Utility of late gadolinium enhancement in pediatric cardiac MRI.
Late gadolinium enhancement (LGE) cardiac magnetic resonance (MR) imaging sequence is increasingly used in the evaluation of pediatric cardiovascular disorders, and although LGE might be a normal feature at the sites of previous surgeries, it is pathologically seen as a result of extracellular space expansion, either from acute cell damage or chronic scarring or fibrosis. LGE is broadly divided into ischemic and non-ischemic patterns. LGE caused by myocardial infarction occurs in a vascular distribution and always involves the subendocardial portion, progressively involving the outer regions in a waveform pattern. Non-ischemic cardiomyopathies can have a mid-myocardial (either linear or patchy), subepicardial or diffuse subendocardial distribution. Idiopathic dilated cardiomyopathy can have a linear mid-myocardial pattern, while hypertrophic cardiomyopathy can have fine, patchy enhancement in hypertrophied and non-hypertrophied segments as well as right ventricular insertion points. Myocarditis and sarcoidosis have a mid-myocardial or subepicardial pattern of LGE. Fabry disease typically affects the basal inferolateral segment while Danon disease typically spares the septum. Pericarditis is characterized by diffuse or focal pericardial thickening and enhancement. Thrombus, the most common non-neoplastic cardiac mass, is characterized by absence of enhancement in all sequences, while neoplastic masses show at least some contrast enhancement, depending on the pathology. Regardless of the etiology, presence of LGE is associated with a poor prognosis. In this review, we describe the technical modifications required for performing LGE cardiac MR sequence in children, review and illustrate the patterns of LGE in children, and discuss their clinical significance.


Burden of anemia in patients with osteoarthritis and rheumatoid arthritis in French secondary care.
Arthritic disorders can be the cause of hospitalizations, especially among individuals 60 years and older. The objective of this study is to investigate associations between health care resource utilization in arthritis patients with and without concomitant anemia in a secondary care setting in France. This retrospective cohort study utilized data on secondary care activity in 2001 from the Programme de Médicalisation des Systèmes d'Information database. Two cohorts were defined using ICD-10 codes: patients with an arthritis diagnosis with a concomitant diagnosis of anemia; and arthritis patients without anemia. Health care resource utilization for both populations was analyzed separately in public and private hospitals. Study outcomes were compared between the cohorts using standard bivariate and multivariable methods. There were 300,865 hospitalizations for patients with arthritis only, and 2,744 for those with concomitant anemia. Over 70% of patients with concomitant anemia were in public hospitals, compared with 53.5% of arthritis-only patients. Arthritis patients without anemia were younger than those with concomitant anemia (mean age 66.7 vs 74.6, public hospitals; 67.1 vs 72.2, private hospitals). Patients with concomitant anemia/arthritis only had a mean length of stay of 11.91 (SD 14.07)/8.04 (SD 9.93) days in public hospitals, and 10.68 (SD 10.16)/9.83 (SD 7.76) days in private hospitals. After adjusting for confounders, the mean (95% CI) additional length of stay for arthritis patients with concomitant anemia, compared with those with arthritis only, was 1.56 (1.14-1.98) days in public and 0.69 (0.22-1.16) days in private hospitals. Costs per hospitalization were €;480 (227-734) greater for arthritis patients with anemia in public hospitals, and €;30 (-113-52) less in private hospitals, than for arthritis-only patients. Arthritis patients with concomitant anemia have a longer length of stay, undergo more procedures, and have higher hospitalization costs than nonanemic arthritis patients in public hospitals in France. In private hospitals, concomitant anemia was associated with modest increases in length of stay and number of procedures; however, this did not translate into higher costs. Such evidence of anemia-related health care utilization and costs can be considered as a proxy for the clinical significance of anemia.


Neural evidence for inequality-averse social preferences.
A popular hypothesis in the social sciences is that humans have social preferences to reduce inequality in outcome distributions because it has a negative impact on their experienced reward. Although there is a large body of behavioural and anthropological evidence consistent with the predictions of these theories, there is no direct neural evidence for the existence of inequality-averse preferences. Such evidence would be especially useful because some behaviours that are consistent with a dislike for unequal outcomes could also be explained by concerns for social image or reciprocity, which do not require a direct aversion towards inequality. Here we use functional MRI to test directly for the existence of inequality-averse social preferences in the human brain. Inequality was created by recruiting pairs of subjects and giving one of them a large monetary endowment. While both subjects evaluated further monetary transfers from the experimenter to themselves and to the other participant, we measured neural responses in the ventral striatum and ventromedial prefrontal cortex, two areas that have been shown to be involved in the valuation of monetary and primary rewards in both social and non-social contexts. Consistent with inequality-averse models of social preferences, we find that activity in these areas was more responsive to transfers to others than to self in the 'high-pay' subject, whereas the activity of the 'low-pay' subject showed the opposite pattern. These results provide direct evidence for the validity of this class of models, and also show that the brain's reward circuitry is sensitive to both advantageous and disadvantageous inequality.


Antigens on HTLV-infected cells recognized by leukemia and AIDS sera are related to HTLV viral glycoprotein.
Cross-reactive antigens of molecular size of 61,000 to 68,000 daltons are found on the surface of human cells infected by human T-cell leukemia-lymphoma virus (HTLV). They are recognized by antibodies from patients with adult T-cell leukemias and lymphomas, from healthy carriers of HTLV, and from patients with the acquired immunodeficiency syndrome (AIDS). The latter finding has been one of the major reasons for suggesting an association of HTLV with AIDS. However, whether these antigens are of cellular or viral origin has not been clear. These antigens have now been shown to be associated with the presence of viral proteins in the cells, and a cross-reactive glycoprotein of molecular size of 46,000 daltons has been found to be a consistent structural part of viruses purified from several HTLV-producer cell lines. The findings thus suggest a viral (HTLV) origin of these antigens.


Target population's requirements on a community-based intervention for stimulating physical activity in hard-to-reach physically disabled people: an interview study.
Purpose: To explore ideas of the target population about a community-based intervention to stimulate physical activity in hard-to-reach physically disabled people. Materials and methods: Semi-structured interviews were performed with 21 physically disabled people, and analyzed using thematic analyses. Findings were interpreted using the integrated Physical Activity for People with a Disability and Intervention Mapping model. Results: The intervention should aim to stimulate intrinsic motivation and raise awareness for the health effects of physical activity. It should provide diverse activities, increase visibility of these activities, and improve image of physical activity for physically disabled people. Participants suggested to provide individual coaching sessions, increase marketing, present role models, and assign buddies. Potential users should be approached personally through intermediate organizations, or via social media and word of mouth promotion. Participants suggested that users, government, sponsors, and health insurers should finance the intervention. Self-responsibility for being physically active was strongly emphasized by participants. Conclusions: An intervention to stimulate physical activity in hard-to-reach physically disabled people should be individualized, include personal support, and should include marketing to improve image of physical activity of physically disabled people. The intervention that fulfills these requirements should be developed and tested for effects in future research. Implications for rehabilitation An intervention to stimulate physical activity in physically disabled people should aim to raise awareness for the health effects of physical activity, stimulate intrinsic motivation, offer diverse activities, increase the visibility of the possible activities, and improve the image of physical activity for physically disabled people. An intervention should include both individual- and environmental-level intervention methods. Physically disabled people most emphasized individual-level characteristics of an intervention. For intervention development, professionals should take into account that physically disabled people believe that being physically active is a person's own responsibility.


Consolidation and Maintenance Therapies for Newly Diagnosed Multiple Myeloma in the Era of Novel Agents.
Advances in therapy in multiple myeloma have resulted in significant improvements in patient outcomes; however, relapse remains problematic. Strategies to improve outcomes following autologous stem cell transplantation (ASCT) include consolidation to intensify therapy and improve depth of response and maintenance therapy to achieve long-term disease control. Immunomodulatory drugs (IMiDs), including thalidomide and lenalidomide, are appealing as maintenance therapy given their oral administration; however, the cumulative toxicities of thalidomide have limited its efficacy in maintenance therapy. Maintenance lenalidomide is better tolerated, and multiple studies have demonstrated an improvement in progression-free survival (PFS), but its impact on overall survival (OS) remains controversial. Additional concerns regarding the risk of second primary malignancies and significant cost of long-term lenalidomide therapy have also been raised. Proteasome inhibitors, particularly, bortezomib have also been incorporated in consolidation and maintenance regimens alone or in combination with an IMiD. Preliminary studies have suggested bortezomib maintenance may benefit patients with adverse cytogenetics, including t(4;14) and deletion 17p. Determination of the optimal consolidation and maintenance regimen and duration of therapy post-transplantation is a focus of several ongoing randomized studies.


Carbon dioxide laser in ophthalmic plastic and orbital surgery.
The CO2 laser cuts tissue by flash boiling extracellular or intracellular water molecules in contact with the beam. This vaporization sterilizes the tissue and seals capillaries. The CO2 laser seems most useful in ophthalmology to vaporize lymphangiomas and capillary hemangiomas and to provide hemostasis in patients with bleeding disorders. The cutting beam of the CO2 laser can be attached to the operating microscope to facilitate surgery deep within the orbit. The effectiveness of the CO2 cutting action depends upon water content of the tissue rather than tissue color as with argon and krypton lasers. Skin incisions show less scarring when made with conventional scalpel, but more precise surface cutting lasers may allow more precise microsurgical excision of eyelid tumors than can now be accomplished with a scalpel.


Image-based AI diagnostic performance for fatty liver: a systematic review and meta-analysis.
The gold standard to diagnose fatty liver is pathology. Recently, image-based artificial intelligence (AI) has been found to have high diagnostic performance. We systematically reviewed studies of image-based AI in the diagnosis of fatty liver. We searched the Cochrane Library, Pubmed, Embase and assessed the quality of included studies by QUADAS-AI. The pooled sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were calculated using a random effects model. Summary receiver operating characteristic curves (SROC) were generated to identify the diagnostic accuracy of AI models. 15 studies were selected in our meta-analysis. Pooled sensitivity and specificity were 92% (95% CI: 90-93%) and 94% (95% CI: 93-96%), PLR and NLR were 12.67 (95% CI: 7.65-20.98) and 0.09 (95% CI: 0.06-0.13), DOR was 182.36 (95% CI: 94.85-350.61). After subgroup analysis by AI algorithm (conventional machine learning/deep learning), region, reference (US, MRI or pathology), imaging techniques (MRI or US) and transfer learning, the model also demonstrated acceptable diagnostic efficacy. AI has satisfactory performance in the diagnosis of fatty liver by medical imaging. The integration of AI into imaging devices may produce effective diagnostic tools, but more high-quality studies are needed for further evaluation.


Total synthesis of malagashanine: a chloroquine potentiating indole alkaloid with unusual stereochemistry.
The first total synthesis of malagashanine, a chloroquine potentiating indole alkaloid, is presented. A highly stereoselective cascade annulation reaction was developed to generate the tetracyclic core of the Malagasy alkaloids. This chemistry is likely to be broadly applicable to the synthesis of other members of this stereochemically unique family of natural products.


Vegaviidae, a new clade of southern diving birds that survived the K/T boundary.
The fossil record of Late Cretaceous-Paleogene modern birds in the Southern Hemisphere includes the Maastrichtian Neogaeornis wetzeli from Chile, Polarornis gregorii and Vegavis iaai from Antarctica, and Australornis lovei from the Paleogene of New Zealand. The recent finding of a new and nearly complete Vegavis skeleton constitutes the most informative source for anatomical comparisons among Australornis, Polarornis, and Vegavis. The present contribution includes, for the first time, Vegavis, Polarornis, and Australornis in a comprehensive phylogenetic analysis. This analysis resulted in the recognition of these taxa as a clade of basal Anseriformes that we call Vegaviidae. Vegaviids share a combination of characters related to diving adaptations, including compact and thickened cortex of hindlimb bones, femur with anteroposteriorly compressed and bowed shaft, deep and wide popliteal fossa delimited by a medial ridge, tibiotarsus showing notably proximally expanded cnemial crests, expanded fibular crest, anteroposterior compression of the tibial shaft, and a tarsometatarsus with a strong transverse compression of the shaft. Isolated bones coming from the Cretaceous and Paleogene of South America, Antarctica, and New Zealand are also referred to here to Vegaviidae and support the view that these basal anseriforms were abundant and diverse at high southern latitudes. Moreover, vegaviids represent the first avian lineage to have definitely crossed the K-Pg boundary, supporting the idea that some avian clades were not affected by the end Mesozoic mass extinction event, countering previous interpretations. Recognition of Vegaviidae indicates that modern birds were diversified in southern continents by the Cretaceous and reinforces the hypothesis indicating the important role of Gondwana for the evolutionary history of Anseriformes and Neornithes as a whole.


[Hydrogen exchange and proteolytic degradation of ribonuclease A. Similarities and distinctions of the kinetic mechanisms].
The studies by IR spectroscopy of the temperature dependence of the H-D exchange rate of the RNase A peptide NH atoms permit one to characterize two types of conformation fluctuations, local and global. A comparison with the temperature dependence of the proteolytic degradation rate of RNase A shows that similar in nature fluctuations allow for the H-D exchange of NH atoms and the splitting of peptide bonds of the native protein. In the low temperature region, both processes occur through local fluctuations, by way of the EX2 mechanism, and in the high temperature region, they occur through global fluctuations with the overall denaturation desorganization of the native structure, by way of the EX1 mechanism. The biphasic dependence of the rate of H-D exchange and proteolytic degradation of RNase A on urea concentration is also explained by the combination of local and global fluctuations.


Serum ferritin, erythrocyte protoporphyrin and hemoglobin are valid indicators of iron status of school children in a malaria-holoendemic population.
In many African populations, the prevalences of both iron deficiency and malarial infection exceed 50%. The control of iron deficiency anemia is of urgent public health importance, but assessment of iron status in these contexts has been controversial because of the effects of malarial disease on common iron status indicators. We assessed iron status in 3605 school children in Zanzibar by measuring hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin concentrations. Malaria parasitemia was quantified by counting against leukocytes. Iron deficiency was highly prevalent: 62.4% of hemoglobin concentrations were <110 g/L, 59.7% of EP values were >80 micromol/mol heme, and 41.5% of ferritin concentrations were <12 microg/L. Prevalence of Plasmodium falciparum parasitemia was 60.6%, but <1% of children had densities above 5000 parasites/microL blood. Neither hemoglobin nor EP concentration was associated with malaria parasite density, but prevalence of abnormal values increased by < or = 25% with parasite density. Erythrocyte protoporphyrin and hemoglobin were strongly inversely related regardless of parasite density. The relationship of EP to hemoglobin was slightly attenuated when parasite density exceeded 1000 parasites/microL blood. Ferritin rose by 1.5 microg/L per 1000 parasites/microL for parasite densities >1000 parasites/microL, but the relationship of ferritin to hemoglobin or EP was strong even when parasite densities exceeded this cutoff. The population prevalences of iron deficiency were not significantly biased by malarial infection. In this population of school children, iron status assessment using these indicators was not seriously influenced by malarial infection. We hypothesize that these indicators perform reliably in populations in which malarial infection is infrequently associated with disease; namely older children and adults in holoendemic environments.


Labor management and mode of delivery among migrant and Spanish women: does the variability reflect differences in obstetric decisions according to ethnic origin?
Based on previous findings showing both better birth outcomes in migrant than in Spanish women and different rates of medical intervention according to mother's origin, we hypothesize that mode of delivery decisions to solve similar problems differ according to ethnic origin. Ethnic differences for maternal characteristics, medical intervention, and mode of delivery were evaluated in 16,589 births from a Maternity Hospital in Madrid (Spain). Multinomial logistic regression analysis was used to evaluate the effect of mother's ethnic origin on the mode of delivery, adjusting for mother's age, parity, gestational age, birth weight, and epidural anesthesia. Compared with the Spanish mothers, the risk of having a Caesarean section is significantly higher in Latin Americans and significantly lower for the Chinese. Both low birth weight and macrosomic deliveries are at higher risk for Caesarean section. The interventionist system characterizing Spain is being extended to all ethnic groups and, at the same time, different medical interventions are applied to similar problems depending on women's ethnic origin. Obstetric interventions might be contributing to the increasing trend of low birth weight and late preterm/early full term deliveries (37-38 weeks) observed in Spain. Behavioral and cultural values of the women and of the health care providers may contribute to systematic differences in labor management and mode of delivery.


Bronchiectasis: Experience of Surgical Management at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.
Bronchiectasis is one of the major health problems in Ethiopia. We analyzed the outcome of surgery done for bronchiectasis in a resource-limited setup. A retrospective cross-sectional analysis of 22 patients who underwent surgery for bronchiectasis in Tikur Anbessa specialized hospital (TASH) during the period 2012 - 2017 were done. There were 13(59%) female and 9(41%) male patients with a mean age of 34.1 +/-16.9 years. The mean duration of symptoms was 2.2 years. Blood streak sputum, 13(59%), dyspnea, 9(49.9%), fetid sputum, 8(36.4%), dry cough, 6(27.3%), chest pain, 6(27.3%) and massive hemoptysis 3(13.6%) were the main presenting symptoms. In 20(91%) of the patients, previous history of TB treatment was identified. Recurrent childhood infection, 1(4.5%), and tumor obstruction, 1(4.5%), were also seen. Bronchiectasis was left sided in 12(54.5%), right-sided in 7(31.8%) and bilateral in 3(13.6%) patients. The disease affected multiple lung lobes in 9(40.9%), left lower lobe in 6(27.3%) and left upper lobe in 3(13.6%) cases. Indications for surgery were the failure of medical management in 10(45.5%), destroyed lung in 9(40.9%), and massive hemoptysis in 3(13.6%) cases. The procedures performed were lobectomy in 14(63.6%) and pneumonectomy in 8(36.4%) cases. Postoperative complications occurred in 5(22.7%) patients with one (4.5%) death. On the other hand, 77.3% of operated patients had significant improvement compared to their preoperative symptoms. In a resource-limited setup like TASH, localized bronchiectasis can be treated surgically with an acceptable result. Proper selection and preparation with complete resection of the involved segments are needed for maximum control of symptoms and better outcomes.


Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice.
The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02).


[Dynamics of diphtheria morbidity and population immunity].
Observations on the stratum immune to diphtheria among the population, carried out over a period of many years and involving more than 37,000 people, have shown its gradual decrease in all adult age groups. In recent years the number of adults susceptible to diphtheria exceeded the number of susceptible children by 10.6%, and in some age groups by 18.5-21.8%, which makes for the total increase of diphtheria morbidity in recent years owing to its rise among adults. Regular revaccination of the adult population against diphtheria, made simultaneously with that against tetanus, is recommended.


Sitagliptin: a review of its use in patients with type 2 diabetes mellitus.
Sitagliptin (Januvia(®), Xelevia™, Glactiv(®), Tesavel(®)) is an orally administered, potent and highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4) and was the first agent of its class to be approved for use in the management of adults with type 2 diabetes. Numerous randomized placebo- or active comparator-controlled trials have demonstrated the efficacy of sitagliptin in terms of improving glycaemic control in patients with type 2 diabetes, including its use as monotherapy, initial combination therapy (usually with fixed-dose combinations of sitagliptin/metformin), or add-on therapy to metformin or to other antihyperglycaemic drugs, with or without metformin. The primary endpoint of the clinical trials was the reduction from baseline in glycosylated haemoglobin (HbA1c), although sitagliptin also showed beneficial effects for other endpoints, such as the proportion of patients who achieved target HbA1c, and reductions from baseline in fasting plasma glucose (FPG) levels and 2-h postprandial glucose (PPG) levels. Sitagliptin was generally well tolerated in clinical trials, had a low risk of hypoglycaemia (although this depends on background therapy) and had a neutral effect on body weight. Despite concerns regarding a possible increased risk of rare pancreatic adverse events (e.g. pancreatitis) with glucagon-like peptide-1 (GLP-1)-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, no causal association has been found; regulators in Europe recently conducted a review of available data, concluding that there is little evidence that these drugs could cause pancreatic inflammation or pancreatic cancer. A similar review is planned in the USA and postmarketing surveillance will continue. Thus, oral sitagliptin is an effective and generally well tolerated treatment option for the management of patients with type 2 diabetes.


Profits, community role, and hospital closure: an urban and rural analysis.
The number of hospital closures increased substantially after the implementation of Medicare's Prospective Payment System (PPS). This acceleration in closures raised a number of concerns over current payment policies and their impact on access. This paper investigates hospital closures that occurred in 1985 through 1988. A hospital's financial status and mission or community standing were found to be determinants of hospital closure. Closed hospitals are much less likely to be publicly owned but more likely to offer fewer facilities and services, and have fewer cases. This may suggest that the patients directly affected by the closure can be absorbed by other hospitals or other nonhospital providers. Profitability is associated with the Medicare case-mix index and the share of Medicare patients. The findings also suggest that the case mix index may be rewarding some small hospitals in excess of the costs attributable to case-mix. For both urban and rural hospitals, a low share of Medicare patients increased the risk of hospital closure, independently of the relationship between Medicare share and profit. The share of Medicare patients also affected closure indirectly, through its effects on profit. Competition appears to affect the odds of closure through its effects on the number of cases. In addition, hospitals in areas with small or declining population are more at risk than other hospitals in both urban and rural areas.


Creation of a fully active, cytosolic form of human type I 3beta-hydroxysteroid dehydrogenase/isomerase by the deletion of a membrane-spanning domain.
Human 3beta-hydroxysteroid dehydrogenase/steroid Delta(5)-Delta(4)-isomerase (3beta-HSD/isomerase) is a bifunctional, single enzyme protein that is membrane-bound in the endoplasmic reticulum (microsomes) and mitochondria of cells in the placenta (type I) and in the adrenals and gonads (type II). Two membrane-binding domains (residues 72-89 and 283-310) have been predicted by analyses of hydrophobicity in the type I and II isoenzymes (90% regional homology). These putative membrane domains were deleted in the cDNA by PCR-based mutagenesis, and the two mutant enzymes were expressed by baculovirus in insect Sf9 cells. Differential centrifugation of the Sf9 cell homogenate containing the 283-310 deletion mutant revealed that 94% of the 3beta-HSD and isomerase activities were in the cell cytosol, 6% of the activities were in the microsomes, and no activity was in the mitochondria. This is the opposite of the subcellular distribution of the wild-type enzyme with 94% of the activities in the microsomes and mitochondria and only 6% activity in the cytosol. The organelle distribution of the 72-89 deletion mutant lies between these two extremes with 72% of the enzyme activity in the cytosol and 28% in the microsomes/mitochondria. The integrity of the subcellular organelle preparations was confirmed by electron microscopy. Western immunoblots confirmed the presence of the 283-310 deletion mutant enzyme and the absence of the wild-type enzyme in the insect cell cytosol. The unpurified, cytosolic 383-310 deletion mutant exhibited 3beta-HSD (22 nmol/min per mg) and isomerase (33 nmol/min per mg) specific activities that were comparable with those of the membrane-bound, wild-type enzyme. The isomerase reaction of the cytosolic 283-311 deletion mutant requires activation by NADH just like the isomerase of the microsomal or mitochondrial wild-type enzyme. In contrast, the 72-89 deletion mutant had low 3beta-HSD and isomerase specific activities that were only 12% of the wild-type levels. This innovative study identifies the 283-310 region as the critical membrane domain of 3beta-HSD/isomerase that can be deleted without compromising enzyme function. The shorter 72-89 region is also a membrane domain, but deletion of this NH(2)-terminal region markedly diminishes the enzyme activities. Purification of the active, cytosolic 283-310 deletion mutant will produce a valuable tool for crystallographic studies that may ultimately determine the tertiary/quaternary structure of this key steroidogenic enzyme.


[A hormonal drug melatonin in the treatment of cognitive function disorders in parkinsonism].
Pineal hormone melatonin, which is known to possess neuroptotector and nootrope activity, also produces a significant therapeutic effect with respect to various brain pathologies. The review of original and published data suggests that it is expedient to use melatonin in the treatment of cognitive disorders accompanying Parkinson's disease.


Simultaneous Superiorly Based Pharyngeal Flap and Tonsillectomy: Evaluation of Speech and Pain Outcomes.
Controversy remains whether to perform a pharyngeal flap simultaneously with a tonsillectomy in patients with velopharyngeal insufficiency. The aim of this study is to revisit the speech outcomes and complications associated with the combined superiorly based pharyngeal flap and tonsillectomy procedure, while comparing pain outcomes. We hypothesize that the combined procedure will improve speech outcomes with minimal complications, but patients will experience more pain in the combined procedure.A 5-year retrospective review of registry data from Boys Town National Research Hospital was conducted from 2014 to 2019. Data collection included age, surgeries performed, length of stay, pain medication administration occurrences, immediate postoperative complications, postoperative speech outcomes specifically related to articulation (audible nasal airway emissions) and resonance (hypernasality).Eighty-eight patients had a superiorly based pharyngeal flap over this 5-year period. Eighteen patients (20%) had a simultaneous procedure performed. There were no patients who had immediate postoperative complications such as upper airway obstruction or bleeding complications that necessitated a reoperation. One of the patients had a pharyngeal flap dehiscence that required a revision pharyngeal flap in the combined group. Nasal airway emissions and hypernasality were eliminated in 58.3% and 75%of the combined patients, respectively. The total number of narcotic administration occurrences were significantly higher in the combined group than the pharyngeal flap only group (9.0 versus 7.0; P = 0.03).A number of velopharyngeal patients will present with hypertrophied tonsils. We believe that it is safe and beneficial to perform the combined procedure in the same setting.


Continuous monitoring of a restriction enzyme digest of DNA on a microchip with automated capillary sample introduction.
Continuous analysis of a DNA restriction enzyme digest on a microfabricated device is demonstrated with minimal intervention and enhanced time resolution. A 62-base-pair fragment of dsDNA containing a KpnI site was used to demonstrate this process. A capillary was used to transfer sample from a single reaction mix to a microfabricated chip with parallel separation lanes. The 6-carboxyfluorescein-labeled DNA fragments were detected with a CCD camera as they separated in the lanes, which were filled with linear polyacrylamide. The products of the restriction enzyme digest were monitored for up to 60 min at an average sampling rate of 1 injection/46 s, with consecutive injections as short as 1 injection/14 s. The digest was injected directly into the chip, eliminating the need for any sample-handling steps after addition of the enzyme to the reaction mix. The effects of temperature and restriction enzyme concentration were briefly examined, as well. This work shows the potential of this method to provide valuable information about the process of restriction enzyme cleavage.


Separation and analysis of subcellular organelles in a human promyelocytic leukemia cell line, HL-60: application to the study of myeloid lysosomal enzyme synthesis and processing.
We describe a system for analysis of the intracellular pathways in the biosynthesis and packaging of functionally important proteins in human myeloid cells. The human promyelocytic cell line HL-60 was used since peripheral blood neutrophils are terminally differentiated and do not actively synthesize protein. Cells were disrupted by nitrogen cavitation and subcellular organelles in postnuclear supernatant separated on a discontinuous gradient of Percoll modified to resolve organelles important in protein synthesis. This Percoll gradient separated azurophilic granules from less dense organelles and partially separated the less dense organelles from one another. Approximate densities of organelles identified by electron microscopy and by biochemical markers are azurophilic granules, 1.102 g/mL; endoplasmic reticulum, 1.039 g/mL; Golgi apparatus, 1.032 g/mL; and plasma membrane, 1.027 g/mL. We validated the utility of this method of subcellular fractionation by examining intracellular transport of myeloperoxidase, a myeloid lysosomal enzyme present in azurophilic granules. The subunits of mature myeloperoxidase (molecular weight [mol wt] = 59,000 and 13,500) cosediment with biochemical markers for lysosomes, whereas the large-mol wt (89,000) precursor forms cosediments with biochemical markers of less dense organelles. Within the limits of assay sensitivity, the 89,000-mol wt precursor is enzymatically inactive and has no spectral evidence for a heme group, suggesting that precursors of myeloperoxidase may undergo proteolytic maturation in a prelysosomal compartment with concomitant incorporation of a heme group and acquisition of enzymatic activity. This system of analysis should be suitable for the identification, subcellular localization, and maturational analysis of other myeloid lysosomal enzymes as well as functionally important membrane proteins.


Distinct sequence elements involved in the glucocorticoid regulation of the mouse mammary tumor virus promoter identified by linker scanning mutagenesis.
In the proviral DNA of mouse mammary tumor virus (MMTV), sequences up to approximately equal to 200 base-pairs from the RNA start site are required for stimulation of transcription by glucocorticoid hormones in cultured cells. A total of 26 mutant plasmids with clustered point mutations or small deletions in the hormone control region of the MMTV long terminal repeat were constructed, linked to the coding portion of the Herpes simplex virus thymidine kinase gene, and introduced by transfection into LTK- cells. Transcription from mutant DNA in the presence or absence of hormone was quantified by S1 nuclease protection assays. Our analysis revealed the presence of at least three control elements that affect the extent of transcription stimulation by glucocorticoid hormones: (1) a distal element, between -181 and -172 base-pairs from the RNA initiation site. Linker scanning mutants in this segment have a reduction of up to 20-fold in the hormone response with respect to wild type. (2) An element around position -120, defined by a mutation of 4 base-pairs between -121 and -117, which causes a fivefold reduction. (3) An element from approximately equal to -78 to -70, defined by a mutant with also a roughly fivefold lower stimulation. The first two are included in areas that have been shown by others to interact in vitro with hormone-receptor complexes; the last one overlaps the in vitro binding site of a nuclear protein factor. A mutant lacking all three elements (-193 to -70) is completely non-inducible by glucocorticoids. Together with earlier results obtained with 5' deletion mutants, the data show that the largest contribution to the stimulatory response is made by the distal element, which however does require the presence of both more-proximal ones for the response to be maximal. In the absence of the distal one, the two proximal elements together produce a residual stimulation in the order of 5 to 10% of wild type, while the -70 element alone is ineffective. In addition, we show that a functional TATA homology is required for maximum stimulation. It appears that transcriptional regulation of MMTV by glucocorticoid hormones is achieved by the concerted action of multiple sequence modules, not all of which correspond to receptor binding sites in vitro.


Evaluation of Student Peer- and Self-Grading in an Integrated Pharmacotherapy Course.
To determine if student peer- and self-grades correlate with faculty grades on case vignettes. This study involved first professional-year students enrolled in an Integrated Pharmacotherapy course. The course included three modified team-based learning (TBL) activities (each consisting of individual and team readiness assurance tests, followed by three open-note case vignettes completed in teams). Each student uploaded completed case vignettes to the learning management system and was assigned to complete a self- and a random, anonymous peer-grade using a provided key. Peer- and self-grades were compared to faculty grades using a null multilevel model to determine the intraclass correlation coefficient (ICC). Faculty time spent grading was captured, and students were surveyed to determine the perceived value of peer- and self-grading. Faculty- and peer-grades had a slightly higher correlation than faculty- and self-grades (ICC = 0.75 vs 0.73, respectively). The ICC between all three grader groups was 0.74. Faculty spent an average of 2.5 h grading the cases after each TBL session. Students reported spending a median of 36 min on the peer- and self-grades for each TBL session. Overall, students agreed that both the self- and peer-grading activities helped identify gaps in knowledge (90% and 56%, respectively). A total of 78% of students agreed that self-grading was beneficial for their learning. There was a moderate-to-good correlation between peer-, self-, and faculty- grades for case vignettes. Faculty time may be saved through student self- or peer-grading.


Cloning and identification of hepatocellular carcinoma down-regulated mitochondrial carrier protein, a novel liver-specific uncoupling protein.
We report the identification of a novel cDNA fragment that shows significantly reduced expression in cancerous tissue compared with paired non-cancerous liver tissue in patients with hepatocellular carcinoma (HCC). The full-length transcript of 1733 bp encodes a protein of 308 amino acids that has all the hallmark features of mitochondrial carrier proteins. We designate the novel protein as HDMCP (HCC-down-regulated mitochondrial carrier protein). The HDMCP orthologs in human, mouse, and rat are found to exhibit close similarity in protein sequence and gene organization, as well as exclusive expression in the liver. Moreover, conserved syntenic regions have been demonstrated at the HDMCP gene locus in the human, mouse, and rat genome. Taken together, we suggest that HDMCP might have a conserved and unique biological function in the liver. Overexpression of HDMCP in transiently transfected cancer cells results in the loss of staining by MitoTracker dye, indicating that HDMCP could induce the dissipation of mitochondrial membrane potential (DeltaPsim). However, HDMCP-mediated disruption of DeltaPsim is not related to mitochondrial permeability transition or apoptosis. In addition, we further demonstrate that the dissipation of DeltaPsim is accompanied by significant reduction of cellular ATP in 293T cells overexpressing HDMCP or uncoupling protein 2 (UCP2). Our present findings suggest that HDMCP might be one of the long postulated uncoupling proteins that catalyze the physiological "proton leak" in the liver. The down-regulation of HDMCP in HCC cancer cells might result in the elevation of DeltaPsim, a common phenomenon found in cancer cells.


Hedgehog serves as a mitogen and survival factor during embryonic stem cell neurogenesis.
Hedgehog (Hh) signaling is involved in a wide range of important biological activities. Within the vertebrate central nervous system, Sonic Hedgehog (Shh) can act as a morphogen or mitogen that regulates the patterning, proliferation, and survival of neural stem cells (NSCs). However, its role in embryonic stem cell (ESC) neurogenesis has not been explored in detail. We have previously shown that Hh signaling is required for ESC neurogenesis. In order to elucidate the underlying mechanism, we utilized the Sox1-GFP ESC line, which has a green fluorescent protein (GFP) reporter under the control of the Sox1 gene promoter, providing an easy means of detecting NSCs in live cell culture. We show here that ESC differentiation in adherent culture follows the ESC--> primitive ectoderm --> neurectoderm transitions observed in vivo. Selective death of the Sox1-GFP-negative cells contributes to the enrichment of Sox1-GFP-positive NSCs. Interestingly, Shh is expressed exclusively by the NSCs themselves and elicits distinct downstream gene expression in Sox1-GFP-positive and -negative cells. Suppression of Hh signaling by antagonist treatment leads to different responses from these two populations as well: increased apoptosis in Sox1-GFP-positive NSCs and decreased proliferation in Sox1-GFP-negative primitive ectoderm cells. Hedgehog agonist treatment, in contrast, inhibits apoptosis and promotes proliferation of Sox1-GFP-positive NSCs. These results suggest that Hh acts as a mitogen and survival factor during early ESC neurogenesis, and evidence is presented to support a novel autocrine mechanism for Hh-mediated effects on NSC survival and proliferation.


Emerging roles for R-loop structures in the management of topological stress.
R-loop structures are a prevalent class of alternative non-B DNA structures that form during transcription upon invasion of the DNA template by the nascent RNA. R-loops form universally in the genomes of organisms ranging from bacteriophages, bacteria, and yeasts to plants and animals, including mammals. A growing body of work has linked these structures to both physiological and pathological processes, in particular to genome instability. The rising interest in R-loops is placing new emphasis on understanding the fundamental physicochemical forces driving their formation and stability. Pioneering work in Escherichia coli revealed that DNA topology, in particular negative DNA superhelicity, plays a key role in driving R-loops. A clear role for DNA sequence was later uncovered. Here, we review and synthesize available evidence on the roles of DNA sequence and DNA topology in controlling R-loop formation and stability. Factoring in recent developments in R-loop modeling and single-molecule profiling, we propose a coherent model accounting for the interplay between DNA sequence and DNA topology in driving R-loop structure formation. This model reveals R-loops in a new light as powerful and reversible topological stress relievers, an insight that significantly expands the repertoire of R-loops' potential biological roles under both normal and aberrant conditions.


Control of vertebrate left-right asymmetry by a snail-related zinc finger gene.
A gene encoding a zinc finger protein of the Snail family, cSnR, is expressed in the right-hand lateral mesoderm during normal chick development. Antisense disruption of cSnR function during the hours immediately preceding heart formation randomized the normally reliable direction of heart looping and subsequent embryo torsion. Implanted ectopic sources of intercellular signal proteins that are involved in establishing normal left-right information randomized the handedness of heart development and also altered the asymmetry of cSnR expression. cSnR thus appears to act downstream of these signals, or perhaps in parallel with the latest expressed of them, the Nodal protein, in controlling the anatomical asymmetry.


[Aspiration lipectomy, late results, unsatisfactory results and their correction].
When new techniques become available and subsequently are adopted by a large number of surgeons, improvements occur and an average complication rate becomes apparent. It is the analysis of the unfavourable results and the complications that stimulates improvement. After nine years of experience in suction lipectomy this technique has become in our hands a very safe procedure. If the empiric laws of surgery are observed, complications are extremely rare. Good indication and choice of the right patient are the key to success and it is important to realize that the amount of volume reduction is dictated by the limited retractile elasticity of the skin.


Ear Lobule Rejuvenation in Face-Lifting: The Role of Fat Augmentation.
Ear lobule ptosis and deflation are characteristics of facial aging. A rhytidectomy without rejuvenation of a deflated ear lobule may fail to address all aspects of facial aging. Fillers have been used to treat ear lobule deflation; however, autologous fat transfer has never been utilized for ear lobule rejuvenation. This investigation studies the success of autologous fat transfer to the ear lobule as part of volume augmentation rhytidectomy. A retrospective review of patients who underwent rhytidectomy between 2000 and 2014 by a single surgeon was performed. Patients between 2000 and 2004 who did not receive autologous fat transfer served as controls (group A). Patients between 2010 and 2014 who received autologous fat transfer to the ear lobule formed the treatment group (group B). Three independent observers reviewed preoperative and postoperative photographs for both groups at 1 year postoperatively. The following ear lobule volume grading scale was applied to numerically assess the patients: concave = 0, flat = 1, convex = 2, and round = 3. Groups A and B each consisted of 65 consecutive patients (130 ears). In group A, the mean preoperative ear lobule grading score was 1.20, and the mean postoperative score was 1.22 (mean difference, 0.02; P = 0.42). In group B, the mean preoperative ear lobule grading score was 0.98, and the mean postoperative score was 2.00 (mean difference, 1.02; P < 0.0001). In patients receiving autologous fat transfer to the ear lobule during rhytidectomy, there was a significant change from a deflated ear lobule preoperatively to a more voluminous lobule at 1 year postoperatively.


Uncovering the unknown: A grounded theory study exploring the impact of self-awareness on the culture of feedback in residency education.
Self-assessment and reflection are essential for meaningful feedback. We aimed to explore whether the well-known Johari window model of self-awareness could guide feedback conversations between faculty and residents and enhance the institutional feedback culture. We had previously explored perceptions of residents and faculty regarding sociocultural factors impacting feedback. We re-analyzed data targeting themes related to self-assessment, reflection, feedback seeking and acceptance, aiming to generate individual and institutional feedback strategies applicable to each quadrant of the window. We identified the following themes for each quadrant: (1) Behaviors known to self and others - Validating the known; (2) Behaviors unknown to self but known to others - Accepting the blind; (3) Behaviors known to self and unknown to others - Disclosure of hidden; and (4) Behaviors unknown to self and others - Uncovering the unknown. Normalizing self-disclosure of limitations, encouraging feedback seeking, training in nonjudgmental feedback and providing opportunities for longitudinal relationships could promote self-awareness, ultimately expanding the "open" quadrant of the Johari window. The Johari window, a model of self-awareness in interpersonal communications, could provide a robust framework for individuals to improve their feedback conversations and institutions to design feedback initiatives that enhance its quality and impact.


Services for adults with ADHD: work in progress: Commentary on . . . Specialist adult ADHD clinics in East Anglia.
Magon and colleagues highlight a number of relative strengths and weaknesses very reminiscent of those we have seen over the years in the development of similar services for children and adolescents. It is clear that we all have a lot of work to do to improve our approach to the transition from child to adult services. There was clear evidence that adult services can adapt to manage ADHD, but there is also a clear need for increased upskilling of clinicians in the practical management of medication and other treatments. I disagree with Magon and colleagues about the role of primary care and believe that treatment initiation and ongoing monitoring should, for the time being, remain in secondary care and that, because of the volume of work that will come our way, this will need to become a core rather than specialist task. As with other aspects of psychiatric care, there is a clear role for specialist nurses in delivering a significant proportion of the core care.


Self-processing photopolymer materials for versatile design and fabrication of holographic sensors and interactive holograms.
The aim of this paper is to discuss the benefits as well as the limitations of utilizing photopolymer materials in the design of holograms that are responsive to changes in their environment, such as changes in the concentration of a specific substance, temperature, and pressure. Three different case studies are presented, including both surface and volume phase holograms, in order to demonstrate the flexibility in the approach of utilizing holographic photopolymers for the design of sensors and interactive optical devices. First, a functionalized surface relief hologram is demonstrated to operate as an optical sensor for the detection of metal ions in water. The sensitivity and selectivity of the sensor are investigated. The second example demonstrates a volume transmission hologram recorded in a temperature-sensitive photopolymer and the memory effects of its exposure to elevated temperature. Finally, a pressure-sensitive reflection hologram that changes color under application of pressure is characterized, and its potential application in document authentication is described.


[Metabolic features in chondroitin sulfate in the normal functioning of connective tissue].
In the propoced review, the literature data on the metabolic characteristics of chondroitin sulfate in the normal functioning of connective tissue. Described their own data on the study of the reaction of connecting structures of the knee rabbits experimental arthritis by intra-articular intra-articular injection of chondroitin sulface (the drug "mukosat").


Bringing Rounds Back to the Patient: A One-Year Evaluation of the Chiefs' Service Model for Inpatient Teaching.
The Chiefs' Service (CS), a structured approach to inpatient teaching rounds, focuses on resident education and patient-centered care without disrupting patient census sizes or admitting cycles. It has five key elements: morning huddles; bedside rounds; diagnostic "time-outs"; day-of-discharge rounds; and postdischarge follow-up rounds. The authors hypothesized the CS model would be well received by residents and considered more effective than more-traditional rounds. The CS was implemented on Penn Presbyterian Medical Center's general medicine inpatient service using a quasi-experimental design. Its first year (January 2013-January 2014) was evaluated with a mixed-methods approach. Residents completed end-of-rotation evaluation questionnaires; 20 CS and 10 traditional service (TS) residents were interviewed. Measures of resident agreement on questionnaire items were compared across groups using independent sample t testing. A modified grounded theory approach was used to assess CS residents' perspectives on the CS elements and identify emergent themes. The questionnaires were completed by 183/188 residents (response rate 97%). Compared with TS residents, CS residents reported significantly greater satisfaction in the domains of resident education and patient care, and they rated the overall value of the rotation significantly higher. The majority of CS residents found the CS elements to be effective. CS residents described the CS as focused on resident education, patient-centered care, and collaboration with an interdisciplinary team. The CS approach to inpatient rounding is seen by residents as valuable and is associated with positive outcomes in terms of residents' perceptions of learning, interdisciplinary communication, and patient care.


Innervation of teeth: qualitative, quantitative, and developmental assessment.
Anatomical characteristics of tooth innervation provide insights into functional capabilities as well as limitations of this organ. In this review, innervation will be discussed from two major viewpoints. The first part will present distribution of nerve fibers in the tooth; nerve pathways, both autonomic and sensory, will be discussed mostly from a descriptive standpoint. In the second part, quantitation of neural units along key points of the pathways will be presented at milestones in tooth and organism development and aging.


Algal Sex Determination and the Evolution of Anisogamy.
Algae are photosynthetic eukaryotes whose taxonomic breadth covers a range of life histories, degrees of cellular and developmental complexity, and diverse patterns of sexual reproduction. These patterns include haploid- and diploid-phase sex determination, isogamous mating systems, and dimorphic sexes. Despite the ubiquity of sexual reproduction in algae, their mating-type-determination and sex-determination mechanisms have been investigated in only a limited number of representatives. These include volvocine green algae, where sexual cycles and sex-determining mechanisms have shed light on the transition from mating types to sexes, and brown algae, which are a model for UV sex chromosome evolution in the context of a complex haplodiplontic life cycle. Recent advances in genomics have aided progress in understanding sexual cycles in less-studied taxa including ulvophyte, charophyte, and prasinophyte green algae, as well as in diatoms.


Chronic undernutrition and traditional weaning foods are associated with fat stores in Ariaal infants of Northern Kenya.
The high proportion of human infant fat is hypothesized to protect infant brains by mobilizing against growth disturbances caused by acute nutritional and pathogen stress during weaning. However, individuals who experience chronic nutritional stress have been shown to store fat rather than mobilize fat stores, although this has not been demonstrated during infancy. This study investigated the relationship between fat development, diet, and nutritional status among 239 breastfeeding Ariaal infants, a group of settled pastoralists who experience both acute and chronic nutritional stress residing in Marsabit District, Kenya. This study had three goals: 1) To investigate the pattern of fat accumulation among Ariaal infants compared with a reference population; 2) to explore the relationship between chronic nutritional stress and fat deposits; and 3) to determine the relationship between traditional weaning foods, particularly cow's milk, and infant's fat. Infants, particularly infants experiencing chronic nutritional stress, were found to accumulate fat deposits in a manner that suggests reduced oxidation of fat stores. Infant upper arm fat area significantly increases with age over the weaning period compared with reference populations, who show a decline in body fat. Chronically undernourished infants were particularly likely to have increased levels of upper arm fat compared with normal infants or acutely undernourished infants. In addition, infants who consume cow's milk are significantly fatter than those that do not. These results suggest that Ariaal infants have both physiological and cultural mechanisms for fat storage in the face of their nutritionally stressed environment.


Institutional Cost of Unplanned 30-Day Readmission Following Open and Endovascular Surgery.
Vascular surgical patients have a high rate of readmission, and the cost of readmission for these patients has not been described. Herein, we characterize and compare institutional index hospitalization and 30-day readmission cost following open and endovascular vascular procedures. The American College of Surgeons National Surgical Quality Improvement Program database was used to identify inpatient open and endovascular procedures at a single institution, from January 2011 through June 2012. Variable and fixed costs for index hospitalization and unplanned 30-day readmissions were obtained using SAP BusinessObjects. Patient characteristics and outcome variables were analyzed using Student t tests or Wilcoxon rank-sum nonparametric tests for continuous variables and Fisher exact tests for categorical variables. One thousand twenty-six inpatient procedures were included in the analysis. There were 605 (59%) open and 421 (41%) endovascular procedures with a 30-day unplanned readmission rate of 16.9% and 17.8%, respectively (P = .679). The mean index hospitalization costs for open and endovascular procedures were US$27 653 and US$23 999, respectively (P = .146). The mean costs for 30-day unplanned readmission for open and endovascular procedures were US$19 117 and US$17 887, respectively (P = .635). Among open procedures, the mean cost for patients not readmitted was US$28 321 compared to US$31 115 for those readmitted (P = .003). Among endovascular procedures, the mean cost for patients not readmitted was US$26 908 compared to US$32 262 for those readmitted (P = .028). The cost of index hospitalization and 30-day unplanned readmission are similar for open and endovascular procedures. Readmitted patients had a higher mean index hospitalization cost irrespective of open or endovascular procedure.


The effect of marjoram (Origanum majorana) tea on the hormonal profile of women with polycystic ovary syndrome: a randomised controlled pilot study.
In traditional medicine, marjoram herb (Origanum majorana) is locally reputed for its ability to restore hormonal balance and to regulate the menstrual cycle. Therefore, this pilot study aimed to investigate the effects of marjoram tea on the hormonal profile of women with polycystic ovary syndrome (PCOS) in a randomised, double-blind, placebo-controlled trial. Twenty-five patients were assigned to receive marjoram tea or a placebo tea twice daily for 1 month (intervention group: n = 14; placebo group: n = 11). The hormonal and metabolic parameters measured at baseline, as well as after the intervention, were: follicle-stimulating hormone, luteinising hormone, progesterone, oestradiol, total testosterone, dehydroepiandrosterone-sulphate (DHEA-S), fasting insulin and glucose, homeostasis model assessment for insulin resistance (HOMA-IR) and glucose to insulin ratio. Marjoram tea significantly reduced DHEA-S and fasting insulin levels (P < 0.05) by a mean (SD) of 1.4 (0.5) μmol L(-1) and 1.9 (0.8) μU mL(-1) , respectively. In comparison to the placebo group, the change was only significant for DHEA-S (P = 0.05) but not for insulin (P = 0.08). HOMA-IR was not reduced significantly in the intervention group (P = 0.06), although the change was significant compared to the placebo group (P < 0.05). The results obtained in the present study show the beneficial effects of marjoram tea on the hormonal profile of PCOS women because it was found to improve insulin sensitivity and reduce the levels of adrenal androgens. Further research is needed to confirm these results and to investigate the active components and mechanisms contributing to such potential beneficial effects of marjoram herb.


Renin release selectively stimulated by prostaglandin I2 in isolated rat glomeruli.
Renal glomeruli were isolated from rat kidneys using a passive mechanical sieving technique. Glomerular microsomal fraction, glomerular homogenate, or intact glomeruli were incubated with [1-14C]arachidonic acid, and the profile of prostaglandin (PG) synthesis was determined by thin-layer chromatography. The three incubation systems produced 15.3, 20.8, and 40.4% 6-keto-PGF1 alpha; 19.1, 23.5, and 15.3 PGF2 alpha; 5.7, 9.1, and 3.9% thromboxane (TX) B2; 36.0, 35.1, and 37.0% PGE2; and 23.9, 11.3, and 3.4% PGD2, respectively. Glomeruli were placed in suspension within glass chambers and superfused with Krebs solution. Superfusion with 1.6 x 10(-4) M arachidonic acid stimulated a significant release of renin from glomeruli, whereas 2.7 x 10(-6) M PGE1, PGE2, PGF2 alpha, TXB2, PGD2, or a stable analog of PGH2 had no effect on renin. When the rapid breakdown of PGI2 was counteracted by either increasing the concentration to 1.7 x 10(-4) M or stabilizing in Krebs at pH 9.4, it stimulated a significant increase in renin release. Reducing the arachidonic acid concentration to 1.6 x 10(-5) M eliminated both renin release and PGI2 synthesis, while increased PGE2 synthesis persisted. Finally, using an inhibitor of PGI2 synthesis, azo analog 1 (2.8 x 10(-6) M), 6-keto-PGF1 alpha produced in response to arachidonic acid was eliminated, as was the concurrent release of renin, but PGE2 synthesis was not affected. These results suggest that the mechanism of direct interaction between renal PG and renin in isolated glomeruli is selectively due to the action of PGI2.


White matter changes in stroke patients. Relationship with stroke subtype and outcome.
White matter changes (WMC), detected by imaging techniques, are frequent in stroke patients. The aim of the study was to determine how WMC relate to stroke subtypes and to stroke outcome. We made a systematic Medline search for articles appearing with two of the following key words: either 'WMC or white matter lesions or leukoencephalopathy or leukoaraiosis' and 'stroke or cerebral infarct or cerebral hemorrhage or cerebrovascular disease or transient ischemic attack (TIA)'. WMC, as defined radiologically, are present in up to 44% of patients with stroke or TIA and in 50% of patients with vascular dementia. WMC are more frequent in patients with lacunar infarcts, deep intracerebral hemorrhages, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cerebral amyloid angiopathy. After an acute ischemic stroke, WMC are associated with a higher risk of death or dependency, recurrent stroke of any type, cerebral bleeding under anticoagulation, myocardial infarction, and poststroke dementia. WMC in stroke patients are often associated with small-vessel disease and lead to a higher risk of death, and poor cardiac and neurological outcome. However, several questions remain open and need further investigations.


Effects of cholecystokinin on taste preference and sensitivity in rats.
Cholecystokinin octapeptide (CCK-8) reduced the amount consumed or the number of licks of several concentrations of sucrose in short-term tests with rats that were hungry, satiated, or fed ad lib. The suppressive effect of CCK-8 was generally smaller in the hungry than in the satiated or ad-lib condition. In the satiated and ad-lib conditions, there was no effect of sucrose concentration on the magnitude of the CCK-8 effect. In hungry rats, the concentration-intake function for sucrose was lowered and flattened by both CCK and natural satiety. In order to determine whether a taste change is involved in this short-term reduction of sucrose intake, integrated chorda tympani responses were measured before and after iv infusions of CCK-8 or NaCl. The peak response to 0.3 M sucrose significantly increased after two 5-microgram infusions of CCK-8. Peak and tonic responses to sucrose and saline tended to increase after CCK-8 but not NaCl infusions. These results indicate that CCK-8 reduces sucrose intake in situations in which postingestional factors are minimal and that sucrose concentration has little effect on the size of this suppression. A change in perceived taste intensity or quality may play a role in the inhibitory effect of CCK-8 on intake.


[Gamma-topography of the cerebrospinal fluid passages of the spinal cord in traumatic injuries of the brachial plexus at the preganglionic level].
Gamma-topography of the cerebrospinal fluid tracts of the spinal cord (GCTSC) was conducted in 28 patients with traumatic injuries of the brachial plexus at the preganglionic level. The object of GCTSC was to identify the character of damage inflicted to the spinal cord, its meninges, and the roots at the preganglionic level in the presence of the pain syndrome. Spatial-temporal distribution of the radiopharm agent in the submeningeal space served as the basis for setting apart radiological signs characterizing the anatomical disorders and disturbances in cerebrospinal fluid dynamics in the submeningeal space of the spinal cord. The radiological picture was always composed of adhesive-cicatricial and adhesive-cystic processes with arachnoid cysts or cerebrospinal fistulas in the cervicothoracic segment of the spinal cord.


Primary Care Patients' and Providers' Perspectives about an Online Weight Management Program: a Qualitative Study.
Primary care providers (PCPs) often take the lead role in caring for patients with overweight and obesity; however, few PCPs counsel patients about weight loss. Online weight management programs that are integrated within primary care may help address this gap in care. To identify perceptions of and experience with online weight management programs in general and with a proposed online program, to identify barriers to use, and to improve the design and content of our intervention, which included an online program plus population health management (PHM) support from primary care practices. A mixed qualitative methods study including three patient focus groups and seven semi-structured interviews with healthcare providers. A total of 13 adult patients (age range, 20-70) with body mass index (BMI) 27-35 kg/m2 attended the focus groups. In-person semi-structured interviews were conducted with seven healthcare providers (three PCPs, two population health managers, one primary care nurse, and one registered dietitian). We developed and used semi-structured focus groups and interview guides. The focus group and interviews were recorded and transcribed. Using grounded theory, we analyzed the transcripts to identify and extract common concepts and themes. Although patients and healthcare providers expressed positive opinions about online weight management programs, few patients had experience with them, and providers stated that such programs are not being widely implemented in primary care settings. Some participants highlighted the flexibility and low cost as strengths of online weight management tools compared with in-person programs. All participants had favorable opinions about our proposed intervention and were overwhelmingly positive about the combination of an online program and PHM support. This study highlights the potential value of online weight management programs and PHM support in primary care. NCT02656693.


The effect of an electronic health record system on nursing staff time in a nursing home: a longitudinal cohort study.
Nursing homes are increasingly introducing electronic health record (EHR) systems into nursing practice; however, there is limited evidence about the effect of these systems on nursing staff time. To investigate the effect of introducing an EHR system on time spent on activities by nursing staff in a nursing home. An observational work sampling study was undertaken with nursing staff between 2009 and 2011 at two months before, and at 3, 6, 12, and 23 months after implementation of an EHR system at an Australian nursing home. An observer used pre-determined tasks to record activities of the nursing staff at nine-minute intervals. There was no significant change in registered nurses and endorsed enrolled nurses' time on most activities after implementation. Personal carers' time on oral-communication reduced, and time on documentation increased at most measurement periods in the first 12 months after implementation. At 23 months, time on these activities had returned to pre-implementation levels. Nursing staff time on direct care remained stable after implementation. No considerable change was observed in time spent on other activities after implementation. Findings suggest that successful introduction of an EHR system in a nursing home may not interfere with nursing staff time on direct care duties. However, there is scope for improving the support provided by EHR systems through incorporation of functions to support collaborative nursing care.


Telomeric attrition with age and temperature in Eastern mosquitofish (Gambusia holbrooki).
Telomeric attrition has repeatedly been found to correlate with the ageing of organisms; however, recent research is increasingly showing that the determinants of attrition dynamics are not well understood. This study examined the relative telomere lengths in Eastern mosquitofish, Gambusia holbrooki, kept at different temperatures and at different ages. Newly born fry were randomly selected for one of four treatment groups: 20, 30, 20-30, and 30-20 °C, where the third and fourth treatment groups were gradually changed from their starting temperature to their final temperature between days 10 and 14. Telomere length was measured, and it was found that length decreased with age and that fish exposed to the 20 °C treatment had significantly shorter telomeres than those that received the 30-20 °C treatment. Telomeric attrition with age agrees with results previously found in studies of telomeres; however, the variation in attrition with temperature was not simply predictable and may be the synergistic effects of temperature and some other factor.


Regulation of type III secretion systems.
Type III secretion systems are utilised by numerous Gram-negative bacteria to efficiently interact with a host. Appropriate expression of type III genes is achieved through the integration of several regulatory pathways that ultimately co-ordinate the activity of a central transcriptional activator usually belonging to the AraC family. The complex regulatory cascades allow this virulence strategy to be utilised by different bacteria even if they occupy diverse niches that define a unique set of environmental cues. Simulating the appropriate combination of signals in vitro to allow a meaningful interpretation of the type III assembly and secretion regulatory cascade remains a common goal for researchers. Pieces of the puzzle slowly emerge to provide insightful views into the complex regulatory networks that allow bacteria to assemble and utilise type III secretion to efficiently colonise a host.


Cardiometabolic risk management in type 2 diabetes and obesity.
Type 2 diabetes has become an epidemic in the United States, mainly due to an increase in obesity and sedentary lifestyle. Diabetes is considered a cardiovascular risk equivalent, and cardiovascular death remains the most common cause of death in this population. The cardiovascular complications of diabetes, beginning as early as 10 years before the development of frank hyperglycemia, are strongly linked to the development of insulin resistance and the ensuing metabolic disarray often referred to as the metabolic syndrome. To provide proper therapy for cardiovascular prevention, the downstream effects of insulin resistance must be understood. The most important aspect of treating patients with the metabolic syndrome is the realization that treatment must begin before the development of frank hyperglycemia, particularly if cardiovascular events are to be avoided. Thus, in addition to managing the hyperglycemia that develops with the onset of diabetes, insulin resistance, dyslipidemia, and hypertension must also be properly addressed.


Rh2(esp)2-catalyzed allylic and benzylic oxidations.
The dirhodium(II) catalyst Rh2(esp)2 allows direct solvent-free allylic and benzylic oxidations by T-HYDRO with a remarkably low catalyst loading. This method is operationally simple and scalable at ambient temperature without the use of any additives. The high catalyst stability in these reactions may be attributed to a dirhodium(II,II) catalyst resting state, which is less prone to decomposition.


Compression Strength of PLA Bolts Produced via FDM.
The aim of this research was to define the compression strength of polylactic acid bolts produced using the fused deposition modelling method. In accomplishing this, static and cyclic compression tests for different metric thread sizes were carried out in accordance with ISO 4014. Tests were conducted on M42, M48, M56, M60, and M64 threads, while samples with three different types of pitch-one nominal and two fine threads-were prepared for each diameter. Standard ISO 604 for defining the compression modulus Ec was implemented as the test basis. Accordingly, the mean compression modulus value Ec for all measurements was 917.79 ± 184.99 MPa. Cyclic compression tests were then carried out on samples with the M64 × 4 thread. Fifty thread loading cycles were carried out for each variant to obtained different strain amplitude values and strain frequencies. Our work indicated that the values of the storage modulus defined in cyclic tests E' increased, while the values of the loss modulus E″ decreased when the value of the strain frequency increased. We found it not possible to determine the nature of the changes in the value of the storage modulus E' in the function of the strain amplitude. We did, however, observe an increase in the value of the loss modulus E″, together with the increase in the tested range of the strain amplitude. The determined mechanical values can be therefore be used for designing threaded connections made of polylactic acid using the fused deposition modelling method.


Applications of Carbon Dots for the Photocatalytic and Electrocatalytic Reduction of CO2.
The photocatalytic and electrocatalytic conversion of CO2 has the potential to provide valuable products, such as chemicals or fuels of interest, at low cost while maintaining a circular carbon cycle. In this context, carbon dots possess optical and electrochemical properties that make them suitable candidates to participate in the reaction, either as a single component or forming part of more elaborate catalytic systems. In this review, we describe several strategies where the carbon dots participate, both with amorphous and graphitic structures, in the photocatalysis or electrochemical catalysis of CO2 to provide different carbon-containing products of interest. The role of the carbon dots is analyzed as a function of their redox and light absorption characteristics and their complementarity with other known catalytic systems. Moreover, detailed information about synthetic procedures is also reviewed.


Phaeobacter piscinae sp. nov., a species of the Roseobacter group and potential aquaculture probiont.
Four heterotrophic, antimicrobial, motile, marine bacterial strains, 27-4T, 8-1, M6-4.2 and S26, were isolated from aquaculture units in Spain, Denmark and Greece. All four strains produced the antibiotic compound tropodithietic acid, which is a key molecule in their antagonism against fish pathogenic bacteria. Cells of the strains were Gram-reaction-negative, rod-shaped and formed star-shaped aggregates in liquid culture and brown-coloured colonies on marine agar. The predominant cellular fatty acids were C18 : 1ω7c, C16 : 0, C11 methyl C18 : 1ω7c and C16 : 0 2-OH, and the polar lipids comprised phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an aminolipid, a phospholipid and an unidentified lipid. The strains grew optimally at 31-33 °C. Growth was observed at a salt concentration between 0.5 and 5-6 % NaCl with an optimum at 2-3 %. The pH range for growth of the strains was from pH 6 to 8-8.5 with an optimum at pH 7. Based on 16S rRNA gene sequence analysis, the strains are affiliated with the genus Phaeobacter. The genome sequences of the strains have a DNA G+C content of 60.1 % and share an average nucleotide identity (ANI) of more than 95 %. The four strains are distinct from the type strains of the closely related species Phaeobactergallaeciensis and Phaeobacterinhibens based on an ANI of 90.5-91.7 and 89.6-90.4 %, respectively, and an in silico DNA-DNA hybridization relatedness of 43.9-46.9 and 39.8-41.9 %, respectively. On the basis of phylogenetic analyses as well as phenotypic and chemotaxonomic properties, the isolates are considered to represent a novel species, for which the name Phaeobacter piscinae sp. nov. is proposed. The type strain is 27-4T (=DSM 103509T=LMG 29708T).


Probing the Role of a Regional Quantitative Assessment of Amyloid PET.
In clinical practice, the amy-PET is globally inspected to provide a binary outcome, but the role of a regional assessment has not been fully investigated yet. To deepen the role of regional amyloid burden and its implication on clinical-neuropsychological features. Amy-PET and a complete neuropsychological assessment (Trail Making Test, Rey Auditory Verbal Learning Test, semantic verbal fluency, Symbol Digit, Stroop, visuoconstruction) were available in 109 patients with clinical suspicion of Alzheimer's disease. By averaging the standardized uptake value ratio and ELBA, a regional quantification was calculated for each scan. Patients were grouped according to their overall amyloid load: correlation maps, based on regional quantification, were calculated and compared. A regression analysis between neuropsychological assessment and the regional amyloid-β (Aβ) load was carried out. Significant differences were observed between the correlation maps of patients at increasing levels of Aβ and the overall dataset. The Aβ uptake of the subcortical gray matter resulted not related to other brain regions independently of the global Aβ level. A significant association of semantic verbal fluency was observed with ratios of cortical and subcortical distribution of Aβ which represent a coarse measure of differences in regional distribution of Aβ. Our observations confirmed the different susceptibility to Aβ accumulation among brain regions. The association between cognition and Aβ distribution deserves further investigations: it is possibly due to a direct local effect or it represents a proxy marker of a more aggressive disease subtype. Regional Aβ assessment represents an available resource on amy-PET scan with possibly clinical and prognostic implications.


Interleukin-22 Polymorphisms in Plasmodium falciparum-Infected Malaria Patients.
Background and Objectives. Malaria infection, caused by Plasmodium falciparum, is the most lethal and frequently culminates in severe clinical complications. Interleukin-22 (IL-22) has been implicated in several diseases including malaria. The objective of this study was to investigate the role of IL-22 gene polymorphisms in P. falciparum infection. Material and Methods. Ten single-nucleotide polymorphisms (SNPs), rs976748, rs1179246, rs2046068, rs1182844, rs2227508, rs2227513, rs2227478, rs2227481, rs2227491, and rs2227483, of IL-22 gene were genotyped through PCR-based assays of 250 P. falciparum infection. IL-22 gene promoter activity. We found that the rs2227481 TT genotype (odds ratio 0.254, confidence interval = 0.097-0.663, P. P. falciparum infection. P. P. P. P. The study suggests that IL-22 polymorphisms in rs2227481 and rs2227483 could contribute to protection against P. falciparum infection. IL-22 gene promoter activity.


Pleural effusions in critically ill patients.
Pleural effusions (PEs) are common in critically ill patients mainly as a consequence of severe cardiopulmonary disorders frequently encountered in these patients. Their impact on the pathophysiology of acute respiratory failure remains unknown. They are usually small and uncomplicated transudates that are easily overlooked on a supine portable chest X-ray and do not require drainage or infectious exudates that always require thoracocentesis. The diagnosis of PEs in critically ill patients has been revolutionized with the advent of chest ultrasound allowing easy bedside quantification of pleural fluid and making thoracocentesis a safe procedure especially in high-risk patients on mechanical ventilation. CT provides a much more accurate evaluation of the size and location of PEs and is extremely helpful in the guidance of catheters into loculated fluid collections. Hemothorax in critically ill patients is usually related to trauma or surgical interventions and requires early drainage and possibly surgical exploration.


[Value of the basophil stimulation test in the diagnosis of juvenile bronchial asthma].
The diagnostic value of histamine liberation from basophil granulocytes (BST) was investigated in asthmatic children with house dust, house dust mite or moulds allergy. BST corresponded at about 80% to skin prick test (PRICK) and radio-allergo-sorbens test (RAST) in 178 patients. The relevance of the results of BST, PRICK and RAST for the asthmatic symptoms was proved by bronchial provocation in 77 children. BST corresponded clearly better to the inhalation test than PRICK and RAST. Correspondence of BST in house dust mite allergy amounted to 94%, in house dust allergy to 100%, and in moulds allergy to 77%. Overall correspondence of BST was 92%. Even when RAST and PRICK showed different results correspondence of BST attained 91%. In cases with identical results of BST, PRICK and RAST the bronchial provocation test corresponded in 98%. It is concluded, that if history fits to BST, RAST and PRICK bronchial provocation is no longer essential for the diagnosis of relevant allergens in perennial childhood asthma. This seems to hold also in cases of house dust or house dust mite allergy, where the result of PRICK or RAST is different. Especially in childhood the use of BST in the diagnostic procedure provides the following advantages: risks of bronchial provocation and the necessary hospitalisation can be avoided, cooperation of the patient is not needed, and costs can be reduced.


The irreversible loss of a decomposition pathway marks the single origin of an ectomycorrhizal symbiosis.
Microbial symbioses have evolved repeatedly across the tree of life, but the genetic changes underlying transitions to symbiosis are largely unknown, especially for eukaryotic microbial symbionts. We used the genus Amanita, an iconic group of mushroom-forming fungi engaged in ectomycorrhizal symbioses with plants, to identify both the origins and potential genetic changes maintaining the stability of this mutualism. A multi-gene phylogeny reveals one origin of the symbiosis within Amanita, with a single transition from saprotrophic decomposition of dead organic matter to biotrophic dependence on host plants for carbon. Associated with this transition are the losses of two cellulase genes, each of which plays a critical role in extracellular decomposition of organic matter. However a third gene, which acts at later stages in cellulose decomposition, is retained by many, but not all, ectomycorrhizal species. Experiments confirm that symbiotic Amanita species have lost the ability to grow on complex organic matter and have therefore lost the capacity to live in forest soils without carbon supplied by a host plant. Irreversible losses of decomposition pathways are likely to play key roles in the evolutionary stability of these ubiquitous mutualisms.


Biotic and Environmental Drivers of Plant Microbiomes Across a Permafrost Thaw Gradient.
Plant-associated microbiomes are structured by environmental conditions and plant associates, both of which are being altered by climate change. The future structure of plant microbiomes will depend on the, largely unknown, relative importance of each. This uncertainty is particularly relevant for arctic peatlands, which are undergoing large shifts in plant communities and soil microbiomes as permafrost thaws, and are potentially appreciable sources of climate change feedbacks due to their soil carbon (C) storage. We characterized phyllosphere and rhizosphere microbiomes of six plant species, and bulk peat, across a permafrost thaw progression (from intact permafrost, to partially- and fully-thawed stages) via 16S rRNA gene amplicon sequencing. We tested the hypothesis that the relative influence of biotic versus environmental filtering (the role of plant species versus thaw-defined habitat) in structuring microbial communities would differ among phyllosphere, rhizosphere, and bulk peat. Using both abundance- and phylogenetic-based approaches, we found that phyllosphere microbial composition was more strongly explained by plant associate, with little influence of habitat, whereas in the rhizosphere, plant and habitat had similar influence. Network-based community analyses showed that keystone taxa exhibited similar patterns with stronger responses to drivers. However, plant associates appeared to have a larger influence on organisms belonging to families associated with methane-cycling than the bulk community. Putative methanogens were more strongly influenced by plant than habitat in the rhizosphere, and in the phyllosphere putative methanotrophs were more strongly influenced by plant than was the community at large. We conclude that biotic effects can be stronger than environmental filtering, but their relative importance varies among microbial groups. For most microbes in this system, biotic filtering was stronger aboveground than belowground. However, for putative methane-cyclers, plant associations have a stronger influence on community composition than environment despite major hydrological changes with thaw. This suggests that plant successional dynamics may be as important as hydrological changes in determining microbial relevance to C-cycling climate feedbacks. By partitioning the degree that plant versus environmental filtering drives microbiome composition and function we can improve our ability to predict the consequences of warming for C-cycling in other arctic areas undergoing similar permafrost thaw transitions.


Modulation of smooth muscle contractility by CHASM, a novel member of the smoothelin family of proteins.
Cyclic nucleotides acting through their associated protein kinases, the cGMP- and cAMP-dependent protein kinases, can relax smooth muscles without a change in free intracellular calcium concentration ([Ca2+]i), a phenomenon referred to as Ca2+ desensitization. The molecular mechanisms by which these kinases bring about Ca2+ desensitization are unknown and an understanding of this phenomenon may lead to better therapies for treating diseases involving defects in the contractile response of smooth muscles such as hypertension, bronchospasm, sexual dysfunction, gastrointestinal disorders and glaucoma. Utilizing a combination of real-time proteomics and smooth muscle physiology, we characterized a distinct subset of protein targets for cGMP-dependent protein kinase in smooth muscle. Among those phosphoproteins identified was calponin homology-associated smooth muscle (CHASM), a novel protein that contains a calponin homology domain and shares sequence similarity with the smoothelin family of smooth muscle specific proteins. Recombinant CHASM was found to evoke relaxation in a concentration dependent manner when added to permeabilized smooth muscle. A co-sedimentation assay with actin demonstrated that CHASM does not possess actin binding activity. Our findings indicate that CHASM is a novel member of the smoothelin protein family that elicits Ca2+ desensitization in smooth muscle.


The moderating effects of acculturation on the relation of parenting strategies to unhealthy weight control behaviors in Hispanic daughters.
There is a dearth of research regarding the association of child and parent traits to the use of unhealthy weight control behaviors among minority girls with obesity. This study examined the moderating effects of mothers' and daughters' acculturation in the relation of parenting strategies (setting limits, monitoring and discipline) to unhealthy weight control behaviors in Hispanic girls with obesity. Participants included 148 Hispanic mother-daughter dyads (Mage = 39.1, SD = 6.4 years; Mage = 11.3, SD = 1.5 years, respectively). Two-thirds of the mothers were born in Mexico and 46% of them reported low levels of acculturation. In contrast, almost all daughters (90%) were born in the United States and reported high levels of acculturation. Participants were recruited through school nurses and social agencies community coordinators. Mothers and daughters completed surveys on demographic, acculturation, unhealthy weight control behaviors (daughters only) and parenting strategies (mothers only), and had their height, weight, and adiposity assessed. Results from a hierarchical regression analysis revealed that daughters' acculturation, but not mothers' acculturation, moderated the relation of parenting limit setting to daughters' reported engagement in unhealthy weight control behaviors (β = 1.12, p = 0.007). That is, mothers who used more limit setting were less likely to have daughters engaging in unhealthy weight control behavior and this association was stronger among low acculturated girls than among their highly acculturated counterparts. Future research should assess cultural influences and parenting practices in a sample of Hispanic mothers and their adolescent daughters of varied weight statuses and acculturation levels.


Eukaryote-like serine/threonine kinases and phosphatases in bacteria.
Genomic studies have revealed the presence of Ser/Thr kinases and phosphatases in many bacterial species, although their physiological roles have largely been unclear. Here we review bacterial Ser/Thr kinases (eSTKs) that show homology in their catalytic domains to eukaryotic Ser/Thr kinases and their partner phosphatases (eSTPs) that are homologous to eukaryotic phosphatases. We first discuss insights into the enzymatic mechanism of eSTK activation derived from structural studies on both the ligand-binding and catalytic domains. We then turn our attention to the identified substrates of eSTKs and eSTPs for a number of species and to the implications of these findings for understanding their physiological roles in these organisms.


Effect of Cytochrome P450 (CYP) 2D6 Genetic Polymorphism on the Inhibitory Action of Antidepressants on CYP2D6-Mediated Dopamine Formation from p-Tyramine.
The inhibitory effects of antidepressants, such as imipramine, desipramine, and fluvoxamine, on dopamine formation from p-tyramine catalyzed by cytochrome P450 (CYP) 2D6.2 (Arg296Cys, Ser486Thr) and CYP2D6.10 (Pro34Ser, Ser486Thr), were compared with those on dopamine formation catalyzed by CYP2D6.1 (wild type), to investigate the effect of a CYP2D6 polymorphism on neuroactive amine metabolism in the brain. Inhibition constants (Ki) of the antidepressants toward dopamine formation catalyzed by CYP2D6.1, CYP2D6.2, and CYP2D6.10, which were expressed in recombinant Escherichia coli, were compared. Imipramine and desipramine competitively or non-competitively inhibited dopamine formation mediated by CYP2D6.1, CYP2D6.2, and CYP2D6.10 with Ki values of 3.9-4.9, 5.9-9.6, and 26.7-37.5 µM, respectively. The maximal velocity (Vmax) values for dopamine formation by all CYP2D6 variants gradually increased with increasing fluvoxamine concentrations up to 40-100 µM, indicating that fluvoxamine stimulated dopamine formation. These results suggest that the inhibition/stimulation of CYP2D6-mediated dopamine formation by these antidepressants would be affected by CYP2D6 polymorphism in the brain. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.


Clinical value of free-thyroxin measurements.
Although discrepancies have been reported between free thyroxin (fT4) in serum and actual thyrometabolic status, the concentration of free thyroid hormones in blood is thought to be an important determinant of the thyrometabolic status of patients. Therefore, the diagnostic value of fT4 measurement has been emphasized. This prompted us to evaluate the diagnostic significance of direct fT4 measurement. We conclude that: (a) The different fT4 radioimmunoassays we examined did not excel the total thyroxin, fT4 index, or thyroxin/thyroxin-binding globulin ratio in the laboratory assessment of thyroid status and alterations in thyroid hormone-thyroxin-binding globulin relationships. (b) The fT4 values obtained by direct or indirect methods always shifted in parallel to total thyroxin with respect to borderline increased or decreased total thyroxin, subclinical hypothyroidism, isolated hypertriiodothyroninemia, and thyroxin substitution.


Synthesis of (R)-mellein by a partially reducing iterative polyketide synthase.
Mellein and the related 3,4-dihydroisocoumarins are a family of natural products with interesting biological properties. The mechanisms of dihydroisocoumarin biosynthesis remain largely speculative today. Here we report the synthesis of mellein by a partially reducing iterative polyketide synthase (PR-PKS) as a pentaketide product. Remarkably, despite the head-to-tail homology shared with several fungal and bacterial PR-PKSs, the mellein synthase exhibits a distinct keto reduction pattern in the synthesis of the pentaketide. We present evidence to show that the ketoreductase (KR) domain alone is able to recognize and differentiate the polyketide intermediates, which provides a mechanistic explanation for the programmed keto reduction in these PR-PKSs.


Inhibition of microsomal oxidation of alcohols and of hydroxyl-radical-scavenging agents by the iron-chelating agent desferrioxamine.
Rat liver microsomes (microsomal fractions) catalyse the oxidation of straight-chain aliphatic alcohols and of hydroxyl-radical-scavenging agents during NADPH-dependent electron transfer. The iron-chelating agent desferrioxamine, which blocks the generation of hydroxyl radicals in other systems, was found to inhibit the following microsomal reactions: production of formaldehyde from either dimethyl sulphoxide or 2-methylpropan-2-ol (t-butylalcohol); generation of ethylene from 4-oxothiomethylbutyric acid; release of 14CO2 from [I-14C]benzoate; production of acetaldehyde from ethanol or butanal (butyraldehyde) from butan-1-ol. Desferrioxamine also blocked the increase in the oxidation of all these substrates produced by the addition of iron-EDTA to the microsomes. Desferrioxamine had no effect on a typical mixed-function-oxidase activity, the N-demethylation of aminopyrine, nor on the peroxidatic activity of catalase/H2O2 with ethanol. H2O2 appears to be the precursor of the oxidizing radical responsible for the oxidation of the alcohols and the other hydroxyl-radical scavengers. Chelation of microsomal iron by desferrioxamine most likely decreases the generation of hydroxyl radicals, which results in an inhibition of the oxidation of the alcohols and the hydroxyl-radical scavengers. Whereas desferrioxamine inhibited the oxidation of 2-methylpropan-2-ol, dimethyl sulphoxide, 4-oxothiomethylbutyrate and benzoate by more than 90%, the oxidation of ethanol and butanol could not be decreased by more than 45-60%. Higher concentrations of desferrioxamine were required to block the metabolism of the primary alcohols than to inhibit the metabolism of the other substrates. The desferrioxamine-insensitive rate of oxidation of ethanol was not inhibited by competitive hydroxyl-radical scavengers. These results suggest that primary alcohols may be oxidized by two pathways in microsomes, one dependent on the interaction of the alcohols with hydroxyl radicals (desferrioxamine-sensitive), the other which appears to be independent of these radicals (desferrioxamine-insensitive).