Honey collected from different floras of Chandigarh Tricity: a comparative study involving physicochemical parameters and biochemical activities.
Different monofloral honeys have a distinctive flavor and color because of differences in physicochemical parameters because of their principal nectar sources or floral types. Honey samples were collected from Apis mellifera colonies forged on 10 floras to analyze the quality of honey in terms of standards laid by Honey Grading and Marking Rules (HGMR), India, 2008 and Codex Alimentarious Commission (CAC), 1969 . The honey samples were analyzed for various physicochemical parameters of honey quality control, i.e., pH, total acidity, moisture, reducing sugars, non-reducing sugars, total sugars, water insoluble solids (WIS), ash content, 5-hydroxymethylfurfural content, and diastase value. The antioxidant potential was estimated using Folin-Ciocalteu reagent. Further, honey samples were assayed for antibacterial activities against clinical isolates of Staphylococcus aureus and Escherichia coli using the hole-plate diffusion method. The physicochemical variation in the composition of honey because of floral source shows Ziziphus honey with high pH and diastase values along with low acidity, whereas Helianthus honey contained high reducing sugar and low moisture content. Amomum, Brassica, Acacia, and Citrus contained lowest amount of non-reducing sugars, ash, WIS, and moisture, respectively. Lowest 5-hydroxymethylfurfural (HMF) value was detected in Amomum honey, while highest HMF value was observed with Eucalyptus. The maximum antibacterial and antioxidant potential was observed in Azadirachta and Citrus, respectively. The quality of honey produced by local beekeepers met HGMR and CAC standards, and the chemical composition and biological properties of honey were dependent on the floral source from which it was produced.


Evidence for a local endothelin-angiotensin-atrial natriuretic peptide systemin bovine mature follicles in vitro: effects on steroid hormones and prostaglandin secretion.
Recent evidence suggests the presence of a functional endothelin-angiotensin-atrial natriuretic peptide system at the ovarian level. This study aimed to investigate 1) the local interrelationships among angiotensin II (Ang II), endothelin-1 (ET-1), and atrial natriuretic peptide (ANP); 2) the possible effect of each vasoactive peptide on the secretion of steroid hormones and prostaglandins (PGs) in isolated bovine mature follicles; and 3) the expression of mRNAs for Ang II, ET-1, and ANP receptors in the theca layer of follicles at different developmental stages. Each preovulatory follicle obtained before the LH surge (based on the concentrations of steroids and PGs) received implants of 4 capillary dialysis membranes into the theca layer. The follicles were then incubated in organ culture chambers and perfused with Ringer's solution for 12 h. Stimulation by infusion of the different substances into the microdialysis system was carried out between 4 and 8 h. The infusion of ET-1 (10(-7) M) stimulated the release of ANP and estradiol but inhibited the release of androstenedione and progesterone. The infusion of ANP (10(-7) M) stimulated the release of Ang II, progesterone, and androstenedione. Moreover, the infusion of Ang II (10(-5) M) inhibited the release of ANP but stimulated the release of ET-1, progesterone, and estradiol. All three peptides examined increased PGE(2) and PGF(2) release. In the reverse transcription-polymerase chain reaction analysis, expression of the mRNAs for ET type A and type B, and Ang II type 1 receptors did not change with the follicular size and the intrafollicular estradiol concentrations. Expression of the mRNA for the Ang II type 2 receptor dropped in follicles when the estradiol concentration ranged from 20 to 180 ng/ml and increased again when the estradiol concentration was > 180 ng/ml. The levels of expression of ANP type C receptor mRNA were slightly greater in follicles with estradiol concentrations > 20 ng/ml than in follicles with estradiol concentrations < 20 ng/ml. These results demonstrate a complex interaction among Ang II, ET-1, and ANP that may contribute to increasing the follicular production of PGs and modulate steroidogenesis in the bovine mature follicle, thus providing evidence for a local functional endothelin-angiotensin-ANP system.


Integrated RPA-CRISPR/Cas12a system towards Point-of-Care H. pylori detection.
The rapidly advanced CRISPR/Cas biosensing technology provides unprecedent potential for the development of novel biosensing systems. It provides a new approach for realizing rapid, sensitivity and highly specific pathogen nucleic acid detection, with the capability to combine other technologies, including Polymerase Chain Reaction or isothermal amplifications. The detection of Helicobacter pylori (H. pylori), one of the most common human pathogens to cause various gastroduodenal diseases, has also been explored with the assistance of CRISPR/Cas systems. However, gaps still remain for the development of end-user friendly sensing systems.In this study, a combined RPA-CRISPR/Cas12a biosensing system has been established. It shown the capability to quantitively detect the presence of H. pylori genome DNA with 4 orders of magnitude linear range, and sensitivity of 1.4 copies/µL. The overall reaction can be done within 45 mins at room temperature, which eliminates the needs for heating instrumentation. In addition, with the addition of pullulan as a protective reagent, the potential of storing CRISPR/Cas12a system reagents by using a freeze-dry approach has also been demonstrated.Clinical Relevance - This study represents a novel exploration to applying CRISPR/Cas12a-based biosensing technology to the detection of pathogen DNA with improved potential for the development of Point-of-Care diagnostics. This critical aspect of our technology will contribute to address the newly emerged pathogenic threats and support public health systems.


Severe exacerbation of rosacea induced by cinnamon supplements.
The authors report a case of a 68-year-old Caucasian female with type 2 diabetes mellitus who experienced an acute exacerbation of her rosacea 2 weeks after self-initiating cinnamon oil pills to lower her blood sugar levels. Historically, cinnamon oil has been used for a variety of medicinal purposes, but recently the use of cinnamon oil in lowering blood glucose and cholesterol levels in patients with type 2 diabetes is being investigated and gaining popularity amongst the general population. The use of cinnamon has commonly produced cutaneous side effects of irritant or allergic contact dermatitis and been reported to have vasodilatory effects. Yet, there are no reports of cinnamon use triggering a rosacea exacerbation in the literature.


A framework for the management of the pediatric airway.
Critical airway incidents in children are a frequent problem in pediatric anesthesia and remain a significant cause of morbidity and mortality. Young children are at particular risk in the perioperative period. Delayed management of airway obstruction can quickly lead to serious complications due to the short apnea tolerance in children. A simple, time critical, and pediatric-specific airway management approach combined with dedicated teaching, training, and frequent practice will help to reduce airway-related pediatric morbidity and mortality. There is currently no pediatric-specific universal framework available to guide practice. Current algorithms are modifications of adult approaches which are often inappropriate because of differences in age-related anatomy, physiology, and neurodevelopment. A universal and pragmatic approach is required to achieve acceptance across diverse pediatric clinicians, societies, and groups. Such a framework will also help to establish minimum standards for pediatric airway equipment, personnel, and medications whenever pediatric airway management is required.


SiC/Tb and Si/Tb multilayer coatings for extreme ultraviolet solar imaging.
Narrowband SiC/Tb and Si/Tb multilayers are fabricated with as much as a 23% normal-incidence reflectance near a 60 nm wavelength and spectral bandpass (FWHM) values of 9.4 and 6.5 nm, respectively. The structural properties of the films are investigated using extreme ultraviolet and x-ray reflectometry and transmission electron microscopy. Thermal stability is investigated in films annealed to as high as 300 degrees C. Because of their superior thermal stability, relatively high reflectance, and narrower spectral bandpass, Si/Tb multilayers are identified as optimal candidates for solar physics imaging applications, where the peak response can be tuned to important emission lines such as O v near 63.0 nm and Mg x near 61.0 nm. We describe our experimental procedures and results, discuss the implications of our findings, and outline prospects for improved performance.


Exposure to parental psychopathology and offspring's risk of suicide-related thoughts and behaviours: a systematic review.
The primary objective of this systematic review was to identify and synthesise analytic studies examining the association between exposure to parental psychopathology in childhood and the nature of subsequent suicide-related thoughts (SRT) and suicide-related behaviour (SRB) (severity of ideation, planned/unplanned attempts/lethality) and to describe the direction, and magnitude of associations. The secondary objective was to determine if the associations from the primary objective differ by the type(s) and timing of parental psychopathology, sex/gender of the parent and child and is mediated by child psychiatric symptoms and family functioning. A systematic review was conducted using guidelines from the PRISMA statement. MEDLINE, CINAHL, EMBASE, psycINFO, Web of Science and grey literature sources were searched by two reviewers to March, 2017. Studies were included if they examined any parental psychopathology (Diagnostic and Statistical Manual of Mental Disorders criteria or equivalent) or SRT or SRB and offspring SRT or SRB occurring from birth <25 years of age. Out of 10 231 studies identified, 54 were included for review. Studies were clinically and methodologically heterogeneous with none at low risk of bias (ROB). Nine studies with moderate ROB indicated a significantly increased risk of offspring SRT, suicide attempts (SA) and suicide among those exposed to maternal SA and suicide in childhood or adolescence. In the remaining 45 studies with higher ROB this association persisted. Several studies (67%) did not confirm that the exposure occurred in the offspring's childhood or adolescence. Findings were suggestive of a mediating effect of offspring psychiatric symptoms, however, few studies examined mediation and effect modification of contextual variables. Offspring exposed to maternal SA are at an increased risk of these same behaviours early in life. Prospective attention to the types and timing of maternal and paternal psychopathology and the intermediate pathways to offspring SRT and SRB onset is needed and could have implications for informing modifiable targets for early intervention and prevention.


Interprofessional education and the basic sciences: Rationale and outcomes.
Interprofessional education (IPE) aims to improve patient outcomes and the quality of care. Interprofessional learning outcomes and interprofessional competencies are now included in many countries' health and social care professions' accreditation standards. While IPE may take place at any time in health professions curricula it tends to focus on professionalism and clinical topics rather than basic science activities. However generic interprofessional competencies could be included in basic science courses that are offered to at least two different professional groups. In developing interprofessional activities at the preclinical level, it is important to define explicit interprofessional learning outcomes plus the content and process of the learning. Interprofessional education must involve interactive learning processes and integration of theory and practice. This paper provides examples of IPE in anatomy and makes recommendations for course development and evaluation.


ATP-gamma-S shifts the operating point of outer hair cell transduction towards scala tympani.
ATP receptor agonists and antagonists alter cochlear mechanics as measured by changes in distortion product otoacoustic emissions (DPOAE). Some of the effects on DPOAEs are consistent with the hypothesis that ATP affects mechano-electrical transduction and the operating point of the outer hair cells (OHCs). This hypothesis was tested by monitoring the effect of ATP-gamma-S on the operating point of the OHCs. Guinea pigs anesthetized with urethane and with sectioned middle ear muscles were used. The cochlear microphonic (CM) was recorded differentially (scala vestibuli referenced to scala tympani) across the basal turn before and after perfusion (20 min) of the perilymph compartment with artificial perilymph (AP) and ATP-gamma-S dissolved in AP. The operating point was derived from the cochlear microphonics (CM) recorded in response low frequency (200 Hz) tones at high level (106, 112 and 118 dB SPL). The analysis procedure used a Boltzmann function to simulate the CM waveform and the Boltzmann parameters were adjusted to best-fit the calculated waveform to the CM. Compared to the initial perfusion with AP, ATP-gamma-S (333 microM) enhanced peak clipping of the positive peak of the CM (that occurs during organ of Corti displacements towards scala tympani), which was in keeping with ATP-induced displacement of the transducer towards scala tympani. CM waveform analysis quantified the degree of displacement and showed that the changes were consistent with the stimulus being centered on a different region of the transducer curve. The change of operating point meant that the stimulus was applied to a region of the transducer curve where there was greater saturation of the output on excursions towards scala tympani and less saturation towards scala vestibuli. A significant degree of recovery of the operating point was observed after washing with AP. Dose response curves generated by perfusing ATP-gamma-S (333 microM) in a cumulative manner yielded an EC(50) of 19.8 microM. The ATP antagonist PPADS (0.1 mM) failed to block the effect of ATP-gamma-S on operating point, suggesting the response was due to activation of metabotropic and not ionotropic ATP receptors. Multiple perfusions of AP had no significant effect (118 and 112 dB) or moved the operating point slightly (106 dB) in the direction opposite of ATP-gamma-S. Results are consistent with an ATP-gamma-S induced transducer change comparable to a static movement of the organ of Corti or reticular lamina towards scala tympani.


Functional brain connectivity when cooperation fails.
Functional connectivity during cooperative actions is an important topic in social neuroscience that has yet to be answered. Here, we examined the effects of administration of (fictitious) negative social feedback in relation to cooperative capabilities. Cognitive performance and neural activation underlying the execution of joint actions was recorded with functional near-infrared spectroscopy (fNIRS) on prefrontal regions during a task where pairs of participants received negative feedback after their joint action. Performance (error rates (ERs) and response times (RTs)) and intra- and inter-brain connectivity indices were computed, along with the ConIndex (inter-brain/intra-brain connectivity). Finally, correlational measures were considered to assess the relation between these different measures. Results showed that the negative feedback was able to modulate participants' responses for both behavioral and neural components. Cognitive performance was decreased after the feedback. Moreover, decreased inter-brain connectivity and increased intra-brain connectivity was induced by the feedback, whereas the cooperative task pre-feedback condition was able to increase the brain-to-brain coupling, mainly localized within the dorsolateral prefrontal cortex (DLPFC). Finally, the presence of significant correlations between RTs and inter-brain connectivity revealed that ineffective joint action produces the worst cognitive performance and a more 'individual strategy' for brain activity, limiting the inter-brain connectivity. The present study provides a significant contribution to the identification of patterns of intra- and inter-brain functional connectivity when negative social reinforcement is provided in relation to cooperative actions.


Optical Coherence Tomography Reveals Distinct Patterns of Retinal Damage in Neuromyelitis Optica and Multiple Sclerosis.
Neuromyelitis optica (NMO) and relapsing-remitting multiple sclerosis (RRMS) are difficult to differentiate solely on clinical grounds. Optical coherence tomography (OCT) studies investigating retinal changes in both diseases focused primarily on the retinal nerve fiber layer (RNFL) while rare data are available on deeper intra-retinal layers. To detect different patterns of intra-retinal layer alterations in patients with NMO spectrum disorders (NMOSD) and RRMS with focus on the influence of a previous optic neuritis (ON). We applied spectral-domain OCT in eyes of NMOSD patients and compared them to matched RRMS patients and healthy controls (HC). Semi-automatic intra-retinal layer segmentation was used to quantify intra-retinal layer thicknesses. In a subgroup low contrast visual acuity (LCVA) was assessed. NMOSD-, MS- and HC-groups, each comprising 17 subjects, were included in analysis. RNFL thickness was more severely reduced in NMOSD compared to MS following ON. In MS-ON eyes, RNFL thinning showed a clear temporal preponderance, whereas in NMOSD-ON eyes RNFL was more evenly reduced, resulting in a significantly lower ratio of the nasal versus temporal RNFL thickness. In comparison to HC, ganglion cell layer thickness was stronger reduced in NMOSD-ON than in MS-ON, accompanied by a more severe impairment of LCVA. The inner nuclear layer and the outer retinal layers were thicker in NMOSD-ON patients compared to NMOSD without ON and HC eyes while these differences were primarily driven by microcystic macular edema. Our study supports previous findings that ON in NMOSD leads to more pronounced retinal thinning and visual function impairment than in RRMS. The different retinal damage patterns in NMOSD versus RRMS support the current notion of distinct pathomechanisms of both conditions. However, OCT is still insufficient to help with the clinically relevant differentiation of both conditions in an individual patient.


Catalytic carbene/alkyne metathesis (CAM): a versatile strategy for alkyne bifunctionalization.
Metal carbene, as a reactive intermediate, has shown versatile applications in modern organic synthesis. One of the priorities in this area is exploration of stable carbene precursors with structural diversity. Catalytic carbene/alkyne metathesis (CAM) with readily available and stable materials, such as α-carbonyl diazo compounds, provides an effective approach for the in situ generation of vinyl carbene intermediates, which is difficult to directly access with other carbene precursors. Thus, novel cascade transformations involving the CAM process for the straightforward construction of polycyclic frameworks have been well documented. Challenges including side reaction control and asymmetric catalysis in this area need to be explored. This review will summarize the recent advances in this field and be divided by the type of the terminating carbene reactions.


Investigating strength and frequency effects in recognition memory using type-2 signal detection theory.
Criterion- versus distribution-shift accounts of frequency and strength effects in recognition memory were investigated with Type-2 signal detection receiver operating characteristic (ROC) analysis, which provides a measure of metacognitive monitoring. Experiment 1 demonstrated a frequency-based mirror effect, with a higher hit rate and lower false alarm rate, for low frequency words compared with high frequency words. In Experiment 2, the authors manipulated item strength with repetition, which showed an increased hit rate but no effect on the false alarm rate. Whereas Type-1 indices were ambiguous as to whether these effects were based on a criterion- or distribution-shift model, the two models predict opposite effects on Type-2 distractor monitoring under some assumptions. Hence, Type-2 ROC analysis discriminated between potential models of recognition that could not be discriminated using Type-1 indices alone. In Experiment 3, the authors manipulated Type-1 response bias by varying the number of old versus new response categories to confirm the assumptions made in Experiments 1 and 2. The authors conclude that Type-2 analyses are a useful tool for investigating recognition memory when used in conjunction with more traditional Type-1 analyses.


Cideb Deficiency Aggravates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Exacerbating the Oxidative Burden in Colonic Mucosa.
Abnormal lipid metabolism is one of many factors that contribute to the development of ulcerative colitis (UC). As a lipid droplet-associated protein, Cideb facilitated the export of lipids from enterocytes and promoted intestinal lipid absorption. We found that Cideb was upregulated in the colonic mucosa of both UC patients and dextran sodium sulfate (DSS)-induced mouse colitis, but its roles in the pathogenesis of UC are still ill-defined. Acute colitis was induced with DSS in Cideb-null and wild-type mice, and the inflammation and oxidative stress were evaluated in the colonic mucosa. Moreover, triglyceride accumulation and oxidative stress were further analyzed in polarized Caco-2 cells with overexpression of Cideb. Our present data indicated that Cideb-null mice were more susceptible to DSS-induced colitis, and consumption of a high-fat diet exacerbated the deterioration of DSS-induced colitis in Cideb-null mice. Moreover, Cideb deficiency increased the colonic oxidative stress in DSS-treated mice and more significant under a high-fat diet condition. In exploring the mechanism, we found that Cideb deficiency elevated the lipid content in both feces and the colonic mucosa of DSS-treated mice, especially those fed with a high-fat diet. The in vitro evidence proved that Cideb expression reduced triglyceride accumulation and oxidative stress in polarized Caco-2 cells in the presence of oleic acid. Our data suggest that Cideb plays a protective role against the development of UC by reducing the lipid accumulation and oxidative damage in the colonic mucosa. Therefore, Cideb could be a potential therapeutic target for UC.


A facile approach for oil-water separation using superhydrophobic polystyrene-silica coated stainless steel mesh bucket.
Inspired by traditional shaduf technology in the irrigation field, we fabricated a superhydrophobic stainless steel mesh bucket by layering polystyrene and SiO2 nanoparticles through a facile dip coating technique for effective oil-water separation. The superhydrophobic steel mesh bucket could effectively lift oil as well as microplastic pollutants from the water surface. The water contact angle of a two-layered polystyrene-silica coating was 158.5° ± 2°, while the oil contact angle was nearly 0°. The oil-water separation performance of superhydrophobic mesh was tested using several kinds of oil. The separation efficiency achieved for low viscous oil was 99.33 %, while 86.66 % efficiency was recorded for high viscous oil. The superhydrophobic mesh showed high durability against mechanical tests including bending, folding, twisting, adhesive tape tearing (25 cycles), and sandpaper abrasion (20 cycles). The mesh presented admirable thermal and chemical durability. The present superhydrophobic steel mesh bucket is a suitable candidate for large-scale application.


The impact of the amino-acid sequence on the specificity of copper(II) interactions with peptides having nonco-ordinating side-chains.
The review presents specific interactions that occur in complexes of Cu(II) ions with peptides composed only of amino acids with nonco-ordinating side chains. Three classes of such peptides are discussed. The first type (NSFRY analogues) is characterised by the presence of a specific combination of bulky and aromatic residues, leading to a formation of multiple weak interactions around Cu(II) that result in an extremely high stability of complexes. The second class is composed of complexes of vasopressins and oxytocins, achieving superstability through a pre-conformation in the peptide molecule. The third group are oligopeptides containing one or two proline residues. These peptides form exotic macrochelate loops with Cu(II) in a result of the break-point effect of Pro residues. Particular emphasis in the review was given to stability constants of complexes, compared to oligoglycine or oligoalanine peptides.


Apparent coordinated and communal hunting behaviours by Erabu sea krait Laticauda semifactiata.
Opportunistic observations of Erabu sea kraits (Laticauda semifaciata) provide evidence that this species undertake a novel foraging tactic; coordinated communal hunting. Erabu sea kraits prey on cryptic fish species in highly complex reef habitats. Intra- and interspecific cooperative hunting strategies may increase chances for all members of the hunting party to encounter and capture prey in these complex habitats. Here, we observed 52 instances of communal hunting by Erabu sea kraits with conspecifics and other predatory fishes at recreational dive sites in Southern Lombok, Indonesia. These observations highlight the potential higher cognitive capacity of sea kraits to coordinate activities around communal hunting events.


Minimally Invasive Surgical Versus Transcatheter Aortic Valve Replacement: A Retrospective Observational Single-Center Study in Japan.
This study aimed to compare the outcomes of minimally invasive aortic valve replacement (MICS-AVR) versus transfemoral transcatheter aortic valve replacement (TF-TAVR) in Asian patients. We conducted a retrospective, observational, single-center study in Japan, including cases of MICS-AVR (n = 202) and TF-TAVR (n = 248) between 2014 and 2021. In a total of 450 cases, propensity score matching was performed at a ratio of 1:1, resulting in 96 pairs. Furthermore, we performed competing-risk regression and mediation analyses to determine the treatment effect on outcomes of interests, considering death as a competing risk, and to evaluate the mediation effect of paravalvular leak (PVL) severity. There were similar incidences of all-cause death, cardiac death, stroke and cerebral hemorrhage, and aortic valve reintervention between the 2 groups. However, the TF-TAVR cohort had a longer hospital length of stay and higher rates of significant PVL compared with the MICS-AVR cohort. Multivariable-adjusted Cox regression analyses revealed that heart failure hospitalization (hazard ratio [HR] = 0.129, 95% confidence interval [CI]: 0.038 to 0.445, p = 0.001) and permanent pacemaker implantation (HR = 0.050, 95% CI: 0.006 to 0.409, p = 0.005) favored MICS-AVR. Competing-risk regression analyses confirmed similar findings. All outcomes were unrelated to PVL severity. To our knowledge, this is the first comparative study of clinical outcomes in Asian patients undergoing MICS-AVR versus TF-TAVR, revealing that MICS-AVR could be a feasible and efficient alternative to TF-TAVR. Future larger-scale randomized controlled trials are needed to validate the present results.


Adrenaline activation of prejunctional beta-adrenoceptors in guinea-pig atria.
1. Adrenaline in a concentration of 1.0 microM depressed the stimulation-induced efflux of tritium from the guinea-pig atria incubated with [3H]-noradrenaline, whereas adrenaline in a concentration of 0.5 nM significantly enhanced the stimulation-induced efflux of tritium. This enhancement was blocked by metoprolol (0.1 microM) and thus appears to be mediated by beta-adrenoceptors. 2. In guinea-pig atria incubated with unlabelled adrenaline and then with [3H]-noradrenaline, both catecholamines were released by field stimulation. In such atria metoprolol, practolol, oxprenolol or propranolol decreased the stimulation-induced efflux of tritium. These effects did not occur if the atria were incubated with unlabelled noradrenaline and then with [3H]-noradrenaline, suggesting that neuronally released adrenaline activates prejunctional beta-adrenoceptors. 3. The effect of oxprenolol in decreasing the release of tritium from guinea-pig atria, incubated with unlabelled adrenaline and then with [3H]-noradrenaline was greater in the presence of phentolamine. This may reflect the alpha-adrenoceptor blocking activity of oxprenolol.


Factors contributing to nonadherence to oral hypoglycemic medications among ambulatory type 2 diabetes patients in Southwestern Nigeria.
The overall goal of the study was to evaluate the probable reasons for patients' nonadherence to prescribed oral hypoglycemic medications in an ambulatory care setting in Nigeria with a view to identifying points for necessary intervention to improve adherence and treatment outcomes. Also, the recommended non-drug management options for diabetes patients with emphasis on self monitoring of blood glucose were assessed. A cross-sectional study was conducted at a 200-bed secondary health care facility in Southwestern Nigeria between 2(nd) April and 31(st) May 2008. Copies of pre-tested questionnaire were administered directly to 121 ambulatory patients with type 2 diabetes at the study site. Information on socio-demographic characteristic, probable barriers that affect adherence to prescribed oral hypoglycemic medications, non-drug treatment options for diabetes, and patients' self management efforts were obtained. Descriptive and chi-square statistics were used to evaluate the distribution of respondents' opinion. The response rate was almost 100%. The commonly cited intentional nonadherence practice included dose omission (70.2%). Almost 50% respondents were fed up with daily ingestion of drugs and 19.8% were inconvenienced with taking medications outside home and gave these as reasons for the dose omission. Forgetfulness (49.6%) and high cost of medication (35.5%) were mentioned as major non-intentional reasons for nonadherence. Aside oral medications, 82.6% and 95.0% of respondents respectively, reported moderate exercise and dietary restrictions as part of the prescribed treatment modalities. More than two third of respondents (81.8%) had never monitored blood glucose by themselves. Significant association exist between sex, occupation and patients' tendencies to forget doses of prescribed oral medications (p<0.05). Nonadherence behaviors among ambulatory patients with type 2 diabetes occur mostly, as omission and forgetfulness of doses of medication. Efforts are needed to increase the medication adherence and self management practices of these patients in Nigeria so they can realize the full benefits of prescribed therapies.


Common transcriptional gene profile in neurospheres-derived from pATSCs, pBMSCs, and pNSCs.
Gene expression profiles of adult progenitor cells could give important clues for the molecular mechanisms of adult stem cell proliferation and differentiation behaviors. Adult bone marrow stromal cells (BMSCs), adipose tissue stromal cells (ATSCs), and neural stem cells (NSCs) have common neuropotential characteristics. They can make neurospheres and can differentiate into neurons and glia in vitro and in vivo. In this study, we found commonly expressed genes in neurospheres from non-human primate BMSCs, ATSCs, and NSCs using Affymetrix cDNA microarray system. The expressed genes from three distinct neurosphere populations (non-human primate derived ATSCs neurosphere, pATSCs-NS; non-human primate derived BMSCs neurosphere, pBMSCs-NS; non-human primate derived NSCs neurosphere, pNSCs-NS) were compared to baseline to calculate fold change. The number of enriched genes was 820 (pATSCs-NS), 856 (pBMSCs-NS), and 1010 (pNSCs-NS). Scatter plots of expression levels of all the genes indicated that the correlation coefficients between the three samples are fairly close to each other and have many similarities at the transcriptional levels. Finally, we found that the expression of 184 genes is enriched in all three categories, 9 selected to regulation of cell cycle, 5 transcription factor, 9 receptor activity, 11 development, and 4 cell-cell signaling. This overlapping gene set of commonly expressed gene products represents a molecular signature of neural lineage related function.


Impact of Heated Tobacco Products, E-Cigarettes, and Cigarettes on Inflammation and Endothelial Dysfunction.
In addition to the market launch of heated tobacco products (HTPs) and the JUUL as well as the EVALI, they caused a widespread discussion on the risk reduction compared to a combustible cigarette. Furthermore, first data showed harmful effects on the cardiovascular system. We, therefore, conducted investigations including a control group with a nicotine-free liquid. Forty active smokers were studied in two different approaches during and after consuming an HTP, a cigarette, a JUUL, or a typical electronic cigarette with or without nicotine in a partly double-blinded randomised, cross-over trial. Inflammation, endothelial dysfunction, and blood samples (full blood count, ELISA, multiplex immunoassay) were analysed, and arterial stiffness was measured. In addition to the cigarette, an increase in the white blood cell count but also in proinflammatory cytokines was shown for the various nicotine delivery systems. These correlated with the parameters of arterial vascular stiffness as a clinical parameter of endothelial dysfunction. It can be shown that even a single consumption of the different nicotine delivery system or cigarette leads to a significant inflammatory reaction followed by endothelial dysfunction and increased arterial stiffness causing cardiovascular disease. Inflammation, endothelial dysfunction, and arterial stiffness should be addressed in long-term observational studies.


Morphometric analysis of mitochondria in lymphocytes of patients with exacerbations of chronic obstructive pulmonary disease - pilot study.
Exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events in the course of the disease, negatively influencing health status and disease progression. Therefore, there is a strong need for deeper understanding of the pathology of ECOPD to elaborate new therapeutic approaches and ameliorate prognoses. Contributions of mitochondria to pathobiology of COPD are still under investigation, although growing evidence suggests their important role in this disease. The aim of our study was to assess the morphometric parameters of mitochondria in lymphocytes of patients with ECOPD. Lymphocytes were isolated from the peripheral blood of patients with COPD. Transmission electron microscopy was used to assess absolute number of mitochondria per cell, mitochondrial content, and morphometric parameters of individual mitochondria. We also counted indexes for elongation and interconnectivity. Eighteen patients (9 with ECOPD and 9 in the stable period of the disease) were analyzed. We observed significantly lower length of mitochondrion (P=0.03) and significant decrease both in elongation (P=0.03) and interconnectivity indexes (P=0.04) in ECOPD patients. The morphometric parameters of mitochondria in lymphocytes derived from patients during the early period of ECOPD requiring hospitalization are altered in comparison to patients in the stable period of the disease. This suggests their contribution to pathobiology of ECOPD. These preliminary outcomes should be further validated in larger size samples.


The mitochondrial transport protein SLC25A43 affects drug efficacy and drug-induced cell cycle arrest in breast cancer cell lines.
The mitochondria have been identified as key players of apoptosis, cell proliferation and cell cycle regulation. However, the role of mitochondria in breast cancer and treatment failure remains unclear. We have previously shown a common deletion of the gene SLC25A43 in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This gene is coding for a mitochondrial inner membrane transporter and, to date, little is known about the function of this protein. We have also found that low protein expression of SLC25A43 significantly correlates with a lower S phase fraction in HER2-positive breast cancer. The aim of this study was to investigate whether knockdown (KD) of SLC25A43 could have an effect on the cytotoxicity of different cytostatic drugs using MCF10A, MCF7 and BT-474 cells. Following siRNA-mediated KD of SLC25A43, one non-malignant and two breast cancer cell lines were exposed to the anthracycline epirubicin or the taxane paclitaxel. The HER2-positive breast cancer cells were also exposed to the targeted therapy trastuzumab and dual exposure to trastuzumab and paclitaxel. We found that KD of SLC25A43 resulted in a decreased cytotoxic effect of paclitaxel in the two cancer cell lines (P<0.05). Further analysis of cell cycle phase distribution showed that KD increased the paclitaxel-induced G2/M block in these two cell lines (P<0.05). KD of SLC25A43 also reduced the inhibitory effect of trastuzumab on cell proliferation in the HER2-positive cancer cell line BT-474 (P<0.05), and the drug-induced G0/G1 block (P<0.05). Moreover, SLC25A43 influenced the percentage of Ki-67-positive cells. Our findings demonstrate that the mitochondrial protein SLC25A43 affects drug efficacy and cell cycle regulation following drug exposure in breast cancer cell lines.


Microbial community composition of the ileum and cecum of broiler chickens as revealed by molecular and culture-based techniques.
The microbial communities of the ileum and cecum of broiler chickens from a conventional and an organic farm were investigated using conventional culture techniques as well as cloning and sequencing of 16S rRNA genes. Eighty-five percent of the 557 cloned sequences were <97% related to known cultured species. The chicken ileum was dominated by lactobacilli, whereas the cecum harbored a more diverse microbial community. The cecum was dominated by a large group of bacteria with hitherto no close cultured relatives but most closely related to Faecalibacterium prausnitzii. Approximately 49 and 20% of the cecal clones belonged to this cluster in conventional and organic broiler chickens, respectively. We were, however, able to recover a number of these phylotypes by cultivation, and the isolates were shown to be butyric acid producers. The investigation was a descriptive rather than a comparative study of 2 different rearing systems; however, several differences were observed. For instance, Clostridium perfringens was found in significantly higher numbers in the birds from the organic farm compared with the conventional broilers, probably due to the addition of salinomycin to the conventional feed. In the ileum, the abundance of the different Lactobacillus species differed between the 2 broiler types. The culture-based and culture-independent techniques complemented each other well. Strengths and limitations of the different methods are discussed.


Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.
Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time.


Risedronate reduces the risk of first vertebral fracture in osteoporotic women.
Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score = -3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg ( n = 328) or placebo ( n = 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P = 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P = 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P = 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause.


An assessment of chromosomal rearrangements in neopolyploids of Lilium hybrids.
Two types of newly induced polyploids (neopolyploids) of Lilium hybrids were monitored for the occurrence of chromosomal rearrangements through genomic in situ hybridization (GISH) technique. One of the populations was obtained through crossing an allotriploid Longiflorum x Oriental hybrid (LLO) with an allotetraploid Longiflorum x Trumpet hybrid (LLTT), both of which were derived from somatic chromosome doubling. The other type of allopolyploid population was derived from meiotic chromosome doubling in which numerically unreduced (2n) gametes from two different interspecific hybrids, namely, Longiflorum x Asiatic (LA) and Oriental x Asiatic (OA), were used to get backcross progeny with the Asiatic parents. GISH clearly discriminated the three constituent genomes (L, T, and O) in the complements of the progeny obtained from mitotic chromosome doubling. A total of 26 individuals were analyzed from this population and there was no evidence of chromosomal rearrangements. However, in the case of meiotically doubled allopolyploid progeny, considerable frequencies of chromosomal rearrangements were observed through GISH. The so-called chromosomal rearrangements in meiotic polyploids are the result of homoeologous recombination rather than translocations. Furthermore, evidence for the occurrence of meiotic recombination in the LA hybrids has been confirmed with GISH on meiotic chromosomes. Thus, there was evidence that neopolyploids of Lilium hybrids did not possess any noticeable chromosome rearrangements.


Functional profiling of gut microbial and immune responses toward different types of dietary fiber: a step toward personalized dietary interventions.
Dietary fiber plays a crucial role in maintaining gut and overall health. The objective of this study was to investigate whether different types of dietary fiber elicited specific changes in gut microbiota composition and the production of short-chain fatty acids. To test this, a longitudinal crossover study design was employed, in which healthy adult women consumed three distinct dietary fiber supplements: Inulin (fructo-oligosaccharide), Vitafiber (isomalto-oligosaccharide), and Fibremax (mixture of different fiber) during a one-week intervention period, followed by a 2-week washout period. A total of 15 g of soluble fiber was consumed daily for each supplement. Samples were collected before and after each intervention to analyze the composition of the gut microbiota by 16S rRNA sequencing and fecal levels of short-chain fatty acids measured using nuclear magnetic resonance. Phenotypic changes in peripheral blood mononuclear cells were studied in subsets of participants with higher SCFA levels post-intervention using spectral flow cytometry. The results revealed substantial stability and resilience of the overall gut bacterial community toward fiber-induced changes. However, each supplement had specific effects on gut bacterial alpha and beta diversity, SCFA production, and immune changes. Inulin consistently exerted the most pronounced effect across individuals and certain taxa were identified as potential indicators of SCFA production in response to inulin supplementation. This distinguishing feature was not observed for the other fiber supplements. Further large-scale studies are required to confirm these findings. Overall, our study implies that personalized dietary fiber intervention could be tailored to promote the growth of beneficial bacteria to maximize SCFA production and associated health benefits.


Effects of aging and comorbidities on nutritional status and muscle dysfunction in patients with COPD.
Chronic obstructive pulmonary disease (COPD) is a prevalent, complex and debilitating disease which imposes a formidable burden on patients and the healthcare system. The recognition that COPD is a multifaceted disease is not new, and increasing evidence have outlined the importance of its extra-pulmonary manifestations and its relation to other comorbid conditions in the clinical course of the disease and its societal cost. The relationship between aging, COPD and its comorbidities on skeletal muscle function and nutritional status is complex, multidirectional and incompletely understood. Despite this, the current body of knowledge allows the identification of various, seemingly partially independent factors related both to the normal aging process and to the independent deleterious effects of chronic diseases on muscle function and body composition. There is a dire need of studies evaluating the relative contribution of each of these factors, and their potential synergistic effects in patients with COPD and advanced age/comorbid conditions, in order to delineate the best course of therapeutic action in this increasingly prevalent population.


[Experience in the differential diagnosis of peripapillary "geographic" choroid disease and tuberculous chorioretinitis].
The etiology of peripapillary choriopathy (so-called geographic serpiginous choroiditis) is still unknown. This condition should be differentiated from tuberculous chorioretinitis because both abnormalities are characterized by a prolonged chronic course with involvement of the choroid and retina in young and middle-aged patients. The present study analyzes the results of a follow-up of 32 patients with peripapillary choriopathy; before these patients were admitted to hospital, ocular tuberculosis was diagnosed in 19 and suspected in 13 of them by local specialists. The authors came to a conclusion that the major differential diagnostic criteria here should be specific features of the ophthalmoscopic picture and of fluorescent angiograms of the fundus oculi, as well as the results of tuberculin diagnosis and tentative therapy.


Simian virus 40 gene A regulation of cellular DNA synthesis. II. In nonpermissive cells.
The stimulation of host macromolecular synthesis and induction into the cell cycle of serum-deprived G0-G1-arrested mouse embryo fibroblasts were examined after infection of resting cells with wild-type simian virus 40 or with viral mutants affecting T antigen (tsA58) or small t antigen (dl884). At various times after virus infection, cell cultures were analyzed for DNA synthesis by autoradiography and flow microfluorimetry. Whereas mock-infected cultured remained quiescent and displayed either a 2N DNA content (80%) or a 4N DNA content (15%), mouse cells infected with wild-type simian virus 40, tsA58 at 33 degrees C, or dl884 were induced into active cell cycling at approximately 18 h postinfection. Although dl884-infected mouse cells were induced to cycle initially at the same rate as wild type-infected cells, they became arrested earlier after infection and also failed to reach the saturation densities of wild-type simian virus 40-infected cells. Infection with dl884 also failed to induce loss of cytoplasmic actin cables in the majority of the infected cell population. Mouse cells infected with tsA58 and maintained at 39.5 degrees C showed a transient burst of DNA synthesis as reflected by changes in cell DNA content and an increase in the number of labeled nuclei during the first 24 h postinfection; however, after the abortive stimulation of DNA synthesis at 39.5 degrees C shift experiments demonstrated that host DNA replication was regulated by a functional A gene product. It is concluded that both products of the early region of simian virus 40 DNA play a complementary role in recruiting and maintaining simian virus 40-infected cells in the cell cycle.


Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas.
To help further define the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of corneal neovascularization, the expression of VEGF and of its receptors Flt-1 and Flk-1 was investigated in various inflammatory corneal diseases. Polyclonal antibodies to VEGF and its receptors were used for immunohistochemical staining of frozen sections of 38 human corneas with various degrees of neovascularization and inflammation. In addition, a panel of monoclonal antibodies was used to characterize the composition of the inflammatory infiltrates and to confirm the presence of neovascularization. Furthermore, VEGF concentrations were determined in vascularized corneas using a sensitive enzyme-linked immunosorbent assay. VEGF was expressed by epithelial cells, by corneal endothelial cells, by vascular endothelial cells of limbal vessels and of newly formed vessels in the stroma, and weakly by keratocytes. Furthermore, VEGF expression was often markedly increased in inflamed corneas on epithelial cells and on vascular endothelial cells, particularly in the vicinity of macrophage infiltrates, and on fibroblasts in scar tissue. Correspondingly, VEGF concentrations were significantly higher in vascularized corneas compared with normal control corneas (P < 0.001). Expression of both VEGF receptors, Flt-1 and Flk-1, was increased on endothelial cells of newly formed vessels in the stroma of inflamed corneas compared with limbal vessels of normal control corneas. In addition, Flt-1 was also expressed by corneal endothelial cells and by macrophages, whereas Flk-1 expression was lacking. These results demonstrate that VEGF, Flt-1, and Flk-1 are strongly expressed in inflamed and vascularized human corneas and, thus, may play an important role in corneal neovascularization.


Combining data from 2 nested case-control studies of overlapping cohorts to improve efficiency.
Researchers subject to time and budget constraints may conduct small nested case-control studies with individually matched controls to help optimize statistical power. In this paper, we show how precision can be improved considerably by combining data from a small nested case-control study with data from a larger nested case-control study of a different outcome in the same or overlapping cohort. Our approach is based on the inverse probability weighting concept, in which the log-likelihood contribution of each individual observation is weighted by the inverse of its probability of inclusion in either study. We illustrate our approach using simulated data and an application where we combine data sets from 2 nested case-control studies to investigate risk factors for anorexia nervosa in a cohort of young women in Sweden.


Clinical therapeutic effects of platelet-rich plasma in patients with burn wound healing: A protocol for systematic review and meta-analysis.
In clinical settings, burn wounds are frequently encountered. Since burn wounds are a form of physical injury, they can have long-term adverse effects on the human body. It has been a significant challenge to treat burn wounds completely. Since traditional treatment strategies have been unable to heal burn wounds completely, they lack the efficacy to cure the wounds without long-term effects, such as heavy scarring. Reportedly, platelet-rich plasma (PRP) has shown potential to accelerate wound healing. Yet, there are no conclusive reports on a methodological comparative study of research that has assessed the medical benefits of PRP for treating individuals carrying burn wounds. Thus, the present meta-analysis and systematic study aims to assess the medical benefits of PRP for treating patients carrying burn wounds. The authors will conduct a comprehensive search for randomized controlled trials that evaluate the safeness and efficiency of PRP to treat burn wounds. The search includes 3 Chinese language databases (WanFang database, Chinese BioMedical Literature database, and China National Knowledge Infrastructure) and 4 English language databases (Cochrane Library, EMBASE, Web of Science, and MEDLINE). These electronic databases will be searched from their establishment till May 2021. A pair of independent authors will be selecting eligible studies for extracting data. The same authors will employ the Cochrane risk of bias tool to evaluate the bias risk. We will make use of RevMan (version: 5.3) software to complete data synthesis. The present protocol will establish practical and targeted results evaluating the efficacy and safeness of using PRP to treat burn wounds. The current study also provides a reference for clinical use of PRP. Stronger evidence about the effectiveness and safety of using PRP to treat and heal burn wounds will be provided for clinicians to refer. Ethics approval is unrequired. March 31, 2021.osf.io/whauj. (https://osf.io/whauj/).


Long-term reproducibility optimization of an x-ray process for bone architectural evaluation during osteoporosis.
Non-invasive and in vivo assessment of bone architectural changes at high resolution is of considerable interest in osteoporosis. In this note, the use of an x-ray acquisition system in the evaluation of the architectural quality of trabecular bone by radiographic texture analysis is optimized to achieve good long-term reproducibility. First, radiographic and digitization processes are modelled and defined. Procedures to make radiographs and their digital images are fixed. Then, measurements of the modulation transfer function (MTF) of the entire acquisition chain were completed. These measurements provide an MTF in excess of 30% at a spatial frequency of 2.5 lp/mm. Also, results of a fractal texture analysis made on digital images of calcaneus radiographs show a mean coefficient of variation of 2.07%. These data show that good long-term reproducibility can make the x-ray acquisition system efficient for patient follow-up, or evaluation of treatment regimes for osteoporosis. Finally, it is shown that fractal texture parameters are statistically different in an osteoporotic population and in a control group. Therefore, this system should also be of medical interest.


An Unobtrusive Fall Detection System Using Ceiling-mounted Ultra-wideband Radar.
Falls are among the most devastating events that can happen to an older person. Automatic fall detection systems aim to solve this problem by alerting carers and family the moment a fall occurs. This paper presents the development of an unobtrusive fall detection system using ultra-wideband (UWB) radar. The proposed system employed a ceiling-mounted UWB radar to avoid object occlusion and allow for flexible implementation. An innovative pre-processing method was developed to effectively enhance motion and reduce noise from raw UWB data. We designed a trial protocol composed of common types of falls in older population and activities of daily living (ADL). A fall detection algorithm based on convolutional neural networks was developed with simulated falls and ADLs obtained from ten participants following the trial protocol in a clear and cluttered living environment. The fall detection system achieved an accuracy of 93.97%, with a sensitivity of 95.58% and specificity of 92.68%.


Responsibility for quality improvement and patient safety: hospital board and medical staff leadership challenges.
Concern about the quality and safety of health care persists, 10 years after the 1999 Institute of Medicine report To Err is Human. Despite growing awareness of quality and safety risks, and significant efforts to improve, progress is difficult to measure. Hospital leaders, including boards and medical staffs, are accountable to improve care, yet they often address this duty independently. Shared responsibility for quality and patient safety improvement presents unique challenges and unprecedented opportunities for boards and medical staffs. To capitalize on the pressure to improve, both groups may benefit from a better understanding of their synergistic potential. Boards should be educated about the quality of care provided in their institutions and about the challenges of valid measurement and accurate reporting. Boards strengthen their quality oversight capacity by recruiting physicians for vacant board seats. Medical staff members strengthen their role as hospital leaders when they understand the unique duties of the governing board. A quality improvement strategy rooted in synergistic efforts by the board and the medical staff may offer the greatest potential for safer care. Such a mutually advantageous approach requires a clear appreciation of roles and responsibilities and respect for differences. In this article, we review these responsibilities, describe opportunities for boards and medical staffs to collaborate as leaders, and offer recommendations for how boards and medical staff members can address the challenges of shared responsibility for quality of care.


Optimal settings for different tooth types in the virtual bracket removal technique.
To determine the optimal settings for reconstructing the buccal surfaces of different tooth types using the virtual bracket removal (VBR) technique. Ten postbonded digital dentitions (with their original prebonded dentitions) were enrolled. The VBR protocol was carried out under five settings from three commonly used computer-aided design (CAD) systems: OrthoAnalyzer (O); Meshmixer (M); and curvature (G2), tangent (G1), and flat (G0) from Geomagic Studio. The root mean squares (RMSs) between the reconstructed and prebonded dentitions were calculated for each tooth and compared with the clinically acceptable limit (CAL) of 0.10 mm. The overall prevalences of RMSs below the CAL were 66.80%, 70.08%, 62.30%, 94.83%, and 56.15% under O, M, G2, G1, and G0, respectively. For the upper dentition, the mean RMSs were significantly lower than the CAL for all tooth types under G1 and upper incisors and canines under M and G2. For the lower dentition, the mean RMSs were significantly lower than the CAL for all tooth types under G1 and lower incisors and canines under M, G2, and G0 (all P < .05). Additionally, the mean RMSs of all teeth under G1 were significantly lower than those under the other settings (all P < .001). The optimal settings varied among different tooth types. G1 performed best for most tooth types compared to the other four settings.


Effects of Tinospora cordifolia (Menispermaceae) on the proliferation, osteogenic differentiation and mineralization of osteoblast model systems in vitro.
Ancient Indian ayurvedic literature prescribes Tinospora cordifolia as a remedy to rheumatoid arthritis, inflammatory and allied diseases of musculo skeletal system. To investigate the effects of the alcoholic extract of Tinospora cordifolia (TC) on the proliferation, differentiation and mineralization of bone like matrix on osteoblast model systems in vitro and hence its possible use as a potential anti-osteoporotic agent. Two in vitro osteoblast model systems were used in the study viz., human osteoblast-like cells MG-63 and primary osteoblast cells isolated from femur of rats. Cell growth and viability was assessed by standard colorimetric assays like MTT assay. The cell differentiation into osteoblastic lineage was evaluated by the activities of bone marker alkaline phosphatase. The effect of the extract on matrix mineralization was assessed by alizarin red-s staining and Von kossa staining. Cell morphology was studied by phase contrast microscopy and light microscopy (Giemsa/crystal violet staining). Results indicate that the alcoholic extract of TC at a dosage of 25μg/ml stimulated the growth of osteoblasts, increased the differentiation of cells into osteoblastic lineage and increased the mineralization of bone like matrix on both the osteoblast model systems used in the study. Cell morphology studies clearly indicated the increase in cell numbers and absence of adverse change in the cell morphology on treatment with the extract. TC extract has a potential influence on osteogenesis and hence its use could be explored as a potential anti-osteoporotic agent.


Association of low red blood cell folate concentrations with coronary artery disease in Iranians: a matched case-control study.
It is not fully established whether the increasing risk of coronary artery disease (CAD) is associated with high plasma homocysteine levels or components of the homocysteine remethylation pathway, e.g. vitamin B(12) or 5-methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this study, we tested the hypothesis that 5-MTHF in RBC, which represents the long-term folate status of individuals, may be a more reliable marker of homocysteine remethylation pathway disturbances, and its deficiency may be associated with CAD in Iranians. Plasma total homocysteine (tHcy), vitamin B(12), and plasma and RBC 5-MTHF were measured in 200 angiographically documented patients and 200 controls matched for sex and age. In the plasma, tHcy levels were significantly higher in cases compared to controls (geometric mean 12.9 +/- 6.5 vs. 10.6 +/- 5.6 micromol/l, p = 0.04). However, RBC 5-MTHF (527.2 +/- 185.9 vs. 461.3 +/- 117.9 nmol/l, p = 0.007) and vitamin B(12) (254.2 +/- 132.8 vs. 182.2 +/- 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients. RBC 5-MTHF was a strong and independent predictor of plasma tHcy (beta = -0.01, p = 0.003, r(2) = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a 2.5-fold increased prevalence of CAD compared to subjects in the highest quartile. The association of CAD in the first quartile with red-cell 5-MTHF remained significant when adjusted for plasma tHcy, vitamin B(12), hypertension and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1-3.9, p = 0.01). However, the association between CAD in the highest quartile and plasma tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF, vitamin B(12), hypertension and hypercholesterolemia (OR 1.27, confidence interval: 0.96-1.69, p = 0.11). In this study, the association between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study disturbances in the homocysteine remethylation pathway in Iranians.


Nutrient and temperature limitation of bacterioplankton growth in temperate lakes.
Limitation of bacterioplankton production by nutrients and temperature was investigated in eight temperate lakes in summer. Six of the lakes were resampled in autumn. The lakes differ in nutrient content, water color, and concentration of dissolved organic carbon. Nutrients (phosphorus, nitrogen, and organic carbon) were added alone and in all possible combinations to filtered lake water inoculated with bacteria from the lake. After incubation for 36-40 h at in situ temperatures (ranging from 7 to 20 degrees C), the response in bacterioplankton production was determined. The effect of increased temperature on bacterioplankton growth was also tested. Bacterioplankton production was often limited by phosphorus alone, organic carbon alone, or the two in combination. Phosphorus limitation of bacterioplankton production was more common in the summer, whereas limitation by organic carbon was more frequently observed in the autumn. There was a close balance between limitation by phosphorus and organic carbon in the epilimnion in the summer. In the hypolimnion in the summer, bacterioplankton growth was primarily phosphorus-limited. The effect of phosphorus additions decreased with increasing phosphorus concentrations in the lakes. However, there were no correlations between the effect of added organic carbon and water color, dissolved organic carbon concentration, or phosphorus concentration. When temperature was low (in the hypolimnion in the summer, and throughout the water column in the autumn) temperature also limited bacterioplankton production. Thus, temperature and inorganic nutrients or organic compounds can limit bacterioplankton growth both alone and simultaneously. However, at low temperatures, temperature is the most important factor influencing bacterioplankton growth.


Adiponectin and mortality in patients with chronic kidney disease.
Adiponectin is presumed to possess antiatherogenic and cardioprotective properties. Limited data exist on the relationship between adiponectin and mortality in the earlier stages of chronic kidney disease. The Modification of Diet in Renal Disease study was a randomized, controlled trial that was conducted between 1989 and 1993. Adiponectin was measured in frozen samples that were obtained at baseline (N = 820). Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of adiponectin with all-cause and cardiovascular mortality. Mean +/- SD age was 52 +/- 12 yr, and mean +/- SD glomerular filtration rate (GFR) rate was 33 +/- 12 ml/min per 1.73 m2. Eighty-five percent of participants were white, and 60% were male. Mean +/- SD adiponectin was 12.8 +/- 8.0 mug/ml. Triglycerides, insulin resistance, glucose, body mass index, GFR, C-reactive protein, and albumin were inversely related and proteinuria and HDL cholesterol were directly related to adiponectin. During the 10-year follow-up period, 201 (25%) participants died of any cause, and 122 (15%) from cardiovascular disease. In multivariable adjusted Cox models, a 1-mug/ml increase in adiponectin was associated with a 3% (hazard ratio 1.03; 95% confidence interval 1.01 to 1.05; P = 0.02) increased risk for all-cause and 6% (hazard ratio 1.06; 95% confidence interval 1.03 to 1.09; P < 0.001) increased risk for cardiovascular mortality. High, rather than low, adiponectin is associated with increased mortality in this cohort of patients with chronic kidney disease stages 3 to 4. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.


Margin of Stability May Be Larger and Less Variable during Treadmill Walking Versus Overground.
Margin of stability (MOS) is considered a measure of mechanical gait stability. Due to broad application of treadmills in gait assessment experiments, we aimed to determine if walking on a treadmill vs. overground would affect MOS during three speed-matched conditions. Eight healthy young participants walked on a treadmill and overground at Slow, Preferred, and Fast speed-matched conditions. The mean and variability (standard deviation) of the MOS in anterior-posterior and mediolateral directions at heel contact were calculated. Anterior-posterior and mediolateral mean MOS values decreased with increased speed for both overground and treadmill; although mediolateral mean MOS was always wider on the treadmill compared to overground. Due to lack of optic flow and different proprioceptive inputs during treadmill walking, subjects may employ strategies to increase their lateral stability on treadmill compared to overground. Anterior-posterior MOS variability increased with speed overground, while it did not change on treadmill, which might be due to the fixed speed of treadmill. Whereas, lateral variability on both treadmill and overground was U-shaped. Walking at preferred speed was less variable (may be interpreted as more stable) laterally, compared to fast and slow speeds. Caution should be given when interpreting MOS between modes and speeds of walking. As sagittal plane walking is functionally unstable, this raises the consideration as to the meaningfulness of using MOS as a global measure of gait stability in this direction.


Hydrogen peroxide signaling through tumor necrosis factor receptor 1 leads to selective activation of c-Jun N-terminal kinase.
Binding of tumor necrosis factor-alpha (TNFalpha) to its receptor, TNF-R1, results in the activation of inhibitor of kappaB kinase (IKK) and c-Jun N-terminal kinase (JNK) pathways that are coordinately regulated and important in survival and death. We demonstrated previously that in response to hydrogen peroxide (H2O2), the ability of TNFalpha to activate IKK in mouse lung epithelial cells (C10) was inhibited and that H2O2 alone was sufficient to activate JNK and induce cell death. In the current study, we investigated the involvement of TNF-R1 in H2O2-induced JNK activation. In lung fibroblasts from TNF-R1-deficient mice the ability of H2O2 to activate JNK was inhibited compared with fibroblasts from control mice. Additionally, in C10 cells expressing a mutant form of TNF-R1, H2O2-induced JNK activation was also inhibited. Immunoprecipitation of TNF-R1 revealed that in response to H2O2, the adapter proteins, TRADD and TRAF2, and JNK were recruited to the receptor. However, expression of the adaptor protein RIP, which is essential for IKK activation by TNFalpha, was decreased in cells exposed to H2O2, and its chaperone Hsp90 was cleaved. Furthermore, data demonstrating that expression of TRAF2 was not affected by H2O2 and that overexpression of TRAF2 was sufficient to activate JNK provide an explanation for the inability of H2O2 to activate IKK and for the selective activation of JNK by H2O2. Our data demonstrate that oxidative stress interferes with IKK activation while promoting JNK signaling, creating a signaling imbalance that may favor apoptosis.


Chemical modification of DNA with muta-carcinogens. I. 3-Amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole: metabolic activation and structure of the DNA adducts.
3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) are potent mutagen/carcinogens isolated from pyrolyzates of tryptophan and glutamic acid, respectively, and they have been found to exist in many cooked foods. Trp-P-2 and Glu-P-1 bind to DNA covalently after metabolic activations. The compounds are oxidized to the corresponding hydroxylamines (N-OH-Trp-P-2 and N-OH-Glu-P-1) by microsomes. N-OH-Trp-P-2 and N-OH-Glu-P-1 are the proximate forms of Trp-P-2 and Glu-P-1, respectively. They are further activated by cytosol to the O-acyl derivatives, which bind covalently with DNA. The structures of the modified nucleic acid bases were identified as 3-(C8-guanyl)amino-1-methyl-5H-pyrido[4,3-b]indole (Gua-Trp-P-2) and 2-(C8-guanyl)amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Gua-Glu-P-1). These initial events caused by Trp-P-2 and Glu-P-1 were established chemically, both in vitro and in vivo.


Volunteer kinematics and reaction in lateral emergency maneuver tests.
It is important to understand human kinematics and muscle activation patterns in emergency maneuvers for the design of safety systems and for the further development of human models. The objective of this study was to quantify kinematic behavior and muscle activation in simulated steering tests in several realistic conditions. In total 108 tests were performed with 10 volunteers undergoing purely lateral maneuvers at 5 m/s^2 deceleration or simulated lane change maneuvers at 5 m/s^2 peak acceleration and peak yaw velocity of 25 °/s. Test subjects were seated on a rigid seat and restrained by a 4-point belt with retractor. Driver subjects were instructed to be relaxed or braced and to hold the steering wheel while passenger subjects were instructed to put their hands on their thighs. Subjects were instrumented with photo markers that were tracked with 3D high- speed stereo cameras and with electromyography (EMG) electrodes on 8 muscles. Corridors of head displacement, pitch and roll and displacement of T1, shoulder, elbow, hand and knee were created representing mean response and standard deviation of all subjects. In lane change tests for the passenger configuration significant differences were observed in mean peak of head left lateral displacement between the relaxed and the braced volunteers, i.e. 171 mm (σ=58, n=21) versus 121 mm (σ=46, n=17), respectively. Sitting in a relaxed position led to significantly lower muscle activity of the neck muscles. It was concluded that significantly more upper body motion and lower muscle activity was observed for relaxed subjects than for braced subjects.


Genomic organization of the 3' region of the human thyroglobulin gene.
The genomic organization of the 3' end of the human Thyroglobulin (Tg) gene has not previously been characterized. We isolated and characterized seventeen lambda phage clones from a human genomic library that included nucleotides 6263 to 8410 of the Tg mRNA, encompassing the last thirteen 3' exons of the Tg gene. The region contained exons ranging in size from 94 to 222 nucleotides, split by introns of 1 to 64 kb. We estimate a total of 48 exons in the Tg gene. All the intron-exon boundaries were sequenced. We found that the splicing sequences diverged considerably from the 3' and 5' consensus. However, the GT-AG rule was perfectly respected in all the exons. A total of 5788 intronic bases and most of the sequences contained in the 13 exons were analyzed (1846 bases). One sequence variation, TT to CC at positions 8377-8378, was found in the 3' untranslated segment. The three tyrosine residues involved in thyroid hormones synthesis (amino acids 2554, 2568, and 2747) at the carbosyl termini of Tg, are encoded by exons 44, 45, and 48. The knowledge of the precise organization of the Tg gene should help to direct studies of Tg gene mutations in families in which a defect in the synthesis of Tg occurs.


High-throughput multiplex single-nucleotide polymorphism analysis for red cell and platelet antigen genotypes.
Transfusion recipients who become alloimmunized to red cell or platelet (PLT) antigens require antigen-negative blood to limit adverse transfusion reactions. Blood collection facilities use regulated and unregulated antibodies to phenotype blood, the cost of which can be prohibitive depending on the antisera and demand. An alternative strategy is to screen blood for these antigens with genomic DNA and the associated single-nucleotide polymorphisms (SNPs). A multiplex polymerase chain reaction (PCR)-oligonucleotide extension assay was developed with genomic DNA and a SNP genotyping platform (GenomeLab SNPstream, Beckman Coulter) to identify SNPs related to D, C/c, E, S/s, K/k, Kp(a/b), Fy(a/b), FY0 (-33 promoter silencing polymorphism), Jk(a/b), Di(a/b), and human PLT antigen (HPA)-1a/1b. A total of 372 samples were analyzed for 12 SNPs. The genotypes were compared to the blood group and PLT antigen phenotypes. Individual sample results varied from 98 to 100 percent for 11 of 12 SNPs. D was correctly identified in 292 of 296 (98.6%) D+ donors. The RHCE exon 5 E/e SNP analysis had the lowest concordance (89.5%). Thirty-three R(1)R(1) and 1 r"r were correctly identified. PCR-restriction fragment length polymorphism (RFLP) on selected samples confirmed the presence of the FY0 silencing polymorphism in nine donors. Homozygous HPA-1b/1b was identified in four donors, which was confirmed by PCR-RFLP (n = 4) and anti-HPA-1a serology (n = 2). The two HPA-1a-negative donors were recruited into the plateletpheresis program. The platform has the capacity to genotype thousands of samples per day. The suite of SNPs provides genotype data for all blood donors within 36 hours of the start of testing.


[Vagotomy in emergency surgery for duodenal ulcer].
We examined acid-producing stomach functions, local hemodynamics and motility of the stomach and duodenum in performing organ preservation surgery: combined gastric vagotomy, selective proximal vagotomy and extended selective proximal vagotomy. Changes of hemodynamics and motility in the early postoperative period are related to the technical peculiarities of performing various types of vagotomy. Restoration of the functional state of the stomach and duodenum takes place in the late postoperative period. The acid-producing function in the late postoperative period is reduced to the safe level concerning ulceration, irrespective of the vagotomy type.


Phage-induced bacterial morphological changes reveal a phage-derived antimicrobial affecting cell wall integrity.
In a looming post-antibiotic era, antibiotic alternatives have become key players in the combat against pathogens. Although recent advances in genomic research allow scientists to fully explore an organism's genome in the search for novel antibacterial molecules, laborious work is still needed in order to dissect each individual gene product for its antibacterial activity. Here, we exploited phage-induced bacterial morphological changes as anchors to explore and discover a potential phage-derived antimicrobial embedded in the phage genome. We found that, upon vibriophage KVP40 infection, Vibrio parahaemolyticus exhibited morphological changes similar to those observed when treated with mecillinam, a cell wall synthesis inhibitor, suggesting the mechanism of pre-killing that KVP40 exerts inside the bacterial cell upon sieging the host. Genome analysis revealed that, of all the annotated gene products in the KVP40 genome that are involved in cell wall degradation, lytic transglycosylase (LT) is of particular interest for subsequent functional studies. A single-cell morphological analysis revealed that heterologous expression of wild-type KVP40-LT induced similar bacterial morphological changes to those treated with the whole phage or mecillinam, prior to cell burst. On the contrary, neither the morphology nor the viability of the bacteria expressing signal-peptide truncated- or catalytic mutant E80A- KVP40-LT was affected, suggesting the necessity of these domains for the antibacterial activities. Altogether, this research paves the way for the future development of the discovery of phage-derived antimicrobials that is guided through phage-induced morphological changes.


Highly Efficient Flexible Quantum Dot Solar Cells with Improved Electron Extraction Using MgZnO Nanocrystals.
Colloidal quantum dot (CQD) solar cells have high potential for realizing an efficient and lightweight energy supply for flexible or wearable electronic devices. To achieve highly efficient and flexible CQD solar cells, the electron transport layer (ETL), extracting electrons from the CQD solid layer, needs to be processed at a low-temperature and should also suppress interfacial recombination. Herein, a highly stable MgZnO nanocrystal (MZO-NC) layer is reported for efficient flexible PbS CQD solar cells. Solar cells fabricated with MZO-NC ETL give a high power conversion efficiency (PCE) of 10.4% and 9.4%, on glass and flexible plastic substrates, respectively. The reported flexible CQD solar cell has the record efficiency to date of flexible CQD solar cells. Detailed theoretical simulations and extensive characterizations reveal that the MZO-NCs significantly enhance charge extraction from CQD solids and diminish the charge accumulation at the ETL/CQD interface, suppressing charge interfacial recombination. These important results suggest that the low-temperature processed MZO-NCs are very promising for use in efficient flexible solar cells or other flexible optoelectronic devices.


Hypoxia induces trimethylated H3 lysine 4 by inhibition of JARID1A demethylase.
Histone H3 lysine 4 (H3K4) trimethylation (H3K4me3) at the promoter region of genes has been linked to transcriptional activation. In the present study, we found that hypoxia (1% oxygen) increased H3K4me3 in both normal human bronchial epithelial Beas-2B cells and human lung carcinoma A549 cells. The increase of H3K4me3 from hypoxia was likely caused by the inhibition of H3K4 demethylating activity, as hypoxia still increased H3K4me3 in methionine-deficient medium. Furthermore, an in vitro histone demethylation assay showed that 1% oxygen decreased the activity of H3K4 demethylases in Beas-2B nuclear extracts because ambient oxygen tensions were required for the demethylation reaction to proceed. Hypoxia only minimally increased H3K4me3 in the BEAS-2B cells with knockdown of JARID1A, which is the major histone H3K4 demethylase in this cell line. However, the mRNA and protein levels of JARID1A were not affected by hypoxia. GeneChip and pathway analysis in JARID1A knockdown Beas-2B cells revealed that JARID1A regulates the expression of hundreds of genes involved in different cellular functions, including tumorigenesis. Knocking down of JARID1A increased H3K4me3 at the promoters of HMOX1 and DAF genes. Thus, these results indicate that hypoxia might target JARID1A activity, which in turn increases H3K4me3 at both the global and gene-specific levels, leading to the altered programs of gene expression and tumor progression.


Studies of SARS virus vaccines.
1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.


Successive overrelaxation for support vector machines.
Successive overrelaxation (SOR) for symmetric linear complementarity problems and quadratic programs is used to train a support vector machine (SVM) for discriminating between the elements of two massive datasets, each with millions of points. Because SOR handles one point at a time, similar to Platt's sequential minimal optimization (SMO) algorithm which handles two constraints at a time and Joachims' SVMlight which handles a small number of points at a time, SOR can process very large datasets that need not reside in memory. The algorithm converges linearly to a solution. Encouraging numerical results are presented on datasets with up to 10,000,000 points. Such massive discrimination problems cannot be processed by conventional linear or quadratic programming methods, and to our knowledge have not been solved by other methods. On smaller problems, SOR was faster than SVMlight and comparable or faster than SMO.


Electronic cigarette vapor disrupts key metabolic pathways in human lung epithelial cells.
The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells.


[Histomorphometric indices of the pancreas in intoxication with alcohol and narcotics].
The results of histomorphometric examinations of the pancreas in drug- and alcohol-addiction as well as in acute intoxications are described. They show that, in chronic alcoholic intoxication as compared with opiomania, there are more pronounced interlobular sclerosis and lipomatosis, which is manifested by an enlarged middle lobe of the stroma (containing fat and connective tissue fibers), by a higher density of islands of Langerhans and by their higher sectional area. Autolysis and edema of the stroma are more severe in an acute intoxication with drugs than in other cases of fatal outcome. A possibility is demonstrated to differentiate between various types of the so-called long-term exogenous intoxication and to discriminate between different types of thanatogenesis typical of various cases of acute intoxications. Data are presented that demonstrate the advantage of the quantitative analysis of histological preparations over the qualitative one.


Stem cells in prostate cancer.
Tumors constitute complex ecosystems with multiple interactions among neoplastic cells displaying various phenotypes and functions and where the tumoral niche is built with an active participation of the host environment that also impacts the malignant progression of the tumor cells. Irrespective of the cell of origin of prostate adenocarcinoma, mounting evidences support the existence of a hierarchy within neoplastic prostate cells that contributes to the heterogeneity of these tumors. At the origin of this hierarchy are small populations of tumor cells with high self-renewal potential and also capable of generating progeny tumor cells that lose self-renewal properties as they acquire more differentiated phenotypes. These cancer stem cells (CSC) depend on active gene networks that confer them with their self-renewal capacity through symmetrical divisions whereas they can also undergo asymmetrical division and differentiation either as stochastic events or in response to environmental cues. Although new experimental evidences indicate that this is can be a reversible process, thus blurring the distinction between CSCs and non-CSCs, the former are considered as the drivers of tumor growth and evolution, and thus a prime target for therapeutic intervention. Of particular importance in prostate cancer, CSCs may constitute the repository population of androgen-insensitive and chemotherapy-resistant tumor cells responsible for castration-resistant and chemotherapy-insensitive tumors, thus their identification and quantification in primary and metastatic neoplasms could play important roles in the management of this disease.


Leveraging Maslow's Hierarchy of Needs to Build Nursing's More Inclusive Future.
There is growing evidence that nurses have not seen meaningful change because of their employer's diversity, equity, inclusion, and belonging (DEIB) programs. At the same time, efforts are increasing to end DEIB programs and education in academic and work settings. These dynamics present a myriad of challenges negatively impacting any efforts to course correct and progress to build a diverse, inclusive, and pluralistic future. It is critical to urgently address these headwinds and challenges since there is evidence that discriminatory and racist acts germinate in schools of nursing. Almost half (44%) of nurses recently surveyed stated that a culture of racism in nursing schools exists; 60% of Black/African American respondents reported racism/discrimination and nearly 80% believed that more DEIB training was needed. The lack of diversity and inclusion in nursing conflicts squarely with an increasingly diverse and globalized health care consumer base. The overall goal of this article is to leverage a well-embraced framework such as Maslow's Hierarchy of Needs to generate more awareness, understanding, and acceptance of DEIB principles, which directionally sets up a positive future for everyone. Equality, diversity, equity, belonging, mattering, and human flourishing set up a more positive outlook for improved nurse and patient outcomes and for health care overall. With the harms that continue in nursing and society overall, comes emotion and discomfort that must be better understood, distributed, and not quelled. Aligning Maslow's Hierarchy of Needs and DEIB helps leaders recognize the human's needs in everyone and apply Maslow's theory to all therefore increasing inclusiveness.


Predictors of bleeding and time dependence of association of bleeding with mortality: insights from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel--Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38).
The balance between benefit (ischemia protection) and risk (bleeding) is a key consideration in choosing the intensity of antiplatelet therapy for patients with acute coronary syndromes. The goals of this analysis were to identify baseline characteristics that independently predict bleeding and to determine how bleeding events impact the subsequent mortality in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel--Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38). Multivariable Cox regression analyses adjusted for treatment, baseline, and procedural variables were used to determine the predictors for serious (TIMI major or minor) bleeding. To analyze the hazard ratio and time dependency of bleeding on mortality, we used iterative day-to-day landmark analyses after the bleed. From the 13 420 patients with acute coronary syndromes included in this analysis, 534 (4.0%) experienced a serious bleeding event. Variables with the highest strength of association with risk of serious bleeding were female sex, use of a glycoprotein IIb/IIIa inhibitor, duration of intervention, age, assignment to prasugrel, regional characteristics, admission diagnosis of ST-elevation myocardial infarction, femoral access for angiography, creatinine clearance, hypercholesterolemia, and arterial hypertension. Serious bleeding was associated with a significantly increased adjusted hazard ratio of 5.84 (95% confidence interval 4.11 to 8.29) for mortality. However, the hazard ratio did not differ statistically from baseline risk by 40 days after the bleeding event. The major predictors of serious bleeding were a combination of patient and procedural characteristics and antiplatelet therapies. Although serious bleeding was strongly associated with mortality within the first month of the bleeding event, this association was not significant beyond 40 days. http://www.clinicaltrial.gov. Unique identifier NCT00097591.


Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality.
There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA2 group IIA (sPLA2-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated sPLA2-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA2-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator-based (LASSO-based) regression analysis additionally identified sPLA2-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma sPLA2-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies sPLA2-IIA as a therapeutic target to reduce COVID-19 mortality.


Sensory habituation of auditory receptor neurons: implications for sound localization.
Auditory receptor neurons exhibit sensory habituation; their responses decline with repeated stimulation. We studied the effects of sensory habituation on the neural encoding of sound localization cues using crickets as a model system. In crickets, Teleogryllus oceanicus, sound localization is based on binaural comparison of stimulus intensity. There are two potential codes at the receptor-neuron level for interaural intensity difference: interaural difference in response strength, i.e. spike rate and/or count, and interaural difference in response latency. These are affected differently by sensory habituation. When crickets are stimulated with cricket-song-like trains of sound pulses, response strength declines for successive pulses in the train, and the decrease becomes more pronounced as the stimulus intensity increases. Response decrement is thus greater for receptors serving the ear ipsilateral to the sound source, where intensity is higher, resulting in a decrease in the interaural difference in response strength. Sensory habituation also affects response latency, which increases for responses to successive sound pulses in the stimulus train. The change in latency is independent of intensity, and thus is similar for receptors serving both ears. As a result, interaural latency difference is unaffected by sensory habituation and may be a more reliable cue for sound localization.