EP2-receptor stimulated cyclic AMP synthesis in cultured human non-pigmented ciliary epithelium.
Prostaglandins are locally produced mediators of physiologic function which act through specific receptors to influence cellular response pathways. We have conducted a series of experiments designed to obtain a preliminary pharmacologic characterization of the prostaglandin E2 receptor subtype mediating increased synthesis of adenosine 3',5'-cyclic monophosphate (cyclic AMP) in an SV40 transformed line of human non-pigmented ciliary epithelium (ODMC2). Human non-pigmented epithelial (NPE) cells were grown to confluency, preincubated with indomethacin (to prevent endogenous PGE2 synthesis) and with isobutyl-methyl-xanthine (to prevent breakdown of cAMP), challenged with PGE2 or receptor-selective prostanoids and extracted. Prostanoid-stimulated cAMP synthesis was determined using a protein binding assay and normalized to cellular protein. Prostanoid agonists known to be relatively selective for the EP2 receptor subtype stimulated cAMP synthesis by human NPE cells. EP1 and EP3, IP, FP and DP selective prostanoids had negligible effects on stimulation of cAMP synthesis. The results of these studies lead us to conclude that human NPE cells express receptors of the EP2 subtype which mediate PGE2 stimulated synthesis of cyclic AMP.


Crystallization of FAPbI3: Polytypes and stacking faults.
Molecular dynamics simulations are performed to study the crystallization of formamidinium lead iodide. From all-atom simulations of the crystal growth process and the δ-α-phase transitions, we try to reveal the formation of various stack-faulted intermediate defected structures and report various polytypes of formamidinium lead iodide that are observed from simulations.


Relationship between lipid abnormalities and insulin resistance in Japanese school children.
Dyslipidemia and insulin resistance (IR) are risk factors for coronary heart disease (CHD) in adults. To help prevent the development of CHD, it may be useful to understand the relationship between lipid abnormalities and IR during childhood. IR was assessed by the homeostasis model approximation index. We studied 1175 Japanese school children (642 boys and 533 girls), aged between 7 and 12 years. Obesity was defined by the body mass index standard deviation score (BMISD) (obese: BMISD > or = 2.0). BMISD was most significantly associated with IR in nonobese children (P=0.000). Associations of IR with lipid-related parameters were affected by BMISD. After being corrected by BMISD, in nonobese children, log triglycerides (TG), apoB and low-density lipoprotein (LDL) size in boys and log TG, LDL size, and high-density lipoprotein (HDL) cholesterol in girls were still significantly associated with IR (P=0.000 to 0.017). In obese children, all parameters except for LDL cholesterol in boys and LDL size in girls were significantly associated with IR (P=0.000 to 0.030). Multiple regression analysis showed that log TG and LDL size in nonobese children, log TG in obese boys and LDL size in obese girls were independently associated with IR. Children with IIb and IV hyperlipidemia had significantly higher IR than those with normolipidemia and IIa, even after correcting for BMISD and age. Our results suggest that in addition to controlling body weight, it may be important for school children to characterize lipid phenotypes to prevent progression to CHD and/or type 2 diabetes and to identify subjects who are at high risk for these disorders.


Biofabrication of silver nanoparticles using bacteria from mangrove swamp.
The last decade has observed a rapid advancement in utilising biological system towards bioremediation of metal ions in the form of respective metal nanostructures or microstructures. The process may also be adopted for respective metal nanoparticle biofabrication. Among different biological methods, bacteria-mediated method is gaining great attention for nanoparticle fabrication due to their eco-friendly and cost-effective process. In the present study, silver nanoparticle (AgNP) was synthesised via continuous biofabrication using Aeromonas veronii, isolated from swamp wetland of Sunderban, West Bengal, India. The biofabricated AgNP was further purified to remove non-conjugated biomolecules using size exclusion chromatography, and the purified AgNPs were characterised using UV-visible spectroscopy, X-ray diffraction, field emission scanning electron microscopy and transmission electron microscopy (TEM). Additionally, the presence of proteins as capping and stabilising agents was confirmed by the amide-I and amide-II peaks in the spectra obtained using attenuated total reflection Fourier transform infrared spectroscopy. The size of biofabricated AgNP was 10-20 nm, as observed using TEM. Additionally, biofabricated AgNP shows significant antibacterial potential against E. coli and S. aureus. Hence, biofabricated AgNP using Aeromonas veronii, which found resistant to a significant concentration of Ag ion, showed enhanced antimicrobial activity compared to commercially available AgNP.


Disruption of YWHAE gene at 17p13.3 causes learning disabilities and brain abnormalities.
There is a broad phenotypic spectrum of patients with 17p13.3 deletions. One of the most prominent feature is lissencephaly caused by haploinsufficiency of the gene PAFAH1B1. The deletion of this gene and those distal to it, results in Miller-Dieker syndrome, however there have been many reports of patients with haploinsufficiency of the distal genes alone. The deletions of these genes including YWHAE CRK and TUSC5 have been studied extensively and YWHAE has been postulated to be the cause of neurological abnormalities. The patients with deletions of the Miller-Dieker syndrome distal region present with variable clinical features including brain abnormalities, growth retardation, developmental delay, facial dysmorphisms and seizures. While there have been many patients reported to have deletions involving the YWHAE gene along with other genes, here we present the first detailed clinical description of a patient with deletion of YWHAE alone, allowing a more accurate characterization of the pathogenicity of YWHAE haploinsufficiency. The patient reported here demonstrated brain abnormalities, learning disabilities, and seizures supporting the role of YWHAE in these features. We review the literature and use this case report to better characterize and further confirm the genotype-phenotype relationship of the genes within the critical region of Miller-Dieker Syndrome.


Enabling a young man with minimal motor behavior to manage independently his leisure television engagement.
Persons with severe spastic tetraparesis and minimal motor behavior may be confined to a wheelchair or bed and have virtually no chances of constructive engagement with their immediate environment. A possible way to modify this situation may involve the use of technology. The present study (a) assessed specific technology to enable a young adult to manage his leisure television engagement independently and (b) carried out a social validation assessment of the technology-supported performance involving 90 teacher trainees as raters. The intervention period with the new technology included 67 sessions, during which the participant performed independently 392 of the 408 television-management responses, i.e., turning on the television, finding a channel with a preferred program, setting the volume, and turning off the television. He also indicated preference for using the technology as opposed to not using it. The raters provided relatively high (positive) scores for the technology-supported performance compared to the baseline performance. Implications of the findings are discussed.


Measuring transaminases in patients with rheumatoid arthritis on weekly methotrexate: does timing of blood testing matter?
The change in transaminase levels over a single week during therapy with methotrexate (MTX) has not been investigated or reported to date. In clinical practice, it is common to observe abnormal transaminase levels upon routine blood work for toxicity monitoring. Many have suggested that such lab abnormalities can sometimes be attributed to sampling blood for toxicity monitoring proximately following MTX dosing. The aim of our study was to evaluate changes in transaminase levels (AST/ALT) over 1 week after MTX administration in rheumatoid arthritis (RA) patients. In this small proof of concept study, we evaluated 13 patients with RA taking stable doses of methotrexate and background medications (e.g., NSAIDs and prednisone), but no other disease-modifying anti-rheumatic drugs (DMARDs). All patients were on a stable dose of folic acid. Patients received their usual doses of MTX administered at a specified time, and then sequential blood samples were obtained over the course of 7 days. Peripheral blood was obtained at each time point to measure serum transaminases. We did not observe any significant change in sequential transaminases over 1 week in relationship to MTX administration. It is possible that MTX therapy alone does not lead to significant weekly transaminase variations, contrary to our clinical expectations. The addition of other medications (i.e., NSAIDs) to stable MTX regimen may result in transaminase abnormalities.


Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists.
The Placental Pathology Practice Guideline Development Task Force, a multidisciplinary group, has prepared this guideline to assist those involved with placental examination. It provides recommendations related to indications and methods for placental examination as well as sample worksheets. An algorithm for the handling of placentas summarizes the recommendations of the guideline. A summary of specific findings of placental examination together with their pathogenesis and clinical associations is also provided. Recommendations related to reporting with sample reporting formats are included. The guideline is intended as an educational tool, and its use should be guided by the individual circumstances and care setting of specific cases.


Relational closeness moderates the association between maternal overcontrol and children's depressive symptoms.
Though numerous studies have examined the relationship between parental overcontrol (OC) and child anxiety, few have examined the association between OC and children's depressive symptoms. However, there are conceptual reasons to believe that overcontrolling parenting may also be relevant to depressive symptomatology, as well as to anticipate that other aspects of the parent-child relationship may moderate the association between the two. In this study we examine the association between self-reported maternal OC and child depressive symptoms, as moderated by multiple indicators of closeness within the parent-child relationship. An ethnically and socioeconomically diverse sample of children (N = 106, M(age) = 10.27 years) and their mothers participated in this cross-sectional study. Mothers reported on their overcontrolling parenting and children reported on their depressive symptoms. Children and mothers participated in structured interviews that were analyzed for we-talk, a behavioral measure of closeness; they also self-reported their closeness. Results indicated that child we-talk, child self-reported closeness, and maternal we-talk moderated the association between maternal OC and child depressive symptoms, such that OC and depressive symptoms were positively associated only at low levels of relational closeness. The results provide initial evidence for an association between parental OC and child depressive symptoms, and point to the need for more research on the role of children's perceptions in moderating the association between parenting and child depressive symptoms.


Tumoral calcinosis--clinicopathological study of five cases.
Five cases of tumoral calcinosis were studied during the period of January-february 1999 in MIMER medical college, Talegaon, a rural place 35kms. from Pune. All the Five patients were females residing in nonendemic area for Dracunculosis. They were from 5th-6th decade. They were otherwise healthy and had normal serum calcium and phosphorus levels and no eosinophilia. All had large, hard subcutaneous lump around hip joint. The skin overlying the swelling was normal. Histologically all cases showed similar morphology, the lesions were composed of large and small deposits of calcium. The foreign-body giant cell reaction was seen in two cases. There were no eosinophils and lymphocytes. On multiple sectioning none of the cases revealed any evidence of dead or living parasite. Old and recent necrosis was absent. These cases are presented since the condition is comparatively rare and it appeared in crops in our Institute.


Laparoscopic ovarian drilling as first line of treatment in infertile women with polycystic ovary syndrome.
Laparoscopic ovarian drilling (LOD) is used as a first line of treatment, as a second line of treatment after patients have proved resistant to clomiphene or as a third line of treatment after failed ovulation induction with gonadotropins. We present the postoperative pregnancy rates of 57 women to evaluate a potential optimal time of LOD together with the other treatment regimens of infertile women with polycystic ovary syndrome (PCOS). Data on the preoperative and operative treatment, and background data were evaluated for their influence on pregnancy rates. The pregnancy rate was 61% among women with PCOS who had LOD. No difference was found in the clinical data between the women who became pregnant and those who did not. Likewise, no difference was found between the women who had pre- and/or postoperative medical ovulation treatment and those who had none. The median time to pregnancy after LOD was 135 days. LOD alone resolves infertility within 4-6 months in 50-60% of couples. A strategy with diagnostic laparoscopy and LOD as the first line of treatment of infertility in women with PCOS will shorten the time to pregnancy for many women, reduce the need for medical ovulation induction and enable diagnosis of those women with anatomic infertility, who can achieve pregnancy only by in vitro fertilization treatment.


Hinge-Shift Mechanism Modulates Allosteric Regulations in Human Pin1.
Allostery, which is regulation from distant sites, plays a major role in biology. While traditional allostery is described in terms of conformational change upon ligand binding as an underlying principle, it is possible to have allosteric regulations without significant conformational change through modulating the conformational dynamics by altering the local effective elastic modulus of the protein upon ligand binding. Pin1 utilizes this dynamic allostery to regulate its function. It is a modular protein containing a WW domain and a larger peptidyl prolyl isomerase domain (PPIase) that isomerizes phosphoserine/threonine-proline (pS/TP) motifs. The WW domain serves as a docking module, whereas catalysis solely takes place within the PPIase domain. Here, we analyze the change in the dynamic flexibility profile of the PPIase domain upon ligand binding to the WW domain. Substrate binding to the WW domain induces the formation of a new rigid hinge site around the interface of the two domains and loosens the flexibility of a rigid site existing in the Apo form around the catalytic site. This hinge-shift mechanism enhances the dynamic coupling of the catalytic positions with the PPIase domain, where the rest of the domain can cooperatively respond to the local conformational changes around the catalytic site, leading to an increase in catalytic efficiency.


Differences in microbial community structure and nitrogen cycling in natural and drained tropical peatland soils.
Tropical peatlands, which play a crucial role in the maintenance of different ecosystem services, are increasingly drained for agriculture, forestry, peat extraction and human settlement purposes. The present study investigated the differences between natural and drained sites of a tropical peatland in the community structure of soil bacteria and archaea and their potential to perform nitrogen transformation processes. The results indicate significant dissimilarities in the structure of soil bacterial and archaeal communities as well as nirK, nirS, nosZ, nifH and archaeal amoA gene-possessing microbial communities. The reduced denitrification and N2-fixing potential was detected in the drained tropical peatland soil. In undisturbed peatland soil, the N2O emission was primarily related to nirS-type denitrifiers and dissimilatory nitrate reduction to ammonium, while the conversion of N2O to N2 was controlled by microbes possessing nosZ clade I genes. The denitrifying microbial community of the drained site differed significantly from the natural site community. The main reducers of N2O were microbes harbouring nosZ clade II genes in the drained site. Additionally, the importance of DNRA process as one of the controlling mechanisms of N2O fluxes in the natural peatlands of the tropics revealed from the results of the study.


HLA-DR and the development of rheumatoid arthritis.
Susceptibility to develop Rheumatoid arthritis (RA) maps to a highly conserved amino acid motif ("the shared epitope") expressed in the third hypervariable region of different HLA-DRB1 alleles. This motif, namely QKRAA, QRRAA or RRRAA helps the development of RA by an unknown mechanism. However, it is now established that the shared epitope can 1. Shape the T cell repertoire. 2. Interact with 70 kD heat shock proteins.


The efficacy of Tc-99m sestamibi for sentinel node mapping in breast carcinomas: comparison with Tc-99m antimony sulphide colloid.
To study the value of periareolar intra-dermal injection of Tc-99m sestamibi (MIBI) for sentinel node mapping in breast carcinoma. Fifty patients with early-stage breast cancer were included in our study. 17.5 MBq Tc-99m-MIBI was injected intradermally to 25 patients and the remainders were injected with the same dose of Tc-99m-antimony sulphide colloid. Anterior and lateral static images were taken at 2 minutes. If sentinel lymph node was not detected, delayed imaging by up to 180 minutes was carried out. The patients were operated on 2-4 hours post-injection. Sentinel lymph node biopsy was performed by the aid of gamma probe and blue dye during surgery. In the Tc-99m-MIBI group, 23 patients had lymph nodes on scintigraphy images, and sentinel nodes were detected during surgery in all 23 patients. In the Tc-99m-antimony sulphide colloid group, 24 patients had lymph nodes on scintigraphy images, and sentinel nodes were identified during surgery in 24 patients. We concluded that 99mTc-MIBI is a suitable radiopharmaceutical for sentinel node detection.


Benefit in phase 1 oncology trials: therapeutic misconception or reasonable treatment option?
Novel treatments for cancer are tested initially in phase 1 trials enrolling patients with advanced disease who have exhausted standard treatment options. Although these trials are designed to evaluate safety and to define dosing for future efficacy trials, most patients volunteer with the hope of obtaining medical benefit. Do phase 1 oncology trials promote a 'therapeutic misconception' among eligible patients about the personal meaning of trial participation, or do they offer them a reasonable prospect of direct medical benefit as compared with available alternatives? Recent evidence on outcomes of phase 1 oncology trials is examined systematically, with the aim of accurately assessing the prospect of direct medical benefit for participants and drawing implications for informed consent. We argue that, in view of important uncertainties, aggregate data from phase 1 trials relating to the surrogate outcomes of tumor shrinkage and stable disease do not permit any definitive estimate of a 'clinical benefit rate.' Nevertheless, these trials do offer participants a prospect of direct medical benefit. As a result, accurately informed patients may reasonably decide to enroll in phase 1 oncology trials in hopes of obtaining benefit, after considering the anticipated risks and available clinical alternatives. Motivation to enroll in these studies to receive personal benefit does not, in itself, compromise informed consent.


An Anion-Switchable Dual-Function Rotaxane Catalyst.
In situ switching of the associated anions of a rotaxane catalyst between Cl- and TFPB- exposes its dialkylammonium and imidazolium stations, respectively, thereby selectively catalyzing the reactions of a mixture of trans-cinnamaldehyde and an aliphatic thiol to yield the Michael adduct and the thioacetal product, respectively.


MazF Endoribonucleolytic Toxin Conserved in Nitrospira Specifically Cleaves the AACU, AACG, and AAUU Motifs.
MazF is an endoribonucleolytic toxin that cleaves intracellular RNAs in sequence-specific manners. It is liberated in bacterial cells in response to environmental changes and is suggested to contribute to bacterial survival by inducing translational regulation. Thus, determining the cleavage specificity provides insights into the physiological functions of MazF orthologues. Nitrospira, detected in a wide range of environments, is thought to have evolved the ability to cope with their surroundings. To investigate the molecular mechanism of its environmental adaption, a MazF module from Nitrospira strain ND1, which was isolated from the activated sludge of a wastewater treatment plant, is examined in this study. By combining a massive parallel sequencing method and fluorometric assay, we detected that this functional RNA-cleaving toxin specifically recognizes the AACU, AACG, and AAUU motifs. Additionally, statistical analysis suggested that this enzyme regulates various specific functions in order to resist environmental stresses.


Nursing Student Preference for Block Versus Nonblock Clinical Models.
Clinical experiences are essential in undergraduate nursing student education to develop professionalism and integrate theory into practice. However, little evidence is available to guide curricular planners in determining the appropriate and effective use of different clinical models in nursing education. Nursing students and four schools of nursing in two western Canadian provinces participated in this descriptive exploratory study examining student preference for clinical models. Thematic analysis of qualitative data addressed two research questions: What type of clinical model is preferred by nursing students? and How does clinical structure influence nursing students' perceived learning? Nonblock clinical practice is preferred by students with respect to a balanced lifestyle, concurrent integration of theory and practice, and critical reflection, whereas the block model is preferred for assimilation, consolidation, and socialization. Integration of both clinical models is recommended within undergraduate nursing curricula, as each model can facilitate student learning. [J Nurs Educ. 2017;56(3):152-157.].


[Fat cardiomyopathy in patients with severe degree of obesity. Case report].
Currently, the world is constantly increasing the number of people with obesity. As was shown by the Framingham study, obesity is a risk factor for many cardiovascular diseases. The effect of obesity on the structure and function of the heart is manifested in the form of cardiac remodeling, the effect on energy metabolism in the heart and infiltration of both myocardium with lipids, and an increase in the accumulation of adipose tissue in the pericardium, imbalance of adipokines and activation of inflammatory markers. Cardiac remodeling occurs primarily due to thickening of the left ventricle (LV) walls and an increase in the LV myocardium mass. Systolic dysfunction of the heart is less common in obese individuals compared with diastolic dysfunction. However, more modern methods (tissue Doppler, visualization of the deformation of the chambers of the heart strain imaging) reveal a subclinical decrease in systolic function in people with obesity. It is not fully known whether obesity is associated with systolic dysfunction, regardless of other risk factors. In any case, it has been proven that heart failure in people with obesity can develop independently of other risk factors. As an illustration, we give an example when the presence of obesity and concomitant pathology (arterial hypertension, diabetes) led to the development of systolic dysfunction with a decrease in the LV ejection fraction to 35% (fat cardiopathy), which show the potential for the influence of both obesity itself and in combination with concomitant diseases to lead to severe systolic heart failure.


Percutaneous CT-guided radiofrequency ablation for patients with extrahepatic oligometastases of hepatocellular carcinoma: long-term results.
The aim of this study was to evaluate the therapeutic outcome of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for extrahepatic oligometastases of hepatocellular carcinoma (HCC). Institutional review board approval was obtained for this retrospective study, and all patients provided written informed consent. Between April 2004 and December 2015, 116 oligometastases (diameter, 5-50 mm; 20.3 ± 10.4) in 79 consecutive HCC patients (73 men and 6 women; average age, 50.3 years ±13.0) were treated with RFA. We focussed on patients with 1-3 extrahepatic metastases (EHM) confined to 1-2 organs (including the lung, adrenal gland, bone, lymph node and pleura/peritoneum) who were treated naïve with curative intent. Survival, technical success and safety were evaluated. The log-rank test and Cox proportional hazards regression models were used to analyse the survival data. No immediate technical failure occurred, and at 1 month, the technique effectiveness rate was determined to be 95.8%. After a median follow-up time of 28.0 months (range, 6-108 months), the 1-, 2- and 3-year overall survival (OS) rates were 91, 70 and 48%, respectively, with a median survival time of 33.5 months. Time to unoligometastatic progression (TTUP) of less than 6 months (p < 0.001) and a Child-Pugh score of more than 5 (p = 0.001) were significant indicators of shorter OS. The 1-, 2- and 3-year disease free survival (DFS) rates were 34, 21 and 8%, respectively, with a median DFS time of 6.8 months. DFS was better for those with lung metastases (p = 0.006). Major complication occurred in nine (9.5%, 9/95) RFA sessions without treatment-related mortality. CT-guided RFA for oligometastatic HCC may provide favourable efficacy and technical success with a minimally invasive approach.


A Novel Use for Potassium Alum as Controlling Agent Against Periplaneta americana (Dictyoptera: Blattidae).
In this work, we present our results on the use of potassium alum as an environmentally friendly insecticide. This compound has the potential to rid our homes, schools, hotels, restaurants, and ships of cockroach infestations. This compound is environmentally friendly and has no hazardous effects on plant, animal, or human ecosystems. Alum was approved for medical use a long time ago. In our laboratory, we developed a novel method using potassium alum as an environmentally friendly insecticide to kill the most common cockroach in the subtropical region, Periplaneta americana (L.). Adult and nymph-staged cockroaches were left to feed on potassium alum per individual insect after a period of food deprivation. The mortality was recorded as LT50. The younger nymphs the third and early fourth instars died within 4 d of feeding after consuming an average of 0.3 mg per individual insect. Gravid females were highly susceptible to alum toxicity and experienced a higher mortality rate, with an average of 3 mg per individual female. The oothecae of the normal untreated females were 8.1 mm long and 4.13 mm wide and weighed 94 mg. The eggs laid by the treated gravid females were underweight and exhibited a dwarfism shape, and these eggs did not hatched if the females consumed the potassium alum before laying eggs. The results revealed that the adult male and female cockroaches have to consume 1 mg and 2.7 mg, respectively, of potassium alum to kill 100% of them after 1 month of ingestion. The potassium alum had to be ingested by the cockroaches to affect mortality. The effect of potassium alum was attributed to chronic toxicity and not acute toxicity. The potential applications of this novel technique will be discussed.


A behavior-genetic approach to multiple chemical sensitivity.
This report emphasizes the application of behavior-genetic designs to the study of sensitivity to toxic chemicals, and features of multiple chemical sensitivity and substance abuse that are polar opposites. The implications of these issues for future research are discussed in relation to twin, adoption, and sibling pair studies, as well as in relation to the degree to which genetically selected lines of rodents that have been developed in the alcoholism field are applicable to multiple chemical sensitivity.


Effect of an antiseptic mouthwash on plaque accumulation.
This study was undertaken to determine the effect of sodium peroxyborate monohydrate bitartarate on plaque accumulation in comparison with "no oral hygiene" and "brushing once before breakfast." Fifteen male resident students between the ages of 18 to 22 years volunteered for the study. 1. In all three stages of the study regeneration of plaque were observed in all individuals within 24 hours after thorough prophylaxis. 2. The tendency to plaque accumulation varied from person to person, from tooth to tooth in the same individual, and even on different surfaces of the same tooth. 3. The plaque scores and the range of plaque scores were lower on the first 2 days with the use of mouthwash when compared with tooth brushing on the corresponding days. 4. A reduction of 30.62% was observed with the use of mouthwash when it was compared with "no oral hygiene." 5. Plaque accumulation was 17.7% more with mouthwash than with use of the toothbrush. 6. A negligible reduction in efficacy (0.38%) was observed with this mouthwash in comparison with 1% H2O2, used under pressure.


Three-dimensional visualization of the molecular architecture of cell-cell junctions in situ by cryo-electron tomography of vitreous sections.
Cryo-electron tomography of vitreous sections is currently the only method for visualizing the eukaryotic ultrastructure at close to native state with molecular resolution. Here, we describe the detailed procedure of how to prepare suitable vitreous sections from mammalian skin for cryo-electron tomography, how to align the projection images of the tilt-series, and finally how to perform sub-tomogram averaging on macromolecular complexes with periodic arrangement such as desmosomes.


IMPACT-ALS: summary of results from a European survey of people living with ALS.
The IMPACT-ALS survey collected the experiences of people living with ALS (plwALS) across nine European countries. We aimed to better understand the functional burden of ALS to ensure the experiences of plwALS inform the development of person-centered therapies. The content was informed by the US IMPACT-ALS survey, with adjustments relevant to the European population. Questionnaires consisted of four modules, each of which was pilot tested in advance of distribution. Data were captured using the Qualtrics software and were analyzed in SPSS. 857 respondents completed the survey, with a participation rate ranging from 0.2% to 6.3% across the nine participating countries. The majority were male and aged 55-74 years old. In the previous 2 weeks, symptoms experienced included weakness (81%), fatigue (61%), speech impairment (38%), pain (27%), and depression and other mood changes (23%). Eighty-two percent of respondents reported fears, of which the most common were leaving family too soon (68%) and death from respiratory failure (50%). Lifestyle changes since diagnosis were reported by 89% of respondents, with less time spent doing most daily activities but more time on the internet (81%), reading (56%) and communicating with family and friends (55%). Stopping progression of ALS was the most desired impact for a new therapy for 68% respondents. The European IMPACT-ALS survey has generated insights into the complex experiences of plwALS. The data provide unique patient perspectives on common symptoms, fears, functional limitations, lifestyle changes, and wishes for future therapies that will enhance patient-centric care in ALS.


Study on the Formation of Novel Threadlike Structure through Intravenous Injection of Heparin in Rats and Refined Observation in Minipigs.
Objective. To study if the novel threadlike structure (NTS) was caused by coagulation during injecting urethane intraperitoneally and the source of NTS. Methods. Twenty-two SD rats were anaesthetized by urethane injected intraperitoneally. Heparin was injected at 5 minutes before the anaesthesia from femoral vein in 11 rats, and saline was given in the other 11 rats randomly. Six Chinese minipigs were carried to look for NTS. One sample was taken to be stained by DAPI/Phalloidin and observed by a laser scanning confocal microscope. Results. In the group of heparin, 10 rats were found to have NTS with appearance rate of 90.9%, and 9 rats were found to have NTS with the appearance rate of 80.1%. Both groups have 1.81 average numbers of NTS in each rat without significant difference (P > 0.05). In the observation of pigs, the NTS was found to prolong from the serous membranes of abdominal wall and organ surface. Histological observation showed elongated nuclei and alignment which is similar to the characteristics of PVS. Conclusion. There is no strong evidence to say that the NTS on organ surface was caused by coagulation of blood. The source of NTS might be a prolonged structure from serous membrane in abdominal cavity during the development and more or less retained after birth.


Peri-implantitis induced by a retained retraction cord.
This paper presents a case of purulent peri-implantitis at an implant in the maxillary right lateral incisor position. The lesion was unresponsive to close debridement and, thus, open flap surgery was performed. Profound bone loss was evident around the implant and a retained retraction cord at the cervical portion of the implant was observed. Treatment included a sequence of decontamination steps and guided bone regeneration with the aim of eliminating the etiology and enhancing implant survival. In the presented case, it can be speculated that the retraction cord served as a plaque retentive factor which ultimately led to bacterial accumulation and periimplant disease. Thus, it is crucial to ensure that no plaque retentive factors (cement remnants, retraction cord, ill-fitting margins of crowns, etc.) are present when restoring an implant. Plaque retentive factors might result in a destructive effect on the peri-implant tissues and bone.


Tight junction defects are seen in the buccal mucosa of patients receiving standard dose chemotherapy for cancer.
Oral mucositis is one of the most common and debilitating side effects of chemotherapy treatment. Patients are often unable to eat and drink, which can lead to poor clinical outcomes and extensive resource utilisation. The primary aim of this study was to determine the molecular integrity of oral epithelial tight junctions in patients undergoing chemotherapy. The secondary aim was to correlate these changes with proinflammatory cytokines and matrix metalloproteinase profiles. Patients (n = 23) were recruited from the Royal Adelaide Hospital between 2000 and 2003. Reach patient underwent two oral buccal mucosa biopsies (4 mm): one prior to chemotherapy treatment and a second one after chemotherapy treatment. Oral buccal mucosa biopsies were also taken from seven healthy volunteers with no history of cancer, chemo- or radiotherapy treatment or inflammatory disorders. Routine haematoxylin and eosin staining was performed to determine epithelial thickness. Immunohistochemical staining was performed for claudin-1, zonular occludens-1, occludin, interleukin-1β, tumour necrosis factor, interleukin-6, matrix metalloproteinase-2 and metalloproteinase-9. Patients receiving standard dose chemotherapy had significant epithelial atrophy. Elevations in all cytokines and matrix metalloproteinases were seen, with significant lamina propria staining for interleukin-6 and tumour necrosis factor. Matrix metalloproteinase-2 appeared most upregulated within the oral epithelium. These changes coincided with altered tight junction staining properties. Changes in the staining intensity and localisation were both noted, with clear cytoplasmic staining for zonular occludens-1 and claudin-1 in patients treated with chemotherapy. Chemotherapy causes defects in oral tight junctions, coupled with altered cytokine and matrix metalloproteinase profiles. Tight junction disruption in the epithelium may contribute to ulcer development or lead to poor tissue integrity, and the timing of these events may be a target for preventative treatment.


Strategies to rescue mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) from NK cell mediated cytotoxicity.
The aim of this paper is to study the function of allogeneic and autologous NK cells against Dental Pulp Stem Cells (DPSCs) and Mesenchymal Stem Cells (MSCs) and to determine the function of NK cells in a three way interaction with monocytes and stem cells. We demonstrate here that freshly isolated untreated or IL-2 treated NK cells are potent inducers of cell death in DPSCs and MSCs, and that anti-CD16 antibody which induces functional split anergy and apoptosis in NK cells inhibits NK cell mediated lysis of DPSCs and MSCs. Monocytes co-cultured with either DPSCs or MSCs decrease lysis of stem cells by untreated or IL-2 treated NK cells. Monocytes also prevent NK cell apoptosis thereby raising the overall survival and function of NK cells, DPSCs or MSCs. Both total population of monocytes and those depleted of CD16(+) subsets were able to prevent NK cell mediated lysis of MSCs and DPSCs, and to trigger an increased secretion of IFN-gamma by IL-2 treated NK cells. Protection of stem cells from NK cell mediated lysis was also seen when monocytes were sorted out from stem cells before they were added to NK cells. However, this effect was not specific to monocytes since the addition of T and B cells to stem cells also protected stem cells from NK cell mediated lysis. NK cells were found to lyse monocytes, as well as T and B cells. By increasing the release of IFN-gamma and decreasing the cytotoxic function of NK cells monocytes are able to shield stem cells from killing by the NK cells, resulting in an increased protection and differentiation of stem cells. More importantly studies reported in this paper indicate that anti-CD16 antibody can be used to prevent NK cell induced rejection of stem cells.


Sphenopalatine ganglion block for the treatment of myofascial pain of the head, neck, and shoulders.
This study examined the effectiveness of sphenopalatine ganglion block (SPGB) for myofascial pain syndrome of the head, neck, and shoulders using a double-blind, placebo-controlled, crossover study design with comparison to an internal standard consisting of trigger point injections (TPI). Patients (n = 23) were randomly assigned to receive either: (1) SPGB with 4% lidocaine, then TPI with 1% lidocaine, and finally SPGB with saline placebo or (2) SPGB with saline placebo, then TPI with 1% lidocaine, and finally SPGB with 4% lidocaine. Each respective treatment within each protocol was given sequentially at 1-week intervals for both groups. Prior to the first treatment, all patients assessed their average intensity of pain and pain at that particular moment using a visual analog pain scale. Pain intensity and pain relief were reassessed 30 minutes after each treatment and at 6 hours, 24 hours and 1 week using visual analog pain and pain relief scales. Pain intensity and pain relief data were transformed into natural logarithm units, and the statistical significance of SPGB with 4% lidocaine versus SPGB with placebo, SPGB with 4% lidocaine versus TPI, and TPI versus SPGB with placebo were tested by mixed-model analysis of variance. The magnitude of the differences in pain intensity and pain relief ratings were also compared via computation of 95% confidence intervals. The analgesic effect of SPGB with 4% lidocaine was no better than placebo. Mixed-model analysis of variance revealed improved analgesia with administration of TPIs as compared to SPGB with 4% lidocaine and placebo over the entire week of observations (pain relief scores). This study suggests that SPGB with 4% lidocaine is no more efficacious than placebo and less efficacious than administration of standard trigger point injections in the treatment of myofascial pain of the head, neck, and shoulders.


Usability of a Fourier transform spectroradiometer for absolute surface spectral solar UV irradiance measurements.
The suitability of a commercially available Fourier transform spectrometer equipped with a fiber-coupled global entrance optic as a reference spectroradiometer for the measurement of spectral solar ultraviolet irradiance at ground level has been investigated. The instrument has been characterized with respect to the wavelength uncertainty, and a calibration of the spectral irradiance responsivity has been performed by using the calculable irradiance of a high temperature black-body radiator and by using a secondary irradiance standard lamp. The relative standard uncertainty of solar irradiance measurements in the wavelength range from 310 nm to 400 nm with this spectroradiometer, based on the described methodology, is 1.6% for solar zenith angles of less than 60°.


Repetition of verbal fluency task attenuates the hemodynamic activation in the left prefrontal cortex: Enhancing the clinical usefulness of near-infrared spectroscopy.
In applications of near-infrared spectroscopy (NIRS) in clinical psychiatry settings in Japan, a phonemic verbal fluency test (VFT) that includes "switching" (the ability to shift efficiently to a new word subcategory) to assess phonemic fluency is employed to capture disease-specific hemodynamic changes in the prefrontal cortex (PFC). In this study, to extend the specific features of this test, the VFT was repeated to examine an activation change in NIRS measurements in 20 healthy males. Without task performance change, the hemodynamic activation induced by the VFT was significantly attenuated in the left PFC through repetition of the task. These findings suggest that the left PFC is involved in processing of the VFT. Further, it may be possible to extend the current VFT using this repetition to provide a more sensitive examination of the left PFC, whose dysfunction has been reported in several psychiatric diseases such as major depression, bipolar disorder, and schizophrenia.


The Effects of Naturalistic Light on Diurnal Plasma Melatonin and Serum Cortisol Levels in Stroke Patients during Admission for Rehabilitation: A Randomized Controlled Trial.
Background: Stroke patients admitted for rehabilitation often lack sufficient daytime blue light exposure due to the absence of natural light and are often exposed to light at unnatural time points. We hypothesized that artificial light imitating daylight, termed naturalistic light, would stabilize the circadian rhythm of plasma melatonin and serum cortisol levels among long-term hospitalized stroke patients. Methods: A quasi-randomized controlled trial. Stroke patients in need of rehabilitation were randomized between May 1, 2014, and June 1, 2015 to either a rehabilitation unit equipped entirely with always on naturalistic lighting (IU), or to a rehabilitation unit with standard indoor lighting (CU). At both inclusion and discharge after a hospital stay of at least 2 weeks, plasma melatonin and serum cortisol levels were measured every 4 hours over a 24-hour period. Circadian rhythm was estimated using cosinor analysis, and variance between time-points. Results: A total of 43 were able to participate in the blood collection. Normal diurnal rhythm of melatonin was disrupted at both inclusion and discharge. In the IU group, melatonin plasma levels were increased at discharge compared to inclusion (n = 23; median diff, 2.9; IQR: -1.0 to 9.9, p = 0.030) and rhythmicity evolved (n = 23; p = 0.007). In the CU group, melatonin plasma levels were similar between discharge and inclusion and no rhythmicity evolved. Overall, both patient groups showed normal cortisol diurnal rhythms at both inclusion and discharge. Conclusions: This study is the first to demonstrate elevated melatonin plasma levels and evolved rhythmicity due to stimulation with naturalistic light.


DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells.
Blastocyst-derived embryonic stem cells (ESCs) and gonad-derived embryonic germ cells (EGCs) represent two classic types of pluripotent cell lines, yet their molecular equivalence remains incompletely understood. Here, we compare genome-wide methylation patterns between isogenic ESC and EGC lines to define epigenetic similarities and differences. Surprisingly, we find that sex rather than cell type drives methylation patterns in ESCs and EGCs. Cell fusion experiments further reveal that the ratio of X chromosomes to autosomes dictates methylation levels, with female hybrids being hypomethylated and male hybrids being hypermethylated. We show that the X-linked MAPK phosphatase DUSP9 is upregulated in female compared to male ESCs, and its heterozygous loss in female ESCs leads to male-like methylation levels. However, male and female blastocysts are similarly hypomethylated, indicating that sex-specific methylation differences arise in culture. Collectively, our data demonstrate the epigenetic similarity of sex-matched ESCs and EGCs and identify DUSP9 as a regulator of female-specific hypomethylation.


Ligand-detected relaxation dispersion NMR spectroscopy: dynamics of preQ1-RNA binding.
An NMR-based approach to characterizing the binding kinetics of ligand molecules to biomolecules, like RNA or proteins, by ligand-detected Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments is described. A (15)N-modified preQ1 ligand is used to acquire relaxation dispersion experiments in the presence of low amounts of the Fsu class I preQ1 aptamer RNA, and increasing ligand concentrations to probe the RNA small molecule interaction. Our experimental data strongly support the conformational selection mechanism postulated. The approach gives direct access to two parameters of a ligand-receptor interaction: the off rate and the population of the small molecule-receptor complex. A detailed description of the kinetics underlying the ligand binding process is of crucial importance to fully understanding a riboswitch's function and to evaluate potential new antibiotics candidates targeting the noncoding RNA species. Ligand-detected NMR relaxation dispersion experiments represent a valuable diagnostic tool for the characterization of binding mechanisms.


A Novel and Practical Chromatographic "Fingerprint-ROC-SVM" Strategy Applied to Quality Analysis of Traditional Chinese Medicine Injections: Using KuDieZi Injection as a Case Study.
Fingerprinting is widely and commonly used in the quality control of traditional Chinese medicine (TCM) injections. However, current studies informed that the fingerprint similarity evaluation was less sensitive and easily generated false positive results. For this reason, a novel and practical chromatographic "Fingerprint-ROC-SVM" strategy was established by using KuDieZi (KDZ) injection as a case study in the present article. Firstly, the chromatographic fingerprints of KDZ injection were obtained by UPLC and the common characteristic peaks were identified with UPLC/Q-TOF-MS under the same chromatographic conditions. Then, the receiver operating characteristic (ROC) curve was used to optimize common characteristic peaks by the AUCs value greater than 0.7. Finally, a support vector machine (SVM) model, with the accuracy of 97.06%, was established by the optimized characteristic peaks and applied to monitor the quality of KDZ injection. As a result, the established model could sensitively and accurately distinguish the qualified products (QPs) with the unqualified products (UPs), high-temperature processed samples (HTPs) and high-illumination processed samples (HIPs) of KDZ injection, and the prediction accuracy was 100.00%, 93.75% and 100.00%, respectively. Furthermore, through the comparison with other chemometrics methods, the superiority of the novel analytical strategy was more prominent. It indicated that the novel and practical chromatographic "Fingerprint-ROC-SVM" strategy could be further applied to facilitate the development of the quality analysis of TCM injections.


Severe Acute Respiratory Distress Syndrome Secondary to Concomitant Influenza A and Rhinovirus Infection Complicated by Methicillin-resistant Staphylococcus aureus Pneumonia in an Early Pregnancy Patient With Vaping-induced Lung Injury.
Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury characterized by rapid onset of widespread inflammation in the lungs. Multiple risk factors, including pneumonia, non-pulmonary sepsis, aspiration of gastric contents or inhalation injury, have been reported, to cause ARDS. We present a case of a healthy young woman in her first trimester with vaping-induced lung injury who presented with spontaneous pneumothorax and acute respiratory distress syndrome with concomitant influenza A and rhinovirus infection followed by methicillin-resistant Staphylococcus aureus pneumonia.


Assessment of arterial blood oxygenation in various states of acute respiratory failure.
The study contains an analysis of the clinical course of 48 patients with acute respiratory failure. The degree of arterial hypoxaemia and respiratory failure were correlated with the value of true pulmonary shunt of non-oxygenated blood. Measurements of the shunt were carried out serially during treatment and it was calculated from the shunt equation of Berggren. It was found that the pulmonary shunt is a good index of arterial blood oxygenation in cases of acute respiratory failure. The value of 47% of shunt was accepted as that with is incompatible with survival. It was demonstrated that determinations of pulmonary shunt are superior to A-aP02 measurements in assessment of the ventilatory function of the lungs.


Faculty experience and engagement in a longitudinal integrated clerkship.
The authors sought to understand rewards and challenges of teaching third-year medical students in the University of Colorado School of Medicine (CUSOM) Denver Health Longitudinal Integrated Clerkship (DH-LIC) compared to teaching in rotation-based clerkships (RBCs). The authors considered implications for the recruitment and retention of faculty in clinical educational programs. Preceptors completed surveys at baseline and year-end. Of eligible faculty, 28 of 40 completed both baseline and year-end surveys. The majority (85.2%) of faculty were satisfied with the DH-LIC and 85.7% continued to teach in year-two of the program. Faculty reported increased satisfaction from teaching and improved teaching and mentoring skills. Faculty familiarity with DH-LIC students was significantly higher than with students previously taught (p = .004); 89.3% of faculty knew their DH-LIC student well enough to tailor instruction to individual learning needs. Teaching techniques utilized at baseline and end of year differed significantly; faculty reported asking questions to promote thinking, providing feedback to students, and providing students with practice in clinical reasoning more frequently in the DH-LIC. Innovative models of education such as LICs offer a strategy to recruit and retain excellent, invested faculty in outpatient settings.


Multimodality treatment of unresectable hepatic metastases from pancreatic glucagonoma.
Glucagonomas are pancreatic islet cell tumors arising from the alpha cells which belong to neuroendocrine tumors. They frequently metastasize to the liver. We report the case of a 52- year old man with a pancreatic glucagonoma with synchronous multiple liver metastases treated by surgery, transarterial chemoembolization, percutaneous radiofrequency thermal ablation and long-acting octreotide. Our report confirms that a multimodal approach is very effective in patients with unresectable liver metastases from pancreatic endocrine tumors providing long-lasting palliation and probably prolonging survival.


Radiophosphate imaging and bone densitometry in renal osteodystrophy.
The histologic features of renal osteodystrophy vary from dialysis osteomalacia to osteitis fibrosa cystica. Commensurate with this, the number of osteoblasts and osteoclasts changes with the stage of the disease; the osteoblasts are virtually absent in dialysis osteomalacia and are numerous in osteitis fibrosa. Radiophosphate accretion in bone increases with increasing osteoblastic activity, and the bone mineral status is determined by the net difference in osteoblastic and osteoclastic activity. The application of radionuclide imaging and dual radiographic absorptiometry mineral measurements in patients with renal osteodystrophy, renal transplants, and following parathyroidectomy for secondary hyperparathyroidism is reviewed.


Increased water use efficiency does not prevent growth decline of Pinus canariensis in a semi-arid treeline ecotone in Tenerife, Canary Islands (Spain).
Intrinsic water-use efficiency of Pinus canariensis (Sweet ex Spreng.) growing at a semi-arid treeline has increased during the past 37 years. Tree-ring width by contrast has declined, likely caused by reduced stomatal conductance due to increasing aridity. Rising atmospheric CO2 concentration (Ca ) has been related to tree growth enhancement accompanied by increasing intrinsic water-use-efficiency (iWUE). Nevertheless, the extent of rising Ca on long-term changes in iWUE and growth has remained poorly understood to date in Mediterranean treeline ecosystems. This study aimed to examine radial growth and physiological responses of P. canariensis in relation to rising Ca and increasing aridity at treeline in Tenerife, Canary Islands, Spain. We evaluated temporal changes in secondary growth (tree-ring width; TRW) and tree ring stable C isotope signature for assessing iWUE from 1975 through 2011. Precipitation was the main factor controlling secondary growth. Over the last 36 years P. canariensis showed a decline in TRW at enhanced iWUE, likely caused by reduced stomatal conductance due to increasing aridity. Our results indicate that increasing aridity has overridden the potential CO2 fertilization on tree growth of P. canariensis at its upper distribution limit.


Threshold of octave masking as a predictor of temporary threshold shift following repeated noise exposure.
Cumulative auditory effects of repeated exposure to a 3-min 110 dB SPL white noise were examined in 20 subjects (10 male, 10 female). Statistical analysis revealed greater 8-kHz temporary threshold shift in female ears despite equivalent preexposure 8-kHz thresholds across gender. Cumulative effects were seen in thresholds of octave masking scores, especially in female subjects, possibly reflecting increased susceptibility following the second noise exposure.


Congenital juvenile granulosa cell tumour of the testis: report of a case showing extensive degenerative changes.
Juvenile granulosa cell tumour is a rare neoplasm of the testis which occurs predominantly in infancy and which may be associated with sex chromosomal abnormalities. We report an unusual case with deceptive histological features resulting from extensive degenerative changes. In the pedunculated intra-abdominal mass resected from a 1-month-old male baby with 45,X/46,X,iso(Yq) mosaicism, there were multiple large cystic spaces devoid of cellular lining or lined by flat nondescript cells, mimicking various cystic lesions such as multicystic mesothelioma, cystic lymphangioma and cystic dysplasia. The cysts were separated by a highly vascularized fibrous stroma. Only in very rare cysts and the smaller cysts in the region of the pedicle were granulosa cells identified, permitting a diagnosis of juvenile granulosa cell tumour to be made.


Feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation.
BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-) particles do not. HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is also its Env protein, but the mechanism is distinctive. Unlike other tetherin antagonists, FIV Env cannot act in trans to rescue vpu-deficient HIV-1. It must be incorporated specifically into FIV virions to be active. Also unlike other retroviral antagonists, but similar to Ebola virus Env, it does not act by downregulating or degrading tetherin. FIV Env might exclude tetherin locally or direct assembly to tetherin-negative membrane domains. Other distinctive features are apparent, including evidence that this virus evolved an equilibrium in which tetherin is both restriction factor and cofactor, as FIV requires tetherin for optimal particle release.


Reaction of O2 with the hydrogen atom in water up to 350 degrees C.
The reaction of the H* atom with O2, giving the hydroperoxyl HO2* radical, has been investigated in pressurized water up to 350 degrees C using pulse radiolysis and deep-UV transient absorption spectroscopy. The reaction rate behavior is highly non-Arrhenius, with near diffusion-limited behavior at room temperature, increasing to a near constant limiting value of approximately 5 x 10(10) M(-1) s(-1) above 250 degrees C. The high-temperature rate constant is in near-perfect agreement with experimental extrapolations and ab initio calculations of the gas-phase high-pressure limiting rate. As part of the study, reaction of the OH* radical with H2 has been reevaluated at 350 degrees C, giving a rate constant of (6.0 +/- 0.5) x 10(8) M(-1) s(-1). The mechanism of the H* atom reaction with the HO2* radical is also investigated and discussed.


The thickness of the glomerular basement membrane in irradiated and unirradiated Wistar rats and C-57 BL mice of different age groups.
In both Wistar rats and C-57 BL mice, the thickness of the glomerular basement membrane increases progressively with age. This change, which can be measured in cohorts of manageable size, produces a measurement of biological age--if one accepts the assumption that it correlates with the viability of the organism that exhibit it. Whole-body exposure to x-rays has no observable influence on this age-related change.


References for Haplotype Imputation in the Big Data Era.
Imputation is a powerful in silico approach to fill in those missing values in the big datasets. This process requires a reference panel, which is a collection of big data from which the missing information can be extracted and imputed. Haplotype imputation requires ethnicity-matched references; a mismatched reference panel will significantly reduce the quality of imputation. However, currently existing big datasets cover only a small number of ethnicities, there is a lack of ethnicity-matched references for many ethnic populations in the world, which has hampered the data imputation of haplotypes and its downstream applications. To solve this issue, several approaches have been proposed and explored, including the mixed reference panel, the internal reference panel and genotype-converted reference panel. This review article provides the information and comparison between these approaches. Increasing evidence showed that not just one or two genetic elements dictate the gene activity and functions; instead, cis-interactions of multiple elements dictate gene activity. Cis-interactions require the interacting elements to be on the same chromosome molecule, therefore, haplotype analysis is essential for the investigation of cis-interactions among multiple genetic variants at different loci, and appears to be especially important for studying the common diseases. It will be valuable in a wide spectrum of applications from academic research, to clinical diagnosis, prevention, treatment, and pharmaceutical industry.


Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13).
We describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13. Submissions were made by three free-modeling (FM) methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network. Two systems assembled fragments produced by a generative neural network, one using scores from a network trained to regress GDT_TS. The third system shows that simple gradient descent on a properly constructed potential is able to perform on par with more expensive traditional search techniques and without requiring domain segmentation. In the CASP13 FM assessors' ranking by summed z-scores, this system scored highest with 68.3 vs 48.2 for the next closest group (an average GDT_TS of 61.4). The system produced high-accuracy structures (with GDT_TS scores of 70 or higher) for 11 out of 43 FM domains. Despite not explicitly using template information, the results in the template category were comparable to the best performing template-based methods.


[Development of whole process quality control and management system of traditional Chinese medicine decoction pieces based on traditional Chinese medicine quality tree].
The whole process quality control and management of traditional Chinese medicine (TCM) decoction pieces is a system engineering, involving the base environment, seeds and seedlings, harvesting, processing and other multiple steps, so the accurate identification of factors in TCM production process that may induce the quality risk, as well as reasonable quality control measures are very important. At present, the concept of quality risk is mainly concentrated in the aspects of management and regulations, etc. There is no comprehensive analysis on possible risks in the quality control process of TCM decoction pieces, or analysis summary of effective quality control schemes. A whole process quality control and management system for TCM decoction pieces based on TCM quality tree was proposed in this study. This system effectively combined the process analysis method of TCM quality tree with the quality risk management, and can help managers to make real-time decisions while realizing the whole process quality control of TCM. By providing personalized web interface, this system can realize user-oriented information feedback, and was convenient for users to predict, evaluate and control the quality of TCM. In the application process, the whole process quality control and management system of the TCM decoction pieces can identify the related quality factors such as base environment, cultivation and pieces processing, extend and modify the existing scientific workflow according to their own production conditions, and provide different enterprises with their own quality systems, to achieve the personalized service. As a new quality management model, this paper can provide reference for improving the quality of Chinese medicine production and quality standardization.


Whole-genome sequencing investigation of animal-skin-drum-associated UK anthrax cases reveals evidence of mixed populations and relatedness to a US case.
There have been two anthrax cases affecting people that played and/or made animal-skin drums in the UK during the last 10 years, with single fatal occurrences in Scotland in 2006 and London in 2008. Investigations by the Health Protection Agency (now Public Health England) employing multi-locus-variable number tandem repeat analysis had previously linked the clinical cases to spores associated with animal skins and drums the patients had been in contact with. In this study, whole-genome sequencing of 23 Bacillus anthracis isolates harvested during the investigations was performed. High-quality draft assemblies of these genomes provided greater characterization of the B. anthracis strains present and placed them all upon a new branch of the global phylogeny. Although closely related, the clinical isolates from the two events, and another isolated from a drum-skin-associated case in New York in 2006, were distinct from each other. Multiple distinct genotypes were found during both investigations, implying either multiple contamination events or a single heterogeneous contamination. One environmental isolate from the Scottish incident was more closely related to London isolates than to the other Scottish isolates. As B. anthracis of this subgroup was present at both geographically and temporally distinct events, it may be more widespread at the source of contamination. All isolates were distinct from currently characterized West African strains, despite this being the likely origin of the drums and hides, therefore adding to our knowledge of B. anthracis diversity in the region.


The use of patient-led goal setting in the intervention of chronic low back pain in adults: a narrative review.
Chronic low back pain (cLBP) impacts millions of adults annually. Several nonsurgical interventions are recommended for treating this condition, however, limited literature exists regarding the impact patient-led goals may have on outcomes in the treatment of cLBP. The purpose of this narrative review is to identify gaps and synthesize literature examining the associations of patient-led goals combined with care for cLBP. A total of 12 studies were reviewed and findings were synthesized. Patient-led goal setting may serve as an effective intervention for adults with cLBP. Current outcome measures may not align with patient-led goals. Further investigation is required to understand patient-led goals with ancillary treatments and specific age groups, such as adults over age 65.


Effects of halothane anesthesia on equine liver function.
Effects of halothane anesthesia were investigated in ponies prepared surgically with chronic external biliary fistulas (T tubes) to determine the effects on liver function and biliary excretion during 2 hours of anesthesia. Four studies were performed on 2 ponies, 2 to 6 months after surgery with the enterohepatic circulation held intact between studies. Intravenous bile acid infusion was used to maintain steady-state bile flow, bilirubin, and bile acid excretion during each study. Compared with the immediate 2-hour preanesthesia values (base line), halothane caused a 138% increase in bilirubin excretion, a 60% increase in biliary bilirubin concentration, and a 43% increase in PCV. Halothane anesthesia also caused a 16% reduction in plasma bilirubin, a 46% reduction in biliary bile acid concentration, and a 27% reduction in bile acid excretion. The bile acid independent fraction of bile flow appeared to increase. Plasma aspartate transaminase concentration did not change during anesthesia. The ratio of conjugated bilirubin fractions in bile [82% to 83% disconjugates of glucuronide and glucoside (2 forms) and 17% to 18% monoconjugates of glucoside, glucuronide, and xyloside] did not change during anesthesia and less than 1% was excreted unconjugated. Halothane anesthesia did not appear to affect adversely the activity of the transferase-conjugating enzymes in the presence of an increased bilirubin load. Seemingly, greatly increased conjugated bilirubin excretion observed during halothane anesthesia was most likely the result of a combination of increased hepatic clearance from plasma and increased hepatic bilirubin production from turnover of free hepatic heme or heme from the induced cytochrome P-450 system.(ABSTRACT TRUNCATED AT 250 WORDS)


Transforming growth factor-beta1 in a sterilized tissue derived from the pig small intestine submucosa.
The extracellular matrices of connective tissues contain growth factors such as transforming growth factor (TGF)-beta1. The possibility arises, therefore, that animal connective tissues that have been excised and rendered acellular in the sterilization, lyophilization, and other preparative processes for human use may still retain active growth factors that could contribute to the clinical efficacy of the product. We therefore analyzed 4M guanidine HCl extracts of a sterilized, acellular matrix, Oasis Wound Matrix, for the presence of TGF-beta1 by a sandwich enzyme-linked immunosorbent assay using the soluble type II receptor for TGF-beta to capture the growth factor, and for biological activity by testing the capacity of the extracts to inhibit 3[H]thymidine incorporation into Mv1Lu cells (mink lung epithelial cells). The enzyme-linked immunosorbent assay determined that TGF-beta1 was present at a concentration of 710.9 +/- 157.7 pg/g dry weight of tissue in Oasis and 768.1 +/- 182.1 pg/g dry weight of tissue in SIS (porcine small intestinal submucosa), the disinfected precursor of Oasis. The growth inhibition assays demonstrated that the Oasis extracts inhibited the proliferation of Mv1Lu cells in culture, consistent with the TGF-beta1 in the material having biological activity. Most of the TGF-beta1 survives the sterilization and lyophilization processes in the preparation of the Oasis Wound Matrix, and is functional in its ability to bind to its receptor and, apparently, in its capacity to inhibit growth.


Mapping QTLs associated with drought resistance in sorghum (Sorghum bicolor L. Moench).
Drought is a major abiotic stress factor limiting crop production. Identification of genetic factors involved in plant responses to drought stress will provide a solid foundation to improve drought resistance. Sorghum is well adapted to hot dry environments and regarded as a model for studying drought resistance among the grasses. Significant progress in genome mapping of this crop has also been made. In sorghum, rapid premature leaf death generally occurs when water is limited during the grain filling period. Premature leaf senescence, in turn, leads to charcoal rot, stalk lodging, and significant yield loss. More than 80% of commercial sorghum hybrids in the United States are grown under non-irrigated conditions and although most of them have pre-flowering drought resistance, many do not have any significant post-flowering drought resistance. Stay-green is one form of drought resistance mechanism, which gives sorghum resistance to premature senescence under soil moisture stress during the post-flowering period. Quantitative trait locus (QTL) studies with recombinant inbred lines (RILs) and near-isogenic lines (NILs) identified several genomic regions associated with resistance to pre-flowering and post-flowering drought stress. We have identified four genomic regions associated with the stay-green trait using a RIL population developed from B35 x Tx7000. These four major stay-green QTLs were consistently identified in all field trials and accounted for 53.5% of the phenotypic variance. We review the progress in mapping stay-green QTLs as a component of drought resistance in sorghum. The molecular genetic dissection of the QTLs affecting stay-green will provide further opportunities to elucidate the underlying physiological mechanisms involved in drought resistance in sorghum and other grasses.


Olleya algicola sp. nov., a marine bacterium isolated from the green alga Ulva fenestrata.
A strictly aerobic, Gram-stain-negative, rod-shaped, motile by gliding and yellow-pigmented bacterium, designated strain 3Alg 18T, was isolated from the Pacific green alga Ulva fenestrata. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain was affiliated to the family Flavobacteriaceae of the phylum Bacteroidetes, being most closely related to the type strains of recognized species of the genus Olleya, with 16S rRNA gene sequence similarity of 97.9-99.3 %. Strain 3Alg 18T grew in the presence of 0.5-5 % (w/v) NaCl and at 4-37 °C, and hydrolysed aesculin, casein, gelatin, starch and Tweens 20, 40 and 80. The prevalent fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH, iso-C16:0 2-OH, iso-C17 : 0 3-OH, summed feature 3, iso-C16 : 0 3-OH, anteiso-C15 : 0 and C15 : 0. The polar lipid profile contained phosphatidylethanolamine, three unidentified aminolipids and four unidentified lipids. The major respiratory quinone was menaquinone MK-6. The genomic DNA G+C content was 34.6 mol%. On the basis of 16S rRNA gene sequence data, and chemotaxonomic and phenotypic characteristics, strain 3Alg 18T represents a novel species of the genus Olleya, for which the name Olleya algicola sp. nov. is proposed. The type strain is 3Alg 18T (=KCTC 22024T=KMM 6133T).


Is it necessary to classify developmental trajectories over time? A critical note.
This paper is a critical note regarding the classification of developmental trajectories. Although the results should be interpreted with caution, it seems that this classification can be interesting for descriptive purposes. For answering additional research questions relating to the prediction and/or the consequences of a different development over time, the classification of developmental trajectories does not seem to be necessary. However, it should be realized that the present analysis employs a relatively simple classification method and that there are some new promising developments within the field of classification methods, which can be of interest.


Is sonic Hedgehog involved in human fracture healing? --a prospective study on local and systemic concentrations of SHH.
Sonic Hedgehog (SHH) is a new signalling pathway in bone repair. Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis. Some in vitro and animal studies has already proven its potential for bone regeneration. However, no data on the role of SHH in the human fracture healing have been published so far. Seventy-five patients with long bone fractures were included into the study and divided in 2 groups. First group contained 69 patients with normal fracture healing. Four patients with impaired fracture healing formed the second group. 34 volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SHH levels were measured in fracture haematoma and serum of 16 patients with bone fractures. Fracture haematoma and patients serum both contained lower SHH concentrations compared to control serum. The comparison between the patients' serum SHH level and the control serum revealed lower levels for the patients at all measurement time points. Significantly lower concentrations were observed at weeks 1 and 2 after fracture. SHH levels were slightly decreased in patients with impaired fracture healing without statistical significance. This is the first study to report local and systemic concentration of SHH in human fracture healing and SHH serum levels in healthy adults. A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found. SHH concentrations in fracture haematoma and serum were lower than the concentration in control serum for the rest of the healing period. Our findings indicate that there is no relevant involvement of SHH in human fracture healing. Fracture repair process seem to reduce the SHH level in human. Further studies are definitely needed to clarify the underlying mechanisms.


Crushing injury of the hand; prevention of ischemic contracture.
Crushing injury of the hand usually causes "explosive" damage. Subsequent swelling of the palmar structures further impairs venous outflow, and hemorrhage into structural spaces increases the pressure. The arterial system and the large dorsal veins, however, are seldom obstructed and provide adequate circulation unless hampered by improper bandaging. A bandage that compresses the dorsal veins causes back-pressure, which increases the swelling further and brings about ischemia. Swelling and pain cause the patient to restrict exercise of the injured hand, which permits contractures to develop. The author has averted this sequence in more than 100 cases by preserving integrity of veins during debridement, arresting hemorrhage, bandaging the hand with compression dressings in functional flexion, and reducing swelling with hyaluronidase. In these cases, on removal of bandages in 24 hours, swelling was reduced and continued to diminish. All patients exercised the hand at this time without discomfort and only a few required aspirin for pain.


The independent influences of heat strain and dehydration upon cognition.
Many researchers have addressed the potential effects of hyperthermia and dehydration on cognition, often revealing contradictory outcomes. A possible reason for this inconsistency is that experiments may have been inadequately designed for such effects. In this study, the impact of hyperthermia, dehydration and their combination on cognition were evaluated in eight young males, after accounting for a range of experimental limitations. Passive heating and thermal clamping at two mean body temperatures (36.5, 38.5 °C) were performed under three hydration states (euhydrated, 3 and 5% dehydrated) to assess their effects on difficulty-matched working memory and visual perception tasks, and on a difficulty manipulated perceptual task. Data were analysed according to signal detection theory to isolate changes in response sensitivity, bias and speed. Neither moderate hyperthermia (P = 0.141) nor dehydration (P > 0.604) modified response sensitivity, nor did they significantly interact (P > 0.698). Therefore, the ability to distinguish correct from incorrect responses was unaffected. Nevertheless, hyperthermia, but not dehydration (P = 0.301), reduced the response bias (-0.08 versus 2.2 [normothermia]; P = 0.010) and reaction time (mean reduction 49 ms; P < 0.001), eliciting more liberal and faster responses (P = 0.010). Response bias was reduced for the memory relative to the perceptual task (P = 0.037), and this effect was enhanced during hyperthermia (P = 0.031). These observations imply that, once potentially confounding influences were controlled, moderate hyperthermia, significant dehydration and their combined effects had insufficient impact to impair cognition within the memory and perceptual domains tested. Nonetheless, moderate hyperthermia elicited more liberal and rapid responses.


[Toxicological characterization of calcium ketopantoylaminobutyrate].
The investigation of toxicity of calcium ketopantoylaminobutyrate (Ca-KPAB) showed that this newly synthesized compound belongs to the class of low-toxicity substances. The LD 50 of Ca-KPAB for oral administration is lower than that of pantogam. No toxicity manifestations and local irritant activity was observed upon chronic administration of Ca-KPAB. The therapeutic index of Ca-KPAB is more than 17 times that of pantogam.


Diagnosis, prevention and treatment of aspirin-induced asthma and rhinitis.
Bronchial asthma is not a homogenous disease. Several variants of asthma can be distinguished. One of them is aspirin-induced asthma. In this distinct clinical syndrome, aspirin and most other nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase-1 precipitate rhinitis and asthma attacks. This type of asthma affects 5-10% of adult asthmatics, but remains largely underdiagnosed. The natural history of aspirin-induced asthma (AIA) has been described, based on an extensive pan-European survey. Aspirin provocation tests with improved diagnostic accuracy have been developed, although no in-vitro tests has been found to be of diagnostic value. Recent interest in AIA has been stirred by the finding of alterations in arachidonate metabolic pathways, leading to cysteinyl-leukotriene overproduction. LTC4 synthase is overexpressed in bronchi and its mRNA is upregulated in peripheral blood eosinophils. The gene coding for LTC4 synthase exists in two common alleles, one of which appears to be associated with a severe, steroid-dependent type of asthma. New highly specific COX-2 inhibitors appear to be a safe alternative for patients with aspirin-induced asthma.


Characterization of Pasteurella multocida associated with pneumonia in bighorn sheep.
Pasteurella multocida is a highly diverse group of bacteria recognized as important pathogens. Although P. multocida is not ordinarily associated with disease in Rocky Mountain bighorn sheep (Ovis canadensis canadensis), numerous isolates were cultured in high numbers from free-ranging bighorn sheep in the Hells Canyon area of Idaho, Washington, and Oregon (USA) during the winter of 1995-96. Animals captured in Hells Canyon and held in captivity, and their offspring, also harbored P. multocida. Biochemical utilization tests on 90 isolates identified three subspecies: P. multocida multocida a (n = 54); P. multocida multocida b (n = 13); and P. multocida gallicida (n = 15); and a non-speciated biotype, U6 (n = 8). Genomic DNA digestion with restriction endonuclease Hha I separated the isolates into 62 unique restriction fragment length polymorphism profiles. Capsular type A was predominant (72% of isolates). Only one isolate type, which may have been transmitted from a feral goat, was capsular type D, possessed the structural gene, toxA, for dermonecrotoxin detected by polymerase chain reaction, and produced toxin as determined by monoclonal antibody immunoblot. In conclusion, bighorn sheep in this study carried diverse types of generally non-toxigenic P. multocida associated with epizootic pneumonia.


[TPM1 gene mutation is associated with dilated cardiomyopathy in Kazaks in Xinjiang].
Detect the relationship between TPM1 gene mutations and dilated cardiomyopathy (DCM) of Kazaks and Hans in Xinjiang. TPM1 gene was screened from 31 family members in a Kazak family with familiar DCM (FDCM), 100 patients with idiopathic DCM (IDCM, 50 Kazaks and 50 Hans), and in 100 healthy controls (50 Kazaks and 50 Hans). All the samples were the inpatients or outpatients of First Affiliated Hospital of Xinjiang University from 2012 to 2014. PCR was used to amplify 9 exons and nearby introns of the TPM1 gene. The amplified products were sequenced and compared with the standard sequence with CHROMAS software and BLAST software in Pubmed to identify mutation sites. The relationship between TPM1 gene mutations in the Kazak IDCM and healthy volunteers, between Han and Kazak IDCM and healthy volunteers was analyzed. Tropomyosin was qualitatively and quantitatively detected by ELISA in all subjects. A novel variant (c.524 G > T) was identified in two FDCM patients at exon 3, this mutation caused an amino acid substitution, Gln111His. The FDCM, IDCM from Kazak and Han, healthy volunteers from Kazak and Han were founded a rs1071646 (c.644C > A, Ala151Ala). There was a significant difference in the genotype distribution (χ(2) = 13.36, P = 0.001) and allele frequency (χ(2) = 10.25, P = 0.001) between Kazaks with IDCM and Kazak controls of rs1071646, while these parameters were similar between Han IDCM patients and Han controls (all P > 0.05). The tropomyosin content of Kazak and Han IDCM patients were significantly lower than Kazak and Han controls ((1 764.2 ± 350.9) ng/L vs. (2 369.7 ± 345.9) ng/L, P = 0.001). TPM1 gene of rs1071646 polymorphism is a possible independent risk factor for IDCM in Kazaks but not Han Chinese.


Inherited and predisposing factors in the development of gastric dilatation volvulus in dogs.
This review article summarizes what is known as well as what is undetermined concerning the inherited and environmental pathogenesis of gastric dilatation volvulus in dogs. The disorder primarily affects large and giant, deep-chested breeds. A concise description of a typical dog affected with gastric dilatation volvulus is presented.


Evolutionary branching of dispersal strategies in structured metapopulations.
Dispersal polymorphism and evolutionary branching of dispersal strategies has been found in several metapopulation models. The mechanism behind those findings has been temporal variation caused by cyclic or chaotic local dynamics, or temporally and spatially varying carrying capacities. We present a new mechanism: spatial heterogeneity in the sense of different patch types with sufficient proportions, and temporal variation caused by catastrophes. The model where this occurs is a generalization of the model by Gyllenberg and Metz (2001). Their model is a size-structured metapopulation model with infinitely many identical patches. We present a generalized version of their metapopulation model allowing for different types of patches. In structured population models, defining and computing fitness in polymorphic situations is, in general, difficult. We present an efficient method, which can be applied also to other structured population or metapopulation models.


Design and synthesis of pyrrolidine-5,5'-trans-lactams (5-oxo-hexahydropyrrolo[3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease. 4. Antiviral activity and plasma stability.
A series of chiral, (S)-proline-alpha-methylpyrrolidine-5,5-trans-lactam serine protease inhibitors has been developed as antivirals of human cytomegalovirus (HCMV). The SAR of the functionality on the proline nitrogen has shown that derivatives of para-substituted phenyl ureas > para-substituted phenyl sulfonamides > para-substituted phenyl carboxamide for activity against HCMV deltaAla protease, producing para-substituted phenyl ureas with single figure nM potency (K(i)) against the viral enzyme. The SAR of the functionality on the lactam nitrogen has defined the steric and electronic requirements for high human plasma stability while retaining good activity against HCMV protease. The combination of high potency against HCMV deltaAla protease and high human plasma stability has produced compounds with significant in vitro antiviral activity against human cytomegalovirus with the 6-hydroxymethyl benzothiazole derivative 72 being equivalent in potency to ganciclovir. The parent benzothiazole 56 had good pharmacokinetics in dogs with 29% bioavailability and good brain and ocular penetration in guinea pigs.


Inhibitory changes after age 60 and their relationship to measures of attention and memory.
This study examined the relationship between age and inhibitory functioning within a sample of older adults ranging in age from 60 to 85 years old. On the basis of earlier research, and confirmed by factor analysis, measures typically referred to as frontal lobe tasks were used as measures of inhibitory functioning. Findings demonstrated that inhibitory processes continued to decline with advancing age within the older sample. In addition, the role of inhibition in age-related performance deficits on a verbal list learning measure and an attention measure was examined. Hierarchical regression analyses showed that inhibition accounted for a significant proportion of the age-related variance on the two cognitive measures, whereas measures of reading speed accounted for a smaller proportion of the variance. In addition, when inhibition was first covaried out, reading speed no longer accounted for a significant proportion of the age-related variance. It is argued that inhibition is an important contributor to age-related performance decrements in cognition.


Measuring continuity and discontinuity following stroke.
To design and test a valid, reliable, and parsimonious instrument to measure continuity and discontinuity of self following stroke. A 45-item scale with a 3-point response set was developed. The conceptual basis, "continuity and discontinuity in the experience of self," was derived from an existential-phenomenological study of stroke survivors. Study instruments included the Barthel Index (measure of functional abilities) and the pre- and poststroke QoL Cantril Ladder. The instruments were administered one time, in random order, to 55 stroke survivors in the United States in rehabilitation hospitals and in the community. Data were analyzed using a principal components factor analysis. A 2-factor solution with 10 items per factor was derived. Cronbach's alpha for Factor 1 (discontinuity of self) was .874 and for Factor 2 (continuity of self) was .869. Continuity and discontinuity were inversely related; continuity was related to functional abilities, but discontinuity was not. Use of this instrument validated findings from a qualitative study, which showed that life following stroke was a paradoxical sense of both continuity and discontinuity in the experience of self. This instrument can be used to measure the effectiveness of nursing interventions aimed at increasing stroke survivors' sense of continuity.


Encephalopathy and rhabdomyolysis induced by iotrolan during epiduroscopy.
We describe a complication of epiduroscopy with encephalopathy and rhabdomyolysis associated with the contrast medium iotrolan. A 76-yr-old man with failed back surgery syndrome underwent epiduroscopy. Sufficient lysis could not be achieved in the epidural space above the level of L4 due to dense adhesions and scar tissue. After epidural injections of iotrolan and mepivacaine, he developed motor weakness and hypoesthesia in both legs, which lasted for three hours. He also became confused, agitated, disoriented, and developed neck stiffness and tremors involving the head and legs. Computed tomography revealed diffuse contrast enhancement within the intracranial cerebrospinal fluid (CSF) spaces, indicating an intraoperative dural tear. Marked increases in serum creatinine phosphokinase and myoglobin indicated subsequent acute rhabdomyolysis. Crystalloid infusion and semi-recumbent positioning facilitated iotrolan absorption from the CSF, and the patient recovered uneventfully. Dural tear during epiduroscopy may allow access of contrast media into the CSF. Neurotoxicity secondary to iotrolan within the CSF was a likely contributing factor to the encephalopathy and subsequent rhabdomyolysis. This is an instructive example of the importance of diagnosing inadvertent dural tear during epiduroscopy under iotrolan, for avoidance of adverse events such as encephalopathy and rhabdomyolysis.


Optimal strategies for mapping complex diseases in the presence of multiple loci.
Recent advances in genome technology have led to mapping and subsequent isolation, by positional cloning, of a number of genes for common and/or complex human diseases. It therefore will be possible to utilize information about a known locus in the search for additional, perhaps less penetrant, genes for a particular disease. It is also unclear, under these situations, what the optimal sampling strategy should be. To address these questions, we have calculated the expected LOD score for localizing one locus in a variety of two-locus models of disease, for four different pedigree structures, and under three different scenarios regarding knowledge/testing of one of the two loci. These design considerations are evaluated by use of a cost function that incorporates the costs of ascertaining different family structures, the relative costs of genotyping and mutation testing family members, and the amount of information provided by each family structure and testing scenario. The results indicate that, in most cases, affected sib pairs are a particularly poor strategy, especially when linkage or mutation data are available at the known locus. We also demonstrate that prescreening the sample of families for mutations at known susceptibility loci is, in general, a cost-effective strategy.


Family planning in conflict: results of cross-sectional baseline surveys in three African countries.
Despite the serious consequences of conflict for reproductive health, populations affected by conflict and its aftermath face tremendous barriers to accessing reproductive health services, due to insecurity, inadequate numbers of trained personnel and lack of supplies. Family planning is often particularly neglected. In six conflict-affected areas in Sudan, northern Uganda and the Democratic Republic of Congo, household surveys of married or in-union women of reproductive age were conducted to determine baseline measures of family planning knowledge, attitudes and behaviors regarding contraception. Health facility assessments were carried out to assess baseline measures of family planning services availability. Data were double-entered into CSPro 3.2 and exported to SAS 9.2, which was used to calculate descriptive statistics. The studies' purposes were to guide program activities and to serve as a baseline against which program accomplishments could be measured. Knowledge of modern contraceptive methods was low relative to other sub-Saharan African countries, and use of modern methods was under 4% in four sites; in two sites with prior family planning services it was 12% and 16.2%. From 30% to 40% of women reported they did not want a child within two years, however, and an additional 12% to 35% wanted no additional children, suggesting a clear need for family planning services. The health facilities assessment showed that at most only one-third of the facilities mandated to provide family planning had the necessary staff, equipment and supplies to do so adequately; in some areas, none of the facilities were prepared to offer such services. Family planning services are desired by women living in crisis situations when offered in a manner appropriate to their needs, yet services are rarely adequate to meet these needs. Refugee and internally displaced women must be included in national and donors' plans to improve family planning in Africa.


CD4 binding affinity determines human immunodeficiency virus type 1-induced alpha interferon production in plasmacytoid dendritic cells.
Plasmacytoid dendritic cells (PDC) are major producers of type I interferons (IFN) in response to human immunodeficiency virus type 1 (HIV-1) infection. To better define the underlying mechanisms, we studied the magnitude of alpha IFN (IFN-alpha) induction by recombinant viruses containing changes in the Env protein that impair or disrupt CD4 binding or expressing primary env alleles with differential coreceptor tropism. We found that the CD4 binding affinity but not the viral coreceptor usage is critical for the attachment of autofluorescing HIV-1 to PDC and for subsequent IFN-alpha induction. Our results illustrate the importance of the gp120-CD4 interaction in determining HIV-1-induced immune stimulation via IFN-alpha production.


Better differential diagnosis of iron deficiencyanemia from beta-thalassemia trait.
Iron deficiency anemia (IDA) and ß- Thalassemia Trait (ß-TT) are the most common forms of microcytic anemia. This study was conducted to compare the validity of these discrimination indices in differentiating ß- Thalassemia Trait (β-TT) from IDA by calculating their sensitivity, specificity and Youden's index. Totally 323 subjects (173 children and 150 adult) with microcytic anemia were involved in this study. We calculated 10 discrimination indices in all patients with IDA and β-TT. We divided the patients into two different groups as younger and older than 10 years. None of indices showed sensitivity and specificity of 100% in the patients older than 11 years, but only Shine and Lal Index showed sensitivity close to 90% and specificity of 100% in the patients younger than 10 years. The most accurate discriminative index for patients younger than 10 years was Shine & Lal and in case of patients older than 11 years it was RDWI. Youden's index for Shine & Lal & RBC Count and for RDWI & RBC Count indices has most diagnostic value for younger and older than 10 years, respectively. None of the indices was completely sensitive and specific in differentiation between β-TT and IDA. MCHD mean and median were very close to normal values for both IDA and β-TT patients, but in case of MHDL we have found mean and median were significantly higher than normal values in β-TT and lower than those in IDA patients. In our study, Youden's index of RBC and S & L were the highest and the most reliable discrimination indices in differentiating β-TT from IDA in the patients younger than 10 years and for patients older than 11 years, the most reliable discrimination indices were RBC and RDWI.