A descriptive study of blind children in nurseries with sighted children.
In a longitudinal descriptive and qualitative study, nine blind pre-school children have been observed in natural interactional settings in their nurseries. The objective was to give a detailed description of the blind child's activities and social situation in a group of sighted children. The results showed that the blind child's overall behaviour in the pre-school setting was different when compared with the sighted children's behaviour, as shown in activities like orientation, exploration and play. The blind children seldom participated in sighted children's play and they seldom initiated contact with the other children. The sighted children initially showed an interest in the blind child but as their initiatives were often neglected, they were not encouraged to proceed. The teachers played an important role for the blind children, both as a visual interpreter and as a play-mate. However, many of the teachers had great difficulties in understanding the blind child's way of functioning. Alternative pre-school settings for blind children are discussed.


[Molecular methods in thrombophilic states diagnostics].
Molecular genetic methods passed into the field of investigation of thrombophilic states in 90th years of last century, along with the first discoveries of coagulation inhibitors (AT III, protein C and protein S). They have acquired a widespread use above all with the detection of the molecular basis of activated protein C (APC) resistance in 1994 by prof. Bertina. At the present time, a wide range of molecular genetic markers, linked with a clearly documented increased risk of thrombophilia are adapted. They include mutations of factor V Leiden 506R/Q, of protrombin 20210G/A, MTHFR 677C/T in homozygous form, mutation of PAI-1 4G/5G, mutations of different coagulation inhibitors and finally a range of polymorphisms with still not precisely defined increased risk for thrombophilia (F XIII Val34leu, platelets glycopeproteins, endothelial protein C receptor and trombomodulin). From the methodological viewpoint, all these techniques are based on the principle polymerase chain reaction (PCR). In the last period of time, however there was a rapid evolution, allowing a significant improvement in their laboriousness. Nowadays, splitting with the aid of restriction endonucleases, real time PCR or allel specific primers for PCR. The second, where molecular genetic methods are currently under use, is pathophysiological investigation of the single coagulation processes. Here, in a fact, most significant progress has been in the field of APC resistance made elucidation. Although still in the 90th years of the past century the genetical cause of these coagulation disturbance was unequivocally documented its clinically heterozygous appears not yet fully understood at the moment. Similarly, in prothrombin mutation, only the latest investigations have outlined the probable mechanism of expression. Concerning the future evolution of molecular genetic methods, there can be observed a clear cut tendency to better understanding the pathophysiologic cause of thrombophilia in comparison with the searching for new coagulation defects which consecutively bear lesser a relative risk of thrombosis.


Lacticaseibacillus paracasei: Occurrence in the Human Gut Microbiota and K-Mer-Based Assessment of Intraspecies Diversity.
Alignment-free approaches employing short k-mers as barcodes for individual genomes have created a new strategy for taxonomic analysis and paved a way for high-resolution phylogeny. Here, we introduce this strategy for the Lacticaseibacillus paracasei species as a taxon requiring barcoding support for precise systematics. Using this approach for phylotyping of L. paracasei VKM B-1144 at the genus level, we identified four L. paracasei phylogroups and found that L. casei 12A belongs to one of them, rather than to the L. casei clade. Therefore, we propose to change the specification of this strain. At the genus level we found only one relative of L. paracasei VKM B-1144 among 221 genomes, complete or available in contigs, and showed that the coding potential of the genome of this "rare" strain allows its consideration as a potential probiotic component. Four sets of published metagenomes were used to assess the dependence of L. paracasei presence in the human gut microbiome on chronic diseases, dietary changes and antibiotic treatment. Only antibiotics significantly affected their presence, and strain-specific barcoding allowed the identification of the main scenarios of the adaptive response. Thus, suggesting bacteria of this species for compensatory therapy, we also propose strain-specific barcoding for selecting optimal strains for target microbiomes.


Arteriocaliceal Fistula: A Life-Threatening Condition After Retrograde Intrarenal Surgery.
Background: Retrograde intrarenal surgery (RIRS) has emerged as a viable and safe option for renal stones <2 cm. Because of its high efficiency and relative safety, experienced endourologists have applied it to even larger stones. We present a case of arteriocaliceal fistula, which is a rare postoperative complication of RIRS. Case Presentation: A 52-year-old man with a rich history of endourologic procedures and extracorporeal shockwave lithotripsy caused by inferior caliceal calculi was subjected to RIRS. This was complicated by transient intraoperative hemorrhage, followed by recurrent hematuria and clot retention several days postoperatively. Renal arteriography revealed the presence of an arteriocaliceal fistula. This was completely resolved with selective arterial embolization. Conclusion: This case highlights that early detection and timely intervention are crucial to avoid serious consequences of post-RIRS hemorrhage resulting from arteriocaliceal fistula.


Bloody neonatal diaper.
As part of the ongoing effort to minimize health care expenses, mothers and newborns are being discharged after shorter hospital stays. Problems that previously would have been noticed in the hospital nursery are now being seen in the emergency department. We report the case of a 1-day-old infant who was brought to our ED with grossly bloody stool. An Apt test was performed to determine whether the blood was of infant or maternal origin. After determining that the blood was the infant's, we transferred the child to a pediatric specialty center, where a diagnosis of necrotizing enterocolitis was made.


Structural plasticity in the eight-helix fold of a trematode haemoglobin.
The three-dimensional structure of recombinant haemoglobin from the trematode Paramphistomum epiclitum, displaying the highest oxygen affinity so far observed for (non)vertebrate haemoglobins, has previously been determined at 1.17 A resolution (orthorhombic space group P2(1)2(1)2(1)). In the present communication, the three-dimensional structure of wild-type P. epiclitum haemoglobin is reported at 1.85 A resolution in a monoclinic crystal form (R factor = 16.1%, R(free) = 22.0%). Comparison of P. epiclitum (recombinant versus wild-type ferric Hb) structures in the two crystal forms shows structural differences in the haem proximal and distal sites which have not been reported for other known haemoglobin structures previously.


Risk of papillary thyroid cancer in women in relation to smoking and alcohol consumption.
Both smoking and alcohol consumption may influence thyroid function, although the nature of these relations is not well understood. We examined the influence of tobacco and alcohol use on risk of papillary thyroid cancer in a population-based case-control study. Of 558 women with thyroid cancer diagnosed during 1988-1994 identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (N = 410). Controls (N = 574) were identified by random digit dialing, with a response proportion of 73.6%. We used logistic regression to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with cigarette smoking and alcohol consumption. A history of ever having smoked more than 100 cigarettes was associated with a reduced risk of disease (OR = 0.7, 95% CI = 0.5-0.9). This reduction in risk was most evident in current smokers (OR = 0.5, 95% CI = 0.4-0.7). Women who reported that they had ever consumed 12 or more alcohol-containing drinks within a year were also at reduced risk (OR 0.7, 95% CI = 0.5-1.0). Similar to the association noted with smoking, the reduction in risk was primarily present among current alcohol consumers. The associations we observed, if not due to chance, may be related to actions of cigarette smoking and alcohol consumption that reduce thyroid cell proliferation through effects on thyroid stimulating hormone, estrogen, or other mechanisms.


[Angiographic findings of vertebral dissecting aneurysm. Report of two cases and review of literature].
The authors report two cases of vertebral dissecting aneurysm. The first case, a 49-year-old female, developed severe headache and computed tomography scan showed subarachnoid hemorrhage (SAH), but 4-vessel cerebral angiography failed to show an aneurysm. The second angiograms obtained 2 weeks later showed possible aneurysmal dilatation on the right vertebral artery. The third angiograms, 2.5 months after SAH, disclosed a right vertebral fusiform aneurysm on the arterial phase and it was diagnosed as a dissecting aneurysm since the contrast medium remained until the very late venous phase. The previous angiograms were reviewed using the subtraction technique, which revealed retention of the contrast medium. The second case, a 42-year-old female, suffered from SAH. Left vertebral angiography revealed a fusiform aneurysmal tapered narrowing just distal to the aneurysm, which was a typical "pearl and string sign." The subtraction film of the venous phase also showed retention of the contrast medium in the aneurysmal portion. These findings accurately diagnosed dissecting aneurysm of the vertebral artery. Since the classical true diagnostic "double lumen sign" was rarely observed in the angiograms, it was not easy to diagnose dissecting aneurysm of the vertebral artery. The authors emphasize the angiographic findings of retention of the contrast medium in the venous phase as a "true diagnostic sign" for correct diagnosis of dissecting aneurysm.


Giant pumping of single-file water molecules in a carbon nanotube.
Achieving a fast, unidirectional flow of single-file water molecules (UFSWM) across nanochannels is important for membrane-based water purification or seawater desalination. For this purpose, electro-osmosis methods are recognized as a very promising approach and have been extensively discussed in the literature. Utilizing molecular dynamics simulations, here we propose a design for pumping water molecules in a single-walled carbon nanotube in the presence of a linearly gradient electric (GE) field. Such a GE field is inspired by GE fields generated from charged ions located adjacent to biological membrane water nanochannels that can conduct water in and out of cells and can be experimentally achieved by using the charged tip of an atomic force microscope. As a result, the maximum speed of the UFSWM can be 1 or 2 orders of magnitude larger than that in a uniform electric (UE) field. Also, inverse transportation of water molecules does not exist in case of the GE field but can appear for the UE field. Thus, the GE field yields a much more efficient UFSWM than the UE field. The giant pumping ability as revealed is attributed to the nonzero net electrostatic force acting on each water molecule confined in the nanotube. These observations have significance for the design of nanoscale devices for readily achieving controllable UFSWM at high speed.


Ticks produce highly selective chemokine binding proteins with antiinflammatory activity.
Bloodsucking parasites such as ticks have evolved a wide variety of immunomodulatory proteins that are secreted in their saliva, allowing them to feed for long periods of time without being detected by the host immune system. One possible strategy used by ticks to evade the host immune response is to produce proteins that selectively bind and neutralize the chemokines that normally recruit cells of the innate immune system that protect the host from parasites. We have identified distinct cDNAs encoding novel chemokine binding proteins (CHPBs), which we have termed Evasins, using an expression cloning approach. These CHBPs have unusually stringent chemokine selectivity, differentiating them from broader spectrum viral CHBPs. Evasin-1 binds to CCL3, CCL4, and CCL18; Evasin-3 binds to CXCL8 and CXCL1; and Evasin-4 binds to CCL5 and CCL11. We report the characterization of Evasin-1 and -3, which are unrelated in primary sequence and tertiary structure, and reveal novel folds. Administration of recombinant Evasin-1 and -3 in animal models of disease demonstrates that they have potent antiinflammatory properties. These novel CHBPs designed by nature are even smaller than the recently described single-domain antibodies (Hollinger, P., and P.J. Hudson. 2005. Nat. Biotechnol. 23:1126-1136), and may be therapeutically useful as novel antiinflammatory agents in the future.


Old species and new concepts in the taxonomy of Pomacea (Gastropoda: Ampullariidae).
The taxonomic history of the South American genus Pomacea Perry, 1810, and some shifts of systematic concepts during recent decades are briefly reviewed. Too many pre-evolutionist, shell-defined species created a gibberish, the only acceptable solution of which being perhaps a conventional, somewhat authoritarian decision based on expertise. The addition of other sources of morphological, biochemical, ecological or genetic information should not solve the problem if it is not accompanied by a sound reappraisal of the species concepts. Since the assumptions of each concept differ, any correspondence between them is irrelevant, and may drive to incompatible results. The shell variability of Pomacea canaliculata was acknowledged for most authors throughout more than a century. A recent insight into its life-history traits demonstrated they are as variable as the morphology. These findings stress the need of determining the ecological identity of any pest apple-snail population at a local scale, because its invading ability may be not exactly correlated to its taxonomical identity. Probably, all the canaliculata-like apple snails constitute a single, very variable "species" in most senses, even though different subsets may be recognized under other incommensurable concepts.


A pestivirus DNA vaccine based on a non-antibiotic resistance Escherichia coli essential gene marker.
Antibiotic resistance genes are widely used to produce plasmid DNA vaccines, but risk unwanted exposure to antibiotic residues and the spread of resistance genes. To overcome the limitations of existing selection technologies, we developed an alternative system applying the widely used household biocide triclosan as the selective agent and an endogenous growth essential target gene, fabI, as the plasmid-borne marker in Escherichia coli. The fabI/triclosan system enables efficient, non-antibiotic selection of transformed bacteria, with improved safety and plasmid production features. Here we aimed to evaluate the performance of this non-antibiotic selection system using a plasmid DNA vaccine against bovine viral diarrhoea virus as an example. The new system displayed high-yield plasmid DNA production in a standard E. coli host strain and growth media. Notably, the purified pDNA provided efficient in vitro protein expression and a strong in vivo neutralising antibody response in a mouse model, with measures comparable to that of the parental plasmid DNA based on ampicillin resistance. The fabI/triclosan system requires only low levels of triclosan for selection (1 μM) and residual triclosan in isolated DNA was below the limit of detection (< 20 parts per trillion). The fabI/triclosan selection system provides a simple, non-antibiotic resistance marker for plasmid selection, applicable to DNA vaccines and possibly other recombinant vaccine applications.


Spectroscopic study of tetradecyltrimethylammonium bromide Pt-C14TAB nanoparticles: structure and stability.
The vibrational spectra of platinum nanoparticles (12 nm) capped with tetradecyltrimethylammonium bromide, C(14)TAB, were investigated by Fourier transform infrared (FTIR) spectroscopy. We have shown that the thermal decay of Pt-C(14)TAB nanoparticles in N(2), H(2), and O(2) atmospheres leads to the release of the hydrocarbon chain of the surfactant and the formation of a strongly bonded layer of ammonium cations on the platinum surface. The platinum atoms accessible to CO chemisorption were not reducible by hydrogen in the temperature range from 30 to 200 degrees C. A FTIR spectrum of C(14)TAB adsorbed on Pt nanoparticles was dramatically perturbed as compared with pure C(14)TAB. New intense and broad bands centered at 1450 cm(-1) and 760 cm(-1) are making their appearance in Pt-C(14)TAB. It may be speculated that new bands are the result of coupling between conducting electrons of Pt and molecular vibrations of adsorbed C(14)TAB, and as a consequence, specific vibrational modes of ammonium cation are transformed into electron-vibrational modes.


The kappa-like pre-B receptor: surplus biology or a missing link?
After the demonstration that surrogate JCkappa polypeptides could covalently bind mu heavy chain and upon the characterization of the Vkappa-like component of the kappa-like pre-B cell receptor, it became evident that germline transcription is not sterile. The present review discusses the concept of the alternative usage of kappa-like pre-B cell receptors and classical pre-B cell receptors utilizing the lambda-like surrogate light chain composed of lambda5 and VpreB. We propose that both kappa-like and lambda-like pre-B cell receptors work in concert in a fail-safe mechanism to promote light chain rearrangement, heavy chain allelic exclusion and B-lymphocyte maturation.


Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene.
Previous studies defined a DNA element necessary for glucocorticoid repression of the pro-opiomelanocortin (POMC) gene. The glucocorticoid receptor (GR) binds this negative glucocorticoid response element (nGRE) with an in vitro affinity similar to that of GR for positive GREs. However, whereas GR binds GREs as homodimers, a novel GR complex which forms with nGRE appears to contain three GR molecules. Biochemical characterization of this complex as well as equilibrium binding studies suggest that it is formed by sequential binding of a GR homodimer followed by binding of a GR monomer on the opposite side of the double helix. The DNA-binding domain (DBD) of GR is sufficient for differential binding of GRE and nGRE, as bacterially-expressed DBD formed unique nGRE complexes that contain three GR polypeptides. Thus, the POMC nGRE provides the first example of an interaction between GR and DNA in which GR binds otherwise than as a homodimer. Despite its high affinity for GR, the nGRE differs significantly from GREs in that it does not activate transcription in any context. As the nGRE appears insufficient on its own to confer hormone responsiveness, other POMC promoter elements are likely to be required to mediate glucocorticoid repression.


Helminth infection does not reduce risk for chronic inflammatory disease in a population-based cohort study.
Parasitic helminth infections can suppress symptoms of allergy, type 1 diabetes, arthritis, and inflammatory bowel disease in animal models. We analyzed data from a large, population-based cohort study to determine whether common childhood enterobiasis protects against these diseases. We collected information on individual prescriptions filled for the drug mebendazole against Enterobius vermicularis for all children born in Denmark 1995-2008 from the National Register of Medicinal Product Statistics (n = 924,749; age 0-14 years); 132,383 of these children (14%) filled a prescription for mebendazole, 102,482 of the children (11%) had a household peer who was registered with a filled mebendazole prescription, and the remaining 689,884 children (75%) comprised the reference group. Children diagnosed with asthma, type 1 diabetes, juvenile arthritis, ulcerative colitis, or Crohn's disease were identified from the National Patient Registry. We used Poisson regression to estimate confounder-adjusted incidence rate ratios for first in- or outpatient hospital diagnosis of chronic inflammatory disease according to history of mebendazole treatment prescribed to children in the study. Chronic inflammatory disease was diagnosed in 10,352 children during 6.4 million person-years of follow-up. The incidence rate ratios was 1.07 for asthma (95% confidence interval [CI]: 1.00-1.13), 1.05 for type 1 diabetes (95% CI: 0.79-1.12), 1.13 for juvenile arthritis (95% CI: 0.94-1.37), 0.77 for ulcerative colitis (95% CI: 0.41-1.46), and 1.44 for Crohn's disease (95% CI: 0.82-2.53). Results were not modified by number of treatments or age at treatment. Based on a population-based analysis, enterobiasis does not reduce risk for asthma, type 1 diabetes, arthritis, or inflammatory bowel disease.


Concurrent administration of donepezil HCl and risperidone in patients with schizophrenia: assessment of pharmacokinetic changes and safety following multiple oral doses.
This open-label, multiple-dose trial investigated the effect of concurrent administration of donepezil HCl with risperidone on the pharmacokinetics (PK) and safety profiles of both drugs. Sixteen male patients with schizophrenia, who were receiving stable, physician-optimized risperidone (1-4 mg twice daily), and 15 healthy age- and weight-matched male controls, received donepezil HCl 5 mg daily for 7 days. Patients with schizophrenia remained on their physician-optimized dose of risperidone throughout the study. Pharmacokinetic parameters (C(max), t(max) and AUC) were assessed from plasma drug concentrations measured in blood collected before, during and after administration (for 12 h after risperidone on days 0 and 7, and for 24 h after donepezil HCl on day 7). The mean age of all the subjects was 38.5 years. Donepezil PK parameters were similar between patients taking donepezil HCl + risperidone (AUC(0-24 h) = 329.0 +/- 17.2 ng x h ml(-1)) and controls taking donepezil HCl alone (AUC(0-24 h) = 354.7 +/- 28.2 ng x h ml(-1)). Pharmacokinetic parameters for risperidone and 9-OH risperidone were not altered in patients with schizophrenia after 7 days of donepezil HCl administration (AUC(0-12 h) standardized by dose: risperidone = 59.6 +/- 16.3 ng.h ml(-1) at day 0, 56.0 +/- 15.8 ng x h ml(-1) at day 7; 9-OH risperidone = 162.1 +/- 19.2 ng x h ml(-1) at day 0, 163.3 +/- 15.0 ng x h ml(-1) at day 7). The most common adverse event in both treatment groups was diarrhoea (6/16 risperidone + donepezil HCl patients and 9/16 donepezil HCl only subjects). There were no significant changes in physical examination, ECG, vital signs or treatment-emergent abnormal laboratory values associated with either of the treatment regimens. No subject developed extrapyramidal side-effects following donepezil administration. These results suggest that once-daily dosing of 5 mg donepezil HCl does not alter the PK of risperidone in patients with schizophrenia. The combination of risperidone and donepezil HCl was well tolerated.


Rock n' Seeds: A database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation.
Advancing functional ecology depends fundamentally on the availability of data on reproductive traits, including those from tropical plants, which have been historically underrepresented in global trait databases. Although some valuable databases have been created recently, they are mainly restricted to temperate areas and vegetative traits such as leaf and wood traits. Here, we present Rock n' Seeds, a database of seed functional traits and germination experiments from Brazilian rock outcrop vegetation, recognized as outstanding centers of diversity and endemism. Data were compiled through a systematic literature search, resulting in 103 publications from which seed functional traits were extracted. The database includes information on 16 functional traits for 383 taxa from 148 genera, 50 families, and 25 orders. These 16 traits include two dispersal, six production, four morphological, two biophysical, and two germination traits-the major axes of the seed ecological spectrum. The database also provides raw data for 48 germination experiments, for a total of 10,187 records for 281 taxa. Germination experiments in the database assessed the effect of a wide range of abiotic and biotic factors on germination and different dormancy-breaking treatments. Notably, 8255 of these records include daily germination counts. This input will facilitate synthesizing germination data and using this database for a myriad of ecological questions. Given the variety of seed traits and the extensive germination information made available by this database, we expect it to be a valuable resource advancing comparative functional ecology and guiding seed-based restoration and biodiversity conservation in tropical megadiverse ecosystems. There are no copyright restrictions on the data; please cite this paper when using the current data in publications; also the authors would appreciate notification of how the data are used in publications.


Determination of outer-sphere dipolar time correlation functions from high-field NMR measurements. Example of a Gd(3+) complex in a viscous solvent.
We consider a diamagnetic species carrying a nuclear spin and having a purely outer-sphere dynamics with respect to a Gd(3+) complex. The maximal structural and dynamic information attainable from the paramagnetic relaxation (rate) enhancement (PRE) of this nuclear spin due to the Gd(3+) electronic spin is the outer-sphere dipolar time correlation function (OS-DTCF) of the relative position of these spins. We show how to determine this OS-DTCF by a model-free analysis of high-field PRE measurements, which accounts for the relative diffusion coefficient of the spin carrying species derived from pulsed-gradient spin-echo experiments. The method rests on the spectral characterization of the OS-DTCF through a PRE property, the "star" relaxivity, which can be measured over an unexpectedly large frequency range by combining multiple field and temperature NMR experiments. It is illustrated in the case of the (1)H spins on the three diamagnetic probes tert-butanol CHD(2)(CD(3))(2)COD and glycerol (CD(2)OD)(2)CHOD and CHDOD-CDOD-CD(2)OD interacting with Gddtpa(2-) (dtpa(5-)=diethylen triamin pentaacetate) in a viscous glycerol-d8/D(2)O solvent. The general usefulness of the OS-DTCF for the description of the liquid state and electronic spin relaxation is discussed.


Diagnosing ectopic pregnancy in the emergency setting.
Ectopic pregnancy is the implantation of a fertilized egg outside the uterine endometrial cavity. For women presenting to the emergency department with abdominal pain and/or vaginal bleeding, ectopic pregnancy is an important diagnostic consideration. The diagnosis is made based on laboratory values and ultrasound imaging findings. The ultrasound appearance of both normal early pregnancy and ectopic pregnancy are variable and often subtle, presenting diagnostic challenges for radiologists. This pictorial essay describes and illustrates the sonographic findings of ectopic pregnancy and reviews the differential diagnoses that can mimic ectopic pregnancy on ultrasound. With the possibility of medical management, the value of early detection and prompt initiation of treatment has increased in improving clinical outcomes and preventing the complications of ectopic pregnancy.


Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase.
Drug resistance (DR) of HIV-1 can be examined genotypically or phenotypically. Although sequencing is the gold standard of the genotypic resistance testing (GRT), high-throughput GRT targeted to the codons responsible for DR may be more appropriate for epidemiological studies and public health research. We used a Japanese database to design and synthesize sequence-specific oligonucleotide probes (SSOP) for the detection of wild-type sequences and 6 DR mutations in the clade B HIV-1 reverse transcriptase region. We coupled SSOP to microbeads of the Luminex 100 xMAP system and developed a GRT based on the polymerase chain reaction (PCR)-SSOP-Luminex method. Sixteen oligoprobes for discriminating DR mutations from wild-type sequences at 6 loci were designed and synthesized, and their sensitivity and specificity were confirmed using isogenic plasmids. The PCR-SSOP-Luminex DR assay was then compared to direct sequencing using 74 plasma specimens from treatment-naïve patients or those on failing treatment. In the majority of specimens, the results of the PCR-SSOP-Luminex DR assay were concordant with sequencing results: 62/74 (83.8%) for M41, 43/74 (58.1%) for K65, 70/74 (94.6%) for K70, 55/73 (75.3%) for K103, 63/73 (86.3%) for M184 and 68/73 (93.2%) for T215. There were a number of specimens without any positive signals, especially for K65. The nucleotide position of A2723G, A2747G and C2750T were frequent polymorphisms for the wild-type amino acids K65, K66 and D67, respectively, and 14 specimens had the D67N mutation encoded by G2748A. We synthesized 14 additional oligoprobes for K65, and the sensitivity for K65 loci improved from 43/74 (58.1%) to 68/74 (91.9%). We developed a rapid high-throughput assay for clade B HIV-1 DR mutations, which could be customized by synthesizing oligoprobes suitable for the circulating viruses. The assay could be a useful tool especially for public health research in both resource-rich and resource-limited settings.


Epigenetic suppression of GAD65 expression mediates persistent pain.
Chronic pain is a common neurological disease involving lasting, multifaceted maladaptations ranging from gene modulation to synaptic dysfunction and emotional disorders. Sustained pathological stimuli in many diseases alter the output activities of certain genes through epigenetic modifications, but it is unclear how epigenetic mechanisms operate in the development of chronic pain. We show here that in the rat brainstem nucleus raphe magnus, which is important for central mechanisms of chronic pain, persistent inflammatory and neuropathic pain epigenetically suppresses Gad2 (encoding glutamic acid decarboxylase 65 (GAD65)) transcription through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in impaired γ-aminobutyric acid (GABA) synaptic inhibition. Gad2 knockout mice showed sensitized pain behavior and impaired GABA synaptic function in their brainstem neurons. In wild-type but not Gad2 knockout mice, HDAC inhibitors strongly increased GAD65 activity, restored GABA synaptic function and relieved sensitized pain behavior. These findings suggest GAD65 and HDACs as potential therapeutic targets in an epigenetic approach to the treatment of chronic pain.


[Influence of occlusal contacts of implant on adjacent teeth and antagonists displacements].
This study examined the optimum occlusal contacts of implant prostheses to maintain good oral condition after treatment. Three subjects who had two contiguously missing teeth (first and second molars) were selected. The displacement path of the implant, the adjacent tooth and the antagonistic tooth during clenching were measured using the type M-3 three-dimensional tooth displacement transducer. The occlusal contacts of implant prostheses changed according to the following four conditions. A contact: the inner inclination of the upper buccal cusp, B contact: the inner inclination of the upper lingual cusp, C contact: the outer inclination of the upper lingual cusp, and ABC contact: including the above three contacts. The measurements were performed at least six months after implant surgery. In each subject, the implants and the adjacent teeth were not affected by the change of the occlusal contact of the implant prosthesis, but the opposing teeth were affected. In the case of implantation in the lower side, the opposing tooth displaced in the buccal direction with A contact and C contact, which was a different direction to that of the natural tooth. The antagonist with B contact displaced in the lingual direction, which was the same direction as that of the natural tooth. The antagonist with ABC contact displaced in the lingual or buccal direction. It is concluded that the occlusal adjustment of implants needs much care: in the case of only A contact or C contact, non-physiological distortion might occur in periodontal tissues of the opposing teeth of the implant.


The shared signal hypothesis: Facial and bodily expressions of emotion mutually inform one another.
Decades of research show that contextual information from the body, visual scene, and voices can facilitate judgments of facial expressions of emotion. To date, most research suggests that bodily expressions of emotion offer context for interpreting facial expressions, but not vice versa. The present research aimed to investigate the conditions under which mutual processing of facial and bodily displays of emotion facilitate and/or interfere with emotion recognition. In the current two studies, we examined whether body and face emotion recognition are enhanced through integration of shared emotion cues, and/or hindered through mixed signals (i.e., interference). We tested whether faces and bodies facilitate or interfere with emotion processing by pairing briefly presented (33 ms), backward-masked presentations of faces with supraliminally presented bodies (Experiment 1) and vice versa (Experiment 2). Both studies revealed strong support for integration effects, but not interference. Integration effects are most pronounced for low-emotional clarity facial and bodily expressions, suggesting that when more information is needed in one channel, the other channel is recruited to disentangle any ambiguity. That this occurs for briefly presented, backward-masked presentations reveals low-level visual integration of shared emotional signal value.


S 47445 counteracts the behavioral manifestations and hippocampal neuroplasticity changes in bulbectomized mice.
S 47445 is a positive allosteric modulator of glutamate AMPA-type receptors that possesses procognitive, neurotrophic and enhancing synaptic plasticity properties. Its chronic administration promotes antidepressant- and anxiolytic-like effects in different rodent models of depression. We have evaluated the behavioral effects of S 47445 in the bilateral olfactory bulbectomy mice model (OB) and the adaptive changes in those proteins associated to brain neuroplasticity (BDNF and mTOR pathway). Following OB surgery, adult C57BL/6J male mice were chronically administered S 47445 (1, 3 and 10 mg/kg/day; i.p.) and fluoxetine (18 mg/kg/day; i.p.), and then behaviorally tested in the open field test. Afterwards, the expression levels of BDNF, mTOR, phospho-mTOR, 4EBP1 and phospho-4EBP1 were evaluated in hippocampus and prefrontal cortex. Both drugs reduced the OB-induced locomotor activity, a predictive outcome of antidepressant efficacy, with a similar temporal pattern of action. S 47445, but not fluoxetine, showed an anxiolytic effect as reflected by an increased central activity. Chronic administration of S 47445 reversed OB-induced changes in BDNF and phopho-mTOR expression in hippocampus but not in prefrontal cortex. The chronic administration of S 47445 induced antidepressant- and anxiolytic-like effects at low-medium doses (1 and 3 mg/kg/day, i.p.) associated with the reversal of OB-induced changes in hippocampal BDNF and mTOR signaling pathways.


Comparison of the efficacy of ambroxol hydrochloride and N -acetylcysteine in the treatment of children with bronchopneumonia and their influence on prognosis.
The aim of the present study was to compare the efficacy of ambroxol hydrochloride and N-acetylcysteine in the treatment of children with bronchial pneumonia and their influence on prognosis. A total of 120 children with bronchial pneumonia, admitted to The Affiliated Yantai Yuhuangding Hospital of Qingdao University from July 2015 to August 2018, were enrolled in the study. Among them, 58 children were treated with N-acetylcysteine and comprised the experimental group, and 62 children were treated with ambroxol hydrochloride and comprised the control group. Children's physical signs (such as fever, short breath, cough and pulmonary rales) and the adverse reactions to treatment were observed, and the disappearance time of the signs was recorded. In addition, the cellular immune function indicators and the quality of life after treatment were investigated. There was no significant difference in clinical data between the two groups (P>0.05). The effective rate in the experimental group was significantly higher than that in the control group (P<0.05). The disappearance time of symptoms, such as fever, cough, asthma and rales in the lung, was significantly shorter in the experimental group than that in the control group (P<0.05). The hospitalization time of patients in the experimental group was shorter than that in the control group (P<0.05). After treatment, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and complement C3 were significantly increased in the experimental group (P<0.01), and the IgA and IgG in the experimental group were significantly higher than those in the control group (P<0.01). The incidence of adverse reactions in the experimental group was significantly lower than that in the control group (P<0.05). In conclusion, N-acetylcysteine has a significant effect on the treatment of bronchopneumonia in children providing a quick relief from symptoms, such as lung rales, and therefore is worthy of use in clinic.


[Hyperthermic treatment of benign prostatic hyperplasia by a prostathermer].
Prostate thermotherapy consisting of 6 sessions of intrarectal 60 min irradiation of 915 MHz microwave generated by a prostathermer (Blodan, Isreal) was performed once or twice a week on 30 patients with benign prostatic hyperplasia. Excluding 2 cases who refused further therapy at the first session because of rectal discomfort, 28 cases were evaluated for the efficacy of the treatment. Good or fair improvement in subjective symptoms was observed in 24 (85.7%) of the cases. Nocturia was significantly relieved from 2.9 to 2.0 a night. Among the objective responses, no improvement was achieved as to residual urine or prostate size, while a significant increase of maximum or average flow rate on uroflowmetry was observed. Adverse effects were minor or moderate, including 2 cases of urethral bleeding and rectal discomfort, 2 cases of lower urinary tract infection and 1 case of hypotension, which occurred at the 5th session. The scoring criteria taking into account of both subjective and objective responses showed that the efficacy is good in 10 cases (33.3%) and fair or good in 20 cases (66.7%). These results indicated the usefulness of the prostathermer as one of non-surgical therapies for benign prostatic hyperplasia.


A recombinant subunit vaccine that protects progeny chickens from infectious bursal disease.
The major protective immunogen of infectious bursal disease virus (IBDV), VP2, was produced in a highly immunogenic form by expression in the yeast Saccharomyces cerevisiae. The recombinant protein, formulated as an oil-emulsion vaccine, induced both virus neutralising and ELISA antibodies in specific pathogen free hens. These antibodies were passed, via the egg yolk, to progeny chickens and protected them against a challenge infection with virulent IBDV. The protective efficacy of maternal antibodies to the recombinant VP2, as assessed by ELISA, was comparable to that of antibodies to the whole virus. The recombinant subunit vaccine induced anamnestic serum antibody responses in hens primed previously with live virus, and hence can replace the conventional inactivated vaccines administered to breeding hens.


Carbamide peroxide nanoparticles for dental whitening application: Characterization, stability and in vivo/in situ evaluation.
Carbamide peroxide is the popular home dental whitening agent. However, it has critical stability. Nanoparticles have been applied to develop products with advantages properties as better efficacy and stability increase. The aim of this study was the characterization of carbamide peroxide polymeric nanoparticles, their bleaching efficacy, effects on pulp damage and stability evaluation. Particle size demonstrated a spherical morphology and bimodal distribution (11 and 398 nm). Nanoparticles presented high entrapment efficiency (98.94%) and the zeta potential value was slightly positive (+10.26 mV). Regardless of the zeta potential, the steric effect may contribute to carbamide peroxide nanoparticle stabilization. The stability studies conducted at room temperature suggested that carbamide peroxide nanoparticles could maintain all the parameters evaluated (size, polydispersity index, zeta potential, entrapment efficiency, pH and content) for at least 90 days. Instability index was determined by dispersion analyzer (LUMiSizer ®), was 0.018, and the light transmission profile did not present sedimentation. Carbamide peroxide nanoparticles were able to prevent thermal degradation and photostability. Clinical efficacy of the whitening gels was obtained by color change in the spectrophotometer and the results showed that all the evaluated gels containing the nanoparticles (0, 1, 2 and 5% of real carbamide peroxide) were effective at bleaching after 2 h of home whitening treatment (during 30 days). After the treatment, the extracted teeth showed no in situ pulp damage by histological evaluation. The nanotechnology strategy of converting carbamide peroxide into polymeric nanoparticles revealed a new product with improved stability, a good approach for carbamide peroxide delivery.


Effect of conditioning method and testing method on strength of lithium-induced taste aversion learning.
Here the authors evaluated the effect of the method of conditioning (bottle or intraoral [IO] infusion) on the strength of a flavor-drug association when measured in a standard 1-bottle consumption test or when measured by IO infusion in a taste reactivity test. When tested with the bottle test in Experiment 1, rats conditioned by bottle displayed stronger taste avoidance than those conditioned by IO infusion. When tested for rejection reactions with the taste reactivity test in Experiment 2, rats conditioned by infusion displayed a stronger aversion than did rats conditioned by bottle. The results suggest that when the contextual cues of conditioning are similar at conditioning and testing, a stronger association is evident regardless of the individual specifics of each method. These results may shed light on recent reports that different neural mechanisms are involved in conditioning by active consumption and passive infusion.


Spatiotemporal Changes of Chemical Fertilizer Application and Its Environmental Risks in China from 2000 to 2019.
Chemical fertilizers are important inputs in agricultural production. They not only increase crop yield but also bring many negative effects, such as agricultural non-point source pollution. Therefore, a scientific understanding of the regional differences in chemical fertilizer application and its environmental risks is of significance to promote China's agricultural development. In this study, we analyzed the spatiotemporal pattern of chemical fertilizer application intensity (CFAI) in China since 2000, evaluated the environmental risks of provincial CFAI, and investigated the internal mechanism behind them. The results showed that the total amount and intensity of chemical fertilizer application in China from 2000 to 2019 presented a trend of increasing first and then decreasing. In 2000 and 2019, provincial CFAI in eastern China was generally higher than that in central and western China, and the environmental risks of provincial CFAI were spatially characterized by "high in the north and low in the south". Factors such as poor soil conditions, unreasonable farming structure and backward fertilization methods are the main reasons for the continuous increase in the total amount and intensity of chemical fertilizer application, while the construction of ecological civilization and the transformation of society and economy are the main reasons for their decline. Finally, measures such as targeted fertilization, adjusting the use structure of chemical fertilizers, improving fertilization methods and replacing chemical fertilizers with organic fertilizers are proposed to promote the quantity reduction and efficiency increase of chemical fertilizer application in China.


Mutations of TP53, amplification of EGFR, MDM2 and CDK4, and deletions of CDKN2A in malignant astrocytomas.
We investigated the frequency and mutual relationship of molecular alterations in 33 malignant astrocytomas (28 glioblastomas and 5 anaplastic astrocytomas). The genetic alterations analyzed were: deletion of CDKN2a/p16 gene, TP53 mutations, and amplification of EGFR, MDM2 and CDK4. The most common genetic alteration was EGFR amplification which was revealed in 15 cases (45%). TP53 mutation was identified in 9 cases (27%) and CDKN2/p16 deletion was detected in 13 cases (41%). Either MDM2 and CDK4 amplifications were less frequent, as they were identified in 4 (12%) and 1 (3%) case, respectively. Of the 15 cases showing the amplification of EGFR, 9 had CDKN2/p16 deletion (60%, p = 0.04). On the other hand, CDKN2/p16 deletion and EGFR amplification rarely occurred with TP53 mutations (2 of 14 cases with CDKN2/p16 deletion, 14%). These results confirm the existence of at least two different pathways leading to the formation of a glioblastoma.


[A case of intrapancreatic duodenal duplication communicating with the biliopancreatic channel].
Intestinal duplications are rare and are usually diagnosed in the first two years of infancy. They can occur at any level of the alimentary tract from the oral cavity to the anus. Duodenal duplication accounts for approximately 7% of all intestinal duplications. A previously healthy 4-year 6-month old boy was admitted with progressive increasing vomiting. Physical examination was normal, the serum amylase level was moderately increased. Upper gastrointestinal series showed an extrinsic compression defect of the proximal duodenum. Ultrasonography showed a 3 cm diameter cyst in the head of the pancreas. A duplication was suggested. Helical CT cholangiography showed a communication between duplication and the biliopancreatic common channel. The biliary tree was normal. Surgical resection of the intrapancreatic lesion was performed. Microscopic examination of the specimen revealed a duodenal duplication.


Clinical manifestations, pathogenesis, and effect of antibiotic treatment on Lyme borreliosis in dogs.
Borrelia burgdorferi, the causative agent of Lyme disease, infects humans and animals. In humans, the disease primarily affects the skin, large joints, and the nervous system days to months after infection. Data generated with appropriate animal model help to understand the fundamental mechanisms of the disease. 1) More clearly define the clinical manifestation and pathogenetic mechanisms of Lyme disease in dogs; 2) evaluate the effect of antibiotics in dogs infected with B. burgdorferi; 3) describe the effects of corticosteroids on dogs persistently infected with B. burgdorferi. Specific-pathogen-free beagles were infected with B. burgdorferi using ticks collected in an endemic Lyme disease area. Clinical signs were recorded daily. Antibody titers were measured by ELISA at two-week intervals. B. burgdorferi organisms were detected in tissues by culture and PCR. Synovial fluids were evaluated microscopically and with a chemotaxis cell migration assay. Histological sections were examined for pathological lesions. Specific cytokine up-regulation in tissues was detected by RT-PCR. In three separate experiments, B. burgdorferi-infected dogs received antibiotic treatment (amoxicillin; azithromycin; ceftriaxone; doxycycline) for 30 consecutive days. Two subclinical persistently infected dogs received oral prednisone for 14 consecutive days starting at day 420 post-infection. Dogs developed acute arthritis in the joints closest to the tick bites after a median incubation period of 68 days. Synovial membranes of lame and non-lame dogs produced the chemokine IL-8 in response to B. burgdorferi. Antibiotic treatment prevented or resolved episodes of acute arthritis, but failed to eliminate the bacterium from infected dogs. Corticosteroid treatment reactivated Lyme disease in persistently infected dogs, which had not received antibiotics previously. B. burgdorferi disseminates through tissue by migration following tick inoculation, produces episodes of acute arthritis, and establishes persistent infection. The spirochete survives antibiotic treatment and disease can be reactivated in immunosuppressed animals.


Microfluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma.
The clinical outcome of SARS-CoV-2 infections, which can range from asymptomatic to lethal, is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets. However, the affinity of polyclonal antibody responses in plasma is difficult to measure. Here we used microfluidic antibody affinity profiling (MAAP) to determine the aggregate affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples of 42 seropositive individuals, 19 of which were healthy donors, 20 displayed mild symptoms, and 3 were critically ill. We found that dissociation constants, K d, of anti-receptor-binding domain antibodies spanned 2.5 orders of magnitude from sub-nanomolar to 43 nM. Using MAAP we found that antibodies of seropositive individuals induced the dissociation of pre-formed spike-ACE2 receptor complexes, which indicates that MAAP can be adapted as a complementary receptor competition assay. By comparison with cytopathic effect-based neutralisation assays, we show that MAAP can reliably predict the cellular neutralisation ability of sera, which may be an important consideration when selecting the most effective samples for therapeutic plasmapheresis and tracking the success of vaccinations.


Norcantharidin combined with Coix seed oil synergistically induces apoptosis and inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation.
The immune system plays a critical role in exerts effects in the growth and progression of hepatocellular carcinoma (HCC), which needs interacting approaches for effective therapy. In this study, we have found that the Norcantharidin (NCTD) + Coix lacryma-jobi seed oil (CLSO) combination exhibited more potent antitumor effects in an terms of cytotoxicity and apoptotic induction in human HepG2 and HepG2/ADM cells than NCTD or CLSO alone. In vivo, administration of NCTD+CLSO combinations significantly suppressed the formation of tumor in Hepal-1 hepatoma-bearing mice. Furthermore, we found that the in vitro co-cultures of HepG2 or HepG2/ADM cells with PBMCs from healthy donors led to an increase in the number of CD4 + CD25 + T cells. This increase was down-regulated by the combination effectively. Down-regulation of FoxP3 mRNA and protein expression occurred during the combination in the co-cultures. The amount of Tregs of Hepal-1 hepatoma-bearing mice was significantly decreased in the combination treated group. The combination down-regulated the expression of FoxP3, CTLA-4 and Tregs related cytokine (TGF-β and IL-10) in the serum of tumor bearing mice. Taken together, these results suggest that the most valuable aspect of the NCTD+CLSO combined use improves the anti-tumor activity and regulates tumor infiltrating Tregs.


Urinary cytopathology in primary bladder amyloidosis.
Amyloidosis results from the accumulation of unique extracellular proteins which are not able to be degraded via the usual mechanism of lysosomal proteolysis. Isolated collections of amyloid within the bladder are extremely uncommon, and a cytopathologic description in voided urine has not been described to date. A retrospective review was performed at a tertiary-care hospital, and 3 patients with isolated bladder amyloidosis and corresponding voided urine specimens were identified. The following clinical data were collected for each case: age, gender, treatment and follow-up information. The patient age range was 76-84 years, with 2 males and 1 female. Amyloidosis was never clinically suspected. In 1 patient, a urinary amyloid manifested, which was thought to represent extraneous debris at the time of original diagnosis. Two patients never manifested signs of systemic amyloidosis or multiple myeloma, and the third was found to have a monoclonal gammopathy. Our results show the difficulty of diagnosing urinary amyloid in the absence of clinical suspicion. Further, the presence of urinary amyloid is unlikely in patients with bladder amyloidosis as the cohesive nature of the protein makes spontaneous shedding uncommon. Testing for systemic amyloidosis is warranted and if the disease is localized, a favorable outcome can be expected.


Alpha interferon gene deletions in adults, children and infants with acute lymphoblastic leukemia.
DNA from 76 cases of acute lymphoblastic leukemia (ALL) was tested with a cDNA probe encoding the alpha 2B interferon (IFN) gene transcript. Deletions were found in three of ten pre-B, three of 21 T-cell, four of 22 common and one of 23 null ALL cases. Amongst those with null ALL were 20 infants, most with characteristic translocations, none of whom had deletion of alpha IFN genes. The results confirm that alpha IFN gene deletions may occur without visible abnormalities of chromosome 9p and show that they occur across a wide range of ALL phenotypes. The results suggest that alpha IFN gene deletions may be rare events in null ALL of infants but their incidence and cellular consequences remain unknown.


Characterization of blood vessels in bone marrow from patients with chronic myeloid leukemia and polycythemia vera.
Angiogenesis is a feature of hematological malignancies which may provide prognostic information. However, there is, as yet, no established marker for leukemia-associated vessels in bone marrow. In this study, immunohistochemical stainings for von Willebrand factor (vWf), CD34, Tie-2, angiomodulin, glycodelin, cycloxygenase-2 (Cox-2) and endoglin were compared in order to identify the bone marrow vasculature. Chronic myeloid leukemia (CML), a disease displaying intense angiogenesis, and polycythemia vera (PV), a disease with a low microvascular density (MVD), were studied, as well as normal bone marrow. Only vWf, CD34 and Tie-2 stained the bone marrow endothelium. Although more vessels were stained for vWf than for CD34, there was no evidence that vWf stained more disease-associated vessels. In double staining, Tie-2 co-localized with CD34, but vessels staining only for Tie-2 were also found. However, the number of Tie-2-positive vessels did not correlate to either the MVD or the disease. Angiomodulin, glycodelin, Cox-2 and endoglin did not stain vessel-like structures. In conclusion, estimating the MVD by means of CD34 staining appears to be the most reliable method, but none of the tested molecules qualified as a specific marker for leukemia-associated vessels in the bone marrow.


Targeting of protein kinase C-epsilon during Fcgamma receptor-dependent phagocytosis requires the epsilonC1B domain and phospholipase C-gamma1.
Protein kinase C-epsilon (PKC-epsilon) translocates to phagosomes and promotes uptake of IgG-opsonized targets. To identify the regions responsible for this concentration, green fluorescent protein (GFP)-protein kinase C-epsilon mutants were tracked during phagocytosis and in response to exogenous lipids. Deletion of the diacylglycerol (DAG)-binding epsilonC1 and epsilonC1B domains, or the epsilonC1B point mutant epsilonC259G, decreased accumulation at phagosomes and membrane translocation in response to exogenous DAG. Quantitation of GFP revealed that epsilonC259G, epsilonC1, and epsilonC1B accumulation at phagosomes was significantly less than that of intact PKC-epsilon. Also, the DAG antagonist 1-hexadecyl-2-acetyl glycerol (EI-150) blocked PKC-epsilon translocation. Thus, DAG binding to epsilonC1B is necessary for PKC-epsilon translocation. The role of phospholipase D (PLD), phosphatidylinositol-specific phospholipase C (PI-PLC)-gamma1, and PI-PLC-gamma2 in PKC-epsilon accumulation was assessed. Although GFP-PLD2 localized to phagosomes and enhanced phagocytosis, PLD inhibition did not alter target ingestion or PKC-epsilon localization. In contrast, the PI-PLC inhibitor U73122 decreased both phagocytosis and PKC-epsilon accumulation. Although expression of PI-PLC-gamma2 is higher than that of PI-PLC-gamma1, PI-PLC-gamma1 but not PI-PLC-gamma2 consistently concentrated at phagosomes. Macrophages from PI-PLC-gamma2-/- mice were similar to wild-type macrophages in their rate and extent of phagocytosis, their accumulation of PKC-epsilon at the phagosome, and their sensitivity to U73122. This implicates PI-PLC-gamma1 as the enzyme that supports PKC-epsilon localization and phagocytosis. That PI-PLC-gamma1 was transiently tyrosine phosphorylated in nascent phagosomes is consistent with this conclusion. Together, these results support a model in which PI-PLC-gamma1 provides DAG that binds to epsilonC1B, facilitating PKC-epsilon localization to phagosomes for efficient IgG-mediated phagocytosis.


Nutritional status in peritoneal dialysis: studies in body composition, lipoprotein metabolism and peritoneal function.
This thesis is based on clinical studies including virtually all patients treated with peritoneal dialysis in Gothenburg during the 1990s. The patients had a fundamentally altered body composition compared to healthy subjects, characterised by a reduction in body cell mass and body fat already at start of dialysis. During PD treatment. a further decrease in body cell mass was observed. Energy stores tended to normalise during the first years of treatment and remained constant thereafter, or declined subsequently. Extracellular water, calculated from the four-compartment model, was increased when patients started PD treatment and increased further, in parallel to the reduction in body cell mass. These alterations were seen in combination with a normal. or slightly reduced, body weight. Standard methods of assessing nutritional status may therefore not be valid in the dialysis population. Prediction equations to estimate total body water, used in measurements of dialysis adequacy, give erroneous results in PD patients, as shown in a study on our PD population. This may have important clinical consequences, especially in wasted patients. Reduced muscle mass is a marker of protein-energy malnutrition, and therefore simple and reliable methods to measure muscle mass are warranted. When lean body mass was calculated from creatinine generation rate and compared to lean body mass estimated from measurements of total body potassium. the agreement between the two methods was low. Furthermore, when repeated measurements of creatinine generation rate were performed, the variation coefficient was unacceptably high. Thus. creatinine generation rate cannot be recommended as a method to evaluate somatic protein status in PD patients. The lipoprotein metabolic derangements are pronounced in PD patients. in which a further increase in cholesterol and cholesterol-rich apoB-containing lipoproteins are added to the already pre-existing renal dyslipidemia. characterised by increased concentration of triglycerides and triglyceride-rich complex lipoproteins. There are indications that dialytic variables may influence this development. When peritoneal function was assessed by the Peritoneal Dialysis Capacity test at start of dialysis, it was observed that peritoneal function reflected patient characteristics and co-morbidity. Patients with systemic disease had enhanced diffusion capacity compared to patients with primary renal disorders. Furthermore, in patients with more severe co-morbidity. peritoneal protein losses were increased. Finally, elderly patients had ultrafiltration conditions that were different from those of younger patients. Peritoneal function remained essentially stable during medium-long term follow up. Body composition features in dialysis patients are similar to those seen in severe disease in general. Thus, it is difficult to separate the effects of malnutrition from the effects of the underlying disease. Specific standards for nutritional status adapted for patients with renal failure are required.


Detection of interferon regulatory factor-1 in lamina propria mononuclear cells in Crohn's disease.
The transcription factor, interferon regulatory factor (IRF)-1, is stimulated by interferon-gamma and regulates the expression of several genes implicated in the pathogenesis of inflammatory bowel disease, including interleukin-6, major histocompatibility complex class II molecules, and inducible nitric oxide synthase. Interferon regulatory factor-1 also stimulates naive CD4+ T-cells to differentiate into T-helper-1 cells, the T-cell subset that appears to be upregulated in Crohn's disease. The purpose of this study was to examine the expression of IRF-1 in the nuclei of lamina propria mononuclear cells in situ in colonoscopic biopsy specimens from pediatric patients with Crohn's disease, in patients with ulcerative colitis, and in control patients with no histopathologic abnormalities. Archival paraffin-embedded tissue sections were obtained from 25 pediatric patients with Crohn's disease, 6 patients with ulcerative colitis, and 12 control patients who had undergone colonoscopy. Tissue sections were stained with polyclonal rabbit anti-human antisera to IRF-1 and horseradish-peroxidase-conjugated, biotinylated, goat anti-rabbit secondary antibody. Slides were scored and scores compared among patient groups using analysis of variance. Patients with Crohn's disease had significantly higher IRF-1 scores (95% confidence interval [CI], 1.70-2.04) than patients with ulcerative colitis (95% CI, 0.92-1.23) or control subjects (95% CI, 1.11-1.52). Increased expression of IRF-1 in lamina propria mononuclear cells from patients with Crohn's disease may be relevant to the pathogenesis of Crohn's disease.


The feasibility of collecting in-flight EEG data from helicopter pilots.
An assessment of whether valid EEG data could be collected on helicopter pilots in flight was conducted. Each subject provided eyes-open/eyes-closed EEG in the laboratory and in a helicopter. During flights, EEG's were monitored on the ground in real-time via radio telemetry. Analyses were conducted on the data recorded from Fz, Cz, Pz, P3, P4, O1, and O2 from eight subjects. Delta activity at one recording site (Fz) was higher in the aircraft than in the laboratory probably because of increased eye movements. Both theta and alpha activity at several sites also were increased in the aircraft, and alpha activity at all electrodes showed the expected augmentation from eyes-opened to eyes-closed; however, there were no interactions indicative of problems detecting normal alpha changes due to eye closure in the aircraft. Beta activity recorded from Cz and O1 was elevated during flight testing, but it was concluded that at least the O1 effect was due to muscle artifact in the more active environment. While there were more recording artifacts in the helicopter than in the laboratory, the overall results show it is possible to telemeter EEG from helicopter pilots in flight. Follow-on studies are needed to assess whether recordings can be obtained while pilots are performing flight-related tasks.


A beta-carboline alkaloid from the Papua New Guinea marine sponge hyrtios reticulatus.
A new 1-imidazoyl-3-carboxy-6-hydroxy-beta-carboline alkaloid, named hyrtiocarboline (1), was isolated from a Papua New Guinea marine sponge, Hyrtios reticulatus. The structure was elucidated from spectroscopic data, including (1)H-(15)N HMBC NMR experiments, which provided complementary (15)N chemical shift information in support of the structure. This compound showed selective antiproliferative activity against H522-T1 non-small cell lung, MDA-MB-435 melanoma, and U937 lymphoma cancer cell lines.


Buddhism-as-a-meaning-system for coping with late-life stress: a conceptual framework.
Religion is increasingly conceptualized as a meaning system for adjustment and coping. Most of the conceptualizations are grounded in the Judeo-Christian tradition. They may thus not be applicable to Buddhism, which provides a distinct tenor of meaning for coping. This article seeks to construct a conceptual framework of Buddhism-as-a-meaning-system for coping with late-life stress. Literature review and conceptualization were employed. Under this framework, Buddhism functions as a meaning system involving existential meaning, cognitive meaning, and behavioral meaning. There is reason to believe that this framework promises to offer a holistic conceptual map of Buddhist coping in late life. Thus, it could serve as a guide for further empirical and theoretical exploration in the uncharted terrains of Buddhist coping in old age. In addition, gerontological practitioners could use this framework as a frame of reference when working with elderly Buddhist clients who are in stressful circumstances.


Isolation, characterization, and evaluation of wild isolates of Lactobacillus reuteri from pig feces.
Lactic acid bacteria (LAB) are a well-used probiotics for health improvements in both humans and animals. Despite of several benefits, non-host-specific LAB showed poor probiotics effects due to difficulty in colonization and competition with normal flora. Therefore, the feasibility of porcine LAB isolates was evaluated as a probiotics. Ten of 49 Lactobacillus spp. isolates harbored 2 approximately 10 kb plasmid DNA. Seven strains were selected based on the safety test, such as hemolytic activity, ammonia, indole, and phenylalanine production. After safety test, five strains were selected again by several tests, such as epithelial adherence, antimicrobial activity, tolerance against acid, bile, heat, and cold-drying, and production of acid and hydrogen peroxide. Then, enzyme profiles (ZYM test) and antibiotics resistance were analyzed for further characterization. Five Lactobacillus reuteri isolates from pig feces were selected by safety and functional tests. The plasmid DNA which was able to develop vector system was detected in the isolates. Together with these approaches, pig-specific Lactobacillus spp. originated from pigs were selected. These strains may be useful tools to develop oral delivery system.


Improvement of Segmental Lordosis in Transforaminal Lumbar Interbody Fusion: A Comparison of Two Techniques.
Study Design Retrospective review. Objective The purpose of this study was to determine the radiographic impact of a transforaminal lumbar interbody fusion (TLIF) versus a cantilever TLIF technique on segmental lordosis, segmental coronal alignment, and disk height. Methods A retrospective review was done of all patients undergoing TLIF procedures from 2006 to 2011 by three spine surgeons. Traditional TLIF versus cantilever TLIF results were compared, and radiographic outcomes were assessed. Results One hundred one patients were included in the study. Patients undergoing the cantilever TLIF procedure had a significantly greater change in segmental lordosis and disk height compared with those who underwent the traditional procedure (p > 0.0001). Conclusions The cantilever TLIF technique can lead to greater change in segmental lordosis based upon radiographic outcomes.


[Electrocardiographic characteristics of patients with left circumflex-related myocardial infarction in the acute phase without tented T waves or definite ST elevation].
Acute myocardial infarction (AMI) causing ST depression and T wave inversion has been diagnosed as subendocardial or non-Q myocardial infarction. However, some patients eventually develop strictly posterior infarction with a lesion of the left circumflex coronary artery (LCX). This study attempted to determine the electrocardiographic (ECG) characteristics of such myocardial infarction in 32 patients with definite AMI in whom ECG showed no hyperacute T waves or ST elevation and the LCX was an infarct-related coronary artery. ECG on admission (< 6 hours from the onset), at 24 hours, and on the 14th day were analyzed to evaluate QRS, ST, T, and U waves using calipers and magnifying lens. Sixty-six patients with normal circulation served as controls. The characteristic ECG findings on admission were ST depression in chest leads, and prominent positive U waves in leads V2 or V3 with relatively small T waves. Based on these results we proposed new ECG criteria: 1) ST depression > or = 0.1 mV in 2 consecutive chest leads, 2) prominent positive U wave > or = 0.1 mV in leads V2 or V3, 3) T/U ratio in leads V2 or V3 < or = 4. Considering two of the above criteria as positive, the sensitivity was 71.9%, the specificity 97.0%, and the diagnostic accuracy 88.8%. In 85.2% of the patients, ST depression returned to the baseline by 24 hours. As the amplitude of the U waves decrease gradually, the T/U ratio increased. The R/S ratio in leads V1 or V2 became > or = 1 by 24 hours in 46.4% and the amplitude of R wave in lead V1 increased gradually. T waves in the right precordial leads increased with time. These findings were consistent with isolated strictly posterior myocardial infarction. From these results we identified new ECG criteria: 1) R/S ratio in leads V1 or V2 > or = 1, 2) R wave > or = 0.7 mV in lead V1, 3) T wave > or = 0.5 mV in lead V1. Considering any of the above criteria as positive, the sensitivity was 72.0%, the specificity 87.9%, and the diagnostic accuracy 86.7% on the 14th day. These new ECG criteria of strictly posterior myocardial infarction with the LCX as an infarct-related coronary artery apply at less than 6 hours or at 24 hours from the onset of the symptoms.


A hard look at angiotensin receptor blockers in heart failure.
Multiple trials over the past several years have examined indications for angiotensin receptor blockers (ARBs) in the treatment of left ventricular dysfunction, both acutely after myocardial infarction and in chronic heart failure. Yet despite these data, there is still confusion regarding the efficacy of ARBs as monotherapy in these patient populations, as well as the specific indications for combination ARB/angiotensin-converting enzyme (ACE) inhibitor therapy. We examine the key differences among the trials-including the ACE inhibitor dose, the ARB and its dose, blood pressure reduction, and patient populations-to present our perspective on ARB use, alone or in combination with ACE inhibitors, in patients with chronic heart failure and post-myocardial infarction left ventricular dysfunction. We conclude that ACE inhibitors remain the first-line therapy for left ventricular dysfunction. Angiotensin receptor blockers should be reserved for monotherapy in ACE intolerant patients and for combination therapy in symptomatic class II/III patients with chronic heart failure.


Adult supraglottitis.
Airway management of supraglottitis in the adult is controversial as regards the choice between observation and acute intervention. This study was undertaken to determine whether factors exist that place patients at higher risk of airway obstruction and to review conservative treatment outcome. Of 46 cases during an 8-year period, seven required tracheostomy and 39 were observed. Odynophagia and fever were present in all patients. Yearly clusters of up to six cases in 1 month were detected. White blood cell count and heart rate were significantly more elevated in those who underwent tracheostomy. A symptom duration of less than 24 hours was associated (p < 0.05, chi 2 analysis) with airway compromise as well. There was no associated morbidity or mortality, and mean hospital stay was 5.2 days for those observed and 7.9 days for those who underwent tracheostomy.


The complete chloroplast genome of the Tibetan medicinal plant Rhodiola kirilowii.
Rhodiola kirilowii is a widely used Tibetan medicine. Here, we report the complete sequence of the chloroplast genome of R. kirilowii. The genome was 150,896 bp in length with 131 genes comprising 85 protein-coding genes, 37 tRNA genes, 8 rRNA genes and 1 pseudogene, with 20 of them occurring in double copies. Phylogenomic analysis suggested that R. kirilowii forms a clade with R. rosea, R. yunnanensis, R. fastigiata and R. crenulata in Rhodiola genus.


Benign cementoblastoma. Case report.
Benign cementoblastoma is a rare benign odontogenic tumour of mesenchymal origin. A case of a 24-year-old man with benign cementoblastoma is presented. The lesion manifested as a round, radiopaque mass attached to the root of the left first molar of the mandible. The tooth was extracted and the lesion was removed. A diagnosis of benign cementoblastoma was made microscopically. There has been no evidence of recurrence during the three-year follow-up period. A review of the literature and a discussion of the histologic features of this case are included.


Development and Validation of Prognostic Nomograms to Predict Overall and Cancer-Specific Survival for Patients with Adenocarcinoma of the Urinary Bladder: A Population-Based Study.
Adenocarcinoma of the bladder (ACB) rarely occurs but is associated with poor outcome. We aim to establish reliable nomograms for estimating cancer-specific survival (CSS) and overall survival (OS) of ACB patients. ACB patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). A total of 1,149 patients were randomly divided into training cohort (n = 692) and validation cohort (n = 457). Multivariate Cox proportional hazards regression models were employed to identify independent prognostic factors. Nomograms predicting OS and CSS were constructed utilizing screened factors. The performance of nomograms was internally and externally validated by calibration curves, the receiver operating characteristic (ROC) curves, concordance index (C-index), and decision curve analysis (DCA). OS nomogram incorporated age, race, histologic grade, American Joint Committee of Cancer (AJCC) stage, metastasis, surgery, chemotherapy, and tumor size. The C-indices were 0.754 (95% CI: 0.732-0.775) for training set and 0.743 (95% CI: 0.712-0.767) for validation set. Meanwhile, the calibration plots for 3- and 5-year OS displayed fine concordance between actual and predicted outcomes. In addition, higher areas under the curve (AUCs) were seen in training cohort (3-year: 0.799 vs. 0.630; 5-year: 0.797 vs. 0.648) and validation cohort (3-year: 0.802 vs. 0.662; 5-year: 0.752 vs. 0.660). Finally, DCA curves of the nomograms exhibited larger net benefits than AJCC stage. CSS nomogram showed similar results. Our study constructed and validated nomograms with improved discriminative abilities and clinical benefits to predict the survival outcomes of ACB patients. The models might assist clinicians in optimizing therapeutic management on individual levels.


Circadian Mechanisms: Cardiac Ion Channel Remodeling and Arrhythmias.
Circadian rhythms are involved in many physiological and pathological processes in different tissues, including the heart. Circadian rhythms play a critical role in adverse cardiac function with implications for heart failure and sudden cardiac death, highlighting a significant contribution of circadian mechanisms to normal sinus rhythm in health and disease. Cardiac arrhythmias are a leading cause of morbidity and mortality in patients with heart failure and likely cause ∼250,000 deaths annually in the United States alone; however, the molecular mechanisms are poorly understood. This suggests the need to improve our current understanding of the underlying molecular mechanisms that increase vulnerability to arrhythmias. Obesity and its associated pathologies, including diabetes, have emerged as dangerous disease conditions that predispose to adverse cardiac electrical remodeling leading to fatal arrhythmias. The increasing epidemic of obesity and diabetes suggests vulnerability to arrhythmias will remain high in patients. An important objective would be to identify novel and unappreciated cellular mechanisms or signaling pathways that modulate obesity and/or diabetes. In this review we discuss circadian rhythms control of metabolic and environmental cues, cardiac ion channels, and mechanisms that predispose to supraventricular and ventricular arrhythmias including hormonal signaling and the autonomic nervous system, and how understanding their functional interplay may help to inform the development and optimization of effective clinical and therapeutic interventions with implications for chronotherapy.


Evaluation of Gram-positive rod surveillance for early anthrax detection.
Since 2003, Connecticut laboratories have reported Gram-positive rod (GPR) isolates detected within 32 h of inoculation from blood or cerebrospinal fluid. The objectives were to rapidly identify inhalational anthrax and unusual Clostridium spp. infections, and to establish round-the-clock laboratory reporting of potential indicators of bioterrorism. From 2003 to 2006, Connecticut's GPR surveillance system identified 1134 isolates, including 657 Bacillus spp. (none B. anthracis) and 241 Clostridium spp. Reporting completeness and timeliness improved to 93% and 92%, respectively. Baseline rates of Bacillus spp., Clostridium spp. and other GPR findings have been established and are stable. Thus far, no cases of anthrax and no unusual clusters of Clostridium spp. have been detected by the GPR surveillance system. This system would probably have confirmed the inhalational anthrax case in Pennsylvania in 2006 3 days sooner than traditional reporting. Using audits and ongoing evaluation, the system has evolved into a highly functional 24/7 laboratory telephone reporting system with almost complete reporting.


In It for the Long Haul: RE-AIM Evaluation of a Preschool Programme Implementing and Maintaining Adult-Initiated Motor Skill Development and Physical Activity across a Two-Year Period.
Good motor skills (MS) are considered important for children's social, psychological and physical development and general physical activity (PA) levels. The Motor skill in Preschool study (MiPS) aimed to optimize children's MS through weekly PA sessions. The aim of this study is to use the RE-AIM framework to report the two-year implementation process of MiPS since the programme's initiation. Data were collected through a staff questionnaire based on the RE-AIM framework. Data were collected at three months, one year and two years after initiation. Results show that the pedagogical staff believes that the programme promotes MS in children. Implementation measures only showed medium to low fidelity concerning the core element of performing adult-initiated PA sessions with a duration of at least 45 min 4 days a week. The largest barrier was finding the time to plan these PA sessions. Still, the content of the PA sessions achieved high fidelity scores and the programme was deemed suitable for staff's everyday practice and in alignment with the stated pedagogical goals. The mandatory competence development course was highly valued as strong implementation support. It is notable that there is a large variation in the implementation among the preschools with some struggling more than others.


Interstitial duplication of the short arm of chromosome 1 in a newborn with congenital heart disease and multiple malformations.
Interstitial duplications of chromosomes 1p are rare, with only 14 cases previously reported in the literature, and those have not revealed a unique syndrome. The phenotypes include multiple congenital abnormalities and both intra- and extra-uterine growth retardation. In general, the patients do poorly and do not survive beyond the age of several months. We report a newborn male with karyotype 46, XY, inv dup(1)(qter--> p34.3::p34.3-->p32.3::34.3-->pter) with multiple congenital abnormalities including congenital heart disease and co-existing portal and pulmonary hypertension. The chromosome 1 origin of the extra material was confirmed with fluorescent in situ hybridization (FISH). Review of the GDB [Human Genome Database, 1990] reveals that the duplicated region includes the locus EDN2 that encodes endothelin-1, a potent vasoconstrictor, making genetic overdosage of this protein a likely etiology of the pulmonary hypertension. The diffuse abnormalities show effects in multiple cell lines and suggest that this region of chromosome 1p could be involved in determining cell migration and/or differentiation during organogenesis.


A multivariate classification study of attentional orienting in patients with right hemisphere lesions.
To characterize patterns of orienting dysfunction that were typical to patients with lesions in the right hemisphere (RH). Brain lesions in the right hemisphere are commonly associated with dysfunction of visual orienting (e.g., visual neglect and extinction). In a clinical study of these symptoms, the multicomponent nature of attentional orienting calls upon a multivariate statistical design with careful selection of neurocognitive variables. Thirty-eight patients with verified brain lesions and four patients with peripheral motor dysfunction after poliomyelitis were included in the study. Cognitive function was evaluated in all patients. Three reaction-time (RT) measures derived from the cue-target paradigm were selected as features in a data-driven multivariate classification scheme to generate natural subgroups of patients. Four subgroups were generated, with only RH patients allocated to two of them. All patients within one of the RH subgroups were characterized by a pattern of impairment earlier described as a "disengage failure" by Posner et al. ( 5, 6), signs of visual neglect on Behavioral Inattention Test, and a severely impaired cognitive function. Results for the other RH subgroup were heterogeneous on both experimental and clinical variables. Age and cognitive function were found to strongly influence two of the features, but could not predict the clusters generated from the RT measures. The present findings show that the cue-target paradigm together with multivariate clustering of selected feature variables can serve as a useful tool to explore and characterize patients with right hemisphere lesions. Although the concept of "disengage failure" was suited to describe the typical RT pattern in patients with neglect, other neurocognitive models and concepts can be applied to the results in the current study.


Large breathing effect induced by water sorption in a remarkably stable nonporous cyanide-bridged coordination polymer.
While metal-organic frameworks (MOFs) are at the forefront of cutting-edge porous materials, extraordinary sorption properties can also be observed in Prussian Blue Analogs (PBAs) and related materials comprising extremely short bridging ligands. Herein, we present a bimetallic nonporous cyanide-bridged coordination polymer (CP) {[Mn(imH)]2[Mo(CN)8]} n (1Mn; imH = imidazole) that can efficiently and reversibly capture and release water molecules over tens of cycles without any fatigue despite being based on one of the shortest bridging ligands known - the cyanide. The sorption performance of {[Mn(imH)]2[Mo(CN)8]} n matches or even outperforms MOFs that are typically selected for water harvesting applications with perfect sorption reversibility and very low desorption temperatures. Water sorption in 1Mn is possible due to the breathing effect (accompanied by a dramatic cyanide-framework transformation) occurring in three well-defined steps between four different crystal phases studied structurally by X-ray diffraction structural analysis. Moreover, the capture of H2O by 1Mn switches the EPR signal intensity of the MnII centres, which has been demonstrated by in situ EPR measurements and enables monitoring of the hydration level of 1Mn by EPR. The sorption of water in 1Mn controls also its photomagnetic behavior at the cryogenic regime, thanks to the presence of the [MoIV(CN)8]4- photomagnetic chromophore in the structure. These observations demonstrate the extraordinary sorption potential of cyanide-bridged CPs and the possibility to merge it with the unique physical properties of this class of compounds arising from their bimetallic character (e.g. photomagnetism and long-range magnetic ordering).


The normal human choroid is endowed with a significant number of lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1)-positive macrophages.
Lymphatic vessel endothelial hyaluronic acid receptor (LYVE-1) is a newly discovered lymphatic endothelium-specific marker that is also expressed by a subpopulation of macrophages. To date, there is no report on its expression in the posterior human uvea. The purpose of this study was to investigate the expression of LYVE-1 in normal human choroids. Eyes of body/cornea donors (55-89 years of age; 4-9 hours postmortem) were obtained. Choroids were dissected and prepared for cryosections followed by immunohistochemistry with anti-human LYVE-1 antiserum and immunogold labeling. In addition, anti-human antibodies against macrophage markers (CD68, MHC class II) and lymphatic (podoplanin) and blood vascular endothelium (CD31, vWF) were used. For documentation, light-, fluorescence-, confocal laser scanning-, and electron-microscopy were used. The normal human choroidal stroma contained 274 +/- 86 LYVE-1 positive cells/mm(2). The cells displayed irregular shapes with a relatively uniform diameter of 32 mum. Costaining with CD68 and negativity for CD31, podoplanin, and melan-A/HMB45, as well as electron microscopic features, suggest these LYVE-1(+) cells to be macrophages. Besides that, no classic LYVE-1(+)/podoplanin(+) lymphatic vessels were detected within the normal adult human choroid. The normal adult human choroid does not contain typical lymph vessels, but is endowed with a significant number of LYVE-1 positive macrophages. These cells may be involved in choroidal hyaluronic acid metabolism or contribute to temporary formation of lymphatic channels under inflammatory conditions.


The prevalence of hearing impairment and its burden on the quality of life among adults with Medicare Supplement Insurance.
To estimate the impact of hearing impairment on quality of life from a physical and mental standpoint. Data were obtained from the Health Update Survey, which contains questions on demographics, comorbid conditions, and the Veterans RAND 12-item health status/quality of life survey. It was fielded on a random sample of 15,000 adults with an AARP(®) Medicare Supplement plan, insured by UnitedHealthcare. Respondents were divided into those with hearing impairments and others, based on their response to a survey question. Univariate and multivariate analyses were conducted to estimate the likelihood of hearing impairment and its impact on quality of life while controlling for respondent demographics and comorbid conditions. Of the 5,515 eligible respondents, 10.4% reported having hearing impairments. The strongest predictor of hearing impairment was older age, while those with 4 years of college or more were least likely to have hearing impairments. Those with hearing impairments averaged significantly lower physical component and mental component scores, exceeding those of numerous other chronic conditions. This is the first known study of hearing impairment among those with Medigap coverage. Hearing impairment was strongly associated with lower quality of life from both a physical and mental health standpoint.


Short-acting versus a long-acting preparation of theophylline ('Xantivent') in the treatment of reversible bronchospasm.
A study was carried out in 30 patients with chronic obstructive pulmonary disease to compare the effectiveness and tolerance of a standard theophylline preparation given 4-times daily with that of a long-acting preparation given in comparable dosage twice daily. All patients were treated for the first 2 weeks with the standard theophylline and dosage was adjusted to optimal levels according to individual patient tolerance. Patients were then treated for the following 2 weeks with the long-acting theophylline preparation. Mean daily dosage was 10.82 mg/kg body weight during the standard and slightly lower at 9.90 mg/kg during the long-acting theophylline treatment periods. Assessments of clinical symptoms and measurements of pulmonary functions were made on entry and at the end of each treatment period, and theophylline serum levels were determined at 0 hour and 5 hours after the last dose. The results showed that the improvement in clinical symptoms was significantly more pronounced after the long-acting theophylline period. In addition, pulmonary functions also showed a greater tendency for improvement after this period. The long-acting preparation was better tolerated and therapeutic theophylline serum levels of 10 to 20 micrograms/ml were achieved at 0 hour of dosing in 36.7% and at 5 hours of dosing in 60.0% of all patients, while therapeutic serum levels were achieved only in 6.7% and 20.0%, respectively, after the standard theophylline. The optimal starting dose of the long-acting theophylline preparation ('Xantivent') appeared to be between 11 and 13 mg/kg body weight to achieve therapeutic serum levels over 24 hours.


FK228 induces mitotic catastrophe in A549 cells by mistargeting chromosomal passenger complex localization through changing centromeric H3K9 hypoacetylation.
Previous studies have shown that histone deacetylase inhibitors (HDACis) can kill cancer cells. In addition, HDACis can induce mitotic catastrophe in cancer cells due to insufficient localization of chromosomal passenger complex (CPC) to the centromere. However, the mechanisms behind these phenomena remain unclear. In this study, we found that a HDACi, FK228, affected multiple epigenetic modification characteristics of the centromere, including enhanced acetylation of histone H3 lysine 9 (H3K9), decreased trimethylation of H3K9, and decreased phosphorylation of histone H3 serine 10 (H3S10) and centromere protein A (CENP-A). These epigenetic changes implied that H3K9 hyperacetylation inhibits the CPC recruitment, induces impaired centromere assembly and function, and eventually leads to aberrant mitosis. These data suggested that hypoacetylation of histone in the pericentromere is the most important landmark for recruiting CPC and leading to the mitotic catastrophe in HDACi-induced killing of cancer cells.


Psychological components of pain.
Patients with complex orofacial pain conditions often do not respond as expected to dental care. This article discusses the many psychoanalytic factors that are involved in the pain experience of these patients.


Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Boostrix(®)): results of two randomized trials.
Pertussis can cause significant morbidity in elderly patients, who can also transmit this disease to infants and young children. There is little data available on the use of acellular pertussis vaccines in recipients ≥65 years of age. Two studies examined the safety and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine (Boostrix(®)) in healthy ≥65 year olds. In Study A subjects received single doses of Tdap and seasonal influenza vaccine either co-administered or given one month apart. In Study B subjects received either Tdap or tetanus-diphtheria (Td) vaccine. Antibodies were measured before and one month after vaccination. Reactogenicity and safety were actively assessed using diary cards. A total of 1104 subjects 65 years of age and older received a Tdap vaccination in the two studies. In study A, no differences in immune responses to Tdap or influenza vaccine were observed between co-administered or sequentially administered vaccines. In study B, Tdap was non-inferior to Td with respect to diphtheria and tetanus seroprotection, and anti-pertussis GMCs were non-inferior to those observed in infants following a 3-dose diphtheria, tetanus and acellular pertussis (DTaP) primary vaccination series, in whom efficacy against pertussis was demonstrated. Reports of adverse events were similar between Tdap and Td groups. Tdap was found to be immunogenic in subjects ≥65 years, with a safety profile comparable to US-licensed Td vaccine. Tdap and influenza vaccine may be co-administered without compromise of either the reactogenicity or immunogenicity profiles of the two vaccines.


Involvement of peripheral purinoceptors in sympathetic modulation of capsaicin-induced sensitization of primary afferent fibers.
Purinoceptors are distributed in primary afferent terminals, where transmission of nociceptive information is modulated by these receptors. In the present study, we evaluated whether the activation or blockade of purinoceptors of subtypes P2X and P2Y in the periphery affected the sensitization of primary afferents induced by intradermal injection of capsaicin (CAP) and examined their role in sympathetic modulation of sensitization of primary nociceptive afferents. Afferent activity was recorded from single Adelta- and C-primary afferent fibers in the tibial nerve in anesthetized rats. Peripheral pretreatment with alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP), a P2X-selective receptor agonist, could potentiate the CAP-induced enhancement of responses of Adelta- and C-primary afferent nociceptive fibers to mechanical stimuli in sympathetically intact rats. After sympathetic denervation, the enhanced responses of both Adelta- and C-fibers after CAP injection were dramatically reduced. However, this reduction could be restored when P2X receptors were activated by alpha,beta-meATP. A blockade of P2X receptors by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid could significantly reduce the CAP-induced sensitization of Adelta- and C-fibers. Pretreatment with uridine 5'-triphosphate, a P2Y-selective receptor agonist, did not significantly affect or restore the CAP-induced sensitization of Adelta- and C-fibers under sympathetically intact or sympathectomized conditions. Our study supports the view that ATP plays a role in modulation of primary afferent nociceptor sensitivity mainly by P2X receptors. Combined with our previous study, our data also provide further evidence that the sensitization of primary afferent nociceptors is subject to sympathetic modulation by activation of P2X as well as alpha(1)-adrenergic receptors.


Herbal Ingestion During Pregnancy and Post-Partum Period is A Cause For Concern.
The potential harms of herbs to the pregnant mothers and their foetuses as well as the effect of herbs taken by nursing mothers on their babies remain largely unknown. Common perception is that herbal medicines ingestion during pregnancy and confinement period is a common practice among multi-racial Malaysian mothers. The purpose of this study was to explore the usage of herbal medicines during pregnancy and post-partum period among mothers who gave birth at a tertiary hospital in a metropolitan city of Malaysia. This cross sectional study was conducted between October and December 2010. The subjects were interviewed twice after giving birth: before hospital discharge and 6 to 8 weeks later. A total of 323 mothers were recruited for this study. The prevalence of herbs ingestion during pregnancy was 13.9%, with half of the users consuming it during the first trimester. A total of 163 (52.9%) mothers ingested herbs during the post-partum period. Significantly more Chinese (p=0.01) and Malay (p=0.04) mothers ingested herbs during pregnancy and post-partum period, respectively. Infants of mothers who ingested herbs had a higher rate of neonatal jaundice compared to infants of mothers who did not ingest herbs during the post-partum period (P=0.001).


Sensitivity Uniformity Ratio as a New Index to Optimize the Scanning Geometry for Fluorescent Molecular Tomography.
Molecular fluorescence imaging is widely used as a noninvasive method to study the cellular and molecular mechanisms. In the optical imaging system, the sensitivity is the change of the intensity received by the detector for the changed optical characteristics (fluorescence) in each sample point. Sensitivity could be considered as a function of imaging geometry. A favor imaging system has a uniform and high-sensitivity coefficient for each point of the sample. In this study, a new parameter was proposed which the optimal angle between the source and detector could be determined based on this parameter. For evaluation of the new method, a two-dimensional mesh with a radius of 20 mm and 5133 nodes was built. In each reconstruction, 0.5-mm fluorescence heterogeneity with a contrast-to-purpose ratio of fluorescence yield of 10 was randomly added at different points of the sample. The source and the detector were simulated in different geometric conditions. The calculations were performed using the NIRFAST and MATLAB software. The relationship between mean squared error (MSE) and sensitivity uniformity ratio (SUR) was evaluated using the correlation coefficient. Finally, based on the new index, an optimal geometrical strategy was introduced. There was a negative correlation coefficient (R = -0.78) with the inverse relationship between the SUR and MSE indices. The reconstructed images showed that the better image quality achieved using the optimal geometry for all scanning depths. For the conventional geometry, there is an artifact in the opposite side of the inhomogeneity at the shallow depths, which has been eliminated in the reconstructed images achieved using the optimal geometry. The SUR is a powerful computational tool which could be used to determine the optimal angles between the source and detector for each scanning depth.