Persuading physicians to test their patients' level of kidney functioning: the effects of message frame and point of view.
A two-part field experiment was conducted to determine the effects of message frame (gain vs. loss) and point of view (personal vs. impersonal) on physicians' intentions and behavior to test their patients' level of kidney functioning. One hundred and fifty-one physicians returned a survey that accompanied one of four different experimental cover letters or a generic control letter. One hundred and twelve (74%) of these physicians also completed and returned a follow-up survey sent approximately 4 months later. Physicians who received a letter (vs. the generic-letter control group) believed their patients were more susceptible to kidney disease, believed that kidney disease had more severe consequences, and also demonstrated greater intentions and behavior to test their patients' level of kidney functioning. Additionally, there was a significant frame by point of view interaction effect, in that physicians receiving the gain-framed personal letter or the loss-framed impersonal letter demonstrated greater intentions and behavior than physicians receiving other versions of the letter. These results extend the theoretical scope of the EPPM by suggesting that threat to other can motivate behavior change, and also can have significant practical application for the development of messages targeting physicians.


Mitral transcatheter technologies.
Mitral valve regurgitation (MR) is often diagnosed in patients with heart failure and is associated with worsening of symptoms and reduced survival. While surgery remains the gold standard treatment in low-risk patients with degenerative MR, in high-risk patients and in those with functional MR, transcatheter procedures are emerging as an alternative therapeutic option. MitraClip(®) is the device with which the largest clinical experience has been gained to date, as it offers sustained clinical benefit in selected patients. Further to MitraClip implantation, several additional approaches are developing, to better match with the extreme variability of mitral valve disease. Not only repair is evolving, initial steps towards percutaneous mitral valve implantation have already been undertaken, and initial clinical experience has just started.


Multifunctional ferrofluid-infused surfaces with reconfigurable multiscale topography.
Developing adaptive materials with geometries that change in response to external stimuli provides fundamental insights into the links between the physical forces involved and the resultant morphologies and creates a foundation for technologically relevant dynamic systems1,2. In particular, reconfigurable surface topography as a means to control interfacial properties3 has recently been explored using responsive gels4, shape-memory polymers5, liquid crystals6-8 and hybrid composites9-14, including magnetically active slippery surfaces12-14. However, these designs exhibit a limited range of topographical changes and thus a restricted scope of function. Here we introduce a hierarchical magneto-responsive composite surface, made by infiltrating a ferrofluid into a microstructured matrix (termed ferrofluid-containing liquid-infused porous surfaces, or FLIPS). We demonstrate various topographical reconfigurations at multiple length scales and a broad range of associated emergent behaviours. An applied magnetic-field gradient induces the movement of magnetic nanoparticles suspended in the ferrofluid, which leads to microscale flow of the ferrofluid first above and then within the microstructured surface. This redistribution changes the initially smooth surface of the ferrofluid (which is immobilized by the porous matrix through capillary forces) into various multiscale hierarchical topographies shaped by the size, arrangement and orientation of the confining microstructures in the magnetic field. We analyse the spatial and temporal dynamics of these reconfigurations theoretically and experimentally as a function of the balance between capillary and magnetic pressures15-19 and of the geometric anisotropy of the FLIPS system. Several interesting functions at three different length scales are demonstrated: self-assembly of colloidal particles at the micrometre scale; regulated flow of liquid droplets at the millimetre scale; and switchable adhesion and friction, liquid pumping and removal of biofilms at the centimetre scale. We envision that FLIPS could be used as part of integrated control systems for the manipulation and transport of matter, thermal management, microfluidics and fouling-release materials.


I could take the judgment if you could just provide the service: non-prescription syringe purchase experience at Arizona pharmacies, 2018.
Community pharmacies are important for health access by rural populations and those who do not have optimum access to the health system, because they provide myriad health services and are found in most communities. This includes the sale of non-prescription syringes, a practice that is legal in the USA in all but two states. However, people who inject drugs (PWID) face significant barriers accessing sterile syringes, particularly in states without laws allowing syringe services programming. To our knowledge, no recent studies of pharmacy-based syringe purchase experience have been conducted in communities that are both rural and urban, and none in the Southwestern US. This study seeks to understand the experience of retail pharmacy syringe purchase in Arizona by PWID. An interview study was conducted between August and December 2018 with 37 people living in 3 rural and 2 urban Arizona counties who identified as current or former users of injection drugs. Coding was both a priori and emergent, focusing on syringe access through pharmacies, pharmacy experiences generally, experiences of stigma, and recommendations for harm reduction services delivered by pharmacies. All participants reported being refused syringe purchase at pharmacies. Six themes emerged about syringe purchase: (1) experience of stigma and judgment by pharmacy staff, (2) feelings of internalized stigma, (3) inconsistent sales outcomes at the same pharmacy or pharmacy chain, (4) pharmacies as last resort for syringes, (5) fear of arrest for syringe possession, and (6) health risks resulting from syringe refusal. Non-prescription syringe sales in community pharmacies are a missed opportunity to improve the health of PWID by reducing syringe sharing and reuse. Yet, current pharmacy syringe sales refusal and stigmatization by staff suggest that pharmacy-level interventions will be necessary to impact pharmacy practice. Lack of access to sterile syringes reinforces health risk behaviors among PWID. Retail syringe sales at pharmacies remain an important, yet barrier-laden, element of a comprehensive public health response to reduce HIV and hepatitis C among PWID. Future studies should test multilevel evidence-based interventions to decrease staff discrimination and stigma and increase syringe sales.


NTAKalpha and beta isoforms stimulate breast tumor cell growth by means of different receptor combinations.
Neural- and thymus-derived activator for ErbB kinases (NTAK) is a recently described member of the neuregulin family that binds directly to ErbB3 and ErbB4 and transactivates ErbB2. Rat NTAK has at least five alternative-spliced isoforms: alpha1, alpha2a, alpha2b, beta, and gamma. In order to understand their biological properties, this study focused on the NTAK alpha2a and beta isoforms, which have different EGF-like domains. The effect of these isoforms on cell growth and tyrosine phosphorylation in human breast cancer cells, MDA-MB-453 and T47D, was examined using the recombinant proteins. In terms of cell growth, NTAKalpha2a and NTAKbeta preferentially stimulate T47D cells and MDA-MB-453 cells, respectively, in a dose-dependent manner. Although both NTAKs induce the highest level of tyrosine phosphorylation of ErbB2, NTAKalpha2a and NTAKbeta preferentially induce ErbB3 and ErbB4 phosphorylation, respectively. Thus, NTAKalpha2a and NTAKbeta stimulate cell growth in different ways, by means of different combinations of receptors.


Sparse Coding Using the Locally Competitive Algorithm on the TrueNorth Neurosynaptic System.
The Locally Competitive Algorithm (LCA) is a biologically plausible computational architecture for sparse coding, where a signal is represented as a linear combination of elements from an over-complete dictionary. In this paper we map the LCA algorithm on the brain-inspired, IBM TrueNorth Neurosynaptic System. We discuss data structures and representation as well as the architecture of functional processing units that perform non-linear threshold, vector-matrix multiplication. We also present the design of the micro-architectural units that facilitate the implementation of dynamical based iterative algorithms. Experimental results with the LCA algorithm using the limited precision, fixed-point arithmetic on TrueNorth compare favorably with results using floating-point computations on a general purpose computer. The scaling of the LCA algorithm within the constraints of the TrueNorth is also discussed.


[Head injuries in children. Considerations on 3,715 consecutive cases].
The authors present their personal experience of 3715 cases of head injury in pediatric patients, occurring during the last three years (1997-1999), admitted to the Emergency ward at the "Anna Meyer" children's hospital in Florence. A prospective study was made, starting from the evaluation made by the paediatric surgeon and following the subsequent diagnostic and clinical course. Depending on the severity of injury, this took the form of immediate discharge with a written sheet of instructions, "short observation" (up to 12 hours) in an Emergency ward and/or admission to neurosurgery or general medicine or to intensive care. The authors also analyse the diagnostic and instrumental tests carried out at the various stages (cranial X-ray, direct cranial CT, EEG) and the specialist consultations required (neurosurgery, neurology, paediatrics, resuscitation). Data for injured children transferred from other hospitals for neurosurgery were excluded from the study which only included patients examined primarily at our hospital. If admitted for more than 48 hours, a neurosurgical outpatient check-up was programmed one week later. In more severe cases, patients were admitted to day hospital between six months and one year later. Injuries were minor in 91% of cases and the age of patients ranged between 5 days and 14 years; moreover, 60% of the patients observed were male. Only 1.5% of cases seen in Emergency were admitted to hospital and 8.4% of all head injuries, with a total stay of between 1 and 6 days. There were 4 deaths in severely polytraumatised patients. There was only one case of firearm injury which was not fatal. Head X-rays were performed in 13.4% of patients showing evidence of fracture in 19.1% of cases. Direct cranial CT was performed in 10.2% of cases with pathological findings in 23.9% of cases. Neurosurgery was performed in one of the 5.9% patients admitted to hospital. The late sequelae to head injury included one case of epilepsy that occurred 7 months after injury. Anamnesis showed that the most frequent reason leading to head injury was lack of adult supervision and that the majority of severe injuries were caused by road accidents, both as pedestrians and as passengers. Lastly, the authors emphasise the importance of recognising and correctly treating so-called secondary cerebral damage, which has a non-immediate onset but is potentially severe, and identifying the risk factors for head injury in order to reduce the incidence and severity.


Increased indoleamine 2,3-dioxygenase (IDO) activity in idiopathic generalized epilepsy.
Indoleamine 2,3-dioxygenase (IDO) is a cytokine-inducible enzyme that participates in tryptophan (trp) and serotonin metabolism with an ability to modulate neuroinflammation. Several recent studies have shown associations between cytokines and epilepsy. In this study we investigated whether activation of IDO is associated with epilepsy. Kynurenine (kyn)/trp serum ratio, as an indicator of IDO activity was analyzed in 271 carefully classified epilepsy patients, and 309 healthy adults. IDO activity was increased in patients with unclassified idiopathic generalized epilepsy (IGE) (n=11; p=0.05), in juvenile myoclonic epilepsy (JME) (n=25; p=0.04) and in patients those with temporal lobe epilepsy but no hippocampal sclerosis (TLE-HS) (n=103; p=0.05) compared to the control subjects. In patients with idiopathic (but not cryptogenic or symptomatic) etiology of epilepsy, IDO activity was increased compared to the control subjects (p<0.05). Patients with extra-TLE or TLE+HS had IDO activity comparable to the control subjects. Patients who were one-month seizure-free prior to sampling had increased IDO activity compared to the control subjects (p=0.03). Increased IDO activity appeared to be associated with idiopathic generalized epilepsies such as unclassified IGE and JME, two of the most common types of primary generalized epilepsy. We also found a trend of increased IDO activity in patients with TLE-HS. Our results suggest that increased IDO activity may represent an adaptive metabolic phenomenon in epilepsy, which may also have a neuroprotective or anticonvulsive role by downregulating neuroinflammation in the brain.


Short term results of pterygium surgery with adjunctive amniotic membrane graft.
The objective of this study is to present the 3 months results of pterygium excision with adjunctive amniotic membrane graft. In a non-comparative case series study, the medical records of all patients who had pterygium excision with adjunctive amniotic membrane transplant on bare sclera from December 2009 to August 2010 were reviewed. All the patients were followed up for 3 months. The data collected were sex, age, occupation, type of pterygium (primary or recurrent), extent of pterygium, post-operative complications and recurrent pterygium growth. Thirty eyes of 30 consecutive patients were operated on. There were 14 males and 16 females (M:F =1:1); age range 25 to 70 years (mean: 48.3 SD + 12.01). Twenty-six eyes had primary and 4 recurrent pterygia. Stage 3 pterygium accounted for most of the cases (53.3%) followed by stage 2 (36.7%) and stage 4 (10%). Nineteen patients (63.3%) had occupations with considerable exposure to actinic damage. Of these, manual laborers accounted for the highest number contributing 13 (43.3%) out of the 19 cases. Of the 30 patients 2 had a reoccurrence giving a recurrence rate of 6%. One patient developed dellen 1 week post-operatively with complete resolution following conservative large soft contact lens application. Short term results suggests that adjunctive amniotic membrane transplant with pterygium excision is effective and safe. A larger randomized clinical trial with a longer follow-up period is however recommended.


Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line.
First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro transfection results from BCPV-siRNA, a newly developed biodegradable transfection agent, BCPV, is being probed for transfection performance in an animal model.


Suomi NPP VIIRS solar diffuser screen transmittance model and its applications.
The visible infrared imaging radiometer suite on the Suomi National Polar-orbiting Partnership satellite calibrates its reflective solar bands through observations of a sunlit solar diffuser (SD) panel. Sunlight passes through a perforated plate, referred to as the SD screen, before reaching the SD. It is critical to know whether the SD screen transmittance measured prelaunch is accurate. Several factors such as misalignments of the SD panel and the measurement apparatus could lead to errors in the measured transmittance and thus adversely impact on-orbit calibration quality through the SD. We develop a mathematical model to describe the transmittance as a function of the angles that incident light makes with the SD screen, and apply the model to fit the prelaunch measured transmittance. The results reveal that the model does not reproduce the measured transmittance unless the size of the apertures in the SD screen is quite different from the design value. We attribute the difference to the orientation alignment errors for the SD panel and the measurement apparatus. We model the alignment errors and apply our transmittance model to fit the prelaunch transmittance to retrieve the "true" transmittance. To use this model correctly, we also examine the finite source size effect on the transmittance. Furthermore, we compare the product of the retrieved "true" transmittance and the prelaunch SD bidirectional reflectance distribution function (BRDF) value to the value derived from on-orbit data to determine whether the prelaunch SD BRDF value is relatively accurate. The model is significant in that it can evaluate whether the SD screen transmittance measured prelaunch is accurate and help retrieve the true transmittance from the transmittance with measurement errors, consequently resulting in a more accurate sensor data product by the same amount.


Patient outcomes and pathology practice: An introduction to the College of American Pathologists Conference XXXIV on Molecular Pathology: Role in Improving Patient Outcome.
This article provides an abbreviated conceptual framework for viewing general issues of outcomes research and management and consideration of the emerging interest in patient-referenced outcomes in medicine and pathology. Specific issues addressed are the reasons for increased interest in outcomes research within the past decade; a review of the current language of outcomes management and research; a critique of the advantages and weaknesses of contemporary outcomes analysis and research methods; a summary of the responses of government, regulatory and accreditation organizations, medical societies, and the College of American Pathologists to the outcomes movement; and, in conclusion, a discussion of opportunities provided through outcomes management for enhanced involvement by pathologists in the care of patients.


Enrichment of Mango Fruit Leathers with Natal Plum (Carissa macrocarpa) Improves Their Phytochemical Content and Antioxidant Properties.
Natal plum fruit (Carissa macrocarpa) is indigenous to South Africa and a rich source of cyanidin derivatives. Indigenous fruits play a major role in food diversification and sustaining food security in the Southern African region. Agro-processing of indigenous are practiced adopted by the rural African communities in order to reduce the postharvest wastage of fruit commodities. In the current study, Natal plum was added to mango pulp at different ratios (mango and Natal plum (5:1, 3:1, 2:1)) to develop a healthy-functional snack (fruit leather). The effects of added Natal plum on the availability of antioxidant constituents and in vitro antioxidant properties of a mango-based fruit leather were evaluated by comparing with mango fruit leather. Fruit leather containing mango and Natal plum (2:1) retained the highest content of cyanidin-3-O-glucoside chloride, cyanidin- 3-O-β-sambubioside, epicatechin, apigenin, kaempferol, luteolin, quercetin-3-O-rhamnosyl glucoside, catechin, quinic, and chlorogenic acids, and in vitro antioxidant activity. Proximate analysis showed that 100 g of fruit leather (2:1) contained 63.51 g carbohydrate, 40.85 g total sugar, 0.36 g fat, and 269.88 cal. Therefore, enrichment of mango fruit leather with Natal plum (2:1) increases its phytochemical content and dietary phytochemical intake, especially for school children and adolescents.


Inhibition of inflammatory mediators by neobavaisoflavone in activated RAW264.7 macrophages.
Flavonoids and coumarins are the major bioactive constituents identified in Psoralea corylifolia. The active fraction isolated from fruits, seeds and roots possesses antibacterial, antioxidative and immunomodulatory properties. Neobavaisoflavone is one of the flavonoids found in Psoralea corylifolia. In the present study we investigated in vitro the anti-inflammatory activity of neobavaisoflavone. Macrophages play an important role in inflammation through the release of inflammatory mediators involved in the immune response. Inappropriate and prolonged macrophage activation is largely responsible for the pathology of acute and chronic inflammatory conditions. Neobavaisoflavone significantly inhibited the production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokines: IL-1β, IL-6, IL-12p40, IL-12p70, TNF-α in LPS+IFN-γ- or PMA- stimulated RAW264.7 macrophages.


Fluoroquinolone Prophylaxis in Autologous Stem Cell Transplantation: Worthy of a Second Look.
Prophylaxis with fluoroquinolone (FQ) for patients undergoing autologous stem cell transplantation (ASCT) remains controversial. We performed a retrospective review of patients undergoing ASCT with and without bacterial prophylaxis to compare endpoints of interest. In accordance with institutional policy, patients undergoing ASCT for multiple myeloma routinely receive levofloxacin prophylaxis during their period of neutropenia, whereas patients undergoing the ASCT for lymphoma do not. We retrospectively examined patients with multiple myeloma (MM) or lymphoma undergoing ASCT between July 2015 and July 2018 for evidence of positive blood cultures. A total of 172 patients underwent ASCT for lymphoma and 343 underwent ASCT for MM. The 2 cohorts were similar in terms of baseline characteristics. Almost 20% (35 of 172) of the patients with lymphoma and 5.2% (18 of 342) of those with MM had a bloodstream infection (BSI). BSI occurred an average of 2 days earlier in patients with lymphoma compared with patients with MM (day +5 versus day +7; P = .0003). The 2 cohorts recovered absolute neutrophil count at the same time. Hospital length of stay was 2 days shorter for patients with MM (median, 20 days versus 18 days; P = .01). The majority of the organisms were gram-negative in both cohorts. Of the organisms commonly tested for FQ sensitivity, only 1 of 25 was resistant in the lymphoma cohort, compared with 7 of 9 in the MM cohort (P < .0001), with 4 being multidrug resistant. The odds of developing a BSI were 4.6 times greater in the lymphoma cohort compared with the MM cohort (95% confidence interval [CI], 2.52 to 8.40; P < .0001). In total, 23 of 172 patients with lymphoma (13.4%) and 28 of 342 patients with MM (8.2%) developed Clostridium difficile infection (odds ratio, 1.73; 95% CI, .96 to 3.11; P = .066). Two infection-related deaths occurred in the MM cohort. Our data indicate that FQ prophylaxis reduces the risk of BSI in patients undergoing ASCT but increases the incidence of resistant organisms. We recommend routine antimicrobial prophylaxis in patients undergoing ASCT to reduce the risk of BSI, along with a systematic and regular review of outcomes.


Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential.
The human Werner and Bloom syndromes (WS and BS) are caused by deficiencies in the WRN and BLM RecQ helicases, respectively. WRN, BLM and their Saccharomyces cerevisiae homologue Sgs1, are particularly active in vitro in unwinding G-quadruplex DNA (G4-DNA), a family of non-canonical nucleic acid structures formed by certain G-rich sequences. Recently, mRNA levels from loci containing potential G-quadruplex-forming sequences (PQS) were found to be preferentially altered in sgs1Delta mutants, suggesting that G4-DNA targeting by Sgs1 directly affects gene expression. Here, we extend these findings to human cells. Using microarrays to measure mRNAs obtained from human fibroblasts deficient for various RecQ family helicases, we observe significant associations between loci that are upregulated in WS or BS cells and loci that have PQS. No such PQS associations were observed for control expression datasets, however. Furthermore, upregulated genes in WS and BS showed no or dramatically reduced associations with sequences similar to PQS but that have considerably reduced potential to form intramolecular G4-DNA. These findings indicate that, like Sgs1, WRN and BLM can regulate transcription globally by targeting G4-DNA.


Pediatric cancer genetics.
The current review will focus on the current knowledge of the contribution of both germline and somatic mutations to the development and management of cancer in pediatric patients. It has long been thought that genetic mutations in both germline and somatic cells can contribute to the development of cancer in pediatric patients. With the recent advances in genomic technologies, there are now over 500 known cancer predisposition genes. Recent studies have confirmed an 8.5-14% germline mutation rate in cancer predisposition genes in pediatric cancer patients. The discovery of both germline and somatic cells mutation(s) in pediatric cancer patients not only aids in the management of current disease, but can also have direct implications for future management as well as the medical management of family members.


Immunological comparison between human and rat plasminogen activators in blood and the vessel wall.
To evaluate the rat as an experimental model for plasminogen activator research, the ability of antibodies specific for human tissue type plasminogen activator and urokinase to suppress the plasminogen activator activity in whole plasma and in the vessel wall was studied in both rat and man. Plasminogen activator activity in plasma was assayed on fibrin plates containing plasminogen. Plasminogen activator in the vessel wall was shown by the fibrin side technique. Antibodies against human tissue type melanoma cell activator and urokinase were raised in goats and mixed into the fibrin film or the fibrin plates. In both species antibodies to melanoma cell activator were able to suppress the plasminogen activator activity completely in plasma and in the vessel wall. Anti-urokinase, however, had no suppressing effect. In rat plasma the inhibitory effect on the fibrinolytic activity was seen only with high concentrations of antibodies against melanoma cell activator, which suggests that rat plasminogen activator in plasma and vessel walls is similar to, but not identical with, human tissue type plasminogen activator.


Nutrient restriction in utero induces remodeling of the vascular extracellular matrix in rat offspring.
The uterine environment may influence the development of chronic diseases later in life. The authors hypothesized that maternal nutritional restriction prenatally induces remodeling of offspring blood vessels such that they become stiff and contribute to the development of adult hypertension. To test this hypothesis, the authors studied the blood vessels of offspring of dams that were exposed to 50% maternal food restriction (MFR) from e10 to term as compared to age-matched controls. In aortas of MFR offspring, there was a significant increase in elastin and glycosaminoglycans (GAG) at 1 day of age. By 2 months of life, there was a significant increase in collagen and a decrease in GAG in MFR offspring aortas. A redistribution of elastin was also noted in MFR offspring, with a significant decrease in the interelastin laminae at both 1 day and 2 months. In mesenteric arterioles of MFR offspring, there was a decrease in GAG in 1-day-old and 2-month-old MFR offspring. There were no changes in elastin in both age groups in mesenteric arterioles, and by 2 months of life, collagen deposition was also found in these resistance vessels. There was a significant increase in expression of matrix metalloproteinase 9 (MMP-9) mRNA in 1-day-old MFR aortas, while both MMP-9 and MMP-2 expression was increased in the 4-month-old MFR aortas. These results indicate a significant remodeling of the extracellular matrix occurs in both conduit and resistance vessels. By 2 months of life, the compositions of both vessel types are consistent with stiff vessels, a contributing factor to hypertension.


[Rapid immunochromatographic tests for detection of malaria: principles and strategies for use].
Malaria is a parasitological emergency requiring safe quick accurate diagnosis so that appropriate therapy can be implemented. A number of rapid diagnostic tests based on detection of HRP2 Ag, enzymes, LDH or aldolase are now available. However the use of these tests is restricted to trained, experienced staff in special situations. The purpose of this report is to describe the different tests on the market and clarify the limitations for their use.


Suppression and the upward spread of masking.
The purpose of this study is to clarify the role of suppression in the growth of masking when a signal is well above the masker in frequency (upward spread of masking). Classical psychophysical models assume that masking is primarily due to the spread of masker excitation, and that the nonlinear upward spread of masking reflects a differential growth in excitation between the masker and the signal at the signal frequency. In contrast, recent physiological studies have indicated that upward spread of masking in the auditory nerve is due to the increasing effect of suppression with increasing masker level. This study compares thresholds for signals between 2.4 and 5.6 kHz in simultaneous and nonsimultaneous masking for conditions in which the masker is either at or well below the signal frequency. Maximum differences between simultaneous and nonsimultaneous masking were small (< 6 dB) for the on-frequency conditions but larger for the off-frequency conditions (15-32 dB). The results suggest that suppression plays a major role in determining thresholds at high masker levels, when the masker is well below the signal in frequency. This is consistent with the conclusions of physiological studies. However, for signal levels higher than about 40 dB SPL, the growth of masking for signals above the masker frequency is nonlinear even in the nonsimultaneous-masking conditions, where suppression is not expected. This is consistent with an explanation based on the compressive response of the basilar membrane, and confirms that suppression is not necessary for nonlinear upward spread of masking.


Bone-forming capacity of mesenchymal stromal cells when cultured in the presence of human platelet lysate as substitute for fetal bovine serum.
In tissue engineering, strategies are being developed to repair large bone defects by combining biomaterials and bone marrow-derived multipotent mesenchymal stromal cells (MSCs). For expansion of MSCs under good manufacturing practice conditions, human platelet lysate (PL) can serve as substitute for fetal bovine serum (FBS) in culture media. We compared the in vivo bone-forming capacity of passage 3 MSCs cultured with either PL or FBS for nine different human donors. We also tested the growth kinetics, antigen expression profile, and the multilineage differentiation capacity in vitro of these MSCs. The in vivo bone-forming capacity was determined by seeding culture-expanded MSCs onto biphasic calcium phosphate scaffolds. Hybrid constructs were implanted subcutaneously in nude mice, retrieved after 6 weeks, and analyzed using histomorphometry. PL-supplemented cultures resulted in significantly larger colonies, shorter culture time period, and higher population doublings between P1 and P3 compared to FBS-containing cultures. No differences were observed in antigen expression profiles or differentiation capacities into the osteoblastic, chondrogenic, and adipogenic lineages, qualitatively. In vivo bone formation with PL-supplemented cultures of MSCs was demonstrated in 9/9 donors versus 6/9 for FBS-supplemented cultures. These results warrant the use of PL for ex vivo expansion of human MSCs for bone tissue engineering applications.


Nurses as knowledge workers: is there evidence of knowledge in patient handoffs?
Patient care handoffs are critical to ensuring continuity of care and patient safety. Current definitions of handoffs focus on information, but preventing errors and improving quality require knowledge. The objective of this study was to determine whether knowledge and wisdom were exchanged during medical and surgical patient care handoffs and to discover how these were expressed. The study was a directed content analysis of 93 handoffs using the data/information/knowledge/wisdom framework. Results indicated knowledge was present in all handoffs, comprising 41% of the phrases across the two types of units. No wisdom was coded. The percentage and types of knowledge phrases differed between medical and surgical units. Handoffs could be more knowledge based by linking handoff content to patient problems and goals. Future handoffs could be computationally derived, context-specific, and linked to problem-focused care plans and patient summaries. Improved data visualization and cognitive support are needed.


Biological management of Sclerotinia sclerotiorum in pea using plant growth promoting microbial consortium.
The beneficial plant-microbe interactions play crucial roles in protection against large number of plant pathogens causing disease. The present study aims to investigate the growth promoting traits induced by beneficial microbes namely Pseudomonas aeruginosa PJHU15, Trichoderma harzianum TNHU27, and Bacillus subtilis BHHU100 treated singly and in combinations under greenhouse and field conditions to control Sclerotinia sclerotiorum. Plants treated with three microbe consortium enhanced plant growth maximally both in the presence and absence of the pathogen. Increase in plant length, total biomass, number of leaves, nodules and secondary roots, total chlorophyll and carotenoid content, and yield were recorded in plants treated with microbial consortia. Also, a decrease in plant mortality was observed in plants treated with microbial consortia in comparison to untreated control plants challenged with S. sclerotiorum. Furthermore, the decrease in disease of all the treatments can be associated with differential improvement of growth induced in pea.


Mechanism of intermolecular purine-purine-pyrimidine triple helix stabilization by comb-type polylysine graft copolymer at physiologic potassium concentration.
We previously reported a novel strategy to stabilize purine motif triplex DNA within a mammalian gene promoter at physiologically relevant pH, temperature, and potassium (K(+)) concentrations by a comb-type poly(L-lysine)-graft-dextran copolymer [Ferdous et al., (1998) Nucleic Acids Res. 26, 3949-3954]. Here we describe the major contribution(s) of the copolymer to stabilize the purine motif triplex DNA at physiological K(+) concentrations. Self-aggregation through guanine-quartet formation of guanine-rich (G-rich) triplex-forming oligonucleotides (TFOs) has long been proposed for K(+)-mediated inhibition of the purine motif triplex formation. However, this was not the case for the severe inhibitory effect of K(+) observed under our reaction conditions. Rather significant decrease in rate of triplex formation involving a G-rich TFO was a major factor to confer K(+) inhibition. Interestingly, in the presence of the copolymer the rate of triplex formation was tremendously increased and K(+)-induced dissociation of preformed triplexes was not observed. Moreover, the triplex-promoting/stabilizing efficiency of the copolymer was amazingly higher than that of physiological concentrations of spermine. An absolute increase in binding constant of the TFO to the target duplex could therefore be the predominant mechanistic source for the copolymer-mediated triplex stabilization under physiological conditions in vitro.


Economic evaluation of a web-based menu planning intervention to improve childcare service adherence with dietary guidelines.
Despite the known benefits of healthy eating in childhood, few Australian childcare services provide food that is consistent with dietary guidelines. The effectiveness of a web-based menu planning intervention to increase childcare service provision of healthy foods and decrease provision of discretionary foods in long day-care services in Australia was assessed in a randomised controlled trial. Here we consider the costs, consequences, cost-effectiveness and budget impact of the intervention using data collected within the trial. The prospective trial-based economic evaluation involved 54 childcare services across New South Wales (NSW), Australia. Services were randomised to a 12-month intervention or usual care. The intervention involved access to a web-based menu planning and decision support tool and online resources. Effectiveness measures included mean number of food groups, overall menu and individual food group compliance with dietary guidelines, and mean servings of food groups at 12 months. Costs (reported in $AUD, 2017/18) were evaluated from both health sector and societal perspectives. The direct cost to support uptake of the intervention was calculated, as were costs to each childcare service. The incremental cost of the intervention was calculated as the net difference in the cost to undertake menu planning and review plus the direct cost of the intervention. Incremental cost-effectiveness ratios (ICERs) including uncertainty intervals were estimated for differences in costs and effects between intervention and control groups. A relative value index was calculated to determine overall value for money. Over the 12 months of the trial, we calculated a difference in cost between usual practice and intervention groups of - $482 (95% UI - $859, - $56). While the measured increase in menu and food group compliance within the trial did not reach statistical significance, there were significant improvements in mean servings of fruit and discretionary food, represented in the cost-consequence analysis. The calculated relative value index of 1.1 suggests that the intervention returns acceptable value for money for the outcomes generated. Compared to usual practice, web-based programmes may offer an efficient and sustainable alternative for childcare services to improve the provision of healthy foods to children in their care. Australian New Zealand Clinical Trials Registry ACTRN12616000974404.


R-curve behavior and toughening mechanisms of resin-based dental composites: effects of hydration and post-cure heat treatment.
To test the hypothesis that the fracture resistance of two different particulate resin composites degrade after water hydration and improve after post-cure heat treatment, and to correlate those changes with salient failure micromechanisms. Two composites with different filler morphology were selected, denoted microhybrid (Filtek Z250) and nanofill (Filtek Supreme plus). Following initial light curing, hydrated samples were aged in water for 60 days at room temperature while post-cured samples were heat treated at 120 degrees C for 90 min. Fracture resistance was assessed using fracture resistance curves (R-curves) utilizing pre-cracked compact tension, C(T), specimens. The flexural strength of the hydrated composites also was evaluated in four-point bending using unnotched beams. Scanning electron microscopy (SEM) of crack paths and fracture surfaces was performed to determine the micromechanisms of fracture and toughening. The results were compared by two-way ANOVA and Tukey's multiple comparison test (p< or =0.05). SEM observations revealed a predominantly interparticle matrix crack path for all cases except the hydrated nanofill composite, which showed evidence of particle matrix debonding. Hydration lowered the strength for both composites and the peak toughness for the nanofill composite. The strength decrease was attributed to resin matrix plasticization and hydrolytic degradation in both cases, with additional interfacial degradation causing a larger strength decline and concomitant peak toughness decrease in the nanofill composite. The post-cure heat treatment noticeably changed the R-curve shape causing the peak toughness to be reached after shorter amounts of crack extension. Such changes help explain the increases in strength reported in other studies and is attributed to improved resin matrix properties. Results from this study provide new insight into the micromechanisms of fracture in resin-based dental composites which should aid the future development and improvement of these materials.


LoSWEET14, a Sugar Transporter in Lily, Is Regulated by Transcription Factor LoABF2 to Participate in the ABA Signaling Pathway and Enhance Tolerance to Multiple Abiotic Stresses in Tobacco.
Sugar transport and distribution plays an important role in lily bulb development and resistance to abiotic stresses. In this study, a member of the Sugar Will Eventually be Exported Transporters (SWEET) gene family, LoSWEET14, from Oriental hybrid lily 'Sorbonne' was identified. LoSWEET14 encodes a protein of 278 amino acids and is capable of transporting sucrose and some types of hexoses. The transcript level of the LoSWEET14 gene was significantly increased under various stress conditions including drought, cold, salt stresses, and abscisic acid (ABA) treatment. Overexpression of LoSWEET14 in tobacco (Nicotiana tabacum) showed that the transgenic lines had larger leaves, accumulated more soluble sugars, and were more resistant to drought, cold, and salt stresses, while becoming more sensitive to ABA compared with wild-type lines. Promoter analysis revealed that multiple stress-related cis-acting elements were found in the promoter of LoSWEET14. According to the distribution of cis-acting elements, different lengths of 5'-deletion fragments were constructed and the LoSWEET14-pro3(-540 bp) was found to be able to drive GUS gene expression in response to abiotic stresses and ABA treatment. Furthermore, a yeast one hybrid (Y1H) assay proved that the AREB/ABF (ABRE-binding protein/ABRE-binding factor) from lilies (LoABF2) could bind to the promoter of LoSWEET14. These findings indicated that LoSWEET14 is induced by LoABF2 to participate in the ABA signaling pathway to promote soluble sugar accumulation in response to multiple abiotic stresses.


Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia.
mTORC1 is a critical regulator of cell growth that integrates multiple signals and is deregulated in cancer. We previously reported that mTORC1 regulation by hypoxia involves Redd1 and the Tsc1/Tsc2 complex. Here we show that Redd1 induction by hypoxia is tissue dependent and that hypoxia signals are relayed to mTORC1 through different pathways in a tissue-specific manner. In the liver, Redd1 induction is restricted to the centrilobular area, and in primary hepatocytes, mTORC1 inhibition by hypoxia is independent of Redd1. Furthermore, Tsc1/Tsc2 and Arnt (Hif-1β) are similarly dispensable. Hypoxia signaling in hepatocytes involves Lkb1, AMP-activated protein kinase (AMPK), and raptor. Differences in signal relay extend beyond hypoxia and involve AMPK signaling. AMPK activation (using 5-aminoimidazole-4-carboxamide riboside [AICAR]) induces raptor phosphorylation and inhibits mTORC1 in both mouse embryo fibroblasts (MEFs) and hepatocytes, but whereas mTORC1 inhibition is Tsc1/Tsc2 dependent in MEFs, it is independent in hepatocytes. In liver cells, raptor phosphorylation is essential for both AMPK and hypoxia signaling. Thus, context-specific signals are required for raptor phosphorylation-induced mTORC1 inhibition. Our data illustrate a heretofore unappreciated topological complexity in mTORC1 regulation. Interestingly, topological differences in mTORC1 regulation by the tumor suppressor proteins Lkb1 and Tsc1/Tsc2 may underlie their tissue specificity of tumor suppressor action.


Natural Products for Acetaminophen-Induced Acute Liver Injury: A Review.
The liver plays a vital role in metabolism, synthesis, and detoxification, but it is susceptible to damage from various factors such as viral infections, drug reactions, excessive alcohol consumption, and autoimmune diseases. This susceptibility is particularly problematic for patients requiring medication, as drug-induced liver injury often leads to underestimation, misdiagnosis, and difficulties in treatment. Acetaminophen (APAP) is a widely used and safe drug in therapeutic doses but can cause liver toxicity when taken in excessive amounts. This study aimed to investigate the hepatotoxicity of APAP and explore potential treatment strategies using a mouse model of APAP-induced liver injury. The study involved the evaluation of various natural products for their therapeutic potential. The findings revealed that natural products demonstrated promising hepatoprotective effects, potentially alleviating liver damage and improving liver function through various mechanisms such as oxidative stress and inflammation, which cause changes in signaling pathways. These results underscore the importance of exploring novel treatment options for drug-induced liver injury, suggesting that further research in this area could lead to the development of effective preventive and therapeutic interventions, ultimately benefiting patients with liver injury caused by medicine.


Interactions of stealth conjugated polymer nanoparticles with human whole blood.
Photoluminescent conjugated polymeric nanoparticles (CPNs) exhibit favourable properties as fluorescent probes due to their brightness, high photostability, tunable emission spectra and ease of surface modification. Potential cellular and clinical applications of these new diagnostic agents are easily envisioned, providing a rationale to study CPN biocompatibility. Here, stealth formulations of poly phenylene vinylene (PPV) and poly phenylene ethinylene (PPE) were manufactured and their interactions with human blood components assessed. CPNs were colloidally stable in isotonic fluids, but showed photoluminescence quenching in whole blood and plasma at levels as low as 10% supplementation. At concentrations >150 μg mL-1, stealth CPNs caused ∼10% erythrocyte haemolysis, which was likely due to unbound pegylated surfactant present in the formulation. Incubation of CPNs with both whole blood and isolated platelets showed no platelet activation, increases in platelet-monocyte aggregates or induction of platelet aggregation. Interestingly, PPE-CPN formulations inhibited adenosine diphosphate (ADP)-induced platelet aggregation in a dose-dependent manner, while PPV-CPNs did not show this effect. In conclusion, stealth CPN formulations exhibiting neutrally charged, pegylated surfaces do not stimulate platelet activation or aggregation, but may induce a low degree of haemolysis in the presence of free surfactant and can inhibit physiological mediators of platelet aggregation, such as ADP.


Control of growth and differentiation in vitro of human keratinocytes cultured in serum-free medium.
Normal human proliferative keratinocytes can be serially cultured in serum-free medium. The medium and culture conditions that have been developed support the growth of these cells in the absence of a feeder layer and in the absence of contaminating fibroblasts. Using this system, the nutritional and hormonal factors that affect the growth and differentiation of these cells have been studied in the absence of undefined supplements. The data suggest that the control of proliferation and differentiation in keratinocytes may take place by unique mechanisms. The defined serum-free conditions that have been developed provide an excellent system for the study of nutritional disorders that affect human epidermal cells. In addition, the culture system can be used to propagate large numbers of cells for use in autografts for cases of severe burns.


Risk factors for the development of obesity in children surviving ALL and NHL.
We investigated obesity [body mass index (BMI) >95th percentile] and being heavy (BMI >85th percentile) in 95 children in first remission more than 2 years after treatment for acute lymphoblastic leukemia or non-Hodgkin lymphoma seen at our institution. Height, weight and BMI at diagnosis, end of treatment and follow-up, and blood pressure at diagnosis were adjusted by z-score for age and sex. At follow-up, obesity and overweight were not more prevalent than in the general population. Median BMI z-scores rose significantly between diagnosis (0.38) and treatment end (0.62) but not during follow-up (0.70). Median weight z-scores rose significantly during both periods (diagnosis 0.23, treatment end 0.49, and follow-up 0.68). Median height z-scores were 0.51, 0.14, and 0.16 for the same 3 time points, respectively. Repeated measures, multivariate logistic regression identified Hispanic ethnicity, younger age at diagnosis, and a positive age:weight interaction as being associated with obesity and being heavy at follow-up. There was no association with diagnosis, sex, age alone, radiation dose or field, metabolic diagnosis in patient/family, height z-score at diagnosis, duration of treatment, and systolic or diastolic blood pressure. Obesity and overweight were a combination of weight gain and height loss during treatment although weight continued to increase after treatment. We did not identify disease-related parameters associated with these effects.


Syntheses, structures and magnetic properties of macrocyclic Schiff base-supported homodinuclear lanthanide complexes.
Five new homodinuclear lanthanide complexes with the general formula [(acac)4Ln2(L)] (Ln3+ = Dy3+ (1), Tb3+ (2), Ho3+ (3), Er3+ (4), and Gd (5)) were synthesized by one-pot [2 + 2] condensation of 2,6-diformyl-4-methylphenol and 1,3-diaminopropane in the presence of various lanthanide acetylacetonates. The eight-coordinate Ln(iii) centre adopts a slightly distorted square antiprism geometry with D4d symmetry. Theoretical analysis and magnetic measurements reveal that the corresponding Dy complex 1 exhibits slow magnetic relaxation behavior, characteristic of a typical SMM with the intramolecular ferromagnetic Dy3+Dy3+ interaction.


Creep Behavior of Poly(lactic acid) Based Biocomposites.
Polymer composites containing natural fibers are receiving growing attention as possible alternatives for composites containing synthetic fibers. The use of biodegradable matrices obtained from renewable sources in replacement for synthetic ones is also increasing. However, only limited information is available about the creep behavior of the obtained composites. In this work, the tensile creep behavior of PLA based composites, containing flax and jute twill weave woven fabrics, produced through compression molding, was investigated. Tensile creep tests were performed at different temperatures (i.e., 40 and 60 °C). The results showed that the creep behavior of the composites is strongly influenced by the temperature and the woven fabrics used. As preliminary characterization, quasi-static tensile tests and dynamic mechanical tests were carried out on the composites. Furthermore, fabrics (both flax and jute) were tested as received by means of quasi-static tests and creep tests to evaluate the influence of fabrics mechanical behavior on the mechanical response of the resulting composites. The morphological analysis of the fracture surface of the tensile samples showed the better fiber-matrix adhesion between PLA and jute fabric.


[Situational analysis of periodontal disease burden for adults in China from 1990 to 2019 and its incidence trend prediction].
Objective: To analyze the burden and changing trends of periodontal disease in adults of the mainland of China from 1990 to 2019, and to predict the incidence trends of periodontal disease in the next 25 years, with a goal to provide a basis for reducing the burden of periodontal disease and formulating relevant prevention and treatment measures. Methods: Data on the incidence, prevalence, and disability adjusted life years (DALY) rate of periodontal disease among adults in mainland China from 1990 to 2019 were extracted from the global burden of disease study 2019 (GBD 2019) database. The estimated annual percent change (EAPC) was used to estimate the temporal trend of periodontal disease, and the age-period-cohort model (APC) was used to predict the age-standardized incidence of periodontal disease in Chinese adults from 2020 to 2044. Results: From 1990 to 2019, the incidence, prevalence, and DALY rate of adult periodontal disease in mainland China showed an increasing trend, with EAPCs of 0.3 (95%CI: 0.1-0.6), 0.5 (95%CI: 0.1-0.8), and 0.5 (95%CI: 0.1-0.8), respectively. The incidence and prevalence of periodontitis among the population aged 35-39 years old and 40-44 years old increased the most significantly, with EAPCs of 0.8 and 0.7, respectively, whereas the change in periodontal disease prevalence tended to be stable and the increase trend in prevalence was lower in the elderly group (EAPC=0.4). The incidence (EAPC=2.1), prevalence (EAPC=2.6) and DALY rate (EAPC=2.6) of periodontal disease in females increased more than those in males (EAPC=1.9, 2.4, and 2.4, respectively), of which the prevalence had exceeded that of males in 2019. The APC model predicted that the prevalence of periodontal disease in the period of 2020-2044 in China would still be on an upward trend, and the increase rate would be higher in females than in males. Conclusions: The burden of periodontal disease among adults in China had been increasing over the past 30 years, especially among young and middle-aged adults as well as females, and the incidence of periodontal disease will continue to increase over the next 25 years.


β-lactam Therapeutic Drug Management in the PICU.
To determine whether contemporary β-lactam anti-infective dosing recommendations in critically ill children achieve concentrations associated with maximal anti-infective activity. The secondary objective was to describe the microbiological and clinical outcomes associated with β-lactam therapeutic drug management. Electronic Medical Record Review. A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA. Patients admitted to the PICU from September 1, 2014, to May 31, 2017, with sepsis and those receiving extracorporal therapy with either extracorporeal membrane oxygenation or continuous renal replacement therapy that had routine β-lactam therapeutic drug management. None. Eighty-two patients were in the total cohort and 23 patients in the infected cohort accounting for 248 samples for therapeutic drug management analysis. The median age was 1 year (range, 4 d to 18 yr) with a mean weight of 19.7 ± 22.3 kg (range, 2.7-116 kg). Twenty-three patients (28%) had growth of an identified pathogen from a normally sterile site. Seventy-eight of 82 patients (95%) had subtherapeutic anti-infective concentrations and did not attain the primary pharmacodynamic endpoint. All patients in the infected cohort achieved a microbiological response, and 22 of 23 (95.7%) had a positive clinical response. Overall, 95% of patients had subtherapeutic anti-infective concentrations and did not achieve the requisite pharmacodynamic exposure with current pediatric dosing recommendations. All patients achieved a microbiological response, and 95.7% achieved clinical response with active β-lactam therapeutic drug management. These data suggest β-lactam therapeutic drug management is a potentially valuable intervention to optimize anti-infective pharmacokinetics and the pharmacodynamic exposure. Further, these data also suggest the need for additional research in specific pediatric populations and assessing clinical outcomes associated with β-lactam therapeutic drug management in a larger cohort of pediatric patients.


Do Personality Factors Assessed Before Cochlear Implantation Predict Hearing-Related Quality Of Life After Cochlear Implantation in Postlingually Deafened Adults?
Studies have shown that cochlear implants improve deaf patients' hearing-related quality of life (hrQoL), but the degree of improvement varies considerably between patients. This study investigated whether personality factors contribute to hrQoL outcome after cochlear implantation. Fifty adult patients with postlingual hearing loss who received a unilateral cochlear implant were administered the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI; a personality inventory) and the Nijmegen Cochlear Implant Questionnaire (NCIQ; a hrQoL questionnaire). The NEO-FFI was administered only before implantation; the NCIQ was administered before implantation and 12 months after implant activation. A linear regression analysis was computed to detect whether NCIQ scores at 12 months were predicted by the NEO-FFI personality factors (i.e., Extraversion, Neuroticism, Openness to Experience, Agreeableness, and Conscientiousness) assessed before implantation. HrQoL scores had significantly improved 12 months after cochlear implantation in all subdomains of the NCIQ. Of the five personality factors, solely Neuroticism was negatively associated to the NCIQ subdomain self-esteem (β = -0.34; p = 0.013) at 12 months after cochlear implantation. While significant improvement of hrQoL was seen 12 months after implant activation, this improvement was barely predicted by the Big-Five personality traits measured before implantation. Only Neuroticism was found to moderately influence postimplantation hrQoL in our patients, in the way that higher degrees of Neuroticism tend to go along with lower degrees of self-esteem (as conceptualized by the NCIQ). The failure to detect personality effects on hrQoL could partly be due to the low levels of Extraversion and Openness to Experience observed in our sample of patients with hearing loss.


Modulation of cytokine and beta-defensin 2 expressions in human gingival fibroblasts infected with Chlamydia pneumoniae.
Human beta-defensin 2 is an antimicrobial peptide that is produced by several epithelial cells after stimulation with micro-organisms and inflammatory mediators. Gram-negative bacteria, which are typically detected in periodontal pockets in periodontitis, elicit a stronger antibacterial peptide response of human beta-defensin 2 by epithelial cells. In this study, we investigated whether Chlamydia pneumoniae is able both to enter and grow in human gingival fibroblasts (HGF), to modify the production of cytokines, and is involved in regulation of beta-defensin 2 expression. Gingival fibroblasts discarded from periodontal procedures on healthy young individuals were infected with viable C. pneumoniae or with heat- or ultraviolet-inactivated organisms at a multiplicity of infection of 4 inclusion-forming units per cell. Our results demonstrate that after 48 h of incubation with viable C. pneumoniae, gingival fibroblasts showed a proliferative response as seen by both colorimetric assay and direct cell count (40% and 45%, respectively). Moreover, cells incubated with viable or ultraviolet light-inactivated C. pneumoniae organisms showed an increase in the levels of interleukin-6, interleukin-10 and human beta-defensin 2 in a time-dependent fashion, while the cells infected with heat-killed bacteria did not show a significant production either of the cytokines or beta-defensin 2 at any time. In conclusion, we demonstrate the correlation between multiplication of C. pneumoniae in human gingival fibroblasts and release of interleukin-6, interleukin-10 and up-regulation of beta-defensin 2, suggesting that gingival fibroblasts may be a periodontium niche for obligate intracellular C. pneumoniae and may play a role in innate gingival immune system and inflammatory response mechanisms of periodontitis.


Hypoxic regulation of endothelial glyceraldehyde-3-phosphate dehydrogenase.
The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is induced by hypoxia in endothelial cells (EC). To define the mechanisms by which GAPDH is regulated by hypoxia, EC were exposed to cobalt, other transition metals, carbon monoxide (CO), deferoxamine, or cycloheximide in the presence or absence of hypoxia for 24 h, and GAPDH protein and mRNA levels were measured. GAPDH was induced in cells by the transition metals cobalt, nickel, and manganese and by deferoxamine, and GAPDH mRNA induction by hypoxia was blocked by cycloheximide. GAPDH induction by hypoxia, unlike that of other hypoxia-regulated genes, was not inhibited by CO or by 4,6-dioxoheptanoic acid, an inhibitor of heme synthesis. GAPDH induction was not altered by mediators of protein phosphorylation, a calcium channel blocker, a calcium ionophore, or alterations in redox state. GAPDH induction by hypoxia or transitional metals was partially blocked by sodium nitroprusside but was not altered by the inhibitor of nitric oxide synthase N omega-nitro-L-arginine. These findings suggest that GAPDH induction by hypoxia in EC occurs via mechanisms other than those involved in other hypoxia-responsive systems.


Sonority constraints on onset-rime cohesion: evidence from native and bilingual Filipino readers of English.
Research in English suggests that syllables can be analyzed in terms of two subunits-the onset (defined as the initial consonant or consonant cluster) and the rime (the unit formed by the vowel and following consonant/s). This study investigated whether nonnative readers of English, which in the case of the present study were native Filipino speakers, also make use of onset-rime units, particularly when some features of their native language (namely infixation and reduplication) appear to foster no awareness of such units. In two lexical decision experiments, monosyllabic English words were presented, divided in between their first and second consonants (e.g., B LIND), at their onset-rime boundary (e.g., BL IND), or at their antibody boundary (e.g., BLI ND). Results indicated that the processes of infixation and reduplication did not affect the English word processing of native Filipino speakers. Rather, results for both native Filipino and native English speakers suggest that onsets composed of an "s + consonant" sequence (e.g., STAMP) are less cohesive than onsets comprised of a stop-liquid sequence (e.g., BLIND). It was concluded that not only may sonority constraints underlie onset cohesiveness, but that such phonetic properties may also be involved in visual word recognition.


LncRNA GIHCG promotes development of ovarian cancer by regulating microRNA-429.
To explore whether lncRNA GIHCG participates in the pathogenic progression of ovarian cancer (OC) and its underlying mechanism. Expression levels of GIHCG and microRNA-429 in 30 OC tissues and normal ovarian tissues were detected by quantitative Real time-polymerase chain reaction (qRT-PCR). Subsequently, 15 pairs of OC tissues and paracancerous tissues were selected for correlation analyses of GIHCG, microRNA-429 and the overall survival (OS) of OC patients using Kaplan-Meier method. Pearson correlation analyses were conducted for investigating the correlation between GIHCG and microRNA-429. GIHCG expression in OC cell lines (HEY, A2780 and HO8910) and normal epithelial OC cell line (IOSE-386) was detected by qRT-PCR. After transfection of GIHCG overexpression plasmid in HEY cells, cell cycle, proliferation and colony formation ability were detected by flow cytometry, cell counting kit-8 (CCK-8) and colony formation assay. MicroRNA-429 expression in HEY cells overexpressing GIHCG was detected by qRT-PCR. Rescue experiments were conducted by co-transfection of GIHCG overexpression plasmid and microRNA-429 mimics, followed by cell cycle and colony formation detection. GIHCG was highly expressed, whereas microRNA-429 was lowly expressed in OC tissues than that of paracancerous tissues. OC patients with higher expression of GIHCG showed shorter OS than those with lower expression. However, OC patients with higher expression of microRNA-429 had longer OS than those with lower expression. GIHCG expression was positively correlated to microRNA-429. In vitro experiments showed that GIHCG was highly expressed in HEY, A2780 and HO8910 cells than that of IOSE-386 cells. GIHCG overexpression in HEY cells promoted cell cycle and colony formation abilities, which were reversed by microRNA-429 overexpression. GIHCG is highly expressed in OC, which promotes OC development by stimulating cell cycle progression and cell proliferation by regulating microRNA-429.


Baseline characteristics of participants in the Appropriate Blood Pressure Control in Diabetes trial.
The ABCD (Appropriate Blood Pressure Control in Diabetes) trial is a large, prospective, randomized clinical trial designed to compare the effects of intensive with moderate blood pressure control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in non-insulin-dependent diabetes (NIDDM). The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and of an angiotensin-converting enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations: a hypertensive one (diastolic blood pressure of > or = 90.0 mm Hg at the time of randomization) and a normotensive one (diastolic blood pressure of 80.0-89.0 mm Hg at the time of randomization). A total of 950 men and women aged 40-74 years were randomized and are being followed for 5 years at a single center. There were 470 randomized participants in the hypertensive population and 480 randomized participants in the normotensive population. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized patients at the time of entry into the trial and evaluates the balance between the treatment groups within each population.


The role of psychosocial factors in fibromyalgia syndrome.
The main objective of this review was to evaluate the role of psychosocial factors in the development of fibromyalgia syndrome. Review of the literature concerning the influence of psychosocial factors. In fibromyalgia syndrome psychosocial factors are relevant at different etiological levels. They can be classified into predisposing, triggering and stabilising/"chronifying" factors. Due to the increasing knowledge about the influence of psychosocial factors for the development of fibromyalgia, the biomedical model has to be expanded to a biopsychosocial model. The biopsychosocial concept has an impact on the therapeutic approach. Strong evidence for the model is provided by the good results of interdisciplinary treatment studies.


Odor-mediated aggregation enhances the colonization ability of Drosophila melanogaster.
Animal aggregation is a general phenomenon in ecological systems. Aggregations are generally considered as an evolutionary advantageous state in which members derive the benefits of mate choice and protection against natural enemies, balanced by the costs of limiting resources and intraspecific competition. Many insects use chemical information to find conspecifics and to form aggregations. In this study, we describe a spatio-temporal simulation model designed to explore and quantify the effects of the strength of chemical attraction, on the colonization ability of a fruit fly (Drosophila melanogaster) population. We found that the use of infochemicals is crucial for colonizing an area. Fruit flies subject to an Allee effect that are unable to respond to chemical information could not successfully colonize the area and went extinct within four generations. This was mainly caused by very high mortality due to the Allee effect. Even when the Allee effect did not play a role, the random dispersing population had more difficulties in colonizing the area and is doomed to extinction in the long run. When fruit flies had the ability to respond to chemical information, they successfully colonized the orchard. This happened faster, for stronger attraction to chemical information. In addition, more fruit flies were able to find the resources and the settlement on the resources was much higher. This resulted in a reduced mortality due to the Allee effect for fruit flies able to respond to chemical information. Odor-mediated aggregation thus enhances the colonization ability of D. melanogaster. Even a weak attraction to chemical information paved the way to successfully colonize the orchard.


[X-ray computed tomography in the diagnosis of pulmonary tuberculosis].
The paper provides a detailed analysis of 120 cases of pulmonary tuberculosis that was mainly detected by X-ray computed tomography (XCT). The study was performed on third-generation XCT plants. The authors highly appreciate the contribution of XCT to the diagnosis of tuberculosis with emphasis on some organizational issues. They suggest that third-forth-generation XCT plants that show its high effectiveness in detecting major lung diseases, including tuberculosis, and cost-efficiency should be widely introduced into the outpatient setting.


Videoconferencing in facilities providing care for elderly people.
Two studies were conducted to test the feasibility of delivering care by videoconferencing to facilities providing care for elderly people. Both used equipment connected by ISDN lines at 384 kbit/s. During the first study, no consultations, care plans or assessments were conducted. During the second study, 120 assessments were conducted in just over two weeks, both face to face and by videoconference. Why was one project so successful and the other not? The reasons related to ownership, planning, participants and location. A comparison of the two projects highlights some of the considerations necessary to ensure the success of any telehealth project.


Handedness and hobby preference.
The objective of this study was to investigate the relationship between handedness and hobby preference in healthy individuals. For this reason, the Annett handedness questionnaire and a standard questionnaire on preference for hobbies were administered to 879 healthy young men (age, M = 22.3, SD = 4.8 yr.). Analysis showed more cultured individuals were much less likely to be strongly right-handed. Especially, pure right-handedness highly overrepresented among those who mainly preferred doing sports, pure left-handedness among those who preferred reading books, collecting, or going to the cinema/theater, and mixed-handedness among those who preferred arts, like playing music, drawing, or handicraft. The findings support evidence that handedness is associated with hobby preference.


Teleseismic detection of a slow precursor to the great 1989 macquarie ridge earthquake.
Low-frequency spectra for the 1989 Macquarie Ridge earthquake (magnitude 8.2) show an amplitude increase and a phase-delay decrease below 6 millihertz that require a short-term slow precursor. This earthquake can be modeled as a compound event in which a fast-rupturing, ordinary earthquake was initiated by an episode of slow, smooth deformation that began more than 100 seconds before the main shock. The moment released in the slow precursor was large, about 3 x 10(20) newton-meters, equivalent to an event of magnitude 7.6. The data are consistent with the precursor being generated in a region of the oceanic upper mantle below the main rupture.


Lipoprotein lipase secretion by human monocyte-derived macrophages.
Human monocyte-derived macrophages in culture produced lipoprotein lipase. Although freshly isolated blood monocytes did not secrete much lipase activity, 1 d in culture was sufficient to trigger measureable enzyme production. During 3 wk in culture, maximal activity was attained after 7 d. At all times, the culture medium contained more enzyme activity than did a serum-heparin eluate or a detergent extract of the cell layer. The lipase activity was stimulated by serum and was inhibited by preincubation with antiserum to bovine lipoprotein lipase or when assayed at a high salt concentration. Furthermore, the enzyme bound to a heparin-Sepharose affinity column at physiological ionic strength. Cells cultured from a subject with primary lipoprotein lipase deficiency secreted no detectable enzyme. Since macrophages are prominent components of atherosclerotic lesions in man, their ability to synthesize and secrete lipoprotein lipase may be important to atherogenesis.


Trogocytosis by Entamoeba histolytica Mediates Acquisition and Display of Human Cell Membrane Proteins and Evasion of Lysis by Human Serum.
We previously showed that Entamoeba histolytica kills human cells through a mechanism that we termed trogocytosis ("trogo-" means "nibble"), due to its resemblance to trogocytosis in other organisms. In microbial eukaryotes like E. histolytica, trogocytosis is used to kill host cells. In multicellular eukaryotes, trogocytosis is used for cell killing and cell-cell communication in a variety of contexts. Thus, nibbling is an emerging theme in cell-cell interactions both within and between species. When trogocytosis occurs between mammalian immune cells, cell membrane proteins from the nibbled cell are acquired and displayed by the recipient cell. In this study, we tested the hypothesis that through trogocytosis, amoebae acquire and display human cell membrane proteins. We demonstrate that E. histolytica acquires and displays human cell membrane proteins through trogocytosis and that this leads to protection from lysis by human serum. Protection from human serum occurs only after amoebae have undergone trogocytosis of live cells but not phagocytosis of dead cells. Likewise, mutant amoebae defective in phagocytosis, but unaltered in their capacity to perform trogocytosis, are protected from human serum. Our studies are the first to reveal that amoebae can display human cell membrane proteins and suggest that the acquisition and display of membrane proteins is a general feature of trogocytosis. These studies have major implications for interactions between E. histolytica and the immune system and also reveal a novel strategy for immune evasion by a pathogen. Since other microbial eukaryotes use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections.IMPORTANCEEntamoeba histolytica causes amoebiasis, a potentially fatal diarrheal disease. Abscesses in organs such as the liver can occur when amoebae are able to breach the intestinal wall and travel through the bloodstream to other areas of the body. Therefore, understanding how E. histolytica evades immune detection is of great interest. Here, we demonstrate for the first time that E. histolytica acquires and displays human cell membrane proteins by taking "bites" of human cell material in a process named trogocytosis ("trogo-" means "nibble"), and that this allows amoebae to survive in human serum. Display of acquired proteins through trogocytosis has been previously characterized only in mammalian immune cells. Our study suggests that this is a more general feature of trogocytosis not restricted to immune cells and broadens our knowledge of eukaryotic biology. These findings also reveal a novel strategy for immune evasion by a pathogen and may apply to the pathogenesis of other infections.


Type III collagen can be present on banded collagen fibrils regardless of fibril diameter.
Monoclonal antibodies that recognize an epitope within the triple helix of type III collagen have been used to examine the distribution of that collagen type in human skin, cornea, amnion, aorta, and tendon. Ultrastructural examination of those tissues indicates antibody binding to collagen fibrils in skin, amnion, aorta, and tendon regardless of the diameter of the fibril. The antibody distribution is unchanged with donor age, site of biopsy, or region of tissue examined. In contrast, antibody applied to adult human cornea localizes to isolated fibrils, which appear randomly throughout the matrix. These studies indicate that type III collagen remains associated with collagen fibrils after removal of the amino and carboxyl propeptides, and suggests that fibrils of skin, tendon, and amnion (and presumably many other tissues that contain both types I and III collagens) are copolymers of at least types I and III collagens.


MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.
Inhibition of the interaction between MDM2 and p53 has emerged as a promising strategy for combating cancer, including the treatment of glioblastoma (GBM). Numerous MDM2 inhibitors have been developed and are currently undergoing rigorous testing for their potential in GBM therapy. Encouraging results from studies conducted in cell culture and animal models suggest that MDM2 inhibitors could effectively treat a specific subset of GBM patients with wild-type TP53 or functional p53. Combination therapy with clinically established treatment modalities such as radiation and chemotherapy offers the potential to achieve a more profound therapeutic response. Furthermore, an increasing array of other molecularly targeted therapies are being explored in combination with MDM2 inhibitors to increase the effects of individual treatments. While some MDM2 inhibitors have progressed to early phase clinical trials in GBM, their efficacy, alone and in combination, is yet to be confirmed. In this article, we present an overview of MDM2 inhibitors currently under preclinical and clinical investigation, with a specific focus on the drugs being assessed in ongoing clinical trials for GBM patients.


Induction of systemic resistance in plants.
When a pathogen is perceived by a host plant, a series of defense responses can be activated. One of these are "local" defenses that occur rapidly at the site of pathogen invasion. Another are "systemic" defenses that are induced in uninoculated parts of the plant. Recently, molecular genetic studies have revealed genes that are signaling components of systemic resistance pathways. Cloning of these genes and characterization of the function of their proteins is now providing insights to processes regulating plant defense against pathogens. Evidence that "systemic" defenses are important for resistance is that when the way is blocked in transgenic plants or in mutants, the plant's defense is compromised. When the pathway is stimulated by exogenous compounds or in mutants, the host resistance is strengthened. A detailed understanding of this pathway is important for both practical and theoretical reasons.


Microbial organic acid production as carbon dioxide sink.
Mixed-substrate conversions are an under-regarded option to fix carbon dioxide in significant amounts. In such a conversion, carbon dioxide together with one other carbon source such as glucose is converted to a single carbon product. With mixed-substrate conversions, it is possible to incorporate carbon dioxide into products with higher oxidation states than the co-substrate. Using abundant co-substrates such as glucose, glycerol or methanol, it is possible to produce organic acids anaerobically, using CO 2 both as an electron acceptor and as an additional carbon source. Here, we outline the thermodynamic feasibility to produce industrially important organic acids with this approach to provide guidance for future metabolic engineering endeavours.


[Clinicophysiological changes in the human body during prolonged head-down tilt hypokinesia].
By clinical-physiological and biochemical methods adaptation to prolonged (182 days) head-down tilting (--4.5 degrees) was investigated. It was found that man exposed to hypokinesia for a month or longer, with countermeasures lacking, showed polymorphic clinical-physiological and biochemical disorders accompanied by a decline of his adaptive capabilities. This may aggravate further adaptation and readaptation processes.


Serum Retinol Concentrations, Race, and Socioeconomic Status in of Women of Childbearing Age in the United States.
Vitamin A is an essential nutrient during pregnancy and throughout the lifecycle due to its role in the development of critical organ systems. Because maternal tissue is progressively depleted of vitamin A to supply fetal demands, women who become pregnant while possessing marginal vitamin A reserves are at increased risk of vitamin A inadequacy as pregnancy progresses. Few studies have assessed the relationship between socioeconomic factors and retinol status in women of childbearing age. We used the National Health and Nutrition Examination Survey (NHANES) to assess the relationship between serum retinol concentrations and socioeconomic factors in women of childbearing age. Women 14-45 years of age (n = 3170) from NHANES cycles 2003-2004 and 2005-2006 were included. Serum retinol concentrations were divided into categories according to World Health Organization criteria. All statistical procedures accounted for the weighted data and complex design of the NHANES sample. A p-value of < 0.05 was considered statistically significant. The poverty score and race were significantly associated with vitamin A status after adjustment for confounders. Odds of retinol concentrations of <1.05 µmol/L were 1.85 times higher for those of lower socioeconomic status when compared to those of higher status (95% CI: 1.12-3.03, p = 0.02), and 3.1 times higher for non-Hispanic blacks when compared to non-Hispanic whites (95% CI: 1.50-6.41, p = 0.002). Dietary intakes of retinol activity equivalents were significantly lower in groups with higher poverty scores (p = 0.004). Conclusion There appear to be disparities in serum vitamin A levels in women of childbearing age related to income and race in the United States.


Haemoglobin A1c: analysis and standardisation.
The measurement of glycated haemoglobin has become centrally important in the monitoring of glycaemic control in the patient with diabetes. A number of analytical techniques have been described to measure this important haemoglobin fraction, and the fraction measured depends on the technique used; this has resulted in laboratories reporting different fractions i.e., HbA1, HbA1c and total glycated haemoglobin. This paper outlines methods currently used in clinical laboratories for the measurement of this glycated fraction. It describes the principles behind these methods and goes on to describe the new IFCC reference method, which will be used in the future to standardise methods used in the clinical laboratory. Analytical goals and factors that interfere with methods are also discussed.


Influences on university students' intention to receive recommended vaccines: a cross-sectional survey.
To explore predictors of university students' intention to receive a recommended vaccine and the main sources of vaccine-related information accessed by university students. Participants were recruited from University College London (UK) in summer 2015. 177 university students participated. The majority of participants were female (58%), White (68%) and had no religion (58%). Participants were aged 18 to 42 (mean age=23.6). Primary outcome measures included vaccine attitude, perceived subjective norm, perceived behavioural control, perceived self-efficacy, past receipt of recommended childhood vaccines, perceived adverse reaction to past vaccination and needle fear. As a secondary outcome sources of vaccine-related information were assessed. Students classified as high intenders were more likely to have received all recommended childhood vaccines (OR 3.57; 95% CI 1.21 to 10.59; p=0.022), be less afraid of needles (OR 2.44; 95% CI 1.12 to 5.36; p=0.026) and to have lived in the UK until at least the age of 4 compared with those not living in the UK until at least the age of 4 (OR 0.39; 95% CI 0.18 to 0.83; p=0.015) and those who lived both in the UK and elsewhere (OR 0.42; 95% CI 0.04 to 4.06; p=0.424). The multivariable model explained 25.5% of variance in intention to receive a recommended vaccine. The internet was the most commonly reported source of vaccination information. Findings provide an indication of the factors that may need to be addressed by interventions aiming to increase uptake of recommended vaccines in a university population. Future research is recommended using a prospective cohort design.


Olfactory connectivity mediates sleep-dependent food choices in humans.
Sleep deprivation has marked effects on food intake, shifting food choices toward energy-dense options. Here we test the hypothesis that neural processing in central olfactory circuits, in tandem with the endocannabinoid system (ECS), plays a key role in mediating this relationship. We combined a partial sleep-deprivation protocol, pattern-based olfactory neuroimaging, and ad libitum food intake to test how central olfactory mechanisms alter food intake after sleep deprivation. We found that sleep restriction increased levels of the ECS compound 2-oleoylglycerol (2-OG), enhanced encoding of food odors in piriform cortex, and shifted food choices toward energy-dense food items. Importantly, the relationship between changes in 2-OG and food choices was formally mediated by odor-evoked connectivity between the piriform cortex and insula, a region involved in integrating feeding-related signals. These findings describe a potential neurobiological pathway by which state-dependent changes in the ECS may modulate chemosensory processing to regulate food choices.


Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer.
This article aims to discuss elacestrant, an oral selective estrogen receptor downregulator approved by the Food and Drug Administration (FDA) in January 2023 for the treatment of hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. PubMed, Embase, Medline, Clinicaltrials.gov, and the National Comprehensive Cancer Network (NCCN) were searched from inception to August 31, 2023. Clinical trials published in English were included and relevant information regarding methodology and results were extracted. Phase 1 and 3 trials showed elacestrant was safe and improved progression-free survival in patients with endocrine receptor 1 (ESR1) mutations who failed cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) plus 1 prior endocrine therapy compared with standard of care (SOC) (fulvestrant, anastrozole, letrozole, or exemestane monotherapy). Elacestrant maintains a comparable adverse event profile with other endocrine therapies and offers an alternative to typical sequential therapy which can delay the use of or be used after traditional chemotherapy. Elacestrant is currently being studied in CDK 4/6 inhibitor naïve patients and as a component of combination therapy for first-line use which could lead to future indications. Elacestrant gained FDA approval in January 2023 and can be considered in patients with HR+ HER2- advanced breast cancer and ESR1 mutations who have progressed despite therapy with either CDK 4/6i plus aromatase inhibitors (AI) or fulvestrant or chemotherapy.


Comparison of Burnet's clonal selection theory with tumor cell-clone development.
Increasing evidence has shown that Darwin's theory of evolution provides vital insights into the emergence and etiology of different types of cancer. On a microscopic scale, cancer stem cells meet the conditions for the Darwinian process of natural selection. In particular, cancer stem cells undergo cell reproduction characterized by the emergence of heritable variability that promotes replication and cell survival. Methods: Evidence from previous studies was gathered to compare Burnet's clonal selection theory with the tumor evolution theory. Results: The findings show that the Darwinian theory offers a general framework for understanding fundamental aspects of cancer. As fundamental theoretical frameworks, Burnet's clonal selection theory and the tumor evolution theory can be used to explain cancer cell evolution and identify the beneficial adaptations that contribute to cell survival in tissue landscapes and tissue ecosystems. Conclusions: In conclusion, this study shows that both Burnet's clonal selection theory and the tumor evolution theory postulate that cancer cells in tissue ecosystems evolve through reiterative processes, such as clonal expansion, clonal selection, and genetic diversification. Therefore, both theories provide insights into the complexities and dynamics of cancer, including its development and progression. Finally, we take into account the occurrence of biologic variation in both tumor cells and lymphocytes. It is important to note that the presence of lymphocyte variations appears to be advantageous in the framework of tumor defense but also dangerous within the framework of autoimmune disease development.


Digital and Non-Digital Solidarity between Older Parents and Their Middle-Aged Children: Associations with Mental Health during the COVID-19 Pandemic.
We incorporated intergenerational digital communication (frequency of texting, video call, and social media interaction) into the intergenerational solidarity paradigm and identified new types of intergenerational and digital solidarity with adult children among older parents during the COVID-19 pandemic. In addition, we examined whether those types are associated with older parents' mental health (depressive symptoms, psychological well-being, and self-esteem). We used the 2021/2022 wave of the Longitudinal Study of Generations (LSOG), and a sample of 519 older parents (mean age = 69 years). Latent class analysis identified four classes describing intergenerational and digital solidarity with adult children (distant-but-digitally connected, tight-knit-traditional, detached, and ambivalent). We found that older parents who had distant-but-digitally connected and tight-knit-traditional relationships with their adult children reported better mental health, compared to those who had detached and ambivalent relationships with their adult children during the COVID-19 pandemic. Our findings suggest that intergenerational digital communication should be considered as a digital solidarity in intergenerational solidarity paradigm, which is useful for measuring multidimension of intergenerational relationships within family members during and after the pandemic.


Clonal separation of mature melanocytes from premelanocytes in a diploid human cell strain: spontaneous and induced pigmentation of premelanocytes.
Strains of pigmented melanocytes can be derived reproducibly from normal human skin. Published procedures have been modified here to yield a strain, 'Nohm-1', comprising many unpigmented cells as well as cells with various degrees of pigmentation observable by light microscopy. The unpigmented cells contain early melanosomes (pigment organelles) and the specific enzyme tyrosinase. They are on average smaller and less dendritic than the pigmented cells. Nohm-1 cells show normal chromosomal banding patterns and normal proliferative behaviour, including senescence. They form no tumours in immunodeficient (nude) mice. Nohm-1 cells have been cloned and yield two distinct types of colony, depending on the progenitor cell. Well-pigmented melanocytes engender pure colonies of pigmented cells, but cells with little or no pigment can produce both unpigmented and pigmented progeny. Thus there is a separate cell type, or premelanocyte, which can differentiate spontaneously and stably in culture; this cell type includes both unpigmented and faintly pigmented cells. Usefully, most premelanocytes are viable after frozen storage, unlike well-pigmented melanocytes. Some components of the culture medium affect the proportion of pigmented cells in Nohm-1 cultures, and hence probably the ratio of mature melanocytes to premelanocytes. Rapid pigmentation can be induced artificially and simply, by using a medium with increased extracellular pH and tyrosine concentration.


How Sexually Dimorphic Are Human Mate Preferences?
Previous studies on sex-differentiated mate preferences have focused on univariate analyses. However, because mate selection is inherently multidimensional, a multivariate analysis more appropriately measures sex differences in mate preferences. We used the Mahalanobis distance (D) and logistic regression to investigate sex differences in mate preferences with data secured from participants residing in 37 cultures (n = 10,153). Sex differences are large in multivariate terms, yielding an overall D = 2.41, corresponding to overlap between the sexes of just 22.8%. Moreover, knowledge of mate preferences alone affords correct classification of sex with 92.2% accuracy. Finally, pattern-wise sex differences are negatively correlated with gender equality across cultures but are nonetheless cross-culturally robust. Discussion focuses on implications in evaluating the importance and magnitude of sex differences in mate preferences.


Sexual health in a new cultural context: a resource for international students in regional Australia.
A large number of international students enrol in Australian higher education and contribute to Australia's multicultural population. Diverse cultural backgrounds and life experiences impact international students' knowledge of sexual health and healthy relationships. Along with unfamiliarity of the Australian healthcare system, this may place international students at risk of poor sexual health. We explored the sexual health priorities of international students with 12 male and 16 female international students aged between 18 and 49 years, for the development of a sexual health and relationship information resource for international students. Interviews were recorded, transcribed verbatim and coded thematically in Nvivo 12. Students noted that cultural norms about sex inhibited their ability to access information and they had concerns about their relationship behaviours within the Australian cultural context. Some participants noted challenges with accessing information and care and were enthusiastic about increasing international student access to reliable information and access to services. Based on the findings from these interviews, we developed a resource specifically for international students and evaluated its design and content through three focus group discussions with international students. This evaluation data informed refinements made to the resource. The resource Kit contains sexual health and relationship information and provides links to reputable online sexual health information. The Kit has been widely distributed to international students and is currently being further evaluated for use and acceptability.


Actinobacillus actinomycetemcomitans serotype d-specific antigen contains the O antigen of lipopolysaccharide.
Actinobacillus actinomycetemcomitans is a gram-negative, facultatively anaerobic bacterium which is associated especially with aggressive forms of periodontitis. Contradictory results on the localization of the A. actinomycetemcomitans serotype-specific antigen have been reported. The aim of the present study was to characterize the A. actinomycetemcomitans serotype d-specific antigen. The antigen was isolated by affinity chromatography. The affinity column was prepared from immunoglobulin G isolated from rabbit antiserum raised against A. actinomycetemcomitans serotype d. The isolated antigen was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and silver staining, all of which revealed a ladder-like structure typical for the O antigen of lipopolysaccharide (LPS). In a displacement enzyme-linked immunosorbent assay (ELISA), the isolated antigen displaced in a concentration-dependent manner the binding of the polyclonal rabbit antiserum raised against A. actinomycetemcomitans serotype d to the competing whole-cell serotype d antigen. The isolated antigen contained LPS, and an equal concentration of LPS isolated from A. actinomycetemcomitans serotype d gave a similar displacement curve in the ELISA. In order to test the immunogenic properties of the isolated antigen, it was used to immunize a rabbit. The antiserum raised against the isolated antigen displayed specificity in Western blotting and ELISA similar to that of antibody raised against LPS isolated from A. actinomycetemcomitans serotype d. In conclusion, our results show that the A. actinomycetemcomitans serotype d-specific antigen contains the O-antigenic structure of LPS.