanistic actions of NO in ischemia and reperfusion injury, along with the compound's potential therapeutic benefits.


Transporter-mediated protection against thiopurine-induced hematopoietic toxicity.
Thiopurines are effective immunosuppressants and anticancer agents, but intracellular accumulation of their active metabolites (6-thioguanine nucleotides, 6-TGN) causes dose-limiting hematopoietic toxicity. Thiopurine S-methyltransferase deficiency is known to exacerbate thiopurine toxicity. However, many patients are highly sensitive to thiopurines for unknown reasons. We show that multidrug-resistance protein 4 (Mrp4) is abundant in myeloid progenitors and tested the role of the Mrp4, an ATP transporter of monophosphorylated nucleosides, in this unexplained thiopurine sensitivity. Mrp4-deficient mice experienced Mrp4 gene dosage-dependent toxicity caused by accumulation of 6-TGNs in their myelopoietic cells. Therefore, Mrp4 protects against thiopurine-induced hematopoietic toxicity by actively exporting thiopurine nucleotides. We then identified a single-nucleotide polymorphism (SNP) in human MRP4 (rs3765534) that dramatically reduces MRP4 function by impairing its cell membrane localization. This SNP is common (>18%) in the Japanese population and indicates that the increased sensitivity of some Japanese patients to thiopurines may reflect the greater frequency of this MRP4 SNP.


Ultrastructure of precapillary sphincters and the neurovascular unit.
Neurons communicate with vasculature to regulate blood flow in the brain, a process maintained by the neurovascular unit (NVU). This interaction, termed neurovascular coupling, is believed to involve astrocytes or molecules capable of traversing the astrocytic endfeet. The precise mechanism, however, remains elusive. Using large 3D electron microscopy datasets, we can now study the entire NVU in context of vascular hierarchy. This study presents evidence supporting the role of precapillary sphincters as a nexus for neurovascular coupling and endothelial transcytosis. It also highlights the role of fibroblast-synthesized collagen in fortifying first-order capillaries. Furthermore, I demonstrate how astrocytic endfeet establish a barrier for fluid flow and reveal that the cortex's microvasculature is semicircled by an unexpected arrangement of parenchymal neuronal processes around penetrating arterioles and arterial-end capillaries in both mouse and human brains. These discoveries offer insights into the NVU's structure and its operational mechanisms, potentially aiding researchers in devising new strategies for preserving cognitive function and promoting healthy aging.


Normal range of lumbar spine flexion in adult Nigerians.
One hundred patients, fifty males and fifty females, without any back pain or disease, were studied. Their ages ranged between 14 years and 70 years. The lumbar flexion measurement was taken using the MacRae and Wright modified Schober's method. The values for males were higher than females and the younger the patient, the higher was the value of the lumbar flexion, up to the third decade. The method could be adopted to show improvements during treatment of low back pain by orthopaedic and physiotherapic practices.


High-throughput computational structure-based characterization of protein families: START domains and implications for structural genomics.
SkyLine, a high-throughput homology modeling pipeline tool, detects and models true sequence homologs to a given protein structure. Structures and models are stored in SkyBase with links to computational function annotation, as calculated by MarkUs. The SkyLine/SkyBase/MarkUs technology represents a novel structure-based approach that is more objective and versatile than other protein classification resources. This structure-centric strategy provides a multi-dimensional organization and coverage of protein space at the levels of family, function, and genome. The concept of "modelability", the ability to model sequences on related structures, provides a reliable criterion for membership in a protein family ("leverage") and underlies the unique success of this approach. The overall procedure is illustrated by its application to START domains, which comprise a Biomedical Theme for the Northeast Structural Genomics Consortium as part of the Protein Structure Initiative. START domains are typically involved in the non-vesicular transport of lipids. While 19 experimentally determined structures are available, the family, whose evolutionary hierarchy is not well determined, is highly sequence diverse, and the ligand-binding potential of many family members is unknown. The SkyLine/SkyBase/MarkUs approach provides significant insights and predicts: (1) many more family members (approximately 4,000) than any other resource; (2) the function for a large number of unannotated proteins; (3) instances of START domains in genomes from which they were thought to be absent; and (4) the existence of two types of novel proteins, those containing dual START domain and those containing N-terminal START domains.


Measurement of cumulative physiological dysregulation in an older population.
The allostatic load framework postulates that an important pathway connecting the social environment with health involves biological responses to stressful stimuli and the subsequent dysregulation of interrelated physiological systems. We formulate a new measure for cumulative physiological dysregulation using a grade of membership model estimated with biodemographic data from a national sample of older Taiwanese persons. We investigate associations between the measure and physical, psychological, and cognitive function. The results provide insights into the relationships between a set of biological profiles and various health outcomes, identify limitations of earlier approaches, and underscore next steps in the development of improved for mulations of physiological dysregulation.


Studies of marine sulfated polymannuroguluronate on endothelial cell proliferation and endothelial immunity and related mechanisms.
Anti-proliferation action and enhancement of endothelial cell immunity and related mechanisms by marine sulfated polymannuroguluronate (SPMG) were investigated in the present studies. Endothelial cell proliferation was evaluated by MTT assay. Intercellular adhesion molecule-1 (ICAM-1) expression was analyzed by flow cytometry. The interaction of SPMG with basic fibroblast growth factor (bFGF) was evaluated by surface plasmon resonance. Results showed that SPMG exhibited a significant inhibitory effect against proliferation in both normal human umbilical vein endothelial cells (HUVEC) and bFGF-treated HUVEC, the action of which was completely abrogated by bFGF antibody. SPMG exerted high affinity to bFGF in a multivalent pattern, characterized by one molecule SPMG binding to 3 - 4 molecules of bFGF. Moreover, SPMG enhanced ICAM-1 expression in HUVEC and prevented and restored bFGF-treated downregulation of ICAM-1 expression in HUVEC, the expression of which was not counteracted by bFGF antibody. In conclusion, this is the first report demonstrating that SPMG exerted an anti-proliferation effect dependent on the bFGF-regulated pathway and afforded upregulatory activity on ICAM-1 expression regardless of the involvement of bFGF.


Bioaccessibility of phytoene and phytofluene is superior to other carotenoids from selected fruit and vegetable juices.
Phytoene and phytofluene are major abundant dietary carotenoids largely ignored in the context of agro-food and health. The bioaccessibility of phytoene and phytofluene in tomato, carrot, blood orange (sanguinello cultivar), and apricot juices was analysed following simulated gastro-intestinal digestion with coffee cream as a lipid source, and compared with that of other main carotenoids from these matrices. The bioaccessibility of phytoene and phytofluene, and also total carotenoid bioaccessibility, followed the order: sanguinello>apricot>tomato>carrot. Phytoene was consistently the carotenoid with the highest bioaccessibility, up to 97%, generally followed by phytofluene. The higher bioaccessibility of these carotenoids could mainly be due to their marked difference in chemical structure and matrix distribution. For most juices, cis-isomers presented a higher bioaccessibility than their all-trans counterparts (P<0.05). The dietary source that provided highest amounts of potentially absorbable phytoene/phytofluene was by far tomato juice (5mg/250mL juice).


Deciphering the nuclear bile acid receptor FXR paradigm.
Originally called retinoid X receptor interacting protein 14 (RIP14), the farnesoid X receptor (FXR) was renamed after the ability of its rat form to bind supra-physiological concentrations of farnesol. In 1999 FXR was de-orphanized since primary bile acids were identified as natural ligands. Strongly expressed in the liver and intestine, FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of conditions such as cholestasis, fatty liver disease, cholesterol gallstone disease, intestinal inflammation and tumors. Furthermore, given the importance of FXR in the gut-liver axis feedbacks regulating lipid and glucose homeostasis, FXR modulation appears to have great input in diseases such as metabolic syndrome and diabetes. Exciting results from several cellular and animal models have provided the impetus to develop synthetic FXR ligands as novel pharmacological agents. Fourteen years from its discovery, FXR has gone from bench to bedside; a novel nuclear receptor ligand is going into clinical use.


Iterative PET Image Reconstruction Using Translation Invariant Wavelet Transform.
The present work describes a Bayesian maximum a posteriori (MAP) method using a statistical multiscale wavelet prior model. Rather than using the orthogonal discrete wavelet transform (DWT), this prior is built on the translation invariant wavelet transform (TIWT). The statistical modeling of wavelet coefficients relies on the generalized Gaussian distribution. Image reconstruction is performed in spatial domain with a fast block sequential iteration algorithm. We study theoretically the TIWT MAP method by analyzing the Hessian of the prior function to provide some insights on noise and resolution properties of image reconstruction. We adapt the key concept of local shift invariance and explore how the TIWT MAP algorithm behaves with different scales. It is also shown that larger support wavelet filters do not offer better performance in contrast recovery studies. These theoretical developments are confirmed through simulation studies. The results show that the proposed method is more attractive than other MAP methods using either the conventional Gibbs prior or the DWT-based wavelet prior.


Patella Fractures: Approach to Treatment.
Patellar fracture morphology varies based on the mechanism of injury. Most fractures are either a result of direct impact or through an indirect eccentric extensor contraction injury. Each fracture pattern requires appropriate preoperative planning and individualization of the fixation method. Displaced fractures affect the extension apparatus, and often require surgical fixation. Surgical treatment is recommended in fractures with any of the following features: articular step-off > 2 mm, > 3 mm of fracture displacement, open fractures, and displaced fractures affecting the extensor mechanism. Meticulous handling of the soft-tissue envelope is of the utmost importance, given the patella's tenuous blood supply and limited soft-tissue envelope. Incongruent articular surface can result in detrimental long-term effects; therefore, surgical treatment is directed toward anatomic reduction and fixation. The evolution of patellar fracture fixation continues to maximize options to balance rigid fixation with low-profile fixation constructs. Improving functional outcomes, minimizing soft-tissue irritation, and limiting postoperative complications are possible by using the therapeutic principles of rigid anatomical fixation and meticulous soft-tissue handling.


Interleukin-21 Drives Proliferation and Differentiation of Porcine Memory B Cells into Antibody Secreting Cells.
Immunological prevention of infectious disease, especially viral, is based on antigen-specific long-lived memory B cells. To test for cellular proliferation and differentiation factors in swine, an outbred model for humans, CD21+ B cells were activated in vitro with CD40L and stimulated with purported stimulatory cytokines to characterize functional responses. IL-21 induced a 3-fold expansion in total cell numbers with roughly 15% of all B cells differentiating to IgM or IgG antibody secreting cells (ASCs.) However, even with robust proliferation, cellular viability rapidly deteriorated. Therefore, a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) were evaluated as survival and maintenance factors. BAFF was effective at enhancing the viability of mature B cells as well as ASCs, while APRIL was only effective for ASCs. Both cytokines increased approximately two-fold the amount of IgM and IgG which was secreted by IL-21 differentiated ASCs. Mature B cells from porcine reproductive and respiratory virus (PRRSV) immune and naïve age-matched pigs were activated and treated with IL-21 and then tested for memory cell differentiation using a PRRSV non-structural protein 7 ELISPOT and ELISA. PRRSV immune pigs were positive on both ELISPOT and ELISA while naïve animals were negative on both assays. These results highlight the IL-21-driven expansion and differentiation of memory B cells in vitro without stimulation of the surface immunoglobulin receptor complex, as well as the establishment of a defined memory B cell culture system for characterization of vaccine responses in outbred animals.


A longitudinal study of sero-conversion to tick-borne pathogens in smallholder dairy youngstock in Tanzania.
A longitudinal study of sero-conversion of youngstock to the tick-borne pathogens Theileria parva, T. mutans, Anaplasma marginale, Babesia bigemina and B. bovis was conducted over two years on smallholder dairy farms in Tanga region, Tanzania. There was evidence of maternal antibodies to all tick-borne pathogens in animals less than 18 weeks of age. Seroprevalence increased as expected with age in animals older than this but seroprevalence profiles underestimated the force of infection due to waning antibody levels between samplings. By the end of the 2-year study, less than 50% of study animals had seroconverted to each of the tick-borne pathogens investigated, consistent with the low levels of tick attachment observed on the study animals. Some associations between seroconversion to tick-borne pathogens, and counts of their known tick vectors on the animals, were identified as expected. However, some were not, suggesting that counts of some tick species may act as an index of rates of attachment of other vector species. Variation in acaricide treatment frequencies was not associated with variations in tick-borne pathogen seroprevalence suggesting that acaricides may be used more frequently than necessary on many farms. Most animals were zero-grazed, a management system associated with a significantly lower likelihood that animals seroconverted to any tick-borne pathogen except A. marginale. Seroprevalence varied locally with farm location (particularly for Babesia spp.) but was not well predicted by indices of ecological conditions. Our findings suggest that attempts to achieve a state of 'endemic stability' for tick-borne pathogens may be unreasonable on the smallholder dairy farms studied but reductions in the frequency of use of acaricides may be possible following prospective studies of effects on mortality and morbidity due to tick-borne pathogens.


Cardiovascular protection effect of chlorogenic acid: focus on the molecular mechanism.
Vascular endothelial cells have a variety of functions such as the control of blood coagulation, vascular permeability, and tone regulation, as well as quiesce of immune cells. Endothelial dysfunction is a cardiovascular events predictor, which is considered the initial stage in atherosclerosis development. It is characterized by alterations in endothelium functions due to imbalanced vasodilators and vasoconstrictors, procoagulant and anticoagulant mediators, as well as growth inhibitor and promotor substances. Chlorogenic acid (CGA) is the primary polyphenol in coffee and some fruits. It has many health-promoting properties, especially in the cardiovascular system. Many studies investigated the efficacy and mechanism of this compound in vascular health. CGA has several vascular benefits such as anti-atherosclerosis, anti-thrombosis, and anti-hypertensive. This review focuses on the molecular mechanism of CGA in vascular health.


From "magic bullets" to specific cancer immunotherapy.
The immune system is able to specifically target antigen-expressing cancer cells. The promise of immunotherapy was to eliminate cancer cells without harming normal tissue and, therefore, with no or very few side effects. Immunotherapy approaches have, for several decades, been tested against several tumours, most often against malignant melanoma. However, although detectable immune responses have regularly been induced, the clinical outcome has often been disappointing. The development of molecular methods and an improved understanding of tumour immunosurveillance led to novel immunotherapy approaches in the last few years. First randomised phase III trials proved that immunotherapy can prolong survival of patients with metastatic melanoma or prostate cancer. The development in the field is very rapid and various molecules (mainly monoclonal antibodies) that activate the immune system are currently being tested in clinical trials and will possibly change our treatment of cancer. The ultimate goal of any cancer therapy and also immunotherapy is to cure cancer. However, this depends on the elimination of the disease originating cancer stem cells. Unfortunately, cancer stem cells seem resistant to most available treatment options. Recent developments in immunotherapy may allow targeting these cancer stem cells specifically in the future. In this review, we summarise the current state of immunotherapy in clinical routine and the expected developments in the near future.


Risk stratification and stroke prevention therapy care gaps in Canadian atrial fibrillation patients (from the Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation chart audit).
The objectives of this national chart audit (January to June 2013) of 6,346 patients with atrial fibrillation (AF; ≥18 years without a significant heart valve disorder) from 647 primary care physicians were to (1) describe the frequency of stroke and bleed risk assessments in patients with nonvalvular AF by primary care physicians, including the accuracy of these assessments relative to established predictive indexes; (2) outline contemporary methods of anticoagulation used; and (3) report the time in the therapeutic range among patients prescribed warfarin. An annual stroke risk assessment was not undertaken in 15% and estimated without a formal risk tool in 33%; agreement with CHADS2 score estimation was seen in 87% of patients. Major bleeding risk assessment was not undertaken in 25% and estimated without a formal risk tool in 47%; agreement with HAS-BLED score estimation was observed in 64% with physician overestimation in 26% of patients. Antithrombotic therapy included warfarin (58%), dabigatran (22%), rivaroxaban (14%), and apixaban (<1%). Among warfarin-treated patients, the median international normalized ratio was 2.4 and time in therapeutic range (TTR) was 73%; however, the TTR was <50% in 845 (25%), 50% to 69% in 674 (20%), and ≥70% in 1,827 (55%) patients. In conclusion, we describe a contemporary real-world elderly population with AF at important risk for stroke. There is apparent overestimation of bleeding risk in many patients. Warfarin was the dominant stroke prevention treatment; however, the suggested TTR target was achieved in only 55% of these patients.


Poly-L-lysine as an Effective and Safe Desquamation Inducer of Urinary Bladder Epithelium.
Induced desquamation of urinary bladder epithelial cells, also called urothelial cells, is frequently used in studies of bladder epithelial regeneration and also in treating recurrent bacterial cystitis. Positively charged polymer chitosan is known to cause large-scale desquamation of terminally differentiated urothelial cells called umbrella cells. Aiming to compare the desquamation ability of another polycation poly-L-lysine, we studied the effect of this polymer on the functional and structural integrity of the urothelium in ex vivo and in vivo experiments. The urothelium was analyzed by measuring transepithelial electrical resistance, and the structural changes of its luminal surface were analyzed with scanning electron microscopy. The results revealed a selective and concentration-dependent desquamation effect of poly-L-lysine on superficial urothelial cells followed by quick regeneration of the urothelium, which functionally and structurally recovers in 2 to 3 h after poly-L-lysine-induced injury. Poly-L-lysine was thus proven to be a promising polymer to be used when desquamation of urothelial cells is required in basic and potentially clinical studies.


Cumulative Live-Birth Rates by Maternal Age after One or Multiple In Vitro Fertilization Cycles: An Institutional Experience.
The aim of this retrospective study is to investigate the cumulative live birth rate (CLBR) following one or more completed in vitro fertilization (IVF) cycles (up to 6 cycles) stratified by maternal age and type of infertility. In this retrospective study, five hundred forty-seven women who received 736 fresh ovarian stimulation/embryo transfer cycles between January 2016 and December 2016 were included in the study at a tertiary care center located in Lebanon. In all women, the live birth rate for the first cycle was 33.0% [95% confidence interval (CI): 27.8-38.2]. The CLBR showed an increase with each successive fresh cycle to reach 56.9% (95% CI: 51.2-62.4) after 3 cycles and 67.9% (95% CI: of 62.5-73.0) after 6 cycles. The CLBR following 6 cycles reached 69.9% (95% CI: 63.8-75.6) in women younger than 35 years. In women older than 40 years, however, the live birth rate for the first cycle was significantly low at 3.1% (95% CI: 0.3-9.5) with a plateau in success rates after 4 cycles reaching 21.9% (95% CI: 9.2-40.0). Couples with different types of infertility had CLBRs ranging from 65% to 72%, with the exception of women with low ovarian reserve, where CLBRs reached 29.4% (95% CI: 10.3-56.0). The CLBR at a referral center in a Middle Eastern country reached 67.9 % after 6 cycles, with variations by age and type of infertility treatment. These findings are encouraging for patients insisting to extend their treatment beyond 4 to 5 cycles.


A human-specific allelic group of the MHC DRB1 gene in primates.
Diversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the HLA loci are the most polymorphic in the human genome. One characteristic of HLA diversity is long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species. Modern humans have disseminated across the world after their exodus from Africa, while chimpanzees have remained in Africa since the speciation event between humans and chimpanzees. It is thought that modern humans have recently acquired resistance to novel pathogens outside Africa. In the present study, we investigated HLA alleles that could contribute to this local adaptation in humans and also studied the contribution of natural selection to human evolution by using molecular data. Phylogenetic analysis of HLA-DRB1 genes identified two major groups, HLA Groups A and B. Group A formed a monophyletic clade distinct from DRB1 alleles in other Catarrhini, suggesting that Group A is a human-specific allelic group. Our estimates of divergence time suggested that seven HLA-DRB1 Group A allelic lineages in humans have been maintained since before the speciation event between humans and chimpanzees, while chimpanzees possess only one DRB1 allelic lineage (Patr-DRB1*03), which is a sister group to Group A. Experimental data showed that some Group A alleles bound to peptides derived from human-specific pathogens. Of the Group A alleles, three exist at high frequencies in several local populations outside Africa. HLA Group A alleles are likely to have been retained in human lineages for a long period of time and have not expanded since the divergence of humans and chimpanzees. On the other hand, most orthologs of HLA Group A alleles may have been lost in the chimpanzee due to differences in selective pressures. The presence of alleles with high frequency outside of Africa suggests these HLA molecules result from the local adaptations of humans. Our study helps elucidate the mechanism by which the human adaptive immune system has coevolved with pathogens over a long period of time.


A novel validation algorithm allows for automated cell tracking and the extraction of biologically meaningful parameters.
Automated microscopy is currently the only method to non-invasively and label-free observe complex multi-cellular processes, such as cell migration, cell cycle, and cell differentiation. Extracting biological information from a time-series of micrographs requires each cell to be recognized and followed through sequential microscopic snapshots. Although recent attempts to automatize this process resulted in ever improving cell detection rates, manual identification of identical cells is still the most reliable technique. However, its tedious and subjective nature prevented tracking from becoming a standardized tool for the investigation of cell cultures. Here, we present a novel method to accomplish automated cell tracking with a reliability comparable to manual tracking. Previously, automated cell tracking could not rival the reliability of manual tracking because, in contrast to the human way of solving this task, none of the algorithms had an independent quality control mechanism; they missed validation. Thus, instead of trying to improve the cell detection or tracking rates, we proceeded from the idea to automatically inspect the tracking results and accept only those of high trustworthiness, while rejecting all other results. This validation algorithm works independently of the quality of cell detection and tracking through a systematic search for tracking errors. It is based only on very general assumptions about the spatiotemporal contiguity of cell paths. While traditional tracking often aims to yield genealogic information about single cells, the natural outcome of a validated cell tracking algorithm turns out to be a set of complete, but often unconnected cell paths, i.e. records of cells from mitosis to mitosis. This is a consequence of the fact that the validation algorithm takes complete paths as the unit of rejection/acceptance. The resulting set of complete paths can be used to automatically extract important biological parameters with high reliability and statistical significance. These include the distribution of life/cycle times and cell areas, as well as of the symmetry of cell divisions and motion analyses. The new algorithm thus allows for the quantification and parameterization of cell culture with unprecedented accuracy. To evaluate our validation algorithm, two large reference data sets were manually created. These data sets comprise more than 320,000 unstained adult pancreatic stem cells from rat, including 2592 mitotic events. The reference data sets specify every cell position and shape, and assign each cell to the correct branch of its genealogic tree. We provide these reference data sets for free use by others as a benchmark for the future improvement of automated tracking methods.


Intriguing circles: Conflicts and controversies in circular RNA research.
Circular RNAs (circRNAs) are covalently closed RNA circles without a 5' cap or 3' tail. Since the landmark discovery of ciRS-7/CDR1as functioning as a miR-7 sponge in 2013, circRNAs have become a hot topic in RNA research. CircRNAs have been found to play active roles in cancer, cardiovascular diseases, neurological disorders, and many other diseases. They can function as microRNA (miRNA) sponges, protein scaffolds, and even translation templates. However, as circRNA research expands, many divergent views have emerged. For example, are most circRNAs competent in serving as miRNA sponges? What kinds of circRNAs are most likely to sponge miRNAs? Apart from sponging miRNAs, what could the functions of most circRNAs be? What are the features of circRNAs that are translatable? Many researchers have claimed that circRNAs are abundant, stable, conserved, and specific molecules, which hold great potential in serving as biomarkers. However, circRNA abundance is variable and some circRNAs are abundant while others are not. In addition, their stability and conservation may vary under different circumstances. Furthermore, it is unclear whether circRNA biogenesis is more likely to be regulated by RNA binding proteins or transcription factors. All of these are open questions that remain to be answered by researchers in this field. Discussing and investigating these questions will advance the understanding of this class of novel molecules and may propel inspiring new ideas for future studies. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.


Challenges of congenital heart disease in grown-up patients.
Nowadays, more than 90% of all children born with congenital heart disease (CHD) reach adult life. Although initially considered to be cured, the majority of them continue to need specialised follow-up because they require re-do interventions or are at increased risk of cardiovascular complications and premature death. Arrhythmias are the most common cause of unscheduled hospital visits for grown-up CHD (GUCH) patients, accounting for one third of emergency admissions in these patients. Some GUCH patients are also at increased risk for sudden cardiac death. The principles of arrhythmia management and the prevention of sudden cardiac death in GUCH patients are similar to those used in adults with acquired heart disease, but are not evidence based. Decompensated heart failure is the other leading cause of death. Conventional medical heart-failure therapy for left ventricular dysfunction is not effective in GUCH patients at highest risk of heart failure, i.e., those with right or single ventricular failure. Careful haemodynamic assessment and structural interventions are the first step to consider in GUCH patients presenting with heart failure symptoms. Adults with moderate or complex CHD and regular follow-up in specialised GUCH centres have a survival benefit compared with patients without such follow-up. Cardiac surgery in GUCH patients should be performed by surgeons trained in treatment of CHD, i.e., surgeons also operating on paediatric patients. A structured transition programme with a defined transfer of care from the paediatric to the adult care environment is important to avoid lapses of care in today's adolescents with CHD. For GUCH patients with an intervention performed decades ago and no specific cardiac follow-up in later life, referral to a specialised GUCH centre is recommended and may save lives.


The N-pact factor: evaluating the quality of empirical journals with respect to sample size and statistical power.
The authors evaluate the quality of research reported in major journals in social-personality psychology by ranking those journals with respect to their N-pact Factors (NF)-the statistical power of the empirical studies they publish to detect typical effect sizes. Power is a particularly important attribute for evaluating research quality because, relative to studies that have low power, studies that have high power are more likely to (a) to provide accurate estimates of effects, (b) to produce literatures with low false positive rates, and (c) to lead to replicable findings. The authors show that the average sample size in social-personality research is 104 and that the power to detect the typical effect size in the field is approximately 50%. Moreover, they show that there is considerable variation among journals in sample sizes and power of the studies they publish, with some journals consistently publishing higher power studies than others. The authors hope that these rankings will be of use to authors who are choosing where to submit their best work, provide hiring and promotion committees with a superior way of quantifying journal quality, and encourage competition among journals to improve their NF rankings.


[Feasibility study for whole plant medicinal use of Tribulus terrestris].
The content differences of leaf, plant and fruit of Tribulus terrestris was compared to study the feasibility of whole plant medicinal use. The samples were collected in three typical habitats and six different production areas of T. terrestris. The main medicinal ingredients saponins and flavonoids were determined in root, stem, leaf and fruit during the harvest time. The two ingredients were abounded in leaf and more than 2.61 times as in other parts of the plant. The results showed that there were no differences between the whole plant and the fruit. It should pay more attentions on the collection, preservation and utilization of the leaf of T. terrestris in the harvesting and processing stage. The whole plant for medical use was feasibility based on the content of the ingredients.