Developmental aspects of X chromosome inactivation in eutherian and metatherian mammals.
The single active X principle has served for two decades as a focal point for research on the cyclic activation and inactivation of gene loci. Differences in X chromosome inactivation patterns of eutherian and marsupial mammals provide probes for investigating the mechanisms of the X inactivation process. In eutherian mammals, the X chromosome is inactivated early in meiotic prophase in males and remains inactive throughout the rest of spermatogenesis. During meiosis in females, the inactive X chromosome is activated so that both X chromosomes are active in oocytes. During the early cleavage divisions of female embryos, the paternally derived X is activated. It and the maternally derived X remain active until differentiation begins in early embryogenesis. At that time, the paternally derived X is inactivated in cells that give rise to extraembryonic membranes, whereas a random process determines which X chromosome is inactivated in cells that give rise to the embryo itself. Although less is known about developmental aspects of X inactivation in female marsupials, it is clear that the paternal X is preferentially inactive in postembryonic somatic cells. Furthermore, the paternal X is partially active at some loci in some cell types, indicating that it is not regulated as a single unit. The successful adaptation of a small (80-150 g), fecund marsupial to simple laboratory conditions now enables extensive experimentation on the large number of marsupials at various developmental stages. This capability, coupled with the application of newly developed cellular and molecular techniques to questions about X chromosome inactivation, shows great promise for advancing our understanding of the mechanisms that control the cyclic behavior of X chromosome activity.


Review of electrical stimulation, botulinum toxin, and their combination for spastic drop foot.
Spastic drop foot is a functional impairment causing significant morbidity and mortality. Multiple treatments are available for this condition, but it is often not clear which treatment or combination of treatments is optimal for a given patient. One relatively recent therapy is the use of functional electrical stimulation to stimulate the peroneal nerve. Another is the use of botulinum toxin injections in the spastic ankle plantar flexors. While reasons exist to think these two treatments might work effectively in combination, there is no clear consensus in the literature. In this article, I review the background of the pathophysiology of spastic drop foot and its treatment options. I present some of the theoretical reasons why functional electrical stimulation and botulinum toxin injections could work synergistically and present a literature review on the topic. Recommendations for future research are discussed.


Pterostilbene in Combination With Mitochondrial Cofactors Improve Mitochondrial Function in Cellular Models of Mitochondrial Diseases.
Mitochondrial diseases are genetic disorders caused by mutations in genes in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) that encode mitochondrial structural or functional proteins. Although considered "rare" due to their low incidence, such diseases affect thousands of patients' lives worldwide. Despite intensive research efforts, most mitochondrial diseases are still incurable. Recent studies have proposed the modulation of cellular compensatory pathways such as mitophagy, AMP-activated protein kinase (AMPK) activation or the mitochondrial unfolded protein response (UPRmt) as novel therapeutic approaches for the treatment of these pathologies. UPRmt is an intracellular compensatory pathway that signals mitochondrial stress to the nucleus for the activation of mitochondrial proteostasis mechanisms including chaperones, proteases and antioxidants. In this work a potentially beneficial molecule, pterostilbene (a resveratrol analogue), was identified as mitochondrial booster in drug screenings. The positive effects of pterostilbene were significantly increased in combination with a mitochondrial cocktail (CoC3) consisting of: pterostilbene, nicotinamide, riboflavin, thiamine, biotin, lipoic acid and l-carnitine. CoC3 increases sirtuins' activity and UPRmt activation, thus improving pathological alterations in mutant fibroblasts and induced neurons.


Understanding and affirming the sexual/relationship realities of end-stage renal disease patients and their significant others.
End-stage renal disease (ESRD) frequently occurs within the social context of relationships and has many predictable consequences in the experience of patients and their significant others. Relationship and sexual issues and concerns must be assessed early in the treatment process and be continually attended to as patients seek new levels of coping. Sex-role conflicts, changes in sexual functioning and sexual self-esteem, challenges to both physical and emotional intimacy, and the life-altering consequences of chronic illness are all very real for ESRD patients. If a holistic perspective on the health care needs of ESRD patients is to be a reality, it will contain a concern for, active attention to, and involvement in the relationship/sexual dimension of life.


Renal gunshot wounds: methods of salvage and reconstruction.
Over the past 14 years, 2079 patients have been seen at our institution with renal trauma. Of these, 84 sustained gunshot wounds (81 unilateral, 3 bilateral; a total of 87 renal units). We evaluated this group to characterize the nature of their injuries and establish a methodology for renal salvage and reconstruction. Preoperative radiographic staging was performed with excretory urography (IVP) or computed tomographic (CT) scanning. The injuries were classified into five categories: 16 contusions (18.4%), 12 minor lacerations (13.8%), 44 major lacerations (50.5%), six vascular injuries (6.9%), and nine combination laceration and vascular injury (10.3%). Most patients had multiple organ injuries, with 79 requiring associated surgical procedures (94%). The mean injury Severity Score (ISS) was 26.7 (range, 4-59). Based on radiographic and clinical staging criteria, 69 renal injuries were surgically explored (79.3%), and 12 patients underwent nephrectomy (13.8%). Forty-six renal units were reconstructed (66.6%) by various methods, including renorrhaphy, omental pedical flaps, mesh or peritoneal patch grafts, partial nephrectomy, and vascular repair. Overall, 75 renal units were salvaged (86.2%). Early renal vascular control was achieved in all patients who underwent renal exploration. Follow-up functional studies were done in 24 (28.5%): none had delayed nephrectomy or postinjury hypertension. Overall, 79 patients survived (94%); however, mortality was not related to renal injury. These findings suggest that aggressive radiographic staging coupled with early vascular control and careful selection of reconstructive techniques can ensure a high renal salvage rate in patients with renal gunshot injuries.


The effect of war on marriage, divorce and birth rates.
The impact of war on marriage, divorce, and birth rates in the United States from 1933 to 1986 is explored. The author concludes that "the involvement of the nation in military activities was accompanied by a decrease in marriage and birth rates but not by any change in divorce rates. Mobilization of the armed forces and demobilization had no discernible impact on divorce, marriage or birth rates."


NF-κB Members Left Home: NF-κB-Independent Roles in Cancer.
Nuclear factor-κB (NF-κB) has been long considered a master regulator of inflammation and immune responses. Additionally, aberrant NF-κB signaling has been linked with carcinogenesis in many types of cancer. In recent years, the study of NF-κB members in NF-κB unrelated pathways provided novel attractive targets for cancer therapy, specifically linked to particular pathologic responses. Here we review specific functions of IκB kinase complexes (IKKs) and IκBs, which have distinctly tumor promoting or suppressing activities in cancer. Understanding how these proteins are regulated in a tumor-related context will provide new opportunities for drug development.


X-ray phase-contrast microtomography of soft tissues using a compact laboratory system with two-directional sensitivity.
X-ray microtomography is a nondestructive, three-dimensional inspection technique applied across a vast range of fields and disciplines, ranging from research to industrial, encompassing engineering, biology, and medical research. Phase-contrast imaging extends the domain of application of x-ray microtomography to classes of samples that exhibit weak attenuation, thus appearing with poor contrast in standard x-ray imaging. Notable examples are low-atomic-number materials, like carbon-fiber composites, soft matter, and biological soft tissues. We report on a compact and cost-effective system for x-ray phase-contrast microtomography. The system features high sensitivity to phase gradients and high resolution, requires a low-power sealed x-ray tube, a single optical element, and fits in a small footprint. It is compatible with standard x-ray detector technologies: in our experiments, we have observed that single-photon counting offered higher angular sensitivity, whereas flat panels provided a larger field of view. The system is benchmarked against known-material phantoms, and its potential for soft-tissue three-dimensional imaging is demonstrated on small-animal organs: a piglet esophagus and a rat heart. We believe that the simplicity of the setup we are proposing, combined with its robustness and sensitivity, will facilitate accessing quantitative x-ray phase-contrast microtomography as a research tool across disciplines, including tissue engineering, materials science, and nondestructive testing in general.


Daridorexant, an Orexin Receptor Antagonist for the Management of Insomnia.
Insomnia is a common sleep disorder that is diagnosed primarily by patients' subjective reported symptoms. Daridorexant is a new dual orexin receptor antagonist that was recently approved by Food and Drug Administration for insomnia characterized by difficulty falling asleep and/or maintaining sleep. The orexin neuropeptide signaling system plays a role in wakefulness, and blocking the wake-promoting neuropeptides results in diminished wake signaling, thus exerting a sedative effect using an entirely different mechanism of action than the classical sleep promoting agents. The drug has quick onset of action, high volume of distribution, and high protein binding. Pharmacokinetics and pharmacodynamic parameters were similar in patients of different sex and age and were not significantly affected by race, body size, or mild-to-moderate kidney impairment. Dose limitation to 25 mg in moderate liver impairment and no use in severe liver impairment are recommended. The drug undergoes hepatic CYP3A4 metabolism; thus, caution with strong CYP3A4 inhibitors and inducers is warranted. The drug was approved based on phase 3 trials involving study 1 and study 2. Study 1 noted daridorexant at doses of 25 and 50 mg demonstrated a statistically significant improvement in wake time after sleep onset, latency to persistent sleep, and self-reported total sleep time against placebo at months 1 and 3. Similarly in study 2, compared with placebo, the 25 mg dose demonstrated statistically significant improvement in wake time after sleep onset, latency to persistent sleep, and self-reported total sleep time at months 1 and 3. Treatment-emergent adverse events were similar for daridorexant and placebo, with nasopharyngitis and headache most frequently reported. Daridorexant is a novel agent with demonstrated efficacy in sleep onset and maintenance and decrease in daytime sedation. Preliminary results from a 1-year extension study note similar incidences of mild-to-moderate side effects as noted in previous trials. Further studies are needed to establish its place in the pharmacological treatment of insomnia.


Pyrrophens: Pyrrole-Based Hexadentate Ligands Tailor-Made for Uranyl (UO22+) Coordination and Molecular Recognition.
Derivatives of a novel pyrrole-containing Schiff base ligand system (called "pyrrophen") are presented which feature substituted phenylene linkers (R1 = R2 = H (H2L1); R1 = R2 = CH3 (H2L2)) and a binding pocket modeled after macrocyclic species. These ligands bind neutral CH3OH in the solid state through pyrrolic hydrogen-bonding. The interaction of the uranyl cation (UO22+) and H2L1-2 yields planar hexagonal bipyramdial uranyl complexes, while the Cu2+ and Zn2+ complexes were found to self-assemble as dinuclear helicate complexes (M2L2) with H2L1 under identical conditions. The favorable binding of UO22+ over Zn2+ provides insight into the molecular recognition of uranyl over other metal species. Structural features of these complexes are examined with special attention to features of the UO22+ coordination environment which distinguish them from other related salophen and porphyrinoid complexes.


Computer simulations of adsorption and diffusion for binary mixtures of methane and hydrogen in titanosilicates.
Equilibrium molecular dynamics (MD) simulations of equimolar mixtures of hydrogen and methane were performed in three different titanosilicates: naturally occurring zorite and two synthetic titanosilicates, ETS-4 and ETS-10. In addition, single-component MD simulations and adsorption isotherms generated using grand canonical Monte Carlo simulations were performed to support the mixture simulations. The goal of this study was to determine the best membrane material to carry out hydrogen/methane separations. ETS-10 has a three-dimensional pore network. ETS-4 and zorite have two-dimensional pore networks. The simulations carried out in this study show that the increased porosity of ETS-10 results in self-diffusion coefficients for both hydrogen and methane that are higher in ETS-10 than in either ETS-4 or zorite. Methane only showed appreciable displacement in ETS-10. The ability of the methane molecules to move in all three directions in ETS-10 was demonstrated by the high degree of isotropy shown in the values of the x, y, and z components of the self-diffusion coefficient for methane in ETS-10. From our simulations we conclude that ETS-10 would be better suited for fast industrial separations of hydrogen and methane. However, the separation would not result in a pure hydrogen stream. In contrast, ETS-4 and zorite would act as true molecular sieves for separations of hydrogen and methane, as the methane would not move through membranes made of these materials. This was indicated by the near-zero self-diffusion coefficient of methane in ETS-4 and zorite.


Computer-based cognitive rehabilitation research in a military treatment facility: Recruitment, compliance, and lessons learned.
Evidence-based approaches to cognitive rehabilitation are limited; however, new technologies such as brain-training computer programs provide opportunities for novel interventions. This paper describes a randomized controlled training study in a military treatment facility with service members who had combat-related cognitive symptoms. It examines challenges in study design and implementation, and provides "lessons learned" with proposed solutions. Participants were randomly assigned to one of two 6-week computer-based cognitive training (CBCT) programs or a treatment-as-usual (TAU) control group. Feasibility assessments included reasons for consent refusal, compliance, and drop-out rates. The intended sample size for the study was 114 participants before attrition. Of 291 patients referred over 2.5 years, 120 were eligible, 38 consented to participate, and 18 completed the study. Forty-two percent of the participants assigned to CBCT groups completed the required 30 sessions in 6.5 to 32 weeks. Study-design factors that affected enrollment and compliance included eligibility restrictions, lack of a computer-based control condition, and inflexible scheduling. Successful implementation of a high-dose computer-based clinical trial will require design changes such as expanded inclusion criteria, control by sham computer program or wait-list, dosing flexibility, and web-based options.


Magnetic resonance imaging of graded skeletal muscle injury in live rats.
Increasing number of stretch-shortening contractions (SSCs) results in increased muscle injury. Fischer Hybrid rats were acutely exposed to an increasing number of SSCs in vivo using a custom-designed dynamometer. Magnetic resonance imaging (MRI) imaging was conducted 72 hours after exposure when rats were infused with Prohance and imaged using a 7T rodent MRI system (GE Epic 12.0). Images were acquired in the transverse plane with typically 60 total slices acquired covering the entire length of the hind legs. Rats were euthanized after MRI, the lower limbs removed, and tibialis anterior muscles were prepared for histology and quantified stereology. Stereological analyses showed myofiber degeneration, and cellular infiltrates significantly increased following 70 and 150 SSC exposure compared to controls. MRI images revealed that the percent affected area significantly increased with exposure in all SSC groups in a graded fashion. Signal intensity also significantly increased with increasing SSC repetitions. These results suggest that contrast-enhanced MRI has the sensitivity to differentiate specific degrees of skeletal muscle strain injury, and imaging data are specifically representative of cellular histopathology quantified via stereological analyses.


Subject specific muscle synergies and mechanical output during cycling with arms or legs.
Upper (UL) and lower limb (LL) cycling is extensively used for several applications, especially for rehabilitation for which neuromuscular interactions between UL and LL have been shown. Nevertheless, the knowledge on the muscular coordination modality for UL is poorly investigated and it is still not known whether those mechanisms are similar or different to those of LL. The aim of this study was thus to put in evidence common coordination mechanism between UL and LL during cycling by investigating the mechanical output and the underlying muscle coordination using synergy analysis. Twenty-five revolutions were analyzed for six non-experts' participants during sub-maximal cycling with UL or LL. Crank torque and muscle activity of eleven muscles UL or LL were recorded. Muscle synergies were extracted using nonnegative matrix factorization (NNMF) and group- and subject-specific analysis were conducted. Four synergies were extracted for both UL and LL. UL muscle coordination was organized around several mechanical functions (pushing, downing, and pulling) with a proportion of propulsive torque almost 80% of the total revolution while LL muscle coordination was organized around a main function (pushing) during the first half of the cycling revolution. LL muscle coordination was robust between participants while UL presented higher interindividual variability. We showed that a same principle of muscle coordination exists for UL during cycling but with more complex mechanical implications. This study also brings further results suggesting each individual has unique muscle signature.


Clinical evaluation of the InnerSpace fibreoptic intracranial pressure monitoring device.
The aim of this study is the clinical evaluation of the intraparenchymal ICP monitor InnerSpace OPX 100. Sixty-four Inner Space OPX 100 transducers in 51 patients with severe head injury (42), intracranial spontaneous bleeding (6) or hypoxia (3) were studied. The transducer was placed in the frontal white matter. Thirty-nine patients received one catheter, eleven patients two catheters and one patient three catheters. The study period ranged from 10 hours-25 days; total study time was 421.5 days (mean duration 6.6 days). In nine cases (14.1%) an inadequate location of the ICP transducer was found, but the accuracy of the measurement was not influenced. Dislocation of the transducer occurred in eight cases (12.5%) due to inadequate handling. A failed transducer was observed in four cases (6.3%) because of a damaged optical fibre (1) or inadequate handling (3). In one patient (1.9%) a minor local infection developed. In eleven cases (17%) a haematoma around the ICP sensor was observed. Six haematomas were small; five haematomas were larger than 1 cm in diameter. In two patients a large frontal haematoma developed after exchange of the transducer. Operative evacuation was necessary in both cases. Zero shift was below 2 mmHg in all catheters. It is concluded that the InnerSpace intraparenchymal ICP monitor is a reliable device: the rate of catheter related intracerebral haematomas, however, is not acceptable. This could be improved by a better fixation of the catheter in the burr hole in order to avoid micromovements of the transducer.


Proactive Locomotor Adjustments Are Specific to Perturbation Uncertainty in Below-Knee Prosthesis Users.
Sensory-motor deficits associated with below-knee amputation impair reactions to external perturbations. As such, below-knee prosthesis users rely on proactive control strategies to maintain locomotor stability. However, there are trade-offs (metabolic, comfort, etc.) associated with proactive strategies. We hypothesize that because proactive control strategies are costly, prosthesis users and non-impaired participants will use a priori knowledge (timing, direction) of an impending lateral perturbation to make specific gait adaptations only when the timing of the perturbation is known and the adaptation can be temporally-limited. This hypothesis was partially supported. When the perturbation timing was predictable, only prosthesis users, and only on their impaired side, increased their lateral margin of stability during the steps immediately preceding the perturbation when perturbation direction was either unknown or known to be directed towards their impaired side. This strategy should reduce the likelihood of requiring a corrective step to maintain stability. However, neither group exhibited substantial proactive adaptations compared to baseline walking when perturbation timing was unpredictable, independent of perturbation direction knowledge. The absence of further proactive stabilization behaviors observed in prosthesis users in anticipation of a certain but temporally unpredictable perturbation may be partially responsible for impaired balance control.


Competitive kinetics versus stopped flow method for determining the degradation rate constants of steroids by ozonation.
Steroids are classified as endocrine disrupting chemicals; they are persistent with low biodegradability and are hardly degraded by conventional methods. Ozonation process has been effective for steroids degradation and the determination of the kinetics is a fundamental aspect for the design and operation of the reactor. This study assessed two methods: competitive kinetics and stopped flow, for determining the degradation kinetics of two steroids, estradiol (E2) and ethinylestradiol (EE2) in spiked water. Experiments were performed at pH 6, 21 °C, and using tertbutyl alcohol as scavenger of hydroxyl radicals; competitive kinetics method used sodium phenolate as reference compound. For the stopped flow, the experiments were performed in a BioLogic SFM-3000/S equipment. For both methods, the second order rate constants were in the order of 10(6) and 10(5) M(-1) s(-1) for E2 and EE2 respectively. The competitive kinetics can be applied with assurance and reliability but needing an additional analysis method to measure the residual concentrations. Stopped flow method allows the evaluation of the degradation kinetics in milliseconds and avoids the use of additional analytical methodologies; this method allows determining the reaction times on line. The methods are applicable for degradation of other emerging contaminants or other steroids and could be applied in water treatment at industrial level. Finally, it is important to consider the resources available to implement the most appropriate method, either competitive kinetics or the stopped-flow method.


Optimal charged mutations in the complementarity-determining regions that prevent domain antibody aggregation are dependent on the antibody scaffold.
Therapeutic antibodies need to be highly resistant to aggregation due to the high concentrations required for subcutaneous delivery and the potential immunogenicity of antibody aggregates. Human antibody fragments-such as single-domain antibodies (VH or VL)-are typically much less soluble than full-length antibodies. Nevertheless, some aggregation-resistant VH domains have been discovered that are negatively charged at neutral pH and/or enriched in negatively charged residues within the complementarity-determining regions (CDRs). To better understand how to engineer diverse domain antibodies to resist aggregation, we have investigated the solubilizing activity of positively and negatively charged mutations within hydrophobic CDRs of multiple VH scaffolds that differ in their net charge. We find that negatively charged mutations inserted near the edges of hydrophobic CDRs are more effective than positively charged ones at inhibiting aggregation for VH scaffolds that are negatively or near-neutrally charged. In contrast, positively charged CDR mutations prevent aggregation better than negatively charged ones for a VH scaffold that is highly positively charged. Our findings suggest that the net charge of the antibody scaffold is a key determinant of the optimal CDR mutations for preventing aggregation. We expect that our findings will improve the design of aggregation-resistant antibodies with single- and multidomain scaffolds.


Differential effects of chronic hypoxia and feed restriction on the expression of leptin and its receptor, food intake regulation and the endocrine stress response in common carp.
Appetite suppression is a common response to hypoxia in fish that confers significant energy savings. Yet little is known about the endocrine signals involved in the regulation of food intake during chronic hypoxia. Thus, we assessed the impact of chronic hypoxia on food intake, the expression of the potent anorexigenic signal leptin and its receptor (lepr), the mRNA levels of key hypothalamic appetite-regulating genes, and the activity of the hypothalamic-pituitary-interrenal (HPI) axis in common carp, Cyprinus carpio. Fish exposed to 10% O(2) saturation for 8 days were chronically anorexic and consumed on average 79% less food than normoxic controls. Hypoxia also elicited gradual and parallel increases in the expression of liver leptin-a-I, leptin-a-II, lepr and erythropoietin, a known hypoxia-responsive gene. In contrast, the liver mRNA levels of all four genes remained unchanged in normoxic fish pair-fed to the hypoxia treatment. In the hypothalamus, expression of the appetite-regulating genes were consistent with an inhibition and stimulation of hunger in the hypoxic and pair-fed fish, respectively, and reduced feed intake led to a decrease in lepr. Although both treatments elicited similar delayed increases in plasma cortisol, they were characterized by distinct HPI axis effector transcript levels and a marked differential increase in pituitary lepr expression. Together, these results show that a reduction in O(2) availability, and not feed intake, stimulates liver leptin-a expression in common carp and suggest that this pleiotropic cytokine is involved in the regulation of appetite and the endocrine stress response during chronic hypoxia.


Few genetic and environmental correlations between life history and stress resistance traits affect adaptation to fluctuating thermal regimes.
Laboratory selection in thermal regimes that differed in the amplitude and the predictability of daily fluctuations had a marked effect on stress resistance and life history traits in Drosophila simulans. The observed evolutionary changes are expected to be the result of both direct and correlated responses to selection. Thus, a given trait might not evolve independently from other traits because of genetic correlations among these traits. Moreover, different test environments can induce novel genetic correlations because of the activation of environmentally dependent genes. To test whether and how genetic correlations among stress resistance and life history traits constrain evolutionary adaptation, we used three populations of D. simulans selected for 20 generations in constant, predictable and unpredictable daily fluctuating thermal regimes and tested each of these selected populations in the same three thermal regimes. We explored the relationship between genetic correlations between traits and the evolutionary potential of D. simulans by comparing genetic correlation matrices in flies selected and tested in different thermal test regimes. We observed genetic correlations mainly between productivity, body size, starvation and desiccation tolerance, suggesting that adaptation to the three thermal regimes was affected by correlations between these traits. We also found that the correlations between some traits such as body size and productivity or starvation tolerance and productivity were determined by test regime rather than selection regime that is expected to limit genetic adaptation to thermal regimes in these traits. The results of this study suggest that several traits and several environments are needed to explore adaptive responses, as genetic and environmentally induced correlations between traits as results obtained in one environment cannot be used to predict the response of the same population in another environment.


Protein Dynamics in the Plant Extracellular Space.
The extracellular space (ECS or apoplast) is the plant cell compartment external to the plasma membrane, which includes the cell walls, the intercellular space and the apoplastic fluid (APF). The present review is focused on APF proteomics papers and intends to draw information on the metabolic processes occurring in the ECS under abiotic and biotic stresses, as well as under non-challenged conditions. The large majority of the proteins detected are involved in "cell wall organization and biogenesis", "response to stimulus" and "protein metabolism". It becomes apparent that some proteins are always detected, irrespective of the experimental conditions, although with different relative contribution. This fact suggests that non-challenged plants have intrinsic constitutive metabolic processes of stress/defense in the ECS. In addition to the multiple functions ascribed to the ECS proteins, should be considered the interactions established between themselves and with the plasma membrane and its components. These interactions are crucial in connecting exterior and interior of the cell, and even simple protein actions in the ECS can have profound effects on plant performance. The proteins of the ECS are permanently contributing to the high dynamic nature of this plant compartment, which seems fundamental to plant development and adaptation to the environmental conditions.


Follicle Stimulating Hormone and Anti-Müllerian Hormone among Fertile and Infertile Women in Ile-Ife, Nigeria: Is there A Difference?
Reduced ovarian reserve predicts poor ovarian response and poor suc- cess rates in infertile women who undergo assisted reproductive technology (ART). Ovarian reserve also decreases with age but the rate of decline varies from one woman to another. This study aims to detect differences in ovarian reserve as measured by basal serum follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) between a matched cohort of fertile and infertile regularly menstruating women, 18-45 years of age. This case-control study involved 64 fertile and 64 subfertile women matched by age at recruitment. Peripheral blood samples were taken from the women recruited from the Gynecological and Outpatient Clinics of Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. Serum FSH and AMH were quantified using ELISA at the Metabolic Research Laboratory of LAUTECH Teaching Hospital, Ogbomoso, Nigeria. A significant difference existed in the mean FSH of fertile (6.97 ± 3.34) and infertile (13.34 ± 5.24, P=0.013) women. We observed a significant difference in AMH between fertile (2.71 ± 1.91) and infertile (1.60 ± 2.51, P=0.029) women. There was a negative correlation between FSH and AMH in both fertile (r=-0.311, P=0.01) and infertile (r=-0.374, P=0.002) women. The difference in ovarian reserve observed in this study suggests that reduced ovarian reserve in regularly menstruating women may be associated with early ovarian ageing or subfertility.


Proteomic Workflows for Biomarker Identification Using Mass Spectrometry - Technical and Statistical Considerations during Initial Discovery.
Identification of biomarkers capable of differentiating between pathophysiological states of an individual is a laudable goal in the field of proteomics. Protein biomarker discovery generally employs high throughput sample characterization by mass spectrometry (MS), being capable of identifying and quantifying thousands of proteins per sample. While MS-based technologies have rapidly matured, the identification of truly informative biomarkers remains elusive, with only a handful of clinically applicable tests stemming from proteomic workflows. This underlying lack of progress is attributed in large part to erroneous experimental design, biased sample handling, as well as improper statistical analysis of the resulting data. This review will discuss in detail the importance of experimental design and provide some insight into the overall workflow required for biomarker identification experiments. Proper balance between the degree of biological vs. technical replication is required for confident biomarker identification.


Carabus of Subgenus Cathoplius C.G. Thomson, 1875, with description of their life-way, life-cycle and pre-imaginal morphology (Coleoptera: Carabidae) .
According to current taxonomy, Subgenus Cathoplius C.G. Thomson, 1875, within the Genus Carabus Linnaeus, 1758 (in the broad sense), includes two species: C. (Cathoplius) asperatus (Dejean, 1826), monotypic with a northern distribution, and the southern polytypic substitutive species C. (Cathoplius) stenocephalus Lucas, 1866. The authors describe the life-way, life-cycle and pre-imaginal characters of the taxa currently ascribed to Subgenus Cathoplius, with details never provided before. Cathoplius are ground beetles adapted to live in arid environments and extreme habitats such as sub-desert areas. All of them are strictly helicophagous, both during the pre-imaginal stages and as adults, and are localized in a narrow fringe along the Atlantic coast of northwestern Africa. Several data and observations on the eco-ethology of the different taxa, obtained both in field and in laboratory, are reported. The life-cycle of Cathoplius belongs to the winter breeding type, with an extremely high fecundity rate concentrated in a very short period of time, that has no similarity to any other Carabus species. Eggs, larvae and pupae of the different species and subspecies of Cathoplius are described and illustrated. Larval characters clearly place Subgenus Cathoplius into the lineage of Neocarabi, confirming it as a monophyletic and homogeneous assemblage. Hybridization trials between some taxa led to a reduced survival rate of the progeny, thus confirming their specific or subspecific differentiation as proposed by classical taxonomy. Furthermore, hybridization results suggest that C. (Cathoplius) stenocephalus aliai could be considered as a distinct species. Notes about the origin, biogeography and phylogeny of Cathoplius are also provided.


Effect of intravenous dopamine infusion on intramural blood flow distribution and fluid absorption in the feline small intestine.
The aim of the study was to investigate the effects of dopamine on the intestinal mucosal blood flow and transport function. Dopamine was infused intravenously at 20 micrograms X kg-1 X min-1 in anesthetized cats. Total and intramural blood flow in an isolated jejunal segment was measured by a combined drop-flow and 85Kr clearance technique. Net fluid transport was recorded by two independent perfusion methods. Unidirectional sodium transport was estimated from luminal 22Na disappearance. Dopamine induced a pronounced mucosal vasodilatation up to 400% of control values. Concomitantly, net fluid and sodium absorption increased by 50%. The effect on sodium transport was due to a pronounced decrease in tissue-to-lumen sodium flux, a pattern similar to the one seen on alpha-adrenergic stimulation. The effect of dopamine on blood flow was unaffected by phentolamine, 1 mg X kg-1, whereas the absorptive response was abolished. The findings indicate that dopamine induces a mucosal vasodilation via one mechanism (possibly dopaminergic) and enhances fluid transport via another mechanism, probably alpha-adrenergic.


Non-invasive prenatal testing (NIPT) and pregnant women's views on good motherhood: a qualitative study.
Women's views on responsible motherhood influence decision-making regarding participation in prenatal screening. Previous studies showed that the probabilistic nature of the first-trimester combined test and the potential requirement for subsequent invasive diagnostics serve as legitimate reasons for women to exclude prenatal screening from their moral responsibilities. These moral barriers might now be less relevant with the introduction of the non-invasive prenatal test (NIPT) resulting in women feeling a moral duty to use NIPT screening as part of responsible motherhood. This qualitative study explores the impact of NIPT on women's moral beliefs about the meaning of prenatal screening in relation to responsible motherhood. We performed semi-structured interviews with 29 pregnant women who were offered NIPT as a first-tier screening test within a Dutch nationwide study (TRIDENT-2). Results show that the inherent uncertainty about the fetus's health despite improved accuracy and the lack of treatment for a detected disorder, combined with the possibility to obtain information about actionable anomalies through the fetal anomaly scan, support women's perspectives that NIPT is not an obligation of responsible motherhood. Acceptance of NIPT is considered to be a free decision related to the information each woman needs to be a good mother for her child and her family. Women's views may change when NIPT has expanded to include treatable or preventable conditions.


Altered tactile spatial attention in the early blind.
To investigate whether superior tactile acuity in the blind is due to alterations of attentional selection mechanisms, event-related brain potentials (ERPs) were measured in a group of early blind and a group of sighted individuals who performed a difficult tactile spatial selection task. We found systematic differences in the attentional processing of tactile events between early blind and sighted individuals. The blind not only responded faster to tactile targets, but also showed attentional modulations of early somatosensory ERP components (P100 and N140). In contrast, ERP effects of spatial attention in the sighted only emerged at longer-latencies (about 200 ms post-stimulus). Our findings suggest that increased use of one sense due to sensory deprivation, such as touch in blind people, leads to alterations of attentional selection mechanism within modality-specific cortex.


Aortic valve stenosis: what do people know? A heart valve disease awareness survey of over 8,800 people aged 60 or over.
Little is known about the level of public knowledge and concern towards aortic valve disease. Therefore, a survey was conducted to evaluate the awareness of the general population regarding different diseases with special emphasis on aortic stenosis (AS). A total of 8,860 people aged 60 years or older in nine European countries took part in the survey. Cancer was the disease that respondents were most concerned about (27.5%), while only 1.7% were most concerned about heart valve disease. Seventeen percent (17%) of survey participants claimed to be familiar with heart valve disease, yet only 7% could correctly identify AS; 44.3% of respondents knew the correct number of valves in the human heart. After providing some general information about AS, 41.1% of respondents then said they were more concerned about the condition; 4.5% even recognised the symptoms in themselves. Over half of the respondents (54.2%) claimed that their general practitioners only rarely or never use the stethoscope to check their heart, which may eventually lead to an underdiagnosis of AS. Despite its high prevalence, high morbidity and mortality, as well as good treatment options, the vast majority of respondents were neither concerned nor fully aware of AS.


Child and adolescent psychiatrists' practices in assisting their adolescent patients who smoke to quit smoking.
This national study examined the practices and perceptions of smoking cessation activities among child and adolescent psychiatrists. A random sample of child and adolescent psychiatrists was identified from the membership list of the American Academy of Child and Adolescent Psychiatry and was mailed a valid and reliable 34-item questionnaire. A total of 184 responses (47%) were received. A plurality (48%) of psychiatrists reported being self-taught in smoking cessation techniques. A majority (67%) of psychiatrists were in the maintenance stage for asking about smoking status. However, only 19% consistently made attempts to assess willingness to quit, and 30% consistently gave messages urging the smoker to quit. The perceived number of barriers for addressing smoking was negatively correlated with psychiatrists' levels of confidence (r = -0.35, p <.001) and preparedness (r = -0.39, p <.001) in addressing smoking cessation. Estimations by the psychiatrists of youths who smoked were 61% of those with conduct disorders, 46% of those with schizophrenia, and 40% of those with attention-deficit/hyperactivity disorder. Considering the perceived high rate of patient smoking and the lack of formal training in smoking cessation, more postgraduate education is needed to adequately prepare child and adolescent psychiatrists for addressing tobacco cessation.


Outcomes of ultrasound-guided percutaneous microwave ablation versus surgical resection for symptomatic large hepatic hemangiomas.
Purpose: Microwave ablation (MWA) has become increasingly popular as a minimally invasive treatment for benign and malignant liver tumors. However, few studies have demonstrated the benefits and disadvantages of MWA compared to surgical resection (SR) for large hepatic hemangiomas. This study aimed to evaluate the safety and effectiveness of MWA compared to SR for large (5-10 cm) hepatic hemangiomas. Methods and materials: This retrospective comparative study included 112 patients with large, symptomatic hepatic hemangiomas who had been treated with MWA (n = 44) or SR (n = 68) and followed up for a median of 44 months using enhanced computed tomography (CT) or magnetic resonance imaging (MRI). Intraoperative information, postoperative recovery time, postoperative discomfort and complications and treatment effectiveness between groups were compared using a chi-square test or an independent t-test. Results: The operative time was significantly shorter (31.3 ± 21.76 versus 148.1 ± 59.3 min, p < .001) and the blood loss (10.2 ± 60.6 versus 227.9 ± 182.9 mL, p < .0001) and rate of prophylactic abdominal drainage [1 (2.3%) versus 57 (83.8%), p < .001] were significantly lower in the MWA group than in the SR group. Postoperative recovery of the MWA group in regard to indwelling catheter time, normal diet time, incision cicatrization time and hospital stay (p < .001) was significantly better than the SR group. However, no statistically significant difference in effectiveness was noted between the groups (p = .58). Conclusions: MWA may be as effective as SR, and potentially safer for treating large, symptomatic hepatic hemangiomas. To confirm our findings, large-sample, multicentered, randomized controlled trials are needed.


Duration of right ventricular contraction predicts the efficacy of bosentan treatment in patients with pulmonary hypertension.
In patients with pulmonary hypertension (PH), elevated endothelin-1 levels are associated with prolonged duration of right ventricular (RV) contraction, which induces leftward ventricular septal bowing with impaired left diastolic filling. We hypothesized that baseline RV contraction duration predicts efficacy of endothelin receptor antagonist, bosentan. Eighteen PH patients (age 57, range 35-79 years, 33% male) received bosentan. Six minute walk distance (6-MWD) and echocardiography were performed at baseline and after 1 year follow-up. After 1 year of treatment, 6-MWD increased (mean 60 +/- 41 m) in 67% of patients (responders). Baseline RV contraction duration was longer in responders, compared with non-responders (612 +/- 66 vs. 514 +/- 23 ms; P < 0.01). A baseline RV contraction duration >550 ms was associated with improved 6-MWD (sensitivity 83%, specificity 83%; P < 0.01). An improvement of 6-MWD during bosentan treatment was associated with a decrease in RV contraction duration and could be predicted by a baseline RV contraction duration >550 ms.


Examination Under Anesthesia for Posterior Wall Acetabular Fracture A Survey of the OTA Membership.
The purpose of this survey was to learn more about the indications, criteria, and methods surgeons use for performing examination under anesthesia (EUA) for "intermediate" sized posterior wall acetabular fractures (those involving 20% to 40% of the posterior wall) and to find what criteria are used to determine hip instability. An 18 question survey was posted on the Ortho- paedic Trauma Association's website and was used to gather anonymous data from orthopaedic surgeons regarding their approach to the intermediate sized posterior wall fracture. Considerable variability existed among re- sponses to many of the questions asked. Based on the an - swers given to the survey, a consensus of 75% or more of respondents was found for the following: 1. Supine position for the examination (100%); 2. "Live" fluoroscopy is used during the examination (97%); 3. The AP and obturator oblique are the x-rays most frequently used (81% and 76%, respectively); 4. The hip is placed in flexion and adduction during the exam (100% and 84%, respectively); 5. Axial load is applied during the examination (90%); Finally, 6. instabil - ity is defined as subluxation on exam by most respondents (98%), and any perceived visible subluxation is what defines instability (88%). Most surgeons agreed with the following: 1. Supine is the position of choice for the examination; 2. "Live" fluoroscopy is used during the examination; 3. The AP and obturator oblique are the x-rays most frequently used; 4. The hip is placed in flexion and adduction during the exam; 5. Axial load is applied during the examination; and 6. Instability is defined as subluxation on exam.


PROMIS Depression and Anxiety in shoulder surgery patients.
The purpose of this study was to assess the prevalence of depression and anxiety symptoms in patients undergoing shoulder surgery using the National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety computer adaptive tests, and to determine the factors associated with more severe symptoms. Additionally, we sought to determine whether PROMIS Depression and Anxiety were associated with functional outcomes after shoulder surgery. This was a retrospective analysis of 293 patients from an urban population who underwent elective shoulder surgery from 2015 to 2018. Survey questionnaires included preoperative and two-year postoperative data. Bivariate analysis was used to identify associations and multivariable analysis was used to control for confounding variables. Mean two-year PROMIS Depression and Anxiety scores significantly improved from preoperative scores, with a greater improvement observed in PROMIS Anxiety. Worse PROMIS Depression and Anxiety scores were also significantly correlated with worse PROMIS Physical Function (PF) and American Shoulder and Elbow Surgeons scores (ASES). After controlling for confounding variables, worse PROMIS Depression was an independent predictor of worse PROMIS PF, while worse PROMIS Anxiety was an independent predictor of worse PROMIS PF and ASES scores. Mean two-year PROMIS Depression and Anxiety scores improved after elective shoulder surgery and several patient characteristics were associated with these scores. Worse functional outcomes were associated with worse PROMIS Depression and Anxiety; however, more severe two-year PROMIS Anxiety was the strongest predictor of worse functional outcomes. Cite this article: Bone Joint J 2022;104-B(4):479-485.


[Mass spectrometry of peptides].
Recent progress in biochemistry has shown the occurrence of many important peptides, among antibiotics, immunostimulants, hormones and neuromediators. The mass spectrometric study of these components by classical ionization techniques such as electron impact, chemical ionization or field desorption require a prior chemical derivatization because of their amphoteric properties, their low volatility and low thermostability. Recent improvements in methods of ionization, fast atom bombardment, secondary ion mass spectrometry, or mass spectrometry/mass spectrometry have made it possible to study the structure of peptides with more than 15 amino acid residues and eased mass spectra interpretation. Through the different methodologies described in this review three characteristic informations can be obtained concerning the molecular mass of peptides, the nature of constituent amino acids and the peptidic sequence and even quantitative measurements can be performed.


[A trial approach to the ideal control-management and systematization of clinical laboratory].
Clinical laboratory examinations have continued to expand with the increase in demand for medical care. However, recent high-technology, medical care has made introduction of a new system of quality control in the clinical laboratory indispensable. First, regarding personnel (clinical laboratory technicians), reducing staff hours led to a drop in the employment of newcomers and subsequent aging of the staff. Next, introducing a system to save labor is extremely expensive, making the cost effectiveness very poor and consequently making it difficult to introduce such a system in many laboratories. This symposium was initiated to assist the search for ways in which the present clinical laboratory can survive despite rising personnel expenses and reagent costs, while reducing medical expenses. And at the same time developing a guide to establishing our ideal for the clinical laboratory of the 21st century.


Comparing apples to apples: policymakers take a shine to comparative effectiveness research.
Comparative effectiveness research is gaining attention as a potential means to standardize quality, improve outcomes, and control medication costs. By implementing such research programs and establishing clearinghouses for comparative effectiveness data, government officials, policymakers, payers, researchers, and others hope that practitioners and consumers alike will use this information to make informed decisions about medications and other aspects of care. Pharmacists will have a role in the comparative effectiveness movement, particularly regarding their pharmacologic expertise and their skills as educators.


Thin pyramidal cones in nematic liquid crystals.
The present study investigates the arrangement of hollow pyramidal cone shells and their interactions with degenerate planar anchoring on the inner and outer surfaces of particles within the nematic host. The shell thickness is in order of the nematic coherence length. The numerical behavior of colloids is determined by minimizing the Landau-de Gennes free energy in the presence of the Fournier surface energy and using the finite element method. Colloidal pyramidal cones can orient parallel and perpendicular with the far director orientation. In the parallel alignment, we found the splay director distortion into the pyramid with two boojum defects at the inner and outer tips. The director shows bending distortion without defect patterns when the pyramid is aligned perpendicularly. They induce long-range dipolar interaction and can form nested structures in close contact.


Examining Ethno-Racial Related Differences in Child Molester Typology: An MTC:CM3 Approach.
Sex offender typologies have been developed in an effort to better understand the heterogeneity of sexual offending as well as offenders' varied risk and therapeutic needs. Perhaps the most well-known and validated child molester typology is the Massachusetts Treatment Center: Child Molester Typology-Version 3 (MTC:CM3). However, this typology was developed and validated using primarily White sex offenders. The current study aimed to replicate this typology in an ethno-racially diverse sample of incarcerated White, Black, and Latino child molesters ( N = 499). Overall, we found that the MTC:CM3 was applicable to non-White child molesters but that there were differences in the proportion of offenders of different ethno-racial groups in Axis I type classifications. We found no differences in Axis II type classifications. Specifically, Black offenders were more often classified as socially incompetent and sexually attracted to adults compared with White and Latino offenders. Whereas White offenders were more often classified as socially incompetent and sexually fixated on children when compared with Black offenders, Latino offenders were more often classified as high in social competence and sexually attracted to adults than Black offenders. On Axis II, the majority of all three subsamples were classified as not having sexual contact with children beyond the offense, unlikely to inflict physical harm on victims, and as not having sadistic interests. Addressing these typological characteristics in the development and implementation of prevention and treatment efforts might increase the responsiveness of specific sex offender populations.


Metamagnetic Anomalies near Dynamic Phase Transitions.
We report the existence of anomalous metamagnetic fluctuations in the vicinity of the dynamic phase transition (DPT) that do not occur for the corresponding thermodynamic behavior of simple ferromagnets. Our results demonstrate that key characteristics associated with the DPT are qualitatively different from conventional thermodynamic phase transitions. We also provide evidence that these differences are tunable by showing that the presence of metamagnetic fluctuations and the size of the critical scaling regime depend strongly on the amplitude of the oscillating field that is driving the DPT in the first place.


[Factors influencing prognosis of stage D2 prostatic cancer following endocrine therapy: comparison between short-term cancer death and long-term survival group].
To clarify factors affecting prognosis following endocrine therapy, stage D2 patients who died from prostatic cancer within 3 years and those under well-controlled state longer than 5 years were compared with respect to background factors and response to endocrine therapy. Thirty-five and 18 cases, respectively, were studied. Differences between the two groups were bone pain, anemia, tumor grade, number of bone metastasis, and response to endocrine therapy. Performance status in long-term survival groups tended to be better than that in short-term cancer death groups.


PROTECTIVE EFFECTS OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS ON PROGRESSION OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES.
To investigate the effects of dipeptidyl peptidase-4 (DPP4) inhibitors on the progression of diabetic retinopathy (DR) in patients with Type 2 diabetes based on the DR severity scale. The medical records of 82 patients with Type 2 diabetes enrolled from 2005 to 2015 were retrospectively reviewed. Fundus photographs were graded using Early Treatment Diabetic Retinopathy Study methods. The associations between baseline risk factors and progression of DR were investigated. Seven of 28 patients treated with DPP4 inhibitors and 26 of 54 treated with other hypoglycemic agents showed progression of retinopathy, defined as one or more steps on the Early Treatment Diabetic Retinopathy Study scale (P = 0.043). Only treatment with DPP4 inhibitors significantly reduced the progression of DR in patients after propensity score matching (P = 0.009). Treatment with DPP4 inhibitors was associated with a lower risk of DR progression (P = 0.011). Treatment with DPP4 inhibitors was the independent protective factor against the progression of DR, aside from improving glycemic control. This is the first study to show the benefits of DPP4 inhibitors in reducing DR progression, and provides encouraging preliminary data for further evaluation of DPP4 inhibitors in the progression of DR in a randomized, double-blind, placebo-controlled trial.


A Review of Mercury Exposure and Health of Dental Personnel.
Considerable effort has been made to address the issue of occupational health and environmental exposure to mercury. This review reports on the current literature of mercury exposure and health impacts on dental personnel. Citations were searched using four comprehensive electronic databases for articles published between 2002 and 2015. All original articles that evaluated an association between the use of dental amalgam and occupational mercury exposure in dental personnel were included. Fifteen publications from nine different countries met the selection criteria. The design and quality of the studies showed significant variation, particularly in the choice of biomarkers as an indicator of mercury exposure. In several countries, dental personnel had higher mercury levels in biological fluids and tissues than in control groups; some work practices increased mercury exposure but the exposure levels remained below recommended guidelines. Dental personnel reported more health conditions, often involving the central nervous system, than the control groups. Clinical symptoms reported by dental professionals may be associated with low-level, long-term exposure to occupational mercury, but may also be due to the effects of aging, occupational overuse, and stress. It is important that dental personnel, researchers, and educators continue to encourage and monitor good work practices by dental professionals.


[Epidemiological studies on thyroid cancer in Nagasaki City].
We studied 89 cases of thyroid cancer registered at the Nagasaki Tumor Registry during the period from 1973--1977. The incidence of thyroid cancer tended to be higher in persons exposed to the atomic bomb, especially women, than in the nonexposed population. Compared with nonexposed individuals, the relative risk for thyroid cancer was increased in distally as well as proximally exposed persons, but not in early entrants to the bombed city. In 83 histologically examined patients, papillary carcinomas were highly predominant, they were more prevalent in the exposed than in the nonexposed population.


Dissociation, hemispheric asymmetry, and dysfunction of hemispheric interaction: a transcranial magnetic stimulation approach.
The authors investigated the hypothesis that dissociation may represent a functional dysconnectivity syndrome using a transcranial magnetic stimulation (TMS) approach. Transcranial magnetic stimulation investigations that included motor thresholds and the transcallosal conduction time (TCT) reflecting the interhemispheric transfer were performed in 74 right-handed students. All subjects completed the Dissociative Experience Scale. The high dissociators had a significantly lower left hemispheric excitability than right hemispheric excitability. They also had a significantly shorter TCT from the left to the right hemisphere than did the low dissociators. These results suggest that the neural basis of dissociation may involve a cortical asymmetry with a left hemispheric superiority or, alternatively, a lack of right hemispheric integration.


Convergent linkage evidence from two Latin-American population isolates supports the presence of a susceptibility locus for bipolar disorder in 5q31-34.
We performed a whole genome microsatellite marker scan in six multiplex families with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the closely related population of the Central Valley of Costa Rica. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved markers on 5q31-33, a region implicated by the previous studies of BP in Costa Rica. Because of these concordant results, a follow-up study with additional markers was undertaken in an expanded set of Colombian and Costa Rican families; this provided a genome-wide significant evidence of linkage of BPI to a candidate region of approximately 10 cM in 5q31-33 (maximum non-parametric linkage score=4.395, P<0.00004). Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease association with variants of the enthoprotin and gamma-aminobutyric acid receptor genes.


A potent weapon in the battle against HIV: your own immune system.
The goal of HIV vaccines is to teach the immune system new and hopefully better ways to win the battle against the virus. There are different types of immune responses, those we were born with (innate immunity) and those we "learn" (acquired immunity). HIV vaccines exploit the side of the immune system that is learned (acquired) by providing information to cells in new ways in hopes of enhancing their learning and making them more effective fighters.


Lethal influenza B myocarditis in a child and review of the literature for pediatric age groups.
We report on the case of a 5 year-old girl who developed fulminant myocarditis due to acute infection with influenza virus type B. Cardiac arrest occurred suddenly, resuscitation efforts were not successful, and the patient died of congestive heart failure 24 h after admission to the hospital. Lymphocytic infiltration of cardiac tissues and virologic studies confirmed the suspected diagnosis of acute viral myocarditis. In conclusion, influenza virus type B is one of the infective agents that can cause rapid and fatal myocarditis in previously healthy children. Early cardiac support may be the only option to prevent fatal outcome.


Malakoplakia of the Prostate as a Mimicker of Prostate Cancer on Prostate Health Index and Magnetic Resonance Imaging-Fusion Prostate Biopsy: A Case Report.
Background: Isolated malakoplakia of the prostate is a rare inflammatory condition that has been clinically mistaken for prostatic malignancies. The development of Prostate Imaging Reporting and Data System (PI-RADS) classifications, and Prostate Health Index (PHI) has led to more accurate diagnosis of clinically significant disease and stratification of patients that may be at risk of prostate cancer. Case Presentation: We present a case of a 75-year-old male who was on follow-up with our hospital for elevated prostate specific antigen (PSA). He was admitted for an episode of urosepsis, which was treated with antibiotics and subsequently underwent further workup and was found to have a raised PHI, as well as a high PI-RADS classification and was later found to have malakoplakia based on histology of prostate tissue obtained during targeted magnetic resonance imaging (MRI)-guided fusion prostate biopsy. Conclusion: To our understanding, this is the first case where a prostate lesion has been labeled as a PI-RADS 5 lesion, with elevated PHI that has subsequently been proven histologically to be malakoplakia. An important possible confounder is the interval between the MRI and the episode of urosepsis and it is well known that urosepsis can affect the PSA and MRI result. We present this case to highlight the potential for a false diagnosis of prostate cancer, in spite of laboratory and radiological findings.


Quality of life and people living with AIDS: relationship with sociodemographic and health aspects.
to analyze the relationship of sociodemographic and health dimensions with the quality of life of people living with the human immunodeficiency virus. descriptive and quantitative study. The subjects were 131 seropositive people treated in a specialized center of the Norte-Fluminense municipality, Brazil. A form with sociodemographic and health data was applied, as well as the World Health Organization instrument for the assessment of the quality of life of people with the human immunodeficiency virus. the statistical analysis revealed a significant difference in the assessment of the various dimensions of quality of life by the subjects for gender, education, employment, personal income, medical condition, self-perception of sickness, history of hospitalizations, and bodily alterations due to the antiretroviral drugs. professional nursing and health care, as well as public policies in the area, should valorize the quality of life approach, considering the conditions related to its configuration.


Pseudoclaudication as a manifestation of diabetic neuropathy.
We present the case of a 64-year-old male Type 1 diabetic patient with painful diabetic neuropathy masquerading as intermittent claudication. Examination of the peripheral circulation (both arterial and venous) was normal. An MRI scan excluded lumbar spinal stenosis and nerve root compression as the cause of claudication. The case suggests that, in the absence of other identifiable causes and in the presence of peripheral diabetic neuropathy, "intermittent claudication" may be due to the neuropathy itself.


Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors.
The hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components N,N-dimethyltryptamine (DMT) and 5-methoxy-DMT (5-MeO-DMT), as well as the monoamine oxidase (MAO) inhibitors (MAOIs) harmine and harmaline for oral activity. The present study examined the effects of 5-MeO-DMT in combination with MAOIs in rats using the behavioral pattern monitor, which enables analyses of patterns of locomotor activity and exploration. Interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg) and the 5-HT(2A) antagonist MDL 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in MAOI-treated animals. 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. In rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-MeO-DMT had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. The ability of harmaline to shift 5-MeO-DMT to a biphasic locomotor pattern was shared by the selective MAO(A) inhibitor clorgyline, whereas the selective MAO(B) inhibitor (-)-deprenyl was ineffective. The late hyperactivity induced by the combination of 1.0 mg/kg 5-MeO-DMT and 0.3 mg/kg clorgyline was blocked by pretreatment with MDL 11,939. Pretreatment with WAY-100635 failed to attenuate either the early hypoactivity or the late hyperactivity. The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by the inhibition of MAO(A). Furthermore, 5-HT(2A) receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAO(A) inhibitors.


Methods for Assessing Health Outcomes Associated with Food Insecurity in the United States College Student Population: A Narrative Review.
In the United States, college students experience disproportionate food insecurity (FI) rates compared to the national prevalence. The experience of acute and chronic FI has been associated with negative physical and mental health outcomes in this population. This narrative review aims to summarize the current methodologies for assessing health outcomes associated with the experience of FI in college students in the United States. To date, assessing the health outcomes of FI has predominately consisted of subjective assessments, such as self-reported measures of dietary intake, perceived health status, stress, depression, anxiety, and sleep behaviors. This review, along with the emergence of FI as an international public health concern, establishes the need for novel, innovative, and objective biomarkers to evaluate the short- and long-term impacts of FI on physical and mental health outcomes in college students. The inclusion of objective biomarkers will further elucidate the relationship between FI and a multitude of health outcomes to better inform strategies for reducing the pervasiveness of FI in the United States college student population.


Association between early weight gain and later adiposity in Sri Lankan adolescents.
Early growth pattern is increasingly recognized as a determinant of later obesity. This study aimed to identify the association between weight gain in early life and anthropometry, adiposity, leptin, and fasting insulin levels in adolescence. A cross-sectional study was conducted in 366 school children aged 11-13 years. Weight, height, and waist circumference (WC) were measured. Fat mass (FM) was assessed using bioelectrical impedance analysis. Blood was drawn after a 12-h fast for insulin and leptin assay. Birth weight and weight at 6 months and at 18 months were extracted from Child Health Development Records. An increase in weight SD score (SDS) by ≥0.67 was defined as accelerated weight gain. Linear mixed-effects modeling was used to predict anthropometry, adiposity, and metabolic outcomes using sex, pubertal status, accelerated weight gain as fixed factors; age, birth weight, and family income as fixed covariates, and school as a random factor. Children with accelerated weight gain between birth and 18 months had significantly higher body mass index (BMI) SDS, WC SDS, height SDS, %FM, fat mass index (FMI), fat free mass index (FFMI), and serum leptin levels in adolescence. Accelerated weight gain between 6 and 18 months was associated with higher BMI SDS, WC SDS, %FM, and FMI, but not with height SDS or FFMI. Accelerated weight gain at 0-6 months, in children with low birth weight, was associated with higher height SDS, BMI SDS, WC SDS, %FM, and FMI; in children with normal birth weight, it was associated with BMI SDS, WC SDS, height SDS, and FFMI, but not with %FM or FMI. Effects of accelerated weight gain in early life on anthropometry and adiposity in adolescence varied in different growth windows. Accelerated weight gain during 6-18 months was associated with higher FM rather than linear growth. Effects of accelerated weight gain between 0 and 6 months varied with birth weight.


Improving mental, physical, and social functioning through participation in a 3-week cognitive processing therapy-based intensive PTSD treatment.
Research has supported the utility of brief intensive treatment programs (ITPs) which utilize interventions, such as Cognitive Processing Therapy (CPT), for reducing severity of symptoms among veterans with posttraumatic stress disorder (PTSD). These treatments have produced large overall reductions in PTSD severity and demonstrated the persistence of these gains following treatment. However, the potential effects of ITPs on mental, physical, and social functioning following treatment completion has been largely unexplored. We utilized data from 204 veterans and 5 service members who completed a 3-week CPT-based ITP and 3-month follow-up assessments. We used a two-stage mixed effects location-scale model approach to initially model each participant's amount of PTSD change over time and used these estimates to predict mental, physical, and social functioning three months following treatment. Veterans reported moderate improvements in mental, physical, and social functioning from pre-treatment to 3-month follow-up (ds = 0.52,.42,.55, and.47, respectively). Results indicated that reductions in PTSD severity during treatment, rather than fluctuation in symptom reporting from one assessment to the next, significantly predicted improved mental, physical, and social functioning at follow-up. This study supports the ability of ITPs to enact meaningful improvement in functioning among veterans with PTSD in a short timeframe.


Serum microRNA-139-5p is downregulated in lung cancer patients with lytic bone metastasis.
Bone remodeling can be interrupted by tumor cells which leads to an inappropriate balance of osteoblasts and osteoclasts. As the progenitors of osteoblasts, mesenchymal stem cells (MSCs) have been reported to exhibit an abnormal osteogenic differentiation potential in some cancer‑related bone lesions. However, the evidence is very limited in terms of the biological alterations of MSCs in the bone metastasis of non‑small cell lung cancers (NSCLC). We investigated the expression and function of miR‑139‑5p in MSC osteogenic differentiation in vitro in normal and NSCLC-exposed condition. Then, we compared the serum miR‑139‑5p in stage IV lung adenocarcinoma cancer patients with and without lytic bone metastasis. We found that MSCs exhibited a significant increase in miR‑139‑5p expression after exposure to osteogenic differentiation induction medium. However, Notch1, which was confirmed as a target of miR‑139‑5p by luciferase and western blot assays, showed a marked downregulated expression together with its pathway downstream factors during MSC osteogenesis. miR‑139‑5p positively regulated MSC osteogenic differentiation but this effect was abrogated significantly by Notch1 knockdown. After exposure to conditions of lung cancer cells A549 and L9981, MSCs exhibited significant downregulation of miR‑139‑5p expression and early osteogenic marker ALP activity. Furthermore, we demonstrated that the expression of serum miR‑139‑5p from lung adenocarcinoma patients with lytic bone metastasis was significantly lower compared to that in patients with metastases in other organs. The potential roles of miR‑139‑5p as a biomarker and treatment target in monitoring and controlling bone metastasis in lung cancer patients are worthy of being further explored.


Yeast as a model system to study metabolic impact of selenium compounds.
Inorganic Se forms such as selenate or selenite (the two more abundant forms in nature) can be toxic in Saccharomyces cerevisiae cells, which constitute an adequate model to study such toxicity at the molecular level and the functions participating in protection against Se compounds. Those Se forms enter the yeast cell through other oxyanion transporters. Once inside the cell, inorganic Se forms may be converted into selenide through a reductive pathway that in physiological conditions involves reduced glutathione with its consequent oxidation into diglutathione and alteration of the cellular redox buffering capacity. Selenide can subsequently be converted by molecular oxygen into elemental Se, with production of superoxide anions and other reactive oxygen species. Overall, these events result in DNA damage and dose-dependent reversible or irreversible protein oxidation, although additional oxidation of other cellular macromolecules cannot be discarded. Stress-adaptation pathways are essential for efficient Se detoxification, while activation of DNA damage checkpoint and repair pathways protects against Se-mediated genotoxicity. We propose that yeast may be used to improve our knowledge on the impact of Se on metal homeostasis, the identification of Se-targets at the DNA and protein levels, and to gain more insights into the mechanism of Se-mediated apoptosis.


Endurance training and L-arginine intake: Their effect on antioxidant indices in the heart muscles of rats.
Background: One of the side effects of doing sports activities is the increase of free radicals and oxidative stress. Aim: The present study aimed to investigate the effect of 8 weeks of increasing endurance training with L-arginine supplementation on oxidative indices in the cardiac organ of male Wistar rats. Methods: 32 male Wistar rats were divided into four groups control, L-arginine, endurance training, and L-arginine plus endurance training. Animals in the endurance training groups completed increasing endurance training on a motorized treadmill (60-min/session, 5 times/week) for 8 weeks. Animals in the L-arginine groups consumed an L-arginine solution daily (4 mg/kg/body weight). In the supplement group, L-arginine was given to the mice as a solution in water and as a gavage. Forty- eight hours after the last endurance training session, a heart tissue sample was taken and placed in an RNAlater liquid. Spectrophotometry and an ELISA kit were used to calculate the concentrations of glutathione peroxidase (GPX), malondialdehyde (MDA), and superoxide dismutase (SOD). Results: The present study showed that endurance training and L-arginine consumption did not affect SOD activity. L-arginine intake increased GPX. Endurance training caused a significant increase in MDA compared to the supplemented group (p = 0.01). Also, the consumption of L-arginine significantly increased the total antioxidant capacity TAC in the supplement group compared to the control group (p = 0.001). Conclusion: It seems that taking an L-arginine supplement can increase antioxidant enzymes.


Bean Consumption Accounts for Differences in Body Fat and Waist Circumference: A Cross-Sectional Study of 246 Women.
Beans and other legumes have multiple nutritional qualities that reduce the risk of many diseases. However, the link between legume intake and obesity remains unclear. Therefore, the present study was designed to examine the association between bean intake, body fat percentage (BF%), and waist circumference, in 246 women. BF% was measured using dual-energy X-ray absorptiometry (DXA). Bean intake was assessed using the Block Food Frequency Questionnaire and indexed using total cups of bean-based food items and also factor scores derived from a factor analysis showing adherence to a bean-based dietary pattern. Bean consumption was expressed as cups per 1000 kilocalories. R\egression results showed that the relationship between bean intake (total cups) and BF% was inverse and linear (F = 7.4, P=0.0069). Moreover, with bean consumption being divided into tertiles, there were mean differences across groups in BF% (F = 7.4, P=0.0008) and waist circumference (F = 4.2, P=0.0164). Specifically, women who consumed moderate or high amounts of beans had less body fat and smaller waists than those with low intakes. Similarly, using tertiles to categorize participants based on adherence to a bean-based dietary pattern, developed using factor analysis, those with low adherence had higher BF% (F = 7.9, P=0.0005) and larger waists (F = 4.5, P=0.0118) than their counterparts. The associations remained significant after adjusting for potential confounders. In conclusion, beans and other legumes seem to have dietary qualities that may be beneficial in the battle against obesity.


Integrating the actions of melatonin on human physiology.
Melatonin has a diverse range of physiological effects in humans. Reported effects include modulation of the sleep-wake, thermoregulatory, cognitive, cardiovascular and immune systems. While integrating these broad-ranging effects is difficult when current paradigms are used, the diverse effects of melatonin on human physiology may be better understood by shifting our theoretical perspective. Traditionally, research has treated melatonin as a classical hormone for which a defined effect in physiological systems and a mechanism of action can be elucidated. In this article, we suggest that it may be more appropriate to view melatonin as an evolutionally stable timing signal to which each species has adapted the timing of physiological processes. From this perspective, it appears that the physiological role of melatonin in humans falls into two categories. The first relates to the self-regulation of circadian timing by the suprachiasmatic nucleus-pineal complex. The second relates to the promotion of restorative or anabolic physiological processes. In humans, elevated melatonin levels have been associated with reduced core temperature, increased heat loss, decreased cardiovascular output, reduced alertness and enhanced immune responsiveness. Taken together, these changes suggest that melatonin may increase the propensity for physiological processes promoting nocturnal sleep or processes that occur during the sleep period.


RNAi-induced K-Ras gene silencing suppresses growth of EC9706 cells and enhances chemotherapy sensitivity of esophageal cancer.
To analyze the growth, proliferation, apoptosis, invasiveness and chemotherapy sensitivity of EC9706 cells after K-Ras gene silencing, an expression carrier pSilencer-siK-Ras was constructed, and the EC9706 cell line was transfected using a liposome technique. Six groups were established: Control, siRNA NC (transfected with empty vector pSilencer2.1); Ras siRNA (transfected with pSilencer-siK-Ras2); Paclitaxel; Paclitaxel + siRNA NC; and Ras siRNA +Paclitaxel. After the treatment, RT-PCR, Western blotting, MTT assay, flow cytometry and the Transwell technique were used to assess expression of K-Ras mRNA and protein in EC9706 cells, as well as cell growth, proliferation, apoptosis and invasiveness. The effect of Paclitaxel chemotherapy was also tested. pSilencer-siK-Ras2 effectively down-regulated expression of K-Ras mRNA and protein in EC9706 cells, growth being significantly inhibited. Flow cytometry indicated obvious apoptosis of cells in the experimental group, with arrest in the G1 phase; cell migration ability was also reduced. After pSilencer-siK-Ras2 transfection or the addition of Paclitaxel, EC9706 cells were suppressed to different extents; the suppressive effect was strengthened by combined treatment. The results suggested that RNAi-induced K-Ras gene silencing could enhance chemotherapy sensitivity of esophageal cancer.


Characteristics of clients who access mobile compared to clinic HIV counselling and testing services: a matched study from Cape Town, South Africa.
Studies within sub-Saharan African countries have shown that mobile services increase uptake of HIV counselling and testing (HCT) services when compared to clinics and are able to access different populations, but these have included provider-initiated HCT in clinics. This study aimed to compare the characteristics of clients who self-initiated HCT at either a mobile or a clinic service in terms of demographic and socio-economic variables, also comparing reasons for accessing a particular health service provider. This study took place in eight areas around Cape Town. A matched design was used with one mobile HCT service matched with one or more clinics (offering routine HCT services) within each of the eight areas. Adult clients who self-referred for an HIV test within a specified time period at either a mobile or clinic service were invited to participate in the study. Data were collected between February and April 2011 using a questionnaire. Summary statistics were calculated for each service type within a matched pair and differences of outcomes from pairs were used to calculate effect sizes and 95% confidence intervals. 1063 participants enrolled in the study with 511 from mobile and 552 from clinic HCT services. The proportion of males accessing mobile HCT significantly exceeded that of clinic HCT (p < 0.001). The mean age of participants attending mobile HCT was higher than clinic participants (p = 0.023). No significant difference was found for socio-economic variables between participants, with the exception of access to own piped water (p = 0.029). Participants who accessed mobile HCT were significantly more likely to report that they were just passing, deemed an "opportunistic" visit (p = 0.014). Participants who accessed clinics were significantly more likely to report the service being close to home or work (p = 0.035). An HCT strategy incorporating a mobile HCT service, has a definite role to play in reaching those population groups who do not typically access HCT services at a clinic, especially males and those who take advantage of the opportunity to test. Mobile HCT services can complement clinic services.


Penetration of the signal sequence of Escherichia coli PhoE protein into phospholipid model membranes leads to lipid-specific changes in signal peptide structure and alterations of lipid organization.
In order to obtain more insight in the initial steps of the process of protein translocation across membranes, biophysical investigations were undertaken on the lipid specificity and structural consequences of penetration of the PhoE signal peptide into lipid model membranes and on the conformation of the signal peptide adopted upon interaction with the lipids. When the monolayer technique and differential scanning calorimetry are used, a stronger penetration is observed for negatively charged lipids, significantly influenced by the physical state of the lipid but not by temperature or acyl chain unsaturation as such. Although the interaction is principally electrostatic, as indicated also by the strong penetration of N-terminal fragments into negatively charged lipid monolayers, the effect of ionic strength suggests an additional hydrophobic component. Most interestingly with regard to the mechanism of protein translocation, the molecular area of the peptide in the monolayer also shows lipid specificity: the area in the presence of PC is consistent with a looped helical orientation, whereas in the presence of cardiolipin a time-dependent conformational change is observed, most likely leading from a looped to a stretched orientation with the N-terminus directed toward the water. This is in line also with the determined peptide-lipid stoichiometry. Preliminary 31P NMR and electron microscopy data on the interaction with lipid bilayer systems indicate loss of bilayer structure.


A versatile bis-porphyrin tweezer host for the assembly of noncovalent photoactive architectures: a photophysical characterization of the tweezers and their association with porphyrins and other guests.
A bis(Zn(II)-porphyrin) tweezer host with anthracene components as apex and side-arms has been synthesized. Mono- (pyridine) and bidentate (4,4'-bipyridine) guests were used as models for single and double axial coordination inside the cavity, respectively. A series of dipyridylporphyrin guests with different substitution patterns and excited-state energy levels have association constants with the tweezers that are of the order of 10(6) M(-1), which is indicative of complexation with the inside of the cavity. This complexation can only occur upon an important distortion of the cavity that opens the bite by about 30 %. This characteristic, in conjunction with their ability to reduce the bite distance by rotation around single bonds, makes these porphyrin tweezers amongst the most versatile so far reported, with tuning of the bite distance in the range of approximately 5-20 Angstroms. Energy transfer to the free-base guest within the triporphyrin complex is nearly quantitative (95-98 %) and the rates of transfer are consistent with a Förster mechanism that is characterized by a reduced orientation factor.


Increasing access to psychiatric care during the COVID-19 pandemic through mental health clinical pharmacy specialist services.
Higher rates of mental health conditions, increased incidence of psychiatric diagnoses, and symptom relapse with minimal access to psychotherapeutic services are reported during the COVID-19 pandemic. A local area clinic in the United States that exists to serve underprivileged patients helps to combat poor psychiatric outcomes by offering psychiatric clinics, pharmacotherapy management, and medications at reduced or no cost. Recruitment and data collection were conducted from May 3, 2021, to March 3, 2022. Patients were seen by psychiatrists or the mental health clinical pharmacy specialist (MHCPS), and consent was obtained for the completion of satisfaction surveys. Five-point Likert scale comparisons were utilized to assess patient-perceived differences in clinician care. The primary study objective was to determine if access to care could be increased with the addition of an MHCPS, and secondary objectives included evaluating patient perceptions of clinician care as well as reporting MHCPS interventions. Participant baseline demographics and common psychiatric diagnoses are reported. An MHCPS was incorporated into the clinic during the study allowing for 1 additional patient care period per month. The most frequent score among all surveys was 4.8 (P > .05) on a 5-point scale, indicating no statistically significant differences between clinician care. MHCPS interventions are reported. The addition of an MHCPS allowed for additional patient care appointments for the clinic each month. MHCPS care offered no significant differences from psychiatrist care based on patient satisfaction surveys, highlighting the utility of pharmacist involvement for managing psychiatric disease states and increasing access to mental health services.


Renal risk and response in amyloidosis.
In this issue of Blood, Palladini and colleagues address incidence of and risk factors for end-stage renal disease (ESRD) and proffer a new renal response system for patients with amyloid light-chain (AL) amyloidosis using a test set of 461 patients from Pavia, Italy, and a validation set of 271 patients from Heidelberg, Germany. Validation of organ response criteria has trailed behind the progress made in the field of AL amyloidosis in diagnosis, prognosis, and hematologic response, but Palladini and colleagues' study helps breach this gap.


Long-Range and Directional Allostery of Actin Filaments Plays Important Roles in Various Cellular Activities.
A wide variety of uniquely localized actin-binding proteins (ABPs) are involved in various cellular activities, such as cytokinesis, migration, adhesion, morphogenesis, and intracellular transport. In a micrometer-scale space such as the inside of cells, protein molecules diffuse throughout the cell interior within seconds. In this condition, how can ABPs selectively bind to particular actin filaments when there is an abundance of actin filaments in the cytoplasm? In recent years, several ABPs have been reported to induce cooperative conformational changes to actin filaments allowing structural changes to propagate along the filament cables uni- or bidirectionally, thereby regulating the subsequent binding of ABPs. Such propagation of ABP-induced cooperative conformational changes in actin filaments may be advantageous for the elaborate regulation of cellular activities driven by actin-based machineries in the intracellular space, which is dominated by diffusion. In this review, we focus on long-range allosteric regulation driven by cooperative conformational changes of actin filaments that are evoked by binding of ABPs, and discuss roles of allostery of actin filaments in narrow intracellular spaces.


[Food-borne illnesses: a survey of regional reference laboratories in Italy.].
Many problems exist in the surveillance of human food-borne illnesses, and one of the most important is identifying the responsible microorganisms. For this reason, a survey was carried out to identify regional reference laboratories and laboratories with the capacities necessary for identification of pathogenic microorganisms in Italy. All 21 Italian regions and autonomous provinces completed the survey except three (Basilicata, Tuscany and Sardinia).Only 6% of the identified laboratories were found to have been formally designated as regional reference laboratories. Seventy-one percent of all laboratories reported having the capacity to diagnose over half (>7/13) of the listed bacteria, 69% over half of the listed parasites (> 4/8) and 51% over half of the listed viruses (>2/4). No differences were found in the capability to diagnose bacterial and parasitic infections, between laboratories in northern, central and southern Italy, while a significant difference was found in the capability to diagnose viral infections between laboratories in the three geographical areas (p <0.01). This study clearly shows that there is a need to improve diagnostic capacities of regional reference laboratories and laboratories involved in the surveillance of food-borne illnesses in Italy.


Internal fixation of an intertrochanteric femoral fracture after Birmingham hip resurfacing arthroplasty.
The Birmingham hip system is one of the most popular designs for hip resurfacing. Fractures associated with the Birmingham Hip Resurfacing (BHR) are mostly subcapital fractures. Other traumatic periprosthetic fractures are rarely reported. We report an intertrochanteric fracture which occurred after a Birmingham hip resurfacing. The fracture was treated with a reversed distal femoral locking plate, with a very satisfying clinical and radiological result.


Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.
To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.


Multiple L double-stranded RNA species of Saccharomyces cerevisiae: evidence for separate encapsidation.
The L double-stranded (ds) RNA component of Saccharomyces cerevisiae may contain up to three dsRNA species, each with a distinct sequence but with identical molecular weights. These dsRNAs have been separated from each other by denaturation and polyacrylamide gel electrophoresis. The 3' terminal sequences of the major species, LA dsRNA, were determined. Secondary structural analysis supported the presence of two stem and loop structures at the 3' terminus of the LA positive strand. In strain T132B NK-3, both the LA and LC species are virion encapsidated. Two distinct classes of virions were purified from this strain, each with a different RNA polymerase activity and with distinct protein components. The heavy virions harbored LA dsRNA, whereas the LC dsRNA species co purified with the light virion peak. Thus, LA and LC dsRNAs, when present in the same cell, may be separately encapsidated.


[Clinical experience with agomelatine for the treatment of depression in elderly patients in outpatient practice].
Objective. To determine the therapeutic efficacy and safety of agomelatine (valdoxan) in elderly patients with mild and moderate depression during outpatient treatment. Material and methods. The 60-79-year-old age group consisted of 20 patients with mild and moderate depressive episode who received agomelatine. Mild and moderate depressive episode was determined according to depressive disorder criteria of ICD-10. The therapeutic dose for agomelatine treatment was 25 or 50 mg/day once daily (in the evening) during 6 weeks. Results. Depressive symptoms reduced during the first 2 weeks of therapy with agomelatine. Agomelatine was effective in reducing both anxiety and depressive symptoms as well as significantly improved the health-related quality of the patient's life. Agomelatine did not negatively impact on cognitive function and had not pronounced and serious adverse events. Agomelatine can be recommended for use in clinical practice for the treatment of elderly outpatients with mild and moderate depression disorders.


Carinal Compression from Primary Mediastinal Germ Cell Tumor.
Mediastinal masses can present as a medical emergency when there is central airway obstruction, superior vena cava (SVC) syndrome, direct mediastinal extension of tumor, or obstruction of the central pulmonary vasculature. Diagnostic evaluation may include the need for invasive tissue biopsy under anesthesia, which can pose several distinct risks for patients. Among the many etiologies of mediastinal tumors, primary mediastinal germ cell tumors are a rare form with a favorable prognosis.


Tools for building a comprehensive modeling system for virtual screening under real biological conditions: The Computational Titration algorithm.
Computational tools utilizing a unique empirical modeling system based on the hydrophobic effect and the measurement of logP(o/w) (the partition coefficient for solvent transfer between 1-octanol and water) are described. The associated force field, Hydropathic INTeractions (HINT), contains much rich information about non-covalent interactions in the biological environment because of its basis in an experiment that measures interactions in solution. HINT is shown to be the core of an evolving virtual screening system that is capable of taking into account a number of factors often ignored such as entropy, effects of solvent molecules at the active site, and the ionization states of acidic and basic residues and ligand functional groups. The outline of a comprehensive modeling system for virtual screening that incorporates these features is described. In addition, a detailed description of the Computational Titration algorithm is provided. As an example, three complexes of dihydrofolate reductase (DHFR) are analyzed with our system and these results are compared with the experimental free energies of binding.