Mechanically Tunable Hollow Silica Ultrathin Nanoshells for Ultrasound Contrast Agents.
Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4-3.8 nm and diameters from 2-23 nm.


The outcome of treatment of 313 patients with T-1 (UICC) prostate cancer treated with external beam irradiation.
Three hundred and thirteen patients with UICC T-1 N-0 M-0 prostate cancer were treated with external beam irradiation in 1973 and 1974 or in 1978, and their outcome determined 3-10 years after treatment. Survival over the first 5 years was comparable to that expected for a group of age matched normal males (77% vs. 81%), but during the second 5-year interval, there was a decrease in survival below that expected (51% vs 62%), a reflection of death in patients who developed metastasis as a first recurrence (18%). Overall, 72% of patients were free of any recurrence at 5 years and, 88% free of infield recurrence. The development of metastatic recurrence was significantly related to grade; at 5 years 87% of grade I, 79% of grade II and 69% of grade III patients were free of metastasis. There was a trend for increased local recurrence with increasing grade, but it was not statistically significant. There was a dose/response relation for complications, and radiation doses above 6500 cGy are associated with an increase in complication from 6% to 11% (p = .09). Complications requiring hospitalization for evaluation or management occurred in 30 (10%) of 313 patients. There were no deaths from complications and less than 2% of patients required surgical correction of complications. External beam radiation offers the patient with early prostate cancer a favorable opportunity for cure without the morbidity of impotence, incontinence, and occasional death experienced following LND and radical prostatectomy. Lymph node dissection does not seem necessary for most patients with T-1 prostate cancer as the positive yield in those with Grades I and II cancers is less than the complications of the procedure, and extensive involvement can be detected by non-invasive means.


16S rRNA nanopore sequencing for rapid diagnosis of causative bacteria in bovine mastitis.
The rapid identification of specific bacterial pathogens in bovine mastitis is crucial for appropriate antimicrobial treatment. Sequencing of 16S rRNA gene amplicons is a proven, useful strategy for diagnosing bacterial infections. In this study, the use of 16S rRNA analysis with nanopore sequencer for the rapid identification of causative bacteria in bovine mastitis, was evaluated. DNA was extracted from 122 milk samples from cattle with suspected mastitis based on clinical symptoms. 16S rRNA gene amplicon sequencing was conducted using a nanopore sequencer. The efficacy of bacterial identification was verified by comparison with conventional culture methods. Nanopore sequencing identified the causative bacteria with high accuracy within approximately 6 h from the time of sample collection. When the major causative bacteria of bovine mastitis (Escherichia coli, Streptcoccus uberis, Klebsiella pneumoniae, and Staphylococcus aureus) were detected by nanopore sequencing, 98.3% of the results were consistent with identification through conventional culturing methods. 16S rRNA gene analysis using a nanopore sequencer enabled the rapid and accurate identification of bacterial species in bovine mastitis.


Altered bladder function as the only and late presenting symptom of ependymoma of the filum terminale.
Tumors of the spinal cord present as a rule with posterior pain with or without radiation to the limbs, with loss of strength and/or sensory disturbances. We report a case in which acute retention of urine was the only presenting symptom.


Efficient preparation of terminal conjugated dienes by coupling of dienol phosphates with grignard reagents under iron catalysis.
An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the presence of Fe(acac)3 is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone of Diparopsis castanea according to a very expeditious strategy.


Application of MDPF and fluorescamine XV chiroptical properties of MDPF condensation compounds with dipeptides in situ.
2-Methoxy-2,4-diphenyl-3(2H)-furanone (MDPF) reacts readily with the free amino group of a dipeptide to form a pyrrolinone-type chromophore with absorption maxima at 275-285 and 370-390 nm. A simple test tube procedure is described which allows in situ correlation of the absolute configuration of the NH2-terminal amino acid of a dipeptide with the chiroptical properties of its chromophoric derivative. In several cases, unexpected deviation of the chiroptical characteristics from previously established empirical rules is observed.


Successful amelioration of tinnitus in a stroke patient by low-dose gabapentin.
Bilaterally progressive tinnitus and hearing impairment occurred in a hypertensive patient shortly after an episode of right ganglionic hemorrhage. Audiometric tests showed a mixed sensorineural and conduction hearing loss. When low-dose gabapentin was administrated for the pre-existing postherpetic thoracic neuralgia, the tinnitus dramatically improved but recurred after discontinuation of the drug. Hearing function did not change. In view of a controversy of gabapentin and tinnitus in previous trials, the findings in this patient support that low-dose gabapentin benefits the subgroup of tinnitus patients with secondary contributing factors, such as stroke.


Pediatric liver transplantation in Australia and New Zealand: The case for a collaborative anesthetic database.
Liver transplantation is conducted with strict oversight of organizational structure and clinical practice. However, specific regulations pertaining to the delivery of anesthetic services are lacking and consideration of departmental structure and mechanisms for quality control must occur at a local level. Busy centers collect and process sufficient data to guide this process but those with low case loads may not generate enough data for useful analysis. In Australia and New Zealand, pediatric liver transplants are performed at only four locations. As these operations are not equally distributed geographically or temporally there are periods of low activity at some centers. As anesthesia affects patient outcome, quality assurance activities are important in this setting. Provide a global overview of the structure and function of liver transplantation networks. Identify issues related to provision of pediatric anesthetic services with specific reference to Australasia. Examine anesthetic data from a single pediatric center to illustrate benefits and limitations of such activity. Pediatric liver transplant centers from Australia and New Zealand were surveyed to determine the organizational and logistical issues related to a liver transplant service. An audit of 15 years of liver transplants from a single center was conducted for benchmarking purposes and to identify changes in anesthetic practice over time. Pediatric liver transplants performed in Queensland from January 2005 to December 2019 were reviewed. Changes in transfusion practice reflected international trends. Morbidity and mortality were comparable to international data. Important complications such as hepatic artery and portal vein thrombosis were uncommon and did not generate enough data for further analysis. Combining the anesthetic liver transplant data from all sites in a single registry would expand data collection and generate broadly applicable findings. We propose the establishment of an Australasian pediatric anesthetic liver transplant database.


Subtypes of muscarinic receptors on adrenergic nerves and vascular smooth muscle of the canine saphenous vein.
Experiments were designed to characterize pre- and postjunctional muscarinic receptors in the canine saphenous vein. In rings contracted by 2-Hz electrical stimulation, acetylcholine produced concentration-dependent relaxations that result from prejunctional inhibition of norepinephrine release from adrenergic nerve endings (prejunctional effect). In quiescent preparations, acetylcholine caused concentration-dependent contractions (postjunctional effect). Both responses to acetylcholine were inhibited in a competitive manner by atropine, pirenzepine and gallamine. The affinity of atropine for pre- and postjunctional muscarinic receptors was similar (pKB = 8.7 and 9.2, respectively). However, gallamine displayed higher affinity for the prejunctional than for the postjunctional receptor (pKB = 6.1 and 4.7, respectively), whereas the converse was true for pirenzepine (pKB = 6.5 and 8.1). The data support the presence in the canine saphenous vein of two muscarinic receptor subtypes, M1 postjunctionally and M2 prejunctionally, which are distinguishable by selective antagonists.


Is Routine Screening of Young Asymptomatic MEN1 Patients Necessary?
Recent clinical practice guidelines recommend that routine screening of MEN1 mutation carriers should start at the age of 5 years. The occurrence of clinically relevant MEN1 organ manifestations in children (≤18 years) was evaluated. Two prospective collected databases of MEN1 patients (n = 166) who underwent annual screening were retrospectively analyzed for organ manifestations in MEN1 patients ≤18 years. The follow-up was based on the most recent screening examination until December 2015. Twenty [11 females, 9 males, (12%)] of 166 MEN1 patients were diagnosed with at least one organ manifestation at age ≤18 years. The most frequent manifestation was mild asymptomatic pHPT (n = 9, 45%, age range 8-18 years). Eight (40%) young patients had pNENs (three non-functioning pNENs, five insulinomas, age range 9-18 years). All five insulinomas were diagnosed based on hypoglycemic symptoms. The other organ manifestations were asymptomatic pituitary adenomas in six patients (30%, age range 15-18 years) and a bronchial carcinoid in one 15-year-old patient. Only six (30%) patients ≤18 years had clinically relevant organ manifestations. Symptomatic or severe manifestations in MEN1 patients rarely occur below the age of 16 years. With regard to psychological burden and cost-effectiveness, routine screening of asymptomatic MEN1 patients should be postponed at least until the age of 16 years.


[Outcome in traumatic brain injury : Considered from a neurological viewpoint].
There are many studies on the prognosis and mortality for the acute care of traumatic brain injury (TBI) during the first year. Prediction of the long-term outcome after TBI is more difficult, and can be ascribed to indistinct methods and the necessity of taking into account multiple influencing factors. The main factors that determine the long-term outcome of TBI are described. A summary of the relevant literature and experience of the reintegration of TBI patients are presented. The major factors predicting the long-term outcome of TBI are well-known. They can be measured by International Classification of Functioning, Disability and Health (ICF) of the World Health Organization and self-reported quality of life, which are important for the prognosis. Returning to work has a particularly positive effect on the quality of life. Environmental factors are most predictive of long-term TBI outcome. The awareness of the interaction of all these factors requires a individualized long-term rehabilitation.


Postsurgical Intrauterine Adhesions after Hysteroscopic Myomectomy Using the Myoma Pseudocapsule Preservation Technique Evaluated bv Second-look Hysteroscopy: A Retrospective Comparative Study.
To analyze the frequency and risk factors of postsurgical intrauterine adhesions (IUAs) using second-look hysteroscopy (SLH) in patients undergoing hysteroscopic myomectomy performed using the myoma pseudocapsule preservation technique for submucosal myoma. Retrospective cohort study. University hospital from January 2017 to December 2019. A total of 124 patients underwent hysteroscopic myomectomy and SLH. None. Surgical duration, intraoperative blood loss, number of enucleated myomas, volume of specimen, and postsurgical IUA evaluated by SLH. Postsurgical IUA were found in 5 of 124 cases (4.0%) at SLH. There were no cases of IUA formation in cases in which a single myomas was resected (0 of 83 cases, 0%); all cases were multiple myomas (5 of 41 cases, 12.2%), and IUA significantly occurred more frequently in cases of multiple myoma (p = .003). Univariate analyses showed that the IUA group contained a significantly larger number of enucleated uterine myoma (p <.001), required a longer operation (p = .003), and displayed an increased volume of intraoperative bleeding (p = .007), and the heavier the specimen, the greater the number of patients that had inserted an intrauterine device than the group that did not display postsurgical IUA. Multivariate logistic regression analysis of the risk factors of postsurgical IUA showed that the number of enucleated myomas was strongly associated with IUA (odds ratio, 1.45; 95% confidence interval, 1.06-1.97). The frequency of postsurgical IUA after hysteroscopic myomectomy was high in cases of multiple myoma and may be a risk factor. SLH should be actively pursued in cases where the patient desires to bear children, and an informed consent should be attained before performing surgery.


Increased cervical electrical activity during oestrus in progestagen treated ewes: Possible role in sperm transport.
The aim of this investigation was to characterize the pattern of cervical myoelectrical activity (EMG) in the sheep, during the periovulatory period, after synchronization of oestrus with progestagen and eCG. EMG was measured with a computerised modular system in five ewes previously fitted with a pair of monopolar Teflon needle electrodes in the muscle layers of the cervix. Each ewe was submitted to oestrus synchronization treatment with intravaginal progestagen sponge during 12 days, and the administration of 500 IU of eCG at the withdrawal of sponge. EMG was recorded in each animal during 19 h, starting 44 h after withdrawal of sponge. The number and duration of events were determined every hour during the experiment. Two distinct event durations were identified: one lasting less than 200 s and another lasting between 300 and 500 s. The two types of events analysed (less than 200 s and lasting between 300 and 500 s) had a similar pattern during the period of observation although they were not in synchrony. For events lasting less than 200 s, activity increased between 48 and 50 h after sponge withdrawal, with the peak of activity being observed between 51 and 53 h. For events of 300-500 s duration, the peak of activity was observed between 48 and 50h after sponge withdrawal and activity was maintained until 51-53 h. The increase in cervical motility observed in progestagen-eCG treated ewes is in keeping with the increase in cervical activity observed by others in natural cycling animals, and suggests that exogenous hormones used in synchronization protocols had no deleterious action on cervical motility during periovulatory period. The enhanced activity of cervical muscle layer found around the time of mating and/or AI suggests it may play an important role as a regulatory mechanism of sperm transport. Taking advantage of the cervical responsiveness to various drugs, experimental modulation of cervical activity could be used to facilitate cervical sperm transport and consequent improve of fertility after cervical AI.


[Radial and proximo-distal distribution of hydrolytic enzymes in the small intestine at rest and during digestion].
Alpha-amylase was present in considerable amount in the chyme in rats both at rest and during digestion, in the latter case its level being increased. Activity of intrinsic intestinal enzymes dominated in the homogenate of the mucosa. Transition from fasting to feeding and digestion increased the level of alkaline phosphatase and dipeptidase activities in the homogenate of the mucosa. The data obtained suggest the final stages of biopolymers' hydrolysis to be localized in various enterocyte structures. The surface mucus, owing to absorbed pancreatic enzymes, binding proteins and other types of physiologically active molecules, is assumed to play the role of a specific molecular filter and take part in the initial stages of digestion.


Double-bundle bone-patellar tendon-bone and gracilis in ACL reconstruction.
An original technique for the reconstruction of the anterior cruciate ligament is explained. Two bundles are reconstructed using the central third of the patellar tendon and the gracilis tendon, passed through four tunnels but requiring only two interference screws for fixation. Level of evidence V.


Enteral absorption and biotransformation of the food additive octyl gallate in the rat.
Following oral administration of 14C-labelled octyl gallate in a single dose of 15 mg/kg to female rats, only 20-30% of the radioactivity administered was detected in the tissues, while 60-80% of the dose was found in the contents of the gastro-intestinal tract up to 12 hr after administration. Isotope dilution analysis demonstrated the presence of the unchanged ester in the tissues. In the liver, the highest concentration of the ester demonstrated was 1.6 micrograms/g. in a rat killed 10 min after treatment. In the 24 hr following ip administration of labelled octyl gallate, about 91% of the administered radioactivity was recovered. Most of this was in the form of metabolites, only 9% being accounted for as unchanged ester.


Characterization of circulating monocytes expressing HLA-DR or CD71 and related soluble factors for 2 weeks after severe, non-thermal injury.
Severe injury is associated with changes in monocytes that may contribute to poor outcomes. Longitudinal characterization of monocyte response patterns after trauma may provide added insight into these immunological alterations. Venous blood obtained seven times during post-injury days 1 through 13 from 61 patients with an injury severity score >20 was assessed by flow cytometry for monocytes (CD14+) expressing HLA-DR or CD71 (transferrin receptor) and for circulating levels of interleukin (IL) 1alpha, IL-1beta, IL-6, soluble CD14 (sCD14), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), and endotoxin. Urine neopterin was measured by high-pressure liquid chromatography, expressed as a neopterin-creatinine ratio. Trauma patients had leucocytosis days 1 through 13, monocytosis days 5 through 13, reduced proportions of CD14+HLA-DR+ cells days 2 through 5, and elevated proportions of CD14+CD71+ cells days 1 through 13. Neopterin was elevated all days, peaking on day 10. sCD14 was elevated days 2 through 13, and there were sporadic elevations of IL-1alpha, IL-1beta, IL-6, TNF-alpha, PGE(2), TXB(2), and endotoxin. Sepsis syndrome patients (n = 6) had larger and more prolonged reductions in CD14+HLA-DR+ cells and higher neopterin values, in comparison with uneventful patient outcomes. Altered proportions of monocytes expressing HLA-DR and CD71 and elevated sCD14 and urine neopterin levels, for up to 2 weeks after severe injury, underscores an extended period of profound immunological effects. Additional studies to more fully assess temporal monocyte response patterns after severe injury, including activation, may be warranted.


Lipid oxidation and its implications to meat quality and human health.
Lipid oxidation not only negatively influences the sensory characteristics but also the functional characteristics of meat. During the process, various primary and secondary by-products are formed depending upon the types of fatty acids, oxygen availability, and the presence of pro- and antioxidants. Some of the lipid oxidation products only influence the quality of meat but others are implicated to various diseases and human health. Therefore, prevention of lipid oxidation in meat is important for meat quality and for human health as well. The imbalance of oxidants and antioxidants that favors oxidants in the biological system is called oxidative stress in the body. Although the body is equipped with defense enzymes and antioxidant compounds, there are many sources of oxidants or free radicals that can destroy the oxidants/antioxidants balance. Therefore, supply of extra antioxidants through food can help maintaining the balance in favor of antioxidants and help preventing various diseases and malfunctions of our body.


An unusual adverse drug reaction?
Adult Still Disease (ASD) is a rare (incidence 1-1,6/1,000,000 in Europe) seronegative polyarthropathy diagnosed with clinical criteria, excluding other etiologies. Minocycline, a semisynthetic derivative of tetracycline, has been associated with many adverse effects. We present the case of a 18-years-old man with a high suspicion of an adverse drug reaction (ADR), that was finally diagnosed of ASD. In order to exclude other diseases, laboratory test, radiology and allergological studies were performed. The results of the allergological studies excluded the possibility of an ADR. The rest of the results determined the diagnosis of ASD. It's necessary to emphasize the importance of an accurate differential diagnosis in cases like this, because many diseases may mimic an ADR, and may be underdiagnosed (or misdiagnosed).


Analysis of restriction fragment length polymorphism of cytochrome P450 3A43 gene and evaluation of the incidence of CYP3A43*1B allele in europeoid residents of West Siberia.
Analysis of restriction fragment length polymorphism is proposed for detecting CYP3A43 gene c1047 > T mutation. The incidence of this mutation (CYP3A43*1B allele) was evaluated in 102 europeoid residents of West Siberia and it was found to be 12.25%.


Emulsification and encapsulation properties of conjugates formed between whey protein isolate and carboxymethyl cellulose under acidic conditions.
In this study, carboxymethyl cellulose (CMC) was used to interact with whey protein isolate (WPI) to prepare conjugates as emulsifiers and embedding agents, which can be used under acidic conditions. Firstly, the effects of ratios and pH values on the formation of WPI-CMC conjugates were investigated. The turbidity and particle size of WPI were reduced in the presence of CMC at pH 4.6 (near the isoelectric point). Then the characterization of physicochemical properties indicated that electrostatic interactions played a major role in the formation of WPI-CMC conjugates, thereby changing the structure and function of conjugates. CMC and WPI reached the optimal aggregation state at pH 4.6 and a ratio of 4:1. The conjugates exhibited excellent emulsifying activity and stability for the oil-in-water emulsions. WPI-CMC conjugates also could provide protection to allicin by preventing degradation under environmental stresses, while maintaining its antioxidant activity.


The economic production of anti-microbial factor from human promyelocytes in low serum containing medium under chemostat cultivation.
It proves that a purifed Anti-Microbial Factor (AMF) from human promyelocytes has strong activity on Gram(-) and Gram(+) bacteria, showing 0.5 (μg/ml) of Minimal Bacterical Concentration (MBC) on bothE. coli andS. aureus. For mass production of AMF, chemostat cultivation is recommended to accumulate cells out of the reactor since it is an intracellular protein and its system requires only 1% serum in the medium. Its production process proves to be closely growth-related. 1.7×10(-8) (μg/viable cell/day) of maximum specific AMF production rate is estimated at 0.026 h(-1) of dilution rate, maintaining 6×10(6) (viable cell/ml). Ca. 300 (mg/ml) of crude AMF can be obtained for 50 days of continuous cultivation under optimal conditions. The cell growth reaches relatively fast steady state.


Familial disease with a risk of sudden death: a longitudinal study of the psychological consequences of predictive testing for long QT syndrome.
Since 1996, in the Netherlands, cardiac and molecular screening has been performed in families with the long QT syndrome, a potentially life-threatening but treatable cardiac arrhythmia syndrome. The psychological consequences of predictive cardiac and molecular screening in these families are relatively unknown. A psychological study was initiated to investigate the extent and course of distress caused by this new form of predictive genetic testing. We carried out a prospective study to assess the extent and course of disease-related anxiety and depression, caused by predictive genetic testing, in applicants and their partners from the time of first consultation until 18 months after the disclosure of the result of genetic testing. Seventy-seven applicants and 57 partners were investigated for measures of distress in 3 assessments. Those individuals who received an uncertain electrocardiogram result seemed especially vulnerable for distress, at least in the short term. The distress levels in the whole group of applicants were largely restored within 18 months. However, the disease-related anxiety scores in carriers remained relatively increased at long term. As compared with partners of noncarriers, partners of mutation carriers had higher levels of disease-related anxiety at all 3 assessments. Predictive testing for long QT syndrome consisting of cardiologic testing followed by molecular testing leads to distress, especially in carriers with an uncertain electrocardiogram and their partners at first visit. These distress levels return to normal at long term. However, for carriers with an uncertain electrocardiogram, the incidence of clinically relevant distress was high, most probably also caused by the consequences of having the disease.


Endovascular Repair for Abdominal Aortic Aneurysm in Mainland China: A Systematic Review and Meta-Analysis.
The aim of this study was to evaluate the safety, applicability, and outcomes of the endovascular aneurysm repair (EVAR) technique for patients in mainland China with abdominal aortic aneurysm (AAA) by performing a systematic review. We conducted a systematic search using the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to identify Chinese studies on the management of AAAs using the EVAR technique published in English between January 2000 and December 2020. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The included studies investigated the clinical outcomes and postprocedural complications of using EVAR techniques. Sixteen studies reported a total of 3,024 AAA patients. The follow-up period ranged from 1 to 133 months. The mean follow-up time was 38.5 months, the mean age was 69.2 years, and the mean aneurysm diameter was 56.1 mm. The pooled technical success rate was 95% (95% confidence interval [CI]: 92-96%). The endoleak rate was 7% (95% CI: 6-8%). The rate of endoleak requiring reintervention was 3% (95% CI: 3-4%). The 30-day morbidity rate was 9% (95% CI: 6-14%). The 30-day mortality rate was 2% (95% CI: 1-3%). The follow-up mortality was 5% (95% CI: 3-8%). The results of the study showed that using the EVAR technique for treating patients in mainland China with AAAs produced encouraging mid-term outcomes. Long-term outcomes should be examined in future research.


Tissue microarrays.
New high-throughput screening technologies have led to the identification of hundreds of genes with potential roles in cancer or other diseases. For evaluation of promising candidate genes, however, in-situ analysis of high numbers of clinical tissue samples is mandatory. The tissue microarray (TMA) technology greatly facilitates such analysis. In this method minute tissue samples (0.6 mm in diameter) from up to 1000 different tissues can be analyzed on one microscope glass slide. All in-situ methods suitable for histological studies can be applied to TMAs without major changes in protocols, including immunohistochemistry, fluorescence in-situ hybridization, or RNA in-situ hybridization. Because all tissues are analyzed simultaneously with the same batch of reagents, TMA studies provide an unprecedented degree of standardization, speed, and cost efficiency.


Distinct characteristics of single starch-binding domain SBD1 derived from tandem domains SBD1-SBD2 of halophilic Kocuria varians alpha-amylase.
Kocuria varians alpha-amylase contains tandem starch-binding domains SBD1-SBD2 (SBD12) that possess typical halophilic characteristics. Recombinant tandem domains SBD12 and single domain SBD1, both with amino-terminal hexa-His tag, were expressed in and purified to homogeneity from Escherichia coli. The circular dichroism (CD) spectrum of His-SBD12 was characterized by a positive peak at 233 nm ascribed to the aromatic stacking. Although the signal occurred in the far UV region, it is an indication of tertiary structure folding. CD spectrum of single domain His-SBD1 exhibited the same peak position, signal intensity and spectral shape as those of His-SBD12, suggesting that the aromatic stacking must occur within the domain, and that two SBD domains in SBD12 and SBD1 has a similar folded structure. This structural observation was consistent with the biological activity that His-SBD1 showed binding activity against raw starch granules and amylose resin with 70-80% efficiency compared with binding of equimolar His-SBD12. Although the thermal unfolding rate of SBD12 and SBD1 were similar, the refolding rates of SBD12 and SBD1 from thermal melting were greatly different: His-SBD12 refolded slowly (T(1/2) = ~84 min), while refolding of single domain His-SBD1 was found to be 20-fold faster (T(1/2) = 4.2 min). The possible mechanism of this large difference in refolding rate was discussed. Maltose at 20 mM showed 5-6 °C increase in thermal melting of both His-SBD12 and His-SBD1, while its effects on the time course of unfolding and refolding were insignificant.


Micellar behavior of aqueous solutions of dodecyldimethylethylammonium bromide, dodecyltrimethylammonium chloride and tetradecyltrimethylammonium chloride in the presence of alpha-, beta-, HPbeta- and gamma-cyclodextrins.
Conductivity, static fluorescence and (1)H NMR measurements have been carried out to study the micellar behavior of aqueous solutions of dodecyldimethylethylammonium bromide (DDAB), dodecyltrimethylammonium chloride (DTAC) and tetradecyltrimethylammonium chloride (TDAC) in absence and presence of alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HPbeta-CD) and gamma-cyclodextrin (gamma-CD). The conductivity measurements were carried out at 298.15 K. The influence of cyclodextrins on the micellar parameters, such as cmc* (apparent critical micellar concentration), beta (degree of ionization) have been analyzed. Thermodynamics of the systems was discussed in terms of the change in standard free energy of micellization, DeltaG(m)(0). Micellization was found to be less spontaneous in presence of cyclodextrins. The fluorescence intensity of the surfactant solutions is enhanced by the addition of cyclodextrins. The association constants obtained from conductivity and fluorescence data suggest the binding of gamma-CD with the surfactants to be strongest among all the cyclodextrins used. (1)H NMR chemical shift changes provide powerful means for probing the cyclodextrin-micellar interactions and inclusion of surfactant is shown by the change in the chemical shift of some of the guest and host protons in comparison with the chemical shifts of the same protons in the free compounds.


Integrator enforces the fidelity of transcriptional termination at protein-coding genes.
Integrator regulates the 3′-end processing and termination of multiple classes of noncoding RNAs. Depletion of INTS11, the catalytic subunit of Integrator, or ectopic expression of its catalytic dead enzyme impairs the 3′-end processing and termination of a set of protein-coding transcripts termed Integrator-regulated termination (IRT) genes. This defect is manifested by increased RNA polymerase II (RNAPII) readthrough and occupancy of serine-2 phosphorylated RNAPII, de novo trimethylation of lysine-36 on histone H3, and a compensatory elevation of the cleavage and polyadenylation (CPA) complex beyond the canonical polyadenylation sites. 3′ RNA sequencing reveals that proximal polyadenylation site usage relies on the endonuclease activity of INTS11. The DNA sequence encompassing the transcription end sites of IRT genes features downstream polyadenylation motifs and an enrichment of GC content that permits the formation of secondary structures within the 3′UTR. Together, this study identifies a subset of protein-coding transcripts whose 3′ end processing requires the Integrator complex.


H. pylori positivity and various pathological, endoscopic and clinical features correlated with each other.
To investigate the relationship between dyspepsia symptom scores and endoscopic appearances, and histopathological findings and helicobacter pylori positivity in patients having dyspepsia symptom. The study was conducted at the gastroenterology outpatient clinic of Adnan Menderes University, School of Medicine, Aydin, Turkey from April 2012 to July 2012 and comprised patients between 18-65 years of age who were admitted with dyspepsia. Glasgow dyspepsia severity scoring was done with questions posed orally to the patients. In histopathological evaluation of biopsy specimens according to Sydney criteria, chronic inflammation, activity, atrophy, intestinal metaplasia and helicobacter pylori parameters were used. Total number of eosinophils and number of mast cells were recorded. Of the 60 patients with dyspepsia, 38(63.3%) were female and 22(36.7%) were male. The degree of activation and severity of inflammation increased significantly with increasing helicobacter pylori positivity(r=0.459'p<0.0001; r=0.475'p<0.0001). A significant relationship was found between inflammation, activation and the number of mast cells (p<0.05).There was no relationship between helicobacter pylori intensity and the eosinophil count (r=0.171; p=0.093). There was also a statistically significant correlation between severity of inflammation and activation and the number of eosinophils (r=0.313;p=0.002;r=0.245;p=0.016). Mast cell density was seen to have a role in the inflammatory processes of helicobacter pylori infection.


Anatomy in Nazi Germany: The Use of Victims' Bodies in Academia and Present-Day Legacies.
After decades of denial, German academic medicine was reluctant to accept responsibility for its complex collaboration with the Nazi regime. Consequently, much of this history needs further detailed exploration, as legacies from this history still exist in the form of "Books, Bones and Bodies." Specifically, this concerns the legacies of anatomists' use of bodies of Nazi victims in teaching and research, as "data" have become anatomical knowledge and specimens from victims continue to be discovered.


Correlates of hazardous drinking among Veterans with and without hepatitis C.
Hazardous drinking is a major barrier to antiviral treatment eligibility among hepatitis C (HCV) patients. We evaluated differences in substance-related coping, drinking-related consequences, and importance and confidence in ability to change alcohol use among hazardous drinkers with and without HCV (N = 554; 93.5% male). We examined group differences between HCV+ patients (n = 43) and their negative HCV counterparts (n = 511). Results indicate a higher percentage of HCV+ patients report using substances to cope with possible symptoms of PTSD (P < .05) and depression (P < .01), and endorse more lifetime drinking-related negative consequences than HCV patients (P < .01). Furthermore, HCV+ patients place greater importance on changing alcohol use (P < .01) but report less confidence in their ability to change (P < .01). Use of brief assessment and feedback with skills-based interventions to decrease alcohol use may be well-received by HCV+ patients.


Biochemical characterization and structural analysis of ulvan lyase from marine Alteromonas sp. reveals the basis for its salt tolerance.
Marine macroalgae have gained considerable attention as renewable biomass sources. Ulvan is a water-soluble anionic polysaccharide, and its depolymerization into fermentable monosaccharides has great potential for the production of bioethanol or high-value food additives. Ulvan lyase from Alteromonas sp. (AsPL) utilizes a β-elimination mechanism to cleave the glycosidic bond between rhamnose 3-sulfate and glucuronic acid, forming an unsaturated uronic acid at the non-reducing end. AsPL was active in the temperature range of 30-50 °C and pH values ranging from 7.5 to 9.5. Furthermore, AsPL was found to be halophilic, showing high activity and stability in the presence of up to 2.5 M NaCl. The apparent Km and kcat values of AsPL are 3.19 ± 0.37 mg mL-1 and 4.19 ± 0.21 s-1, respectively. Crystal structure analysis revealed that AsPL adopts a β-propeller fold with four anti-parallel β-strands in each of the seven propeller blades. The acid residues at the protein surface and two Ca2+ coordination sites contribute to its salt tolerance. The research on ulvan lyase has potential commercial value in the utilization of algal resources for biofuel production to relieve the environmental burden of petrochemicals.


fMLP-OMe analogs substituted at the methionine residue: an insight into the receptor properties.
In order to obtain an insight into the mode of binding at the for-Met-Leu-Phe-OH (fMLP) receptor, three fMLP-OMe analogs (1-3) were synthesized in which the Met residue was substituted by Gln 1, Asn 2, and Ser 3. We evaluated the influence of the charge variation and/or the shift of its position on neutrophil biological responses.


Delayed-onset adenosine deaminase deficiency with a novel synonymous mutation and a case series from China.
Adenosine deaminase (ADA) is a key enzyme in the purine salvage pathway. Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency. To date, few Chinese cases have been reported. We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature. Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive. This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.


A multicentre simulation study of planar whole-body bone scintigraphy in Sweden.
Whole-body bone scintigraphy is a clinically useful non-invasive and highly sensitive imaging method enabling detection of metabolic changes at an early stage of disease, often earlier than with conventional radiologic procedures. Bone scintigraphy is one of the most common nuclear medicine methods used worldwide. Therefore, it is important that the examination is implemented and performed in an optimal manner giving the patient added value in the subsequent care process. The aim of this national multicentre survey was to investigate Swedish nuclear medicine departments compliance with European practice guidelines for bone scintigraphy. In addition, the effect of image acquisition parameters on the ability to detect metabolic lesions was investigated. Twenty-five hospital sites participated in the study. The SIMIND Monte Carlo (MC) simulation and the XCAT phantom were used to simulate ten fictive patient cases with increased metabolic activity distributed at ten different locations in the skeleton. The intensity of the metabolic activity was set into six different levels. Individual simulations were performed for each site, corresponding to their specific camera system and acquisition parameters. Simulated image data sets were then sent to each site and were visually evaluated in terms of if there was one or several locations with increased metabolic activity relative to normal activity. There is a high compliance in Sweden with the EANM guidelines regarding image acquisition parameters for whole-body bone scintigraphy. However, up to 40% of the participating sites acquire lower count density in the images than recommended. Despite this, the image quality was adequate to maintain a stable detection level. None of the hospital sites or individual responders deviated according to the statistical analysis. There is a need for at least 2.5 times metabolic activity compared to normal for a lesion to be detected. The imaging process is well harmonized throughout the country and there is a high compliance with the EANM guidelines. There is a need for at least 2.5 times the normal metabolic activity for a lesion to be detected as abnormal.


Interference of pentobarbital and verapamil with the reactivity of middle cerebral artery of cat exposed to experimental subarachnoid hemorrhage.
1. Pentobarbital and verapamil produced concentration-dependent vasodilation in segments of middle cerebral artery of either control or exposed to experimental subarachnoid hemorrhage (SAH) cats precontracted with 5-hydroxytryptamine (5-HT, 10(-5) M) or K+ (75 mM), the potency to evoke relaxation being greater for verapamil than pentobarbital. 2. Pentobarbital (10(-4) M and 10(-3) M) or verapamil (10(-6) M) inhibited the contractions induced by 10(-5) M 5-HT or 75 mM K+ in both kinds of vessels. 3. Pentobarbital (10(-3) M) and verapamil (10(-6) M) reduced the concentration-dependent contractions induced by Ca2+ addition in control and SAH arteries previously exposed to Ca2+-free medium containing K+ or 5-HT. 4. All these vasodepressor effects of pentobarbital and verapamil were similar in control and SAH vessels, suggesting that the sensitivity of them to these agents is unaffected by SAH.


Laparoendoscopic Single-Site Radical Cystectomy vs Conventional Laparoscopic Radical Cystectomy for Patient with Bladder Urothelial Carcinoma: Matched Case-Control Analysis.
Laparoendoscopic single-site surgery (LESS) is increasingly popular in urology. However, data on LESS radical cystectomy (LESS-RC) are immature, and no adequate comparative study has assessed conventional laparoscopic radical cystectomy (CL-RC) vs LESS-RC. The primary aim of this study was to compare efficiency and safety of LESS-RC and CL-RC for patients with bladder urothelial carcinoma (BUC). A retrospective and case-matched control comparative analysis was performed of patients who underwent LESS-RC (n = 54) and CL-RC (n = 108) from January 2011 to June 2015. Oncologic, complication and perioperative outcomes were collected and evaluated. LESS-RC vs CL-RC was associated with less estimated blood loss (EBL; median, 270 vs 337.5 mL; p = 0.014), postoperative pain (median, 4.0 vs 6.0 scores; p = 0.001), and shorter convalescence (time to ambulation and oral intake, median, 2.5 vs 3 days; p = 0.002 and 5 vs 6 days; p = 0.004, respectively). No significant differences were noted for LESS-RC and CL-RC regarding the lymph node yield (median: 18 vs 20; p = 0.101). Median follow-up time was 33.5 months (interquartile range [IQR]: 23-41.3 months) and 33 months (IQR: 23-43 months) for the LESS-RC and CL-RC groups, respectively. No significant differences were noted for LESS-RC and CL-RC regarding estimated 24-month overall survival (86.7% vs 88.1%, p = 0.703), cancer-specific survival (88.3% vs 90.9%, p = 0.539), and recurrence-free survival (80.2% vs 87.5%, p = 0.619), even when substratified according to tumor stage (pT3 or higher) and lymph node status (pN+). Early, late, and 90-day overall complication rates were similar. In multivariate analyses, LESS-RC was not associated with recurrence and worse survival rates, but was associated with 90-day overall complications. This study demonstrated that LESS-RC and CL-RC have comparable efficiency and safety for patients with BUC. Compared to CL-RC, LESS-RC was with less postoperative pain, lower EBL, and more rapid convalescence, but was associated with 90-day overall complications.


Clinical research with targeted drugs in paediatric oncology.
The development of targeted drugs in paediatric oncology has been notoriously slow, in part due to the peculiarities of this rare and highly heterogeneous population. To provide therapeutic breakthroughs for the highest risk subgroups of childhood cancer, innovative research solutions have been implemented in the last several years by different international collaborative groups and regulators. Here, we discuss and summarise some of these approaches, as well as challenges and unmet needs that are still being addressed. A wide range of topics were covered in this review including molecular diagnosis optimisation, innovative research methodologies, big data approaches, trial enrolment strategies, and improvements in regulation and preclinical research platforms.


Psychosocial syndemic associated with increased suicidal ideation among men who have sex with men in Shanghai, China.
We intended to verify the syndemic effect of psychosocial health conditions on suicidal ideation among men who have sex with men (MSM) in Shanghai, China; design a comprehensive framework for the identification of the MSM with suicidal ideation; and provide suggestion for suicidality intervention among MSM. A cross-sectional study was conducted among 547 MSM in 4 districts in Shanghai. Sociodemographic, psychosocial, and suicidal ideation information of the participants was collected. Logistic regressions were performed to assess the relationship between psychosocial variables and suicidal ideation and to verify the syndemic effect of psychosocial factors. Of the MSM sample, 10.6% reported suicidal thoughts in the past year. In univariate analysis, depression, anxiety, loneliness, impulsivity, involuntary subordination (IS), social support, and risky sex were associated with suicidal ideation. Multivariate analysis found that IS (ORm = 2.92, 95% confidence interval [CI] = 1.55-5.51) and risky sex (ORm = 3.79, 95% CI = 1.44-9.97) remained significant. The MSM with more than 5 psychosocial health problems were nearly 4 times more likely (adjusted odds ratio = 4.68, 95% CI = 2.23-9.80) to have had suicidal ideation in the past year. The study confirmed the syndemic effect of psychosocial health problems in magnifying the risk of suicidality among MSM. More integrated and holistic approaches in the identification of high-risk groups and intervention of suicidality among MSM are needed.


Retrospect and Prospect for Lung Cancer in China: Clinical Advances of Immune Checkpoint Inhibitors.
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths in China. The recent emergence of immunotherapy treatment options, such as the use of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors, has also led to a paradigm shift in the treatment of non-small cell lung cancer, and has provided promising directions for the treatment of small cell lung cancer. This review provides a summary of the developmental process of immunotherapy, especially immune checkpoint inhibitors in lung cancer, ongoing international and domestic clinical trials in this field, and the challenges and considerations related to the use of immunotherapy in Chinese patients with lung cancer, with the aim of providing detailed information for future immunotherapy-related clinical trials in China. Research regarding immune checkpoint inhibitors in China is several years behind similar research in several developed countries. However, although PD-1/PD-L1 inhibitor-related clinical trials remain in their early stages in China, increased efforts by Chinese clinicians, researchers, and government staff have been directed toward trying to introduce novel drugs into the clinical setting. Because of the specific characteristics of Chinese patients with lung cancer (such as high epidermal growth factor receptor mutation rates, later disease stages, and different toxicity profiles), large-scale clinical trials targeting the Chinese population or Chinese participation in multinational trials should be promoted. IMPLICATIONS FOR PRACTICE: As the leading cause of cancer-related morbidity and mortality, lung cancer is a major public health problem in China. Immunotherapy based on programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors may result in new treatment directions and a paradigm shift for Chinese patients with lung cancer. Although checkpoint inhibitor-related clinical trials remain in their early stages in China, increased efforts by Chinese clinicians, researchers, and government staff have been directed toward trying to introduce novel drugs into the clinical setting by encouraging the development of large-scale clinical trials targeting the Chinese population and promoting Chinese patients with lung cancer to participate in international trials.


Geographic patterns of non-carpeted floor dust loading in Syracuse, New York (USA) homes.
Residential floor dust loading was measured on the smooth floor surface of 488 houses in Syracuse, New York, during the summers of 2003 and 2004. Using U.S. Environmental Protection Agency (EPA) wipe methods, pre-weighed Ghost Wipes, Lead Wipes, or Whatman Filters were employed to collect duplicate samples from (predominantly) kitchens. The collection efficiency of the various media was determined from multiple wipe tests and side-by-side comparisons. The results were normalized and aggregated at the census tract level to determine whether spatial patterns of dust loading could be observed. Loading was found to be log-normally distributed, with a geometric mean value of 0.311 g m(-2) (29 mg of dust per square foot of floor); 95% of the observations fell in the range of 0.042-2.330 g m(-2) (4-216 mg foot(-2)). The sampling for floor dust loading shows some bias for day of the week in which visits to the residential properties were made. After a first-order correction for this effect, results were aggregated by census tract and mapped in a geographic information system (GIS); strong spatial patterns can be identified in an inverse distance weighted mapping. The geographic patterns exhibit a strong correlation with socio-economic/demographic covariates extracted from the 2000 census summaries. Dust mass on the floors is positively correlated with renter-occupied properties and family size; it is negatively correlated with measures of household income.


Ageing and structural effects on the sorption characteristics of Cd2+ by clinoptilolite and Y-type zeolite studied using isotope exchange technique.
This research investigates the long-term kinetics of Cd(2+) sorption and desorption by calcium-exchanged clinoptilolite (CaCpt) and Y-type (CaY) zeolite using isotopic exchange with (109)Cd while maintaining pH at circumneutral values. The effects of Si/Al ratio and crystal structure of these zeolitic materials on intracrystalline transport of Cd are discussed. A first-order kinetic model was developed to describe the progressive transfer of Cd(2+) to a less reactive form within the zeolite structure, following initial sorption and subsequent desorption of Cd subject to different initial contact times. The kinetic model differentiates between two forms of sorbed Cd(2+) designated 'labile' and 'non-labile' in which the labile form is in immediate equilibrium with the free Cd(2+) ion activity in solution. A model combining diffusion and first-order kinetics for cation exchange was also employed to determine Cd(2+) diffusivity and intracrystalline exchange rates in CaY and CaCpt. The efficiency of Permeable Reactive Barriers (PRBs) containing zeolitic materials in protecting water systems against lateral flow of metal-contaminated leachate was simulated for three contrasting zeolites. The slow transfer of Cd between labile and non-labile forms was particularly important in moderating high concentration pulses of Cd traversing the PRB. In addition, the reversibility of Cd fixation effectively restored the sorption capability of the zeolite through slow leakage to drainage water.


Lipid composition and temperature adaptation of the nervous system of the leech Hirudo medicinalis L.
The lipid composition of the nervous system of the leech Hirudo medicinalis was investigated following acclimatization of animals at 25 degrees C and 5 degrees C. Choline, ethanolamine, and serine plus inositol phosphoglycerides are the major phospholipid classes of the leech ganglionic chain; minor amounts of lysophosphatidylcholine, phosphatidic acid, and sphingomyelin are also present. Neither the phospholipid pattern nor the cholesterol to total phospholipid molar ratio was dependent on the acclimatization temperature, whereas the fatty acid patterns of choline and serine plus inositol phosphoglycerides were significantly affected. Both for choline and serine plus inositol phosphoglycerides, a significant increase of the unsaturation index and a decrease of saturated to unsaturated fatty acid ratio was observed in animals acclimatized at 5 degrees C in comparison with those acclimatized at 25 degrees C. These observations, which point to increased lipid fluidity of the nervous system of cold-adapted leeches, are strengthened by results obtained by the fluorescence polarization method using 1,6-diphenyl-1,3,5-hexatriene as a probe: a decrease of the fluorescence polarization value was observed throughout the temperature range selected (5-40 degrees C).


Target validation of G-protein coupled receptors.
G-protein coupled receptors (GPCRs) represent possibly the most important target class of proteins for drug discovery. Over 30% of clinically marketed drugs are active at this receptor family. These drugs exhibit their activity at <10% of all known GPCRs. A major challenge for the pharmaceutical industry is to associate the many novel GPCRs with disease to identify the drugs of the future. This process consists of a collection of experimental paradigms that together can be loosely labelled 'target validation'.


Intra-and inter-observer variability of point of care ultrasound measurements to evaluate hemodynamic parameters in healthy volunteers.
Point-of-care ultrasound (POCUS) is a valuable tool for assessing the hemodynamic status of acute patients. Even though POCUS often uses a qualitative approach, quantitative measurements have potential advantages in evaluating hemodynamic status. Several quantitative ultrasound parameters can be used to assess the hemodynamic status and cardiac function. However, only limited data on the feasibility and reliability of the quantitative hemodynamic measurements in the point-of-care setting are available. This study investigated the intra- and inter-observer variability of PoCUS measurements of quantitative hemodynamic parameters in healthy volunteers. In this prospective observational study, three sonographers performed three repeated measurements of eight different hemodynamic parameters in healthy subjects. An expert panel of two experienced sonographers evaluated the images' quality. The repeatability (intra-observer variability) was determined by calculating the coefficient of variation (CV) between the separate measurements for each observer. The reproducibility (inter-observer variability) was assessed by determining the intra-class correlation coefficient (ICC). 32 subjects were included in this study, on whom, in total, 1502 images were obtained for analysis. All parameters were in a normal physiological range. Stroke volume (SV), cardiac output (CO), and inferior vena cava diameter (IVC-D) showed high repeatability (CV under 10%) and substantial reproducibility (ICC 0.61-0.80). The other parameters had only moderate repeatability and reproducibility. We demonstrated good inter-observer reproducibility and good intra-observer repeatability for CO, SV and IVC-D taken in healthy subjects by emergency care physicians.


Attention fluctuations impact ongoing maintenance of information in working memory.
Working memory maintains information in a readily accessible state and has been shown to degrade as the length of the retention interval increases. Previous research has suggested that this decline is attributable to changes in precision as well as sudden loss of item representations. Here, by measuring trial-to-trial variations in performance, we examined an orthogonal distinction between the maximum number of items that an individual can store, and the probability of achieving that maximum. Across two experiments, we replicated the finding that performance declines after long (10 s) retention intervals, as well as past observations that forgetting was due to probabilistic dropping of individual items rather than all-or-none losses of the stored memories. Critically, longer retention intervals did not reduce the maximum amount of information that could be stored in working memory. Instead, lower attentional control accounted for a decreased probability of maintaining the maximum number of items in working memory. Thus, longer retention intervals impact working memory storage via fluctuations in attentional control that lower the probability of achieving a stable maximum storage capacity.


Combined hemodynamic and scintigraphic assessment of piroximone (MDL 19,205) and comparison with dobutamine and nitroprusside.
The acute hemodynamic responses to intravenous infusion of piroximone (MDL 19,205), a nonglycoside, noncatecholamine agent with positive inotropic activity in vitro, were compared with those of intravenous dobutamine and sodium nitroprusside, respectively, in 2 groups of patients with New York Heart Association class III or IV symptoms. Each drug was titrated to optimal dosage (dobutamine, 12.5 +/- 3.9 micrograms/kg/min; nitroprusside, 2.5 +/- 0.6 micrograms/kg/min; piroximone 1.4 +/- 0.6 mg/kg) and simultaneous hemodynamic and scintigraphic values were measured. In group 1, the increase in cardiac index was slightly greater with piroximone than with dobutamine (from 1.6 +/- 0.5 to 2.7 +/- 0.6 vs 2.4 +/- 0.6 liters/min/m2, p less than 0.025) and only piroximone significantly decreased left ventricular (LV) filling pressure (from 29 +/- 7 to 22 +/- 8 mm Hg, p less than 0.05). Both agents increased heart rate and systolic blood pressure. In group 2, cardiac index increased similarly with nitroprusside and piroximone (1.5 +/- 0.6 to 2.6 +/- 0.8 and 1.6 +/- 0.5 to 2.6 +/- 0.5 liters/min/m2, difference not significant), whereas LV filling pressure decreased slightly less with piroximone (29 +/- 7 to 24 +/- 10 vs 30 +/- 7 to 20 +/- 11 mm Hg, difference not significant). Only nitroprusside reduced mean arterial pressure (88 +/- 13 to 72 +/- 12 mm Hg, p less than 0.001 between drugs). In group 1, systolic blood pressure to end-systolic volume ratio increased in 9 of 10 patients taking both piroximone and dobutamine, whereas in group 2, this ratio increased in 7 of 8 patients taking piroximone and declined in 7 of 8 taking nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)


Predicting nonelective hospitalization: a model based on risk factors associated with diabetes mellitus.
Nonelective hospitalizations for urgent or emergent reasons are frequent events for patients with diabetes mellitus, and their occurrence is difficult to predict. A model for predicting nonelective hospitalizations is described. It is based on risk factors: prior visits to the emergency room, hypoalbuminemia, cardiomegaly, anemia, systolic hypotension, and hyperglycemia. To test the model, the authors conducted a prospective cohort study in which 429 ambulatory patients with diabetes mellitus were stratified into three risk levels for hospitalization and followed for two years. Patients in higher risk groups were more likely to be hospitalized (high risk, 58.1%; medium-risk, 40.2%; low risk, 26.6%, p less than 0.01) and had more hospitalizations per patient (1.47 vs. 0.80 vs. 0.46, p less than 0.01) and more hospital days per patient (14.6 vs. 8.6 vs. 5.3, p less than 0.01). When the two-year study period was divided into four six-month intervals, there was no significant difference across the four periods. This study demonstrates the validity of the model for predicting nonelective hospitalizations of patients with diabetes mellitus over time.


Transsternal radical thymectomy for myasthenia gravis: a 15-year review.
Thymectomy is an accepted therapeutic modality for patients with myasthenia gravis. The selection of patients for operation and the surgical approach are controversial. We reviewed 52 patients (aged 18 months to 82 years; mean age, 34 years) treated with transsternal radical thymectomy between 1972 and 1987. Patients were symptomatically staged according to the modified Osserman classification. There was one hospital death and postoperative follow-up was obtained on 51 patients. Improvement after thymectomy was observed in 3 of 11 patients (27%) in Osserman stage I, 16 of 25 patients (64%) in Osserman stage IIA, and 13 of 15 patients (86%) in combined Osserman stages IIB, III, and IV. Preoperative Osserman stage, patient sex, and thymic histology correlated with postoperative clinical response. Transsternal radical thymectomy is effective therapy for myasthenia gravis. Sustained improvement is obtained in patients with moderate and advanced disease. The majority of patients with ocular disease do not benefit from operation.


Endometrial prostaglandin F content in women wearing nonmedicated or progestin-releasing intrauterine devices.
Prostaglandin F (PGF) was measured in endometrial samples from eight women wearing Lippes Loops and 14 women wearing Progestaserts after 6 months' use of the intrauterine devices (IUDs). In addition, in 37 women wearing dydrogesterone-T IUDs, endometrial PGF was measured after 1 month, 3 to 7 months, and 8 to 12 months of use. Endometrial samples were also obtained from 51 women without IUDs. The following means and standard errors of endometrial PGF, expressed in picograms per microgram of endometrial protein, were obtained in women without IUDs: early proliferative phase, 3.11 +/- 1.0; midproliferative phase, 4.1 +/- 0.7; late proliferative phase, 4.4 +/- 1.0; midluteal phase, 7.13 +/- 1.0; and late secretory phase, 6.08 +/- 1.0. The midproliferative phase mean was significantly different from the midsecretory phase mean (P is greater than 0.05). Except for one group, no differences were noted during the midproliferative and midsecretory phases among the groups of women wearing medicated and nonmedicated IUDs, when compared with values for women without IUDs. The only difference noted was during the midsecretory phase in the dydrogesterone group at 8 to 12 months. In these women, the mean endometrial PGF content was 2.8 +/- 0.8, significantly different (P is greater than 0.05) from that of women without IUDs (6.1 +/- 1.0).


Retinoic acid delineates the topography of neuronal plasticity in postnatal cerebral cortex.
Retinoic acid is well recognized to promote neuronal differentiation in the embryonic nervous system, but how it influences the postnatal cerebral cortex remains largely unknown. The domain of highest retinoic acid actions in the cortex of the mouse constricts postnatally to a narrow band that includes the dorsal visual stream and the attentional and executive networks. This band of cortex, which is distinguished by the retinoic acid-synthesizing enzyme RALDH3, exhibits signs of delayed maturation and enhanced plasticity compared to the surrounding cortex, as indicated by suppression of parvalbumin, neurofilament, cytochrome oxidase and perineuronal net maturation, and persistence of the embryonic, polysialated form of the neural cell-adhesion molecule PSA-NCAM. During the first postnatal week, the RALDH3-expressing territory translocates in the caudal cortex from the medial limbic lobe to the adjacent neocortex. This topographical shift requires the neurotrophin NT-3 because in mice lacking neuronal NT-3 the RALDH3 enzyme maintains its early postnatal pattern up to adulthood. In the NT-3-null mutants, expression of the markers, whose topography colocalizes with RALDH3 in the normal cortex, matches the abnormal RALDH3 pattern. This indicates that the uneven retinoic acid distribution serves a role in patterning the maturation and to some extent function of the normal postnatal cerebral cortex.


Nevus of Ota: morphological patterns and distribution in 47 Yemeni cases.
Nevus of Ota is a rare pigmentary disorder characterized by melanocytic hamartoma of the skin along the distribution of trigeminal nerve branches. To study the morphological features of nevus of Ota, and their relation with facial regions and trigeminal branches areas. Patients with nevus of Ota who attended Kuwait University Hospital dermatology clinic and a private dermatology clinic in Sana'a, Yemen, between January 2008 and December 2010, were clinically evaluated. The morphology of nevus of Ota was classified to homogenous, speckled or mixed. The distribution of the lesions was assessed based on both facial regions and areas supplied by the trigeminal nerve. Forty-seven patients with nevus of Ota (F = 38, M = 9) were evaluated. Eighty percent of patients were females. Mixed (homogenous and speckled) appearance was seen in 47% of all patients. Periocular region was the most commonly affected facial region (67%), and the maxillary area was the most commonly involved trigeminal branch area (94%). Forty-seven percent of cases had scleral pigmentation. Interesting features of nevus of Ota involving the nasal septum and crossing the midline of the face were noted. To the best of our knowledge, this is the first study that examines the distribution and morphology of nevus of Ota in Middle Eastern population. Including the morphological appearance of the nevus is practical and more clinically descriptive, and therefore should be integrated in the classification in future studies.


Non-commutative Calculus, Optimal Transport and Functional Inequalities in Dissipative Quantum Systems.
We study dynamical optimal transport metrics between density matrices associated to symmetric Dirichlet forms on finite-dimensional C ∗ -algebras. Our setting covers arbitrary skew-derivations and it provides a unified framework that simultaneously generalizes recently constructed transport metrics for Markov chains, Lindblad equations, and the Fermi Ornstein-Uhlenbeck semigroup. We develop a non-nommutative differential calculus that allows us to obtain non-commutative Ricci curvature bounds, logarithmic Sobolev inequalities, transport-entropy inequalities, and spectral gap estimates.


Tuberculosis and latent tuberculosis infection among healthcare workers in Kisumu, Kenya.
To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya. We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection. We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P < 0.01). Healthcare workers at facilities in western Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers.


The membrane systems of the cardiac muscle cell of Meganychtiphanes norvegica (m. sars), euphauciacea, crustacea.
The membrane systems of cardiac muscle cells of the euphausiacean Meganychtiphanes norvegica are described. Transverse tubules are found both at the Z-band level (TZ-tubules) and at the H-band level (Th-tubules). Within the sarcomere narrow longitudinal tubules branch off from the TZ-tubules. At the H-band level these tubules expand forming flattened cisternae in dyadic and triadic couplings with the sarcoplasmic reticulum (SR). Adjacent myofibrils are separated by a well developed SR. Modifications of the SR are seen at the H-band level where junctional cisternae are formed.


Fatigue as an important aspect of quality of life in patients with acute myeloid leukemia.
Quality of life (QL) was evaluated in 101 patients with AML undergoing intensive and prolonged treatment at 12 sequential time points by using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C 30 questionnaire and the profile of mood states scale (POMS). For those patients having completed the course of inpatient treatment (n=37), QL improved from the beginning of chemotherapy to the end of inpatient treatment. Patients who subsequently went off protocol did not differ significantly in their self-assessed QL when compared with patients who completed therapy. Fatigue was more closely related to QL than nausea/emesis or appetite loss, but did not correlate with hemoglobin levels.


Binding of a biotinylated neurotrophic ACTH(4-9) analogue, Org 2766, to neurofilament-positive cells in primary or cell line cultures.
To study the putative binding sites of the neurotrophic peptide Org 2766, an analogue of ACTH(4-9) [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH], biotinylated forms of the peptide were used. After fixation, cultures of rat spinal cord and dorsal root ganglia were incubated with 4-10 microM of biotinyl-Org 2766 (b-Org 2766). Binding of both N- and C-terminally biotinylated Org 2766 was seen to phase-bright, round cells with thin processes, but not to flat, orthogonal-shaped cells with tapering processes. The b-Org 2766 binding was displaceable by an excess of nonbiotinylated Org 2766. Light and electron microscopy showed that the biotinylated peptide binds to a cytoplasmatic component as well as to the cell membrane. Double-labeling experiments with b-Org 2766 and an antibody (RT-97) to a high molecular weight neurofilament protein in dorsal root ganglion cultures showed, using fluorescence and confocal scanning laser microscopy, that all b-Org 2766 binding cells were neurofilament positive. Biotinylated Org 2766 did also bind to the neuronally differentiated cells in cultures of the human neuroblastoma cell line SK-N-SH, but not to those differentiated into epithelial cells. The present data suggest that the neurotrophic peptide Org 2766 binds specifically to cell types with neuronal characteristics.


Design and evaluation of a power tiller vegetable seedling transplanter with dibbler and furrow type.
Vegetable production plays a vital role in ensuring food security in Bangladesh. However, the majority of vegetable seedlings are currently transplanted manually, which is not only time-consuming but also labor-intensive and costly. In this context, a semi-automated transplanter can be considered as an alternative solution for mechanized seedling transplanting. To mechanize seedling operations, two types of transplanters were designed, fabricated and tested: the power tiller-operated semi-automatic dibbler vegetable seedling (DVS) transplanter and the furrow opener vegetable seedling (FVS) transplanter. The goal was to evaluate their performance and impact on field crop productivity. In the DVS transplanter design, the larger sprocket was adjusted to enhance the precision of hole-making by pressing the dibbler into the soil, creating holes where seedlings would be transplanted. On the other hand, the FVS transplanter utilized a furrow opener to create furrows, and the seedling is placed in these furrow at a specific distance from the furrow opener wall, where the distance between seedlings within the furrow could be adjusted based on the specific requirements of the seedling crop. The results of the evaluation indicated that both transplanters successfully planted seedlings without any missing placements, while hole covering was achieved at 115 and 118.2% for the DVS and FVS transplanters, respectively. The field capacity and field efficiency for both transplanters were determined to be 0.05 ha h-1 and 61.18%, respectively, with a coefficient of variation of 5% or less. Field tests conducted with brinjal crops at a forward speed of 1.2 km h-1 and a spacing of 0.7 × 0.6 m demonstrated that both designs yielded higher yield productivity compared to manual transplantation. Additionally, no issues related to vegetative development were observed. Both transplanters exhibited promising performance and significant potential in terms of accurately transplanting seedlings, and ensuring satisfactory transplantation quality. Furthermore, these transplanters offer several advantages, including less time-consuming, lower labor demands and even distribution of seedlings. This design encourages small to medium-level farmers seeking to engage in mechanized vegetable farming practices.


Lewis acid mediated reactions of 1-cyclopropyl-2-arylethanones with allenic esters: a facile synthetic protocol for the preparation of dihydrofuro[2,3-h]chromen-2-one derivatives.
TMSOTf-mediated reactions of 1-cyclopropyl-2-arylethanones with allenic esters afford a novel method for the synthesis of dihydrofuro[2,3-h]chromen-2-one derivatives in moderate to good yields. This process is a sequential reaction involving a nucleophilic ring-opening reaction of the cyclopropane by H(2)O, two intermolecular aldol-type reactions and one intramolecular aldol-type reaction, a cyclic transesterification, dehydration, and aromatization mediated by Lewis acid.


Dermatomyositis associated with fallopian tube carcinoma.
Dermatomyositis (DM) is an idiopathic inflammatory myopathy associated with characteristic cutaneous and extracutaneous manifestations, including malignancy. Primary fallopian tube carcinoma (FTC) is the least common site of origin for a malignant neoplasm of the female genital tract. This report describes the first documented case of DM and concurrent FTC in the United States. A 62-year-old woman presented with DM and was subsequently found to have FTC. During her clinical course, she had improvement in strength and function with treatment of the underlying FTC, which also correlated with lower creatinine phosphokinase levels. An association between DM and FTC may exist because of significant functional strength improvements after tumor removal and chemotherapy.


Primary biliary cirrhosis (PBC)-CREST overlap syndrome with coexistence of Sjögren's syndrome and thyroid dysfunction.
Calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, a limited form of systemic sclerosis, is sometimes complicated by primary biliary cirrhosis (PBC). A 52- and 61-year-old Japanese woman with PBC-CREST overlap syndrome accompanied by Sjögren's syndrome, and Hashimoto's thyroiditis, and Graves' disease, respectively, are reported. They had suffered from Raynaud's phenomena, sclerodactyly, morning stiffness, arthralgia, and sicca symptoms during these several years. They exhibited an increased level of alkaline phosphatase, gamma-glutamyl transpeptidase, positive antibodies against mitochondria and centromere, and hyperglobulinemia without any cholestatic symptoms. Histological findings from liver biopsy specimens were consistent with those of PBC. Clinically, they were diagnosed as both asymptomatic PBC and incomplete CREST syndrome. Their human leukocyte antigen typing showed both DR4 and DR8 positive. The association of the four autoimmune conditions is clinically and etiologically important. Although a combination of these diseases is rare, it is of importance to keep in mind that various autoimmune diseases could occur simultaneously. Of critical importance is that an active diagnostic attitude towards them is admirable, and that early diagnosis and therapy are needed.


Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance.
We have evaluated the efficacy of plant sterol preparations from two different sources and in two different physical forms in lowering the plasma cholesterol of a total of 46 patients with type II hyperlipoproteinemia when given in addition to appropriate diet therapy. In addition, the mechanisms of the hypocholesterolemic effect were investigated in 7 patients by a sterol balance technique. The maximal mean cholesterol lowering in response to any preparation was 12 percent, although it was much greater in some individual patients. Sterol balance data showed that plant sterols inhibit cholesterol absorption with maximal negative cholesterol balance in adults at a dose of 3 g/day of a tall oil sterol suspension. Interestingly, maximal plasma cholesterol reduction in the adult outpatients on this preparation was seen at the same dose level. Since the tall oil sterol suspension is relatively palatable and is poorly absorbed, it has potential value as an adjunct to dietary therapy in patients with mild hypercholesterolemia for whom long-term drug therapy is deemed advisable.


Object Permanence and the Relationship to Sitting Development in Infants With Motor Delays.
This study examines object permanence development in infants with motor delays (MD) compared with infants with typical development (TD) and in relation to sitting skill. Fifty-six infants with MD (mean age = 10 months) and 36 with TD (mean age = 5.7 months) were assessed at baseline and then at 1.5, 3, and 6 months postbaseline. A scale was developed to measure object permanence (Object Permanence Scale [OPS]), and the Gross Motor Function Measure sitting subsection (GMFM-SS), and the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) were administered. Interrater reliability of the OPS was excellent and correlation between the OPS and Bayley-III cognitive scores was moderately positive. Compared with TD, infants with MD were delayed in development of object permanence but demonstrated increased understanding over time and as sitting skills improved. In children with MD, object permanence, as quantified by the OPS, emerges in conjunction with sitting skill.


Structure of a TRAPPII-Rab11 activation intermediate reveals GTPase substrate selection mechanisms.
Rab1 and Rab11 are essential regulators of the eukaryotic secretory and endocytic recycling pathways. The transport protein particle (TRAPP) complexes activate these guanosine triphosphatases via nucleotide exchange using a shared set of core subunits. The basal specificity of the TRAPP core is toward Rab1, yet the TRAPPII complex is specific for Rab11. A steric gating mechanism has been proposed to explain TRAPPII counterselection against Rab1. Here, we present cryo-electron microscopy structures of the 22-subunit TRAPPII complex from budding yeast, including a TRAPPII-Rab11 nucleotide exchange intermediate. The Trs130 subunit provides a "leg" that positions the active site distal to the membrane surface, and this leg is required for steric gating. The related TRAPPIII complex is unable to activate Rab11 because of a repulsive interaction, which TRAPPII surmounts using the Trs120 subunit as a "lid" to enclose the active site. TRAPPII also adopts an open conformation enabling Rab11 to access and exit from the active site chamber.


Adjunctive usage of a non-comedogenic moisturizer with adapalene gel 0.1% improves local tolerance: a randomized, investigator-blinded, split-face study in healthy Asian subjects.
Adapalene gel 0.1% is an efficacious treatment for acne vulgaris in Asians. It is generally well tolerated, but may still cause cutaneous side effects among patients with sensitive skin. To assess the ability of a moisturizing lotion (Cetaphil®) in improving the local tolerance of adapalene. In this 4-week, randomized, investigator-blinded, split-face study among 30 healthy volunteers of Chinese origin, adapalene gel was applied once daily to the whole face and the moisturizing lotion was applied once daily to only one side of the face according to the randomization scheme. At each study visit, both investigators and subjects reported better tolerance on the side of moisturizing lotion + adapalene gel than the side of adapalene gel only, with significant differences reported by the subjects during the first 2 weeks (p = 0.039 and 0.013, respectively). Global worst score, defined as the average of worst scores for erythema, desquamation, dryness, stinging/burning and pruritus, was significantly lower for the side of moisturizing lotion + adapalene gel than for the side of adapalene gel alone (0.43 ± 0.34 vs. 0.59 ± 0.44, p = 0.032). The adjunctive usage of an effective moisturizer improves local tolerance of adapalene gel and may contribute to better adherence.


A patch-based super resolution algorithm for improving image resolution in clinical mass spectrometry.
Mass spectrometry imaging (MSI) and histology are complementary analytical tools. Integration of the two imaging modalities can enhance the spatial resolution of the MSI beyond its experimental limits. Patch-based super resolution (PBSR) is a method where high spatial resolution features from one image modality guide the reconstruction of a low resolution image from a second modality. The principle of PBSR lies in image redundancy and aims at finding similar pixels in the neighborhood of a central pixel that are then used to guide reconstruction of the central pixel. In this work, we employed PBSR to increase the resolution of MSI. We validated the proposed pipeline by using a phantom image (micro-dissected logo within a tissue) and mouse cerebellum samples. We compared the performance of the PBSR with other well-known methods: linear interpolation (LI) and image fusion (IF). Quantitative and qualitative assessment showed advantage over the former and comparability with the latter. Furthermore, we demonstrated the potential applicability of PBSR in a clinical setting by accurately integrating structural (i.e., histological) and molecular (i.e., MSI) information from a case study of a dog liver.


Quality improvement project identifies factors associated with delay in IBD diagnosis.
Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking. To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD. This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis. The median [IQR] diagnosis sub-intervals were: (a) patient = 2.1 months [0.9-5.1]; (b) GP = 0.3 months [0.0-0.9]; (c) secondary care = 1.1 months [0.5-2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1-15.0]) than ulcerative colitis (3.3 months [1.9-7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course. Time to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course.


Primary pulmonary hypertension in infancy: report of two autopsy cases.
Two cases of unexplained plexogenic pulmonary arteriopathy in infancy were studied by patho-anatomical approach. The patients were boys, age 7 months and 2 years 2 months. Pulmonary arteries revealed Grade 3 and Grade 4 hypertensive changes, respectively, after Heath and Edwards' criteria. The configuration of the media of the pulmonary trunk suggested that though these cases were very young, pulmonary arterial pressure had been elevated since some time after birth.


Force feedback and basic laparoscopic skills.
Not much is known about the exact role of force feedback in laparoscopy. This study aimed to determine whether force feedback influences movements of instruments during training in laparoscopic tasks and whether force feedback is required for training in basic laparoscopic force application tasks. A group of 19 gynecologic residents, randomly divided into two groups, performed three laparoscopic tasks in both the box trainer and the virtual reality (VR) trainer. The box-VR group began with the box trainer, whereas the VR-box group began with the VR trainer. The three selected tasks included different levels of force application. The box trainer provides natural force feedback, whereas the VR trainer does not provide force feedback. The performance of the two groups was compared with regard to time, path length, and depth perception. For the tasks in which force plays hardly a role, no differences between box-VR group and the VR-box group were found. During a task in which force application (pulling and pushing forces) plays a role, the box-VR group outperformed VR-box group in the box trainer. Moreover, training with the box trainer had a positive effect on subsequent performance of the task with the VR trainer. This was not found the other way around. No differences were found between box-VR and the VR-box group in tasks not requiring force application. Force feedback influences basic laparoscopic skills during tasks in which pulling and pushing forces are applied. For these tasks, the switch from the trainer without force feedback to the one with natural force feedback has a detrimental effect on performance. Therefore, training for tasks in which forces play an important role (e.g., stretching, grasping) should be done using systems with natural force feedback, whereas eye-hand coordination can be trained without force feedback.


Awe liberates the feeling that "my body is mine".
Awe is an emotional response to perceptually vast stimuli that transcend one's current frames of reference. Previous research indicated that awe promotes a smaller self, which led to the creation of a small-self hypothesis. Thus, we shed new light on this hypothesis in terms of sense of body ownership using a rubber hand illusion experiment; through it, we showed that awe evokes an increased sense of body ownership over the rubber hand and this effect was prominent among participants who experienced small self. Our findings suggest that awe might provoke a "liberation of the self" in terms of a sense of body ownership as awe has been thought to liberate existing schemas, hence informing the demonstrable implications of the psychological mechanisms of awe.


C-reactive protein, Neopterin and Beta2 microglobulin levels pre and post TB treatment in The Gambia.
Tuberculosis is one of the leading causes of morbidity and mortality in developing countries. Analysis of the host immune response may help with generating point-of-care tests for personalised monitoring. Thus, the aim of this study was to assess the relationship between immune activation markers: C-reactive protein (CRP), Beta2 microglobulin (B2M) and Neopterin, disease severity prior to treatment and response to therapy in adult pulmonary TB patients. HIV negative adult pulmonary TB index cases (n = 91) were recruited from the TB clinic at MRC, The Gambia. Plasma samples were collected at enrolment and at 2 and 6 months following TB treatment initiation. An enzyme linked immunosorbent assay (ELISA) was performed for evaluation of CRP, B2M and Neopterin levels and correlated with clinical and microbiological parameters including strain of infection. Disease severity was determined using Chest X-ray (CXR), Body Mass Index (BMI) and sputum smear grade. Plasma levels of all three markers were highly elevated in patients at recruitment and declined significantly during TB therapy. No correlation with disease severity was seen at recruitment. CRP showed the most significant decrease by 2 months of treatment (p < 0.0001) whereas levels of B2M and Neopterin showed little change by 2 months but a significant decrease by 6 months of treatment (p = 0.0002 and p < 0.0001 respectively). At recruitment, B2M levels were significantly higher in subjects infected with Mycobacterium africanum (Maf) compared with those infected with Mycobacterium tuberculosis sensu stricto (Mtb) (p = 0.0075). In addition, while CRP and Neopterin showed a highly significant decline post-treatment regardless of strain (p < 0.0001 for all), B2M showed differential decline depending on strain (p = 0.0153 for Mtb and p = 0.0048 for Maf) and levels were still significantly higher at 6 months in Maf compared to Mtb infected subjects (p = 0.0051). Our findings suggest that activation markers, particularly CRP, may have a role in identifying good response to TB therapy regardless of the strain of infection and could be further developed as point-of-care tests. In addition, B2M levels may allow differentiation between Mtb and Maf-infected subjects.


Association between serum lipids, glucose tolerance, and insulin sensitivity during 12 months of celiprolol treatment.
The study was undertaken to evaluate the development and association of parameters related to the metabolic syndrome during celiprolol treatment. Hyperinsulinemic euglycemic clamp and independent oral glucose tolerance tests (OGTT) were performed on 25 nondiabetic patients with controlled hypertension and dyslipidemia. The tests were carried out during the patients' previous antihypertensive monotherapy (beta- or Ca-blocker, or an ACE inhibitor), and after 6 and 12 months of celiprolol treatment. About one third of patients were randomized to a control group in which treatment was kept unchanged. Insulin sensitivity index (ISI), measured by the euglycemic clamp test, increased 35% in the celiprolol group at 6 months and remained at that level at 12 months, independent of the previous treatment (p = 0.03, compared to the change in the control group). During a 2 hour OGTT, incremental glucose area under the curve (AUC) decreased from 4.5 to 1.9 hr x mmol/l during 6 months of celiprolol treatment, and decreased further to 1.5 hr x mmol/l at 12 months (p < 0.001). Insulin AUC decreased from 113 to 72 hr x mU/l, and decreased further to 68 hr x mU/l (p < 0.01). All insulin parameters in OGTT were highly significant (p < 0.0001) and inversely associated with ISI. Insulin AUC had the best linear correlation with ISI (r = -0.682, p < 0.0001). Glucose parameters in OGTT correlated only weakly and inversely with insulin sensitivity. From the fasting serum lipids, triglycerides showed an inverse (p < 0.001) and HDL a weak (p < 0.05) positive association with ISI. Four out of 20 metabolic, clinical, and demographic parameters proved to be independently significant predictors for ISI in multiple regression analysis. These were insulin AUC, fasting insulin levels, triglyceride values, and age. The coefficient of determination in this four-parameter linear model was 69%. In this preliminary, observer-masked trial with a limited control group, celiprolol improved the impaired insulin sensitivity and glucose tolerance of dyslipidemic hypertensive patients. A fairly predictive model can be formulated to evaluate the peripheral insulin sensitivity of hypertensive patients with suspected metabolic syndrome using OGTT with serum insulin determinations.


Effects of fasting, temperature, and photoperiod on preproghrelin mRNA expression in Chinese perch.
Preproghrelin, a gut/brain peptide, plays an important role in the regulation of food intake and energy homeostasis in teleost and mammals. In the present study, we obtained the full-length preproghrelin cDNA in Chinese perch. The preproghrelin messenger RNA (mRNA) tissue expression showed that level was much higher in stomach and pituitary than in other tissues. The fasting study showed, after gastric emptying (3-6 h), short-term fasting (6-12 h) increased preproghrelin expression in the stomach. While in the pituitary, fasting reduced preproghrelin expression at 1, 3, 12, and 48 h, presenting state fluctuation of self-adjustment. The temperature study showed that the mRNA expression of preproghrelin was the highest in the brain at 26 °C and highest in the stomach at 32 °C, respectively, with different optimum temperature in these two tissues, reflecting spatiotemporal differences of regulation by central nervous system and peripheral organs. The photoperiod study showed that normal light (11 h of lightness and 13 h of darkness) led to highest preproghrelin expression, both in the brain and in the stomach, than continuous light or continuous dark, proving food intake is adapted to natural photoperiod or normal light in this study. These results all indicated that tissue-specific preproghrelin expression of Chinese perch could be significantly affected by environmental factors. Short-term fasting of 6 h after gastric emptying, 26 °C, and normal light led to higher preproghrelin expression, which indicated potential appetite increase in Chinese perch.


The restorative management of hypodontia with implants: 2. Planning and treatment with implants.
The first paper discussed the clinical features of patients with hypodontia. A range of treatment options were considered with examples given. In this second paper, the implant treatment option for patients is discussed in detail.