Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease.
This study sought to test 2 hypotheses: 1) fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent of clinical factors, renal function, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from angiotensin-converting enzyme inhibitor therapy. FGF-23 is an endocrine regulator of mineral metabolism and markedly elevated levels are associated with cardiovascular events in patients with chronic kidney disease. Data in patients with SIHD are more sparse. FGF-23 levels were measured in 3,627 patients with SIHD randomly assigned to trandolapril or placebo within the PEACE (Prevention of Events With Angiotensin-Converting Enzyme) trial and followed up for a median of 5.1 years. After adjustment for clinical risk predictors, left ventricular ejection fraction, markers of renal function, and established cardiovascular biomarkers, FGF-23 concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (quartile 4 hazard ratio: 1.73; 95% confidence interval, 1.09 to 2.74; p = 0.02) and significantly improved metrics of discrimination. Furthermore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced cardiovascular death or incident heart failure (hazard ratio: 0.45; 95% confidence interval: 0.28 to 0.72), whereas there was no clinical benefit in the remaining patients (hazard ratio: 1.07; 95% confidence interval: 0.75 to 1.52; p interaction = 0.0039). This interaction was independent of and additive to stratification based on renal function. Elevated levels of FGF-23 are associated with cardiovascular death and incident heart failure in patients with SIHD and identify patients who derive significant clinical benefit from angiotensin-converting enzyme inhibitor therapy regardless of renal function. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy [PEACE]: NCT00000558).


Formation of food aversions in cancer patients receiving repeated infusions of chemotherapy.
Patients receiving emetogenic chemotherapy for cancer have been found to develop aversions to normal dietary items consumed in close temporal relation to treatment administrations. These aversions are presumed to develop via conditioning processes as demonstrated in experimental studies of food aversion learning. The present study used a prospective, longitudinal design to evaluate the possible role of conditioning in the formation of aversions to normal dietary items in women receiving adjuvant chemotherapy for breast cancer. Patients were monitored for the development of aversions to foods and beverages consumed in the 24 hr periods before and after each of eight consecutive chemotherapy infusions beginning with the initial infusion. Data on the prevalence, course, and prediction of aversions to normal dietary items are reported. These results pointed to similarities and differences between aversions formed to normal dietary items during chemotherapy treatment and aversions formed to taste stimuli during experimental conditioning studies. In addition to their theoretical significance, results also suggest possible strategies for preventing the clinical problem of aversions to normal dietary items in chemotherapy patients.


Porcine blood cell separation by porous cellulose acetate membranes.
Leukocytes were separated from whole porcine blood using laboratory prepared polymeric asymmetric porous membranes from cellulose acetate (CA) and by applying standard blood cell separation methods: centrifugation in a Ficoll solution gradient and in sucrose solution concentration gradient. Leukocytes, obtained by different separation methods were characterised by their quantity, type, viability and growth ability. Membranes prepared by a wet phase inversion process from different cellulose acetate/acetone/water and magnesium chlorate VII systems, were characterised according to: permeability to deionised water, surface morphology and by the determination of the flux of the permeate during the whole porcine blood separation. Cellulose acetate membranes prepared from 300 μm thick cast solution (14.8 wt% of cellulose acetate, 19.9 wt% of water, 2.3 wt% of Magnesium perchlorate, and 63.0 wt% of acetone), have separation characteristics comparable with the standard separation methods; in the dead-end mode filtration, 21.3% of leukocytes from porcine whole blood are separated. The leukocyte number in peripheral blood before separation was 450,000 ml(-1); the number passed through after was 95,000±6620. The main interest of the study was to introduce the CA membrane filters for the continus technological separation of the leukocyte/lymphocytes from animal (= porcine, bovine, horse..) blood.


Gross-total resection of malignant gliomas in elderly patients: implications in survival.
Malignant gliomas in elderly patients are frequently under represented in neuro-oncology trials because of presumed low tolerability of gross-total resection and radiochemotherapy treatments. Thus, the balance of benefit versus adverse response of standard glioma therapy remains controversial. We hypothesized that older patients with malignant gliomas might also take advantage of extensive surgical procedures. We analyzed retrospectively 138 consecutive malignant glioma patients. Sixty-two patients were >65 years whereas seventy-six were <or= 65 years. Evaluation consists of clinical features at diagnosis, neurological functional status, surgical procedures, post-operative complications and the predictive value of the former variables for survival. At diagnosis, elderly patients showed a larger burden of comorbidities but they did not influence outcome significantly. Gross-total resection was associated with a longer survival as compared to biopsy and subtotal resection in both groups of elderly (P=0.05 and 0.001, respectively) and younger patients (P=0.004 and 0.003). Concerning complications, the only difference between both collectives was a higher incidence of psychosyndrome in the elderly group (P=0.016). Our results indicate that gross-total resection of malignant gliomas in elderly patients is associated with a survival benefit without increased morbidity.


The taxonomic and phylogenetic status of digeneans from the genus Timoniella (Digenea: Cryptogonimidae) in the Black and Baltic seas.
Timoniella spp. are cryptogonimid flukes (Digenea: Cryptogonimidae) that parasitize the guts of fish in brackish waters. Timoniella imbutiforme, a species from the Mediterranean Sea, is recorded in the Black Sea, while T. balthica has been described from the Baltic Sea. In this paper, we clarify the taxonomic status of Timoniella populations in the Baltic and Black seas. Adults and metacercariae of Timoniella spp. were sampled from localities in the Mediterranean Sea (France), Black Sea (Ukraine) and Baltic Sea (Germany) and subjected to molecular and morphological analysis, including Bayesian phylogenetic reconstruction based on concatenated sequences of ITS1-ITS2-28S. This allowed us to construct a new key to species of the genus Timoniella. Our results suggest that T. balthica forms part of the Boreal-Atlantic relict fauna of the Black Sea and should now be considered a junior synonym of T. imbutiforme.


Synthesis of DNA fragments containing 5,6-dihydrothymine, a major product of thymine gamma radiolysis.
5,6-Dihydrothymine is one of the most important products of base damage by gamma irradiation of DNA in anoxic conditions. This modified base is unstable in the deprotection conditions used for classical synthesis of oligonucleotides. For its incorporation in synthetic DNA fragments, a new set of amino protecting groups has been developed. The 5,6-dihydrothymidine phosphoramidite was successfully employed for the synthesis of two 14-mers and one 17-mer bearing this defect at positions corresponding to restriction enzymes sites. The presence of the modified base still intact in the oligonucleotides was evidenced by mass spectrometry in pyrolytic conditions.


Para-adrenal teratoma: CT presentation.
In the case we have reported, computerized tomography detected a mass in the right adrenal area and characterized it as a typical cystic teratoma in a para-adrenal location.


Consistent across-tissue signatures of differential gene expression in Crohn's disease.
An approach based on analysis of variance was applied to raw expression data on 44,760 transcripts in order to identify those with significant differential expression across ileum and colon in Crohn's disease (CD) and ulcerative colitis (UC). The design treated tissue as a block effect, thereby removing this effect statistically and increasing the power to test for effects of disease states (control, CD, and UC). A significant F-statistic for the disease effect was not correlated with the ratios CD/control or UC/control, evidently because many transcripts with high-expression ratios to the control showed inconsistent patterns across tissues. Of 1,053 transcripts showing a significant effect of disease state at the 1% level by the bootstrap test, 508 showed significant difference at the 1% level in a post hoc test for difference between the mean scores for CD and control. These included a number of genes relevant to the mechanism of pathogenesis of CD and a number of genes mapping to genomic regions that have previously shown linkage to CD in association studies.


Proximity Extension Assay in Combination with Next-Generation Sequencing for High-throughput Proteome-wide Analysis.
Understanding the dynamics of the human proteome is crucial for developing biomarkers to be used as measurable indicators for disease severity and progression, patient stratification, and drug development. The Proximity Extension Assay (PEA) is a technology that translates protein information into actionable knowledge by linking protein-specific antibodies to DNA-encoded tags. In this report we demonstrate how we have combined the unique PEA technology with an innovative and automated sample preparation and high-throughput sequencing readout enabling parallel measurement of nearly 1500 proteins in 96 samples generating close to 150,000 data points per run. This advancement will have a major impact on the discovery of new biomarkers for disease prediction and prognosis and contribute to the development of the rapidly evolving fields of wellness monitoring and precision medicine.


Mixed chimerism following hematopoietic stem cell transplantation in pediatric thalassemia major patients: a single center experience.
Stable mixed chimerism (MC) may result in cure for thalassemia major patients following hematopoietic stem cell transplantation (HSCT), but rejection can occur. Twenty-eight HSCTs for thalassemia major were reviewed retrospectively to evaluate the clinical course of MC with possible risk factors and predictors of outcome, with a median follow-up of 1669 days (811-3576 days). Chimerism was detected by fluorescence in situ hybridization (FISH) or multiplex polymerase chain reaction depending on the sex match between the donor and the recipient. Primary rejection, stable MC and full donor chimerism was detected in 3.6%, 17.8% and 78.6% of patients, respectively. Clinically, 4/5 patients with stable MC had thalassemia trait with donor chimerism as low as 14%. One patient was started on pRBC transfusions at 2.5 years postHSCT. Stable MC can result in cure for thalassemia major patients. The clinical picture remains as the best guide for intervention until a more reliable predictor is available.


Evaluation of Early Insulin Glargine Administration in the Treatment of Pediatric Diabetic Ketoacidosis.
In the management of diabetic ketoacidosis (DKA), the standard of care is to administer insulin glargine after ketoacidosis has resolved and the patient is transitioning from intravenous (IV) insulin to subcutaneous insulin; however, there is evidence to suggest that earlier administration of insulin glargine may accelerate resolution of ketoacidosis. The objective of this research is to determine the efficacy of early subcutaneous insulin glargine on time to resolution of ketoacidosis in children with moderate to severe DKA. This retrospective chart review evaluated children age 2 to 21 years old admitted for moderate to severe DKA who received insulin glargine within 6 hours of hospital admission (early insulin glargine) compared with those who received insulin glargine greater than 6 hours from admission (late insulin glargine). The primary outcome was duration of time the patient received IV insulin. A total of 190 patients were included. The median time on IV insulin was lower in patients who received early insulin glargine compared with those who received late insulin glargine (17.0 [IQR, 14-22.8] vs 22.9 hours [IQR, 4.3-29.3]; p = 0.0006). Resolution of DKA was faster in patients who received early insulin glargine compared with those who received late insulin glargine (median, 13.0 [IQR, 9.8-16.8] vs 18.2 hours [IQR, 12.5-27.6]; p = 0.005). Length of pediatric intensive care unit (PICU) and hospital stay and incidences of hypoglycemia and hypokalemia were similar between the 2 groups. Children with moderate to severe DKA who received early insulin glargine had a significantly lower time on IV insulin, as well as significantly faster time to resolution of DKA when compared with those who received late insulin glargine. There were no significant differences observed in hospital stay and rates of hypoglycemia and hypokalemia.


Evaluation of Temporal Trends of Lead Exposure in Korean Workers Using Workplace Monitoring Data.
Lead, which is widely used in various industrial settings, is a major health hazard for manufacturing workers. Therefore, control of lead exposure has been implemented in an effort to prevent lead-related health problems. In this study, our aim was to evaluate temporal trends in occupational lead exposure in Korean lead workers using data from monitoring of workplace exposure. A nationwide work environment monitoring database, data from a work environment monitoring institution, and data extracted from a review paper were utilized. Different versions of standard industrial classification codes were aligned with the 10th Korean Standard Industrial Classification, which is generally consistent with the 4th revision of the International Standard Industrial Classification. The multiple data sources were combined and temporal trends over the period from 1994-2021 were estimated. In addition, separate estimation of temporal trends in the storage battery manufacturing industry over the period from 1987-2021 was also performed. A total of 444,296 personal airborne lead measurements were used for the estimation process. The temporal trends in occupational exposure to lead declined by -6% annually over the study period. In particular, levels of lead exposure in the storage battery manufacturing industry showed a steeper decline of -12% annually. Findings of our study showed that occupational exposure to lead declined over the period from 1994 to 2021 in Korea. However, adverse effects of exposure to lead on health should be regarded with caution. The results will be useful in conduct of epidemiological studies examining lead-related effects on health.


Outpatient total knee arthroplasty: is it economically feasible in the hospital setting?
With the removal of total knee arthroplasty (TKA) from the Medicare inpatient-only list, outpatient TKA can now be offered, irrespective of payer, in multiple sites. We compared time- and cost-effectiveness of outpatient TKA performed in a hospital outpatient department (HOPD) to that at an inpatient academic medical center (AMC). We reviewed all outpatient TKAs performed at our AMC and our HOPD from August 2018 to July 2019. Time efficiency by phase of care was determined, and cost data were obtained from the hospital financial department. Patient selection for outpatient surgery was identical for each site of care. We identified 21 knees that had surgery at the HOPD and 65 knees that had surgery at the AMC. Demographics were similar in both groups. The AMC group had significantly longer in-facility to operating room (Δ (difference) = 33.5 minute, P = .0003), postanesthesia care unit to discharge (Δ = 158.8 minute, P < .0001) and in-facility to discharge (Δ = 199.3 minute, P < .0001) time periods compared to the HOPD group. The HOPD was significantly more cost-effective for the preoperative period (Δ = $75.7, P < .0001), postoperative period (Δ = $315.1, P < .0001), and total cost (Δ = $241, P < .0001). Outpatient TKAs performed in an HOPD spend significantly less time within the facility than the ones performed in an AMC and cost significantly less. It is expected that approval of Medicare TKAs at ambulatory surgery centers will further improve cost and efficiency.


Variable neutralization of several nonspecific antibacterial systems in fresh, defibrinated human blood by sodium polyanetholsulfonate and sodium amylosulfate.
Fresh, defibrinated human blood (80 vol%, i.e., 80% [vol/vol] of a 2-ml final assay volume) from two healthy adult donors killed "delayed serum-sensitive" (DSS) and "promptly serum-sensitive" (PSS) strains of Serratia marcescens, PSS control strain Escherichia coli C, Bacillus subtilis strain ATCC 6633, and Micrococcus lysodeikticus ATCC 4698 in a kinetic manner comparable to that of fresh human serum (80 vol%). However, heat-inactivated (56 degrees C, 30 min), defibrinated human blood revealed markedly reduced or a total lack of beta-lysin activity against the B. subtilis assay strain. Similarly, lysozyme activity of defibrinated blood was diminished somewhat by heat treatment, as determined with the M. lysodeikticus assay strain. Addition of 500 mug of sodium polyanetholsulfonate (SPS) per ml to 80 vol% of fresh, defibrinated human blood completely neutralized blood bactericidal activity against all assay strains of S. marcescens, E. coli C, and B. subtilis; however, SPS at this concentration failed to abolish lysozyme activity for prolonged periods of incubation. Addition of 500 mug of sodium amylosulfate (SAS) per ml to 80 vol% of fresh defibtinated human blood resulted in protection of cell inocula of DSS strains of S. marcescens only; SAS failed to protect cell inocula of the PSS strains of S. marcescens, E. coli C, B. subtilis, and M. lysodeikticus for extended periods of observation. Based on these data, it is recommended that blood culture specimens that are first drawn into specimen containers (such as Vacutainer tubes or the like) at the patient's bedside, and which contain >/=250 mug of SPS per ml, be diluted into suitable broth media with at least >/=250 mug of SPS per ml by the receiving laboratory within 2 to 4 h after procurement of the specimen. This procedure would ensure continued, adequate neutralization of the specimen's inherent beta-lysin, lysozyme, and complement- and antibody-mediated bactericidal activities.


The multi-level regulation of clownfish metamorphosis by thyroid hormones.
Most marine organisms have a biphasic life cycle during which pelagic larvae transform into radically different juveniles. In vertebrates, the role of thyroid hormones (THs) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrated analysis of metamorphosis of a marine teleost, the false clownfish (Amphiprion ocellaris). We show how THs coordinate a change in color vision as well as a major metabolic shift in energy production, highlighting how it orchestrates this transformation. By manipulating the activity of liver X regulator (LXR), a major regulator of metabolism, we also identify a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild, explaining how hormones coordinate energy needs with available resources during the life cycle.


Contribution to the co-rotating magnetic field model of the pulsar.
A new general solution of the electromagnetic field equations convenient for rotating field problems is used to analyse the case of low plasma number density. Two localized pulse emitting regions rotating with the star at approximately twice the velocity of light radius are predicted.


Bio-coatings as immobilized microalgae cultivation enhancement: A review.
Bio-coatings serve as artificial scaffolds for immobilizing microalgae to facilitate cell concentration and harvesting. It has been used as an additional step to enhance the natural microalgal biofilm cultivation and to promote new opportunities in artificially-immobilize cultivation technology of microalgae. This technique is able to enhance biomass productivities, enable energy and cost saving, water volume reduction and ease of biomass harvesting since the cells are physically isolated from the liquid medium. However, scientific discoveries of bio-coatings for process intensification are still lacking and their working principles remained unclear. Therefore, this critical review aims to shed light on the advancement of cell encapsulation systems (hydrogel coating, artificial leaf, bio-catalytic latex coating, and cellular polymeric coating) over the years and aid in the selection of appropriate bio-coating techniques for various applications. Discussion on the different preparation routes of bio-coatings, as well as the exploration towards the potential of bio-based coating materials such as natural/synthetic polymers, latex binders, and algal organic matters are also included, with a focus on sustainable pursuits. This review also presents in-depth investigations into the environmental applications of bio-coatings in wastewater remediation, air purification, carbon bio-fixation, and bio-electricity. The field of bio-coating in microalgae immobilization gives rise to a new ecofriendly strategy with scalable cultivation footprint and a balanced environmental risk aligning with the United Nation's Sustainable Development Goals with potential towards the contribution of Zero Hunger, Clean Water and Sanitation, Affordable and Clean Energy, and Responsible Consumption and Production.


Quantum neural network cost function concentration dependency on the parametrization expressivity.
Although we are currently in the era of noisy intermediate scale quantum devices, several studies are being conducted with the aim of bringing machine learning to the quantum domain. Currently, quantum variational circuits are one of the main strategies used to build such models. However, despite its widespread use, we still do not know what are the minimum resources needed to create a quantum machine learning model. In this article, we analyze how the expressiveness of the parametrization affects the cost function. We analytically show that the more expressive the parametrization is, the more the cost function will tend to concentrate around a value that depends both on the chosen observable and on the number of qubits used. For this, we initially obtain a relationship between the expressiveness of the parametrization and the mean value of the cost function. Afterwards, we relate the expressivity of the parametrization with the variance of the cost function. Finally, we show some numerical simulation results that confirm our theoretical-analytical predictions. To the best of our knowledge, this is the first time that these two important aspects of quantum neural networks are explicitly connected.


Re-Epithelialization of Pathological Cutaneous Wounds Is Improved by Local Mineralocorticoid Receptor Antagonism.
Impaired cutaneous wound healing is a social burden. It occurs as a consequence of glucocorticoid treatment in several pathologies. Glucocorticoids (GC) bind not only to the glucocorticoid receptor but also to the mineralocorticoid receptor (MR), both expressed by keratinocytes. In addition to its beneficial effects through the glucocorticoid receptor, GC exposure may lead to inappropriate MR occupancy. We hypothesized that dermatological use of MR antagonists (MRA) might be beneficial by overcoming the negative impact of GC treatment on pathological wounds. The potent GC clobetasol, applied as an ointment to mouse skin, or added to cultured human skin explants, induced delayed wound closure and outgrowth of epidermis with reduced proliferation of keratinocytes. Delayed wound re-epithelialization was rescued by local MRA application. Normal skin was unaffected by MRA. The benefit of MR blockade is explained by the increased expression of MR in clobetasol-treated mouse skin. Blockade of the epithelial sodium channel by phenamil also rescued cultured human skin explants from GC-impaired growth of the epidermis. MRA application over post-biopsy wounds of clobetasol-treated skin zones of healthy volunteers (from the Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy clinical trial) also accelerated wound closure. In conclusion, we propose repositioning MRA for cutaneous application to improve delayed wound closure occurring in pathology.


Reversible redox reactions in an epitaxially stabilized SrCoO(x) oxygen sponge.
Fast, reversible redox reactions in solids at low temperatures without thermomechanical degradation are a promising strategy for enhancing the overall performance and lifetime of many energy materials and devices. However, the robust nature of the cation's oxidation state and the high thermodynamic barrier have hindered the realization of fast catalysis and bulk diffusion at low temperatures. Here, we report a significant lowering of the redox temperature by epitaxial stabilization of strontium cobaltites (SrCoO(x)) grown directly as one of two distinct crystalline phases, either the perovskite SrCoO(3-δ) or the brownmillerite SrCoO(2.5). Importantly, these two phases can be reversibly switched at a remarkably reduced temperature (200-300 °C) in a considerably short time (< 1 min) without destroying the parent framework. The fast, low-temperature redox activity in SrCoO(3-δ) is attributed to a small Gibbs free-energy difference between two topotatic phases. Our findings thus provide useful information for developing highly sensitive electrochemical sensors and low-temperature cathode materials.


Optimization of performance characteristics in diesel engine utilizing Chlorella vulgaris fuel-a green approach towards sustainable development.
Sustainable renewable energy fuel is used to reduce fossil fuel consumption and mitigate global warming pollution. The effect of diesel and biodiesel blends on engine combustion, performance, and emissions were studied at various engine loads, compression ratios, and engine speed. Chlorella vulgaris biodiesel is derived through a transesterification process and diesel and biodiesel blends are prepared at 20% incremental volume up to CVB100. The performance such as brake thermal efficiency reduced by 1.49%, specific fuel consumption increased by 2.78%, and exhaust gas temperature increased by 0.43% for CVB20 as compared to diesel. Similarly, emissions were reduced such as smoke, particulate matters. CVB20 shows close performance and lower emission than diesel at a 15.5 compression ratio and 1500 rpm engine speed. The increasing compression ratio has a positive impact on engine performance and emission except for NOx. Similarly, increasing engine speed has a positive impact on engine performance and emission except for exhaust gas temperature. The performance of a diesel engine fueled with a blend of diesel and Chlorella vulgaris biodiesel is optimized by varying compression ratio, engine speed, load, and blend. It was found that at 8 compression ratio, 1835 rpm speed, 88% engine load, and 20% biodiesel blend the maximum BTE obtained 34% while minimum SFC 0.158 kg/kWh is obtained employing research surface methodology tool.


Variation of electron beam uniformity with beam angulation and scatterer position for total skin irradiation with the Stanford technique.
The influence of different scatterer-degraders and beam angulations on beam uniformity for total skin electron irradiation using the six dual beam Stanford technique is investigated. The 6 MeV high dose rate total skin electron irradiation mode on a linear accelerator was used. Beam profiles and percentage depth doses in the patient plane for single, dual, and six dual beams were measured for different dual beam angulations and acrylic scatterer-degraders of different thicknesses mounted on the treatment head or in front of the patient in the treatment plane. It is demonstrated that, with the same electron nominal energy, total skin irradiation techniques with different beam penetrations can be obtained by inserting various beam scatterer-degraders into the beam, either mounted on the accelerator head or close to the patient. For our patient treatment, a beam penetration was selected so that the 80% dose lay at 8-9 mm and the 50% dose at 15-16 mm depth. This was achieved by mounting a 0.32-cm thick acrylic beam scatterer-degrader on the accelerator head. A uniform vertical profile was obtained for gantry angulations of +/- 21 degrees. To implement a total skin electron irradiation technique using the Stanford method, the required depth of penetration needs to be selected. Based on this, the appropriate combination of scatterer-degraders and dual beam angulations to produce a uniform beam in the treatment plane needs to be determined. Different techniques with different beam penetrations can be developed using the same high dose rate mode on the linear accelerator by a proper choice of scatterer-degraders and beam angulations.


The pipe and the pinwheel: is pressure an effective stimulus for the 9+0 primary cilium?
Almost universally, the effective stimulus for mammalian 9+0 primary cilia has been taken to be bending. In this article I point out that in several physiological contexts there is great advantage in detecting pressure differences across the cell wall, i.e. axially directed forces pushing fluid to and fro through the hollow cilium and its basal body beneath. The form of the cilium--a fluid-filled pipe that connects to an intricate pinwheel-shaped basal body--is well configured for detecting fluid flow. Pressure-detection calls for compressible elements within the cell, but it effectively matches form and function in a range of cases. The "pipe and pinwheel" scheme suggests that the bulbous swellings commonly found near the tip of some primary cilia are compliant, pressure-sensitive elements which act like the bulb of an eye-dropper. In looking exclusively at the bending of cilia, we might be missing aspects of a dual-stimulus system.


Structure of the RZZ complex and molecular basis of its interaction with Spindly.
Kinetochores are macromolecular assemblies that connect chromosomes to spindle microtubules (MTs) during mitosis. The metazoan-specific ≈800-kD ROD-Zwilch-ZW10 (RZZ) complex builds a fibrous corona that assembles on mitotic kinetochores before MT attachment to promote chromosome alignment and robust spindle assembly checkpoint signaling. In this study, we combine biochemical reconstitutions, single-particle electron cryomicroscopy, cross-linking mass spectrometry, and structural modeling to build a complete model of human RZZ. We find that RZZ is structurally related to self-assembling cytosolic coat scaffolds that mediate membrane cargo trafficking, including Clathrin, Sec13-Sec31, and αβ'ε-COP. We show that Spindly, a dynein adaptor, is related to BicD2 and binds RZZ directly in a farnesylation-dependent but membrane-independent manner. Through a targeted chemical biology approach, we identify ROD as the Spindly farnesyl receptor. Our results suggest that RZZ is dynein's cargo at human kinetochores.


Motor cortex hemodynamic response to goal-oriented and non-goal-oriented tasks in healthy subjects.
Motor disorders are one of the world's major scourges, and neuromotor rehabilitation is paramount for prevention and monitoring plans. In this scenario, exercises and motor tasks to be performed by patients are crucial to follow and assess treatments' progression and efficacy. Nowadays, in clinical environments, quantitative assessment of motor cortex activities during task execution is rare, due to the bulkiness of instrumentation and the need for immobility during measurements [e.g., functional magnetic resonance imaging (MRI)]. Functional near-infrared spectroscopy (fNIRS) can contribute to a better understanding of how neuromotor processes work by measuring motor cortex activity non-invasively in freely moving subjects. Exploit fNIRS to measure functional activation of the motor cortex area during arm-raising actions. All subjects performed three different upper limbs motor tasks: arm raising (non-goal-oriented), arm raising and grasping (goal oriented), and assisted arm raising (passive task). Each task was repeated ten times. The block design for each task was divided into 5 seconds of baseline, 5 seconds of activity, and 15 seconds of recovery. Sixteen healthy subjects (11 males and 5 females) with an average (+/- standard deviation) of 37.9 (+/- 13.0) years old. Cerebral hemodynamic responses have been recorded in two locations, motor cortex (activation area) and prefrontal cortex (control location) exploiting commercial time-domain fNIRS devices. Haemodynamic signals were analyzed, separating the brain cortex hemodynamic response from extracerebral hemodynamic variations. The hemodynamic response was recorded in the cortical motor area for goal-oriented and not-goaloriented tasks, while no response was noticed in the control location (prefrontal cortex position). This study provides a basis for canonical upper limb motor cortex activations that can be potentially compared to pathological cerebral responses in patients. It also highlights the potential use of TD-fNIRS to study goal-oriented versus non-goaloriented motor tasks. Impact: the findings of this study may have implications for clinical rehabilitation by providing a better understanding of the neural mechanisms underlying goal-oriented versus non-goal-oriented motor tasks. This may lead to more effective rehabilitation strategies for individuals with motor disorders and a more effective diagnosis of motor dysfunction supported by objective and quantitative neurophysiological readings.


In vitro genotoxic perspective of Tamiflu.
The aim of this study was to investigate the genotoxic and/or cytotoxic effects of Tamiflu, commercial form of the oseltamivir antiviral and most frequently prescribed for the treatment of influenza infections, on cultured human peripheral lymphocytes by using sister chromatid exchange (SCE), chromosomal aberration (CA), and cytokinesis-blocked micronucleus (CBMN) assays. Cells were treated with 0.5, 1, 2 μg/mL oseltamivir, the Tamiflu capsule ingredient, for 24 or 48 h in the absence or presence of an exogenous metabolic activation system (S9 mix). The test chemical did not demonstrate any genotoxic effect dose-dependently but it showed a weak cytotoxicity on cells in this study. On the other hand, some concentrations of Tamiflu (2 μg/mL without S9 mix for 48 h and 1 μg/mL with S9 mix) induced SCE and also decreased significantly the proliferation index (PI) (48 h period) and the nuclear division index (NDI) (24 h period) (P < 0.05) in the absence of S9 mix. Considering the results, Tamiflu did not induce significant increases of CA or micronucleated cells in vitro in cultured peripheral blood lymphocytes under the treatment conditions used but weak SCE induction was observed. On the other hand, the weak cytotoxic effects observed disappeared in the cultures treated in presence of the S9 mix.


Functional neuroimaging of migraine.
This review summarizes the history of migraine imaging and key findings of studies on functional neuroimaging in migraine and describes how these data have changed our view of the disorder. Functional neuroimaging during migraine attacks and also interictally has initiated the description of "the migraine brain". These studies have led to the demonstration of cortical spreading depression in migraine with aura, the crucial role for the brainstem during migraine attacks, and cortical hypersensitivity in migraineurs modulated by the trigeminal pathway, explaining sensory sensitization such as photophobia and osmophobia.


Panax ginseng Meyer cv. Silvatica phenolic acids protect DNA from oxidative damage by activating Nrf2 to protect HFF-1 cells from UVA-induced photoaging.
Long-wave ultraviolet A (UVA) causes skin aging by damaging the fine structures of the skin, such as elastic fibers and collagen fibers, through oxidation. Currently, the use of plant extracts to protect skin from photoaging is a popular method. Panax ginseng C.A. Meyer exerts commendable anti-photoaging and antioxidant effects. P. ginseng Meyer cv. Silvatica, also known as forest ginseng (FG), is a type of ginseng cultivated by artificially simulating the growth environment of wild ginseng aged >15 years. However, there are only a few reports on its anti-photoaging effect on the skin caused by UVA stimulation. To investigate whether isolated and extracted FG can inhibit skin photoaging as well as to explore its action mechanism. The FG extract (FGE) was obtained from the supernatant of FG after water extraction and alcohol precipitation with the D101 resin. The composition and content of phenolic acids in FGE were determined by high-performance liquid chromatography (HPLC). The MTT assay was performed to detect cell viability. The ratio of SA-β-GAL-positive cells, CoL-I level, 8-OHdG concentration, MDA, GSH, GPx, SOD, and CAT activity were measured using relevant kits. Furthermore, cell cycle alterations and ROS accumulation were assessed by flow cytometry. The expressions of p53, p21, p16, and Keap1 protein were detected by Western blotting. The Nrf2 translocation was monitored by immunofluorescence staining. The findings revealed that FGE significantly restored UVA injury-induced cell viability, reduced the proportion of SA-β-GAL-positive cells, and increased the level of CoL-I secretion in a dose-dependent manner, where the main ingredients were chlorogenic acid, protocatechuic acid, salicylic acid, p-hydroxybenzoic acid, vanillic acid, ferulic acid, and caffeic acid. Further studies indicated that this phenolic acid mixture (PAM) could alleviate UVA-induced HFF-1 cell cycle arrest and protect the DNA from oxidative damage caused by UVA stimulation. Moreover, the expressions of cell cycle regulatory proteins p53, p21, and p16 and the accumulation of ROS were inhibited, the translocation of Nrf2 into the nucleus was promoted, the expression of Keap1 protein was inhibited, the activity of intracellular antioxidant indicators GSH, GPx, SOD, and CAT was enhanced, and the expression of malondialdehyde (MDA) was inhibited. Collectively, our results demonstrated that FG phenolic acids protect DNA from oxidative damage by activating Nrf2 to safeguard the skin from photoaging induced by UVA stimulation.


Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder.
To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM). The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug". The annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to "No drug". A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed. There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.


Self-reported emotional and behavioral symptoms, parent-adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans.
The presence of posttraumatic stress disorder (PTSD) in male war veterans has been linked with family dysfunction and psychopathology in their children [1, 2]. This study aimed to evaluate self-reported emotional and behavioral symptoms, parent-adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans and determine the degree that parent-child bonding and family functioning contributed to adolescent behavior problems. Internalizing and externalizing behavior problems, parent-child bonding and family functioning were assessed in a sample of clinically referred Croatian PTSD veterans adolescent offspring (N = 122) and non-PTSD veteran adolescent offspring (N = 122) matched for age, sex, educational level, family income, parental employment status, ethnicity, and residential area. Youth Self-Report, Parental Bonding Instrument, Family Assessment Device were used. Adolescent offspring of PTSD veterans reported having significantly more internalizing and externalizing problems than non-PTSD veteran offspring, and also more difficulties in their family functioning, lower levels of maternal and paternal care, and more impaired mother-child and father-child bonding than control subjects. Internalizing symptoms were associated with family dysfunction, while externalizing symptoms were associated with paternal overcontrol/overprotection, and low maternal and paternal care. In conclusion, the increase in internalizing and externalizing symptoms as well as family and parental dysfunction among clinically referred adolescent offspring of PTSD veterans compared to their non-PTSD veteran counterparts indicates a need for early detection and interventions targeting both adolescent psychopathology and family relationships.


Pulse oximetry in the adult ED patient with sickle cell.
We performed a retrospective chart review of adult patients with sickle cell presenting with vasoocclusive crisis to determine the association between pulse oximetry and emergency department (ED) disposition. Subjects were divided into a NORMAL (pulse oximetry > or = 95%) and a LOW (pulse oximetry <95%) group. Two hundred ten consecutive charts showed no significant difference between NORMAL (n = 163) and LOW (n = 47) groups regarding admission or discharge from the ED ( P > .05). A higher percentage in the LOW group received chest radiographs (40.9% vs 29%, P < .05), suggesting that pulse oximetry may have influenced ordering of this test. No significant differences in historical and physical exam characteristics were found. The pulse oximetry level does not appear to be associated with a particular ED disposition in adult sickle cell anemia.


Secondary structure of the alpha-amylase polypeptide inhibitor tendamistat from Streptomyces tendae determined in solution by 1H nuclear magnetic resonance.
Complete sequence-specific 1H nuclear magnetic resonance assignments were obtained for the backbone hydrogen atoms in Tendamistat, a protein with 74 residues. From NOESY observation of 1H-1H short distance constraints, measurements of the spin-spin couplings 3JHN alpha and a qualitative identification of slowly exchanging amide protons, two antiparallel beta-sheets containing three and four strands, respectively, were identified. The peptide segments outside the beta-sheets do not form regular secondary structure. Preliminary data were obtained on the relative spatial arrangements of the two beta-sheets.


Appointment Pathways: Yield Management via Cause-and-Effect Modeling in the Outpatient Setting at Mayo Clinic.
Patients have multiple outpatient appointments for various reasons. Analyzing patients' related appointments provides insight into referral patterns, leading to recommendations for ideal care and more efficient planning. We model these appointments with causal graphs via Judea Pearl's causal graph approach. Once we define the causal relationships in the appointment data, we leverage a graph database and visualization software to investigate valuable patterns and relationships in patient care over time. The Pathways tool allows yield management at specialty, provider, or appointment levels. Leaders use this tool to anticipate a patient's downstream appointments; the tool provides insights into staffing and the impact of growing demand.


Staged transverse preputial island flap urethroplasty for some proximal hypospadias with moderate-to-severe chordee.
We aimed to assess the outcome of staged transverse preputial island flap (TPIF) urethroplasty for repairing certain cases of primary proximal hypospadias with moderate-to-severe chordee in children. Nighty-two consecutive boys who underwent either one-stage or staged TPIF urethroplasty for the repair of proximal hypospadias with moderate-to-severe chordee between August 2015 and December 2019 were evaluated retrospectively. Patients were divided into two groups: one-stage TPIF urethroplasty group (n = 44) and staged TPIF urethroplasty group (n = 48). We noted and compared the postoperative complications, including urethrocutaneous fistula, urethral diverticula, residual penile curvature, and urethral stricture in both groups. Both groups were followed up for 1-5 years, with an average of 3 years. No cases of residual or recurrence of penile chordee were reported in either group. In Group A, 9 patients (9/44, 20.4%) had postoperative urethrocutaneous fistula, and all patients underwent urinary fistula repair or urethroplasty. In Group B, postoperative urethrocutaneous fistula occurred in 2 cases (2/48, 4.1%), and one patient developed a urethrocutaneous fistula after the first operation, which was successfully repaired during the second operation. A urethrocutaneous fistula occurred in 1 case after completion of the second-stage operation; urethral fistula repair was performed successfully 6 months later. There were 2 cases of urethral stricture in Group A (2/44, 4.5%) and none in Group B. There were 6 cases of urethral diverticulum in Group A (6/44, 13.6%) and no cases of urethral diverticulum in Group B. The operative success rates were 61.3% and 95.8% in Group A and Group B, respectively (P < 0.001). Compared with one-stage TPIF urethroplasty, staged TPIF urethroplasty in the treatment of certain cases of primary proximal hypospadias with moderate-to-severe chordee resulted in fewer postoperative fistulas, urethral strictures and urethral diverticula. The staged TPIF urethroplasty procedure was effective in reducing the operation difficulty and complication rate of hypospadias, improving the curative effect of complex hypospadias and having good clinical application value.


SFRR-E Young Investigator AwardeeαB-crystallin modulation after acute exercise in skeletal muscle: the role of oxidative stress and fiber composition.
αB-crystallin (CRYAB) is a member of the small heat shock proteins implicated in various biological functions, particularly in skeletal muscle where it is involved in adaptive remodelling processes, activation of gene transcription and stabilization of nascent proteins.In this research we analysed αB-crystallin' response in mouse gastrocnemius at 15' and 30' of recovery from an acute aerobic exercise (1hour), correlating its modulation with oxidative stress level and fiber composition, red (RG) and white gastrocnemius (WG).We found for the first time that the acute exercise lead to a short term, specific increase of phospho-αB-crystallin level (pCRYAB) in the RG, while no changes were observed in the WG. Moreover, this induction was correlated with increased level of 4-hydroxynonenal (HNE),suggesting a putative role for oxidative stress in driving CRYAB, but not hsp70 or hsp27, activity during exercise. Any increased level of αB-crystallin' protein was observed neither in RG nor in WG. These data were also supported by our in vitro experiments showing a significant enhancement of pCRYAB in H2O2-treated C2C12 myotubes.Although our results seem suggest a fiber-dependent role of CRYAB, further experiments are in progress to clarify both the molecular pathway driving CRYAB phosphorylation and its fiber-specific induction after exercise -induced oxidative stress.This work was supported by MIUR - PRIN 2012 grant.


Fifty years later: Emerging functions of IgE antibodies in host defense, immune regulation, and allergic diseases.
Fifty years ago, after a long search, IgE emerged as the circulating factor responsible for triggering allergic reactions. Its extremely low concentration in plasma created significant hurdles for scientists working to reveal its identity. We now know that IgE levels are invariably increased in patients affected by atopic conditions and that IgE provides the critical link between the antigen recognition role of the adaptive immune system and the effector functions of mast cells and basophils at mucosal and cutaneous sites of environmental exposure. This review discusses the established mechanisms of action of IgE in pathologic immediate hypersensitivity, as well as its multifaceted roles in protective immunity, control of mast cell homeostasis, and its more recently revealed immunomodulatory functions.


The anti-inflammatory influence of Cinnamomum burmannii against multi-walled carbon nanotube-induced liver injury in rats.
Carbon nanotubes (CNTs) are extensively used in nanotechnology due to their unique physico-chemical properties. CNTs were implicated in many disorders connected with human health. So, we aimed in this study to provide new insight into the role of aqueous C. burmannii in treating the possible hepatotoxic effects of multi-walled carbon nanotube (MWCNTs) exposure. A total of 32 male albino rats were divided into 4 groups: control group, cinnamon-treated group, MWCNT-treated, and cinnamon- and MWCNT-treated group. To achieve the aim of this study, evaluation of percentage change of body weight, oxidant, and antioxidant status including lipid peroxidation (LPO), nitrite, total thiols, glutathione contents (GSH), the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S transferase (GST) was done. Histopathological examination and the rate of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), cyclooxygenase-1 (COX-1), and tumor necrotic factor-α were performed. Oral administration of aqueous C. burmannii to those MWCNT-treated rats resulted in a significant reduction in LPO and total thiol contents with a significant elevation in the activities of SOD, CAT, and GPX, while GSH content and GST activity were not significantly affected. We observed a significant downregulation in the rate of previous pro-inflammatory cytokines. All this improvement in these examined markers resulted in a significant modulation in the hepatic histopathological lesions caused by MWCNTs. Aqueous C. burmannii extract exhibited a potential defensive effect on the hepatic injury triggered by MWCNTs through upgrading the antioxidant system and downregulating the rate of pro-inflammatory cytokines.


Fermented foods: An update on evidence-based health benefits and future perspectives.
In recent years, an unstoppable trend toward minimally processed foods has increased the popularity of fermented foods as a beneficial nutritional and functional strategy. Within food fermentations, complex microbial communities trigger different biochemical reactions that result in the release of multiple bioactive compounds with beneficial effects on human health. In the present review the latest studies on fermented foods are summarized. Special attention has been paid on the health benefits of main fermented foods available nowadays, the principal bioactive compounds responsible for such properties as well as the future trends of research studies regarding their potentialities. This review emphasizes the need of clinical evidence to ensure that fermented foods may entail a significant improvement on well-being. Fermented foods may represent a non-invasive strategy to face multiple disorders, as hypertension, diabetes, hyperlipidemia, oxidative stress and multiple cognitive disordes, among others. Release of bioactive compounds, microbial enzymatic conversions or probiotic activities are the main responsible for such interesting properties. However, the need of well-designed clinical trials is a must in order to obtain conclusive results. Bioavailability and biodisponibility of bioactive compounds as well as the design of precision probiotics are also another focus of interest in which it must be deepen.


A Retrospective Study of Factors Influencing the Survival of Modified Meek Micrografting in Severe Burn Patients.
Modified Meek micrografting is a common method for treating severe burn patients. This study was to analyze the factors affecting the survival of modified Meek micrografting, thereby improving the survival rate of skin grafts. Eighty-three patients who underwent modified Meek micrografting were analyzed. According to the survival rate of skin graft after operation, the patients were divided into good skin survival group (GSSG, survival rate ≥ 70%, 47 cases) and poor skin survival group (PSSG, survival rate < 70%, 36 cases). The baseline data, surgical information, perioperative laboratory indicators, and prognosis of the patients were statistically analyzed. The univariate analysis and repeated measurement showed the burn severity, Meek skin graft area, duration of anesthesia, the postoperative sepsis shock, the mortality, the neutrophils percentage on the third day after surgery (NEU3), and the growth rate of neutrophils percentage from the first to third day after surgery (NEU3-1%) in the GSSG were significantly lower than those in the PSSG, whereas the perioperative average albumin levels and the perioperative average pre-albumin levels were higher. Receiver operating characteristic curve showed that the NEU3 had a good predictive value for the survival of skin slices. Maintaining perioperative albumin levels at a high level, controlling perioperative infection, and shortening the operation time as much as possible may improve the survival rate of modified Meek micrografting.


The association between suicidal ideation and increased mortality from natural causes.
Despite strong evidence for increased suicide mortality among individuals experiencing thoughts of suicide, the effect of suicidal ideation on increased natural mortality has not been evaluated. The present study aimed to assess whether there is excess mortality from all natural causes or from specific natural causes that is attributable to suicidal ideation. Adjustments were made for a range of demographic, mental health and physical health measures to examine evidence for specific mechanisms of the relationship. A community-based Australian cohort of 861 older adults was followed for up to 17 years. Vital status and cause of death were ascertained from a national death registry. After adjusting for demographics, physical health and mental health, presence of suicidal ideation was associated with a 23% increase in the risk of mortality from natural causes (p=0.034). The increased mortality was largely attributable to heart disease deaths (hazard ratio=1.43, p=0.041). There was a limited number of deaths from respiratory disease or stroke, and modest rates of suicidal ideation in the cohort. Assessment of suicidal ideation was brief, while adjustment for mental health symptoms relied on non-diagnostic measures. Although the relationship between suicidal ideation and mortality from natural causes was partly explained by physical and mental health status, thoughts of suicide independently accounted for an increased risk of mortality. Further research should examine whether this relationship is mediated by poorer health behaviours among individuals experiencing thoughts of suicide.


The risky business of advanced paternal age: neurodevelopmental and psychosocial implications for children of older fathers.
The last several decades are notable for an increase in the percentage of births attributable to men in their 40s and 50s. There is general recognition of offspring health risks related to advanced maternal age, however, fewer patients and providers are informed about the impacts of advanced paternal age (APA). This review examined the literature investigating the association between APA and offspring outcomes, specifically, neurodevelopmental, psychiatric, academic, and behavioral impairment, the impact of paternal health decline and death, and the influence of age on parenting behaviors. This analysis revealed that children, and even grandchildren, of older fathers face significantly increased incidence rates of psychiatric disease and behavioral impairment. The data do not show evidence of superior parenting behaviors among men with APA. Finally, children of men with APA are significantly more likely to experience early bereavement, which is associated with psychological and developmental consequences. An understanding of the degree to which APA can negatively impact the offspring is imperative for patient counseling and development of practice guidelines.


In older patients with NSTE-ACS, clopidogrel safely reduced bleeding compared with ticagrelor at 1 year.
Gimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020;395:1374-81. 32334703.


Chagas' cardiomyopathy: the economic burden of an expensive and neglected disease.
Chagas' cardiomyopathy (CC) is a rising etiology for heart failure (HF) that previously was restricted to some countries of Latin America. The chronic CC cases cause now a profound socio-economic impact. However this issue has not been well studied if compared to other causes of HF. The objective of this study was to assess the cost burden of CC during acute decompensated HF admissions (ADHF), and compare this cost to the other etiologies of HF. By the end of 2006 we started a five year follow-up of 577 consecutive adult patients admitted at a high complexity cardiology university hospital in the city of Sao Paulo, Brazil. This study shows the data of the first admission of each patient of this follow-up. Patients were divided in two groups: CC (58 patients) and non-chagasic (NC) (519 patients). Mortality was different among groups, 19/58 (32.8%) in CC vs 113/519 (21.8%) in NC (p=0.046). The prevalence of signs of inadequate perfusion was higher in the CC group at admission, but in a multivariated analysis chagasic etiology and presence of diabetes were independent predictors of higher costs per day of hospitalization adjusted by mortality. Median costs per day were US$ 308 (277-542) vs US$ 467 (323-815) for NC and CC respectively (p<0.001). Treating ADHF patients with CC etiology was more expensive and mortality was higher in this population at the first admission of this follow-up. This could be explained by the severity of Chagas' cardiomyopathy disease.


Diagnosis of tuberculosis with autoimmune hepatitis-systemic lupus erythematosus overlap syndrome: a case report.
There is ample evidence indicating that immunosuppressive therapy or immune dysregulation in systemic lupus erythematosus increases the risk for tuberculosis. Interestingly, a few case reports suggest that tuberculosis could also be a risk factor for systemic lupus erythematosus and other autoimmune diseases. We report the case of a 32-year-old Indian patient who was co-diagnosed with tuberculosis, systemic lupus erythematosus, and autoimmune hepatitis without any history of prior immunosuppression. This stresses the complex relationship between tuberculosis and autoimmune diseases. Further research is warranted in this field to unfold the complex relationship between tuberculosis and systemic lupus erythematosus. It is essential to establish clear guidelines for the management of coexisting tuberculosis and systemic lupus erythematosus to promote individualized treatment.


The impact of photoperiods and melatonin on gonadal development in juvenile Turkish hamsters (Mesocricetus brandti).
The reproductive response of both intact adult and juvenile Turkish hamsters has been thoroughly studied and shown to be similar, unlike the golden hamster where juveniles remain aphotoperiodic until approximately 8 weeks of age. Unstudied to date, however, is the role of the pineal and its hormone melatonin in generating the testicular response to photoperiod in juvenile Turkish hamsters. Therefore, in this study we examined the reproductive response of prepubertal male Turkish hamsters, subjected to four different photoperiods (8L:16D, 16L:8D, 20L:4D, and 24L:0D) with altered pineal gland function. At 15 days of age, long-day-born (16L:8D) hamsters were either pinealectomized, received melatonin implants, or remained untreated. Testes sizes were measured every 2 weeks. Testicular growth occurred only in untreated and beeswax implanted groups in 16L:8D. Exposure to other photoperiods inhibited testicular development in untreated and beeswax implanted animals. Removal of the pineal gland, masking of the daily melatonin rhythm with constant release subcutaneous melatonin implants, or eliminating the daily rhythm of melatonin by continuous light exposure resulted in inhibition of gonadal development. These results demonstrate that juvenile Turkish hamsters respond similarly to adults on all photoperiods and under all conditions of pineal function tested.


Preoperative enteral immunonutrition improves postoperative outcome in patients with gastrointestinal cancer.
The purpose of this study was to evaluate the effect of preoperative immunonutrition pharmaceutics (IMPACT) diet versus standard enteral nutrition (EN) on the nutritional status and immunity of patients with colorectal or gastrointestinal (GI) cancer and to evaluate whether it influences the incidence of postoperative complication. Sixty patients with GI cancer were randomly divided into 2 groups, immunonutrition (IM) and control diet (CT), each of which was fed with IMPACT and conventional diet, respectively, for 7 days before surgical procedures. Variables of nutritional status and immunity, postoperative complications, infections, and the days of postoperative hospitalization were measured. There were no significant differences in the immunological and nutritional variables between the 2 groups preoperatively. The incidence of postoperative complications was significantly lower and the days of postoperative hospitalization were significantly decreased in the IM group. Serum concentrations of both prealbumin (PALB) and transferrin (TRF) were lower in the IM than in the CT group on postoperative day 3 (P<0.01). TRF continued to be significantly lower in the CT group than in the IM group between day 4 and day 7. However, PALB was significantly lower than before operation in the IM group on postoperative day 3 and TRF was significantly higher in the IM than the CT group on postoperative day 3 (P<0.05). Both PALB and TRF were significantly higher in the IM than the CT group on postoperative day 7 (P<0.05). Postoperative immunoglobulin G (IgG) level in the IM group was higher than that in the CT group (13.35+/-2.06 g/l vs. 9.59+/-2.23 g/l, P<0.05). CD4/CD8 ratio was significantly higher in the IM group (2.10+/-0.51 vs. 1.62+/-0.52, P<0.05). Preoperative enteral IM in patients with GI cancer improves nutritional status and immunity and decreases the incidence of postoperative complications and infections.


Measles vaccination after exposure to natural measles.
When an extensive measles epidemic broke out in Turku in late 1975, the availability of a previous study on measles vaccination reactions in 442 children permitted a comparative evaluation to be made on reactions to and the efficacy of measles vaccine (Schwartz strain) administered after exposure to natural measles. In a preliminary study, nine children were vaccinated one to 14 days after exposure to natural measles but before prodromal symptoms appeared. Only one of these nine children developed symptoms and signs comparable to those of the natural disease. In five day-care centers the children were vaccinated when five or more children out of 30 to 40 at each center had measles. In only five of 74 exposed children were the signs and symptoms comparable to those of natural measles. No marked differences in signs and symptoms after the vaccinations were observed between the exposed and nonexposed children. It is concluded that vaccination is safe, can usually prevent measles, even when administered after a prolonged interval following exposure to natural disease, and can usually control an epidemic in progress.


MYB3 plays an important role in lignin and anthocyanin biosynthesis under salt stress condition in Arabidopsis.
Nuclear-localized Arabidopsis MYB3 functions as a transcriptional repressor for regulation of lignin and anthocyanin biosynthesis under high salt conditions. Salinity stress is a major factor which reduces plant growth and crop yield worldwide. To improve growth of crops in high salinity environments, plant responses to salinity stress must be tightly controlled. Here, to further understand the regulation of plant responses under high salinity conditions, the function of the MYB3 transcription factor was studied as a repressor to control accumulation of lignin and anthocyanin under salt stress conditions. Nuclear-localized MYB3 forms a homodimer. It is ubiquitously expressed, especially in vascular tissues, with expression highly induced by NaCl in tissues such as roots, leaves, stems, and flowers. myb3 mutant plants exhibited longer root growth in high NaCl conditions than wild-type plants. However, several NaCl responsive genes were not significantly altered in myb3 compared to wild-type. Interestingly, high accumulation of lignin and anthocyanin occurred in myb3 under NaCl treatment, as well as increased expression of genes involved in lignin and anthocyanin biosynthesis, such as phenylalanine ammonia lyase 1 (PAL1), cinnamate 4-hydroxylase (C4H), catechol-O-methyltransferase (COMT), 4-coumaric acid-CoA ligase (4CL3), dihydroflavonol reductase (DFR), and leucoanthocyanidin dioxygenase (LDOX). According to yeast two-hybrid screenings, various transcription factors, including anthocyanin regulators Transparent Testa 8 (TT8) and Enhancer of Glabra 3 (EGL3), were isolated as MYB3 interacting proteins. MYB3 was characterized as a transcriptional repressor, with its repressor domain located in the C-terminus. Overall, these results suggest that nuclear-localized MYB3 functions as a transcriptional repressor to control lignin and anthocyanin accumulation under salinity stress conditions.


Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice.
Damage of oligodendrocytes after ischemia has negative impact on white matter integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1) overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV-NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral artery occlusion. The effect of NT-1 on neural function was evaluated by neurobehavioral tests. Proliferated oligodendrocyte progenitor cells (OPCs), newly matured oligodendrocytes, and remyelination were semi-quantified by immunohistochemistry. The role of NT-1 in oligodendrogenesis was further explored by examining specific NT-1 receptors and their function. Netrin-1 overexpression was detected in neurons and astrocytes 2 weeks after AAV-NT-1 gene transfer and significantly improved the neurobehavioral outcomes compared with the control (P<0.05). In comparison with the control, proliferated OPCs, newly matured oligodendrocytes, and remyelination were greatly increased in the ipsilateral hemisphere of AAV-NT-1-transduced mice. Furthermore, both NT-1 receptors deleted in colorectal carcinoma and UNC5H2 were expressed on OPCs whereas only UNC5H2 was expressed in myelinated axons. Our study indicated that NT-1 promoted OPC proliferation, differentiation, and increased remyelination, suggesting that NT-1 is a promising factor for white matter repairing and remodeling after ischemia.


Concept analysis: an approach to teaching physiologic variables.
Establishment of a knowledge base for nursing practice has been an ongoing goal of nurse professionals for the past decade. Because nurses are especially concerned with management of the body's potential or actual response to illness, the development and use of materials that reflect these body responses seems appropriate. This article is an effort to promote the use of concepts as a basis for nursing practice. A concept analysis approach for didactic instruction, currently being used for organizing and synthesizing pathophysiologic data present in literature, is presented. The process is exemplified by excerpts from the concept "inflammation." Advantages and disadvantages identified by graduate students for the use of concepts and the analysis process as a teaching/learning strategy are included.


Modulation of IgD and CD20 by ligation of CD5 on tonsillar B cells.
The CD5 molecule, pan T cell marker, has been known to be expressed on a minor population of B cells, termed B-1 cells. However, the physiological function and pathological role of CD5+B (B-1) cells remain to be fully elucidated in humans. In the present study, we aimed to clarify the significance of CD5 expression on the B lymphocytes in human tonsil. Using flow cytometric analysis by three-colour immunofluorescence staining, we observed a majority of the cell surface CD5-positive (sCD5+) B cells among the sIgD+ B-cell population, as previously described. Contrary to our expectation, approximately half of the sIgD+/sCD5+ B cells expressed CD38 on their cell surface. Furthermore, a small number of sCD5+ were observed in the sIgD- B cell population. The addition of anti-CD5 monoclonal antibody (MoAb) to the culture induced downmodulation of sCD20 and sIgD of the tonsillar B cells, resulting in an increase of sCD38-/sIgD- (memory) B cells during the 10 day culture periods in the CD40/l cell culture system. Our findings suggest that ligation of CD5 might transduce the signal to regulate B cell maturation.


Protein-losing enteropathy in systemic lupus erythematosus: report of a severe, persistent case and review of pathophysiology.
Protein-losing enteropathy (PLE) is a rare manifestation of systemic lupus erythematosus (SLE). We report a severe and resistant case of PLE, discuss pathophysiology and possible role of cytokines in the disease process. We also present a review of the current literature.


Influence of needle diameter on spinal anaesthesia puncture failures for caesarean section: A prospective, randomised, experimental study.
Spinal anaesthesia represents the technique of choice for elective caesarean section. The purpose of this study was to compare the puncture failure rates with 25, 26 or 27 gauge (G) pencil-point, Whitacre type (with introducer) needles during spinal anaesthesia for caesarean section. Prospective, randomised, experimental study in healthy subjects. We recruited 330 adults, consecutively scheduled parturients, randomised into three groups. The subarachnoid puncture procedure was standardised. The flexibility of the three needle types was assessed in vitro, and a force was applied using a dynamometer. The occurrence of postdural puncture headache was also evaluated. The number of spinal puncture failures was significantly higher in the 27G group, than in the 25G (P=0.006) group and the 26G (P<0.001) group, but did not differ between the 25G and 26G groups (P=0.606). Ten postdural puncture headaches were observed without significant differences among the groups. This prospective study showed that puncture failures occur less frequently with the use of 25G or 26G pencil-point needles as compared to 27G needles, probably due to the higher flexibility of the latter. This characteristic was demonstrated in vitro, in a reproducible model. This experiment suggests that a 26G pencil-point needle is the optimal gauge for performing spinal anaesthesia for scheduled caesarean sections.


Immuno-electron microscopic study of calcitonin gene-related peptide (CGRP) in axis cylinders of the vagus nerve. CGRP is present in both myelinated and unmyelinated fibers.
The localization of immunoreactive calcitonin gene-related peptide (IR-CGRP) in vagus nerve fibers of the rat was studied with pre-embedding electron immunocytochemistry. IR-CGRP was localized in a small number (approximately 5%) of myelinated fibers and approximately 50% of unmyelinated fibers of the vagus. The immumoreactivity was observed in the dense cored vesicles (75-150 nm) and in the axoplasm, but absent in the clear vesicles.


Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets.
A meta-analysis of publicly available transcriptomic datasets was performed to identify metabolic pathways profoundly implicated in the progression and treatment of inflammatory bowel disease (IBD). The analysis revealed that genes involved in tryptophan (Trp) metabolism are upregulated in Crohn's disease (CD) and ulcerative colitis (UC) and return to baseline after successful treatment with infliximab. Microarray and mRNAseq profiles from multiple experiments confirmed that enzymes responsible for Trp degradation via the kynurenine pathway (IDO1, KYNU, IL4I1, KMO, and TDO2), receptor of Trp metabolites (HCAR3), and enzymes catalyzing NAD+ turnover (NAMPT, NNMT, PARP9, CD38) were synchronously coregulated in IBD, but not in intestinal malignancies. The modeling of Trp metabolite fluxes in IBD indicated that changes in gene expression shifted intestinal Trp metabolism from the synthesis of 5-hydroxytryptamine (5HT, serotonin) towards the kynurenine pathway. Based on pathway modeling, this manifested in a decline in mucosal Trp and elevated kynurenine (Kyn) levels, and fueled the production of downstream metabolites, including quinolinate, a substrate for de novo NAD+ synthesis. Interestingly, IBD-dependent alterations in Trp metabolites were normalized in infliximab responders, but not in non-responders. Transcriptomic reconstruction of the NAD+ pathway revealed an increased salvage biosynthesis and utilization of NAD+ in IBD, which normalized in patients successfully treated with infliximab. Treatment-related changes in NAD+ levels correlated with shifts in nicotinamide N-methyltransferase (NNMT) expression. This enzyme helps to maintain a high level of NAD+-dependent proinflammatory signaling by removing excess inhibitory nicotinamide (Nam) from the system. Our analysis highlights the prevalent deregulation of kynurenine and NAD+ biosynthetic pathways in IBD and gives new impetus for conducting an in-depth examination of uncovered phenomena in clinical studies.


Study of the metabolism of steroids in larvae of the fleshfly Sarcophaga bullata.
1. Larvae of the fleshfly Sarcophaga bullata were injected with several 3H C21 and C19 steroids. After different incubation times, the larvae were homogenized and the metabolites were extracted and fractionated by Sephadex LH 20-, paper- and thin-layer chromatography. The chromatographic mobility of the labeled zones was compared with that of standard steroids. 2. Progesterone and 17 alpha-hydroxypregnenolone were metabolized to 17 alpha-hydroxyprogesterone. Androstenedione, 17 alpha-hydroxyprogesterone and dehydroepiandrosterone were converted to testosterone. Transformation of pregnenolone to progesterone or 17 alpha-hydroxypregnenolone was not observed. 3. C21 or C19 steroid formation from cholesterol could not be demonstrated. 4. Sixteen metabolites, different from all our standard substances have been found. Their structure remains to be elucidated.


Characterization of Weissella kimchii PL9023 as a potential probiotic for women.
From more than 100 lactic acid bacteria, Weissella kimchii PL9023 was selected as producing the most hydrogen peroxide and was characterized as a probiotic for women. W. kimchii PL9023 inhibited the growth and adherence of vaginal isolates of Candida albicans, Escherichia coli, Staphylococcus aureus and Streptococcus agalactiae. The surface components involved in adherence of W. kimchii PL9023 to vaginal epithelial cells appeared to be glycoproteins, as determined by susceptibility to proteinase K, heat, or periodate. W. kimchii PL9023 did not produce harmful metabolites or enzymes. The results of this study suggest that W. kimchii PL9023 is a potential probiotic for vaginal health.


Zap1 activation domain 1 and its role in controlling gene expression in response to cellular zinc status.
The Zap1 transcription factor is a central player in zinc homeostasis in yeast. This protein regulates the expression of genes involved in zinc accumulation and storage. For most of its target genes, Zap1 activates expression in zinc-limited cells and this function is inhibited in replete cells. Zap1 has two activation domains, AD1 and AD2, which are independently regulated by zinc status. In this study, we characterized AD1 and its regulation by zinc. AD1 was mapped using deletions to residues 332-402 of Zap1. The region required for the zinc responsiveness of this activation domain, designated 'ZRD(AD1), was mapped to residues 182-502. Thus, AD1 is embedded within its larger zinc-responsive domain. Using a combination of in silico analysis, random mutagenesis and site-directed mutagenesis, we identified key residues within ZRD(AD1) required for its regulation by zinc. Most of these residues are cysteines and histidines that could potentially serve as Zn(II) ligands. These results suggest that ZRD(AD1) senses zinc by direct Zn(II) binding. Consistent with this hypothesis, purified ZRD(AD1) bound multiple Zn(II) ions. Finally, our results indicate that, in the context of the full-length Zap1 protein, AD1 and AD2 are both critical to the full control of gene expression in response to zinc.


Identification of gold nanoparticle in lymphocytes: a confirmation of direct intracellular penetration effect.
Nanoparticles differ from the same material at larger scale in chemical and physical properties. The effect of nanoparticle on the blood cell still needs scientific verification. The direct effect of gold nanoparticles on lymphocyte was direct assessed by in vitro assay. In this work, the author reported additional results from specific observation on lymphocyte exposure to gold nanoparticle. This result confirms for direct intracellular penetration effect.


Motor, sensory and autonomic nerve terminals containing NAP-22 immunoreactivity in the rat muscle.
Neuron-enriched acidic protein having a molecular mass of 22 kDa, NAP-22, is a Ca(2+)-dependent calmodulin-binding protein and is phosphorylated with protein kinase C (PKC). This protein is localized to the biological membrane via myristoylation and found in the membrane fraction of the brain and in the synaptic vesicle fraction. Recent studies showed that NAP-22 is localized in the membrane raft domain in a cholesterol-dependent manner and suggest a role for NAP-22 in maturation and/or maintenance of nerve terminals by controlling cholesterol-dependent membrane dynamics. The present study revealed the immunohistochemical distribution of NAP-22 in the peripheral nerves in rat muscles. In all examined muscles, nerve terminals in the motor endplates showed NAP-22 immunoreactivity associated with the membranes of synaptic vesicles and nerve terminals. In the muscle spindles, annulospiral endings, which made spirals around the intrafusal muscles, showed intense NAP-22 immunoreactivity. Autonomic nerve fibers around the intramuscular blood vessels also showed the immunoreactivity for NAP-22. NAP-22 immunoreactivity in these peripheral nerves was observed from birth to adulthood (100 days after birth). Though growth-associated protein-43 (GAP-43) immunoreactivity in these nerves was observed from birth, this immunoreactivity decreased from 20 days after birth. These findings suggest that NAP-22 is distributed and regulates functions in the motor, sensory and autonomic nerve terminals in the peripheral nervous system.


Characterization of intestinal gene expression profiles in Crohn's disease by genome-wide microarray analysis.
Genome-wide microarray expression analysis creates a comprehensive picture of gene expression at the cellular level. The aim of this study was to investigate differential intestinal gene expression in patients with Crohn's disease (CD) and controls with subanalysis of confirmed CD susceptibility genes, associated pathways, and cell lineage. In all, 172 biopsies from 53 CD and 31 control subjects were studied. Paired endoscopic biopsies were taken at ileocolonoscopy from five specific anatomical locations including the terminal ileum (TI) for RNA extraction and histology. The 41,058 expression sequence tags were analyzed using the Agilent platform. Analysis of all CD biopsies versus controls showed 259 sequences were upregulated and 87 sequences were downregulated. Upregulated genes in CD included SAA1 (fold change [FC] +7.5, P = 1.47 × 10(-41)) and REGL (FC +7.3, P = 2.3 × 10(-16)), whereas cellular detoxification genes including-SLC14A2 (FC-2.49, P = 0.00002) were downregulated. In the CD TI biopsies diubiquitin (FC+11.3, P < 1 × 10(-45)), MMP3 (FC+7.4, P = 1.3 × 10(-11)), and IRTA1 (FC-11.4, P = 4.7 × 10(-12)) were differentially expressed compared to controls. In the colon SAA1 (FC+6.3, P = 5.3 × 10(-8)) was upregulated and thymic stromal lymphopoietin (TSLP) (FC-2.3, P = 2.7 × 10(-6)) was downregulated comparing noninflamed CD and control biopsies, and the colonic inflammatory CD signature was characterized by downregulation of the organic solute carriers-SLC38A4, SLC26A2, and OST alpha. Of CD susceptibility genes identified by genome-wide association scan IL-23A, JAK2, and STAT3 were upregulated in the CD group, confirming the dysregulation of Th17 signaling. These data characterize the dysregulation of a series of specific inflammatory pathways highlighting potential pathogenic mechanisms as well as areas for translation to therapeutic targets.


An appraisal of the effects of usual vs recent alcohol intake on blood pressure.
1. In a population-based study of 343 men from two public utilities, 260 subjects reported drinking alcohol at least once a week. In these subjects a comparison was made of the relative effects on blood pressure of either their usual alcohol intake (assessed from a 7-day retrospective diary) or recent alcohol intake (alcohol consumed at the last drinking session in the 24 h prior to blood pressure measurement). 2. Both usual and recent alcohol intake showed similar correlations with level of blood pressure (BP). After adjustment of BP for the potential confounding influences of body mass index, age and smoking status, systolic and diastolic BP remained highest in those subjects with the highest reported levels of both usual and recent alcohol intake. 3. In regression analyses comprising only those subjects who reported drinking in the 24 h before BP measurement, a 3-4 fold greater effect of usual rather than recent intake on both systolic and diastolic BP was predicted from the b coefficients. Regression analysis also demonstrated that the relationship between usual alcohol intake and BP was independent of recent intake, while the relationship between recent intake and BP was no longer significant when usual alcohol intake was entered into the regression equation. 4. These observations suggest that consistent regular drinking is a more important determinant of the alcohol/BP relationship than intake in the previous 24 h.


ROMA: an in vitro approach to defining target genes for transcription regulators.
We describe an in vitro transcription-based method called ROMA (run-off transcription-microarray analysis) for the genome-wide analysis of transcription regulated by sigma factors and other transcriptional regulators. ROMA uses purified RNA polymerase with and without a regulatory protein to monitor products of transcription from a genomic DNA template. Transcribed RNA is converted to cDNA and hybridized to gene arrays allowing for the identification of genes that are specifically activated by the regulator. We discuss the use of ROMA to define sigma factor regulons in Bacillus subtilis and its broad application to defining regulons for other transcriptional regulators in various species.


Intestinal absorption characteristics of the low solubility thiocarboxanilide UC-781.
The aim of this study was to determine the intestinal absorption characteristics of the antiviral agent UC-781 and to optimize the experimental conditions of the in vitro system for low solubility compounds. The absorption potential of UC-781 was studied with the Caco-2 system and with the rat intestinal perfusion technique. The low solubility of UC-781 required the use of solubility/dissolution rate enhancing agents (e.g. VitE-TPGS, Gelucire 44/14). The creation of sink conditions in the receiver compartment of the Caco-2 system was a prerequisite to reliably study the transport of this poorly soluble compound. After inclusion of VitE-TPGS in the acceptor solution, UC-781 could be characterized as a class II drug of the Biopharmaceutical Classification System (low solubility, high permeation across membranes). A significant concentration-dependent decrease in transport of UC-781 was observed upon increasing the concentration of VitE-TPGS in the apical compartment. This observation contrasts to the absorption enhancing properties of VitE-TPGS, and can probably be attributed to a decrease in the concentration of free UC-781 when using higher concentrations of the solubility/dissolution rate enhancing agents. The use of Gelucire 44/14 as a solubilizing agent resulted in a batch-dependent degradation of UC-781. The inclusion of the solubility/dissolution rate-enhancing agent VitE-TPGS did not result in absorption enhancement in the intestinal perfusion technique.


Induction of antigen-specific CD8+ cytolytic T cells by the exogenous bacterial antigen streptolysin O in rhesus monkeys.
We have characterized the T cell responses induced by streptolysin O (SLO), a sulfhydryl-activated hemolysin secreted by streptococci, by applying long-term in vitro culture and cloning rhesus monkey (Macaca mulatta) T cells. T cell lines specific for SLO were obtained from three rhesus monkeys. These T cell lines required autologous antigen-presenting cells (APC) to proliferate in response to SLO and did not respond to purified protein derivative. Phenotypic analysis showed that the cells from two of three SLO-specific T cell lines were more than 85% CD3+CD4-CD8+ after prolonged in vitro culture. The rh 1842 CD8+ T cell line proliferative response to SLO was inhibited by the addition of anti-major histocompatibility complex (MHC) class I and anti-CD8 but not of anti-MHC class II and anti-CD4 monoclonal antibody (mAb). This cell line was able to lyse P815 target cells in the presence of anti-CD3 mAb and did not show natural killer activity. Moreover, specific lysis of autologous but not allogeneic non-rosetting E- cell targets pulsed with SLO was observed. Such lysis was inhibited by the addition of anti-MHC class I mAb. In the attempt to identify the restriction elements involved in SLO presentation APC from six unrelated rhesus monkeys and three humans were used. A CD4+ rh 1842 T cell clone responded when SLO was presented by one of six, and a CD8+ rh 1842 T cell clone by four of six rhesus monkeys APC. Both CD4+ and CD8+ T cell clones did not respond when SLO was presented by human APC. However, both clones responded when APC from all donors were used in conjunction with anti-CD3 mb. Furthermore, SLO required active processing to be presented to CD4+ and CD8+ T cell clones as glutaraldehyde fixation of APC before but not after antigen pulsing inhibited T cell proliferation. The SLO-specific CD8+ cytolytic T cells described here could play a role in the regulation of the immune response occurring during streptococcal infections and/or could participate in the pathogenesis of poststreptococcal nonsuppurative sequelae.


Stress and nursing in the pig: role of HPA axis and endogenous opioid peptides.
To determine the effect of stress on nursing, and the roles of HPA activity and opioid peptides, nine sows had their piglets removed for 2 h and were treated as follows: (a) control; (b) nose-snare restraint for 20 min; (c) naloxone injections (i.v. 2 mg/kg); and (d) snare + naloxone. After the treatment, the piglets were returned, milk ejections were timed, and the sows' blood sampled every 10 min for cortisol, growth hormone (GH), and prolactin assays. Piglet removal increased cortisol and decreased prolactin and GH. This was reversed when the piglets were returned. Restraint increased cortisol and decreased GH, but did not affect prolactin. Naloxone alone increased cortisol and decreased GH but did not increase the effect of restraint. The rise in GH following the piglets' return was abolished by the combination of restraint and naloxone. Neither restraint nor naloxone delayed the latency to first milk ejection or reduced the frequency. No unsuccessful nursings were observed. First milk ejections occurred when cortisol levels were elevated. Stress-induced activity of the hypothalamo-pituitary-adrenocortical (HPA) axis does not inhibit milk ejection in the pig, but this is not due to a protective opioid action. Endogenous opioids protect lactogenic hormones against inhibition by stress.


A periodic cytoskeletal lattice in striated muscle.
The axial periodicities of electron density in striated muscle fibers extend over four orders of magnitude, ranging from the sarcomere repeat (2000-3000 nm) to a residue repeat in the alpha-helix of structural proteins (0.15 nm). A prevailing idea about the regular arrangement of structures in the contractile apparatus maintains that long-range axial spacings, related to the organization of sarcomere repeats, are essentially independent of the short-range periodicities with molecular dimensions. This is a central theme of the sliding filament hypothesis but is only supported by evidence from measured spacings near the upper and lower limits in the spectrum of dimensions, leaving a wide gap in resolved structural information extending from about 460 down to 50 nm. Several independent morphological methods show an electron-dense cross-striation of low amplitude with a pseudo-period of 230 nm, out of phase with the sarcomere repeat, in myofibrils of frog twitch fibers. Averaged images of embedded muscle fibers indicate that the sarcomere repeat contains five symmetrical pairs of these striations, which are coordinated with discrete repeats of the major molecular periods in the thick and thin filaments, in register within A and I bands. The pseudo-period therefore correlates short-range molecular repeats in the filaments with long-range registry of the sarcomere repeats in myofibrils. This raises the interesting possibility that the 230-nm pseudo-periodicity identifies a replicated axial structure in myofibrils that integrates the organization of the major structural proteins into the sarcomere repeat. The density distribution in sarcomeres of isolated unstained myofibrils also establishes that symmetrical pairs of striations with intrinsically low amplitudes are independently distorted out of uniform register in stretched sarcomeres. This behavior is consistent with the properties of N lines. The out-of-phase arrangement of 230-nm striations in the sarcomere repeat of twitch fibers should produce special diffraction effects in the region of the gap in the spectrum of periodicities recorded from muscle, with maxima at spacings extending from 200 to 80 nm. Correspondence between the diffraction spectrum of myofibril models containing a 230-nm spaced axial pseudo-period and the observed very low-angle X-ray diffraction spacings from living muscle (Huxley and Brown, 1967) suggests that the 230-nm pseudo-periodicity is a regular detectable component of striated muscle, resembling the structure of naturally occurring leptomeric fibrils in extrafusal and intrafusal fibers (Karlson and Andersson-Cedergren, 1968).(ABSTRACT TRUNCATED AT 400 WORDS)


Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities.
A series of five new 2-(1-benzofuran-2-yl)-2-oxoethyl 4-(un/substituted)benzoates 4(a-e), with the general formula of C₈H₅O(C=O)CH₂O(C=O)C₆H₄X, X = H, Cl, CH₃, OCH₃ or NO₂, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a-e) were characterized by FTIR, ¹H-, (13)C- and ¹H-(13)C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% ± 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% ± 1.06%) in metal chelating (MC) activity.


Modified bare-back micro-retrograde tibial arterial access to facilitate peripheral endovascular therapy.
Patients with critical limb threatening ischemia often present with complex segmental peripheral arterial chronic total occlusions, which might not be amenable to traditional antegrade revascularization techniques. For these patients, alternative retrograde revascularization techniques could be necessary. In the present report, we describe a novel modified retrograde cannulation technique using a bare back technique that eliminates the need for conventional tibial access sheath placement and, instead, facilitates distal arterial blood sampling, blood pressure monitoring, retrograde administration of contrast agents and vasoactive substances, and a rapid-exchange strategy. This cannulation strategy can serve as part of the armamentarium in the treatment of patients with complex peripheral arterial occlusions.


Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy.
Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis.


VSP417-6, a variant-specific surface protein encoded at a sixth locus within the vsp417 gene subfamily of Giardia intestinalis.
A sixth locus (vsp417-6) belonging to the vsp417 gene subfamily, a subset of the family of genes that encodes 'variant-specific' surface proteins (VSP) in Giardia, is described. The sequence of vsp417-6(A-I), the ortholog representing the vsp417-6 locus in isolates of the type A-I (Assemblage A, Group I) genotype of Giardia intestinalis, was determined from a cloned 5.5-kb Hind III fragment of genomic DNA derived from isolate Ad-1/C1. The gene encodes a 704 residue polypeptide (VSP417-6(A-I), Mr 71,674) that has 75% identity (92% similarity) over a 718 residue overlap with the prototype of the VSP417 subfamily, VSP417-1(A-I)-encoded by the vsp417-1 (syn. tsa417) locus in type A-I isolates. Alignment of VSP417-6(A-I) with the deduced sequences of other known members of this subfamily identified one polypeptide, encoded by a gene found in type A-II (Assemblage A, Group II) isolates, whose homology with VSP417-6(A-I) (91% identity, 98% similarity over 713-residues) indicated that it was VSP417-6(A-II), the VSP417-6 ortholog in type A-II isolates. Sequence-based phylogenetic analyses of known VSP417 subfamily members defined several loci that predate the emergence of the A-I and A-II sublineages of G. intestinalis. Related sequences that may correspond to additional, uncharacterised vsp417 subfamily genes were identified in genomic DNA by Southern hybridisation using subfamily- and locus-specific probes. Variant-specific expression of vsp417-1 and vsp417-6 within axenic cultures of G. intestinalis was detected by in situ mRNA hybridization, indicating that these genes are functional and that they are expressed in an alternative fashion with other vsp genes in these organisms.