Control of the light harvesting function of chloroplast membranes: the LHCII-aggregation model for non-photochemical quenching.
Dissipation of excess excitation energy within the photosystem II light-harvesting antenna (LHCII) by non-photochemical quenching (NPQ) is an important photoprotective process in plants. An update to a hypothesis for the mechanism of NPQ [FEBS Letters 292, 1991] is presented. The impact of recent advances in understanding the structure, organisation and photophysics of LHCII is assessed. We show possible locations of the predicted regulatory and quenching pigment-binding sites in the structural model of the major LHCII. We suggest that NPQ is a highly regulated concerted response of the organised thylakoid macrostructure, which can include different mechanisms and sites at different times.


Increased half-life of mu immunoglobulin mRNA during mouse B cell development increases its abundancy.
When B cells encounter antigen, the cells mature into terminally differentiated plasma cells and the amount of steady-state immunoglobulin (Ig) mu mRNA is increased 23-60-fold over the amount seen in earlier B cell stages. Most of this dramatic increase in Ig gene mRNA accumulation could be due to post-transcriptional regulation. We have treated a series of mouse cell lines fixed at different stages of B cell differentiation with an adenosine nucleotide analog 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) which specifically blocks synthesis of new RNA polymerase II transcripts. The amount of mu heavy chain cytoplasmic RNA, measured by quantitative Northern blot analysis at various times post DRB treatment, is reflective of the transcript's stability. The mu mRNA half-life values observed from the earliest-stage lymphomas (70Z/3 and WEHI-231) are about 1.9-4 hr, whereas the t1/2 of mu mRNA in the hybridomas (Hyb54.3C2 and IdG11) is about 13-17 hr. There is, therefore, a nine-fold maximal increase in half-life of the mu mRNA in the Hyb54.3C2 over that observed in the earliest stage (70Z/3) cells.


Using the bootstrap to establish statistical significance for relative validity comparisons among patient-reported outcome measures.
Relative validity (RV), a ratio of ANOVA F-statistics, is often used to compare the validity of patient-reported outcome (PRO) measures. We used the bootstrap to establish the statistical significance of the RV and to identify key factors affecting its significance. Based on responses from 453 chronic kidney disease (CKD) patients to 16 CKD-specific and generic PRO measures, RVs were computed to determine how well each measure discriminated across clinically-defined groups of patients compared to the most discriminating (reference) measure. Statistical significance of RV was quantified by the 95% bootstrap confidence interval. Simulations examined the effects of sample size, denominator F-statistic, correlation between comparator and reference measures, and number of bootstrap replicates. The statistical significance of the RV increased as the magnitude of denominator F-statistic increased or as the correlation between comparator and reference measures increased. A denominator F-statistic of 57 conveyed sufficient power (80%) to detect an RV of 0.6 for two measures correlated at r = 0.7. Larger denominator F-statistics or higher correlations provided greater power. Larger sample size with a fixed denominator F-statistic or more bootstrap replicates (beyond 500) had minimal impact. The bootstrap is valuable for establishing the statistical significance of RV estimates. A reasonably large denominator F-statistic (F > 57) is required for adequate power when using the RV to compare the validity of measures with small or moderate correlations (r < 0.7). Substantially greater power can be achieved when comparing measures of a very high correlation (r > 0.9).


Spontaneously hypertensive rats exhibit supersensitivity to the hypertensive and hyperthermic effects of thyrotropin releasing hormone.
The effect of thyrotropin releasing hormone (TRH) on colonic temperature and systolic blood pressure of age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. Administration of TRH produced dose-dependent increases in body temperature and systolic blood pressure. TRH-induced changes in both responses were of greater magnitude in SHR rats compared to WKY rats. The results provide the first evidence that SHR rats exhibit supersensitivity to non-neuroendocrinological effects of TRH and that TRH may play a role in the pathophysiology of elevated blood pressure.


Structure-activity studies on the upstream splice junction of a semisynthetic intein.
Protein trans-splicing by split inteins holds great potential for the chemical modification and semisynthesis of proteins. However, the structural requirements of the extein sequences immediately flanking the intein are only poorly understood. This knowledge is of particular importance for protein labeling, when synthetic moieties are to be attached to the protein of interest as seamlessly as possible. Using the semisynthetic Ssp DnaB intein both in form of its wild-type sequence and its evolved M86 mutant, we systematically varied the sequence upstream of the short synthetic Int(N) fragment using both proteinogenic amino acids and unnatural building blocks. We could show for the wild-type variant that the native N-extein sequence could be reduced to the glycine residue at the (-1) position directly flanking the intein without significant loss of activity. The glycine at this position is strongly preferred over building blocks containing a phenyl group or extended alkyl chain adjacent to the scissile amide bond of the N-terminal splice junction. Despite their negative effects on the splicing yields, these unnatural substrates were well processed in the N-S acyl shift to form the respective thioesters and did not result in an increased decoupling of the asparagine cyclization step at the C-terminal splicing junction. Therefore, the transesterification step appeared to be the bottleneck of the protein splicing pathway. The fluorophore 7-hydroxycoumarinyl-4-acetic acid as a minimal N-extein was efficiently ligated to the model protein, in particular with the M86 mutant, probably because of its higher resemblance to glycine with an aliphatic c-α carbon atom at the (-1) position. This finding indicates a way for the virtually traceless labeling of proteins without inserting extra flanking residues. Due to its overall higher activity, the M86 mutant appears most promising for many protein labeling and chemical modification schemes using the split intein approach.


Intubation Biomechanics: Clinical Implications of Computational Modeling of Intervertebral Motion and Spinal Cord Strain during Tracheal Intubation in an Intact Cervical Spine.
In a closed claims study, most patients experiencing cervical spinal cord injury had stable cervical spines. This raises two questions. First, in the presence of an intact (stable) cervical spine, are there tracheal intubation conditions in which cervical intervertebral motions exceed physiologically normal maximum values? Second, with an intact spine, are there tracheal intubation conditions in which potentially injurious cervical cord strains can occur? This study utilized a computational model of the cervical spine and cord to predict intervertebral motions (rotation, translation) and cord strains (stretch, compression). Routine (Macintosh) intubation force conditions were defined by a specific application location (mid-C3 vertebral body), magnitude (48.8 N), and direction (70 degrees). A total of 48 intubation conditions were modeled: all combinations of 4 force locations (cephalad and caudad of routine), 4 magnitudes (50 to 200% of routine), and 3 directions (50, 70, and 90 degrees). Modeled maximum intervertebral motions were compared to motions reported in previous clinical studies of the range of voluntary cervical motion. Modeled peak cord strains were compared to potential strain injury thresholds. Modeled maximum intervertebral motions occurred with maximum force magnitude (97.6 N) and did not differ from physiologically normal maximum motion values. Peak tensile cord strains (stretch) did not exceed the potential injury threshold (0.14) in any of the 48 force conditions. Peak compressive strains exceeded the potential injury threshold (-0.20) in 3 of 48 conditions, all with maximum force magnitude applied in a nonroutine location. With an intact cervical spine, even with application of twice the routine value of force magnitude, intervertebral motions during intubation did not exceed physiologically normal maximum values. However, under nonroutine high-force conditions, compressive strains exceeded potentially injurious values. In patients whose cords have less than normal tolerance to acute strain, compressive strains occurring with routine intubation forces may reach potentially injurious values.


Antioxidant and antimutagenic activities of Mexican oregano (Lippia graveolens Kunth).
Free essential oil methanolic extracts from three different geographical populations of Lippia graveolens in México were screened for antioxidant and antimutagenic properties by the DPPH and Kado microsuspension assay, respectively. Total phenolic and flavonoid contents as well as HPLC identification and quantification of naringenin and rosmarinic acid were also carried out. In addition, a taxonomical phenetic analysis was performed. The L. graveolens extracts showed varying content of phenols and flavonoids. Significant concentration of rosmarinic acid was found for the first time in the species. All the extracts were capable of scavenging DPPH radicals in a concentration dependent fashion; the IC50 values correlate with the phenolic content. None of the extracts was toxic to TA100 and TA98 strains at the concentrations tested; moreover, the extracts at a concentration equivalent to 200 microg of gallic acid inhibited a 39 and 30% the mutagenicity induced by 4-nitro-o-phenylenediamine and sodium azide, respectively. The results suggest that the Mexican oregano is a source of polar bioactive ingredients for the food industry.


A comparison of the effects of prednisolone and methylprednisolone on human lymphoblastoid cells.
Methylprednisolone is more effective than prednisolone in mediating long-term cytolysis and immediate inhibition of nucleoside uptake in human lymphoblastoid cells. This suggests that methylation of prednisolone makes it more potent by aiding interaction with a cellular target rather than increasing its stability.


Using a Combined All-Inside, Inside-Out, and Outside-In Technique to Repair Bucket-Handle Medial Meniscal Tears Without a Safety Incision.
We describe a combined all-inside, inside-out, and outside-in technique for the repair of unstable bucket-handle medial meniscal tears. Notably, a greater incidence of neurovascular complications has been associated with meniscal repair techniques that employ an accessory skin incision, especially when damage involves the body of the medial meniscus. However, with the operative knee in relative extension, passing inside-out needles anteromedial to the posterior horn and posterior to the semitendinosus tendon and saphenous nerve allows for the needles to exit the posteromedial knee through a "safe zone." Therefore, we reduce iatrogenic damage by avoiding the necessity of a large safety incision while still maintaining suture placement versatility and meniscal fragment stabilization. Thus, the objective of this Technical Note is to outline an efficient technique for treating bucket-handle medial meniscal tears that yields a strong, durable repair while avoiding damage to adjacent neurovascular structures and eliminating the need for a posteromedial safety incision.


Effects of a leukocyte depleting arterial line filter on perioperative morbidity in patients undergoing cardiac surgery: a controlled randomized trial.
Activated leukocytes may increase morbidity in cardiac surgery. The objective of this study is to investigate the influence on morbidity of leukocyte-depleting blood filters placed into the arterial line of cardiopulmonary bypass circuits. Simple, blind, prospective, randomized and controlled clinical trial carried out in a cardiac surgery ICU at a university center. We included 159 consecutive low-risk patients (ie, Parsonnet score < 10) undergoing cardiac surgery who were initially stratified in three risk levels according to the Parsonnet score at admission into the hospital (ie, low, < 4; middle, 4 to 7; and high, 8 to 10). Once stratified, all patients were randomized to undergo cardiopulmonary bypass either with a conventional blood filter or with a leukocyte filter (randomization ratio, 2:1). The outcome variable was morbidity. Patients were considered to have a high morbidity if any of the following clinical situations were present (ie, pulmonary dysfunction, cardiac dysfunction, perioperative infections, postoperative hyperthermia, and hyperdynamic states). The leukocyte filter was used in 52 patients and the conventional filter in 107 patients. The morbidity rate was similar in both groups, but patients with leukocyte filter had a lower incidence of perioperative infections, fever, and hyperdynamic states as compared with patients with the conventional filter. Leukocyte filtration in patients undergoing cardiac surgery with extracorporeal perfusion showed no measurable effects on postoperative morbidity. However, although not statistically significant, a decrease was observed in the rates of perioperative infection, fever, and hyperdynamic states.


Phase II trial of amsacrine (m-AMSA) in advanced ovarian carcinoma.
A phase II study of 4'-(9-acridinylamino)methanesulfon-m-anisidide (amsacrine, m-AMSA) was carried out in previously treated patients with advanced ovarian carcinoma. The dose of amsacrine was 90 mg/m2 every 3 weeks in 34 patients having received prior extensive chemotherapy and/or radiotherapy, and 120 mg/m2 in 5 patients who had previously only received moderate amounts of chemotherapy. Among patients evaluable for response the median number of courses was 3 (range 2-17). Two patients (5%) experienced complete response for 15+ months. Leucopenia was the most frequent toxic effect. WBC nadir was 2700/mm3 (range 1000-7300). Other toxic effects were of lesser significance and included thrombocytopenia, anemia, nausea and vomiting. It is concluded that amsacrine has only marginal activity in patients with previously treated ovarian carcinoma.


Morphological characterization and molecular fingerprinting of Nostoc strains by multiplex RAPD.
Morphological parameters studied for the twenty selected Nostoc strains were mostly found to be consistent with the earlier reports. But the shape of akinetes observed in this study was a little deviation from the existing descriptions and heterocyst frequency was also found to be different in different strains in spite of growing in the same nitrogen free media. Multiplex RAPD produced reproducible and completely polymorphic amplification profiles for all the strains including some strain specific unique bands which are intended to be useful for identification of those strains. At least one to a maximum of two unique bands was produced by different dual primer combinations. For ten strains out of twenty, strain specific bands were found to be generated. Cluster analysis revealed a vast heterogeneity among these Nostoc strains and no specific clustering based on geographical origin was found except a few strains. It was also observed that morphological data may not necessarily correspond to the genetic data in most of the cases. CCC92 (Nostoc muscorum) and CCC48 (Nostoc punctiforme) showed a high degree of similarity which was well supported by high bootstrap value. The level of similarity of the strains ranged from 0.15 to 0.94. Cluster analysis based on multiplex RAPD showed a good fit revealing the discriminatory power of this technique.


[Safety of rush immunotherapy with Hymenoptera venom].
To determine the incidence and nature of adverse events associated with the induction of rush Hymenoptera venom immunotherapy. Between 1998 and 2003, we administered venom immunotherapy to 48 patients allergic to bee or wasp venom, by means of a rush immunotherapy protocol (3 days). We observed no severe adverse reactions in any patients. 12 patients developed only local reactions at the site of injections that did not required any pharmacological treatment. Two patients experienced mild systemic reactions consisting of diffuse urticaria on day 3. Both adverse reactions were treated with intravenous antihistamines. Our experience confirms that rapid venom immunotherapy is safe and should be considered in every case especially for patients during the stinging insect season when a rapid protection is required.


Extracorporeal Membrane Oxygenation (ECMO) Training Program in A Pediatric Cardiac Intensive Care Unit: An 8-Year Single-Center Experience in Argentina.
Extracorporeal membrane oxygenation (ECMO) for temporary cardiopulmonary support is one of the most intense and technologically complex therapies offered in medicine. It is a high-risk procedure that requires specific knowledge and technical skills to perform it with good results. The main goal of this study is to describe our extracorporeal membrane oxygenation (ECMO) training program based on the study of specialized nurses and physicians of a simulation teaching experience, conducted in a pediatric cardiac intensive care unit. The program was developed as a theoretical-practical course with final exam and annual maintenance training sessions, caring for ECMO patients, its implementation and results. A descriptive study for registered nurses, intensivists, and cardiac surgeons. A self-administered, anonymous, and voluntary survey was conducted to assess the long-term perception about the program. Demographic data to describe the population was required, and questions about satisfaction and confidence in acquired skills and competences were asked. A descriptive statistical analysis was performed; patient survival and complications were compared before and after ECMO program using chi-square test, and P<0.05 was considered statistically significant. Twenty-four training courses were performed for 68 professionals. More than 88% of the professionals considered the course components to be adequate and complete; and 94% felt trained to manage the ECMO circuit. Most valued activities were workshops and clinical cases. Since the implementation of the training program, 88 patients were assisted, with a survival rate at discharge of 58%, higher than in the previous period (P=0.03). More than 80% of the professionals considered the workshops and simulations as the most useful components. Reliance on the circuit care was higher than in training problem scenarios. Since 2013 we assisted 88 patients on ECMO, with a survival rate at discharge of 58%, within international standards results.


Confocal assessment of the effects of fourth-generation fluoroquinolones on the cornea.
To evaluate the toxicity of fourth-generation fluoroquinolone antibiotic solutions on the rabbit corneal epithelium. In vivo confocal microscopy was used to assess epithelial structure in 18 rabbits, and tight junction integrity of superficial epithelial cells was evaluated with ZO-1 labeling in 10 rabbits. Eyes were bathed with commercial solutions of moxifloxacin (Vigamox) or gatifloxacin (Zymar) solution for 3 minutes, rinsed with balanced salt solution, and immediately examined. Balanced salt solution rinsing alone served as the control. A decrease in epithelial cell size was observed after treatment with Zymar (P < 0.05, two-way repeated-measures analysis of variance), but not with Vigamox or the control. Normal ZO-1 organization was observed in controls and eyes treated with Vigamox. ZO-1 staining in eyes treated with Zymar was disrupted, patchy, and generally weaker than that in control eyes. After short-term, intensive exposure to Vigamox, corneal epithelial integrity and tight junction organization are maintained. Zymar induces a loss of superficial epithelial cells and breakdown of tight junctions under similar conditions.


Cytophotometry of nucleic acids and morphometry of motor neurons and oligodendroglia in the spinal cord of rats treated with CCNU (lomustine).
CCNU, a nitrosourea derivative, is a potent agent used in cancer chemotherapy and effective also in therapy of brain tumors. This cytostatic is considered to be free of neurotoxic effects. To establish the influence of CCNU on the central nervous system, the drug was administered in oil suspension, intragastrically, to adult rats. The animals received four doses of the drug in 7 days intervals, including three doses of 2.5 mg and the fourth of 5.0 mg. On the 7th day after the last dose experimental rats were sacrificed, their spinal cord removed, fixed in Baker's solution and embedded in paraffin. The sections were stained according to Einarson and subjected to Feulgen reaction for morphometric, karyometric and cytophotometric studies. The measurements of motor neurons and oligodendroglia from anterior horns of the cervical, thoracic and lumbar spinal cord were performed with scanning microscope "Morphoquant" coupled to the KSR 4100 computer. CCNU administration lead to morphometric, karyometric and cytophotometric changes in examined cells. The karyometric and cytophotometric changes were statistically significant and more extensive than morphometric changes which were insignificant. Furthermore, CCNU caused a statistically significant decrease of DNA content in motor neurons and oligodendrocytes in all examined parts of the spinal cord.


Determinants affecting pregnant women's utilization of prenatal screening for Down syndrome: a review of the literature.
Uptake rates for Down syndrome screening (DSS) in the Netherlands are low compared with those in Northern European countries (27% versus 61% in the United Kingdom and 90% in Denmark). These differences are unexpected, especially since the countries have similar cultural and social values. To analyse factors that underlie differences in uptake we reviewed current literature on individual characteristics and healthcare system factors, which determine potential influential factors on utilization of DSS. Arguments "Against abortion" and "Down syndrome (DS) not severe enough condition to terminate pregnancy" correlated with declining DSS, whereas "Perceived guidance of healthcare professional," "Perceived negative attitude of society towards DS" and "Preparation/Early termination" correlated with accepting DSS. However, the majority of determinants were used both in favour of accepting or declining DSS. Decision making regarding DSS seems a process with influences on different levels and subtle interactions rather than a dichotomous process. Utilization may also be influenced by the implicit way it is being offered, as an extra option or as part of routine care and how this offer is perceived by the social environment. Finally, national healthcare system characteristics, although underrepresented in the examined studies, may also influence participation in DSS.


Postnatal changes in [3H]fucosyl glycoconjugates axonally transported into hamster optic nerve endings.
The subsynaptosomal distribution of [3H]fucosyl glycoproteins axonally transported into the optic nerve endings of neonatal and adult hamsters changed dramatically at eye-opening. In 12 day-old previsual hamsters, the highest concentration of incorporated fucose was in the axoplasmic reticulum/synaptic vesicle fraction (51%), with only 6% in the dense synaptic membrane fraction. By the end of the eye-opening period four days later proportional labeling of the dense synaptic membrane fraction had increased four-fold to 23% of total sub-synaptosomal radioactivity. Labeling of the synaptic membrane doubled again in adults (41%). Total synaptosomal radioactivity was greatest in 16 day-olds. These results imply that utilization o [3H]fucose by the retinal ganglion cells, as well as composition of the synaptic membrane, change in association with the onset of functional visual activity.


Open-sky pupilloplasty during phakic penetrating keratoplasty to treat a fixed, dilated pupil.
We report a technique in which penetrating keratoplasty is performed in conjunction with open-sky pupilloplasty in a phakic patient. The technique was used in a 27-year-old man with poor vision and severe light sensitivity in the left eye dating back to an episode of presumed herpes simplex keratouveitis 13 years previously. Examination showed a best corrected visual acuity of 20/40, a paracentral midstromal corneal scar, a fixed dilated pupil, and a clear lens. Postoperatively, the pupil was relatively round with a diameter of approximately 4.0 mm, the cosmetic result was favorable, the photophobia had resolved, and the lens and corneal transplant were clear.


Clinical evaluation of trimethoprim-containing ophthalmic solutions in humans.
We studied trimethoprim in combination with sulfacetamide and polymyxin B and also in combination with polymyxin B alone (without the sulfacetamide) to determine the efficacy and safety of these new antibiotic combinations in the eyes of patients with bacterial conjunctivitis or blepharitis. Patients were selected for the study if they showed at least three of the following criteria: (1) symptoms of a surface ocular infection; (2) a purulent discharge; (3) a polymorphonuclear neutrophilic response on Giemsa stain; (4) a history of recent exposure to an infected individual; (5) a history of an inadequately treated surface bacterial infection. Trimethoprim-sulfacetamide-polymyxin B and polymyxin B-neomycin-gramicidin (Neosporin, the control) eliminated bacteria from the eyes of patients with conjunctivitis or blepharitis with equal effectiveness. There was no loss of effectiveness when trimethoprim-polymyxin B was compared with trimethoprim-sulfacetamide-polymyxin B, suggesting that the sulfacetamide was not a necessary component. The combination antibiotic containing trimethoprim and polymyxin B appears to be an effective topical antibiotic solution for the treatment of ocular surface infections.


Immune Responses in Fully Vaccinated Individuals Following Breakthrough Infection with the SARS-CoV-2 Delta Variant in Provincetown, Massachusetts.
A cluster of over a thousand infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. Immune responses in breakthrough infections with the SARS-CoV-2 delta variant remain to be defined. Humoral and cellular immune responses were assessed in 35 vaccinated individuals who were tested for SARS-CoV-2 in the Massachusetts Department of Public Health outbreak investigation. Vaccinated individuals who tested positive for SARS-CoV-2 demonstrated substantially higher antibody responses than vaccinated individuals who tested negative for SARS-CoV-2, including 28-fold higher binding antibody titers and 34-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant. Vaccinated individuals who tested positive also showed 4.4-fold higher Spike-specific CD8+ T cell responses against the SARS-CoV-2 delta variant than vaccinated individuals who tested negative. Fully vaccinated individuals developed robust anamnestic antibody and T cell responses following infection with the SARS-CoV-2 delta variant. These data suggest important immunologic benefits of vaccination in the context of breakthrough infections.


Evaluation of extracellular matrix proteins and tissue inhibitor of matrix metalloproteinases-2 on bovine inner cell mass outgrowth in vitro.
Effects of extracellular matrix proteins and tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) on bovine inner cell mass (ICM) outgrowth and proteinase production in vitro were determined. Inner cell masses were isolated immunosurgically from day 7 embryos (day 0 = onset of estrus) and cultured for 96 h. In experiment 1, cellular outgrowth and gelatinase production were evaluated for ICM cultured on collagen IV, fibronectin, or laminin. More (P < 0.05) ICM generated cellular outgrowth on fibronectin (71%). compared with collagen IV (0%) or laminin (15%). Inner cell mass and outgrowth areas were greatest (P < 0.05) on fibronectin after 96 h of culture, compared with laminin. Although the incidence of cellular outgrowth on laminin was limited, numbers of cells in outgrowths supported by laminin were similar (P > 0.10) to fibronectin except at 72 h of culture, where more (P < 0.05) cells were in laminin than in fibronectin outgrowths. Gelatinase activity was not detected in conditioned medium. In experiment 2, cellular outgrowth and plasminogen activator production by ICM cultured on fibronectin in medium containing 0 or 10 microg/ml TIMP-2 were evaluated. Inner cell mass and outgrowth areas, and numbers of cells in outgrowths were greater (P < 0.05) in 10 compared with 0 microg/ml TIMP-2 at 96 h of culture. Mean plasminogen activator activity in conditioned medium from ICM cultured in 10 microg/ml TIMP-2 was greater (P < 0.05) compared with 0 microg/ml TIMP-2 (16.2 +/- 4.8 versus 6.7 +/- 1.4 x 10(-3) IU/ml, respectively). These results demonstrate that cellular outgrowth from bovine ICM is supported by fibronectin and is stimulated by TIMP-2.


Mindset and team communication in pharmacists: Examination of pharmacist's self-views.
Pharmacists provide care in a complex adaptive system, which requires action and teamwork to address unexpected outcomes. We assessed practicing pharmacists' self-views of growth mindset and team communication across multiple practice settings. The validated Growth Mindset and Team Communication (GMTC) tool, a multicomponent quantitative and qualitative survey instrument was used to conduct a descriptive study of pharmacist self views. Survey instrument was distributed electronically to all licensed North Carolina pharmacists. The survey consisted of 4 sections: (1) growth mindset self-evaluation (14 questions), (2) team communication self-evaluation (13 questions), (3) description of previous teamwork experience (1 question), and (4) demographics (8 questions). Data were analyzed using descriptive statistics, and responses to the open-ended question were assessed using qualitative content analysis. A total of 507 pharmacists participated in the survey. Participants reported primary practice settings, 42.1% in community, 38.9% in health system, and 17.3% in other settings, and 52.1% reported more than 20 years' total pharmacy experience. The total GMTC scale average score was 81.9 ± 7.9 out of 108 possible points. The growth mindset subscale indicated an overall average score of 43.5 ± 4.4 out of 56 possible points The team communication subscale indicated an overall average score of 38.3 ± 5.2 out of 52 possible points. The self-view of a growth mindset was not affected by years of pharmacy experience or primary practice site, but additional teamwork credentials were positively correlated with the overall GMTC score driven by the team communication subscale. A growth mindset is prevalent among experienced pharmacists from multiple practice settings. Pharmacists recognize teamwork as an essential work element and rate their team communication skills highly.


Retrospective study into the delivery of telephone cardiopulmonary resuscitation to "999" callers.
Cardiopulmonary resuscitation (CPR) is an essential part of the chain of survival, with early administration directly affecting the patient's chance of survival. Pre-arrival telephone CPR instructions provide callers who have no CPR training on how to undertake this intervention. With the emergency medical dispatcher unable to see the caller or the patient, it is possible that problems will arise, presenting barriers, that stop the caller undertaking effective CPR. To examine how commonly barriers to telephone CPR occur and whether this affects the time it takes to perform the intervention. A retrospective quantitative analysis was undertaken using a convenience sample of 100 emergency calls. Calls were identified in the emergency control room as cardiac arrests and confirmed by the responding paramedics as cardiac arrests. The calls were listened to, established if CPR instructions were given, if the instructions were followed, if anything hindered the instructions undertaken, and the time taken to reach key points. 18 cases had bystander CPR administered. An additional 56 of cases had CPR instructions provided but "barriers" in 49% (n = 27) hindered the effectiveness of these. The median time to recognition of cardiac arrest was 40 seconds, with time to first ventilation being 4 min 10 s and time to first compression 5 min 30 s. These times were notably higher in those cases where a barrier to effective telephone CPR existed. Barriers to undertaking telephone CPR occurred with a high degree of frequency. These barriers affect the ability of the caller to perform rapid and effective telephone CPR.


Highly efficient synthesis of aromatic azos catalyzed by unsupported ultra-thin Pt nanowires.
Aromatic azos were synthesized using unsupported ultra-thin platinum nanowires as catalysts under mild reaction conditions and the reaction mechanism was proposed.


Applying the transtheoretical model to female and male perpetrators of intimate partner violence: gender differences in stages and processes of change.
The Transtheoretical Model has been recently applied to men seeking services at battering intervention and prevention programs (Eckhardt, Babcock, & Homack, 2004; Murphy & Baxter, 1997). This study considers whether women arrested for intimate partner violence differ from male perpetrators in terms of stages of change and processes of change. No gender differences were found regarding stage of change. In general, all individuals presenting for treatment were in the early stages of change. The use of various processes of change was strongly related to stage of change, with individuals in the more advanced stages of change using more behavioral and experiential strategies to become nonviolent. However, except for the use of social liberation strategies, there were no gender differences in the use of the various processes. These findings suggest that the Transtheoretical Model may apply to female perpetrators equally as well as to male perpetrators. Intervention programs designed for male batterers using the Transtheoretical Model may also be helpful in the treatment of women arrested for domestic violence.


The discordance between primary breast cancer lesions and pulmonary metastatic lesions in expression of aldehyde dehydrogenase 1-positive cancer cells.
We evaluated the expression of aldehyde dehydrogenase 1 (ALDH1) between primary breast lesions and pulmonary metastatic (PM) lesions in breast cancer patients. We retrospectively analyzed the clinicopathological features and the expression statuses of ER, PR, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions and evaluated the discordance rates in the expressions of these markers between the primary and metastatic lesions, and also the prognostic value of these factors. None of the PM patients had metastases at any other sites, and all had undergone curative breast cancer surgery. The pulmonary operation was partial resection in 15 (88 %) patients and lobectomy in 2 (12 %) patients. The median overall survival (OS) after resection of the PNs (OS) was 48 months. The discordance rates in the expressions of ER, PR, HER2, Ki67 and ALDH-1 between the primary and metastatic lesions were 0, 29, 21, 43 and 50 %, respectively. There was significant discordance in the biomarkers between the primary tumors and the metastatic lesions.


Activation of the cell cycle machinery and the isoflavonoid biosynthesis pathway by active Rhizobium meliloti Nod signal molecules in Medicago microcallus suspensions.
We have shown that treatment of Medicago microcallus suspensions with the cognate Rhizobium meliloti Nod signal molecule NodRm-IV(C16:2,S) can modify gene expression both qualitatively and quantitatively. At concentrations of 10(-6) - 10(-9) M, this host specific plant morphogen but not the inactive non-sulfated molecule stimulated cell cycle progression as indicated by the significantly enhanced thymidine incorporation, elevated number of S phase cells, increase in kinase activity of the p34cdc2-related complexes and enhancement of the level of expression of several cell cycle marker genes, the histone H3-1, the cdc2Ms and the cyclin cycMs2. The presented data suggest that at least part of the physiological role of the Nod factor may be linked to molecular events involved in the control of the plant cell division cycle. In situ hybridization experiments with antisense H3-1 RNA probe indicated that only certain cells of the calli were able to respond to the Nod factor. High (10(-6) M) but not low (10(-9) M) concentrations of the active Nod factors induced the expression of the isoflavone reductase gene (IFR), a marker gene of the isoflavonoid biosynthesis pathway in most callus cells. Our results indicate that Medicago cell responses to the Nod signal molecules can be investigated in suspension cultures.


The effect of 2-(4-methyl-1-piperazinylmethyl) acrylophenone dihydrochloride on the alkylation of tubulin.
2-(4-Methyl-1-piperazinylmethyl) acrylophenone dihydrochloride (MPMAP) is a novel inhibitor of microtubule assembly in vitro and in vivo whose molecular mechanism of action has not been investigated (M. L. Mallevais, A. Delacourte, I. Lesieur, D. Lesieur, M. Cazin, C. Brunet, and M. Luyckx (1984) Biochimie 66, 477-482). We have examined the effect of MPMAP on the alkylation of tubulin by iodo[14C]acetamide and N,N'-ethylenebis(iodoacetamide) (EBI). MPMAP is a very potent inhibitor of tubulin alkylation by iodo[14C]acetamide. MPMAP gives half-maximal inhibition at a concentration of 15 microM. MPMAP also inhibits the alkylation of denatured tubulin and of aldolase, implying that it reacts strongly with sulfhydryl groups. MPMAP does not, however, interfere with formation by EBI of a crosslink between cysteines 239 and 354 in the beta subunit of tubulin, suggesting that these sulfhydryls are located in a cleft in the tubulin molecule.


The significance of multiple blue-grey dots (granularity) for the dermoscopic diagnosis of melanoma.
The presence of multiple blue-grey dots (MBGD) is widely used by clinicians to decide if a pigmented lesion should be removed, but only little is known about their significance. To evaluate the significance of MBGD for the dermoscopic diagnosis of melanoma. In part 1 we retrospectively evaluated 340 pigmented lesions for the presence and morphological appearance of granularity. One hundred and seventy melanomas were included and matched with 170 benign and dysplastic naevi which were randomly chosen from our collection. In part 2, 3773 lesions were examined prospectively in at-risk patients: all lesions with granularity were recorded, surgically removed and subjected to histopathological examination. In part 1, granularity was found in 26.5% of the benign lesions and 93.5% of melanomas. The presence of granularity, granularity at the periphery, irregularly distributed granularity and granularity in association with red and white colour were statistically highly significant for the diagnosis of melanoma (P < 0.001). In part 2, granularity was found in 1.08% of the 3773 lesions and more frequently in sun-damaged skin. Sensitivity for the diagnosis of melanoma was 85% and specificity 99%. After the revision of many lesions with MBGD, we concluded that the term 'granularity' better describes this entity. Lesions with irregular granularity (periphery, irregularly distributed) should be removed especially if they are associated with red, blue or white colour. Lesions with a benign dermoscopy pattern which have granularity with a regular appearance and involving only a small portion of the lesion do not require surgical excision.


Glass Probe Stimulation of Hair Cell Stereocilia.
Hair cells are designed to sense mechanical stimuli of sound using their apical stereocilia hair bundles. Mechanical deflection of this hair bundle is converted into an electrical signal through gating of mechano-electric transduction channels. Stiff probe stimulation of hair bundles is an invaluable tool for studying the transduction channel and its associated processes because of the speed and ability to precisely control hair bundle position. Proper construction of these devices is critical to their ultimate performance as is appropriate placement of the probe onto the hair bundle. Here we describe the construction and use of a glass probe coupled to a piezo-electric actuator for stimulating hair bundles, including the basic technique for positioning of the stimulating probe onto the hair bundle. These piezo-electric stimulators can be adapted to other mechanically sensitive systems.


Clinical presentation, imaging and response to interferon-alpha therapy in Erdheim-Chester disease: case-based review.
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis associated with BRAFV600E mutations in more than 50% of cases and presenting with 95% with skeletal lesions. However, cutaneous, pulmonary, large vessels and central nervous system involvement can also occur. We report a case of a 25-year-old woman who was admitted in 2018 for exploration of diffuse bone pain and rashes on the face. Her current symptoms had started 14 months earlier and consisted of bone pain, affecting the legs. She had periodic low-grade fever, asthenia and xanthelasma-like papules appeared on face. At admission, physical examination showed bilateral and symmetrical long bone pain, especially in the knees and multiple xanthelasma-like papules around the eyelids, cheeks and chin. Laboratory tests revealed elevated erythrocyte sedimentation rate and C-reactive protein. Magnetic resonance (MR) imaging showed multiple mixed bone lesions with a hyperintensive MR signal on PD FS and hypointense signal on T1of the femur and tibia. Bone scintigraphy indicated bilateral and symmetrical metaphyseal and diaphyseal increased uptake. Abdominal computed tomography (CT) scan showed infiltration of the perirenal fat. Biopsy of the skin revealed histiocytic infiltration, which was CD68-positive and CD100-positive, confirming the diagnosis of ECD. Patient was treated with interferon-α (IFN-α) plus methylprednisolone. After 6 months of treatment her clinical condition partly improved: a reduction of pain on visual analogue scale (VAS) scale, significant decrease of methylprednisolone dose and specific dynamics according to bone MR imaging data, however, no change in symptoms attributed to skin rash was noted. We also provide the literature review results of IFN-α treatment efficacy in Erdheim-Chester disease involving the skin and musculoskeletal system with MR imaging changes.


Everyday executive function predicts adaptive and internalizing behavior among children with and without autism spectrum disorder.
Individuals with autism spectrum disorder (ASD) demonstrate challenges with executive function (EF), adaptive behavior, and mental health, all of which place long-term wellbeing at risk. In the current study we examined the relation between parent-rated EF and adaptive functioning and internalizing symptoms (anxiety, depression), as we expected that identifying the specific EF domains most closely related to these indices of functioning would illuminate opportunities for targeted intervention. Participants included 59 children and adolescents with ASD (M = 10.1 years) and 67 who were typically developing (TD) (M = 9.4 years) matched on age, IQ, mental age, and maternal education. Caregivers completed the Behavior Rating Inventory of EF (BRIEF) and Behavior Assessment System for Children, Second Edition (BASC-2). Parents rated children with ASD as demonstrating significantly more challenges across most of the examined BRIEF and BASC-2 indices and scales, with the exception of organization of materials (BRIEF) and anxiety (BASC-2). For both groups, metacognitive EF processes emerged as strongly associated with practical, conceptual, and social skills, though different BRIEF scales emerged as significant across the component subdomains. In terms of the relation with mental health, BRIEF index scores were unrelated to anxiety for both groups. Behavior regulation, however, was significantly associated with depression symptoms for children with and without ASD. The findings highlight the possibility that targeting particular EF domains among individuals with and without ASD may not only have direct benefit for behavior regulation and metacognitive abilities, but may also extend to other areas of life, including adaptive behavior and concomitant internalizing symptomatology. Autism Res 2018, 11: 284-295. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. We examined whether parents' ratings of their children's flexibility and ability to monitor their behavior predicted adaptive skills (e.g., ability to complete day-to-day personal tasks, communicate, and socialize) and symptoms of anxiety and depression among children with and without autism spectrum disorder. For both groups, children's abilities to manage and monitor their behavior were strongly related to adaptive skills. Children's flexibility and ability to inhibit inappropriate behavior and control their emotions was associated with depression symptoms for both groups.


Properties of morphologically variant haploid frog cells formed by combined treatment with Mengo virus and the polyene antibiotic mediocidin.
Comparisons have been made of cell surface glycoproteins, concanavalin A agglutinability, and cloning efficiencies in liquid media of ICR 2A (haploid frog cells), ICR 2A M (three cloned populations of haploid frog cells resistant to 5 microgram per ml of the polyene antibiotic mediocidin), and ICR 2A M/MV cells (five cloned populations of morphologically variant haploid frog cells produced by exposure of the parental cells to the combined effects of mediocidin and an RNA mammalian virus, Mengo virus). Independently isolated ICR 2A M/MV clones exhibited altered cell surface glycoproteins, increased concanavalin A agglutinability, and enhanced cloning efficiency in liquid media when compared with ICR 2A parental cells. In contrast, ICR 2A M cells had properties similar to ICR 2A cells, with the exception of the former's increased resistance to mediocidin. The differences in properties between ICR 2A M/MV and ICR 2A cells suggest that alterations resembling transformation have occurred in ICR 2A M/MV cells as a consequence of combined treatment with mediocidin and Mengo virus.


Effects of long-term chilled storage of red deer epididymides on DNA integrity and motility of thawed spermatozoa.
We have carried out a study on the influence of prolonged cold storage (5 degrees C) of Iberian red deer epididymides on post-thaw sperm motility and DNA integrity. Twenty-nine pairs of testes, with attached epididymides, were collected during November and December. Spermatozoa from one of each of the pairs were immediately recovered, evaluated and frozen (control). The remaining epididymides were cooled to 5 degrees C and stored for 24, 96 and 192 h (experimental groups), after which spermatozoa were collected and frozen. Samples were evaluated before freezing, after thawing, and after a 2-h period of incubation at 37 degrees C. Motility was evaluated by means of a CASA system and chromatin stability was assessed following the Sperm Chromatin Structure Assay (SCSA). Our results showed that, during the first 96 h, the motility (total and progressive) did not significantly decline when assessed after cryopreservation, although there was a significant decline when epididymides had been stored for 192 h at 5 degrees C (P<0.001). The present study demonstrates that motility and DNA status of thawed spermatozoa collected from refrigerated epididymes, at least 96 h post-mortem, were good enough to consider their eventual use. Most importantly, sperm DNA integrity after thawing was apparently not affected by storage time, even after 192 h.


Incidence and effect of hypothermia in seriously injured patients.
Hypothermia is a well recognized consequence of severe injury, even in temperate climates, and the physiologic consequences of hypothermia are known to be detrimental. To analyze the frequency and risk factors for hypothermia and its effect on patient outcome, we prospectively studied 94 intubated injured patients at a regional trauma center during a 16-month period. Esophageal temperature probes were placed in the field or ER and core temperatures (T) were followed for 24 hours or until rewarming. Patients were designated as normothermic (greater than 36 degrees C), mildly hypothermic (34 degrees C-36 degrees C) or severely hypothermic (less than 34 degrees C) based on initial T. The risk factors for hypothermia evaluated included age, severity and location of injuries, blood alcohol level, blood transfusion requirements, and time spent in the field, ER, or OR. The average initial T was 35 degrees C, with no seasonal variation. Injury severity and survival correlated with severe hypothermia. Normothermic patients had an average ISS of 28 with a 78% survival. Severely hypothermic patients had an average ISS of 36 with a 41% survival (p less than 0.05). Patient age strongly correlated with outcome although there was no relationship between age and initial temperature. Sixty-two per cent of patients tested were positive for blood alcohol, and one half were legally intoxicated (BAC greater than 100 mg%). However, no consistent correlation was found between alcohol intoxication and initial temperature or patient survival. Blood transfusion requirements paralleled injury severity and patients receiving greater than 10 unit transfusions had significantly lower core temperature (p less than 0.05). The average temperature change was positive in the ER, OR, and ICU with time to rewarming correlating with the aggressiveness of warming measures.(ABSTRACT TRUNCATED AT 250 WORDS)


Using joint models to study the association between CD4 count and the risk of death in TB/HIV data.
The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model. We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data. Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84). In this paper we have shown that the "current value" association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes.


Parathyroid exploration in the reoperative neck: improved preoperative localization with 4D-computed tomography.
Reoperation for hyperparathyroidism (HPT) carries an increased risk for morbidity and failure to cure. Accurate preoperative localization minimizes operative risk but is often difficult to achieve in the reoperative setting. Four-dimensional computed tomography (4D-CT) is an emerging technique that uses functional parathyroid anatomy for precise preoperative localization. We evaluated 4D-CT as a tool for localization of hyperfunctioning parathyroid tissue in the reoperative setting. A prospective endocrine database was queried to identify 45 patients who underwent reoperative parathyroidectomy after preoperative localization using 4D-CT. The patients were categorized into 1 of 3 groups: group 1 included those who had previous neck surgery for non-HPT conditions; group 2 included those who had undergone a previously unsuccessful neck exploration for HPT; and group 3 included patients with HPT who had a previous neck exploration with resection of at least 1 hypercellular parathyroid. The sensitivity of 4D-CT for localization was 88% compared with 54% for sestamibi imaging. Four-dimensional CT more often correctly localized (p=0.0003) and lateralized (p=0.005) hyperfunctional parathyroid tissue than sestamibi did. Four-dimensional CT successfully localized hyperfunctional parathyroid tissue in 18 (82%) of 22 group 1 patients, 10 (91%) of 11 group 2 patients, and 8 (67%) of 12 group 3 patients. Three patients were lost to followup. At a mean followup of 9.8 months, 39 (93%) of 42 patients were surgically cured and 3 patients (7%; 2 in group 3) had persistent HPT. Four-dimensional-CT is an ideal tool for preoperative localization of hyperfunctioning parathyroid tissue in the reoperative setting. Localization and successful reoperation are most difficult in patients who have undergone an earlier operation that included resection of at least one hypercellular parathyroid suggesting multigland disease.


Microsomal lipid peroxidation: the role of NADPH--cytochrome P450 reductase and cytochrome P450.
The role of NADPH--cytochrome P450 reductase and cytochrome P450 in NADPH- and ADP--Fe3(+)-dependent lipid peroxidation was investigated by using the purified enzymes and liposomes prepared from either total rat-liver phospholipids or a mixture of bovine phosphatidyl choline and phosphatidyl ethanolamine (PC/PE liposomes). The results suggest that NADPH- and ADP--Fe3(+)-dependent lipid peroxidation involves both NADPH--cytochrome P450 reductase and cytochrome P450. Just as in the case of cytochrome P450-linked monooxygenations, the role of these enzymes in lipid peroxidation may be to provide two electrons for O2 reduction. The first electron is used for reduction of ADP--Fe3+ and subsequent addition of O2 to the perferryl radical (ADP--Fe3(+)-O2-), which then extracts an H atom from a polyunsaturated lipid (LH) giving rise to a free radical (LH.) that reacts with O2 yielding a peroxide free radical (LOO.). The second electron is then used to reduce LOO. to the lipid hydroperoxide (LOOH). In the latter capacity, reduced cytochrome P450 can be replaced by EDTA--Fe2+ or by the superoxide radical as generated through redox cycling of a quinone such as menadione.


Fumarate dependent protein composition under aerobic and anaerobic growth conditions in Escherichia coli.
In the absence of sugars, C4-dicarboxylates (C4DC) like fumarate represent important substrates for growth of Escherichia coli. Aerobically, C4DCs are oxidized to CO2 whereas anaerobically, C4DCs are used for fumarate respiration. In order to determine the impact of fumarate under aerobic and anaerobic conditions, proteomes of E. coli W3110 grown aerobically or anaerobically with fumarate and/or the non-C4DC substrate glycerol were comparatively profiled by nanoLC-MS/MS. Membrane enrichment allowed sensitive detection of membrane proteins. A total of 1657 proteins of which 646 and 374 were assigned to the cytosol or membrane, respectively, were covered. Presence of fumarate triggered changes (≥ 2fold) to the levels of 211 and 76 proteins under aerobic and anaerobic growth, respectively. The fumarate induced changes included proteins encoded by genes regulated by the C4DC two-component system DcuS-DcuR (DctA, DcuB, FumB, FrdABC proteins) catalyzing uptake and initial catabolic steps. Many of the proteins displaying altered levels are not part of the DcuS-DcuR regulon, including proteins of citric acid cycle and associated pathways (aerobic), proteins involved in motility and chemotaxis (anaerobic), and oxidative stress. Their genes are mostly preceded by cAMP receptor protein (CRP) sites, some by DcuR-like sites. Testing of selected genes confirmed regulation by CRP and DcuS-DcuR. SIGNIFICANCE: Global protein profiling of the soluble and the membrane fraction provides a comprehensive view on the protein pattern of E. coli grown aerobically and anaerobically with or without fumarate. The results disclose during aerobic growth besides the known impact of the C4-dicarboxylates (C4DC) on carbon utilization and citric acid cycle major adaptations in amino acid metabolism. In contrast, protein alterations in the presence of fumarate under anaerobic conditions point to enhanced motility and chemotaxis. Only proteins (transporters, initial metabolic steps) feeding external C4DCs to the central pathways were regulated by the C4DC two-component system DcuS-DcuR, whereas other protein levels were controlled in an indirect manner by CRP triggered catabolite control and other mechanisms. Consequently, metabolic and transcriptional regulation by C4DCs is apparently effected by a network of the DcuS-DcuR system with important contribution by catabolite control.


Revised criterion for diagnosis of ineffective esophageal motility is associated with more frequent dysphagia and greater bolus transit abnormalities.
Ineffective esophageal motility (IEM) has been defined by the presence of > or = 30% liquid swallows with contraction amplitude < 30 mmHg (ineffective swallows) in the distal esophagus ("old" IEM). A recent study with combined multichannel intraluminal impedance and manometry (MII-EM) raised the question whether the manometric diagnosis of IEM should be based on a new definition: > or = 50% ineffective liquid swallows ("new" IEM). The aim of this study was to evaluate the association between the number of ineffective liquid swallows and symptoms and bolus transit in patients with "new" or "old" IEM who underwent MII-EM studies using 10 liquid and 10 viscous swallows. There were 150 patients with "old" IEM included in the study. The patients diagnosed with "old" IEM (N = 150) (group A) were compared with those who retained a manometric diagnosis of IEM by the new definition (N = 101) (group B). The patients who did not retain their manometric diagnosis of IEM by the new definition (N = 49) (group C) were compared with group B. IEM was characterized as mild (normal bolus transit for both liquid and viscous swallows), moderate (abnormal bolus transit either for liquid or viscous swallows), or severe (abnormal bolus transit for both liquid and viscous swallows). There was no statistical difference in frequency of mild, moderate, or severe IEM and frequency of symptoms between group A and B. Group C had a significantly higher frequency of mild IEM and significantly lower frequency of severe IEM than group B. Heartburn (25.7%vs 10.2%, P= 0.03) and dysphagia (24.8%vs 12.3%, P= 0.08) showed a trend towards a greater frequency in group B than in group C. Our study indicates that IEM with > or = 50% ineffective liquid swallows is frequently associated with bolus transit abnormalities and esophageal symptoms. Our results underscore the rationale for using the new definition of IEM.


An improved procedure for the electrochemical determination of serum ionized calcium.
The "Orion model 99-20 serum calcium flow-through system" has been rendered insensitive to protein poisoning by the plascing of a dialysis membrane in front of the electrode membrane, making the addition of trypsin and triethanolamine to standards unnecessary. Flow dependency of the results obtained has been investigated.


Barriers to treatment adherence for female Tuberculosis (TB) patients during the COVID-19 pandemic: Qualitative evidence from front-line TB interventions in Bengaluru City, India.
Available evidence shows that India's ongoing COVID-19 pandemic response has adversely affected the national tuberculosis elimination program. The study attempted to understand the barriers to successful treatment adherence for female tuberculosis (TB) patients due to disruptions caused by the pandemic. The study draws on qualitative in-depth interviews conducted with patients and TB health visitors from Bengaluru city before and during the pandemic period using a grounded theory approach. While TB has the potential to push female patients who worked in informal arrangements to joblessness and poverty, the pandemic situation has exacerbated these vulnerabilities. The pandemic situation slowed down or suspended vital frontline interventions such as active case finding, distribution of medicine, follow-up of sputum examination, monitoring of medicine intake, and patient support measures. The pandemic-induced barriers to treatment adherence for the vulnerable TB patients can lead to adverse treatment outcomes including disease relapse and drug resistance. It is hence suggested that there is an urgent need for recasting the frontline TB interventions in India in the context of the pandemic in order to achieve the goal of TB elimination.


Physicochemical properties of dipalmitoyl phosphatidylcholine after interaction with an apolipoprotein of pulmonary surfactant.
We studied the interaction between an apolipoprotein of pulmonary surfactant and the principal lipid found in this material, dipalmitoyl phosphatidylcholine. The apolipoprotein was extracted from canine surfactant and purified to greater than 90% homogeneity. The apolipoprotein was mixed for 16 h at room temperature with dipalmitoyl phosphatidylcholine dispersed in a buffer containing 0.1 M NaCl and 3mM CaCl2. Unbound lipid, unbound protein, and recombinants of lipid and protein were separated by density gradient centrifugation. 71% of the apolipoprotein was found associated with dipalmitoyl phosphatidylcholine. In comparable experiments using bovine plasma albumin about 13% of the albumin was recovered with the lipid. The physicochemical state of the lipid in the apolipoprotein-lipid complex was modified after binding of the protein. A distinct phase transition at 42 degrees C could no longer be detected, and the rate of adsorption to an air-liquid interface of the apolipoprotein-lipid complex was greater than that of the lipid alone. Surface tension vs. surface area isotherms of the dipalmitoyl phosphatidylcholine-apolipoprotein materials, however, were similar to those exhibited by pure dipalmitoyl phosphatidylcholine. The results suggest a physiological role for this apolipoprotein. It may bind to dipalmitoyl phosphatidylcholine under conditions expected in vivo, and may modify the physical properties of the aggregated dipalmitoyl phosphatidylcholine to form domains of lipid in a liquid-crystalline array. The complex dipalmitoyl phosphatidylcholine and apolipoprotein would have the physical properties necessary for its physiological function, allowing it to absorb to the alveolar interface and reduce its surface tension to less than 10 dynes/cm. Dipalmitoyl phosphatidylcholine, by itself, is in a gel-crystalline array below its phase transition temperature (42 degrees C) and would be incapable of effecting these actions.


Longitudinal surface plasmon resonance assay enhanced by magnetosomes for simultaneous detection of Pefloxacin and Microcystin-LR in seafoods.
A simple longitudinal surface plasmon resonance (LSPR) assay for the simultaneous detection of Pefloxacin and Microcystin-LR in seafoods has been developed for the first time using antibody-functionalized gold nanorods as signal probes and antigen-ovalbumin modified biological magnetosomes as signal amplification probes. The gold nanorods exhibit two different LSPR peaks, at around 695nm and 863nm, the positions of which were sensitive to changes in the local environment but can be subjected to simultaneous UV-vis detection. The biological magnetosomes produced by the magnetotactic bacteria not only act as a substrate for the immobilization of artificial antigen, but also enable signal enhancement and rapid separation, because of good dispersivity, biocompatibility and superparamagnetic properties. Under optimal conditions, magnetosome-enhanced LSPR assays showed a good linear response over the range 1-20ngmL(-1) (R(2)=0.9978 and R(2)=0.9992) with little adsorption to Enrofloxacin, Sarafloxacin, Ciprofloxacin, Norfloxacin, Microcystin-RR, Microcystin-LW, and Microcystin-LF, and compared with magnetosome-free LSPR assays, the response signal was amplified 2.5-5.0 fold. Furthermore, LSPR assays were successful in the analysis of Pefloxacin and Microcystin-LR in naturally contaminated seafood samples and high recoveries were achieved. Indications are that this LSPR assay promises reliable simultaneous detection of Pefloxacin and Microcystin-LR in seafoods, and holds the potential of novel applications in exploiting this multiple simultaneous UV-vis detection.


A supervised multi-spike learning algorithm based on gradient descent for spiking neural networks.
We use a supervised multi-spike learning algorithm for spiking neural networks (SNNs) with temporal encoding to simulate the learning mechanism of biological neurons in which the SNN output spike trains are encoded by firing times. We first analyze why existing gradient-descent-based learning methods for SNNs have difficulty in achieving multi-spike learning. We then propose a new multi-spike learning method for SNNs based on gradient descent that solves the problems of error function construction and interference among multiple output spikes during learning. The method could be widely applied to single spiking neurons to learn desired output spike trains and to multilayer SNNs to solve classification problems. By overcoming learning interference among multiple spikes, our method has high learning accuracy when there are a relatively large number of output spikes in need of learning. We also develop an output encoding strategy with respect to multiple spikes for classification problems. This effectively improves the classification accuracy of multi-spike learning compared to that of single-spike learning.


Complications in Patients with Chronic Kidney Disease.
Chronic kidney disease (CKD) is a widespread condition that predisposes patients to a myriad of complications, including cardiovascular disease, electrolyte and acid-base derangements, anemia, mineral-bone disease, and volume excess. The frequency of CKD complications increases with the stage of disease, becoming nearly ubiquitous in later stages. The complications of CKD have profound implications for patient management, laboratory monitoring, medication prescribing, and follow up. Management of CKD seeks to slow disease progression and mitigate the risks posed by these complications.


Evolution of Vertebrate Hormones and Their Receptors: Insights from Non-Osteichthyan Genomes.
Homeostatic control and reproductive functions of humans are regulated at the molecular levels largely by peptide hormones secreted from endocrine and/or neuroendocrine cells in the central nervous system and peripheral organs. Homologs of those hormones and their receptors function similarly in many vertebrate species distantly related to humans, but the evolutionary history of the endocrine system involving those factors has been obscured by the scarcity of genome DNA sequence information of some taxa that potentially contain their orthologs. Focusing on non-osteichthyan vertebrates, namely jawless and cartilaginous fishes, this article illustrates how investigating genome sequence information assists our understanding of the diversification of vertebrate gene repertoires in four broad themes: (a) the presence or absence of genes, (b) multiplication and maintenance of paralogs, (c) differential fates of duplicated paralogs, and (d) the evolutionary timing of gene origins.


Iliotibial Band Syndrome in Runners: Biomechanical Implications and Exercise Interventions.
Iliotibial band syndrome (ITBS) has known biomechanical factors with an unclear explanation based on only strength and flexibility deficits. Neuromuscular coordination has emerged as a likely reason for kinematic faults guiding research toward motor control. This article discusses ITBS in relation to muscle performance factors, fascial considerations, epidemiology, functional anatomy, strength deficits, kinematics, iliotibial strain and strain rate, and biomechanical considerations. Evidence-based exercise approaches are reviewed for ITBS, including related methods used to train the posterior hip muscles.


Photo-aging evaluation - In vitro biological endpoints combined with collagen density assessment with multi-photon microscopy.
Ultraviolet exposure has profound effect on the dermal connective tissue of human skin. We aimed to develop and validate an evaluation method/methodology using a full-thickness reconstructed skin model, to assess the anti-photoaging efficacy of cosmetic ingredients and sunscreen formulas by blending multi relevant biological endpoints including the newly developed dermal collagen quantification method with Multi-photon microscopy. The response of ex vivo human skin to UVA exposure was first characterized with multiphoton microscopy. Reconstructed full-thickness skin models was then used to reproduce the data and to create a proof-of-concept study by treating the models with sunscreen prototypes A or B, which differ on their UVA absorption properties, and systemic Vitamin C (Vit C). After exposure to UVA, the collagen density was quantified via multiphoton microscopy with automatic imaging processing. Histology, fibroblasts number, metalloprotease 1 (MMP1) secretion were also assessed. UVA exposure induced pronounced reduction in collagen density and increased MMP1 secretion within both ex vivo human skin and reconstructed skin. Histological damage and fibroblast disappearance was observed with reconstructed skin. Within the proof-of-concept study prototype B, possessing higher UVA filtration, gave better protection than prototype A on the UV associated biological markers, and association with Vit C boosted sunscreen formula efficacy. The photoaging evaluation method, consists of multi biological markers as well as dermal collagen quantification, is a relevant mean to assess the pre-clinical efficacy of anti-photoaging ingredients and sunscreen products. This approach is also beneficial for evaluating the efficacy of sunscreens and photoprotective ingredients.


The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior.
The molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. The expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. MiR-371 underexpression correlated with non-organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5α-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5α-dihydrotestosterone. Our data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.


Hyperstimulated human preovulatory follicular fluid, luteinized cells of unruptured follicles, and corpus luteum contain pregnancy-associated plasma protein A (PAPP-A).
Radioimmunoassay, gel filtration, and immunoperoxidase methods were used to study the occurrence, properties, and concentration of pregnancy-associated plasma protein A (PAPP-A) in the human ovary and in the follicular fluid from 97 hyperstimulated follicles from 29 infertile women participating in an in vitro fertilization program. At the detection level of 15 micrograms/l, PAPP-A was found in 83 of 97 follicular fluids, the levels ranging from undetectable to 483 micrograms/l (median, 130 micrograms/l). In gel filtration, PAPP-A immunoreactivity of follicular fluid eluted in the same volume as placental PAPP-A, and the dose-response curves of follicular fluid PAPP-A and purified PAPP-A were parallel. The PAPP-A concentration was not affected by prior treatment with a protease inhibitor. Follicular fluid aspirates containing the ovum had a higher PAPP-A concentration than those in which no ovum was detected (P less than 0.01), whereas no difference was found in the PAPP-A concentrations between follicles yielding an ovum which was fertilized and cleaved and those yielding an unfertilizable oocyte. There was a correlation between PAPP-A and estradiol or progesterone concentrations, and between the PAPP-A concentration and the volume of follicular fluid aspirate. In hyperstimulated unruptured follicles, PAPP-A was localized in the luteinized granulosa and theca interna cells, but not if luteinization was not observed. Corpus luteum cells were also PAPP-A positive, whereas unstimulated Graafian follicles were negative. Our results indicate that PAPP-A appears in the hyperstimulated follicle shortly before ovulation and may thus play a part in the early events of human reproduction.


Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells.
Catecholamine secretion from PC-12 cells can be triggered by agents that increase intracellular Ca2+ and is enhanced by phorbol esters and agents that elevate intracellular cAMP concentrations. In mutant PC-12 cells lacking cAMP-dependent protein kinase (PK-A) in which protein kinase C (PK-C) was down-regulated, Ca2+-dependent secretion occurred normally but was no longer enhanced by cAMP or phorbol esters. In digitonin-permeabilized PC-12 cells that lacked PK-C and PK-A, a range of calmodulin (CaM) inhibitors failed to block Ca2+-triggered catecholamine release. Moreover, Mn2+, a CaM activator, failed to trigger catecholamine release whereas Ba2+, which does not activate CaM, supported secretion. These results indicate that the basic mechanism of stimulus/secretion coupling in PC-12 cells does not absolutely require a regulated protein phosphorylation- or calmodulin-dependent step.


A directional passive air sampler for monitoring polycyclic aromatic hydrocarbons (PAHs) in air mass.
A passive air sampler was developed for collecting polycyclic aromatic hydrocarbons (PAHs) in air mass from various directions. The airflow velocity within the sampler was assessed for its responses to ambient wind speed and direction. The sampler was examined for trapped particles, evaluated quantitatively for influence of airflow velocity and temperature on PAH uptake, examined for PAH uptake kinetics, calibrated against active sampling, and finally tested in the field. The airflow volume passing the sampler was linearly proportional to ambient wind speed and sensitive to wind direction. The uptake rate for an individual PAH was a function of airflow velocity, temperature and the octanol-air partitioning coefficient of the PAH. For all PAHs with more than two rings, the passive sampler operated in a linear uptake phase for three weeks. Different PAH concentrations were obtained in air masses from different directions in the field test.


N6-methyladenosine modification of REG1α facilitates colorectal cancer progression via β-catenin/MYC/LDHA axis mediated glycolytic reprogramming.
Aerobic glycolysis has been considered as a hallmark of colorectal cancer (CRC). However, the potential functional regulators of glycolysis in CRC remains to be elucidated. In the current study, we found that Regenerating islet-derived protein 1-alpha (REG1α) was significantly increased in both CRC tissues and serum, and positively associated with CRC patients' lymph node metastasis, advanced tumor stage, and unfavorable prognosis. Ectopic expression of REG1α contributed to various tumorigenic properties, including cell proliferation, cell cycle, migration, invasion, and glycolysis. In contrast, REG1α deficiency in CRC cells attenuated malignant properties and glucose metabolism. Mechanically, REG1α promoted CRC proliferation and metastasis via β-catenin/MYC axis-mediated glycolysis upregulation. Moreover, the malignant behaviors governed by REG1α could be effectively abolished by silencing of Wnt/β-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1α expression was mediated by METTL3 in an m6A-dependent manner. Overall, our work defines a novel regulatory model of the METTL3/REG1α/β-catenin/MYC axis in CRC, which indicates that REG1α could function as a novel biomarker and a potential therapeutic target for patients with CRC.


Reproducibility of speckle-tracking-based strain measures of left ventricular function in a community-based study.
The reproducibility of echocardiographic measurements of myocardial strain, performed in a community-based setting, has not been reported previously. The reproducibility of left ventricular strain measurements was examined in two samples of 20 participants each from the Offspring Cohort of the Framingham Heart Study (mean age, 63 ± 9 years; 59% women). Two-dimensional speckle-tracking-based measurements of global peak left ventricular strain in systole were performed in the apical four-chamber, apical two-chamber, and midventricular parasternal short-axis views. Interobserver intraclass correlation coefficients were ≥0.84 for all global strain measurements, with average coefficients of variation of ≤4% for global longitudinal and circumferential strain and <8% for global transverse and radial strain. For left ventricular strain measurements performed in each of the three views, intraobserver intraclass correlation coefficients were ≥0.91 among time points spanning a total 8-month period. The average coefficients of variation were <6% for global longitudinal and circumferential strain and <9% for global transverse and radial strain. Interobserver and intraobserver reproducibility findings were similar in analyses adjusting for frame rate. Excellent reproducibility of global longitudinal and circumferential strain measurements and very good reproducibility of global transverse and radial strain measurements were observed. Taken together, these findings demonstrate the reproducibility of performing echocardiographic strain measurements in a large, epidemiologic community-based setting.


A prospective and comparative study between stapled hemorrhoidopexy and hemorrhoidal artery ligation with mucopexy.
The aim of this study was to compare the efficacy between stapled hemorrhoidopexy (Longo technique) and transanal hemorrhoidal artery ligation with mucopexy (THDm) in the treatment of hemorrhoidal disease. From June 2009 to January 2011, 81 patients having grade II or III hemorrhoidal disease underwent prospective evaluation followed by surgery at two centers (27 Longo and 54 THDm). Symptoms (bleeding, tenesmus, prolapse, fecal incontinence, pain) and the satisfaction score were compared on the first post-operative day and at 1, 6, 12, and 24 months thereafter. The follow-up was 24 months. There was no difference in mean length of stay. One complication (recto-vaginal fistula) was observed after Longo. The prolapse score was significantly lower after THDm than after Longo on the first post-operative day (P < 0.0015). Bleeding score after THDm was significantly lower on the first post-operative day (P = 0.04), but higher thereafter (P = 0.03 and P = 0.04). Tenesmus score after THDm was significantly lower for the first three months (P < 0.06 and 0.001). On the first post-operative day and at one month, the visual analog pain score was significantly lower after THDm than that after Longo (P < 0.0003 et P < 0.01). On the first post-operative day and at one month, the satisfaction score was higher after THDm than after Longo (P < 0.001). THDm was safe and effective. Short-term outcomes after THDm were better than after Longo but long-term results seemed to be similar.


Enhancing water purification through F and Zn-modified Fe-MCM-41 catalytic ozonation.
Due to its low interfacial electron migration ability and highly hydrophilic, Fe-MCM-41 (FeM) had poor activity and stability during catalytic ozonation. To this end, the secondary metal Zn and Si-F group were introduced into the framework of FeM to create surface potential difference and hydrophobic sites. Comparative characterizations showed that there existed rich acid sites with great potential difference on F-Fe-Zn-MCM-41 (FFeZnM). Additionally, because of the existence of hydrophobic and electron-withdrawing Si-F unit, the electron migration ability, hydrophobicity and acidity of FFeZnM were enhanced. The greater O3 mass transfer was induced by Si-F group and O3 was directly activated at Fe and Zn Lewis acid sites into •OH, •O2- and 1O2. With •OH acting as main species, FFeZnM/O3 achieved the superior IBP removal (93.4%, 30 min) and TOC removal (46.6%, 120 min) over those of sole O3 and F-FeM/O3 processes, respectively. HCO3-, Cl-, NO3- and SO42- hindered IBP degradation by FFeZnM/O3, but high concentration humic acid (HA) exhibited promotion by forming HA-IBP complex. IBP degradation by FFeZnM/O3 was enhanced with tap water, river water, and effluent from the secondary sedimentation tank of the sewage plant acting as medium. This study proposed an innovative approach to catalyst design for catalytic ozonation.


EPEC: a cocktail of virulence.
Genomics studies are prompting a re-evaluation of the diversity of Escherichia coli pathovars and how this diversity corresponds to virulence.


Congenital autonomic dysfunction with universal pain loss.
Three patients who appear to have a previously undescribed congenital neuropathy are described. None is of Ashkenazi Jewish extraction, but each seems to fulfill the clinical diagnostic criteria for familial dysautonomia. All lack overflow tears, fungiform papillae, and deep-tendon reflexes; intradermal administration of histamine did not produce an axon flare. Intraocular instillation of dilute mecholyl produced miosis in the one patient tested. In contrast to patients with familial dysautonomia, the three patients had universal loss of pain sensation, profound hypotonia, and unusual facies. Pathologic examination of the sural nerve in one patient was not consistent with the usual findings in familial dysautonomia. These patients are believed to have a previously undescribed congenital neuropathy.


Smoothing out drug resistance.
Smoothened inhibitors have emerged as successful treatment alternatives for Hedgehog pathway-dependent tumors, but they are linked with the appearance of drug resistance. In this issue of Cancer Cell, Kim and colleagues overcome such resistance by combining approved drugs itraconazole and arsenic trioxide, thus opening a path toward new treatment options.


Physical activity and plasma cyclic adenosine monophosphate levels in manic-depressive patients and healthy adults.
Intense exercise for one hour induced a significant increase in plasma cyclic adenosine monophosphate (cAMP) in 5 healthy volunteers. In 44 manic-depressive patients, cAMP levels correlated more strongly with mood ratings than with activity scores. The authors conclude that physical activity is one of the factors which contribute to changes of cAMP levels in affective illness.


'Lateral elbow tendinopathy' is the most appropriate diagnostic term for the condition commonly referred-to as lateral epicondylitis.
A plethora of terms that have been used to describe lateral epicondylitis including tennis elbow (TE), epicondylalgia, tendonitis, tendinosis and tendinopathy. These terms usually have the prefix extensor or lateral elbow. Lateral elbow tendinopathy seems to be the most appropriate term to use in clinical practice because other terms make reference to inappropriate aetiological, anatomical and pathophysiological terms. The correct diagnostic term is important for the right treatment.


Galectin-8 and -9 as prognostic factors for cervical cancer.
Galectins are carbohydrate-binding proteins with multiple effects on cell biology. Research shows that they play an important role in tumor development and progression. Therefore, in this study, the presence of Galectin-8 and -9 (Gal), both already known as prognostic factors in other tumor entities, were investigated in cervical cancer. Our aim was to examine the association of Gal-8 and -9 expression with histopathological markers and survival of the patients. Gal-8 and -9 expression was investigated in 250 cervical cancer samples by immunohistochemistry. The staining was evaluated using the immunoreactive score (IRS). The results were correlated to clinical and pathological data. The correlation of Gal-8 and -9 expression with overall and relapse-free survival was analyzed. Expression of Gal-8 was associated with negative N-status and lower FIGO status. Detection of Gal-9 was connected to negative N-status and lower grading regarding all specimens. A correlation of Gal-9 with lower FIGO status was detected for squamous cell carcinoma (SCC) only. Expression of Gal-8 was associated with relapse-free survival of SCC patients in a positive manner. Gal-9 expression was associated with better overall survival. Our results suggest that expression of both galectins is inversely associated with tumor stage and progression. Gal-8 expression is associated with relapse-free survival of patients with SCC, while presence of Gal-9 in cervical cancer is associated with a better prognosis in regard of overall survival.


Acute and mutigenerational effects of environmental concentration of the antifouling agent dichlofluanid on the mysid model, Neomysis awatschensis.
A broad-spectrum fungicide, dichlofluanid is widely used in antifouling paints and agricultural pesticides. In this study, the acute and chronic effects of sublethal concentrations, namely, no observable effect concentration (NOEC) and 50% lethal concentration (LC50) of dichlofluanid (1/10 NOEC, NOEC, 1/10 LC50, and LC50) were evaluated on the marine mysid, Neomysis awatschensis. Acute toxicity test (96 h) showed higher sensitivity to dichlofluanid in juvenile mysids (LC50 3.1 μg L-1) than adults (LC50 24.5 μg L-1), with lower survival rate and reduction in food consumption. Exposure with dichlofluanid considerably induced oxidative imbalance, as NOEC (0.006 μg L-1 for juveniles and 0.074 μg L-1 for adults) and 1/10 LC50 values increased intracellular concentrations of malondialdehyde and glutathione, and the enzymatic activities of catalase and superoxide dismutase, whereas exposure to LC50 value decreased the values of oxidative parameters. Enzymatic activity of acetylcholinesterase decreased considerably when exposed to LC50 value. In the case of chronic effects, exposure to NOEC for 4 weeks markedly decreased the juvenile survival rate, while adults showed tolerance. Multigenerational monitoring in response to NOEC showed a significant growth retardation with an increase in intermolt duration as well as a decrease in the number of newborn mysids from females of the third generation. Consistent exposure to environmentally relevant sublethal concentrations of dichlofluanid would be detrimental to mysid individuals and the survival of the mysid population.


[Osteoarticular lesions in pain perception deficit disorders in children].
Deficiency of pain perception may be at the origin of bone and/or joint lesions. In children, these lesions frequent give rise to surprising and misleading radiological images as a result of the usual lack of immobilization due to a delayed diagnosis. Alterations in bone structure at the metaphyses and corticoperiosteal ossifications can suggest malignant affections. Trauma is generally the predominant factor in the etiology of these lesions.


Auditory semantic, syntactic, and retention errors made by aphasic subjects on the Token Test.
The Token Test was administered to 25 mild aphasic and 25 matched normal subjects for the purpose of determining the linguistic nature of the auditory verbal comprehension error responses. As was expected, the aphasic subjects obtained significantly poorer scores on the Token Test than did the normal subjects, with minimal overlap between the two groups. In Parts I-IV, the errors were exclusively semantic, and reflected only the amount of required verbal memory. In Part V, the syntactic structures vary, and the aphasic subjects showed a similar pattern of difficulty as did the normal subjects. Syntactic errors were more prevalent than semantic errors in Part V, suggesting that syntactic complexity was the most important factor in verbal comprehension on this part. In comparison to previous research utilizing the Token Test with normal children, the aphasic subjects in the present study generally had high error rates on the same items as did the children.


The effect of low dose hormone therapy on mammographic breast density.
To evaluate the effect of two standard and one low dose continuous hormone therapy regimens on mammography. One hundred and thirty-two non-hysterectomized postmenopausal women were randomly allocated either to conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, n=38), 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA, n=44) or 17beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (low E2/NETA, n=50). Treatment was continuous and the study period lasted 12 months. Main outcome measures were the changes according to Wolfe classification between baseline and 12-month mammograms. Five (13.2%) women in the CEE/MPA group showed an increase in breast density. Fourteen (31.8%) women on E2/NETA and 6 (12.2%) on low E2/NETA treatment revealed an increase in breast density. No woman exhibited an involution of fibroglandular tissue. Different hormone therapy regimens have a variable impact on breast density probably depending on the steroid used. Low dose hormone therapy associates with significantly lesser increase in breast density.


Somatic Embryogenesis in Lisianthus (Eustoma russellianum Griseb.).
Somatic embryogenesis is, for the main floricultural crops, a promising system for commercial scale-up, providing cloned material to be traded as seedlings. Somatic embryos, having the contemporary presence of root apical meristem and shoot apical meristem, can be readily acclimatized. For Lisianthus it is possible to induce embryogenic callus from leaf fragments of selected genotypes and to obtain embryos either in agarized substrate or in liquid suspension culture. The production of somatic embryos in liquid medium is high and can be modulated in order to synchronize the cycle and the size of the neoformed structures. The possibility to use the liquid substrate with high propagation rates reduces labor costs and could support the costs of eventual automation. In this paper we report a stepwise protocol for somatic embryogenesis in the species Eustoma russellianum.


Non-ketotic C6-C10-dicarboxylic aciduria: biochemical investigations of two cases.
Two boys, who are not related, with hypoglycemia and C6-C10-dicarboxylic aciduria were investigated. Besides substantial amounts of adipic, suberic and sebacic acids, the urinary metabolic profile of organic acids contained 5-OH-caproic acid and caproylglycine. During acute attacks the concentrations of adipic, suberic and sebacic acids were 300--530, 160--200 and 35--200 micrograms/mg creatinine, respectively, and the excretions of 5-OH-caproic acid and caproylglycine were 75--330 and 41--260 micrograms/mg creatinine, respectively. It is argued that the biosynthesis of adipic acid passes through an omega-oxidation, that the production of 5-OH-caproic acid is caused by an omega-1-oxidation, and that caproylglycine formation passes through a glycine-N-acylase catalysed conjugation of accumulated caproic acid in the patients. Suberic acid and sebacic acid are in the same way omega-oxidation products of accumulated caprylic acid and capric acid, respectively. From the excretion pattern presented it is hypothesized that the patients suffer from a defect in the dehydrogenation of fatty acids in the beta-oxidation pathway. The biological significance of the findings is discussed.


Fat Intake and Hypertension Among Adults in China: The Modifying Effects of Fruit and Vegetable Intake.
Evidence on the combined effect of fruit and vegetable intake and total fat intake on hypertension is scarce. This study aimed to explore the relationship among fruit and vegetable intake, fat intake, and hypertension risk among Chinese adults. Individuals who participated in the China Health and Nutrition Survey (2004, 2006, 2009, and 2011) and were free of hypertension at baseline (n=4,368) were categorized into quartiles (Q1, lowest; Q4, highest) according to their dietary fruit and vegetable intake and fat intake. Generalized estimation equation models, adjusted for confounders, were used to explore the relationship of fat intake with hypertension and systolic and diastolic blood pressure among all adults and within quartiles of fruit and vegetable intake. Data analyses were performed in 2018. A total of 1,086 adults developed hypertension during follow-up. In the total population, the OR of the highest quartile of fat intake was 1.40 (95% CI=1.12, 1.75) compared with the lowest. Among individuals with low fruit and vegetable intake, the odds of hypertension for those in Q3 (OR=1.97, 95% CI=1.37, 2.83) and Q4 (OR=1.81, 95% CI=1.14, 2.90) of fat intake, compared with individuals in Q1, were even higher than for the overall sample. For each 50-gram increase in FI per day, the ORs of hypertension increased from fat intake Q1 to Q4 among all respondents and those with low fruit and vegetable intake, but not among those with high fruit and vegetable intake. Systolic blood pressure increased by 1.08 mm Hg (95% CI=0.03, 2.13) per 50-gram fat intake per day increment in the fruit and vegetable intake Q1 group, whereas the association was not significant in the fruit and vegetable intake Q2-Q4 groups. Fruit and vegetable intake modifies the relationship between fat intake and hypertension, whereby high fruit and vegetable intake may offset the detrimental effect of fat intake on hypertension. Increased fruit and vegetable intake and controlled fat intake are recommended to prevent hypertension in Chinese adults.


High-frequency audiometry in the evaluation of critical noise intensity.
We investigated a total of 537 subjects (68 men, 469 women) working in the textile industry to ascertain their hearing level in the conventional hearing range as well as in the high-frequency (HF) range. The persons we tested work at three different noise-levels [80-84, 85-89, 90-94 dB (A), measured as leq). The differences in the hearing thresholds between this three groups mentioned were checked by means of discriminant analysis. The first hearing level changes at a noise-level below 90 dB (A) leq develop mainly in the HF range. In the conventional hearing range, however, the hearing levels remain unchanged even over long exposure times. Noise-induced hearing loss in the conventional range occurs only in the sound level group of 90 to 94 dB (A) leq without attaining any social importance. The tests show that, if the noise-level 90 dB (A) leq is not exceeded, no noise-induced hearing impairments involving social hearing loss are to be observed. Thus we assume that an auditory risk criterion of 85 dB (A) leq is sufficient to prevent hearing loss of any social importance.


Selected topics in personnel selection: primarily in the early to mid-years of the 20th century.
A brief historical review is presented of the events in the USA relating to personnel selection in business and industry from 1903 to 2003. Emphasis is placed on the early periods of the century through the midyears. Involved in these events have been applied psychologists, the American Psychological Association, Government Agencies, Federal, Circuit Courts of Appeals, and the Supreme Court.


Bone mass measurements.
The clinical application of bone densitometry is one of the advances in the field of osteoporosis that has led to the increased patient awareness of this increasingly prevalent disease. Bone densitometry has made it possible for clinicians to diagnose osteoporosis before the first fracture has occurred; predict risk for fracture in postmenopausal women, men, and in patients who are receiving glucocorticoids; and can be used as a surrogate marker to follow the efficacy of therapies and to examine those patients that might be osteoporosis-specific therapeutic nonresponders.


Late post transplant HIV infection with BK viremia and allograft tuberculosis in a renal transplant recipient with Kaposi sarcoma.
In this report, we discuss a case of a 51-year-old African renal transplant who presented with metastatic Kaposi sarcoma 1 year after transplant. The Kaposi sarcoma was treated with a switch of immunosuppressants and chemotherapy. Six years after transplant, he presented with chronic allograft nephropathy, allograft tuberculosis, BK viremia, and was diagnosed to have contracted HIV infection.