Technology Trends for Massive MIMO towards 6G.
At the dawn of the next-generation wireless systems and networks, massive multiple-input multiple-output (MIMO) in combination with leading-edge technologies, methodologies, and architectures are poised to be a cornerstone technology. Capitalizing on its successful integration and scalability within 5G and beyond, massive MIMO has proven its merits and adaptability. Notably, a series of evolutionary advancements and revolutionary trends have begun to materialize in recent years, envisioned to redefine the landscape of future 6G wireless systems and networks. In particular, the capabilities and performance of future massive MIMO systems will be amplified through the incorporation of cutting-edge technologies, structures, and strategies. These include intelligent omni-surfaces (IOSs)/intelligent reflecting surfaces (IRSs), artificial intelligence (AI), Terahertz (THz) communications, and cell-free architectures. In addition, an array of diverse applications built on the foundation of massive MIMO will continue to proliferate and thrive. These encompass wireless localization and sensing, vehicular communications, non-terrestrial communications, remote sensing, and inter-planetary communications, among others.


Potential Risk of Choline Alfoscerate on Isoflurane-Induced Toxicity in Primary Human Astrocytes.
Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.


Applications of ultrasound for image-guided drug delivery in cancer chemotherapy.
Many challenges persist in the field of cancer drug delivery. The field of image-guided drug delivery emerged from the need for accurate in vivo quantification of various pharmacokinetic and therapeutic delivery parameters. Today it continues to be an essential tool in delivery system R&D while providing innovative noninvasive strategies for advancement. This article will focus specifically on the role of ultrasound in this area. Ultrasound provides a novel means by which drugs can be delivered through guided placement of a local delivery device, or through the destruction of ultrasound contrast agents at the target location. The techniques developed by our research group have examined these areas and have also led to a more thorough understanding into the parameters that affect drug release kinetics in vivo from in situ-forming implants. In addition, we have developed a new ultrasound contrast agent capable of extravascular delivery to tumors for improved detection and eventual treatment. Both areas will be discussed in this research spotlight.


[Application of VEGF165 plasmid in treatment of critical lower limb ischemia].
In the study we assessed the clinical and histological benefits of gene therapy in no-option patients with critical lower limb ischemia. We administrated VEGF165 (Vascular Endothelial Growth Factor) plasmid to 10 patients. The plasmid was injected intramuscularly into lower limb. In the study we evaluated: clinical outcomes, venous blood VEGF protein concentration before and after (7th, 14th, 28th and 90th day) administration of plasmid. From patients who required amputation we obtained samples of muscles, which were examined histological and by PCR (Polymerase Chain Reaction) for detection of plasmid genes. Only two patients from the group did not require amputation due to the therapy. In eight patients the operation was essential. Serum VEGF concentration was higher than in healthy controls (p < 0.05). We observed increase of the concentration of the cytokine on the 14th day an decrease on the 90th day after administration of plasmid (p < 0.05). Histological analysis did not reveal any sings of new blood vessels formation in the samples taken from amputated limbs. There was also no signs of expression of plasmid primers in PCR. The therapy is safe. We did not observe significant improvement in patient's clinical state. The therapy needs further investigations.


[Estrogen, hormonal therapy and Aging].
Recent data suggests that a "window of opportunity" to decrease the risk of mortality and coronary heart disease (CHD) exists, when initiation hormone replacement therapy (HRT) in menopausal women aged of 50 to 59 years, or within the 10 years following the onset of menopause. The risks of HRT are rare, especially in young postmenopausal women with symptoms who use HRT for long periods of time, and have lower rates of mortality and CHD than comparable postmenopausal women who do not use HRT Newer evidence suggests that there are distinct differences between synthetic molecules and estradiol ; the physiological hormone may be preferable especially from a non-oral delivery system as thrombosis risk is the lowest with such therapy. In addition, natural progesterone does not reverse the benefits of estrogen, particularly in the nervous system and the vessels, and seems to be neutral on breast cancer risk. HRT must be individualized and tailored according to symptoms and each woman's individual risk profile, her preferences and expectations.


Altered pH(i) regulation and Na(+)/HCO3(-) transporter activity in choroid plexus of cilia-defective Tg737(orpk) mutant mouse.
Tg737(orpk) mice have defects in cilia assembly and develop hydrocephalus in the perinatal period of life. Hydrocephalus is progressive and is thought to be initiated by abnormal ion and water transport across the choroid plexus epithelium. The pathology is further aggravated by the slow and disorganized beating of motile cilia on ependymal cells that contribute to decreased cerebrospinal fluid movement through the ventricles. Previously, we demonstrated that the hydrocephalus phenotype is associated with a marked increase in intracellular cAMP levels in choroid plexus epithelium, which is known to have regulatory effects on ion and fluid movement in many secretory epithelia. To evaluate whether the hydrocephalus in Tg737(orpk) mutants is associated with defects in ion transport, we compared the steady-state pH(i) and Na(+)-dependent transport activities of isolated choroid plexus epithelium tissue from Tg737(orpk) mutant and wild-type mice. The data indicate that Tg737(orpk) mutant choroid plexus epithelium have lower pH(i) and higher Na(+)-dependent HCO(3)(-) transport activity compared with wild-type choroid plexus epithelium. In addition, wild-type choroid plexus epithelium could be converted to a mutant phenotype with regard to the activity of Na(+)-dependent HCO(3)(-) transport by addition of dibutyryl-cAMP and mutant choroid plexus epithelium toward the wild-type phenotype by inhibiting PKA activity with H-89. Together, these data suggest that cilia have an important role in regulating normal physiology of choroid plexus epithelium and that ciliary dysfunction in Tg737(orpk) mutants disrupts a signaling pathway leading to elevated intracellular cAMP levels and aberrant regulation of pH(i) and ion transport activity.


Phototherapy, photochemotherapy, and bone marrow transplantation.
Recent preclinical and clinical investigations indicate that phototherapy and photochemotherapy may have applications that go far beyond their "traditional" roles in the treatment of skin disorders, selected solid tumors, and neonatal hyperbilirubinemia. Bone marrow transplantation is one area that may benefit substantially from these new developments. This review focuses on new applications of phototherapy and photochemotherapy that pertain to the inactivation of tumor cells in autologous bone marrow grafts, the prevention and treatment of acute and chronic graft-versus-host disease, the prevention of transfusion-induced allosensitization and graft rejection, and the inactivation of pathogenic viruses and parasites in bone marrow grafts and blood products.


Long non-coding RNA 2310069B03Rik functions as a suppressor of Ucp1 expression under prolonged cold exposure in murine beige adipocytes.
Specific conditions, such as exposure to cold, can induce the production of brown-like adipocytes in white adipose tissue. These adipocytes express high levels of uncoupling protein 1 (UCP1) and energy expended by generating heat. Thus, these are a potential target for the prevention or treatment of obesity. The present study involved a comprehensive analysis of the adipose tissue to understand the relationship between long non-coding RNA (lncRNA) 2310069B03Rik and UCP1. Cold exposure increased both lncRNA 2310069B03Rik and Ucp1 expression in inguinal white adipose tissue (iWAT). However, overexpression of lncRNA 2310069B03Rik suppressed the Ucp1 mRNA expression and the promoter activity of UCP1 in the iWAT primary adipocytes. In addition, compared to the early induction of Ucp1 expression by cold stimulation, the induction of lncRNA 2310069B03Rik expression was later. These results suggest that lncRNA 2310069B03Rik functions as a suppression factor of Ucp1 expression.


Implications for Drug Characterization in Glucose Tolerance Tests Without Insulin: Simulation Study of Power and Predictions Using Model-Based Analysis.
In antihyperglycemic drug development, drug effects are usually characterized using glucose provocations. Analyzing provocation data using pharmacometrics has shown powerful, enabling small studies. In preclinical drug development, high power is attractive due to the experiment sizes; however, insulin is not always available, which potentially impacts power and predictive performance. This simulation study was performed to investigate the implications of performing model-based drug characterization without insulin. The integrated glucose-insulin model was used to simulate and re-estimated oral glucose tolerance tests using a crossover design of placebo and study compound. Drug effects were implemented on seven different mechanisms of action (MOA); one by one or in two-drug combinations. This study showed that exclusion of insulin may severely reduce the power to distinguish the correct from competing drug effect, and to detect a primary or secondary drug effect, however, it did not affect the predictive performance of the model.


Oxidative Status Profile in Different Tissues of Parastacus brasiliensis promatensis (Crustacea, Decapoda, Parastacidae) over a Seasonal Cycle.
The objective of this study was to assess annual redox balance by quantifying activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), as well as measuring lipid peroxidation levels by determination of thiobarbituric acid-reactive substances, in different tissues of male and female crayfish collected from an area little affected by anthropogenic impacts. A total of 37 male and 32 female of Parastacus brasiliensis promatensis were collected over an annual cycle, and gill, muscle, hepatopancreas, and gonad samples were harvested and subjected to the aforementioned analyses via spectrophotometry. Comparison of the annual oxidative status response profile in gill and in hepatopancreas between males and females revealed differences only in SOD activity. In abdominal muscle, this comparison revealed a distinct profile of SOD and GST activity, as well as of lipid peroxidation. SOD activity in gonads of females increased in the summer when compared to autumn; conversely, CAT and GST levels did not differ over the year. During reproduction, a possible increase of the energy requirements led to an increase in lipid peroxidation in all tested tissues, in males and females alike. It was least evident in female gonad tissue, which suggests this tissue type is relatively protected; within this context, one may establish a tissue-specific grading of Lipid Peroxidation intensity in females of the species during the spring: gonads < muscle < gills < hepatopancreas. Our results show that the responses of the defenses analyzed antioxidants, as well as lipid peroxidation levels, were sex and tissue dependent and a clear pattern of seasonal variation.


Reaction of imidazole-citrate-deformed glycogen phosphorylase with amino acids.
Incubation of phosphorylase with L-valine in the presence of 0.4 M imidazole citrate results in a time-dependent decrease in the absorption of the enzyme-bound cofactor pyridoxal 5'-phosphate at 333 nm and the generation of a new absorption maximum at 415 nm which appears to be due to an enzyme-bound coenzyme-amino-acid aldimine adduct. Consequently, the enzyme is inactivated to less than 10% of its initial activity. The formation of the adduct of phosphorylase b with L-valine (0.1 M) proceeds with t1/2 approximately 8 min at pH 6.8 and 25 degrees C and is slightly inhibited by AMP. Phosphorylase a reacts five times more slowly than phosphorylase b. The decrease in enzymic activity is linked to the formation of the coenzyme-amino-acid adduct and is not due to resolution of the enzyme. Both the original absorption spectrum and phosphorylase activity are restored by gel filtration in the absence of L-valine and imidazole citrate. Similar reactions occur with other L-amino acids, an exception being L-cysteine which leads to resolution of the enzyme [Shaltiel, S., Hedrick, J. L. & Fischer, E. H. (1966) Biochemistry 5, 2108-2116]. No reaction is observed with D-amino acids or in the absence of imidazole citrate. Pyridoxal-reconstituted phosphorylase rapidly produces with amino acids not only the aldimine adduct but also a species absorbing at 318 nm. Enzyme-bound pyridoxal 5'-phosphate and pyridoxal exhibit a positive CD signal in the region of 333 nm; in contrast, the absorption bands of the coenzyme-amino-acid adducts at 415 nm and 318 nm are optically inactive. Neither pyridoxal-5'-phosphate-reconstituted nor pyridoxal-reconstituted phosphorylase in imidazole citrate catalyses any of the common pyridoxal-5'-phosphate-mediated reactions of amino acids, e.g. transamination, decarboxylation or racemization, thus testifying to the high degree of reaction specificity of phosphorylase.


Recent concepts regarding extra-hepatic portal hypertension.
Extra-hepatic portal hypertension (EHPH) defined as non cirrhotic, presinusoidal and prehepatic portal hypertension, with obstruction and cavernomatous transformation of the main portal vein, entails a high, early and prolonged risk of gastro-intestinal bleeding (GIB) mainly from esophageal and/or gastric varices, and less often a risk of cholangiopathy or protein-losing enteropathy. Diagnosis of EHPH may be done with non invasive imaging techniques. Assessment of bleeding risk is based on results of endoscopic examination. Occurence of a bleeding episode or onset during follow-up of endoscopic signs of high risk of GIB require radical eradication of varices. Radical cure of EHPH is achieved at best by bypass surgery restoring a physiological portal flow, and as a second choice by shunt surgery. Endoscopic therapy has a place as first line treatment of GIB episodes, and also in a few cases with poor extrahepatic portal network contra-indicating efficient vascular surgery.


Sevoflurane downregulates IGF‑1 via microRNA‑98.
Insulin-like growth factor (IGF)-1 functions as a neuroprotective hormone and may protect against cognitive impairment, which may occur as a result of sevoflurane exposure. The aim of the present study was to assess the effect of sevoflurane on the production of IGF‑1 and investigate the molecular mechanisms underlying this regulation. The BRL rat hepatocyte cell line and adult mice were exposed to 1 or 2 minimal alveolar concentrations sevoflurane for 4 or 8 h. IGF‑1 and microRNA‑98 levels were quantified using an enzyme‑linked immunosorbent assay, western blotting and reverse transcription‑quantitative polymerase chain reaction analyses. The importance of microRNA‑98 in the regulation of IGF‑1 by sevoflurane was investigated using a microRNA‑98 inhibitor. Sevoflurane treatment reduced IGF‑1 levels and simultaneously upregulated microRNA‑98 expression levelsin rat hepatocytes and adult mice. Inhibition of microRNA‑98 attenuated this effect. Therefore, sevoflurane may reduce the synthesis of IGF‑1 by upregulating microRNA‑98 expression.


Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study.
Common polymorphisms in the CRP gene are associated with plasma CRP levels in population-based studies, but associations with age-related events are uncertain. A previous study of CRP haplotypes in older adults was broadened to include longevity and cause-specific mortality (all-cause, noncardiovascular (non-CV), and cardiovascular (CV)). Common haplotypes were inferred from four tagSNPs in 4512 whites and five tagSNPs in 812 blacks from the Cardiovascular Health Study, a longitudinal cohort of adults over age 65. Exploratory analyses addressed early versus late mortality. CRP haplotypes were not associated with all-cause mortality or longevity overall in either population, but associations with all-cause mortality differed during early and late periods. In blacks, the haplotype tagged by 3872A (rs1205) was associated with increased risk of non-CV mortality, relative to other haplotypes (adjusted hazard ratio for each additional copy: 1.42, 95% CI: 1.07, 1.87). Relative to other haplotypes, this haplotype was associated with decreased risk of early but not decreased risk of late CV mortality in blacks; among whites, a haplotype tagged by 2667C (rs1800947) gave similar but nonsignificant findings. If confirmed, CRP genetic variants may be weakly associated with CV and non-CV mortality in older adults, particularly in self-identified blacks.


A Study of Dietary and BMI Changes Over Time in Mothers of Children with Food Allergies.
Few follow-up surveys have been conducted with regard to the changes in diet of mothers of children with food allergy. We examined changes in food and BMI over time in the mothers of children with food allergies. A total of 146 mothers completed a diet survey twice, with the first conducted in 2013-2016 and the second in 2018, and the dietary changes were examined. Furthermore, among the 120 mothers who eliminated eggs from their diet in the first survey, 98 continued to eliminate eggs and 22 reintroduced eggs during the second survey, and the change over time was examined. Additionally, factors related to BMI were analyzed. We observed a change in the amount of egg intake over time within each group. As the number of children who consumed eggs as the causative food declined, the amount of eggs consumed by the concerned mothers significantly increased (median: 7.8 g/1,000 kcal→12.7 g/1,000 kcal) (p<0.01), even in children who continued to not consume eggs. We found a negative correlation between BMI in mothers of children with FA and vegetable protein. The mothers indicated that their awareness on food allergy improved, which we believe led to increased consumption of foods that had been restricted thus far. BMI was believed to be related to synchronization with the elimination-substitution diet.


Multiple propionyl coenzyme A-supplying pathways for production of the bioplastic poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in Haloferax mediterranei.
Haloferax mediterranei is able to accumulate the bioplastic poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with more than 10 mol% 3-hydroxyvalerate (3HV) from unrelated carbon sources. However, the pathways that produce propionyl coenzyme A (propionyl-CoA), an important precursor of 3HV monomer, have not yet been determined. Bioinformatic analysis of H. mediterranei genome indicated that this strain uses multiple pathways for propionyl-CoA biosynthesis, including the citramalate/2-oxobutyrate pathway, the aspartate/2-oxobutyrate pathway, the methylmalonyl-CoA pathway, and a novel 3-hydroxypropionate pathway. Cofeeding of pathway intermediates and inactivating pathway-specific genes supported that these four pathways were indeed involved in the biosynthesis of 3HV monomer. The novel 3-hydroxypropionate pathway that couples CO2 assimilation with PHBV biosynthesis was further confirmed by analysis of (13)C positional enrichment in 3HV. Notably, (13)C metabolic flux analysis showed that the citramalate/2-oxobutyrate pathway (53.0% flux) and the 3-hydroxypropionate pathway (30.6% flux) were the two main generators of propionyl-CoA from glucose. In addition, genetic perturbation on the transcriptome of the ΔphaEC mutant (deficient in PHBV accumulation) revealed that a considerable number of genes in the four propionyl-CoA synthetic pathways were significantly downregulated. We determined for the first time four propionyl-CoA-supplying pathways for PHBV production in haloarchaea, particularly including a new 3-hydroxypropionate pathway. These results would provide novel strategies for the production of PHBV with controllable 3HV molar fraction.


A Systematic Review of the Different Calculation Methods for Measuring Jump Height During the Countermovement and Drop Jump Tests.
The heights obtained during the countermovement jump and drop jump tests have been measured by numerous studies using different calculation methods and pieces of equipment. However, the differences in calculation methods and equipment used have resulted in discrepancies in jump height being reported. The aim of this systematic review was to examine the available literature pertaining to the different calculation methods to estimate the jump height during the countermovement jump and drop jump. A systematic review of the literature was undertaken using the SPORTDiscus, MEDLINE, CINAHL, and PubMed electronic databases, with all articles required to meet specified criteria based on a quality scoring system. Twenty-one articles met the inclusion criteria, relating various calculation methods and equipment employed when measuring jump height in either of these two tests. The flight time and jump-and-reach methods provide practitioners with jump height data in the shortest time, but their accuracy is affected by factors such as participant conditions or equipment sensitivity. The motion capture systems and the double integration method measure the jump height from the centre of mass height at the initial flat foot standing to the apex of jumping, where the centre of mass displacement generated by the ankle plantarflexion is known. The impulse-momentum and flight time methods could only measure the jump height from the centre of mass height at the instant of take-off to the apex of jumping, thus, providing statistically significantly lower jump height values compared with the former two methods. However, further research is warranted to investigate the reliability of each calculation method when using different equipment settings. Our findings indicate that using the impulse-momentum method via a force platform is the most appropriate way for the jump height from the instant of take-off to the apex of jumping to be measured. Alternatively, the double integration method via a force platform is preferred to quantify the jump height from the initial flat foot standing to the apex of jumping.


The 5-Item Modified Frailty Index Predicts Adverse Outcomes in Trauma.
The 5-item modified frailty index (mFI-5) has been shown to predict adverse outcomes in surgery; yet, its role in trauma patients is unclear. We hypothesized that increasing frailty, as indicated by increasing mFI-5 scores, would correlate with worse outcomes and greater mortality in trauma patients. We performed a retrospective review of patients captured by our 2018 Spring and Fall Trauma Quality Improvement Program registry. The mFI-5 was calculated by assigning one point for each comorbidity present: diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and functionally dependent health status. Outcomes included complications, length of stay, mortality, and discharge location. A total of 3364 patients were included; 68.0% (n = 2288) were not frail, 16.5% (n = 555) were moderately frail, and 15.5% (n = 521) were severely frail. Higher frailty scores were associated with greater rates of unplanned intubations (P < 0.01) and unplanned admissions to the intensive care unit (P < 0.01). Rates of nonhome discharge (P < 0.0001) were significantly higher in the severe frailty group compared with the moderate and no frailty groups. On multivariable regression adjusting for demographics and injury details, severe frailty was predictive of any complication (odds ratio [OR], 1.53; 95% confidence interval [95% CI], 1.12-2.11; P < 0.01), failure to rescue (OR, 2.88; 95% CI, 1.47-5.66; P = 0.002), nonhome discharge (OR, 1.88; 95% CI, 1.47-2.40; P < 0.0001), and mortality (OR, 1.83; 95% CI, 1.07-3.15; P = 0.03). Frailty is not only associated with longer hospitalizations but also with more complications, adverse discharge locations, and increased odds of mortality. The mFI-5 is a quick and intuitive tool that can be used to determine an individual's frailty at the time of admission.


Segregation in like-charged polyelectrolyte-surfactant mixtures can be precisely tuned via manipulation of the surfactant mass ratio.
In this study, we consider segregative phase separation in aqueous mixtures of quaternary ammonium surfactants didecyldimethylammonium chloride (DDQ) and alkyl (C12, 70%; C14 30%) dimethyl benzyl ammonium chloride (BAC) upon the addition of poly(diallyldimethylammonium) chloride (pDADMAC) as a function of both concentration and molecular weight. The nature of the surfactant type is dominant in determining the concentration at which separation into an upper essentially surfactant-rich phase and lower polyelectrolyte-rich phase is observed. However, for high-molecular-weight pDADMAC there is a clear indication of an additional depletion flocculation effect. When the BAC/DDQ ratio is tuned, the segregative phase separation point can be precisely controlled. We propose a phase separation mechanism for like-charged quaternary ammonium polyelectrolyte/surfactant/water mixtures induced by a reduction in the ionic atmosphere around the surfactant headgroup and possible ion pair formation. An additional polyelectrolyte-induced depletion flocculation effect was also observed.


An efficient robotic tendon for gait assistance.
A robotic tendon is a spring based, linear actuator in which the stiffness of the spring is crucial for its successful use in a lightweight, energy efficient, powered ankle orthosis. Like its human analog, the robotic tendon uses its inherent elastic nature to reduce both peak power and energy requirements for its motor. In the ideal example, peak power required of the motor for ankle gait is reduced from 250 W to just 77 W. In addition, ideal energy requirements are reduced from nearly 36 J to just 21 J. Using this approach, an initial prototype has provided 100% of the power and energy necessary for ankle gait in a compact 0.95 kg package, seven times less than an equivalent motor/gearbox system.


Partial rejuvenation of a colloidal glass.
We study the effect of shear on the aging dynamics of a colloidal suspension of synthetic clay particles. We find that a shear of amplitude gamma reduces the relaxation time measured just after the cessation of shear by a factor exp(-gamma/gamma(c)), with gamma(c) approximately 5%, and is independent of the duration and the frequency of the shear. This simple law for the rejuvenation effect shows that the energy involved in colloidal rearrangements is proportional to the shear amplitude gamma rather than gamma(2), leading to an Eyring-like description of the dynamics of our system.


Digital tools for brownfield redevelopment: Stakeholder perspectives and opportunities.
Brownfield redevelopment is a complex process often involving a wide range of stakeholders holding differing priorities and opinions. The use of digital systems and products for decision making, modelling, and supporting discussion has been recognised throughout literature and industry. The inclusion of stakeholder preferences is an important consideration in the design and development of impactful digital tools and decision support systems. In this study, we present findings from stakeholder consultation with professionals from the UK brownfield sector with the aim of informing the design of future digital tools and systems. Our research investigates two broad themes; digitalisation and the use of digital tools across the sector; and perceptions of key brownfield challenge areas where digital tools could help better inform decision-makers. The methodology employed for this study comprises the collection of data and information using a combination of interviews and an online questionnaire. The results from these methods were evaluated both qualitatively and quantitatively. Findings reveal a disparity in levels of digital capability between stakeholder groups including between technical stakeholder types, and that cross-discipline communication of important issues may be aided by the development of carefully designed digital tools. To this end, we present seven core principles to guide the design and implementation of future digital tools for the brownfield sector. These principles are that future digital tools should be: (1) Stakeholder driven, (2) Problem centred, (3) Visual, (4) Intuitive, (5) Interactive, (6) Interoperable, and (7) Geospatial data driven.


[Impact and related mechanism of exogenous receptor activity modifying protein 1 on calcitonin gene-related peptide modified bone marrow mesenchymal stem cells on the migration of vascular smooth muscle cells in vitro].
To investigate the impact of calcitonin gene-related peptide (CGRP) modified bone marrow mesenchymal stem cell (MSC) on the migration of vascular smooth muscle cell (VSMC) and related mechanisms. The MSC and VSMC were isolated from rats and cultured, CGRP was transfected to MSC with the high expression lentivirus vector, VSMC was transfected with high expression lentivirus vector of receptor activity modifying protein 1 (RAMP1) and the silence expression lentivirus vector of RAMP1. Then MSC was co-cultured with VSMC. Experimental groups were as follows: (1) Ang II group (MSC + VSMC + Ang II); (2) MSC(CGRP+) group (MSC(CGRP+) + VSMC + Ang II); (3) MSC(CGRP+) RAMP1(-) group (MSC(CGRP+) + VSMC(RAMP1-) + Ang II); (4) MSC(CGRP+) RAMP1(+) group (MSC(CGRP+) + VSMC(RAMP1+) + Ang II); (5) RAMP1(+) group (MSC + VSMC(RAMP1+) + Ang II). Transwell assay was applied to detect the migration of smooth muscle cells, Western blot was applied to detect the protein expression of cells in various groups. VSMC migration number was significantly lower in MSC(CGRP+) group compared with Ang II group (50.8 ± 2.6 vs. 71.4 ± 2.3, P < 0.05), but higher than in MSC(CGRP+) RAMP1(+) group (50.8 ± 2.6 vs. 30.4 ± 3.0, P < 0.05). When RAMP1 expression reduced in VSMC, compared with MSC(CGRP+) RAMP1(+) group, VSMC migration increased in the MSC(CGRP+) RAMP1(-) group compared to MSC(CGRP+)RAMP1(+) (69.0 ± 5.6 vs. 30.4 ± 3.0, P < 0.05) and was similar to Ang II group (69.0 ± 5.6 vs. 71.4 ± 2.3, P > 0.05) and RAMP1(+) group (71.6 ± 3.4). According to the result of Western blot, P-P65 protein expression in MSC(CGRP+) group was lower than that in Ang II group (0.475 ± 0.022 vs.0.642 ± 0.035, P < 0.05). P-P65 protein expression in MSC(CGRP+)RAMP1(-) group was higher than that in MSC(CGRP+) RAMP1(+) group (0.670 ± 0.030 vs. 0.373 ± 0.041, P < 0.05), and there was no difference between MSC(CGRP+)RAMP1(-) group and Ang II group (P > 0.05). P-P65 protein expression was similar between RAMP1(+) group (0.643 ± 0.039) and Ang II group (P > 0.05). CGRP inhibits VSMC migration through RAMP1. NF-κB and RAMP1 play crucial role in the inhibiting effects of CGRP on VSMC migration. Thus, RAMP1-CGRP signaling inhibits VSMC migration through NF-κB signal pathways.


A very rare pathogen in peritoneal dialysis peritonitis: Serratia liquefaciens.
Peritoneal dialysis (PD) peritonitis has been decreasing in frequency in recent years. However, it still causes significant morbidity and mortality. Nearly 1%-6% of all peritonitis attacks result in death. Hospitalizations, loss of PD access, and intravascular catheter insertion for hemodialysis are some examples of morbidity. Approximately 15%-20% of the infectious mortality of PD patients is attributed to peritonitis. The responsible pathogens are usually Gram-positive bacteria, but unusual pathogens may be present. Prognosis is worse when Gram-negative and fungal pathogens are involved. We report a case of Serratia liquefaciens peritonitis due to defiance of hygienic practices which presented with severe abdominal pain and fever and led to loss of PD access.


The impact of public awareness, infrastructure, and technological development with economic growth on solid waste management of European countries: does governance quality matters.
Solid waste generation is a significant problem affecting the ecosystem, human health, and safety. However, the issue is not given the attention it truly deserves. Consequently, this study is aimed at assessing the impact of various factors, such as economic growth, public awareness, infrastructure, and technological advancements, on generating municipal waste in the European Union (EU) for the period 1995-2020. Furthermore, the study incorporated the mediating effect of economic growth and government effectiveness with public awareness, infrastructure, and technological development to reduce waste generation. By employing the bias-corrected method of moments, the study finds that overall waste generation does not decrease over time in EU economies. Furthermore, Denmark is the top-ranked country among the sampled countries to generate waste. However, Finland is at the top in government effectiveness. The empirical findings showed that economic growth is the significant reason for the increase in solid waste production. Additionally, the interaction effects of economic growth with public awareness, infrastructure, and technological development are positive. However, the individual impact of public awareness, infrastructure, and technological development is positive in reducing waste generation. Governance effectiveness is a significant tool to lower waste generation in European economies.


[Preparation and evaluation of Sudan Red I molecularly imprinted polymer].
The molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using Sudan Red I as the template. To investigate the influence of porogenic solvent and the amount of template on recognition property, selective chromatographic evaluation and frontal chromatography were performed. The results indicated that the obtained MIP had the best affinity and selectivity to the template when the molar ratio of template to functional monomer was 1:8 and a mixture of 30 mL methanol and 10 mL acetonitrile was used as the porogenic solvent. The imprinted factor of optimal MIP for Sudan Red I was 2.32, and the total amount of the immobilized ligand was 0.50 micromol/g. This MIP displayed good specific recognition property for Sudan Red I and was used as the sorbent of solid phase extraction (SPE) to determine trace Sudan Red I in chili powders. The linear range was from 10 to 500 micromol/L with a correlation coefficient of 0.999. The detection limit was 3.3 micromol/L, the spiked recovery was between 95.87% and 98.41%, and the relative standard deviation (RSD) was lower than 3.1%. The developed method can be used for the routine detection of Sudan Red I in chili powders.


Squamous metaplasia in colorectal polyps.
Two cases of rectal polyps that showed foci of squamous metaplasia are reported. In one, the squamous metaplasia was observed in an area of intramucosal adenocarcinoma. This finding tends to reinforce the contention previously made by some authors that squamous metaplasia in colorectal polyps may represent the precursor of primary colorectal squamous cell carcinoma or colorectal adenocarcinoma with squamous components (adenoacanthoma or adenosquamous carcinoma).


Pregnancy-Onset Panic Disorder: Incidence, Comorbidity and Associated Factors.
The present study aimed to investigate the incidence rate of pregnancy-onset panic disorder (POPD) among Turkish pregnant women using a diagnostic interview. Additionally, we examined whether the independent socio-demographic or clinical risk factors were associated with the risk of panic disorder in these women. The study sample comprised 1475 consecutive pregnant women who presented to the obstetric outpatient clinics of two research centers. The rate of POPD in these participants was 1.3% (Group 1, n=20). The 20 women with POPD were compared with 250 pregnant women without pregnancy-onset depression or anxiety (Group 2; controls). Panic disorder and other anxiety or mood disorders were determined by means of the Structured Clinical Interview for DSM-IV. Comorbid Axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R Personality Disorders. The incidence rate of panic disorder was 1.3% (n=20). In group 1, 55% (n=11) of the women with POPD had an additional mood or anxiety disorder. In addition, the prevalence rate of any cluster C personality disorder, including avoidant, passive-aggressive and obsessive-compulsive personality disorders, were significantly greater in the group 1 women with POPD than the control pregnant women without a panic disorder (group 2). The women with POPD were more likely than the controls to have a cluster C Axis II disorder and a history of a pre-existing anxiety or mood disorder.


Effects of ketamine on voltage-dependent calcium currents and membrane potentials in single bullfrog atrial cells.
This study was undertaken to assess the effect of ketamine on L-type calcium channel current (I(Ca)) and membrane action potential in the bullfrog single atrial myocyte. Bullfrog single atrial myocytes were prepared by enzymatic dispersion. Whole-cell voltage-clamp technique and current clamp technique were used to monitor I(Ca), membrane resting potential, and action potential. Ketamine (10(-5)-10(-3) M) showed dose-dependent inhibition of I(Ca) in a reversible manner. The 50% inhibitory concentration (IC(50)) of ketamine on I(Ca) was estimated to be 0.92 x 10(-5) M. Use-dependent block of I(Ca) was not observed. The resting membrane potential was depolarized at a high concentration (10(-4) M) of ketamine. Reduction of the plateau phase and prolonged duration of the action potential were observed in the presence of a high concentration of ketamine (10(-4) M). Ketamine has an inhibitory effect on I(Ca) in the bullfrog single atrial myocyte, and a high dose (10(-4) M) of ketamine prolonges the duration of the action potential. The mechanism of inhibition of I(Ca) seems to be a direct effect on the L-type calcium channel, not like an open channel blocker.


Three parallel linkage groups of human acidic keratin genes.
Two regions of human genomic DNA, each containing several keratin genes, were isolated and partially sequenced. The keratin genes are inactive, having suffered deleterious mutations. Both regions contain at least four keratin genes arranged in a head-to-tail orientation including a pseudogene for keratin K#16. Within each segment there are two keratin genes in close linkage with only 1.5 kb of DNA between them. Sequence comparison of the two regions showed 98.9% identity in both the coding and the intronic segments of the pseudogenes. The pseudogenes show 94% identity to their functional counterparts. Southern hybridization analysis showed that the segments are paralogous, not allelic. The regions are products of two independent, recent duplication events. The first occurred approximately 24 million years ago, after the separation of primates from the rhesus/baboon line. The second is specific for the human lineage, having occurred approximately 3.8 million years ago. Analysis of the genomic DNAs of primates showed the presence of only one of the regions in the DNAs of gibbon and gorilla, while rhesus monkey and baboon were missing both copies. We conclude that the human keratin genes are still actively evolving, with new duplications having occurred as recently as after the separation of human and gorilla ancestors.


Sarcoidosis and spondyloarthritis: A coincidence or common etiopathogenesis?
Sarcoidosis is a multisystem granulomatous disease. Co-existence with spondyloarthritis (SA) has been more described as an adverse effect of anti-TNF α therapy than an association. We report herein a case of a typical sarcoidosis confirmed by histological proofs and an advanced SA with a bamboo column. A 48-years-old woman presented with inflammatory back pain for 5 years and ankle swelling for 1 year. On physical examination, she had an exaggerated dorsal kyphosis and disappearance of lumbar lordosis with limitation in motion of the cervical and lumbar spine. Laboratory tests did not show an inflammatory syndrome or hypercalcemia. Plain radiographies of the spine and pelvic revealed a triple ray appearance with sacroiliitis grade 4. Chest radiography and CT confirmed the presence of bilateral hilar lymph nodes and parenchymal nodes. Bronchoscopy and biopsies were performed showing non-calcified granulomatous reaction without cell necrosis. The diagnosis of SA was performed based on 9 points of Amor criteria associated with pulmonary sarcoidosis. She was treated with 15 mg per week of methotrexate and 1mg/kg/day of prednisone for pulmonary disease with good outcomes. Sarcoidosis may be associated to SA besides paradoxical drug effect. The same physio pathological pathways mediate by TNF α are arguments for association than hazardous coincidence.


Occupational exposure to particles and mitochondrial DNA - relevance for blood pressure.
Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and cardiovascular response, measured as blood pressure. We investigated 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal sampling of the welders' exposure to respirable dust was performed during work hours (average sampling time: 6.8 h; range: 2.4-8.6 h) and blood pressure was measured once for each subject. We measured relative mtDNA copy number by quantitative PCR and methylation of the mitochondrial regulatory region D-loop and the tRNA encoding gene MT-TF by bisulfite-pyrosequencing. We calculated the relative number of unmethylated D-loop and MT-TF as markers of mtDNA function to explore the modification of mtDNA on the association between particle exposure and blood pressure. General linear models were used for statistical analyses. Welders had higher mtDNA copy number (β = 0.11, p = 0.003) and lower DNA methylation of D-loop (β = -1.4, p = 0.002) and MT-TF (β = -1.5, p = 0.004) than controls. Higher mtDNA copy number was weakly associated with higher personal respirable dust exposure among welders with exposure level above 0.7 mg/m3 (β = 0.037, p = 0.054). MtDNA function modified the effect of welding fumes on blood pressure: welders with low mtDNA function had higher blood pressure than controls, while no such difference was found in the group with high mtDNA function. Increased mtDNA copy number and decreased D-loop and MT-TF methylation were associated with particle-containing welding fumes exposure, indicating exposure-related oxidative stress. The modification of mtDNA function on exposure-associated increase in blood pressure may represent a mitochondria-environment interaction.


Acidrine in the management of gastritis and duodenitis. A double-blind placebo controlled clinical trial.
Thirty-nine adult out-patients with dyspepsia and endoscopically proven gastritis and/or duodenitis without ulcer, completed a double-blind, placebo controlled, 8-week clinical trial of either Acidrine (twenty-one patients) or placebo (eighteen patients), at a daily dosage of 2 tablets t.i.d. Treatment with Acidrine resulted in a significant improvement in symptoms and in the endoscopic appearance of the gastritis and duodenitis when compared with placebo.


Role of 2-Dimensional Autocorrelation Descriptors in Predicting Antimalarial Activity of Artemisinin and its Aanalogues: A QSAR Study.
Malaria, one of the World's biggest billers' is on the schedule for biomedical research and public health policies. The introduction of the artemisinin, a Chinese traditional drug from Artemisia annua is a revolution in the treatment of malaria. Artemisinin-based combination treatment (ACT) is considered to be the best strategy for uncomplicated Falciparum malaria. The presence of 1,2,4-trioxane system in artemisinin is responsible for its antimalarial activity. In this study, twenty-nine analogues of artemisinin were taken into account for QSAR studies along with artemisinin. The most active analogue of artemisinin 21 was energy minimized. All the structures were prepared from the active conformer 21 and energy was minimized to the stable state using MMFF94 force field using ChemBioDraw-12. Genetic Algorithm is used to decide the descriptors best required for the model generation. The test set and training set division were done by using hierarchal clustering module available with NCSS statistical software. The antimalarial activity of the artemisinin and its substituted analogues has been analyzed through the multiple linear regression (MLR) using various physiochemical and structural descriptors obtained from PADEL software. The models were prepared using the Sigma Plot version 11. The calculated 2D autocorrelation descriptors and the MLR model suggest that artemisinin and its analogues hold the scope in the optimization of antimalarial activity.


Scooter injuries in children in a midwestern metropolitan area.
We describe the use of nonmotorized scooters and utilization of safety equipment in a Midwestern suburb. Schoolchildren in second to sixth grades of a local school district completed a survey distributed by school nurses and teachers in spring 2001, including topics of scooter ownership, riding patterns, and utilization of safety gear. Three thousand eighty-seven surveys were distributed, with a 74.4% response rate; 93.2% of children had ridden a scooter, and 71.4% owned a scooter. Children rode in many locations, with 93% riding on the sidewalk, 86.5% in the driveway, 35.5% in a parking lot, and 20% in the street. Of those owning scooters, 91.2% reported owning a helmet, 61.2% kneepads, 59.4% elbow pads, 43.8% wrist guards, and 35.5% riding gloves. Among those owning scooters, 54.6% reported wearing helmets while using their scooter, whereas 10% or less wore riding gloves, kneepads, elbow pads, or wrist guards. Helmet use decreased as grade increased; 50.7% of all second graders reported wearing helmets, compared with 22.7% of sixth graders (P < 0.001). Of those owning scooters, 32.2% reported being injured while riding their scooter. Of those injured, 54% reported wearing helmets. Many children ride scooters and own safety gear; however, few children wear their safety equipment when riding their scooter. Children wear helmets less frequently as they age. Physicians should continue to educate patients and their parents as to potential injuries on scooters and encourage the use of safety gear, especially helmets, when riding scooters.


Adenylyl cyclase activities in ovarian tissues. IV. Gonadotrophin-induced desensitization of the luteal adenylyl cyclase throughout pregnancy and pseudopregnancy in the rabbit and the rat.
We measured the adenylyl cyclase (AC) activity in dissected CL and the responsiveness of the AC system to LH, FSH, and prostaglandin (PG)E1 at different times following the administration of high doses of hCG or hLH to pseudopregnant and pregnant rats and rabbits. In rabbits, ovulatory doses of hCG promoted desensitization of the AC system in both CL of pregnancy and CL of pseudopregnancy (PSP), but at varying rates. At least a 50% decline in the LH-stimulated AC system was demonstrable 2 h after the hCG injection in CL obtained during PSP and the first 18 days of pregnancy. However, after day 21, AC activity was unaltered at 2 or 24 h after hCG injection, necessitating as much as 72 h for the AC system to become desensitized to LH. It seems that CL in the last third of pregnancy are afforded partial protection from the desensitizing effects of hCG. This protective effect was found not to be conferred upon follicles contained in ovaries after day 21 of pregnancy or upon newly, hCG-induced 3-day-old CL in 24-day pregnant rabbit ovaries. hCG-induced desensitization of CL adenylyl cyclase in rabbits was prevented neither by cauterization of tertiary follicles not by the continued administration of estradiol-17beta (1.5 mug SC twice daily), suggesting that this effect of hCG is due to a direct interaction with the CL, and not due to interruption of the follicular estrogen supply. In rats, the injection of an ovulatory dose of hCG (50 IU SC into prepubertal rats; 50 IU ip plus 50 IU SC into mature rats) also induced desensitization of the AC system in ovaries of superovulated prepubertal rats and in CL of pseudopregnant and pregnant rats. Desensitization of the AC system was not detectable at 2 h, was 30% of total by 6 h, and was complete at 24 h after hCG injection. Both regression of the CL and desensitization of the AC system in CL are induced only by doses of hCG which are ovulatory and not subovulatory. Desensitization of AC appears to precede functional luteolysis, at least in the pseudopreganant rabbit. Thus, the apparent close association between hCG-induced luteolysis and the desensitization of the adenylyl cyclase system in CL would suggest that desensitization may be a marker for luteal regression.


Genotypic and Phenotypic Variations in Botrytis spp. Isolates from Single Strawberry Flowers.
Gray mold, caused by Botrytis spp., is among the most devastating diseases affecting strawberry worldwide. The great diversity present in the pathogen enhances its ability to survive and adapt in the field. In this study, we explored the genotypic and phenotypic diversity present in single strawberry flowers. In total, 192 isolates were collected from 19 flowers and four farms, and 9 to 12 isolates were collected from each flower. Forty-two haplotypes were found using microsatellite fragment analysis. Multiple haplotypes of two different Botrytis spp. (Botrytis cinerea and B. fragariae) were found in 12 flowers. In the remaining seven flowers, the single-spore isolates examined were of identical haplotypes. In three flowers, the two Botrytis spp. were found to coexist. Isolates were either sensitive (zero chemical class resistance) or resistant to one, two, three, four, or five chemical classes of fungicides. Resistance to multiple fungicides was commonly observed in both species but resistance to boscalid and penthiopyrad was only found in B. cinerea isolates. Resistance to cyprodinil was found in B. fragariae for the first time in the United States. Each haplotype was generally linked to a single resistance profile; however, a single resistance profile often was represented by multiple haplotypes. Isolates from the same flower of multiple haplotypes were largely identical in resistance profiles. This study is a first detailed investigation of genotypic diversity combined with phenotypic analysis of Botrytis spp. at the single-tissue level. It demonstrates that high genotypic and phenotypic diversity is present not only within fields but also in individual blossoms as well. This information is important for understanding the epidemiology of Botrytis and also has implications for fungicide resistance management, particularly related to resistance monitoring practices.


Prevalence of Histoplasmosis among Persons with Advanced HIV Disease, Nigeria.
We sought to determine the prevalence of probable disseminated histoplasmosis among advanced HIV disease (AHD) patients in Nigeria. We conducted a cross-sectional study in 10 sites across 5 of 6 geopolitical zones in Nigeria. We identified patients with urinary samples containing CD4 cell counts <200 cells/mm3 or World Health Organization stage 3 or 4 disease who also had >2 clinical features of disseminated histoplasmosis, and we tested them for Histoplasma antigen using a Histoplasma enzyme immune assay. Of 988 participants we recruited, 76 (7.7%) were antigen-positive. The 76 Histoplasma antigen-positive participants had significantly lower (p = 0.03) CD4 counts; 9 (11.8%) were also co-infected with tuberculosis. Most antigen-positive participants (50/76; 65.8%; p = 0.015) had previously received antiretroviral treatment; 26/76 (34.2%) had not. Because histoplasmosis is often a hidden disease among AHD patients in Nigeria, Histoplasma antigen testing should be required in the AHD package of care.


Linearity optimization of multi-octave analog photonic links based on power weighting, polarization multiplexing and bias control.
We present and demonstrate an approach to linearizing analog photonic links (APLs) with substantially enhanced multi-octave spurious-free dynamic range (SFDR). Combining with power weighting, polarization multiplexing and bias control techniques, the proposed approach enables the second-order harmonic distortion (HD2) and third-order intermodulation distortion (IMD3) to be suppressed simultaneously. To maximize the RF output power, an optimization model is established. The simulation results indicate that the maximum RF power can be attained when the power weighting factor and polarization incident angle are equal to 0.5 and 0.34 radians, respectively. The link is validated with a proof-of-principle experiment. The third-order SFDR is 112.3 dB·Hz2/3, corresponding to the improvement of 15.5 dB as compared with a quadrature-biased link. The second-order SFDR reaches as high as 94.6 dB·Hz1/2. Furthermore, the adjacent channel power ratio (ACPR) is measured to be up to 54.6 dBc, which is 5.4 dB greater than that of a quadrature-biased link. Finally, the system tolerances for the RF and optical input power are also investigated in terms of error vector magnitudes (EVMs). Therefore, by introducing optimization model, our scheme provides further insight into the APL linearization technique and a better performance is also achieved.


[The assessment of radiation hazards in the "MIR" and ISS orbits from the data of vehicle and personal dosimetric monitoring].
The paper describes the procedure of estimating total radiation risk to crewmembers during lifetime and possible lifetime reduction in consequence of participation in the Mir and ISS missions in different periods of the solar activity. The procedure includes analysis of data of vehicle and personal dosimetry, and calculations of radiation doses in various Mir compartments and accumulated by body tissues of cosmonauts. Calculated doses showed good consistency with the doses measured with R-16 on board Mir and personal dosimeters. To a first approximation, estimation of doses to cosmonauts and radiation risk as a result of participation in ISS missions took into account similarity of the Mir and ISS basal modules (geometry, dimensions and mass values) and was performed with the use of the space station shielding model that had been described elsewhere. The model of ISS radiation shielding will be updated as data of dosimetry of ISS compartments and phantom studies are available.


The dilemma for women of color in clinical trials.
Women in general and women of color in particular have been noticeably absent from clinical research, be it phase I pharmacokinetic drug trials or natural history observational studies. This paper examines several questions about the role of women of color in clinical research: Who participates in clinical trials and why? Do women of color face a particular dilemma in deciding to participate? A biologic construct for race and gender research issues is presented. Given the variations of pharmacokinetics and pharmacodynamics that may be race- or gender-related, certain obstacles must be addressed in order to facilitate responsible research. Those obstacles include the history of abuse of vulnerable populations in the name of clinical research, discrimination in medical care, and the lack of understanding of the combined impact of gender, race, ethnicity, and class on behavior and health.


NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up.
Diabetic nephropathy constitutes a major long-term complication in patients with type 1 diabetes mellitus (T1D) and its diagnosis is based on microalbuminuria. The aim of this observational follow-up study was to explore the role of neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C in unravelling early diabetic nephropathy even in patients with normoalbuminuria. Fifty-six euthyroid patients with T1D, with mean age 13.1 (SD: 3.2) years, and 49 healthy controls with mean age 12.8 (SD: 6.6) were recruited. Besides standard blood chemistry and urinary albumin excretion, serum NGAL (ELISA) and cystatin C (nephelometry) were measured at enrollment and after 12-15 months. GFR was calculated with the bedside Schwartz formula (eGFR) and the Lund strategy formula (L-eGFR). At baseline, mean NGAL levels were not significantly different between children with diabetes and controls. At re-evaluation, mean NGAL value and mean eGFR value in patients with diabetes were increased (p=0.032 and p=0.003 respectively). At both baseline and reevaluation, NGAL was positively correlated with cystatin C (r=0.41, p<0.001), systolic arterial pressure z-score (r=0.3, p=0.031) and creatinine (r=0.32, p=0.010). NGAL correlated negatively with eGFR (r=-0.26, p=0.049) and L-eGFR (r=-0.33, p=0.010). Cystatin C had a negative correlation to eGFR (r=-0.29, p=0.025) and a positive one with creatinine (r=0.35, p=0.009) at reevaluation. No statistically significant correlation was found between cystatin C and microalbuminuria (p=0.736). NGAL and cystatin C, known markers of renal injury, correlate with renal function decline in T1D, suggesting that they may be used as supplementary tests to urine albumin excretion in order to unmask early renal dysfunction.


Radical scavenging and NO-releasing properties of selected beta-adrenoreceptor antagonists.
It is claimed that novel beta-adrenolytic drugs possess superior antioxidant properties as compared to classical selective or non-selective beta-adrenoceptor antagonists. Here we tested this notion by analyzing radical scavenging properties of selected beta-adrenolytic drugs and their ability to release nitric oxide in biological preparations. Selective beta1-adrenolytics such as nebivolol, atenolol, metoprolol and non-selective beta-adrenolytics with alpha1-receptor blocking properties such as carvedilol and labetalol were chosen for analysis. NO-releasing properties of nebivolol and carvedilol distinguished third generation beta-adrenolytics from their older counterparts while the reactivity towards hydroxyl and peroxyl radicals discerns only carvedilol but not nebivolol. Thus, superior clinical efficacy of third generation beta-adrenolytics may be related to their ability to release NO rather then to their direct antioxidant properties.


Elevated ecto-5'-nucleotidase: a missing pathogenic factor and new therapeutic target for sickle cell disease.
Although excessive plasma adenosine is detrimental in sickle cell disease (SCD), the molecular mechanism underlying elevated circulating adenosine remains unclear. Here we report that the activity of soluble CD73, an ectonucleotidase producing extracellular adenosine, was significantly elevated in a murine model of SCD and correlated with increased plasma adenosine. Mouse genetic studies demonstrated that CD73 activity contributes to excessive induction of plasma adenosine and thereby promotes sickling, hemolysis, multiorgan damage, and disease progression. Mechanistically, we showed that erythrocyte adenosine 5'-monophosphate-activated protein kinase (AMPK) was activated both in SCD patients and in the murine model of SCD. AMPK functions downstream of adenosine receptor ADORA2B signaling and contributes to sickling by regulating the production of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), a negative allosteric regulator of hemoglobin-O2 binding affinity. Preclinically, we reported that treatment of α,β-methylene adenosine 5'-diphosphate, a potent CD73 specific inhibitor, significantly decreased sickling, hemolysis, multiorgan damage, and disease progression in the murine model of SCD. Taken together, both human and mouse studies reveal a novel molecular mechanism contributing to the pathophysiology of SCD and identify potential therapeutic strategies to treat SCD.


[Retrospectively analysis of the difference of bleeding frequency and hemophilic arthropathy between hemophilia A and hemophilia B patients].
Objective: To analyze the difference of bleeding frequency, plain radiographic (X-ray) , risk factors in hemophilic arthropathy progression and the Arnold-Hilgartner classification. Methods: A retrospective study was conducted in 211 hemophilia patients hospitalized in our medical center between January 2007 and December 2010, some patients with hemarthrosis were followed up for 5 years. Results: All patients were male, including 150 hemophilia A (HA) and 61 hemophilia B (HB) . The HA patients bled more frequently than HB patients with annualized total bleeding rate 20.5 (0-48) vs 13 (1-40) ; annualized joint bleeding rate 13.5 (0-38) vs 8 (0-33) , especially in moderate hemophilia [26 (1-48) vs 12 (1-36) , P<0.001; 18 (0-36) vs 7.5 (0-26) , P=0.001], but severe hemophilia had no difference in bleeding frequency [33 (1-41) vs 26 (1-40) , P=0.702; 22 (0-36) vs 18 (0-33) , P=0.429]. The condition of the affected joints of 108 HA and 54 HB was evaluated on roentgenography. In HA patients, the Arnold-Hilgartner classification increased with the severity ratings (r=0.063, P=0.004) . However, similar associations were not found in HB patients (r=0.045, P=0.082) . Five years later, 36 HA and 19 HB patients received the same joint X-ray, there were no significant differences in joints radiographic progression between the total HA and HB groups (z=1.941, P=0.052) . However, significant difference between moderate HA and HB was observed (z=0.076, P=0.002) . Multivariate unconditioned Logistic analysis showed that annualized joint bleeding rate [P<0.001, OR=1.166 (95%CI 1.097-1.239) ] and articular structural injuries [P=0.018, OR=2.842 (95% CI 1.196-6.755) ] were independent risk factors for the joints radiographic progression. Conclusion: The study suggests that there was a difference in bleeding phenotype between HA and HB, especially in moderate hemophilia. HB patients showed mild but progressive development over time, compared with HA patients. Annualized joint bleeding rate and articular structural injuries were independent risk factors for the joints radiographic progression.


COEXISTENCE OF ADDISON'S DISEASE AND PERNICIOUS ANEMIA: IS THE NEW CLASSIFICATION OF AUTOIMMUNE POLYGLANDULAR SYNDROME APPROPRIATE?
A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man was admitted due to fatigue, malaise and inappetence. He had a history of primary hypothyroidism and was on levothyroxine substitution therapy. One year before, he was diagnosed with normocytic anemia and vitamin B12 deficiency, which was treated with vitamin B12 substitution therapy. Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the diagnosis of Addison's disease was established. Additional laboratory workup showed positive parietal cell antibodies. However, his vitamin B12 levels were increased due to vitamin B12 supplementation therapy, which was initiated earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell antibodies and atrophic gastritis, the patient was diagnosed with pernicious anemia. Hydrocortisone supplementation therapy was administered and titrated according to urinary-free cortisol levels. Electrolyte disbalance and red blood cell count were normalized. This case report demonstrates rather unique features of pernicious anemia in a patient with Addison's disease. It also highlights the link between type II and type III APS. Not only do they share the same etiological factors, but also overlap in pathophysiological and clinical characteristics. This case report favors older classification of APS, which consolidates all endocrine and other organ-specific autoimmune diseases into one category. This is important since it might help avoid pitfalls in the diagnosis and treatment of patients with APS.


Proteomics profiling reveals a distinct high-risk molecular subtype of hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease, likely encompassing several subtypes of disease with distinct biological mechanisms (ie, molecular subtypes). Current models based solely on clinical data have yielded limited accuracy in predicting the risk of major adverse cardiovascular events (MACE). Our aim in this study was to derive molecular subtypes in our multicentre prospective cohort of patients with HCM using proteomics profiling and to examine their longitudinal associations with MACE. We applied unsupervised machine learning methods to plasma proteomics profiling data of 1681 proteins from 258 patients with HCM who were prospectively followed for a median of 2.8 years. The primary outcome was MACE, defined as a composite of arrhythmia, heart failure, stroke and sudden cardiac death. We identified four molecular subtypes of HCM. Time-to-event analysis revealed significant differences in MACE-free survival among the four molecular subtypes (plogrank=0.007). Compared with the reference group with the lowest risk of MACE (molecular subtype A), patients in molecular subtype D had a higher risk of subsequently developing MACE, with an HR of 3.41 (95% CI 1.54 to 7.55, p=0.003). Pathway analysis of proteins differentially regulated in molecular subtype D demonstrated an upregulation of the Ras/mitogen-activated protein kinase and associated pathways, as well as pathways related to inflammation and fibrosis (eg, transforming growth factor-β pathway). Our prospective plasma proteomics study not only exhibited the presence of HCM molecular subtypes but also identified pathobiological mechanisms associated with a distinct high-risk subtype of HCM.


Support for adults with autism spectrum disorder without intellectual impairment: Systematic review.
Adults with autism spectrum disorder without intellectual impairment may benefit from a range of support services. This article presents the results of a systematic review assessing the effectiveness of supportive interventions for adults with autism spectrum disorder without intellectual impairment. A total of 32 studies were included; most focused on younger male participants. Although evidence was lacking for most types of intervention, employment programmes and social skills training were found to be effective for more proximal outcomes such as social skills. Evidence that any intervention improves mental health or well-being was very limited. Most interventions focused on mitigating specific deficits, rather than on providing broader support. Further research is needed on the effectiveness of supportive interventions such as advocacy and mentoring.


Origin of Jahn-Teller distortion and orbital order in LaMnO3.
The origin of the cooperative Jahn-Teller distortion and orbital order in LaMnO3 is central to the physics of the manganites. The question is complicated by the simultaneous presence of tetragonal and GdFeO3-type distortions and the strong Hund's rule coupling between e{g} and t{2g} electrons. To clarify the situation we calculate the transition temperature for the Kugel-Khomskii superexchange mechanism by using the local density approximation+dynamical mean-field method, and disentangle the effects of superexchange from those of lattice distortions. We find that superexchange alone would yield T{KK} approximately 650 K. The tetragonal and GdFeO3-type distortions, however, reduce T{KK} to approximately 550 K. Thus electron-phonon coupling is essential to explain the persistence of local Jahn-Teller distortions to greater than or approximately 1150 K and to reproduce the occupied orbital deduced from neutron scattering.


[Impact of transrectal microwave hyperthermia on hemodynamics and prostatic cell membranes in chronic prostatitis].
An Aden-Ch apparatus programming complex made in our country was used for transrectal microwave hyperthermia in 75 patients with chronic prostatitis. In addition to its good clinical results achieved in most patients, the complex restored hemodynamics and stabilized the status of prostatic cell membranes. The complex described in the paper may be recommended for the treatment of chronic prostatitis.


Calcineurin mediates bladder smooth muscle hypertrophy after bladder outlet obstruction.
Bladder outlet obstruction (BOO) leads to compensatory bladder hypertrophy. However, the hypertrophy mechanism remains elusive. We report that calcineurin (Cn) is involved in bladder hypertrophy. Partial BOO was surgically induced in 10-week-old female Wistar rats. The bladder was excised 2, 4 and 6 weeks following surgery in 9 rats each. Histological study was performed at each time point. Cn expression was examined by Western blot analysis. Myosin heavy chain expression was evaluated on gels stained with Coomassie blue. Primary cultured bladder smooth muscle cells were infected with recombinant adenoviruses encoding a constitutive active form of CnA (DeltaCnA), CnB and lacZ, and cell size was measured. In histological findings bladder smooth muscle hypertrophy was observed 2 and 4 weeks after surgery. However, the thickened muscles became thinner 6 weeks after BOO. CnA expression 2 weeks after BOO increased 3.2-fold compared with that of controls. Expression significantly decreased 4 and 6 weeks after surgery. In contrast, CnB expression was unchanged throughout hypertrophy development. Changes in myosin heavy chain expression correlated with changes in CnA. We observed significant hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. Moreover, FK506, which is a potent inhibitor of Cn, blocked hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. These data suggest that Cn has an important role in the induction of bladder smooth muscle hypertrophy.


Biomechanical comparison of cervical spine reconstructive techniques after a multilevel corpectomy of the cervical spine.
An in vitro biomechanical study of several reconstructive techniques after a two-level cervical corpectomy. To evaluate, compare, and quantitate the stability of several reconstructive strategies (anterior, posterior, or anterior/posterior with or without instrumentation) after a multilevel cervical corpectomy. Several clinical and biomechanical studies have questioned the stability of stand-alone long-segment anterior plate fixation after a multilevel (>or=2) corpectomy. The large cantilever forces generated within the stabilized construct, particularly at the caudal screw-bone interface, have led to plate and screw dislodgement and the need for further surgical intervention. The addition of posterior segmental instrumentation has been shown to improve overall stability and decrease local stresses on the anterior fusion construct (graft and plate). Seven fresh-frozen cadaveric human cervical spines (C1-T1) were harvested. The C1-C2 and C7-T1 vertebral bodies were embedded in poly-methylmethacrylate (PMMA). Three VICON cameras tracked three-dimensional segmental motions at the ends of the fusion construct after a two-level corpectomy and placement of a strut graft with or without instrumentation. Pure moments (flexion/extension, lateral bending, and axial rotation) were applied to the C1 level of each specimen. The motion segments were loaded to a maximum of 2 Nm using dead weights. Testing was first performed on the intact specimens. Then, a two-level corpectomy at the C4 and C5 levels was performed. A PMMA strut graft was then placed into the corpectomy site. Biomechanical testing was then repeated among three different reconstruction techniques: 1) anterior cervical locking plate (PEAK; Depuy-Acromed, Raynham, MA) with dual unicortical screw fixation at C3 and C6; 2) posterior cervical instrumentation (Summit; Depuy-Acromed) using a 3.0-mm rod with segmental lateral mass screw fixation from C3 to C6; and 3) a combined anterior-posterior instrumentation using the anterior PEAK plate and posterior Summit rod system. In all pure moments tested (flexion/extension/lateral bending/axial rotation) the combined anterior-posterior instrumentation reconstruction model and the posterior-only instrumentation model were significantly more rigid than the anterior-only instrumentation model (P < 0.05). Interestingly, no statistically significant difference was noted between the combined anterior plate/posterior instrumentation model and the posterior instrumentation-only model. The biomechanical results obtained suggest that posterior segmental instrumentation confers significant stability to a multilevel cervical corpectomy regardless of the presence or absence of anterior instrumentation. In cases in which the stability of a multilevel reconstruction procedure is tenuous, the surgeon should strongly consider the placement of segmental posterior instrumentation to significantly improve the overall stability of the fusion construct.


Medial Femoral Condyle Free Flap for Persistent Osseous Nonunion of the First Metatarsophalangeal Joint: A Preliminary Report of a New Surgical Indication for the Medial Femoral Condyle Free Flap.
Recalcitrant or persistent nonunions of the metatarsophalangeal (MTP) joint occur following failed MTP surgery for MTP fusion, failed MTP prosthesis, for hallux rigidus or due to infection and erosion. A deficient soft tissue envelope and compromised vascular supply of tissues in this region compound further attempts to salvage the great toe and preserve function. The medial femoral condyle (MFC) free flap provides vascularized corticocancellous bone and periosteum and has been successfully used for a variety of complex hindfoot and ankle pathologies. We present an additional indication with a small cohort study demonstrating its use in persistent nonunions of the first MTP joint. A retrospective review was completed of all MFC flaps used for revision of failed first MTP joint fusion from January 2019 to November 2022. Demographic information, comorbidities, as well as clinical and radiologic follow-up was obtained from the patient charts. Three patients were included with MTP nonunion and an average of 7.5 (range, 5-11) failed prior surgeries. Mean age at index surgery was 50 (range, 46-57) years. An osseous union was achieved in all patients after 82 (range, 75-88) days. Hardware removal was possible after 81 (range, 55-98) days. Mean follow-up was 17 (range, 5-31) months. We note a 100% flap success rate without returns to the operating room. The lengths of the bone flaps were 2 to 4 cm, the volumes were 8 to 12 cm3. Fixation was performed with 1 intramedullary K-wire. The recipient vessel in all patients was the dorsalis pedis artery or a tributary thereof. All arterial anastomoses were performed under the operating microscope. The MFC free flap is a reasonable option for salvage of complex recalcitrant or persistent nonunions of the first MTP joint. More prospective long-term studies with functional outcomes are necessary to confirm these findings. Level IV, retrospective case series.


Graph theory as a proxy for spatially explicit population models in conservation planning.
Spatially explicit population models (SEPMs) are often considered the best way to predict and manage species distributions in spatially heterogeneous landscapes. However, they are computationally intensive and require extensive knowledge of species' biology and behavior, limiting their application in many cases. An alternative to SEPMs is graph theory, which has minimal data requirements and efficient algorithms. Although only recently introduced to landscape ecology, graph theory is well suited to ecological applications concerned with connectivity or movement. This paper compares the performance of graph theory to a SEPM in selecting important habitat patches for Wood Thrush (Hylocichla mustelina) conservation. We use both models to identify habitat patches that act as population sources and persistent patches and also use graph theory to identify patches that act as stepping stones for dispersal. Correlations of patch rankings were very high between the two models. In addition, graph theory offers the ability to identify patches that are very important to habitat connectivity and thus long-term population persistence across the landscape. We show that graph theory makes very similar predictions in most cases and in other cases offers insight not available from the SEPM, and we conclude that graph theory is a suitable and possibly preferable alternative to SEPMs for species conservation in heterogeneous landscapes.


Activity monitoring in men's college soccer: a single season longitudinal study.
Performance in soccer has been characterized previously using time-motion analyses; however, it is unclear if men's college soccer shares performance characteristics with women's college or men's professional soccer. The purpose of this study was to compare proportions of matches spent walking, jogging, running, and sprinting in men's college soccer. Twenty-two male college soccer players wore global positioning system units during matches. Proportions of walking, jogging, running, high-speed running, and sprinting were calculated for each player based on time period (first half, second half, extra time) and outcome (win, loss, tie). Multivariate analyses of variance were run for each time period to compare positions. Means, 95% confidence intervals, and effect sizes were calculated for each position based on time period and match outcome. There were differences in low-speed and high-speed activities based on position, with forwards and midfielders demonstrating increased high-speed activities. Positional differences may require different physiological profiles and should be a consideration during training.


α-Methyltyrosine, a tyrosine hydroxylase inhibitor, decreases stress response in zebrafish (Danio rerio).
In this article, we show that the tyrosine hydroxylase inhibitor α-Methyl-l-tyrosine (AMPT) decreased the responsiveness of the zebrafish stress axis to an acute stressful challenge. These effects were specific for responses to stimulation, since unstimulated (basal) cortisol levels were not altered by AMPT. Moreover, AMPT decreased the stress response 15min after stimulation, but not after that time period. To our knowledge, this is the first report about the effects of AMPT on the neuroendocrine axis of adult zebrafish in acute stress responses. Overall, these results suggest a mechanism of catecholamine-glucocorticoid interplay in neuroendocrine responses of fish, pointing an interesting avenue for physiological research, as well as an important endpoint that can be disrupted by environmental contamination. Further experiments will unravel the mechanisms by which AMPT blocked the cortisol response.


Coronary artery fistula after cardiac transplantation.
A cardiac transplant recipient with multiple coronary artery fistulae draining into the right ventricle is described. These fistulae presumably resulted from repeated endomyocardial biopsies. The diagnosis of coronary artery fistulae was made at the annual coronary arteriography. The magnitude of the shunt remained small over eight years of follow-up.


Isolation and characterization of four lipolytic preparations from rat skeletal muscle.
Four different lipolytic preparations have been isolated from rat skeletal muscle. Two of these, provisionally designated monopalmitin lipase (MPL) and monomyristin lipase (MML), are associated with insoluble cellular particulate fractions. The other two enzymes, provisionally designated tricaproin lipase (TCL) and monolaurin lipase (MLL), are found in the high-speed supernatant fraction. Taken as a group, these enzymes are capable of hydrolyzing short-chain triglycerides (acyl moieties of C(3) to C(8)) and monoglycerides of lauric, myristic, palmitic, stearic, and oleic acids. All of these enzymes have a serine residue at or near the catalytic site as they are strongly inhibited by diisopropyl fluorophosphate. The two particulate preparations contain a sulfhydryl group and are sensitive to p-chloromercuribenzoate and N-ethylmaleimide, while the soluble preparations are not. The MLL, MML, and MPL preparations all have alkaline pH optima, while the TCL preparation has an acidic optimum. Buffer type is important: some buffer compounds completely inhibited one or more preparations. Of the soluble enzymes, MLL withstood heating to 60 degrees C, while TCL is completely inactivated at this temperature. Of the particulate preparations, only MML was stable to lyophilization. It is concluded that there are at least four lipolytic enzymes in rat skeletal muscle. The possible significance of the presence of these enzymes in muscle is discussed.


Chlorsulfuron resistant transgenic tobacco as a tool for broomrape control.
Broomrape (Orobanche ramosa L.) is the most important parasitic plant that infests tobacco (Nicotiana tabacum L.). Chemical treatment of the soil is not effective and crop rotation is not acceptable to solve this problem because of the long viability period of Orobanche seeds in the soil. Application of systemic herbicides in the field with herbicide resistant tobacco could be a successful tool for broomrape control. Several tobacco cultivars were transformed with a mutant ahas3R gene for resistance to the herbicide chlorsulfuron (Glean, DuPont). Transformed plants were selfed and the segregation of resistance was followed in the next generation. The efficiency of the herbicide was demonstrated in greenhouse and field trials. An Orobanche/tobacco growth system was used in order to prove the lethal effect of the herbicide to the attached broomrape plants.


Susceptibility of Enterobacter to cefamandole: evidence for a high mutation rate to resistance.
Cefamandole minimum inhibitory concentrations (MICs) of 10 strains of Enterobacter were determined by the ICS agar dilution and broth dilution procedures. Agar dilution MICs ranged from 1 to 8 mug/ml, with an inoculum of 10(4) organisms/spot. Broth dilution MICs were consistently higher, with an inoculum of approximately 7 x 10(5) organisms/ml. Seven strains showed MICs of >/=64 mug/ml. There was a marked inoculum effect in broth, and skipped tubes were often observed. Variants resistant to 32 mug/ml or more were isolated by direct selection and were shown to occur at a frequency of approximately 10(-6) to 10(-7). A mutant showing a 16-fold increase in agar dilution MIC was also isolated by indirect selection. These variants and others isolated from broth in the presence of cefamandole were tested for ability to inactivate the antibiotic, using both a biological and a chemical procedure. Two distinct classes of variants were seen. Twelve of 28 were shown by both methods to inactivate the antibiotic, whereas the others, including the indirectly selected mutant, did not. The wild types were also negative by both tests. The higher cefamandole MICs of Enterobacter in broth, thus, appeared to reflect a high frequency of resistant variants that were not detected with the inoculum and end point criteria usually used in agar dilution methods. The ability of some variants to inactivate cefamandole may have resulted from a mutation that extended the activity of Enterobacter cephalosporinase to include this antibiotic.


2017Spring PaduaMuscleDays, roots and byproducts.
The second 2017 issue of EJTM volume 27 contains the collection of abstracts from the 2017Spring PaduaMuscleDays conference, that was held March 23-25 in Montegrotto, Euganei Hills, Padova, Italy. In addition to a brief history of the Padova Myology Meetings held during the last 30 years, the present and the future of the PaduaMuscleDays conference are discussed with special reference to new media and the options they offer to spread to a larger audience the results of the many workshops held in the Hotel Augustus conference hall and in the Aula Guariento of the Accademia Galileiana di Scienze, Lettere ed Arti, one of the hidden treasures of the medioeval Padua, Italy. Preliminary announcements of the 2017 and 2018 events, in particular of the Giovanni Salviati Memorial, will follow.


Nicotine alters progesterone and estradiol levels during the first trimester of pregnancy in Wistar rats.
This study was designed to investigate the effect of nicotine on serum progesterone and estradiol levels as possible cause of abortion during first trimester of gestation in female Wistar rats. Fourteen female rats with regular estrous cycles in the same phase of cycle were divided into two groups (Control and Nicotine-treated) with each group receiving 1ml of distilled water and 1mg/kg of nicotine respectively for the first seven days of pregnancy (GD1-7). The animals were sacrificed on the 8th day and blood samples were collected for hormonal analyses. Ovaries and uteruses were excised, weighed, and prepared for histological study. This study revealed a significant decrease in serum progesterone and estradiol levels in the nicotine-treated group when compared to controls. The histological findings equally showed degeneration in the cytoarchitecture of the ovary of the nicotine-treated group. The observed hormonal imbalances and alteration in the cytoarchitecture of the ovary caused by nicotine in the first trimester of pregnancy may result in abortion during this period.


The C-terminal extension (CTE) of the nuclear hormone receptor DNA binding domain determines interactions and functional response to the HMGB-1/-2 co-regulatory proteins.
Previously, we and others reported that the high mobility group proteins, HMGB-1/-2, enhance DNA binding in vitro and transactivation in situ by the steroid hormone subgroup of nuclear receptors but did not influence these functions of class II receptors. We show here that the DNA binding domain (DBD) is sufficient to account for the selective influence of HMGB-1/-2 on the steroid class of receptors. Furthermore, the use of chimeric DBDs reveals that this selectivity is dependent on the C-terminal extension (CTE), amino acid sequences adjacent to the zinc finger core DBD. HMGB-1/-2 interact directly with the DBDs of steroid but not class II receptors, and this interaction requires the CTE. This in vitro interaction correlates with a requirement of the CTE for maximal HMGB-1/-2 enhancement of DNA binding in vitro and transcriptional activation in cells. Finally, class II receptor DBDs have a much higher intrinsic affinity for DNA than steroid receptor DBDs, and this affinity difference is also dependent on the CTE. These results reveal the importance of the steroid receptor CTE for DNA binding affinity and functional response to HMGB-1/-2.


Effects of Kinesio Taping and compression stockings on pain, edema, functional capacity and quality of life in patients with chronic venous disease: a randomized controlled trial.
The aim of this study was to compare the effects of Kinesio Taping and compression stockings on pain, edema, functional capacity and quality of life in patients with chronic venous disease (CVD). This is a prospective, randomized, controlled, single-blind clinical trial. The study was conducted in a physiotherapy and rehabilitation unit of a university hospital. A total of 62 patients with early-stage CVD were allocated to either an experimental group or a control group. Experimental group (n = 29) received Kinesio Taping intervention once a week for four weeks, while control group (n = 29) received compression stockings for four weeks. All patients additionally undertook an exercise training programme including calf muscle pump exercises, flexibility exercises and diaphragmatic breathing. Visual analogue scale, lower limb circumference measurements, 6-minute walk test and Short Form 36 questionnaire were applied before and after four weeks of treatment. Control group showed statistically significant improvements in pain (P < 0.001), ankle circumferences (right, P = 0.002; left, P = 0.037), calf circumferences (right, P = 0.020; left, P = 0.022), knee circumference (left, P = 0.039) and thigh circumferences (right, P = 0.029; left, P = 0.002) compared with experimental group. There were no significant differences between groups with respect to functional capacity and quality of life (P > 0.05). Both groups significantly improved 6-minute walk distance (P < 0.001) and Short Form 36 physical component summary (experimental group, P = 0.002; control group, P = 0.006). This study demonstrated that Kinesio Taping and compression stockings revealed similar improvements of functional capacity and quality of life in patients with CVD. The symptoms of pain and edema caused by CVD can be decreased more efficiently with compression stockings than Kinesio Taping intervention.


Effect of standardized training in combination with masseter sensitization on corticomotor excitability in bruxer and control individuals: a proof of concept study.
Recently, it has been proposed that bruxism could represent an overlearned behavior due to the absence of corticomotor plasticity following a relevant tooth-clenching task (TCT). This study assessed the modulatory effects of a nerve growth factor (NGF) injection on masseter muscle corticomotor excitability, jaw motor performance, pain, and limitation in bruxer and control participants following a TCT. Participants characterized as definitive bruxers or controls were randomly assigned to have injected into the right masseter muscle either NGF or isotonic saline (IS), resulting in a study with 4 arms: IS_Control (n = 7), IS_Bruxer (n = 7); NGF_Control (n = 6), and NGF_Bruxer (n = 8). The primary outcome was the masseter motor evoked potential (MEP) amplitude measured at baseline and after a TCT. After the interventions, significantly higher and lower MEP amplitude and corticomotor map area were observed, respectively, in the IS_Control and NGF_Control groups (P < 0.05). Precision and accuracy depended on the series and target force level with significant between-group differences (P < 0.01). NGF-induced masseter muscle sensitization, in combination with a training-induced effect, can significantly impact the corticomotor excitability of the masseter muscle in control participants indicating substantial changes in corticomotor excitability, which are not observed in bruxers. These preliminary findings may have therapeuthic implications for the potential to "detrain" and manage bruxism, but further studies with larger sample sizes will be needed to test this new concept.


Stable carbon and nitrogen isotope values of dorsal spine age rings indicate temporal variation in the diet of striped marlin (Kajikia audax) in waters around Cabo San Lucas, Mexico.
Billfishes, such as marlin, are top pelagic predators that play an important role in maintaining the stability of marine food webs. Notwithstanding the importance of these species, there remain gaps in our knowledge on their movements, foraging, and trophic status in the early stage of life. We measured the δ(13)C and δ(15)N values in each annual growth band deposited in the dorsal spine from striped marlin caught off Cabo San Lucas, Mexico, to produce retrospective isotopic profiles that would enable us to detect any significant isotopic changes across development. The samples were analyzed using an elemental analyzer coupled to an isotope ratio mass spectrometer. There was no relationship between the size of striped marlin and the δ(15) N values. Differences in δ(15)N mean values across different age classes were not significant and the variation in δ(15)N values through the marlins' life cycle was less than 2‰. However, the mean δ(15)N values between individuals varied by up to 6‰. The δ(13)C values increased as a function of age, and the mean δ(13)C values varied significantly between age classes. Fin spines can be used to construct retrospective isotopic histories for the investigation of trophic dynamics and migratory histories in billfishes, for which population dynamics are often poorly known.


Medicaid Disenrollment and Disparities in Access to Care: Evidence from Tennessee.
To assess the effects of Tennessee's 2005 Medicaid disenrollment on access to health care among low-income nonelderly adults. We use data from the 2003-2008 Behavioral Risk Factor Surveillance System. We examined the effects of Medicaid disenrollment on access to care among adults living in Tennessee compared with neighboring states, using difference-in-difference models. Evidence suggests that Medicaid disenrollment resulted in significant decreases in health insurance and increases in cost-related barriers to care for low-income adults living in Tennessee. Statistically significant changes were not observed for having a personal doctor. Medicaid disenrollment is associated with reduced access to care. This finding is relevant for states considering expansions or contractions of Medicaid under the Affordable Care Act.


Awareness and Perception of Plastic Surgery among Healthcare Professionals in Pune, India: Do They Really Know What We Do?
Purpose. The aim of this study is to understand the level of awareness and knowledge of plastic surgery in healthcare professionals in a tertiary health care facility in Pune, India. This study also aims to highlight the perception of the medical professionals about plastic surgery and what they think a plastic surgeon does. Materials and Methods. A questionnaire-based survey was done at B.J Medical College and Sassoon Hospital, Pune in 2011. Feedback evaluation forms from hundred resident doctors and faculty were evaluated and analyzed. Results. There is not much awareness about plastic surgery as a specialty amongst health care providers. Plastic surgery is mostly perceived as cosmetic surgery, and the other spectrum of the patients we cater to goes largely unnoticed. Of all the clinical conditions given to the participants, there was not a single clinical condition where the respondents favored unanimously for plastic surgeons. Conclusion. Plastic surgery as a specialty is poorly understood by our medical colleagues, and the onus of creating and improving the awareness and perception of our specialty lies on us. Herculean unified efforts at individual as well as global level will help us achieve this goal.


Treatment of febrile episodes in neutropenic leukemic patients with the antibiotic combinations piperacillin or ceftazidime plus amikacin: results of a randomized study.
Seventy-six consecutive neutropenic patients with hematologic malignancies, admitted to the "Department of Hematology" of Rome between March and September 1986, were randomly assigned to receive either piperacillin (300 mg/kg in four divided doses) or ceftazidime (100 mg/kg in four divided doses) plus amikacin (15 mg/kg in two divided doses) whenever they developed a febrile episode (temperature greater than 38 degrees C thrice over 12 hours, not related to drugs or transfusions, or else temperature greater than 38.5 degrees C). After 72 hours of antibiotic therapy, in case of persistent fever, piperacillin or ceftazidime was added to the ceftazidime + amikacin or piperacillin + amikacin combination, respectively. The antibiotic treatment was, however, modified according to in vitro susceptibility if a positive culture was present. Success without regimen modification was observed in both antibiotic combinations in 52.6% of cases. Considering the empiric cross of antibiotics, the response rate reached 78%. Neither toxicity nor side effects were observed in the reported groups. Considering blood isolates, we observed a greater incidence of gram-positive organisms compared with gram-negatives (28 cases vs 5 cases, 84.7% vs 15.3% respectively). Fungal infections were documented in four cases, two in each group. Even though no statistical difference was found between the two groups as far as patients not responding to the first antibiotic combination are concerned, piperacillin seems to have had more efficacy (twelve patients responding to the addition of piperacillin vs seven patients responding to the addition of ceftazidime). Piperacillin + amikacin seems to be as effective as ceftazidime + amikacin in the empirical therapy of febrile episodes in neutropenic patients.