Primary cultures of dispersed cells of rat pineal gland. I. Fine structure and indole metabolism.
In vitro indole metabolism and ultrastructural morphology of the pineal gland of male rats were examined. A comparison of the effect of norepinephrine stimulation on indole synthesis in whole cultured glands and preparations of dispersed pineal cells is discussed. Our studies on the performance of dispersed cells during the first 24 h after preparation indicate a strong dependence of pineal cells upon physical attachment to the culture dish and probably also on cell-to-cell contact.


Mouthwash and oral cancer risk: an update.
The possible relationship between mouthwash use and oral cancer risk has been the subject of at least 10 case-control studies published over the last three decades. Three of these reported relative risks above unity and seven no consistent association. Only a few studies, moreover, included information on different types of mouthwash, and addressed the issue of alcohol-containing mouthwash. Thus, critical review of published data revealed that a link between mouthwash use, specifically alcohol-containing mouthwash, and oral cancers is not supported by epidemiological evidence.


Signalling through phospholipase C beta 4 is not essential for midbrain dopaminergic neuron survival.
The most prominent progressive neurodegenerative movement disorder, Parkinson's disease, is attributed to selective loss of dopamine neurons in the substantia nigra pars compacta, resulting in severe deficiency of dopamine. The homeo-domain gene, Pit x 3, is essential for proper development of midbrain dopaminergic neurons in the substantia nigra pars compacta and might be involved in midbrain dopaminergic survival pathways. The mGluR1-signaling downstream-effector phospholipase C beta 4 was identified in a suppression subtractive hybridization screen comparing wild-type and Pit x 3-deficient Aphakia midbrain dopaminergic neurons. Expression pattern analysis revealed that phospholipase C beta 4 was expressed in midbrain dopaminergic neurons of the substantia nigra pars compacta and part of the ventral tegmental area, whereas expression of mGluR1alpha was predominantly observed in the more vulnerable midbrain dopaminergic neurons in the lateral substantia nigra pars compacta. However, clear expression of phospholipase C beta 4 in spared midbrain dopaminergic neurons of Aphakia mice located in the ventral tegmental area, indicated that induction and maintenance of phospholipase C beta 4 expression is Pit x 3-independent in these neurons. Furthermore, we report here a normal distribution of midbrain dopaminergic cell bodies and axonal projection to the striatum in phospholipase C beta 4-/- mice, indicating that signaling of phospholipase C beta 4 is not essential for the survival of midbrain dopaminergic neurons.


Protein Expression of PI3K/AKT/mTOR Pathway Targets Validated by Gene Expression and its Correlation with Prognosis in Canine Mammary Cancer.
Mammary cancer is the main type of neoplasia in female dogs and is considered an adequate model for the biological and therapeutic study of cancer in women. The PIK3CA/AKT/mTOR pathway plays a central role in cellular homeostasis and is often dysregulated in cancer. The increased expression of PI3K protein in the literature is associated with a poor prognosis, and alterations in the PIK3CA gene can lead to changes in downstream pathways. Thus, the objective of this study was to validate the protein expression to confirm the gene expression of proteins belonging to the main pathway PI3K and PTEN, and their downstream pathways through ZEB1, ZEB2, HIF1A, VHL, CASP3 and PARP1 relating to prognosis in canine mammary cancer. For protein studies, the samples came from 58 female dogs with mammary neoplasia, immunohistochemistry was performed and its analysis by the histoscore method. For the genetic evaluation, the samples came from 13 patients, the DNA was extracted and the analysis for quantitative expression. Through immunohistochemistry, PI3K positivity was significantly associated with affected regional lymph node, distant metastasis, patients with HER2+, Triple Negative and Luminal B phenotypes, and the lowest survival rates. Through gene expression, we observed higher gene expression of ZEB2 and PARP1 both among patients who were alive and who died, which was not true for the expressions of PIK3CA and HIF1A. In conclusion, the data observed in this work are promising in the study of new molecular prognostic markers such as PI3K, ZEB2 and PARP1 for canine mammary cancer.


Local proteins associated with methamphetamine-induced nigrostriatal dopaminergic neurotoxicity.
The present study aimed to examine the proteins involved in the methamphetamine (MA)-induced nigrostriatal dopaminergic toxicity. Infusion of anisomycin into striatum and substantia nigra both abolished the MA-induced striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) depletions, indicating a critical role of local protein synthesis in determining such dopaminergic toxicity. Moreover, local protein synthesis blockade reversed this neurotoxicity via a temperature-independent mechanism. We then employed a proteomic approach, two-dimensional gel electrophoresis (2-DE) in conjunction with mass spectrometry analysis, to identify the protein candidates associated with the MA-induced neurotoxicity. In striatal samples, 2-DE analysis revealed that the intensities of nine protein spots were altered by MA treatment. Mass spectrometry analysis allowed us to identify five proteins, including an up-regulated protein, alpha-synuclein, and four down-regulated proteins, ATPase, F-actin capping protein beta subunit, ubiquitin carboxy-terminal hydrolase/PGP 9.5, and peroxidase. MA-altered expression levels of alpha-synuclein and ubiquitin carboxy-terminal hydrolase/PGP 9.5 in striata were confirmed by western blotting analysis. Taken together, these results suggest that local up-regulation of alpha-synuclein and down-regulation of ubiquitin carboxy-terminal hydrolase/PGP 9.5 could be linked to the MA-induced dopaminergic terminal toxicity.


Reproducibility of rest and exercise left ventricular ejection fraction and volumes in chronic aortic regurgitation.
To assess the variability of rest and exercise radionuclide ventriculography in patients with aortic regurgitation (AR), 22 patients in stable condition with chronic AR underwent radionuclide ventriculography at rest and during exercise for measurement of left ventricular volumes and ejection fraction (EF) on 2 occasions 3 months apart. For the group, there were no significant differences between the findings of the 2 studies except for a slightly lower exercise end-systolic volume on the second study. The inter-study differences and variabilities (expressed as the standard deviation of differences) for rest and exercise EF and change in EF were 0 +/- 0.04, +0.02 +/- 0.05 and +0.01 +/- 0.05, respectively. Thus, although mean differences were minor, considerable individual variability occurred, the magnitude of which was similar to that reported for other patient populations. In 3 patients who had an initial normal response to exercise (increase in EF greater than or equal to 0.05), the response became abnormal and in 2 who initially had an abnormal response, the response normalized. This variability must be considered in clinical decision-making or in research study design for patients with chronic AR.


A report on the 3rd Workshop on Heritable Disorders of Connective Tissue.
The 3rd Workshop on Heritable Disorders of Connective Tissue was held at the National Institutes of Health from 16th to 18th November, 2000. The Workshop was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Office of Rare Diseases, March of Dimes, Coalition for Heritable Disorders of Connective Tissue, and the Foundation for Basic Cutaneous Research. It was supported by specific grants R13 AR46912 (US Public Health Service) and 4-FY00-4511 (March of Dimes Birth Defects Foundation). The Workshop was divided into six sessions, featuring 29 invited presentations. In addition to the invited participants, more than eighty guests (scientists, NIH staff, and members of the Coalition for Heritable Disorders of Connective Tissue) attended.


Moderate aging does not modulate morphological responsiveness of the neuromuscular system to chronic overload in Fischer 344 rats.
The purpose of this investigation was to determine the effect of aging on neuromuscular adaptations to chronic overload. Eight young adult (8 months old) and eight aged (22 months old) Fischer 344 rats underwent unilateral synergist ablation to overload the plantaris and soleus muscles of that hindlimb and to provide control muscles from the contralateral hindlimb. Cytofluorescent staining and confocal microscopy were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs). Histochemical staining and light microscopy were used to assess adaptations of myofibers to chronic overload. Results demonstrate that NMJs of young adult and aged muscles did not undergo morphological remodeling as a result of 4 weeks of chronic overload. In contrast, myofibers of young and aged rats displayed significant (P<0.05), but similar hypertrophy ( approximately 18%) following that 4 week intervention. In both age groups, however, this hypertrophy was detected in the plantaris, but not the soleus. These data indicate that moderate aging (the equivalent of 65 years in human lifetime) does not modify the sensitivity of the neuromuscular system to chronic overload.


Strategies to advance vaccine technologies for resource-poor settings.
New vaccine platform and delivery technologies that can have significant positive impacts on the effectiveness, acceptability, and safety of immunizations in developing countries are increasingly available. Although donor support for vaccine technology development is strong, the uptake of proven technologies by the vaccine industry and demand for them by purchasers continues to lag. This article explains the challenges and opportunities associated with accelerating the availability of innovative and beneficial vaccine technologies to meet critical needs in resource-poor settings over the next decade. Progress will require increased dialog between the public and private sectors around vaccine product attributes; establishment of specifications for vaccines that mirror programmatic needs; stronger encouragement of vaccine developers to consider novel technologies early in the product development process; broader facilitation of research and access to technologies through the formation of centers of excellence; the basing of vaccine purchase decisions on immunization systems costs rather than price per dose alone; possible subsidization of early technology adoption costs for vaccine producers that take on the risks of new technologies of importance to the public sector; and the provision of data to purchasers, better enabling them to make informed decisions that take into account the value of specific product attributes.


Nervous system involvement by pancreatic cancer.
From 1,229 consecutive patients with pancreatic cancer, seven patients who developed nervous system metastasis were evaluated retrospectively. Nervous system metastasis frequently antedated the diagnosis of the primary cancer (five out of seven patients). Four patients had cerebral metastasis. Brain computed tomography or magnetic resonance imaging revealed single or multiple cyst-like lesions with ring enhancement in half of these patients. Three patients had spinal metastasis which caused myelopathy in two. The metastatic lesions were localized to the thoracic level. Radiation therapy directed to the metastatic sites could not change the clinical course.


Chromatographic characterization of synthetic peptides: SPf66 malaria vaccine.
The development and validation of a quantitative size-exclusion chromatography (SEC) method for SPf66 malaria vaccine was achieved. The results show the reliability of the analytical method for the intended use. SPf66 malaria vaccine characterization was perforrmed using both relative techniques such as the conventional SEC and absolute techniques: mass spectrometry and multi-angle laser-light scattering detection. The relative and absolute molecular masses were in the 4600-18,000 Da range. The results clearly indicate the presence of the monomer and dimer species, whereas the third species could be the trimer or tetramer.


Myasthenic crisis as an initial presentation of myasthenia gravis in an 81-year-old following endoscopic myotomy for Zenker's diverticulum.
In this article, we present the case of a patient with previously undiagnosed myasthenia gravis who underwent an endoscopic procedure for Zenker's diverticulum. The patient was readmitted due to ongoing dysphagia and severe respiratory distress caused by myasthenic crisis. This case demonstrates that myasthenia gravis, although rare, can occur in elderly patients and present with other sequelae that may mask the underlying diagnosis.


Merkel cell carcinoma of the upper extremity: case report and an update.
Merkel cell carcinoma is a rare but aggressive cutaneous primary small cell carcinoma. It is commonly seen in elderly affecting the head, neck, and extremities. Macroscopically may be difficult to distinguish MCC from other small cells neoplasms especially oat cell carcinoma of the lung. It is presented a case report concerning a 72 years old male with a MMC on the dorsal aspect of the right wrist. The patient underwent a diagnostic excisional biopsy and after the histological confirmation of the diagnosis a second excision was performed to achieve free margins. No postoperative radiation or adjuvant chemotherapy was given and within 9 years follow up no recurrence was reported. Although most cases present as localized disease treatment should be definitive due to high rates of local or systemic recurrence. Treatment includes excision of the lesion, lymphadenectomy, postoperative radiotherapy and chemotherapy depending on the stage of the disease. Even when locoregional control is achieved close surveillance is required due to high rates of relapse.


A new convenient methodology based on dihydropyridine derivative for selective fluorimetric analysis of baclofen: Application to spiked urine and content uniformity evaluation.
Baclofen belongs to skeletal muscle relaxant and is used for the treatment of muscle spasticity that originated from multiple sclerosis or a spinal cord injury and other cases as hiccups. In the current analytical study, a new, convenient and selective fluorimetric method for baclofen analysis has been developed and validated. The analytical methodology depends on Hantzsch reaction that leads to formation of dihydropyridine fluorescent derivative. The primary amino moiety in baclofen condensed with two equivalents of acetylacetone in the presence of formaldehyde and acetate buffer solutions. Spectrofluorimetric monitoring of the product was accomplished at emission wavelength of 477.3 nm after excitation at 419.9 nm. The method exhibited linearity when baclofen concentration plotted against the fourescence response in the range of 0.3-6.0 µg/mL. Adjustment of the reaction variables and studying validation parameters according to directives of ICH were performed perfectly. Ultimately, the proposed approach was applied successfully for baclofen analysis in raw material, dosage form and spiked urine and it was also extended to test content uniformity.


Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for inhalation conscious sedation in children having dental treatment: a randomised controlled trial.
We studied 411 children aged 3-10 years who were referred for dental treatment. They were randomly allocated to have inhalation conscious sedation with either sevoflurane/nitrous oxide mixture or nitrous oxide alone. Dental treatment was satisfactorily completed in 215/241 children who were given sevoflurane/nitrous oxide mixture (89%) compared with 89/170 who were given nitrous oxide alone (52%) (Chi square 70.3, p < 0.0001). All children remained conscious and responsive to verbal contact throughout the treatment and in the recovery room. No adverse side-effects were recorded in either group and there were no significant differences in oxygen saturation, heart rate, recovery profile, or time to discharge home between the groups. The study concluded that, for every 100 children treated with sevoflurane/nitrous oxide mixture, 37 children would be saved a general anaesthetic if given combined sevoflurane and nitrous oxide mixture rather than nitrous oxide alone. The use of sevoflurane in low concentrations 0.1-0.3% to supplement nitrous oxide and oxygen for inhalation conscious sedation is safe, practical, and significantly more effective than nitrous oxide alone in children having dental treatment.


Immunologic monitoring in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is characterized by progressive defects in humoral- and cell-mediated immunity. These defects are manifested as a propensity to develop infections with encapsulated bacteria, and less frequently, with gram-negative enterics. In addition, reactivation of viruses such as herpesvirus is not uncommon. Treatment of the disease further exacerbates immunosuppression by depleting immune effectors and broadening the spectrum of potentially offending pathogens. Risk of infection can potentially be reduced by administration of intravenous immunoglobulin and use of prophylactic antibiotics for individuals who are at high risk. Current work focuses on development of cellular and cytokine therapy to facilitate immune reconstitution in patients with CLL, thereby reducing morbidity and mortality and potentially improving survival.


The Modified Barium Swallow Database.
Every center that carries out the modified barium swallow (MBS) has a potential storehouse of useful clinical and radiological information filed away in the patient's files and in the center's video library. The modified barium swallow database automates the recording, storage, and analysis of this information. This project utilizes a standardized clinical and radiological data form which provides a consistent approach to the reporting of the MBS results. The information on the data form is entered into the MBS database software program for decoding and permanent storage. This database program, designed for the computer novice, is menu driven to simplify operation. Once the patient information is verified on the computer screen, the program can generate different types of reports for clinical and research purposes. The program has routines to search for patients with any clinical or radiological findings of interest. The ability to group and recall patients with specific findings has been an aid in teaching, peer review, and research. The program has been modified based upon feedback and experience at three centers in Toronto that have used it for 9 months.


Aligned nano-porous microwave exfoliated graphite oxide ionic actuators with high strain and elastic energy density.
A high-density aligned nanoporous activated microwave exfoliated graphite oxide (aMEGO) ionic actuator is studied. Before applying an external electric field, the cations and anions are randomly distributed in the composite. After applying the electric field, ions ingress in between the aligned aMEGO sheets through the nanopores to compensate the charges on the electrodes, resulting in the separation of neighboring sheets and unidirectional electro actuation.


Heterologous expression of a broad-spectrum chimeric antimicrobial peptide in Lactococcus lactis: Its safety and molecular modeling evaluation.
Over the last decade, global increase in antibiotic consumption is a major concern in the word. Antimicrobial peptides (AMPs) known as potential alternative and were considered as a safe antimicrobial agent. However, current approaches for production and purification of AMPs are costly and time-consuming. Here we show that heterologous expression of a chimeric peptide was successfully developed in Lactococcus lactis as a safe and cost-effective recombinant protein expression platform. Minimum inhibitory concentrations (MICs) of His-tag purified peptide was determined against a broad spectrum of human pathogenic bacteria consistence of Gram-positive, Gram-negative and resistance strains in deferent range from 7.24 ± 0.4 to 156.24 ± 3.0 μg/mL. Furthermore, our results showed that the peptide was not toxic to HEK and HeLa cells and even at concentrations as high as 250 μg/mL exhibited minimal hemolysis against RBCs. Additional characteristics such as thermal, protease and 50% human plasma stability were determined for cLFchimera. Molecular modeling analysis demonstrated that fusion of His-tag to the C-terminal of chimeric peptide increased peptide stability during 10 ns simulation in water. Overall, the chimeric peptide has a considerable antibacterial activity with low hemolysis, low or none in toxicity and good temperature resistance and also high stability in serum. We anticipate the established expression system could be developed and used more effectively in probiotic strains in future studies.


[Epidemiology, etiology and mechanism of atrial fibrillation].
Atrial fibrillation affects about 750 000 people in France, and its incidence is growing rapidly as the population ages. The main cause used to be rheumatic heart disease, but arterial hypertension is now responsible for about 80 % of cases. The mechanisms are complex. Many cases are due to pulmonary vein foci, but comorbidities can lead to different mechanisms.


Development of amphotericin B liposomes bearing antibody specific to Candida albicans.
Liposomes expressing external antibody specific for Candida albicans and encapsulating amphotericin B were developed and characterized in this study. Antibody was first modified by the covalent attachment of palmitic acid residues. Liposomes were produced by reverse-phase evaporation and modified antibody was incorporated into these liposomes via the hydrophobic interaction between the palmitic acid and the phospholipids composing the liposomes. The liposomes were characterized as to the amount of amphotericin B by spectroscopy and for the presence of antibody by protein analysis and secondary immunolabeling by fluorescent and electron microscopic methods. Immunogold labeling showed that the antibody was being expressed externally on the liposomes in the electron microscopic studies and the specificity of these liposomes for C. albicans was observed by secondary immunofluorescence.


Dependence of fluorescent protein brightness on protein concentration in solution and enhancement of it.
Fluorescent proteins have been widely used in biology because of their compatibility and varied applications in living specimens. Fluorescent proteins are often undesirably sensitive to intracellular conditions such as pH and ion concentration, generating considerable issues at times. However, harnessing these intrinsic sensitivities can help develop functional probes. In this study, we found that the fluorescence of yellow fluorescent protein (YFP) depends on the protein concentration in the solution and that this dependence can be enhanced by adding a glycine residue in to the YFP; we applied this finding to construct an intracellular protein-crowding sensor. A Förster resonance energy transfer (FRET) pair, involving a cyan fluorescent protein (CFP) insensitive to protein concentration and a glycine-inserted YFP, works as a genetically encoded probe to evaluate intracellular crowding. By measuring the fluorescence of the present FRET probe, we were able to detect dynamic changes in protein crowding in living cells.


Executive function orchestrates regulation of task-relevant gait fluctuations.
Humans apply a minimum intervention principle to regulate treadmill walking, rapidly correcting fluctuations in the task-relevant variable (step speed: SS) while ignoring fluctuations in the task-irrelevant variables (step time: ST; step length: SL). We examined whether the regulation of fluctuations in SS and not in ST and SL depends on high-level, executive function, processes. Young adults walked on a treadmill without a cognitive requirement and while performing the cognitive task of dichotic listening. SS fluctuations became less anti-persistent when performing dichotic listening, meaning that taxing executive function impaired the ability to rapidly correct speed deviations on subsequent steps. Conversely, performing dichotic listening had no effect on SL and ST persistent fluctuations. Findings suggest that high-level brain processes are involved only in regulating gait task-relevant variables.


Downregulation of ERp57 expression is associated with poor prognosis in early-stage cervical cancer.
We investigated the clinical significance of ERp57 in the progression of cervical cancer. mRNA and protein expression of ERp57 in cervical neoplasias were examined. ERp57 mRNA expression was significantly decreased in cervical cancers. Immunohistochemistry revealed that ERp57 expression in 123 cervical cancers was down-regulated compared to cervical intraepithelial neoplasias or normal tissues (p < 0.001). Low ERp57 expression was significantly associated with worse overall survival (HR = 12.19, p = 0.018). Low ERp57 expression independently predicts a poor outcome for patients with cervical cancer, supporting the notion that ERp57 may be a promising novel cancer target.


Overlapping status of frailty and fear of falling: an elevated risk of incident disability in community-dwelling older adults.
Although overlapping frailty and fear of falling (FoF) are likely to increase with population aging, the combined effect of frailty and FoF on incident disability is not yet well understood. The purpose of this study is to examine whether frailty combined with FoF increased the risk of incident disability in older adults. Our secondary purpose was to clarify the synergistic effect of frailty and FoF on incident disability. This is a prospective study. Participants were 9372 older adults (mean age 73.5 years). Frailty status was assessed using the Japanese Cardiovascular Health Study index, and FoF was measured using two closed questions. Incident disability was prospectively monitored by their long-term care insurance records. During the follow-up period (mean duration 23.4 months), 487 (5.2%) participants developed disability. The proportion of incident disability linearly increased according to FoF level regardless of baseline frailty status. Frail participants with FoF had a higher risk of incident disability than those with frailty only or neither (adjusted hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.95-3.54). Frailty in combination with excessive FoF further increased the risk of incident disability (adjusted HR 4.30, 95% CI 2.56-7.23) although no synergistic effect was observed (relative excessive risk due to interaction 1.69, 95% CI - 0.55, 3.93). The overlapping status of frailty and FoF, especially excessive FoF, increases the risk of incident disability in older adults.


On the difficulties of characterizing weak protein interactions that are critical for neurotransmitter release.
The mechanism of neurotransmitter release has been extensively characterized, showing that vesicle fusion is mediated by the SNARE complex formed by syntaxin-1, SNAP-25 and synaptobrevin. This complex is disassembled by N-ethylmaleimide sensitive factor (NSF) and SNAPs to recycle the SNAREs, whereas Munc18-1 and Munc13s organize SNARE complex assembly in an NSF-SNAP-resistant manner. Synaptotagmin-1 acts as the Ca2+ sensor that triggers exocytosis in a tight interplay with the SNAREs and complexins. Here, we review technical aspects associated with investigation of protein interactions underlying these steps, which is hindered because the release machinery is assembled between two membranes and is highly dynamic. Moreover, weak interactions, which are difficult to characterize, play key roles in neurotransmitter release, for instance by lowering energy barriers that need to be overcome in this highly regulated process. We illustrate the crucial role that structural biology has played in uncovering mechanisms underlying neurotransmitter release, but also discuss the importance of considering the limitations of the techniques used, including lessons learned from research in our lab and others. In particular, we emphasize: (a) the promiscuity of some protein sequences, including membrane-binding regions that can mediate irrelevant interactions with proteins in the absence of their native targets; (b) the need to ensure that weak interactions observed in crystal structures are biologically relevant; and (c) the limitations of isothermal titration calorimetry to analyze weak interactions. Finally, we stress that even studies that required re-interpretation often helped to move the field forward by improving our understanding of the system and providing testable hypotheses.


The Dilute Fermi Gas via Bogoliubov Theory.
We study the ground state properties of interacting Fermi gases in the dilute regime, in three dimensions. We compute the ground state energy of the system, for positive interaction potentials. We recover a well-known expression for the ground state energy at second order in the particle density, which depends on the interaction potential only via its scattering length. The first proof of this result has been given by Lieb, Seiringer and Solovej (Phys Rev A 71:053605, 2005). In this paper, we give a new derivation of this formula, using a different method; it is inspired by Bogoliubov theory, and it makes use of the almost-bosonic nature of the low-energy excitations of the systems. With respect to previous work, our result applies to a more regular class of interaction potentials, but it comes with improved error estimates on the ground state energy asymptotics in the density.


Trauma induced eagle syndrome.
Eagle syndrome is characterized by secondary calcification and elongation of the styloid process. Eagle syndrome is often associated with sharp, intermittent pain along the path of the glossopharyngeal nerve located in the hypopharynx and at the base of the tongue. In some cases, the stylohyoid apparatus can compress the internal and/or the external carotid arteries and their perivascular sympathetic fibres, resulting in a persistent pain radiating throughout the carotid territory. The pathogenesis of the syndrome is not understood. The authors report the case of a 52-year-old woman with post traumatic Eagle syndrome-like pain and pseudoarthrosis of the stylohyoid ligament.


Tonsillectomy to Effectively Treat a Patient with Behçet's Disease.
Behçet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. We herein report a 27-year-old woman who had suffered from a recurrent fever and tonsillitis for nearly ten years with BD for who tonsillectomy was effective.


Activation of the locus coeruleus after amygdaloid kindling.
Substantia nigra (SN) and locus coeruleus (LC) neurons are implicated in the propagation and suppression of amygdaloid seizures. Both structures are activated concomitant with amygdaloid seizure discharges. Their mechanisms of activation, however, remain to be elucidated. SN firing is not associated with the induction of Fos immunoreactivity (ir), a marker of excitatory neuronal activation. LC has not been studied. The purpose of this investigation was to determine if amygdala-kindled generalized seizures could induce Fos-ir in the LC. Female Sprague-Dawley rats were killed after generalized seizures induced by amygdala electrical stimulation and stained by using Fos immunocytochemistry. The number of Fos-ir neurons was compared between 15 animals with generalized seizures and four implanted, unstimulated controls. LC-ir neurons were significantly (p < 0.05) more prevalent after seizures than in control animals. Their numbers correlated very highly with Fos-ir in the central nucleus of the amygdala (p < 0.0001). No Fos induction was observed in LC in controls or in the SN in either group. Amygdala-induced generalized seizures result in Fos-ir in the LC but not in the SN. This is consistent with different mechanisms of activation possibly involving disinhibition in the SN and direct excitation in the LC.


Framework for the analysis of nanotechnologies' impacts and ethical acceptability: basis of an interdisciplinary approach to assessing novel technologies.
The genetically manipulated organism (GMO) crisis demonstrated that technological development based solely on the law of the marketplace and State protection against serious risks to health and safety is no longer a warrant of ethical acceptability. In the first part of our paper, we critique the implicitly individualist social-acceptance model for State regulation of technology and recommend an interdisciplinary approach for comprehensive analysis of the impacts and ethical acceptability of technologies. In the second part, we present a framework for the analysis of impacts and acceptability, devised-with the goal of supporting the development of specific nanotechnological applications-by a team of researchers from various disciplines. At the conceptual level, this analytic framework is intended to make explicit those various operations required in preparing a judgement about the acceptability of technologies that have been implicit in the classical analysis of toxicological risk. On a practical level, we present a reflective tool that makes it possible to take into account all the dimensions involved and understand the reasons invoked in determining impacts, assessing them, and arriving at a judgement about acceptability.


A survey of hemoglobin quaternary structures.
We perform an analysis of the quaternary structure and dimer/dimer interface in the crystal structures of 165 human hemoglobin tetramers; 112 are in the T, 17 the R, 14 the Y (or R2) state; 11 are high-affinity T state mutants, and 11 may either be intermediates between the states, or off the allosteric transition pathway. The tertiary structure is fixed within each state, in spite of the different ligands, mutations, and chemical modifications present in individual entries. The geometry of the tetramer assembly is essentially the same in all the R or the Y state entries; it is slightly different in high salt and low salt crystals of T state hemoglobins. The dimer/dimer interface differs in terms of size, chemical composition and polar interactions, between the states. It is loosely packed, like crystal packing contacts or the subunit interface of weakly associated homodimers, and unlike most oligomeric proteins, which have close-packed interfaces. The loose packing is most obvious in the liganded forms, where the tetramer is known to dissociate at low concentration. We identify cavities that contribute to the loose packing of the α1β2 and α2β1 contacts. Two pairs of cavities occur recurrently in both the T and the R state tetramers. They may contribute to the allosteric mechanism by facilitating the subunit movements and the tertiary structure changes that accompany the transition from T to R to Y.


Hydrophobic derivatives of guar gum hydrolyzate and gum Arabic as matrices for microencapsulation of mint oil.
Guar gum hydrolyzate (GGH) modified with n-octenyl succinic anhydride (OSA) and oleic acid having induced hydrophobicity was evaluated for encapsulation of mint oil and compared with gum Arabic (GA) and GA-OSA as wall material. Spray dried microcapsules prepared with these wall materials were evaluated for qualitative changes by principal component analysis and for percent retention of mint oil during 8-week storage. Results revealed that microcapsules with GGH-OSA and GGH-oleate showed slightly lower retention of mint oil as compared to GA. GA-OSA microcapsules showed better retention of mint oil than GA itself, as observed from the t1/2, the time required for the mint oil to come down to 50% of its original content. The t1/2 of mint oil in microcapsules of GA, GGH-oleate, GGH-OSA and GA-OSA was 26.12, 23.50, 24.11 and 29.67 weeks, respectively. The results suggested that GGH-OSA has the potential to replace gum Arabic for encapsulation of mint oil.


Prediction of violence in male schizophrenia using sMRI, based on machine learning algorithms.
Violent behavior in patients with schizophrenia (SCZ) is a major social problem. The early identification of SCZ patients with violence can facilitate implementation of targeted intervention. A total of 57 male SCZ patients were recruited into this study. The general linear model was utilized to compare differences in structural magnetic resonance imaging (sMRI) including gray matter volume, cortical surface area, and cortical thickness between 30 SCZ patients who had exhibited violence and 27 SCZ patients without a history of violence. Based on machine learning algorithms, the different sMRI features between groups were integrated into the models for prediction of violence in SCZ patients. After controlling for the whole brain volume and age, the general linear model showed significant reductions in right bankssts thickness, inferior parietal thickness as well as left frontal pole volume in the patients with SCZ and violence relative to those without violence. Among seven machine learning algorithms, Support Vector Machine (SVM) have better performance in differentiating patients with violence from those without violence, with its balanced accuracy and area under curve (AUC) reaching 0.8231 and 0.841, respectively. Patients with SCZ who had a history of violence displayed reduced cortical thickness and volume in several brain regions. Based on machine learning algorithms, structural MRI features are useful to improve predictive ability of SCZ patients at particular risk of violence.


Pollination by deceit, floral sex ratios and seed set in dioecious Rubus chamaemorus L.
Male and female flowers of the dioecious perennial herb Rubus chamaemorus L. are similar in general appearance. However, female flowers are somewhat smaller, do not produce any pollen, and contain very small amounts of nectar. Syrphids and bumblebees, which are important pollinators of R. chamaemorus, showed a strong preference for male flowers. Male flowers were also less often rejected by flower visitors than were female flowers, and two different groups of syrphid species stayed longer in male than in female flowers. These observations suggest that female flowers of R. chamaemorus attract pollinators by deceit.Hand-pollination experiments indicated that pollen availability limited seed production of R. chamaemorus in female dominated habitats but not in areas with an equal floral sex ratio. We suggest that the relative importance of factors limiting female reproductive success is not constant, but is influenced by the floral sex ratio of the population. This should apply also to other dioecious species that show variable sex ratios on either a local or regional scale.


Expression of hyaluronan synthases and hyaluronidases in the MG63 osteoblast cell line.
The expression of hyaluronan synthases (1, 2 and 3) and hyaluronidases (1, 2, 3, 4 and PH20) was examined in the MG63 osteoblast cell line induced to mineralize in vitro and compared to the rate of glycosaminoglycan production. Real-time PCR analysis demonstrated a 13-fold decrease in hyaluronan synthase 3 expression in mineralising MG63 cells; no significant change in hyaluronan synthase 2 expression in mineralising cells and hyaluronan synthase 1 was not expressed. In mineralising MG63 cells a 62-fold increase in hyaluronidase 2, a 13-fold increase in hyaluronidase 3, and a 3-fold increase in hyaluronidase 4 expression were observed when compared to non-mineralising cells; hyaluronidase 1 and PH20 expression was not detected. After 5 weeks in mineralising culture conditions a 2-fold increase in total 3H-glucosamine incorporation was observed in cells when compared to 24 h or 5 week control cultures. This was made up of a 5-fold decrease in hyaluronan production, a 2-fold increase in chondroitin sulphate/dermatan sulphate and a 10-fold increase in 3H-glucosamine incorporation into the non-glycosaminoglycan fraction. A 3-fold increase in 35SO4 incorporation into chondroitin sulphate/dermatan sulphate was also observed. Thus there is co-ordinate expression of genes that control hyaluronan metabolism such that there is a general decrease in the expression of hyaluronan synthases, an increase in the expression of hyaluronidases and a corresponding decrease in hyaluronan production by mineralising MG63 cells.


Negative pressure wound therapy in the treatment of diabetic foot ulcers may be mediated through differential gene expression.
Negative pressure wound therapy (NPWT) has been successfully used as a treatment for diabetic foot ulceration (DFU). Its mechanism of action on the molecular level, however, is not fully understood. We assessed the effect of NPWT on gene expression in patients with type 2 diabetes (T2DM) and DFU. We included two cohorts of patients-individuals treated with either NPWT or standard therapy. The assignment to NWPT was non-randomized and based on wound characteristics. Differential gene expression profiling was performed using Illumina gene expression arrays and R Bioconductor pipelines based on the 'limma' package. The final cohort encompassed 21 patients treated with NPWT and 8 with standard therapy. The groups were similar in terms of age (69.0 versus 67.5 years) and duration of T2DM (14.5 versus 14.4 years). We identified four genes differentially expressed between the two study arms post-treatment, but not pre-treatment: GFRA2 (GDNF family receptor alpha-2), C1QBP (complement C1q binding protein), RAB35 (member of RAS oncogene family) and SYNJ1 (synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1). Interestingly, all four genes seemed to be functionally involved in wound healing by influencing re-epithelialization and angiogenesis. Subsequently, we utilized co-expression analysis in publicly available RNA-seq data to reveal the molecular functions of GFRA2 and C1QBP, which appeared to be through direct protein-protein interactions. We found initial evidence that the NPWT effect on DFUs may be mediated through differential gene expression. A discovery of the specific molecular mechanisms of NPWT is potentially valuable for its clinical application and development of new therapies.


Draft Genome Sequence for Frankia sp. Strain BMG5.11, a Nitrogen-Fixing Bacterium Isolated from Elaeagnus angustifolia.
Frankia sp. strain BMG5.11, which was isolated from Elaeagnus angustifolia nodules, is able to infect other actinorhizal plants, including Elaeagnaceae, Rhamnaceae, Colletieae, Gymnostoma, and Myricaceae Here, we report the 11.3-Mbp draft genome sequence of Frankia sp. strain BMG5.11, with a G+C content of 69.9% and 9,926 candidate protein-encoding genes.


[Clinical evaluation of propess for induction of term pregnancy].
To explore the efficacy and safety of continuously released prostaglandin E(2) (PGE(2)) suppository-propess used for induction of term pregnancy. A multicenter, prospective, case control clinical study was carried out, propess was used in 100 cases as study group, the suppository without PGE(2) was used in 49 cases as control group. The cervical maturity (by Bishop scoring), the time to labor starting, membrane rupture and delivery, the application of oxytocin, ceserean section rate, fetal and neonatal condition were compared between 2 groups after inserting of the suppository. At the same time, side effects caused by propess were investigated. Bishop score was increased >or= 2 points in 93% cases, >or= 3 points in 87% cases in study group, whereas only 4% cases whose Bishop score increased >or= 2 points in control group. The time to labor starting, membrane rupture, and delivery was shortened obviously in study group than that in control group after inserting suppository. The application of oxytocin was much less in study group, cesarean section rate was reduced in study group (32% vs 61%). There was no significant difference between 2 groups in fetal and neonatal conditions. The overstimulation of uterine contraction and mild gastrointestinal tract reaction occurred in 3 cases and 2 cases respectively in study groups. Propess can be used for induction of term pregnancy effectively and safely.


Evaluating trial of scar in patients with a history of caesarean section.
To analyze the outcome of trial of scar in patients with previous caesarean section and to assess the fetal and maternal complications after trial of scar. The study was conducted at Military Hospital, Rawalpindi, Pakistan, with 375 pregnant patients who had a previous delivery by caesarean and who had regular antenatal checkup. Data were recorded on special pro-forms designed for the purpose. The results from the 375 patients who had one previous lower segment caesarean section due to non-recurrent causes were analyzed and compared with national and international studies. Indications of previous caesarean section (non-recurrent causes) included malpresentations, fetal distress/cord prolapse, failure to progress, severe pregnancy-induced hypertension/eclampsia and twins with abnormal lie of the first twin. 0 218 patients reported spontaneous labor. Among these patients, 176 delivered vaginally and 42 patients had repeat caesarean sections. There were a total of 157 patients who experienced induction of labor. 97 patients were induced by cervical ripening with mechanical method, followed by artificial rupture of membranes and augmentation (if required) with syntocinon infusion. 60 patients were induced with prostaglandin E(2) vaginal tablet. This study concludes that females with a prior caesarean are at increased risk for subsequent caesareans, regardless of mode of delivery. Eliminating vaginal-birth-after-caesarean will not eliminate the risk. Therefore, vaginal birth after caesarean should be encouraged in selected cases from obstetric units to reduce the risks of repeated caesarean sections. Failed vaginal-birth-after-caesarean can result in increased morbidity than that with elective caesarean section.


Trends in Type 1 Diabetic Ketoacidosis During COVID-19 Surges at 7 US Centers: Highest Burden on non-Hispanic Black Patients.
The impact of the COVID-19 pandemic on individuals with type 1 diabetes remains poorly defined. We examined United States trends in diabetic ketoacidosis (DKA) among individuals with type 1 diabetes (T1D) during the COVID-19 pandemic at 7 large US medical centers and factors associated with these trends. We compared DKA events among children and adults with T1D during COVID-19 surge 1 (March-May 2020) and COVID-19 surge 2 (August-October 2020) to the same periods in 2019. Analysis was performed using descriptive statistics and chi-square tests. We found no difference in the absolute number of T1D patients experiencing DKA in 2019 vs 2020. However, a higher proportion of non-Hispanic Black (NHB) individuals experienced DKA in 2019 than non-Hispanic White (NHW) individuals (44.6% vs 16.0%; P < .001), and this disparity persisted during the COVID-19 pandemic (48.6% vs 18.6%; P < .001). DKA was less common among patients on continuous glucose monitor (CGM) or insulin pump in 2020 compared to 2019 (CGM: 13.2% vs 15.0%, P < .001; insulin pump: 8.0% vs 10.6%, P < .001). In contrast to annual DKA totals, a higher proportion of patients had DKA during COVID-19 surges 1 and 2 compared to the same months in 2019 (surge 1: 7.1% vs 5.4%, P < .001; surge 2: 6.6% vs 5.7%, P = .001). DKA frequency increased among T1D patients during COVID-19 surges with highest frequency among NHB patients. DKA was less common among patients using CGM or insulin pumps. These findings highlight the urgent need for improved strategies to prevent DKA among patients with T1D-not only under pandemic conditions, but under all conditions-especially among populations most affected by health inequities.


Effect of isoflurane on neutrophil phagocytic function during pregnancy.
General anesthesia has been considered an independent risk factor for postcesarean infection, but the mechanism for this association has not been delineated. The purpose of this prospective investigation was to determine if phagocytic response of neutrophils was impaired by in vitro exposure to isoflurane, a commonly used anesthetic. Twelve milliliter venous blood samples were withdrawn from 18 term patients during labor. Neutrophils were separated by Ficoll gradient centrifugation. Aliquots of 2 x 10(6) neutrophils/ml were exposed to anesthesia using an airtight modular incubator chamber through which a 0.5% isoflurane:50% N(2)O + 50% O(2) mixture flowed at a rate of 4 l/min for 90 min at 37. Neutrophils were assayed for phagocytosis by incubation with Escherichia coli conjugated with fluorescein isothiocyanate for 30 min at 37. Phagocytosis was assessed by flow cytometry. Neutrophils from the same patient that were not exposed to anesthesia served as controls. The mean percentage of phagocytizing neutrophils in the isoflurane-treated group was 82.8 +/- 24 compared to 83.5 +/- 22 in the control group. The difference between the two groups was not significant. In vitro exposure to the general anesthetic isoflurane for 90 min does not significantly alter the phagocytic capacity of neutrophils.


Evaluating the DETERMINE Your Nutritional Health Checklist and the Mini Nutritional Assessment as tools to identify nutritional problems in elderly Europeans.
To evaluate two short questionnaires for assessing the nutritional situation of elderly people, the DETERMINE Your Nutritional Health Checklist of the Nutrition Screening Initiative (NSI checklist) and the Mini Nutritional Assessment (MNA), by comparing equivalent cumulative scores with data on dietary intake, anthropometrics and blood biochemistries. Information similar to the questions of the NSI and MNA lists was collected by SENECA: the Survey in Europe on Nutrition and the Elderly, a Concerted Action. Records collected in 1993, could be used from 1161 European elderly men and women born between 1913 and 1918, mostly community dwelling, whose diet, lifestyle and health were studied twice, in 1989 and 1993. The MNA classified 55% of the examinees as well-nourished, 44% as at risk of malnutrition and 1% as malnourished. The NSI categorised the elderly people differently: 11% as good, 41% at moderate nutritional risk, 48% at high nutritional risk. Biochemical, dietary and anthropometric indices did not differ either between NSI categories or between MNA categories. Using serum albumin values (< 30 g/l) and lymphocyte counts (< 1500/ml) as standards, specificity and sensitivity of both instruments for identifying at-risk groups were below 0.6. Only with body weight loss (> or = 10%) as criterion variable were higher sensitivities (0.75 (NSI), 0.96 (MNA)) and specificities (0.54 (NSI), 0.60 (MNA)) found. It is concluded that in an apparently healthy elderly population both assessment tools are of limited value.


The respiratory effects of tilidine hydrochloride.
A standard 50-mg dose of tilidine hydrochloride (Valoron) was administered to 20 patients in the postoperative phase of open-heart surgery. No significant change in respiratory status, as measured by arterial blood gas analysis, was demonstrated with this dosage.


Chemical and thermochemical aspects of the ozonolysis of ethyl oleate: decomposition enthalpy of ethyl oleate ozonide.
Neat ethyl oleate was ozonized in a bubble reactor and the progress of the ozonolysis was followed by infrared (FT-IR) spectroscopy and by the differential scanning calorimetry (DSC). The ozonolysis was conducted till a molar ratio O3/C=C≈1 when the exothermal reaction spontaneously went to completion. A specific thermochemical calculation on ethyl oleate ozonation has been made to determine the theoretical heat of the ozonization reaction using the group increment approach. A linear relationship was found both in the integrated absorptivity of the ozonide infrared band at 1110 cm(-1) and the ozonolysis time as well as the thermal decomposition enthalpy of the ozonides and peroxides formed as a result of the ozonation. The DSC decomposition temperature of ozonated ethyl oleate occurs with an exothermal peak at about 150-155 °C with a decomposition enthalpy of 243.0 kJ/mol at molar ratio O3/C=C≈1. It is shown that the decomposition enthalpy of ozonized ethyl oleate is a constant value (≈243 kJ/mol) at any stage of the O3/C=C once an adequate normalization of the decomposition enthalpy for the amount of the adsorbed ozone is taken into consideration. The decomposition enthalpy of ozonized ethyl oleate was also calculated using a simplified thermochemical model, obtaining a result in reasonable agreement with the experimental value.


Genetic characterisation of staphylococci of food-producing animals in Senegal. PVL detection among MSSA.
Food-producing animals can be a vehicle for staphylococcal species as well as their virulence and antimicrobial resistance genes. This work aimed to analyse the diversity of staphylococcal species in food-producing animals in Dakar/Senegal, and to determine the antimicrobial resistance phenotype/genotype and virulence factors of recovered isolates. Nasal samples of 149 cows and 199 chickens (348 animals) were collected from one slaughterhouse and a local market respectively, and were inoculated on selective media for staphylococci recovery. For S. aureus isolates, molecular typing (spa-type, MLST) was performed by PCR/sequencing, and the presence of 27 virulence genes (exfoliative and toxic shock toxins, PVL, haemolysins and enterotoxins) as well as the gene scn were analysed by PCR. Susceptibility to twelve antibiotics was studied by disc-diffusion method for all staphylococci; the resistance genes involved were screened by PCR. Staphylococcus spp. was present in 3 and 26.8% of chicken and cow nasal samples, respectively. Seven S. aureus isolates and forty isolates of other staphylococcal species were identified. S. aureus isolates were recovered from cow (n = 6) and chicken (n = 1) samples, belonging to four genetic lineages: t084/ST15 (n = 1); t10579/ST291 (n = 3); t355, t4690/ST152 (n = 2); and t6618/ST6 (n = 1). All S. aureus were methicillin-susceptible, penicillin-resistant (blaZ), and two of them were also tetracycline-resistant [tet(K)]. All the isolates carried at least one of the virulence genes tested. The PVL genes were detected in three ST15 and ST152 isolates. They all harboured haemolysins encoding genes and lacked the scn gene. The other staphylococci recovered were S. sciuri (n = 16), S. simulans (n = 11), S. hyicus (n = 5), S. haemolyticus (n = 4), S. chromogenes (n = 3), and S. hominis (n = 1); they were all methicillin-susceptible and 27.5% tetracycline-resistant [tet(K) and tet(L)]. A low prevalence of S. aureus was detected among food-producing animals, all susceptible to methicillin. However, the presence of virulence genes (lukF/lukS-PV, eta, tst, sea and see) is worrisome to the extent that they could be transferred to derived food and therefore, to humans.


Evaluation of delayed auditory feedback (DAF) effect: comparison between subjective judgments and objective measures.
The effect of Delayed Auditory Feedback (DAF) on speech duration was evaluated subjectively and measured objectively in 30 subjects (10 normals, 10 nonfluent aphasics and 10 fluent aphasia). The average correlation coefficient between the subjective and objective data was .52 for 180 msec. delay and .46 for 360 msec. delay. Analysis of variance of data derived from the two methods showed the same highly significant differences among groups, delay and tasks. We conclude from these results that both objective and subjective procedures are equally useful in evaluating DAF effect on speech duration, and that both may also be valuable in assessing other types of behavior.


Iopamidol in the diagnosis of suspected upper gastro-intestinal perforation.
Forty patients, mainly post-operative, were examined for suspected leakage from the oesophagus and/or stomach using iopamidol. Oesophageal leaks were demonstrated in seven patients, tracheo-oesophageal fistulae in two and an unsuspected gastro-jejunostomy intusussception in one. Only two cases were regarded as technically unsatisfactory due to poor coating. Normal examinations were found in 28 (70%) patients. This was confirmed by the subsequent clinical course. Aspiration into the bronchial tree occurred in five (12.5%) patients without ill-effects. Furthermore no adverse side effects as a result of the administration of iopamidol were recorded. It is concluded that a non-ionic medium such as iopamidol is the agent of choice in the detection of oesophageal and gastric perforation, particularly in post-operative patients where there is an increased risk of aspiration.


Chronic sinusitis among pediatric patients with chronic respiratory complaints.
We examined the prevalence of chronic sinusitis among children who presented to allergy clinics with chronic (> or = 3 months) respiratory symptoms. Ninety-one patients, ranging from 2 to 17 years of age with 62% male and 72% white, completed the study. Fifty-nine percent of patients had positive skin test results, and 25.3% had chronic asthma. Paranasal sinuses were examined by coronal sinus computed tomographic scan. Sixty-three percent (58 to 91) had chronic sinusitis, 5.5% (5 of 91) had concha bullosa, 1% (1 of 91) had foreign body, and 19% (19 of 91) had deviated nasal septums. Among symptoms of sneezing, nasal congestion, postnasal drip, coughing, wheezing, rhinorrhea, and headache, no single symptom was an acceptable predictor of abnormality on computed tomographic scan examinations. Combining the symptoms of moderate to severe rhinorrhea and cough with minimum sneezing had a specificity of 95% and a sensitivity of 38% in predicting the presence of chronic sinusitis. Allergic rhinitis (p = 0.27), mild deviated nasal septum (p = 0.11), unobstructive concha bullosa (p = 0.13), and passive exposure to cigarette smoke (p = 0.53) were not risk factors associated with sinus abnormalities. Age (r = 0.30, p = 0.004) in pediatric patients with chronic respiratory symptoms was the single risk factor significantly associated with abnormalities on sinus computed tomographic scan. Seventy-three percent of children 2 to 6 years of age, 74% of children 6 to 10 years of age, and 38% of children older than 10 had chronic sinusitis.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of refractive outcomes with toric intraocular lens implantation.
To evaluate and compare the accuracy of different methods to measure and predict postoperative astigmatism with toric intraocular lens (IOL) implantation. Ein-Tal Ophthalmology Center, Tel-Aviv, Israel. Retrospective case series. Postoperative corneal astigmatism was measured with 3 devices (IOLMaster 500; optical low-coherence reflectometry [OLCR]-based Lenstar LS 900; Atlas topographer) and compared with the manifest astigmatic refractive outcome in patients with toric IOLs. The error in the predicted residual astigmatism was calculated by vector analysis according to the measurement and calculation method used to predict the required toric IOL cylinder power. The centroid errors in predicted residual astigmatism were against the rule with the Alcon and Holladay toric calculators (0.53 to 0.56 diopter [D]), were lower with the Baylor nomogram (0.21 to 0.26 D), and were lowest for the Barrett toric calculator (0.01 to 0.16 D) (P <.001). The Barrett toric calculator had the lowest median absolute error in predicted residual astigmatism (0.35 to 0.54 D, all devices) compared with the Alcon and Holladay toric calculators with or without the Baylor nomogram (P <.021). The Barrett toric calculator and the OLCR device achieved the most accurate results; 75.0% and 97.1% of eyes were within ±0.50 D and ±0.75 D of the predicted residual astigmatism, respectively. Prediction of astigmatic outcomes with toric IOLs can be improved with appropriate measuring devices and methods to establish the required toric IOL power.


Multiple activation states of VLA-4. Mechanistic differences between adhesion to CS1/fibronectin and to vascular cell adhesion molecule-1.
We examined the effects of a stimulatory anti-beta 1 mAb (TS2/16) and different divalent cations on VLA-4-mediated cell adhesion to vascular cell adhesion molecule-1 (VCAM-1), to the fibronectin-derived CS1 peptide, and to larger fibronectin fragments. Using optimal binding conditions (in the presence of mAb TS2/16 and 1.0 mM Mn2+), the levels of VLA-4-mediated adhesion to VCAM-1 and to CS1 peptide were virtually indistinguishable, and half-maximal inhibition of adhesion to both ligands was achieved using similar levels of an anti-alpha 4 antibody. However, using suboptimal adhesion conditions, two critical differences between adhesion to CS1 peptide (or larger fibronectin fragments) and VCAM-1 were consistently observed. First, stimulation by added mAb TS2/16 had a substantially greater effect on adhesion to CS1 than to VCAM-1 and second, Ca2+ was much less able to support adhesion to CS1 than to VCAM-1. These two differences between adhesion to CS1 peptide and to VCAM-1 were most obvious among cell lines which synthesized inactive or partly active VLA-4 but were not obvious for fully active VLA-4. Together, these results not only reveal crucial differences in the mechanisms of VLA-4 binding to its two ligands, but also lead to increased understanding of the variable activation states of VLA-4. The differential ability to utilize Ca2+ displayed by VLA-4 in different states of activation and the activation of inactive or partly active VLA-4 by the addition of Mn2+ both point to divalent cation sites playing an essential role in determining VLA-4 regulation and ligand specificity.


Binding sites for inositol trisphosphate in the bovine adrenal cortex.
Binding sites for inositol trisphosphate (IP3) have been identified in bovine adrenal cortex, employing [32P]IP3 prepared from human erythrocytes radiolabeled with [32P]ATP. IP3 was bound to adrenal microsomes with high affinity (Kd = 5 nM) and low capacity (186 fmol/mg protein). During kinetic studies, half-maximal binding was reached in less than one min at 4 degrees C, and dissociation was even more rapid with t1/2 of about 10 sec. [32P]IP2 showed no binding to the microsomal sites, which represent putative receptors at which IP3 acts to elevate intracellular calcium concentration during the actions of peptide hormones such as angiotensin II.


Conjoint analysis of circulating tumor cells and solid tumors for exploring potential prognostic markers and constructing a robust novel predictive signature for breast cancer.
Distance metastasis is the leading cause of death for breast cancer patients, and circulating tumor cells (CTCs) play a key role in cancer metastasis. There have been few studies on CTCs at the molecular level due to their rarity, and the heterogeneity of CTCs may provide special information for solid tumor analysis. In this study, we used the gene expression and clinical information of single-cell RNA-seq data of CTCs of breast cancer and discovered a cluster of epithelial cells that had more aggressive characteristics. The differentially expressed genes (DEGs) between the identified epithelial cells cluster and others from single-CTCs were selected for further analysis in bulk sequence data of solid breast cancers. Eighteen genes closely related to the specific CTC epithelial phenotype and breast cancer patient prognosis were identified. Among these 18 genes, we selected the GARS gene, which has not been studied in breast cancer, for functional research and confirmed that it may be a potential oncogene in breast cancer. A risk score was established by the 18 genes, and a high-risk score was strongly associated with a high metastasis rate and poor survival prognosis in breast cancer. The high-risk score group was related to a defective immune infiltration environment in breast cancer, and the immune checkpoint therapy response rate was lower in this group. The drug-sensitive analysis shows that the high-risk score patients may be more sensitive to AKT-mTOR and the cyclin-dependent kinase (CDK) pathways drugs than low-risk score patients. Our 18-gene risk score shows good prognostic and predictive values and might be a personalized prognostic marker or therapy guide marker in breast cancer patients.


A genome-wide in situ hybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain.
In eukaryotic cells, RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. In the vertebrate brain, RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. Several RBPs with activities that are important for the proper function of adult brain have been identified, but how many RBPs exist and where these genes are expressed in the developing brain is uncharacterized. Here we describe a comprehensive catalogue of the unique RBPs encoded in the mouse genome and provide an online database of RBP expression in developing brain. We identified 380 putative RBPs in the mouse genome. Using in situ hybridization, we visualized the expression of 323 of these RBP genes in the brains of developing mice at embryonic day 13.5, when critical fate choice decisions are made and at P0, when major structural components of the adult brain are apparent. We demonstrate i) that 16 of the 323 RBPs examined show neural-specific expression at the stages we examined, and ii) that a far larger subset (221) shows regionally restricted expression in the brain. Of the regionally restricted RBPs, we describe one group that is preferentially expressed in the E13.5 ventricular areas and a second group that shows spatially restricted expression in post-mitotic regions of the embryonic brain. Additionally, we find a subset of RBPs that share the same complex pattern of expression, in proliferating regions of the embryonic and postnatal NS and peripheral tissues. Our data show that, in contrast to their proposed ubiquitous involvement in gene regulation, most RBPs are not uniformly expressed. Here we demonstrate the region-specific expression of RBPs in proliferating vs. post-mitotic brain regions as well as cell-type-specific RBP expression. We identify uncharacterized RBPs that exhibit neural-specific expression as well as novel RBPs that show expression in non-neural tissues. The data presented here and in an online database provide a visual filter for the functional analysis of individual RBPs.


Assessment of target volume doses in radiotherapy based on the standard and measured calibration curves.
In radiation treatments, estimation of the dose distribution in the target volume is one of the main components of the treatment planning procedure. To estimate the dose distribution, the information of electron densities is necessary. The standard curves determined by computed tomography (CT) scanner that may be different from that of other oncology centers. In this study, the changes of dose calculation due to the different calibration curves (HU-ρel) were investigated. Dose values were calculated based on the standard calibration curve that was predefined for the treatment planning system (TPS). The calibration curve was also extracted from the CT images of the phantom, and dose values were calculated based on this curve. The percentage errors of the calculated values were determined. The statistical analyses of the mean differences were performed using the Wilcoxon rank-sum test for both of the calibration curves. The results show no significant difference for both of the measured and standard calibration curves (HU-ρel) in 6, 15, and 18 MeV energies. In Wilcoxon ranked sum nonparametric test for independent samples with P<0.05, the equality of monitor units for both of the curves to transfer 200 cGy doses to reference points was resulted. The percentage errors of the calculated values were lower than 2% and 1.5% in 6 and 15 MeV, respectively. From the results, it could be concluded that the standard calibration curve could be used in TPS dose calculation accurately.


Selection of horseradish peroxidase variants with enhanced enantioselectivity by yeast surface display.
We report a method for in vitro selection of catalytically active enzymes from large libraries of variants displayed on the surface of the yeast S. cerevisiae. Two libraries, each containing approximately 2 x 10(6) variants of horseradish peroxidase (HRP), were constructed; one involved error-prone PCR that sampled mutations throughout the coding sequence, whereas the other involved complete combinatorial enumeration of five positions near the active site to non-cysteine residues. The enzyme variants displayed on the yeast surface were allowed to modify it with a fluorescently labeled substrate. A combination of positive and negative selection applied to the active-site-directed library resulted in variants with up to an 8-fold altered enantioselectivity, including its reversal, toward L/D-tyrosinol. In contrast, the library constructed by using error-prone PCR yielded no HRP variants with a significantly improved enantioselectivity.


Appearance of a nonfunctional isozyme of hepatic glycogen synthase in late gestation.
Glycogen levels, glycogen synthase activities, and glycogen synthase protein levels were determined in liver tissues obtained from 14- to 19-day-old fetal mice, newborn mice, and adult mice. The results of these experiments demonstrate a significant increase in the quantity of hepatic glycogen synthase beginning at Day 17 of gestation and reaching adult levels at birth. However, during the same time period, there is a dramatic decrease in total glycogen synthase activity suggesting that the accumulating glycogen synthase molecules are unable to transfer UDP-glucose to glycogen. These inversely coordinated changes in the quantity and activity of glycogen synthase are consistent with the suggestion that glycogen synthesis in the near-term fetal mouse is being maintained by preexisting enzyme, while accumulating enzyme molecules may represent a quiescent isozyme.


Haemoptysis in COVID-19 pneumonia.
Pulmonary artery pseudoaneurysm is a differential diagnosis to be considered in COVID-19 patients presenting with or developing haemoptysis in order to facilitate early recognition as delayed management could be catastrophic https://bit.ly/3rQTrDT.


Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study.
Since there are few treatment options for young people with type 2 diabetes, we aimed to assess the efficacy and safety of dapagliflozin as add-on therapy in children, adolescents, and young adults with type 2 diabetes receiving metformin, insulin, or both. This multicentre, placebo-controlled, double-blind, randomised phase 3 study was undertaken at 30 centres in five countries (Hungary, Israel, Mexico, Russia, and the USA). Participants aged 10-24 years with type 2 diabetes and HbA1c concentration of 6·5-11% (48-97 mmol/mol) were randomly assigned 1:1 to oral dapagliflozin 10 mg or placebo during a 24 week double-blind period, which was then followed by a 28 week open-label safety extension in which all participants received dapagliflozin. Participants and study personnel were masked and participants were randomly assigned treatment (placebo or study drug) using an interactive web and voice response system. The primary outcome was between-group differences in change in HbA1c concentration from baseline to 24 weeks (intention-to-treat analysis). A prespecified sensitivity analysis of the primary outcome was also assessed in the per-protocol population, which included only protocol-compliant participants. This trial is registered with ClinicalTrials.gov, NCT02725593. Between June 22, 2016, and March 15, 2019, 72 participants (19 [26%] of whom were aged 18-24 years) were randomly assigned (39 to dapagliflozin and 33 to placebo). Mean age was 16·1 (SD 3·3) years. In the intention-to-treat analysis, after 24 weeks, mean change in HbA1c concentration was -0·25% (95% CI -0·85 to 0·34; -2·7 [-9·3 to 3·7] mmol/mol) for dapagliflozin and 0·50% (-0·18 to 1·17; 5·5 [-2·0 to 12·8] mmol/mol) for placebo. The between-group difference was -0·75% (95% CI -1·65 to 0·15; -8·2 [-18·0 to 1·6] mmol/mol; p=0·10). In a sensitivity analysis in the per-protocol population (34 in the dapagliflozin group and 26 in the placebo group) after 24 weeks, mean change was -0·51% (-1·07 to 0·05; -5·6 [-11·7 to 0·5] mmol/mol) for dapagliflozin and 0·62% (-0·04 to 1·27; 6·8 [-0·4 to 13·9] mmol/mol) for placebo. The between-group difference was -1·13% (-1·99 to -0·26; -12·4 [-21·8 to -2·8] mmol/mol; p=0·012). Adverse events occurred in 27 (69%) dapagliflozin-assigned participants and 19 (58%) placebo-assigned participants over 24 weeks, and in 29 (74%) participants who received dapagliflozin over 52 weeks. Hypoglycaemia occurred in 11 (28%) dapagliflozin-assigned and six (18%) placebo-assigned participants who received dapagliflozin over 24 weeks and in 13 participants (33%) who received dapagliflozin over 52 weeks; none were considered as serious adverse events. No adverse events of diabetic ketoacidosis occurred. The primary outcome of change in HbA1c concentration was not significant in the intention-to-treat analysis of children, adolescents, and young adults with type 2 diabetes receiving dapagliflozin in addition to standard-of-care treatment. A prespecified sensitivity analysis of protocol-compliant participants showed a significant difference in HbA1c concentration between groups. No new safety signals were identified and there was a low risk of severe hypoglycaemia. AstraZeneca.


Pulmonary mechanic and lung histology injury induced by Crotalus durissus terrificus snake venom.
In the present work we investigated the effects of Crotalus durissus terrificus venom (CdtV) on the pulmonary mechanic events [static and dynamic elastance, resistive (DeltaP1) and viscoelastic pressures (DeltaP2)] and histology after intramuscular injection of saline solution (control) or venom (0.6 microg/g). The static and dynamic elastance values were increased significantly after 3 h of venom inoculation, but were reduced at control values in the other periods studied. The DeltaP1 values that correspond to the resistive properties of lung tissue presented a significant increase after 6h of CdtV injection, reducing to basal levels 12h after the venom injection. In DeltaP2 analysis, correspondent to viscoelastic components, an increase occurred 12 h after the venom injection, returning to control values at 24 h. CdtV also caused an increase of leukocytes recruitment (3-24 h) to the airways wall as well as to the lung parenchyma. In conclusion, C. durissus terrificus rattlesnake venom leads to lung injury which is reverted, after 24 h of inoculation.


Staphostatins: an expanding new group of proteinase inhibitors with a unique specificity for the regulation of staphopains, Staphylococcus spp. cysteine proteinases.
A novel type of cysteine proteinase inhibitor (SspC) has been recently recognized in Staphylococcus aureus (Massimi, I., Park, E., Rice, K., Muller-Esterl, W., Sauder, D.N., and McGavin, M.J. (2002) J Biol Chem 277: 41770-41777). In this paper we have identified homologous proteins encoded in the genome of S. aureus and other coagulase-negative Staphylococci. Collectively we refer to these proteins as staphostatins as they specifically inhibit cysteine proteinases (staphopains) from Staphylococcus spp. The primary structure of staphostatins seems to be unique, although they resemble cystatins in size (105-108 residues). Recombinant staphostatin A, a product of the scpB gene and staphostatin B (SspC) from S. aureus have been characterized in details. Similar to the cystatins, the staphostatins interact specifically with their target proteinases forming tight and stable non-covalent complexes, staphostatin A with staphopain A and staphostatin B with staphopain B. However, in contrast to the cystatins, each of which inhibits broad range of cathepsins, complex formation between staphostatin and staphopain appears to be exclusive, with no cross interaction observed. In addition, the activities of several tested cysteine proteinases of prokaryotic- and eukaryotic-origin were not affected by staphostatins. Such narrow specificity limited to staphopains is presumed to be required to protect staphylococcal cytoplasmic proteins from being degraded by prematurely activated/folded prostaphopains. This function is guaranteed through the unique co-expression of the secreted proteinase and the intracellular inhibitor from the same operon, and represents a unique mechanism of regulation of proteolytic activity in Gram-positive bacteria.


Gamma Knife radiosurgery for obsessive compulsive disorder.
Gamma Knife radiosurgical capsulotomy has been performed for over 40 years as a rarely used surgical intervention for the treatment of obsessive-compulsive disorder. Over time, the procedure has evolved in many ways with most significant modifications being made in target location, number of isocenters and prescribed dose, subsequently producing changes in lesion size and geometry. Long-term clinical response data and adverse outcomes to the earlier empiric treatment parameters have resulted in shifting the target from its initial location within the midpoint of the anterior limb of internal capsule to a currently used point that includes its most ventral portion as well as the ventral striatum. This led to the contemporary Gamma Knife ventral capsulotomy procedure that focuses on ventral capsule/ventral striatum. Many of the early studies, despite demonstrating efficacy in some patients, were complicated by clinically relevant radiation-induced adverse effects. More recent studies have demonstrated strong efficacy with diminished adverse effects with well-placed lesions created at lower radiation doses. Advances in neuroimaging technology such as diffusion tensor imaging (DTI) based fiber tracking may provide further insight into precisely targeting of the ventral capsule/striatum based on patient-specific variations in white matter connectivity.


Effects of a single dose of isosorbide-5-mononitrate on the left ventricular diastolic function in systemic hypertension.
The effect of a single dose of isosorbide-5-mononitrate on left ventricular (LV) diastolic function was assessed by radionuclide ventriculography in 18 hypertensive patients. The effect of the mononitrate on atrial filling also was assessed. As expected, there was a significant decrease in mean blood pressure (120 +/- 17 to 102 +/- 18 mm Hg, p less than 0.005). Global LV ejection fraction did not show a significant change, increasing slightly from 64 +/- 9 to 68 +/- 8% (difference not significant). The mononitrate prolonged the time to peak filling rate from 176 +/- 36 to 195 +/- 29 ms (p less than 0.0001). The percentage of time to peak filling rate from diastole also increased, from 46 to 53% (p less than 0.05), whereas the normalized peak filling rate did not change (2.36 +/- 0.6 to 2.31 +/- 0.6 end-diastolic volumes/s, difference not significant). This effect on LV diastolic function was closely related to a certain reduction in preload, as suggested by the reduction in mean left atrial filling (45 +/- 12 to 40 +/- 13 counts/s, p less than 0.005) and LV diastolic counts, suggesting that the "impairment" of diastolic function induced by nitrates is secondary to the reduction in venous return to the left atrium. The mononitrate did not affect the mean right atrial filling rate (50 +/- 12 to 52 +/- 13 counts/s) and the right ventricular end-diastolic counts, suggesting a primary vasodilatory effect of nitrates on the pulmonary vascular bed.


Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells: evidence for an adipose tissue-vascular loop.
Inflammation is pivotal in atherosclerosis. C-reactive protein (CRP), in addition to being a cardiovascular risk marker, may also be proatherogenic. We have previously shown that in addition to the liver, human aortic endothelial cells (HAECs) synthesize and secrete CRP. Whereas CRP levels are increased in obesity, metabolic syndrome, and diabetes, levels of adiponectin are reduced in these conditions. We tested the hypothesis that adiponectin reduces CRP synthesis and secretion in HAECs under normoglycemic (5.5 mmol/L glucose) and hyperglycemic conditions (15 mmol/L glucose). Adiponectin dose-dependently reduced CRP mRNA and protein from HAECs. Adiponectin treatment of HAECs significantly decreased IkappaB phosphorylation and NFkappaB binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NFkappaB activity and decreased CRP mRNA and protein. These effects of adiponectin were mimicked by AICAR, an activator of AMPK, and reversed by inhibition of AMPK. Thus, adiponectin reduces CRP synthesis and secretion from HAECs under hyperglycemia via upregulation of AMP kinase and downregulation of NFkappaB. Similar findings were observed in rat primary hepatocytes. Thus, in obesity and diabetes, the hypoadiponectinemia could exacerbate the proinflammatory state by inducing CRP production.


Overview: Themes in Innate Lymphoid Cell Biology.
Since their initial identification more than 10 years ago, innate lymphoid cells (ILCs) have emerged as denizens of an immune realm parallel to that of T cells. Here I highlight basic similarities shared by all and underscore features related to development, tissue residency and regulation that distinguish ILCs from T cells. I further discuss the potential of ILCs as promising targets for therapeutic intervention in human diseases.


Evaluation of the cytotoxic activity of triphenyl phosphate on mouse spermatocytes cells.
Triphenyl phosphate (TPhP) is one of the most commonly found organophosphorus flame retardants (OPFRs) in the environment and the general population. Continuous daily exposure to TPhP may adversely impact male reproductive health. However, few researches were conducted to investigate the direct effects of TPhP on the progress of sperm growth and development. In this study, mouse spermatocyte GC-2spd (GC-2) cells were selected as an in vitro model, the impact of oxidative stress, mitochondrial impairment, DNA damage, cell apoptosis and the related molecular mechanisms were investigated using high content screening (HCS) system. Our study indicated that cell viability was decreased significantly in a dose-dependent manner after TPhP treatment with the half lethal concentration (LC50) at 105.8, 61.61 and 53.23 μM for 24, 48 and 72 h. A concentration-related apoptosis occurrence was observed in GC-2 cells after TPhP exposure for 48 h. In addition, the elevated intracellular reactive oxygen species (ROS) and the total antioxidant capacity (T-AOC) also observed after exposing to 6, 30 and 60 μM of TPhP. Furthermore, based on the enhancement of pH2AX protein and alteration of nuclear morphology or DNA content, DNA damage might be induced by higher concentration of TPhP treatment. Simultaneously, alteration of mitochondrial structure, enhancement of mitochondrial membrane potential (MMP), reduction of cellular adenosine triphosphate (ATP) content, altered expression of Bcl-2 family proteins, release of cytochrome c and increase of caspase-3 and caspase-9 activity demonstrated that caspase-3 dependent mitochondrial pathway might play a key role in the process of GC-2 cell apoptosis. Taken together, these results showed that TPhP was a mitochondrial toxicant and apoptotic inducer, which might trigger alike responses in human spermatogenic cells. Therefore, the potential reproductive toxicity of TPhP should not be ignored.


Determination of emission probabilities of gamma photons in the decay of (56)Co.
The emission probabilities of gamma photons in the decay of (56)Co were determined at Czech Metrology Institute (CMI) by means of an HPGe detector. This detector was calibrated experimentally and by MCNP-computation in the energy range from 40 to 2754keV for a point source geometry and source-to-detector distance of 25cm. Experimental and computed peak and total efficiencies were compared and calibration curves were determined. Full-peak efficiencies were calculated for all (56)Co gamma-ray energies, and were used to calculate the emission probabilities. A set of point sources was prepared from a (56)Co solution. The solution was standardized using the 4pibeta-gamma coincidence method, and an ampoule was sent to international reference system for activity measurement of gamma-ray emitting radionuclides (SIR). Each point source was measured with the HPGe detector at a source-to-detector distance of 25cm. Coincidence emission probabilities of all the gamma photons were calculated and used to determine the summing correction factors.


Crystal structure of TcpK in complex with oriT DNA of the antibiotic resistance plasmid pCW3.
Conjugation is fundamental for the acquisition of new genetic traits and the development of antibiotic resistance in pathogenic organisms. Here, we show that a hypothetical Clostridium perfringens protein, TcpK, which is encoded by the tetracycline resistance plasmid pCW3, is essential for efficient conjugative DNA transfer. Our studies reveal that TcpK is a member of the winged helix-turn-helix (wHTH) transcription factor superfamily and that it forms a dimer in solution. Furthermore, TcpK specifically binds to a nine-nucleotide sequence that is present as tandem repeats within the pCW3 origin of transfer (oriT). The X-ray crystal structure of the TcpK-TcpK box complex reveals a binding mode centered on and around the β-wing, which is different from what has been previously shown for other wHTH proteins. Structure-guided mutagenesis experiments validate the specific interaction between TcpK and the DNA molecule. Additional studies highlight that the TcpK dimer is important for specific DNA binding.


Patients with immunoglobulin light chain amyloidosis undergoing autologous stem cell transplantation have superior outcomes compared with patients with multiple myeloma: a retrospective review from a tertiary referral center.
The underlying plasma cell clones in multiple myeloma (MM) and Ig light-chain amyloidosis (AL) appear to be different not only in terms of 'tumor burden' but also in terms of their underlying biology. High-dose chemotherapy with auto-SCT is one method of reducing the clone size and thereby improving OS. Post-auto-SCT outcomes between the two diseases have never been formally compared. Among all patients with a diagnosis of AL or MM who received auto-SCT as primary therapy at the Mayo Clinic, Rochester, there were higher CR rates (40% versus 29%, P<0.0001) in the AL group. The respective median OS for the AL and MM patients was 113 and 59.5 months, respectively, P<0.0001. Among patients achieving CR, MM patients had a fivefold risk of death as compared with AL patients. Although auto-SCT cannot be offered to all patients with either AL or MM, it appears that for those well enough to be chosen for the procedure, greater benefit is derived among the AL patients. This difference in survival is most notable among those patients who achieve CR, suggesting very different plasma cell biology between the two diseases.


Keys to open the door for blood donors to return.
Because of demographic changes, the worldwide shortage of blood will likely be aggravated in the foreseeable future. Hence, the retention of already active blood donors (BDs) is becoming more and more important. Moreover, a substantial increase in blood donations could be achieved by a relatively small increase in BD return. Blood donation services are therefore well advised to understand their BDs' motivations to become regular and committed BDs and to consider this in planning BD retention programs. Focusing on the published literature of the last decade, we summaries some key recommendations in considering BD retention strategies. Whereas starting a career as a BD is mainly driven by external stimuli, becoming a committed BD needs a well-developed identity role; that is, a BD with a high level of intrinsic motivation. Active communications with the BD right from the beginning, introducing distinct measures to support the development of a BD's distinct identity, increasing convenience of the blood donation process, having well-trained and motivated staff, applying distinct measures to reduce anxiety as well as adverse events, making BDs satisfied with their blood donation experience, appropriate use of incentives, quickly recapturing temporarily deferred BDs, and appealing to BDs' personal motivations and moral norms--all of these are major keys to achieving this important aim.


Effects of secretin on acute and chronic effects of morphine.
The effects of intracerebroventricularly (ICV) administered secretin on the analgesic, tolerance-inducing, and dependence-inducing actions of morphine were investigated, in adult, male CFLP mice. Secretin administered doses ICV did not itself affect pain sensitivity in a heat-radiant tail flick test. However, it depressed the acute nociceptive effect of a single subcutaneous (SC) dose of morphine (4 mg/kg) after ICV (1 or 10 ng/animal) secretin administration. A dose of 10 ng secretin facilitated the development of acute morphine tolerance. On the other hand, none of the doses applied had any influence on chronic morphine tolerance, where animals were implanted SC with a morphine- containing pellet and the pain sensitivity was measured 3 days later. Morphine withdrawal signs were also evaluated by injecting naloxone. In a 100-ng dose, secretin increased the latency of the withdrawal jumping response; the peptide did not modify the other abstinence signs. These data suggest that central secretin administration can modify the analgesic effect of morphine.


Lactation in Anesthesiology.
There are several work-related barriers to breastfeeding among physician mothers including: lack of appropriate place for breastmilk expression, unpredictable and inflexible schedules, and lack of time to breastfeed or express milk. In a survey of physician mothers, those who were in surgical and procedural subspecialties, including anesthesiology, reported a lack of lactation facilities in close proximity to the operating room as a barrier to breastfeeding. Unlike other physicians and clinicians in different health care environments, anesthesiology is unique in that there is often no built-in time for breaks or a predictable end time to the operating room schedule. A break system is typically established, within an institution, for meal break relief for trainees, Certified Registered Nurse Anesthetist, and Anesthesia Assistants. This system for breaks may not be sufficient to accommodate the frequency or length required for lactation sessions. In addition, these break systems do not typically provide relief for supervising anesthesiologists for meals or lactation sessions. A study of physician mothers across specialties identified anesthesiologists as significantly more likely than women of other medical specialties to self-report maternal discrimination. The study defined maternal discrimination as discrimination based on pregnancy, maternity leave, or breastfeeding. As a workforce and specialty, we must support our breastfeeding anesthesiologists and facilitate lactation needs on return to the workplace.


Simultaneous sonographic demonstration of tumor thrombus in the inferior vena cava and patient main renal vein in renal carcinoma.
With the introduction of new imaging modalities the optimal protocol for the evaluation of renal tumors is under close review. Angiographers frequently are faced with the question of whether to proceed to inferior venacavography following a selective renal angiogram that demonstrates a patent renal vein. We report a case of renal cell carcinoma in which the main renal vein was shown by ultrasound to be unequivocally patent but at the same time there was considerable tumor extension into the inferior vena cava. The necessity of full examination of the inferior vena cava, either by venacavography or ultrasound, in all cases of renal cell carcinoma is stressed.


Attacking pain at its source: new perspectives on opioids.
The treatment of severe pain with opioids has thus far been limited by their unwanted central side effects. Recent research promises new approaches, including opioid analgesics acting outside the central nervous system, targeting of opioid peptide-containing immune cells to peripheral damaged tissue, and gene transfer to enhance opioid production at sites of injury.


Complex effects on CaV2.1 channel gating caused by a CACNA1A variant associated with a severe neurodevelopmental disorder.
P/Q-type Ca2+ currents mediated by CaV2.1 channels are essential for active neurotransmitter release at neuromuscular junctions and many central synapses. Mutations in CACNA1A, the gene encoding the principal CaV2.1 α1A subunit, cause a broad spectrum of neurological disorders. Typically, gain-of-function (GOF) mutations are associated with migraine and epilepsy while loss-of-function (LOF) mutations are causative for episodic and congenital ataxias. However, a cluster of severe CaV2.1 channelopathies have overlapping presentations which suggests that channel dysfunction in these disorders cannot always be defined bimodally as GOF or LOF. In particular, the R1667P mutation causes focal seizures, generalized hypotonia, dysarthria, congenital ataxia and, in one case, cerebral edema leading ultimately to death. Here, we demonstrate that the R1667P mutation causes both channel GOF (hyperpolarizing voltage-dependence of activation, slowed deactivation) and LOF (slowed activation kinetics) when expressed heterologously in tsA-201 cells. We also observed a substantial reduction in Ca2+ current density in this heterologous system. These changes in channel gating and availability/expression manifested in diminished Ca2+ flux during action potential-like stimuli. However, the integrated Ca2+ fluxes were no different when normalized to tail current amplitude measured upon repolarization from the reversal potential. In summary, our findings indicate a complex functional effect of R1667P and support the idea that pathological missense mutations in CaV2.1 may not represent exclusively GOF or LOF.


Validation of the Brazilian Portuguese CAPE-V Instrument-Br CAPE-V for Auditory-Perceptual Analysis.
The Consensus Auditory Perceptual Evaluation of Voice (CAPE-V) scale is a modern, clinical-scientific approach to voice analysis. It has been translated and culturally adapted to Brazilian Portuguese, but it still lacks validation. To validate the Brazilian Portuguese version of the CAPE-V scale using the previously translated and culturally adapted version. Forty voice samples were selected (30 dysphonic, 10 nondysphonic), and the degree of vocal deviation was evaluated by a committee of three voice specialists. Nine voice specialists judged the 40 voice samples plus 20% repetition (total of 48 samples) using the CAPE-V. To ensure construct validity of the CAPE-V, its analysis was compared to the Grade-Roughness-Breathiness-Asthenia-Strain (GRBAS) scale that was performed 48-72 hours later. Finally, the intra- and inter-rater reliability values were verified and the correlation between the nine judges and the previously defined evaluation was analyzed. The Brazilian CAPE-V presented significant intra (0.860-0.997) and inter-rater reliability values (0.707-0.964) for the overall degree and strong correlation with GRBAS (above 0.828). Deviant voice quality had greater consensus among raters than normal voices. A strong correlation was observed between the analysis of the nine raters and that of the committee. CAPE-V is an important diagnostic instrument that contributes to the standardization of vocal quality evaluation in several languages, including Brazilian Portuguese. Thus, its usefulness is neither related to a single language nor to a single set of raters.


Lessons to Build an Educational Model for Higher Education Institutions Defined as Anchor Institutions to Tackle Public Health Crises: A Pilot Study on COVID-19 Vaccine Hesitancy Among Faculty and Students in Hebert L. College in the Bronx, NY.
Coronavirus disease 2019 exacerbated health inequities in Bronx Communities. This study explored vaccine hesitancy among a random sample of faculty and students from Hebert Lehman College. Findings suggest faculty are largely vaccinated (87%), while 59% of students are unvaccinated. Significant gaps in information were found related to safety and complications. This suggests universities need to adopt an educational model with a multipronged social support strategy to gain students' trust and a greater sense of belonging.


Water lilies as emerging models for Darwin's abominable mystery.
Water lilies are not only highly favored aquatic ornamental plants with cultural and economic importance but they also occupy a critical evolutionary space that is crucial for understanding the origin and early evolutionary trajectory of flowering plants. The birth and rapid radiation of flowering plants has interested many scientists and was considered 'an abominable mystery' by Charles Darwin. In searching for the angiosperm evolutionary origin and its underlying mechanisms, the genome of Amborella has shed some light on the molecular features of one of the basal angiosperm lineages; however, little is known regarding the genetics and genomics of another basal angiosperm lineage, namely, the water lily. In this study, we reviewed current molecular research and note that water lily research has entered the genomic era. We propose that the genome of the water lily is critical for studying the contentious relationship of basal angiosperms and Darwin's 'abominable mystery'. Four pantropical water lilies, especially the recently sequenced Nymphaea colorata, have characteristics such as small size, rapid growth rate and numerous seeds and can act as the best model for understanding the origin of angiosperms. The water lily genome is also valuable for revealing the genetics of ornamental traits and will largely accelerate the molecular breeding of water lilies.