Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model.
Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability (HRV) and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective β-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective β1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability (HRV) was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were measured. Measurements were carried out at baseline, at 0 hour after EPI infusion, and at 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in HRV and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the β2-adrenoceptor.


Differential gene expression of activating Fcγ receptor classifies active tuberculosis regardless of human immunodeficiency virus status or ethnicity.
New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased approaches to determine gene signatures in single-site populations. The present study utilized a targeted approach, reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), to validate these genes in a multisite study. We analysed ex vivo whole blood RNA from a total of 523 participants across four sub-Saharan countries (Ethiopia, Malawi, South Africa, and The Gambia) with differences in TB and human immunodeficiency virus (HIV) status. We found a number of genes that were expressed at significantly lower levels in participants with active disease than in those with latent TB infection (LTBI), with restoration following successful TB treatment. The most consistent classifier of active disease was FCGR1A (high-affinity IgG Fc receptor 1 (CD64)), which was the only marker expressed at significantly higher levels in participants with active TB than in those with LTBI before treatment regardless of HIV status or genetic background. This is the first study to identify a biomarker for TB that is not affected by HIV status or geo-genetic differences. These data provide valuable clues for understanding TB pathogenesis, and also provide a proof-of-concept for the use of RT-MLPA in rapid and inexpensive validation of unbiased gene expression findings.


Tertiary initiation of replication in bacteriophage T4. Deletion of the overlapping uvsY promoter/replication origin from the phage genome.
Tertiary initiation of bacteriophage T4 DNA replication is resistant to the RNA polymerase inhibitor rifampicin and apparently involved in the activity of recombination hot spots in the T4 genome (Kreuzer, K. N., and Alberts, B. M. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 3345-3349). One of the origins that function by the tertiary mechanism maps at the promoter for gene uvs Y. A deletion and a linker-insertion mutation in the uvsY promoter/origin region were generated by in vitro manipulations and then placed into the T4 genome using the insertion/substitution system (Selick, H. E., Kreuzer, K. N., and Alberts, B. M. (1988) J. Biol. Chem. 263, 11336-11347). Both resulting phage strains are uvsY- mutants, but they differ in that one has a deletion of the minimal tertiary origin and the other does not. The effects of the uvsY mutations on tertiary origin activity were assayed by infecting tertiary origin plasmid-bearing Escherichia coli with the two phage mutants. The tertiary origin plasmids replicated extensively after infection by either uvsY- phage mutant, demonstrating that the uvsY protein is not required for tertiary initiation. The extent of plasmid replication was increased dramatically as a result of either mutation, indicating that the uvsY protein plays some negative role in either the initiation or subsequent processing of plasmid replicative intermediates. The phage strain with an origin deletion induced the replication of a tertiary origin plasmid with which it shared no homology. Therefore, plasmid-phage recombination is not required for the replication of tertiary origin plasmids. The replication of a tertiary origin plasmid is also shown to be independent of the phage genes uvsX, 59, and 46, but markedly reduced by mutations in the T4-induced topoisomerase.


A Survey-Based Needs Assessment of Barriers to Optimal Sickle Cell Disease Care in the Emergency Department.
Guided by an implementation science framework, this needs assessment identifies institutional-, provider-, and patient-level barriers to care of sickle cell disease (SCD) in the emergency department (ED) to inform future interventions conducted by the multicenter Sickle Cell Disease Implementation Consortium. The consortium developed and implemented a validated needs assessment survey administered to a cross-sectional convenience sample of patients with SCD and ED providers caring for them. In total, 516 adolescents and adults with SCD and 243 ED providers from 7 and 5 regions of the United States, respectively, responded to the ED care delivery for SCD survey. Survey results demonstrated that 84.5% of respondents with SCD have an outpatient provider who treats many patients with SCD. In the ED, 54.3% reported not receiving care fast enough and 46.0% believed physicians did not care about them and believed similarly of nurses (34.9%). Consequently, 48.6% of respondents were "never" or "sometimes" satisfied with their ED care. Of surveyed ED providers, 75.1% were unaware of the National Heart, Lung, and Blood Institute recommendations for vaso-occlusive crises, yet 98.1% were confident in their knowledge about caring for patients with SCD. ED providers identified the following factors as barriers to care administration: opioid epidemic (62.1%), patient behavior (60.9%), crowding (58.0%), concern about addiction (47.3%), and implicit bias (37.0%). The results underscore that many patients with SCD are dissatisfied with their ED care and highlight challenges to optimal care on the practice, provider, and patient levels. Exploring these differences may facilitate improvements in ED care.


THE RECOVERY OF TRANSMISSIVITY IN PASSIVE IRON WIRES AS A MODEL OF RECOVERY PROCESSES IN IRRITABLE LIVING SYSTEMS : PART II.
1. Passive iron (steel) wires, when activated after prolonged immersion in nitric acid of 55 to 90 per cent concentration (volumes per cent of HNO(3), specific gravity 1.42) revert spontaneously to the passive state, after a temporary reaction which is transmitted rapidly over the whole length of wire. The duration of this reaction at any region decreases rapidly with increase in the concentration above a certain critical limit of 52 to 54 per cent. In weaker acid (50 per cent and lower) the reaction continues uninterruptedly until all the metal is dissolved. 2. Immediately after this automatic repassivation the wire fails to transmit activation through more than a short distance (1 to 2 cm.); if left undisturbed in the acid it recovers by degrees its power of transmission (as measured by the distance traveled by an activation wave), at first slowly, then more rapidly; eventually, after an interval varying with the concentration of acid and the temperature, the activation wave is transmitted through an indefinite distance as before. 3. The return of complete transmissivity in 55 per cent acid occupies less than a minute (at 20 degrees ); in stronger acid it is more gradual, requiring in 90 per cent acid 20 minutes or more. This "complete recovery time" is nearly proportional to the excess of concentration of acid above the limiting value of 53 to 54 per cent. 4. In a given solution of acid the rate of recovery exhibits a temperature coefficient closely similar to that of most chemical reactions at this temperature (3-20 degrees ), and also to that of the rate of recovery (refractory period) of irritable living tissues after stimulation (Q(10) = about 3). 5. Two definite phases are distinguishable in the recovery process: (1) the redeposition of the continuous passivating surface layer (of oxide or oxygen compound); and (2) the progressive change of the newly passivated wire from the state of incomplete to that of complete transmissivity. The former phase is of brief duration and is indicated by a sudden change in the electrical potential of the wire, from that of active to that of passive iron; this phase is succeeded by the second and more prolonged period during which the passivating layer undergoes the progressive alteration associated with the recovery of transmissivity. This alteration appears to consist in a progressive thinning of the passivating film until a minimal thickness of (probably 1 molecule) is attained. Further thinning is prevented by local electrochemical oxidation. 6. The phenomena of partial or limited transmission during the second phase of the recovery process show a close correspondence with the phenomena of conduction with decrement in irritable living tissues such as nerve. Other analogies with the behavior of irritable tissues (threshold phenomena, distinction between "local" and "propagated" effects, summation, effects resembling electrotonus) are described.


Differences in concentrations of allergenic pollens and spores at different heights on an agricultural farm in West Bengal, India.
The aim of the study was to assess the vertical profile of the major airborne pollen and spore concentration in the lower heights (up to six meters) and to check their allergenic potential causing respiratory allergy in agricultural workers. The study was conducted using rotorod samplers mounted at different heights at weekly intervals for two consecutive years (November 1997-October 1999). The major pollen grains and fungal spores (from mass culture) were collected in bulk and studied by skin-prick tests to detect allergenicity. Of the recorded pollen, 10 major and perennial types (e.g., Poaceae, Cheno-Amaranthaceae, Cyperaceae, Areca, etc.) were considered for comparative analyses. The tree pollen count showed more or less good correlation with increasing heights, whereas herb/shrub members are dominant at lower heights during all the three seasons (winter, summer and rains). The 10 major and perennial fungal spore types included Aspergilli group, Cladosporium, Nigrospora, etc. The smaller spores were dominant at greater heights and larger spores and conidia were more prevalent at lower levels. The total spore count was higher just after the rainy season during winter. In terms of allergenicity, Saccharum officinarum (sugar cane) of Poaceae, showed highest reactivity (70.58%) in skin test carried out in 189 adult agricultural field workers with respiratory disorders living inside the study area. Among fungal spores, Aspergillus japonicus was the strongest allergen, evoking 74.07% positive reactions. Drechslera oryzae, the pathogen causing brown spot of rice was also found to be a potent allergen.


Childhood trauma and psychotic disorders: a systematic, critical review of the evidence.
There is controversy over whether childhood trauma (CT) is a causal factor in the development of psychosis. This review aims to identify and critically analyze the association between CT and psychotic disorders. Studies investigating CT and psychotic disorder were identified by searches of electronic databases and manual searches of references lists, and 46 studies were identified. Forty studies had no control group, only psychiatric control groups, or unmatched, nonpopulation control groups and thus had methodologies that were inadequate to determine the relationship between CT and psychosis. Six studies used appropriate control groups. Three studies found an association between CT and psychosis, 2 found potentially real associations that failed to reach statistical significance, and 1 found no association, tentatively suggesting a relationship between CT and psychotic disorders. Several methodological problems were found in the studies in the review, including the highest quality studies, which limit the strength of the conclusions that can be drawn from them. These were lack of statistical power, lack of attention to moderating or mediating variables, the way in which CT was measured, and the use of cross-sectional research designs. These problems, some of which may be unavoidable in CT research, suggest the need for new and innovative methodologies in the investigation of CT and psychosis. Directions for further research are explored.


Keratoplasty Outcomes in Patients With Uveitis.
To examine the corneal transplant failure rates and associations with uveitic eye disease. The retrospective chart review identified 70 eyes from 42 patients with uveitis that underwent 40 primary transplants and 30 repeat transplants at 2 major academic centers over a 9-year period. The graft failure rate was calculated. Variables hypothesized to be associated with graft failure were analyzed as covariates using a Cox proportional hazards analysis clustered by the patients to determine their association with failure rates. Of the 70 grafts, the mean duration of follow-up for patients was 40.6 months (range 4-90 months) and the median survival time was 24.1 months (interquartile range of 9-290 months). Twenty-two patients (52%) had graft failure. There was a higher rate of graft failure in patients with infectious uveitis as compared to those with noninfectious uveitis (hazard ratio 2.46, P = 0.031). Patients with successful grafts had their inflammation controlled for a longer period of time before transplantation as compared to those with failed grafts (38.6 vs. 13.6 months, P = 0.004). Worse preoperative visual acuities were significantly associated with graft failure (P < 0.001). There is limited knowledge of corneal transplant outcomes in uveitic patients in the current literature. In our study, over half of the grafts failed. Infectious uveitis (especially viral) was a strong predictor of graft failure. A shorter period of inflammation control before transplantation, previously failed grafts, and worse preoperative visual acuity were also associated with graft failure.


Chronically endurance-trained individuals preserve skeletal muscle mitochondrial gene expression with age but differences within age groups remain.
Maintenance of musculoskeletal function in older adults is critically important for preserving cardiorespiratory function and health span. Aerobic endurance training (ET) improves skeletal muscle metabolic function including age-related declines in muscle mitochondrial function. To further understand the underlying mechanism of enhanced muscle function with ET, we profiled the gene transcription (mRNA levels) patterns by gene array and determined the canonical pathways associated with skeletal muscle aging in a cross-sectional study involving vastus lateralis muscle biopsy samples of four subgroups (young and old, trained, and untrained). We first analyzed the sedentary individuals and then sought to identify the pathways impacted by long-term ET (>4 years) and determined the age effect. We found that skeletal muscle aging in older sedentary adults decreased mitochondrial genes and pathways involved in oxidative phosphorylation while elevating pathways in redox homeostasis. In older adults compared to their younger counterparts who chronically perform ET however, those differences were absent. ET did, however, impact nearly twice as many genes in younger compared to older participants including downregulation of gene transcripts involved in protein ubiquitination and the ERK/MAPK pathways. This study demonstrates that in individuals who are chronically endurance trained, the transcriptional profile is normalized for mitochondrial genes but aging impacts the number of genes that respond to ET including many involved in protein homeostasis and cellular stress.


Rapid Estimation of Tadalafil by Reverse-phase High-performance Liquid Chromatography Method in Bulk and Tablet Formulation.
The simple, selective, precise and accurate reverse-phase high-performance liquid chromatography method was developed and validated for analysis of tadalafil in bulk and tablet dosage form. The column was Inertsil C18 (150×4.6 mm; 5 μm) in isocratic mode. The mobile phase used was phosphate buffer (10 mM, pH 3.2) and acetonitrile (50:50% v/v) at the flow rate of 1.0 ml/min with ultraviolet detection at 295 nm at ambient temperature. The retention time for tadalafil was found to be 4.01 min. Linearity was observed in the concentration range from 60 to 140 μg/ml for tadalafil with a correlation coefficient of (r (2)) 0.9998. The method was validated according to International Conference on Harmonisation guidelines in terms of linearity, accuracy, precision and specificity. Hence, the proposed method can be utilized for routine quality control of tadalafil in bulk and tablet dosage form.


Phenotype analysis of hematopoietic CD34+ cell populations derived from human umbilical cord blood using flow cytometry and cDNA-polymerase chain reaction.
A strategy to phenotype rare populations of hematopoietic cells expressing the cell-surface marker CD34 was studied. The antigenic phenotype of umbilical core blood (CB) CD34+ cells was investigated using flow cytometry and compared with the mRNA-phenotype determined by cDNA-polymerase chain reaction (cDNA-PCR) analysis. The cDNA-PCR method allowed an mRNA evaluation of small numbers of cells. Monoclonal antibodies and oligonucleotide primers that recognize myeloid, lymphoid, erythroid and platelet/megakaryocytic cell membrane antigens or corresponding mRNA transcripts were used. Evaluation by flow cytometry showed that the vast majority of CD34+ CB cells coexpressed CD38, CD18, HLA-DR, and CD33. Rare subpopulations of CD34+CD38-, CD34+CD18-, CD34+HLA-DR-, and CD34+CD33- were also identified. A large proportion of CD34+ CB cells expressed CD13, CD45R, and to a lesser extent CD71. The CD36, CD51, and CD61 antigens were identified on a small number of CD34+ cells. The three-color flow cytometry analysis showed that CD34+ cells stained with antibodies to CD61 and CD36 or CD51 can be divided into subsets that may represent progenitor cells committed to the erythroid and/or megakaryocytic lineage. A variety of other lineage-specific cell-surface antigens including pre-T-cell marker CD7 and markers of early B cells, ie, CD10 and CD19, were not coexpressed with CD34+. Using the cDNA-PCR it was seen that the mRNA phenotype of a small number of sorted CD34+ cells (purity > 98%) was negative for the markers CD2, CD14, CD16, CD20, CD21, CD22, CD41b, and glycophorin A that are expressed on differentiated cells but positive for CD34, CD7, CD19, CD36, and CD61. The results suggest that circulating CD34+CD7+ and CD34+CD19+ CB cells cannot be distinguished by flow cytometry but can be detected by cDNA-PCR. This indicates that CB either contains very low numbers of these progenitors or that the antigen density of CD7 and CD19 on CD34+ cells is below the detection limit of the flow cytometer. In contrast to flow cytometry, cDNA-PCR allows the phenotypic analysis of cells even if their number is small. Thus, the cDNA-PCR method can be useful in linking phenotype analyses, ie, markers of differentiation, to studies on gene expression within rare populations of hematopoietic stem cells.


A partially grouped logrank test.
We propose a modified version of the standard logrank test for survival data in which the first contribution to the statistic is based on grouping of data before a pre-selected grouping time. The grouping is accomplished by artificially constructing the first table based on the product limit estimates of the proportions surviving at the grouping time. Remaining contributions to the statistic are identical to that of the standard logrank statistic. The approach has the advantage of being uninfluenced by non-proportional hazards differences prior to the grouping time while being almost as efficient as the usual logrank test for proportional-hazards alternatives. The statistic is particularly useful for interim monitoring in situations where early difference between treatments are unimportant and/or lagged treatment effects are anticipated. We report simulation studies to verify and investigate the test's properties.


Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension.
Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.


A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K727, K733) with the oxime HI-6 and obidoxime in sarin-poisoned rats and mice.
The ability of two novel bispyridinium oximes K727 and K733 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. To investigate the reactivating efficacy of the oximes, the rats were administered intramuscularly with atropine and oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of sarin at a dose of 24 µg/kg (LD50). The activity of acetylcholinesterase was measured at 60 min after sarin poisoning. The LD50 value of sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of sarin at five different doses. In vivo determined percentage of reactivation of sarin-inhibited rat blood, diaphragm and brain acetylcholinesterase showed that the potency of both novel oximes K727 and K733 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be the most efficient reactivator of sarin-inhibited acetylcholinesterase. While the oxime HI-6 was able to reduce the acute toxicity of sarin >3 times, both novel oximes and obidoxime decreased the acute toxicity of sarin <2 times. Based on the results, we can conclude that the reactivating and therapeutic efficacy of both novel oximes K727 and K733 is significantly lower compared to the oxime HI-6 and, therefore, they are not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute sarin poisoning.


Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity.
Ferulic acid, a bacterial metabolite of anthocyanins, seems likely to be a primary mediator of the health benefits associated with anthocyanin-rich diets, and has long been employed in Chinese cardiovascular medicine. In rodent studies, it has exerted wide-ranging antioxidant and anti-inflammatory effects, the molecular basis of which remains rather obscure. However, recent studies indicate that physiologically relevant concentrations of ferulic acid can boost expression of Sirt1 at mRNA and protein levels in a range of tissues. Sirt1, a class III deacetylase, functions to detect a paucity of oxidisable substrate, and in response works in various ways to promote cellular survival and healthful longevity. Sirt1 promotes 'cell cleansing' and cell survival by boosting autophagy, mitophagy, mitochondrial biogenesis, phase 2 induction of antioxidant enzymes via Nrf2, and DNA repair-while inhibiting NF-kB-driven inflammation, apoptosis, and cellular senescence, and boosting endothelial expression of the protective transcription factor kruppel-like factor 2. A deficit of the latter appears to mediate the endothelial toxicity of the SARS-CoV-2 spike protein. Ferulic acid also enhances the activation of AMP-activated kinase (AMPK) by increasing expression and activity of its activating kinase LKB1-whereas AMPK in turn amplifies Sirt1 activity by promoting induction of nicotinamide phosphoribosyltranferase, rate-limiting for generation of Sirt1's obligate substrate NAD+. Curiously, AMPK acts by independent mechanisms to potentiate many of the effects mediated by Sirt1. Hence, it is proposed that ferulic acid may exert complementary or synergistic health-promoting effects when used in conjunction with clinically useful AMPK activators, such as the nutraceutical berberine. Additional nutraceuticals which might have potential for amplifying certain protective effects of ferulic acid/berberine are also discussed.


Life in the slow lane revisited: ontogenetic separation between chimpanzees and humans.
This study investigates the evolution of human growth by analyzing differences in body mass growth trajectories among three populations: the Ache of eastern Paraguay, the US (NHANES, 1999-2000), and captive chimpanzees. The relative growth statistic "A" from the mammalian growth law is allowed to vary with age and proves useful for comparing growth across different ages, populations, and species. We demonstrate ontogenetic separation between chimpanzees and humans, and show that interspecific differences are robust to variable environmental conditions. The human pattern of slow growth during the lengthened period from weaning to the beginning of the adolescent growth spurt is found among the Ache (low energy availability and high disease load) and also in the US (high energy availability and low disease load). The human growth pattern contrasts with that of the chimpanzee, where absolute growth rates and relative "A" values are faster and less prolonged. We suggest that selection has acted to decrease human growth rates to allow more time for increased cognitive development with lower body-maintenance costs.


Patients and carers' perspectives of participating in a pilot tailored exercise program during chemoradiotherapy for high grade glioma: A qualitative study.
To describe glioblastoma patients' and carers' perspectives of participating in a tailored exercise intervention during chemoradiotherapy. A pilot study was conducted to evaluate if exercise was a feasible and safe therapy in patients with glioblastoma undergoing chemoradiotherapy. Patients received a supervised exercise intervention involving an individualised prescription of moderate-intensity aerobic and resistance exercise twice weekly, performed at the hospital when they attended for treatment. Semi-structured interviews were conducted with participants and their carers. Recordings were analysed using thematic analysis. 19 patients and 15 carers participated. Benefits and challenges of participating in the exercise intervention were described. Benefits included an individually tailored exercise program, improvements in health, regaining a sense of control, interacting with people, keeping active and benefits for carers. Challenges included managing symptoms associated with diagnosis and treatment, juggling treatment and exercise, and difficulties engaging in the program. Patients and carers expressed positive perceptions and experiences of participating in exercise during chemoradiotherapy; however, some challenges were experienced. These results support the quantitative pilot study which demonstrated that supervised exercise is feasible, safe and well tolerated by patients receiving chemoradiotherapy for glioblastoma. Randomised controlled trials now need to be conducted with this population.


Insulin hypoglycemia and growth hormone secretion in sheep: a paradox revisited.
Although insulin-induced hypoglycemia is a potent stimulus for growth hormone (GH) secretion in humans, hypoglycemia was reported to suppress GH in sheep. We investigated whether GH suppression in sheep during insulin hypoglycemia resulted from the dose of insulin administered or the fed state of the animal. Saline or insulin (0.05, 0.2, 1.0, or 5.0 U/kg) intravenous boluses were administered to eight fasted ewes in a crossover experiment. In another experiment, four sheep were fed 2 h before intravenous administrations of either 0.2 or 5 U/kg of insulin. All doses of insulin resulted in comparable hypoglycemia, although the duration of hypoglycemia increased directly with insulin dose. Hypoglycemia in fasted animals stimulated GH secretion. The GH rise above baseline was inversely related to the insulin dose, and the insulin doses of 1 and 5 U/kg resulted in late suppression of GH below baseline concentrations. Insulin administration to fed animals caused an identical degree of hypoglycemia but no increase in GH. Insulin-hypoglycemia stimulates GH secretion in sheep in a manner similar to humans, and the response is dependent on both fed state and insulin dose.


Free-hand placement of high thoracic pedicle screws with the aid of fluoroscopy: evaluation of positioning by CT scans in a four-year consecutive series.
To evaluate the feasibility, safety and accuracy of pedicle screw placement in the upper thoracic spine using the free-hand technique with the aid of fluoroscopy; to analyze the methods used to verify correct screw positioning intra and postoperatively. All patients with instability of the cervicothoracic or upper thoracic spine and at least one screw placed in the segment T1-T6 as part of a posterior construct entered the study. Only C-arm intraoperative fluoroscopy was used to guide screw placement. We obtained excellent positioning in 98.07% of the screws. CT scans precisely demonstrated pedicle wall and anterolateral body violations. There was no hardware failure, no neurological or vascular injury and no loss of alignment during the follow-up period. Pedicle screws can be safely placed in the upper thoracic spine when strict technical principles are followed. Only a CT scan can precisely demonstrate vertebral body and medial pedicle cortical violations.


Cardiorespiratory health, reaction time and aging.
Visual simple and choice reaction time (RT) tests were administered to 64 male and female volunteers 23 to 59 years of age. One half of the subjects were runners involved in rigorous training programs averaging 42 miles per week. The other half of the subjects were sedentary adults. Eighty simple and 100 choice reaction time trials were given with a variable foreperiod ranging from 400 to 1100 msec. Five catch trials were given in both simple and choice reaction time conditions. The results indicated that there was a gradual decline in RT performance as age increased. However, this trend was not evident in the trained group. Reaction time remained constant with age within the trained group. It was concluded that a high state of cardiorespiratory training may prevent cognitive decrements in performance with age.


Estimation of apparent agonist affinity constants using desensitization of the ileal muscarinic receptor.
The effects of short-term desensitization of muscarinic receptors and decreasing the extracellular calcium concentration have been studied using the isolated guinea pig ileum. Desensitization required stimulation of the receptor and was more marked against agonists of low intrinsic efficacy. The process was non-specific in that the responses to histamine were also affected. Application of null methods of analysis to pre- and postdesensitization concentration-response curves enabled an affinity constant to be derived. The values were consistently higher than those estimated using the irreversible antagonist, phenoxybenzamine. In contrast application of null methods to concentration-response curves in normal and low calcium concentrations enabled an affinity constant for pilocarpine to be calculated, which was very similar to that obtained using the irreversible antagonist. It is concluded that desensitization cannot be used to determine agonist affinity constants inasmuch as it results in overestimations.


BarleyBase--an expression profiling database for plant genomics.
BarleyBase (BB) (www.barleybase.org) is an online database for plant microarrays with integrated tools for data visualization and statistical analysis. BB houses raw and normalized expression data from the two publicly available Affymetrix genome arrays, Barley1 and Arabidopsis ATH1 with plans to include the new Affymetrix 61K wheat, maize, soybean and rice arrays, as they become available. BB contains a broad set of query and display options at all data levels, ranging from experiments to individual hybridizations to probe sets down to individual probes. Users can perform cross-experiment queries on probe sets based on observed expression profiles and/or based on known biological information. Probe set queries are integrated with visualization and analysis tools such as the R statistical toolbox, data filters and a large variety of plot types. Controlled vocabularies for gene and plant ontologies, as well as interconnecting links to physical or genetic map and other genomic data in PlantGDB, Gramene and GrainGenes, allow users to perform EST alignments and gene function prediction using Barley1 exemplar sequences, thus, enhancing cross-species comparison.


An audit of trauma laparotomy in children and adolescents highlights the role of damage control surgery and the need for a trauma systems approach to injury in this vulnerable population.
This study reviews the indications and outcome of emergency laparotomy for paediatric trauma in a South African trauma centre. This was a retrospective study of all children less than 18 years of age who underwent an emergency laparotomy for trauma between December 2012 and October 2020 at Grey's Hospital in Pietermaritzburg. During the eight-year period under review, a total of 136 children of which 107 were male underwent a laparotomy for trauma. The median age was 14 years. There were 80 (57.1%) blunt mechanisms, and the rest were penetrating mechanisms. A total of 46 (33%) patients required ICU admission. Thirty-four patients developed a complication. These included nine cases of pneumonia, one case of renal failure, two patients developed abdominal collections, three woundrelated complications, three neurological complications and one miscellaneous complication. There were seven (5%) deaths. The penetrating cohort were older than the blunt cohort. Solid viscera were more likely to be injured in the blunt cohort and hollow viscera more likely in the penetrating cohort. A total of 16 (11%) patients underwent damage control surgery (DCS). Of this cohort, there were three female children. Six sustained blunt trauma and ten penetrating trauma. A total of six (37%) of these children died. Emergency laparotomy for trauma in children is not infrequent in Pietermaritzburg and there is a high incidence of penetrating trauma in this cohort. The response to increased degrees of physiological derangement is the application of DCS. Ongoing efforts to develop and strengthen a paediatric trauma service appear to be justified.


Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation.
Hydrogen peroxide produces concentration-dependent relaxation of precontracted isolated bovine intrapulmonary arterial rings by a mechanism which is independent of the endothelium or prostaglandin mediators. Relaxant responses to hydrogen peroxide concentrations of up to 100 microM were markedly attenuated by the inhibitor of soluble guanylate cyclase activation, methylene blue (10 microM). Micromolar concentrations of hydrogen peroxide elicit time- and concentration-dependent increase in arterial levels of guanosine 3',5'-cyclic monophosphate that are associated with decreases in force. Soluble guanylate cyclase activity is markedly activated by enzymatically generated hydrogen peroxide in a manner that is most closely associated with the concentration of catalase present in the assay, by a mechanism that is inhibited by superoxide anion and the inactivation of catalase. Our data are most consistent with the involvement of compound I, a species of catalase formed during the metabolism of peroxide, in the mechanism of guanylate cyclase activation. The nature of this mechanism of arterial relaxation suggests that it could contribute to the regulation of pulmonary vascular tone by oxygen tension.


Arteriovenous malformations in elderly patients.
This article discusses the presentation, natural history, and management of arteriovenous malformations (AVMs) in elderly patients, based on our experience at the Dartmouth-Hitchcock Medical Center. We also present a review of the literature. In our series of 50 patients with AVMs who were operated on by one surgeon, six patients were 65 years old or older at the time of presentation. All six patients presented with intracerebral hemorrhage, and one patient had developed a seizure disorder 2 months before hemorrhaging. In three patients, the clinical course was consistent with the occurrence of two hemorrhages within a 48-hour period. The patients' preoperative neurological status varied from intact to moribund. In two patients, the diagnosis of AVM was made intraoperatively. Preoperative angiography revealed the diagnosis in the remaining patients. All the patients underwent surgical excision of their AVMs. Despite concurrent medical illnesses, all patients tolerated the procedure well with no new, persistent neurological deficits. At follow-up, all patients showed sufficient neurological recovery to return to the community and four of the patients were neurologically intact. Based on this experience and a review of the literature, we conclude that AVMs in elderly patients are not benign lesions and that surgical excision should be considered among the management options for these patients.


Debilitating erosive lichenoid interface dermatitis from checkpoint inhibitor therapy.
As the list of anti-tumor immunotherapy agents and the list of cancers treated by these novel agents grow, a subset of patients are experiencing immune-related adverse events as a result of prolonged stimulation of the immune system. Many different immune related adverse events including colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, and cutaneous reactions can result from blocking these inhibitory pathways. The full spectrum of cutaneous immune related adverse events secondary to checkpoint inhibitor therapy is still being defined. The reported varied presentations include lichenoid reactions and bullous pemphigoid, amongst others. We present a severe cutaneous reaction, a case of debilitating erosive lichenoid dermatitis. This case emphasizes both the wide range of possible cutaneous reactions and the potential severity of these reactions.


Global Surgery: Could systems thinking be the key to success?
Surgery and anaesthesia care is progressively making its way into the Global Public Health arena, which was d omi na ted by ma ter nal an d c hild h e al th an d communicable diseases in low-and middle-income countries (LMICs). Global Surgery (GS) could potentially make an impact on survival and quality of life in all age groups for a variety of disease conditions. After success in highlighting knowledge, policy and advocacy gaps, Global Surgery is transitioning from problem identification to designing and implementing solutions. A shared vision will lay out priorities to achieve the common goal of providing safe and affordable surgical and anaesthesia care in under-developed and developing countries. A systematic thinking approach could amplify the impact of such efforts by highlighting the bigger picture, enabling Global Surgery leaders in such countries to build multidisciplinary coalitions and utilise crosslevel interactions between Global Surgery and other initiatives.


Changes in basal body temperature and simple reaction times during the menstrual cycle.
Previous studies have shown cyclic changes in the activation levels and performance of different tasks throughout the menstrual cycle. The aim of this study was to examine if changes in the reaction time to both light and sound stimuli may be associated with basal body temperature changes and subjective assessments of General and High Activation during the different phases of a menstrual cycle characterized by high (preovulatory and midluteal phase) and low (menstrual and early follicular phase) levels of oestrogen and progesterone. The study included measurements of basal body temperature, simple reaction times to light and sound and self-assessment of General and High Activation during the menstrual, early follicular, late follicular and luteal phase. The sample consisted of 19 female subjects with regular menstrual cycles. The results obtained in this study indicate lower basal body temperature values during phases with low sex hormone levels, while the activation assessments suggest stable levels of both General and High Activation throughout the menstrual cycle. Similar patterns of change have been shown for reaction times in visual and auditory sensory modalities. Reaction times were shorter during phases characterized by high sex hormone levels, while phases with low hormone levels were associated with longer reaction times. From the modified text on correlations in the data analysis section, it is evident that they were calculated from averaged data from all phases of the menstrual cycle. Therefore, they do not reflect intraindividual but rather interindividual variations between the observed variables, and are not related to the hypotheses of this paper.


Neuroprotective effects of liquiritin on cognitive deficits induced by soluble amyloid-β1-42 oligomers injected into the hippocampus.
This study assessed the modulating effects of liquiritin against cognitive deficits, oxidative damage, and neuronal apoptosis induced by subsequent bilateral intrahippocampal injections of aggregated amyloid-β1-42 (Aβ1-42). This study also explored the molecular mechanisms underlying the above phenomena. Liquiritin was orally administered to rats with Aβ1-42-induced cognitive deficits for 2 weeks. The protective effects of liquiritin on the learning and memory impairment induced by Aβ1-42 were examined in vivo by using Morris water maze. The rats were then euthanized for further studies. The antioxidant activities of liquiritin in the hippocampus of the rats were investigated by biochemical and immunohistochemical methods. The apoptosis of the neurons was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. Liquiritin at doses of 50-100 mg/kg significantly improved the cognitive ability, restored the abnormal activities of glutathione peroxidase and superoxide dismutase, and decreased the levels of malondialdehyde,8-hydroxy-2'-deoxyguanosine and protein carbonyl in the hippocampus of rats with Alzheimer's disease. Moreover, neural apoptosis in the hippocampus of Aβ1-42-treated rats was reversed by liquiritin. Liquiritin can significantly ameliorate Aβ1-42-induced spatial learning and memory impairment by inhibiting oxidative stress and neural apoptosis.


[Difficulties in the management of precarious patients and precarious migrants].
General practitioners encounter difficulties in the management of patients in precarious situations. In order to identify and understand these difficulties, a survey combining both quantitative et qualitative approaches was conducted among general practitioners of the Meurthe-et-Moselle department. Quantitative data were collected by self-administered questionnaires sent to all 856 general practitioners and 28 general practitioners grouped by geographic sector participated in 6 focus groups. Among the 46.5% of respondents, 92.5% doctors declared that they encountered difficulties in the management of precarious patients. 87.5% declared that they had an average or insufficient knowledge of the existing medical social organizations on their territory and two-thirds were interested in specific training. Analysis of the interviews showed that experience facilitates multidisciplinary networking, a good relationship with patients and ultimately their monitoring. Financial access to care is a major obstacle, which doctors consider to be a political issue. Ideas for improvement were proposed in response to the obstacles related to the characteristics of the medical consultation itself. Confirming the results of the questionnaire survey, training appeared to be essential to identify vulnerability and facilitate the doctor-patient relationship. We showed that the difficulties experienced by physicians contributes to socio-cultural inequalities in access to health care. Patient support, an enhanced self image and social ties were identified as major determinants of access to health. The development of training of physicians and multidisciplinary structures should be encouraged.


Direct Access Dental Hygienists' Perceptions Concerning Geriatric Curriculum in Entry-Level Dental Hygiene Programs.
Purpose: The growing geriatric population has unique and often complex oral health care needs. The purpose of this study was to explore the perceptions regarding direct access dental hygienists (DH) regarding the geriatric curriculum needed in dental hygiene education programs to prepare DHs to provide direct access care for geriatric populations.Methods: Purposive and network sampling strategies were used to recruit eligible direct access DHs from across the United States for this qualitative study. Semi-structured telephone interviews were conducted until was met. Demographic data were analyzed using descriptive statistics. Open coding techniques were used to identify themes.Results: Ten direct access DHs agreed to participate. Nine themes emerged from the data analysis: combining didactic and hands-on experience, how direct access differs from traditional practice, importance of a standardized course in entry-level programs, need for a specialty course in geriatrics, understanding the geriatric patient, understanding direct access settings, modifications to treatment modalities, process of care, and interprofessional knowledge. Participants indicated that entry-level dental hygiene students should be exposed to hands-on clinical rotations, have a standardized aging and geriatrics course, and potentially incorporate geriatrics as a specialty tract within dental hygiene programs.Conclusion: Geriatrics may not be covered in sufficient depth to prepare entry-level dental hygiene students for work with these populations in direct access settings. Findings from this study may be used to support improvements in geriatric curriculum for entry-level dental hygiene programs. Future research is needed to determine necessary focus and most effective way to disseminate this curricular content.


A new biological membrane for pericardial closure.
In an attempt to develop a new and better biological membrane for the pericardium, we evaluated the use of glutaraldehyde treated human amniotic membrane (AM) and compared it to polytetraflouroethylene (PTFE) membrane as a pericardial substitute. Four dogs underwent a right thoracotomy. Two 4 x 3-cm portions of pericardium, 3-4 cm apart, were excised in each animal and both sites replaced with a similar sized patch of 0.8% glutaraldehyde-treated AM and 0.2-mm PTFE membrane respectively. The AM was sutured to the pericardial defect with its smooth surface facing the epicardium. After 18 weeks, the materials were evaluated. The AM patches revealed minimal extrapericardial and no epicardial adhesion. The PTFE patches had moderate to severe epicardial adhesions and severe extrapericardial adhesions. Histopathological examination of AM patches revealed that the integrity of the AM was preserved, however, neovascularization and slight lymphocytic infiltration were observed. In the PTFE patches, there were severe inflammatory infiltration and fibroblast proliferation into both surfaces. AM patches by virtue of their low immunogenicity evoke very minimal host to graft reaction. These AM grafts, however, tear easily unless carefully sutured. Improved methods of treatment may improve suturing strength. We conclude that AM performs satisfactorily and is superior to PTFE as a pericardial substitute.


Aldehyde Dehydrogenase Enzyme Functions in Acute Leukemia Stem Cells.
The enzymes that belong to the aldehyde dehydrogenase family are expressed in a variety of cells; yet activity of their main members characterizes stem cells, both normal and malignant. Several members of this family perform critical functions in stem cells, in general, and a few have been shown to have key roles in malignant tumors and their recurrence. In particular, ALDH1A1, which localizes to the cytosol and the nucleus, is an enzyme critical in cancer stem cells. In acute myeloid leukemia (AML), ALDH1A1 protects leukemia-initiating cells from a number of antineoplastic agents, and proves vital for the establishment of human AML xenografts in mice. ALDH2, which is located in mitochondria, has a major role in alcohol metabolism by clearing ethanol-derived acetaldehyde. Haematopoietic stem cells require ALDH2 for protection against acetaldehyde, which can cause damage to DNA, leading to insertions, deletions, chromosomal rearrangements, and translocations. Mutations compromise stem cell function, and thereby threaten blood homeostasis. We review here the potential of targeting the enzymatic activity of aldehyde dehydrogenases in acute leukemia.


Metal-Catalyzed Domino Synthesis of Benzophenanthridines and 6 H-Naphtho[2,3- c]-chromenes.
A new and efficient synthesis of tetracyclic phenanthridines and benzo[ c]chromenes has been described involving a metal-mediated two-step domino strategy. The first step involved efficient palladium-catalyzed domino carbopalladation/cross coupling, and the second step involved iron-catalyzed domino isomerization/cyclodehydration. The important features of this strategy include high yields, generality, wide substrate scope, and broad functional group tolerance. A plausible mechanism has been proposed to explain the formation of the product.


Presentation characteristics and clinical outcome of patients with giant cell arteritis followed by a single center.
Giant cell arteritis (GCA) is a large vessel vasculitis that may cause significant morbidity in the elderly population. We aimed to evaluate presentation characteristics, treatment, and outcome in a cohort of patients with GCA diagnosed and followed in a single center. A retrospective chart review revealed 84 (41 M/43 F) registered patients diagnosed with GCA between 1990 and 2020. Clinical features at presentation and follow-up, radiographical imaging, temporal artery biopsy (TAB), and laboratory findings were retrieved from digital medical records or hard-copy patient files. Of these, 33 patients' follow-up period was less than 12 months; hence, relapses and treatment outcomes were examined in the remaining 51 (60.5%) patients. A total of 84 patients were included in the cohort. The mean age at diagnosis was 68.4 ± 7.9 years (range: 49-85). At presentation, 60 (71.4%) patients had headache, 22 (26.2%) had symptoms compatible with polymyalgia rheumatica (PMR), and 23 (27.4%) had visual loss. Three (3.6%) patients had solid organ malignancies while two had hematologic malignancies (2.4%) before GCA diagnosis. TAB was obtained in 63 (75%) patients, in 47 of whom (74.6%) the pathological findings were consistent with GCA. A PET/ CT scan has been performed before glucocorticoids (GCs) initiation in 43 (51.2%) patients and of these, 37 (86.0%) revealed uptake consistent with large vessel involvement. The median follow-up time of the 51 patients was 3.7 (IQR: 1.8-6.8) years. GCs were started promptly after the diagnosis. During the follow-up period, 28 (54.9%) patients experienced a relapse. Thirty-nine (78%) patients were under GC treatment, with a mean dosage of 4.8 ± 2.8 g/day at the final visit. At the final visit, 20.3% (17:84) had died whereas 9.8% (5:51) had permanent vision loss. Treatment of GCA is challenging. GCA causes serious morbidities and increased mortality. PET/CT is highly effective in detecting large vessel vasculitis in GCA and could perhaps replace TAB in the future.


A study of regulatory policies and relevant issues concerning electronic cigarette use in Taiwan.
Recent technological innovations have increased the amount of tobacco products available to smokers. In particular, electronic cigarettes, sometimes call e-cigarettes, have received substantial attention as their sales have rapidly increased. Electronic cigarettes were invented in China and now have become prevalent worldwide. Electronic cigarettes can be considered fashionable and come in numerous flavors; accordingly, many young adults and students have begun to use e-cigarettes. However, like traditional tobacco products, e-cigarettes have negative influences on human health. After e-cigarettes were introduced into Taiwan, they have not been effectively managed and regulated because of insufficient supporting measures. Related legislation in developed countries can serve as a reference for Taiwan. For this study, the development of e-cigarettes is described and a theoretical analysis was performed from the administration and legal perspectives. In addition to clarifying related problems and offering measures to prevent students from using e-cigarettes, we propose suggestions to help governments improve their strategies to protect students' health.


Alterations in the basement membrane (heparan sulfate) proteoglycan in diabetic mice.
We have grown the EHS (Engelbreth-Holm, Swarm) tumor in normal and genetically diabetic mice (db/db) and measured some components of basement membrane produced in the tumor. These studies showed similar amounts of total protein in control and diabetic tissue and similar patterns of proteins on SDS gel electrophoresis of extracts of the tissue. Laminin, a basement membrane specific glycoprotein utilized as an attachment factor by epithelial cells, was present in increased amounts in diabetic tissue. In contrast, the amount of BM-1 (heparan sulfate) proteoglycan was reduced. Less 35S-sulfate was incorporated into this proteoglycan, and the proteoglycan, but not its component glycosaminoglycans, was heterogeneous in size. The data indicate that either the synthesis of proteoglycan was decreased or its degradation was increased in diabetic tissue. Since the heparan sulfate proteoglycan serves to block the passage of anionic macromolecules through the basement membrane, decreased levels could account for the increased porosity of diabetic basement membrane. Compensatory synthesis of the basement membrane components to restore normal permeability could account for the thickened basement membranes observed in diabetes.


Matricryptins derived from collagens and proteoglycans.
Controlled proteolysis of extracellular matrix components releases bioactive fragments or unmasks cryptic sites that play key roles in controlling various physio-pathological processes including angiogenesis, tissue remodeling, wound healing, inflammation, tumor growth, and metastasis. We review here the structure and mechanisms of release of i) the proteolytic fragments (matricryptins) cleaved from collagens, proteoglycans and glycosaminoglycans, and ii) the matricryptic sites existing in these molecules. The cell surface receptors and the signaling pathways they trigger to exert their biological activities is discussed with the major physio-pathological processes they control. Their involvement in autoimmune and inherited diseases is reported. Most matricryptins issued from collagens, proteoglycans and glycosaminoglycans exhibit anti-angiogenic and anti-tumor properties and their use as potential drugs and as potential disease markers is discussed. Perspectives for identifying the common structural features, if any, of the matricryptins and their use in combination with chemotherapy and radiotherapy in the treatment of cancer are presented.


The dentition in the osteogenesis imperfecta syndromes.
The deciduous and permanent teeth in some patients with osteogenesis imperfecta syndromes are blue or brown and opalescent. As shown by radiologic examination, the pulp chambers and root canals are completely or partially obliterated by abnormal dentin. The junctions between the crowns and roots are more constricted than normal. Deciduous opalescent teeth lose their enamel readily and wear more easily than normal. Unusual wear does not occur as frequently in permanent opalescent teeth as in deciduous teeth. No relationship has been shown between the number of fractures or deformity and the degree to which the teeth are affected. In contrast, other patients with osteogenesis imperfecta have normal teeth. These clinical differences in the dentitions support the concept of genetic heterogeneity is osteogenesis imperfecta and provide information useful in genetic counseling. The differential diagnosis of opalescent teeth in osteogenesis imperfecta is not difficult provided that detailed clinical and radiologic examinations of the dentition are performed. Patients with osteogenesis imperfecta and opalescent teeth should be evaluated as soon as the deciduous teeth erupt, so that an attempt can be made to prevent loss of tooth structure. However, methods of dental care in osteogenesis imperfecta are not well delineated and deserve further study.


Emerging novel coronavirus (2019-nCoV)-current scenario, evolutionary perspective based on genome analysis and recent developments.
Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade's first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as 'Public Health Emergency of International Concern' on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.


Dietary modification of yolk lipid with menhaden oil.
Due to the numerous proposed cardiovascular benefits associated with consumption of omega-3 fatty acids, marketing of an egg enriched by omega-3 fatty acid may benefit the egg producer. Effects on yolk composition of a standard laying hen diet enriched with 3% menhaden oil (test diet), versus an isocaloric (control) diet containing no added fat, were evaluated for 18 wk. Dietary menhaden oil did not alter egg production, egg weight, total yolk fat, or yolk cholesterol. However, yolk contents of omega-6 and omega-3 fatty acids were influenced by diet. Arachidonic acid decreased and eicosapentaenoic acid increased in eggs from hens fed the test diet following 1 wk of dietary treatment. Docosahexaenoic acid and linolenate increased in eggs from hens fed the test diet at 2 and 3 wk of the trial, respectively. These alterations in yolk composition resulted in a decrease in the ratio of omega-6 to omega-3 fatty acids from 18 for eggs from hens fed the control diet to 3 for eggs from hens fed the test diet. At Weeks 14 and 18, hens (n = 10 per diet) were killed and necropsied. No change in gross scoring of hepatic lipidosis was observed. Histologically, significantly greater scores for hepatocellular lipid infiltration were recorded for liver sections from hens fed menhaden oil than for control hens. Increased microscopic hepatic lipid infiltration observed with dietary omega-3 administration may have significance for flocks predisposed to fatty liver syndrome and may also provide a unique system in which to study the effects of dietary omega-3 fatty acids on liver lipid metabolism.


Is iron status associated with highly unsaturated fatty acid status among Canadian Arctic Inuit?
Impaired fatty acid synthesis was noted in iron deficient animal models. Human data, however, are scarce. Although Canadian Inuit have a traditional diet rich in heme iron and long chain n-3 fatty acids, recent literature has also indicated the presence of prevalent iron deficiency. We aimed to explore whether the presence of iron deficiency would affect fatty acid status and an estimate of the activity of desaturase 5 (Δ5), which is crucial in the biosynthesis of highly unsaturated n-3 fatty acids among Canadian Inuit. Erythrocyte membrane fatty acid composition was utilized as an indicator of fatty acid status and serum ferritin and circulating hemoglobin level were measured as the indicators of iron status. Data analyzed were collected among 1511 Canadian Inuit adult participants in the International Polar Year Inuit Health Survey, 2007-2008. Only 13.7% of survey participants had iron deficiency; however, serum ferritin showed a moderate positive association with highly unsaturated n-3 fatty acids after adjusting for age, waist and C-reactive protein (r = 0.172, P < .0001). Serum ferritin correlated significantly with Δ5 after further adjusting for highly unsaturated n-3 fatty acids (r = 0.126, P < .0001). Although the current study only demonstrated a weak link between ferritin and Δ5, the latter association underscores a possible health risk caused by a nutrient interaction related to reduced iron intake and decreased highly unsaturated n-3 fatty acid biosynthesis. Future studies are recommended to evaluate iron status in relation to highly unsaturated n-3 fatty acid biosynthesis and status among indigenous people undergoing rapid dietary transitions.


Effect of dietary energy level and oil source on broiler performance and response to an inflammatory challenge.
Broiler chicks were fed one of five diets from 3 d of age: a low energy diet containing 7% cellulose (ME 2,714 kcal/kg), or high energy diets containing approximately 7% of either tallow, corn oil, safflower oil, or fish oil (each 3,302 kcal/kg). Half of the chicks were injected intra-abdominally with Salmonella typhimurium lipopolysaccharide (LPS) on Day 11, sephadex on Day 13, and Freund's complete adjuvant on Day 15; samples were collected on Day 16. The uninjected chicks served as controls. In a second experiment, 3-d-old chicks were fed one of eight isocaloric diets containing tallow as the sole supplemental fat source, or tallow plus either 2% corn oil, 1, 1.5, or 2% fish oil, or fish meal at an amount to provide 1, 1.5 or 2% supplemental oil. Half of the chicks were injected intra-abdominally with S. typhimurium LPS on Days 10, 12 and 14; the uninjected chicks served as controls. Samples were taken on Day 15. In Experiment 1, the cellulose diet decreased performance to 10 d of age relative to the other diets, whereas immunogen injection decreased weight gain and feed efficiency and increased indices of inflammation among all dietary groups. Fish oil at approximately 7% of the diet did not improve weight gain. Fish oil diets improved weight gain and feed efficiency in Experiment 2 relative to the other diets, in spite of minimal effects on indices of inflammation. Injection of LPS decreased performance and increased inflammation across dietary treatment, although the second LPS injection was less potent in altering performance responses and inflammation compared to the first injection, indicating that repeated injections of LPS amy cause the chicks to become refractory to that stimulus. The fish meal diets resulted in poorer performance than similar levels of lipid provided as fish oil. Lower levels of dietary fish oil were more efficacious in improving broiler performance than higher levels, and fish oil provided from fish meal was not as efficacious as oil per se, possibly due to nonlipid components of the meal.


Evaluating the effectiveness of teacher training in Applied Behaviour Analysis.
Interventions for children with autism based upon Applied Behaviour Analysis (ABA) has been repeatedly shown to be related both to educational gains and to reductions in challenging behaviours. However, to date, comprehensive training in ABA for teachers and others have been limited. Over 7 months, 11 teachers undertook 90 hours of classroom instruction and supervision in ABA. Each teacher conducted a comprehensive functional assessment and designed a behaviour support plan targeting one behaviour for one child with an autistic disorder. Target behaviours included aggression, non-compliance and specific educational skills. Teachers recorded observational data for the target behaviour for both baseline and intervention sessions. Support plans produced an average 80 percent change in frequency of occurrence of target behaviours. Questionnaires completed by parents and teachers at the end of the course indicated a beneficial effect for the children and the educational environment. The potential benefits of teacher implemented behavioural intervention are discussed.


The role of salivary function on oropharyngeal colonization.
Aspiration of oropharyngeal flora is the most common route of acquiring Gram-negative pneumonia, a major nosocomial infection. Epidemiologic studies indicate that the elderly are at increased risk for developing these life-threatening pneumonias. The primary objective of this study was to determine the effects of salivary oral defenses against Gram-negative colonization. The study population consisted of 41 male outpatients, age 70 and older, seen at the Denver VAMC. The group included subjects with both diminished and normal salivary flow. Each subject answered a questionnaire regarding overall health, medication use, and symptoms of salivary dysfunction. We then collected whole saliva, unstimulated and stimulated parotid saliva, and performed a throat swab on each patient. For each throat culture, analysis was done to identify Gram-negative bacteria. Flow rates between colonized (n = 6) and noncolonized subjects (n = 34) were compared. While there were no significant differences in the flow rates between the two groups, a trend was noticed in that flow rates were lower for all three flow measures in the colonized group (whole, 22% decrease; unstimulated, 22% decrease; and stimulated, 28% decrease). These preliminary findings suggest that subjects with diminished salivary flow may possibly be at increased risk for oropharyngeal Gram-negative colonization. Research on the role that saliva plays in oropharyngeal bacterial colonization is continuing.


Spectral domain optical coherence tomography imaging in optic disk pit associated with outer retinal dehiscence.
A 37-year-old Bangladeshi male presented with an inferotemporal optic disk pit and serous macular detachment in the left eye. Imaging with spectral domain optical coherence tomography (OCT) revealed a multilayer macular schisis pattern with a small subfoveal outer retinal dehiscence. This case illustrates a rare phenotype of optic disk maculopathy with macular schisis and a small outer retinal layer dehiscence. Spectral domain OCT was a useful adjunct in delineating the retinal layers in optic disk pit maculopathy, and revealed a small area of outer retinal layer dehiscence that could only have been detected on high-resolution OCT.


A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing.
We used a quantitative, high-density genetic interaction map, or E-MAP (Epistatic MiniArray Profile), to interrogate the relationships within and between RNA-processing pathways. Due to their complexity and the essential roles of many of the components, these pathways have been difficult to functionally dissect. Here, we report the results for 107,155 individual interactions involving 552 mutations, 166 of which are hypomorphic alleles of essential genes. Our data enabled the discovery of links between components of the mRNA export and splicing machineries and Sem1/Dss1, a component of the 19S proteasome. In particular, we demonstrate that Sem1 has a proteasome-independent role in mRNA export as a functional component of the Sac3-Thp1 complex. Sem1 also interacts with Csn12, a component of the COP9 signalosome. Finally, we show that Csn12 plays a role in pre-mRNA splicing, which is independent of other signalosome components. Thus, Sem1 is involved in three separate and functionally distinct complexes.


The time course of semantic richness effects in visual word recognition.
The richness of semantic representations associated with individual words has emerged as an important variable in reading. In the present study we contrasted different measures of semantic richness and explored the time course of their influences during visual word processing as reflected in event-related brain potentials (ERPs). ERPs were recorded while participants performed a lexical decision task on visually presented words and pseudowords. For word stimuli, we orthogonally manipulated two frequently employed measures of semantic richness: the number of semantic features generated in feature-listing tasks and the number of associates based on free association norms. We did not find any influence of the number of associates. In contrast, the number of semantic features modulated ERP amplitudes at central sites starting at about 190 ms, as well as during the later N400 component over centro-parietal regions (300-500 ms). Thus, initial access to semantic representations of single words is fast and word meaning continues to modulate processing later on during reading.


[Hair grooming syncope].
Syncope is a frequent topic in pediatric emergency rooms. Most of them are vasovagal syncopes. Some specific forms have been admitted, according to their etiopathogenic and clinical characteristics. Hair-grooming syncope is a rare variety which is not yet fully recognized. The records of children referred to our Pediatric Cardiology clinic from 1993 to 1996 because of fainting were evaluated. Patients with clinical data in possible relation with hair-grooming syncope were elected for the present study. Physical, cardiological and neurological examinations were recorded as well as basic complementary examinations. Head-upright tilt test was performed in all cases. Four girls, with a mean age of 9.5 years, presented sudden and brief loss of consciousness and postural tone in temporal relationship with several hair care acts. No body or neck position was associated with faint. Three patients had previously suffered other syncopal episodes without relation with hair care. Head-upright tilt test was positive in three cases and inconclusive in a girl with clear antecedents of clinically vasovagal syncope. Hair-grooming syncope is a rare and benign variety of neurocardiogenic syncope that should be considered in girls that complain of loss of consciousness during different hair care acts, even if seizures are present.


Cervical cancer screening in Korea: report on the National Cancer Screening Programme in 2008.
The National Cancer Screening Programme (NCSP) began in 1999. The purpose of this report is to evaluate the results of the NCSP for cervical cancer in 2008 and to present essential evidence associated with the cervical cancer screening programme in Korea. Screening results were obtained from the National Cancer Screening Information System. Participation rates and recall rates were calculated with 95% confidence intervals (CIs). The target population of the cervical cancer screening programme in 2008 was 4,701,167 Korean women aged 30 and over, 1,208,581 of whom underwent Papanicolaou (Pap) smear tests (25.7% participation rate). The recall rate was 0.41% (95% CI, 0.40 to 0.42). Although efforts to facilitate participation and to reduce disparities in cervical cancer screening among Korean women are needed, the results do provide support for evidence-based strategies for control of cervical cancer in Korea.


Sirtuins and the circadian clock: bridging chromatin and metabolism.
The circadian clock is a finely tuned system of transcriptional and translational regulation that is required for daily synchrony of organismal physiological processes. Additional layers of complexity that contribute to efficient clock function involve posttranslational modifications and enzymatic feedback loops. SIRT1, the founding member of the sirtuin family of protein deacetylases, was the first sirtuin to be reported to modulate circadian function. SIRT1 affects the circadian clock by its actions in the nucleus. Moreover, recent data implicate SIRT3 and SIRT6 in controlling mitochondrial and nuclear circadian functions, revealing previously unappreciated roles that extend to various subcellular domains, including fatty acid metabolism in the mitochondria. This review focuses on the roles of sirtuins in directing circadian functions in diverse organelles and speculates on the endogenous signals that may mediate the segregated roles of this family of enzymes.


A cDNA microarray gene expression data classifier for clinical diagnostics based on graph theory.
Despite great advances in discovering cancer molecular profiles, the proper application of microarray technology to routine clinical diagnostics is still a challenge. Current practices in the classification of microarrays' data show two main limitations: the reliability of the training data sets used to build the classifiers, and the classifiers' performances, especially when the sample to be classified does not belong to any of the available classes. In this case, state-of-the-art algorithms usually produce a high rate of false positives that, in real diagnostic applications, are unacceptable. To address this problem, this paper presents a new cDNA microarray data classification algorithm based on graph theory and is able to overcome most of the limitations of known classification methodologies. The classifier works by analyzing gene expression data organized in an innovative data structure based on graphs, where vertices correspond to genes and edges to gene expression relationships. To demonstrate the novelty of the proposed approach, the authors present an experimental performance comparison between the proposed classifier and several state-of-the-art classification algorithms.


Reactivation of herpes simplex keratitis following vaccination for COVID-19.
An 82-year-old man with a history of herpes simplex keratitis 40 years previously presented with recurrence, 1 day following vaccination for novel COVID-19. His condition worsened despite topical treatment with ganciclovir gel. A diagnosis of herpetic stromal keratitis was made, requiring systemic aciclovir, topical prednisolone, moxifloxacin and atropine, and oral doxycycline. He improved clinically on treatment, with some residual corneal scarring. Visual acuity improved from 6/36 corrected at presentation, to 6/24 following treatment. Clearly, public and personal health benefits from vaccination are hugely important and we would not suggest avoiding vaccination in such patients. It is, however, important for ophthalmic providers to be aware of the rare potential for reactivation of herpetic eye disease following vaccination to enable prompt diagnosis and treatment.


Effect of Direct Ligament Repair and Tenodesis Reconstruction on Simulated Subtalar Joint Instability.
Subtalar instability is associated with up to 80% of patients presenting with chronic ankle instability but is often not considered in the diagnosis or treatment. Operative procedures to repair ankle instability have shown good clinical results, but the effects of these reconstruction procedures on isolated subtalar instability are not well understood. The goal of this study was to investigate the effect of the Gould modification of the Broström procedure and a new tenodesis reconstruction procedure on ankle and subtalar joint kinematics after simulating a subtalar injury. Kinematic data were collected on 7 cadaveric ankles during inversion through the range of ankle flexion and during internal rotation. Testing was performed on the intact foot; after sectioning the calcaneofibular ligament, cervical ligament, and interosseous talocalcaneal ligament; after the Gould modification of the Broström procedure was performed; and after tenodesis was performed and sutures from the Gould modification removed. The Gould modification of the Broström procedure significantly decreased subtalar and ankle inversion motion and subtalar internal rotation compared to the unstable condition. The tenodesis method restricted internal rotation at the subtalar joint and ankle inversion compared to the intact state. Both operative procedures improved stability of the ankle complex, but tenodesis was unable to restore subtalar inversion and restricted ankle inversion in maximum plantarflexion. The Gould modification of Broström ligament repair may be a favorable operative procedure for the restoration of subtalar and ankle joint kinematics.


Low-contrast letter acuity testing captures visual dysfunction in patients with multiple sclerosis.
To evaluate concurrent and predictive validity for low-contrast letter acuity (L-CLA) testing as a candidate visual component for the Multiple Sclerosis Functional Composite (MSFC). L-CLA testing was conducted in two MS patient cohorts. In the MSFC Validation Study, 137 participants from a Phase III trial of inteferon beta-1a (Avonex) for relapsing-remitting MS were followed. A second cohort included 65 patients with secondary progressive MS who participated in a substudy of the International MS Secondary Progressive Avonex Controlled Trial (IMPACT). The total number of letters read correctly at four contrast levels (100, 5, 1.25, and 0.6%) was correlated with Expanded Disability Status Scale (EDSS), MSFC, Sickness Impact Profile, Multiple Sclerosis Quality of Life Inventory, and brain parenchymal fraction (BPF), as determined by MRI. Low- and high-contrast letter acuity scores correlated with BPF at follow-up in the MSFC Validation Study (5%: r = 0.40, p < 0.0001; 100%: r = 0.31, p = 0.0002). L-CLA also correlated with EDSS (5%: r = -0.35, p < 0.0001; 1.25%: r = -0.26, p = 0.0003) and MSFC (5%: r = 0.47, p < 0.0001; 1.25%: r = 0.45, p < 0.0001). In the IMPACT Substudy, change in L-CLA scores from baseline to year 1 predicted subsequent change in the EDSS from year 1 to 2 at the 5% (p = 0.0142) and the 1.25% (p = 0.0038) contrast levels, after adjusting for change in MSFC scores from baseline to year 1. Low-contrast letter acuity (L-CLA) scores demonstrate concurrent and predictive validity in patients with relapsing-remitting and secondary progressive multiple sclerosis (MS). L-CLA testing provides additional information relevant to the MS disease process that is not entirely captured by the Multiple Sclerosis Functional Composite.


Defective Viral Genomes Alter How Sendai Virus Interacts with Cellular Trafficking Machinery, Leading to Heterogeneity in the Production of Viral Particles among Infected Cells.
Defective viral genomes (DVGs) generated during RNA virus replication determine infection outcome by triggering innate immunity, diminishing virulence, and, in many cases, facilitating the establishment of persistent infections. Despite their critical role during virus-host interactions, the mechanisms regulating the production and propagation of DVGs are poorly understood. Visualization of viral genomes using RNA fluorescent in situ hybridization revealed a striking difference in the intracellular localization of DVGs and full-length viral genomes during infections with the paramyxovirus Sendai virus. In cells enriched in full-length virus, viral genomes clustered in a perinuclear region and associated with cellular trafficking machinery, including microtubules and the GTPase Rab11a. However, in cells enriched in DVGs, defective genomes distributed diffusely throughout the cytoplasm and failed to interact with this cellular machinery. Consequently, cells enriched in full-length genomes produced both DVG- and full-length-genome-containing viral particles, while DVG-high cells poorly produced viral particles yet strongly stimulated antiviral immunity. These findings reveal the selective production of both standard and DVG-containing particles by a subpopulation of infected cells that can be differentiated by the intracellular localization of DVGs. This study highlights the importance of considering this functional heterogeneity in analyses of virus-host interactions during infection.IMPORTANCE Defective viral genomes (DVGs) generated during Sendai virus infections accumulate in the cytoplasm of some infected cells and stimulate antiviral immunity and cell survival. DVGs are packaged and released as defective particles and have a significant impact on infection outcome. We show that the subpopulation of DVG-high cells poorly engages the virus packaging and budding machinery and do not effectively produce viral particles. In contrast, cells enriched in full-length genomes are the primary producers of both standard and defective viral particles during infection. This study demonstrates heterogeneity in the molecular interactions occurring within infected cells and highlights distinct functional roles for cells as either initiators of immunity or producers and perpetuators of viral particles depending on their content of viral genomes and their intracellular localization.


[Successfully resected advanced gastric carcinoma after combined chemotherapy of TS-1 plus CDDP--a case report].
A 66-year-old man complained of epigastralgia and a close examination was done. A type 3 gastric carcinoma was found. The tumor invading the pancreas and swelling lymphnodes around the stomach were confirmed according to abdominal CT. We considered it difficult to resect the tumor completely, and so we used combined chemotherapy of TS-1 plus CDDP. TS-1 was taken at 120 mg/day for 28 days followed by 14 days rest. CDDP was injected at 140 mg on day 8. Because the tumor in the stomach changed to scar and swelling lymphnodes diminished after two courses of therapy, total gastrectomy was done. After operation, combined chemotherapy of LV and 5-FU resulted in no recurrence to date. Although combined chemotherapy of TS-1 plus CDDP is effective for advanced gastric carcinoma, the number of days TS-1 is taken and the duration of the preoperative chemotherapy must be investigated in forthcoming study.


[Current surgical concepts and future perspectives in the treatment of pancreatic cancer].
Over the past 20 years, the concept of pancreatic surgery has been updated and surgical skills has improved dramatically. With the significant improvement of surgical safety and increase of resection rate for pancreatic cancer, some traditional surgical issues such as surgical indications, timing and extent of resection are being re-evaluated. The improvement of patients' prognosis is the gold standard for judging the surgical indications. The traditional criteria of "unresectable" based on morphology will be constantly broken through, and the estimation of resectability will transition from "what can we resect" to "what should we resect". Except for clinical research, standard extent of lymph node dissection is recommended. However, for borderline resectable and locally advanced pancreatic cancer after neoadjuvant treatment, extended lymph node dissection is recommended. All kinds of surgical approaches are feasible. The approach is subject to the needs of anatomy, anatomy is subject to the needs of radical treatment, and radical treatment is subject to the needs of improving prognosis. For some patients with locally advanced pancreatic cancer, sub-adventitial divestment of superior mesenteric artery and "Heidelberg triangle" cleaning are helpful to improve the resection rate and reduce the local recurrence rate,however, the impact on the long-term prognosis still needs to be further observed clinically. The quality of pancreaticojejunostomy has more influence on the incidence of pancreatic fistula than the type of pancreaticojejunostomy. For the centers with high volume patients and the surgeons with rich personal experience, laparoscopic or robot assisted surgery has the advantages of minimally invasive, but for pancreatic head carcinoma, it is not enough evidence to prove the oncological advantages of laparoscopic pancreaticoduodenectomy and robotic-assistant pancreaticoduodenectomy.


Autonomic Nervous System Functioning Related to Nocturnal Sleep in Patients With Chronic Fatigue Syndrome Compared to Tired Controls.
Autonomic nervous system (ANS) dysfunction is common in chronic fatigue syndrome (CFS). One of the main complaints in CFS is unrefreshing sleep. We aimed to study the nocturnal cardiac ANS in different sleep stages in patients filling the 2015 Institute of Medicine CFS diagnostic criteria. In this case series study, the nocturnal heart rate variability and blood pressure (BP) variables in polysomnography were studied in groups of patients with CFS (n = 8) and tired controls (n = 8) aged 16-49 years. Five of the patients with CFS and controls were female. The heart rate variability and BP parameters and heart rate were studied in all sleep stages and wake. The amount of low-frequency oscillations of the electrocardiography R-R-intervals spectra (LF; predominantly reflects sympathetic activity) was higher for patients with CFS in all sleep stages compared to controls (P < .001). During wake, the amount of LF was lower for the patients with CFS (P < .05). The amount of high-frequency oscillations (HF; reflects parasympathetic activity) was lower in stage N3 sleep in the patients with CFS than for the controls (P < .0001), but, in total, HF was higher in patients with CFS (P < .001). Patients with CFS had higher overall nocturnal systolic and mean BP (P < .0001) and lower heart rate (P < .0001) than controls. No significant differences were found in sleep stage distributions. The results suggest a nocturnal dysfunction of the cardiac ANS in CFS, presenting as lower parasympathetic tone in deep sleep and higher sympathetic tone asleep.


PTSD and public stigma: Examining the relationship between public stigmas attached to PTSD and self-esteem, spirituality, and well-being.
The main goal of the present study was to examine the association between personal characteristics and public stigma toward posttraumatic stress disorder (PTSD) survivors. Two hundred and ninety (N = 290) Israeli participants completed a survey that included demographic, self-esteem, spirituality, well-being, and stigma questionnaires. Descriptive statistics, correlations, linear regressions, and structural-equation modeling were conducted in order to examine the study model and hypotheses. The study findings demonstrate that self-esteem is associated with higher levels of belief that mental-health professionals can provide effective treatment for PTSD survivors, that survivors can recover and maintain normal relationships, and that survivors are not inclined to neglect their appearance and feel comfortable and calm with PTSD survivors. Spirituality is associated with a belief in professionals' ability to effectively treat PTSD and lower levels of belief that survivors are easily noticeable. Well-being is associated with a belief that survivors are careless with their hygiene and feel anxious around PTSD survivors. Muslim participants were more likely than Jewish participants to believe that survivors can fully recover, are careless with their hygiene, and that it is relatively easy to spot survivors. They were also more likely to feel anxious around survivors. Acquaintance with a PTSD survivor was associated with lower levels of belief that it would be difficult to maintain a relationship with a survivor and a stronger belief that survivors are relatively easy to spot. These findings make an important contribution to our understanding of the relationship between personal characteristics and the public stigmas attached to PTSD survivors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Effect of Genistein Supplementation on Exercise-Induced Inflammation and Oxidative Stress in Mice Liver and Skeletal Muscle.
Background and objectives: The purpose of this study was to investigate the influences of oral high-dose genistein (GE) administration on exercise-induced oxidative stress, inflammatory response and tissue damage. Materials and Methods: Thirty-two mice were randomly divided into control group (Con; sedentary/0.5% CMC-Na), GE administrated group (GE; sedentary/GE dosed), exercise group (Ex; exercise/0.5% CMC-Na), or GE administrated plus exercise group (GE + Ex; exercise/GE dosed), mice in the GE and GE + Ex group were given GE orally at the dose of 200 mg/kg weight. Results: Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, liver interleukin (IL)-6, IL-1β, superoxide dismutase 1 (SOD1), catalase (CAT), hemeoxygenase-1 (HO-1) gene expression levels and skeletal muscle IL-6, nuclear factor erythroid 2-related factor (Nrf2), and HO-1 gene expression levels increased immediately after exhaustive exercise. GE supplementation increased liver protein carbonyl concentrations. On the other hand, GE supplementation significantly decreased SOD1, CAT gene expression levels in the liver and Nrf2, and HO-1 gene expression levels in the skeletal muscles. Conclusions: Acute exercise induced organ damage, inflammation, and oxidative stress in skeletal muscles and the liver. However, a single dose of GE supplementation before exercise did not lead to favorable antioxidant and anti-inflammatory effects in this study.


Stress, coping, and mental health-seeking behaviors: gender differences in OEF/OIF health care providers.
Health care providers (HCPs) are often placed in positions of heightened stress when serving in military operations. As military HCPs have a large number of female providers, there is a concern that gender may influence both risk and resiliency within the health care provider subgroup. The purpose of this secondary analysis of the 2005 Department of Defense Survey of Health Related Behaviors Among Active Duty Military Personnel (data collected April through August 2005) is to describe stress, coping, and health-seeking behaviors of Operation Enduring Freedom and Operation Iraqi Freedom deployed military health care providers and the role gender may have for both health care officers and specialists. Female HCP responses indicate the lives of these women are significantly impacted by their family responsibilities. Reluctance of females to seek mental health care is concerning with perhaps more concern over career than personal well-being. Findings included (a) concern about performance, odds ratio (OR) = 1.86, 95% confidence interval (CI) [0.43, 8.12] for enlisted females, OR = 2.83, 95% CI [0.31, 25.66] for female officers; (b) problems with money, OR = 1.6 CI [0.69, 3.7] for enlisted females; (c) having a drink to cope, OR = 3.26, 95% CI [0.22, 48.68] for enlisted females; and (d) damage military career to seek mental health care, OR = 1.78, 95% CI [0.59, 5.39] for female officers. Results indicate needed provider awareness concerning mental health-seeking behavior and sensitivity toward gender differences that contribute to unique manifestations of operational stress outcomes.


Cross-reactions among Group A streptococci. I. Precipitin and bactericidal cross-reactions among types 33, 41, 43, 52, and Ross.
Strains of four streptococcal types, 33, 41, 43, 52, and a nontypable strain, Ross, cross-reacted in precipitin and bactericidal tests. The homologous reactions, which determined the type, afforded the major protection and developed promptly and regularly in the serum of rabbits during immunization. The associated cross-reactions, on the other hand, appeared in the serum of certain rabbits only, were often not as strong as the associated homologous reactions, and required for their presence a longer period of immunization than the homologous reactions. Agar gel analysis of the homologous precipitin reactions revealed, as would be expected, reactions of serological identity, while those cross-reactions which were strong enough to test in this way formed bands of precipitate which joined with spur formation on the side of the homologous reaction. These experiments and others referred to in the text suggest that cross-protection, as demonstrated in bactericidal tests, is sufficiently widespread to be a factor in streptococcal immunity, if a corresponding protection occurs in vivo. Thus, streptococcal infection with one of the cross-reacting strains might confer, in addition to strong homologous protection, a certain amount of cross-protection.


Large nerve cells with long axons in the granular layer and white matter of the murine cerebellum.
The murine cerebellum was investigated by light microscopy using an improved modification of Ehrlich's methylene blue supravital staining technique. The dye exhibited a special affinity for the perikarya as well as the axons of Purkinje cells. In addition, large fusiform or stellate nerve cells which were characterised by long descending axons were seen to be distributed diffusely within the granular layer and the subcortical white matter. These findings indicate the existence of a 2nd type of projection neuron besides the Purkinje cells and are therefore in full accordance with older neuroanatomical observations based on silver impregnation. When correlated with recent studies on the occurrence of different calcium-binding proteins, the results show that the large perikarya demonstrated immunohistochemically within the granular layer seem to belong to the group of methylene blue positive neurons. Nevertheless, the definitive association of a single neuron with a nerve cell class is only possible if the axon is stained and clearly identifiable. Because of its selectivity for a special type of nerve cell, including its axon, the histological method used in this study may therefore also be suitable for investigating other parts of the brain and the spinal cord.


Midwives speaking out on COVID-19: The international confederation of midwives global survey.
Maternity services around the world have been disrupted since the outbreak of the COVID-19 pandemic. The International Confederation of Midwives (ICM) representing one hundred and forty-three professional midwifery associations across the world sought to understand the impact of the pandemic on women and midwives. The aim of this study was to understand the global impact of COVID-19 from the point of view of midwives' associations. A descriptive cross-sectional survey using an on-line questionnaire was sent via email to every midwives' association member of ICM. The survey was developed and tested by a small global team of midwife researchers and clinicians. It consisted of 106 questions divided into seven discreet sections. Each member association was invited to make one response in either English, French or Spanish. Data were collected between July 2020 and April 2021. All respondents fulfilling the inclusion criteria irrespective of whether they completed all questions in the survey were eligible for analysis. All data collected was anonymous. There were 101 surveys returned from the 143 member associations across the world. Many countries reported being caught unaware of the severity of the infection and in some places, midwives were forced to make their own PPE, or reuse single use PPE. Disruption to maternity services meant women had to change their plans for place of birth; and in many countries maternity facilities were closed to become COVID-19 centres. Half of all respondents stated that women were afraid to give birth in hospitals during the pandemic resulting in increased demand for home birth and community midwifery. Midwifery students were denied access to practical or clinical placements and their registration as midwives has been delayed in many countries. More than 50% of the associations reported that governments did not consult them, and they have little or no say in policy at government levels. These poor outcomes were not exclusive to high-, middle- or low-income countries. Strong recommendations that stem from this research include the need to include midwifery representation on key government committees and a need to increase the support for planned out of hospital birth. Both these recommendations stand to enhance the effectiveness of midwives in a world that continues to face and may face future catastrophic pandemics.