Radiation dose reduction in computed skeletal radiography. Effect on image quality.
To evaluate the effect of radiation dose reduction on image ++quality in computed musculoskeletal radiography and determine optimal exposure range. In 11 corpses, 1 hand and 1 hip were examined with film-screen radiography, and a series of computed radiographs was obtained using exactly the same technique except for the exposure, which was 100, 50, 25, 12.5, 6.25, and 1.56% of the mAs numbers used for the film-screen images. The computed hip radiographs were processed in 2 different ways, one simulating the film-screen images and one using contrast enhancement. Four radiologists reviewed the images regarding the following parameters: cortical bone, trabecular bone, joint space, and soft tissue, giving each a diagnostic quality rating on a scale from 1 to 5. The median and mean values were found for the pooled results. For the hands, the computed radiographs were ranked inferior to the film-screen images for all parameters except soft tissue, where the computed radiographs scored higher. The computed images with 50 and 25% exposure were ranked equal to the 100% ones. The quality rating slowly declined with lower exposures. For the hips, the 100 and 50% computed radiographs were generally similar to or slightly better than the film-screen images. The decline was somewhat faster than for the hands. The contrast-enhanced hip images scored less than the nonenhanced images at any given exposure for all parameters except soft tissue, where the contrast-enhanced images scored better at all exposures. The difference between nonenhanced and enhanced images became less at the lower exposures. Lowering the exposure in computed musculoskeletal radioagrphy below the level of film-screen radiography is feasible, especially in the peripheral skeleton. Contrast enhancement seems to be valuable only in the evaluation of soft-tissue structures.


Effect of estradiol on hypothalamic GnRH and pituitary and serum LH and FSH in ovariectomized pigs.
Two experiments were conducted to measure pituitary gonadotropins, hypothalamic-gonadotropin releasing hormone (GnRH) and pituitary response to GnRH during periods when serum luteinizing hormone (LH) was suppressed by estradiol-17 beta (e2) in ovariectomized pigs. In the first experiment, 10 ovariectomized gilts were assigned to two groups of five each according to time of slaughter (24 or 36 h after injection). Within each group, gilts were given corn oil (n = 2) or 400 micrograms E2 (n = 3). Neither serum nor anterior pituitary (AP) concentrations of follicle-stimulating hormone (FSH) were affected by E2. Serum LH was suppressed from 12 to 26 h after E2. Concentrations of LH in AP were unchanged at 24 h, but increased at 36 h after E2 injection. Concentrations of GnRH in medial basal hypothalamus (MBH), stalk-median eminence (SME) and hypophyseal portal area (HPA) were lower at 24 h after E2 than in oil-treated gilts. At 36 h after E2, suppressive effects of E2 on LH in serum had subsided and concentrations of LH in AP and GnRH in MBH and SME were greater than in oil-treated controls. The observation that E2 suppressed LH in serum without a detectable suppression of LH in AP led to the hypothesis that E2 had caused the suppression of serum LH by suppression of GnRH release. In a second experiment, 12 ovariectomized gilts were assigned to receive corn oil (n = 4), 400 micrograms E2 (n = 4) or 400 micrograms E2 plus GnRH (1.5 micrograms/h; n = 4). Patterns of LH in sera of E2-treated animals were similar to those in the first experiment, with serum LH in E2-treated gilts suppressed from 4 to 32 h after treatment. However, in gilts receiving GnRH in addition to E2, serum LH concentrations during 20 to 32 h after treatment were intermediate between gilts receiving E2 alone and controls. Thus the pituitary of the pig is capable of responding to GnRH when LH is normally suppressed by E2. These experiments provide two lines of evidence that suppression of serum LH by E2 is due at least in part to suppression of GnRH. These experiments also establish the hypothalamus as a site for negative feedback of E2 in the female pig.


The Neural Codes Underlying Internally Generated Representations in Visual Working Memory.
Humans can construct rich subjective experience even when no information is available in the external world. Here, we investigated the neural representation of purely internally generated stimulus-like information during visual working memory. Participants performed delayed recall of oriented gratings embedded in noise with varying contrast during fMRI scanning. Their trialwise behavioral responses provided an estimate of their mental representation of the to-be-reported orientation. We used multivariate inverted encoding models to reconstruct the neural representations of orientation in reference to the response. We found that response orientation could be successfully reconstructed from activity in early visual cortex, even on 0% contrast trials when no orientation information was actually presented, suggesting the existence of a purely internally generated neural code in early visual cortex. In addition, cross-generalization and multidimensional scaling analyses demonstrated that information derived from internal sources was represented differently from typical working memory representations, which receive influences from both external and internal sources. Similar results were also observed in intraparietal sulcus, with slightly different cross-generalization patterns. These results suggest a potential mechanism for how externally driven and internally generated information is maintained in working memory.


Increasing diversity of swine parvoviruses and their epidemiology in African pigs.
Detection of infectious viral agents has been on the increase globally with the advent and usage of more sensitive and selective novel molecular techniques in the epidemiological study of viral diseases of economic importance to the swine industry. The observation is not different for the pig-infecting member of the subfamily Parvovirinae in the family Parvoviridae as the application of novel molecular methods like metagenomics has brought about the detection of many other novel members of the group. Surprisingly, the list keeps increasing day by day with some of them possessing zoonotic potentials. In the last one decade, not less than ten novel swine-infecting viruses have been added to the subfamily, and ceaseless efforts have been in top gear to determine the occurrence and prevalence of the old and new swine parvoviruses in herds of pig-producing countries worldwide. The story, however, is on the contrary on the African continent as there is presently a dearth of information on surveillance initiatives of the viruses among swine herds of pig-producing countries in the region. Timely detection and characterization of the viral pathogens is highly imperative for the implementation of effective control and prevention of its spread. This review therefore presents a concise overview on the epidemiology of novel porcine parvoviruses globally and also provides up-to-date highlights on the reported cases of the viral agents in the African sub-region.


Effects of general central nervous system depressants with and without calcium ionophore A23187 of rat cerebellar cyclic guanosine 3',5'-monophosphate.
Rat cerebellar cyclic guanosine 3',5'-monophosphate (cGMP) concentrations were determined by radioimmune methods after sacrifice with focused microwave fixation in animals pretreated with either ethanol, pentobarbital, or diethyl ether, either alone or in combination with the calcium ionophore A23187. Both pentobarbital sodium and diethyl ether produced a dose-dependent depression of cerebellar cGMP. When A23187 was administered alone, significant increases of cerebellar levels of cGMP were observed. The administration of A23187 to animals acutely intoxicated with ethanol, pentobarbital, or diethyl ether resulted in significant depression of cerebellar cGMP levels.


The neurodevelopmental basis of math anxiety.
Math anxiety is a negative emotional reaction to situations involving mathematical problem solving. Math anxiety has a detrimental impact on an individual's long-term professional success, but its neurodevelopmental origins are unknown. In a functional MRI study on 7- to 9-year-old children, we showed that math anxiety was associated with hyperactivity in right amygdala regions that are important for processing negative emotions. In addition, we found that math anxiety was associated with reduced activity in posterior parietal and dorsolateral prefrontal cortex regions involved in mathematical reasoning. Multivariate classification analysis revealed distinct multivoxel activity patterns, which were independent of overall activation levels in the right amygdala. Furthermore, effective connectivity between the amygdala and ventromedial prefrontal cortex regions that regulate negative emotions was elevated in children with math anxiety. These effects were specific to math anxiety and unrelated to general anxiety, intelligence, working memory, or reading ability. Our study identified the neural correlates of math anxiety for the first time, and our findings have significant implications for its early identification and treatment.


[Prevention of mitochondrial diseases: a hope through assisted reproductive technologies].
Mitochondrial diseases are a heterogenic and poorly studied group of diseases, considered serious in most cases and currently without treatment. Although assisted reproduction proposed strategies to prevent them, such as pre-implantation genetic diagnosis, these techniques are not sufficiently successful. However, the recent publication of two assistedreproduction techniques – meiotic spindle transfer in nonhuman primates and pronuclear transfer in humans – generate a clear ray of hope for the prevention of these diseases. This review analyzes the characteristics and meaning of these new findings and their future clinical implications.


Deposition of fibronectin and laminin in the basement membrane of the rat parietal yolk sac: immunohistochemical and biosynthetic studies.
Rat parietal yolk sacs (PYS) at gestational ages 7.5, 9.5, 11.5, 13.5, 14.5, and 16.5 d were reacted with antibodies against laminin or plasma fibronectin. At all times studied, laminin consistently gave a positive reaction with Reichert's membrane and with the cytoplasm of PYS cells. In contrast, fibronectin gave a negative reaction with Reichert's membrane at day 7.5, was weakly positive at day 9.5, and from then on was increasingly positive with maximum reactivity at 14.5 d. By electron microscopic immunohistochemistry, antilaminin reacted strongly with 14.5-d Reichert's membrane and with the contents of the rough endoplasmic reticulum RER cisternae of the PYS cells. Antifibronectin had some spotty reactivity with Reichert's membrane, but the cytoplasm of the PYS cells was negative. The contents of the vitelline vessels and the interface between trophoblast and Reichert's membrane were strongly positive. Metabolic labeling of PYS cells in organ culture clearly demonstrated the presence of laminin, type IV procollagen, and entactin both in the medium and in tissues, but fibronectin was absent. No component in the medium bound to gelatin-Sepharose columns. These studies demonstrate that PYS cells, which actively synthesize and secrete basement membrane components, do not synthesize any detectable fibronectin. Furthermore, the anti-fibronectin staining pattern in the vitelline vessels and trophoblast-Reichert's membrane interface strongly suggests that the fibronectin present in Reichert's membrane is derived from the maternal circulation and is merely "trapped" in the membrane.


Specificity of resistance training responses in neck muscle size and strength.
This study examined hypertrophy after head extension resistance training to assess which muscles of the complicated cervical neuromuscular system were used in this activity. We also determined if conventional resistance exercises, which are likely to evoke isometric action of the neck, induce generalized hypertrophy of the cervical muscle. Twenty-two active college students were studied. [mean (SE) age, weight and height: 21 (1) years, 71 (4) kg and 173 (3) cm, respectively]. Subjects were assigned to one of three groups: RESX (head extension exercise and other resistance exercises), RES (resistance exercises without specific neck exercise), or CON (no training). Groups RESX (n = 8) and RES (n = 6) trained 3 days/week for 12 weeks with large-muscle mass exercises (squat, deadlift, push press, bent row and mid-thigh pull). Group RESX also performed three sets of ten repetitions of a head extension exercise 3 days/week with a load equal to the 3 x 10 repetition maximum (RM). Group CON (n = 8) was a control group. The cross-sectional area (CSA) of nine individual muscles or muscle groups was determined by magnetic resonance imaging (MRI) of the cervical region. The CSA data were averaged over four contiguous transaxial slices in which all muscles of interest were visible. The 3 x 10 RM for the head extension exercise increased for RESX after training [from 17.9 (1.0) to 23.9 (1.4) kg, P < 0.05] but not for RES [from 17.6 (1.4) to 17.7 (1.9) kg] or CON [from 10.1 (2.2) to 10.3 (2.1) kg]. RESX showed an increase in total neck muscle CSA after training [from 19.5 (3.0) to 22.0 (3.6) cm2, P < 0.05], but RES and CON did not [from 19.6 (2.9) to 19.7 (2.9) cm2 and 17.0 (2.5) to 17.0 (2.4) cm2, respectively]. This hypertrophy for RESX was due mainly to increases in CSA of 23.9 (3.2), 24.0 (5.8), and 24.9 (5.3)% for the splenius capitis, and semispinalis capitis and cervicis muscles, respectively. The lack of generalized neck muscle hypertrophy in RES was not due to insufficient training. For example, the CSA of their quadriceps femoris muscle group, as assessed by MRI, increased by 7 (1)% after this short-term training (P < 0.05). The results suggest that: (1) the splenius capitis, and semispinalis capitis and cervicis muscles are mainly responsible for head extension; (2) short-term resistance training does not provide a sufficient stimulus to evoke neck muscle hypertrophy unless specific neck exercises are performed; and (3) the postural role of head extensors provides modest loading in bipeds.


Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?
Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.


Recent advances in porous nanoparticles for drug delivery in antitumoral applications: inorganic nanoparticles and nanoscale metal-organic frameworks.
Nanotechnology has provided new tools for addressing unmet clinical situations, especially in the oncology field. The development of smart nanocarriers able to deliver chemotherapeutic agents specifically to the diseased cells and to release them in a controlled way has offered a paramount advantage over conventional therapy. Areas covered: Among the different types of nanoparticle that can be employed for this purpose, inorganic porous materials have received significant attention in the last decade due to their unique properties such as high loading capacity, chemical and physical robustness, low toxicity and easy and cheap production in the laboratory. This review discuss the recent advances performed in the application of porous inorganic and metal-organic materials for antitumoral therapy, paying special attention to the application of mesoporous silica, porous silicon and metal-organic nanoparticles. Expert opinion: The use of porous inorganic nanoparticles as drug carriers for cancer therapy has the potential to improve the life expectancy of the patients affected by this disease. However, much work is needed to overcome their drawbacks, which are aggravated by their hard nature, exploiting the advantages offered by highly the ordered pore network of these materials.


Acceptability of the Medication Adherence for Patients Support intervention to improve adherence to patients prescribed medications for hypertension or comorbidities, as an adjunct to primary care: A qualitative study.
Tailored interventions delivered via text and voice messages can improve adherence to multiple medications. However, no such intervention has been developed in the UK primary-care setting. We conducted focus groups with 12 patients with hypertension, type 2 diabetes, or both conditions, presumed to be non-adherent and recruited from deprived neighborhoods, to assess the acceptability and inform the development of an intervention to provide ongoing support for adherence, as an adjunct to primary-care consultations. Patients recommended ways to improve the tailored content and delivery of the intervention; like highly interactive messages to report both medication taking and determinants of medication adherence.


The minipig as a platform for new technologies in toxicology.
The potential of the minipig as a platform for future developments in genomics, high density biology, transgenic technology, in vitro toxicology and related emerging technologies was reviewed. Commercial interests in the pig as an agricultural production species have driven scientific progress in these areas. There is no equivalent economic driver for progress in the dog or the monkey. As a result the available knowledge-bases are much greater for pigs (than for dogs or monkeys) in many areas (physiology, disease, genetics, immunology etc). Fundamental genomic knowledge and phenotypic characterization in regard to the pig is well in advance of the dog or the monkey and basic knowledge of the pig is therefore likely to stay ahead of the other two species. While the emerging technologies are essentially "species neutral" and can in principle be applied to all species, for all the technologies that we examined, basic knowledge and technical capabilities are greater for the pig than the dog or monkey. In concrete terms, in application to safety testing we have seen that: (i) The Göttingen minipig is well positioned for the performance of toxicogenomics studies, (ii) The close sequence homology between pigs and humans suggest that minipigs will be useful for the testing of biotechnology products (and possibly for in silico toxicology) and (iii) the minipig is the only non-rodent toxicology model where transgenic animals can be readily generated, and reproductive technologies are well developed in the pig. These properties should also make the minipig an interesting model for the testing of biotechnology products. These factors all support the idea that the minipig is well placed to meet the challenges of the emerging technologies and the toxicology of the future; it also seems likely that the minipig can be an advantageous model for the testing of biotechnology products.


The inadequacy of using means to compare medical costs of smokers and nonsmokers.
The costs associated with health risks have become a primary focus in the field of health promotion. Unfortunately, the nature and quality of medical cost data are not ideal for simple comparisons of health risk groups. Most health promotion professionals have had little or no training on how to interpret cost data and are thus unaware of the limitations and problems inherent in cost comparisons. This report illustrates the problems encountered when using cost data, using examples from a medical claims dataset. Specifically, the potential errors that result from comparing group means are shown. A set of alternatives for practitioners and researchers to consider when comparing costs for different groups are offered.


A one-layer recurrent neural network for constrained nonsmooth optimization.
This paper presents a novel one-layer recurrent neural network modeled by means of a differential inclusion for solving nonsmooth optimization problems, in which the number of neurons in the proposed neural network is the same as the number of decision variables of optimization problems. Compared with existing neural networks for nonsmooth optimization problems, the global convexity condition on the objective functions and constraints is relaxed, which allows the objective functions and constraints to be nonconvex. It is proven that the state variables of the proposed neural network are convergent to optimal solutions if a single design parameter in the model is larger than a derived lower bound. Numerical examples with simulation results substantiate the effectiveness and illustrate the characteristics of the proposed neural network.


Evaluation of Dietary Intake in Individuals with Mild Cognitive Impairment.
The phase of mild cognitive impairment (MCI) holds significant importance for postponing the onset of dementia. Therefore, MCI has become a central focus in research related to dementia prevention. The purpose of this study was to investigate the dietary intake and dietary patterns of MCI patients in Taiwan. In total, 40 subjects were enrolled in this cross-sectional study that was conducted from July 2019 to September 2021 at the Linkou Chang Gung Memorial Hospital. The results of the clinical dementia rating (CDR) and mini-mental state examination (MMSE) were obtained from medical records. Participants were divided into two groups: a healthy group (MMSE ≥ 26 points, CDR = 0) and an MCI group (MMSE ≥ 26 points, CDR = 0.5). Results indicated that the MCI group had significantly higher copper and lower low-fat meat intake compared to the healthy group. Furthermore, the high MIND (Mediterranean dietary approaches to stop hypertension intervention for neurodegenerative delay) diet score represented a lower risk of MCI. After adjusting for age, gender, diabetes mellitus, hypertension, and calorie intake in the multivariate regression analysis, calcium and fruit intake levels were positively associated with the MMSE, whereas low-fat meat intake was negatively associated with the CDR. In conclusion, the prevalence of MCI demonstrated a close correlation with nutrient intake, including copper and calcium. Furthermore, a MIND diet, particularly one high in n-3 polyunsaturated fatty acids, might be useful for preventing MCI. However, more extensive research with larger populations is needed to confirm this potential.


Does moonlight increase predation risk? Meta-analysis reveals divergent responses of nocturnal mammals to lunar cycles.
The risk of predation strongly affects mammalian population dynamics and community interactions. Bright moonlight is widely believed to increase predation risk for nocturnal mammals by increasing the ability of predators to detect prey, but the potential for moonlight to increase detection of predators and the foraging efficiency of prey has largely been ignored. Studies have reported highly variable responses to moonlight among species, calling into question the assumption that moonlight increases risk. Here, we conducted a quantitative meta-analysis examining the effects of moonlight on the activity of 59 nocturnal mammal species to test the assumption that moonlight increases predation risk. We examined patterns of lunarphilia and lunarphobia across species in relation to factors such as trophic level, habitat cover preference and visual acuity. Across all species included in the meta-analysis, moonlight suppressed activity. The magnitude of suppression was similar to the presence of a predator in experimental studies of foraging rodents (13.6% and 18.7% suppression, respectively). Contrary to the expectation that moonlight increases predation risk for all prey species, however, moonlight effects were not clearly related to trophic level and were better explained by phylogenetic relatedness, visual acuity and habitat cover. Moonlight increased the activity of prey species that use vision as their primary sensory system and suppressed the activity of species that primarily use other senses (e.g. olfaction, echolocation), and suppression was strongest in open habitat types. Strong taxonomic patterns underlay these relationships: moonlight tended to increase primate activity, whereas it tended to suppress the activity of rodents, lagomorphs, bats and carnivores. These results indicate that visual acuity and habitat cover jointly moderate the effect of moonlight on predation risk, whereas trophic position has little effect. While the net effect of moonlight appears to increase predation risk for most nocturnal mammals, our results highlight the importance of sensory systems and phylogenetic history in determining the level of risk.


Inclined surfaces in diamond: broadband antireflective structures and coupling light through waveguides.
Control of the sidewall angle of diamond microstructures was achieved by varying the gas mixture, bias power and mask shape during inductively coupled plasma etching. Different etch mechanisms were responsible for the angle of the lower and upper part of the sidewall formed during diamond etching. These angles could to some extent be controlled separately. The developed etch process was used to fabricate wideband antireflective structures with an average transmission of 96.4% for wavelengths between 10 and 50 µm. Smooth facetted edges for coupling light through waveguides from above were also demonstrated.


A quantitative method for assessing the third complement factor (C3) attached to the surface of opsonized Pseudomonas aeruginosa: interrelationship between C3 fixation, phagocytosis and complement consumption.
A direct enzyme-linked immunoassay is described for the determination of C3 that becomes attached to the surface of bacteria upon incubation in serum. The assay uses horseradish peroxidase-conjugated rabbit antiserum specific for human C3. In this study various Pseudomonas aeruginosa strains, Escherichia coli and Staphylococcus aureus were opsonized under different conditions and the amount of C3 fixed to the bacterial surface was measured directly. The extent of C3 fixation was compared with the percentage of phagocytosis by human polymorphonuclear leukocytes and with the complement consumption in the fluid phase. It was demonstrated that C3 fixation closely correlated with the percentage of phagocytosis but not with complement consumption. The method can be performed with relatively simple equipment and could be used in routine laboratories in order to determine the extent of opsonization of Pseudomonas aeruginosa and other bacteria and to detect opsonic defects in the sera of patients.


A Curriculum for Lumbar Puncture Training in Internal Medicine Residency.
This article was migrated. The article was not marked as recommended. Background: Lumbar puncture (LP), although not mandatory for internal medicine (IM) residents to perform, remains a vital procedure for hospitalized patients. The optimal method for training residents in LP is not established. Objective: We implemented, and evaluated a curriculum (online video, post-video quiz, group discussion, checklist, simulation training) for training PGY-2 IM residents in performing LPs. Methods: We surveyed residents after completion of the curriculum and compared LP logs for the cohort who participated in this training to the prior year of residents without the curriculum. Results: Overall survey response rate was 65%. 98% of residents found the pre-course materials useful; 92% agreed or strongly agreed that the in-person training session helped them to correctly perform an LP. 90% of residents found simulation training useful and 84% responded that the training session increased their confidence to perform an LP. However, compared to the prior residency class who did not have LP training, the initial class that underwent training did not perform more LPs during their residency: median 2 (inter-quartile range 0-5) vs. 2 (inter-quartile range 0-4.25), respectively (p = 0.98). Conclusion: Despite not leading to an increase in LP rates, our curriculum was very well received by PGY-2 IM residents.


Evaluation of the size effect of hydrophobic ring substitution on 9-O position of berberine on DNA binding.
The interaction of deoxyribonucleic acid (DNA) with medicinally significant small molecules has long piqued the interest of researchers because its applications are directly related to the discovery of new classes of drugs. Keeping this in mind, here we report berberine derivatives and their interaction with calf thymus DNA (CT-DNA). In this report we discussed on the structural perspectives and thermodynamic characteristics of the interaction of four 9-O-substituted berberines (BRDR1 to BRDR4) with CT-DNA. The binding affinity of BRDR-DNA complexes increased with increasing the cycloalkane ring size of the substitution except BRDR2. The binding constant value obtained from UV-Visible spectral analysis was 1.12 × 106 for BRDR1, 0.37 × 106 for BRDR2, 1.72 × 106 for BRDR3 and 3.20 × 106 for BRDR4. Ferrocyanide quenching experiments revealed unequivocally that the analogues except BRDR2 had a partly intercalative binding to DNA. From the ITC experiment it was found that the bindings of BRDR1, BRDR3 and BRDR4 to DNA was favoured by negative enthalpy and positive entropy while BRDR2 was driven by positive enthalpy and positive entropy. In all cases the hydrophobic interaction plays a crucial role. Thus, the complete multispectroscopic and thermodynamic binding studies may be useful for new drug design and development.Communicated by Ramaswamy H. Sarma.


Aging-related cell type-specific pathophysiologic immune responses that exacerbate disease severity in aged COVID-19 patients.
Coronavirus disease 2019 (COVID-19) is especially severe in aged patients, defined as 65 years or older, for reasons that are currently unknown. To investigate the underlying basis for this vulnerability, we performed multimodal data analyses on immunity, inflammation, and COVID-19 incidence and severity as a function of age. Our analysis leveraged age-specific COVID-19 mortality and laboratory testing from a large COVID-19 registry, along with epidemiological data of ~3.4 million individuals, large-scale deep immune cell profiling data, and single-cell RNA-sequencing data from aged COVID-19 patients across diverse populations. We found that decreased lymphocyte count and elevated inflammatory markers (C-reactive protein, D-dimer, and neutrophil-lymphocyte ratio) are significantly associated with age-specific COVID-19 severities. We identified the reduced abundance of naïve CD8 T cells with decreased expression of antiviral defense genes (i.e., IFITM3 and TRIM22) in aged severe COVID-19 patients. Older individuals with severe COVID-19 displayed type I and II interferon deficiencies, which is correlated with SARS-CoV-2 viral load. Elevated expression of SARS-CoV-2 entry factors and reduced expression of antiviral defense genes (LY6E and IFNAR1) in the secretory cells are associated with critical COVID-19 in aged individuals. Mechanistically, we identified strong TGF-beta-mediated immune-epithelial cell interactions (i.e., secretory-non-resident macrophages) in aged individuals with critical COVID-19. Taken together, our findings point to immuno-inflammatory factors that could be targeted therapeutically to reduce morbidity and mortality in aged COVID-19 patients.


Coordinating ERK signaling via the molecular scaffold Kinase Suppressor of Ras.
Many cancers, including those of the colon, lung, and pancreas, depend upon the signaling pathways induced by mutated and constitutively active Ras. The molecular scaffolds Kinase Suppressor of Ras 1 and 2 (KSR1 and KSR2) play potent roles in promoting Ras-mediated signaling through the Raf/MEK/ERK kinase cascade. Here we summarize the canonical role of KSR in cells, including its central role as a scaffold protein for the Raf/MEK/ERK kinase cascade, its regulation of various cellular pathways mediated through different binding partners, and the phenotypic consequences of KSR1 or KSR2 genetic inactivation. Mammalian KSR proteins have a demonstrated role in cellular and organismal energy balance with implications for cancer and obesity. Targeting KSR1 in cancer using small molecule inhibitors has potential for therapy with reduced toxicity to the patient. RNAi and small molecule screens using KSR1 as a reference standard have the potential to expose and target vulnerabilities in cancer. Interestingly, although KSR1 and KSR2 are similar in structure, KSR2 has a distinct physiological role in regulating energy balance. Although KSR proteins have been studied for two decades, additional analysis is required to elucidate both the regulation of these molecular scaffolds and their potent effect on the spatial and temporal control of ERK activation in health and disease.


Danish register-based study on the association between specific cardiovascular drugs and fragility fractures.
To determine whether drugs used in treatment of cardiovascular diseases (CVD-drugs), including hypertension, increase the risk of fragility fractures in individuals above the age of 65 years. Retrospective nationwide cohort study. Danish nationwide national registers. All individuals in Denmark ≥ 65 years who used specified CVD-drugs in the study period between 1999 and 2012. Time-dependent exposure to CVD-drugs (nitrates, digoxin, thiazides, furosemide, ACE inhibitors, angiotensin receptor antagonists, β-blockers, calcium antagonists and statins) was determined by prescription claims from pharmacies. The association between use of specific CVD-drugs and fragility fractures was assessed using multivariable Poisson regression models, and adjusted incidence rate ratios (IRRs) were calculated. Overall, 1,586,554 persons were included, of these 16.1% experienced a fall-related fracture. The multivariable Poisson regression analysis showed positive associations between fracture and treatment with furosemide, thiazide and digoxin. IRRs during the first 14 days of treatment were for furosemide IRR 1.74 (95% CI 1.61 to 1.89) and for thiazides IRR 1.41 (1.28 to 1.55); IRR during the first 30 days of treatment with digoxin was 1.18 (1.02 to 1.37). Use of furosemide, thiazides and digoxin was associated with elevated rates of fragility fractures among elderly individuals. This may warrant consideration when considering diuretic treatment of hypertension in elderly individuals.


The Aedes albopictus (Diptera: Culicidae) microbiome varies spatially and with Ascogregarine infection.
The mosquito microbiome alters the physiological traits of medically important mosquitoes, which can scale to impact how mosquito populations sustain disease transmission. The mosquito microbiome varies significantly within individual mosquitoes and among populations, however the ecological and environmental factors that contribute to this variation are poorly understood. To further understand the factors that influence variation and diversity of the mosquito microbiome, we conducted a survey of the bacterial microbiome in the medically important mosquito, Aedes albopictus, on the high Pacific island of Maui, Hawai'i. We detected three bacterial Phyla and twelve bacterial families: Proteobacteria, Acitinobacteria, and Firmicutes; and Anaplasmataceae, Acetobacteraceae, Enterobacteriaceae, Burkholderiaceae, Xanthobacteraceae, Pseudomonadaceae, Streptomycetaceae, Staphylococcaceae, Xanthomonadaceae, Beijerinckiaceae, Rhizobiaceae, and Sphingomonadaceae. The Ae. albopictus bacterial microbiota varied among geographic locations, but temperature and rainfall were uncorrelated with this spatial variation. Infection status with an ampicomplexan pathosymbiont Ascogregarina taiwanensis was significantly associated with the composition of the Ae. albopictus bacteriome. The bacteriomes of mosquitoes with an A. taiwanensis infection were more likely to include several bacterial symbionts, including the most abundant lineage of Wolbachia sp. Other symbionts like Asaia sp. and several Enterobacteriaceae lineages were less prevalent in A. taiwanensis-infected mosquitoes. This highlights the possibility that inter- and intra-domain interactions may structure the Ae. albopictus microbiome.


Clinical and radiographic evaluation of pulpotomies in primary molars with formocresol, glutaraldehyde and ferric sulphate.
This in vivo study aimed to assess and compare the relative clinical and radiographic success of formocresol, glutaraldehyde and ferric sulphate as medicaments following pulpotomies in primary molars at three-monthly intervals over one year. The study was carried out on 90 primary molars in 54 children aged from 3 to 9 years. Selected teeth were equally distributed and randomly assigned to formocresol, glutaraldehyde and ferric sulphate pulpotomy medicament groups (30 in each group). The teeth were then evaluated clinically and radiographically at three-monthly intervals over one year. The resulting data were tabulated and statistically analysed using the chi-square test. After one year, the clinical success rate was 100% with glutaraldehyde, 96.7% with ferric sulphate, and 86.7% with formocresol. The radiological success rate gradually decreased over the year in all pulpotomy medicament groups. Radiological success rates in formocresol, glutaraldehyde, and ferric sulphate groups were 56.7%, 83.3%, and 63.3%, respectively. Two per cent glutaraldehyde may be recommended as a more effective alternative to formocresol and ferric sulphate as a pulpotomy medicament.


Protective effects of Genistein on the cognitive deficits induced by chronic sleep deprivation.
Sleep deprivation has been widely reported to cause cognitive dysfunction, and elevation in oxidative stress and inflammation in the body, including the brain, have been suggested as the main factors. Genistein (GE) is an isoflavone widely present in leguminous plants, and it was found to exert a wide spectrum of biological activities, including antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, and antimetastatic effects. In this study, the protective effect of GE on chronic sleep deprivation (CSD)-induced cognitive dysfunction was investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 25 days. GE was orally administrated (10, 20, and 40 mg/kg) during the sleep deprivation process totally for 25 days. Cognitive behavioral tests were conducted to study the learning and memory using the object location recognition (OLR) task, novel object recognition (NOR) test, and the Morris water maze (MWM) task. Additionally, the cortex and hippocampus were dissected to measure the oxidative stress markers and the antioxidant element nuclear erythroid-2-related factor 2 (Nrf2) and its downstream targets, including glutamate cysteine ligase catalytic, glutamate cysteine ligase modifier, heme oxygenase 1, and quinone oxidoreductase 1, as well as nuclear factor kappa B (NF-κB) p65, nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) protein expression. Moreover, the pro-inflammatory cytokines (TNF-α, interleukin [IL]-6, and IL-1β) level was examined in the serum. The current results showed that GE could dose-dependently ameliorate the cognitive deficits of CSD-treated mice in the OLR, NOR, and MWM tasks. In addition, GE treatment significantly elevated the activities of total antioxidant capacity and superoxide dismutase and the level of glutathione and lowered the content of malondialdehyde in the cortex and hippocampus of CSD-treated mice. Furthermore, GE administration effectively activated the antioxidant element Nrf2 and its downstream targets in the cortex and hippocampus of CSD-treated mice. Moreover, GE treatment significantly suppressed CSD-induced NF-κB p65, iNOS, and COX-2 activation in the cortex and hippocampus, as well as inhibited CSD-induced pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) release in the serum. Taken together, all these results suggested that GE has substantial potential as a therapeutic intervention for the alleviation of CSD-induced deleterious effects.


Suppressive effects of a quinoxaline-analogue (Rob 803) on pathogenic immune mechanisms in collagen-induced arthritis.
The anti-arthritic effects of the synthetic compound 9-chloro-2,3 dimethyl-6-(N,N-dimetylamino-2-oxoethyl)-6H-indolo[2,3-b] quinoxaline (Rob 803) was evaluated by treating Dark Agouti rats with collagen-induced arthritis using three different protocols. Daily subcutaneous treatment with 40 mg/kg/day of Rob 803 from the day of immunization and 14 days forward suppressed arthritis severity significantly and delayed the onset of clinical arthritis. In contrast, similar treatment initiated when individual rats had developed clinical disease (at a score of 2 points) did not suppress disease. Oral treatment with 35 mg/kg/day of Rob 803 from the day of immunization and 21 days forward resulted in a trend towards disease suppression. In vitro analysis of rats treated subcutaneously with Rob 803 revealed an inhibition of T cell proliferation but no effect on the generation of an anti-CII immunoglobulin G response. Further in vitro analysis demonstrated that Rob 803 also inhibited the generation of nitric oxide in macrophages, although at higher concentrations than needed for inhibitory effects on T cell proliferation. Thus we report that early subcutaneous administration of the synthetic substance Rob 803 has anti-rheumatic effects that are probably mediated by affecting the proliferative capacity of lymph node T cells. Rob 803 should be considered as a new candidate substance for anti-rheumatic treatment.


Breast carcinoma with asymptomatic metastasis to the gallbladder.
The biliary tract is an unusual site of metastasis from breast carcinoma, and this has rarely been reported in the literature. We report the case of a 42-year-old woman diagnosed with invasive lobular carcinoma of the breast who underwent laparoscopic cholecystectomy for an incidental finding of gallbladder wall thickening on ultrasonography, which was subsequently confirmed to be consistent with metastasis from the breast primary.


Trait neuroticism and emotion neurocircuitry: Functional magnetic resonance imaging evidence for a failure in emotion regulation.
Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala-ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation.


Clinical evaluation of free T4 techniques.
This paper describes the specificity and sensitivity performances of the new FT4 immunoextraction methods as compared to FT4I and sensitive TSH measurement. Only the Sclavo Lisophase, Clinical Assays 2 step, Spiria FT4, Mallinckrodt Spac ET and Abbott TDX methods offered improved diagnostic accuracy as compared to FT4I. The use of the albumin dependent analogue FT4 methods decreased test specificity and significantly increased laboratory costs relative to FT4I. Preliminary data is presented concerning the performance of a sensitive TSH assay in the clinical conditions where the diagnostic accuracy of FT4I is compromised. Diagnostic sensitivity for detection of "true" hypo and hyperthyroidism appears excellent as does test specificity when an appropriate reference range is selected. As the different tests had equivalent sensitivity for detection of "true" thyroid disease, a model was developed for the calculation of the relative laboratory cost effectiveness of using each test as a first line test of thyroid function. The model was constructed on the basis of reagent and technical costs, the prevalence of the clinical states, test specificity and the projected clinical and laboratory response to an abnormal result. The model suggested that the use of the albumin-dependent analogue methods would increase costs 3 fold compared to FT4I, whereas the use of the specific FT4 methods (Clinical Assays 2 step, Spiria FT4, Mallinckrodt Spac ET and Abbott TDX) would decrease costs 2 fold compared to FT4I. Sensitive TSH methods were projected to have equivalent or lower costs compared to the specific FT4 methods, depending on whether FT4I or specific FT4 was used as the confirmatory test. It thus appeared that sensitive TSH measurement may become the most cost effective first line test of thyroid function.


Context of action of proline dehydrogenase (ProDH) in the Hypersensitive Response of Arabidopsis.
Proline (Pro) dehydrogenase (ProDH) potentiates the oxidative burst and cell death of the plant Hypersensitive Response (HR) by mechanisms not yet elucidated. ProDH converts Pro into ∆1 pyrroline-5-carboxylate (P5C) and can act together with P5C dehydrogenase (P5CDH) to produce Glu, or with P5C reductase (P5CR) to regenerate Pro and thus stimulate the Pro/P5C cycle. To better understand the effects of ProDH in HR, we studied the enzyme at three stages of the defense response differing in their ROS and cell death levels. In addition, we tested if ProDH requires P5CDH to potentiate HR. Control and infected leaves of wild type and p5cdh plants were used to monitor ProDH activity, in vivo Pro catabolism, amino acid content, and gene expression. Wild type plants activated ProDH at all HR stages. They did not consume Pro during maximal ROS accumulation, and maintained almost basal P5C levels at all conditions. p5cdh mutants activated ProDH as wild type plants. They achieved maximum oxidative burst and cell death levels producing normal HR lesions, but evidenced premature defense activation. ProDH activation has different effects on HR. Before the oxidative burst it leads to Pro consumption involving the action of P5CDH. During the oxidative burst, ProDH becomes functionally uncoupled to P5CDH and apparently works with P5CR. The absence of P5CDH does not reduce ROS, cell death, or pathogen resistance, indicating this enzyme is not accompanying ProDH in the potentiation of these defense responses. In contrast, p5cdh infected plants displayed increased ROS burst and earlier initiation of HR cell death. In turn, our results suggest that ProDH may sustain HR by participating in the Pro/P5C cycle, whose action on HR must be formally evaluated in a future.


Geophysicists take a tour around the solar system.
Never one to take its middle name too literally, the American Geophysical Union indulged the interests of a range of extraterrestrial researchers at its spring meeting last month in Montreal. In a session on the big icy bodies of the outer solar system, attendees saw the first view of the face of Pluto. In another session, on dating small rock samples, listeners heard evidence that the moon might have been battered in its youth. And a session ostensibly devoted to Earth's mantle yielded news that some form of plate tectonics seems to be operating on Venus.


Hyperhomocysteinemia in a young woman presenting with acute myocardial infarction: Case report.
Homocysteine (Hcy), a sulfur-containing amino acid that is formed by demethylation of dietary methionine to cystein. Elevated homocysteine level is known to be associated with coronary artery disease. We present a case of acute myocardial infarction in a 25-year-old woman, associated with hyperhomocysteinaemia. Her other risk factors for coronary artery disease were smoking, a moderately high LDL level, and a family history of sudden cardiac death. This case illustrates the need to include plasma homocysteine measurement in the setting of acute coronary syndromes in women with premature atherosclerosis, even in the presence of traditional risk factors for coronary artery disease.


Childhood epidermolysis bullosa acquisita. Detection in a 5-year-old girl.
A 5 1/2-year-old girl with a blistering disease involving the skin and the oral, ocular, and anogenital mucosa is described. The initial clinical, histologic, and immunofluorescence findings suggested a diagnosis of cicatricial pemphigoid. However, immunoelectron microscopy demonstrated linear deposits of several immunoreactants within the sub-lamina densa region of the dermoepidermal junction, consistent with the diagnosis of epidermolysis bullosa acquisita. Although epidermolysis bullosa acquisita is considered a disease of adult onset, it should be included in the differential diagnosis of blistering diseases in children.


Vitamin A deficiency and associated factors in preschoolers from the outskirts of La Plata, Buenos Aires.
Vitamin A deficiency (VAD) has been recognized as an important public health problem in developing countries. Preschoolers account for risk groups within vulnerable populations. The objective of this study was to determine the prevalence of VAD and associated factors in a sample of preschoolers. Cross-sectional study with children aged 1-6 years receiving social assistance and seen at primary health care centers in the outskirts of the city of La Plata, Buenos Aires. Vitamin A levels were determined by measuring serum retinol with a liquid chromatography; anthropometric parameters and dietary intake were recorded. A multinomial logistic regression model was used to assess the association among outcome measures. Data from 624 children were analyzed. The geometric mean of retinol was 23.8 pg/dL (95 % CI: 23.3-24.3). The prevalence of VAD and the risk for VAD were 24.3 % and 57.4 %, respectively. Retinol levels were significantly lower among boys, low-weight children, and those with low intake (below the first tertile of distribution). The multivariate analysis showed a significant association between VAD and male sex (odds ratio: 1.93; 95 % CI: 1.15-3.24) and between VAD and low intake (odds ratio: 1.48; 95 % CI: 1.15-2.62). The prevalence of VAD (24.3 %) is a major public health problem in this population. VAD-associated factors were male sex and low vitamin A intake.


The spectrum of mutations causing HPRT deficiency: an update.
Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease, which is characterized by hyperuricemia, severe motor disability, and self-injurious behavior. Mutations in the same gene also cause less severe clinical phenotypes with only some portions of the full syndrome. A large database of 271 mutations associated with both full and partial clinical phenotypes was recently compiled. Since the original database was assembled, 31 additional mutations have been identified, bringing the new total to 302. The results demonstrate a very heterogeneous collection of mutations for both LND and its partial syndromes. The differences between LND and the partial phenotypes cannot be explained by differences in the locations of mutations, but the partial phenotypes are more likely to have mutations predicted to allow some residual enzyme function. The reasons for some apparent exceptions to this proposal are addressed.


Analysis of human cerebrospinal fluid monoamines and their cofactors by HPLC.
The presence of monoamines and their cofactors (the pterins and vitamin B6 (pyridoxal phosphate (PLP))) in human cerebrospinal fluid (CSF) can be used as indicators of the biosynthesis and turnover of dopamine and serotonin in the brain. In addition, abnormalities in the CSF levels of these molecules are associated with various neurological diseases, including genetic diseases leading to dopamine and serotonin deficiency. Here, we provide a set of quantitative high-performance liquid-chromatography (HPLC) approaches to determine CSF levels of monoamines and their cofactors. This protocol describes step-by-step procedures for CSF sample preparation for the analysis of different molecules, HPLC calibration and analysis, and data quantification and interpretation. Unlike plasma/tissue/blood samples, CSF requires minimal sample preparation: in this protocol, only the analysis of PLP requires mixing with trichloroacetic acid to release the protein-bound vitamin, centrifugation, and mixing of the supernatant with phosphate buffer and sodium cyanide for derivatization in alkaline conditions. Monoamines are analyzed by HPLC with coulometric electrochemical detection (ED), pterins are analyzed by HPLC with coupled coulometric electrochemical and fluorescence detection, and PLP is analyzed by HPLC with fluorescence detection. The quantification of all compounds is achieved by external calibration procedures, and internal quality control and standards are analyzed in each run. We anticipate that investigation of dopamine and serotonin disturbances will be facilitated by measurements of these compounds in human CSF and other biological samples. The estimated time for the different procedures primarily depends on the electrochemical detector stabilization. Overnight stabilization of this detector is advised, and, after that step, preanalytical equilibration rarely exceeds 3 h.


Proceedings: Cephazolin in obstetrics.
The pharmacodynamics of a new cephalosporin--cephazolin--have been evaluated in clinical obstetrics with particular reference to antibiotic prophylaxis for the cardiac patient, and the prophylaxis and treatment of choriamnionitis and intrauterine pneumonia. Cephazolin effectively crosses the placental barrier. It slowly concentrates in the amniotic fluid when the fetus is alive. This new drug may be used for phophylactic cover in the above clinical situations.


An Improved Adeno-Associated Virus Vector for Neurological Correction of the Mouse Model of Mucopolysaccharidosis IIIA.
Patients with the lysosomal storage disease mucopolysaccharidosis IIIA (MPSIIIA) lack the lysosomal enzyme N-sulfoglucosamine sulfohydrolase (SGSH), one of the many enzymes involved in degradation of heparan sulfate. Build-up of un-degraded heparan sulfate results in severe progressive neurodegeneration for which there is currently no treatment. Experimental gene therapies based on gene addition are currently being explored. Following preclinical evaluation in MPSIIIA mice, an adeno-associated virus vector of serotype rh10 designed to deliver SGSH and sulfatase modifying factor 1 (SAF301) was trialed in four MPSIIIA patients, showing good tolerance and absence of adverse events with some improvements in neurocognitive measures. This study aimed to improve SAF301 further by removing sulfatase modifying factor 1 (SUMF1) and assessing if expression of this gene is needed to increase the SGSH enzyme activity (SAF301b). Second, the murine phosphoglycerate kinase (PGK) promotor was exchanged with a chicken beta actin/CMV composite (CAG) promotor (SAF302) to see if SGSH expression levels could be boosted further. The three different vectors were administered to MPSIIIA mice via intracranial injection, and SGSH expression levels were compared 4 weeks post treatment. Removal of SUMF1 resulted in marginal reductions in enzyme activity. However, promotor exchange significantly increased the amount of SGSH expressed in the brain, leading to superior therapeutic correction with SAF302. Biodistribution of SAF302 was further assessed using green fluorescent protein (GFP), indicating that vector spread was limited to the area around the injection tract. Further modification of the injection strategy to a single depth with higher injection volume increased vector distribution, leading to more widespread GFP distribution and sustained expression, suggesting this approach should be adopted in future trials.


Kinetics of Na-ATPase activity by the Na,K pump. Interactions of the phosphorylated intermediates with Na+, Tris+, and K+.
To determine the biochemical events of Na+ transport, we studied the interactions of Na+, Tris+, and K+ with the phosphorylated intermediates of Na,K-ATPase from ox brain. The enzyme was phosphorylated by incubation at 0 degrees C with 1 mM Mg2+, 25 microM [32P]ATP, and 20-600 mM Na+ with or without Tris+, and the dephosphorylation kinetics of [32P]EP were studied after addition of (1) 1 mM ATP, (2) 2.5 mM ADP, (3) 1 mM ATP plus 20 mM K+, and (4) 2.5 mM ADP plus Na+ up to 600 mM. In dephosphorylation types 2-4, the curves were bi- or multiphasic. "ADP-sensitive EP" and "K+-sensitive EP" were determined by extrapolation of the slow phase of the curves to the ordinate and their sum was always larger than Etotal. These results required a minimal model consisting of three consecutive EP pools, A, B, and C, where A was ADP sensitive and both B and C were K+ sensitive. At high [Na+], B was converted rapidly to A (type 4 experiment). The seven rate coefficients were dependent on [Na+], [Tris+], and [K+], and to explain this we developed a comprehensive model for cation interaction with EP. The model has the following features: A, B, and C are equilibrium mixtures of EP forms; EP in A has two to three Na ions bound at high-affinity (internal) sites, pool B has three, and pool C has two to three low-affinity (external) sites. The putative high-affinity outside Na+ site may be on E2P in pool C. The A leads to B conversion is blocked by K+ (and Tris+). We conclude that pool A can be an intermediate only in the Na-ATPase reaction and not in the normal operation of the Na,K pump.


Reliability of reference distances used in photogrammetry.
To determine the reliability of the reference distances used for photogrammetric assessment. The sample consisted of 100 subjects with mean ages of 22.97 +/- 2.98 years. Five lateral and four frontal parameters were measured directly on the subjects' faces. For photogrammetric assessment, two reference distances for the profile view and three reference distances for the frontal view were established. Standardized photographs were taken and all the parameters that had been measured directly on the face were measured on the photographs. The reliability of the reference distances was checked by comparing direct and indirect values of the parameters obtained from the subjects' faces and photographs. Repeated measure analysis of variance (ANOVA) and Bland-Altman analyses were used for statistical assessment. For profile measurements, the indirect values measured were statistically different from the direct values except for Sn-Sto in male subjects and Prn-Sn and Sn-Sto in female subjects. The indirect values of Prn-Sn and Sn-Sto were reliable in both sexes. The poorest results were obtained in the indirect values of the N-Sn parameter for female subjects and the Sn-Me parameter for male subjects according to the Sa-Sba reference distance. For frontal measurements, the indirect values were statistically different from the direct values in both sexes except for one in male subjects. The indirect values measured were not statistically different from the direct values for Go-Go. The indirect values of Ch-Ch were reliable in male subjects. The poorest results were obtained according to the P-P reference distance. For profile assessment, the T-Ex reference distance was reliable for Prn-Sn and Sn-Sto in both sexes. For frontal assessment, Ex-Ex and En-En reference distances were reliable for Ch-Ch in male subjects.


[Assessment of global and regional left ventricular function with a 16-slice spiral-CT using two different software tools for quantitative functional analysis and qualitative evaluation of wall motion changes in comparison with magnetic resonance imaging].
To determine global and regional left ventricular (LV) function from retrospectively gated multidetector row computed tomography (CT) by using two different semiautomated analysis tools and to correlate the results with those of magnetic resonance imaging (MRI). Nineteen patients (5 females, 14 males, mean age 69 years) underwent 16-slice spiral-CT (MS-CT) with standard technique without administration of beta-blockers for a decrease in the cardiac rate. Ten series of images were reconstructed at every 10 % of the RR-interval. With commercially available software capable of semiautomated contour detection, end-diastolic and end-systolic LV volumes (EDV and ESV) were determined from short-axis multiplanar CT reformations (MPR). Axial images of the end-systolic and end-diastolic cardiac phase were transformed to 3D volumes (3D) to determine EDV and ESV by using a threshold-supported reconstruction algorithm dependent on the contrast enhancement of the left ventricle. Steady-state free-precession cine MR images were acquired in short-axis orientation on the same day in all but one patient. Regional wall motion was assessed qualitatively in 17 left ventricular segments and classified as normo-, hypo-, a- or dyskinetic. Bland-Altman analysis was performed to calculate limits of agreement and systematic errors between CT and MRI. For MPR/3D, mean end-diastolic (144.4/142.8 mL +/- 67.5/67.1) and end-systolic (66.4/68.7 mL +/- 52.1/49.9) LV volumes as determined with MS-CT correlated well with MRI measurements (147.6 mL +/- 67.6 [ r = 0.98/0.96] and 73.3 mL +/- 55.5 [ r = 0.98/0.98], respectively [ p <.001]). LV stroke volume (77.6/74.1 +/- 19.2/23.4 mL for CT vs. 74.4 mL +/- 18.4 for MRI, r = 0.92/0.74) and LV ejection fraction (58.6/55.9 % +/- 13.5/13.7 for CT vs. 55.6 % +/- 13.5 for MRI, r = 0.95/0.91) also showed good correlation (p <.001). Regional wall motion analysis revealed agreement between CT and MRI in 316/323 (97.8 %) myocardial segments. Semiautomated analysis of 16-detector row CT data sets enables global and regional volumetric and functional analysis. The CT results correlate well with MRI findings for short axis MPR and for 3D volume reconstructions, with a higher statistical spread for the 3D method. The underestimation of end-systolic and end-diastolic volumes with CT may be caused by partial volume averaging due to the lower temporal resolution as compared with MRI.


Morphology, Histology, and Transcriptome Analysis of Gonadal Development in Octopus minor (Sasaki, 1920).
Octopus minor is an economically important species, but little is known about the histological pattern and regulatory mechanisms during gonadal development. In this study, we investigated the annual changes in total body weight (TW), gonad somatic index (GSI), gonadal histological features, and transcriptome of O. minor. The results indicated that both females and males showed a similar TW trend. The GSI peaked in June in females, while it remained constant at around 3% in males. Nine and four histological stages were observed in ovaries and testes, respectively. Our field sampling results implied that O. minor might have overwintering periods for both eggs and larvae. Transcriptome analysis revealed that a total of 1095 and 2468 genes were significantly expressed during ovarian and testicular development, separately. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis displayed that 126 GO terms and 5 KEGG pathways were significantly enriched in the ovarian group of advanced vitellogenic oocytes vs vitellogenic oocytes (AVO vs VO). The pathways "Ribosomal", "Cell cycle", and "Progesterone-mediated oocyte maturation" were predicted to promote yolk deposition. Additionally, the testicular comparison group of spent vs mature (Spent vs Mature) showed significant enrichment in 674 GO terms and 13 KEGG pathways, suggesting that energy metabolism and cell repair pathways may be involved in the spermatogenesis process. This work revealed the development process of the gonads and shed light on the potential regulatory pathways of O. minor, providing novel insights and laying a molecular basis for artificial breeding.


Is research keeping up with changes in landscape policy? A review of the literature.
Several innovative directions for landscape policy development and implementation have emerged over recent years. These include: (i) an expansion of scope to include all landscape aspects and landscape types, (ii) an increased emphasis on public participation, (iii) a focus on designing measures appropriate for different contexts and scales, and (iv) encouraging support for capacity-building. In this paper, we evaluate the extent to which these policy directions are reflected in the practice of academic landscape research. We evaluate all research papers published in three leading landscape journals over six years, as well as published research papers relating directly to the European Landscape Convention. The latter, which was adopted in 2000, establishes a framework for landscape protection, planning and management in Europe and is to date the only international legal instrument of its kind. Results indicate that whilst policy innovations do not appear to be a major stimulus for academic research, studies nevertheless address a range of landscape aspects, types and scales (albeit with a slight bias towards bio-physical landscape aspects). However, geographical representativeness of research is weak and dominated by the United States and northern/western Europe, and research capacity likewise appears to be unevenly distributed. Landscape research is also limited in the extent to which it involves stakeholders or develops innovative methods for doing so, notwithstanding that this remains a key challenge for policy-makers. Results point to the potential for landscape research to address areas (topical and geographical) which have received little attention to date, as well as suggesting mutual benefits of stronger links between policy and academia.


Transgenic manipulation of the metabolism of polyamines in poplar cells.
The metabolism of polyamines (putrescine, spermidine, and spermine) has become the target of genetic manipulation because of their significance in plant development and possibly stress tolerance. We studied the polyamine metabolism in non-transgenic (NT) and transgenic cells of poplar (Populus nigra x maximowiczii) expressing a mouse Orn decarboxylase (odc) cDNA. The transgenic cells showed elevated levels of mouse ODC enzyme activity, severalfold higher amounts of putrescine, a small increase in spermidine, and a small reduction in spermine as compared with NT cells. The conversion of labeled ornithine (Orn) into putrescine was significantly higher in the transgenic than the NT cells. Whereas exogenously supplied Orn caused an increase in cellular putrescine in both cell lines, arginine at high concentrations was inhibitory to putrescine accumulation. The addition of urea and glutamine had no effect on polyamines in either of the cell lines. Inhibition of glutamine synthetase by methionine sulfoximine led to a substantial reduction in putrescine and spermidine in both cell lines. The results show that: (a) Transgenic expression of a heterologous odc gene can be used to modulate putrescine metabolism in plant cells, (b) accumulation of putrescine in high amounts does not affect the native arginine decarboxylase activity, (c) Orn biosynthesis occurs primarily from glutamine/glutamate and not from catabolic breakdown of arginine, (d) Orn biosynthesis may become a limiting factor for putrescine production in the odc transgenic cells, and (e) assimilation of nitrogen into glutamine keeps pace with an increased demand for its use for putrescine production.


Spectrum of enteropathogens detected by the FilmArray GI Panel in a multicentre study of community-acquired gastroenteritis.
The European, multicentre, quarterly point-prevalence study of community-acquired diarrhoea (EUCODI) analysed stool samples received at ten participating clinical microbiology laboratories (Austria, Finland, France, Germany, Greece, Ireland, Italy, Portugal, Romania, and the UK) in 2014. On four specified days, each local laboratory submitted samples from ≤20 consecutive patients to the Austrian Study Centre for further testing with the FilmArray GI Panel (BioFire Diagnostics, Salt Lake City, UT, USA). Of the 709 samples from as many patients received, 325 (45.8%) tested negative, 268 (37.8%) yielded only one organism, and 116 (16.4%) yielded multiple organisms. Positivity rates ranged from 41% (30 of 73 samples) in France to 74% (59 of 80 samples) in Romania. With the exception of Entamoeba histolytica and Vibrio cholerae, all of the 22 targeted pathogens were detected at least once. Enteropathogenic Escherichia coli, Campylobacter species, toxigenic Clostridium difficile, enteroaggregative E. coli, norovirus and enterotoxigenic E. coli were the six most commonly detected pathogens. When tested according to local protocols, seven of 128 positive samples (5.5%) yielded multiple organisms. Overall, the FilmArray GI Panel detected at least one organism in 54.2% (384/709) of the samples, as compared with 18.1% (128/709) when testing was performed with conventional techniques locally. This underlines the considerable potential of multiplex PCR to improve routine stool diagnostics in community-acquired diarrhoea. Classic culture methods directed at the isolation of specific pathogens are increasingly becoming second-line tools, being deployed when rapid molecular tests give positive results. This optimizes the yield from stool examinations and dramatically improves the timeliness of diagnosis.


Antigenic mapping of the surface proteins of infectious hepatitis B virus particles.
To identify further the surface proteins of the native virus, hepatitis B virus (HBV) particles purified from HBe antigen (Ag)-positive human sera were used as immunogens to produce murine monoclonal antibody (MAb)-secreting hybridomas. The specific binding of antibodies to the HBV envelope (env) proteins was determined in indirect radioimmunoassay and by Western blot analysis. Six MAbs directed against major hepatitis B surface antigen (HBsAg) recognized conformational epitopes on S proteins (P24s/GP27s). Three preS2-specific MAbs reacted with the middle env proteins (GP33s/GP36s) in the 22 nm HBsAg spherical particles. One MAb, F222, was found to react specifically with the two very large (VL) HBV surface proteins with Mr 54K and 66K. The epitope recognized by F222 was located on the protruding N terminus which, in the assembled virus particles, was readily split off by trypsin or V8 protease treatment. The presence of these VL proteins appeared to correspond to the presence of the large env proteins (P39s/GP42s). The data described here indicate that F222 probably recognized an assembled topographic site which could be involved in virus entry into hepatocytes. Moreover, our results suggest that the preS-coded part of the HBV env proteins, which is sensitive to proteases in vitro, could be unstable in vivo and stabilized by immunoglobulins.


Cardiogenic shock following nasal septoplasty: a case report and review of the literature.
Nasal septoplasty is a surgical procedure offered to patients with chronic snoring secondary to nasal obstruction. We describe a case of cardiogenic shock following the administration of metoprolol to treat hypertension, (likely) induced by systemic absorption of topical epinephrine used during a routine nasal septoplasty. A 29-yr-old male, with no significant medical history, was scheduled for nasal septoplasty for mild nasal obstruction. Following routine anesthetic induction, cotton balls, soaked with epinephrine (1:1000), were applied to the nasal mucosa. The patient became hypertensive with a blood pressure of 207/123 mmHg. Intravenous metoprolol was administered. Severe pulmonary edema ensued, with resulting hypoxic respiratory failure and cardiogenic shock. The patient was transferred to a tertiary care facility for percutaneous cardiopulmonary bypass. After five days of cardiopulmonary bypass support and six weeks of intensive care monitoring, the patient's cardiac status returned to normal limits. A hypertensive response, following systemically absorbed topical vasoconstrictors, including both phenylephrine and epinephrine, can be associated with dire consequences when treated with a beta-adrenergic blocking drug and, possibly, calcium channel blockers. To prevent severe complications including; pulmonary edema, cardiogenic shock, cardiac arrest, and, possibly, death, these drug interactions need to be appreciated.


[Synthesis of leucine- and methionine-enkephalin using papain].
Thiol protease papain has been used for synthesis of leucine-and methionineenkephalin from methyl esters of N-protected amino acids. The synthesis was carried out in basic medium, minimizing the hazard of the secondary peptide hydrolysis. The reaction products remain in solution during the whole process. The yields at the final stage of the synthesis were 89% (leucineenkephalin) and 79% (methionineenkephalin).


Study of the impact of laws regulating tobacco consumption on the prevalence of passive smoking in Spain.
In 2005, the Spanish parliament passed the Spanish anti-smoking law. This legislation restricted tobacco smoking in public places, including recreation venues (bars and restaurants), but smoking was not completely prohibited in bars and restaurants. The law was enforced in January 2006. With the objective of analysing the impact that this law has had on the general Spanish population, the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) designed and implemented a survey of a representative sample of the general Spanish population on two separate occasions: in 2005 and in 2007 (12 months after the ban came into effect). Two epidemiological, observational and cross-sectional surveys were performed among a random and representative sample of the general Spanish population, using the Computer-Assisted Telephone Interview system. In the first survey, a total of 6533 subjects were interviewed, of whom 3907 (59.8%) were non-smokers and in the second, a total of 3289 subjects were interviewed, of whom 2174 (65.9%) were non-smokers. The overall prevalence of exposure to environmental tobacco smoke (ETS) decreased from 49.5% in 2005 to 37.9% in 2007 (22% reduction). The greatest reduction in prevalence of ETS exposure was in workplaces (from 25.8% to 11%, a decrease of 58.8%). Smaller reductions occurred in the home (from 29.5% to 21.4%, a decrease of 27%) and in recreation venues (from 37.4% to 31.8%, a decrease of 8%). Implementation of the smoking ban resulted in a significant decrease in exposure to ETS.


Malaria in Southern Venezuela: The hottest hotspot in Latin America.
Malaria elimination in Latin America is becoming an elusive goal. Malaria cases reached a historical ~1 million in 2017 and 2018, with Venezuela contributing 53% and 51% of those cases, respectively. Historically, malaria incidence in southern Venezuela has accounted for most of the country's total number of cases. The efficient deployment of disease prevention measures and prediction of disease spread to new regions requires an in-depth understanding of spatial heterogeneity on malaria transmission dynamics. Herein, we characterized the spatial epidemiology of malaria in southern Venezuela from 2007 through 2017 and described the extent to which malaria distribution has changed country-wide over the recent years. We found that disease transmission was focal and more prevalent in the southeast region of southern Venezuela where two persistent hotspots of Plasmodium vivax (76%) and P. falciparum (18%) accounted for ~60% of the total number of cases. Such hotspots are linked to deforestation as a consequence of illegal gold mining activities. Incidence has increased nearly tenfold over the last decade, showing an explosive epidemic growth due to a significant lack of disease control programs. Our findings highlight the importance of spatially oriented interventions to contain the ongoing malaria epidemic in Venezuela. This work also provides baseline epidemiological data to assess cross-border malaria dynamics and advocates for innovative control efforts in the Latin American region.


Psychosocial and Cultural Determinants of Interest and Uptake of Skin Cancer Genetic Testing in Diverse Primary Care.
Translational research in genomics has limited reach and requires efforts to broaden access and utility in diverse populations. Skin cancer is common and rates are rising, including among Hispanics. Germline variants in the melanocortin-1 receptor (MC1R) gene are common in the population and confer moderate risk for melanoma and basal cell cancers across skin types. Feedback about MC1R risk status may promote skin cancer risk awareness and risk reduction. We examined the level of interest in pursuing MC1R testing, and patterns of interest across skin cancer perceived threat and control attitudes, cultural beliefs (family influence on health, health system distrust, cancer fatalism, skin cancer misconceptions), and health literacy. We used a study website to inform primary care patients in Albuquerque, NM about the benefits and drawbacks of MC1R testing. Website logon, request of a saliva test kit, and return of the test kit (yes vs. no) were primary assessments of study interest and uptake. Of 499 participants provided with a test offer, 33% requested and returned the test. Lower family influence on participants' health was an important factor both overall and within ethnicity subgroups, and may indicate that primary care patients interested in skin cancer genetic testing see themselves as proactive health seekers, independent from family encouragement. Lower self-efficacy for skin cancer prevention was also an important characteristic of those who tested. As evidence for common genetic markers for skin cancer accumulates, these findings suggest characteristics of those most likely to pursue genetic testing for skin cancer risk.


Shear wave elastography evaluation of liver, pancreas, spleen and kidneys in patients with familial mediterranean fever and amyloidosis.
Amyloid deposits in a visceral organ can contribute to tissue stiffness that could be measured with shear wave elastography (SWE). We aimed to investigate changes in organ stiffness in conjunction with laboratory parameters in patients with Familial Mediterranean Fever (FMF) and amyloidosis. This prospective study included 27 FMF patients, 11 patients with amyloidosis, and 38 healthy controls. Median shear wave elasticity values of the liver, spleen, both kidneys, and pancreas on SWE were compared among study and control groups. The mean values of CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) were compared by the t-test and the median of SAA (serum amyloid A protein) was compared with the Mann-Whitney U test between FMF groups with and without amyloidosis. Spearman's correlation analysis was performed to reveal the association between stiffness values and laboratory parameters. The median liver, spleen, kidney, and pancreas elasticity values were significantly higher in the FMF group with amyloidosis compared to control subjects. The median kidney stiffness values in the FMF group with or without amyloidosis were significantly higher compared to control subjects. Median liver stiffness values in FMF patients with amyloidosis were significantly higher than FMF patients without amyloidosis. There were statistically significant positive correlations between the CRP (p = 0.001, r = 0.56), ESR (p = 0.001, r = 0.61), and SAA (p = 0.002, r = 0.53) levels with spleen stiffness, and CRP (p = 0.006, r = 0.48) and ESR (p = 0.001,r = 0.61) levels with pancreas stiffness, and ESR (p = 0.004, r = 0.51) levels with the left kidney stiffness. SWE could be a potential tool for noninvasive follow-up of FMF patients and also amyloid deposition. Both acute inflammation and amyloidosis in the FMF patients could increase organ stiffness.


The isolation and partial characterization of a highly pathogenic herpesvirus from the harbor seal (Phoca vitulina).
This report describes the first isolation and partial characterization of a herpesvirus from the harbor seal (Phoca vitulina). The virus was isolated during a disease outbreak in a group of young seals nursed in a seal orphanage in The Netherlands. Almost half of the seals died with symptoms of acute pneumonia and focal hepatitis and the virus was isolated of organs of most of the dead animals. Seven out of ten seals of which paired serum samples were obtained showed seroconversion in a virus neutralization test during this outbreak. The virus was tentatively characterized as a herpesvirus (seal herpesvirus: SeHV or phocid herpesvirus 1) on the basis of its characteristic morphology in electron microscopy, buoyant density in sucrose, sensitivity to ether and heat treatment and its antigenic relationship with other probable members of the Alphaherpesvirinae subfamily. The virus caused cytopathic changes within 24 hours after inoculation in seal kidney cells, consisting of a focal rounding of cells and syncytium formation. No cytopathic changes were observed in the cells of nine other mammalian species tested.


Pathogenesis and prevention of risk of cardiovascular events in patients with pneumococcal community-acquired pneumonia.
It is now well recognized that cardiovascular events (CVE) occur quite commonly, both in the acute phase and in the long-term, in patients with community-acquired pneumonia (CAP). CVE have been noted in up to 30% of patients hospitalized with all-cause CAP. One systematic review and meta-analysis of hospitalized patients with all-cause CAP noted that the incidence rates for overall cardiac events were 17.7%, for incident heart failure were 14.1%, for acute coronary syndromes were 5.3% and for incident cardiac arrhythmias were 4.7%. In the case of pneumococcal CAP, almost 20% of patients studied had one or more of these cardiac events. Recent research has provided insights into the pathogenesis of the acute cardiac events occurring in pneumococcal infections. With respect to the former, key involvements of the major pneumococcal protein virulence factor, pneumolysin, are now well documented, whilst systemic platelet-driven neutrophil activation may also contribute. However, events involved in the pathogenesis of the long-term cardiovascular sequelae remain largely unexplored. Emerging evidence suggests that persistent antigenaemia may predispose to the development of a systemic pro-inflammatory/prothrombotic phenotype underpinning the risk of future cardiovascular events. The current manuscript briefly reviews the occurrence of cardiovascular events in patients with all-cause CAP, as well as in pneumococcal and influenza infections. It highlights the close interaction between influenza and pneumococcal pneumonia. It also includes a brief discussion of mechanisms of the acute cardiac events in CAP. However, the primary focus is on the prevalence, pathogenesis and prevention of the longer-term cardiac sequelae of severe pneumococcal disease, particularly in the context of persistent antigenaemia and associated inflammation.


Manganese enhanced magnetic resonance imaging.
Manganese is an essential metal that participates as a co-factor in a number of critical biological functions such as electron transport, detoxification of free radicals, and synthesis of neurotransmitters. Like other heavy metals, high concentrations of manganese are toxic. For example, chronic overexposure to manganese leads to movement disorders. In order to maintain this balance between being an essential participant in enzyme function and being a toxic heavy metal, a rich biology has evolved to transport and store manganese. Paramagnetic forms of manganese ions are potent MRI relaxation agents. Indeed, Mn(2+) was the first contrast agent proposed for use in MRI. Recently, there is renewed interest in combining the strong MRI relaxation effects of Mn(2+) with its unique biology in order to expand the range of information that can be measured by MRI. Manganese Enhanced MRI is being developed to give unique tissue contrast, assess tissue viability, act as a surrogate marker of calcium influx into cells and trace neuronal connections. In this article we review recent work and point out prospects for the future uses of manganese enhanced MRI.


Increased carotid intima-media thickness in remote and urban Indigenous Australians: impact of diabetes and components of the metabolic syndrome.
Indigenous Australians have rates of cardiovascular (CVD) mortality some seven to 10-fold higher than non-Indigenous Australians aged 25-64 years. We aimed to evaluate the impact of type 2 diabetes and components of the metabolic syndrome on carotid intima-media thickness (CIMT) as a marker of cardiovascular risk in Indigenous Australians living in remote and urban environments and in Australians of European ancestry. CIMT was measured by high-resolution B-mode ultrasound imaging of the common carotid artery in 119 remote Indigenous, 144 urban Indigenous and 122 urban European Australians with and without diabetes. In nondiabetic participants, CIMT was lowest in Europeans (mean (SD) 0.64 mm (0.10)), higher in urban Indigenous Australians (0.67 mm (0.12)) and highest in remote Indigenous Australians (0.73 mm (0.15), P < 0.001). CIMT was higher with diabetes with the same pattern observed between populations: 0.73 mm, 0.79 mm and 0.82 mm, respectively (P < 0.001). Traditional risk factors (age, male gender, blood pressure and HbA1c) explained 35-45% of the variance of CIMT within each population group. However, differences in CIMT between population groups were maintained after adjustment for these cardiovascular risks plus cholesterol and smoking (P < 0.001). Factor analysis revealed that variables of the metabolic syndrome, together with smoking and elevated C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR), are likely to explain the higher CIMT in Indigenous Australians (and the urban-remote gradient). Unmeasured variables (genetic, psychosocial and socioeconomic) may also contribute to higher CIMT in these populations. Glycaemic control and metabolic syndrome components contribute significantly to premature atherogenesis in Indigenous Australians and we recommend that therapy should be targeted accordingly.


Analysis of the sequence diversity of the P1, HC, P3, NIb and CP genomic regions of several yam mosaic potyvirus isolates: implications for the intraspecies molecular diversity of potyviruses.
Partial sequences from serologically characterized yam mosaic potyvirus (YMV) isolates were determined in conserved (helper-component proteinase, HC; nuclear inclusion b, NIb) and variable (first protein, P1; third protein, P3; and coat protein, CP) regions of the potyviral genome in order to investigate the intraspecies molecular diversity of YMV. Multiple sequence alignments and pairwise comparisons were used to quantify the sequence polymorphism in these regions. Two levels of diversity were observed among YMV isolates: above 90% nucleotide (nt) sequence identities were found between YMV isolates of the same group (intragroup) regardless of the region considered, whereas identities between isolates from different groups (intergroup) were lower and depended upon the protein chosen. For instance, the average intergroup nt sequence identity between YMV isolates was about 65% in the P1 protein and the N terminus of the CP while there was more than 80% nt identity in the HC, P3 and NIb proteins. Thus P3 appeared to be conserved between YMV isolates even though this region was variable between potyvirus species. Similar analysis of the intraspecies molecular diversity of other potyviruses (potato virus Y, zucchini yellow mosaic virus, plum pox virus, pea seed-borne mosaic virus) led to the same results: (i) two levels of intraspecies molecular diversity were found (intragroup and intergroup); (ii) intraspecies molecular diversity differed from interspecies molecular diversity in the P3, P1 and N-terminal regions.


A Touchscreen Motivation Assessment Evaluated in Huntington's Disease Patients and R6/1 Model Mice.
Apathy is pervasive across many neuropsychiatric disorders but is poorly characterized mechanistically, so targeted therapeutic interventions remain elusive. A key impediment has been the lack of validated assessment tools to facilitate translation of promising findings between preclinical disease models and patients. Apathy is a common symptom in Huntington's disease. Due to its established genetic basis and the availability of defined animal models, this disease offers a robust translational framework for linking motivated behavior with underlying neurobiology and an ideal context in which to evaluate a quantitative, translational apathy assessment method. In this study we therefore aimed to demonstrate the validity of using touchscreen-delivered progressive ratio tasks to mirror apathy assessment in Huntington's disease patients and a representative mouse model. To do this we evaluated Huntington's disease patients (n = 23) and age-matched healthy controls (n = 20), and male R6/1 mice (n = 23) and wildtype controls (n = 29) for apathy-like behavior using touchscreen-delivered progressive ratio tasks. The primary outcome measure of the assessment was breakpoint, defined as the highest number of touchscreen responses emitted before task engagement ceased. Patients and R6/1 mice were both found to exhibit significantly reduced breakpoints relative to their respective control groups, consistent with apathy-like behavior. This performance was also not associated with motoric differences in either species. These data demonstrate the utility of touchscreen-delivered progressive ratio tasks in detecting clinically relevant motivational deficits in Huntington's disease. This approach may offer a platform from which clinically relevant mechanistic insights concerning motivation symptoms can be derived and provide an effective route for translation of promising preclinical findings into viable therapeutic interventions.


The Association between Tinea Pedis and Feet-Washing Behavior in Patients with Diabetes: A Cross-sectional Study.
To examine the correlations between elements of feet-washing behavior, presence of tinea pedis (TP), and patients' background characteristics in order to identify a concrete intervention method to prevent TP. A cross-sectional study of 30 patients with diabetes (16 with TP) who were admitted to or visited the university hospital. The presence of TP was confirmed by the detection of dermatophytes by direct microscopy. Data on elements of feet-washing behavior, such as scrubbing between the toes, were collected by observing recorded videos of participants normally washing their feet as they do at home. The patients' background characteristics included demographic data; diabetes-related factors; patient knowledge regarding diabetes, foot problems, and TP prevention; purpose for feet washing; and any difficulties in feet washing. The number of times patients scrubbed between their toes while washing with soap was significantly lower in patients with TP (odds ratio, 0.95; P = .036; with a cutoff value of 35 times) and those who had difficulty in reaching their feet with their hands (B = -14.42, P = .041). An effective foot-washing protocol should include specific instructions for patients to scrub between their toes at least 35 times in all 8 spaces while washing with soap. Appropriate advice is also needed for individuals who have difficulty reaching their feet with their hands. Education about appropriate foot-washing behavior may potentially prevent TP.


Characterization of the African swine fever virion protein j18L.
The African swine fever virus (ASFV) open reading frame (ORF) that is named jl8L in the Malawi (LIL20/1) isolate and E199L in the Ba71V isolate encodes a cysteine rich protein of 195 amino acids with a predicted molecular mass of 21.7 kDa and a hydrophobic domain near the C terminus. There are several possible motifs for glycosylation, phosphorylation and myristoylation. Rabbit antisera and monoclonal antibodies raised against a recombinant ASFV j18L protein expressed as a fusion protein with glutathione S-transferase (GST) identified proteins of 19.0-20 kDa in cells infected with different ASFV strains and with a recombinant vaccinia virus expressing j18L. The monoclonal antibodies detected a protein of 20.0 kDa whereas rabbit antisera detected two proteins with relative molecular masses of 15.0 and 20.0 kDa in purified extracellular ASF virions. In ASFV-infected cells, the j18L protein was expressed late post-infection and was localized mainly in the viral factories.


[Free autologous iliac graft in femoral head osteonecrosis].
Failures of hip arthroplasties in younger patients led us to choose, in Steinberg III and IV stages, a resection of the necrosis and a "filling in" with a free autologous cancellous iliac graft. Indications for an iliac graft are the necrosis at Steinberg III and IV stages, with a Kerboull angle inferior to 180 degrees, a necrotic depth inferior to 1.5 cm, in patients under 55. Its advantages allow to avoid the microsurgical techniques of vascularized grafts and the complications of a possible secondary arthroplasty, as it sometimes occurs after an osteotomy. The long period of non-weightbearing after the graft is a relative inconvenient well tolerated by younger patients. However, the number of cases is still not sufficient to be statistically significant. Good results are maintained after 6 to 15 years.


Wound swab and wound biopsy yield similar culture results.
The question remains whether wound swabs yield similar culture results to the traditional gold standard, biopsies. Swabs are not invasive and easy to perform. However, they are believed to capture microorganisms from the surface rather than microorganisms that have invaded tissue. Several studies compared swabs and biopsies using different populations and sampling methods, complicating the ability to draw conclusions for clinical practice. This study aimed to compare swab and biopsy in clinical practice, by including a variety of wounds and using standard sampling and culture procedures. Swabs (Levine technique) and biopsies were taken for microbiological culture in a standardized manner from the same location of one wound for each patient. Statistical analyses were performed to determine overall agreement, and observed agreement and kappa for specific microorganisms. A variety of wounds of 180 patients from different healthcare facilities in The Netherlands were included. Skin flora was more frequently cultured from swabs, resulting in similar recovery rates when excluding skin flora (1.34 vs 1.35). Swabs were able to identify all microorganisms cultured from biopsies in 131 wounds (72.8%) wounds. Most frequently identified organisms were Staphylococcus aureus, Pseudomonas aeruginosa, and beta-haemolytic streptococci species. Observed agreement and kappa for these organisms varied between 87.2 and 97.8% and 0.73 and 0.85, respectively. This study demonstrates that swabs and biopsies tend to yield the same culture results when taken from the same location. For frequently occurring microorganisms, agreement between the two methods was even higher. Therefore, there seems to be no direct need for invasive biopsy in clinical practice.


Cytogenetic damage induced by radiotherapy. Evaluation of protection by amifostine and analysis of chromosome aberrations persistence.
To evaluate the cytogenetic damage induced by radiotherapy, the effect of concomitant amifostine and the persistence of translocations and dicentrics after the treatment. Blood samples from 16 head and neck cancer patients were obtained at different times, just before treatment, at the 1st and 22nd sessions, at the end of radiotherapy, and one, four and 12 months later. Solid stain and fluorescent in situ hybridization (FISH) techniques were applied to analyse chromosome aberrations. In all the analysis the frequencies of dicentrics plus rings were slightly lower in the group of patients receiving concomitant amifostine, but in each sampling point the differences were not significant. The persistence of translocations and dicentrics one year after radiotherapy was very similar, with a decline of more than 50%. For all the chromosome aberrations considered, a negative correlation between their initial yield and the percentage of this yield remained 12 months after radiotherapy was observed (p < 0.05). No significant protection by amifostine against radiation-induced chromosome damage was observed in head and neck cancer patients treated only with radiotherapy. In these cases, the persistence of translocations and dicentrics during the first year after radiotherapy is similar and related to their initial yield.