Comparative study of pressure- and nutrient-induced germination of Bacillus subtilis spores.
Germination experiments with specific germination mutants of Bacillus subtilis, including a newly isolated mutant affected in pressure-induced germination, suggest that a pressure of 100 MPa triggers the germination cascades that are induced by the nutrient germinant alanine (Ala) and by a mixture of asparagine, glucose, fructose, and potassium ions (AGFK), by activating the receptors for alanine and asparagine, GerA and GerB, respectively. As opposed to germination at 100 MPa, germination at 600 MPa apparently short-cuts at least part of the Ala- and AGFK-induced germination pathways. Inhibitors of nutrient-induced germination (HgCl(2) and Nalpha-P-tosyl-L-arginine methyl ester) also inhibit pressure-induced germination at 600 MPa, suggesting that germination at 600 MPa involves activation of a true physiological germination pathway and is therefore not merely a physico-chemical process in which water is forced into the spore protoplast.


Gamma-frequency neuronal activity is diminished in adults with attention-deficit/hyperactivity disorder: a pharmaco-MEG study.
Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder affecting approximately 4-7% of children and persisting in 2-5% of adults. The core symptoms include pervasive inattention and inappropriate levels of hyperactivity-impulsivity. High-frequency gamma activity has been implicated in the temporal binding of stimulus properties across cortical areas, and is known to be crucial for complex information processing and attentional processes in particular. Thus, we evaluated the amplitude of gamma-frequency neural responses in adults with and those without ADHD, and tested whether stimulant medications, the most common treatment for ADHD, modulate gamma activity in affected adults. Participants underwent two sessions (~75 min apart) of auditory stimulation using stimuli known to elicit 40 Hz gamma-band responses as magnetoencephalography data were acquired. Between sessions, the ADHD group (who were in maintenance therapy) were administered their daily stimulant medication and both groups were told to relax. The primary results indicated that gamma activity was weaker in the ADHD group during session one (pre-drug), but not session two (post-drug), and that gamma activity significantly increased following stimulant administration in adults with ADHD. These results suggest that ADHD is associated with reduced cortical gamma activity and that stimulants may ameliorate this abnormality.


Volume capacity and pressure characteristics of the continent ileostomy reservoir.
The volume capacity and the pressure characteristics of the ileal reservoir were studied at intervals postoperatively in 28 patients with continent ileostomy. The reservoir volume increased during the first 6 months from 100 ml to approximately 700 ml, after which it remained stable. The basal pressure increased during filling to a maximum of roughly 10 cm H2O. Under 'physiological conditions' the basal pressure was around 4 cm H2O before emptying. Two types of pressure waves occurred, small pressure fluctuations with a frequency of 7-8/min and larger phasic waves appearing when approximately 40% of the reservoir volume capacity had been reached. The occurrence of both types of pressure waves decreased with time. The total motor activity, expressed as the area underneath the pressure waves, decreased considerably during the 1st year after operation, indicating an adaptation of the intestinal smooth muscle to distension. The results confirm the original concept proposed by Kock that the ileal reservoir constructed in this manner is a low-pressure reservoir.


Divergent metabolic pathways for propane and propionate utilization by a soil isolate.
The metabolism of propane and propionate by a soil isolate (Brevibacterium sp. strain JOB5) was investigated. The presence of isocitrate lyase in cells grown on isopropanol, acetate, or propane and the absence of this inducible enzyme in n-propanol- and propionate-grown cells suggested that propane is not metabolized via C-terminal oxidation. Methylmalonyl coenzyme A mutase and malate synthase are constitutive in this organism. The incorporation of (14)CO(2) into pyruvate accumulated during propionate utilization suggests that propionate is metabolized via the methyl-malonyl-succinate pathway. These results were further substantiated by radiorespirometric studies with propionate-1-(14)C, -2-(14)C, and -3-(14)C as substrate. Propane -2-(14)C was shown, by unlabeled competitor experiments, to be oxidized to acetone; acetone and isopropanol are oxidized in this organism to acetol. Cleavage of acetol to acetate and CO(2) would yield the inducer for the isocitrate lyase present in propane-grown cells.


Hemicelluloses of cell walls of a proso millet cell suspension culture.
Cell wall composition of a stable suspension of proso millet (Panicum miliaceum L. cv Abarr) cells is similar to those of tissues and cell suspensions of other graminaceous species. Extraction of hemicelluloses with step-wise increasing concentrations of alkali yields materials that, like those of embryonal cells of maize coleoptiles, comprise mostly glucuronoarabinoxylan, xyloglucan, and small amounts of (1-3),(1-4)-beta-d-glucan. As in the walls of embryonal cells of the maize coleoptile, 5-arabinosyl and 3-arabinosyl comprise much higher proportions of the total hemicellulosic sugars than in walls of developed or elongated cells. Unlike cells of many dicotyledonous species, millet cells do not elongate or undergo observable differentiation during the stationary phase of culture, and consequently, their wall composition is remarkably consistent throughout the culture cycle. The proso millet cell suspension culture constitutes a reasonable model for study of cell wall biogenesis in embryonal cells of a graminaceous species, but because of marked changes in the composition of hemicelluloses in these species during cell enlargement, additional model systems should be sought.


The cross-sectional and longitudinal association between perceived neighborhood walkability characteristics and depressive symptoms in older Latinos: the "¡Caminemos!" study.
Evaluate the cross-sectional and longitudinal association between perceived walkability-related neighborhood characteristics (e.g., traffic safety) and depressive symptoms among community-dwelling older Latino adults. We used baseline, 12-month, and 24-month in-person interview data collected from Latinos aged ≥ 60 years participating in an exercise intervention at 27 senior centers (N = 570). In cross-sectional analyses, lower perceived neighborhood crime, indicative of greater neighborhood walkability, was associated with a lower odds of elevated symptoms of depression (odds ratio [OR] = 0.90; 95% confidence interval [CI] = [0.82, 0.996]; p = .04) after adjusting for demographic characteristics, linguistic acculturation, and medical comorbidities. Associations between Neighborhood Environment Walkability scales and incident depressive symptoms at 12- and/or 24-months were not statistically significant, but the point estimate for crime safety was consistent with cross-sectional findings (OR = 0.83; 95% CI = [0.64, 1.07]; p = .16), suggesting a protective effect for lower perceived neighborhood crime. Lower perceived neighborhood crime is associated with reduced presence of elevated symptoms of depression in older Latinos.


Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.
Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity.


Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women.
Transdermal progesterone is being used in some countries as a purported treatment for menopausal symptoms, either alone or prescribed in conjunction with estrogen, but little information exists regarding the biological activity and effectiveness of this method of delivery of progesterone in protecting the endometrium from excess proliferation. This study was designed to evaluate the use of sequential transdermal progesterone. End-points evaluated included endometrial cellular response and bleeding pattern as well as plasma hormone levels and salivary progesterone estimations. Twenty-seven postmenopausal women were treated with continuous transdermal estrogen (28-day cycle) and a cream containing 16, 32 or 64 mg of progesterone in each 4-cm extrusion from a tube of Pro-Feme administered daily in a sequential (days 15-28 of cycle) regimen. Blood and endometrial samples were analyzed for progesterone response prior to therapy, after the first 14 days of unopposed transdermal estrogen and following 14 days of transdermal progesterone. Saliva samples were taken during the last 14 days of the 84-day study, when the final progesterone cream therapy was being applied. Hormone assay indicated that physiological levels of estradiol were achieved, but progesterone levels were insufficient to induce any detectable change in the endometrium. Only one patient experienced bleeding during the study period. Levels of salivary progesterone were so variable as to be considered completely unreliable in determining the potential influence on biological activity. Pro-Feme transdermal progesterone administered in a 16-, 32- or 64-mg daily dose for 14 days in a sequential regimen does not appear to be effective in inducing a secretory change in a proliferative endometrium. Salivary progesterone levels were not of value in managing the therapy of postmenopausal women.


Insulin resistance and not BMI is the major determinant of early vascular impairment in patients with morbid obesity.
Several factors contribute to the development of atherogenesis in patients with obesity. The aim of our study was to evaluate the different roles of insulin resistance, strictly correlated to visceral adiposity, and the body mass index (BMI), an estimate of overall adiposity, on early vascular impairment in patients with morbid obesity. We enrolled 65 morbidly obese subjects (BMI 44.6 ± 7 kg/m(2)) who were free of previous cardiovascular events and 28 nonobese subjects (control group) in a cross-sectional study. The presence of glycemia and insulinemia, the levels of lipids and liver parameter and the ultrasonographic assessment of the flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) and visceral fat area (VFA) were evaluated in all subjects. In the obese patients with a median HOMA value of ≥ 3.5, the FMD was significantly lower (p < .05) and the left carotid maximum-IMT was significantly higher (p < .05) than those observed in the group with lower HOMA values. No vascular differences were found between the two groups that were subdivided according to the BMI median value. Both the left max-IMT and FMD exhibited a significant correlation with HOMA-IR ("ρ" .292, p=0.02 , "ρ"-.292, p=0.02 respectively) but not with BMI. According to a multivariate analysis, the VFA was an independent predictor of a reduced FMD (β - .541, p.002; p of the model .002), while age (β .611 p < .0001) and HOMA-IR (β .399 p < .001) were independent predictors of the left max-IMT (p of the model .002). The HOMA-IR, which is strictly related to visceral fat and is an index of metabolic impairment, and not BMI, which reflects of global adiposity, can be used to identify early vascular impairment in patients with morbid obesity.


Transcriptome coexpression map of human embryonic stem cells.
Human embryonic stem (ES) cells hold great promise for medicine and science. The transcriptome of human ES cells has been studied in detail in recent years. However, no systematic analysis has yet addressed whether gene expression in human ES cells may be regulated in chromosomal domains, and no chromosomal domains of coexpression have been identified. We report the first transcriptome coexpression map of the human ES cell and the earliest stage of ES differentiation, the embryoid body (EB), for the analysis of how transcriptional regulation interacts with genomic structure during ES self-renewal and differentiation. We determined the gene expression profiles from multiple ES and EB samples and identified chromosomal domains showing coexpression of adjacent genes on the genome. The coexpression domains were not random, with significant enrichment in chromosomes 8, 11, 16, 17, 19, and Y in the ES state, and 6, 11, 17, 19 and 20 in the EB state. The domains were significantly associated with Giemsa-negative bands in EB, yet showed little correlation with known cytogenetic structures in ES cells. Different patterns of coexpression were revealed by comparative transcriptome mapping between ES and EB. The findings and methods reported in this investigation advance our understanding of how genome organization affects gene expression in human ES cells and help to identify new mechanisms and pathways controlling ES self-renewal or differentiation.


Raising the bar on recruitment and retention.
Although finding and keeping talented staff is a problem that affects virtually every healthcare organization, Falls Church, Virginia-based Inova Health System found itself particularly challenged by a fiercely competitive market and failing employee retention system. Large percentages of staff in Inova's finance division were employed for less than one year. To address this staffing crisis, department leadership joined with human resource representatives and employees to pursue a practical strategy emphasizing self-analysis, responsive solutions, and promotion of recruitment activities. In less than a year, the division had exceeded its expectations--vacancies were significantly reduced, use of temporary replacements had ceased, and members of the public were recognizing the organization as an industry leader.


Non-hyperpolarizing GABAB receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1.
γ-Aminobutyric acid is the principal inhibitory neurotransmitter in adults, acting through ionotropic chloride-permeable GABAA receptors (GABAARs), and metabotropic GABABRs coupled to calcium or potassium channels, and cyclic AMP signalling. During early development, γ-aminobutyric acid is the main neurotransmitter and is not hyperpolarizing, as GABAAR activation is depolarizing while GABABRs lack coupling to potassium channels. Despite extensive knowledge on GABAARs as key factors in neuronal development, the role of GABABRs remains unclear. Here we address GABABR function during rat cortical development by in utero knockdown (short interfering RNA) of GABABR in pyramidal-neuron progenitors. GABABR short interfering RNA impairs neuronal migration and axon/dendrite morphological maturation by disrupting cyclic AMP signalling. Furthermore, GABABR activation reduces cyclic AMP-dependent phosphorylation of LKB1, a kinase involved in neuronal polarization, and rescues LKB1 overexpression-induced defects in cortical development. Thus, non-hyperpolarizing activation of GABABRs during development promotes neuronal migration and morphological maturation by cyclic AMP/LKB1 signalling.


Reduction in Egg Fertility of Aedes albopictus Mosquitoes in Greece Following Releases of Imported Sterile Males.
Aedes albopictus, an invasive mosquito species, is currently well established in many European countries, posing high risks to human health. A preliminary trial using repetitive releases of irradiated sterile male mosquitoes was designed, implemented and evaluated for the first time in Greece. The main scope of this trial was to investigate the efficacy of sterile insect technique (SIT) on wild population egg hatch rate in Greece using mass-produced sterile male mosquitoes from another country (Italy). The study was conducted in Vravrona area, close to Athens International Airport (Attica Region). The number of eggs laid in ovitraps was similar in all intervention and control plots. However, a significant reduction in egg hatch rate was recorded in the SIT plot in comparison with both control plots starting two weeks after the first release. This trial validates the logistics (transportation, releases handling and monitoring) as a major step towards implementing efficient, environmentally safe control approaches as an additional tool against the invasive Aedes species in Greece and more widely in Europe.


My approach to superficial inflammatory dermatoses.
Superficial inflammatory dermatoses are very common and comprise a wide, complex variety of clinical conditions. Accurate histological diagnosis, although it can sometimes be difficult to establish, is essential for clinical management. Knowledge of the microanatomy of the skin is important to recognise the variable histological patterns of inflammatory skin diseases. This article reviews the non-vesiculobullous/pustular inflammatory superficial dermatoses based on the compartmental microanatomy of the skin.


Monoclonal antibody therapy in multiple myeloma.
The therapeutic landscape of multiple myeloma (MM) has evolved spectacularly over the past decade with the discovery and validation of proteasome inhibitors and immunomodulatory agents as highly active agents, both in front-line therapy as well as in the relapse and maintenance settings. Although previous attempts to apply available monoclonal antibodies (Mabs) to the treatment of patients with MM has until recently been disappointing, novel targets specifically explored in the context of MM have recently lead to the first approvals of Mabs for the treatment of patients with MM. We have performed a literature search to identify preclinical targeting of MM, including in vitro and in vivo models using monoclonal antibodies, as well as clinical trials of monoclonal antibodies in patients with MM. Sources used were peer-reviewed publications, congress abstracts and on-line clinical trials data (such as clinicaltrials.gov). Several targets have been evaluated in preclinical models and a growing number of agents are being evaluated in clinical trials, as single agents or in combination and under various antibody formats. Two agents, targeting for the first time CD38 and SLAMF7, respectively, have recently been approved for the treatment of patients with MM. The recent approval of these two antibodies is expected to have a strong impact on treatment modalities and outcome in patients with MM, including both transplant eligible and elderly patients.


Whole-cell fluorescent biosensors for bioavailability and biodegradation of polychlorinated biphenyls.
Whole-cell microbial biosensors are one of the newest molecular tools used in environmental monitoring. Such biosensors are constructed through fusing a reporter gene such as lux, gfp or lacZ, to a responsive promoter. There have been many reports of the applications of biosensors, particularly their use in assaying pollutant toxicity and bioavailability. This paper reviews the basic concepts behind the construction of whole-cell microbial biosensors for pollutant monitoring, and describes the applications of two such biosensors for detecting the bioavailability and biodegradation of polychlorinated biphenyls (PCBs).


A Direct and Simple Method to Assess Drosophila melanogaster's Viability from Embryo to Adult.
In Drosophila melanogaster, viability assays are used to determine the fitness of certain genetic backgrounds. Allelic variations can result in partial or complete loss of viability at different stages of development. Our lab has developed a method to assess viability in Drosophila from embryo to fully mature adult. The method relies on quantifying the number of progeny present at different stages during development, starting with hatched embryos. After embryos have been quantified, additional stages are counted, including L1/L2, pupae, and mature adults. After all stages have been examined, a statistical analysis such as the chi-square test is used to determine if there is a significant difference between the starting number of progeny (hatched embryos) and later stages culminating in the observed number of adults, thus rejecting or accepting the null hypothesis (that the number of hatched embryos will be equal to the number of larvae, pupae, and adults recorded throughout the stages of development). The primary advantage of this assay is its simplicity and accuracy, as it does not require an embryo rinse to transfer them to the food vial, avoiding losses from technical errors. Although the protocol described here does not directly examine L2/L3 larvae, additional steps can be added to account for these. Comparing the number of hatched embryos, L1, pupae, and adults can help determine if viability was compromised during the L2/L3 stages for further studies (the use of colored food helps with visual identification of larvae). Overall, this method can help Drosophila researchers and educators determine when viability is compromised during the fly life cycle. Routine assessment of stocks using this assay can prevent accumulation of secondary mutations that may affect the phenotype of the originally isolated mutant, especially if the original mutations affect fitness. For this reason, our lab maintains multiple copies of each of our Dm ime4 alleles and routinely checks the purity of each stock with this method in addition to other molecular analyses.


Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming.
Synaptic vesicles must be primed to fusion competence before they can fuse with the plasma membrane in response to increased intracellular Ca2+ levels. The presynaptic active zone protein Munc13-1 is essential for priming of glutamatergic synaptic vesicles in hippocampal neurons. However, a small subpopulation of synapses in any given glutamatergic nerve cell as well as all gamma-aminobutyratergic (GABAergic) synapses are largely independent of Munc13-1. We show here that Munc13-2, the only Munc13 isoform coexpressed with Munc13-1 in hippocampus, is responsible for vesicle priming in Munc13-1 independent hippocampal synapses. Neurons lacking both Munc13-1 and Munc13-2 show neither evoked nor spontaneous release events, yet form normal numbers of synapses with typical ultrastructural features. Thus, the two Munc13 isoforms are completely redundant in GABAergic cells whereas glutamatergic neurons form two types of synapses, one of which is solely Munc13-1 dependent and lacks Munc13-2 whereas the other type employs Munc13-2 as priming factor. We conclude that Munc13-mediated vesicle priming is not a transmitter specific phenomenon but rather a general and essential feature of multiple fast neurotransmitter systems, and that synaptogenesis during development is not dependent on synaptic secretory activity.


Search for nucleation sites in smaller fragments of chymotrypsin inhibitor 2.
There is a region of well-ordered structure in the transition state of folding of chymotrypsin inhibitor 2 (CI2) that consists of N-terminal residues in the unique alpha-helix (residues 12 to 24) plus some long range interactions, in particular those of Ala16 with Ile57 and Leu49 in the hydrophobic core. This is proposed to be a nucleation site. A crucial question for understanding the initiation of protein folding is: when is the nucleation site formed? Is the alpha-helix pre-formed in the nominally unfolded state, or does it require long-range interactions to be stabilized? To answer this question, we have characterized a series of N-terminal fragments of CI2, each containing an increasing number of subsets of the regular secondary structure. Four small fragments have been examined by circular dichroism and two-dimensional 1H and 15N NMR spectroscopy. The smallest, [1-5], comprises the sequence corresponding to the first beta-strand of the intact protein; the second, [1-13], contains also a type III reverse turn, the second beta-strand, and a type II reverse turn; the third [1-25], consists additionally of the sequence corresponding to the alpha-helix (residues 12 to 24); the fourth, [1-28], contains, in addition, the turn following the alpha-helix. All the fragments have disordered, non-compact structure in aqueous solution. In the structure-promoting co-solvent, trifluoroethanol, alpha-helical structure is stabilized in [1-25] and [1-28] in the region corresponding to the alpha-helix in the intact protein; however, the helix is frayed at both ends and is only fractionally populated, being in dynamic equilibrium with extended conformations. These observations indicate that there is little drive for independent formation of local secondary structure in CI2, and this is reflected in the highly concerted nature of the folding reaction of this protein. The nucleation site of folding of CI2 does not accumulate in the starting state for the folding reaction, but remains embryonic until there are sufficient long range interactions to stabilize it.


High-resolution comparative mapping of mouse chromosome 17.
We have constructed a high-resolution genetic linkage map spanning the proximal 32 cM of mouse chromosome 17 including the t complex. Simple sequence repeats at D17Tu1 and D17Mit6 were employed to identify 121 recombinants among 374 offspring of a (C57BL/6 x CAST/Ei) x C57BL/6 backcross. In contrast to previously reported interspecific Mus domesticus x Mus spretus backcrosses, we did not observe inversion polymorphisms with our cross. This and the relatively high frequency of DNA polymorphisms between C57BL/6 and CAST/Ei allowed us to put 32 RFLV markers and 32 PCR markers on a single map. We present the localization of four new DNA markers and determined map positions for 10 other loci, which previously had been assigned to intervals of the t complex only through the study of partial t haplotype chromosomes.


Anterior shoulder instability: diagnostic criteria determined from prospective analysis of 121 MR arthrograms.
To determine magnetic resonance (MR) arthrographic criteria in the diagnosis of anterior glenohumeral instability. In 121 patients with diagnoses proved surgically, the labrum, glenohumeral ligaments, and capsular insertion types were assessed prospectively with gadolinium-enhanced MR arthrography. Findings were compared in stable and unstable shoulders. Operative results showed 59 normal, 57 torn, and five deficient labra. In 37 unstable shoulders, 31 had discrete inferior labral-ligamentous lesions and six had capsular laxity. MR arthrograms showed labral abnormalities with 92% sensitivity, 92% specificity. Inferior labral-ligamentous lesions enabled prediction of anterior instability with 76% sensitivity (capsular laxity was missed in all shoulders), 98% specificity. Inferior labral-ligamentous abnormalities were strongly associated with unstable shoulders (P << .0001), whereas noninferior labral-ligamentous abnormalities were related to stable shoulders (P = .01). Capsular insertion types showed no significant differences between stable and unstable shoulders (P > .8). On MR arthrograms, inferior labral-ligamentous abnormalities were most closely correlated with anterior glenohumeral instability. Capsular insertion sites had no role in the prediction of shoulder instability.


Effects of High Light Stress on Carotenoid-Deficient Chloroplasts in Pisum sativum.
The effects of high light stress on chloroplast ultrastructure and protein and mRNA composition were investigated in carotenoid-deficient peas (Pisum sativum, L.). In low light, the thylakoid membrane polypeptide pattern was altered, with several prominent chlorophyll-binding proteins present in diminished amounts. This change was found to be reflected in the ultrastructural organization of internal chloroplast membranes. In contrast to the normal grana stacking found in the controls, carotenoid-deficient plastids contained long, unstacked lamellae. Exposure to photooxidative light that resulted in destruction of >70% of chlorophyll did not lead to changes in total RNA and total cellular protein patterns. This treatment did lead to gross alterations in the chloroplast structure. Within 24 hours the plastid was seen as a swollen vesicle with only a few membrane remnants still present. Accumulation of five plastid-encoded mRNAs encoding a diverse array of photosynthetic proteins was found to be affected in different ways. While psaA mRNA was rapidly reduced by more than 75%, levels of psbF/E and atpB/E were reduced by 50%. psbA and petA mRNAs, on the other hand, appeared to be more resistant to photobleaching and remained relatively unchanged during 24 hours of high fluence-rate light treatment.


Food Safety and Sanitation Implementation Impasse on Adolescents in Kenyan High Schools.
The ability to combat food-borne illnesses in food facilities and institutional catering units require sufficient knowledge on food safety and sanitation standards by food producers and consumers. The aim of the study was to investigate the food safety and sanitation knowledge of food handlers in Kenyan high schools. A cross-sectional study was carried out among 204 food handlers in 50 schools. Questions about knowledge and practice toward food safety and sanitation were asked. Respondents were the most knowledgeable on food contamination (93%), while participants were the least knowledgeable on the importance of protective attire when distributing foods to learners (50%). One-way ANOVA revealed a significant difference between gender and food handlers' behavior and practice (F = 19.886, ρ = 0.00 < 0.05) as well as between job tenure and practice of food safety and sanitation (F = 17.874, ρ = 0.00 < 0.05). Multiple regression analysis established that knowledge contributed to 44.1% of the behavior and practice of the food handlers. It is concluded that food handlers have a fair knowledge despite lack of training, motivation, and facilities to maintain quality standards. It is recommended that the Kenyan Government develop and implement guidelines through school feeding policy that would ensure that food safety and sanitation practices are implemented and utilized by Kenyan high schools.


Recurrent herpes labialis in a military brass band.
80-90% of the adult population is known to have neutralizing antibodies to herpes simplex virus type 1 (HSV1), of these 18-32% suffer from occasional recurrent herpes labialis (RHL). It is thought that local trigger factors as external traumata, UV-light and chemical stimuli, or systemic factors like fever or common cold, may induce RHL. The aim of the present study was to investigate the frequency of RHL in a military brass band and compare this with the frequency of the disease in a control population of soldiers from the same unit. Both populations were national servicemen aged 19-22 yr. The diagnosis of RHL was based on the presence of herpetic vesicles in the labial region. Of the diagnosed cases, 10% were confirmed by laboratory procedures according to standard methods. The incidence of RHL over a period of 8 months was twice as frequent in the group of brass and woodwind players as in the control group of soldiers from the same military unit. This may indicate that the mechanical trauma to the labial tissue which occurs during playing may cause the increased frequency of RHL in musicians.


Tendon bone healing can be enhanced by demineralized bone matrix: a functional and histological study.
Rotator cuff repair surgery has high failure rates, with tendon reattachment to bone remaining a challenging clinical problem. Increasing the integrity of the healing tendon-bone interface has been attempted by adopting a number of different augmentation strategies. Because of chondrogenic and osteogenic properties we hypothesise that demineralized bone matrix (DBM) augmentation of a healing tendon-bone interface will result in improved function, and a morphology that more closely resembles that of a normal enthesis, compared with nonaugmented controls in an ovine patellar tendon model. The right patellar tendon was detached from its insertion and reattached to an osteotomized bone bed using suture anchors. Two groups were analyzed, the control group (without augmentation) and the DBM group (DBM interposed between the tendon and bone). Animals were sacrificed at 12 weeks. Force plate, mechanical, and histomorphometric analyses were performed. Tendon repairs failed at a rate of 33 and 0% for the control and DBM groups, respectively. DBM augmentation resulted in significantly improved functional weight bearing and increased amounts of fibrocartilage and mineralized fibrocartilage. This study shows that DBM enhances tendon-bone healing and may reduce the high failure rates associated with rotator cuff repair clinically.


Neonatal intensive care: communication and attachment.
Birth has traditionally been recognized as a family-centred event where immediate exposure to the infant occurs and where the family begins, through direct contact, touch and voice, to form an attachment to the infant. In high-risk pregnancy and delivery, medical and technological advances distance the family from the birth event. This article describes some aspects of a research project with identified factors that facilitate and hinder family and mother attachment to the infant during periods of separation subsequent to premature delivery or other problems which require management in a neonatal intensive care unit (NICU). The project was exploratory. It involved observation of care, participation in care, individual unstructured interviews, focus group interviews and also use of Leske's (1986, 1991a,b) critical care family needs inventory, which was modified and responded to by family members (n = 109) in an attempt to quantify and validate their needs. Six constructs were derived from the inventory and then ranked by mothers (n = 100). The findings from this process were triangulated to observation and interview data in order to confirm factors that facilitate and hinder the process of attachment during family and mother-infant separation. The results of the study imply that when the family and mother are supported by an individualized approach to care and appropriate communication is used, attachment can be facilitated.


Cyclohexanedione Herbicides Are Selective and Potent Inhibitors of Acetyl-CoA Carboxylase from Grasses.
Biochemical studies of plant species susceptible to the cyclohexanedione herbicides, alloxydim, sethoxydim, and clethodim, have demonstrated that these selective grass herbicides inhibit acetyl-coenzyme A carboxylase, the second enzyme common to both fatty acid and flavonoid biosynthetic pathways. The K(i)s for the cyclohexanediones tested ranged from 0.02 to 1.95 micromolar, depending on the species. The enzyme isolated from broadleaf plants was much less sensitive to inhibition by these herbicides (K(i)s from 53 micromolar to 2.2 millimolar). These results may explain the mechanism of action of these herbicides and their selectivity for monocotyledonous species.


The maize gene terpene synthase 1 encodes a sesquiterpene synthase catalyzing the formation of (E)-beta-farnesene, (E)-nerolidol, and (E,E)-farnesol after herbivore damage.
Maize (Zea mays) emits a mixture of volatile compounds upon attack by the Egyptian cotton leafworm (Spodoptera littoralis). These substances, primarily mono- and sesquiterpenes, are used by parasitic wasps to locate the lepidopteran larvae, which are their natural hosts. This interaction among plant, lepidopteran larvae, and hymenopteran parasitoids benefits the plant and has been termed indirect defense. The committed step in the biosynthesis of the different skeletal types of mono- and sesquiterpenes is catalyzed by terpene synthases, a class of enzymes that forms a large variety of mono- and sesquiterpene products from prenyl diphosphate precursors. We isolated a terpene synthase gene, terpene synthase 1 (tps1), from maize that exhibits only a low degree of sequence identity to previously identified terpene synthases. Upon expression in a bacterial system, the encoded enzyme produced the acyclic sesquiterpenes, (E)-beta-farnesene, (E,E)-farnesol, and (3R)-(E)-nerolidol, the last an intermediate in the formation of (3E)-4,8-dimethyl-1,3,7-nonatriene. Both (E)-beta-farnesene and (3E)-4,8-dimethyl-1,3,7-nonatriene are prominent compounds of the maize volatile blend that is emitted after herbivore damage. The biochemical characteristics of the encoded enzyme are similar to those of terpene synthases from both gymnosperms and dicotyledonous angiosperms, suggesting that catalysis involves a similar electrophilic reaction mechanism. The transcript level of tps1 in the maize cv B73 was elevated after herbivory, mechanical damage, and treatment with elicitors. In contrast, the increase in the transcript level of the tps1 gene or gene homolog in the maize cv Delprim after herbivory was less pronounced, suggesting that the regulation of terpene synthase expression may vary among maize varieties.


Paramphistomum spp: improved artificial excystment and in vitro culture of immature and adult stages.
The aims of the present study were to establish an adequate excystment method for metacercariae of Paramphistomum spp. and to compare the in vitro survival of paramphistomids in three different culture media. In a preliminary study, 31 different assays were performed solely with the purpose of obtaining the best percentage of metacercariae excystment. Once the best excystment method was selected, 21 further assays using 100 metacercariae/assay were carried out to determine the average percentage of excystment. For the in vitro culture of paramphistomids, the Hedon-Fleig, Rohrbacher, and RPMI-1640 culture media were compared by using 24-well immunoplates containing newly excysted flukes or 50-ml capacity tissue-culture flasks for adult paramphistomids. Results indicated an average of 69.0% excystment, the best culture medium to support the survival of immature and adult stages of the trematode being Hedon-Fleig and Rohrbacher, respectively. The best percentage of survival obtained was on day 4 (80%), with some immature and adult trematodes remaining alive until days 10 and 11, respectively.


In vivo and in vitro evaluation of occlusal indicator sensitivity.
Indicators used to locate and eliminate occlusal disharmonies have not demonstrated specific sensitivity and reliability. The sensitivity and reliability of articulating papers, foils, silk strips, and T-Scan systems used as occlusal indicators were investigated. The effect of saliva on the materials also was determined. In the in vitro part of the study, a test model (mounted in an articulator and in a universal testing machine) was established with the use of maxillary and mandibular dentate casts. Articulating papers, foils, silk strips, and the T-Scan system were used to examine the loss of sensitivity of the recording materials after 3 consecutive strokes. The differences in the contact points of the test model determined by each of the recording materials were evaluated both in the articulator and in a universal testing machine. In the in vivo part of the study, occlusal contact recordings of 3 subjects were made before and after drying their mouths. The significance of the differences between the strokes repeated more than once was evaluated with the Friedman 2-way analysis of variance and Kruskal-Wallis tests. To examine the effect of the oral environment, the Wilcoxon matched-pairs signed-ranks test was applied. In all statistical analyses, the level of significance was alpha=.05. The results demonstrated significant differences in the sensitivity of the recording materials tested (P<.001). The sensitivity of all recording materials decreased after multiple use (P<.001), and the loss of recording accuracy was significant (P<.001). All recording materials except the T-Scan were affected by the presence of saliva (P<.01). Within the limitations of this study, the results indicated that multiple use of the recording materials tested may lead to inaccurate occlusal analysis results. It is recommended that the recording materials be used only once and that the teeth be dry during occlusal analysis.


Left atrial tamponade: diagnosis by transesophageal echocardiography.
A 60-year-old white man became hypotensive and dyspneic 3 days after right pneumonectomy for bronchogenic carcinoma. Transthoracic echocardiography was nondiagnostic because of technical difficulty. Transesophageal echocardiography demonstrated a loculated posterior pericardial effusion with isolated diastolic left atrial collapse. The hemodynamic disturbance resolved after drainage of the effusion. Transesophageal echocardiography plays a valuable role in the diagnosis of postoperative cardiac tamponade.


Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?
Dedifferentiated liposarcoma (DDLPS) has been defined as a tumor composed of well-differentiated liposarcoma associated with a nonlipogenic undifferentiated sarcoma and is genetically characterized by a 12q13-15 amplicon with MDM2 amplification. Some peripheral (extremities, trunk wall, head/neck) undifferentiated pleomorphic sarcomas (UPS) without areas of well-differentiated liposarcoma present an MDM2 amplification. We addressed whether they are true DDLPS or not. We compared the clinical data, histologic data, MDM2 status (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]), genomic profile (array comparative genomic hybridization), and follow-up of 19 patients with peripheral UPS with MDM2 amplification and 62 with peripheral conventional DDLPS retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). For a control cohort, we described 153 patients from the Conticabase, with peripheral UPS without expression of MDM2 by IHC. By IHC, tumor cells were positive for MDM2 in 59 conventional DDLPS and in all UPS with MDM2 amplification. FISH analysis and/or quantitative polymerase chain reaction showed amplification of MDM2 in 54 conventional DDLPS and in all UPS with MDM2 amplification. The 2-year overall survival rates of UPS with MDM2 amplification, conventional DDLPS, and UPS without expression of MDM2 were 93.3%, 90.7%, and 73.9%, respectively. Such similarities in the clinical characteristics, morphology, genomic profile, and follow-up of peripheral UPS with MDM2 amplification and peripheral conventional DDLPS strongly suggest that peripheral UPS with MDM2 amplification are in fact DDLPS. Faced with histologic diagnosis of UPS, a systematic IHC evaluation of MDM2 allows a selection of cases for FISH analysis permitting the diagnosis of DDLPS.


[Disease burden on road injury in the Chinese population, in 1990 and 2013].
Objective: To explore the disease burden of road injuries in China. Methods: The results of Global Burden of Disease 2013 including death rate, disability-adjusted of life years (DALY), years of life lost due to premature mortality (YLL), years lived with disability (YLD), were used to describe the burden caused by road injuries in 2013 and the trends from 1990 to 2013, in China. Results: In 2013, there were 313 676 deaths caused by traffic accidents in China. Death rate, rates on DALY, YLL and YLD were 22.52 per 100 000, 1 076.54 per 100 000, 971.21 per 100 000 and 105.34 per 100 000, respectively. Rates on deaths, YLL and YLD appeared higher in males, pedestrians than in females and other types of road travelers. Burden of injuries caused by traffic accidents was seen higher in those aged 15 to 49-year-old. From 1990 to 2013, the overall death rate on road injuries increased by 0.54 per 100 000 in China, with an increase of 2.34 per 100 000 and 0.81 per 100 000, respectively in males and pedestrians. The rates on DALY, YLL and YLD decreased by 164.21 per 100 000, 115.06 per 100 000 and 49.06 per 100 000, respectively. Conclusions: During the past 20 years, achievements had been made on road injury prevention and control, with the decrease of disease burden caused by road accidents. Males, young adults and pedestrians should be called for more attention to prevent road injuries.


Bullous pyoderma gangrenosum as the presenting sign of fatal acute myelogenous leukemia.
Bullous pyoderma gangrenosum begins as a bulla, nodule or nonulcerated erythematous plaque that blisters or ulcerates to form a superficial ulcer surrounded by a hemorrhagic, bullous border, which is surrounded by a blue-gray halo. Bullous pyoderma gangrenosum is most commonly associated with hematologic malignancies, specifically, acute myelogenous leukemia (AML). We report a patient whose initial presentation with bullous pyoderma gangrenosum prompted the appropriate diagnostic evaluation and confirmation of AML, which was ultimately fatal. We emphasize that a thorough hematologic investigation, including bone marrow biopsy, should be performed in all patients who present with lesions clinically suggestive of bullous pyoderma gangrenosum because the skin lesion may be the only indicator of the underlying hematologic disorder.


AMP-activated protein kinase and nitric oxide regulate the glucose sensitivity of ventromedial hypothalamic glucose-inhibited neurons.
The mechanisms by which glucose regulates the activity of glucose-inhibited (GI) neurons in the ventromedial hypothalamus (VMH) are largely unknown. We have previously shown that AMP-activated protein kinase (AMPK) increases nitric oxide (NO) production in VMH GI neurons. We hypothesized that AMPK-mediated NO signaling is required for depolarization of VMH GI neurons in response to decreased glucose. In support of our hypothesis, inhibition of neuronal nitric oxide synthase (nNOS) or the NO receptor soluble guanylyl cyclase (sGC) blocked depolarization of GI neurons to decreased glucose from 2.5 to 0.7 mM or to AMPK activation. Conversely, activation of sGC or the cell-permeable analog of cGMP, 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), enhanced the response of GI neurons to decreased glucose, suggesting that stimulation of NO-sGC-cGMP signaling by AMPK is required for glucose sensing in GI neurons. Interestingly, the AMPK inhibitor compound C completely blocked the effect of sGC activation or 8-Br-cGMP, and 8-Br-cGMP increased VMH AMPKalpha2 phosphorylation. These data suggest that NO, in turn, amplifies AMPK activation in GI neurons. Finally, inhibition of the cystic fibrosis transmembrane regulator (CFTR) Cl(-) conductance blocked depolarization of GI neurons to decreased glucose or AMPK activation, whereas decreased glucose, AMPK activation, and 8-Br-cGMP increased VMH CFTR phosphorylation. We conclude that decreased glucose triggers the following sequence of events leading to depolarization in VMH GI neurons: AMPK activation, nNOS phosphorylation, NO production, and stimulation of sGC-cGMP signaling, which amplifies AMPK activation and leads to closure of the CFTR.


Capsulotomy.
The development of posterior capsule opacification secondary to extracapsular cataract extraction is a common occurrence. The patient complains of decreased visual acuity, glare, and sensitivity to light. The YAG laser posterior capsulotomy has become standard treatment for this anomaly: an opening is created in the opacified posterior capsule, which immediately improves visual acuity. This review describes the indications, preparation, procedure, follow-up, and complications associated with using a yttrium-aluminum-garnet (YAG) laser to perform capsulotomy.


Direct interactions between Epstein-Barr virus leader protein LP and the EBNA2 acidic domain underlie coordinate transcriptional regulation.
The Epstein-Barr virus nuclear leader protein LP (EBNALP) and EBNA2 are expressed first in lymphocyte infection, coordinately regulate cell and viral gene transcription, and are critical for lymphocyte outgrowth into lymphoblastoid cell lines (LCLs). We have now found that EBNALP readily associated with EBNA2 or with the EBNA2 C-terminal acidic activation domain (E2AD) when both components were expressed by bacteria. In lymphoblasts, EBNALP and EBNA2 did not stably associate. However, EBNALP deleted for only 10 C-terminal amino acids stably associated with EBNA2 in lymphoblasts or with EBNA2 acidic activating domain from bacteria. The E2AD was essential for EBNALP coactivation of the latent membrane protein 1 promoter in lymphoblasts; EBNALP could coactivate with a deficient mutant EBNA2, EBNA2W(454)T, but not with EBNA2 deleted for E2AD. Moreover, EBNALP 31 amino acids (dW2Y1) with 24 C- or N-terminal amino acids was a specific and efficient affinity matrix for EBNA2 or EBNALP. Even an EBNALP 22-aa peptide, dW2, specifically bound EBNALP or EBNA2. These biochemical interactions between EBNALP and EBNA2 enable coordinated transcriptional regulation of cell and viral gene expression in lymphoblasts only when the interaction is unstable; deletion of the EBNALP C-terminal 10 aa stabilized association with EBNA2 and prevented coactivation. Because EBNALPd10 dominantly inhibited EBNALP coactivation with EBNA2, EBNALPd10 expression in LCLs may be useful in assessing the role of EBNALP coactivation in LCL growth or survival.


Effects of Chloramphenicol on the Circadian Rhythm of Neurospora crassa.
Chloramphenicol, an inhibitor of mitochondrial protein synthesis, shortened the period length of the circadian rhythm in the Timex strain of Neurospora crassa by 2 hours. Both the l(+) threo and d(-) threo optical isomers had the same effect on the period of the rhythm, whereas only the d(-) threo isomer significantly inhibited mitochondrial protein synthesis. Tetracycline, another inhibitor of mitochondrial protein synthesis, did not change the period of the circadian rhythm. The effect of chloramphenicol on the circadian rhythm is, therefore, presumably not directly related to inhibition of mitochondrial protein synthesis, suggesting that chloramphenicol has other effects.


The anti-proliferative effect of sulindac and sulindac sulfide on HT-29 colon cancer cells: alterations in tumor suppressor and cell cycle-regulatory proteins.
Nonsteroidal anti-inflammatory drugs lower the incidence of and mortality from colon cancer. Sulindac reduces the number and size of polyps in patients with familial adenomatous polyposis. We have shown that sulindac and sulindac sulfide reversibly reduce the proliferation rate of HT-29 colon cancer cells, alter their morphology, induce them to accumulate in the G0/G1 phase of the cell cycle, and sulindac sulfide induces cell death by apoptosis. In this study we confirmed that sulindac and sulindac sulfide prevent HT-29 cells from progressing from the G0/G1 into the S phase. This block in cell cycle progression is associated with an initial rise, then an abrupt decrease in the levels of p34cdc2 protein. Sulindac and sulindac sulfide decrease the levels of mitotic cyclins, induce the levels of p21WAF-1/cip1, and reduce the total levels of pRB, with a relative increase in the amount of the underphosphorylated form of pRB in a time- and concentration-dependent manner. In addition, these compounds reduce the levels of mutant p53. These responses are not associated with intestinal cell differentiation and occur independent of the ability of these compounds to induce apoptosis. We conclude that sulindac and sulindac sulfide reduce the levels of major components of the molecular cell cycle machinery and alter the levels of several tumor suppressor proteins in a manner consistent with cell cycle quiescence. These mechanisms may be operative in vivo to account, in part, for the anti-neoplastic effects of these compounds.


Poisoning among the elderly.
Poisonings continue to be an important public health problem. Herein, we analyzed the epidemiology of poisonings in elderly individuals. Retrospective cohort study conducted between 2011 and 2019 in a university hospital. We analyzed demographic variables, type of poison involved, suicidal or accidental nature of the poisoning, and the probability of admission, or death to the hospital. A total of 880 (6.1%) of the 14,300 poisonings treated in the same period occurred in people over 65 years of age. The most numerous group were individuals between 65-69 years-old (39%), followed by the group of 70-75 years-old (20%), being men 57%. In 88% of the cases a single poison participated, being by frequency alcohol (51.6%), drugs (29.5%), and household or industrial products (12.8%). Alcohol intoxication predominated in men up to 75 years of age, and above this age drug or suicidal intoxication predominated, mainly in women. A total of 145 (16%) subjects were hospitalized, the drugs most frequently implicated being digoxin and benzodiazepines. The probability of hospital admission was associated with intoxication by metformin, digoxin, lithium or with the age of the patient (OR per year = 1.03; 95% CI: 1.0-1.06). A total of 19 patients died (2.16%), mainly due to suicidal caustic ingestion (OR = 5.7: 95% CI: 1.4-23.6) or by drugs, directly related to metformin (OR = 10.1; 95% CI: 2.4-42.4). The prevalence of poisoning in the elderly is not negligible, and physicians should have a high index of suspicion in a complex situation.


Interaction of cellular hydrogenase, cytochrome c3, and desulfoviridin in Desulfovibrio vulgaris Miyazaki with their antibodies.
Anti-sera for hydrogenase, cytochrome c3, and desulfoviridin (abbreviated as anti-hyd, anti-c3, and anti-dvn, respectively) were raised in mice, and used to locate these antigens in cells of Desulfovibrio vulgaris Miyazaki. The activity of the intact cells to absorb H2 with methyl viologen or sulfite as an electron acceptor was cumulatively inhibited by treating the cells with anti-hyd and anti-c3 but unaffected by anti-dvn treatment. The activity of the intact cells to produce H2 from formate was also inhibited by anti-c3 treatment, but the inhibition by anti-hyd treatment was not significant. The fluorescent antibody technique applied to intact cells of D. vulgaris Miyazaki indicated that both hydrogenase and cytochrome c3 are localized on the surface of the cell. These results are not exactly in conformity with the hydrogen-cycling hypothesis for proton gradient formation in the energy metabolism in Desulfovibrio. The procedure described in the present paper provides a new technique to elucidate the roles of proteins by applying anti-sera to intact cells without destroying the cellular structure.


Effects of gamma-irradiation on acute myelogenous leukemia blasts: in vitro studies of proliferation, constitutive cytokine secretion, and accessory cell function during T cell activation.
Generation of cellular immune responses against acute myelogenous leukemia (AML) blasts is a possible therapeutic approach in leukemia therapy. However, when using native AML blasts as stimulator cells during ex vivo generation of leukemia-reactive T cells, one has to ensure that the T cell population is not contaminated with proliferating AML blasts. Our results demonstrate that gamma-irradiation could be used to stop AML blast proliferation for all patients investigated. However, gamma-irradiation also caused a dose-dependent reduction in the constitutive AML blast secretion of the potentially T cell stimulatory cytokines IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). At the same time, gamma-irradiation resulted in a dose-dependent decrease in anti-CD3-stimulated proliferative responses of T cell clones in the presence of AML blast accessory cells. When using 50 Gy irradiation, however, AML blast expansion was avoided, and anti-CD3 and PHA-stimulated T cell proliferation was detected in the presence of accessory AML blasts for most AML/T cell combinations investigated. When AML blasts were cultured with GM-CSF + IL-4 to develop a dendritic cell phenotype, enhanced T cell proliferation in the presence of in vitro precultured AML blasts was observed for most patients even after 50 Gy irradiation. We conclude that when using native AML blasts as accessory cells during in vitro generation of leukemia-reactive T cells, an irradiation dose of 50 Gy can be used for a majority of AML patients to avoid the risk of leukemia cell expansion during culture and with the maintenance of AML blast accessory cell function. However, when in vitro expanded cells are used in clinical trials, this antiproliferative effect should be documented with appropriate in vitro testing for every patient so that the possibility of decreased sensitivity to gamma-irradiation in exceptional patients is excluded.


Nonfatal opioid overdoses before and after Covid-19: Regional variation in rates of change.
The Covid-19 pandemic and its accompanying public-health orders (PHOs) have led to (potentially countervailing) changes in various risk factors for overdose. To assess whether the net effects of these factors varied geographically, we examined regional variation in the impact of the PHOs on counts of nonfatal overdoses, which have received less attention than fatal overdoses, despite their public health significance. Data were collected from the Overdose Detection Mapping Application Program (ODMAP), which recorded suspected overdoses between July 1, 2018 and October 25, 2020. We used segmented regression models to assess the impact of PHOs on nonfatal-overdose trends in Washington DC and the five geographical regions of Maryland, using a historical control time series to adjust for normative changes in overdoses that occurred around mid-March (when the PHOs were issued). The mean level change in nonfatal opioid overdoses immediately after mid-March was not reliably different in the Covid-19 year versus the preceding control time series for any region. However, the rate of increase in nonfatal overdose was steeper after mid-March in the Covid-19 year versus the preceding year for Maryland as a whole (B = 2.36; 95% CI, 0.65 to 4.06; p = .007) and for certain subregions. No differences were observed for Washington DC. The pandemic and its accompanying PHOs were associated with steeper increases in nonfatal opioid overdoses in most but not all of the regions we assessed, with a net effect that was deleterious for the Maryland region as a whole.


Peripartum ovarian masses.
The presentation and management of ovarian tumours complicating pregnancy may have altered with changes in obstetric practice and developments in diagnostic imaging and pathology. A retrospective review of the presentation, management, pathological findings and pregnancy outcome of all women whose pregnancies were complicated by an ovarian tumour was undertaken. We found 84 cases where ovarian masses complicated pregnancy. Thirteen presented in association with an ectopic pregnancy. Forty-seven cases were asymptomatic and 29 of these were discovered incidentally at caesarean section despite the routine use of ultrasound. Twenty-two cases were symptomatic, presenting with mass, pain or bleeding. Aspiration cytology was helpful in only 53% while histology allowed definitive diagnosis for all tumours. Benign cystic teratoma was the most common tumour found. There was one tumour of borderline malignancy in this series. Examination of the ovaries at the time of caesarean section should be a routine practice since the majority of asymptomatic ovarian masses were discovered incidentally and not antenatally, having been missed at the time of routine ultrasound. Although differentiation of functional from neoplastic lesions can be difficult, most lesions are benign and selective conservative management may be considered.


Sensing Coated Iron-Oxide Nanoparticles with Spectral Induced Polarization (SIP): Experiments in Natural Sand Packed Flow-Through Columns.
The development of nanoparticle-based soil remediation techniques is hindered by the lack of accurate in situ nanoparticle (NP) monitoring and characterization methods. Spectral induced polarization (SIP), a noninvasive geophysical technique, offers a promising approach to detect and quantify NPs in porous media. However, its successful implementation as a monitoring tool requires an understanding of the polarization mechanisms, the governing NP-associated SIP responses and their dependence on the stabilizing coatings that are typically used for NPs deployed in environmental applications. Herein, we present SIP responses (0.1-10 000 Hz) measured during injection of a poloxamer-coated superparamagnetic iron-oxide nanoparticle (SPION) suspension in flow-through columns packed with natural sand from the Borden aquifer. An advective-dispersive transport model is fitted to outflow SPION concentration measurements to compute average concentrations over the SIP spatial response domain (within the columns). The average SPION concentrations are compared with the real and imaginary components of the complex conductivity. Excellent correspondence is found between the average SPION concentrations in the columns and the imaginary conductivity values, suggesting that NP-mediated polarization (that is, charge storage) increases proportionally with increasing SPION concentration. Our results support the possibility of SIP monitoring of spatial and temporal NP distributions, which can be immediately deployed in bench-scale studies with the prospect of future real-world field applications.


Burn Wound Mucormycosis: A Case Study on Poor Wound Healing.
Mucormycosis is a rare, rapidly progressive and often fatal fungal infection. The rarity of the condition lends itself to unfamiliarity, delayed treatment, and poor outcomes. Diagnosis of fungal infections early enough to enable appropriate treatment occurs in less than half of affected patients. A 56-year-old male with a history of diabetes mellitus II, hepatitis C, and intravenous drug abuse was involved in a rollover motor vehicle accident. He sustained circumferential partial and full-thickness burns to his lower extremities with 20% BSA burns. He ultimately required a below-knee amputation of his right lower extremity due to poor wound healing and nonviability of the soft tissue and foot. Debridement found muscle fibers that were necrotic and purulent. Pathology revealed Mucor species with extensive vascular invasion. This case and discussion highlights the importance of maintaining vigilance for mycotic infections and acting appropriately when there are concerning signs and symptoms of serious wound complications. Caretakers of severe trauma patients should have a high level of suspicion for complications and be cognizant of the American Burn Association's guidelines for systemic inflammatory response syndrome and sepsis. Progressive necrosis outside the confines of the original burn wound should raise concern for impaired wound healing, an immunocompromised state or an underlying infection.


[Weekly Paclitaxel and Cisplatin in the Treatment of Elderly Advanced Non-small Cell Lung Cancer.].
Lung cancer is one of the most common cancers in the world. The number of elderly lung cancer patients is expected to rapidly increase. Therefore, the management of elderly lung cancer patients is becoming a major challenge in the field of oncology. This study was to evaluate the efficacy and safety of weekly paclitaxel (PTX) and cisplatin (DDP) as the first-line chemotherapy on advanced NSCLC patients of more than 70 years old. Fifty chemotherapy-naive patients with advanced NSCLC more than 70 years old were administrated weekly paclitaxel and pisplatin regiment: PTX 80 mg/m(2) intravenous infusion for 1 h, d1, d8 (given routine premedications before PTX), DDP 20 mg/m(2) intravenous infusion, d1, d8, every 21 days. Total 50 patients were enrolled, and 48 patients were evaluable for response. The ORR (overall response rate) was 39.6%; median survival time (MST) was 14.8 months; One year survival rate was 58.3%. Most common adverse events were leucopenia (60%), anemia (62%), nausea and vomiting (30%), alopecia (100%). There were no chemotherapy-related deaths. The patients of advanced NSCLC more than 70 years old can tolerate weekly paclitaxel and cisplatin and can get benefit from this regiment.


PERSISTENT CORNEAL EPITHELIAL DEFECT AFTER PARS PLANA VITRECTOMY.
To investigate the incidence, risk factors, and clinical course of persistent corneal epithelial defects (PCED) after pars plana vitrectomy (PPV). The charts of 426 consecutive patients (511 eyes) who received PPV from January 2008 to December 2011 were reviewed. Corneal complications were defined as the presence of corneal epithelial defects, corneal edema, or superficial punctate keratopathy at least 1 week after vitrectomy. The PCED was defined as corneal epithelial defects lasting longer than 2 weeks after vitrectomy despite conventional treatment. The demographic, preoperative, intraoperative, and postoperative data were compared between PCED and non-PCED corneal complication groups to evaluate the risk factors and clinical outcomes. Postoperative corneal complications developed in 103 of 460 (22.4%) eyes. Diabetes was associated with postoperative corneal epithelial defects (P = 0.021) and superficial punctate keratopathy (P = 0.022) but not corneal edema (P = 0.925). Among 103 eyes with corneal complications, 21 eyes developed PCED. The eyes with PCED had poor final visual acuity, with 23.8% (5/21) of the eyes in the PCED group having visual acuity of 20/200 or better compared with 51.2% (42/82) of the eyes in the non-PCED group (P = 0.024). Logistic regression analysis demonstrated that diabetes mellitus (P = 0.025), use of perfluoropropane (P = 0.001), and assistance of a first-year resident (P = 0.029) were statistically significant risk factors for PCED after PPV. There was also a high incidence of geographic herpes simplex virus epithelial keratitis among recalcitrant PCEDs lasting longer than 4 weeks (36%, 4/11 eyes). The overall incidence of PCED after PPV was 4.8%. Diabetes mellitus, intravitreal tamponade with perfluoropropane, and assistance of a first-year resident were risk factors for PCED after PPV. Persistent corneal epithelial defects after PPV were correlated with poor postoperative visual outcomes. Early and aggressive management is necessary for patients presenting with corneal epithelial defects after vitrectomy to prevent poor outcomes.


Polygenic adaptation and negative selection across traits, years and environments in a long-lived plant species (Pinus pinaster Ait., Pinaceae).
A decade of genetic association studies in multiple organisms suggests that most complex traits are polygenic; that is, they have a genetic architecture determined by numerous loci, each with small effect-size. Thus, determining the degree of polygenicity and its variation across traits, environments and time is crucial to understand the genetic basis of phenotypic variation. We applied multilocus approaches to estimate the degree of polygenicity of fitness-related traits in a long-lived plant (Pinus pinaster Ait., maritime pine) and to analyse this variation across environments and years. We evaluated five categories of fitness-related traits (survival, height, phenology, functional, and biotic-stress response) in a clonal common-garden network planted in contrasted environments (over 20,500 trees). Most of the analysed traits showed evidence of local adaptation based on Qst -Fst comparisons. We further observed a remarkably stable degree of polygenicity, averaging 6% (range of 0%-27%), across traits, environments and years. We detected evidence of negative selection, which could explain, at least partially, the high degree of polygenicity. Because polygenic adaptation can occur rapidly, our results suggest that current predictions on the capacity of natural forest tree populations to adapt to new environments should be revised, especially in the current context of climate change.


Ab Initio Molecular Dynamics of Temporary Anions Using Complex Absorbing Potentials.
Dissociative electron attachment, that is, the cleavage of chemical bonds induced by low-energy electrons, is difficult to model with standard quantum-chemical methods because the involved anions are not bound but subject to autodetachment. We present here a new computational development for simulating the dynamics of temporary anions on complex-valued potential energy surfaces. The imaginary part of these surfaces describes electron loss, whereas the gradient of the real part represents the force on the nuclei. In our method, the forces are computed analytically based on Hartree-Fock theory with a complex absorbing potential. Ab initio molecular dynamics simulations for the temporary anions of dinitrogen, ethylene, chloroethane, and the five mono- to tetrachlorinated ethylenes show qualitative agreement with experiments and offer mechanistic insights into dissociative electron attachments. The results also demonstrate how our method evenhandedly deals with molecules that may undergo dissociation upon electron attachment and those which only undergo autodetachment.


Voice quality changes following phonatory-respiratory effort treatment (LSVT) versus respiratory effort treatment for individuals with Parkinson disease.
Perceptual ratings of hoarseness and breathiness were used to assess the efficacy of two intensive methods for treating dysarthrophonia in individuals with idiopathic Parkinson disease. One method emphasized phonatory-respiratory effort (the Lee Silverman Voice Treatment, LSVT) and the other emphasized respiratory effort alone (RET). Perceptual ratings were performed by two expert listeners based on random order presentation of the patients' pretreatment and posttreatment recordings of the "Rainbow Passage." The listeners were blinded to the patients and their treatment group. Statistically significant pretreatment to posttreatment improvement in hoarseness and breathiness was observed in the LSVT group but not in the RET group. The present findings are consistent with acoustic and physiologic findings reported previously, providing further evidence for the efficacy of the LSVT.


Hemolytic anemias due to hemoglobinopathies.
Hemoglobinopathies responsible for hemolytic anemias may be divided into two groups. The first one corresponds to thalassemias and the second to the presence of a structurally abnormal hemoglobin (Hb). In thalassemia, the primary biochemical abnormality is a quantitative defect in the biosynthesis of one type of Hb chain. This defect leads to an overall deficit of Hb accumulation in the erythrocyte (hypochromia) together with the presence of an excess of the normally synthesized chains. The unpaired subunits which are less soluble than HbA precipitate, bind to the membrane and ultimately lead to hemolysis. In the second group, the hemolytic anemia is a direct consequence of the physicochemical properties of the structurally abnormal Hb. This molecule may polymerize, precipitate or crystallize within the red blood cell (RBC) leading to membrane alterations and to the destruction of the cell. This chapter will emphasize several examples of structurally abnormal Hbs, such as sickle cell disease and congenital Heinz body hemolytic anemia (CHBHA).


Intelligent Defect Diagnosis of Rolling Element Bearings under Variable Operating Conditions Using Convolutional Neural Network and Order Maps.
Vibration analysis is an established method for fault detection and diagnosis of rolling element bearings. However, it is an expert oriented exercise. To relieve the experts, the use of Artificial Intelligence (AI) techniques such as deep neural networks, especially convolutional neural networks (CNN) have gained the attention of researchers because of their image classification and recognition capability. Most researchers convert the vibration signal into representative time frequency vibration images such as spectrograms and scalograms. These images are used as inputs to train the CNN model for fault diagnosis. Commonly, fault diagnosis is performed under same operating conditions, where models are trained and deployed for prediction under the same operating conditions. However, outside the laboratory environment, in real world applications, different operating conditions, such as variable speed, may be encountered. With the change in speed, the characteristic frequencies of the vibration signal will also change, which will result in changing the vibration image. Consequently, the performance of the CNN model may drop significantly for prediction under different operating conditions. Accessing the training data from all potential operating conditions may not be feasible for most real-world applications. Therefore, there is a need to find some signal properties which are invariant to change in operating conditions and only change due to change in health state so that models trained under one set of operating conditions may predict correctly under different operating conditions. This paper proposes a defect diagnosis method for rolling element bearings, under variable operating conditions (speed and load) based on CNN and order maps. These maps exhibit consistent properties under varying speed; therefore, they can be used to train the CNN model for fault diagnosis under variable speed. The effect of load change on these order maps is experimentally studied and it is found that the proposed method can undertake fault diagnosis on rolling element bearings under variable speeds and loads with high accuracy.


Coronary risk factors, diet and vitamins as possible explanatory factors of the Swedish north-south gradient in coronary disease: a comparison between two MONICA centres.
To investigate whether differences in serum lipids, diet, plasma vitamins or other risk factors explain the higher incidence of cardiovascular disease in the northern parts of Sweden, compared to Göteborg on the west coast. A comparison between the two Swedish MONICA populations in northern Sweden (NSW) and in Göteborg (GOT) in 1990. Norrbotten and Västerbotten counties in the north of Sweden and the city of Göteborg on the west coast. In the north 1583 men and women aged 25-64 years were investigated, and in Göteborg 1574 men and women. Plasma vitamins were examined in a subsample of men aged 40-49 (n = 259). Serum lipids, blood pressure, anthropometric measurements, smoking habits, physical activity, diet, education, and plasma vitamins. NSW men and women had mean serum total cholesterol of 6.30 (standard deviation 1.23) mmol L-1 and 6.12 (1. 33) mmol L-1, compared to 5.75 (1.14) mmol L-1 and 5.67 (1.24) mmol L-1 in GOT men and women (P = 0.0001). NSW men and women were shorter and had higher body mass index than in Göteborg. Cigarette smoking was slightly more prevalent amongst GOT men and women. Göteborg men and women more often had more than compulsory school education, compared to NSW men and women, whereas there were no differences in physical activity during leisure time. There were no differences in vegetable consumption, whereas fruit was consumed more frequently by NSW women compared to GOT women, with a higher intake of fibre and ascorbate. Consumption of wine and total alcohol consumption were higher in Göteborg, whereas NSW men and women drank significantly more coffee. In the subsample of men (aged 40-49) who had plasma vitamins measured, men in Göteborg had slightly higher mean retinol concentrations (P = 0.005) and lutein and zeaxanthine levels (P = 0.006 and 0.009, respectively) compared to northern men, but there were no differences with respect to alpha- or beta-carotene, ascorbic acid or lipid-adjusted vitamin E. NSW men had slightly higher plasma iron and magnesium concentrations (P = 0.005 and 0.001, respectively). The largest and most consistent differences between Göteborg and northern Sweden were found for serum cholesterol, probably reflecting differences in intake of saturated fat. The differences in serum cholesterol may explain a substantial part of the differences in coronary heart disease morbidity and mortality. We found no consistent differences concerning vegetable and fruit consumption. More alcohol was consumed in Göteborg. Differences in education and childhood conditions, as reflected in differences in height, may contribute to the north-south gradient with respect to CHD incidence and mortality.


Development of an in vitro potency assay for human skeletal muscle derived cells.
Potency is a quantitative measure of the desired biological function of an advanced therapy medicinal product (ATMP) and is a prerequisite for market approval application (MAA). To assess the potency of human skeletal muscle-derived cells (SMDCs), which are currently investigated in clinical trials for the regeneration of skeletal muscle defects, we evaluated acetylcholinesterase (AChE), which is expressed in skeletal muscle and nervous tissue of all mammals. CD56+ SMDCs were separated from CD56- SMDCs by magnetic activated cell sorting (MACS) and both differentiated in skeletal muscle differentiation medium. AChE activity of in vitro differentiated SMDCs was correlated with CD56 expression, fusion index, cell number, cell doubling numbers, differentiation markers and compared to the clinical efficacy in patients treated with SMDCs against fecal incontinence. CD56- SMDCs did not form multinucleated myotubes and remained low in AChE activity during differentiation. CD56+ SMDCs generated myotubes and increased in AChE activity during differentiation. AChE activity was found to accurately reflect the number of CD56+ SMDCs in culture, their fusion competence, and cell doubling number. In patients with fecal incontinence responding to SMDCs treatment, the improvement of clinical symptoms was positively linked with the AChE activity of the SMDCs injected. AChE activity was found to truly reflect the in vitro differentiation status of SMDCs and to be superior to the mere use of surface markers as it reflects not only the number of myogenic SMDCs in culture but also their fusion competence and population doubling number, thus combining cell quality and quantification of the expected mode of action (MoA) of SMDCs. Moreover, the successful in vitro validation of the assay proves its suitability for routine use. Most convincingly, our results demonstrate a link between clinical efficacy and the AChE activity of the SMDCs preparations used for the treatment of fecal incontinence. Thus, we recommend using AChE activity of in vitro differentiated SMDCs as a potency measure in end stage (phase III) clinical trials using SMDCs for skeletal muscle regeneration and subsequent market approval application (MAA).


Influence of Mass Media on Italian Web Users During the COVID-19 Pandemic: Infodemiological Analysis.
Concurrently with the COVID-19 pandemic, the world has been facing a growing infodemic, which has caused severe damage to economic and health systems and has often compromised the effectiveness of infection containment regulations. Although this infodemic has spread mainly through social media, there are numerous occasions on which mass media outlets have shared dangerous information, giving resonance to statements without a scientific basis. For these reasons, infoveillance and infodemiology methods are increasingly exploited to monitor information traffic on the web and make epidemiological predictions. The purpose of this paper is to estimate the impact of Italian mass media on users' web searches to understand the role of press and television channels in both the infodemic and the interest of Italian netizens in COVID-19. We collected the headlines published from January 2020 to March 2021 containing specific COVID-19-related keywords published on PubMed, Google, the Italian Ministry of Health website, and the most-read newspapers in Italy. We evaluated the percentages of infodemic terms on these platforms. Through Google Trends, we searched for cross-correlations between newspaper headlines and COVID-19-related web searches. Finally, we analyzed the web interest in infodemic content posted on YouTube. During the first wave of COVID-19, the Italian press preferred to draw on infodemic terms (rate of adoption: 1.6%-6.3%) and moderately infodemic terms (rate of adoption: 88%-94%), while scientific sources favored the correct names (rate of adoption: 65%-88%). The correlational analysis showed that the press heavily influenced users in adopting terms to identify the novel coronavirus (cross-correlations of ≥0.74 to ≤0.89, P value <.001; maximum lag=1 day). The use of scientific denominations by the press reached acceptable values only during the third wave (approximately 80%, except for the television services Rai and Mediaset). Web queries about COVID-19 symptoms also appeared to be influenced by the press (best average correlation=0.92, P<.007). Furthermore, web users showed pronounced interest in YouTube videos of an infodemic nature. Finally, the press gave resonance to serious "fake news" on COVID-19, which caused pronounced spikes of interest from web users. Our results suggest that the Italian mass media have played a decisive role in spreading the COVID-19 infodemic and addressing netizens' web interest, thus favoring the adoption of terms that are unsuitable for identifying COVID-19. Therefore, the directors of news channels and newspapers should be more cautious, and government dissemination agencies should exert more control over such news stories.


Reaction rate of vibrationally excited hydroxyl with ozone.
The reaction of vibrationally excited hydroxyl with ozone was studied in a fast-flow system by observing the effect of ozone concentration on the intensity of hydroxyl emission bands in the 1.4-micro to 2.2-micro wavelength region. Fourier transform spectroscopy was used to obtain spectra of the faint emissions from the excited hydroxyl. Rate constants for the ozone-hydroxyl reaction were calculated for vibrational levels nu = 2 to nu = 9. The rate constants increased with vibrational level in a regular manner up to nu = 5. An abrupt increase occurred for nu = 6 relative to nu = 5, which may suggest a change in mechanism beginning at nu = 6.


Enhanced contextual fear memory in central serotonin-deficient mice.
Central serotonin (5-HT) dysregulation contributes to the susceptibility for mental disorders, including depression, anxiety, and posttraumatic stress disorder, and learning and memory deficits. We report that the formation of hippocampus-dependent spatial memory is compromised, but the acquisition and retrieval of contextual fear memory are enhanced, in central 5-HT-deficient mice. Genetic deletion of serotonin in the brain was achieved by inactivating Lmx1b selectively in the raphe nuclei of the brainstem, resulting in a near-complete loss of 5-HT throughout the brain. These 5-HT-deficient mice exhibited no gross abnormality in brain structures and had normal locomotor activity. Spatial learning in the Morris water maze was unaffected, but the retrieval of spatial memory was impaired. In contrast, contextual fear learning and memory induced by foot-shock conditioning was markedly enhanced, but this enhancement could be prevented by intracerebroventricular administration of 5-HT. Foot shock impaired long-term potentiation and facilitated long-term depression in hippocampal slices in WT mice but had no effect in 5-HT-deficient mice. Furthermore, bath application of 5-HT in 5-HT-deficient mice restored foot shock-induced alterations of hippocampal synaptic plasticity. Thus, central 5-HT regulates hippocampus-dependent contextual fear memory, and 5-HT modulation of hippocampal synaptic plasticity may be the underlying mechanism. The enhanced fear memory in 5-HT-deficient mice supports the notion that 5-HT deficiency confers susceptibility to posttraumatic stress disorder in humans.


Visualization of the Static Aspects of Software: A Survey.
Software is usually complex and always intangible. In practice, the development and maintenance processes are time-consuming activities mainly because software complexity is difficult to manage. Graphical visualization of software has the potential to result in a better and faster understanding of its design and functionality, thus saving time and providing valuable information to improve its quality. However, visualizing software is not an easy task because of the huge amount of information comprised in the software. Furthermore, the information content increases significantly once the time dimension to visualize the evolution of the software is taken into account. Human perception of information and cognitive factors must thus be taken into account to improve the understandability of the visualization. In this paper, we survey visualization techniques, both 2D- and 3D-based, representing the static aspects of the software and its evolution. We categorize these techniques according to the issues they focus on, in order to help compare them and identify the most relevant techniques and tools for a given problem.


Infant mandibular distraction in absence of ascending ramus: case series.
Severe microretrognathia with the absence of ascending mandibular ramus is a challenging deformity and treatment must aim to avoid tracheostomy or remove it as soon as possible. Although it is not often reported, mandibular distraction osteogenesis represents a valid treatment option in infants affected by hypoplastic mandible Pruzansky-Kaban type IIb and III. The authors describe 3 cases of infants affected by severe respiratory insufficiency due to congenital mandibular hypoplasia, with follow up ranging from 4 to 8 years. Clinical and technical considerations on treatment choices and outcomes are discussed starting from review of the literature and direct clinical experience. Early mandibular distraction, specifically bidirectional distraction, is an effective and repeatable technique that leads to mandible lengthening with counterclockwise rotation, pogonion projection increase, anteropositioning of the tongue base, and expansion of oropharyngeal volume with positive effect on the respiratory problems of the infant. Even in Treacher Collins patients, known to have a low decannulation rate, all of these elements are essential for effective speech and swallowing therapy and for a subsequent attempt of decannulation.


Centrilobular liver necrosis induced by hypoxia in chronic ethanol-fed rats.
Rats fed ethanol from 21 to 130 days were subjected to one or more episodes of hypoxia (6% O2) in order to determine if ethanol predisposed to centrilobular liver necrosis induced by hypoxia. Pair-fed control rats were fed the diet regimen in parallel with the ethanol-fed rats through an indwelling gastric cannula. The diet and ethanol were fed continuously 24 hr per day so as to maintain high blood alcohol levels in the ethanol-fed rats. Serum enzyme levels, SGOT and SGPT were measured before and after the hypoxic episodes as an indicator of centrilobular necrosis. Animal livers were studied for centrilobular necrosis by light and electron microscopy. Necrosis was documented to be present when flocculent densities were found in hepatocytic mitochondria or the plasma membrane permitted lanthanum entrance into the cell. The results showed that ethanol feeding to maintain high blood alcohol levels did increase the propensity of the liver to undergo centrilobular necrosis when the rats were subjected to hypoxia (1 hr 45 min to 5 hr 30 min). Centrilobular necrosis was observed in the ethanol-fed rats only. Serum enzyme levels (SGPT and SGOT) rose to very high levels in these rats when they were permitted to die of hypoxia. Serum sediment from the ethanol-fed rats contained numerous cell fragments and free organelles. Since the plasma membranes were missing along the sinusoidal face of centrilobular hepatocytes and microbodies were present, it was concluded that the cell fragments in the blood had originated from necrotic hepatocytes.


Cytologic features and differential diagnosis in a case of extraskeletal mesenchymal chondrosarcoma: a case report.
Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon tumor. On fine needle aspiration (FNA) it has to be distinguished from other benign and malignant soft tissue lesions. FNA was done on an 85-year-old man with painful swelling of the forearm. Smears showed fragments comprised of polygonal cells with eccentric nuclei and peripheral fine cytoplasmic vacuoles embedded in a dense, metachromatic matrix. Cell block showed similar cells in a chondromyxoid stroma. The cells were positive for S100 and negative for cytokeratin. FNA is a useful tool in the diagnosis of EMC in conjunction with radiology. A preoperative diagnosis can be made due to its distinct cytologic and immunohistochemical features, obviating the need for a biopsy.


Chestnut Cultivar Identification through the Data Fusion of Sensory Quality and FT-NIR Spectral Data.
The world production of chestnuts has significantly grown in recent decades. Consumer attitudes, increasingly turned towards healthy foods, show a greater interest in chestnuts due to their health benefits. Consequently, it is important to develop reliable methods for the selection of high-quality products, both from a qualitative and sensory point of view. In this study, Castanea spp. fruits from Italy, namely Sweet chestnut cultivar and the Marrone cultivar, were evaluated by an official panel, and the responses for sensory attributes were used to verify the correlation to the near-infrared spectra. Data fusion strategies have been applied to take advantage of the synergistic effect of the information obtained from NIR and sensory analysis. Large nuts, easy pellicle removal, chestnut aroma, and aromatic intensity render Marrone cv fruits suitable for both the fresh market and candying, i.e., marron glacé. Whereas, sweet chestnut samples, due to their characteristics, have the potential to be used for secondary food products, such as jam, mash chestnut, and flour. The research lays the foundations for a superior data fusion approach for chestnut identification in terms of classification sensitivity and specificity, in which sensory and spectral approaches compensate each other's drawbacks, synergistically contributing to an excellent result.


Gender differences in the effect of salinity on aldicarb uptake, elimination, and in vitro metabolism in Japanese medaka, Oryzias latipes.
Toxicity studies have shown that salinity enhances the toxicity of aldicarb to female Japanese medaka. Although previous studies indicated that biotransformation may be important in these effects, other dispositional factors may play a role in this scenario. Male and female medaka were separately acclimated to three salinity regimens: 1.5, 12, and 20 parts per thousand (per thousand) for 2 weeks. The fish were then aqueously exposed to 96 h LC(20) of [(14)C]aldicarb for 24 h. [(14)C]aldicarb equivalents (aldicarb and its metabolites) were measured in whole-fish homogenates of half the fish. The other half of the population was transferred to clean water for 48 h. During this 48 h period, fish were removed and whole animal homogenates were measured radiometrically at 0, 2, 4, 8, 12, and 24 h time points. Salinity did not have an effect on the uptake of aldicarb in either male or female medaka. Elimination data showed that elimination of [(14)C]aldicarb equivalents was biphasic. Salinity did not have an effect on the elimination half life in either males or females. In vitro metabolism using gill and liver microsomes from fish acclimated to three salinity regimens showed that aldicarb sulfoxide production by male gill microsomes increased 6-fold by salinity compared to a 9-fold increase in female gills. In conclusion, the increased sensitivity of female medaka to salinity enhanced toxicity seems to be caused by a higher metabolic activation of aldicarb to the sulfoxide compared to the males. This study supports the hypothesis that the differential expression and regulation of FMOs is an important factor in determining the sensitivity of euryhaline fish to aldicarb, especially at high salinity regimens.


Characterization of hemorrhagic adnexal lesions with MR imaging: blinded reader study.
To assess the performance of published criteria for differentiation of endometriomas from other hemorrhagic adnexal lesions with magnetic resonance (MR) imaging, 74 lesions with pathologic proof in 46 patients were evaluated by means of a 1.5-T system with use of conventional T1-weighted and either T2-weighted spin-echo (SE) or fast SE sequences. The MR images were independently presented to each of three blinded readers, and receiver operating characteristic (ROC) curve analysis was performed. The criterion of a cyst with high signal intensity on short repetition time (TR)/echo time (TE) images and shading on long TR/TE images had a mean sensitivity of 68%, mean specificity of 83%, and mean accuracy of 76% for diagnosis of endometrioma. Ancillary findings previously reported to be suggestive of endometrioma (eg, low-signal-intensity rims, adhesions, bowel tethering, and implants) were proved inaccurate and showed low interobserver agreement. ROC analysis showed similar area measurements among the three radiologists for diagnosis of endometrioma. MR imaging had only moderate accuracy in distinction of endometriomas from other hemorrhagic adnexal lesions.


Gaps in point of care ultrasound provision and the cost of ultrasound equipment provision: results of a nationwide audit of acute medical units.
Advances in ultrasound technology have allowed an investigation previously restricted to the radiology department to be used more liberally in clinical decision making. Point-of-Care-Ultrasound (PoCUS) has superior diagnostic performance to traditional clinical examination across a range of pathologies in the hands of a suitably experienced practitioner. The utilisation of PoCUS has the potential to greatly influence the delivery of acute care, but little is known about the current level of resource provision within the acute medical setting. To establish the availability of ultrasound equipment and appropriately trained clinicians within Acute Medical Units (AMUs) in the United Kingdom (UK) we asked specific questions with an annual day of care survey, undertaken by the Society for Acute Medicine. We compared data across two years to assess interval changes. 58.1% (75/129) of AMUs had access to dedicated ultrasound equipment in SAMBA'19. This represents a small increase from SAMBA'18. Ultrasound expertise is concentrated across a small number of AMUs. Growth in the number of ultrasound trained clinicians is greatest units with established expertise. The equipment to provide PoCUS is not present on all AMUs and appropriately trained clinicians are not distributed evenly across units. This is likely to affect individual AMUs ability to deliver bedside ultrasound to appropriate patients who may benefit. Bridging the gap to ensure all AMUs have the option to use PoCUS will require planning and investment.


Alteration of sulfation of glycoconjugates, but not sulfate transport and intracellular inorganic sulfate content in cystic fibrosis airway epithelial cells.
The secreted and cell surface high molecular weight glyco-conjugates (HMG) generated by primary cultures of airway epithelial cells from cystic fibrosis (CF) patients are oversulfated. To determine whether this abnormality is maintained in transformed CF airway epithelial cells and whether differences in transport or intracellular accumulation of sulfate can explain this alteration, we assessed sulfate metabolism in paired CF and normal cell lines as well as primary cultures of CF and normal cells. Both 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid-inhibitable and -resistant [35S]sulfate efflux and influx were identical for each pair of CF and normal cell lines. Furthermore, cell content of inorganic sulfate was not significantly different in CF and normal cells. However, compared with primary CF cells that oversulfate HMG transformed CF cells oversulfated cell surface HMG but not HMG released into culture medium. Our results suggest that plasma membrane sulfate transport is not altered in CF airway epithelial cells and the abnormal sulfation of HMG may be due to perturbation in intracellular sulfate activation or transfer of activated sulfate to HMG. The relationship of this abnormality to CF transmembrane conductance regulator mutations remains to be determined.


Chloroplast alkaline fructose 1,6-bisphosphatase exists in a membrane-bound form.
An alkaline fructose 1,6-bisphosphatase activity associated with soybean (Glycine max cv Beeson) chloroplasts appears to be membrane-bound. The pH optimum of the membrane-associated activity corresponds to that found for activity associated with the stroma. Illumination of washed thylakoids results in an increase in alkaline fructose 1,6-bisphosphatase activity in the absence of any added stromal factors. Exposure to pH 8.0 results in a partial release of enzyme activity from the membrane. The activation status of the enzyme does not appear to alter its association with the membrane.