Quercetin ameliorates ferroptosis of rat cardiomyocytes via activation of the SIRT1/p53/SLC7A11 signaling pathway to alleviate sepsis‑induced cardiomyopathy.
Sepsis‑induced cardiomyopathy (SIC) is a manifestation of multiple organ failure as a result of sepsis and is a serious threat to life. Here, the effect and mechanisms of quercetin (QUE) in SIC were assessed. It was found that patients with SIC expressed lower serum levels of glutathione peroxidase 4 (GPX4) and SIRT1 but higher levels of CK‑MB, cTnI, TNF‑α, and IL‑6 compared with healthy individuals. A dose of 80 µM QUE increased the viability and reduced the ferroptosis of H9C2 cells treated with 1.0 µg/ml LPS in vitro. The administration of QUE decreased the levels of MDA, NADPH, lipid peroxidation and cytoplasmic cytochrome C and upregulated the levels of GSH and TOM 20, thus exerting an anti‑oxidative effect via mediating SIRT1 expression. It also activated the SIRT1/p53/SLC7A11 signaling pathway to reduce cellular Fe2+ and PTGS2 levels, decreased cell apoptosis rate, and upregulated the levels of GPX4 and ferritin to inhibit ferroptosis of H9C2 cells in vitro. Injection of QUE into rats activated the SIRT1/p53/SLC7A11 signaling pathway, reduced the levels of CK‑MB, cTnI, inflammatory cell infiltration, MDA, NADPH, cytoplasmic cytochrome C, cellular Fe2+, and PTGS2 but upregulated the levels of GSH, TOM 20, GPX4, and ferritin to alleviate SIC in a dose‑dependent manner in vivo. To conclude, QUE exerted an anti‑ferroptotic effect via activation of the SIRT1/p53/SLC7A11 signaling pathway to dampen SIC both in vivo and in vitro. These findings highlighted a potential therapeutic strategy for the management of SIC.


Behavioral effects of the dopamine autoreceptor agonist PD 128483 alone and in combination with cocaine.
Many of the behavioral effects of cocaine are thought to be mediated via dopamine (DA) reuptake inhibition and a subsequent increase in DA activity. As a DA agonist with selectivity for autoreceptors, PD 128483 has behavioral effects consistent with decreased DA neurotransmission and might be expected to attenuate the behavioral effects of cocaine. The present study was designed to evaluate PD 128483 ((+)-4,5,5a,6,7,8-hexahydro-6-methyl-thiazolo[4,5-f]quinoline-2-amine) alone and in combination with cocaine in three behavioral paradigms. One group of rhesus monkeys (n = 7) was allowed to self-administer cocaine (0.03 or 0.1 mg/kg/injection i.v., fixed-ratio 10, 2 hr/day) in baseline sessions. When behavior was stable, PD 128483 (0.01-0.3 mg/kg/injection i.v.) was made available for self-administration, and failed to maintain responding in three of four monkeys tested. PD 128483 (1.0-10.0 mg/kg i.m.) decreased cocaine self-administration in all four monkeys tested when given before cocaine availability. Another group of monkeys (n = 4) was trained to discriminate cocaine (0.2 or 0.4 mg/kg i.m.) from saline in a two-lever, food-reinforced drug discrimination paradigm. High doses of PD 128483 (3.2-12.8 mg/kg i.m.) substituted for cocaine as a discriminative stimulus in three of four monkeys. Administered in combination with cocaine, PD 128483 had little effect on the cocaine discriminative stimulus up to doses which decreased response rate. PD 128483 (1.0-2.0 mg/kg i.p.) decreased milk intake in rats (n = 9) and, when given in combination with cocaine, shifted the cocaine dose-response function (4.0-16.0 mg/kg i.p.) to the left.(ABSTRACT TRUNCATED AT 250 WORDS)


In Situ Synthesis and Single Crystal Synchrotron X-ray Diffraction Study of ht-Sn3Sb2: An Example of How Complex Modulated Structures Are Becoming Generally Accessible.
Recent developments in X-ray sources and detectors and the parallel development of software for nonstandard crystallography has made analysis of very complex structural problems accessible to nonexperts. Here, we report the successful solution of the structure of ht-Sn3Sb2, an analysis that presents several challenges but that is still manageable in a relatively straightforward way. This compound exists only in a narrow temperature regime and undergoes an unquenchable phase transformation on cooling to room temperature; it contains two elements with close to identical scattering factors, and the structure is incommensurately modulated with four symmetry dependent modulation wave vectors. In this study, an attempt was first made to synthesize the title compound by in-house crystal growth in the stability region of ht-Sn3Sb2, followed by cooling to room temperature. This is known to produce mutiply twinned stistaite and elemental tin, and this sample, freshly prepared, was then reheated in situ at the single crystal materials beamline Crystal at the synchrotron Soleil. This method was unsuccessful as reheating the sample led to loss of Sn from stistaite as revealed by a change in the measured modulation wave vector. The compound was instead successfully synthesized in situ at the beamline by the topochemical reaction of single crystalline stistaite and liquid tin. A well-formed crystal of stistaite was enclosed in a quartz capillary together with a large excess of tin and heated above the melting point of tin but below the melting point of ht-Sn3Sb2. The structure was probed by sychrotron X-ray diffraction using a wavelength close to the absorption edge of Sn to maximize elemental contrast. In the diffraction patterns, first order satellites were observed, making the structure of ht-Sn3Sb2 incommensurately modulated. Further analysis exposes four q-vectors running along the body diagonals of the cubic unit cell (q1' = α α α, q2' = -α α -α, q3' = -α -α α, q4' = α -α -α). To facilitate the analysis, the q vectors were instead treated as axial (q1 = α 0 0, q2 = 0 α 0, q3 = 0 0 α) and an F-type extinction condition for satellites was introduced so that only reflections with hklmnp, mnp all odd or all even, were considered. Further, the modulation functions F(qi) were set to zero, and only modulation functions of the type F(qi') were refined. The final model uses the four modulation functions, F(q1'), F(q2'), F(q3'), and F(q4'), to model occupancy Sn/Sb and positional modulation. The model shows a structure that comprises small NaCl type clusters, typically 7 × 7 × 7 atoms in extension, interspersed between single layers of elemental tin. The terminating layers of tin are slightly puckered, emulating an incipient deformation toward the structure of the layers perpendicular to the [001] direction in elemental tin. It is notable that this model is complementary to that of stistaite. In stistaite, two-dimensionally infinite slabs of rock salt are interspersed between layers of antimony along the trigonal [001] direction, so that the terminating Sb layers are the puckered bilayers typical for elemental Sb. Since all modulation functions are simple first-order harmonics, the structural model describes a locally disordered and most probably dynamic ordering.


Amphotericin B toxicity as related to the formation of oxidatively modified low-density lipoproteins.
The effect of amphotericin B on the oxidation and degradation of low- and high-density lipoproteins was investigated by UV-vis spectroscopy, electron microscopy, electrophoresis, and size-exclusion chromatography. Two formulations of the drug were used: the commercial Fungizone and a new, less toxic, liposomal formulation, AmBisome. It was shown that Fungizone strongly enhanced the oxidative deformation of low-density lipoprotein structure while AmBisome did not bind to this lipoprotein fraction and did not affect its oxidation. It was shown that amphotericin B contained in Fungizone extracted cholesterol from low-density lipoproteins which sensitized them to oxidation. Both formulations of amphotericin B studied here did not bind to high-density lipoprotein and did not affect the process of its oxidation.


Direct Cyanine-dUTP Labeling of RNA for Microarrays.
This is the simplest method to label RNA for use in expression analysis. RNA is reverse-transcribed using both oligo(dT) and random hexamers as primers. The random hexamers improve overall efficiency of labeling, especially at the 5' end of the RNA. Fluorescently labeled dUTP is incorporated into the cDNA. After reverse transcription, the RNA is degraded, and the labeled cDNA is purified from unincorporated Cy dyes. Finally, samples labeled with Cy3 and Cy5 dyes are mixed and combined with blocking nucleotides and used for hybridization.


Cytological Characterization of Anamorphic Fungus Lecanicillium pui and Its Relationship with Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes).
Ophiocordyceps sinensis (syn. Cordyceps sinensis), one of the most valuable medicinal mushrooms, has great economic importance on the Tibetan Plateau. We isolated an anamorphic fungus Lecanicillium pui from natural O. sinensis specimens and found that the optimal temperature for its culture on potato dextrose agar media was 25°C. Cell ultrastructure in L. pui hyphae and spores was characterized by transmission electron microscopy, and it was observed that some primary organelles showed the typical fungal features. Five chemical elements were determined in this fungus and niobium was discovered for the first time even with trace amounts. A species-specific method, nested polymerase chain reaction, was established to investigate the colonization of this fungus. Thus, the extensive distribution of L. pui on O. sinensis, in the shape of hyphae or mycelia, suggested that it may have subtle and chronic effects on the growth of the O. sinensis teleomorphic stage. These findings provide a potential reference, in the view of microbial ecology, for the study on the occurrence and mechanism of development of O. sinensis.


Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation.
Evaluation of endovascular therapies for cerebral vasospasm (CVS) documented in the DeGIR registry from 2018-2021 to analyse the current clinical care situation in Germany. Retrospective analysis of the clinical and procedural data on endovascular spasm therapies (EST) documented anonymously in the DeGIR registry. We analysed: pre-interventional findings of CTP and consciousness; radiation dose applied, interventional-technical parameters (local medication, devices, angiographic result), post-interventional symptoms, complications and mortality. 3584 patients received a total of 7628 EST (median age/patient: 53 [range: 13-100, IQR: 44-60], 68.2 % women) in 91 (2018), 92 (2019), 100 (2020) and 98 (2021) centres; 5388 (70.6 %) anterior circulation and 378 (5 %) posterior circulation (both involved in 1862 cases [24.4 %]). EST was performed once in 2125 cases (27.9 %), with a mean of 2.1 EST/patient. In 7476 times, purely medicated EST were carried out (nimodipine: 6835, papaverine: 401, nitroglycerin: 62, other drug not specified: 239; combinations: 90). Microcatheter infusions were documented in 1132 times (14.8 %). Balloon angioplasty (BA) (additional) was performed in 756 EST (9.9 %), other mechanical recanalisations in 154 cases (2 %) and stenting in 176 of the EST (2.3 %). The median dose area product during ET was 4069 cGycm² (drug: 4002/[+]BA: 8003 [p < 0.001]). At least 1 complication occurred in 95 of all procedures (1.2 %) (drug: 1.1 %/[+]BA: 4.2 % [p < 0.001]). Mortality associated with EST was 0.2 % (n = 18). After EST, overall improvement or elimination of CVS was found in 94.2 % of cases (drug: 93.8 %/[+]BA: 98.1 % [p < 0.001]). In a comparison of the locally applied drugs, papaverine eliminated CVS more frequently than nimodipine (p = 0.001). EST have a moderate radiation exposure and can be performed with few complications. Purely medicated EST are predominantly performed, especially with nimodipine. With (additional) BA, radiation exposure, complication rates and angiographic results are higher or better. When considering drug EST alone, there is evidence for an advantage of papaverine over nimodipine, but a different group size has to be taken into account. In the analysis of EST, the DeGIR registry data are suitable for answering more specific questions, especially due to the large number of cases; for this purpose, further subgroupings should be sought in the data documentation. · In Germany, there are currently no guidelines for the endovascular treatment of cerebral vasospasm following spontaneous subarachnoid hemorrhage.. · In addition to oral nimodipine administration endovascular therapy is used to treat cerebral vasospasm in most hospitals.. · This is the first systematic evaluation of nationwide registry data on endovascular treatment of cerebral vasopasm in Germany.. · This real-world data shows that endovascular treatment for cerebral vasospasm has a moderate radiation exposure and can be performed with few complications overall. With (additional) balloon angioplasty, radiation exposure, complication rates and angiographic therapy results are higher or better.. · Neumann A, Weber W, Küchler J et al. Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. Fortschr Röntgenstr 2023; 195: 1018 - 1026.


The Relationship Between Chronic Pain and Neurocognitive Function: A Systematic Review.
Understanding the relationship between chronic pain and neurocognition has important implications for the assessment and treatment of patient experiencing pain. This paper provides an overview of the current literature examining the neurocognition-chronic pain relationship and suggests future avenues of research, along with a discussion of clinical implications of the literature findings. Consideration of potential moderators and mediators of this relationship, as well as a brief discussion of the importance of future research in special populations at particular risk for these problems, are also a focus of this paper. This systematic review summarizes the findings of clinical studies in which neurocognitive performance was measured in chronic pain samples. A literature search led to the inclusion of 53 articles in the review. Studies of neurocognitive performance in clinical chronic pain samples support a relationship between chronic pain and neurocognitive abnormalities, particularly on tests of memory, attention, and processing speed, with mixed data regarding executive functioning. Several factors may moderate or mediate the relationship between chronic pain and neurocognitive functioning, including mood symptoms, medication side effects, and intensity and/or chronicity of pain. Limitations in the literature include a paucity of methodologically rigorous studies controlling for confounding variables (eg, opioid analgesia) and a limited number of studies examining the relationship between chronic pain and traumatic brain injury (a potential precipitant of both pain and neurocognitive impairment). Nonetheless, findings from the existing literature have significant clinical implications, including for populations with heightened risk of both pain and neurocognitive disorders.


Interactions between dietary flavonoids apigenin or luteolin and chemotherapeutic drugs to potentiate anti-proliferative effect on human pancreatic cancer cells, in vitro.
The objectives were to assess the potential of dietary flavonoids apigenin (Api) and luteolin (Lut) to enhance the anti-proliferative effects of chemotherapeutic drugs on BxPC-3 human pancreatic cancer cells and to investigate the potential molecular mechanism of action. Simultaneous treatment or pretreatment (0, 6, 24 and 42 h) of flavonoids and chemotherapeutic drugs at various concentrations (0-50 μM) were assessed using the MTS cell proliferation assay. Simultaneous treatment with either flavonoid (13, 25 or 50 μM) and chemotherapeutic drugs 5-fluorouracil (5-FU, 50 μM) or gemcitabine (Gem, 10 μM) for 60 h resulted in mostly less-than-additive effects (p<0.05). Pretreatment for 24h with 13 μM of either Api or Lut, followed by Gem for 36 h was optimal to inhibit cell proliferation. Pretreatment of cells with 11-19 μM of either flavonoid for 24h resulted in 59-73% growth inhibition when followed by Gem (10 μM, 36 h). Lut (15 μM, 24h) pretreatment followed by Gem (10 μM, 36 h), significantly decreased protein expression of nuclear GSK-3β and NF-κB p65 and increased pro-apoptotic cytosolic cytochrome c. Pretreatment of BxPC-3 human pancreatic cancer cells with low concentrations of Api or Lut effectively aid in the anti-proliferative activity of chemotherapeutic drugs.


Levels and risk factors for mortality in infants with birth weights between 500 and 1,800 grams in a developing country: a hospital based study.
To determine levels of mortality and risk factors for mortality in infants born with birth weights below 1,800 gms. Prospective descriptive study. Harare Central Hospital in Zimbabwe. All infants born and admitted to Harare Hospital Neonatal Unit between January and May 2000, with birth weight between 500 gms and 1,800 gms. Mothers' age, parity, booking status, mode of delivery, infants' sex, birth weight, use of intensive care, outcome in hospital, age at death and age at discharge from hospital. Four hundred and ninety infants were studied. In hospital, the fatality rate was 39.4%. Only 49.4% of mothers had received antenatal care. The median birth weight of those who died was 1,077 gms (Q1 = 500, Q3 = 1,357) while that of the discharged infants was 1,530 gms (Q1 = 850, Q3 = 1690). Risk factors for mortality were birth weight less than 1,500 gms compared to 1,500 gms or more. Odds Ratio (OR) 7.53 (95% CI = 4.66 to 12.23), breech delivery compared to vaginal delivery, OR 2.40 (95% CI = 1.28 to 4.52) and lack of antenatal care OR 1.59 (95% CI = 1.08 to 2.33). Parity, sex of infant and receiving intensive neonatal care were not significantly associated with mortality. Strategies to reduce mortality in these infants should include better access to early, high quality obstetric care and avoidance of breech delivery in preterm infants. Identification of avoidable factors leading to preterm delivery is critical.


[Diagnostic difficulties of polycystic ovarian syndrome in adolescent girls].
Polycystic ovary syndrome is a heterogeneous disorder characterized by chronic ovulatory dysfunction and hyperandrogenism. It occurs in 6-8% of the female population in the reproductive age. The syndrome may be associated with various metabolic disorders which may impair the quality of life and life expectancy of patients. The diagnosis in adults is usually established by the presence of three criteria. Polycystic ovary syndrome can be also identified in adolescent girls. Although the clinical, hormonal and metabolic features are similar to those found in adult women, it may be difficult to distinguish normal adolescents from those with polycystic ovary syndrome. Irregular menstruation, anovulatory cycles, and acne are not uncommon in adolescents, and polycystic ovary syndrome may mimic physiological anovulation in adolescents. There is a high probability of polycystic ovary syndrome if anovulatory cycles persist for more than 2 years. The diagnosis of polycystic ovary syndrome in adolescents may require a unique set of criteria, however, there are no generally accepted recommendations for the diagnostic work-up. The authors propose that hyperandrogenemia is often the most reliable finding in this age group, and it may be prudent to define adolescent polycystic ovary syndrome according to the Rotterdam consensus criteria. Obesity in adolescent girls may increase the severity of symptoms of polycystic ovary syndrome and this underlines the importance of early diagnosis and treatment.


[Novel gene sequence variants of pbp2b in penicillin-nonsusceptible Streptococcus pneumonia isolates].
To investigate the alternations in gene/amino acid sequence of penicillin-binding protein (PBP)2b from clinical isolates of penicillin-nonsusceptible Streptococcus pneumonia (PNSP) in this region. 24 strains of Streptococcus pneumonia were collected from January to December 2006. The antibiotics susceptibility of these strains was detected. PCR amplification and direct sequencing of pbp2b genes were performed. The sequence variations of PBP genes of the PNSP in this region were studied with sequence BLAST analysis. Three prominent substitutions were common to 13 PNSP isolates with minimal inhibitory concentration (MIC) at least 0.1 mg/L. These included the replacement of Thr(445)--> Ala following the conservative motif SSN, Glu(475)-->Gly and Thr(488)-->Ala/Ser. The exchange of Glu(332)-->Gly was identified in 12 PNSP isolates of which the MIC was at least 0. 25 mg/L. Seven penicillin resistant Streptococcus pneumonia (PRSP) isolates (MIC > or = 3 mg/L) shared the amino acid substitution Ala(618)-->Gly adjacent to third conserved (KTG) motif and the PBP2b sequences of seven PRSP isolates were classified within Baek's group II and were very similar to those of the Korean J77 isolate. Novel gene and amino acid sequence variants in isolate 14, 15, 8, 11 and 24 was identified in this study and these gene sequences have been deposited in the GenBank database and assigned accession no. EU035970, EU056919, EU056920, EU056921 and EU106886. Analysis of pbp2b genes revealed highly similar patterns of nucleotide and amino acid sequence variation among most resistant isolates, while penicillin intermediate Streptococcus pneumonia might be associated with novel gene sequence variants.


Out of pocket expenses in obsessive compulsive disorder.
Despite anecdotal evidence that the out of pocket costs of OCD can be substantial in some cases, there is no evidence on how many people they affect, or the magnitude of these costs. This paper explores the type and quantity of out of pocket expenses reported by a large sample of adults with OCD. Data on out of pocket expenses were collected from participants taking part in the OCTET multi-centre randomised controlled trial. Participants were aged 18+, meeting DSM-IV criteria for OCD, and scoring 16+ on the Yale Brown Obsessive Compulsive Scale. Individual-level resource use data including a description and estimated cost of out of pocket expenses were measured using an adapted version of the Adult Service Use Schedule (AD-SUS): a questionnaire used to collect data on resource use. Forty-five percent (208/465) reported out of pocket expenses due to their OCD. The mean cost of out of pocket expenses was £19.19 per week (SD £27.56 SD), range £0.06-£224.00. Future economic evaluations involving participants with OCD should include out of pocket expenses, but careful consideration of alternative approaches to the collection and costing of this data is needed.


Effect of prenatal exposure to maternal cortisol and psychological distress on infant development in Bengaluru, southern India: a prospective cohort study.
The mental health status of a pregnant woman and its consequent impact on foetal well being is not given much importance compared to the risk imposed by obstetric complications and medical conditions. Maternal psychological distress is a major public health problem and needs timely detection and intervention to prevent any adverse pregnancy outcome. There is ample evidence from literature that justifies the association of prenatal maternal mental stress and elevated cortisol with delayed infant motor and cognitive development; evidence from India being rather limited. The study aim is to prospectively assess the association of maternal psychological distress and cortisol level with motor and cognitive development of the infant. A sample of 2612 eligible pregnant women who have been registered for antenatal care at selected public sector hospitals in Bengaluru will be recruited after obtaining written informed consent. They will be assessed for the presence of maternal psychological distress in the form of depression and anxiety using appropriate scales and saliva samples will be collected for cortisol estimation during early, mid and late pregnancy. Follow up visits after delivery will be done on day 10, 3 months, 8 months and 12 months. The Bayley Scales of Infant and Toddler Development [BSID] (Third edition) will be used to measure both motor and mental milestones in terms of Psychomotor Development Index (PDI) and Mental Development Index (MDI). Logistic regression model will be used to determine the association between the exposure variables and outcomes which will be reported as Odd's Ratio (OR) and 95% confidence intervals (CI). Our study findings could add to the growing evidence that maternal psychological distress during pregnancy adversely influences growth and development in the offspring and subsequent development of the child. While maternal anxiety and depression can be measured by using self reporting instruments, estimation of maternal endogenous cortisol levels could serve as a biomarker of prenatal psychological stress. Findings from this study could be used to focus upon the burden of mental health problems during pregnancy and to consider steps to scale up prenatal mental health services in health care settings.


[Receptor-mediated endocytosis induced macrophage cytosolic acidification and exocytosis].
The effects of Con A, WGA, Zymosan A on macrophage cytosolic pH and outflow of lysosomal content through exocytosis were studied with SNAFL-calcein and FITC-Dextran on ACAS570. The results showed all three ligands could induce macrophage cytosolic acidification in about 10 min and kept at the same level hereafter; outflow of lysosomal fluorescent probe through exocytosis appeared in 15-20 min. In resting conditions, macrophage lysosomes mainly distributed in cell center; after stimulated for 15 min by three ligands, the number of lysosomes increased in membrane periphery, in 25-30 min lysosomes moved back toward cell center. We proposed that ligands induced lysosomal pH rises was a basic factor for outflow of lysosomal content through exocytosis, cytosolic acidification inhibited receptor-mediated endocytosis. Cytosolic acidification and outflow of lysosomal content through exocytosis were the results of cellular self-regulation and self-protection during receptor-mediated endocytosis.


Impact of Vitamin A and Carotenoids on the Risk of Tuberculosis Progression.
Low and deficient levels of vitamin A are common in low- and middle-income countries where tuberculosis burden is high. We assessed the impact of baseline levels of vitamin A and carotenoids on tuberculosis disease risk. We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary tuberculosis case patients in Lima, Peru. We defined case patients as human immunodeficiency virus (HIV)-negative HHCs with blood samples in whom tuberculosis disease developed ≥15 days after enrollment of the index patient. For each case patient, we randomly selected 4 controls from among contacts in whom tuberculosis disease did not develop, matching for sex and year of age. We used conditional logistic regression to estimate odds ratios for incident tuberculosis disease by vitamin A and carotenoids levels, controlling for other nutritional and socioeconomic factors. Among 6751 HIV-negative HHCs with baseline blood samples, 192 had secondary tuberculosis disease during follow-up. We analyzed 180 case patients with viable samples and 709 matched controls. After controlling for possible confounders, we found that baseline vitamin A deficiency was associated with a 10-fold increase in risk of tuberculosis disease among HHCs (adjusted odds ratio, 10.53; 95% confidence interval, 3.73-29.70; P < .001). This association was dose dependent, with stepwise increases in tuberculosis disease risk with each decreasing quartile of vitamin A level. Vitamin A deficiency strongly predicted the risk of incident tuberculosis disease among HHCs of patients with tuberculosis. Vitamin A supplementation among individuals at high risk of tuberculosis may provide an effective means of preventing tuberculosis disease.


Ferroelectric tunnel junctions with graphene electrodes.
Polarization-driven resistive switching in ferroelectric tunnel junctions (FTJs)--structures composed of two electrodes separated by an ultrathin ferroelectric barrier--offers new physics and materials functionalities, as well as exciting opportunities for the next generation of non-volatile memories and logic devices. Performance of FTJs is highly sensitive to the electrical boundary conditions, which can be controlled by electrode material and/or interface engineering. Here, we demonstrate the use of graphene as electrodes in FTJs that allows control of interface properties for significant enhancement of device performance. Ferroelectric polarization stability and resistive switching are strongly affected by a molecular layer at the graphene/BaTiO3 interface. For the FTJ with the interfacial ammonia layer we find an enhanced tunnelling electroresistance (TER) effect of 6 × 10(5)%. The obtained results demonstrate a new approach based on using graphene electrodes for interface-facilitated polarization stability and enhancement of the TER effect, which can be exploited in the FTJ-based devices.


Electromagnetic torque measurements in DIII-D using internal/external magnetic field decomposition.
Given spatially resolved measurements of normal and tangential components of the magnetic field just outside the surface of a magnetically confined plasma, the field at the measurement location can be uniquely decomposed into contributions from the plasma and from external sources. This principle allows direct measurement of the electromagnetic torque on the plasma without knowledge of the distribution of the internal and external currents, similar to the more well-known formalism using the Maxwell stress tensor. The internal/external field decomposition also enables a mixed approach that incorporates any explicitly known current distributions (e.g., from non-axisymmetric coils). We discuss the requirements and limitations of such an approach to torque measurements. Experimental measurements of the torque evolution as a rotating tearing mode locks to the wall in the DIII-D tokamak are consistent with a simple model.


Standardization and evaluation of the CAMP reaction for the prompt, presumptive identification of Streptococcus agalactiae (Lancefield group B) in clinical material.
Primary cultures of clinical material were screened for the presence of colonies suspected of being Streptococcus agalactiae (Lancefield group B). Sixty-three such cultures and 108 other isolates of beta-hemolytic streptococci (groups A, C, and G), encountered during the first 3 months of the investigation, were studied by Lancefield grouping, sodium hippurate hydrolysis, and a standardized CAMP test. All streptococci were inoculated perpendicularly to streaks of a beta-toxin-producing staphylococcus on sheep blood agar plates and incubated aerobically in a candle jar and anaerobically at 37 C. Plates were examined after 5 to 6 and 18 h of incubation. The production of a distinct "arrowhead" of hemolysis was indicative of a positive CAMP reaction. All group B streptococci produced a positive CAMP reaction in the candle jar or anaerobically, usually within 5 to 6 h, and aerobically after 18 h of incubation. All group A streptococci produced a positive reaction only under anaerobic conditions. Groups C and G streptococci were negative under all atmospheres. The CAMP reaction is a prompt and reliable procedure for the presumptive identification of group B streptococci when a candle jar atmosphere is used during incubation.


Validation of a Point-of-Care Quantitative Equine IgG Turbidimetric Immunoassay and Comparison of IgG Concentrations Measured with Radial Immunodiffusion and a Point-of-Care IgG ELISA.
Point-of-care (POC) diagnostic tests with good sensitivity and specificity are needed for diagnosing failure of transfer of passive immunity (FTPI) in foals. Turbidimetric immunoassays (TIA) have these characteristics and provide quantitative results. A commercially available TIA-based POC test (POC-TIA) has not been validated in horses. To validate a POC-TIA and compare results of POC-TIA, a POC-ELISA, and radial immunodiffusion (RID). Heparinized blood samples (n = 127) from 48 hospitalized foals (<12 hour to 48 days). Prospective validation study. IgG concentrations were measured using RID (gold standard), POC-TIA, and POC-ELISA. Agreement between assays was assessed using Bland-Altman analysis. Sensitivity and specificity were calculated using ROC curves. Inter- and intra-assay coefficients of variation (CVs) and linearity were evaluated for POC-TIA. The mean bias (95% limits of agreement) between RID and POC-TIA was -4 (-185 to 176), 27 (-201 to 255), and 308 (-377 to 993) mg/dL for samples with IgG concentrations of <400, 400-800, and >800 mg/dL, respectively. Sensitivity and specificity at optimal cutoff were 94 and 100% for the POC-TIA and 94 and 100% for the POC-ELISA to detect IgG <400 mg/dL, and 85 and 87% (POC-TIA) and 69 and 79% (POC-ELISA) to detect IgG ≤800 mg/dL. Intra- and interassay CVs for POC-TIA ranged between 1.6-3.8 and 11.9-18.8%, respectively. Linearity of the dilution series was preserved (R2 > 0.96). The POC-TIA provided unambiguous results and had sufficient sensitivity, specificity, accuracy, and precision to be used as an alternative to other POC tests to assess FTPI in foals.


Vitamin D Deficiency and a Blunted Parathyroid Hormone Response in Children with Attention-Deficit/Hyperactivity Disorder.
Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neuropsychiatric disorder of childhood. The etiopathogenesis of ADHD has not been fully defined. Recent evidence has suggested a pathophysiological role of vitamin D deficiency in ADHD. In this study, we evaluated the serum levels of 25-hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), calcium (Ca), phosphate (P), and alkaline phosphatase (ALP) in children with ADHD. The study group consisted of 105 children diagnosed with ADHD according to DSM-IV-TR criteria. A control group, matched for age and gender, was composed of 95 healthy children. Venous blood samples were collected, and 25(OH)D, PTH, Ca, P, and ALP levels were measured. The mean serum 25(OH)D, Ca, and P levels of the children with ADHD were significantly lower than those of the healthy controls. There were no significant differences between the groups regarding PTH and ALP. Serum PTH levels were found to be normal, but vitamin D deficiency, hypocalcemia, and hypophosphatemia were observed in children with ADHD. There was no correlation between serum PTH and Ca levels in children with ADHD, whereas, there was a negative correlation between serum PTH and Ca levels in healthy controls. There was no correlation between serum 25(OH)D and PTH levels in children with ADHD, whereas, there was a negative correlation between serum 25(OH)D and PTH levels in healthy controls. There were no significant differences in all parameters' levels among the subtypes of ADHD. The findings suggest that ADHD is associated with vitamin D deficiency, blunted PTH response, and impaired Ca homeostasis in children.


Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis.
Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses. USC-Exos were isolated from the conditioned media of USCs and identified by transmission electron microscopy and flow cytometry. A series of functional assays in vitro were performed to assess the effects of USC-Exos on the activities of wound healing-related cells. Protein profiles in USC-Exos and USCs were examined to screen the candidate molecules that mediate USC-Exos function. The effects of USC-Exos on wound healing in streptozotocin-induced diabetic mice were tested by measuring wound closure rates, histological and immunofluorescence analyses. Meanwhile, the role of the candidate protein in USC-Exos-induced regulation of angiogenic activities of endothelial cells and diabetic wound healing was assessed. Results: USCs were positive for CD29, CD44, CD73 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteoblasts, adipocytes and chondrocytes. USC-Exos exhibited a cup- or sphere-shaped morphology with a mean diameter of 51.57 ± 2.93 nm and positive for CD63 and TSG101. USC-Exos could augment the functional properties of wound healing-related cells including the angiogenic activities of endothelial cells. USC-Exos were enriched in the proteins that are involved in regulation of wound healing-related biological processes. Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC-Exos-induced promotion of angiogenic responses of cultured endothelial cells, as well as angiogenesis and wound healing in diabetic mice. Conclusion: Our findings suggest that USC-Exos may represent a promising strategy for diabetic soft tissue wound healing by promoting angiogenesis via transferring DMBT1 protein.


Mechanistic Basis for Red Light Switching of Azonium Ions.
Azonium ions formed by the protonation of tetra-ortho-methoxy-substituted aminoazobenzenes photoisomerize with red light under physiological conditions. This property makes them attractive as molecular tools for the photocontrol of physiological processes, for example, in photopharmacology. However, a mechanistic understanding of the photoisomerization process and subsequent thermal relaxation is necessary for the rational application of these compounds as well as for guiding the design of derivatives with improved properties. Using a combination of sub-ps/ns transient absorption measurements and quantum chemical calculations, we show that the absorption of a photon by the protonated E-H+ form of the photoswitch causes rapid (ps) isomerization to the protonated Z-H+ form, which can also absorb red light. Proton transfer to solvent then occurs on a microsecond time scale, leading to an equilibrium between Z and Z-H+ species, the position of which depends on the solution pH. Whereas thermal isomerization of the neutral Z form to the neutral E form is slow (∼0.001 s-1), thermal isomerization of Z-H+ to E-H+ is rapid (∼100 s-1), so the solution pH also governs the rate at which E/E-H+ concentrations are restored after a light pulse. This analysis provides the first complete mechanistic picture that explains the observed intricate photoswitching behavior of azonium ions at a range of pH values. It further suggests features of azonium ions that could be targeted for improvement to enhance the applicability of these compounds for the photocontrol of biomolecules.


Feasibility of Social Media-Based Recruitment and Perceived Acceptability of Digital Health Interventions for Caregivers of Justice-Involved Youth: Mixed Methods Study.
Caregiver involvement is critical for supporting positive behavioral health and legal outcomes for justice-involved youth; however, recruiting this population into clinical research studies and engaging them in treatment remain challenging. Technology-based approaches are a promising, yet understudied avenue for recruiting and intervening with caregivers of justice-involved youth. This mixed methods study aimed to assess the feasibility of recruiting caregivers of justice-involved youth using social media into clinical research and to understand caregivers' perceptions of the acceptability of digital health interventions. Caregivers of justice-involved youth were recruited through paid Facebook advertisements to participate in a Web-based survey. Advertisement design was determined using Facebook A/B split testing, and the advertisement with the lowest cost per link click was used for the primary advertisement campaign. Survey participants were offered the option to participate in a follow-up qualitative phone interview focused on the perceived feasibility and acceptability of digital health interventions. Facebook advertisements were successful in quickly recruiting a diverse set of caregivers (80/153, 52.3% female; mean age 43 years, SD 7; 76/168, 45.2% black, 34/168, 20.2% white, and 28/168, 16.7% Latinx; and 97/156, 62.2% biological parents); cost per click was US $0.53, and conversion rate was 11.5%. Survey participants used multiple social media platforms; 60.1% (101/168) of the participants indicated they would participate in a digital health intervention for caregivers of justice-involved youth. Survey respondents' most preferred intervention was supportive and motivational parenting messages via SMS text message. Of the survey respondents, 18 completed a phone interview (12/18, 67% female; mean age 45 years, SD 10; 10/18, 56% black, 7/18, 39% white, and 1/18, 6% Latinx; and 16/18, 89% biological parents). Interview participant responses suggested digital health interventions are acceptable, but they expressed both likes (eg, alleviates barriers to treatment access) and concerns (eg, privacy); their most preferred intervention was video-based family therapy. Recruiting and intervening with caregivers of justice-involved youth through social media and other digital health approaches may be a feasible and acceptable approach to overcoming barriers to accessing traditional in-person behavioral health care.


Ahp2 (Hop2) function in Arabidopsis thaliana (Ler) is required for stabilization of close alignment and synaptonemal complex formation except for the two short arms that contain nucleolus organizer regions.
A cytological comparative analysis of male meiocytes was performed for Arabidopsis wild type and the ahp2 (hop2) mutant with emphasis on ahp2's largely uncharacterized prophase I. Leptotene progression appeared normal in ahp2 meiocytes; chromosomes exhibited regular axis formation and assumed a typical polarized nuclear organization. In contrast, 4',6'-diamidino-2-phenylindole-stained ahp2 pachytene chromosome spreads demonstrated a severe reduction in stabilized pairing. However, transmission electron microscopy (TEM) analysis of sections from meiocytes revealed that ahp2 chromosome axes underwent significant amounts of close alignment (44% of total axis). This apparent paradox strongly suggests that the Ahp2 protein is involved in the stabilization of homologous chromosome close alignment. Fluorescent in situ hybridization in combination with Zyp1 immunostaining revealed that ahp2 mutants undergo homologous synapsis of the nucleolus-organizer-region-bearing short arms of chromosomes 2 and 4, despite the otherwise "nucleus-wide" lack of stabilized pairing. The duration of ahp2 zygotene was significantly prolonged and is most likely due to difficulties in chromosome alignment stabilization and subsequent synaptonemal complex formation. Ahp2 and Mnd1 proteins have previously been shown, "in vitro," to form a heterodimer. Here we show, "in situ," that the Ahp2 and Mnd1 proteins are synchronous in their appearance and disappearance from meiotic chromosomes. Both the Ahp2 and Mnd1 proteins localize along the chromosomal axis. However, localization of the Ahp2 protein was entirely foci-based whereas Mnd1 protein exhibited an immunostaining pattern with some foci along the axis and a diffuse staining for the rest of the chromosome.


Treatment of tumors involving the anterior cranial fossa.
The potential for a tumor of the upper face, either malignant or nonmalignant, to involve the anterior cranial base is often not appreciated. This leads to inadequate preoperative investigation and to surgery performed by the head and neck surgeon without the help of the neurosurgeon. In this way, complete tumor resection may be compromised or delayed. Neither of these situations is desirable. If the potential for anterior cranial fossa invasion is recognized, there should be prior consultation with the neurosurgeon and a combined operative procedure. Exposure of these lesions has considerably improved with experience in congenital craniofacial deformities: this will allow en bloc resection of most pathologies. Immediate reconstruction after resection of nonmalignant tumors is advocated, but in aggressive--particularly in recurrent--malignancies, delayed reconstruction is advised. Careful combined follow-up with frequent blind biopsies should be carried out as indicated.


Reinforced microextraction of polycyclic aromatic hydrocarbons from polluted soil samples using an in-needle coated fiber with polypyrrole/graphene oxide nanocomposite.
The surface of a stainless-steel wire was platinized using electrophoretic deposition method to create a high-surface-area with porous and cohesive substrate. The platinized fiber was coated by the polypyrrole/graphene oxide nanocomposite by electropolymerization and accommodated into a stainless-steel needle to fabricate an in-needle coated fiber. The developed setup was coupled to gas chromatography with flame ionization detection and applied to extract and determine polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, fluoranthene, and pyrene) in complicated solid matrices, along with reinforcement of the extraction by cooling the sorbent, using liquid carbon dioxide. To obtain the best extraction efficiency, the important experimental variables including extraction temperature and time, temperature of cooled sorbent, sampling flow rate, and desorption condition were studied. Under the optimal condition, limits of detection for five studied analytes were in the range of 0.2-0.8 pg/g. Linear dynamic ranges for the calibration curves were found to be in the range of 0.001-1000 ng/g. Relative standard deviations obtained for six replicated analyses of 1 ng/g of analytes were 4.9-13.5%. The reinforced in-needle coated fiber method was successfully applied for the analysis of polycyclic aromatic hydrocarbons in contaminated soil samples.


Demographic and motor features associated with the occurrence of neuropsychiatric and sleep complications of Parkinson's disease.
To determine whether four key neuropsychiatric and sleep related features associated with Parkinson's disease (PD) are associated with the motor handicap and demographic data. The growing number of recognised non-motor features of PD makes routine screening of all these symptoms impractical. Here, we investigated the hypothesis that standard demographic data and the routine assessment of motor signs is associated with the presence of dementia, psychosis, clinically probable rapid eye movement (REM) sleep behavior disorder (cpRBD) and restless legs syndrome (RLS). 775 patients with PD underwent standardised assessment of motor features and the presence of dementia, psychosis, cpRBD and RLS. A stepwise feature elimination procedure with fitted logistic regression models was applied to identify which/if any combination of demographic and motor factors is associated with each of the four studied non-motor features. A within-study out-of-sample estimate of the power of the predicted values of the models was calculated using standard evaluation procedures. Age and Hoehn&Yahr (H&Y) stage were strongly associated with the presence of dementia (p value<0.001 for both factors in the final selected model) while a combination of age, disease duration, H&Y stage, dopamine agonists and catechol-O-methyltransferase (COMT) inhibitors was associated with the presence of psychosis. Disease duration and H&Y stage were the significant indicators of cpRBD, and the lack of significant motor asymmetry was the only significant feature associated with RLS-type symptoms but the evidence of association was weak. Demographic and motor features routinely collected in patients with PD can estimate the occurrence of neuropsychiatric and sleep-related features of PD.


Toxicokinetics and metabolism of pseudocumene (1,2,4-trimethylbenzene) after inhalation exposure in rats.
The objective of this study was to evaluate the toxicokinetics and metabolism of pseudocumene after inhalation exposure. Male Wistar rats were exposed to pseudocumene vapors at nominal concentrations of 25,100 or 250 ppm in the dynamic inhalation chambers for 6 h. Blood samples were collected during (between 1st and 6th h) and after exposure (betwen 6th min and 6th h). Blood concentrations of pseudocumene were estimated by gas chromatography using the headspace technique. During a six-hour exposure, the concentration of pseudocumene in blood increased rapidly within the first 2 h reaching then a plateau. The elimination of pseudocumene from blood followed an open two-compartment model. Urine samples were collected from the exposed animals, and metabolites were analyzed by gas chromatography with a flame ionization detector. Three metabolites were measured in the rat urine after hydrolysis: 3,4-dimethylbenzoic acid (3,4-DMBA), 2,4-dimethylbenzoic acid (2,4-DMBA) and 2,5-dimethylbenzoic acid (2,5-DMBA). A significant linear correlation was found between the level of exposure and the concentration of dimethylbenzoic acids. The enzyme kinetics of pseudocumene biotransformation was calculated by Lineweaver-Burk equation. Metabolic constants, Km (mg/l) and Vmax (mg/h/kg), the parameters for pseudocumene biotransformation by rats were estimated (3,4-DMBA - Km = 28, Vmax = 96; 2,4-DMBA - Km = 7, Vmax = 25; 2,5-DMBA - Km = 7, Vmax = 23).


Detection and characterisation of alloreactive T cells.
T cell alloreactivity is responsible for much of the morbidity and mortality associated with tissue transplantation and graft versus host disease. Immunoassays for ex vivo monitoring and quantitation of alloreactive T cells are being increasingly utilised to provide valuable information for individualised clinical management of transplant recipients. Here we describe detailed methodologies for both traditional and novel assays utilised for the detection, quantitation, and functional characterisation of alloreactive T cells and highlight the key advantages and disadvantages of each system.


Studies on Reliability and Measurement Error of Measurements in Medicine - From Design to Statistics Explained for Medical Researchers.
Reliability and measurement error are measurement properties that quantify the influence of specific sources of variation, such as raters, type of machine, or time, on the score of the individual measurement. Several designs can be chosen to assess reliability and measurement error of a measurement. Differences in design are due to specific choices about which sources of variation are varied over the repeated measurements in stable patients, which potential sources of variation are kept stable (ie, restricted), and about whether or not the entire measurement instrument (or measurement protocol) was repeated or only part of it. We explain how these choices determine how intraclass correlation coefficients and standard errors of measurement formulas are built for different designs by using Venn diagrams. Strategies for improving the measurement are explained, and recommendations for reporting the essentials of these studies are described. We hope that this paper will facilitate the understanding and improve the design, analysis, and reporting of future studies on reliability and measurement error of measurements.


A Comparative Study of Histopathology of Astrocytomas with Intraoperative Cytology with Special Reference to MIB-1 Labelling Index.
Although radiological imaging and surgical techniques have substantially improved, assessment of prognosis by grading astrocytoma has been challenging task for pathologists. We have tried to assess these tumours intraoperatively for rapid diagnosis. Also MIB-1Labelling index (MIB-1 LI) was done to study their proliferative activity. To compare and grade squash smear technique with histopathology to study its utility in diagnosis of astrocytomas. Further, to study correlation of various grades with their MIB-1 labelling index. This study was carried out in the Department of Pathology, SMS Medical College, Jaipur over a period of one year. Forty five cases of radiologically suspected astrocytomas were submitted for intraoperative cytology and later for histopathology. Two techniques were compared for ability to diagnose as well as grade the tumour. Also, MIB-1 LI were performed in biopsy tissue. Histopathological and immunological grades were compared. Out of 45 cases 44(97.7%) correctly diagnosed by squash smear technique. Further significant differences seen in values of MIB-1 LI of high-grade and low-grade astrocytomas. A progressive increase in the MIB-1 LI was observed with increasing grades. In grade I astrocytoma MIB-1 LI was <0.05%. In grade II astrocytoma it varied from 0.8-2.6% except in one case where it was 3.2% who presented with a recurrent mass. In grade III, MIB-1 LI was 3.5% to 7.5%. In grade IV was 10-20%. Intraoperative cytology is fairly accurate and useful in intraoperative consultation. Also, MIB-1 LI can be a useful adjunct for grading particularly in small biopsies.


Adolescent suicide: what can pediatricians do?
Suicide is a major public health concern and the second leading cause of death for adolescents. Faced with an already-high prevalence and increasing rates over the past decade, pediatricians feel inadequately prepared to manage a suicidal patient. This article will review the changing rates of suicide, discuss recent literature on risk factors, identify methods to screen for suicidal thoughts and suggest an approach to counseling a suicidal patient. Finally, there will be a brief discussion on safety planning and public health measures to help reduce suicide rates. Rates of attempted suicide and death by suicide have been increasing for more than a decade. Risk assessment of potential suicidality remains very challenging, as the risk factors are multifactorial. However, some common risk factors persist including sexual minority identification and family or personal history of mental health issues. Although keeping these and other risk factors in mind, regular screening of adolescents for depression and self-harm is important. Finally, the best safety plans and treatment methods appear to be team-based. It remains the responsibility of pediatricians to stay aware of risk factors, regularly screen adolescents and prioritize collaborative safety planning for suicidal patients.


Treatment Preferences for Toothache among Working Poor Canadians.
Working poor (WP) Canadians are those who work ≥ 20 hours/week, are not full-time students, and have annual family incomes <$34,300. They have unique vulnerabilities and face significant barriers to accessing dental care because they rarely receive employment-based dental benefits and are ineligible for publicly funded dental programs. This research aimed to understand whether WP Canadians would prefer extraction rather than tooth restoration and preservation when they have toothache. A cross-sectional stratified sampling study design and telephone survey methodology was used to collect data from a nationally representative sample of 1049 WP individuals aged 18-64 years. A pretested questionnaire included sociodemographic and self-reported oral health questions and asked participants to select their preference for maintaining versus extracting an aching tooth. By using bivariate and logistic regression analyses, we applied the Gelberg-Andersen Behavioral Model for Vulnerable Populations to understand what influences treatment preferences among this population (P ≤ .05). The majority of participants (86%) preferred to save and fill an aching tooth rather than take it out. Those who were older, partially dentate, reported a history of oral pain, had their last dental visit more than 3 years ago, or who only visited the dentist when in pain were significantly more likely to opt for tooth extraction. The majority of WP Canadians value preserving their natural dentition. Effective dental care service delivery in both private and public settings requires an understanding of the possible factors that influence WP persons' preferences for essential treatment modalities in dentistry.


Excitation transport and trapping in a synthetic chlorophyllide substituted hemoglobin: orientation of the chlorophyll S1 transition dipole.
Excitation transport in synthetic zinc chlorophyllide substituted hemoglobin has been observed by pico -second time-resolved fluorescence depolarization experiments. In this hybrid molecular system, two zinc chlorophyllide molecules are substituted into the beta-chains of hemoglobin, while deoxy hemes remain in the alpha-chains. The rate of excitation transfer between the two chlorophyllides is analyzed in terms of the distance and orientation dependences predicted by the F orster dipole-dipole theory. In this analysis, the beta-beta interchromophore geometry is assumed to be that of the deoxyhemoglobin crystal structure. When combined with steady-state fluorescence depolarization data of the complementary hybrid containing zinc chlorophyllide in the alpha-chains, these experiments provide the necessary information to determine the orientation of the S1 transition dipole moment in the zinc chlorophyllide molecule. We also find that the fluorescence lifetime of the zinc chlorophyllide is 1.42 ns when the heme is in the deoxy state but 3.75 ns when the heme is ligated to carbon monoxide. This is explained by irreversible excitation transfer from the S1 state of the zinc chlorophyllide to the lower energy excited states present in deoxy heme.


Early detection of obstructed ureter by ultrasound following renal transplantation.
Serial ultrasound examinations were carried out following 144 renal transplants. Eleven patients (8%) required surgery for ureteric obstruction and in all cases the ultrasound correctly identified the obstruction at an early stage. One false positive result was obtained with the ultrasound and this compared favourably with both the intravenous urogram (IVU) and isotope renogram. There were false positive and false negative results with both the IVU and renogram in addition to which neither of these techniques, particularly the IVU, is as simple or atraumatic for the patient as the ultrasound. Serial ultrasound examinations have a useful role in the detection of ureteric obstruction as well as being of value in the detection of perinephric fluid collections and acute rejection.


Environmental risks and public health.
There are currently a number of initiatives aimed at considering and redefining the role of environmental health. These include an effort under the auspices of the Institute of Medicine Roundtable on Environmental Health and another under the auspices of the American Schools of Public Health. Both will result in conferences to be held in the same month of the New York Academy of Sciences (NYAS) conference on "The Role of Neural Plasticity in Chemical Intolerance", for which this paper is being prepared. This questioning of our definition and of our approach to the field of environmental health is an instructive background on which to consider the issue of environmental risks and public health-the topic given to me by the organizers of the NYAS conference. My approach will be to touch on those issues related to the nervous system and to unexplained symptoms in keeping with the subject of the conference, as well as to discuss some of the broader issues surrounding environmental health.


Efficacy of varicocelectomy on semen parameters and conception rates.
Varicocele, the dilation of the pampiniform plexus of the spermatic cord. It is discovered incidentally in most patients. Symptoms vary, but its impact is especially experienced in the field of fertility and reflected in semen parameters. Varicocelectomy is a surgical approach to correct the varicocele, however, reports are conflicting regarding its success. Our aim was to evaluate the efficacy of varicocelectomy on semen parameters and conception rates in patients who underwent surgery and its association with comorbidities such as diabetes, hypertension, and obesity. This cross-sectional study included the complete medical records of 86 patients. Data collection form included the patient's age, body mass index (BMI), chronic diseases, smoking, surgical history, medication usage, and the reason for performing surgery. Presurgical and postsurgical semen parameters were evaluated 3 months before surgery and an average of 6 months postoperatively. Data were analyzed with SPSS, Chi-square test, and independent and paired t-test. No significant difference was found between primary and secondary infertility regarding semen analysis, postoperative semen analysis indicated an improvement in semen motility at 180 min with no effect on other parameters. Using spontaneous intercourse or in vitro fertilization (IVF) after varicocelectomy was significantly associated with increasing conception rates irrespective of the type of infertility. Diabetes, hypertension, BMI, and smoking did not appear to affect semen parameters. Patients who underwent varicocelectomy had improved sperm motility at 180 min and subsequently had a higher chance of successful conception either through spontaneous intercourse or IVF. Further studies are needed to understand the relationship between conception and sperm motility. Semen parameters were not affected if the patient had comorbidities such as diabetes and hypertension. Furthermore, smoking and BMI did not appear to affect the conception rate.


Dynamic Stark-Induced Coherent π-Electron Rotations in a Chiral Aromatic Ring Molecule: Application to Phenylalanine.
We present the results of a theoretical study on dynamic Stark-induced coherent π-electron rotations in a chiral aromatic ring molecule. This is an extension of our previous papers, which have been published in Mineo , H. [ Phys. Chem. Chem. Phys. 2016 , 18 , 26786 - 26795 ] and Mineo , H. [ J. Phys. Chem. Lett. 2018 , 9 , 5521 - 5526 ]. In those papers, the time-dependent Schrödinger equation was solved under a restricted condition in which a degenerate excited state should be formed at the center of the two relevant excited states by dynamic Stark effects. The dynamic Stark-induced degenerate state (DSIDS) is essential to create unidirectional π-electron rotations. In the present theoretical treatment, the above restriction is relaxed and the DSIDS is set to be at any energy position between the two excited states. This indicates a wide applicability of the dynamic Stark effects to coherent control of photophysical properties in aromatic molecules, such as coherent ring currents and current-induced magnetic fluxes of low-symmetric aromatic molecules. Analytical expressions for the coherent π-electron angular momentum are derived within a three-electronic-state model by using the Laplace transform method. The validity of the developed theoretical procedure is demonstrated by carrying out simulations of the coherent angular momentum of l-phenylalanine. Effects of varying the DSIDS on the time-dependent coherent angular momentum and the populations in the three electronic states are examined, and the results are analyzed using approximate expressions for the time-dependent coherent angular momentum and the populations. Modulations in the time-dependent coherent angular momentum appear when the DSIDS is set at an energy position between the two excited states, while there are no beating modulations when the DSIDS is set at the center position. Such differences originate from whether interferences between the two dressed states take place or not.


Circulating levels of peripheral blood leucocytes and cytokines following competitive cycling.
The objective of the study was to determine if prolonged and strenuous cycling leads to a polarized cytokine response, and/or unique mobilization of circulating leucocyte populations. Resting venous blood samples were collected from 6 amateur cyclists, 24 hr before, and at 10-25 min and 150 min after completion of a 250-km road race (race time: 404 +/- 3.5 min). Total leucocyte counts were significantly elevated following competition. Cell counts of CD3+CD8bright+ lymphocytes were depressed by 50% 150 min after competition. A significant increase in CD4+ cells expressing the IL-2R alpha chain was evident 150 min after competition. IL-6 concentrations were greatly increased, both at 10-25 min and 150 min after competition. Resting TNF-a concentrations were approximately doubled at both time points after competition. Plasma levels of IFN-gamma, IL-10 and IL-12 were below detection thresholds at all time points. These results suggest that performance of a 6.5 h competitive cycle-race does not induce a Type-1 or Type-2-dominated cytokine response, but one that is typical of a proinflammatory cytokine response.


Postmortem Histopathologic Analysis of Neurosyphilis: A Report of 3 Cases With Clinicopathologic Correlations.
Neurosyphilis occurs in the late stage of systemic syphilis infection; early diagnosis and treatment are crucial to the prognosis. We review 3 autopsy cases with different subtypes of neurosyphilis, that is cases with meningovascular, general paresis, and a combination of the 2, respectively. We investigated the gross morphology and leptomeninges, vessels, cerebral cortex, white matter, brainstem, cerebellum, olfactory bulb and spinal cord microscopically. We found that meningovascular inflammation exists in both early and late phases of neurosyphilis, not only in the meningovascular subtype. Vertebrobasilar artery involvement is common and infarcts of the areas perfused by these arteries in young patient highly suggests neurosyphilis. Damage to the cortical architecture and neuropil is the main mechanism of dementia in general paresis and temporal lobe may not firstly be involved as many other diseases with dementia. Early involvement of olfactory bulbs may help in the early diagnosis of the disease. Our findings indicate that many specific features may help in clinical practice and that further research is needed to clarify the mechanisms.


[Legionnaires' disease in cystic fibrosis].
A "new pneumonia" is named legionnaires' disease after a gramnegative bacillus - Legionella pneumophila, unknown until 1977. Sofar it has been observed mostly in older male patients, rarely in children and never before in Germany. The legionnaires' disease in our patient, a five and half years old boy with cystic fibrosis caused a severe dyspnea and multilobular pulmonary densifications on the chest X-ray film. The diagnosis was verified by the rise of the titer in the indirect immune fluorescence test and the success of the therapy with erythromycin.


Isolation of a cDNA clone for human cytochrome c1 from a lambda gt11 expression library.
Antiserum directed against a purified preparation of beef heart cytochrome bc1 complex has been used to screen a human liver cDNA expression library in lambda gt11. The inserts of two recombinants, which gave strong signals, were found to represent cytochrome c1 by epitope selection using nitrocellulose filters containing the expressed proteins. The amino acid sequence deduced from the nucleotide sequence of an insert DNA revealed a high degree of homology with the sequence of bovine cytochrome c1.


Is cerebral microbleed prevalence relevant as a biomarker in amnestic mild cognitive impairment and mild Alzheimer's disease?
Introduction The search for a reliable neuroimaging biomarker in Alzheimer's disease is a matter of intense research. The presence of cerebral microbleeds seems to be a potential biomarker. However, it is not clear if the presence of microbleeds has clinical usefulness to differentiate mild Alzheimer's disease and amnestic mild cognitive impairment from normal aging. We aimed to verify if microbleed prevalence differs among three groups: mild Alzheimer's disease, amnestic mild cognitive impairment due to Alzheimer's disease, and normal controls. Moreover, we studied whether microbleeds were associated with apolipoprotein E allele ɛ4 status, cerebrospinal fluid amyloid-beta, total and phosphorylated tau protein levels, vascular factors, and cognition. Methods Twenty-eight mild Alzheimer's disease patients, 34 with amnestic mild cognitive impairment and 36 cognitively normal elderly subjects underwent: magnetic resonance imaging with a susceptibility-weighted imaging sequence on a 3T scanner, apolipoprotein E genotyping and a full neuropsychological evaluation. Only amnestic mild cognitive impairment and mild Alzheimer's disease underwent cerebrospinal fluid analysis. We compared the groups and verified if microbleeds were predicted by all other variables. Results Mild Alzheimer's disease presented a higher prevalence of apolipoprotein E allele ɛ4 in relation to amnestic mild cognitive impairment and control group. No significant differences were found between groups when considering microbleed presence. Logistic regression tests failed to find any relationship between microbleeds and the variables. We performed three different regression models using different independent variables: Model 1 - amyloid-beta, phosphorylated tau protein, total tau, apolipoprotein E allele ɛ4 status, age, and sex; Model 2 - vascular risk factors, age, and sex; Model 3 - cognitive scores sex, age, and education. Conclusion Although microbleeds might be related to the Alzheimer's disease process, their presence is not a good candidate for a neuroimaging biomarker of the disease, especially in its early phases.


Unconstrained cranial evolution in Neandertals and modern humans compared to common chimpanzees.
A variety of lines of evidence support the idea that neutral evolutionary processes (genetic drift, mutation) have been important in generating cranial differences between Neandertals and modern humans. But how do Neandertals and modern humans compare with other species? And how do these comparisons illuminate the evolutionary processes underlying cranial diversification? To address these questions, we used 27 standard cranial measurements collected on 2524 recent modern humans, 20 Neandertals and 237 common chimpanzees to estimate split times between Neandertals and modern humans, and between Pan troglodytes verus and two other subspecies of common chimpanzee. Consistent with a neutral divergence, the Neandertal versus modern human split-time estimates based on cranial measurements are similar to those based on DNA sequences. By contrast, the common chimpanzee cranial estimates are much lower than DNA-sequence estimates. Apparently, cranial evolution has been unconstrained in Neandertals and modern humans compared with common chimpanzees. Based on these and additional analyses, it appears that cranial differentiation in common chimpanzees has been restricted by stabilizing natural selection. Alternatively, this restriction could be due to genetic and/or developmental constraints on the amount of within-group variance (relative to effective population size) available for genetic drift to act on.


Treating traumatized children: current status and future directions.
Empirical knowledge regarding effective treatments for traumatized children has increased in the past decade, yet much still remains unknown. There is growing support for the efficacy of trauma-focused cognitive behavioral therapy (TF-CBT) for treating PTSD, depressive, and behavioral problems in sexually abused children, and evidence that suggests that this treatment is effective for children exposed to other types of trauma, and for multiply traumatized children. Few other psychosocial treatments have been adequately studied to date. Open psychopharmacological studies have identified several promising medication classes for traumatized children but these need to be tested in randomized, placebo controlled trials. No empirical studies have evaluated the efficacy of early interventions provided to children in the acute aftermath of mass disasters or terrorist acts. More research is needed to test potentially effective treatments for traumatized children, and to identify optimal methods for disseminating and implementing evidence-based treatments to community practitioners.


Postoperative Osteopathic Manipulative Treatment in Children with Esophageal Atresia: Potential Benefits on the Anthropometric Parameters.
Esophageal atresia (EA) is a congenital malformation that affects the normal esophageal development. Surgical treatment, although restoring the integrity of the alimentary tract, may lead to long-term sequelae-like developmental abnormalities and musculoskeletal deformities. We evaluated the effects of osteopathic manipulative treatment (OMT) on the recovery of the range of the right upper limb movement and on the rise of the auxological parameters. A case series of five children affected by type C EA were described. Six OMT sessions were performed over a 4-month period. At each treatment, height, weight, body mass index (BMI) and range of motion (ROM) in elevation of the right upper limb were assessed. OMT was applied to improve scar, larynx, rib cage, and sternum mobility. An average change of 2.3 cm in height and an average increase of 8° in the ROM of the upper limb in the period of study were detected. Additionally, OMT could improve the anthropometric data and the mobility of the right upper limb of children surgically treated for EA. Further studies that evaluate the effectiveness of OMT in post surgical treatment of congenital malformations of the thorax can be considered in the future.


Sex chromosome drive.
Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species.


Synthesis of nickel-monocarbollide complexes by oxidative insertion.
Treatment of the 11-vertex carborane anion [closo-2-CB(10)H(11)](-) with Ni(0) reagents in tetrahydrofuran (THF) affords-via oxidative insertion reactions-12-vertex Ni(II) complexes, isolated as the salts [N(PPh(3))(2)][2,2-L(2)-closo-2,1-NiCB(10)H(11)] (L = CO (1a), CNBu(t) (1b), and CNXyl (1c; Xyl = C(6)H(3)Me(2)-2,6); L(2) = cod (1d; cod = 1,2:5,6-eta-cyclo-octa-1,5-diene)). One CO ligand in 1a is readily replaced by donors L' in the presence of Me(3)NO to give the species [N(PPh(3))(2)][2-CO-2-L'-closo-2,1-NiCB(10)H(11)] (L' = PEt(3) (1e), PPh(3) (1f), CNBu(t) (1g), and CNXyl (1h)). The anionic complexes themselves readily react with hydride abstracting reagents in the presence of donor ligands to yield zwitterionic complexes in which boron vertexes bear substituents that are bound through C, N, or O atoms. Thus, for example, 1c with H(+) and CNXyl gives [2,2,7-(CNXyl)(3)-closo-2,1-NiCB(10)H(10)] (2b), while 1f with Me(+) in the presence of OEt(2) affords [2-CO-2,11-{mu-PPh(2)(C(6)H(4)-o)}-7-OEt(2)-closo-2,1-NiCB(10)H(9)] (4), in which an additional cycloboronation of one phosphine phenyl ring has occurred. In contrast, 1f with Me(+) in the presence of NCMe gives a mixture of the isomers [2-CO-2-PPh(3)-7-{(X)-N(Me)=C(H)Me}-closo-2,1-NiCB(10)H(10)] (X identical with E (5c) and Z (5d)). X-ray diffraction analyses of compounds 1a, 2b, 4, and 5c confirmed their important structural features.


Using a meta-model to build a connection service in an object oriented medical application development environment.
Interoperability is a key issue in distributed health information systems. This paper presents the design and implementation of the Connection Service (CS) component of the HELIOS medical software engineering environment. An exchange message meta-model based on CEN TC251 recommendations and a message description language are proposed. Using this meta-model, the CS is able either to interpret messages expressed in a given syntax (e.g., EDIFACT, ASTM) and map them to the application objects or to automate the translation of the messages in another syntax. It is concluded that this meta-model approach contributes to the management of semantic heterogeneity.


Spectral analysis of sung vowels. I. Variation due to differences between vowels, singers, and modes of singing.
Average 1/3-oct filter spectra of vowels, sung by seven professional male and seven professional female singers , were measured. The material consisted of nine different vowels, sung at six fundamental frequencies (F0, ranging from 98 up to 880 Hz). For each vowel the singers were requested to sing in the following nine modes: neutral, light, dark, pressed, free, loud, soft, straight, and extra vibrato . To study origins of spectral variation, the quantity of spectral variance, based on band filter sound levels, was used. For each fundamental frequency and separately for males and females, portions of total spectral variance associated with the main effects and the interactions of the factors "vowels," " singers ," and "modes of singing," were computed. A considerable decrease in total spectral variance was found when F0 rose from 98 to 880 Hz, mostly due to the reduced spectral variance between vowels. Above about F0 = 660 Hz spectral variation was dominated by differences related to singers and modes of singing. Additional analyses revealed that for all F0 values vowel spectra of the tenor and the soprano singers varied more than those of the bass and the alto singers , there was only a slight dependence of spectral differences between vowels on the mode of singing, and the amount of spectral variation in a vowel, sung by different singers with different modes of singing, was vowel dependent.


Radiation exposure of the spinal interventionalist performing fluoroscopically guided lumbar transforaminal epidural steroid injections.
To evaluate radiation exposure to spinal interventionalists while performing transforaminal epidural steroid injections (TFESIs). Prospective study. Multidisciplinary spine center. One hundred consecutive patients with either herniated nucleus pulposus (HNP) or lumbar spinal stenosis (LSS). Fluroscopically guided lumbar TFESIs. Radiation exposure was monitored by radiography technologists who allocated 4 dosimetry badges to all spinal interventionalists performing fluroscopically guided lumbar TFESIs on patients being treated for radicular pain. Badges were placed on the ring finger, glasses, and the inside and outside of the lead apron worn by the interventionalists. The radiography technologists also wore marked badges outside their lead aprons. One control badge was placed 67in away from the fluoroscopy table and a second badge was placed in a desk more than 500ft away from the procedure to monitor ambient radiation. The average fluoroscopy time per procedure was 15.16 seconds. The average exposure per procedure was 0.7mrem at the ring badge, 0.4mrem at the glasses badge, and 0.3mrem at the outside apron badge. No radiation was detectable at the inside apron or at the outside room control badge. The cumulative exposure to the interventionalists from all 100 procedures was 70mrem at the ring badge, 40mrem at the glasses badge, and 30mrem at the outside apron badge. The radiography technologists' average exposure during these procedures was below the limit of detectablility. Radiation time under fluoroscopy ranged from 5 to 38 seconds. The interventionalist's exposure to radiation was significantly greater during procedures conducted on patients with LSS then during procedures on patients with HNP. Adhering to a radiation safety program that includes maximizing the distance the spinal interventionalist is from the radiation source, decreasing exposure time, and proper shielding is essential when performing fluoroscopically guided lumbar TFESIs. Our study shows that exposure to radiation of the spinal interventionalist performing fluoroscopically guided lumbar TFESIs was well within safety limits when proper techniques were followed.


The positive and negative sleep appraisal measure: Towards a clinical validation of sleep spectrum cognitions.
Sleep disturbance is considered a transdiagnostic process due to high comorbidity with mental health difficulties. In particular, sleep disturbances are a feature of mood disorders. To advance transdiagnostic psychological interventions targeting sleep, the Positive and Negative Sleep Appraisal Measure (PANSAM) was developed. The PANSAM is a theory-driven measure based on an Integrative Cognitive Sleep Model and proposes that positive and negative sleep appraisals for excessively long and short sleep durations play a key role in the development of insomnia, hypersomnia, and reduced need for sleep. This study evaluated clinical validity of this new measure. Participants were those who met bipolar at risk criteria and bipolar diagnoses (bipolar spectrum group) (N = 22), major depressive disorder (unipolar depression group) (N = 18), and a nonclinical group (N = 22). To compare against previous insomnia and bipolar disorder relevant research, administered measures included the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) and the Hypomanic and Positive Predictions Inventory (HAPPI). Analysis of variance (ANOVA) tests revealed that the clinical groups scored significantly higher on the PANSAM. The same was shown for the DBAS and HAPPI. Post hoc analyses showed that the PANSAM scale and subscales had significant correlations with all clinical measures. Effect sizes are reported due to sample size limitations. This study has initially validated the PANSAM with clinical populations and highlighted its applicability to a transdiagnostic approach.


Novel Insights on 6:6 Perfluoroalkyl Phosphonic Acid-Induced Melanin Synthesis Disorders Leading to Pigmentation in Tadpoles.
As alternatives to traditional per- and polyfluoroalkyl substances, perfluoroalkyl phosphonic acids (PFPiAs) are widely present in aquatic environments and can potentially harm aquatic organisms. Pigmentation affects the probability of aquatic organisms being preyed on and serves as an important toxic endpoint of development, but little is known about the impacts of PFPiAs on the development of aquatic organisms. In this study, Xenopus laevis embryos were exposed to 6:6 PFPiA (1, 10, and 100 nM) for 14 days. The developed tadpoles exhibited evident pigmentation with increased melanin particle size and density on the skin. Pathological and behavioral experiments revealed that the retinal layers became thinner, reducing the photosensitivity and disturbing the circadian rhythm of the tadpoles. Compared to the control group, the exposed tadpoles showed higher levels but less changes of melanin throughout the light/dark cycle, as well as distinct oxidative damage. Consequently, the expression level of microphthalmia-associated transcription factor (MITF), a key factor inducing melanin synthesis, increased significantly. Molecular docking analysis suggested that 6:6 PFPiA forms strong interactions in the binding pocket of MITF, implying that it could activate MITF directly. The activation of MITF ultimately promotes melanin synthesis, resulting in pigmentation on tadpoles.


Identification of tetrahydrocarbazoles as novel multifactorial drug candidates for treatment of Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder and the most frequent cause of dementia. To date, there are only a few approved drugs for AD, which show little or no effect on disease progression. Impaired intracellular calcium homeostasis is believed to occur early in the cascade of events leading to AD. Here, we examined the possibility of normalizing the disrupted calcium homeostasis in the endoplasmic reticulum (ER) store as an innovative approach for AD drug discovery. High-throughput screening of a small-molecule compound library led to the identification of tetrahydrocarbazoles, a novel multifactorial class of compounds that can normalize the impaired ER calcium homeostasis. We found that the tetrahydrocarbazole lead structure, first, dampens the enhanced calcium release from ER in HEK293 cells expressing familial Alzheimer's disease (FAD)-linked presenilin 1 mutations. Second, the lead structure also improves mitochondrial function, measured by increased mitochondrial membrane potential. Third, the same lead structure also attenuates the production of amyloid-beta (Aβ) peptides by decreasing the cleavage of amyloid precursor protein (APP) by β-secretase, without notably affecting α- and γ-secretase cleavage activities. Considering the beneficial effects of tetrahydrocarbazoles addressing three key pathological aspects of AD, these compounds hold promise for the development of potentially effective AD drug candidates.


Using a marine microalga as a chassis for polyethylene terephthalate (PET) degradation.
The biological degradation of plastics is a promising method to counter the increasing pollution of our planet with artificial polymers and to develop eco-friendly recycling strategies. Polyethylene terephthalate (PET) is a thermoplast industrially produced from fossil feedstocks since the 1940s, nowadays prevalently used in bottle packaging and textiles. Although established industrial processes for PET recycling exist, large amounts of PET still end up in the environment-a significant portion thereof in the world's oceans. In 2016, Ideonella sakaiensis, a bacterium possessing the ability to degrade PET and use the degradation products as a sole carbon source for growth, was isolated. I. sakaiensis expresses a key enzyme responsible for the breakdown of PET into monomers: PETase. This hydrolase might possess huge potential for the development of biological PET degradation and recycling processes as well as bioremediation approaches of environmental plastic waste. Using the photosynthetic microalga Phaeodactylum tricornutum as a chassis we generated a microbial cell factory capable of producing and secreting an engineered version of PETase into the surrounding culture medium. Initial degradation experiments using culture supernatant at 30 °C showed that PETase possessed activity against PET and the copolymer polyethylene terephthalate glycol (PETG) with an approximately 80-fold higher turnover of low crystallinity PETG compared to bottle PET. Moreover, we show that diatom produced PETase was active against industrially shredded PET in a saltwater-based environment even at mesophilic temperatures (21 °C). The products resulting from the degradation of the PET substrate were mainly terephthalic acid (TPA) and mono(2-hydroxyethyl) terephthalic acid (MHET) estimated to be formed in the micromolar range under the selected reaction conditions. We provide a promising and eco-friendly solution for biological decomposition of PET waste in a saltwater-based environment by using a eukaryotic microalga instead of a bacterium as a model system. Our results show that via synthetic biology the diatom P. tricornutum indeed could be converted into a valuable chassis for biological PET degradation. Overall, this proof of principle study demonstrates the potential of the diatom system for future biotechnological applications in biological PET degradation especially for bioremediation approaches of PET polluted seawater.


The use of interactive computed tomography to predict the esthetic and functional demands of implant-supported prostheses.
Diagnosis, treatment planning, and prediction of a final implant-supported prosthetic design require precise noninvasive presurgical information. In addition, coordination of implant team member services and predetermination of treatment fees are critical to a successful resolution of patient needs and concerns. By combining the use of a clinically verified barium-coated template and interactive computed tomography, the implant team can determine and address the relevant issues affecting treatment outcomes. These issues include: fixture/prosthesis incompatibility; recognition of anatomic limitations and anomalies; the need for presurgical bone augmentation; fixture diameter and distribution; abutment type and angle; bone density; soft-tissue augmentation requirements; accurate fee determination; and medicolegal protection. The data collection methodology and format for the Mecall and Rosenfeld prosthesis prediction analysis are discussed as part of a case presentation.


What can be learned in a context-specific proportion congruence paradigm? Implications for reproducibility.
Crump and Milliken (2009) reported a context-specific proportion congruence (CSPC) effect for inducer and diagnostic sets, the strongest evidence to date of context-specific control. Attempts to replicate/reproduce this evidence have failed, including Experiment 1. Using a picture-word Stroop task, we tackled the question of how to interpret such failures by testing the consistency hypothesis (Hutcheon & Spieler, 2017) and two novel hypotheses inspired by our theorizing about learning opportunities in the CSPC paradigm. Experiment 2 found a CSPC effect when there was no diagnostic set, supporting the consistency hypothesis. Experiment 3 produced novel evidence for item-PC learning in a CSPC paradigm. In contrast, Experiment 4 did not produce strong evidence for location-item conjunctive learning. Our findings suggest failures to replicate/reproduce the CSPC effect do not necessarily indicate a Type I error or instability but instead may indicate episodic representations were organized based on item and not location. This item-PC learning hypothesis uniquely predicted Experiment 3 findings and accommodates findings of all but one prior attempt to replicate/reproduce the CSPC effect for inducer and diagnostic sets, including Experiment 1. Predicting whether future attempts are successful will require deeper understanding of the factors that promote learning of item-PC versus location-PC associations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Thiol-Mediated Chemoselective Strategies for In Situ Formation of Hydrogels.
Hydrogels are three-dimensional networks composed of hydrated polymer chains and have been a material of choice for many biomedical applications such as drug delivery, biosensing, and tissue engineering due to their unique biocompatibility, tunable physical characteristics, flexible methods of synthesis, and range of constituents. In many cases, methods for crosslinking polymer precursors to form hydrogels would benefit from being highly selective in order to avoid cross-reactivity with components of biological systems leading to adverse effects. Crosslinking reactions involving the thiol group (SH) offer unique opportunities to construct hydrogel materials of diverse properties under mild conditions. This article reviews and comments on thiol-mediated chemoselective and biocompatible strategies for crosslinking natural and synthetic macromolecules to form injectable hydrogels for applications in drug delivery and cell encapsulation.


Blockade of 11β-hydroxysteroid dehydrogenase type 1 enzyme inhibits experimental collagenase-induced osteoarthritis.
Osteoarthritis (OA) is a common cause of functional deterioration in the joints of elderly adults and is a significant burden on the health of the aging population. 11β‑hydroxysteroid dehydrogenase type 1 enzyme (11β‑HSD1), which converts cortisone to cortisol, is known to contribute to a number of inflammatory diseases. However, the role of 11β‑HSD1 in human OA remains unclear. The aim of this study was to identify the effects of the selective 11β‑HSD1 inhibitor, BVT‑2733, in murine collagenase‑induced osteoarthritis (CIOA). CIOA mice were treated with BVT‑2733 (100 mg/kg, orally) or control vehicle twice daily for five weeks. Cartilage and bone destruction were subsequently examined. The expression of bone markers and STAT3 phosphorylation in joint tissues were detected using western blot analysis. The concentrations of proinflammatory cytokines were determined by an enzyme‑linked immunosorbent assay. Treatment with BVT‑2733 attenuated cartilage and bone destruction, and reduced the expression of bone markers and p‑STAT3 in the joints of CIOA mice. BVT‑2733 also decreased the serum levels of interleukin (IL)‑1β, IL‑6, IL‑17 and vascular endothelial growth factor. In conclusion, the present study showed that BVT‑2733 inhibits multiple inflammatory signaling pathways in the joints of CIOA mice, suggesting that 11β‑HSD1 inhibition may have therapeutic potential in human OA.


[A preliminary study on immune adjunctive therapy for multidrug-resistant Mycobacterium tuberculosis infection in animal models].
To investigate the effect of adjunctive therapy by immune agents in mice infected with multidrug-resistant tuberculosis (MDR-TB). Sixty-eight adult male BALB/c mice were infected with multidrug-resistant Mycobacterium tuberculosis (MTB) by aerosol route. The mice were randomly divided into a control group, an immuno-treatment group, a drug treatment group and a combination treatment group (drug plus immuno-treatment). In each treatment group, 16 mice were treated at day 21 after infection, and another 4 mice were sacrificed at day 21 after infection (treatment for 0 week) as the blank control group. In the treatment group, 4 mice were sacrificed in turn at the day after treatment for 4, 8, 16 and 20 weeks. Lung and spleen mass index at the day after treatment for 8, 16 and 20 weeks, lung and spleen live bacterial count in each period, serum IFN-γ and IL-10 levels at the day after treatment for 8 weeks were measured. Comparisons of analyzed parameters among groups were performed with the one way ANOVA test, and comparisons of parameters between 2 groups were performed with SNK and Games-Howell test. The lung mass index in the immuno-treatment group (0.66 ± 0.09)%, drug group (0.60 ± 0.07)% and combination therapy group (0.57 ± 0.05)% at the day after treatment for 8 weeks were significantly lower than that of the control group (0.81 ± 0.09)%, (F = 7.364, P < 0.01). Spleen CFU of immuno-treatment group at 16 and 20 weeks [(3.11 ± 0.14) lg CFU and (3.15 ± 0.18) lg CFU] were significantly lower than those of the control group [(3.77 ± 0.35) lg CFU and (4.31 ± 0.06)] (F values were 446.424 and 2107.689, P < 0.01). Spleen tissues of the drug group and the combination therapy group were sterile from 4 weeks. The serum IFN-γ levels of immuno-treatment group, drug group and combination therapy were (5.3 ± 1.9) ng/L, (1.3 ± 0.5) ng/L and (0.9 ± 1.3) ng/L, respectively, being significantly lower than that of the control group (10.3 ± 2.1) ng/L (F = 32.128, P < 0.01). The lung and spleen mass index, lung and spleen CFU, serum IFN-γ and IL-10 between medication group and combination therapy showed no significant differences. Immuno-treatment could mitigate lung tissue inflammation, reduce the number of MTB in mouse spleen tissues and decrease serum IFN-γ levels in the MDR-TB mouse model. However immuno-treatment failed to reduce the number of MTB in lung tissues. There was no adjunctive effect of immuno treatment for MDR-TB mice in reducing the number of MTB and mitigating inflammation.


Genetic Diversity of Brucella Reference and Non-reference Phages and Its Impact on Brucella-Typing.
Virulent phages have been used for many years to type Brucella isolates, but until recently knowledge about the genetic makeup of these phages remains limited. In this work the host specificity and genomic sequences of the original set (deposited in 1960) of VLA Brucella reference phages Tb, Fi, Wb, Bk2, R/C, and Iz were analyzed and compared with hitherto described brucellaphages. VLA phages turned out to be different from homonymous phages in other laboratories. The host range of the phages was defined by performing plaque assays with a wide selection of Brucella strains. Propagation of the phages on different strains did not alter host specificity. Sequencing of the phages TbV, FiV, WbV, and R/CV revealed nucleotide variations when compared to same-named phages previously described by other laboratories. The phages Bk2V and IzV were sequenced for the first time. While Bk2V exhibited the same deletions as WbV, IzV possesses the largest genome of all Brucella reference phages. The duplication of a 301 bp sequence in this phage and the large deletion in Bk2V, WbV, and R/CV may be a result of recombination caused by repetitive sequences located in this DNA region. To identify new phages as potential candidates for lysotyping, the host range and Single Nucleotide Polymorphisms (SNPs) of 22 non-reference Brucella phages were determined. The phages showed lysis patterns different from those of the reference phages and thus represent novel valuable candidates in the typing set.


Sirt1, p53, and p38(MAPK) are crucial regulators of detrimental phenotypes of embryonic stem cells with Max expression ablation.
c-Myc participates in diverse cellular processes including cell cycle control, tumorigenic transformation, and reprogramming of somatic cells to induced pluripotent cells. c-Myc is also an important regulator of self-renewal and pluripotency of embryonic stem cells (ESCs). We recently demonstrated that loss of the Max gene, encoding the best characterized partner for all Myc family proteins, causes loss of the pluripotent state and extensive cell death in ESCs strictly in this order. However, the mechanisms and molecules that are responsible for these phenotypes remain largely obscure. Here, we show that Sirt1, p53, and p38(MAPK) are crucially involved in the detrimental phenotype of Max-null ESCs. Moreover, our analyses revealed that these proteins are involved at varying levels to one another in the hierarchy of the pathway leading to cell death in Max-null ESCs.