GFP tagged Vibrio parahaemolyticus Dahv2 infection and the protective effects of the probiotic Bacillus licheniformis Dahb1 on the growth, immune and antioxidant responses in Pangasius hypophthalmus.
In this study, the pathogenicity of GFP tagged Vibrio parahaemolyticus Dahv2 and the protective effect of the probiotic strain, Bacillus licheniformis Dahb1 was studied on the Asian catfish, Pangasius hypophthalmus. The experiment was carried out for 24 days with three groups and one group served as the control (without treatment). In the first group, P. hypophthalmus was orally infected with 1 mL of GFP tagged V. parahaemolyticus Dahv2 at two different doses (10(5) and 10(7) cfu mL(-1)). In the second group, P. hypophthalmus was orally administrated with 1 ml of the probiotic B. licheniformis Dahb1 at two different doses (10(5) and 10(7) cfu mL(-1)). In the third group, P. hypophthalmus was orally infected first with 1 mL of GFP tagged V. parahaemolyticus Dahv2 followed by the administration of 1 mL of B. licheniformis Dahb1 (combined treatment) at two different doses (10(5) and 10(7) cfu mL(-1)). The growth, immune (myeloperoxidase, respiratory burst, natural complement haemolytic and lysozyme activity) and antioxidant (glutathione-S-transferase, reduced glutathione and total glutathione) responses of P. hypophthalmus were reduced after post infection of GFP tagged V. parahaemolyticus Dahv2 compared to control. However, after administration with the probiotic B. licheniformis Dahb1 at 10(5) cfu mL(-1), P. hypophthalmus showed significant increase in the growth, immune and antioxidant responses compared to 10(7) cfu mL(-1). On the otherhand, the growth, immune and antioxidant responses of P. hypophthalmus infected and administrated with combined GFP tagged Vibrio + Bacillus at 10(5) cfu mL(-1) were relatively higher than that of GFP tagged V. parahaemolyticus Dahv2 and control groups but lower than that of probiotic B. licheniformis Dahb1 groups. The results of the present study conclude that the probiotic B. licheniformis Dahb1 at 10(5) cfu mL(-1) has the potential to protect the P. hypophthalmus against V. parahaemolyticus Dahv2 infection by enhancing the growth, immune and antioxidant responses. The probiotic B. licheniformis Dahb1 would be effectively used in the treatment of aquatic diseases for improvement of aquaculture industry.


Comparison of 3H-misonidazole binding between CHO and 9L cells using the sandwich system.
3H-misonidazole binding of 9L cells was compared with that of CHO cells using an in vitro tumor analog, the sandwich system. In sandwiches there is a gradient of microenvironments, with cells adjacent to the necrotic center subjected to low concentrations of oxygen and glucose and to high concentrations of metabolites. Mixed sandwiches, having 9L and CHO cells interspersed, were used along with sandwiches of each individual cell line. MISO binding was assessed in situ, using autoradiography. Grains per cell were counted and detailed statistics were obtained on the variation in MISO binding among cells located in the same microenvironment. In all cases binding in the regions near the necrotic center was more than 50 times the binding found at the sandwich edge and found in control monolayers, indicating radiobiological hypoxia near the necrotic center. 9L cells began to significantly increase binding of MISO metabolites at a somewhat higher oxygen concentration than did CHO cells. At all oxygen tensions, average per cell binding of the 9L cells was 3 times or more that of the CHO cells, a factor greater than can be explained by the ratio of cell volumes alone. Statistical analyses of the variation in binding among cells in a given microenvironment give some evidence that in the mixed CHO/9L sandwiches there are interactions between the cells of the two different lines which affect the growth patterns of the cells. No preferred binding of misonidazole in the nucleus or cytoplasm was noted within the cells.


Water dispersion of magnetic nanoparticles with selective Biofunctionality for enhanced plasmonic biosensing.
Magnetic nanoparticles (MNPs) are widely used in biosensing, bioimaging, and drug delivery. However, high quality superparamagnetic nanoparticles with uniform size were usually synthesized by thermal decomposition using organic solvents. To be suitable for biomedical applications, a facile and efficient water dispersion of iron oxide MNPs from solvent using an innovative agent, sodium oleate (NaOL) was described. The monodispersed MNPs (4 and 15nm respectively) after transfer was biocompatible and stable at a broad temperature range (4-50°C) over months. More importantly, the NaOL coating allows for surface modification with selective functionality, rendering the aqueous MNPs highly customizable for biofunctionalization. Little effect on the superparamagnetism was observed after the water dispersion. To further evaluate its practical application in biosensing, custom MNPs were prepared for specific cardiac troponin I (cTnI) detection for myocardial infarction diagnosis. Specifically, gold nanorod (GNR) biochip was probed by the MNP-captured cTnI target analyte at varying concentrations. The signal transduction of the GNR sensor is based on the localized surface plasmon resonance (LSPR). The application of the MNPs resulted in a significant enhancement of the plasmonic response of the GNRs. As such, the MNP-mediated LSPR biosenisng showed a three times lower sensitivity as compared to the direct cTnI binding without functional MNPs. Computer simulation further elucidated that the enhancement was distance dependent between the MNP and the surface of the nanorod, which corroborated with experimental results.


Views of emergency research (VERA): a qualitative study of women and their partners' views of recruitment to trials in severe postpartum haemorrhage.
to explore women's and their partners' views of recruitment to emergency trials in severe postpartum haemorrhage (PPH). interview-based qualitative study. In semi-structured in-depth interviews, five recruitment options for a PPH trial in an emergency context were considered. interviews were carried out in participants' homes. nine women who had experienced a severe PPH and six partners. interviewees rejected three options; decision-making by women prior to delivery, and by partners and legal representatives at the time of the emergency. Preferred options were women making antenatal decisions about trial entry themselves, followed by doctors making decisions at the time of the emergency. recruitment options involving women and their partners at the time of an emergency were rejected. Antenatal decision-making raises logistical and ethical considerations for emergency trial teams. Further research is needed to address the possibility of antenatal decisions for emergency trials and to develop and assess supportive post-enrolment recruitment and information strategies which take into account the stressful context of clinical emergencies such as PPH.


Programmed cell death-1 blockade in recurrent disseminated Ewing sarcoma.
Ewing sarcoma (EWS) is a malignant tumour of bone and soft tissue, and although many patients are cured with conventional multimodal therapy, those with recurrent or metastatic disease have a poor prognosis. Genomic instability and programmed cell death ligand-1 (PD-L1) expression have been identified in EWS, providing a rationale for treatment with agents that block the programmed cell death-1 (PD-1) receptor. In this report, we describe a heavily pre-treated patient with recurrent metastatic EWS who achieved a clinical and radiological remission with PD-1 blockade. To our knowledge, this is the first reported case demonstrating efficacy of PD-1 blockade in EWS. This warrants further investigation in particular given the poor prognosis in patients with recurrent or metastatic disease.


Determining the structure-mechanics relationships of dense microtubule networks with confocal microscopy and magnetic tweezers-based microrheology.
The microtubule (MT) cytoskeleton is essential in maintaining the shape, strength, and organization of cells. Its spatiotemporal organization is fundamental for numerous dynamic biological processes, and mechanical stress within the MT cytoskeleton provides an important signaling mechanism in mitosis and neural development. This raises important questions about the relationships between structure and mechanics in complex MT structures. In vitro, reconstituted cytoskeletal networks provide a minimal model of cell mechanics while also providing a testing ground for the fundamental polymer physics of stiff polymer gels. Here, we describe our development and implementation of a broad tool kit to study structure-mechanics relationships in reconstituted MT networks, including protocols for the assembly of entangled and cross-linked MT networks, fluorescence imaging, microstructure characterization, construction and calibration of magnetic tweezers devices, and mechanical data collection and analysis. In particular, we present the design and assembly of three neodymium iron boron (NdFeB)-based magnetic tweezers devices optimized for use with MT networks: (1) high-force magnetic tweezers devices that enable the application of nano-Newton forces and possible meso- to macroscale materials characterization; (2) ring-shaped NdFeB-based magnetic tweezers devices that enable oscillatory microrheology measurements; and (3) portable magnetic tweezers devices that enable direct visualization of microscale deformation in soft materials under applied force.


Congenital syphilis associated with hearing screening failure in southern Brazilian newborns.
To estimate the association between congenital syphilis and neonatal hearing screening failure in the state of Santa Catarina between 2017 and 2019. This is a cross-sectional, retrospective, analytical study with secondary data of neonates from the state of Santa Catarina born between January 2017 and December 2019. We used logistic regression analysis to estimate the association between the main exposure (congenital syphilis) and the study outcome (failure in the Neonatal Hearing Screening). The study included 21,434 newborns evaluated in a Brazilian hearing health care service. A total of 351 (1.6%) newborns failed the Neonatal Hearing Screening, and 364 (1.7%) had congenital syphilis. In the adjusted analysis, newborns with congenital syphilis were 3.25 times as likely to fail the Neonatal Hearing Screening as neonates without this disease (95% CI: 2.01; 5.26). As for maternal age, the sample had a higher prevalence (53.5%) of mothers aged 20-29 years. There was an association between congenital syphilis and failure in Universal Neonatal Hearing Screening in the sample studied. There is a need for investments in public policies to value and strengthen the hearing screening program in the state to provide early diagnosis and intervention.


Sleep diary- and actigraphy-derived sleep parameters of 8-hour fast-rotating shift work nurses: A prospective descriptive study.
Given the harmful effects of night shifts and rotating schedules on nurses' sleep and work performance, shift nurses' sleep patterns have been a research concern. Actigraphy involves acquisition of data using a movement sensor worn continuously on the nondominant wrist, typically for a week or more. Although actigraphy provides objective and accurate sleep data, sleep diaries have been a practical alternative. However, there is a lack of research on the agreement and consistency between the two methods of measuring sleep for shift work nurses. In addition, differences in sleep patterns by shift types among 8-hour fast-rotating shift work nurses has not yet been examined. To evaluate the agreement between the sleep diary and actigraphy methods for sleep assessment, and to compare sleep parameters of 8-hour fast-rotating shift work nurses according to shift type. Descriptive and prospective study design. Two tertiary hospitals in Seoul, South Korea. A total of 94 shift work nurses who wore actigraphy along with completing a sleep diary. Subjective and objective sleep parameters were recorded during a two-week period in a sleep diary and actigraphy, respectively. Bland-Altman plots and intraclass correlation coefficients were used to analyze the agreement between the two methods. Sleep parameters according to shift type were compared using the Kruskal-Wallis and Mann-Whitney U tests. Good agreement was observed between the sleep diary and the actigraphy data for total sleep time (intraclass correlation coefficients = 0.765 or 0.858) and variability in sleep time (intraclass correlation coefficients = 0.838). When compared to the actigraphy data, diary-derived data were overestimated by 41-45 min for total sleep time and 0.4% for variability in sleep time. There was a difference of 2-3 h of sleep quantity by shift type: 5.3-5.8 h for day shifts and 7.1-8.4 h for night shifts. A sleep diary can function as an acceptable alternative to actigraphy for measuring shift work nurses' sleep patterns, specifically total sleep time and variability in sleep time. Given the high variability in sleep among shift work nurses, both personal and organizational efforts are required. Nurses should monitor their sleep quantity and develop their own regular sleep schedules to fit their work schedules. Hospitals should establish healthy schedules for nurses to guarantee sufficient sleep hours before work. Future research on shift work nurses' sleep should examine fluctuations in sleep duration.


Dual-parameter flow cytometry of transitional cell carcinomas. Quantitation of DNA content and binding of carbohydrate ligands in cellular subpopulations.
Quantitative DNA measurements and estimates of blood group-related carbohydrate antigen expression have been used as predictive parameters in transitional cell carcinomas (Ca). To obtain an accurate quantitative characterization of cellular subpopulations on the basis of these parameters, the authors developed a dual-parameter flow cytometric method using a fluorescence-activated cell sorter. With this method single-cell suspensions from 26 transitional cell carcinomas were analyzed by means of propidium iodide (red fluorescence) as DNA ligand, and peanut agglutinin (PNA), wheat germ agglutinin (WGA), and anti-blood group A antibody (aBGA) as carbohydrate ligands. The latter ligands were visualized directly or indirectly by FITC (green fluorescence). The carbohydrate ligand binding was correlated to the DNA content of cell populations in the way that aneuploid populations showed a higher PNA binding (P less than 0.0002) and a lower WGA (P less than 0.01) and aBGA (P less than 0.04) binding than did diploid cell populations. The binding of PNA to aneuploid populations could be further increased (P less than 0.004) by neuraminidase treatments. Thus, aneuploid cells express both neuraminic acid substituted and unsubstituted PNA receptors. The carbohydrate ligand binding was cell cycle-dependent, as it was reduced (less than 0.008) in the G2-M phase. A low WGA (P less than 0.004) or aBGA (P less than 0.02) binding was correlated to tissue invasion. Immunohistochemistry with the carbohydrate ligands showed a good correlation between aBGA (P less than 0.0005) and PNA (P less than 0.004) binding to tumor cells and flow cytometric assay of these, as well as a correlation (P less than 0.003) between cellular location of WGA receptors and flow cytometric assay of these. It seems that dual-parameter flow cytometry represents an important tool in the characterization of bladder tumors.


Stimulation of the conjugation of lipid dienes in hepatic microsomes by 3,3'-dichlorobenzidine.
Pretreatment of male rats with 3,3'-dichlorobenzidine (DCB) resulted in the accumulation of conjugated dienes in lipids from hepatic microsomes. In vitro, these microsomes had 2-fold the NADPH-dependent malondialdehyde (MDA)-forming capacity of microsomes from untreated rats. To determine the mechanisms of the DCB-induced accumulation of diene conjugation, the effects of added DCB on NADPH- or iron + ascorbic acid- (Fe2+-ascorbate-) dependent diene conjugation, oxygen uptake and MDA formation were examined in microsomes from untreated rats in vitro. In the presence of NADPH, added DCB stimulated diene conjugation in microsomal lipids as did in vivo DCB pretreatment but inhibited the uptake of oxygen and the formation of MDA. When Fe2+-ascorbate was substituted for NADPH, the formation of diene conjugation, oxygen uptake, and MDA formation were inhibited by added DCB. The DCB-induced stimulation of diene conjugation, in addition to being strictly NADPH dependent, was carbon monoxide sensitive and was concomitant with the binding of added DCB to microsomal lipids. It is postulated that a metabolite of DCB generated by cytochrome P-450 reacts with membrane lipids both in vivo and in vitro in a manner analogous to the initiation of lipid peroxidation but at the same time prevents the autocatalytic decomposition of the lipids. The DCB-induced diene conjugation is interpreted as predisposing to deleterious changes in microsomes.


Facilitators and barriers to allyship in academic surgery: A qualitative study.
Academic health centers have promoted initiatives to improve diversity, equity and inclusion in medicine. Despite this emphasis, there has been limited discussion on practical strategies for navigating bias within academic surgery. This study analyzes experiences of confronting bias within the department of surgery at the University of Michigan. We conducted telephone interviews (n = 15) from January 2019 to January 2020 with surgeon volunteers at one academic institution. Two investigators conducted interviews following a semi-structured guide based on personal experiences with bias between healthcare workers with diverse identities. Interviews were conducted concurrently with thematic coding, coded independently by two investigators, and discussed until consensus was reached. Analysis proceeded following the inductive and comparative approach of interpretive description. The most common incidents of bias were based on gender and race. They occurred along numerous relationship axes, including physician-patient and resident-faculty. A critical factor in bias response was unambiguously recognizing bias. Responding to bias consists of timing and nature of the response, defined as when the subject responded relative to the incident and the actions done in response to the incident respectively. Barriers to bias response were fear of retribution and extensive energy required to respond. Institutional culture was important, specifically in representation and support from peers and administration. This study probes deeper into equity and inclusivity in the academic field of surgery, offering insight into common barriers to confronting bias. Overall, these findings offer a basic framework for allies to identify bias and to partner with colleagues to address biases in a supportive manner.


Analysis of ectasia after laser in situ keratomileusis: risk factors.
To examine a database of laser in situ keratomileusis (LASIK) procedures for preoperative and operative factors assumed to increase the risk for developing post-LASIK ectasia. Private clinical practice. A computer database was queried for eyes that had LASIK for myopic refractive errors with the following characteristics: preoperative corneal thickness 500 microm or less, mean keratometry greater than 47.0 diopters (D), patient age 25 years or younger, attempted correction greater than -8.0 D, refractive astigmatism not with-the-rule and greater than 2.0 D, and residual stromal bed thickness (RST) 250 microm or less. Flap thickness and RST were measured using ultrasound pachymetry. All recorded information was exported to MS Excel and analyzed for eyes that had ectasia. Of the 9700 eyes in the database, none with the above characteristics developed ectasia over mean follow-up periods exceeding 2 years. Seven eyes had multiple risk factors without ectasia. Three eyes with abnormal preoperative topography developed ectasia. Individual preoperative and operative factors did not in and of themselves increase the risk for ectasia. Unmeasured and unknown factors that affect the individual cornea's biomechanical stability, in combination with some suspected risk factors as well as the current inability to identify corneas at risk for developing ectatic disorders, probably account for most eyes that develop ectasia today.


Butterflyene: an entry into an aesthetically pleasing carbocycle via a Diels-Alder reaction on a tetrasubstituted olefin.
An interesting molecular architecture, butterflyene, resembling the shape of a butterfly has been synthesized via a sequence of cyclocondensation, benzylic oxidation, McMurry coupling and Diels-Alder reaction (DAR), successively. The DAR of the tetrasubstituted double bond of a bicyclopentylidene moiety with various dienes has been performed to prepare the analogues of butterflyene. DFT calculations have also been used to analyze the structural optimization and reaction energies.


[Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome].
Takotsubo is a reversible cardiomyopathy, often triggered by a stressful event. It combines clinical features mimicking a myocardial infarction, transient apical ballooning of the left ventricle, normal coronary arteries and a small rise in troponin level. There is a striking female predominance with mean age ranging from 65 to 76 years among series. Preceding stressful event is documented in 50 to 100% of patients. The most common clinical presentation is an angor-like chest pain with ST-segment elevation on the electrocardiogram (70%). The prognosis is excellent even if serious complications may occur: pulmonary oedema, cardiogenic shock, transient dynamic intraventricular gradient, life-threatening arrhythmias. In-hospital mortality is in the range of 0 to 10%. The recurrence rate is low. The precise physiopathology of the syndrome remains unknown but catecholamine mediated myocardial stunning is the most favored explanation.


Targeting the amyloid-β antibody in the brain tissue of a mouse model of Alzheimer's disease.
Alzheimer's disease is a neurodegenerative disease characterized pathologically by amyloid-β (Aβ) aggregates in the brain. Notwithstanding many promising therapeutics that are under development, early diagnosis of Alzheimer's disease is limited. By targeting the Aβ aggregates, diagnosis can be improved and disease progression reduced. Molecular imaging using monoclonal antibodies to target specific isoforms of Aβ aggregates offer increased specificity in comparison to conventional imaging tracers; however, antibodies that are widely used in histology do not necessarily show similar binding in a dynamic in vivo environment. In this study, the diffusion and binding were studied of a classical monoclonal antibody, 6E10, in the brain of the TgCRND8 mouse model of AD. After intracranial injection of fluorescent 6E10, we observed broad and rapid labelling of Aβ deposits in the cortex and corpus callosum within 4h. Aβ plaques were detected up to 2.5mm away from the injection site in TgCRND8 mice and not in wild type mice at all, demonstrating specificity of binding. The apparent diffusivity and elimination constant of the anti-Aβ antibody were found to be independent of both the age of the animal and the accumulation of Aβ in the extracellular space, suggesting broad applicability of this targeting molecule. Mathematical modelling of the diffusion profiles of the anti-Aβ antibody in the brain parenchyma provides insights into the utility of antibodies as molecular imaging tools and targeted therapeutics.


Binding of both acrosome-intact and acrosome-reacted guinea pig sperm to the zona pellucida during in vitro fertilization.
Mammalian sperm-egg adhesion occurs when sperm bind to the zona pellucida of the egg. In this study with guinea pig gametes, we have asked if sperm can initiate binding to the zona before and after the acrosome reaction and if the sperm surface protein PH-20 is involved in the binding at these two stages. Sperm binding to the zona was examined under a variety of conditions. Sperm were suspended in 0.9% NaCl or capacitated by two different methods. Eggs were immobilized on lectin-coated coverslips, compressed between a coverslip and a glass slide, or free in tissue culture dishes. The sperm-egg interaction was recorded on videotape or assessed after fixation of the eggs with bound sperm. Under all conditions studied, both acrosome-intact and acrosome-reacted sperm initiated binding to the zona. The binding was persistent and not transitory. In particular, acrosome-intact sperm that bound the zona were observed to remain bound for up to 80 min. One acrosome-intact sperm, bound to the zona, was videotaped while it acrosome-reacted. When mixed sperm populations (on the average 24% acrosome-intact and 76% acrosome-reacted) were incubated with eggs for 30 min, an average of 10% of the bound sperm were acrosome-intact. The PH-20 monoclonal antibody has previously been shown to inhibit zona binding by guinea pig sperm of undetermined acrosomal status (P. Primakoff, H. Hyatt, and D. G. Myles (1985), J. Cell Biol. 101, 2239-2244). In this study, when the two populations of sperm were counted separately, PH-20 inhibited the binding of acrosome-reacted but not acrosome-intact sperm. Our results show that both acrosome-intact and acrosome-reacted guinea pig sperm can initiate binding to the zona; however, the binding in the two cases may not occur by the same mechanism.


Regulation of titin-based cardiac stiffness by unfolded domain oxidation (UnDOx).
The relationship between oxidative stress and cardiac stiffness is thought to involve modifications to the giant muscle protein titin, which in turn can determine the progression of heart disease. In vitro studies have shown that S-glutathionylation and disulfide bonding of titin fragments could alter the elastic properties of titin; however, whether and where titin becomes oxidized in vivo is less certain. Here we demonstrate, using multiple models of oxidative stress in conjunction with mechanical loading, that immunoglobulin domains preferentially from the distal titin spring region become oxidized in vivo through the mechanism of unfolded domain oxidation (UnDOx). Via oxidation type-specific modification of titin, UnDOx modulates human cardiomyocyte passive force bidirectionally. UnDOx also enhances titin phosphorylation and, importantly, promotes nonconstitutive folding and aggregation of unfolded domains. We propose a mechanism whereby UnDOx enables the controlled homotypic interactions within the distal titin spring to stabilize this segment and regulate myocardial passive stiffness.


S-adenosyl-L-methionine protects the hippocampal CA1 neurons from the ischemic neuronal death in rat.
We investigated the effect of S-adenosyl-L-methionine (SAMe) on the prevention of the delayed neuronal death in rats subjected to transient and brief forebrain ischemia. As the results, SAMe dose-dependently protected the hippocampal CA1 neurons from degeneration and necrosis, whose effect was suppressed by simultaneous administration of S-adenosyl-L-homocysteine, a potent inhibitor in transmethylation. No protective effect was observed in CDP-choline, phosphatidylcholine and L-methionine. Therefore, it is necessary for the prevention of the delayed neuronal death to enhance cerebral SAMe level and to activate transmethylation using SAMe as a methyl donor in postischemic brain.


[Effects of composite blood-activating decoction on adhesive function of bone marrow stroma cells in radiation injured mice].
To evaluate the effect of commonly used "blood activating and stasis-removing" Chinese herbal drugs on adhesive function of bone marrow stroma cells in acute radiation injured mice. After irradiation by 8 Gy 60Co gamma-ray, each mouse was intraperitoneally injected immediately with 0.2 ml 100% composite blood-activating decoction (CBAD) twice a day for 6 days. On the 7th day, the femura were taken and the bone karyocyte (BMC) suspension was made. According to long term bone marrow culture procedure, on the 12th day, the fibroblastic colony forming units were counted, and on the 28th day, the adhesion of culture stroma cells to normal murine BMC was observed. The adhesion of culture stroma cells to normal murine BMC was 67.8 +/- 17.2% in normal group, while in CBAD group, it was 55.8 +/- 10.5%. The difference was insignificant (P > 0.05). In the control group, the value was 47.7 +/- 13.6%, which was significantly lower than that in normal group (P < 0.02). The commonly used "blood-activating and stasis-removing" Chinese herbal drugs can enhance the adhesive function of bone marrow stroma cells in acute radiation injured mice.


Whole Genome Re-sequencing of Soybean Accession EC241780 Providing Genomic Landscape of Candidate Genes Involved in Rust Resistance.
In this study, whole genome re-sequencing of rust resistant soybean genotype EC241780 was performed to understand the genomic landscape involved in the resistance mechanism. A total of 374 million raw reads were obtained with paired-end sequencing performed with Illumina HiSeq 2500 instrument, out of which 287.3 million high quality reads were mapped to Williams 82 reference genome. Comparative sequence analysis of EC241780 with rust susceptible cultivars Williams 82 and JS 335 was performed to identify sequence variation and to prioritise the candidate genes. Comparative analysis indicates that genotype EC241780 has high sequence similarity with rust resistant genotype PI 200492 and the resistance in EC241780 is conferred by the Rpp1 locus. Based on the sequence variations and functional annotations, three genes Glyma18G51715, Glyma18G51741 and Glyma18G51765 encoding for NBS-LRR family protein were identified as the most prominent candidate for Rpp1 locus. The study provides insights of genome-wide sequence variation more particularly at Rpp1 loci which will help to develop rust resistant soybean cultivars through efficient exploration of the genomic resource.


Differential vulnerability of neurochemically identified subpopulations of retinal neurons in a monkey model of glaucoma.
The vulnerability of subpopulations of retinal neurons delineated by their content of cytoskeletal or calcium-binding proteins was evaluated in the retinas of cynomolgus monkeys in which glaucoma was produced with an argon laser. We quantitatively compared the number of neurons containing either neurofilament (NF) protein, parvalbumin, calbindin or calretinin immunoreactivity in central and peripheral portions of the nasal and temporal quadrants of the retina from glaucomatous and fellow non-glaucomatous eyes. There was no significant difference between the proportion of amacrine, horizontal and bipolar cells labeled with antibodies to the calcium-binding proteins comparing the two eyes. NF triplet immunoreactivity was present in a subpopulation of retinal ganglion cells, many of which, but not all, likely correspond to large ganglion cells that subserve the magnocellular visual pathway. Loss of NF protein-containing retinal ganglion cells was widespread throughout the central (59-77% loss) and peripheral (96-97%) nasal and temporal quadrants and was associated with the loss of NF-immunoreactive optic nerve fibers in the glaucomatous eyes. Comparison of counts of NF-immunoreactive neurons with total cell loss evaluated by Nissl staining indicated that NF protein-immunoreactive cells represent a large proportion of the cells that degenerate in the glaucomatous eyes, particularly in the peripheral regions of the retina. Such data may be useful in determining the cellular basis for sensitivity to this pathologic process and may also be helpful in the design of diagnostic tests that may be sensitive to the loss of the subset of NF-immunoreactive ganglion cells.


Recent advances in computational modeling of fibrin clot formation: A review.
The field of thrombosis and hemostasis is crucial for understanding and developing new therapies for pathologies such as deep vein thrombosis, diabetes related strokes, pulmonary embolisms, and hemorrhaging related diseases. In the last two decades, an exponential growth in studies related to fibrin clot formation using computational tools has been observed. Despite this growth, the complete mechanism behind thrombus formation and hemostasis has been long and rife with obstacles; however, significant progress has been made in the present century. The computational models and methods used in this context are diversified into different spatiotemporal scales, yet there is no single model which can predict both physiological and mechanical properties of fibrin clots. In this review, we list the major strategies employed by researchers in modeling fibrin clot formation using recent and existing computational techniques. This review organizes the computational strategies into continuum level, system level, discrete particle (DPD), and multi-scale methods. We also discuss strengths and weaknesses of various methods and future directions in which computational modeling of fibrin clots can advance.


A novel lymphoid progenitor cell population (LSK(low)) is restricted by p18(INK4c).
The cyclin-dependent kinase inhibitor CDKN2C (p18(INK4c)) restrains self-renewal in hematopoietic stem cells (HSCs) and participates in the development and maturation of lymphoid cells. Deficiency in p18 predisposes mice and humans to hematopoietic lymphoid malignancies such as T-cell leukemia and multiple myeloma. However, the mechanism by which p18 regulates differentiation from HSCs to lymphoid cells is poorly understood. In this study, we found that a progenitor population characterized by its expression of surface markers, Lin(-) Sca-1(+) c-Kit(low) (LSK(low)), was markedly expanded in the bone marrow of p18 knock-out (p18(-/-)) mice. This novel population possessed lymphoid differentiation potential, but not myeloid differentiation potential, both in vitro and in vivo. Whereas LSK(low) cells and common lymphoid progenitors (CLPs) overlapped functionally in generating lymphoid cells, they were distinct cell populations, because they had different gene expression profiles. Unlike CLPs, LSK(low) cells did not express the interleukin-7 receptor. LSK(low) cells were derived from HSCs and were independent of the p18-deleted microenvironment. This cell population may represent a previously unappreciated transitional stage from HSCs to lymphoid progenitors that is strictly restricted by p18 under physiological conditions. Likewise, LSK(low) might serve as a new cellular target of lymphoid malignances in the absence of p18.


Phytohemagglutinin and transmembrane proteins in agglutinated sheep erythrocyte ghost membranes.
Oriented and periodically stacked sheep erythrocyte ghost membrane specimens were prepared by agglutination of the ghosts with phytohemagglutinin M and sedimentation, and were studied by X-ray diffraction. The spatial orientation of the planes of the membranes in the diffracting stack was determined from the lamellar reflections of the periodic stacking. Equatorial diffraction at (10.5 A)-1 and a (1.5 A)-1 reflection were recorded which correlate with side-to-side packed transmenbrane alpha-helices in the agglutinated membrane. A broad (4.6 A)-1 ring with strong equatorial accentuation and broad maxima at about (2.2 A)-1 and (1.2 A)-1 were observed which are attributed to the hydrocarbon chain arrangement in lipid phases of the agglutinated ghost membrane.


A proposed method to measure weak magnetic field based on a hybrid optomechanical system.
Optomechanical systems have long been considered in the field of precision measurement. In this work, measurement of weak magnetic field in a hybrid optomechanical system is discussed. In contrast to conventional measurements based on detecting the change of magnetic flux, our scheme presents an alternative way to measure the magnetic field with a precision of 0.1 nT. We show that the effective cavity resonance frequency will be revised due to the electromagnetic interactions. Therefore, a resonance valley in the transmission spectrum of the probe field will shift in the presence of the magnetic field, and the width of an asymmetric transparency in the optomechanically induced transparency (OMIT) shows a strong dependence on the magnetic field strength. Our results may have potential application for achieving high precision measurement of the magnetic field.


Magnetic resonance imaging with adiabatic pulses using a single surface coil for RF transmission and signal detection.
In order to overcome the problems that arise from nonuniform B1 fields, there has been interest in developing pulses that are insensitive to large variations in RF power. Pulses derived from adiabatic passage principles that can execute spin inversion, excitation, and 90 degrees and 180 degrees plane rotations in the presence of B1 inhomogeneities have recently been described. When driven with optimized modulation functions, these pulses can execute uniform excitation, refocusing, and slice-selective inversion over a 10-fold or greater variation in B1 magnitude. This insensitivity to B1 strength enables the execution of T1- and/or T2-weighted spin-echo imaging experiments using coils, such as the surface coil, with extremely inhomogeneous B1 profiles. We have successfully acquired images with these pulses at 200 MHz using a single surface coil as the transmitter and receiver. Images of the slice definition, the region over which the excitation and refocusing pulses operate with a surface coil, and brain images obtained with slice planes perpendicular to the plane of the surface coil are presented. Results demonstrate that these pulses can be transmitted with a surface coil to yield high-quality T1- and/or T2-weighted images without B1 artifacts.


Chronic and Sudden Serious Illness, COVID-19, and Decision-Making Capacity: Integrating Advance Care Planning Into the Preoperative Checklist for Elective Surgery.
Advance Care Planning (ACP) includes anticipating future medical decisions and designating a medical decision maker in the event of losing the capacity to make one's own medical decisions. Many advantages can be seen to doing ACP before a crisis as well as revisiting these discussions over time as circumstances change. This case presentation is of a 74-year-old woman with multiple medical problems who had ACP discussions in the context of proposed surgery for colon cancer. These conversations highlight the elements of high-quality ACP and the importance of learning what patients mean when they employ phrases commonly referenced in these conversations. The planned surgery was delayed by the COVID-19 pandemic but the discussions helped to guide decision-making when the patient became critically ill with COVID-19.


Neutralizing antibodies associated with exposure factors to Orthopoxvirus in laboratory workers.
Extensive use of Vaccinia virus (VACV) in research has led to associated accidental human exposure in laboratories worldwide. In spite of the social and economic relevance of Bovine Vaccinia outbreaks in Brazil, national data concerning laboratory workers handling these infectious agents are relatively scarce. Therefore, a serological survey was conducted in a Brazilian laboratory to evaluate staff exposure to orthopoxviruses (OPVs). Information concerning direct work with OPVs, vaccination status and laboratory accidents was collected and correlated to serology results. This study presents an opportunity for discussion of routine procedures involving OPVs in laboratories and their intrinsic risks. Aspects of the live attenuated smallpox vaccine are also discussed.


The membrane interactions of antimicrobial peptides revealed by solid-state NMR spectroscopy.
Solid-state NMR spectroscopic techniques provide valuable information about the structure, dynamics and topology of membrane-inserted polypeptides. In particular antimicrobial peptides (or 'host defence peptides') have early on been investigated by solid-state NMR spectroscopy and many technical innovations in this domain have been developed with the help of these compounds when reconstituted into oriented phospholipid bilayers. Using solid-state NMR spectroscopy it could be shown for the first time that magainins or derivatives thereof exhibit potent antimicrobial activities when their cationic amphipathic helix is oriented parallel to the bilayer surface, a configuration found in later years for many other linear cationic amphipathic peptides. In contrast transmembrane alignments or lipid-dependent tilt angles have been found for more hydrophobic sequences such as alamethicin or β-hairpin antimicrobials. This review presents various solid-state NMR approaches and develops the basic underlying concept how angular information can be obtained from oriented samples. It is demonstrated how this information is used to calculate structures and topologies of peptides in their native liquid-disordered phospholipid bilayer environment. Special emphasis is given to discuss which NMR parameters provide the most complementary information, the minimal number of restraints needed and the effect of motions on the analysis of the NMR spectra. Furthermore, recent (31)P and (2)H solid-state NMR measurements of lipids are presented including some unpublished data which aim at investigating the morphological and structural changes of oriented or non-oriented phospholipids. Finally the structural models that have been proposed for the mechanisms of action of these peptides will be presented and discussed in view of the solid-state NMR and other biophysical experiments.


In Situ Cell Signalling of the Hippo-YAP/TAZ Pathway in Reaction to Complex Dynamic Loading in an Intervertebral Disc Organ Culture.
Recently, a dysregulation of the Hippo-YAP/TAZ pathway has been correlated with intervertebral disc (IVD) degeneration (IDD), as it plays a key role in cell survival, tissue regeneration, and mechanical stress. We aimed to investigate the influence of different mechanical loading regimes, i.e., under compression and torsion, on the induction and progression of IDD and its association with the Hippo-YAP/TAZ pathway. Therefore, bovine IVDs were assigned to one of four different static or complex dynamic loading regimes: (i) static, (ii) "low-stress", (iii) "intermediate-stress", and (iv) "high-stress" regime using a bioreactor. After one week of loading, a significant loss of relative IVD height was observed in the intermediate- and high-stress regimes. Furthermore, the high-stress regime showed a significantly lower cell viability and a significant decrease in glycosaminoglycan content in the tissue. Finally, the mechanosensitive gene CILP was significantly downregulated overall, and the Hippo-pathway gene MST1 was significantly upregulated in the high-stress regime. This study demonstrates that excessive torsion combined with compression leads to key features of IDD. However, the results indicated no clear correlation between the degree of IDD and a subsequent inactivation of the Hippo-YAP/TAZ pathway as a means of regenerating the IVD.


Sulfidogenic anaerobic digestion of sulfate-laden waste activated sludge: Evaluation on reactor performance and dynamics of microbial community.
This study investigated the impact of sludge retention times (SRTs: 40, 20, 10 and 5 days) on performance of the sulfidogenic anaerobic digestion (SAD) reactor treating sulfate-laden waste activated sludge and dynamics of sulfate reducing bacteria (SRB). The findings showed that sulfide production, volatile sludge removal efficiency, ammonia release and methane yield decreased by 33.7%, 66.4%, 21.3% and 68.7%, respectively when SRT was shortened from 40 to 5 d. Significant enrichment of hydrolyzers/fermenters (genera Mesotoga and Sulfurovum) was observed at longer SRT (40 d), but shorter SRT (5 d) favors enrichment of diverse SRB (genera Desulfomicrobium and Desulfovibrio). PICRUSt data revealed bacterial communities possessed diverse predicted functions including sulfur metabolism enzymes (e.g. sulfate adenylyltransferase), and their abundance was higher at shorter SRT. Statistical analysis (PCA) confirmed positive relationships between SRB and SAD performance. The findings of this research could be useful for design and optimization of sulfidogenic-based anaerobic digestion process.


Argon laser trabeculoplasty for chronic angle-closure glaucoma uncontrolled by iridotomy.
Nineteen eyes of 19 Japanese patients with medically uncontrollable chronic angle-closure glaucoma following laser iridotomy or surgical iridectomy underwent argon laser trabeculoplasty (ALT), applying low-power and a small number of laser burns over a small extent of the trabecular meshwork. All the eyes had glaucomatous optic disc damage, visual field loss, and intraocular pressure elevation before ALT. In each case, the extent of peripheral anterior synechiae was equal or less than 50% of the angle. The mean follow-up was 35 months. Life-table analysis (Kaplan-Meier method) showed that the probability of success was 66% at the end of three years after ALT. It is concluded that in the cases of uncontrollable chronic angle-closure glaucoma following laser iridotomy or surgical iridectomy, ALT should be tried before filtration surgery.


A Patient-centered Remote Therapy Monitoring Program Focusing on Increased Adherence to Wound Therapy: A Large Cohort Study.
This retrospective study of 510 patients receiving negative pressure wound therapy (NPWT) in a home care setting examines the relationship between remote therapy monitoring (RTM) and patient adherence, as well as determines the impact of patient adherence on wound progression. Adherence to treatment was continuously monitored via RTM, and patients with therapy usage < 16 hours in 1 day received an adherence call. Repeated failures to reach a noncompliant patient led to an escalation call to the caregiver to discuss treatment. Wound volume and surface area were collected to determine the rate of wound size reduction. A total of 3261 calls were made with an average of 6.4 calls per patient. Among the 510 patients, 98% received a welcome call, 87% received at least 1 call due to low adherence, and 30% received an escalation call. The day following an adherence call, 73.5% of patients increased therapy use. As adherence to NPWT increased (< 60% to 90%-100% therapy use), there was an increase in the daily reduction rate in wound volume (1.42% to 2.23%) and surface area (0.86% to 1.45%). The data suggest RTM can be used to influence patient behavior, and there may be a potential relationship between patient behavior and wound healing outcomes. Additional studies are needed to elucidate the relationship between RTM and wound outcomes.


Anonymity and Electronics: Adapting Preparation for Radiology Resident Examination.
Diagnostic radiology resident assessment has evolved from a traditional oral examination to computerized testing. Teaching faculty struggle to reconcile the differences between traditional teaching methods and residents' new preferences for computerized testing models generated by new examination styles. We aim to summarize the collective experiences of senior residents at three different teaching hospitals who participated in case review sessions using a computer-based, interactive, anonymous teaching tool, rather than the Socratic method. Feedback was collected from radiology residents following participation in a senior resident case review session using Nearpod, which allows residents to anonymously respond to the teaching material. Subjective resident feedback was uniformly enthusiastic. Ninety percent of residents favor a case-based board review incorporating multiple-choice questions, and 94% favor an anonymous response system. Nearpod allows for inclusion of multiple-choice questions while also providing direct feedback to the teaching faculty, helping to direct the instruction and clarify residents' gaps in knowledge before the Core Examination.


Trust and Reflection in Primary Care Practice Redesign.
To test a conceptual model of relationships, reflection, sensemaking, and learning in primary care practices transitioning to patient-centered medical homes (PCMH). Primary data were collected as part of the American Academy of Family Physicians' National Demonstration Project of the PCMH. We conducted a cross-sectional survey of clinicians and staff from 36 family medicine practices across the United States. Surveys measured seven characteristics of practice relationships (trust, diversity, mindfulness, heedful interrelation, respectful interaction, social/task relatedness, and rich and lean communication) and three organizational attributes (reflection, sensemaking, and learning) of practices. We surveyed 396 clinicians and practice staff. We performed a multigroup path analysis of the data. Parameter estimates were calculated using a Bayesian estimation method. Trust and reflection were important in explaining the characteristics of practice relationships and their associations with sensemaking and learning. The strongest associations between relationships, sensemaking, and learning were found under conditions of high trust and reflection. The weakest associations were found under conditions of low trust and reflection. Trust and reflection appear to play a key role in moderating relationships, sensemaking, and learning in practices undergoing practice redesign.


Alteration of sensory abilities regulates the spatial scale of nonlethal predator effects.
Many studies have shown that nonlethal predator effects such as trait-mediated interactions (TMIs) can have significant impacts on the structure and function of communities, but the role that environmental conditions play in modulating the scale and magnitude of these effects has not been carefully investigated. TMIs occur when prey exhibit behavioral or physiological responses to predators and may be more prevalent when abiotic conditions increase prey reactions to consumers. The purpose of this study was to determine if turbulence would alter the distance over which prey in aquatic systems respond to chemical cues emitted by predators in nature, thus changing the scales over which nonlethal predator effects occur. Using hard clams and blue crabs as a model predator-prey system, we investigated the effects of turbulence on clam reactive distance to predatory blue crabs in the field. Results suggest that turbulence diminishes clam reactions to predators and that the environmental context must be considered when predicting the extent of indirect predator effects in natural systems.


Malignant glaucoma and central retinal vein occlusion after Nd: YAG laser posterior capsulotomy.
The purpose of this paper is to present the case of malignant glaucoma complicated by CRVO occurring after Nd: YAG laser posterior capsulotomy. A 75 years old woman with pseudophakia and cardiovascular disease had undergone Nd: YAG laser posterior capsulotomy, the day after capsulotomy IOP increased in that eye up to 50 mmHg. Medical treatment alone appeared to be unsuccessful. IOP remained elevated (50 mmHg) and lack of anterior chamber occurred. In the examination, the eye showed circumcorneal congestion, diffuse corneal edema, uniformly flat anterior chamber with dilated, nonreacting pupil, optic disc edema, retinal hemorrhages, dilated tortuous retinal veins and macular edema. Surgical therapy (pars plana vitrectomy and the anterior chamber reformation with air bubble) was performed in urgent course. Twenty four hours after surgical intervention anterior chamber remained deep, IOP reduced to 12,2 mmHg, B-scan ultrasonography did not show any aqueous pockets in the vitreous. In the following 10 days, the IOP remained within normal limits with a well-formed anterior chamber. The final best-corrected visual acuity of the eye was 0.3. Early recognition of malignant glaucoma and proper treatment is the most important step to save the eye from severe consequences and prevent irreversible vision loss.


Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells.
Bispecific T-cell engagers (BiTEs) preferentially targeting tumour-associated antigens and stimulating CD3-mediated signalling are being used in patients to treat acute B-cell lymphoblastic leukemia. However, the potency of BiTEs in solid tumours is limited by their short half-life and their severe toxicity at relevant therapeutic doses. Here we report the design and in vivo performance of a bispecific antibody that simultaneously targets the murine T-cell co-receptor CD3ε and the murine immune checkpoint programmed-death ligand 1 (PD-L1). In multiple syngeneic tumour models, the bispecific antibody generated higher antitumour immune responses than conventional BiTEs targeting tumour-associated antigens and CD3ε. We found that the durable antigen-specific T-cell responses resulted from the rejuvenation of CD8 T cells, owing to the blockade of PD-L1 on dendritic cells (but not on tumour cells) and co-stimulation by B7-1&2 (a peripheral membrane protein on dendritic cells). Bispecific T-cell engagers targeting dendritic cells rather than tumour cells may represent a general means of T-cell rejuvenation for durable cancer immunotherapy.


Cat L4-S1 dermatomes determined using signal averaging.
In view of discrepancies in the earlier literature, a new procedure was devised which used (1) stimuli known to be subthreshold for deep receptor afferents and suprathreshold for hair afferents; (2) averaging techniques applied to dorsal root responses; (3) quantitative mapping of response magnitudes as a function of stimulus location. Dermatomes were obtained for cat L4-S1 dorsal roots which are somewhat larger than the majority of reported whole-root dermatomes, but which are larger than dermatomes approximated from single-unit recordings.


Sweating the assets of flavin cofactors: new insight of chemical versatility from knowledge of structure and mechanism.
Flavins are arguably one of the most versatile cofactors by virtue of the reactivity of the isoalloxazine ring system. A varied catalogue of reactions for the diverse family of flavoenzymes has been reported, leading to unifying concepts in (long-range) electron transfer, oxygen activation, photochemistry and substrate redox reactions. Recent examples of unprecedented flavin chemistry have been reported that uncover hidden depths of the flavoenzyme chemical repertoire. These include ring expansion of flavin through prenylation and formation of the superoxidized flavin-N5 oxide species. These and other new flavin based species are reviewed here and suggest further exciting discoveries await the flavoenzymology field.


Micromechanical properties of strain-sensitive lyriform organs of a wandering spider (Cupiennius salei).
Highly sensitive lyriform organs located on the legs of the wandering spider Cupiennius salei allow the spider to detect nanometer-scale strains in the exoskeleton resulting from locomotion or substrate vibrations. Morphological features of the lyriform organs result in their specialization and selective sensitivity to specific mechanical stimuli, which make them interesting for bioinspired strain sensors. Here we utilize atomic force microscopy (AFM)-based force spectroscopy to probe nano-scale mechanical properties of the covering membrane of two lyriform organs found on Cupiennius salei: the vibration sensitive metatarsal lyriform organ (HS10) and the proprioreceptive tibial lyriform organ (HS8). Force distance curves (FDCs) obtained from AFM measurements displayed characteristic multi-layer structure behavior, with calculated elastic moduli ranging from 150MPa to 500MPa for different regions and indentation depths. In addition, we probed the lyriform organs with a large radius tip, which allowed for probing structural deformation by the application of high forces and large scale deformations without damaging the surface. The viscoelastic behavior of the sensor materials observed in this probing suggests mechanical relaxation times potentially playing a role in the time-dependent behavior of the lyriform organs. Highly sensitive lyriform organs located on the legs of the wandering spider Cupiennius salei allow the spider to detect nanometer-scale strains in the exoskeleton resulting from locomotion or substrate vibrations. Morphological features of the lyriform organs result in their specialization and selective sensitivity to specific mechanical stimuli, which make them an interesting for bioinspired strain sensors. Here we utilize atomic force microscopy (AFM)-based force spectroscopy to probe nano-scale mechanical properties of the covering membrane of two lyriform organs found on Cupiennius salei: the vibration sensitive metatarsal lyriform organ (HS10) and the proprioreceptive tibial lyriform organ (HS8). Force distance curves (FDCs) obtained from AFM measurements displayed characteristic multi-layer structure behavior, with calculated elastic moduli ranging from 150MPa to 500MPa for different regions and indentation depths. The viscoelastic behavior of the sensor materials observed in this probing suggests mechanical relaxation times playing a role in the time-dependent behavior of the lyriform organs.


Reframing the banning of flavored tobacco in unprecedented times- an example from California's Senate bill 793.
Several cities, but only two U.S states, have passed a law banning the sales of flavored tobacco products. It has been suggested that framing tobacco control policy solely in terms of the youth could send the erroneous message that tobacco use is an acceptable behavior for adults. This study was intended to compare the framing of policy between California's Senate Bill (SB) 38 and 793. Seven audio files of hearings on SB-38 (N = 2) and SB-793 (N = 5), held between March 2019 and August 2020, were transcribed and coded for youth issues and the unprecedented events of 2020 that shaped society's views of health and racial/social justice. The Framework Method was used for organizing and analyzing content of the legislative hearings. Many of the same arguments pertaining to youth were presented in hearings on the two bills. The one notable difference was legislators' sense of obligation to younger constituents, which was expressed in hearings on SB-793, but not SB-38. The hearings on SB-793 also differed with respect to greater discussion about the relevance of a tobacco flavor ban to society as a whole. These discussions revolved around the COVID-19 pandemic and potential impact of a ban on communities of color. Discussions on SB-793 about the larger societal impact of flavored tobacco may be a more effective strategy than focusing exclusively on the youth. Thus, legislators from other U.S. states who are contemplating a statewide ban should consider reframing the issue according to California's SB-793.


Immunization with a plasmid DNA expressing rinderpest virus hemagglutinin protein protects rabbits from lethal challenge.
Rinderpest virus haemagglutinin (H) protein was expressed in eukaryotic cells and the plasmid encoding H gene was used for immunization of rabbits. The immunized rabbits were completely protected from lethal challenge with virulent lapinized rinderpest virus. Similar results were also observed in rabbits vaccinated with tissue culture rinderpest (TCRP) vaccine. About 80% of control rabbits vaccinated with empty vector (mock-vaccinated) died after challenge. The thermal reactions and clinical symptoms were less intense in H-DNA vaccinated rabbits as compared to the other two groups. Marked lymphopenia was observed in TCRP and mock-vaccinated rabbits after challenge, however, the H-DNA vaccinated rabbits showed lymphocytosis following challenge. The appearance of lymphocytosis in H-DNA vaccinated rabbits is an interesting finding which needs further investigation.


Near-infrared spectroscopy for arthroscopic evaluation of cartilage lesions: results of a blinded, prospective, interobserver study.
Mechanical tests to grade cartilage damage are limited by the instruments used and by the ability to access all areas of cartilage within a joint. Better methods to diagnose cartilage injury or degeneration are needed. Purpose/ To detect the interobserver variance of arthroscopic cartilage grading by subjective judgment using the International Cartilage Repair Society (ICRS) score and by objective measurement using near-infrared (NIR) spectroscopy. We hypothesized that objective measurement of cartilage lesions by NIR spectroscopy will yield more valid results than routine grading using the ICRS score. Cohort study (diagnosis); Level of evidence, 2. Fifteen patients undergoing arthroscopic knee operations were evaluated by 4 experienced arthroscopists independently. The cartilage lesions within the medial knee compartment were estimated by each observer using the ICRS grade and by measurements with a special arthroscopic NIR spectroscopy probe. The ICRS grading had a poor interobserver agreement, with a mean Fleiss kappa index of κ = 0.173. Only in 10% (6 of 60) of judged cartilage areas did all 4 surgeons grade the cartilage areas with the same result. In 17 areas (28.3%), the surgeons had a variance of 2 or more grades. In the remaining cases, the surgeons varied within 1 grade. The objective NIR spectroscopy-obtained measurements of cartilage resulted in a significant correlation within the observers of R = 0.885 ± 0.036 (P < .001). Our results of interobserver evaluation in real-time arthroscopic cartilage grading suggest that this subjective grading is not satisfactory. This study emphasizes the need for objective measurement techniques for arthroscopic cartilage grading. Near-infrared spectroscopy has a good interobserver correlation. Thus, this method could be developed in the future as a precise method of measuring cartilage lesions.


Fertile transgenic Brachiaria ruziziensis (ruzigrass) plants by particle bombardment of tetraploidized callus.
We have produced transgenic plants of the tropical forage crop Brachiaria ruziziensis (ruzigrass) by particle bombardment-mediated transformation of multiple-shoot clumps and embryogenic calli. Cultures of multiple-shoot clumps and embryogenic calli were induced on solidified MS medium supplemented with 0.5mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 2mg/L 6-benzylaminopurine (BAP) or 4mg/L 2,4-D and 0.2mg/L BAP, respectively. Both cultures were bombarded with a vector containing an herbicide resistance gene (bar) as a selectable marker and the β-glucuronidase (GUS) reporter gene. Sixteen hours after bombardment, embryogenic calli showed a significantly higher number of transient GUS expression spots per plate and callus than multiple-shoot clumps, suggesting that embryogenic callus is the more suitable target tissue. Following bombardment and selection with 10mg/L bialaphos, herbicide-resistant embryogenic calli regenerated shoots and roots in vitro, and mature transgenic plants have been raised in the greenhouse. Polymerase chain reaction (PCR) and DNA gel blot analysis verified that the GUS gene was integrated into the genome of the two regenerated lines. In SacI digests, the two transgenic lines showed two or five copies of GUS gene fragments, respectively, and integration at different sites. Histochemical analysis revealed stable expression in roots, shoots and inflorescences. Transgenic plants derived from diploid target callus turned out to be sterile, while transgenics from colchicine-tetraploidized callus were fertile.


Serum triglycerides in the prediction of coronary artery disease (an Italian experience).
An occupational group living in Rome and composed of 3,007 men aged 46 to 65 years who were free from previous major coronary events was screened for a number of coronary risk factors and then followed up for 10 years. In all, 107 coronary deaths occurred in 10 years. There was a positive relation between coronary death rate and increasing levels of triglycerides, but the difference between the extreme quintile classes was not any more significant after adjustment for cholesterol levels. A cross-classification involving low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels showed a higher coronary artery disease (CAD) mortality in subjects with a higher LDL cholesterol/HDL cholesterol ratio and higher triglycerides. However, the excess risk in this subgroup was largely explained by the mean levels of total cholesterol. The multivariate proportional-hazards Cox model with coronary deaths as the end point, and age and triglycerides as predictors, produced a significant coefficient for triglycerides that became nonsignificant when other lipids alone or in combination (total, HDL and LDL cholesterol and some of their ratio) were fed into the model as further covariates. It is concluded that there is no evidence of an independent role of triglycerides in the prediction of coronary deaths.


Risk factors of diabetes in North Indians with metabolic syndrome.
Metabolic syndrome progresses to diabetes and determinants of this progression like hyperinsulinemia, hypertriglyceridemia and genetic factors have been speculative. The present study was aimed at quantifying the insulin resistance and influence of family history of diabetes in subjects with metabolic syndrome developing prediabetes and diabetes. Consecutive subjects attending the endocrine clinic were evaluated for metabolic syndrome as per definition of International Diabetes Federation, 2005. The family history of diabetes in their first degree relatives was ascertained and Homeostasis model assessment of Insulin resistance (HOMA-IR), Homeostasis model assessment for beta cell function (HOMA-B) and Quantitative insulin sensitivity check index (QUICKI) were calculated in 163 subjects enrolled. HOMA-IR was higher (p<0.05) but HOMA-B and QUICKI were lower (p<0.0001) in subjects with metabolic syndrome+prediabetes or diabetes compared to metabolic syndrome with normal glucose tolerance. HOMA-B was lower and prevalence of prediabetes and diabetes was higher in metabolic syndrome subjects with family history of diabetes than in those without such family history (p<0.05). subjects with metabolic syndrome having prediabetes and diabetes had more severe insulin resistance than those with metabolic syndrome only. Beta cell dysfunction was remarkable and prevalence of prediabetes was high in metabolic syndrome subjects with family history of diabetes. Both the severity of the insulin resistance and family history of diabetes are therefore proposed to be determinants of diminished Beta cell function leading to diabetes in metabolic syndrome.


Freeze fracture aspects of the spiral limbus.
Replicas of the freeze fractured spiral limbus are studied in chinchillas. Zonulae occludentes are demonstrated between the interdental cells and the inner sulcus cells; gap junctions are described connecting interdental cells and inner sulcus cells to one another and they are found between the perilymphatic cells in the spiral limbus.


Improved survival of poor prognosis diffuse histiocytic (large cell) lymphoma managed with sequential induction chemotherapy, "boost" radiation therapy, and autologous bone marrow transplantation.
From 1981 to 1985, 33 patients with the diagnosis of diffuse histiocytic (large cell) lymphoma (DHL) with a poor prognosis received induction multi-drug chemotherapy followed by autologous marrow cryopreservation. Thirty patients who had residual disease after chemotherapy were given "boost" irradiation to these sites, followed immediately by hyperfractionated total body irradiation, 1320 to 1375 cGy in 11 fractions over 4 days, then cyclophosphamide (60 mg/kg/d) for 2 days. All patients received an autologous bone marrow transplant (ABMT), with 15 patients receiving marrow purged with 4-hydroperoxycyclophosphamide. Patients were transplanted either as part of a planned induction-transplant approach (Group I), or as salvage after relapse on the same induction regimen (Group II), or other conventional chemotherapy regimens (Group III). In the entire group, 16 of 33 patients (48%) are alive free of lymphoma with a median follow-up of 32 months (11 to 53 mo). Actuarial (Kaplan-Meier) survival is 51% at 2 years and 46% at 3 years, with only 1 patient dying after 2 years out of 11 at risk. Eight patients (24%) succumbed to early treatment related complications. Nine patients (27%) died from relapse. Patients receiving ABMT as planned sequential therapy post-induction (Group I) did significantly better than patients given ABMT as salvage therapy after relapse on prior chemotherapy (Groups II and III) and better than the historical group of patients treated with chemotherapy alone. At 2 years, the survival in Group I is 79% versus 0% for Group II versus 48% for Group III. Historically, this group of high risk patients had a 2-year disease-free survival of 20% or less with chemotherapy alone.


Dietary aflatoxin B1 intake, genetic polymorphisms of CYP1A2, CYP2E1, EPHX1, GSTM1, and GSTT1, and gastric cancer risk in Korean.
We investigated the effects of aflatoxin B1 (AFB1) intake, genetic polymorphisms of AFB1 metabolic enzymes, and interactions between the polymorphisms and intake of AFB1 with regard to the risk of gastric cancer in Korean. The participants in the study included 477 gastric cancer patients and 477 age- and sex-matched control subjects. Direct interviews and a structured questionnaire were used to determine the level of exposure to AFB1, and the GoldenGate assay and multiplex polymerase chain reaction were used for genotypic analyses of the cytochrome P450 1A2 (CYP1A2), cytochrome P450 1E1, epoxide hydrolase 1, and glutathione S-transferase genes. The probable daily intake of AFB1 was significantly higher among gastric cancer patients than among control subjects (cases vs. controls: 1.91 ± 0.87 vs. 1.65 ± 0.72 ng/kg bw/day, p < 0.0001), and increased AFB1 intake was significantly associated with an elevated risk of gastric cancer (odds ratio 1.94; 95 % confidence interval 1.43-2.63). However, genetic polymorphisms of AFB1 metabolic enzymes were not associated with gastric cancer, with the exception of CYP1A2. Moreover, there was no interaction between AFB1 intake and the genotypes of metabolic enzymes that affect gastric cancer risk. Our results suggest that dietary AFB1 exposure might be associated with a risk of gastric cancer. However, the effect of AFB1 on gastric carcinogenesis may not be modulated by genetic polymorphisms of AFB1 metabolic enzymes.


Optically pumped spin polarization as a probe of many-body thermalization.
Disorder and many body interactions are known to impact transport and thermalization in competing ways, with the dominance of one or the other giving rise to fundamentally different dynamical phases. Here we investigate the spin diffusion dynamics of 13C in diamond, which we dynamically polarize at room temperature via optical spin pumping of engineered color centers. We focus on low-abundance, strongly hyperfine-coupled nuclei, whose role in the polarization transport we expose through the integrated impact of variable radio-frequency excitation on the observable bulk 13C magnetic resonance signal. Unexpectedly, we find good thermal contact throughout the nuclear spin bath, virtually independent of the hyperfine coupling strength, which we attribute to effective carbon-carbon interactions mediated by the electronic spin ensemble. In particular, observations across the full range of hyperfine couplings indicate the nuclear spin diffusion constant takes values up to two orders of magnitude greater than that expected from homo-nuclear spin couplings.


Rapid radiological progression in the first year of early rheumatoid arthritis is predictive of disability and joint damage progression during 8 years of follow-up.
Several prediction models for rapid radiological progression (RRP) in the first year of rheumatoid arthritis have been designed to aid rheumatologists in their choice of initial treatment. The association was assessed between RRP and disability and joint damage progression in 8 years. Patients from the BeSt cohort were used. RRP was defined as an increase of ≥5 points in the Sharp/van der Heijde score (SHS) in year 1. Functional ability over 8 years, measured with the health assessment questionnaire (HAQ), was compared for patients with and without RRP using linear mixed models. Joint damage progression from years 1 to 8 was compared using logistic regression analyses. RRP was observed in 102/465 patients. Over 8 years, patients with RRP had worse functional ability: difference in HAQ score 0.21 (0.14 after adjustment for disease activity score (over time)). RRP was associated with joint damage progression ≥25 points in SHS in years 1-8: OR 4.6. RRP in year 1 is a predictor of worse functional ability over 8 years, independent of baseline joint damage and disease activity. Patients with RRP have more joint damage progression in subsequent years. RRP is thus a relevant outcome on which to base the initial treatment decision.


Physical activity across adulthood and physical performance in midlife: findings from a British birth cohort.
Evidence, mainly from cross-sectional studies, suggests that physical activity is a potentially important modifiable factor associated with physical performance and strength in older age. It is unclear whether the benefits of physical activity accumulate across life or whether there are sensitive periods when physical activity is more influential. To examine the associations of leisure-time physical activity across adulthood with physical performance and strength in midlife, and to test whether there are cumulative benefits of physical activity. Using data on approximately 2400 men and women from the UK Medical Research Council National Survey of Health and Development, followed up since birth in March 1946, the associations of physical activity levels during leisure time self-reported prospectively at ages 36, 43, and 53 years with grip strength, standing balance, and chair rise times, assessed by nurses at age 53 years (in 1999), were examined in 2010. There were independent positive effects of physical activity at all three ages on chair rise performance, and at ages 43 and 53 years on standing balance performance, even after adjusting for covariates. These results were supported by evidence of cumulative effects found when using structured life course models. Physical activity and grip strength were not associated in women and, in men, only physical activity at age 53 years was associated with grip strength. There are cumulative benefits of physical activity across adulthood on physical performance in midlife. Increased activity should be promoted early in adulthood to ensure the maintenance of physical performance in later life.


Applications of genomic research in pediatric endocrine diseases.
Recent advances in molecular genetics have advanced our understanding of the molecular mechanisms involved in pediatric endocrine disorders and now play a major role in mainstream medical practice. The spectrum of endocrine genetic disorders has 2 extremes: Mendelian and polygenic. Mendelian or monogenic diseases are caused by rare variants of a single gene, each of which exerts a strong effect on disease risk. Polygenic diseases or common traits are caused by the combined effects of multiple genetic variants in conjunction with environmental and lifestyle factors. Testing for a single gene is preferable if the disease is phenotypically and/or geneically homogeneous. Next-generation sequencing (NGS) can be applied to phenotypically and genetically heterogeneous conditions. Genome-wide association studies (GWASs) have examined genetic variants across the entire genome in a large number of individuals who have been matched for population ancestry and assessed for a disease or trait of interest. Common endocrine diseases or traits, such as type 2 diabetes mellitus, obesity, height, and pubertal timing, result from the combined effects of multiple variants in various genes that are frequently found in the general population, each of which contributes a small individual effect. Isolated founder mutations can result from a true founder effect or an extreme reduction in population size. Studies of founder mutations offer powerful advantages for efficiently localizing the genes that underlie Mendelian disorders. The Korean population has settled in the Korean peninsula for thousands of years, and several recurrent mutations have been identified as founder mutations. The application of molecular technology has increased our understanding of endocrine diseases, which have impacted on the practice of pediatric endocrinology related to diagnosis and genetic counseling. This review focuses on the application of genomic research to pediatric endocrine diseases using GWASs and NGS technology for diagnosis and treatment.


Clinical outcome, proteome kinetics and angiogenic factors in serum after thermoablation of colorectal liver metastases.
Thermoablation is used to treat patients with unresectable colorectal liver metastases (CRLM). We analyze clinical outcome, proteome kinetics and angiogenic markers in patients treated by cryosurgical ablation (CSA) or radiofrequency ablation (RFA). 205 patients underwent CSA (n = 20), RFA (n = 22), partial hepatectomy (PH, n = 134) or were found truly unresectable (n = 29). Clinical outcome, proteome transitions and angiogenic response in serum were analyzed at various time points after ablation. Median overall survival in CSA patients (17.6 months) was worse (p < 0.0001) when compared to RFA treated patients (51.7 months) and patients after PH (43.4 months). The complication rate was higher in the CSA group (50%) as compared to the RFA group (22%). Proteomics analyses showed consistently more changes in serum protein abundance with CSA compared to RFA. In the first four days after ablation a pro-angiogenic serum response occurred. RFA of CRLM is superior to CSA with a median survival which equals survival in patients after PH. Proteomics analyses suggests a more aggravated serum response to CSA compared to RFA. Thermoablation is associated with changes in serum levels of angiogenic factors favouring a pro-angiogenic environment, but without differences between RFA and CSA.


[Ulcerative colitis].
Ulcerative colitis in children has been seldom described in Chile. The cases of a 14 year old girl and a 10 year old boy with this disease are presented. Both had diarrhea for more than two months--which was continuous in the first case and intermittent in the other one--, bloody stools, weight loss, anemia and abdominal pain. Bacteriological and parasitological examination of stools were negative. Diagnosis of ulcerative colitis was based on barium enema, which showed mucosal ulceration and loss of the normal claustral pattern, rectosigmoidoscopy, that revealed hyperemia, friability and erosions of the corresponding segments of intestinal mucosa, and on histological examination of multiple mucosal biopsies, which disclosed crypt abscess, distorted crypt pattern, inflammation of the lamina propria and decreased number of goblet cells. Both cases were treated with salazosulfapyridine with satisfactory response.


Treatment optimization in MS: Canadian MS Working Group updated recommendations.
The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical recommendations in 2004 to assist clinicians in optimizing the use of disease-modifying therapies (DMT) in patients with relapsing multiple sclerosis. The CMSWG convened to review how disease activity is assessed, propose a more current approach for assessing suboptimal response, and to suggest a scheme for switching or escalating treatment. Practical criteria for relapses, Expanded Disability Status Scale (EDSS) progression and MRI were developed to classify the clinical level of concern as Low, Medium and High. The group concluded that a change in treatment may be considered in any RRMS patient if there is a high level of concern in any one domain (relapses, progression or MRI), a medium level of concern in any two domains, or a low level of concern in all three domains. These recommendations for assessing treatment response should assist clinicians in making more rational choices in their management of relapsing MS patients.


Common carotid segmentation in 18 F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based and manual method.
Carotid atherosclerosis is a major cause of stroke, traditionally diagnosed late. Positron emission tomography/computed tomography (PET/CT) with 18 F-sodium fluoride (NaF) detects arterial wall micro-calcification long before macro-calcification becomes detectable by ultrasound, CT or magnetic resonance imaging. However, manual PET/CT processing is time-consuming and requires experience. We compared a convolutional neural network (CNN) approach with manual segmentation of the common carotids. Segmentation in NaF-PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients were compared for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, and SUVtotal). SUVmean was the average of SUVmeans within the VOI, SUVmax the highest SUV in all voxels in the VOI, and SUVtotal the SUVmean multiplied by the Vol of the VOI. Intra and Interobserver variability with manual segmentation was examined in 25 randomly selected scans. Bias for Vol, SUVmean, SUVmax, and SUVtotal were 1.33 ± 2.06, -0.01 ± 0.05, 0.09 ± 0.48, and 1.18 ± 1.99 in the left and 1.89 ± 1.5, -0.07 ± 0.12, 0.05 ± 0.47, and 1.61 ± 1.47, respectively, in the right common carotid artery. Manual segmentation lasted typically 20 min versus 1 min with the CNN-based approach. Mean Vol deviation at repeat manual segmentation was 14% and 27% in left and right common carotids. CNN-based segmentation was much faster and provided SUVmean values virtually identical to manually obtained ones, suggesting CNN-based analysis as a promising substitute of slow and cumbersome manual processing.


Preloading magnesium attenuates cisplatin-associated nephrotoxicity: pilot randomized controlled trial (PRAGMATIC study).
Cisplatin is one of the most potent chemotherapeutic drugs used in head and neck cancer treatment; however, nephrotoxicity is the major side-effect limiting usage. Magnesium supplementation has been reported to reduce risk in non-controlled studies. We investigated whether preloading with magnesium prevents nephrotoxicity with a low-dose weekly cisplatin regimen. We carried out a prospective pilot, single-blinded, randomized controlled trial to compare cisplatin-associated acute kidney injury (cis-AKI) and acute kidney disease (cis-AKD) between two groups: intravenous 0.9% NaCl 500 ml + KCL 20 mEq over 4 h pre-cisplatin 40 mg/m2 weekly for 7-8 weeks (control group) compared with additional 16 mEq magnesium added to the saline infusion (Mg group) in 30 head and neck cancer patients. Cis-AKI was defined as an increased serum creatinine (SCr) ≥ 0.3 mg/dl within 7 days and cis-AKD is an increased SCr ≥ 0.3 mg/dl between last SCr and baseline pre-chemotherapy SCr. The overall cisplatin tumor response rate and survival were comparable between groups. The baseline characteristics were comparable between groups, although SCr was lower in the controls (0.70 ± 0.17 versus 0.87 ± 0.17 mg/dl, P = 0.01). The incidence of cis-AKI was similar (4.6% versus 1.3%); however, the incidence of cis-AKD was higher for the control group (46.7% versus 6.7%, hazard ratio = 0.082, 95% confidence interval 0.008-0.79, P = 0.03). The time to develop cis-AKD was significantly shorter in the control group (P = 0.007). The magnesium-preloading regimen was safe and significantly showed a decreased incidence of cis-AKD. The encouraging results of our pilot study need to be confirmed in a large-scale randomized controlled trial.


Transfer factor.
It has been more than 30 years since Dr. H. S. Lawrence first reported that it was possible to transfer delayed-type hypersensitivity from sensitized donors to unsensitized recipients with lysates of blood leukocytes. During recent years, research from several laboratories has demonstrated that this effect is immunologically specific. Although the molecules that possess this activity have not been completely characterized, there is a significant body of evidence that they are small polypeptides and that they can interact with antigen molecules in an immunologically specific manner. Studies with immune responses that are under genetic control have demonstrated that the ability of an animal to produce transfer factor is genetically regulated but that transfer of delayed hypersensitivity with transfer factor is not genetically restricted. In fact, when mice of low-responder phenotypes are administered transfer factor from high-responder donors, they express delayed hypersensitivity responses that are comparable to the high responders. Clinical studies have demonstrated that transfer factor is an efficacious method for immunotherapy of certain viral and fungal infections.


Skeletal muscle reoxygenation after high-intensity exercise in mitochondrial myopathy.
This study addressed whether O(2) delivery during recovery from high-intensity, supra-gas exchange threshold exercise would be matched to O(2) utilization at the microvascular level in patients with mitochondrial myopathy (MM). Off-exercise kinetics of (1) pulmonary O(2) uptake VO(2P) (2) an index of fractional O(2) extraction by near-infrared spectroscopy (Δ[deoxy-Hb + Mb]) in the vastus lateralis and (3) cardiac output (Q'(T)) by impedance cardiography were assessed in 12 patients with biopsy-proven MM (chronic progressive external ophthalmoplegia) and 12 age- and gender-matched controls. Kinetics of VO(2P) were significantly slower in patients than controls (τ = 53.8 ± 16.5 vs. 38.8 ± 7.6 s, respectively; p < 0.05). Q'(T), however, declined at similar rates (τ = 64.7 ± 18.8 vs. 73.0 ± 21.6 s; p > 0.05) being typically slower than [Formula: see text] in both groups. Importantly, Δ[deoxy-Hb + Mb] dynamics (MRT) were equal to, or faster than, τVO(2P) in patients and controls, respectively. In fact, there were no between-group differences in τVO(2P)MRTΔ[deoxy-Hb + Mb] (1.1 ± 0.4 vs. 1.0 ± 0.2, p > 0.05) thereby indicating similar rates of microvascular O(2) delivery. These data indicate that the slower rate of recovery of muscle metabolism after high-intensity exercise is not related to impaired microvascular O(2) delivery in patients with MM. This phenomenon, therefore, seems to reflect the intra-myocyte abnormalities that characterize this patient population.


Quantitation and immunohistochemistry of catecholamines in the posterior segment of the eye.
Dopamine, noradrenaline, and adrenaline were assayed with HPLC in the light adapted retinae of carp, frog, chicken, pigeon, rat, guinea-pig, rabbit, cat, pig and cow. Dopamine varied from 0.6 to 2.6 nmol/g wet weight and was not influenced by sympathectomy. The dopamine figures agree with previously published results. Noradrenaline concentrations varied from not detectable to 0.06 nmol/g wet weight in different species. Homolateral sympathectomy significantly decreased the noradrenaline figure in rabbits. There are no previous figures for noradrenaline for most of the species. Adrenaline was not detected in any species. Immunohistochemical analysis showed noradrenaline to be present in choroidal nerves, but noradrenaline immuno-reactivity was not seen in the retina (chicken, rat, guinea-pig, rabbit, cat, cow). It is concluded that dopamine is the major catecholamine in the retina. Noradrenaline was found present only in minute amounts in the assays, and much of its was likely to stem from sympathetic nerve fibres. The study did not demonstrate any noradrenergic neurons in the retina.


Intraoperative iatrogenic peripheral retinal break in 23-gauge transconjunctival sutureless vitrectomy versus 20-gauge conventional vitrectomy.
To compare the incidence of intraoperative iatrogenic peripheral retinal breaks (IPRBs) during 23-gauge transconjunctival sutureless vitrectomy (TSV) and conventional 20-gauge vitrectomy for various indications. This was a single-center, comparative, retrospective, interventional case series of 973 23-gauge TSVs and 402 conventional 20-gauge vitrectomies done by two surgeons between January 2004 and December 2009. The incidence rate of intraoperative IPRBs and risk factors were analyzed in association with various clinical and surgical factors. IPRBs occurred significantly less often during 23-gauge TSV (16 of 973 cases, 1.6 %) than during conventional vitrectomy (25 of 402 cases, 6.2 %, P<0.001). Univariate analysis revealed that conventional vitrectomy and operation time were risk factors for the complication. Multivariate logistic regression analysis also revealed that conventional vitrectomy (P=0.03, OR=2.91), operation time (P<0.01, OR=1.01), and intraoperative induction of posterior vitreous detachment (PVD, P=0.04, OR=1.97) were risk factors for IPRBs. The 23-gauge TSV procedure with the trocar system has a lower incidence of intraoperative IPRBs than conventional 20-gauge vitrectomy. Longer operation time and induction of PVD are also independent risk factors of the complication.


Picturing Prevalence and Inequalities in Cancer Screening Attendance to Population-Based Programs in Portugal.
Screening is effective in reducing cancer-related morbidity and mortality. The aim of this study was to analyze the level of, and income-related inequalities in, screening attendance, in Portugal for population-based screening programs. Data from the Portuguese Health Interview Survey 2019 was used. Variables included in the analysis were self-reported: mammography, pap smear test, fecal occult blood test. Prevalence and concentration indices were computed at national/regional level. We analyzed: up-to-date screening (within recommended age/interval), under-screening (never or overdue screening), and over-screening (due to frequency higher than recommended or screening outside target group). Up-to-date screening rates were 81.1%, 72%, and 40%, for breast, cervical and colorectal cancer, respectively. Never-screening was 3.4%, 15.7%, and 39.9%, for breast, cervical, and colorectal cancer, respectively. Over-screening related with frequency was highest for cervical cancer; in breast cancer, over-screening was observed outside recommended age, affecting one third of younger women and one fourth of older women. In these cancers, over-screening was concentrated among women with higher income. Never-screening was concentrated among individuals with lower income for cervical cancer and higher income for colorectal cancer. Beyond the recommended age, 50% of individuals never underwent screening for colorectal cancer and 41% of women never underwent screening for cervical cancer. Overall, screening attendance was high, and inequalities were low in the case of breast cancer screening. The priority for colorectal cancer should be to increase screening attendance.


Differences in Weight Loss and Gut Hormones: Rouen-Y Gastric Bypass and Sleeve Gastrectomy Surgery.
Bariatric surgery is arguably the most effective therapy for weight loss, and Rouen-Y gastric bypass (RYGB) is considered the "gold-standard" procedure. However, sleeve gastrectomy (SG) surgery has become more prevalent in recent years and it is unclear if weight loss differences occur between these procedures. Herein, we discuss evidence from randomized clinical trials comparing the effectiveness of RYGB and SG on weight loss. Moreover, we highlight gut hormones (e.g., GLP-1, ghrelin, bile acids, etc.) as potentially important mechanisms that contribute to the durability of decreased appetite and opposed fat storage following RYGB and SG. Collectively, although a subtle (∼ 3-5 kg) weight loss difference may exist in favor of RYGB up to 3 years post-operation, it appears that RYGB and SG induce comparable weight loss and changes in gut physiology that parallel reduced disease risk. These findings are clinically relevant for optimizing treatment strategies that combat obesity-related diabetes and cardiovascular disease.


Multi-male mating, probability of conception, and litter size in the prairie vole (Microtus ochrogaster).
We conducted a mating experiment in the laboratory using prairie voles, Microtus ochrogaster, to document that multi-male mating (MMM) can occur in this supposedly monogamous species and to test two hypotheses for the advantages of MMM in female mammals. The two hypotheses are that MMM (1) increases the probability of pregnancy and (2) increases litter size. We also tested the hypothesis that multiple copulations, rather than multiple partners, increases litter size and/or probability of pregnancy. Females were given a choice of mating with any of three males, each of which was tethered in a separate compartment. The mate choice bouts were recorded on videotape. We recorded the number of copulations and number of males with which females mated over a 24 h period. Litter size and probability of pregnancy were not significantly different for females that mated with one, two or three males. Increasing numbers of copulations, independent from the number of males, also did not increase litter size but did significantly increase the probability of pregnancy. MMM, at least in prairie voles, must serve some function other than increasing litter size and probability of conception.


Children with unilateral hearing loss may have lower intelligence quotient scores: A meta-analysis.
In this meta-analysis, we reviewed observational studies investigating differences in intelligence quotient (IQ) scores of children with unilateral hearing loss compared to children with normal hearing. PubMed Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO. A query identified all English-language studies related to pediatric unilateral hearing loss published between January 1980 and December 2014. Titles, abstracts, and articles were reviewed to identify observational studies reporting IQ scores. There were 261 unique titles, with 29 articles undergoing full review. Four articles were identified, which included 173 children with unilateral hearing loss and 202 children with normal hearing. Ages ranged from 6 to 18 years. Three studies were conducted in the United States and one in Mexico. All were of high quality. All studies reported full-scale IQ results; three reported verbal IQ results; and two reported performance IQ results. Children with unilateral hearing loss scored 6.3 points lower on full-scale IQ, 95% confidence interval (CI) [-9.1, -3.5], P value < 0.001; and 3.8 points lower on performance IQ, 95% CI [-7.3, -0.2], P value 0.04. When investigating verbal IQ, we detected substantial heterogeneity among studies; exclusion of the outlying study resulted in significant difference in verbal IQ of 4 points, 95% CI [-7.5, -0.4], P value 0.028. This meta-analysis suggests children with unilateral hearing loss have lower full-scale and performance IQ scores than children with normal hearing. There also may be disparity in verbal IQ scores. Laryngoscope, 126:746-754, 2016.


Traces of mercury in organs from primates with amalgam fillings.
In order to trace possible accumulations of mercury, three vervet monkeys received occlusal amalgam fillings, three others maxillary bone implants of amalgam, and three untreated monkeys served as controls. One year later all animals were sacrificed by transcardial perfusion with glutaraldehyde. Tissue sections from different organs were subjected to silver amplification by autometallography and analyzed at light and electron microscopical levels. It was found that amalgam fillings (total, 0.7-1.2 g) caused deposition of mercury in the following tissues: spinal ganglia, anterior pituitary, adrenal, medulla, liver, kidneys, lungs, and intestinal lymph glands. In monkeys with maxillary silver amalgam implants (total, 0.1-0.3 g), mercury was found in the same organs except for liver, lungs, and intestinal lymph glands. Organs from the three control animals were devoid of precipitate. To evaluate whether silver released from the corroding amalgam fillings added to the staining pattern, tissue sections were exposed to potassium cyanide prior to being autometallographically developed. This treatment removes all traces of silver, leaving mercury sulfide accumulation untouched. By comparing sections that had been exposed to cyanide with untreated parallels no difference was seen in the pattern confirming that mercury was the only catalyst present in the tissue. These results strongly support what has been suggested previously that dental fillings in primates cause absorption of mercury released from amalgam fillings through lungs and intestinal tract, and that depending on exposure mercury is distributed to most organs and will eventually be found in the central nervous system. The present data also show that silver released from the corroding filling is not absorbed.


Comparison of habitual and meal-specific dietary patterns identified by latent class analysis and confirmatory factor analysis in adults: A cross-sectional study.
The aim of this study was to compare characteristics of habitual and meal-specific dietary patterns identified by latent class analysis (LCA) and confirmatory factor analysis (CFA). Participants included 778 adults selected for the present cross-sectional study from local health care centers in Tehran, Iran. Three 24-h dietary recalls evaluated dietary intake. LCA was used to group study participants into exclusive subgroups of individuals with similar patterns of dietary intake. CFA was applied to identify patterns of habitual and meal-specific dietary intake. Analysis of variance was used to compare the average scores of habitual and meal-specific CFA-derived dietary patterns across classes identified by LCA. Using habitual dietary intake, CFA grouped correlated food items into three major factors: fruits and vegetables, mixed, and Western dietary patterns. LCA grouped study participants with similar patterns of habitual intake into four subgroups of individuals: fruits and vegetables, mixed, Western, and low consumer classes. LCA-fruits and vegetables, LCA-Western, and LCA-mixed classes had, respectively, higher mean scores of CFA-fruits and vegetables, CFA-Western, and CFA-mixed dietary patterns compared with other classes (P < 0.001). Similar findings were observed for meal-specific dietary intake, where classes identified by LCA had the highest mean scores of their corresponding dietary pattern identified by CFA. Habitual and meal-specific classes identified by LCA were well characterized by the dietary patterns derived by CFA, suggesting that LCA may be an appropriate statistical approach to classify study participants with similar patterns of intake into exclusive subgroups of individuals.