Cocaine metabolites in the neonate: potential for toxicity.
Recent reports indicate that cocaine metabolites have biologic activity and could be toxic. To explore this possibility, two studies were initiated. The first study aimed to define the distribution of cocaine species by quantifying levels of cocaine and its metabolites norcocaine, benzoylecgonine, and benzoylnorecgonine in newborn cord blood and meconium. The second study sought to determine whether they produced a clinical effect. Compared to cord blood, meconium had a greater number of metabolites and a higher concentration of cocaine metabolites, including the previously undetectable norcocaine and benzoylnorecgonine derivatives. Benzoylecgonine was the most common species found in both sources and was usually lower in concentration in blood. An inverse relation existed between meconium benzoylecgonine levels and the serum catabolic enzyme pseudocholinesterase, implying genetic variability in cocaine metabolism. To determine whether cocaine and/or its metabolites could be linked to a distinct clinical state, a second study focusing on newborn behavior was performed with an independent large cohort of cocaine-exposed infants. Neonates with increased signs of "neuroexcitation" had benzoylecgonine and no cocaine in urine, whereas lethargic neonates had detectable urinary cocaine. These findings support the hypothesis that cocaine metabolites, especially benzoylecgonine, may play a role in altering newborn behavior and produce a clinical syndrome distinct from that related to the parent compound.


Beliefs and practices of Black South African traditional healers regarding hearing impairment.
The study investigated beliefs and practices of Black South African traditional healers regarding hearing impairment. Fifteen Black South African traditional healers were interviewed using a semi-structured interview schedule. An exploratory-descriptive research design incorporating a mixed qualitative/quantitative method was employed and data were collected via individual interviews. Traditional healers reported being consulted for what could possibly reflect a variety of audiological and otological problems, and using a wide range of diagnostic and treatment techniques. Although the healers mentioned infection, organic deterioration, noise exposure, and congenital aspects as cause of hearing impairment; they tended to anthropomorphise the cause of the disease, and the reason for becoming ill was often sought in a supernatural realm. These findings have implications for culturally sensitive practice, collaboration between traditional healers and audiologists, sharing of information regarding hearing impairment, mutual referrals, and involvement of traditional healers in hearing health care.


Implementation of cavity squeezing of a collective atomic spin.
We squeeze unconditionally the collective spin of a dilute ensemble of laser-cooled 87Rb atoms using their interaction with a driven optical resonator. The shape and size of the resulting spin uncertainty region are well described by a simple analytical model [M. H. Schleier-Smith, I. D. Leroux, and V. Vuletić, arXiv:0911.3936 [Phys. Rev. A (to be published)]] through 2 orders of magnitude in the effective interaction strength, without free parameters. We deterministically generate states with up to 5.6(6) dB of metrologically relevant spin squeezing on the canonical 87Rb hyperfine clock transition.


IL-6 and FAS (CD95) serum level in patients suffering from psoriasis and in relation to the lymphocyte subpopulations.
In the presented study the subpopulations of blood lymphocytes as well as serum concentrations of IL-6 and FAS in 20 patients with psoriasis triggered by infection and 17 healthy controls were analyzed. The flow cytometry technique and ELISA method were used. We detected statistically significant higher serum level of interleukin-6 (IL-6) in patients with active disease and tendency to the lowering of FAS level, although not statistically significant. Analysis of the correlation between the parameters showed that it was close to statistical significance for IL-6 and CD 95, p = 0.06 and R = 0.41. IL-6 level correlated positively with percentage of CD45RO+ cells (p = 0.05, R = 0.28) and negatively with percentage of CD3+ cells (p = 0.02, R = -0.34), CD4+ cells (p = 0.02, R = -0.34), CD 45RA+ cells (p = 0.04, R = -0.68).


Fidget spinners: Purported benefits, adverse effects and accepted alternatives.
In the span of a few months, fidget spinners have caught the eyes of millions of children, parents, educators and paediatricians. Fidget spinners, hand-held toys designed to spin freely in your grasp, have become a source of entertainment for consumers of all ages. Despite a lack of scientific evidence, toy marketers have advertised the benefits of fidget spinners for children with attention-deficit/hyperactivity disorder and other disorders (e.g. autism, anxiety, sensory issues). Parents are incentivized by these purported benefits to purchase fidget spinners to improve their child's concentration and decrease stress. While fidget spinners are a new phenomenon, existing therapy toys (e.g. sensory putty) have been used by occupational therapists for similar reasons, with comparably little research supporting these claims. The purpose of this review is to explore literature regarding sensory toys and examine educator/professional-reported concerns and medical adverse effects of using fidget spinners. Due to a recent surge in popularity, fidget spinners and other self-regulatory occupational therapy toys have yet to be subjected to rigorous scientific research. Thus, their alleged benefits remain scientifically unfounded. Paediatricians should be aware of potential choking hazards with this new fad, and inform parents that peer-reviewed studies do not support the beneficial claims.


Molecular-dynamics simulation for liquid chromatographic interactions: effect of mobile phase composition.
A molecular-dynamics simulation method has been applied to investigate the influence of the mobile-phase composition on the retention of solutes in HPLC. The distribution profiles of the distance between two atoms in ODS ligands were constructed to characterize the conformation of ODS ligand molecules. The distinct difference of ODS conformation is observed by comparing molecular models consisting of solvent molecules at each solvent composition. The distribution profiles of the distance between the mobile-phase solvent molecules and ODS ligand molecules were also constructed to characterize the distribution of the solvent molecules at each composition. In all distribution profiles, the difference in the distribution due to a change in the solvent compositions was very clearly found, and the facts seem to be very reasonable. The distribution profiles of the distance between the solute, n-propylbenzene, and the terminal carbon atom in the ODS ligand, and between the solute and the silicon atom in the ODS ligand have been also constructed to see the distribution of the solutes in the separation system. The calculated solute distribution in the ODS-methanol/water system is very consistent with the actual chromatographic retention behaviors.


Serum myeloperoxidase and adenosine deaminase activities in polycystic ovary syndrome.
To evaluate serum myeloperoxidase (MPO) and adenosine deaminase activities and to investigate whether there was a correlation between these and sex hormones, and lipids in polycystic ovary syndrome. Forty-five women with polycystic ovary syndrome and 40 healthy controls were included in this study. Leukocyte counts, serum MPO and adenosine deaminase activities, and high-sensitive C-reactive protein (hs-CRP), sex hormone and lipid levels were assessed. Leukocyte counts and serum MPO activities were higher (p < 0.01 and p < 0.05, respectively) and there was a significant correlation between serum adenosine deaminase and hs-CRP level in women with polycystic ovary syndrome (r = 0.853, p < 0.01). Serum MPO and adenosine deaminase levels did not correlate with sex hormones or lipid profiles in these patients. Polycystic ovary syndrome may involve an inflammatory process by increasing serum MPO activity independent of sex hormones, body mass index and lipid profiles.


Cognitive function and elderly macronutrient intakes from rural diets in Qingdao, China.
Energy provided by macronutrients plays a key role in healthy aging. This study therefore explored the association between macronutrients and cognitive function in elderly populations in rural areas of Qingdao, China. This study included 1,504 participants over the age of 65 recruited from Licha Town, Qingdao City, China. Dietary intake was measured using the Food Frequency Questionnaire, and cognitive function was assessed using the Mini-Mental State Examination. Logistic regression models were used to evaluate the association between dietary macronutrient intake and cognitive function. In addition, restricted cubic bars were applied to determine the dose-response relationship between macronutrient ratios and cognitive performance. A total of 877 adults over the age of 65 were included. After adjusting the weighted multiple variables, significant positive associations were revealed between protein and moderate carbohydrate intake and cognitive ability, but a negative association between fat intake and cognitive performance was identified. After calculating the daily energy supply ratio, similar associations were revealed between fat and protein intake and cognitive function. Furthermore, the ratio of proteins to carbohydrates had a U-shaped relationship with cognitive function (pnonlinearity=0.674), whereas the ratio of proteins to fats was L-shaped with lower cognitive function (pnonlinearity<0.001). Compared with the lowest quartile of the ratio of protein to fat intake, the weighted adjusted OR (95% CI) of the highest quartile was 0.509 (0.314, 0.827) for low cognitive performance. With an adequate carbohydrate supply, appropriately increasing dietary protein intake and reducing fat intake might benefit the cognitive function of elders in rural areas.


In situ detection of Epstein-Barr virus in gastric and colorectal adenocarcinomas.
The association of Epstein-Barr virus (EBV) with lymphoepithelioma-like carcinoma in the nasopharynx, which is common in Chinese from the southern region, is well established. Recently, EBV has also been found to be associated with lymphoepithelioma-like carcinomas (LELCs) and carcinomas with prominent lymphoid infiltrates in the stomach. We investigated for the presence of EBV in 74 cases of gastric adenocarcinoma and 36 cases of colorectal adenocarcinoma from Chinese patients by in situ hybridization (ISH) using an antisense EBER probe. In seven cases (9.5%) of gastric carcinoma, EBER was highly expressed in the adenocarcinoma cells and metastatic tumor cells in regional lymph nodes. In all these cases, the normal gastric epithelium was EBV negative. None of the colorectal carcinomas showed a positive signal. Isolated positive lymphoid cells were frequently found in both tumors. Of the seven positive cases, only one was LELC, and the others were conventional adenocarcinomas of the intestinal type. Five showed expression of the viral RNA in all tumor cells as well as the surrounding dysplastic epithelium. Interestingly, the sixth case showed distinct negative islands of dysplastic glands adjacent to strongly positive dysplastic glands and invasive carcinoma cells. This pattern of positivity, together with negative normal gastric epithelium and positive metastatic tumor, suggested that EBV infection occurred in the dysplastic phase and that an apparent growth advantage was conferred by the EBV infection.


[Biochemical and genetic mechanisms for bacteria to acquire aminoglycoside antibiotic resistance].
Aminoglycoside (AG)-modifying enzymes are the major biochemical basis for the AG resistance of clinically-occurring bacteria. Recent AG resistance profiles can be characterized by the involvement of AAC(6') in combination with other modifying enzymes in Gram negative bacteria. AAC(6')/APH(2") in Staphylococcus aureus is also remarkable. Genetic basis for the emergence or alteration of AG resistance profiles includes point mutations in the regulatory region or specific sites of the coding region of AG-modifying enzyme genes, and rearrangement of the genes caused by transposon and/or integron. In addition, semisynthetic AG antibiotics such as amikacin, arbekacin (ABK) and isepamicin were also reviewed for their stability to AG-modifying enzymes. ABK that has been widely used as an anti-MRSA drug in Japan is distinct from the other AGs because its monoacetylated derivatives (3"-N-acetylABK and 2'-N-acetylABK) by AG acetyltransferases, AAC(3) and AAC(2'), respectively, retain clear antibiotic activities. Based on this novel aspect and the lack of modification sites for APH(3') and ANT(4'), ABK should be regarded as the most refractory AG for bacteria to acquire resistance.


Coping behaviors of children hospitalized for cardiac surgery: a secondary analysis.
While the coping behaviors of hospitalized children continue to be an area of interest for researchers, systematic documentation in the literature concerning children's coping remains limited. In this descriptive secondary analysis, 23 master's thesis case studies were analyzed to determine how researchers described the range of coping behaviors that children used while hospitalized for cardiac surgery. The analysis sought to determine patterns of coping in both preschool and school-age children. A second aim was to validate further and refine the dimensions and items of the Children's Coping Behaviors Category System developed by Ritchie, Caty, and Ellerton in 1987. Results revealed that a broad range of names and labels of behavior was used to describe children's coping. The predominant patterns of behavior that emerged were direct action and information-seeking. Differences between preschool and school-age children's reported behaviors were evident. The coping category system was validated further and refinements are suggested.


Safe application of a 13-Gy split dose total body irradiation schedule prior to bone marrow transplantation.
Two conditioning regimens for bone marrow transplantation for patients with acute lymphoblastic leukaemia were compared. Both regimens (VVRAPID and VVRAPID-X) incorporated the same cytotoxic chemotherapy but differed in the radiation dose; VVRAPID employed a single fraction of 10.5 Gy and VVRAPID-X employed 10.5 Gy followed 4 days later by a further dose of 2.5 Gy. The 13-Gy split-fraction schedule was well tolerated with no significant increase in infection or requirement for blood products. An increase in gastrointestinal toxicity occurred but responded to increased oral anti-diarrhoeal agents. Overall survival and relapse rates did not differ significantly between the two groups. There was a trend for the 13-Gy schedule to reduce the graft failure rate following T cell-depleted bone marrow transplants.


Metabotropic glutamate receptor-mediated use-dependent down-regulation of synaptic excitability involves the fragile X mental retardation protein.
Loss of the mRNA-binding protein FMRP results in the most common inherited form of both mental retardation and autism spectrum disorders: fragile X syndrome (FXS). The leading FXS hypothesis proposes that metabotropic glutamate receptor (mGluR) signaling at the synapse controls FMRP function in the regulation of local protein translation to modulate synaptic transmission strength. In this study, we use the Drosophila FXS disease model to test the relationship between Drosophila FMRP (dFMRP) and the sole Drosophila mGluR (dmGluRA) in regulation of synaptic function, using two-electrode voltage-clamp recording at the glutamatergic neuromuscular junction (NMJ). Null dmGluRA mutants show minimal changes in basal synapse properties but pronounced defects during sustained high-frequency stimulation (HFS). The double null dfmr1;dmGluRA mutant shows repression of enhanced augmentation and delayed onset of premature long-term facilitation (LTF) and strongly reduces grossly elevated post-tetanic potentiation (PTP) phenotypes present in dmGluRA-null animals. Null dfmr1 mutants show features of synaptic hyperexcitability, including multiple transmission events in response to a single stimulus and cyclic modulation of transmission amplitude during prolonged HFS. The double null dfmr1;dmGluRA mutant shows amelioration of these defects but does not fully restore wildtype properties in dfmr1-null animals. These data suggest that dmGluRA functions in a negative feedback loop in which excess glutamate released during high-frequency transmission binds the glutamate receptor to dampen synaptic excitability, and dFMRP functions to suppress the translation of proteins regulating this synaptic excitability. Removal of the translational regulator partially compensates for loss of the receptor and, similarly, loss of the receptor weakly compensates for loss of the translational regulator.


Effect of gossypol-acetic acid on calcium transport and ATPase activity in plasma membranes from ram and bull spermatozoa.
The effects of gossypol acetic acid on the activity of Mg-ATPase and Ca-Mg-ATPase and on calcium uptake by plasma membranes from ram and bull spermatozoa were examined. The three parameters were almost completely inhibited by 10 microM gossypol for both ram and bull sperm. In order to assess the effects of higher gossypol concentrations isolated membrane vesicles were loaded with calcium by operating the ATP-dependent calcium pump after which gossypol was added and calcium uptake followed. At 10 microM gossypol, additional calcium uptake was 85% inhibited while at 40 microM a release of the accumulated calcium was observed. The inhibitory effect of 10 microM gossypol was almost completely reversible by simple dilution of gossypol-treated membranes, whilst at 40 microM the effect was only 50% reversible. The data show a high degree of similarity between bull and ram, suggesting minimal differences between the two species as far as the structure and function of the sperm plasma membrane is concerned.


Adaptive and platform trials in remote damage control resuscitation.
The traditional approach to clinical trial design requires assuming precise values for multiple unknown parameters, resulting in a trial design that is unlikely to perform well if one or more of those assumptions turn out to be incorrect. During conduct of the trial, trial characteristics are often held fixed, even if incoming data suggest that one or more design assumptions were incorrect. This leads to an increased risk of a failed trial. In contrast, an adaptive clinical trial is designed to take advantage of partial, incoming data during the conduct of the trial, modifying key clinical trial characteristics according to prespecified rules, in order to avoid a failed or inconclusive trial, improve statistical efficacy, better treat patients within the trial, or achieve other scientific or ethical goals. The concept of an adaptive trial can be expanded to a platform trial, a clinical trial that is intended to evaluate multiple treatments or combinations of treatments, often for patients with any of a group of related diseases, and to continue beyond the evaluation of any particular treatment. Platform trial design strategies can be applied to the problem of finding the best treatment strategy for patients suffering from posttraumatic hemorrhagic shock. We present the rationale and considerations surrounding adaptive and platform trial design and apply these concepts to the problem of investigating strategies for remote damage control resuscitation.


Body cavity lipomas in six dogs.
Histologically confirmed lipomas were surgically removed from the thoracic or abdominal cavities of six dogs. Three dogs had a large intra-abdominal mass causing severe abdominal distension. Two dogs had a mass extending into the pelvic canal, compressing the colon and causing obstipation. One dog with an intrathoracic mass had a history of coughing and intermittent cyanosis. All dogs had complete resolution of signs after surgical resection of the tumour. Recurrence occurred in one dog with an abdominal lipoma, two years after the initial surgery. This recurrent lipoma was treated successfully by surgical resection.


Microbial contamination of the Tzu-Chi Cord Blood Bank from 2005 to 2006.
In total, 4502 units of cord blood (CB) were collected during a 2-year period from 2005 to 2006 by the Buddhist Tzu-Chi Stem Cells Center. The aim of this study was to analyze the incidence of microbial contamination and type of organism present in the cord blood. The clinical impact of microbial contamination on hematopoietic progenitor cell (HPC) grafts used for HPC transplantation is also discussed. First and second specimens were obtained for microbial assessment. These were collected in laboratory after cord blood collection and after cord blood unit manipulation, respectively. The samples were cultured and the results reviewed. The overall incidence of microbiological contamination was 1.8% (82/4502). Three CB units were contaminated with two different organisms. Infectious organisms comprised 9.4% (8/85) of total isolated microbes. These infectious microorganisms were beta-Streptococci group B, Candida tropicalis and Staphylococcus aureus which were isolated in 6, 1 and 1 of CB units respectively. Escherichia coli, Bacteroides fragilis, Lactobacillus spp., Enterococcus, beta-Streptococcus Group B, Bacteroides valgatus, Corynebacterium spp., Klebsiella pneumonia and Peptococcus spp. were the most frequently encountered microorganisms. A higher contamination rate of the CB units was noted after vaginal delivery (2.16%) compared to caesarian section (0.85%) (p < 0.01). Extensive training in CB collection, good procedures and good protocols can decrease the rate of microbial contamination. The use of a closed collecting system and an ex utero method have the advantage of a lower contamination rate. In our cord blood bank, we use a closed system but an in utero method. Similar to other studies, most of microorganisms reported here as contaminants are non-pathogenic.


Investigation of irradiated volume in linac-based brain hypo-fractionated stereotactic radiotherapy.
Emerging techniques such as brain hypo-fractionated radiotherapy (HF-RT) involve complex cases with limited guidelines for plan quality and normal tissue tolerances. The purpose of the present study was to statistically parameterize irradiated volume independently of dose prescription, or margin to determine what spread in achievable irradiated volume one may expect for a given case. We defined EXT as the total tissue within the external contour of the patient (including the target) and we defined BMP as the contour of the brain minus PTV. Irradiated volumes of EXT and BMP at specific doses (i.e. 50, 60%, etc., of the prescribed dose) were extracted from 135 single-target HF-RT clinical cases, each planned with a single-arc, homogeneous (SAHO) approach in which target maximum dose (Dmax) was constrained to <130% of the prescribed dose. Irradiated volumes were subsequently measured for cases involving 2 targets (N = 29), 3 targets (N = 7) and >3 targets (N = 10) to investigate the effect of target number. We also examined the effect of shape complexity. A series of best fit curves with confidence and prediction intervals were generated for irradiated volume versus total target volume and the resulting model was subsequently validated on a subsequent set of 23 consecutive prospective cases not originally used in curve-fitting. A subset of 30 HF-RT cases were re-planned with a well-published four-arc, heterogeneous (FAHE) radiosurgery planning approach (Dmax could exceed 130%) to demonstrate how technique affects irradiated volume. For SAHO, strong correlation (R2 > 0.98) was found for predicting irradiated volumes. For a given total target volume, irradiated-volume increased by a range of 1.4-2.9× for >3 versus single-targets depending on isodose level. Shape complexity had minor impact on irradiated volume. There was no statistical difference in irradiated volumes between validation and input data (p > 0.2). The FAHE-generated irradiated volumes yielded curves and prediction and confidence bands that agreed well with published data indicating that the proposed approach is feasible for cross-institutional comparisons. A description of irradiated volume for linac-based HF-RT is proposed based on population data. We have demonstrated that the proposed approach is feasible for inter and intra-institutional comparisons.


V(D)J recombination: modulation of RAG1 and RAG2 cleavage activity on 12/23 substrates by whole cell extract and DNA-bending proteins.
Antigen receptor gene rearrangement is directed by DNA motifs consisting of a conserved heptamer and nonamer separated by a nonconserved spacer of either 12 or 23 base pairs (12 or 23 recombination signal sequences [RSS]). V(D)J recombination requires that the rearranging DNA segments be flanked by RSSs of different spacer lengths, a phenomenon known as the 12/23 rule. Recent studies have shown that this restriction operates at the level of DNA cleavage, which is mediated by the products of the recombination activating genes RAG1 and RAG2. Here, we show that RAG1 and RAG2 are not sufficient for 12/23 dependent cleavage, whereas RAG1 and RAG2 complemented with whole cell extract faithfully recapitulates the 12/23 rule. In addition, HMG box containing proteins HMG1 and HMG2 enhance RAG1- and RAG2-mediated cleavage of substrates containing 23 RSS but not of substrates containing only 12 RSS. These results suggest the existence of a nucleoprotein complex at the cleavage site, consisting of architectural, catalytic, and regulatory components.


Complementary DNA sequence of the novel HLA-B*3704 allele.
The novel HLA-B*3704 allele was identified by polymerase chain reaction with sequence specific oligoneucletides (PCR-SSO) in a Spanish Caucasoid individual whose T-lymphocytes showed an ambiguous HLA-B phenotype. The nucleotide sequence of B*3704 was determined after reverse transcription-polymerase chain reaction (RT-PCR) amplification and molecular cloning of its complete coding region. B*3704 differs from B*3701 by a single nucleotide replacement that induces the substitution of histidine for tyrosine 171. Residue 171 is located in the alpha-helix of the alpha-2 domain, lining the A pocket of the peptide-binding site. Therefore, the His171 substitution seen in HLA-B*3704 is likely to affect its antigen-presenting properties and is probably responsible for the differentiated serological phenotype of this allele in comparison with B*3701.


Emergency cesarean section and the 30-minute rule: definitions.
We explored the role that lack of a standard definition and heterogeneity in patient selection criteria in the literature might have on the apparent inability to routinely begin an emergency cesarean section in less than 30 minutes. A review of the literature on emergency cesarean delivery was performed. Although there are some similarities in definitions and the criteria used for patient selection in multiple studies, the variability in the definitions could be responsible for some of the apparent timeliness performance deficiency in the literature. A standard definition and directions for future research are suggested.


Relaxation practice for health in the United States: findings from the National Health Interview Survey.
Despite the popularity of relaxation practices as mind-body therapy in the United States, little is known about those who practice these techniques. Using cross-sectional data from the 2007 National Health Interview Survey Alternative Medicine Supplement, this study examined potential correlates of engagement in relaxation practices, including sociodemographic characteristics, health behaviors, medical conditions, physical activity, drinking, smoking, and prayer for health. Individuals who engaged in relaxation practices were less likely to be older, male, Hispanic, high income, or residents in the South and Midwest. They were more likely to be college-educated, uninsured, and have one to two chronic conditions. Those with higher psychological distress and with asthma and pulmonary diseases practiced relaxation techniques more than individuals without these conditions. Findings suggest that relaxation practice is associated with lifestyles habits such as regular physical activity and prayer for health. Thus, relaxation practice has the potential to enhance health behaviors and lifestyle change.


ECG artifacts during intraoperative high-field MRI scanning.
High-field magnetic resonance imaging (MRI) (1.5 T) has recently been introduced into the neurosurgical operating room for intraoperative resection control and functional neuronavigational guidance. However, long-lasting neurosurgical procedures in an operating room equipped with a high-field MRI scanner raise new challenges to the anesthesiologist. In particular, monitoring of vital signs during anesthesia requires equipment compatible with working in close vicinity to the strong magnetic field. However, even MRI-compatible electrocardiographic (ECG) monitoring interferes with electromagnetic fields, so several ECG artifacts can be observed in static and pulsed magnetic fields. As shown in this study, pulsed high-frequency fields induce characteristic field frequency-based artifacts in the ECG that can imitate malignant arrhythmia or provoke ST-segment abnormalities. The knowledge of possible and characteristic ECG artifacts during high-field MRI is therefore essential to prevent misinterpretation. Moreover, interference-free parameters such as pulse oximetry or invasive blood pressure curves are highly relevant during intraoperative MRI scans.


[Significance of the level of implantation of the 'E-vita open plus' hybrid stent graft into the descending aorta in the development of spinal ischaemic complications].
Spinal ischaemia in patients after reconstruction of the thoracic aorta is referred to the category of the most severe postoperative complications, especially in hybrid interventions. The present study was aimed at assessing the risks for the development of spinal ischaemia in patients after implantation of the 'E-vita open plus' stent graft into the descending portion of the thoracic aorta during hybrid reconstruction. The 'E-vita open plus' hybrid stent graft (Jotec, Germany) was implanted to 18 patients presenting with various pathology of the thoracic aorta (dissection, aneurysms). All operations were carried out in the conditions of moderate hypothermia, circulatory arrest and antegrade perfusion of the brain through the brachiocephalic trunk. It was determined that the distal end of the stent graft was located at the level of Th7-Th12. In 12 (66.7%) cases the 'lower' edge of the stent graft was located at the level of thoracic vertebrae Th8-Th9. Before the operation the number of open pairs of intercostal arteries amounted to 10 [9, 11]. After the operation, the number of the open pairs of the segmental arteries amounted to 3 [1; 4], they were all in the lower thoracic portion; the above-located intercostal arteries were shut by the stent graft. In 17 (94.5%) cases in the early postoperative period there were no signs of spinal ischaemia. Only one (5.5%) patient was clinically diagnosed to have developed transient spinal ischaemia noted to disappear spontaneously within the first 24 hours. A conclusion was made that using the 'E-vita open plus' stent graft in the course of hybrid reconstruction of the thoracic aorta was accompanied by the minimal risk for spinal ischaemic complications. The level of the location of the distal edge of the stent graft is not the determining factor in the risks of spinal complications in of such similar operations.


Intrapartum transmission of group A streptococcus.
Intrapartum transmission of group A streptococcus has not been well documented. As the incidence of severe infections due to this organism has recently increased, it is important to assess if such transmission occurs. We observed two cases of severe neonatal infections due to group A streptococcus, one of which was fatal, that appeared to have been transmitted from the mother during birth. Perinatal prophylaxis, which has been recommended for infections due to group B streptococcus, should be evaluated for infections due to group A streptococcus.


Knowledge and Practice of Health Care Providers Towards Proper Face Mask Utilization to Minimize the Extent of COVID-19 Infection in Amhara Region Referral Hospitals, Ethiopia.
The novel coronavirus disease (COVID-19) pandemic began in early 2020, causing tens of thousands of deaths, over a million cases, and widespread socioeconomic disruption. The aim of the study was to assess health care workers' knowledge and practice of proper face mask utilization to prevent the spread of COVID-19 infection in Amhara region referral hospitals, Ethiopia. A cross-sectional institutional-based quantitative study design was conducted from May 15 to 30/2020 using pre-tested self-administrated questionnaire and analyzed by using SPSS version 20.0. The study included 422 health care providers, and the sample size was determined using a single population proportion formula with the assumption of a p value of 0.05. Data were collected using a consecutive sampling technique from all referral hospitals and were analyzed using descriptive statistics. Finally, the outcome was presented in the form of a text and a table. The overall knowledge and practice of health care providers regarding proper face mask utilization were 278 (65.8%) and 252 (59.5%), respectively. Of them, 284 (67.3%) knew that face masks were worn with the white side facing in, 264 (62.6%) knew that face masks had three layers, and 331 (78.4%) knew that surgical face masks were worn for up to 8 hours. The respondent's knowledge of proper face mask usage was high, in comparison with another studies but the proper utilization of face mask was relatively low. Ethiopian ministry of health in collaboration with Amhara region, zonal and woreda health institution works together to increase utilization of face mask and to alleviate scarcity of resource and provide training to the health care providers about the proper utilization of face mask to tackle COVID-19.


Medicaid prescription cost containment and schizophrenia: a retrospective examination.
In 2002, the Mississippi Division of Medicaid enacted several policies to curb prescription spending including increasing prescription copayments from $1 to $3 per brand, a cap of 7 prescriptions per month, a 34-day supply limitation, and a 5% reduction in dispensing fees. The objectives of this study were to examine the influence of these policies on (1) compliance to antipsychotic medications and (2) mental health care utilization and payments among patients with schizophrenia. This study used a 12-month pretest and 12-month posttest longitudinal design to compare the effect of these policies among patients with schizophrenia in Minnesota and Indiana, who had less restrictive cost-containment using administrative claims data. Generalized estimating equations were used to run difference in difference models to compare medication compliance (proportion of days covered) and health care utilization in Mississippi to the control states. After policy adoption, patients in Mississippi were 4.87% less compliant with antipsychotic treatments and experienced 20.5% more 90 day antipsychotic treatment gaps than patients in the control states. Although these policies did not affect inpatient or emergency department care among patients with schizophrenia, there was a 3.7% reduction in outpatient mental health visits and a 4.2% reduction in mental health care payments. Despite the potential for savings, policy makers should consider carefully the potential adverse consequences that may arise from implementing aggressive cost-containment policies among patient with severe mental illness.


Primary breast lymphoma successfully treated with combination therapy including local radiation therapy: a report of two cases.
Recently, a combination of local irradiation and chemotherapy has been suggested as a standardized treatment for localized lymphoma. However, it has been difficult to establish a standard treatment for localized primary breast lymphoma simply because of its rarity. We report two cases of primary breast lymphoma successfully treated with a combination therapy including local radiation therapy. A 46-year-old woman with stage I primary breast lymphoma was irradiated with 30 Gy to the involved breast by 4 MV X-rays and 9 Gy to the involved field by electron beam after tumorectomy. Then three cycles of CHOP therapy were performed. She has been well and has shown no evidence of disease for 58 months. A 72-year-old woman with stage II primary breast lymphoma was treated with three cycles of CHOP therapy followed by irradiation with 40 Gy per breast by 4 MV X-rays. She is well and has been disease-free for 49 months. We suggest that a combination of local irradiation and short course of chemotherapy can be useful in the treatment of primary breast lymphoma.


Removal of hexavalent chromium with a lignocellulosic substrate extracted from wheat bran.
In this paper, a new recovery system of the toxic hexavalent chromium Cr(VI) is proposed that uses a lignocellulosic substrate derived from the industrial treatment process of wheat bran. We studied the adsorption mechanism of Cr(VI) onto the lignocellulosic substrate and showed that the adsorption reaction consumes a large amount of protons goes along the reduction of Cr(VI) into Cr(III). The oxidation of lignin moieties takes place concurrently to the chromium reduction and leads to the formation of hydroxyl and carboxyl functions. The latter contribute to an increase in the number of ion-exchange sites for the reduced chromium. The maximum adsorption capacity for hexavalent chromium was found at about 35 mg g(-1) in an acidic medium. This is comparable to other natural substrates and ordinary adsorbents.


1,2-Difunctionalization-type (hetero)arylation of unactivated alkenes triggered by radical addition/remote (hetero)aryl migration.
A novel difunctionalization-type (hetero)arylation of unactivated alkenes has been developed via remote 1,4(5)-(hetero)aryl migration triggered by radical alkene azidation, trifluoromethylation, or phosphonylation. The overall process serves as an unusual and reliable approach for straightforward access to diversely substituted ketones with broad functional group compatibility from readily available substrates and reagents.


Catching objects thrown to oneself: Testing control strategies for object interception in a novel domain.
A considerable amount of research has been performed to determine the strategies people use to intercept moving objects. Much of this research has been done using target objects such as baseballs and Frisbees that are launched to people from distances ranging from 10 m to 50 m. This research has qualified the range of domains in which each strategy is effective, but there is still controversy regarding which strategy has the most general application. The present research sought to further reduce the range of possible domains in which these strategies work by testing object interception in a situation that had never been tested before, where people launch the target objects to themselves. A strategy based on controlling optical velocity--acting to keep the optical velocity of the object at zero--provided the best match to catcher ground movements and optical trajectories. These results suggest that control of optical velocity is currently the best explanation of effective interception of both other- and self-launched objects.


Hepatitis C virus infects T cells and affects interferon-gamma signaling in T cell lines.
It has been reported that hepatitis C virus (HCV) may infect and replicate in human T cells, particularly in perihepatic lymph nodes, but the extent and consequence of T-cell infection in patients is unclear. This study is conducted to characterize the parameters and functional consequences of HCV infection in T lymphocytes. By using a lymphotropic HCV strain, we showed that HCV could infect T cell lines (Molt-4 and Jurkat cells) in vitro. Both positive- and negative-strand HCV RNA were detected for several weeks after infection. Viral proteins could also be detected by immunofluorescence studies. Moreover, infectious HCV particles were produced from Molt-4 cell cultures, and could be used to infect naïve T cell lines. HCV could also infect human primary CD4+ T cells, particularly naïve (CD45RA+CD45RO-) CD4+ cells, in culture. The amounts of STAT-1 and phosphorylated STAT-1 proteins in the infected Molt-4 cells were significantly less than those in uninfected cultures, suggesting the possibility of defect in interferon-gamma signaling. Indeed, T-bet and STAT-1 mRNA levels after interferon-gamma stimulation in infected Molt-4 were suppressed. In conclusion, HCV could infect and transiently replicate in T cells and that HCV replication suppressed the IFN-gamma/STAT-1/T-bet signaling due to the reduction of STAT-1 and inhibition of its activation (phosphorylation).


Percutaneous renal mass biopsy: historical perspective, current status, and future considerations.
Percutaneous renal mass biopsy has evolved over the last decade with improvements on previous pitfalls including low tissue yield, high non-diagnostic rates, and complications. As understanding of tumor biology and natural history of renal cortical neoplasms has improved, percutaneous renal mass biopsy is poised to have an expanding role in an area characterized by individualized management and refined risk stratification. Areas covered: This review summarizes the evolution of renal mass biopsy to its current state with respect to outcomes, indications, and clinical guidelines. Expert opinion: With improved understanding of differential biological potential of renal cortical neoplasms combined with technical improvements in diagnostic yield and accuracy, utilization of renal mass biopsy is becoming an important adjunct to patient care in a broad range of clinical scenarios, including active surveillance, thermal ablation, and use of primary systemic therapy in localized and advanced settings.


Screening for ectopic pregnancy in symptom-free women at increased risk.
To determine the ectopic pregnancy rate among symptom-free women at increased risk undergoing a screening program involving transvaginal sonography and serum hCG testing. Consecutive symptom-free women at increased risk for ectopic pregnancy were studied prospectively by transvaginal sonography and serum hCG measurement to detect ectopic pregnancy before the onset of symptoms. Between September 1993 and May 1996, 143 symptom-free pregnant women with pregnancies of a gestational age of less than 7 weeks were screened. Eight had ectopic pregnancies, 129 had intrauterine pregnancies, and six had trophoblast in regression. Among the eight women with ectopic pregnancies, one was initially diagnosed as having an intrauterine pregnancy. This women returned 1 week later with abdominal pain, and an ectopic pregnancy with intra-abdominal bleeding was found. Ectopic pregnancies were present in 5.6% (95% confidence interval 2.5%, 10.7%) of the women screened. This was significantly lower than reported in a previous study. The ectopic pregnancy rate in the population that was offered screening was low. Thus, it is questionable whether the possible benefits (prevention of complications and reassurance of the woman) outweigh possible detriments (false-positive diagnosis, financial costs, and emotional stress that could be induced by screening.


Standard versus no post-filter ionized calcium monitoring in regional citrate anticoagulation for continuous renal replacement therapy (NPC trial).
Current guidelines recommend monitoring of post-filter ionized calcium (pfCa) when using regional citrate anticoagulation during continuous renal replacement therapy (RCA-CRRT) to determine citrate efficiency for the prevention of filter clotting. However, the reliability of pfCa raises the question of whether routine monitoring is required. Reducing the frequency of pfCa monitoring could potentially reduce costs and workload. Our objective was to test the efficacy and safety of no pfCa monitoring among critically ill patients receiving RCA-CRRT. This study was a non-inferiority randomized controlled trial conducted between January 2021 and October 2021 at King Chulalongkorn Memorial Hospital, Thailand. Critically ill patients who were treated with RCA-CRRT were randomized to receive either standard pfCa monitoring (aiming pfCa level of 0.25-0.35 mmol/L), or no pfCa monitoring, in which a constant rate of citrate infusion was maintained at pre-determined citrate concentrations of 4 mmol/L with blinding of pfCa levels to treating clinicians. The primary outcome was the filter lifespan. Non-inferiority would be demonstrated if the upper limit of the 95% confidence interval (CI) for the difference in filter lifespan between the groups was less than 20 h. Fifty patients were randomized to the standard pfCa monitoring group (n = 25) or no pfCa monitoring group (n = 25). The mean filter lifespan was 54 ± 20 h in the standard pfCa monitoring group and 47 ± 23 h in the no pfCa monitoring group (absolute difference 7.1 h; 95% CI -5.3, 19.5, P = .25). When restricting the analysis to circuits reaching the maximum duration of circuit lifespan at 72 h and clotted filters, the filter lifespan was 61 ± 17 h in the standard pfCa group vs 60 ± 19 h in the no pfCa monitoring group (absolute difference 0.9 h; 95% CI -11.5, 13.4, P = .88). Compared with the no pfCa monitoring group, the standard pfCa monitoring group had a significantly higher mean citrate concentrations (4.43 ± 0.32 vs 4 mmol/L, P < .001) and a higher rate of severe hypocalcemia (44% vs 20%, P = .13). No statistical differences were found in filter clotting, citrate accumulation, citrate overload and mortality between the two groups. Among critically ill patients receiving RCA-CRRT, no pfCa monitoring by maintaining the citrate concentrations of 4 mmol/L is feasible. Larger randomized controlled trials should be conducted to ensure the efficacy, safety and cost-effectiveness of this strategy. ClinicalTrials.gov: NCT04792424 (registered 11 March 2021).


Megestrol acetate in the treatment of hormone refractory prostate cancer.
This retrospective study evaluates the efficacy of megestrol acetate in patients with hormone refractory metastatic adenocarcinoma of the prostate. Data are presented from 14 patients with advanced prostatic adenocarcinoma who were treated with 160-320 mg of megestrol acetate daily. Each patient was either asymptomatic or had minimal cancer-related symptoms. Disease response was monitored by prostate-specific antigen levels. The response rate was 14%, with two patients having a partial response. No complete responses were observed. The median time to disease progression was 2 months. Our findings when considered together with results from previously published data demonstrate little activity of megestrol acetate in patients with hormone refractory prostate cancer. Therefore, we cannot recommend megestrol acetate as an effective second-line therapy.


Aquatic toxicity assessment of phosphate compounds.
Tricalcium phosphate and calcium hydrogenorthophosphate are high production volume chemicals, mainly used as foodstuff additives, pharmaceuticals, lubricants, synthetic resin, and disinfectants. Phosphate has the potential to cause increased algal growth leading to eutrophication in the aquatic environment. However, there is no adequate information available on risk assessment or acute and chronic toxicity. The aim of this research is to evaluate the toxic potential of phosphate compounds in the aquatic environment. An aquatic toxicity test of phosphate was conducted, and its physico-chemical properties were obtained from a database recommended in the Organization for Economic Cooperation and Development (OECD) guidance manual. An ecotoxicity test using fish, Daphnia, and algae was conducted by the good laboratory practice facility according to the OECD TG guidelines for testing of chemicals, to secure reliable data. THE RESULTS OF THE ECOTOXICITY TESTS OF TRICALCIUM PHOSPHATE AND CALCIUM HYDROGENORTHOPHOSPHATE ARE AS FOLLOWS: In an acute toxicity test with Oryzias latipes, 96 hr 50% lethal concentration (LC(50)) was >100 (measured:>2.14) mg/L and >100 (measured: >13.5) mg/L, respectively. In the Daphnia test, 48 hr 50% effective concentration (EC(50)) was >100 (measured: >5.35) mg/L and >100 (measured: >2.9) mg/L, respectively. In a growth inhibition test with Pseudokirchneriella subcapitata, 72 hr EC(50) was >100 (measured: >1.56) mg/L and >100 (measured: >4.4) mg/L, respectively. Based on the results of the ecotoxicity test of phosphate using fish, Daphnia, and algae, L(E)C(50) was above 100 mg/L (nominal), indicating no toxicity. In general, the total phosphorus concentration including phosphate in rivers and lakes reaches levels of several ppm, suggesting that phosphate has no toxic effects. However, excessive inflow of phosphate into aquatic ecosystems has the potential to cause eutrophication due to algal growth.


Non-Invasive Fetal Monitoring: A Maternal Surface ECG Electrode Placement-Based Novel Approach for Optimization of Adaptive Filter Control Parameters Using the LMS and RLS Algorithms.
This paper is focused on the design, implementation and verification of a novel method for the optimization of the control parameters (such as step size μ and filter order N) of LMS and RLS adaptive filters used for noninvasive fetal monitoring. The optimization algorithm is driven by considering the ECG electrode positions on the maternal body surface in improving the performance of these adaptive filters. The main criterion for optimal parameter selection was the Signal-to-Noise Ratio (SNR). We conducted experiments using signals supplied by the latest version of our LabVIEW-Based Multi-Channel Non-Invasive Abdominal Maternal-Fetal Electrocardiogram Signal Generator, which provides the flexibility and capability of modeling the principal distribution of maternal/fetal ECGs in the human body. Our novel algorithm enabled us to find the optimal settings of the adaptive filters based on maternal surface ECG electrode placements. The experimental results further confirmed the theoretical assumption that the optimal settings of these adaptive filters are dependent on the ECG electrode positions on the maternal body, and therefore, we were able to achieve far better results than without the use of optimization. These improvements in turn could lead to a more accurate detection of fetal hypoxia. Consequently, our approach could offer the potential to be used in clinical practice to establish recommendations for standard electrode placement and find the optimal adaptive filter settings for extracting high quality fetal ECG signals for further processing. Ultimately, diagnostic-grade fetal ECG signals would ensure the reliable detection of fetal hypoxia.


Effects of torsional rigidity on fracture healing: strength and mineralization in rat femora.
To assess the effects of torsional rigidity and dynamization on fracture healing in a medullary nailed rat femoral model. Randomized study in male Wistar rats with a diaphyseal osteotomy/fracture. Reamed cannulated nailing was performed in sixty rats. One group (twenty rats) received unlocked nails (UL group) and another group received nails with proximal and distal locking that was dynamized after twenty days (DL group). The third group was statically locked (SL group). A fourth group of twenty rats served as the control group. After randomization, the femurs of ten rats in each group at six and twelve weeks were studied clinically, radiologically, and biomechanically, and bone mineralization was measured by dual-energy x-ray absorptiometry (DEXA). Radiographs in two planes revealed clearly visible fractures at six weeks, and at twelve weeks bridging callus was apparent in all three treatment groups. The callus area in the UL group was significantly larger at six weeks than in the other groups, and at twelve weeks the UL and DL groups had larger callus areas than the SL group. Biomechanically, UL nails had reduced maximum bending load at six and twelve weeks, while DL nails had increased fracture energy at six weeks compared with SL nails. Bone mineral content and bone mineral density in the callus segment and diaphysis were increased with DL nails at six weeks. This animal study indicates that (a) interlocked nailing has a beneficial effect on bone healing and (b) although dynamization may have a beneficial effect on the quality of early bone healing, (c) dynamization does not increase the rate of bony union. The clinical implication is that routine early dynamization of locked femoral fractures may not be indicated, reserving dynamization to cases of delayed union.


The human chorion contains definitive hematopoietic stem cells from the fifteenth week of gestation.
We examined the contribution of the fetal membranes, amnion and chorion, to human embryonic and fetal hematopoiesis. A population of cells displaying a hematopoietic progenitor phenotype (CD34++ CD45low) of fetal origin was present in the chorion at all gestational ages, associated with stromal cells or near blood vessels, but was absent in the amnion. Prior to 15 weeks of gestation, these cells lacked hematopoietic in vivo engraftment potential. Differences in the chemokine receptor and β1 integrin expression profiles of progenitors between the first and second trimesters suggest that these cells had gestationally regulated responses to homing signals and/or adhesion mechanisms that influenced their ability to colonize the stem cell niche. Definitive hematopoietic stem cells, capable of multilineage and long-term reconstitution when transplanted in immunodeficient mice, were present in the chorion from 15-24 weeks gestation, but were absent at term. The second trimester cells also engrafted secondary recipients in serial transplantation experiments. Thus, the human chorion contains functionally mature hematopoietic stem cells at mid-gestation.


[Double-edged sword of opioids in the treatment of cancer pain: hyperalgesia].
Hyperalgesia is an occult complication during the treatment of cancer pain, not only related to opioids, but also pertaining to the tumor itself and cancer therapeutic drugs. Yet it is often ignored by clinicians. Patients with cancer pain who were treated with opioids often have sensory abnormalities presented with reduced pain threshold and increased sensitivity to nociceptive stimuli. This phenomenon is clinically called opioid-induced hyperalgesia (OIH). However, due to the complexity of pathogenesis and the lack of clinical diagnostic criteria, the pain management of cancer patients is still facing great challenges. Therefore, this article focuses on the clinical diagnosis, pathogenesis, prevention and treatment of hyperalgesia related to cancer pain treatment, in order to provide a basis for optimal use of opioids in the future.


The "bespoke" upper eyelid blepharoplasty and brow rejuvenation.
Blepharoplasty of the upper eyelids is one of the most commonly performed procedures in aesthetic plastic surgery. In this article, we describe our approach to the patient with aging of the periorbita. At all times, the approach is tailored to the individual's needs, trying to achieve a natural result that will not in any way affect the function of the eyelid. Our current approach and techniques for upper eyelid blepharoplasty and brow lifting are described.


Intracranial tumors mimicking benign paroxysmal positional vertigo.
Benign paroxysmal positional vertigo is a common type of vertigo seen by the otolaryngologist; however, intracranial tumors can mimic benign paroxysmal positional vertigo in their presentation. A review of patients seen in the Department of Otolaryngology at The Ohio State University between July 1992 and August 1996 identified five patients with intracranial pathologic conditions mimicking benign paroxysmal positional vertigo. These patients were first seen with episodic vertigo associated with positional change. Failure of the symptoms to respond to the particle repositioning maneuver or the finding of associated auditory or neurologic symptoms prompted further evaluation by magnetic resonance imaging of the brain, which revealed intracranial pathologic conditions including two meningiomas, a vestibular schwannoma, a glioma, and a lipoma. These findings suggest that patients seen with symptoms like those of benign paroxysmal positional vertigo who do not show improvement after undergoing the particle repositioning maneuver or those who describe associated auditory or neurologic symptoms should have magnetic resonance imaging done to rule out intracranial pathologic conditions. Additionally, benign paroxysmal positional vertigo and intracranial tumors may coexist.


Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection.
During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection. Such degradation subsequently results in the inhibition of type I interferon production in the infected cell. Our data demonstrate a mechanism by which cGAS senses cellular damage upon DENV infection.


Critical assessment of various techniques for the extraction of carotenoids and co-enzyme Q10 from the Thraustochytrid strain ONC-T18.
A variety of techniques for extracting carotenoids from the marine Thraustochytrium sp. ONC-T18 was compared. Specifically, the organic solvents acetone, ethyl acetate, and petroleum ether were tested, along with direct and indirect ultrasonic assisted extraction (probe vs bath) methods. Techniques that used petroleum ether/acetone/water (15:75:10, v/v/v) with 3 h of agitation, or 5 min in an ultrasonic bath, produced the highest extraction yields of total carotenoids (29-30.5 microg g-1). Concentrations up to 11.5 microg g-1 of canthaxanthin and 17.5 microg g-1 of beta;-carotene were detected in extracts stored for 6 weeks. Astaxanthin and echinenone were also detected as minor compounds. Extracts with and without antioxidants showed similar carotenoid concentration profiles. However, total carotenoid concentrations were approximately 8% higher when antioxidants were used. Finally, an easy-to-perform and inexpensive method to detect co-enzymes in ONC-T18 was also developed using silica gel TLC plates. Five percent methanol in toluene as a mobile phase consistently eluted co-enzyme Q10 standards and could separate the co-enzyme fractions present in ONC-T18.


Variable optical attenuators based on SOI with 3 μm top silicon layer.
In this paper, electro-absorption variable optical attenuators (VOAs) have been designed and fabricated on silicon-on-insulator material with a 3 μm thick top silicon layer. We have simulated the impact of doping distance, doping width, doping depth, doping concentration, and doping length on VOA's power consumption at 20 dB attenuation. We have found that the power consumption of VOA at 20 dB attenuation will decrease as the doping distance and doping width get smaller, while the doping depth and doping concentration get larger. We have further demonstrated that the power consumption can also be reduced by increasing the doping length and by taking a series structure theoretically. In this paper, VOAs with different doping structures, doping distances, doping widths, and doping lengths have been fabricated, and the tested results have verified our theoretical analysis. With doping distance of 8 μm, doping width of 15 μm, doping length of 1 cm, doping concentration of 1×1019 cm-3, and doping depth of 0.9 μm, the power consumption of the series VOA at 20 dB attenuation is 470 mW, and the rising/falling time is 54 ns/49.5 ns.


Characterization and function of the bHLH-O protein XHes2: insight into the mechanisms controlling retinal cell fate decision.
Neurons and glial cells differentiate from common multipotent precursors in the vertebrate retina. We have identified a novel member of the hairy/Enhancer of split [E(spl)] gene family in Xenopus, XHes2, as a regulator to bias retinal precursor cells towards a glial fate. XHes2 expression is predominantly restricted to sensory organ territories, including the retina. Using in vivo lipofection in the optic vesicle, we found that XHes2 overexpression dramatically increases gliogenesis at the expense of neurogenesis. This increase in glial cells correlates with a delayed cell cycle withdrawal of some retinal progenitors. In addition, birthdating experiments suggest that XHes2 deviates some early born cell types towards a glial fate that would normally have given rise to neurons. Conversely, a significant inhibition of glial differentiation is observed upon XHes2 loss of function. The gliogenic activity of XHes2 relies on its ability to inhibit neuronal differentiation by at least two distinct mechanisms: it not only negatively regulates XNgnr1 and NeuroD transcription, but it also physically interacts with a subset of proneural bHLH proteins.


Emerging roles for IL-25 and IL-33 in colorectal cancer tumorigenesis.
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, and is largely refractory to current immunotherapeutic interventions. The lack of efficacy of existing cancer immunotherapies in CRC reflects the complex nature of the unique intestinal immune environment, which serves to maintain barrier integrity against pathogens and harmful environmental stimuli while sustaining host-microbe symbiosis during homeostasis. With their expression by barrier epithelial cells, the cytokines interleukin-25 (IL-25) and IL-33 play key roles in intestinal immune responses, and have been associated with inappropriate allergic reactions, autoimmune diseases and cancer pathology. Studies in the past decade have begun to uncover the important roles of IL-25 and IL-33 in shaping the CRC tumour immune microenvironment, where they may promote or inhibit tumorigenesis depending on the specific CRC subtype. Notably, both IL-25 and IL-33 have been shown to act on group 2 innate lymphoid cells (ILC2s), but can also stimulate an array of other innate and adaptive immune cell types. Though sometimes their functions can overlap they can also produce distinct phenotypes dependent on the differential distribution of their receptor expression. Furthermore, both IL-25 and IL-33 modulate pathways previously known to contribute to CRC tumorigenesis, including angiogenesis, tumour stemness, invasion and metastasis. Here, we review our current understanding of IL-25 and IL-33 in CRC tumorigenesis, with specific focus on dissecting their individual function in the context of distinct subtypes of CRC, and the potential prospects for targeting these pathways in CRC immunotherapy.


Calcium spikes in a leech nonspiking neuron.
The NS neurons are nonspiking cells, present as pairs in each midbody ganglion of the leech nervous system, which display a very extensive arborization. They were shown to regulate the coactivation of motoneurons. Here we have investigated the electrophysiological properties of these neurons under the hypothesis that transmission along the extensive neurites requires the aid of voltage-dependent conductances. The results indicate that NS neurons respond to electrical stimulation with a spike-like event, which was not an all-or-none but rather a graded phenomenon that depended on the intensity and duration of the electrical stimulus. The spike-like response was activated at a membrane potential of approximately -50 mV; its amplitude was a logarithmic function of the extracellular Ca2+ concentration and was unaffected by a broad range of changes in the extracellular Na+ concentration; intracellular application of tetraethylammonium (TEA) caused a large increase in its amplitude and duration. These data indicate that NS neurons bear voltage-dependent low-threshold Ca2+ and TEA-sensitive K+ conductances that could contribute to shaping synaptic signals, or transmission along the extensive neuritic tree.


Fluorescence sensing of adenosine deaminase based on adenosine induced self-assembly of aptamer structures.
A new approach is proposed for simple detection of adenosine deaminase (ADA) based on adenosine induced self-assembly of two pieces of single-stranded DNA (ssDNA). These ssDNA are two fragments of the aptamer that has a strong affinity for adenosine and are labeled with carboxyfluorescein and black hole quencher-1, respectively. The complementarities of the bases in the two pieces of ssDNA are insufficient to form a stable structure. In the presence of adenosine, however, the ssDNA can be assembled into the intact aptamer tertiary structure, which results in fluorescence quenching of the carboxyfluorescein-labeled aptamer fragment. As a result, the adenosine-ssDNA complex shows a low background signal, which is rather desired for achieving sensitive detection. Reaction of the complex with ADA causes a great fluorescence enhancement by converting adenosine into inosine that has no affinity for the aptamer. This behaviour leads to the development of a simple and sensitive fluorescent method for assaying ADA activity, with a detection limit of 0.05 U mL(-1), which is more sensitive than most of the existing approaches. Furthermore, the applicability of the method has been demonstrated by detecting ADA in mouse serum samples.


Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway.
Endometriosis (EM) is a prevalent estrogen-dependent disorder that adversely affects the life quality of many reproductive-age women. Previous evidence has suggested the significant role of miR-429 in EM; however, its molecular mechanisms underlying EM pathogenesis are unclarified. Human endometrial stromal cells (HESCs) were identified using immunofluorescence staining and flow cytometry. A mouse EM model was established by endometrial auto-transplantation. RNA and protein expression of molecules was examined using real-time quantitative polymerase chain reaction and western blotting, respectively. In vitro functional experiments showed that inhibiting miR-429 restrained HESC proliferation, migration, and invasiveness. Luciferase reporter assay confirmed that miR-429 targeted hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) in HESCs. HIF1AN silencing offset the negative regulation of miR-429 inhibition on the HIF1A/vascular endothelial growth factor (VEGF) signaling pathway. In vivo experiments showed that depletion of miR-429 attenuated ectopic lesion development in the mouse EM model. Collectively, suppressing miR-429 hinders the invasive behaviors of HESCs and EM progression in mice by targeting HIF1AN and regulating the HIF1A/VEGF signaling pathway.


Twin pregnancies: eating for three? Maternal nutrition update.
The incidence of multifetal pregnancies has increased, mainly because of assisted reproduction treatments. This trend is reflected in increased maternal and neonatal morbidity and mortality. While the optimum maternal nutrition and weight gain patterns for singleton pregnancies is well documented, there is a paucity of information for twin pregnancies. Although it is assumed that optimum nutritional requirements and weight gains would be greater for twin than for singleton gestations, research is needed to establish the optima. This article is a collation of available recommendations for maternal nutrition and weight gain patterns in twin pregnancies.


Severe Drug-Induced Agranulocytosis Successfully Treated with Recombinant Human Granulocyte Colony-Stimulating Factor.
When elderly patients are prescribed many different medications, the risk for developing serious adverse events should be kept in mind. One of these adverse events is agranulocytosis, which, although rare, can be life-threatening if left untreated. The majority of agranulocytosis cases are caused by drugs, including antibiotics. Here, we report a case of severe agranulocytosis in a 96-year-old woman following antibiotic therapy which was successfully managed using recombinant human granulocyte colony-stimulating factor (rhG-CSF) and the appropriate choice of antibiotics to treat her concomitant infection.


Reasons and outcomes for patients receiving ICS/LABA agents prior to, and one month after, emergency department presentations for acute asthma.
Objective: Asthma is a common emergency department (ED) presentation. This study examined factors associated with inhaled corticosteroids/long-acting beta-agonist (ICS/LABA) use; and management and outcomes before and after ED presentation. Methods: Secondary analysis of a prospective cohort study; adults treated for acute asthma in Canadian EDs underwent a structured interview before discharge and were followed-up four weeks later. Patients received oral corticosteroids (OCS) at discharge and, at physician discretion, most received ICS or ICS/LABA inhaled agents. Analyses focused on ICS/LABA vs "other" treatment groups at ED presentation. Results: Of 807 enrolled patients, 33% reported receiving ICS/LABA at ED presentation; 62% were female, median age was 31 years. Factors independently associated with ICS/LABA treatment prior to ED presentation were: having an asthma action plan; using an asthma diary/peak flow meter; influenza immunization; not using the ED as usual site for prescriptions; ever using OCS and currently using ICS. Patients were treated similarly in the ED and at discharge; however, relapse was higher in the ICS/LABA group, even after adjustment. Conclusion: One-third of patients presenting to the ED with acute asthma were already receiving ICS/LABA agents; this treatment was independently associated with preventive measures. While ICS/LABA management improves control of chronic asthma, patients using these agents who develop acute asthma reflect higher severity and increased risk of future relapse.


Measurement and modulation of cytochrome-P450-dependent enzyme activity in cultured human keratinocytes.
The metabolism of xenobiotics by the epidermis can be studied in vitro by using keratinocyte cultures. We present a simple and rapid method for determining the activity of cytochrome P450-dependent enzymes (ethoxycoumarin-O-deethylase, ECOD, and ethoxyresorufin-O-deethylase, EROD) in intact cultured human keratinocytes. Using this method, we studied the effect of a well-known cytochrome P450 inhibitor (proadifen) and of two inducers (phenobarbital and 3-methylcholanthrene). As reported in vivo some imidazole compounds (miconazole and econazole) induced ECOD activity at low concentrations and inhibit it at high concentrations. In contrast, two other imidazoles (clotrimazole and sulconazole) only had an inducing effect on ECOD activity. Imidazole itself had no apparent effect on ECOD activity. In conclusion, this model appears to be useful for studying the biotransforming activity of human skin. It allows a rapid evaluation of the inducing/inhibitory effects of xenobiotics.


Family role in in-patient rehabilitation: the cases of England and Turkey.
This article explores the differences between experiences of family role in in-patient rehabilitation in Turkey and England. The literature predominantly assumes family presence in rehabilitation as positive, because it draws upon Western cases, where care is delivered fully by professionals, and patients may feel isolated during hospital stays. Analyses of other contexts provide a more nuanced view. This qualitative research included in-depth interviews (Turkey: 42, England: 18) with people with disabilities (n = 39), their families (n = 8) and hospital staff (n = 13); hospital ethnography (Turkey), focus groups (England: 3 groups involving 4 doctors, 5 nurses, 6 therapists), and participant-observation (England: 5 families). Thematic analysis highlights experiences of family involvement across different contexts. Families are differently integrated in rehabilitation in England and Turkey. In England, where family presence is regulated and relatively limited, people with disabilities feel more isolated and see family as a major form of support. In Turkey, where family presence is unregulated and intense, they enjoy family as an agent of intra-hospital socialising, but find it disabling when it implies a loss of privacy and individuality. Family involvement in rehabilitation should support social interaction but allow people with disabilities to remain independent.Implications for rehabilitationFamily involvement in rehabilitation can be both enabling and disabling.Existing literature draws upon rehabilitation practices, where family presence is limited and perceived as positive. An analysis of cases, where families are integral to the health care system (e.g., Turkey), can provide a nuanced view of family integration, which can be both enabling and disabling.Rehabilitation processes and health professionals need to integrate families in ways that will enrich social interaction, but still allow people with disabilities to retain their independence.


Octogenarian and centenarian performance on the Fuld Object Memory Evaluation.
The Fuld Object Memory Evaluation (FOME) has considerable utility for cognitive assessment in older adults, but there are few normative data, particularly for the oldest old. In this study, 80 octogenarians and 244 centenarians from the Georgia Centenarian Study completed the FOME. Total and trial-to-trial performance on the storage, retrieval, repeated retrieval, and ineffective reminder indices were assessed. Additional data stratified by age group, education, and cognitive impairment are provided in the Supplemental data. Octogenarians performed significantly better than centenarians on all FOME measures. Neither age group benefitted from additional learning trials beyond Trial 3 for storage and Trial 2 for retention and retrieval. Ineffective reminders showed no change across learning trials for octogenarians, while centenarians improved only between Trials 1 and 2. This minimal improvement past Trial 2 indicates that older adults might benefit from a truncated version of the test that does not include trials three through five, with the added benefit of reducing testing burden in this population.


Microbiological equivalence of serum bacteriostatic and bactericidal activities of the sera from healthy volunteers receiving original meropenem (Meronem) and generic meropenem (Mero).
Several generic meropenem formulations have been approved by Thai Food and Drug Administration, Ministry of Public Health since 2008. Meropenem is a parenteral drug. Therefore, a study demonstrating a biological equivalence of generic meropenem is not required for drug registration in Thailand. The objective of the study was to determine microbiological equivalence of serum bacteriostatic and bactericidal activities of the sera from healthy volunteers receiving original meropenem (Meronem) and generic meropenem (Mero). This was a randomized crossover study in 16 adult healthy volunteers. Each subject received one gram of Meronem and Mero in 50 ml of normal saline via intravenous infusion for 30 minutes. The blood samples were drawn at baseline prior to receiving the study drug, at 30 minutes after initiating infusion, and at 8 hours after initiating infusion. The serum bacteriostatic activity against E. coli ATCC 25922, K. pneumoniae, P. aeruginosa ATCC 27853 and A. baumannii was performed by disk diffusion. The serum bactericidal activity against E. coli ATCC 25922 was performed by Serum Bactericidal Titre. The average inhibition zone diameter of the serum samples from the subjects while receiving Mero against each tested organisms was < 1 mm smaller than that while receiving Meronem and such difference was not significantly different. All serum samples taken at 30 minutes after initiating Meronem and Mero had bactericidal titres against E. coli ATCC 25922 > or = 1:256. Only 3 serum samples taken from the subjects while receiving Mero at 8 hours had less bactericidal titre for 1-fold dilution when compared with that of Meronem. The sera from healthy volunteers receiving Meronem and Mero had microbiological equivalence in terms of serum bacteriostatic and bactericidal activities.


Gene Therapies for Retinitis Pigmentosa that Target Glucose Metabolism.
Retinitis pigmentosa is a blinding disease wherein rod photoreceptors are affected first, due to the expression of a disease gene, leading to the loss of dim light vision. In many cases, cones do not express the disease gene, yet they are also affected and eventually die, typically after most of the rods in their neighborhood have died. The cause of secondary cone death is unclear. Photoreceptors are one of the most energy-demanding cell types in the body and consume a high amount of glucose. At an early stage of degeneration, the cones appear to have a shortage of glucose to fuel their metabolism. This review focuses on gene therapy approaches that address this potential metabolic shortcoming.


The epidemiology and treatment of adult patients with hand burns in Kaunas University of Medicine Hospital in 1985, 1995, 2001 and 2002.
This study reviews the epidemiology of adult patients with hand burns admitted to Kaunas University of Medicine Hospital in Lithuania during selected four years (1985, 1995, 2001 and 2002). Two hundred and forty six cases were reviewed retrospectively with 74.4% of males and 25.6% of females among them. Median of age was 40 years (38 males, 45 females). Fire (71.9%) was the most common cause of injury; scalds (15.4%) were the second most common reason. The median of burned total body surface area was 12%. Analyzing the burns, 58.9% of them occurred in urban area (57.1% full-thickness burns), and 41.1% in rural (42.9% full-thickness burns). The study revealed that 17.1% (42) males and 3.7% (9) females were affected by alcohol at the time of injury. Early skin grafting was performed in 29.4% cases (mostly in 2001, 2002), delayed--70.6% (mostly in 1985, 1995) of all skin grafting operations. Early grafting was found to give better results in the length of hospital stay. Overall, the median of hospital stay significantly decreased and was 24 days (35 days in 1985, 19 days in 2002).


HTLV-I associated and non-associated primary T-cell lymphoma of gastrointestinal tract.
The gastrointestinal (GI) tract is the common extranodal site for non-Hodgkin's lymphoma (NHL), and primary lymphoma of GI tract are mostly of B-cell origin. We have treated 16 patients with primary lymphoma of GI tract between 1981 and 1991, of whom 10 (62%) were of B-cell origin, while 6 (38%) were of T-cell origin. The incidence of T-cell phenotype in our hospital was considered to be much higher than that of previous reports and these 6 patients with primary T-cell lymphoma of GI tract were carefully studied. The primary sites were stomach in 4, ileocecum in 1, and duodenum in 1 case. Their T-cell nature was confirmed by immunohistochemical methods. All were peripheral T-cell lymphomas; one was CD 3+ 4- 8- and the other 5 were CD 3+ 4+ 8-. The antibody against human T-cell leukemia virus type I (HTLV-I) was positive in 3 cases (HTLV-I associated), but negative in 3 (HTLV-I non-associated). The integration of HTLV-I proviral DNA in HTLV-I associated patients was demonstrated by Southern blot analysis after DNA amplification by means of polymerase chain reaction (PCR). The clinical features of the HTLV-I associated and HTLV-I non-associated primary T-cell lymphoma of the GI tract were quite different. HTLV-I associated patients showed leukemic manifestations and tumor involvement of the skin at a later stage of the disease. These observations indicated that HTLV-I can play an important role in the occurrence of primary T-cell lymphoma of GI tract.


Contralateral risk reducing mastectomy in Non-BRCA-Mutated patients.
The use of contralateral risk reducing mastectomy (CRRM) is indicated in women affected by breast cancer, who are at high risk of developing a contralateral breast cancer, particularly women with genetic mutation of BRCA1, BRCA2 and P53. However we should consider that the genes described above account for only 20-30% of the excess familiar risk. What is contralaterally indicated when genetic assessment results negative for mutation in a young patient with unilateral breast cancer? Is it ethically correct to remove a contralateral "healthy" breast? CRRM rates continue to rise all over the world although CRRM seems not to improve overall survival in women with unilateral sporadic breast cancer. The decision to pursue CRRM as part of treatment in women who have a low-to-moderate risk of developing a secondary cancer in the contralateral breast should consider both breast cancer individual-features and patients preferences, but should be not supported by the surgeon and avoided as first approach with the exception of women highly worried about cancer. Prospective studies are needed to identify cohorts of patients most likely to benefit from CRRM.


Implementing community-directed treatment with ivermectin for the control of onchocerciasis in Uganda (1997-2000): an evaluation.
Over the period 1997-2000, an evaluation was made, in 10 districts of Uganda, of the onchocerciasis-control programme based on community-directed treatment with ivermectin (CDTI). This programme is supported by the Ministry of Health, the African Progamme for Onchocerciasis Control (APOC) and The Carter Center Global 2000 River Blindness Programme. The data analysed came from: (1) monthly and annual reports; (2) annual interviews, in randomly-selected communities in selected districts, with heads of household, community leaders and ivermectin distributors; (3) participatory evaluation meetings (PEM); (4) participant observation studies; and (5) key informants. The percentage of treated communities in the 10 study districts achieving satisfactory treatment coverage [i.e. > or = 90% of the annual treatment objective (ATO)] rose from 46.0 in 1997 to 86.8 in 2000. This improvement was largely attributable to the adoption of collective CDTI decision-making by community members, avoidance of paving monetary incentives to the ivermectin distributors, and the satisfaction with the programme of those who had been treated. Coverage improved as the numbers of community members who were involved in choosing the method of distribution and in selecting their own community-directed health workers (CDHW) increased. Health education was also critical in improving individual members' involvement in decision-making, and in mobilizing other community members to take part in CDTI. Involvement of kinship groups, as well as educated community members as supervisors of CDHW, also helped to increase coverage. In a regression model, satisfaction with the programme was revealed as a significant predictor of the achievement of the target coverage (P<0.001). Cost per person, as an indicator for sustainability, varied with the size of the population under treatment, from at least U.S. $0.40 when the district ATO was <15,000 people, to U.S. $0.26 with an ATO of 15,000-40,000 and less than U.S. $0.10 when the district ATO exceeded 40,000 people. These results cast doubt on the validity of the current APOC indicator for sustainability, of a cost of no more than U.S. $0.20/person for all CDTI projects, whatever the size of the population to be treated. Although some women were involved in decision-making, their current involvement as supervisors or CDHW was minimal. Most of the present data were obtained through monitoring and operational-research activities that have been carried out, in an integrated fashion, within the Ugandan CDTI programme since its launch. It is recommended that assessment, monitoring and evaluation be widely used within all CDTI efforts. Operational research should remain focused and appropriate and directly involve the personnel who are executing the programme.


Topology-driven physicochemical properties of pi-electron systems. 1. Does the Clar rule work in cyclic pi-electron systems with the intramolecular hydrogen or lithium bond?
The Clar model predicting stability and electron distribution in benzenoid hydrocarbons seems to be also a good predictor for related properties in lithium o-acylphenolates and to a lesser extent in the phenols themselves. This conclusion is based on analysis of geometry changes in the analogues of naphthalene, phenanthrene, anthracene, and triphenylene, where benzene rings are systematically replaced with a quasi-ring formed as a beta-ketoenol or beta-ketoenolate complex with a lithium cation, i.e., where CH-CH-CH fragments are replaced with O...Li...O or O...H...O fragments. These systems were optimized at the MP2/6-31G(2d,p) level of theory. The energy of bond separation reactions in line with aromaticity indices HOMA and NICSs supported the above statement.


Inhibition of adrenergic neurotransmission in canine tibial artery after exposure to 5-hydroxytryptamine in vitro.
Blood vessels may be exposed to 5-hydroxytryptamine when platelets aggregate and release vasoactive substances at sites of damage or disease. The functional consequences were studied of exposing the dog tibial artery for 2 hr to 5-hydroxytryptamine (10(-6) M) in vitro. During the exposure, unmetabolized 5-hydroxytryptamine was accumulated by the cocaine-sensitive amine uptake mechanism of tibial artery adrenergic nerves. After exposure to [3H]-5-hydroxytryptamine, transmural electrical stimulation caused the release of the tritiated indoleamine which was blocked by tetrodotoxin. After a 1-hr washout of rings of tibial artery exposed previously to 5-hydroxytryptamine, contractions in response to transmural electrical stimulation were depressed, whereas the response to exogenously added norepinephrine was unaffected. That the decreased response to electrical stimulation after exposure to 5-hydroxytryptamine was due to decreased release of norepinephrine from adrenergic nerves was demonstrated in strips of the artery preincubated in [3H]norepinephrine. The inhibition of [3H]norepinephrine release after exposure to 5-hydroxytryptamine, was blocked by the serotonergic antagonist, methiothepin, but not by the alpha adrenergic antagonist, phentolamine, suggesting that serotonergic receptors mediate the inhibition. The inhibition of [3H]norepinephrine release also was prevented by blocking adrenergic neuronal uptake with cocaine before exposure to 5-hydroxytryptamine. These results suggest that 5-hydroxytryptamine is accumulated and released by tibial artery adrenergic nerves as a cotransmitter. In so doing, the indoleamine inhibits adrenergic neurotransmission in the tibial artery by its action at prejunctional serotonergic receptors.


[Cortical efferents in different areas of the cat orbitofrontal cortex].
The efferental relations of different parts of the cat orbitofrontal cortex with other parts of the neocortex are not equal. As to the distribution in different zones of the neocortex they differ in the quantitative and spatial characteristics. The number of efferents originating from the orbitofrontal cortex increases from the medial part of the proreal gyrus to its dorsolateral parts and anterior part of the orbital gyrus. Thus the frontal part of the orbital gyrus has the greatest number of the efferental relations with other parts of the neocortex including the projection visual cortex. The relations disclosed suggest that the cat has the "circles" between the orbitofrontal cortex, parietal cortex and limbic cortex, apparently consequent on the bilateral influences between the three structures.


Dissecting the stem cell niche with organoid models: an engineering-based approach.
For many tissues, single resident stem cells grown in vitro under appropriate three-dimensional conditions can produce outgrowths known as organoids. These tissues recapitulate much of the cell composition and architecture of the in vivo organ from which they derive, including the formation of a stem cell niche. This has facilitated the systematic experimental manipulation and single-cell, high-throughput imaging of stem cells within their respective niches. Furthermore, emerging technologies now make it possible to engineer organoids from purified cellular and extracellular components to directly model and test stem cell-niche interactions. In this Review, we discuss how organoids have been used to identify and characterize stem cell-niche interactions and uncover new niche components, focusing on three adult-derived organoid systems. We also describe new approaches to reconstitute organoids from purified cellular components, and discuss how this technology can help to address fundamental questions about the adult stem cell niche.


In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order.
The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5 of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus, 26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤ 0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤ 0.03 to 0.5), 0.06 (≤ 0.03 to 0.25), and 0.125 (≤ 0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher than those for posaconazole. However, in the clinical setting this may be compensated for by the higher exposure at standard dosing.


Oxygen solubilization by lung surfactant.
To illustrate the concept of solubilization as a possible mode of gas transport in biological systems, dog lung surfactants in varying concentrations were tested for their ability to solubilize oxygen. The degree of gas solubilization was determined by GC, using a modified tonometer as an absorption chamber. The concentration of surfactant was found to be an essential factor for gas solubilization. Surfactant concentration above the CMC yielded anomalously high gas absorption. Solubilization of the gas is thought to occur by a partitioning effect into the interior of surfactant micelles.


Biodegradable cationic nanoparticles loaded with an anticancer drug for deep penetration of heterogeneous tumours.
To enhance limited drug penetration that mediated drug resistance and heterogeneity within the tumour microenvironment, we designed a paclitaxel (PTX) loaded degradable cationic nanogel (DpNG) consisted with acetylated pullulan and low molecular weight polyethyleneimine ((Low)bPEI, 1.8 kDa). The restoration of cationic charge on the DpNG was achieved via HA degradation by hyaluronidase which is secreted in tumour. The size and surface charge of HA-coated DpNG loaded with PTX (HA/DpNG-PTX) was 200-250 nm and 0 mV, respectively. The DpNG-PTX was showed significant cytotoxicity in heterogeneous cancer cells. The IC50 value of DpNG-PTX was 100 times less than that of free PTX. The growth of heterogeneous tumour in Balb/c mice was inhibited via intravenous injection of HA/DpNG-PTX. Furthermore, the invasive distance and amount of HA/DpNG-PTX localised within the deep tissue regions were increased two times than that of PA-PTX. Therefore, the DpNG based drug delivery system could be useful for treatment of heterogeneous tumour.


Alterations of microRNAs and their predicted targeting mRNAs expression in RAW264.7 macrophages infected with Omp25 mutant Brucella melitensis.
Brucellosis is a worldwide zoonosis caused by Brucella species and represents a serious threat to both human and animal health. Omp25 is an important immunogenic and protective antigen in Brucella species; however, the functional mechanism of Omp25 in macrophages has not yet been elucidated. Here, we constructed a Brucella melitensis omp25 deletion mutant (M5-90-Δ omp25) and performed microRNA (miRNA) profiling of infected RAW264.7 cells. Eight differentially expressed miRNAs ( mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-3473a, mmu-miR-149-3p, mmu-miR-671-5p, mmu-miR-1224-5p, mmu-miR-1895, and mmu-miR-5126) were identified, with quantitative real-time PCR (qRT-PCR) analysis confirming the up-regulation of mmu-miR-146-a-5p and mmu-miR-155-5p and down-regulation of mmu-miR-149-3p and mmu-miR-5126. mRNA profiling of B. melitensis M5-90-Δo mp25-infected RAW264.7 cells identified 967 differentially expressed genes (DEGs) (fold change ≥ 2). Among these, we focused on genes that were predicted by TargetScan, miRanda, and PicTar to be the potential targets of the differentially expressed miRNAs. The results suggested that 17 separate genes are potentially targeted by mmu-miR-149-3p, with one of these genes, Tbr1, also targeted by mmu-miR-5126. qRT-PCR analysis confirmed the up-regulation of nine of the predicted target genes. Our findings provide important information about the functional molecules in host cells, including miRNA and their target genes, affected by Omp25 from Brucella. This information is particularly valuable for the prophylaxis and treatment of brucellosis.


Benign breast disease heterogeneity: association with histopathology, age, and ethnicity.
Benign breast biopsies with concurrent multiple benign lesions with different histopathologic diagnoses were termed heterogeneous benign breast disease (HBBD). Multiplicity of benign breast disease (BBD) lesions in a biopsy is a risk factor for progression to breast cancer (BC). Elucidation of the biological characteristics and clinical implications of HBBD may also be relevant to the refinement of risks for BC in women with a BBD diagnosis. In this study, we investigated the association of HBBD with histopathology, age, and ethnicity. A cohort of 4,341 women, 1,208 African Americans and 3,133 Caucasians, diagnosed with BBD, was identified after examination of an excisional breast biopsy. BBD biopsies were categorized as nonproliferative (NP, low risk or risk 1 lesions), proliferative without atypia (P, intermediate risk or risk 2 lesions), and proliferative with atypia (AH, high risk or risk 3 lesions). A BBD biopsy with only a single BBD lesion was termed simple BBD (SBBD). BBD biopsies with multiple lesions were further classified as single level HBBD (SL-HBBD) if the concurrent lesions were within the same risk level, or as multiple level HBBD (ML-HBBD) if lesions fell into more than one risk group. In this cohort, 69% of women with a BBD diagnosis fit the HBBD criteria. Among women with HBBD, ML-HBBD was almost three times more prevalent than SL-HBBD and was significantly more likely to be composed of risk 2 and risk 3 lesions. The likelihood of HBBD was 57% higher in Caucasian American women than in African American women with BBD (OR 1.57; 95% CI: 1.37, 1.81). The average lesion number in HBBD was directly proportional to increasing lesion risk (P < 0.001). Compared to women with risk 1 lesions, the likelihood of HBBD was 5.59 (95% CI: 4.85-6.44) and 17.0 (95% CI: 10.2-28.5) times higher when risk 2 and risk 3 lesions, respectively, were present. Women in the age range of 46-55 years and >55 years had a 3.12 (95% CI: 2.59, 3.75) and a 2.28 (95% CI: 1.94, 2.68) fold higher likelihood of HBBD compared to those < or =45 years. Significant interaction was found between concurrent lesion levels and age (P < 0.01). The likelihood of HBBD was considerably higher across all age groups for risk 3 lesions. Compared to the reference (risk 1, age < or =45), the likelihood of HBBD for risk 2 lesions was 4.4 times greater (95% CI: 3.70, 5.33) in women < or =45 YEARS, BUT THAT LIKELIHOOD INCREASED TO 17.6 (95% CI: 12.8, 24.2) AND 13.4 (95% CI: 10.1, 17.9) TIMES IN WOMEN OF 46-55 AND >55 YEARS, RESPECTIVELY. HBBD is more prevalent in Caucasian American women than in African American women. Women with higher risk BBD lesions are more likely to have HBBD. Lesion number and higher risk BBD lesions are significantly correlated with ML-HBBD. Additionally, the associations of HBBD and lesion risk level are modified by age.