Indirubin potentiates ciprofloxacin activity in the NorA efflux pump of Staphylococcus aureus.
Staphylococcus aureus is a common multidrug-resistant organism in hospital-acquired infections, and the NorA efflux pump mechanism facilitates resistance to quinone compounds. In India, Wrightia tinctoria R. Br. leaves have traditionally been used to treat skin diseases and have been explored for antibacterial and efflux pump inhibition (EPI) compounds. In this study, indirubin isolated from the chloroform extract of W. tinctoria R. Br. leaves was tested for its antibacterial activity against clinically important Gram-positive and Gram-negative bacteria and the minimum inhibitory concentration (MIC) was determined using broth microdilution. The EPI properties of indirubin were investigated using Staphylococcus aureus SA1199B, and its synergistic effects were tested with ciprofloxacin. Indirubin showed antibacterial activity against both the type strain and drug-resistant S. aureus; the MIC was determined to be 12.5 mg/l for S. aureus and 25 mg/l for Staphylococcus epidermidis. However, it synergistically (fractional inhibitory concentration index = 0.45) potentiated the activity of ciprofloxacin, probably by inhibiting the NorA efflux pump. Indirubin exhibited EPI activity nearly comparable to that of reserpine by 4-fold reduction in ciprofloxacin MIC. Our results suggest that the natural compound indirubin could be used in future therapeutic applications as a potential EPI.


[Tadalafil and patients preference in the treatment of erectile dysfunction].
ED treatment has changed fundamentally since phosphodiesterase type 5 inhibitor (PDE5-I) came into clinical use. There are three kinds of PDE5-I available at present, Sildenafil, Vardenafil and Tadalafil. Tadalafil distinguishes from the other two by its uniquely long half-life, which lasts 17.5h, which a pharmacodynamic duration of 36h and not influenced by food and alcohol. Thus it may enable ED patients to accomplish a spontaneous intercourse without the need of prior preparation without, which can boost their confidence and self-esteem and, the most important, improve the relationship with their partner. To know patient preference counts quite a lot in optimizing the medication ED treatment.


Unbound bilirubin measurements in term and late-preterm infants.
Hyperbilirubinemia occurs in over 80% of newborns, and severe bilirubin toxicity can lead to neurological dysfunction and death. Unbound bilirubin (Bf) levels predict the risk of neurodevelopmental handicap, although total serum bilirubin (TSB) is used to manage care. To measure Bf levels in healthy infants, its relationship to TSB, and its response to phototherapy. We hypothesize unexpectedly high Bf levels, poor correlation with TSB and unpredictable response to phototherapy. Healthy infants were studied with simultaneous TSB and Bf measurements. The clinical data recorded included ethnicity, gender, birth weight, gestational age, and mode of delivery, Apgar scores, breast/formula feeds, and phototherapy. One hundred thirty-two infants (3248.9 ± 509.2g, GA 38.7 ± 1.4 weeks), at mean age of the initial sample of 28.5 ± 15.6 h, had a TSB of 7.9 ± 2.7 mg/dl, and a Bf of 5.2 ± 3.2 nM. The correlation between Bf and TSB was significant but not between Bf and TSB for TSB >12 mg/dl. Bf >11nm were in 22.7% and >17 nM in 3.8% of infants. Post-phototherapy TSB and Bf levels were similar to those before treatment. The relationship between TSB and Bf in healthy infants is complex, with the inability of one to predict the other's level in infants with elevated TSB. The mechanism of bilirubin-related neurotoxicity suggests that the management of jaundice in healthy infants requires Bf measurements. Management of jaundice with TSB may result in more infants exposed to phototherapy. However, unexpected elevations of Bf occur in an apparently healthy population.


Health Professionals in a COVID-19 Reference Hospital: Post-traumatic Stress Disorder (PTSD) Levels and Their Associations With Psychological Resilience and Quality of Life.
Introduction The coronavirus disease 2019 (COVID-19) pandemic has affected the quality of life of both the general population and health professionals and has increased the levels of psychopathology among them. The present study aims to map the levels of post-traumatic stress disorder (PTSD), psychological resilience, and quality of life of healthcare professionals who work in a COVID-19 reference hospital in Athens, Greece, one year after the onset of the pandemic. Also, this study focuses on investigating the relationships among the study variables and demographics and examining possible mediating effects. Methods The sample consisted of 400 health professionals from Sotiria Hospital, of whom 102 were men. Participants were asked to complete the Post-Traumatic Stress Scale, Connor-Davidson Resilience Scale, and the WHO Quality of Life Questionnaire. The survey was conducted from May to July 2021. Results The findings show statistical differences in resilience levels regarding marital status and employee education. Also, 13.5% of the staff reported significant PTSD levels, which relate to low levels of psychological resilience and every pillar of quality of life. Conclusions Thus, research findings indicate that resilience levels could have a protective effect on the development of PTSD symptoms. Therefore, the design of group interventions that aim at building health workers' resilience will be discussed.


[Control of organ shape and size by YUAN1 in Arabidopsis thaliana].
Control of organ shape and size by cell proliferationandcell expansion is a fundamental process in plant development. However, little is known about the molecular mechanisms that set the shape and size of determinate organs in plants. We have previously demonstrated that the Arabidopsis gene DA1 controls the final size of organs by restricting cell proliferation. Through an activation tagging screen for modifiers of da1-1, we have identified a semi-dominant mutant (yuan1-1D) with altered leaf shape and size. The yuan1-1D mutation results in reduced plant height, short and round leaves and short petioles due to defects in cell elongation. YUAN1 encodes a PHD zinc finger domain-containing protein. The GFP-YUAN1 fusion protein is localized to the nucleus. Overexpression of YUAN1 leads to round leaves and short petioles. Genetic analyses show that YUAN1 acts independently of DA1, ROTUNDIFOLIA 3 (ROT3) and ROTUNDIFOLIA4 (ROT4) to influence leaf shape and size. Collectively, our findings show that Arabidopsis YUAN1, a PHD zinc finger domain-containing protein, controls organ shape and size by restricting cell elongation, and give insight into how plants control their organ shape and size.


Demonstration of x-ray Thomson scattering using picosecond K-alpha x-ray sources in the characterization of dense heated matter.
We present K-alpha x-ray Thomson scattering from shock compressed matter for use as a diagnostic in determining the temperature, density, and ionization state with picosecond resolution. The development of this source as a diagnostic as well as stringent requirements for successful K-alpha x-ray Thomson scattering are addressed. Here, the first elastic and inelastic scattering measurements on a medium size laser facility have been observed. We present scattering data from solid density carbon plasmas with >1x10(5) photons in the elastic peak that validate the capability of single shot characterization of warm dense matter and the ability to use this scattering source at future free electron lasers and for fusion experiments at the National Ignition Facility (NIF), LLNL.


Simulations and measurements in scanning electron microscopes at low electron energy.
The advent of new imaging technologies in Scanning Electron Microscopy (SEM) using low energy (0-2 keV) electrons has brought about new ways to study materials at the nanoscale. It also brings new challenges in terms of understanding electron transport at these energies. In addition, reduction in energy has brought new contrast mechanisms producing images that are sometimes difficult to interpret. This is increasing the push for simulation tools, in particular for low impact energies of electrons. The use of Monte Carlo calculations to simulate the transport of electrons in materials has been undertaken by many authors for several decades. However, inaccuracies associated with the Monte Carlo technique start to grow as the energy is reduced. This is not simply associated with inaccuracies in the knowledge of the scattering cross-sections, but is fundamental to the Monte Carlo technique itself. This is because effects due to the wave nature of the electron and the energy band structure of the target above the vacuum energy level become important and these are properties which are difficult to handle using the Monte Carlo method. In this review we briefly describe the new techniques of scanning low energy electron microscopy and then outline the problems and challenges of trying to understand and quantify the signals that are obtained. The effects of charging and spin polarised measurement are also briefly explored. SCANNING 38:802-818, 2016. © 2016 Wiley Periodicals, Inc.


Zirconium-based metal-organic framework loaded agarose hydrogels for fluorescence turn-on detection of nerve agent simulant vapor.
Developing reliable sensors that accurately detect deadly chemical gases is critical to global security. Nerve agents are one of the most dangerous chemicals in the world and are often found in gaseous forms in the environment, which remain a challenge to detect because of their low levels. In this paper, a fluorescent probe based on a Zr-based metal-organic framework UiO-66-NH2 was proposed. The specific binding between the Zr-O site of UiO-66-NH2 and diethyl chlorophosphate (DCP) blocked the ligand-to-metal charge transfer (LMCT) process in UiO-66-NH2, thereby enabling the fluorescence turn-on detection of DCP. More importantly, a simple and portable hydrogel soft-solid platform (UiO-66-NH2@Aga) was constructed by incorporating UiO-66-NH2 into the formation process of agarose (Aga) hydrogel for fast and sensitive detection of gaseous DCP. When the hydrogel was exposed to a low concentration of DCP vapor, its fluorescence changed from colorless to bright blue, allowing visualization of the DCP gas for analysis. The UiO-66-NH2@Aga integrated solid-state platform showed an excellent response to DCP vapor in the detection range of 1.98 to 9.90 ppm and with a detection limit of 1.16 ppm. This work opened up a unique way to design a convenient, low cost and practical gas physical examination platform.


[Effect of Kou Yan Qing Ke Li on the prevention and treatment of radiation-induced oral mucositis in patients with nasopharyngeal carcinoma].
The effect of Kou Yan Qing Ke Li on the prevention and treatment of radiation-induced oral mucositis was investigated in patients with nasopharyngeal carcinoma. Sixty patients with nasopharyngeal carcinoma to be treated with radiotherapy were randomized into two groups: the experimental and control groups. The experimental group (30 patients) was treated with Kou Yan Qing Ke Li during the full course of radiotherapy. The control group (30 patients) rinsed their mouths in the same way with mouth washes containing 0.9% sodium chloride injection, lidocaine, dexamethasone, vitamin B2 and B2 gargle liquid mixture, when grade 2 and above radiation-induced oral mucositis appeared in the process of radiation. Radiation-induced oral mucositis was assessed according to the radiation therapy oncology group criteria. The time of occurrence and degree of pain grade were compared between the two groups. The first onset of oral mucositis in the experimental group (12.40 d ± 2.74 d) was later than that in the control group (9.46 d ± 1.39 d) (t = 5.241, P < 0.001), whereas the grade of pain and acute radiation mucositis was lower in the experimental group than that in the control group. The difference was statistically significant. Kou Yan Qing Ke Li could delay the time of occurrence of radiation-induced oral mucositis, reduce the severity of radiation stomatitis, alleviate the pain of patients, improve the clinical symptoms of patients, and effectively prevent and treat radiation-induced oral mucositis in patients with nasopharyngeal carcinoma.


Dopamine beta-hydroxylase gene excluded in four subtypes of hereditary dystonia.
The hereditary dystonias include a clinically heterogeneous group of movement disorders varying in symptoms, age of onset, and drug responsiveness. Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, has been implicated in dystonia because of increased serum levels of DBH in some patients, the influence of catecholaminergic drugs on the human phenotypes, and altered norepinephrine levels in several brain regions in dystonia patients and in genetically dystonic rodents. In addition, markers linked to the dystonia gene in two ethnic groups map close to the DBH locus on human chromosome 9q34. Here we evaluate the inheritance of restriction fragment length polymorphisms near the DBH gene in families with four subtypes of hereditary dystonia: Jewish and non-Jewish, early onset, generalized idiopathic torsion dystonia (ITD); dopa-responsive dystonia; and myoclonic dystonia. In all families, obligate recombination events were observed between the DBH and dystonia genes, thus excluding the DBH gene as the primary defect.


Activatable 19F MRI nanoparticle probes for the detection of reducing environments.
(19)F magnetic resonance imaging (MRI) probes that can detect biological phenomena such as cell dynamics, ion concentrations, and enzymatic activity have attracted significant attention. Although perfluorocarbon (PFC) encapsulated nanoparticles are of interest in molecular imaging owing to their high sensitivity, activatable PFC nanoparticles have not been developed. In this study, we showed for the first time that the paramagnetic relaxation enhancement (PRE) effect can efficiently decrease the (19)F NMR/MRI signals of PFCs in silica nanoparticles. On the basis of the PRE effect, we developed a reduction-responsive PFC-encapsulated nanoparticle probe, FLAME-SS-Gd(3+) (FSG). This is the first example of an activatable PFC-encapsulated nanoparticle that can be used for in vivo imaging. Calculations revealed that the ratio of fluorine atoms to Gd(3+) complexes per nanoparticle was more than approximately 5.0×10(2), resulting in the high signal augmentation.


[Tracheocele in childhood].
Three cases of male children presenting a tracheocele with the common feature of repeating catarrhal affections and frequent cough are described. Results of analytic and roentgenographic studies performed are commented. Authors consider that treatment should be expectant unless any complication is present, then surgery and/or antibiotic treatment should be undertaken.


Functional characterization of kainate receptors in the mouse nucleus accumbens.
Kainate receptors are abundantly expressed in the nucleus accumbens but their functional characterization and their role in synaptic transmission has not yet been investigated. Using patch-clamp recordings in mouse nucleus accumbens slices, we show the presence of functional kainate receptors activated by low concentrations of kainate (100-300 nM) in medium size neurons. These somatodendritic receptors are comprised of the GluR6 subunit, since they are absent in GluR6-deficient mice. Kainate receptors do not directly participate in glutamatergic synaptic transmission evoked by electrical stimulation of cortical afferent fibers in nucleus accumbens neurons. However, application of low concentrations of kainate inhibits cortico-accumbens synaptic transmission, by increasing synaptic failure rate and increasing variation coefficient, thus indicating a presynaptic site of action. Presynaptic kainate receptors are observed both in GluR6 and in GluR5-deficient mice, but are absent in mice devoid of both subunits. Hence, at variance with somatodendritic kainate receptors, presynaptic kainate receptors on cortical afferents are composed of both GluR5 and GluR6 kainate receptor subunits. These results indicate that different subtypes of kainate receptors, representing distinct pharmacological targets, should play important roles in the synaptic integration properties of nucleus accumbens neurons.


Pathways in dental public health.
Dental public health is one of the nine specialties of dentistry recognized by the American Dental Association Commission on Dental Accreditation. Dental public health has been defined as the "science and art of preventing and controlling dental diseases and promoting dental health through organized community efforts. It is that form of dental practice which serves the community as a patient rather than as an individual. It is concerned with the dental health education of the public, with applied dental research, and with the administration of group dental care programs as well as the prevention and control of dental diseases on a community basis." This article will describe the many career and educational pathways dentists may follow to become irvolved in the practice of dental public health.


Citrullinated Antigens with Multiple Citrulline Similar Motif in the Diagnosis of Rheumatoid Arthritis: A Preliminary Single-Center Study.
The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946-0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.


Food protein-induced enterocolitis syndrome - a review of the literature with focus on clinical management.
Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe presentation of non-IgE-mediated gastrointestinal food allergy (non-IgE-GI-FA) with heterogeneous clinical manifestations. Acute FPIES is typically characterized by profuse vomiting and lethargy, occurring classically 1-4 hours after ingestion of the offending food. When continuously exposed to the incriminated food, a chronic form has been described with persistent vomiting, diarrhea, and/or failure to thrive. Although affecting mainly infants, FPIES has also been described in adults. Although FPIES is actually one of the most actively studied non-IgE-GI-FAs, epidemiologic data are lacking, and estimation of the prevalence is based on a limited number of prospective studies. The exact pathomechanisms of FPIES remain not well defined, but recent data suggest involvement of neutrophils and mast cells, in addition to T cells. There is a wide range of food allergens that can cause FPIES with some geographical variations. The most frequently incriminated foods are cow milk, soy, and grains in Europe and USA. Furthermore, FPIES can be induced by foods usually considered as hypoallergenic, such as chicken, potatoes or rice. The diagnosis relies currently on typical clinical manifestations, resolving after the elimination of the offending food from the infant's/child's diet and/or an oral food challenge (OFC). The prognosis is usually favorable, with the vast majority of the case resolving before 5 years of age. Usually, assessment of tolerance acquisition by OFC is proposed every 12-18 months. Of note, a switch to an IgE-mediated FA is possible and has been suggested to be associated with a more severe phenotype. Avoiding the offending food requires education of the family of the affected child. A multidisciplinary approach including ideally allergists, gastroenterologists, dieticians, specialized nurses, and caregivers is often useful to optimize the management of these patients, that might be difficult.


EVOLUTIONARY ADAPTATION TO TEMPERATURE. VII. EXTENSION OF THE UPPER THERMAL LIMIT OF ESCHERICHIA COLI.
What factors influence the ability of populations to adapt to extreme environments that lie outside their current tolerance limits? We investigated this question by exposing experimental populations of the bacterium Escherichia coli to lethally high temperatures. We asked: (1) whether we could obtain thermotolerant mutants with an extended upper thermal limit by this selective screen; (2) whether the propensity to obtain thermotolerant mutants depended on the prior selective history of the progenitor genotypes; and (3) how the fitness properties of these mutants compared to those of their progenitors within the ancestral thermal niche. Specifically, we subjected 15 independent populations founded from each of six progenitors to 44°C; all of the progenitors had upper thermal limits between about 40°C and 42°C. Two of the progenitors were from populations that had previously adapted to 32°C, two were from populations adapted to 37°C, and two were from populations adapted to 41-42°C. All 90 populations were screened for mutants that could survive and grow at 44°C. We obtained three thermotolerant mutants, all derived from progenitors previously adapted to 41-42°C. In an earlier study, we serendipitously found one other thermotolerant mutant derived from a population that had previously adapted to 32°C. Thus, prior selection at an elevated but nonlethal temperature may predispose organisms to evolve more extreme thermotolerance, but this is not an absolute requirement. It is evidently possible to obtain mutants that tolerate more extreme temperatures, so why did they not become prevalent during prior selection at 41-42°C, near the upper limit of the thermal niche? To address this question, we measured the fitness of the thermotolerant mutants at high temperatures just within the ancestral niche. None of the four thermotolerant mutants had an advantage relative to their progenitor even very near the upper limit of the thermal niche; in fact, all of the mutants showed a noticeable loss of fitness around 41°C. Thus, the genetic adaptations that improve competitive fitness at high but nonlethal temperatures are distinct from those that permit tolerance of otherwise lethal temperatures.


An Alternative Measure of Health for Value Assessment: The Equal Value Life-Year.
The quality-adjusted life-year (QALY) is an international standard in cost-effectiveness analysis. A known concern arises from the relatively lower QALY gains attributed to treatments that extend the life of individuals with chronic disability. We analyze here the advantages and disadvantages of the equal value life-year (evLY) as an alternative or a complementary measure to the QALY, and share learned experiences from using this measure in health technology assessments. We present the conceptual rationale for the evLY, describe how it is estimated, and assess the differences in results between analyses based on the evLY and the QALY. We share a how-to guide in estimating the evLY using a downloadable tool and summarize our empirical experience using this measure. Incremental evLYs are feasible and address concerns regarding the risk for a cost-effectiveness analysis to undervalue treatments for people with chronic disabilities. Based on our set of analyses using the evLY, a threshold of $84,000 per evLY gained would be needed to maintain alignment with a threshold of $100,000 per added QALY. The evLY is a measure of health gain that can be used as an alternative or a complement to the QALY to address concerns related to undervaluing treatments that extend the life of individuals with serious illness or chronic disability. We recommend that it be reported within all cost-effectiveness analyses but may have special relevance in the current political environment in the USA, where use of the QALY is often challenged or prohibited.


Prevalence of high-risk HPV genotypes, categorised by their quadrivalent and nine-valent HPV vaccination coverage, and the genotype association with high-grade lesions.
The new nine-valent vaccine against human papillomavirus (HPV) includes the four HPV genotypes (6, 11, 16, and 18) that are targeted by the older quadrivalent HPV vaccine, plus five additional oncogenic types (31, 33, 45, 52, and 58) remain significantly associated with high grade lesions. We aimed to determine the prevalence of high-risk HPV genotypes in unvaccinated subjects and the association of these genotypes with the incidence of high-grade lesions. We also assessed which, if either, of these two HPV vaccines could have prevented these cases. This cross-sectional study, conducted from 4 January 2010 to 30 December 2011, was composed of 595 women attending the Hospital General Universitario de Elche (Spain) gynaecology department who were positively screened for opportunistic cervical cancer by pap smears and HPV detection during a routine gynaecological health check. The pap smear results were classified using the Bethesda system. HPV genotyping was performed with the Linear Array HPV genotyping test, and viruses were classified by the International Agency for Research on Cancer assessment of HPV carcinogenicity. Odds ratios (ORs) with their 95% confidence intervals (95% CI) were estimated by logistic regression, adjusting for age and immigrant status. The prevented fraction among those exposed (PFe-adjusted) was determined as a measure of impact. At least one of the additional five high-risk HPV genotypes present in the nine-valent HPV vaccine was detected in 20.5% of subjects. After excluding women with genotype 16 and/or 18 co-infection, high-risk genotypes (31, 33, 45, 52, and 58) were associated with a higher risk of intraepithelial lesion or malignancy: adjusted OR = 3.51 (95% CI, 1.29-9.56), PFe-adjusted = 0.72 (95% CI, 0.22-0.90). Genotypes that are still non-vaccine-targeted were detected in 17.98% of the women, but these were not significantly associated with high-grade lesions. The greater protection of the nine-valent HPV vaccine is likely to have a positive impact because, in the absence of genotype 16 or 18 infection, these five genotypes on their own remained significantly associated with high-grade lesions.


Polarisation and membrane voltage of ellipsoidal particle with a constant membrane thickness: a series expansion approach.
The estimation of the membrane voltage and the polarisation factor of biological cells provide a base for the study of bio-manipulation techniques, such as dielectrophoresis, electroporation or electrofusion. To model a biological cell, an ellipsoidal particle with an insulating membrane is sometimes employed, but due to the limitation of the confocal nature of the coordinate system, the membrane thickness is assumed to vary with the position, despite the fact that the lipid bilayer membrane has a uniform thickness. The authors present a method to rigorously treat the uniform-thickness condition in a system having an axial symmetry. The method is based on the harmonic expansion of the field, to include the condition of the uniform-membrane thickness as a series expansion of the geometrical factor, and to solve the field problem as an interaction of the harmonic components. The conventional variable thickness model has been identified as being equivalent to neglecting the harmonic interactions in the uniform-thickness model. Numerical calculations are done of the membrane voltage and the polarisation factor, and it has been found that the discrepancy between the proposed rigorous model and the conventional variable thickness model becomes significant when field deformation is large due to the high axial ratio of the ellipsoid.


Eicosanoid actions in insect immunity.
Insects express 3 lines of protection from infections and invasions. Their cuticles and peritrophic membranes are physical barriers. Infections and invasions are quickly recognized within insect bodies, and recognition launches 2 lines of innate immune reactions. Humoral reactions involve induced synthesis of antimicrobial peptides, the bacteriolytic enzyme lysozyme and activation of the prophenoloxidase system. Cellular immune reactions include phagocytosis, nodulation and encapsulation. These reactions entail direct interactions between circulating hemocytes and the invaders. Cellular immune reactions begin immediately after an invasion is detected while antimicrobial peptides typically appear in the hemolymph some hours after infection. Microaggregation is a step in the nodulation process, which is responsible for clearing the bulk of bacterial infections from circulation. Coordinated cellular actions lead to encapsulation of invaders, such as parasitoid eggs, that are very much larger than individual hemocytes. In this paper, we review the roles of eicosanoids as central mediators of insect immune reactions, particularly cellular reactions. We briefly describe insect immune functions, outline eicosanoid biosynthesis and treat eicosanoid actions in cellular immunity of insects. Eicosanoids act in several cellular defense functions, including phagocytosis, microaggregation, nodulation, encapsulation, cell spreading and hemocyte migration toward a source of a bacterial peptide. We also describe our most recent work on the influence of one group of eicosanoids, prostaglandins, on gene expression in an established insect cell line.


Subcutaneous phaeohyphomycosis (mycotic cyst).
Phaeohyphomycosis designates fungal infections caused by pheoid or melanized fungi and characterized histopathologically by the presence of septate hyphae, pseudohyphae, and yeasts. Etiologic agents include Exophiala, Phoma, Bipolaris, Phialophora, Colletotrichum, Curvularia, Alternaria, Exserohilum, and Phialemonium sp. The most common are Exophiala jeanselmei and Wangiella dermatitidis. The clinical presentation depends on the immune status of the host: superficial (tinea nigra and black piedra); cutaneous (scytalidiosis) and corneal; subcutaneous (mycotic cyst); and systemic phaeohyphomycosis in the immunocompromised host. The mycotic cyst is a localized form, characterized by subcutaneous asymptomatic nodular lesions that develop after traumatic implantation of fungi, especially on the extremities. The average size of the cysts is 2.5 cm. KOH examination reveals pigmented yeasts, pseudohyphae, and hyphae. A cutaneous biopsy specimen usually shows an abscess or a suppurative granuloma with pigmented yeasts and pseudohyphae. The treatment of choice is surgical excision, but additional anti-fungal therapy is recommended for recurrent cases and immunocompromised patients.


Scissor Position of the Orthopedic Table for the Resolution of Intertrochanteric and Subtrochanteric Hip Fractures.
During the surgical resolution of intertrochanteric and subtrochanteric hip fractures on an orthopedic table, a fluoroscope needs to be used in orthogonal planes. This requires that the contralateral leg does not obstruct the radioscopic view, so patients are often placed in a hemilithotomy position. This position, also called the Lloyd-Davis position, involves hip flexion, hip abduction, hip external rotation, and knee flexion. However, rare complications, such as acute leg posterior compartment syndrome, have been described. In addition, patients with severe osteoarthritis and joint stiffness or a history of total hip arthroplasty may have difficulty achieving this position, and the well leg may be at risk of injury in a hemilithotomy position. A previously described position called the "scissor position" is, in our opinion, a safer and more efficient technique for placing the well leg on the orthopedic table, using only a pillow and a self-adhesive compression bandage. This simple position allows a lateral fluoroscopic view of the injured femur without overlapping or interference from the other limb.


Is there a similarity between DNA damage in adults with chronic alcoholism and community-dwelling healthy older adults?
Daily alcohol consumption and ageing have been linked with DNA damage, leading to the hypothesis that chronic alcoholism causes DNA damage similar to that which occurs with ageing. Likewise, it has been suggested that chronic alcoholism is the cause of accelerated or premature ageing. The objective of this study was to evaluate the frequency and magnitude of DNA damage among adults with chronic alcoholism and healthy older adults residing in Mexico City. A cross-sectional and comparative study was carried out in a sample of 53 chronic alcoholics of 25-44 years of age (without alcohol ingestion in the past 30 days) without additional diseases, 26 healthy subjects >or=60 years of age, and 25 healthy adults of 25-44 years of age without alcohol addiction, all residents of Mexico City during the past 10 years. DNA damage was evaluated by single-cell gel electrophoresis technique (Comet assay). Our results showed a similar percentage of DNA damage between healthy elderly subjects and chronic alcoholics (62 vs 55%, P >0.05), although average DNA migration was greater in alcoholics than in the elderly (78.1 +/- 33.2 vs 58.6 +/- 26.2, P = 0.09). However, the percentage of subjects with more than six damaged cells was higher in the older adults subjects group than in the group chronic alcoholics (19 vs 35%, P = 0.16). Data suggest that DNA damage is not similar in young subjects with chronic alcoholism that which occurs with ageing.


Laboratory evaluation of two point-of-care test kits for the identification of infectious syphilis.
Syphilis is a sexually transmitted disease that can have atypical clinical presentations. Conventional laboratory tests to confirm the diagnosis are not rapid enough to affect clinical decision on treatment and contact tracing. Rapid point-of-care tests (POCT) can be useful for control of infectious diseases; however, no POCT for syphilis detection is currently available in Canada. The aim of this study is to evaluate two POCTs (RevealTM Rapid TP (Treponema pallidum) Antibody test and DPP® Syphilis Screen and Confirm test) for detection of infectious syphilis. One hundred serum samples with known syphilis serological status, based on treponemal and non-treponemal test results, were analysed in the laboratory with two POCTs by two independent operators in a blind fashion. Results were analysed to evaluate their ability to detect infectious syphilis. The Reveal Rapid TP Antibody POCT showed an overall sensitivity of 95.0% and a specificity of 83.3%, while the DPP Syphilis Screen and Confirm POCT showed a sensitivity of 87.5% and a specificity of 98.3%. Both POCTs gave a sensitivity of 100% on active syphilis samples with Venereal Disease Research Laboratory (VDRL) titres of greater than 1:4, but their sensitivities decreased for samples with low VDRL titres. Both POCTs gave weakly or very weakly reactive results on 11.3%-25.0% of the treponemal antibody positive samples. This laboratory evaluation has shown promising results for both POCTs to detect infectious syphilis. Further evaluations in the field would be required to confirm this preliminary finding.


Effect of Renal Impairment on the Pharmacokinetics of a Single Oral Dose of Danuglipron in Participants With Type 2 Diabetes.
Danuglipron (PF-06882961) is an oral, small-molecule glucagon-like peptide-1 receptor agonist in development for the treatment of type 2 diabetes (T2D) and obesity. Impaired renal function is prevalent in patients with T2D. This Phase 1, open-label study evaluated the effect of renal impairment on the pharmacokinetics, safety, and tolerability of danuglipron (20 mg) in healthy participants with normal renal function (estimated glomerular filtration rate [eGFR] unnormalized for body surface area: ≥90 mL/min), in participants with T2D and normal renal function (eGFR ≥90 mL/min), and in participants with T2D and mild (eGFR 60-89 mL/min), moderate (eGFR 30-59 mL/min), or severe (eGFR <30 mL/min) renal impairment (N = 39). Log-linear regression analyses and analyses of variance showed no evidence of a clinically significant effect of reduced renal function on danuglipron pharmacokinetics. Renal clearance of unchanged danuglipron was minimal (<1% across all renal function groups). Danuglipron pharmacokinetics were similar between healthy participants and participants with T2D and normal renal function. A single 20-mg oral dose of danuglipron was generally safe and well tolerated in all participant groups. In participants with T2D, renal impairment had no clinically meaningful effect on the pharmacokinetic, safety, and tolerability profiles of danuglipron, indicating that dose adjustment of danuglipron will not be required when administered to patients with T2D and reduced renal function.


Impacts of marine heatwaves on top predator distributions are variable but predictable.
Marine heatwaves cause widespread environmental, biological, and socio-economic impacts, placing them at the forefront of 21st-century management challenges. However, heatwaves vary in intensity and evolution, and a paucity of information on how this variability impacts marine species limits our ability to proactively manage for these extreme events. Here, we model the effects of four recent heatwaves (2014, 2015, 2019, 2020) in the Northeastern Pacific on the distributions of 14 top predator species of ecological, cultural, and commercial importance. Predicted responses were highly variable across species and heatwaves, ranging from near total loss of habitat to a two-fold increase. Heatwaves rapidly altered political bio-geographies, with up to 10% of predicted habitat across all species shifting jurisdictions during individual heatwaves. The variability in predicted responses across species and heatwaves portends the need for novel management solutions that can rapidly respond to extreme climate events. As proof-of-concept, we developed an operational dynamic ocean management tool that predicts predator distributions and responses to extreme conditions in near real-time.


Short-term memory loss over time without retroactive stimulus interference.
A key question in cognitive psychology is whether information in short-term memory is lost as a function of time. Lewandowsky, Duncan, and Brown (2004) argued against that memory loss because forgetting in serial recall occurred to the same extent across serial positions regardless of the rate of recall. However, we believe Lewandowsky et al. (2004) only prevented one of two types of rehearsal; they did not prevent nonarticulatory rehearsal via attention. To prevent articulatory and nonarticulatory rehearsal without introducing interference, we presented unevenly timed stimuli for serial recall and, on some trials, required that the timing of stimuli be reproduced in the response. In those trials only, evidence of memory loss over time emerged. Further research is needed to identify whether this memory loss is decay or lost distinctiveness.


A general method for DNA polymorphism identification in genetic assessment and molecular diagnosis.
A general methodology for the analysis of human diseases at the nucleic acid level has been described. This method consists of a semiautomated, nontoxic analytic procedure, staining DNA bands with silver nitrate instead of ethidium bromide after DNA amplification by PCR. This technique provides a sensitive assay with enhanced accuracy and offers the possibility of carrying out the molecular analysis of several polymorphisms in a single day simplifying molecular genetics with diagnostic purposes.


SuSMoST: Surface Science Modeling and Simulation Toolkit.
We present to the scientific community the Surface Science Modeling and Simulation Toolkit (SuSMoST), which includes a number of utilities and implementations of statistical physics algorithms and models. With SuSMoST it is possible to predict or explain the structure and thermodynamic properties of adsorption layers. SuSMoST automatically builds formal graph and tensor-network models based on atomic description of adsorption complexes and helps to do ab initio calculations of interactions between adsorbed species. Using methods of various nature SuSMoST generates representative samples of adsorption layers and computes its thermodynamic quantities such as mean energy, coverage, density, and heat capacity. From these data one can plot phase diagrams of adsorption systems, assess thermal stability of self-assembled structures, simulate thermal desorption spectra, and so forth.


Change in BMI in Children Over the First 30 Months After the Start of the SARS-CoV-2 Pandemic.
Our study aim was to assess body mass index (BMI) change in children in the immediate 6 months of the pandemic, to follow longitudinal BMI change up to 30 months after the pandemic start, and to identify sociodemographic factors associated with these changes. Our study included a retrospective chart review of 1298 children 2 to 18 years old with office visits at an Indianapolis primary care clinic. Body mass index and sociodemographic information were collected at visits during 3 time periods: Prepandemic (March 1, 2019-February 28, 2020), Early Pandemic (June 1, 2020-November 30, 2020), and Late Pandemic (December 1, 2020-September 30, 2022). Data analysis indicated statistically significant increases in BMI monthly rate of change from Prepandemic to Early Pandemic periods. Interestingly, BMI rate of change stabilized from Early Pandemic to Late Pandemic periods but remained positive, suggesting children had slower, but persistent, continued BMI increase after the pandemic initiation.


Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery.
Nanotechnology-based drug design offers new possibilities for the use of nanoparticles in imaging and targeted therapy of tumours. Due to their tumour-homing ability, nano-engineered mesenchymal stem cells (MSCs) could be utilized as vectors to deliver diagnostic and therapeutic nanoparticles into a tumour. In the present study, uptake and functional effects of carboxyl-coated quantum dots QD655 were studied in human skin MSCs. The effect of QD on MSCs was examined using a cell viability assay, Ki67 expression analysis, and tri-lineage differentiation assay. The optimal conditions for QD uptake in MSCs were determined using flow cytometry. The QD uptake route in MSCs was examined via fluorescence imaging using endocytosis inhibitors for the micropinocytosis, phagocytosis, lipid-raft, clathrin- and caveolin-dependent endocytosis pathways. These data showed that QDs were efficiently accumulated in the cytoplasm of MSCs after incubation for 6 h. The main uptake route of QDs in skin MSCs was clathrin-mediated endocytosis. QDs were mainly localized in early endosomes after 6 h as well as in late endosomes and lysosomes after 24 h. QDs in concentrations ranging from 0.5 to 64 nM had no effect on cell viability and proliferation. The expression of MSC markers, CD73 and CD90, and hematopoietic markers, CD34 and CD45, as well as the ability to differentiate into adipocytes, chondrocytes, and osteocytes, were not altered in the presence of QDs. We observed a decrease in the QD signal from labelled MSCs over time that could partly reflect QD excretion. Altogether, these data suggest that QD-labelled MSCs could be used for targeted drug delivery studies.


Meiotic studies of a 38,XY/39,XXY mosaic boar.
Klinefelter's syndrome (KS) is the most common sex chromosome abnormality identified in human males. This syndrome is generally associated with infertility. Men with KS may have a 47,XXY or a 46,XY/47,XXY karyotype. Studies carried out in humans and mice suggest that only XY cells are able to enter and complete meiosis. These cells could originate from the XY cells present in mosaic patients or from XXY cells that have lost one X chromosome. In pig, only 3 cases of pure 39,XXY have been reported until now, and no meiotic analysis was carried out. For the first time in pig species we report the analysis of a 38,XY/39,XXY boar and describe the origin of the supplementary X chromosome and the chromosomal constitutions of the germ and Sertoli cells.


Increasing erucic acid content through combination of endogenous low polyunsaturated fatty acids alleles with Ld-LPAAT + Bn-fae1 transgenes in rapeseed (Brassica napus L.).
High erucic acid rapeseed (HEAR) oil is of interest for industrial purposes because erucic acid (22:1) and its derivatives are important renewable raw materials for the oleochemical industry. Currently available cultivars contain only about 50% erucic acid in the seed oil. A substantial increase in erucic acid content would significantly reduce processing costs and could increase market prospects of HEAR oil. It has been proposed that erucic acid content in rapeseed is limited because of insufficient fatty acid elongation, lack of insertion of erucic acid into the central sn-2 position of the triaclyglycerol backbone and due to competitive desaturation of the precursor oleic acid (18:1) to linoleic acid (18:2). The objective of the present study was to increase erucic content of HEAR winter rapeseed through over expression of the rapeseed fatty acid elongase gene (fae1) in combination with expression of the lysophosphatidic acid acyltransferase gene from Limnanthes douglasii (Ld-LPAAT), which enables insertion of erucic acid into the sn-2 glycerol position. Furthermore, mutant alleles for low contents of polyunsaturated fatty acids (18:2 + 18:3) were combined with the transgenic material. Selected transgenic lines showed up to 63% erucic acid in the seed oil in comparison to a mean of 54% erucic acid of segregating non-transgenic HEAR plants. Amongst 220 F(2) plants derived from the cross between a transgenic HEAR line and a non-transgenic HEAR line with a low content of polyunsaturated fatty acids, recombinant F(2) plants were identified with an erucic acid content of up to 72% and a polyunsaturated fatty acid content as low as 6%. Regression analysis revealed that a reduction of 10% in polyunsaturated fatty acids content led to a 6.5% increase in erucic acid content. Results from selected F(2) plants were confirmed in the next generation by analysing F(4) seeds harvested from five F(3) plants per selected F(2) plant. F(3) lines contained up to 72% erucic acid and as little as 4% polyunsaturated fatty acids content in the seed oil. The 72% erucic acid content of rapeseed oil achieved in the present study represents a major breakthrough in breeding high erucic acid rapeseed.


The burden of skin disease in the United States.
Since the publication of the last US national burden of skin disease report in 2006, there have been substantial changes in the practice of dermatology and the US health care system. These include the development of new treatment modalities, marked increases in the cost of medications, increasingly complex payer rules and regulations, and an aging of the US population. Recognizing the need for up-to-date data to inform researchers, policy makers, public stakeholders, and health care providers about the impact of skin disease on patients and US society, the American Academy of Dermatology produced a new national burden of skin disease report. Using 2013 claims data from private and governmental insurance providers, this report analyzed the prevalence, cost, and mortality attributable to 24 skin disease categories in the US population. In this first of 3 articles, the presented data demonstrate that nearly 85 million Americans were seen by a physician for at least 1 skin disease in 2013. This led to an estimated direct health care cost of $75 billion and an indirect lost opportunity cost of $11 billion. Further, mortality was noted in half of the 24 skin disease categories.


Academic Achievement in School-Aged Children with Single Suture Craniosynostosis Over Time.
Introduction: Children with single suture craniosynostosis (SSC) are at risk for neurocognitive problems. The reported magnitude of differences between children with SSC and their normative peers on standardized tests of academic and intellectual ability are small. Evaluation of real-world academic outcomes of these children and its impact on educational resources have not been conducted. Methods: A retrospective cohort study of academic outcomes of children with SSC was conducted using the data from Ontario's Education Quality and Accountability Office (EQAO) standardized provincial reading, writing and mathematics tests. The need for special education was identified by documentation of the child's need for an Identification, Placement, and Review Committee (IPRC). Results: Of 296 eligible children, 42 participated in the study. Half of the children had sagittal synostosis, while the remaining were 10 (24%) unicoronal, 9 (21%) metopic, and 2 (5%) lambdoid synostosis. Thirty-six (86%) underwent operative management. The EQAO scores of operated children with SSC met the provincial academic standards on the Grade 3 and 6 EQAO scores across the 3 academic subjects. Converted grade-matched EQAO scores decreased in reading and writing over time, while math improved. Of the 21 patients with special education data, one child required an IPRC in Grade 3, while an additional four (24%) required an IPRC in Grade 6. Conclusions: Operated children with SSC had average academic performance, however, their needs appeared to change over time. Future studies are needed to evaluate academic difficulties and special education needs as these children progress through grade school.


[Distal gangrene and cryoglobulinemia related to hepatitis C virus infection with presence of anticardiolipin antibodies].
We report the case of a 63-year old women with toe gangrene, peripheral polyneuropathy, polyarthritis, histologically proven necrotizing vasculitis, in association with type III mixed cryoglobulinemia and hepatitis C virus (HCV) infection. Raised anticardiolipin antibodies (aCL) were found, without beta 2-glycoprotein I. HCV infection is associated with mixed cryoglobulinemia which can cause a vasculitis affecting various organs. The pathogenesis of production and clinical significance of aCL could be associated in this case with HCV infection.


Ligand-induced conformational changes via flexible linkers in the amino-terminal region of the inositol 1,4,5-trisphosphate receptor.
Cytoplasmic Ca2+ signals are highly regulated by various ion transporters, including the inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R), which functions as a Ca2+ release channel on the endoplasmic reticulum membrane. Crystal structures of the two N-terminal regulatory regions from type 1 IP(3)R have been reported; those of the IP(3)-binding core (IP(3)R(CORE)) with bound IP(3), and the suppressor domain. This study examines the structural effects of ligand binding on an IP(3)R construct, designated IP(3)R(N), that contains both the IP(3)-binding core and the suppressor domain. Our circular dichroism results reveal that the IP(3)-bound and IP(3)-free states have similar secondary structure content, consistent with preservation of the overall fold within the individual domains. Thermal denaturation data show that, while IP(3) has a large effect on the stability of IP(3)R(CORE), it has little effect on IP(3)R(N), indicating that the suppressor domain is critical to the stability of IP(3)R(N). The NMR data for IP(3)R(N) provide evidence for chemical exchange, which may be due to protein conformational dynamics in both apo and IP(3)-bound states: a conclusion supported by the small-angle X-ray scattering data. Further, the scattering data show that IP(3)R(N) undergoes a change in average conformation in response to IP(3) binding and the presence of Ca2+ in the solution. Taken together, these data lead us to propose that there are two flexible linkers in the N-terminal region of IP(3)R that join stably folded domains and give rise to an equilibrium mixture of conformational sub-states containing compact and more extended structures. IP(3) binding drives the conformational equilibrium toward more compact structures, while the presence of Ca2+ drives it to a more extended set.


Neonatal eye infections due to Mycoplasma hominis.
In one year Mycoplasma hominis was isolated from 8 out of 250 clinically infected eyes of newborn infants. This infection occurred in only a small proportion of babies whose mothers carried the organism in the vagina. Probably mycoplasma infection of the eye in neonates is commoner than is realized.


Catecholaminergic projections into an interconnected forebrain network control the sensitivity of male rats to diet-induced obesity.
Hindbrain catecholamine neurons convey gut-derived metabolic signals to an interconnected neuronal network in the hypothalamus and adjacent forebrain. These neurons are critical for short-term glycemic control, glucocorticoid and glucoprivic feeding responses, and glucagon-like peptide 1 (GLP-1) signaling. Here we investigate whether these pathways also contribute to long-term energy homeostasis by controlling obesogenic sensitivity to a high-fat/high-sucrose choice (HFSC) diet. We ablated hindbrain-originating catecholaminergic projections by injecting anti-dopamine-β-hydroxylase-conjugated saporin (DSAP) into the paraventricular nucleus of the hypothalamus (PVH) of male rats fed a chow diet for up to 12 wk or a HFSC diet for 8 wk. We measured the effects of DSAP lesions on food choices; visceral adiposity; plasma glucose, insulin, and leptin; and indicators of long-term ACTH and corticosterone secretion. We also determined lesion effects on the number of carbohydrate or fat calories required to increase visceral fat. Finally, we examined corticotropin-releasing hormone levels in the PVH and arcuate nucleus expression of neuropeptide Y ( Npy), agouti-related peptide ( Agrp), and proopiomelanocortin ( Pomc). DSAP-injected chow-fed rats slowly increase visceral adiposity but quickly develop mild insulin resistance and elevated blood glucose. DSAP-injected HFSC-fed rats, however, dramatically increase food intake, body weight, and visceral adiposity beyond the level in control HFSC-fed rats. These changes are concomitant with 1) a reduction in the number of carbohydrate calories required to generate visceral fat, 2) abnormal Npy, Agrp, and Pomc expression, and 3) aberrant control of insulin secretion and glucocorticoid negative feedback. Long-term metabolic adaptations to high-carbohydrate diets, therefore, require intact forebrain catecholamine projections. Without them, animals cannot alter forebrain mechanisms to restrain increased visceral adiposity.


[Long-term results of Burch's cervico-cystopexy. Apropos of 40 cases].
Forty patients with stress urinary incontinence, treated between April 1982 and June 1988 according to Burch's technique, were reviewed. 24 (60%) successes, 8 (20%) major improvements and 8 (20%) failures were recorded with a mean follow-up of 85 months. Compared to the early postoperative findings, a marked deterioration in urinary continence was observed in 4 cases (10%). These results are in contrast with earlier papers reporting remarkable stability of the therapeutic performance of this type of cervicocystopexy. Although too brief to allow reliable statistical analysis, this series simply draws attention to the hypothetical long-term efficacy of Burch's operation.


Temporary biventricular pacing postcardiopulmonary bypass in patients with reduced ejection fraction.
Patients with low ejection fraction (EF) undergoing myocardial revascularization frequently require ventricular pacing following cardiopulmonary bypass (CPB). While the benefits of chronic biventricular (BiV) pacing in patients with low EF are well established, there are little data on acute effects during heart surgery. This study analyzed the response of BiV versus single ventricle lead pacing on hemodynamics and left ventricular (LV) function immediately following CPB. Ten patients with decreased LV EF (mean = 35 +/- 6%) underwent open-heart surgery with CPB. Temporary pacing electrodes were placed on the right atrium, apex of the right ventricle, and lateral wall of the LV after separation from CPB. The hemodynamic effects of three atrio-ventricular (right, left, and BiV) pacing modes were studied for four minutes each. The pacing sequence was randomly allocated with a resting period of three minutes between each mode. Hemodynamic and echocardiographic data of LV function were collected. Statistical analysis was performed with analysis of variance. BiV pacing increased cardiac output by 4%, 13%, and 44% over right ventricular pacing, LV pacing, and pre-bypass values, respectively. The fractional area of change increased significantly with BiV pacing compared to right ventricular and LV pacing (36%, 35% to 44%, p < 0.01). An increased propagation velocity of 49 cm/s compared to 38 cm/s and 40 cm/s for right ventricular and LV pacing, respectively, suggested an improvement in diastolic function. In patients with low EF, BiV pacing immediately after CPB significantly improves LV systolic function and cardiac output, and suggests significantly improved diastolic function.


Interposition bone block arthrodesis for revision hallux metatarsophalangeal joint surgery: a case series.
The operative management of failed hallux metatarsophalangeal joint surgery can be difficult. There is often substantial shortening of the first ray. Arthrodesis of the first metatarsophalangeal joint is one treatment option, but results in further shortening of the first ray. We present a large retrospective series of patients who had an interposition bone block arthrodesis procedure performed using a nonvascularized tricortical autologous iliac crest bone graft in an attempt to maintain first ray length. Twenty-four patients (25 feet) underwent this salvage procedure over a 10-year period. The mean follow-up period was 62 (range, 11-117) months. Indications included failed hallux valgus surgery, Keller's procedures, various other first metatarsal osteotomies, and failed arthrodesis procedures with shortening of the first ray. All patients had tricortical iliac crest grafts inserted into bony defects of mean length 10.7 (range, 8-15) mm. Fixation was achieved using either multiple wires or a low-profile plate. Mean lengthening was 4.4 (range, 0-8) mm. Three feet went on to nonunion requiring further revision surgery and at latest follow-up 2 had united. All patients underwent removal of a stabilizing Kirschner wire. Median patient-reported outcome score using the Foot and Ankle Disability Index was 84.6 (range, 37.5-97.1). These results suggest this procedure was successful in salvaging failed first ray surgery and prevented further shortening. We believe good results can be achieved, but care must be taken to ensure wound closure without excessive tension to permit wound healing. Level IV, retrospective case series.


Morphometric and ultrasonographic study of the human fetal hip joint during intrauterine development.
The main method for the early screening of the developmental dysplasia of the hip (DDH) is the ultrasound imaging. There are several studies about the ultrasound imaging of newborns' hips, but only a few studies include the prenatal period of life. Our aim was to examine the prenatal development of the hip joint through the evolution of the α angle seen on the ultrasound, described in the Graf R method, combined with anatomical dissection. Thirty-one post-mortem fetal hips were analyzed trough anatomical dissection, in 25 cases trough ultrasound imaging, in which the α angle was measured. Based on the morphometric examination, we applied the sine rule and we calculated the α1 angle, which also represents the coverage of the femoral head. Based on the morphometric examination, not only the diameters of the femoral head and of the acetabulum, but also the joint cavity (X) showed an increase during development. Both of the α angles (measured α, calculated α1) showed a decrease as the fetus developed. The decrease of the angles (α, α1) and the increase of the joint cavity during development correspond to the findings of the main research papers: the hip joint is less stable in the perinatal life. The α angle can be accurately determined only after the ossification of the acetabulum had started, in our case after the fetus is older than 18 weeks.


E-test method for testing susceptibilities of Aspergillus spp. to the new triazoles voriconazole and posaconazole and to established antifungal agents: comparison with NCCLS broth microdilution method.
NCCLS document M38-P describes standard parameters for testing the fungistatic activities (MICs) of established agents against filamentous fungi (molds). This study evaluated the in vitro susceptibilities of 15 Aspergillus flavus isolates, 62 A. fumigatus isolates, and 10 isolates each of A. niger, A. nidulans, and A. terreus to voriconazole, posaconazole, itraconazole, and amphotericin B by the E-test and NCCLS M38-P microdilution methods. The agreement (within 3 dilutions) between methods for voriconazole was independent of the E-test incubation time (93.3 to 100% for four of five species at both incubation times). In contrast, with amphotericin B, itraconazole, and posaconazole, E-test results were more dependent on the incubation time for certain species. For A. fumigatus, posaconazole E-test MICs had better concordance with reference values after 48 h (95.2%) than after 24 h (90%), while the highest agreement for itraconazole MICs was after 24 h (90.3 versus 74.2%) of incubation. Better agreement between the methods was also obtained with 24-h E-test amphotericin B MICs for A. flavus (73.3 versus 26.7%) and A. fumigatus (96.7 versus 64.5%). E-test MICs of the four agents had the lowest percentages of agreement with reference values for A. nidulans (60 to 80%). For isolates for which high MICs were obtained for the four agents by the reference method, high MICs were also obtained by E-test at both 24 and 48 h. The utility of in vitro results of either the E-test or the NCCLS broth microdilution (M38-P) method for Aspergillus spp. needs to be established in clinical trials.


Insights on therapeutic potential of clemastine in neurological disorders.
Clemastine, a Food and Drug Administration (FDA)-approved compound, is recognized as a first-generation, widely available antihistamine that reduces histamine-induced symptoms. Evidence has confirmed that clemastine can transport across the blood-brain barrier and act on specific neurons and neuroglia to exert its protective effect. In this review, we summarize the beneficial effects of clemastine in various central nervous system (CNS) disorders, including neurodegenerative disease, neurodevelopmental deficits, brain injury, and psychiatric disorders. Additionally, we highlight key cellular links between clemastine and different CNS cells, in particular in oligodendrocyte progenitor cells (OPCs), oligodendrocytes (OLs), microglia, and neurons.


Mechanisms of electron transfer in catalysis by copper zinc superoxide dismutase.
Activated oxygen intermediates during copper zinc superoxide dismutase (SOD) catalysis were investigated using an isotope fractionation technique and natural abundance reagents. Competitive oxygen kinetic isotope effects (KIEs) are reported for the enzyme-catalyzed disproportionation of superoxide as well as the stoichiometric reaction of reduced SOD with molecular oxygen. Analysis within the context of quantum mechanical electron transfer theory provides evidence against an outer-sphere mechanism for O2*- oxidation. A CuII-O2-I intermediate is, therefore, proposed. The SOD-catalyzed oxidation of O2*- is characterized by an inverse (<1) KIE which is similar to those determined for the analogous reactions of synthetic copper compounds. An inverse kinetic isotope effect upon the enzymatic reduction of O2*- is also observed and proposed to arise from rate-determining proton transfer which leads to the formation of HO2* in the SOD active site.


Why does supragingival calculus form preferentially on the lingual surface of the 6 lower anterior teeth?
Many authors have assumed that the reason supragingival calculus tends to form preferentially on the lingual surface of the 6 lower anterior teeth is because saliva from the adjacent submandibular ducts is a source of calcium and phosphate ions and because loss of CO2 as the saliva enters the mouth increases the local pH. However, the fluid phase of plaque in all locations is supersaturated with respect to the calcium phosphates in calculus and there is always a tendency for calculus to deposit, except after sugar consumption, when plaque pH may fall below the critical level and the plaque fluid becomes unsaturated. pH is least likely to fall below the critical level in plaque lingual to the lower anterior teeth, as this plaque is very thin, sugar concentration after sugar intake is lowest in that area and its clearance rate is fastest, and the high salivary film velocity there promotes loss of any acid formed in plaque. A high salivary film velocity also brings more salivary urea to the site, which facilitates plaque alkalinization. These factors all contribute to the development of shallow Stephan curves of short duration and together provide a more reasonable explanation for the fact that supragingival calculus deposition progresses most easily on the lingual surface of the lower anterior teeth.


Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial.
To determine if minocycline is an effective therapy for seropositive rheumatoid arthritis (RA) when used within the first year of disease. The Rheumatoid Arthritis Investigational Network enrolled 46 patients with RA of <1 year duration into a 6-month study of minocycline (100 mg twice daily) versus placebo. All patients were rheumatoid factor positive. The primary end point of the study was successful completion of 6 months of treatment with no drug toxicity while maintaining 50% improvement in composite symptoms of arthritis. Eighteen of the 46 patients who were enrolled met 50% improvement criteria at 3 months, and maintained at least a 50% improvement for 6 months with no significant drug toxicity. Among them were 15 of the 23 patients (65%) treated with minocycline and 3 of 23 patients (13%) treated with placebo (P < 0.001). In patients with early seropositive RA, therapy with minocycline is superior to placebo.


Antiproliferative activity of aqueous leaf extract of Annona muricata L. on the prostate, BPH-1 cells, and some target genes.
Annona muricata L. has been reported to possess antitumor and antiproliferative properties. Not much work has been done on its effect on BPH-1 cell lines, and no in vivo studies targeting the prostate organ exist. The study determined the effect of A muricata on human BPH-1 cells and prostate organ. The MTT assay was performed on BPH-1 cells using the aqueous leaf extract of A muricata. Cells (1 × 10(5) per well) were challenged with 0.5, 1.0, and 1.5 mg/mL extract for 24, 48, and 72 hours. Cell proliferation and morphology were examined microscopically. BPH-1 cells (1 × 10(4) per well) were seeded into 6-well plates and incubated for 48 hours with 0.5, 1.0, and 1.5 mg/mL A muricata extract. Reverse transcriptase polymerase chain reaction was performed using mRNA extracted from the cells. Possible target genes, Bax and Bcl-2, were examined. Twenty F344 male rats (≈200 g) were gavaged 30 mg/mL (10 rats) and 300 mg/mL (10 rats) and fed ad libitum alongside 10 control rats. Rats were sacrificed after 60 days. The prostate, seminal vesicles, and testes were harvested for histological examination. Annona muricata demonstrated antiproliferative effects with an IC50 of 1.36 mg/mL. Best results were obtained after 48 hours, with near cell extinction at 72 hours. Bax gene was upregulated, while Bcl-2 was downregulated. Normal histological architecture was observed for all testes. Seminal vesicle was significantly reduced in test groups (P < .05) and demonstrated marked atrophy with increased cellularity and the acinii, empty of secretion. Prostate of test groups were reduced with epithelial lining showing pyknotic nucleus, condensation, and marginalization of the nuclear material, characteristic of apoptosis of the glandular epithelium. Furthermore, scanty prostatic secretion with flattening of acinar epithelial lining occurred. Annona muricata has antiproliferative effects on BPH-1 cells and reduces prostate size, possibly through apoptosis.


A prospective cohort study of starchy and non-starchy vegetable intake and mortality risk.
Whether starchy and non-starchy vegetables have distinct impacts on health remains unknown. We prospectively investigated the intake of starchy and non-starchy vegetables in relation to mortality risk in a nationwide cohort. Diet was assessed using 24-h dietary recalls. Deaths were identified via the record linkage to the National Death Index. Hazard ratios (HR) and 95 % CI were calculated using Cox regression. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants aged 18 years or older. Compared to those with no consumption, participants with daily consumption of ≥ 1 serving of non-starchy vegetables had a lower risk of mortality (HR = 0·76, 95 % CI 0·66, 0·88, Ptrend = 0·001). Dark-green and deep-yellow vegetables (HR = 0·79, 95 % CI 0·63, 0·99, Ptrend = 0·023) and other non-starchy vegetables (HR = 0·80, 95 % CI 0·70, 0·92, Ptrend = 0·004) showed similar results. Total starchy vegetable intake exhibited a marginally weak inverse association with mortality risk (HR = 0·89, 95 % CI 0·80, 1·00, Ptrend = 0·048), while potatoes showed a null association (HR = 0·93, 95 % CI 0·82, 1·06, Ptrend = 0·186). Restricted cubic spline analysis suggested a linear dose-response relationship between vegetable intake and death risk, with a plateau at over 300 and 200 g/d for total and non-starchy vegetables, respectively. Compared with starchy vegetables, non-starchy vegetables might be more beneficial to health, although both showed a protective association with mortality risk. The risk reduction in mortality plateaued at approximately 200 g/d for non-starchy vegetables and 300 g/d for total vegetables.


Trajectory tracking control of a pneumatically actuated continuum manipulator in the presence of obstacles by using terminal sliding mode control.
This paper proposes an efficient trajectory planning and dynamic tracking controller scheme for a pneumatic continuum manipulator under the effect of material hysteresis. First of all, generalized governing nonlinear dynamic equations in the form of partial differential equations for pneumatic continuum manipulator dynamics are developed by using discrete Cosserat-rod theory, where the manipulator material hysteresis is modeled by using a fractional order Bouc-Wen model. Then, the trajectory planning for the end-effector of a continuum manipulator is proposed, which accounts for the static obstacles in the workspace and the Jacobian singularity. Subsequently, an adaptive terminal sliding mode controller for the joint space control combined with a simple PI controller for task space control is proposed. The proposed controller guarantees exponential convergence of the manipulator tip positional error in finite time, even in the existence of external disturbances and model uncertainties, without any need for prior knowledge of their upper bounds. Finally, the proposed controller is applied to a two-segment continuum manipulator, the trunk of Robotino-XT, through numerical simulations and the performance gain over two controllers proposed in the literature for similar pneumatic continuum manipulators is demonstrated.


Genetic control of the immune response. Frequency and characteristics of antigen-binding cells in high and low responder mice.
The influence of immunization with (T,G)-A--L on the frequency and characteristics of [(125)I] (T,G)-A--L-binding cells (ABC) was investigated in high and low responder mice, whose ability to respond to (T,G)-A--L is under control of an H-2-linked immune response gene, Ir-1. Unimmunized high and low responder mice have about the same number of ABC in spleen and lymph nodes (6-12 ABC/10(4)). However, after immunization with (T,G)-A--L in aqueous solution, ABC in high responders increase to a much greater extent than they do in low responders. By inhibition of ABC with class-specific anti-Ig sera, it was demonstrated that in nonimmune and primed mice antigen is bound to IgM receptors, which is in agreement with the exclusive production of 19S anti-(T,G)-A--L antibody in primed animals. In contrast, after secondary challenge with antigen, ABC in high and low responder mice have mainly IgG receptors, although under the conditions used for immunization, low responders are not able to produce detectable amounts of 7S anti-(T,G)-A--L antibody. From these results and from the evidence that low responders very probably have a T cell defect, it is suggested that the switchover from IgM to IgG precursor cells can be induced by antigen itself, without the action of specific T cells. Furthermore, the failure of marked proliferation of ABC in low responders after antigenic stimulation is explained by the lack of stimulation by specific T cells. By independent methods it has been shown that all ABC detected in this study are B cells. Preliminary experiments indicate that purified peripheral T cells bind antigen, but much less per cell than do B cells.


Correlation of radiographic and arthroscopic findings with rotator cuff tears and degenerative joint disease.
The purpose of this study was to identify early signs of rotator cuff tear and glenohumeral articular cartilage degeneration by using conventional radiography. A non-weighted anteroposterior oblique and a weighted active abduction view were evaluated for superior humeral migration and matching degenerative changes at the inferolateral acromion and superior aspect of the greater tuberosity in 40 patients who underwent shoulder arthroscopy. Measurements of the glenohumeral distance were performed. Surgical reports were reviewed to determine rotator cuff and glenohumeral articular cartilage status. Matching degenerative changes correlate with complete rotator cuff tear (P =.04); superior migration does not. Severe glenohumeral cartilage loss correlates with narrowing of the superior joint space on the anteroposterior oblique radiograph (P =.02) and with narrowing of the mid joint space on the active abduction view (P =.05). Both glenohumeral articular cartilage degenerative change and rotator cuff injury, before formation of typical sequelae of chronic rotator cuff tear, can be detected with the use of conventional radiography.


Mesenchymal stem cells in lung diseases and their potential use in COVID-19 ARDS: A systematized review.
COVID-19 can converge with the pro-inflammatory immunoregulatory mechanisms of chronic lung diseases. Given the disorders inherent to lung transplantation and the inexistence of other definitive therapeutic alternatives, Adipose tissue-derived Stem Cells (ASCs) presented themselves as a therapeutic hope. The purpose of this review is to assess the basis for the potential use of ASCs in lung diseases unresponsive to conventional therapy, relating to their possible use in COVID-19 ARDS. 35 studies comprised this review, 14 being narrative reviews, 19 preclinical trials and two proofs of concept. COVID-19 can converge with the pro-inflammatory immunoregulatory mechanisms of chronic lung diseases. In view of the disorders inherent to lung transplantation and the inexistence of definitive therapeutic alternatives, Adipose tissue-derived Stem Cells (ASCs) presented themselves as a therapeutic hope. Its detailed reading indicated the absence of serious adverse effects and toxicity to the administration of ASCs and suggested possible effectiveness in reducing lung damage, in addition to promoting the recovery of leukocytes and lymphocytes with its immunomodulatory and anti-apoptotic effects. The revised clinical data suggests optimism in the applicability of ASCs in other immunoinflammatory diseases and in severe COVID-19 ARDS. However, further studies are needed to develop a consensus on the methods of collection of ASCs, the ideal dosage schedule, the most effective time and route of administration, as well as on the definition of indications for the administration of ASCs in cases of COVID-19 for conducting clinical trials in near future.


BVA marks its patron's birthday.
Along with the rest of the nation, BVA is celebrating Queen Elizabeth II's 90th birthday. President Sean Wensley explains how BVA will mark the occasion and looks back to her visit to the Association's headquarters in its centenary year.


Multidrug-Resistant Pseudomonas aeruginosa Triggers Differential Inflammatory Response in Patients With Endophthalmitis.
Infections with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) lead to poor clinical outcomes in endophthalmitis patients, and its interactions with the host immune system remain largely unknown. The current study aimed to determine the association of MDR-PA infection with the cytokine expression profile in patients with endophthalmitis. Vitreous of 12 patients with culture-proven MDR-PA along with 12 samples from antibiotic-susceptible P. aeruginosa (S-PA) and 20 non-infectious controls were included in the study. Expression patterns of IL-6, IL-10, IL-1α, IL-1β, IFN-γ, TNF-α, IL-8, and GM-CSF in the vitreous were analyzed by multiplex immunoassay and correlated with the clinical severity. We also assessed the phosphorylation level of different immune pathway molecules. In the MDR-PA group, significantly (P < 0.05) increased expression of IL-6, IL-8, IL-10, IL-1β, and TNF-α was observed in comparison with the S-PA group. The increased inflammatory mediators in MDR-PA correlated with the disease severity. Additionally, the increased expression of inflammatory mediators was positively correlated to the activation levels of Akt, STAT3, JNK, p70 S6 kinase, and NF-кB (P < 0.05) in the MDR-PA group. The current study shows the differential host immune response and phosphorylation levels of signaling molecules in MDR-PA endophthalmitis, thereby linking antibiotic resistance with distinct immune regulation. This study provides evidence for the use of inflammatory mediator levels of IL-6, IL-8, IL-10, IL-1β, and TNF-α as potential diagnostic biomarkers of MDR endophthalmitis warranting prompt administration of immune modulators to avoid irreversible damage to the retina and vision loss.


Complete paroxysmal atrioventricular block in a 2-year-old girl.
We present a case of atypical syncope in a 2-year-old, otherwise healthy girl. The patient presented with three episodes of syncope without any precipitating factors and no family history of sudden unexpected death. Holter monitoring revealed 24 events of complete atrioventricular block lasting up to 6 seconds. A normal 12-lead electrocardiogram does not necessarily exclude cardiac disease, and Holter monitoring is warranted in children with atypical syncope.


[The prognostic value of CA 19-9 in the preoperative work-up of pancreatic cancer patients].
Carbohydrate antigen (CA) 19-9 is produced by adenocarcinomas of the pancreas, stomach, gall bladder, colon, ovary and lung. Serum CA 19-9 is considered the most sensitive marker for pancreatic cancer, being elevated in 75% or more of patients with pancreatic cancer. In all three cases of pancreatic cancer presented, patients died of their disease quite shortly after diagnosis. Preoperative imaging was unsuccessful in exposing the actual advanced state extent of the disease and even during surgery its real extent was underestimated. The only prognostic indicator of the observed rapid disease progression was a very significant elevation of preoperative serum CA 19-9.


Polish pseudo-words list: dataset of 3023 stimuli with competent judges' ratings.
Pseudo-words are stimuli, which are useful in research concerning lexical processing. As in the case of existing words, they are language dependent; thus, they should be generated for each language separately. The Polish Pseudo-words List (PPwL) is a dataset presenting a set of 3023 stimuli (words of 4-13 letters long). They were generated using an algorithm substituting random letters in existing words with respect to the frequency of letters in certain positions. We put out the raw set for a competent judges' assessment and included the responses in the dataset. PPwL allows the choice of suitable control stimuli for experiments concerning lexical processing.


Cytokeratin 5-Positive Cells Represent a Therapy Resistant subpopulation in Epithelial Ovarian Cancer.
Cytokeratin 5 (CK5) is an epithelial cell marker implicated in stem and progenitor cell activity in glandular reproductive tissues and endocrine and chemotherapy resistance in estrogen receptor (ER)(+) breast cancer. The goal of this study was to determine the prevalence of CK5 expression in ovarian cancer and the response of CK5(+) cell populations to cisplatin therapy. Cytokeratin 5 expression was evaluated in 2 ovarian tissue microarrays, representing 137 neoplasms, and 6 ovarian cancer cell lines. Cell lines were treated with IC(50) (half-maximal inhibitory concentration) cisplatin, and the prevalence of CK5(+) cells pretreatment and posttreatment was determined. Proliferation of CK5(+) versus CK5(-) cell populations was determined using 5-bromo-2'-deoxyuridine incorporation. Chemotherapy-induced apoptosis in CK5(+) versus CK5(-) cells was measured using immunohistochemical staining for cleaved caspase-3. Cytokeratin 5 was expressed in 39.3% (42 of 107) of epithelial ovarian cancers with a range of 1% to 80% positive cells. Serous and endometrioid histologic subtypes had the highest percentage of CK5(+) specimens. Cytokeratin 5 expression correlated with ER positivity (38 of 42 CK5(+) tumors were also ER(+)). Cytokeratin 5 was expressed in 5 of 6 overall and 4 of 4 ER(+) epithelial ovarian cancer cell lines ranging from 2.4% to 52.7% positive cells. Cytokeratin 5(+) compared with CK5(-) cells were slower proliferating. The prevalence of CK5(+) cells increased after 48-hour cisplatin treatment in 4 of 5 cell lines tested. Cytokeratin 5(+) ovarian cancer cells compared with CK5(-) ovarian cancer cells were more resistant to cisplatin-induced apoptosis. Cytokeratin 5 is expressed in a significant proportion of epithelial ovarian cancers and represents a slower proliferating chemoresistant subpopulation that may warrant cotargeting in combination therapy.


Influence of wave-front sampling in adaptive optics retinal imaging.
A wide range of sampling densities of the wave-front has been used in retinal adaptive optics (AO) instruments, compared to the number of corrector elements. We developed a model in order to characterize the link between number of actuators, number of wave-front sampling points and AO correction performance. Based on available data from aberration measurements in the human eye, 1000 wave-fronts were generated for the simulations. The AO correction performance in the presence of these representative aberrations was simulated for different deformable mirror and Shack Hartmann wave-front sensor combinations. Predictions of the model were experimentally tested through in vivo measurements in 10 eyes including retinal imaging with an AO scanning laser ophthalmoscope. According to our study, a ratio between wavefront sampling points and actuator elements of 2 is sufficient to achieve high resolution in vivo images of photoreceptors.


Advance Care Planning in the Nursing Home Setting: A Practice Improvement Evaluation.
This study evaluated a practice improvement initiative conducted over a 6 month period in 15 Canadian nursing homes. Goals of the initiative included: (1) use the Plan-Do-Study-Act (PDSA) model to improve advance care planning (ACP) within the sample of nursing homes; (2) investigate whether improved ACP practice resulted in a change in residents' hospital use and ACP preferences for home-based care; (3) engage participating facilities in regular data collection to inform the initiative and provide a basis for reflection about ACP practice and; (4) foster a team-based participatory care culture. The initiative entailed two cycles of learning sessions followed by implementation of ACP practice improvement projects in the facilities using a PDSA approach by participating clinicians (e.g., physicians, social workers, nurses). Clinicians reported significantly increased confidence in many dimensions of ACP activities. Rates of hospital use and resident preference for home-based care did not change significantly. The initiative established routine data collection of outcomes to inform practice change, and successfully engaged physicians and non-physician clinicians to work together to improve ACP practices. Results suggest recurrent PDSA cycles that engage a 'critical mass' of clinicians may be warranted to reinforce the standardization of ACP in practice.


Is Telehealth Right for Your Practice and Your Patients With Asthma?
Telehealth services are becoming increasingly used to provide care to patients living in rural areas. Little is known about the patient satisfaction with the provision of these services. A prospective cohort pilot study was developed to evaluate the use of telehealth for the delivery of asthma education services in the rural, medically underserved community of Oakes, North Dakota. A certified asthma educator used real-time, audio-visual telehealth technology to meet with patients the local community pharmacy. Patients met with the educator monthly for the first three months of the study, and once every three months thereafter. Patient satisfaction was measured using a five item survey. Eighteen patients completed the study (90 percent completion rate). Patient satisfaction scores were relatively high, typically between 4 and 5 on a 5-point scale. Participants in a rural, medically underserved community found the community pharmacy location and the telehealth technology a convenient means to access a specialty provider for asthma education.


Characterization and Physical and Biological Properties of Tissue Conditioner Incorporated with Carum copticum L.
One of the main problems in dentistry is the injury caused by the long-term application of an ill-fitting denture. The existence of multiple microorganisms along with the susceptibility of the tissue conditioners to colonize them can lead to denture stomatitis. This study is aimed at developing a tissue conditioner incorporated with Carum copticum L. (C. copticum L.) for the effective treatment of these injuries. The Carum copticum L. essential oil composition was determined by gas chromatography-mass (GC-mass) spectrometry. The antimicrobial activity of the essential oil against the standard strains of bacterial and fungal species was determined by broth microdilution methods as suggested by the Clinical and Laboratory Standards Institute (CLSI). The physical and chemical properties of the prepared tissue conditioner were investigated by viscoelasticity, FTIR assays, and the release study performed. Furthermore, the antibiofilm activity of the Carum copticum L. essential oil-loaded tissue conditioner was evaluated by using the XTT reduction assay and scanning electron microscopy (SEM). The main component of the essential oil is thymol, which possesses high antimicrobial activity. The broth microdilution assay showed that the essential oil has broad activity as the minimum inhibitory concentration was in the range of 32-128 μg mL-1. The viscoelasticity test showed that the essential oil significantly diminished the viscoelastic modulus on the first day. The FTIR test showed that Carum copticum L. essential oil was preserved as an independent component in the tissue conditioner. The release study showed that the essential oil was released in 3 days following a sustained release and with an ultimate cumulative release of 81%. Finally, the Carum copticum L. essential oil exhibited significant activity in the inhibition of microbial biofilm formation in a dose-dependent manner. Indeed, the lowest and highest amounts of biofilm formation on the tissue conditioner disks are exhibited in the Streptococcus salivarius and Candida albicans by up to 22.4% and 71.4% at the 64 μg mL-1 concentration of C. copticum L. with a statistically significant difference (P < 0.05). The obtained results showed that the Carum copticum L. essential oil-loaded tissue conditioner possessed suitable physical, biological, and release properties for use as a novel treatment for denture stomatitis.


Effect of Camellia sinensis teas on left ventricular hypertrophy and insulin resistance in dyslipidemic mice.
The control of dyslipidemia using plants is an important subject of studies since it has numerous benefits in cardiovascular protection. The objective of this study was to evaluate the effect of three Camellia sinensis L. teas (green, red, and white) on left ventricular hypertrophy and insulin resistance in low-density lipoprotein receptor knockout (LDLr-/-) mice fed a high-fat diet. The LDLr-/- mice were divided into four experimental groups: Group C: standard feed; Group CT: standard feed and three teas, Group HL: high-fat feed; HLT Group: high-fat feed and three teas. The three types of tea (green, red, and white) originated from different processing of the Camellia sinensis L. plant, and were administered associated once a day at a dose of 25 mg/kg by gavage for 60 days. The teas partially prevented hyperlipidemia, the decrease of the serum levels of high-density lipoproteins (HDL), insulin resistance, and increased C-reactive protein (CRP) levels, and completely prevented left ventricular hypertrophy in LDLr -/- mice of the HLT group. In conclusion, the three Camellia sinensis L. teas used to control genetic dyslipidemia associated with a high-fat diet can be used as an auxiliary treatment associated with the control of lipid intake, thus promoting cardiac protection against hyperlipidemia.


Predictors of Lateral Pelvic Lymph Node Metastasis in Advanced Low Rectal Cancer Treated With Neoadjuvant Chemotherapy.
This retrospective study used magnetic resonance imaging to identify clinicopathological predictors of lateral pelvic lymph node metastasis in patients with advanced low rectal cancer treated with neoadjuvant chemotherapy; only few such studies have been reported. Sixty-one patients with advanced low rectal cancer who underwent total mesorectal excision and lateral pelvic lymph node dissection after neoadjuvant chemotherapy between April 2013 and December 2019 were included in this study. Univariate and multivariate analyses were used to analyze the relationship between lateral pelvic lymph node metastasis and clinicopathological factors, such as lateral pelvic lymph node size, measured before and after neoadjuvant chemotherapy using magnetic resonance imaging. The short-axis diameter of lateral pelvic lymph nodes before neoadjuvant chemotherapy (p=0.003, odds ratio: 2.898, 95% confidence interval=1.534-9.143) was the only identified independent preoperative predictor. Based on the receiver operating characteristic curve analysis, the cut-off value of the short-axis diameter of lateral pelvic lymph nodes before neoadjuvant chemotherapy was 6.8 mm. The area under the curve was 0.761 (95% confidence interval=0.723-0.932). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 77.8%, 72.1%, 53.8%, 88.6%, and 73.8%, respectively. The preoperative predictor of lateral pelvic lymph node metastasis in advanced low rectal cancer treated with neoadjuvant chemotherapy was the short-axis diameter of lateral pelvic lymph nodes before neoadjuvant chemotherapy. When lateral pelvic lymph nodes with short-axis diameters above 6.8 mm are present, lateral pelvic lymph node dissection may be necessary.


Postdischarge smoking cessation in subgroups of hospitalized smokers: A latent class analysis.
Hospitalization presents a window of opportunity to treat smoking, and hospital-initiated smoking treatment has demonstrated effectiveness. Despite effective interventions, not all smokers will discontinue use, highlighting the need to better understand which patients achieve cessation. Traditional regression methods may not capture the complexity of inpatient smoker subgroups. Latent class analysis (LCA) was conducted with data from 397 hospitalized adult cigarette smokers enrolled in a randomized trial. Six categorical indicator variables known to impact cessation were selected to estimate subgroups: health conditions (smoking-related disease [SRD], depressive symptoms, positive screen for alcohol problems) and smoking-related variables (time to first cigarette, cigarettes/day, smoking indoors). The probability of achieving biologically verified 7-day tobacco cessation 6 months after discharged was estimated. A 3-class model best fit the trial data: a Light Smokers subgroup had lower probability for most indicators; a High Health Burden subgroup had high smoking behavior probabilities and similar health problems to the Light Smokers subgroup; and a Heavy Smoking Drinking Depressed subgroup had high nicotine dependence, depressive symptoms, and alcohol misuse probabilities. Probability of biologically verified cessation conditional on class membership was significantly higher (P < .001) for the High Health Burden and the Light Smokers subgroups compared with the Heavy Smoking Drinking Depressed subgroup. Results suggest that subgroups with lower probabilities of alcohol misuse and depression and higher probability of SRD had higher probability of successful cessation after hospital discharge. Hospitalized patients with nicotine dependence combined with behavioral and mental health problems have additional cessation barriers that may require intervention focus.


Circadian rhythm in dihydropyrimidine dehydrogenase activity and reduced glutathione content in peripheral blood of nasopharyngeal carcinoma patients.
Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. Glutathione (GSH) is a tripeptide involved in platinum complex detoxification. This study explored the circadian rhythms of DPD activity and GSH concentration in the peripheral blood of 16 patients with histologically proven nasopharyngeal carcinoma (NPC) in order to guide the establishment of chronotherapeutic schedules for this cancer. DPD activity and GSH concentration were determined by high performance liquid chromatography (HPLC). Both variables displayed significant circadian rhythms (Cosinor analysis: p = 0.009 and 0.012, respectively). Peak DPD activity occurred at about 02:30 h; whereas, peak GSH concentration occurred around 12:40 h. The differences between the peak and nadir mean values were 25.5% and 38.7%, respectively. The study showed that the circadian rhythms in DPD activity and GSH concentration in Chinese NPC are similar to those reported for western patients with colorectal cancer, despite the differences in race and kinds of cancer. These findings imply that the chronotherapeutic schedule of 5-FU and platinum used to treat European colorectal cancer patients probably is applicable to Chinese NPC patients.


Laparoscopic urethrovesical anastomosis: a model to assess surgical competency.
To create a model for the evaluation of resident competency and performance of laparoscopic skills in compliance with Accreditation Council for Graduate Medical Education (ACGME) outcome assessment guidelines for urology residency programs. A model of laparoscopic interrupted urethrovesical anastomosis was developed using chicken skin from a local supermarket. Eight residents at various training levels utilized a simulator with a camera-operating assistant to practice placing interrupted stitches. The time necessary for completion of an anastomosis and the quality of the anastomosis were documented. The time required to recreate a simulated urethrovesical anastomosis by placing six interrupted stitches declined from an initial mean of 60.75 minutes to 20.5 minutes after each resident had performed 20 anastomoses each. The mean improvement was 39.5 minutes, with one postgraduate year-3 resident demonstrating an improvement of 50 minutes. This model can be used by ACGME-certified urology residency programs to assess the laparoscopic skills of residents.


Subcellular localization of glyoxylate cycle enzymes in Ascaris suum larvae.
Evidence is presented on the particulate nature of glyoxylate cycle enzymes in metazoa with the use of 15-day old larvae of the nematode Ascaris suum. Homogenization procedures were developed to disrupt the resistant nematode cuticle. Malate synthase and isocitrate lyase, key enzymes of the glyoxylate cycle, consistently sedimented with mitochondrial enzymes in differential pellets while catalase, a major peroxisomal enzyme, was always soluble. Isopycnic sucrose gradient centrifugation of the differential pellet yielded two protein peaks: one at 1.18 g/cm3 (characteristic for mitochondria), and another at 1.23 g/cm3 (common for glyoxysomes and peroxisomes). Electron microscopy of these fractions revealed that the lighter peak consisted primarily of mitochondria, while the heavier band contained proteinaceous bodies termed "dense granules" morphologically resembling microbodies. SIgnificantly, both malate synthase and isocitrate lyase cosedimented with the mitochondrial marker enzymes in the lighter peak (1.18 g/cm3) and not with the dense granules. Further purification of mitochondria, accomplished by separating dense granules with a step gradient before isopycnic centrifugation, substantiated the evidence that microbodies (glyoxysomes) do not occur in these nematode larvae. Rough-surfaced membranes were alternatively considered as the subcellular site, but the evidence tends to favor localization of the glyoxylate bypass enzymes in the mitochondria.