Dynamic Telecytopathology-Guided Rapid On-Site Assessment of Percutaneous Image-Guided Fine-Needle Aspiration of Hepatic Lesions: An Institutional Review of 178 Cases.
Background: Rapid on-site evaluation (ROSE) of image-guided fine-needle aspiration (IGFNA) of hepatic lesions is necessary to ensure adequate sample collection and render preliminary diagnosis. We review our experience with utilization of telecytopathology for ROSE of IGFNA of liver lesions. Materials and Methods: Cytotechnologists at a remote site transmitted real-time images of Diff-Quik-stained cytology smears of hepatic lesions obtained using an Olympus DP70 digital camera via Ethernet to a pathologist. All live communications were conducted using the Vocera voice communication system. Preliminary telecytopathology ROSE diagnosis was compared with the final diagnosis for accuracy. Results: ROSE using telecytopathology of IGFNAs of hepatic lesion was performed on a total of 178 cases. Preliminary diagnosis of unsatisfactory, benign, suspicious for malignancy, and positive for malignancy was 2%, 28%, 15%, and 55%, respectively, for telecytopathology. The overall concordance between the preliminary and final cytology diagnoses was 94.4%. Nine of the cases were upgraded to suspicious/malignant final diagnosis contributing to an upgrade rate of 5%. One case with preliminary evaluation of positive for malignancy was downgraded to benign cytology on final diagnosis resulting in a downgrade rate of 0.1%. Conclusion: Utilization of telecytopathology is highly effective and accurate for ROSE of IGFNAs of hepatic lesions and may serve as a substitute for conventional microscopy.


Diffuse visual field loss and glaucoma.
It is often claimed that general reduction, or diffuse loss, of perimetric sensitivity is an early sign of glaucoma. Our clinical experience and the results of a few other studies led us to believe otherwise. To investigate factors associated with diffuse field loss we reviewed 4222 Humphrey 30-2 threshold tests from 1582 eyes of 862 patients followed at our department. Most of these patients had ocular hypertension or glaucoma. Each field test was evaluated with the Glaucoma Hemifield Test of the Statpac 2 program. The Glaucoma Hemifield Test classifies field test results as within or outside normal limits regarding localized field loss and general shifts in sensitivity. General reduction of sensitivity without concomitant localized loss was found in 117 tests from 81 eyes of 69 patients. Corresponding patient records were found for 60 eyes of 60 patients. Media opacities or miotic therapy were noted in 46 eyes (77%), 10 eyes (17%) had end-stage field loss, and in 2 eyes (3%) other non-glaucomatous ocular pathology explained the diffuse loss of sensitivity. Thus, general reduction of differential light sensitivity as an isolated finding was almost always associated with reasons other than early to moderate glaucoma in this material mainly consisting of patients with glaucoma or increased intraocular pressure. Since only 2 out of the 1582 eyes had general reduction of sensitivity that was not explained by non-glaucomatous reasons, we conclude that purely diffuse field loss was not a sign of glaucoma.


Interareal coordination of columnar architectures during visual cortical development.
The formation of cortical columns is often conceptualized as a local process in which synaptic microcircuits confined to the volume of the emerging column are established and selectively refined. Many neurons, however, while wiring up locally are simultaneously building macroscopic circuits spanning widely distributed brain regions, such as different cortical areas or the two brain hemispheres. Thus, it is conceivable that interareal interactions shape the local column layout. Here we show that the columnar architectures of different areas of the cat visual cortex in fact develop in a coordinated manner, not adequately described as a local process. This is revealed by comparing the layouts of orientation columns (i) in left/right pairs of brain hemispheres and (ii) in areas V1 and V2 of individual brain hemispheres. Whereas the size of columns varied strongly within all areas considered, columns in different areas were typically closely matched in size if they were mutually connected. During development, we find that such mutually connected columns progressively become better matched in size as the late phase of the critical period unfolds. Our results suggest that one function of critical-period plasticity is to progressively coordinate the functional architectures of different cortical areas--even across hemispheres.


Responses of cyanobacterium Anabaena doliolum during nickel stress.
Growth and biochemical responses of heterocystous nitrogen fixing cyanobacteria Anabaena doliolum were studied upon exposure to various concentrations of nickel (0.1 to 100 microM) for duration of up to 4 days, in view of its tolerance. The growth of the cyanobacterium was increased in terms of cell density (O.D), heterocyst frequency chlorophyll-a, carotenoid and c-phycocynin up to moderate exposure (10 microM for 96 hr of Ni treatment). Protein and total non protein thiol were measured as stress responsive metabolites and frequency of heterocyst and spores were observed in responses to Ni. The present study demonstrated that the tested cyanobacterium exhibited dose specific responses of metal towards studied different morphological, physiological and biochemical parameters.


An injectable synthetic immune-priming center mediates efficient T-cell class switching and T-helper 1 response against B cell lymphoma.
Patients with malignant non-Hodgkin's lymphomas (NHL) of B-cell lineages relapse despite initial anti-tumor response to chemotherapy or antibody treatments. Failure to eliminate the tumor is often because of inadequate priming, low cell numbers and suboptimal phenotype of effector T cells. Here we describe a new biomaterial-based controlled-release paradigm to treat weakly immunogenic NHLs by in-situ amplifying the number of functional, antigen-specific T-helper 1 (Th1) cells following immunotherapy. An injectable, synthetic immune priming center (sIPC) consisting of an in-situ crosslinking, chemokine-carrying hydrogel and both DNA- and siRNA dual-loaded microparticles, is reported. This sIPC chemo attracts a large number of immature dendritic cells (DCs) at the site of administration and efficiently co-delivers both DNA antigens and interleukin-10 (IL10)-silencing siRNA to those cells. Using a murine model of A20 B cell lymphoma, we demonstrate that combination of DNA-antigen delivery and IL10 silencing, synergistically activate recruited immature DCs and cause a strong shift towards Th1 response while suppressing Th2 and Th17 cytokines. sIPC-based immunotherapy showed 45% more CD8+ cytotoxic T cell (CTL) response and 53% stronger CD4+ CTL activity compared to naked DNA vaccine. In addition, in-vivo sIPC immunization induced significant protection (p<0.01) against subsequent tumor challenge. Such a multi-modal, injectable system that simultaneously delivers chemokines, siRNA and DNA antigens to DCs marks a new approach to in-situ priming and modulation during immunotherapy and could provide effective vaccination strategies against cancers and infectious diseases.


Mattis Dementia Rating Scale 2: screening for MCI and dementia.
Identifying patients at higher risk of developing dementia is important. The usefulness of the Mattis Dementia Rating scale-Second Edition (MDRS-2) to detect and differentiate between patients with amnestic mild cognitive impairment (A-MCI), Parkinson's disease and MCI (PD-MCI), PD with dementia (PDD), and Alzheimer's disease (AD) was investigated. In all, 22 healthy controls (HC), 22 A-MCI, 22 PD-MCI, 16 PDD, and 22 AD patients were evaluated using an extensive neuropsychological battery, including the MDRS-2. The MDRS-2 total standardized score detected all groups of patients. The dementia groups performed worse than HC on the 5 MDRS-2 subscales. Alzheimer's disease patients scored higher than PDD on MDRS-2 conceptualization and lower on memory. Healthy controls were better than PD-MCI on MDRS-2 initiation/perseveration and memory and better than A-MCI on memory. No difference was found between the MCI groups. The MDRS-2 is a suitable short scale for MCI and dementia screening but is not specific enough to differentiate between A-MCI and PD-MCI.


Exploring a Possible Link between the Fecal Microbiota and the Production Performance of Pigs.
The backfat thickness of pigs not only affects the physical properties and taste of meat, but it also closely relates to the reproduction performance of sows. Accumulating evidence indicates that, apart from genetic factors, gut microbiota can also modulate the fat deposition and muscle growth. However, the differential microbiota in pigs with different backfat thickness, and whether microbiota affects backfat thickness, remains elusive. Firstly, 16S ribosomal RNA (16S rRNA) gene sequencing was performed on 62 fecal samples from pigs with different backfat thicknesses, and the compositions of microbiota among different groups with different backfat thicknesses were different. The abundance of Lactobacillus. reuteri (L. reuteri) and Prevotella sp RS2 was significantly higher in pigs with low-backfat thickness than that in pigs with middle and high-backfat thickness; meanwhile, the abundance of Desulfovibrio piger was significantly lower (p < 0.05) in pigs with low-backfat thickness. Furthermore, the functional profiling of microbial communities suggested that the abundance of isoquinoline alkaloid biosynthesis and styrene degradation were significantly lower (p < 0.05) in the low-backfat thickness group than that in middle and high-backfat thickness groups. Finally, L. reuteri fed to Meishan piglets was capable of improving the production performance and had the potential to reduce backfat thickness. This study provides new evidence that microbiota can regulate the phenotype of the host, and dietary supplementation with L. reuteri can improve the production performance of piglets.


Chronic radiation exposure of neuroblastoma cells reduces nMYC copy number.
Neuroblastoma accounts for >15% of cancer-associated mortalities of children in the USA. Despite aggressive treatment regimens, the long-term survival for these children remains <40%. The identification of v-Myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (nMYC) gene amplification during diagnosis is associated with poor prognosis in neuroblastoma. There are limited studies examining changes in nMYC copy numbers in response to therapy and its biological effect on cancer cells. The aim of the present study was to evaluate the effect of radiation on nMYC expression and amplification status in high-risk neuroblastoma. The effect of acute (5 Gy) and chronic (25 Gy) radiation on two nMYC-amplified cell lines, SK-N-BE (2) and NB-1691, was investigated. The results demonstrate that, following chronic but not acute radiation, the two cell lines regained their proliferation potential similar to the controls. This increased proliferation was characterized by loss of nMYC mRNA and protein expression. It was also revealed that nMYC loss was accompanied by nuclear localization of c-Myc. Using fluorescent in situ hybridization and quantitative polymerase chain reaction analysis, the results of the present study demonstrated that chronic radiation causes a severe loss of nMYC gene copy number. The present study is the first to provide experimental evidence that prolonged radiation therapy affects nMYC gene copy number in high-risk neuroblastoma but does not significantly improve the prognostic outlook.


Mutagenic and carcinogenic potency indices and their correlation.
We have analyzed a significant number of studies existing in the literature, in which the ability of different short-term tests for predicting carcinogenicity in rodents was investigated. We have separated these studies into two groups. In the better known group of studies, qualitative predictivity was investigated (sensitivity and specificity). In the second group of studies (analyzed in greater detail), positive results were examined for the correlation between carcinogenic potency and potency of response in a given short-term test. There is substantial agreement between qualitative and quantitative predictivity; both appear to be situated between a low and moderate level. We have analyzed the interesting possibility of using the quantitative approach not only for positive data but for combined positive and negative data as well. We have stressed that short-term tests of genotoxicity should be asked to predict only initiation and irreversible alterations in the genome and not to predict a combination of these events, including promotion and modulation of differentiation. Even with regard to only initiation, genotoxicity data should be related to comparative metabolism, as well as to considerations of the significance of different end points and structure-activity relationship data. In conclusion, the information coming from short-term tests of genotoxicity is probably useful but should be used in conjunction with other types of information and only for predicting one particular class of events in the entire process of carcinogenesis.


The role of surface charge in the desolvation process of gelatin: implications in nanoparticle synthesis and modulation of drug release.
The process of moving hydrophobic amino acids into the core of a protein by desolvation is important in protein folding. However, a rapid and forced desolvation can lead to precipitation of proteins. Desolvation of proteins under controlled conditions generates nanoparticles - homogeneous aggregates with a narrow size distribution. The protein nanoparticles, under physiological conditions, undergo surface erosion due to the action of proteases, releasing the entrapped drug/gene. The packing density of protein nanoparticles significantly influences the release kinetics. We have investigated the desolvation process of gelatin, exploring the role of pH and desolvating agent in nanoparticle synthesis. Our results show that the desolvation process, initiated by the addition of acetone, follows distinct pathways for gelatin incubated at different pH values and results in the generation of nanoparticles with varying matrix densities. The nanoparticles synthesized with varying matrix densities show variations in drug loading and protease-dependent extra- and intracellular drug release. These results will be useful in fine-tuning the synthesis of nanoparticles with desirable drug release profiles.


Exposure and Inequality of PM2.5 Pollution to Chinese Population: A Case Study of 31 Provincial Capital Cities from 2000 to 2016.
Fine particulate matter (PM2.5) exposure has been linked to numerous adverse health effects, with some disadvantaged subgroups bearing a disproportionate exposure burden. Few studies have been conducted to estimate the exposure and inequality of different subgroups due to a lack of adequate characterization of disparities in exposure to air pollutants in urban areas, and a mechanistic understanding of the causes of these exposure inequalities. Based on a long-term series of PM2.5 concentrations, this study analyzed the spatial and temporal characteristics of PM2.5 in 31 provincial capital cities of China from 2000 to 2016 using the coefficient of variation and trend analyses. A health risk assessment of human exposure to PM2.5 from 2000 to 2016 was then undertaken. A cumulative population-weighted average concentration method was applied to investigate exposures and inequality for education level, job category, age, gender and income population subgroups. The relationships between socioeconomic factors and PM2.5 exposure concentrations were quantified using the geographically and temporally weighted regression model (GTWR). Results indicate that the PM2.5 concentrations in most of the capital cities in the study experienced an increasing trend at a rate of 0.98 μg m-3 per year from 2000 to 2016. The proportion of the population exposed to high PM2.5 (above 35 μg m-3) increased annually, mainly due to the increase of population migrating into north, east, south and central China. The higher educated, older, higher income and urban secondary industry share (SIS) subgroups suffered from the most significant environmental inequality, respectively. The per capita GDP, population size, and the share of the secondary industry played an essential role in unequal exposure to PM2.5.


p21-activated kinase 1 plays a critical role in cellular activation by Nef.
The activation of Nef-associated kinase (NAK) by Nef from human and simian immunodeficiency viruses is critical for efficient viral replication and pathogenesis. This induction occurs via the guanine nucleotide exchange factor Vav and the small GTPases Rac1 and Cdc42. In this study, we identified NAK as p21-activated kinase 1 (PAK1). PAK1 bound to Nef in vitro and in vivo. Moreover, the induction of cytoskeletal rearrangements such as the formation of trichopodia, the activation of Jun N-terminal kinase, and the increase of viral production were blocked by an inhibitory peptide that targets the kinase activity of PAK1 (PAK1 83-149). These results identify NAK as PAK1 and emphasize the central role its kinase activity plays in cytoskeletal rearrangements and cellular signaling by Nef.


[Analysis of effectiveness of interrupt percutaneous endoscopic lumbar discectomy through interlaminar approach for L5, S1 disc protrusion].
To evaluate the effectiveness of interrupt percutaneous endoscopy lumbar discectomy (PELD) through interlaminar approach for L5, S1 disc protrusion. Between November 2006 and August 2010, 115 patients with L5, S1 disc protrusion were treated, including 79 males and 36 females with an average age of 38 years (range, 14-79 years). All patients showed the dominated symptom of the S1 nerve root. The working channel was established by puncturing through interlaminar approach under the local anesthesia. After the needle was used to make sure no nerve root or dural sac on working face, the disc tissue was excised directly by blind sight. Then the nerve root decompression was observed through the endoscope. In patients with free type, fragment compression was observed through the endoscope, and the disc tissue around the nerve roots was removed, then the free disc tissue around intervertebral space was excised. One patient who failed to puncture changed to miniopen discectomy; 3 patients who failed changed to post lateral approach; and the others underwent interrupt PELD through interlaminar approach. Eighty patients were followed up 18 months on average (range, 12-36 months). The average Oswestry Disability Index (ODI) was reduced to 13% +/- 5% at 12 months after operation and to 12% +/- 8% at last follow-up from 73% +/- 12% at preoperation, showing significant differences (P < 0.01). According to modified Macnab's criterion, the results were excellent in 59 cases, good in 15 cases, fair in 3 cases, and poor in 3 cases at last follow-up, and the excellent and good rate was 92.5%. For the treatment of disc protrusion at the L5, S1 level, interrupt PELD through interlaminar approach should be ideal with short operation time, small trauma, and quick recovery.


Airway management on placental support (AMPS)--the anaesthetic perspective.
Neonatal airway obstruction has been reported to have a high mortality. Antenatal diagnosis of this condition is now possible. Anaesthetic and surgical techniques have been developed that allow neonatal airway obstruction to be managed at delivery, while the fetus remains oxygenated via the placental circulation. Three case studies are presented, and the anaesthetic issues for mother and fetus/neonate are discussed with reference to previously published cases of airway management on placental support. In particular, techniques for uterine relaxation and maintenance of placental circulation are explored. The history of these procedures and issues of planning and logistics are also discussed.


Farmers' adoption of soil and water conservation practices: The case of Lege-Lafto Watershed, Dessie Zuria District, South Wollo, Ethiopia.
In Ethiopia, soil degradation is one of the major causes of low and declining agricultural productivity. As a result of this challenge, the country has been battling to adopt conservation practices. The main objective of this study was to assess farmers' adoption decisions of soil and water conservation (SWC) practices. For the survey, 304 farmers were selected from farming communities in Lege-Lafto Watershed, South Wollo,Ethiopia. Information were gathered using a household survey, and through focus group discussions, key informant interviews, and field observation. A binary logistic regression model and descriptive statistics were used to analyze the data. The results indicated that about 64% of the farmers adopted soil and water conservation practices in the study area. The findings depicted that soil bund, stone bund, stone-faced soil bund, loose stone and brush-wood check dams, hillside terrace, and bund stabilized with vegetation are practiced in the watershed. The analysis result revealed adoption of soil and water conservation practices is significantly and positively influenced by the perception of farmers on erosion problems and SWC practices, family labour, educational level, and membership in local institutions. However, distance from residence to the nearest market and farmland, off-farm activities, and the ratio of cultivable land to family size influenced the adoption of SWC practices negatively. Therefore, improving farmers' educational status, and strengthening local institutions are vital for sustainable land management practices in the country.


Lumbar facet fracture in an adolescent ice hockey player.
A 14-year-old boy was checked hard as he was winding up to shoot in an ice hockey game. He experienced low-back pain during the game but when examined later for complaints of pain and fever, he denied trauma. Plain x-rays were normal, but a bone scan showed increased uptake at L-3. MRI evaluation revealed a lumbar mass; a CT scan showed the mass to be a hematoma and edema secondary to a facet fracture. Acute severe back pain in a hockey player should prompt a careful history and a search for musculoskeletal injury. When trauma in the lumbar spine is suspected and plain radiographs are nondiagnostic, CT scans are more precise than MRI for diagnosing injury.


[New advance of research on therapy of severe acute radiation sickness with mesenchymal stem cells].
Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with self-renewal and multilineage differentiation potential, which have special biological characteristics, such as secreting various cytokines, promoting hematopoiesis, accelerating stem cells homing and reconstructing hematopoietic microenvironment. MSC are collected and amplified easily, and can be transfected by exogenous gene. Many reports indicated that MSC were applied in therapy for variety of tissues and organs injury, meanwhile the treatment for acute radiation sickness has made significant progress. In this review, the biological characteristics and new research advance on MSC in treatment of severe acute radiation sickness are summarized and discussed.


Mesenchymal stem cells anchored with thymidine phosphorylase for doxifluridine-mediated cancer therapy.
Many tumors express thymidine phosphorylase (TYMP) with various levels, however due to tumor heterogeneity, the amount of TYMP is usually not enough to convert prodrug doxifluridine (5'-DFUR) to toxic drug 5-fluorouracil (5-FU). Since human mesenchymal stem cells (hMSCs) have unique features of tumor-tropism and low immunogenicity, the purpose of this study is to use mesenchymal stem cells as carriers to deliver TYMP to cancer cells and then trigger their death by administrating doxifluridine. First, the TYMP gene sequence and core streptavidin (core SA) were constructed into pET-30a(+) plasmid. After bacterial transformation and colony screening, TYMP-SA fusion protein was expressed by IPTG induction and purified by immobilized metal affinity chromatography and characterized by SDS-PAGE and western blot with a clear band at 75 kDa. The characterized TYMP-SA was further anchored on the cell membrane of biotinylated hMSCs via biotin-streptavidin binding. hMSCs anchored with TYMP-SA were then co-cultured with adenocarcinoma A549 cells (with different ratios) and treated with 100 μM prodrug doxifluridine over the course of four days. Our results showed that a 2 : 1 ratio led to the eradication of A549 cells at the end of the experiment with less than 5% confluency, in comparison with the 1 : 1 and 1 : 2 ratios which still had about 13% and 20% confluency respectively. In conclusion, harnessing hMSCs as cell carriers for the delivery of TYMP enzyme to cancer cells could lead to significant cell death post-treatment of the prodrug doxifluridine.


Prognostic factors for death due to invasive aspergillosis after hematopoietic stem cell transplantation: a 1-year retrospective study of consecutive patients at French transplantation centers.
Invasive aspergillosis (IA) is a major cause of death after hematopoietic stem cell transplantation (HSCT). The goal of this retrospective and consecutive survey was to assess prognostic factors of death due to IA after HSCT at the time of diagnosis of IA. All 64 health care centers affiliated with the Société Française de Greffe de Moelle et de Thérapie Cellulaire were contacted to participate in this study of all proven or probable cases of IA that occurred among HSCT recipients in 2002. Data for 51 cases (41 involving allogeneic HSCT and 10 involving autologous HSCT) were collected from patient records and included diagnostic and therapeutic features of IA, outcome, presence of hematological disease, and transplantation data. Cox models were applied to risk factors for death attributed to IA that were initially identified using the usual tests. The proportion of deaths attributed to IA within 4 months after diagnosis was 0.62 (95% confidence interval, 0.47-0.76). Seven factors assessed at diagnosis were determined to be strongly related to death due to IA: age of 12-35 years, dissemination of IA, presence of a pleural effusion, monocyte count of <120 cells/mm3, prolonged administration of steroids within the previous 2 months, receipt of a dose > or =2 mg/kg at the time of diagnosis, and uncontrolled graft-versus-host disease.Conclusions. Our study explored potential risk factors for death due to IA among HSCT recipients as a reference for investigation in larger future studies. These factors should help to identify HSCT recipients who would benefit from more-aggressive antifungal therapies.


Genome-Wide Identification of the A20/AN1 Zinc Finger Protein Family Genes in Ipomoea batatas and Its Two Relatives and Function Analysis of IbSAP16 in Salinity Tolerance.
Stress-associated protein (SAP) genes-encoding A20/AN1 zinc-finger domain-containing proteins-play pivotal roles in regulating stress responses, growth, and development in plants. They are considered suitable candidates to improve abiotic stress tolerance in plants. However, the SAP gene family in sweetpotato (Ipomoea batatas) and its relatives is yet to be investigated. In this study, 20 SAPs in sweetpotato, and 23 and 26 SAPs in its wild diploid relatives Ipomoea triloba and Ipomoea trifida were identified. The chromosome locations, gene structures, protein physiological properties, conserved domains, and phylogenetic relationships of these SAPs were analyzed systematically. Binding motif analysis of IbSAPs indicated that hormone and stress responsive cis-acting elements were distributed in their promoters. RT-qPCR or RNA-seq data revealed that the expression patterns of IbSAP, ItbSAP, and ItfSAP genes varied in different organs and responded to salinity, drought, or ABA (abscisic acid) treatments differently. Moreover, we found that IbSAP16 driven by the 35 S promoter conferred salinity tolerance in transgenic Arabidopsis. These results provided a genome-wide characterization of SAP genes in sweetpotato and its two relatives and suggested that IbSAP16 is involved in salinity stress responses. Our research laid the groundwork for studying SAP-mediated stress response mechanisms in sweetpotato.


[A case of type I hyperprolinemia associated with photogenic epilepsy].
A 9-year-old girl with type I hyperprolinemia, who also had photogenic epilepsy, was reported. She showed epileptic discharges and the regression in speech and motor activities, since 7 years of age. Her plasma proline levels were 3 to 4 times higher than control levels. In urine, iminoglycinuria appeared, when plasma proline value exceeded 0.80 mM. The proline oxidase activity of the liver tissues obtained by biopsy in the patient was about 23.5%, compared to that of controls. In spite of the restriction of proline and protein intake, she showed progressive speech and motor retardation.


The history and importance of aeronautic dentistry.
Current projected missions to Mars will require 18 to 24 months of exposure to microgravity conditions, which might have serious effects on human physiology, including that of the oral cavity. Very few studies have been published on the effect of microgravity on the oral cavity, although it has been reported that microgravity increases the prevalence of periodontitis, dental caries, bone loss and fracture in the jaw bone, pain and numbness in teeth and oral cavity tissue, salivary duct stones, and oral cancer. Aeronautic dentistry is a new field, so further study of the effects of microgravity are required. In this article, we review the role of aeronautic dentistry in space missions and offer our recommendations for the future growth of this field.


Phytate as the sole phosphate source for growth of Tetrahymena.
Phytate, the storage form of phosphate in seeds and grains, is a major form of environmental phosphate loading from fertilizer inputs and agricultural runoff. We have investigated the ability of Tetrahymena populations to grow on phytate as their sole phosphate source. Populations grew equally well in chemically defined medium with phosphate and medium in which the phosphate was replaced with phytate in comparable concentrations between 0.5 mM and 6 mM. Intracellular phytate concentrations of cells grown in phytate showed a 4-6-fold increase over those grown in phosphate when measured during the late stage of exponential growth. These results demonstrate that phytate can provide a source of adequate phosphate for sustained growth in phytate-rich environments.


Effect of Drying Methods on Properties of Potato Flour and Noodles Made with Potato Flour.
This work investigated the impact of three drying methods on structural and functional properties of potato flour (PF), as well as the quality characteristics of fresh noodles made from wheat-potato flours. The results indicated that ethanol drying (ED) and oven drying (OD) had small effects on the properties of starch in potato flour, however, freeze drying (FD) caused some pores and channels on the starch granules and disruption of the long- and short-range ordered structure of starch. The maximum addition of potato flour in fresh noodles was 40% for FD-PF and 50% for both ED-PF and OD-PF. With increasing addition of potato flour in noodles, the L* (lightness) values of noodles decreased gradually, while the a* (redness) and the b* (yellowness) values, as well as the hardness and springiness values of fresh potato noodles increased. This study clearly showed that drying methods have different effects on the properties of potato flour, and in turn the quality of fresh noodles made with potato flour.


Study of inhibition of outgrowth in Bacillus cereus T by ethyl picolinate.
The effects of ethyl picolinate on germination, outgrowth, and sporulation of Bacillus cereus T were studied in a synthetic medium containing glucose. Ethyl picolinate specifically inhibited at two stages, outgrowth and sporulation. The initiation of germination and cell division was not affected. The inhibition of outgrowth by ethyl picolinate could be reversed by enrichment of inoculum with aspartic acid, asparagine, lysine, phenylalanine, and tyrosine among the amino acids and by oxalacetate. Nicotinic acid and nicotinamide also possessed this ability. Ethyl picolinate failed to block outgrowth when added to cultures incubated for a short time after inoculation. Enrichment of the medium with lysine plus zinc sulfate stimulated sporulation in the presence of ethyl picolinate to a significance degree.


Neolithic trepanation decoded- A unifying hypothesis: Has the mystery as to why primitive surgeons performed cranial surgery been solved?
The perplexing mystery of why so many trephined skulls from the Neolithic period have been uncovered all over the world representing attempts at primitive cranial surgery is discussed. More than 1500 trephined skulls have been uncovered throughout the world, from Europe and Scandinavia to North America, from Russia and China to South America (particularly in Peru). Most reported series show that from 5-10% of all skulls found from the Neolithic period have been trephined with single or multiple skull openings of various sizes. The unifying hypothesis proposed by the late medical historian Dr. Plinio Prioreschi (1930-2014) regarding the reason for these trepanations (trephinations) is analyzed. It is concluded that Dr. Prioreschi's cohesive explanation to explain the phenomenon is valid and that his intriguing hypothesis is almost certainly correct. In the opinion of this author, the mystery within an enigma has been solved.


Evaluation of a peer consultation program for burn inpatients. 2000 ABA paper.
A burn survivor may provide unique psychological support to patients who have been burned more recently and enhance their adjustment to burn injury. The purpose of this study was to describe the peer consultation/burn survivor support program at a large regional burn center in the Northwest United States. Over the course of 17 months, three specially trained peer consultants who had survived their own burn injuries in the past made 167 visits to 108 patients, who, in turn, completed evaluation forms for each visit. Findings indicated that patients reported that the peer consultants approached them in an appropriate manner, answered their questions, and provided useful support and information.


Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.
Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific.


Sudden presentation of immune-mediated inner ear disease: characterization and acceptance of a cochleovestibular dysfunction.
Since the McCabe report, growing indirect evidence has accumulated to indicate the implication of immune mechanisms in the pathogenesis of immune-mediated inner-ear disease (IMIED). A clinical study of a group of patients affected by this condition was performed in order to characterize the immune group, based on a recently reported profile, and compared with the vascular, viral and idiopathic aetiologies of sudden deafness. Patients affected by immune-mediated inner-ear disease had the best and the earliest recovery rate of hearing (p = 0.0028 and p = 0.017, respectively). However, this group of patients also had the higher rate of recurrence (p = 0.034), supporting the typical clinical course of the autoimmune disorders. On the basis of the results the criteria used in the diagnosis of the sudden presentation of the immune-mediated inner ear disease could be accepted leading to the characterization of this condition. Likewise, the role of the supporting cells in the pathogenesis of the IMIED is discussed.


Label-free kinase profiling using phosphate affinity polyacrylamide gel electrophoresis.
Herein we describe three applications of label-free kinase profiling using a novel type of phosphate affinity polyacrylamide gel electrophoresis. The phosphate affinity site is a polyacrylamide-bound dinuclear Mn2+ complex that enables the mobility shift detection of phosphorylated proteins from their nonphosphorylated counterpart. The first application is in vitro kinase activity profiling for the analysis of varied phosphoprotein isotypes in phosphorylation status. The activity profiles of six kinds of kinases, glycogen synthase kinase-3beta, cyclin-dependent kinase 5/p35, protein kinase A, mitogen-activated protein kinase (MAPK), casein kinase II, and calmodulin-dependent protein kinase II, were determined using a substrate protein, Tau, which has a number of phosphorylation sites. Each kinase demonstrated characteristic multiple electrophoresis migration bands up-shifted from the nonphosphorylated Tau due to differences in the phosphorylation sites and stoichiometry. The second application is in vivo kinase activity profiling for the analysis of protein phosphorylation involved in intracellular signal transduction. The time course changes in the epidermal growth factor-induced phosphorylation levels of Shc and MAPK in A431 cells were visualized as highly up-shifted migration bands by subsequent immunoblotting with anti-Shc and anti-MAPK antibodies. The third application is in vitro kinase inhibition profiling for the quantitative screening of kinase-specific inhibitors. The inhibition profile of a tyrosine kinase, Abl (a histidine-tagged recombinant mouse Abl kinase), was determined using the substrate Abltide-GST (a fusion protein consisting of a specific substrate peptide for Abl and glutathione S-transferase) and the approved drug Glivec (an ATP competitor). In the kinase assay, the slower migration band, monophosphorylated Abltide-GST, increased time-dependently, whereas the faster migration band, nonphosphorylated Abltide-GST, decreased. The dose-dependent inhibition of Glivec was determined by a change in the ratio of the faster and slower migration bands, which showed an IC50 value of 1.6 microM in the presence of 0.10 mM ATP.


Effects of perioperative blood transfusion in gastric cancer patients undergoing gastrectomy: A systematic review and meta-analysis.
The short-term and long-term effects of perioperative blood transfusion (PBT) on patients with gastric cancer are still intriguing. This systematic review and meta-analysis aimed to investigate the effects of blood transfusion on clinical outcomes in patients with gastric cancer undergoing gastrectomy. We searched PubMed, Web of Science, Embase, and The Cochrane Library on December 31th 2021. The main outcomes were overall survival (OS), disease-free survival (DFS), disease-specific survival (DFS), and postoperative complications. A fixed or random-effects model was used to calculate the hazard ratio (HR) with 95% confidence intervals (CIs). Fifty-one studies with a total of 41,864 patients were included for this review and meta-analysis. Compared with patients who did not receive blood transfusions (NPBT), PBT was associated with worse 5-year OS (HR = 2.39 [95%CI: 2.00, 2.84]; p < 0.001; Multivariate HR = 1.43 [95%CI: 1.24, 1.63]; p < 0. 001), worse 5-year DFS (HR = 2.26 [95%CI: 1.68, 3.05]; p < 0.001; Multivariate HR = 1.45 [95%CI: 1.16, 1.82]; p < 0. 001), and worse 5-year DSS (HR = 2. 23 [95%CI: 1.35, 3.70]; p < 0.001; Multivariate HR = 1.24 [95%CI: 0.96, 1.60]; p < 0.001). Moreover, The PBT group showed a higher incidence of postoperative complications [OR = 2.30 (95%CI:1.78, 2. 97); p < 0.001] than that in the NPBT group, especially grade III-V complications, according to the Clavien-Dindo classification. [OR = 2.50 (95%CI:1.71, 3.63); p < 0.001]. In patients who underwent gastrectomy, PBT was associated with negative survival effects (OS, DFS, DSS) and a higher incidence of perioperative complications. However, more research was expected to further explore the impact of PBT. Meanwhile, strict blood transfusion management should be implemented to minimize the use of PBT.


Effect of shoulder angle on physiological responses during incremental peak arm crank ergometry.
This study examined the effect of shoulder angle and gender on physiological and perceptual responses during incremental peak arm ergometry. Healthy adults (nine males, seven females) volunteered for the study and completed an incremental arm ergometry test on two separate occasions at two different shoulder angles (90 degrees and 45 degrees). Initial work rate was set at 16 W x min-1 and was increased progressively until exhaustion. Cardiorespiratory and perceptual responses were recorded at the end of each minute and compared using separate three-way (position x work rate x gender) repeated-measures analyses of variance. The systematic bias of peak responses was examined using separate two-way (position x gender) analyses of variance, while reproducibility of these parameters was explored using intraclass correlation coefficients, measurement bias/ratio, and 95% ratio limits of agreement. Despite a significantly greater peak heart rate for the 45 degrees position, cardiorespiratory and perceptual responses were similar at peak exercise for both positions. Peak values for all variables, although similar, demonstrated similar and large inter-test variability for men and women. Reduction of the shoulder joint angle to 45 degrees did not enhance peak work rate and peak oxygen consumption during seated upper body exercise. Due to the large inter-test variability, arm ergometry should be conducted using the same seated position.


Multiphasic disseminated encephalomyelitis associated with streptococcal infection.
Multiphasic disseminated encephalomyelitis (MDEM) is a rare peculiar diagnosis which is defined as acute demyelinating central nervous system disease with relapses occurring only within 4 weeks of initial manifestation. This report describes the case of a 6-year-old boy with MDEM diagnosed by clinical findings and magnetic resonance imaging. The disease had a biphasic evolution, and with a second course of high-dose corticosteroids a complete recovery without further relapse was obtained during the following 18 months. Serological evidence of streptococcal infection as specific trigger for MDEM was given. Thus this report raises the question whether an additional penicillin prophylaxis could be valuable for prevention of streptococcus-associated MDEM relapses.


Association between primary Sjögren's syndrome and non-Hodgkin's lymphoma.
Sjögren's Syndrome (SS) is one of the most frequent autoimmune disorders, which affects approximately 1% of the population. It occurs in patients of all ages, but especially females during the fourth and fifth decades of life with a female/male ratio of 9:1. The main target of this disease are the exocrine glands that are infiltrated progressively by lymphocytes and finally destroyed, leading to decreased exocrine secretion. Thus primary SS is usually defined as xerophtalmia (dry eye) and xerostomia (dry mouth) accompanied in 60% of cases by parotid swelling [1]. The most serious complication of Sjögren's Syndrome is the high risk of the occurrence of non-Hodgkin's Lymphoma.


Analysis of risk factors for hospital mortality in patients with chronic obstructive pulmonary diseases requiring invasive mechanical ventilation.
Accurate prediction for prognosis is important for hospitalized patients with chronic obstructive pulmonary disease (COPD) requiring invasive mechanic ventilation (IMV) and for their family members to make end-of-life decisions. The response to therapy in such a patient population has rarely been investigated. The aim of the study was to evaluate the risk factors in these patients and investigate their response to IMV and the relationship between their responses and prognosis. A cohort of 138 patients with COPD requiring IMV >or= 12 hours for acute respiratory failure of diverse etiological factors during a 4-year period were retrospectively studied using prospectively gathered data. All variables potentially related to hospital mortality were evaluated by univariate and multiple stepwise logistic regression analysis. The mean age of all patients investigated was (65.7 +/- 11.6) years and the hospital mortality was 39.9% (31.1% with COPD exacerbation). Correction of acidosis (pH >or= 7.30) was seen in 58 patients (69.9%) in survivors but only 12 patients (21.8%) in nonsurvivors (P < 0.05) after ventilation. Using multivariate logistic analysis, the variables independently associated with hospital mortality were a higher acute physiology score before intubation, lower pH value measured 24 hours after the onset of ventilation and development of multiorgan dysfunction syndrome (MODS). In COPD patients requiring IMV, the postintubation pH value can not only reflect patients' response to treatment, but also serve as an independent determinant of hospital mortality apart from other risk factors such as a higher preintubation APACHE II score and development of MODS. A close correlation between the response to IMV and prognosis was proved in these patients.


Extramedullary myeloid cell tumours--the NIMS experience.
Extramedullary myeloid cell tumours are rare clinical entities, which often pose diagnostic problems. From the pathology record files of Nizam's Institute of Medical Sciences, Hyderabad, 16 cases of EMCTs were traced, over a period of 14 years. The clinical details, follow-up were noted and morphology re-evaluated, and immunohistochemistry with LCA was performed. Of the 16 cases, the distribution was as follows--skin and subcutaneous nodules, lymph nodes, extradural masses presenting with cord compression and one case each with eyelid, orbital and breast masses. The problems in diagnosis are presented and a panel of immunohistochemical markers suggested for proper diagnosis and treatment.


Preparation of Drosophila polytene chromosome squashes for antibody labeling.
Drosophila has long been a favorite model system for studying the relationship between chromatin structure and gene regulation due to the cytological advantages provided by the giant salivary gland polytene chromosomes of third instar larvae. In this tissue the chromosomes undergo many rounds of replication in the absence of cell division giving rise to approximately 1000 copies. The DNA remains aligned after each replicative cycle resulting in greatly enlarged chromosomes that provide a unique opportunity to correlate chromatin morphology with the localization of specific proteins. Consequently, there has been a high level of interest in defining the epigenetic modifications present at different genes and at different stages of the transcription process. An important tool for such studies is the labeling of polytene chromosomes with antibodies to the enzyme, transcription factor, or histone modification of interest. This video protocol illustrates the squash technique used in the Johansen laboratory to prepare Drosophila polytene chromosomes for antibody labeling.


Inferior oblique myectomy, disinsertion, and recession in rhesus monkeys.
Twenty-one myectomies near the insertion, 22 disinsertions, and two recessions were performed. After healing was complete, each animal was sacrificed. Anatomical dissection showed the following:(1) in every disinsertion and myectomy case, the inferior oblique muscle spontaneously reattached itself to the sclera;(2) the site of reattachment following these two procedures varied widely, ranging from the original insertion site to other areas adjacent to the lateral rectus or inferior rectus insertions; (3) disinsertion and myectomy shortened the inferior oblique muscle to two thirds its normal length, while recession shortened the muscle to one third its normal length.


Anaerobic bacteraemia: a review of 17 cases.
Of 93 blood cultures received with a suspicion of anaerobic bacteraemia over a period of two years, only 17 (18.3%) showed anaerobic growth. Twelve grew anaerobes alone while five had a polymicrobial flora. Seven of these patients (4.3%) had pre-existing heart disease while others had history of prior surgery, diabetes mellitus or urinary tract infection. Oropharynx was the commonest portal of entry, followed by gastrointestinal tract. The anaerobes isolated were anaerobic streptococci, Bacteroides fragilis group and Bilophila and Eubacterium species. Fifteen patients developed major complications such as congestive cardiac failure, systemic embolisation, and perforative peritonitis. The mortality rate among the cases with anaerobic bacteraemia was 23.5% in this study.


Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation.
Kindlin-2 belongs to an emerging class of regulators for heterodimeric (α/β) integrin adhesion receptors. By binding to integrin β cytoplasmic tail via its C-terminal FERM-like domain, kindlin-2 promotes integrin activation. Intriguingly, this activation process depends on the N terminus of kindlin-2 (K2-N) that precedes the FERM domain. The molecular function of K2-N is unclear. We present the solution structure of K2-N, which displays a ubiquitin fold similar to that observed in kindlin-1. Using chemical shift mapping and mutagenesis, we found that K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate. We show that while wild-type kindlin-2 is capable of promoting integrin activation, such ability is significantly reduced for its membrane-binding defective mutant. These data suggest a membrane-binding function of the ubiquitin-like domain of kindlin-2, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation.


Phase I-II study of neoadjuvant chemoradiotherapy followed by radical surgery in locally advanced cervical cancer.
The usefulness of neoadjuvant chemotherapy (NAC) regimens has been reported; however, the effect of NAC for advanced stages (especially stage III-IVA) is thought to be insufficient. We conducted a phase I-II study of neoadjuvant chemoradiotherapy consisting of intra-arterial (i.a.) infusion of carboplatin and intracavitary brachytherapy in patients with locally advanced cervical cancer to achieve the new NAC method. Sixteen eligible patients included those with previously untreated stage IIB, III or IVA cancer with bulky tumor. Brachytherapy using iridium-192 was performed with concurrent i.a. chemotherapy with carboplatin (200, 300 and 400 mg/m2). Treatment was repeated every 4 weeks for a total of two cycles. Both hematologic and non-hematologic toxicities were generally mild. Grade 4 hematologic toxicity was observed in 12.5% and there were no grade III or IV non-hematologic toxicities. The optimal dose of carboplatin was determined to be 400 mg/m2. Among 16 patients, six showed complete response (37.5%) and nine showed partial response (56.3%), for an overall response rate of 93.8%. All 15 responding patients underwent radical surgery with a pelvic lymphadenectomy and postoperative radiotherapy. The combination of brachytherapy and i.a. chemotherapy with carboplatin is a promising regimen for NAC in locally advanced cervical cancer.


Fear of intimacy in women: relationship between attachment styles and depressive symptoms.
Preoccupied and fearful attachment have both been associated with depressive symptoms, but it is unclear which attachment style is primarily associated with major depression. While preoccupied attachment denotes a focus on relationships as a source of self-validation, fearful attachment involves an avoidance of relationships for fear of rejection. Present research aims to investigate the relative influence of fearful and preoccupied attachments on self-reported depressive symptoms within both a student and a clinical sample and to examine these associations separately for male and female participants. All participants completed the Relationship Questionnaire and the Beck Depression Inventory. Study 1 assessed attachment ratings and self-reported severity of depression for 71 patients diagnosed with major depression. Study 2 similarly assessed 245 university students, and study 3 compared attachment ratings of the two samples. Both Pearson correlations and partial correlations were examined for both samples. Fearful attachment was associated with self-reported depression severity for females with depression, but attachment styles were unrelated to depression severity for males with depression (study 1). For female university students, both fearful and preoccupied attachment styles were significantly related to depression severity, but again there were no associations for male university students when partial correlations were utilised (study 2). Study 3 revealed significantly higher levels of fearful attachment for women with depression compared with female university students and no significant differences for males overall. For females, the avoidance of intimacy for fear of rejection was associated with a broad spectrum of depressive symptoms. Results highlight gender differences in depressive experiences, and have implications for research into the effects of fearful attachment on social support and the therapeutic alliance. Limitations to this study include the reliance on self-report measures of attachment and depression severity, the small number of male participants in the clinical sample, and the use of a cross-sectional rather than longitudinal design.


Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study.
Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next-generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7-27.0 months). ctDNA-positive or -negative patients with tumors of any stage had similar disease-free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non-tissue derived. Patients with detectable postoperative ctDNA with tissue-derived mutations had comparable DFS with those with non-tissue-derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test.


Genetic variability of hepatitis A virus.
Knowledge of the molecular biology of hepatitis A virus (HAV) has increased exponentially since its identification. HAV exploits all known mechanisms of genetic variation to ensure survival, including mutation and genetic recombination. HAV has been characterized by the emergence of different genotypes, three human antigenic variants and only one major serotype. This paper reviews the genetic variability and molecular epidemiology of HAV. Its evolutionary mechanisms are described with particular emphasis on genetic recombination and HAV mutation rate. Genotypic classification methods are also discussed.


Integrative Conformational Ensembles of Sic1 Using Different Initial Pools and Optimization Methods.
Intrinsically disordered proteins play key roles in regulatory protein interactions, but their detailed structural characterization remains challenging. Here we calculate and compare conformational ensembles for the disordered protein Sic1 from yeast, starting from initial ensembles that were generated either by statistical sampling of the conformational landscape, or by molecular dynamics simulations. Two popular, yet contrasting optimization methods were used, ENSEMBLE and Bayesian Maximum Entropy, to achieve agreement with experimental data from nuclear magnetic resonance, small-angle X-ray scattering and single-molecule Förster resonance energy transfer. The comparative analysis of the optimized ensembles, including secondary structure propensity, inter-residue contact maps, and the distributions of hydrogen bond and pi interactions, revealed the importance of the physics-based generation of initial ensembles. The analysis also provides insights into designing new experiments that report on the least restrained features among the optimized ensembles. Overall, differences between ensembles optimized from different priors were greater than when using the same prior with different optimization methods. Generating increasingly accurate, reliable and experimentally validated ensembles for disordered proteins is an important step towards a mechanistic understanding of their biological function and involvement in various diseases.


Synthetic biodegradable hydrogel delivery of demineralized bone matrix for bone augmentation in a rat model.
There exists a strong clinical need for a more capable and robust method to achieve bone augmentation, and a system with fine-tuned delivery of demineralized bone matrix (DBM) has the potential to meet that need. As such, the objective of the present study was to investigate a synthetic biodegradable hydrogel for the delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol) fumarate) (OPF) constructs were designed and fabricated by varying the content of rat-derived DBM particles (either 1:3, 1:1 or 3:1 DBM:OPF weight ratio on a dry basis) and using two DBM particle size ranges (50-150 or 150-250 μm). The physical properties of the constructs and the bioactivity of the DBM were evaluated. Selected formulations (1:1 and 3:1 with 50-150 μm DBM) were evaluated in vivo compared to an empty control to investigate the effect of DBM dose and construct properties on bone augmentation. Overall, 3:1 constructs with higher DBM content achieved the greatest volume of bone augmentation, exceeding 1:1 constructs and empty implants by 3- and 5-fold, respectively. As such, we have established that a synthetic, biodegradable hydrogel can function as a carrier for DBM, and that the volume of bone augmentation achieved by the constructs correlates directly to the DBM dose.


Monitoring emerging diseases of fish and shellfish using electronic sources.
New and emerging fish and shellfish diseases represent an important constraint to the growth and sustainability of many aquaculture sectors and have also caused substantial economic and environmental impacts in wild stocks. This paper details the results of 8 years of a monitoring programme for emerging aquatic animal diseases reported around the world. The objectives were to track global occurrences and, more specifically, to identify and provide advanced warning of disease threats that may affect wild and farmed fish stocks in the UK. A range of electronic information sources, including Internet newsletters, alerting services and news agency releases, was systematically searched for reports of new diseases, new presentations of known pathogens and known diseases occurring in new geographic locations or new host species. A database was established to log the details of key findings, and 250 emerging disease events in 52 countries were recorded during the period of study. These included 14 new diseases and a further 16 known diseases in new species. Viruses and parasites accounted for the majority of reports (55% and 24%, respectively), and known diseases occurring in new locations were the most important emerging disease category (in which viruses were dominant). Emerging diseases were reported disproportionally in salmonid species (33%), in farmed populations (62%) and in Europe and North America (80%). The lack of reports from some regions with significant aquaculture or fishery production may indicate that emerging diseases are not being recognized in these areas owing to insufficient surveillance or testing or that these events are being under-reported. The results are discussed in relation to processes underpinning disease emergence in the aquatic environment.


A proteomic atlas of insulin signalling reveals tissue-specific mechanisms of longevity assurance.
Lowered activity of the insulin/IGF signalling (IIS) network can ameliorate the effects of ageing in laboratory animals and, possibly, humans. Although transcriptome remodelling in long-lived IIS mutants has been extensively documented, the causal mechanisms contributing to extended lifespan, particularly in specific tissues, remain unclear. We have characterized the proteomes of four key insulin-sensitive tissues in a long-lived Drosophila IIS mutant and control, and detected 44% of the predicted proteome (6,085 proteins). Expression of ribosome-associated proteins in the fat body was reduced in the mutant, with a corresponding, tissue-specific reduction in translation. Expression of mitochondrial electron transport chain proteins in fat body was increased, leading to increased respiration, which was necessary for IIS-mediated lifespan extension, and alone sufficient to mediate it. Proteasomal subunits showed altered expression in IIS mutant gut, and gut-specific over-expression of the RPN6 proteasomal subunit, was sufficient to increase proteasomal activity and extend lifespan, whilst inhibition of proteasome activity abolished IIS-mediated longevity. Our study thus uncovered strikingly tissue-specific responses of cellular processes to lowered IIS acting in concert to ameliorate ageing.


Intraosseous rhabdomyosarcoma of the mandible: a case report.
Rhabdomyosarcoma is the most common soft-tissue sarcoma of the head and neck region in children and adolescents. Oral cavity involvement is relatively uncommon, with tongue, soft palate, hard palate, and buccal mucosa being the sites of predilection. This report presents a rare case of intraosseous oral rhabdomyosarcoma arising in the mandibular bone of a 6-year-old child. Clinical, radiologic, and histopathologic features and possible pathogenesis are discussed.


Hepatic heme-regulated inhibitor (HRI) eukaryotic initiation factor 2alpha kinase: a protagonist of heme-mediated translational control of CYP2B enzymes and a modulator of basal endoplasmic reticulum stress tone.
We have reported previously that the hepatic heme-regulated inhibitor (HRI)-eukaryotic initiation factor 2 alpha (eIF2 alpha) kinase is activated in acute heme-deficient states, resulting in translational shut-off of global hepatic protein synthesis, including phenobarbital (PB)-mediated induction of CYP2B enzymes in rats. These findings revealed that heme regulates hepatic CYP2B synthesis at the translational level via HRI. As a proof of concept, we have now employed a genetic HRI-knockout (KO) mouse hepatocyte model. In HRI-KO hepatocytes, PB-mediated CYP2B protein induction is no longer regulated by hepatic heme availability and proceeds undeterred even after acute hepatic heme depletion. It is noteworthy that genetic ablation of HRI led to a small albeit significant elevation of basal hepatic endoplasmic reticulum (ER) stress as revealed by the activation of ER stress-inducible RNA-dependent protein kinase-like ER-integral (PERK) eIF2 alpha-kinase, and induction of hepatic protein ubiquitination and ER chaperones Grp78 and Grp94. Such ER stress was further augmented after PB-mediated hepatic protein induction. These findings suggest that HRI normally modulates the basal hepatic ER stress tone. Furthermore, because HRI exists in both human and rat liver in its heme-sensitive form and is inducible by cytochrome P450 inducers such as PB, these findings are clinically relevant to acute heme-deficient states, such as the acute hepatic porphyrias. Activation of this exquisitely sensitive heme sensor would normally protect cells by safeguarding cellular energy and nutrients during acute heme deficiency. However, similar HRI activation in genetically predisposed persons could lead to global translational arrest of physiologically relevant enzymes and proteins, resulting in the severe and often fatal clinical symptoms of the acute hepatic porphyrias.


Chronic exposure to IFNα drives medullar lymphopoiesis towards T-cell differentiation in mice.
Interferon-α is a potent antiviral agent and a vigorous adjuvant in the induction of T-cell responses but its use is limited by hematologic toxicity. Interferon-α alters hematopoietic stem cell dormancy and impairs myelocytic and erythrocytic/megakaryocytic differentiation from hematopoietic progenitors. However, the effect of chronic interferon-α exposure on hematopoietic precursors has still not been well characterized. Here, we transduced the liver of mice with an adenoassociated vector encoding interferon-α to achieve sustained high serum levels of the cytokine. The bone marrow of these animals showed diminished long-term and short-term hematopoietic stem cells, reduction of multipotent progenitor cells, and marked decrease of B cells, but significant increase in the proportion of CD8(+) and CD4(+)CD8(+) T cells. Upon adoptive transfer to RAG(-/-) mice, bone marrow cells from interferon-α-treated animals generated CD4(+) and CD8(+) T cells while CD19(+), CD11b(+) and NK1.1(+) lineages failed to develop. These effects are associated with the transcriptional downregulation of transcription factors involved in B-cell differentiation and modulation of key factors for T-cell development. Thus, sustained interferon-α exposure causes hematopoietic stem cells exhaustion and drives common lymphoid progenitors towards T-cell generation.


Bibliometric analysis of post-traumatic stress disorder in forensic medicine: Research trends, hot spots, and prospects.
Post-traumatic stress disorder (PTSD) has various risk factors, complex pathogenesis, and diverse symptoms, and is often comorbid with other injuries and diseases, making forensic diagnosis difficult. To explore the current research status and trends of PTSD, we used the Web of Science Core Collection databases to screen PTSD-related literature published between 2010 and 2021 and CiteSpace to perform bibliometric analysis. In recent years, PTSD-related research has grown steadily. The countries and institutions with the most research results were the United States and England, and King's College London and Boston University, respectively. Publications were identified from 2,821 different journals, including 13 forensic-related journals, but the journal distribution was relatively scattered and there was a lack of professional core journals. Keyword co-occurrence and clustering identified many hot topics; "rat model," "mental health," and "satisfaction" were the topics most likely to have a clear effect on future research. Analysis extracted nine turning points from the literature that suggested that neural network centers, the hypothalamic-pituitary-adrenal axis, and biomarkers were new research directions. It was found that COVID-19 can cause severe psychological stress and induce PTSD, but the relationship needs further study. The literature on stress response areas and biomarkers has gradually increased over time, but specific systemic neural brain circuits and biomarkers remain to be determined. There is a need to expand the collection of different types of biological tissue samples from patients with different backgrounds, screen PTSD biomarkers and molecular targets using multi-omics and molecular biology techniques, and establish PTSD-related molecular networks. This may promote a systematic understanding of the abnormal activation of neural circuits in patients with PTSD and help to establish a personalized, accurate, and objective forensic diagnostic standard.


High-porosity macroporous polymers sythesized from titania-particle-stabilized medium and high internal phase emulsions.
Particle-stabilized high internal phase emulsions have been used to synthesize tough and very high porosity macroporus polymers with a closed-cell pore structure. In this study, we show that Pickering water-in-oil emulsion templates with up to an 85 vol % internal phase can be stabilized by only 1 wt % of titania particles with their surfaces suitably modified by the adsorption of 3.5 +/- 0.5 wt % oleic acid. The pore structure and mechanical properties of the resulting macroporous polymers were tailored by altering the internal phase volume ratio of the emulsion template and the titania particle concentration used to stabilize the emulsion templates. The pore size and pore size distributions increase with increasing internal phase volume of the emulsion template as well as decreasing titania particle concentration used to stabilize the emulsion template. The mechanical properties, namely, Young's modulus and the crush strength of the macroporous polymers, increased with decreasing porosity and increasing foam density. The toughest macroporous polymer had the lowest porosity but also the smallest pore size and narrowest pore size distribution.


Mucosal cytology in the determination of the pubertal status in girls.
To assess and validate the diagnostic value of buccal and vaginal smears in the ambulatory care of girls with potential disorders of puberty. Smears were obtained from 77 girls who presented for assessment of their pubertal status, stained as described by Papanicolaou, examined for signs of estrogenization according to the method of Schmitt, and compared with the clinical status. Vaginal but not buccal smears reflect accurately the changes of sexual maturation, even more sensitive than single serum hormone measurements. Vaginal smears represent a valid, reproducible, and well-tolerated diagnostic tool in the ambulatory care of peripubertal girls to identify their estrogen status with high sensitivity and specificity. The decision to perform confirmative but invasive diagnostic procedures can be based on auxology, physical examination, bone age determination, and analysis of vaginal smears.


Is Lethality Different between Males and Females? Clinical and Gender Differences in Inpatient Suicide Attempters.
According to the gender paradox in suicidology, an important sex difference has been reported with a preponderance of females in nonfatal suicidal behavior and a preponderance of males in completed suicide. Furthermore, females and males present different risk factors for suicide. The present study explored possible clinical differences between male and female psychiatric inpatients who had recently attempted suicide. The study included 177 adult inpatients hospitalized following a suicide attempt at the University Psychiatric Clinic, Sant'Andrea Hospital, Sapienza University of Rome. Clinical features assessed included psychiatric diagnosis, method and lethality of suicide attempts using the Risk/Rescue Rating Scale, the history of suicide attempts, age at onset of psychiatric illness, the presence of substance or alcohol use, and the length of stay. The results found that males and females differed in the method used for the suicide attempt, the scores for risk and rescue, and the length of hospitalization post-suicide attempt. In conclusion, identifying gender characteristics of patients at higher risk of suicide is important for implementing specific suicide prevention strategies and reducing the risk of future suicidal behavior in psychiatric inpatients.


Personal health promotion.
Mortality data on the leading causes of death conceal the relationship to underlying risk factors; if we classified deaths according to risk factors, annually there might be an estimated 350,000 smoking-related deaths, 200,000 alcohol-related deaths and 135,000 nutrition-related cancer deaths. Similarly, five causes of death-heart disease, lung cancer, cirrhosis of the liver, suicide and motor vehicle accidents-contribute most to the risk of dying in the next ten years for a 40-year-old white man. Review of protective factors shows that adopting and maintaining a healthful life-style can contribute to reducing risk. Practicing physicians can assume both direct and indirect roles in promoting personal health maintenance.


A virtual speaker in noisy classroom conditions: supporting or disrupting children's listening comprehension?
Seeing a speaker's face facilitates speech recognition, particularly under noisy conditions. Evidence for how it might affect comprehension of the content of the speech is more sparse. We investigated how children's listening comprehension is affected by multi-talker babble noise, with or without presentation of a digitally animated virtual speaker, and whether successful comprehension is related to performance on a test of executive functioning. We performed a mixed-design experiment with 55 (34 female) participants (8- to 9-year-olds), recruited from Swedish elementary schools. The children were presented with four different narratives, each in one of four conditions: audio-only presentation in a quiet setting, audio-only presentation in noisy setting, audio-visual presentation in a quiet setting, and audio-visual presentation in a noisy setting. After each narrative, the children answered questions on the content and rated their perceived listening effort. Finally, they performed a test of executive functioning. We found significantly fewer correct answers to explicit content questions after listening in noise. This negative effect was only mitigated to a marginally significant degree by audio-visual presentation. Strong executive function only predicted more correct answers in quiet settings. Altogether, our results are inconclusive regarding how seeing a virtual speaker affects listening comprehension. We discuss how methodological adjustments, including modifications to our virtual speaker, can be used to discriminate between possible explanations to our results and contribute to understanding the listening conditions children face in a typical classroom.


The nomenclature of the blond capuchin, Cebus flavius (Schreber, 1799) (Mammalia, Primates, Cebidae).
I review the nomenclatural history of the blond capuchin, Cebus flavius (Schreber), a Brazilian monkey species. The name was published in 1799, not 1774 as generally cited, so the species is correctly known as Cebus flavius (Schreber, 1799).


Future perspectives in the medical treatment of endometriosis.
In the last few years, our understanding of the pathogenesis of endometriosis at the cellular and molecular levels has improved significantly. This may give us the opportunity to use new, specific agents for the treatment of this disorder. Despite the effectiveness of the available treatments, novel therapeutic strategies may improve our ability to eliminate endometriotic lesions when present and to prevent the recurrence of endometriosis after surgical treatment. This review focuses on the new, experimental approaches to the medical treatment of endometriosis and its symptoms. The blockage of aromatase activity in endometriotic lesions with an aromatase inhibitor may represent a new step in the medical treatment of endometriosis. Preliminary clinical studies have demonstrated the efficacy of third-generation nonsteroidal aromatase inhibitors (ie, anastrozole and letrozole) in reducing the intensity of pain symptoms associated with the presence of endometriosis. The new selective progesterone receptor modulators may represent a valid hormonal treatment option. Therapeutic manipulation of the immune system through TNFalpha inhibitors may be beneficial in women with endometriosis. New pharmaceutical agents affecting inflammation, angiogenesis, and matrix metalloproteinase activity may prevent or inhibit the development of endometriosis. Further clinical trials may determine if these new therapies are superior to current medical treatment strategies for endometriosis. Obstetricians & Gynecologists, Family Physicians Learning. After completion of this article, the reader should be able to describe the new experimental medical treatments of endometriosis, state that the clinical use of nonsteroidal aromatase inhibitors for endometriosis appears to be efficacious but is based on preliminary clinical data, and recall that the drugs used for endometriosis in the future may include manipulation of the immune system.


Selective formation of angular tricyclic compounds by ruthenium-mediated ring-rearrangement metathesis.
Unsaturated spirocyclic substrates bearing two alkenyl chains underwent ruthenium-mediated ring-rearrangement metathesis through relaying cyclohexene and cycloheptene moieties to give angularly fused tricyclics. In some instances where two products were expected, high degrees of selectivity were observed. In one instance the structural parameter leading to selectivity was very subtle; in others the transformation favoured the formation of products with a cis-fused cyclohexene moiety. An unusual transformation involving ring-opening, double-bond migration, and then ring-closing was observed.


Unity in diversity: a survey of muscular systems of ctenostome Gymnolaemata (Lophotrochozoa, Bryozoa).
Myoanatomical studies of adult bryozoans employing fluorescent staining and confocal laser scanning microscopy (CLSM) have been chiefly conducted on freshwater bryozoans. The diversity of muscular systems in the marine bryozoans is currently not well known with only two species being studied in more detail. The aim of this study is to unravel the diversity of muscle systems of 15 ctenostome bryozoans by phalloidin-coupled fluorescence stainings combined with CLSM. In general, the myoanatomy of the selected ctenostomes shows significant similarities and consists of 1) muscles associated with the body wall, 2) apertural muscles, 3) lophophoral muscles, 4) tentacle sheath muscles, 5) digestive tract muscles and 6) the prominent retractor muscles. Differences are present in the arrangement of the apertural muscles from generally three muscles sets of four bundles, which in some species can be partially reduced or modified into a bilateral arrangement. The cardiac region of the digestive tract shows a distinct sphincter in four of the six studied clades. In some cases the cardiac region forms a prominent proventriculus or gizzard. Tentacle sheath muscles in victorelloideans and walkerioideans are arranged diagonally and differ from the simple longitudinal muscle arrangements common to all other taxa. Lophophoral base muscles consist of four sets that vary in the size of the sets and in the shape of the inner lophophoral ring, which either forms a complete ring or separate, intertentacular muscle bundles. The stolon-forming walkeridiodean ctenostomes show prominent transverse muscles in their stolons. These are always present in the shorter side stolons, but their occurrence in the main stolon seems to depend on the colony form, being present in creeping but absent in erect colony forms. This study represents the first broad survey of muscular systems in adult ctenostome bryozoans and shows a certain degree of conservation in a series of diverse colony forms belonging to five major clades. However, several myoanatomical features such as the cardiac sphincter, basal (possibly transitory) cystid muscles, tentacle sheath muscles or apertural muscle arrangement vary across taxa and thus show a high potential for the assessment of character evolution within ctenostomes. As such, this study represents an essential contribution towards determining and reconstructing the character states of the bryozoan ground pattern once a reliable phylogenetic tree of the whole phylum becomes available.


Processing limitations in children with specific language impairment: the role of executive function.
Research suggests that children with specific language impairment (SLI) have processing limitations; however, the mechanisms involved have not been well defined or investigated in a theory-guided manner. The theory of constructive operators was used as a framework to explore processes underlying limited processing capacity in children with SLI. Mental attentional capacity, mental attentional interruption, and 2 specific executive functions (shifting and updating) were examined in 45 children with SLI and 45 children with normally developing language, aged 7 to 12 years. The results revealed overall group differences in performance on measures of mental attention, interruption, and updating, but not shifting. The findings supported the premise that mental attention predicted language competence, but that this relationship was mediated partially by updating.


Mortality follow-up of veterans who participated in military chemical and biological warfare agent testing between 1962 and 1972.
Between 1962 and 1972, several thousand U.S. Navy personnel participated in Project SHAD (Shipboard Hazard and Defense). These tests potentially exposed participants to either active chemical or biological warfare agents or their simulants. This study examined mortality risk associated with participating in SHAD tests by comparing the cause-specific mortality of 4927 SHAD veterans to that of 10,927 other Navy veterans. Compared to other Navy veterans, SHAD veterans had an increased risk of overall mortality, which was due primarily to heart disease deaths.


Development and validation of the double duty caregiving scale.
In order to gain an understanding of double duty caregiving (DDC), defined here as the provision of care to elderly relatives by practising health professionals, a DDC scale has been developed. This study tests the psychometric properties of the scale. Survey data were collected from a random sample of 187 female registered nurses who were employed and also provided care to elderly relatives. Nine factors contributing to DDC emerged from exploratory factor analysis. The DDC subscales were moderately correlated with the standardized health measures included in the study.The caregiving interface (degree of blurring between the professional and personal caregiving domains) was significantly negatively correlated with well-being and mental health.This result extends our understanding of the supports needed by those providing DDC.


Depth perception in telemedical consultations.
This study aimed at quantifying diminished depth perception in telemedicine due to the two-dimensional image and to devise coping strategies for the problem. Two hundred and thirty-five patients in the telemedicine room of a Minor Accident and Treatment Service were studied. The magnitude of impaired depth perception was noted. Seven coping strategies were used and the resolution of the problem was measured. Depth perception was judged to be less than 90% of binocular vision in 235 cases. This improved to more than 90% of binocular vision in 99 of the 234 cases (42.13%) when using of all strategies. Improvement by rotation of the camera 30 degrees at a time in the axial plane was the most useful strategy and it occurred in all 235 (100%) cases. Light adjustment and angulation occurred in 206 of 235 cases (87.66%). Comparison with the opposite side helped in 179 of 235 cases (76.17%), skin color and texture in 139 of 235 cases (59.15%), shutting one eye in 103 of 235 cases (43.83%), enlarging the image in 85 of 235 cases (36.17%), and diminishing depth of field of lens in 77 of 235 cases (32.77%). Other visual cues occurred in 63 of 235 cases (26.81%). Impaired depth perception is a significant problem in telemedicine. It can be improved to make a confident diagnosis in most cases by adopting a variety of strategies that are described in this paper.


Maculopapular rash of unsuspected cause: systemic contact dermatitis to cinchocaine.
Topical medications are frequently neglected as the potential cause of systemic drug reactions. In this case report, a patient with a maculopapular eruption attributed to a drug hypersensitivity reaction was submitted to skin patch tests in order to clarify the drug implicated. Incidentally, a positive reaction to cinchocaine was observed. With the ulterior confirmation of the application of an antihemorrhoidal ointment containing cinchocaine, which was omitted during the initial anamnesis, the diagnosis of systemic contact dermatitis to cinchocaine was made.


Reaction dynamics of O((1)D,(3)P) + OCS studied with time-resolved Fourier transform infrared spectroscopy and quantum chemical calculations.
Time-resolved infrared emission of CO(2) and OCS was observed in reactions O((3)P) + OCS and O((1)D) + OCS with a step-scan Fourier transform spectrometer. The CO(2) emission involves Deltanu(3) = -1 transitions from highly vibrationally excited states, whereas emission of OCS is mainly from the transition (0, 0 degrees , 1) --> (0, 0 degrees , 0); the latter derives its energy via near-resonant V-V energy transfer from highly excited CO(2). Rotationally resolved emission lines of CO (v <or= 4 and J <or= 30) were also observed in the reaction O((1)D) + OCS. For O((3)P) + OCS, weak emission of CO(2) diminishes when Ar is added, indicating that O((3)P) is translationally hot to overcome the barrier for CO(2) formation. The band contour of CO(2) agrees with a band shape simulated on the basis of a Dunham expansion model of CO(2); the average vibrational energy of CO(2) in this channel is 49% of the available energy. This vibrational distribution fits with that estimated through a statistical partitioning of energy E* congruent with 18,000 +/- 500 cm(-1) into all vibrational modes of CO(2). For the reaction of O((1)D) + OCS, approximately 51% of the available energy is converted into vibrational energy of CO(2), and a statistical prediction using E* congruent with 30,000 +/- 500 cm(-1) best fits the data. The mechanisms of these reactions are also investigated with the CCSD(T)/6-311+G(3df)//B3LYP/6-311+G(3df) method. The results indicate that the triplet O((3)P) + OCS(X(1)Sigma(+)) surface proceeds via direct abstraction and substitution channels with barriers of 27.6 and 36.4 kJ mol(-1), respectively, to produce SO(X(3)Sigma(-)) + CO(X(1)Sigma(+)) and S((3)P) + CO(2)(X(1)A(1)), whereas two intermediates, OSCO and SC(O)O, are formed from the singlet O((1)D) + OCS(X(1)Sigma(+)) surface without barrier, followed by decomposition to SO(a(1)Delta) + CO(X(1)Sigma(+)) and S((1)D) + CO(2)(X(1)A(1)), respectively. For the ground-state reaction O((3)P) + OCS(X(1)Sigma(+)), the singlet-triplet curve crossings play important roles in the observed kinetics and chemiluminescence.


Gelling Lyotropic Liquid Crystals with the Organogelator 1,3:2,4-Dibenzylidene-d-sorbitol Part I: Phase Studies and Sol-Gel Transitions.
Gelled lyotropic liquid crystals (gelled LLCs) are the combination of an LLC and a gel network. One method for obtaining gelled LLCs is the addition of a low molecular weight gelator, which forms gels via self-assembled fibrillar networks, to an aqueous surfactant solution. A potent gelator for LLCs is the LMW organogelator 1,3:2,4-dibenzylidene-d-sorbitol (DBS). This gelator gels the lamellar Lα phase, the bicontinuous cubic V1 phase, and the hexagonal H1 phase of the system H2O-C12E7 (heptaethylene glycol monododecyl ether) without influencing the phase boundaries as visual phase studies and rheometry show. Varying the DBS mass fraction η, one can adjust the sol-gel transition temperature Tsol-gel of the gelled LLCs. At η = 0.0075, all Tsol-gel values are below the LLC-to-isotropic phase transition temperatures TLLC-iso, that is, the LLCs are formed first while cooling down, followed by gel formation. At η = 0.015, however, Tsol-gel > TLLC-iso, that is, the gel is formed in an isotropic solvent, which becomes an LLC while cooling down. The system H2O-C12E7 is the first where an adjustment of the gelator concentration allowed us to decouple gel and LLC formation for all three LLCs, that is, gel and LLC formation happen one after the other and not simultaneously. This allows us to study whether the structure and thus the properties of gelled LLCs can be manipulated by the order of gel and LLC formation. We discuss our findings in light of the following question: are our gelled LLCs truly orthogonal self-assembled systems, that is, do the LLCs and the gel network form and coexist independently?


The roads to mitochondrial dysfunction in a rat model of posttraumatic syringomyelia.
The pathophysiology of posttraumatic syringomyelia is incompletely understood. We examined whether local ischemia occurs after spinal cord injury. If so, whether it causes neuronal mitochondrial dysfunction and depletion, and subsequent energy metabolism impairment results in cell starvation of energy and even cell death, contributing to the enlargement of the cavity. Local blood flow was measured in a rat model of posttraumatic syringomyelia that had received injections of quisqualic acid and kaolin. We found an 86 ± 11% reduction of local blood flow at C8 where a cyst formed at 6 weeks after syrinx induction procedure (P < 0.05), and no difference in blood flow rate between the laminectomy and intact controls. Electron microscopy confirmed irreversible neuronal mitochondrion depletion surrounding the cyst, but recoverable mitochondrial loses in laminectomy rats. Profound energy loss quantified in the spinal cord of syrinx animals, and less ATP and ADP decline observed in laminectomy rats. Our findings demonstrate that an excitotoxic injury induces local ischemia in the spinal cord and results in neuronal mitochondrial depletion, and profound ATP loss, contributing to syrinx enlargement. Ischemia did not occur following laminectomy induced trauma in which mitochondrial loss and decline in ATP were reversible. This confirms excitotoxic injury contributing to the pathology of posttraumatic syringomyelia.


Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study.
Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM). 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5 ± 3.1 years and mean disease duration 4.3 ± 3.5 years) and 44 age- and gender-matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate) during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal (p = 0.019) and circumferential (p = 0.016) strain rate both at rest and during exercise (p = 0.021). This was more pronounced in T1DM patients with a longer disease duration (p = 0.038). T1DM patients with serum HbA1c > 9% showed impaired longitudinal (p = 0.008) and circumferential strain (p = 0.005) and a reduced E/A-ratio (p = 0.018). In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment.


Twelve-year trends in health insurance coverage among Latinos, by subgroup and immigration status.
We examine twelve-year trends in the Latino uninsured population by ethnic subgroup and immigration status. From 1993 to 1999, most Latino subgroups, particularly Puerto Ricans, had large decreases in Medicaid coverage. For some subgroups these were offset by increases in employer coverage, but not for Mexicans, resulting in a four-percentage-point increase in their uninsured population. During 2000-2004, Medicaid/SCHIP expansions benefited most subgroups and mitigated smaller losses in employer coverage. However, during 1993-2004, the percentage of noncitizen Latinos lacking coverage increased by several percentage points. This was attributable to Medicaid losses during 1993-1999 and losses in employer coverage during 2000-2004.


Target versus actual oxygenation index at initiation of inhaled nitric oxide in neonates with hypoxic respiratory failure: survey results from 128 patient cases.
Inhaled nitric oxide (iNO) is a well-established treatment for neonatal hypoxic respiratory failure (HRF). However, iNO therapy initiation criteria have not been standardized. This report describes a follow-up survey administered to neonatologists who had completed an Awareness, Trial, and Usage Survey. The objectives were to compare stated target oxygenation index (OI) versus actual OI at which iNO is initiated in respondents' patients and identify factors associated with iNO initiation at other levels. Neonatologists provided iNO-treated HRF patient data. Target and actual OI at initiation were determined. Patient groups were stratified by actual OI deviation from target [<4; at (±3); above: 4-10, 11-20, >20; not measured]. Reasons for above-target OI were determined. Of 83 invited neonatologists, 26 (31%) participated, providing data for 128 patients; 85/128 patients (66%) had OI measured at initiation with neonatologist-stated mean target OI 18.8±5.8. Actual mean OI was 26.2±10.3. iNO was initiated ≤ target in 30/85 patients (35%); most [55/85 (65%)] had iNO initiated when OI was above target. Patients aged ≤1 day and those receiving a fraction of inspired oxygen (FiO2) of 1.0 for more than 1 h had highest OIs at initiation. Among surveyed neonatologists who treat infants with HRF with pulmonary hypertension (PH), there is a disparity between stated target versus actual OI for iNO initiation, particularly among infants <1 day old and those receiving FiO2 of 1.0 for more than 1 h. In term/near-term neonates with HRF with PH, neonatologists should consider implementing treatment protocols to ensure iNO initiation at stated target OI levels.


Polymer-drug compatibility: a guide to the development of delivery systems for the anticancer agent, ellipticine.
To establish a method for predicting polymer-drug compatibility as a means to guide formulation development, we carried out physicochemical analyses of polymer-drug pairs and compared the difference in total and partial solubility parameters of polymer and drug. For these studies, we employed a range of biodegradable polymers and the anticancer agent Ellipticine as the model drug. The partial and total solubility parameters for the polymer and drug were calculated using the group contribution method. Drug-polymer pairs with different enthalpy of mixing values were analyzed by physicochemical techniques including X-ray diffraction and Fourier transform infrared. Polymers identified to be compatible [i.e., polycaprolactone (PCL) and poly-beta-benzyl-L-aspartate (PBLA)] and incompatible [i.e., poly (d,l-lactide (PLA)], by the above mentioned methods, were used to formulate Ellipticine. Specifically, Ellipticine was loaded into PBLA, PCL, and PLA films using a solvent casting method to produce a local drug formulation; while, polyethylene oxide (PEO)-b-polycaprolactone (PCL) and PEO-b-poly (d,l-lactide) (PLA) copolymer micelles were prepared by both dialysis and dry down methods resulting in a formulation for systemic administration. The drug release profiles for all formulations and the drug loading efficiency for the micelle formulations were also measured. In this way, we compared formulation characteristics with predictions from physicochemical analyses and comparison of total and partial solubility parameters. Overall, a good correlation was obtained between drug formulation characteristics and findings from our polymer-drug compatibility studies. Further optimization of the PEO-b-PCL micelle formulation for Ellipticine was also performed.


Evolving operational guidance and experiences for radiology and nuclear medicine facilities in response to and beyond the COVID-19 pandemic.
The resulting pandemic from the novel severe acute respiratory coronavirus 2, SARS-CoV-2 (COVID-19), continues to exert a strain on worldwide health services due to the incidence of hospitalization and mortality associated with infection. The aim of clinical services throughout the period of the pandemic and likely beyond to endemic infections as the situation stabilizes is to enhance safety aspects to mitigate transmission of COVID-19 while providing a high quality of service to all patients (COVID-19 positive and negative) while still upholding excellent medical standards. In order to achieve this, new strategies of clinical service operation are essential. Researchers have published peer-reviewed reference materials such as guidelines, experiences and advice to manage the resulting issues from the unpredictable challenges presented by the pandemic. There is a range of international guidance also from professional medical organizations, including best practice and advice in order to help imaging facilities adjust their standard operating procedures and workflows in line with infection control principles. This work provides a broad review of the main sources of advice and guidelines for radiology and nuclear medicine facilities during the pandemic, and also of rapidly emerging advice and local/national experiences as facilities begin to resume previously canceled non-urgent services as well as effects on imaging research.