Gender differences in response to deployment among military healthcare providers in Afghanistan and Iraq.
Despite their growing numbers in the United States military, little has been published on healthcare providers (HCP) or female service members from conflicts in Afghanistan and Iraq. The purpose of this secondary analysis of data from the 2005 Department of Defense (DoD) Survey of Health Related Behaviors Among Active Duty Military Personnel was to determine gender differences in reaction to the impact of operational stress in deployed military healthcare providers. The unweighted study sample selected for this data analysis included results from female and male active duty military personnel over the age of 18 years (n=16,146) deployed at least once to Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF) within the past 3 years (n=1,425), for a final sample consisting of either officer (healthcare officer) or enlisted (healthcare specialist) personnel (n=455) (weighted n=23,440). Indices of psychologic distress and social relations were explored and compared. Enlisted female HCPs were more likely to be African American (42.3%) and single (63.0%) and represented the greater percentage with significant psychologic difficulties, as shown by serious psychologic distress endorsement (11.3%) and positive screen results for depression (32.2%). More harmful drinking patterns (Alcohol Use Disorders Identifications Test [AUDIT] score 8-15) were found in more female HCPs (enlisted 61.8%, officers 76.4%) compared with males (enlisted 41.1%, officers 67.1%). Female HCPs serving in the current military conflicts are reporting significant psychologic distress that may adversely impact their performance within the military, in theaters of operations, and in their lives at home. Implications for clinical care of female service members and veterans of current wars are addressed.


Re-esterified DHA improves ventilatory threshold 2 in competitive amateur cyclists.
Fish oils were studied as ergogenic aids in a number of mixed physical trial designs showing promising results. However, the heterogeneous purity of the studied supplements, combined with the variety of physical tests employed call for more studies to confirm these findings, ideally with standardised supplements. Our aim was to test a supplement highly concentrated in DHA (DHA:EPA ratio equal to approximately 8:1) on a maximal cycling test to elucidate performance improvements mainly due to DHA. A double-blind, placebo controlled, randomised balanced, parallel design, in competitive amateur cyclists was employed. They were all male, older than 18 years old, with training routine of 2 to 4 sessions per week lasting at least one hour each. A ramp cycling test to exhaustion with a subsequent 5 min recovery phase was employed before and after treatment to analyse aerobic metabolism and lactate clearance after the bout. After 30 days of supplementation with 975 mg of re-esterified DHA, the thirty-eight cyclist who completed the study were finally included for statistical analysis. Mean power output at ventilatory threshold 2 (VT2) improved after DHA supplementation both as absolute (△DHA versus △PLA: 6.33-26.54 Watts; CI 95%) and relative (p=0.006) values, paralleled with higher oxygen consumption at VT2 both for absolute (DHA 2729.4 ±304.5, 3045.9 ±335.0; PLA 2792.3 ±339.5, 2845.5 ±357.1; ml·min-1 baseline versus post p=0.025) and relative values (DHA 36.6 ±5.0, 41.2 ±5.4; PLA 37.2 ±5.7, 38.1 ±5.2; ml·kg-1·min-1 baseline versus post p=0.024). Heart rate recovery rate improved during the recovery phase in the DHA group compared to PLA (p=0.005). DHA is capable of improving mean power output at the ventilatory threshold 2 (anaerobic ventilatory threshold) in amateur competitive cyclists. It is unclear if these findings are the result of the specific DHA supplement blend or another factor.


[Construction of a bait plasmid containing human telomerase RNA mutant in yeast three-hybrid system].
To construct a bait plasmid containing human telomerase RNA with multiple point mutations in a yeast three-hybrid system and evaluate the toxicity of the recombinant bait plasmid. The primers were designed according to the hTR sequence and the target mutation sites for inducing T-->A mutations at the 41st, the 80th and 102nd nucleotides of the hTR gene using the overlapping extension PCR (OE-PCR) method. The mutant was cloned into PMD18T vector, confirmed by sequencing, sub-cloned into the bait plasmid PRH3' and identified with PCR and restriction enzyme digestion. The recombinant bait plasmid was then transformed into yeast L40 ura3/pHyblex/ZeoMS2 for toxicity test. Sequence analysis demonstrated successful introduction of point mutations at the target sites without causing random mutation. The recombined bait plasmid constructed showed no obvious toxicity against the host yeast cells. The recombinant plasmid containing the human telomerase RNA mutant (PRH3'-hTRm) has been successfully constructed and can be used as the bait plasmid in yeast three-hybrid system.


Emergent stereoselective interactions and self-recognition in polar chiral active ellipsoids.
In many active matter systems, particle trajectories have a well-defined handedness or chirality. Whether such chiral activity can introduce stereoselective interactions between particles is not known. Here, we developed a strategy to tune the nature of chiral activity of three-dimensionally printed granular ellipsoids without altering their shape or size. In vertically agitated monolayers of these particles, we observed two types of dimers form depending on the chirality of the pairing monomers. Heterochiral dimers moved collectively as a single achiral active unit, while homochiral ones formed a translationally immobile spinner. In active racemic mixtures, the former was more abundant than the latter, indicating that interactions were stereoselective. Through dimer lifetime measurements, we further provide evidence for chiral self-recognition in mixtures of particles with different chiral activities. We lastly show that, at fixed particle number density, changing the net chirality of a dense active liquid fundamentally alters the nature of collective relaxation.


Strategic Foresight in the Federal Government: A Survey of Methods, Resources and Institutional Arrangements.
The goal of this study is to help identify approaches and practices for improving Federal foresight efforts and the means for integrating foresight work into strategic planning and decision making. We present the results of semi-structured interviews with people involved with foresight in 19 Federal agencies, and with two non-Federal experts on foresight in government. We discuss where agencies use similar approaches and where their approaches diverge and include particularly insightful quotes from interviewees. We also discuss "broader observations" regarding the state of strategic foresight efforts across the Federal government and how our findings relate to opportunities and challenges to institutionalizing foresight in the Federal government.


Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment.
Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National Health System hospitals from February 2014 to May 2019. Local researchers were periodically contacted by the investigation team to monitor safety issues. Cancer histories were collected from the medical records and the information was updated at July 30th 2020. Eight Caucasian women developed cancer, which accounts for 0.9% and an accumulated malignancy rate of 298.39 cases per 100,000 patient-years of DMF exposure. At the time of cancer diagnosis, age was between 33 to 67 years and median time on DMF treatment 16.5 months (range 1-53). Two patients had familiar history of cancer. No specific cancer lines were found (breast cancer in 2 cases, thyroid in 3, urothelial carcinoma, cervix and a progression to leiomyosarcoma from a mitotically active leiomyoma). DMF was withdrawn during cancer treatment in 6 patients and reintroduced later. All cancers except one are in complete remission. The patient with leiomyosarcoma died by cancer progression. A relationship between cancers and DMF is unlikely because the malignancy rate was similar to that of the age-and sex-matched general population, and because of the absence of specific tumour cell lines. Nevertheless, as with other immunosuppressive DMTs, clinicians treating MS should be aware of any potential cancer symptom and demand proper testing.


Regulation of insulin-like growth factor-binding protein messenger ribonucleic acid levels in sheep thyroid cells.
The insulin-like growth factors (IGFs) exist primarily bound to cell surface receptors or complexed to specific binding proteins (IGFBPs). The IGFBPs modulate the bioavailability of the IGFs and may enhance or inhibit IGF actions. Several distinct forms of IGFBPs have been described on the basis of size, immunological determinants, and distribution in biological fluids; the IGFBPs may differ as well in their biological function. Sheep thyroid cells produce IGFBPs under hormonal regulation. Cells grown in basal medium or with six-hormone (6H) medium supplements (transferrin, glycyl-histidyl-lysine, hydrocortisone, somatostatin, insulin, and TSH) release nonglycosylated BPs that migrate at 24, 27, 29, and 32 kDa on Western ligand blot. Cells cultured with the thyroid mitogens epidermal growth factor and phorbol ester release additional glycosylated IGFBPs of 40-44 kDa. Immunoprecipitation experiments indicate that 29- and 32-kDa IGFBPs are antigenically related to IGFBP-2, and the 40- to 44-kDa proteins are related to IGFBP-3. Using specific cDNA probes IGFBP-1, -2, and -3, we examined the regulation of IGFBP mRNA levels in sheep thyroid cultures. The rat IGFBP-2 cDNA probe hybridized to an approximately 1.6-kilobase mRNA species in cells under all culture conditions. However, IGFBP-3 mRNA was detectable only in epidermal growth factor- or phorbol ester-treated cells and appeared within 4 h, preceding the release of IGFBP-3 protein into the medium. The 6H additives, which stimulate differentiated function in thyroid cells, inhibited the mRNA levels of both IGFBP-2 and IGFBP-3. IGFBP-1 mRNA was not detectable. The distinct regulation of these IGFBPs suggest that they may play different biological roles in modulating thyroid physiology.


Morphology and histology of the collapsed lunate in advanced kienböck disease.
Morphological and histological changes of 24 collapsed lunates in advanced Kienböck disease were investigated. Articular cartilage of a collapsed lunate were consistently attenuated or disappeared. The proximal articular cartilage facing the radius is generally more affected than the distal articular cartilage facing the capitate. There was one major fracture in addition to multiple minor fractures in the collapsed lunate. Fracture patterns were classified into three types according to the directions of major fracture, namely horizontal type, dual oblique type, and vertical type. There were viable and necrotic areas in the collapsed lunate. Active new bone formation was observed at the junction between the viable and necrotic bone area of the collapsed lunate in advanced Kienböck disease.


The physical map of the human RET proto-oncogene.
The RET proto-oncogene, a transmembrane tyrosine kinase receptor, is involved in the development of at least five different disease phenotypes. RET is activated through somatic rearrangements in a number of cases of papillary thyroid carcinoma while germ-line point mutations are associated with three inherited cancer syndromes MEN 2A, MEN 2B and FMTC. Moreover, point mutations or heterozygous deletions of RET are found in the dominant form of Hirschsprung disease or congenital colonic aganglionosis. We cloned the entire RET genomic sequence in a contig of cosmids encompassing 150 kb, from the CA repeat sTCL-2 to the region upstream the RET promoter, and established the position of the 20 exons of the RET gene with respect to a detailed restriction map based on eight endonucleases. A new highly polymorphic CA repeat sequence was identified within intron 5 of RET (RET-INT5). Finally the orientation of RET on chromosome 10q11.2 made it possible to orientate three other genes rearranged with RET in papillary thyroid carcinomas, namely H4/D10S170 on 10q21, R1 alpha on 17q23 and RFG2/Ele1 on 10q11.2.


Effects of Aspergillus fumigatus and Alternaria alternata on human ciliated epithelium in vitro.
Fungi represent the etiologic agent in a large number of patients with chronic sinusitis. Despite this, no study has examined the effects of fungi on ciliated epithelium. This study evaluates the effects of cultures and filtrates of Aspergillus fumigatus and Alternaria alternata on ciliary beat frequency (CBF) in vitro. CBF was recorded after exposure to either a control or experimental solution. A statistical comparison of control and experimental values was performed to determine significance at P < 0.05. A statistically significant inhibition of CBF in cultures and filtrates of A fumigatus and A alternata was demonstrated. We conclude that a soluble metabolite produced by clinical isolates of both A fumigatus and A alternata causes inhibition of CBF and may represent one virulence factor involved in the development of fungal sinusitis.


Endothelium and regulatory inflammatory mechanisms during organ rejection.
Endothelial integrity is mandatory for physiologic organ function; however, endothelium dysfunction can be caused by systemic inflammation, occurring during sepsis or organ rejection after transplantation. This article will address our current understanding of endothelial involvement in organ transplantation and rejection. Overall, more detailed studies focusing on the endothelial modulation after organ transplantation would be necessary to investigate the role of endothelium activation during organ rejection.


Obesity-induced lymphatic dysfunction is reversible with weight loss.
Obesity induces lymphatic leakiness, decreases initial lymphatic vessel density, impairs collecting vessel pumping and decreases transport of macromolecules. Obesity results in perilymphatic inducible nitric oxide synthase (iNOS) expression and accumulation of T cells and macrophages. Deleterious effects of obesity on the lymphatic system correlate with weight gain. Weight loss restores lymphatic function in obese animals and decreases perilymphatic iNOS and inflammatory cell accumulation. Although clinical and experimental studies have shown that obesity results in lymphatic dysfunction, it remains unknown whether these changes are permanent or reversible with weight loss. In the current study, we used a mouse model of diet-induced obesity to identify putative cellular mechanisms of obesity-induced lymphatic dysfunction, determine whether there is a correlation between these deleterious effects and increasing weight gain, and finally examine whether lymphatic dysfunction is reversible with diet-induced weight loss. We report that obesity is negatively correlated with cutaneous lymphatic collecting vessel pumping rate (r = -0.9812, P < 0.0005) and initial lymphatic vessel density (r = -0.9449, P < 0.005). In addition, we show a significant positive correlation between weight gain and accumulation of perilymphatic inflammatory cells (r = 0.9872, P < 0.0005) and expression of inducible nitric oxide synthase (iNOS; r = 0.9986, P < 0.0001). Weight loss resulting from conversion to a normal chow diet for 8 weeks resulted in more than a 25% decrease in body weight and normalized cutaneous lymphatic collecting vessel pumping rate, lymphatic vessel density, lymphatic leakiness, and lymphatic macromolecule clearance (all P < 0.05). In addition, weight loss markedly decreased perilymphatic inflammation and iNOS expression. Taken together, our findings show that obesity is linearly correlated with lymphatic dysfunction, perilymphatic inflammation and iNOS expression, and that weight loss via dietary modification effectively reverses these deleterious effects.


The High Impact of Staphylococcus aureus Biofilm Culture Medium on In Vitro Outcomes of Antimicrobial Activity of Wound Antiseptics and Antibiotic.
The staphylococcal biofilm-based infections of wounds still pose a significant therapeutical challenge. Treated improperly, they increase the risk of limb amputation or even death of the patient. The present algorithms of infected wound treatment include, among others, the application of antiseptic substances. In vitro wound biofilm models are applied in order to scrutinize their activity. In the present work, using a spectrum of techniques, we showed how the change of a single variable (medium composition) in the standard in vitro model translates not only to shift in staphylococcal biofilm features but also to the change of efficacy of clinically applied wound antimicrobials such as octenidine, polyhexamethylene biguanide, chlorhexidine, hypochlorite solutions, and locally applied gentamycin. The data presented in this study may be of a pivotal nature, taking into consideration the fact that results of in vitro analyses are frequently used to propagate application of specific antimicrobials in hospitals and ambulatory care units.


Establishment of pseudoternary LiO0.5-NiO-MnO2 phase diagram by combinatorial wet process.
A pseudoternary LiO0.5-NiO-MnO2 reaction phase diagram was established using a combinatorial high-throughput materials exploration process to find candidate electrode materials for lithium ion secondary batteries. Each powder library was prepared using our combinatorial wet process based on the electrostatic spray deposition method and results obtained at various firing temperatures in an air atmosphere and an oxide atmosphere. In the air atmosphere, newly composed single phase regions of a layered rock salt-type structure were only found around Li2MnO3 at 800 °C. On the other hand, in the oxide atmosphere, most of the powder library showed the multiphase of the spinel and layered rock salt type structure.


The role of vitamin D deficiency in cardiovascular disease: where do we stand in 2013?
The high worldwide prevalence of vitamin D deficiency is largely the result of low sunlight exposure with subsequently limited cutaneous vitamin D production. Classic manifestations of vitamin D deficiency are linked to disturbances in bone and mineral metabolism, but the identification of the vitamin D receptor in almost every human cell suggests a broader role of vitamin D for overall and cardiovascular health. The various cardiovascular protective actions of vitamin D such as anti-diabetic and anti-hypertensive effects including renin suppression as well as protection against atherosclerosis and heart diseases are well defined in previous experimental studies. In line with this, large epidemiological studies have highlighted vitamin D deficiency as a marker of cardiovascular risk. However, randomized controlled trials (RCTs) on vitamin D have largely failed to show its beneficial effects on cardiovascular diseases and its conventional risk factors. While most prior vitamin D RCTs were not designed to assess cardiovascular outcomes, some large RCTs have been initiated to evaluate the efficacy of vitamin D supplementation on cardiovascular events in the general population. When considering the history of previous disappointing vitamin RCTs in general populations, more emphasis should be placed on RCTs among severely vitamin D-deficient populations who would most likely benefit from vitamin D treatment. At present, vitamin D deficiency can only be considered a cardiovascular risk marker, as vitamin D supplementation with doses recommended for osteoporosis treatment is neither proven to be beneficial nor harmful in cardiovascular diseases.


Pulmonary inflammation and epithelial injury in response to acute ozone exposure in the rat.
To document the time course of the inflammatory response and epithelial injury in the lung following an acute ozone exposure, rats were exposed to 1.0 ppm ozone for periods between 4 and 24 hr. Some of the exposures were followed by postexposure periods in filtered air for up to 20 hr. Bronchoalveolar lavage fluid (BALF) analysis and electron microscopic morphometry on centriacinar regions of lungs fixed by intravascular perfusion were used to assess the degree of pulmonary inflammation and epithelial cell necrosis. Total protein and numbers of neutrophils and epithelial cells in BALF increased as the duration of ozone exposure increased, while BALF macrophages decreased. Quantitation of the neutrophil response in centriacinar lung regions (capillary, interstitial, and epithelial/luminal compartments of the terminal bronchiole and proximal alveolar duct) by morphometry generally correlated with the BALF analysis, and revealed a greater volume per surface area epithelial basal lamina (Vs) of neutrophils in the terminal bronchiole compartments compared to proximal alveoli. Necrosis of epithelial cells in terminal bronchioles, primarily ciliated cells, occurred as early as 4 hr after initiation of ozone exposure, before marked neutrophil migration, and continued during periods of maximal neutrophil influx. We concluded that the early epithelial necrosis in terminal bronchioles during the first few hours of ozone exposure was primarily due to direct ozone toxicity, but could not rule out the possibility of neutrophils contributing to the injury at later time points, especially between 8 and 12 hr of exposure (during periods of maximal neutrophil migration).


Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: next generation sequencing and clinical implications.
Data regarding the clinical characteristics and outcomes of lung metastases (LuM) from colorectal cancer (CRC) are different from those of liver metastases (LiM) from CRC. However, little is known about the genetic features of LuM. This study aimed to identify the different genetic characteristics of LuM and LiM from left-sided microsatellite stable CRC. Tissue samples of the primary tumors and paired metastases from 18 CRC patients with isolated LuM (LuM cohort), 18 patients with isolated LiM (LiM cohort), and 10 locally advanced CRC patients without metastases (control cohort) were selected for next-generation sequencing. Patients in the LiM cohort had matched clinicopathological characteristics with the LuM cohort. The single-nucleotide variations (SNVs), copy number variations (CNVs), pathway alterations, and tumor mutation burdens (TMBs) were also calculated and analyzed. The CNV results showed that ZFHX4, GATA2, and FAM131B amplifications were more common in the metastatic cohorts than in the control cohort, while RECQL4 and FLCN amplifications were common in the controls. The LuM cohort had significantly higher proportions of HNF4A, BRD4, and U2AF1 amplification. The LuM, LiM, and control cohorts were successfully separated using pathway alteration analysis. The LuM cohort had more frequent alterations in the RTK/RAS pathway, HIPPO pathway, KRAS, and MET than the LiM group. The LuM cohort also had relatively higher TMBs than the LiM cohort. CNVs in primary tumors could identify patients with LuM. Targeting the HIPPO pathway or MET and immune checkpoint inhibitors (ICIs) combined with other agents might be novel therapies for LuM.


Radiation recall after capecitabine in a patient with recurrent nasopharyngeal carcinoma: a case report.
Capecitabine has been commonly used in recurrent or metastatic nasopharyngeal carcinoma. However, radiation recall after capecitabine for nasopharyngeal carcinoma has not been reported. We report the case of a 64-year-old Chinese woman with locoregionally advanced nasopharyngeal carcinoma previously treated with induction chemotherapy followed by concurrent chemoradiation 6 years ago. She developed cervical, mediastinal, and abdominal nodal relapses 14 months later. She then received capecitabine with initial excellent tumor response for 1 year but disease recurrence was noticed at the peripancreatic nodal region, which was successfully treated with concurrent chemoradiation with capecitabine. Unfortunately, she developed progressive erythema of the face and neck region at exactly the previous irradiation site for her initial nasopharyngeal carcinoma, 2 months after taking capecitabine. She initially ignored it, but it became more confluent and serious. Eventually, a facial skin biopsy was performed showing nonspecific chronic inflammation only. The diagnosis was most likely radiation recall phenomenon since capecitabine was the only drug she received before development of this dermatological manifestation on her previously irradiated face and neck. Treatment was conservative and supportive albeit with no significant clinical improvement. Radiation oncologists should be aware of this potential risk of capecitabine, especially when it is administered for a long period of time.


Processing follows function: pushing the formation of self-assembled monolayers to high-throughput compatible time scales.
Self-assembled monolayers (SAMs) of organic molecules can be used to tune interface energetics and thereby improve charge carrier injection at metal-semiconductor contacts. We investigate the compatibility of SAM formation with high-throughput processing techniques. Therefore, we examine the quality of SAMs, in terms of work function shift and chemical composition as measured with photoelectron and infrared spectroscopy and in dependency on molecular exposure during SAM formation. The functionality of the SAMs is determined by the performance increase of organic field-effect transistors upon SAM treatment of the source/drain contacts. This combined analytical and device-based approach enables us to minimize the necessary formation times via an optimization of the deposition conditions. Our findings demonstrate that SAMs composed of partially fluorinated alkanethiols can be prepared in ambient atmosphere from ethanol solution using immersion times as short as 5 s and still exhibit almost full charge injection functionality if process parameters are chosen carefully. This renders solution-processed SAMs compatible with high-throughput solution-based deposition techniques.


The course of pregnancy in a patient with nail-patella syndrome.
The nail-patella syndrome is a rare autosomal dominant condition with high penetrance. Pregnancy in such a patient is rare and we believe this to be the first report of a live birth occurring in a patient with nail-patella syndrome. A 25-year-old patient presented in her first pregnancy with nephrotic syndrome associated with characteristic bone abnormalities and nail dysplasia and was later diagnosed to have nail-patella syndrome. In her second pregnancy, the course of her pregnancy was complicated by further deterioration of renal function with superimposed pre-eclampsia resulting in early delivery at 28 weeks. Such pregnancies should be regarded as high risk and managed jointly with the renal physician in a tertiary care centre to ensure an optimal outcome to the mother and baby.


Single-ion solvation free energy: A new cluster-continuum approach based on the cluster expansion method.
Accurate calculation of the solvation free energy of single ions remains an important goal, involving development in the dielectric continuum solvation models, and statistical mechanics with explicit solvent and hybrid discrete-continuum methods. In the last case, many of the research studies involve a quasi-chemical approach using the monomer cycle or the cluster cycle to calculate the solvation free energy of single ions. In this work, a different cluster-continuum approach based on the cluster expansion method was tested for solvation of 16 cations and 32 anions in aqueous solution. The SMD model was used for the dielectric continuum part and three explicit water molecules were introduced in the region of the solute with the highest interaction energy. Harmonic frequency calculations and molecular dynamics sampling of configurations are not required. An empirical γN parameter for cations and another for anions is introduced. The method produces a substantial improvement of the SMD model with a mean absolute deviation of 2.3 kcal mol-1 for cations and 2.9 kcal mol-1 for anions. The analysis of the correlation between theoretical and experimental data produces a linear regression line with a slope of 1.09 for cations and 1.01 for anions. The good results of this approximated cluster expansion approach suggest that the method could be further improved by including more solvent molecules and sampling the configurations.


Cell-cycle kinetics and VSV-G pseudotyped retrovirus-mediated gene transfer in blood-derived CD34+ cells.
As hematopoietic stem and progenitor cells have a low mitotic index, we have quantitated the impact of cytokine combinations on cell cycling of CD34+ cells and, using VSV-G pseudotyped retroviral vectors, correlated our findings with ex vivo gene transfer. We tested nine different combinations of cytokines for induction of human peripheral blood CD34+ cells into cell cycle over 72 hours. Using the 5-bromodeoxyuridine-Hoechst 33258 (BrdU-Hoechst) assay, we measured the cell-cycle kinetics. The combinations of cytokines tested that were most efficient in inducing the CD34+ cells into cycle were stem cell factor (SCF) plus one of the following: interleukin-1 (IL-1), IL-3, granulocyte colony-stimulating factor (G-CSF). The maximum numbers of cells in S+G2M phase were observed after 48 hours of culture. At least 35 +/- 5% of the CD34+ cells remained quiescent in the first G0/G1 phase, however, no matter which cytokine combination was used. Cell-cycle analysis of the CD34+CD38- subset by 7-amino actinomycin D staining did not detect cycling cells during 72 hours of culture with any of the cytokines tested. To investigate whether the cells could be infected by the VSV-G pseudotyped virus containing the neomycin phospho-transferase gene (neo), we exposed CD34+ cells to the virus for 7-8 hours after 0, 36, and 48 hours of cytokine stimulation. Total CD34+ cells and the CD34+CD38- subset were analyzed by polymerase chain reaction (PCR) for reverse-transcribed viral DNA of the neomycin resistance gene (RT-neoDNA). Immediately after exposure to the virus, RT-neoDNA was detectable in CD34+ cells that have been cultured with or without cytokines for 36 to 48 hours. Forty-eight hours postinfection, however, RT-neoDNA could be detected only with cytokine combinations that induced mitosis of the CD34+ cells, consistent with the requirement for mitotic activity for retroviral integration. Similar experiments performed with the 34+CD38- subset showed that RT-reoDNA could not be detected at any time point. Thus, postinfection RT-neoDNA could be immediately detected in noncycling CD34+ cells but not in CD34+CD38- cells. These results suggest during short-term liquid culture, there may be blocks for reverse transcription of retroviral RNA in CD34+CD38-cells in addition to the lack of mitotic activity.


Quality of diabetes care in primary care setting in egypt: an example of health sector reform in developing countries.
The aim of this study was to evaluate the extent of provider adherence to evidence-based guidelines for diabetes care and the extent of glycemic, blood pressure, and lipid control in patients with diabetes in a developing country. A retrospective cohort study was carried out to evaluate diabetes care provided under Health Sector Reform Program (HSRP) in a major medical center in Alexandria, Egypt. Data on care provided for 137 patients were abstracted from medical records. Several process measures were studied including annual proportion of patients with measurements of blood glucose, blood pressure, and lipid levels. Patient outcomes on these measures were also examined. Logistic and poisson regressions were used to study factors related to having measurements done and number of measurements respectively. Multilevel analysis was then used to examine rate of change in patient outcomes and factors associated with this rate over one year of follow-up. For 137 patients with diabetes, annual testing was adequate for fasting blood glucose (FBG) (94.1%), blood pressure (100%), foot (92.7%), and fundus examination (86.6%) was adequate. On the other hand less attention was given to total cholesterol (60.6%), triglycerides (52.6%) and albuminuria (10.3%). At the end of 1 year follow-up, 89.2% did not meet the target level of fasting blood glucose of < 130 mg/dl. A total of 40.2% and 46.7% did not meet the goal of 130 mmHg for systolic and 80 mmHg for diastolic blood pressure. Fifty nine percent, and 76.4% did not meet the goal of total cholesterol level of <200 mg/dl, or triglycerides level of <150 mg /dl respectively. There was evidence of suboptimal treatment with insulin, antihypertensive drugs, and lipid- lowering drugs. This study demonstrates that diabetes care provided under HSRP is unsatisfactory. As a result more effort to increase compliance with evidence based guidelines in diabetes care is needed.


Tuning the Porosity, Water Interaction, and Redispersion of Nanocellulose Hydrogels by Osmotic Dehydration.
Osmotic dehydration (OD) was introduced as a method to reproducibly tune the water content and porosity of cellulose nanofiber (CNF) hydrogels. The hierarchical porosity was followed by electron microscopy (pores with a >100 μm diameter) and thermoporosimetry (mesopores), together with mechanical testing, in hydrogels with solid contents ranging from 0.7 to 12 wt %. Furthermore, a reciprocal correlation between proton conductivity and the ratio of water bound to the nanocellulose network was established, suggesting the potential of these systems toward tunable energy materials.


CXCL12/CXCR4 Axis-Targeted Dual-Functional Nano-Drug Delivery System Against Ovarian Cancer.
Traditional chemotherapy for ovarian cancer is limited due to drug resistance and systemic side effects. Although various targeted drug delivery strategies have been designed to enhance drug accumulation at the tumor site, simply improvement of targeting capability has not consistently led to satisfactory outcomes. Herein, AMD3100 was selected as the targeting ligand because of its high affinity to chemokine receptor 4 (CXCR4), which was highly expressed on ovarian cancer cells. Moreover, the AMD3100 has been proved having blockage capability of stromal cell-derived factor 1 (SDF-1 or CXCL12)/CXCR4 axis and to be a sensitizer of chemotherapeutic therapy. We designed a dual-functional targeting delivery system by modifying paclitaxel (PTX)-loaded PEGylation bovine serum albumin (BSA) nanoparticles (NPs) with AMD3100 (AMD-NP-PTX), which can not only achieve specific tumor-targeting efficiency but also enhance the therapeutic outcomes. AMD3100 was chemically modified to Mal-PEG-NHS followed by reacting with BSA, then AMD-NP-PTX was synthesized and characterized. The targeting efficiency of AMD-NP was evaluated both in vitro and in vivo. The anticancer effect of AMD-NP-PTX was determined on Caov3 cells and ovarian cancer-bearing nude mice. Finally, the potential therapeutic mechanism was studied. AMD-NP-PTX was synthesized successfully and well characterized. Cellular uptake assay and in vivo imaging experiments demonstrated that NPs could be internalized by Caov3 cells more efficiently after modification of AMD3100. Furthermore, the AMD-NP-PTX exhibited significantly enhanced inhibition effect on tumor growth and metastasis compared with PTX, NP-PTX and free AMD3100 plus NP-PTX both in vitro and in vivo, and demonstrated improved safety profile. We also confirmed that AMD-NP-PTX worked through targeting CXCL12/CXCR4 axis, thereby disturbing its downstream signaling pathways including epithelial-mesenchymal transition (EMT) processes and nuclear factor κB (NF-κB) pathway. The AMD-NP-PTX we designed would open a new avenue for dual-functional NPs in ovarian cancer therapy.


The course of the frontal branch of the facial nerve in relation to fascial planes: an anatomic study.
Despite a wealth of literature describing the anatomy of the temporal region, controversy still exists over the depth of the frontal branch of the facial nerve as it travels over the zygomatic arch. It is commonly stated that the frontal branch travels within the superficial musculoaponeurotic system (SMAS) as it crosses the zygomatic arch. Clinically, however, it is apparent that the nerve runs at a deeper level as it crosses the arch, allowing for safe elevation and division of the SMAS to a point at or above the superior border of the zygomatic arch. The purpose of this study was to define the path of the frontal branches along fascial planes and to clarify the relationship of the fascial layers of the cheek and temporal region. Eighteen fresh-frozen cadaver hemifaces were dissected in a layer-by-layer fashion to evaluate the relationship between the nerve and the fascial planes above and below the zygomatic arch. Histologic evaluation was performed on six hemifaces. In all dissections, the frontal branch traveled within the innominate fascia as it crossed the zygomatic arch into the temporal region. A fascial transition zone was identified in a region 1.5 to 3.0 cm above the zygomatic arch and 0.9 to 1.4 cm posterior to the lateral orbital rim, where the frontal branches crossed from the innominate fascia to run within the superficial temporal fascia. As the frontal branch crosses the zygomatic arch, it is within the innominate fascia, a plane deep to the SMAS and superficial temporal fascia.


Giant Cellular Vacuoles Induced by Rare Earth Oxide Nanoparticles are Abnormally Enlarged Endo/Lysosomes and Promote mTOR-Dependent TFEB Nucleus Translocation.
Many nanomaterials are reported to disrupt lysosomal function and homeostasis, but how cells sense and then respond to nanomaterial-elicited lysosome stress is poorly understood. Nucleus translocation of transcription factor EB (TFEB) plays critical roles in lysosome biogenesis following lysosome stress induced by starvation. The authors previously reported massive cellular vacuolization, along with autophagy induction, in cells treated with rare earth oxide (REO) nanoparticles. Here, the authors identify these giant cellular vacuoles as abnormally enlarged and alkalinized endo/lysosomes whose formation is dependent on macropinocytosis. This vacuolization causes deactivation of mammalian target of rapamycin (mTOR), a TFEB-interacting kinase that resides on the lysosome membrane. Subsequently, TFEB is dephosphorylated at serine 142 and translocated into cell nucleus. This nucleus translocation of TFEB is observed only in vacuolated cells and it is critical for maintaining lysosome homeostasis after REO nanoparticle treatment, as knock-down of TFEB gene significantly compromises lysosome function and enhances cell death in nanoparticle-treated cells. Our results reveal that cellular vacuolization, which is commonly observed in cells treated with REOs and other nanomaterials, represents a condition of profound lysosome stress, and cells sense and respond to this stress by facilitating mTOR-dependent TFEB nucleus translocation in an effort to restore lysosome homeostasis.


Use of XyCAM RI for Noninvasive Visualization and Analysis of Retinal Blood Flow Dynamics During Clinical Investigations.
Ocular blood flow plays a critical role in eye health by nourishing the retinal and ocular tissues with oxygen and nutrients and removal of ocular metabolic waste. Imaging of retinal and optic blood flow may provide insights for early and more specific diagnoses of ocular vascular disorder and facilitate eye-based biomarkers applicable to neurological health assessment and research. The ability of the XyCAM RI (Vasoptic Medical Inc., MD, USA) to visualize and to analyze ocular blood flow dynamics XyCAM RI using laser speckle contrast imaging is reviewed and compared with concurrent clinical ophthalmic imaging technologies like optical coherence tomography - angiography (OCT-A), fundus imaging, fluorescein angiography (FA), indocyanine green angiography (ICGA), laser Doppler flowmetry (LDF), and laser speckle flowgraphy (LSFG). XyCAM RI, with its unprecedented imaging capabilities to assess blood flow dynamics provides a powerful tool to ophthalmic researchers and doctors to obtain greater clinical insights into the physiological status of the posterior segment and treatment approaches for various diseases in a very patient-friendly, noninvasive manner, unlike dye-based angiographic techniques such as FA or ICG. XyCAM RI is well suited as a modality that could close the gap between current screening and comprehensive eye exams.


Not All Facial Droops Are Stroke: Miller Fisher Syndrome Presenting as a Stroke Mimic.
Miller Fisher syndrome (MFS) is a rare acquired neuropathy resulting from an acute infection and is believed to be a variant of Guillain-Barre syndrome (GBS). Its characteristic features are triads of ataxia, areflexia and ophthalmolegia, though involvement of cranial nerves is possible. Our case report describes a middle-aged man who presented as a potential stroke patient with left-sided facial droop, dysphagia and weakness. Upon in-depth clinical examination and basic investigations, stroke was deemed unlikely and clinical diagnosis of MFS was reached. This was further confirmed by the presence of anti-GQ1b antibody and anti-GT1a antibody in the serological study. Our patient was closely monitored with spirometry checks and only received supportive therapy throughout his treatment course until he achieved full clinical recovery. From this case we learnt that the clinical manifestations of MFS may vary depending on the presence of different types of autoantibodies. Similar to GBS, management of MFS is also largely supportive. Despite the widespread use of intravenous immunoglobulins with or without plasmapheresis to treat MFS, there is no conclusive evidence yet regarding prioritizing one treatment over another as the disease itself is self-limiting.


Thromboembolic events associated with endovascular treatment of cerebral aneurysms.
To evaluate the rate of peri-procedural thromboembolic events after the endovascular treatment of cerebral aneurysms. The rate of diffusion-positive lesions was assessed in relation to selected procedural and technical factors. 184 patients treated with coil embolization (198 total procedures) between July 2004 and February 2007 were included. In 65, the procedure was coiling alone; in 55, coiling with balloon remodeling; in 48, coiling with Neuroform stenting; and in 30, coiling, Neuroform stenting and balloon remodeling. All patients underwent a routine diffusion weighted magnetic resonance imaging (DWI) within the 72 h after the intervention for the detection of ischemic complications. Regardless of the technique used, thromboembolic complications were more common (p<0.0001) in patients with ruptured aneurysms (33/65, 51%) than in those with unruptured aneurysms (40/133, 30%). Balloon remodeling tended to be associated with a lower rate of DWI positivity than the other techniques. Younger patients (≤60) with unruptured aneurysms had the lowest rates of DWI lesions regardless of the technique used. In this study, peri-procedural DWI-positive lesions occurred in approximately one-third of all cases. These were threefold more common in the setting of ruptured aneurysms. Adjunctive devices did not increase the rate of ischemic events. On the contrary, there was a trend toward fewer DWI abnormalities in the procedures in which balloon remodeling was employed. This may, in part, be related to the application of the conglomerate coil mass technique of balloon remodeling.


[Molecular analysis of IDS gene and prenatal diagnosis in a Chinese family with mucopolysaccharidosis type II].
Mucopolysaccharidosis type II (MPSII) is a lethal, X-linked recessive disorder caused by mutation of iduronate-2-sulfatase (IDS) gene. Up to now there is no really effective treatment for this disorder, therefore it is important to provide an accurate genetic diagnosis and prenatal diagnosis for the MPSII families. In this study, we identify the pathogenic mutation in a Chinese family with MPSII. The 8 years old male proband from a Chinese family was clinically diagnosed with MPSII. There are other 4 patients with similar phenotypes in the family who died at 9, 11, 7 and 10 years of age, respectively. Mutation analysis was carried out by polymerase chain reaction and direct sequencing of all exons and exon/intron boundaries of IDS gene. Denaturing high performance liquid chromatography (DHPLC) analysis was performed to screen the unknown variations of IDS gene in 100 unrelated control males. Two allelic variants of exon 5 (c.684A > G) and exon 6 (c.851C > T) and a nonsense mutation of exon 7 (c.892C > T) were detected in IDS gene of the proband. Heterozygous mutations c.684A > G, c.851C > T and c.892C > T were detected in both proband's mother and maternal grandmother. The unknown variations of c.684A > G and c.851C > T were not found in the 100 unrelated control males. The male fetus (IV11) inherited the same mutation of IDS gene as the proband. Mutation c.892C > T of IDS gene causes MPSII in this family and prenatal diagnosis in one affected fetus was achieved.


Immunotherapy for melanoma.
Immunotherapy for cancers is based on the principle that the host's immune system is capable of generating immune responses against tumor cells. Currently available treatments for melanoma patients are limited by poor response rates. Interferon-a has been approved for adjuvant treatment of stage III melanoma with improved survival. New and more innovative approaches with improved efficacy are needed. We reviewed the various new approaches and strategies for immunotherapy for the treatment of melanoma. Immunotherapy for melanoma includes a number of different strategies with vaccines utilizing whole cell tumors, peptides, cytokine-mediated dendritic cells, DNA and RNA, and antibodies. A variety of approaches can be used to enhance immune reactivity in patients with melanoma. Preclinical studies and initial clinical trials have shown promising results. Additional clinical trials are currently ongoing to evaluate the clinical efficacy and the associated toxicities of these novel treatment strategies.


Anogenital non-gonococcal neisseriae: prevalence and clinical significance.
Over a 13-year period non-gonococcal neisseriae (NGN) were isolated from 114 of 88,670 patients (0.13%) screened for anogenital gonorrhoea at a Genitourinary Medicine Unit. During the same period there were approximately 9000 anogenital gonococcal infections (10%). The prevalence of NGN was 0.09% (27/31,500) in women, 0.04% (20/52,800) in heterosexual men and 1.5% (67/4370) in homosexual men: the differences in prevalence between women and heterosexual men (P < 0.01) and between heterosexual patients and homosexual men (P < 0.001) are highly significant. Neisseria meningitidis was isolated most frequently and accounted for 85% (99/114) of the NGN. Whenever possible, N. meningitidis was serogrouped and its occurrence correlated with patient symptoms. Eleven of 18 heterosexual men who had meningococci isolated from their urethras had urethritis but co-existing chlamydial infection was excluded in only 5. None of 9 women with cervical colonization had clinical evidence of pelvic inflammation. Only one of 49 men with rectal colonization had proctitis. The management of anogenital NGN infection is discussed in relation to our findings and those of previously published studies. Within each patient group the prevalence and incidence of anogenital NGN were similar at the beginning and end of the study period indicating that levels have not been influenced by the advent of AIDS.


Processing time, accent, and comprehensibility in the perception of native and foreign-accented speech.
In this study, a sentence verification task was used to determine the effect of a foreign accent on sentence processing time. Twenty native English listeners heard a set of English true/false statements uttered by ten native speakers of English and ten native speakers of Mandarin. The listeners assessed the truth value of the statements, and assigned accent and comprehensibility ratings. Response latency data indicated that the Mandarin-accented utterances required more time to evaluate than the utterances of the native English speakers. Furthermore, utterances that were assigned low comprehensibility ratings tended to take longer to process than moderately or highly comprehensible utterances. However, there was no evidence that degree of accent was related to processing time. The results are discussed in terms of the "costs" of speaking with a foreign accent, and the relevance of such factors as accent and comprehensibility to second language teaching.


Construction of a physiologically based pharmacokinetic model for 2,4-dichlorophenoxyacetic acid dosimetry in the developing rabbit brain.
A physiologically based pharmacokinetic (PBPK) model that describes the kinetics of organic anions by using 2,4-dichlorophenoxyacetic (2,4-D) as a representative compound was constructed for the developing rabbit brain at near-term pregnancy (Gestation Day 30). The model consisted of brain, body, and venous and arterial compartments for the mother which were linked to the fetus by a placenta. Maternal brain compartments in the model were brain plasma, cerebrospinal fluid (CSF), and brain tissue including hypothalamus, caudate nucleus, hippocampus, forebrain, brainstem, and cerebellum. The fetus consisted of brain, body, amniotic fluid, and venous and arterial compartments. the maternal body had both a central and a deep compartment; the fetal body had only one compartment. Maternal blood flow to the fetus was modeled as blood flowing to the placenta, where it was equilibrated before it reached the fetus. The brain uptake was membrane-limited by the blood-brain barrier, with saturable clearance from the CSF into the venous blood by the choroid plexus in both fetus and mother. The model was used to compare concentrations of 2,4-D in maternal and fetal brain, maternal and fetal plasma, and amniotic fluid over time with experimental data from pregnant rabbits given 2,4-D intravenously (1, 10, or 40 mg/kg). The model adequately simulated the 2-hr time course of 2,4-D concentrations in both mother and fetus. With continued development, this generic PBPK model should be a useful tool for evaluating the safety of organic acid neurotoxicants in the developing brain.


Intravitreal fluocinolone acetonide implant for chronic postoperative cystoid macular edema - two years results.
We report visual and anatomical outcomes of chronic postoperative macular edema treated with a fluocinolone acetonide intravitreal implant. Retrospective study of chronic, post-surgical CME treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed over 24 months. The need for IOP lowering treatment, top-up therapy during follow-up, and complications were also assessed. We analyzed 16 consecutive eyes of 16 patients with chronic, post-surgical CME treated with fluocinolone acetonide intravitreal implant. Surgical indications included cataract surgery, vitrectomy plus membrane peeling and combined phaco-vitrectomy. Baseline mean BRVA of 0.8 ± 0.65 logMAR improved to 0.60 ± 0.4 logMAR (p = 0.02) at 12 months and to 0.7 ± 0.5 logMAR (p = 0.32) at 24 months. At month 12, BRVA improved in 11 eyes, stabilized in 4 eyes, and decreased in 1 eye. At month 24, VA remained improved in 5 eyes, remained stabilized in 5 eyes, and decreased in 1 eye. Mean CRT decreased from 524 ± 132 μm at baseline to 389 μm at month 3, 347 μm at month 6, 355 ± 106 μm (p = 0.0003) at month 12, and 313 ± 83 μm (p = 0.0001) at month 24. At 12 months, CRT improved in 13 eyes and remained unchanged in 2 eyes. At 24 months, CRT improved further in 8 eyes, and stabilized in 3 eyes. Increased IOP (≥21 mmHg) was observed only in 4 eyes, all successfully managed with topical medication. No further side effects were observed in any patient. Visual and anatomic improvements were achieved by a single fluocinolone acetonide implant with few side effects up to 24 months in CME eyes with a long and heavy prior treatment history.


Invasive haemodynamic monitoring: concepts and practical approaches.
The goal of haemodynamic care is to ensure adequate organ blood flow and oxygen supply. Clinical signs of organ perfusion have limited value in estimation of tissue perfusion, but invasive haemodynamic monitoring is needed to gain information of the underlying pathological condition and to guide oxygen delivery and haemodynamic therapy. Many of the available haemodynamic measurements involve pulmonary artery (PA) catheterization. Pressure measurements from PA catheters require meticulous attention to the dynamic properties of the transducer-pressure line system and appreciation of pressure variation owing to respiration. New techniques of continuous measurement of mixed venous oxygen saturation and cardiac output provide valuable trend data, allowing immediate diagnosis and treatment of pathological changes. Fast-response thermistor PA catheters are useful tools for estimating right ventricular function. Although clinicians generally regard PA-catheter data as a valuable therapy guide, few studies showing the beneficial influence on overall outcome have been carried out, and some studies have reported suboptimal understanding and utilization of these data. Transoesophageal echocardiography (TEE) is also a valuable monitor of left ventricular systolic and diastolic function and myocardial ischaemia in anaesthetized patients and in intensive care settings, but it requires a trained operator and is time-consuming. Continuously displayed TEE data, obtainable with automatic border detection, will make TEE even more useful in the near future. More effective monitors of perfusion and oxygenation of individual organs are needed. Less invasive techniques are also constantly sought. Combining data from several noninvasive monitors, including measurements of pulse oximetric O2 saturation, transthoracic impedance cardiac output and transcutaneous oxygen tension, has been reported to reflect closely changes obtained with more invasive monitoring.


Coordination of reaching in children with spastic hemiparetic cerebral palsy under different task demands.
Coordination of reaching with the impaired and non-impaired arm in 10 children with spastic hemiparetic cerebral palsy (SHCP) was examined in a stationary ball and moving ball context. Kinematic data on trunk, arm, and wrist movements, and coordination patterns between joint angles of elbow, shoulder, and trunk, were analyzed to determine how reaching was influenced by impairment and object motion. Results showed longer deceleration time and movement time and greater trunk contribution following decreased elbow and shoulder excursion when reaching with the impaired arm compared to the non-impaired arm. The coordination of joint angle pairs showed little linearity for the impaired arm, indicating more segmented movements of shoulder and elbow. It was also found that coordination patterns between elbow, shoulder, and trunk displayed less similarity when reaching with the impaired arm compared to the non-impaired arm in both stationary and moving ball conditions. Regardless of the timing constraints, children with SHCP could make successful interceptions using the impaired arm, indicating that they coordinated and controlled the degrees of freedom within their own functional possibilities.


Ockelbo virus (Togaviridae: Alphavirus) neutralizing antibodies in experimentally infected Swedish birds.
The ability of native Swedish birds to produce and maintain production of Ockelbo virus neutralizing (Nt) antibodies were evaluated experimentally between 6 June 1990 and 27 July 1991. After experimental infection of 57 birds of the orders Anseriformes and Passeriformes with Ockelbo virus, these birds were examined for Ockelbo virus Nt antibodies at 5 days, and at 1, 3, 6, 9, and 12 mo after inoculation. One month after inoculation, Nt antibodies were more prevalent in birds with a detectable viremia (100%, n = 22) than in non-viremic birds (65%, n = 26). The Nt antibody prevalence varied over time among taxa; detectable antibodies occurred earlier after inoculation and for a longer time in Anseriformes than in Passeriformes. By 5 days after inoculation, antibodies could be detected in 22 (71%) of 31 Anseriformes but in none of 16 Passeriformes. However, at 1 mo the antibody prevalences at 1 mo were similar: 84% among the Anseriformes and 73% among the Passeriformes; at 3 mo the prevalences were 50% in Anseriformes and 15% in Passeriformes. Forty-two percent of the Anseriformes had detectable antibodies even 12 mo after inoculation.


Ileocecal intussusception in an adult: the laparoscopic approach.
Adult intussusception is uncommon and requires a surgical approach. Malignancy is associated with 31% (43/137) of small bowel intussusception and 70% (74/106) of large bowel intussusception. Computerized tomography (CT) findings are pathognomonic for this condition. Often, the patient presents with long-standing, nonspecific complaints. A 63-year-old man presented with sudden onset of abdominal pain. CT demonstrated colonic inflammation. A laparoscopic right hemicolectomy for ileocecal intussusception was performed. The pathology report revealed a lipoma of the cecum. The postoperative course was uneventful, and he was discharged the fifth postoperative day. Despite a high incidence of malignancy, colonic or ileocecal intussusception can be successfully treated by laparoscopic resection. Review of the literature and treatment options are discussed.


Watchman Device Dislodgement Creating a Left Ventricular Outflow Tract Obstruction Requiring Emergency Cardiopulmonary Bypass.
Left atrial appendage (LAA) occlusion device implantation is becoming a more common alternative for stroke prophylaxis in patients with nonvalvular atrial fibrillation (AF) who are not able to tolerate long-term anticoagulation. Studies suggest the procedure has a 98.5% successful deployment rate (Boersma et al., 2016). We present a case where a rare but known complication involving dislodgement and migration of an implanted Watchman LAA occlusion device led to functional stenosis of the aortic valve creating a left ventricular outflow tract (LVOT) obstruction necessitating emergency cardiopulmonary bypass in the electrophysiology lab to safely retrieve the device.


The manifestation of infant hand-use preferences when reaching for objects during the seven--to thirteen-month age period.
Handedness is an aspect of hemispheric specialization whose pattern of expression may signal an unusual specialization that in turn, may underlie several developmental psychopathologies. It is generally believed that infant handedness is neither stable nor reliable and hence, cannot be used as an early marker of potential developmental abnormality of hemispheric specialization. We show that infant hand-use preferences for apprehending objects can be reliably assessed and may be relatively stable throughout the 7-13 month age period. However, the results also demonstrate that identifying infant handedness requires assessment using very large sample sizes with multiple assessment periods because it is likely that there may be many more than three patterns in the development of handedness during infancy.


Nitrogen behavior in a free water surface constructed wetland used as posttreatment for anaerobically treated swine wastewater effluent.
The aim of this study was to evaluate the behavior of total nitrogen (TN) in its different forms in a Free Water Surface constructed wetland (FWS) used as posttreatment for anaerobically treated swine wastewater. The experiment was conducted in a glasshouse from July 2010 to November 2011. The system consists in a FWS mesocosm inoculated with Typha angustifolia L. using as pretreatment an UASB reactor (upflow anaerobic sludge blanket). The operation are based on the progressive increase of the nitrogen loading rate (NLR) (2.0-30.2 kg TN/ha·d) distributed in 12 loads, with an operational time of 20 d. The results indicate that the behavior of the TN in the FWS, mainly depends on the NLR applied, the amount of dissolved oxygen available and the seasonality. The FWS operated with an NLR between 2.0-30.2 kg TN/ha·d, presents average removal efficiency for TN of 54.8%, with a maximum removal (71.7%) between spring-summer seasons (17.3-21.7°C). The availability of dissolved oxygen hinders the nitrification/denitrification processes in the FWS representing a 0.3-5.6% of TN removed.The main route of TN removal is associated with ammonia volatilization processes (2.6-40.7%), mainly to NLR over 25.8 kg TN/ha· d and with temperatures higher than 18°C. In a smaller proportion, the incorporation of nitrogen via plant uptake was 10.8% whereas the TN accumulated in the sediments was a 5.0% of the TN applied during the entire operation (550 d). An appropriate control of the NLR applied, can reduce the ammonia volatilization processes and the phytotoxicity effects expressed as growth inhibition in 80.0% from 496.0 mg NH(+) 4-N/L (25.8 kg TN/ha·d).


Development of a 44K SNP assay focussing on the analysis of a varroa-specific defence behaviour in honey bees (Apis mellifera carnica).
Honey bees are exposed to a number of damaging pathogens and parasites. The most destructive among them, affecting mainly the brood, is Varroa destructor. A promising approach to prevent its spread is to breed for Varroa-tolerant honey bees. A trait that has been shown to provide significant resistance against the Varroa mite is hygienic behaviour, a behavioural response of honey bee workers to brood diseases in general. This study reports the development of a 44K SNP assay, specifically designed for the analysis of hygienic behaviour of individual worker bees (Apis mellifera carnica) directed against V. destructor. Initially, 70,000 SNPs chosen from a large set of SNPs published by the Honey Bee Genome Project were validated for their suitability in the analysis of the Varroa resistance trait 'uncapping of Varroa-infested brood'. This was achieved by genotyping of pooled DNA samples of trait bearers and two trait-negative controls using next-generation sequencing. Approximately 36,000 of these validated SNPs and another 8000 SNPs not validated in this study were selected for the construction of a SNP assay. This assay will be employed in following experiments to analyse individualized DNA samples in order to identify quantitative trait loci (QTL) involved in the control of the investigated trait and to evaluate and possibly confirm QTL found in other studies. However, this assay is not just suitable to study Varroa tolerance, it is as well applicable to analyse any other trait in honey bees. In addition, because of its high density, this assay provides access into genomic selection with respect to several traits considered in honey bee breeding. It will become publicly available via AROS Applied Biotechnology AS, Aarhus, Denmark, before the end of the year 2011.


Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a comprehensive systematic review and meta-analysis.
Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control subjects and between affective states in bipolar disorder patients, including assessment of the effect of treatment of acute episodes on BDNF levels. A systematic review of English language studies without considering publication status was conducted in PubMed (January 1950-November 2014), Embase (1974-November 2014) and PsycINFO (1806-November 2014), and 35 studies comprising a total of 3798 participants were included in the meta-analysis. The results indicated that crude peripheral blood BDNF levels may be lower in bipolar disorder patients overall (Hedges' g=-0.28, 95% CI: -0.51 to -0.04, P=0.02) and in serum of manic (g=-0.77, 95% CI: -1.36 to -0.18, P=0.01) and depressed (g=-0.87, 95% CI: -1.42 to -0.32, P=0.002) bipolar disorder patients compared with healthy control subjects. No differences in peripheral BDNF levels were observed between affective states overall. Longer illness duration was associated with higher BDNF levels in bipolar disorder patients. Relatively low study quality, substantial unexplained between-study heterogeneity, potential bias in individual studies and indications of publication bias, was observed and studies were overall underpowered. It could thus not be excluded that identified differences between groups were due to factors not related to bipolar disorder. In conclusion, limitations in the evidence base prompt tempered conclusions regarding the role of peripheral BDNF as a biomarker in bipolar disorder and substantially improving the quality of further research is warranted.


Kernel Adaptive Filtering Over Complex Networks.
This brief is concerned with the problem of kernel adaptive filtering for a complex network. First, a coupled kernel least mean square (KLMS) algorithm is developed for each node to uncover its nonlinear measurement function by using a series of input-output data. Subsequently, an upper bound is derived for the step-size of the coupled KLMS algorithm to guarantee the mean square convergence. It is shown that the upper bound is dependent on the coupling weights of the complex network. Especially, an optimal step size is obtained to achieve the fastest convergence speed and a suboptimal step size is presented for the purpose of practical implementations. Besides, a coupled kernel recursive least square (KRLS) algorithm is further proposed to improve the filtering performance. Finally, simulations are provided to verify the validity of the theoretical results.


Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathologic study.
To investigate the effect of matrix-degrading enzymes on the malignant potential of oral squamous cell carcinoma, the expression of matrix metalloproteinase-2 (MMP-2/72-kD gelatinase/type IV collagenase) in 46 patients who had neck surgery for oral cancer was studied immunohistochemically. In 20 of 26 patients (76.9%) with lymph node metastases, proMMP-2 was strongly expressed, whereas the production of proMMP-2 in tissue was detected only in 5 of 20 patients (25%) who had no lymph node metastases. In tissue specimens, proMMP-2 was expressed in a diffuse invasive mode and in the advancing front of cancer. Because MMP-2 can degrade type IV collagen composed of basement membrane, these results suggest that the in vivo production of the enzyme by cancer is an indicator of the degree of malignancy, and that the analysis of proMMP-2 expression is useful to evaluate the malignant potential in individual oral squamous cell carcinoma.


Bulbar uretheral stricture repair with buccal mucosa graft urethroplasty.
To evaluate the use of buccal mucosa graft in single stage urethral reconstruction of bulbar urethral stricture. In Armed Forces Institute of Urology Rawalpindi, from Jan 2008 to Oct 2009, 56 patients underwent single stage dorsal onlay urethroplasty using buccal mucosa graft for long bulbar urethral strictures (> 2cm). Urethra was incised along the strictured segment in the 12 o'clock (dorsal) position starting from the distal end. A buccal mucosa graft of required length was harvested. The graft was anchored in a spread fixed fashion to the corporal bodies opposing the dorsally incised strictured urethra. The urethra was rotated back to the normal anatomic position. The margins of urethral incision were sutured to the fixed graft edge and corporal body using interrupted 4-0 vicryl. After completion of right margin's stitches, a 16 Fr silicon catheter was placed and then left margin stitches were completed. Only 54 out of 56 patients could be evaluated because 2 patients were lost to follow up. Mean age of the patients was 48 +/- 11.32 years (range 19-67 yrs). Mean length of the buccal mucosa graft was 3.4 +/- 0.6 cm (range 2.6 - 5.5 cm). Duration of follow up was 4-20 months, mean 16.3 +/- 3.65 months. In 47 (87%) patients, the procedure was successful, 7 (13%) patients developed recurrence, out of these 7 patients, 2 (3.7%) required optical urethrotomy and 5 (9.25%) patients responded to urethral dilatation. Mean operative time was 92 +/- 13.22 minutes. Buccal mucosa graft urethroplasty produces encouraging results in long bulbar urethral strictures. Longer follow up is required.


[Enhanced immunogenicity of xenogenized tumor cells in rats pretreated with cyclophosphamide (author's transl)].
Immunization with xenogenized tumor cells, tumor cells infected with murine leukemia viruses produced strong antitumor immunity. In this study, the immunogenicity of xenogenized tumor cells was compared in cyclophophamide-treated and nontreated rats. CY treatment 3 days before immunization with xenogenized tumor cells enhanced antitumor cell-mediated immunity and antibody responses. However, CY treatment after immunization had no effect. Transfer of thymus cells from normal rats before the tumor challenge abolished the CY-induced augmenting effect. From these results, it is suggested that the elimination of precursors of suppressor T-cells results in enhanced immunogenicity of xenogenized tumor cells.


Mitochondrial DNA in polish centenarians.
Mitochondrial haplogroups can differ in frequency of occurrence in those who are 100 years old and in the rest of the population. These differences are not universally observed; moreover, they are population-specific. We analyzed the haplogroups in 97 Polish 100-year-olds and compared them with those of more than 145 people who served as controls. No statistically significant differences were observed. In additions, we checked D-loop sequences in 31 controls and in some of the centenarians. Statistically significant differences were found for sites 73 and 152 in the D-loop.


MPP+ increases alpha-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastoma SH-SY5Y cells.
Alpha-synuclein is a brain presynaptic protein that is linked to familiar early onset Parkinson's disease and it is also a major component of Lewy bodies in sporadic Parkinson's disease and other neurodegenerative disorders. Alpha-synuclein expression increases in substantia nigra of both MPTP-treated rodents and non-human primates, used as animal models of parkinsonism. Here we describe an increase in alpha-synuclein expression in a human neuroblastoma cell line, SH-SY5Y, caused by 5-100 microM MPP+, the active metabolite of MPTP, which induces apoptosis in SH-SY5Y cells after a 4-day treatment. We also analysed the activation of the MAPK family, which is involved in several cellular responses to toxins and stressing conditions. Parallel to the increase in alpha-synuclein expression we observed activation of MEK1,2 and ERK/MAPK but not of SAPK/JNK or p38 kinase. The inhibition of the ERK/MAPK pathway with U0126, however, did not affect the increase in alpha-synuclein. The highest increase in alpha-synuclein (more than threefold) in 4-day cultures was found in adherent cells treated with low concentrations of MPP+ (5 microM). Inhibition of ERK/MAPK reduced the damage caused by MPP+. We suggest that alpha-synuclein increase and ERK/MAPK activation have a prominent role in the cell mechanisms of rescue and damage, respectively, after MPP+ -treatment.


The potentially coercive nature of some clinical research trial acronyms.
To evaluate the potential coerciveness of clinical research trial (CRT) acronyms, and to make clinicians aware that some CRT acronyms may be coercive to research subjects by subliminally enticing or outwardly promising something that the CRT may not be able to deliver. Analysis of CRT acronyms for pleasantness and meaningfulness as assessed by studies in the behavioral and social psychology literature. Of 2,383 acronyms for CRTs analyzed, 155 acronyms (6.5%) were assessed as possibly, probably, or almost certainly coercive. On a Likert scale from 1 to 5 for pleasantness or meaningfulness, the acronyms identified as almost certainly coercive had a mean pleasantness score of 4.21 (range, 3.70 to 4.57), the acronyms identified as probably coercive had a mean score of 3.79 (range, 2.45 to 5.00), and the acronyms identified as possibly coercive had a mean score of 3.89 (range, 2.81 to 5.00). A distraught or frightened patient with a life-threatening illness who is offered a research study with an acronym of CURE, HOPE, HELP, IMPROVED, LIFE, RESCUE, MIRACL (sic), SAVED, or ALIVE is possibly being coerced by the acronym. Institutional review boards (IRBs) and the medical research community would not tolerate a CRT entitled, "A Surefire Cure for Cancer." They should be no more tolerant of a CRT with an acronym listed above. It is time for researchers, sponsors, and IRBs to take a more responsible approach to potentially coercive CRT acronyms and discourage or prohibit their use.


Site-directed mutagenesis of the subunit PsaC establishes a surface-exposed domain interacting with the photosystem I core binding site.
We have postulated that the orientation of PsaC on the photosystem I core involves electrostatic interactions between charged residues on the core binding site and the subunit [Rodday, S. M., Jun, S.-S., & Biggins, J. (1993) Photosynth. Res. 36, 1-9]. We, therefore, changed eight acidic residues on PsaC to arginine and examined the efficiency of the mutant subunits in the reconstitution of P700-Fx cores in vitro. Reconstitution of the cores by the mutant subunits was determined by analysis of the kinetics of recombination reactions between P700+ and reduced acceptors as measured optically. Restoration of complete forward electron transfer, indicative of efficient subunit binding, was estimated from the ca. 30 ms decay component in the flash transients. Slightly reduced levels of reconstitution were observed for the mutants D24R, E46R/D47R. D61R, and E72R. In contrast, mutants D9R, E27R, and D32R showed significantly lower efficiencies. The presence of the iron-sulfur centers, FA and FB, in these three mutant subunits was confirmed by low-temperature EPR spectroscopy indicating that the polypeptides had folded correctly. We conclude that the introduction of positively charged side chains at positions 9, 27, and 32 seriously disrupts PsaC binding. However, when the wild-type acidic residues in these positions were changed to alanine, only mutant D9A showed a reduced level of reconstitution, suggesting that this aspartate is the most important residue participating in the electrostatic interaction with the core. The results are discussed in relation to the photosystem I crystal structure and support an orientation of PsaC on the core such that center FB is proximal to Fx.


Sodium hydroxide catalyzed monodispersed high surface area silica nanoparticles.
Understanding of the synthesis kinetics and our ability to modulate medium conditions allowed us to generate nanoparticles via an ultra-fast process. The synthesis medium is kept quite simple with tetraethyl orthosilicate (TEOS) as precursor and 50% ethanol and sodium hydroxide catalyst. Synthesis is performed under gentle conditions at 20 °C for 20 min Long synthesis time and catalyst-associated drawbacks are most crucial in silica nanoparticle synthesis. We have addressed both these bottlenecks by replacing the conventional Stober catalyst, ammonium hydroxide, with sodium hydroxide. We have reduced the overall synthesis time from 20 to 1/3 h, ~60-fold decrease, and obtained highly monodispersed nanoparticles with 5-fold higher surface area than Stober particles. We have demonstrated that the developed NPs with ~3-fold higher silane can be used as efficient probes for biosensor applications.


Ultrasonographic monitoring of implant thickness after augmentation rhinoplasty with expanded polytetrafluoroethylene.
Expanded polytetrafluoroethylene (ePTFE), or Gore-Tex (W.L. Gore & Associates, Flagstaff, AZ), is widely used in augmentation rhinoplasty, and the histological changes that it undergoes in the human body have been studied for decades. However, changes in the thickness of ePTFE after its use in augmentation rhinoplasty with a noninvasive object method are not well understood. We report the results of 19 patients (10 male and 9 female patients) who had undergone an uncomplicated augmentation rhinoplasty with Gore-Tex. Ultrasonography was used to evaluate changes in the thickness of Gore-Tex implants and to detect inflammatory reactions around the implants 9-67 months after surgery. Gore-Tex implants were clearly distinguishable from the surrounding tissue with ultrasonography. The postoperative thickness of the implant was decreased by 29%. There was no significant correlation between the degree of change in implant thickness and the length of time after surgery. However, the amount of thickness reduction was associated with the implant's initial thickness at the time of the surgery (R = 0.448; p = 0.001). In addition, four patients (21%) showed fibrosis or granuloma formation around the implant that was detectable via ultrasonography. Gore-Tex implants lost thickness after nasal dorsal augmentation in proportion to their initial thickness, and ultrasonography was useful for evaluating changes in Gore-Tex thickness.


Renal function and outcome of PTRA and stenting for atherosclerotic renal artery stenosis.
Prior studies of percutaneous transluminal renal artery angioplasty and stenting (PTRAS) for atherosclerotic renal artery stenosis (RAS) have shown that renal function is improved in about 25%, stabilizes in about 40%, but worsens in about 25% of patients. The factors predicting benefit remain controversial. We tested the hypothesis that the baseline glomerular filtration rate (GFR) predicts the changes in GFR and blood pressure (BP) after PTRAS. Treated hypertensive patients with positive renal color-coded duplex Doppler velocimetry and clinical criteria were screened by arteriography. Patients (N = 105) were included if they had an RAS >or=70%, a transluminal pressure gradient >or=30 mm Hg and, they had more than 100 days of follow-up. GFR was calculated from the serum creatinine concentration (SCr). Patients were divided by baseline GFR into subgroups with normal to mildly impaired (N = 52) or moderately to severely impaired (N = 53) initial GFR, according to a GFR >or=50 or <50 mL. min-1 respectively. All received PTRAS. For the entire group, after a mean follow-up period of 371 days, there were significant reductions in systolic and diastolic BP (before, 160 +/- 26/91 +/- 12 vs. after, 145 +/- 20/83 +/- 10 mm Hg, respectively; mean +/- SD; P < 0.0001), and a modest increase in the calculated GFR (before, 54 +/- 26 vs. after, 62 +/- 28 mL. min-1; mean +/- SD; P < 0.007). However, in the subgroup of patients with an initially lower GFR there was a significant increase in the calculated GFR (from 33.3 +/- 10 to 54 +/- 24 mL. min-1; mean +/- SD; P < 0.0001) despite no significant change in BP (161 +/- 27/90 +/- 12 vs. 151 +/- 21/86 +/- 12; P = NS). In contrast, in the subgroup with an initially higher GFR, there were significant (P < 0.0001) reductions in systolic BP (from 159 +/- 25 to 138 +/- 16 mm Hg) and diastolic BP (from 91 +/- 11 to 81 +/- 9 mm Hg), but no significant change in the calculated GFR (from 75 +/- 21 to 70.2 +/- 30 mL. min-1; P = NS). The significance of GFR variation in subgroups remained after correction of baseline data to exclude the influence of the expected regression to the mean. Patients with atherosclerotic RAS fulfilling strict criteria of severity may have significant improvements in BP one year after PTRAS but only modest in GFR. The initial GFR may anticipate whether the benefits in the outcome will be in renal function enhancement (those with an initially depressed GFR) or in hypertension control (those with an initially normal or mildly impaired GFR).


Ultrastructure of the spermatozoa from three odontocetes: a killer whale (Orcinus orca), a Pacific white-sided dolphin (Lagenorhynchus obliquidens) and a beluga (Delphinapterus leucas).
Semen was collected from three captive odontocetes: a killer whale (Orcinus orca); a Pacific white-sided dolphin (Lagenorhynchus obliquidens) and a beluga (Delphinapterus leucas). Semen was collected from the killer whale and Pacific white-sided dolphin using behavioural commands, whereas semen from the beluga was collected postmortem. Ultrastructure of the spermatozoa was examined using scanning and transmission electron microscopy. Species differences were more pronounced in the head sections followed by the midpiece and finally, the tail sections. Spermatozoa from the killer whale and beluga were similar but differed from the Pacific white-sided dolphin spermatozoa.


Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women.
Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are strong predictors of type 2 diabetes mellitus (T2D), but their association with cardiovascular disease (CVD) is uncertain. We hypothesized that plasma BCAAs are positively associated with CVD risk and evaluated whether this was dependent on an intermediate diagnosis of T2D. Participants in the Women's Health Study prospective cohort were eligible if free of CVD at baseline blood collection (n=27 041). Plasma metabolites were measured via nuclear magnetic resonance spectroscopy. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BCAAs with incident CVD (myocardial infarction, stroke, and coronary revascularization). We confirmed 2207 CVD events over a mean 18.6 years of follow-up. Adjusting for age, body mass index, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD: HR, 1.13; 95% CI, 1.08-1.18), comparable to LDL-C (low-density lipoprotein cholesterol) with CVD (per SD: HR, 1.12; 95% CI, 1.07-1.17). BCAAs were associated with coronary events (myocardial infarction: HR, 1.16; 95% CI, 1.06-1.26; revascularization: HR, 1.17; 95% CI, 1.11-1.25), and borderline significant association with stroke (HR, 1.07; 95% CI, 0.99-1.15). The BCAA-CVD association was greater (P interaction=0.036) among women who developed T2D before CVD (HR, 1.20; 95% CI, 1.08-1.32) versus women without T2D (HR, 1.08; 95% CI, 1.03-1.14). Adjusting for LDL-C, an established CVD risk factor, did not attenuate these findings; however, adjusting for HbA1c and insulin resistance eliminated the associations of BCAAs with CVD. Circulating plasma BCAAs were positively associated with incident CVD in women. Impaired BCAA metabolism may capture the long-term risk of the common cause underlying T2D and CVD.


Addressing the Psychosocial Needs of Individuals with Communication Disorders: The Integration of Animal-Assisted Therapy within Counseling.
Individuals with speech, language, and communication disorders often present with psychosocial concerns that span the physiological, intrapersonal, and interpersonal domains of functioning. Despite this fact, the provision of counseling service by speech-language pathologist (SLP) that directly addresses clients' psychosocial needs is sparse. Research shows the primary counseling strategy used by therapists is psychoeducation, failing to effectively address the psychosocial concerns. Integrating complementary approaches to traditional counseling in SLP can enhance both the quality of therapeutic intervention and client outcomes. The purpose of this article is to demonstrate the potential of animal-assisted therapy (AAT) as an adjunctive or complementary approach for counseling within SLP. A review of literature demonstrates a need for improved counseling service provision within SLP treatment, as well as the benefits of integrating AAT. A framework for how AAT intentions and techniques fit within SLP Scope of Practice counseling activities is presented, along with case examples to demonstrate how AAT can be integrated within SLP treatment. It is concluded that the integration of AAT as a complementary approach to traditional SLP counseling can enhance both the frequency of counseling services provided and clients' psychosocial outcomes.


Purification and Characterization of a Fibrinolytic Enzyme from Bacillus pumilus 2.g Isolated from Gembus, an Indonesian Fermented Food.
Bacillus pumilus 2.g isolated from gembus, an Indonesian fermented soybean cake, secretes several proteases that have strong fibrinolytic activities. A fibrinolytic enzyme with an apparent molecular weight of 20 kDa was purified from the culture supernatant of B. pumilus 2.g by sequential application of ammonium sulfate precipitation, ion-exchange chromatography, and hydrophobic chromatography. The partially purified enzyme was stable between pH 5 and pH 9 and temperature of less than 60°C. Fibrinolytic activity was increased by 5 mM MgCl2 and 5 mM CaCl2 but inhibited by 1 mM phenylmethylsulfonyl fluoride (PMSF), 1 mM sodium dodecyl sulfate (SDS), and 1 mM ethylenediaminetetraacetic acid (EDTA). The partially purified enzyme quickly degraded the α and β chains of fibrinogen but was unable to degrade the γ chain.


Encapsulation of coagulase-negative staphylococci of bovine origin.
Capsule expression was assessed in six coagulase-negative staphylococcal strains in serum-soft agar and by india ink and electron microscopy. Classification of strains as encapsulated by serum-soft agar and india ink methods differed. Staphylococcus chromogenes, Staph. hyicus, and Staph. simulans grew as diffuse colonies in serum-soft agar and unstained halos were detected in india ink preparations. Staphylococcus hominis and Staph. simulans grew as diffuse colonies in serum-soft agar but no unstained halo was seen in india ink preparations. Staphylococcus hyicus was the only strain that gave negative results with serum-soft agar and india ink assays. Conventional electron microscopy revealed the presence of capsular polysaccharides on the cell surface of Staph. chromogenes, Staph. hominis and Staph. hyicus. Conventional electron microscopic technique used to examine the surface of cells was detrimental to capsule structure. During dehydration the capsule collapsed and appeared as electron dense aggregates at the surface of cells. To confirm results of conventional electron microscopy and to visualize clearly the cell surface, encapsulated Staph. hyicus and unencapsulated Staph. simulans were observed after freeze-fracture and etching by scanning electron microscopy. The fibrous nature of capsular polysaccharides surrounding cells of Staph. hyicus were distinct and confirmed observation by conventional electron microscopy. A rapid transmission electron microscopic technique is described also for observation of capsule. Results of the rapid TEM method agreed with conventional TEM and SEM. The finding that coagulase-negative staphylococci isolated from bovine milk are capable of capsule production may be important when investigating pathogenicity of these micro-organisms.


[Cystic kidney diseases].
Among all inherited cystic kidney diseases, the commonest are polycystic kidney diseases, which include 2 diseases characterized by their pathological characteristics and their mode of inheritance, namely autosomal dominant or recessive. Autosomal dominant polycystic kidney disease is usually diagnosed in adulthood and is related at least to 2 different genes; PKD1 gene on chromosome 16 accounts for 85% of cases. This frequent disease (1 in 1,000 people) leads to end-stage renal failure in most patients at a mean age of 55 years. Renal ultrasonography allows its detection at an early stage, during childhood or adolescence, and even in utero in some cases. Autosomal recessive polycystic kidney disease, related to a single gene mapped to chromosome 6, is a rare disease, usually diagnosed during infancy because of enlarged kidneys and hypertension. The early occurrence of advanced renal failure is uncommon and only 1/3 of patients require renal replacement therapy during childhood. The term "polycystic kidney disease" should be limited to these 2 diseases; however there are many other inherited conditions including renal cysts like tuberous sclerosis or Hippel-Lindau's disease in adults, and several malformative syndromes in children.


Correction of Angle Class II division 1 malocclusion with a mandibular protraction appliances and multiloop edgewise archwire technique.
A Brazilian girl aged 14 years and 9 months presented with a chief complaint of protrusive teeth. She had a convex facial profile, extreme overjet, deep bite, lack of passive lip seal, acute nasolabial angle, and retrognathic mandible. Intraorally, she showed maxillary diastemas, slight mandibular incisor crowding, a small maxillary arch, 13-mm overjet, and 4-mm overbite. After the diagnosis of severe Angle Class II division 1 malocclusion, a mandibular protraction appliance was placed to correct the Class II relationships and multiloop edgewise archwires were used for finishing. Follow-up examinations revealed an improved facial profile, normal overjet and overbite, and good intercuspation. The patient was satisfied with her occlusion, smile, and facial appearance. The excellent results suggest that orthodontic camouflage by using a mandibular protraction appliance in combination with the multiloop edgewise archwire technique is an effective option for correcting Class II malocclusions in patients who refuse orthognathic surgery.


Allometric scaling of interspecific RNA transcript abundance to extend the use of metatranscriptomics in characterizing complex communities.
Metatranscriptomics allows profiling of community mRNA and rRNA transcript abundance under certain environmental conditions. However, variations in the proportion of RNA transcripts across different community size structures remain less explained, thus limiting the possible applications of metatranscriptomics in community studies. Here, we extended the assumptions of the growth-rate hypothesis (GRH) and the metabolic theory of ecology (MTE) to validate the allometric scaling of interspecific RNA transcript (mRNA and rRNA) abundance through metatranscriptomic analysis of mock communities consisting of model organisms. The results suggest that body size imposes significant constraints on RNA transcript abundance. Interestingly, the relationship between the total mitochondrial transcript abundance (mRNA and rRNA slopes were -0.30 and -0.28, respectively) and body size aligned with the MTE assumptions with slopes close to -¼, while the nuclear transcripts displayed much steeper slopes (mRNA and rRNA slopes were -0.33 and -0.40, respectively). The assumed temperature dependence was not observed in this study. At the gene level, the allometric slopes range from 0 to -1. Overall, the above results showed that larger individuals have lesser RNA transcript abundance per tissue mass than smaller ones regardless of temperature. Analyses of field-collected microcrustacean zooplankton samples demonstrated that the correction of size effect, using the allometric exponents derived from the model organism mock community, explains better the patterns of interspecific RNA transcripts abundance within the metatranscriptome. Integrating allometry with metatranscriptomics can extend the use of RNA transcript reads in estimating ecological processes within complex communities.


Effects of Clinical Nurse Educator Professional Role Development: An Evidence-Based Quality Improvement Project.
Centralization of clinical nurse educators (CNEs) from medical-surgical and critical care in a rural Midwestern hospital created role confusion and poor role outcomes. An evidence-based quality improvement project was developed to integrate the Association of Nursing Professional Development's transition to practice fellowship and practice model. Outcomes were focused on CNE self-assessed competency and three nurse-sensitive quality outcomes. Results were mixed but support that CNEs influenced patient quality outcomes and improved their self-assessed competency.


Observation of a new electronic state of CO perturbing W ¹Π(v=1).
We observe photoabsorption of the W(1) ← X(0) band in five carbon monoxide isotopologues with a vacuum-ultraviolet Fourier-transform spectrometer and a synchrotron radiation source. We deduce transition energies, integrated cross sections, and natural linewidths of the observed rotational transitions and find a perturbation affecting these. Following a deperturbation analysis of all five isotopologues, the perturbing state is assigned to the v = 0 level of a previously unobserved (1)Π state predicted by ab initio calculations to occur with the correct symmetry and equilibrium internuclear distance. We label this new state E″ (1)Π. Both of the interacting levels W(1) and E″(0) are predissociated, leading to dramatic interference effects in their corresponding linewidths.


[Qualitative study on the cognition of acquired immunodeficiency syndrome occupational protection among the managers of multi-level stomatology medical institutions].
To understand the current cognition of acquired immunodeficiency syndrome (AIDS) occupational protection among the managers of multi-level stomatology medical institutions in efforts to provide a reference for formulating technical standards for occupational protection. Eighteen managers of oral medical institutions were individually interviewed in-depth using asemi-structured questionnaire on issues related to AIDS occupational protection using the phenomenological research method. Nvivo 12.0 software was used to code and analyze the interview data, and relevant themes were extracted. Three themes were extracted from the data. Occupational protection measures for AIDS in dental medical institutions mainly based on the aspects of standardized operation, standardized prevention, and post-exposure treatment. However, the implementation of these protective measures was often inadequate. Occupational protection training for AIDS was carried out regularly at dental medical institutions, but the training effect was not generally tracked. Several limitations in AIDS occupational protection management; these limitations included the lack of a specific occupational protection system, the difficulty of AIDS screening for outpatients, and the difficulty of AIDS occupational protection supervision. Oral medical institutions should strengthen their occupational protection training and supervision approaches and formulate unified occupational protection standards to reduce occupational exposure and improve hospital management quality and efficiency.


Successful application of PD-1 knockdown CLL-1 CAR-T therapy in two AML patients with post-transplant relapse and failure of anti-CD38 CAR-T cell treatment.
Patients with relapsed/refractory acute myeloid leukemia (R/R AML) often show resistance to chemotherapy and have dismal outcomes. Therefore, it is urgent to develop new treatment strategies to address this problem. With tremendous achievement of chimeric antigen receptor T cells (CAR-T) therapy against B-cell malignancies, many efforts have been devoted to developing CAR-T therapy for R/R AML but with limited success, in part owing to a lack of specific targets. C-type lectin-like molecule-1 (CLL-1) is highly expressed on AML blasts with no expression on normal hematopoietic stem cells, which makes it an ideal target of immunotherapy for AML. Here, we report 2 R/R AML patients who relapsed after allogeneic stem cell transplantation and failed multiline salvage therapies including anti-CD38 CAR-T therapy, but were successfully treated with PD-1 silenced anti-CLL-1 CAR-T therapy. Both patients achieved molecular complete remission with incomplete hematologic recovery at 28 days of evaluation after CLL-1 CAR-T cell infusion. Cytokine release syndrome in cases 1 and 2 were grade 1 and 2, respectively. At the last follow-up, cases 1 and 2 had maintained continuous remission for 8 and 3 months, respectively. Our results demonstrated that CLL-1 CAR-T cells might be an effective and safe salvage therapy for AML patients with posttransplant relapse.


[Spectral properties of the green alga Trebouxia--a phycobiont of cryptoendolithic lichens in the high-latitude polar regions of Antarctica].
An algologically pure culture of the green alga Trebouxia, a phycobiont of cryptoendolithic lichens, was isolated from the sandstone samples collected in the high-altitude polar regions of Antarctica. The absorption and the second-derivative absorption spectra of the acetone extract of the Antarctic phycobiont cells were studied in comparison with those of the Trebouxia phycobiont isolated recently from the Parmeliaceae lichen in the Mid-European climatic zone. The cells of the Antarctic phycobiont were characterized by a lower content of chlorophyll a and a higher ratio of chlorophyll b and carotenoids to chlorophyll a as compared to the Mid-European phycobiont. Furthermore, the carotenoids of the Antarctic phycobiont were more diverse. The low-temperature fluorescence spectra of the Antarctic phycobiont were characterized by an increased intensity of the short-wavelength fluorescence peak of chlorophyll a and a diminished intensity of fluorescence in the long-wavelength spectral region.