The effect of mutation status, pathological features and tumor location on prognosis ın patients with colorectal cancer.
Colorectal cancer is the most common malignancy of the gastrointestinal tract. It is the third most common tumor in both genders and the second reason of cancer-related deaths. In recent years, tumor location has gained importance as a prognostic indicator. In this study, we aimed to analyze if there was a prognostic effect of tumor location, the pathological features, and the mutation status of patients on survival. Two-hundred and ten colorectal cancer patients aged 18 years and older were included into the study. One-hundred and forty-two patients had left-sided tumor and 68 patients had right-sided tumor. Patients who had other malignancies rather than squamous cell skin cancer and in situ cervical cancer were excluded. All statistical tests were carried out using two-sided process, and a p≤0.05 was considered statistically significant. There were 140 men and 70 women in the study. The median age of the patients was 62 years old. There was no statistically significant difference according to tumor location and survival of patients. The overall survival of patients with right-sided tumors was 60.5 months and 47.2 months for left-sided tumors. Disease-free survival of patients was 63.7 months for right-sided tumors and 46 months for left-sided ones. Perineural invasion, grade and stage were crucial prognostic parameters. Disease-free survival was longer for female colorectal cancer patients. According to our study, survival of patients was similar regardless of tumor location. This can be explained by the different sequencing of treatment strategies and divergent population genetics.


Successful ablation of morphology-changing premature ventricular contractions under the guidance of local voltage potentials: A case report.
Premature ventricular contractions (PVCs) stemming from the aortic sinus cusp often have preferential conduction to two exits in the outflow tract and exhibited two different morphologies of PVCs, which may render radiofrequency catheter ablation (RFCA) difficult. A 67-year-old male patient underwent RACF for premature ventricular contractions (PVCs) characterizing by bi-morphology (left and right bundle branch block) on electrocardiogram. Dynamic changes in QRS morphology during ablation and evident local voltage potentials during electro-anatomical mapping were critical for identifying the real foci of origin of PVCs. Successful ablation was achieved at the left-right coronary cusp commissure.


Fabrication of a Microfluidic Flame Atomic Emission Spectrometer: a Flame-on-a-Chip.
This work demonstrates for the first time the fabrication of a microfluidic flame atomic emission spectrometer (FAES), which incorporates a microburner and flame (flame-on-a-chip). An essential part of the device is a thermospray system applied for effective sample introduction, which is more easily miniaturizable and integrable than the conventional nebulization methods. The merits and limitations of the microfluidic flame atomic emission device were demonstrated and discussed. Using a commercial cigarette lighter including butane gas, the flame temperature made the analysis of the most easily excitable alkali metals possible. The calibration diagrams for Li, Na, and K showed proper linearity in the range of 5-100 mg/L. The analytical applicability of the microfluidic FAES device was tested by analyzing various real samples.


Glaucoma screening: analysis of conventional and telemedicine-friendly devices.
Portable, telemedicine-friendly devices offer novel opportunity for screening and monitoring glaucoma in the remote and rural regions of the world. This study examines the effective combination of telemedicine-friendly screening devices for detection of glaucoma in relation with conventional, hospital-based devices. A total of 399 eyes were screened with telemedicine-friendly devices and conventional, hospital-based devices such as ophthalmoscope, tonometer and perimeter. Combination of age and family history of glaucoma alone has a sensitivity of 35.6% (specificity 94.2%, area under the curve 0.81, correctly classified 81.1%) and an addition of telemedicine-friendly or conventional visual field tests optimized the sensitivity to 91.1% (specificity 93.6%, area under the curve 0.95, correctly classified 93%). Analysis indicates good agreement between vertical cup-to-disc ratio by ophthalmoscopy and digital image reading. An addition of intraocular pressure test does not change sensitivity (35.6%) and specificity (94.2%). This study indicates that evaluations of cup-to-disc ratio and visual field, using telemedicine-friendly devices, are most useful tools in screening for glaucoma. When used together these devices may be an alternative for conventional glaucoma screenings.


Differences in the changing trends of monophasic action potential duration and effective refractory period of the ventricular myocardium after myocardial infarction in vivo.
The relationship between monophasic action potential duration (MAPD) and effective refractory period (ERP) is poorly understood after myocardial infarction (MI) in vivo. Forty rabbits were randomized into either a sham operation (SO) group (n=10) or MI group (n=30), both of which underwent thoracotomy, but the left anterior descending coronary artery was occluded in the MI group only. The MAPD and ERP of the endocardial, midmyocardial and epicardial cells of the infarction zone were observed at baseline, 2 days after thoracotomy and then 5 min, 15 min, 30 min, 2 days, 14 days and 60 days after coronary occlusion (CO). At baseline, ERP correlated strongly with MAPD90. During the 5-30 min after CO, both MAPD90 and ERP of the 3 layers of the myocardium shortened markedly (eg, MAPD90 Mid) was approximately 50% of the baseline value at 5 min after CO). MAPD90 and ERP recovered gradually over the 2-60 days after MI. ERPMid exceeded MAPD90 Mid and the post repolarization refractoriness phenomenon appeared during the 5-30 min after CO. The different changing trends of the MAPD and ERP of the mid-myocardial cells may underlie the arrhythmias that occur after MI.


Structure and properties of electronic and hole centers in CsBr from theoretical calculations.
The electronic structure, geometry, diffusion barriers and optical properties of fundamental defects of CsBr are calculated using hybrid functional DFT and TD-DFT methods. The B3LYP functional with a modified exchange contribution has been used in an embedded cluster scheme to model the structure and spectroscopic properties of the self-trapped triplet exciton, interstitial Br atoms and ions, self-trapped holes and Br vacancies. The calculated migration barriers and positions of maxima of optical absorption bands are in good agreement with experiment, justifying the obtained defect geometries. The off-center triplet exciton luminescence energy is also accurately calculated.


[Research in Danish departments of anesthesiology at the turn of the century. A bibliometric analysis].
This investigation was based on the surmise that the scientific activity in the specialty of anaesthesiology and intensive care medicine in Denmark is declining. A quantitative and qualitative analysis of the development in Danish anaesthesiological research during the seven-year period of 1992-1998 was performed with bibliometrical methods and a count of the PhD and doctoral theses produced by Danish anaesthesiologists during that period. In the period investigated, a total of 906 scientific articles were published, of which 749 (83%) originated from university hospitals. Total production decreased by 15% between the two-year periods of 1992-1993 and 1997-1998, whereas the output from university hospitals alone decreased by 10%. The number of scientific publications per anaesthesiologist decreased by 34%, corresponding to 6.7% per year. The quality of the research published, as examined by the cumulative and average impact, showed a slight increase. The number of PhD and doctoral theses per year showed no change. Research activity in Danish anaesthesiology is declining, and the specialty seems to be losing scientific ground, both nationally and internationally.


[Predictive value of 3 different risk stratification models for patients after congenital heart surgeries].
Objective: To evaluate the predictive value of 3 different risk stratification models including the risk adjustment in congenital heart surgery-1 (RACHS-1), Aristotle basic complexity (ABC), and Society of Thoracic Surgeons-European Association for cardiothoracic surgery congenital heart surgery mortality score (STAT) risk scoring system for death and major complications in patients after congenital heart surgeries. Methods: A total of 3 578 patients (age<18 years old) received surgery for congenital heart diseases from January to December 2015 in Fuwai hospital were enrolled, and the clinical data were retrospectively analyzed. The congenital heart disease patients were 1.7 (0.8, 4.5) years old, and the male accounted for 54.3% (1 943 cases).Death after surgery and major complications including use of extracorporeal membrane oxygenation, bedside thoracotomy, peritoneal dialysis for renal failure, bedside hemofiltration for renal failure, tracheotomy, reoperation for mediastinum infection, reoperation for heart in hospital were observed. The area under the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive value for mortality after surgery and major complications with RACHS-1, ABC, and STAT risk scoring systems. Results: The mortality after surgery was 0.4% (14/3 578) , and the rate of major complications was 3.2% (113/3 578) . For mortality after surgery, areas under the ROC curve were 0.682 (95%CI 0.570-0.795, P=0.002), 0.722 (95%CI 0.612-0.832, P<0.001), and 0.753 (95%CI 0.659-0.847, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. For major complications, areas under the ROC curve were 0.709 (95%CI 0.667-0.751, P<0.001), 0.743 (95%CI 0.702-0.784, P<0.001), and 0.731 (95%CI 0.693-0.770, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. Conclusion: STAT risk scoring system is superior to RACHS-1 and ABC risk scoring systems on predicting death after surgery, and ABC risk scoring system is superior to RACHS-1 and STAT risk scoring systems on predicting major complications in Chinese patients with congenital heart disease in the single center.


Usher Syndrome Belongs to the Genetic Diseases Associated with Radiosensitivity: Influence of the ATM Protein Kinase.
Usher syndrome (USH) is a rare autosomal recessive disease characterized by the combination of hearing loss, visual impairment due to retinitis pigmentosa, and in some cases vestibular dysfunctions. Studies published in the 1980s reported that USH is associated with cellular radiosensitivity. However, the molecular basis of this particular phenotype has not yet been documented. The aim of this study was therefore to document the radiosensitivity of USH1-a subset of USH-by examining the radiation-induced nucleo-shuttling of ATM (RIANS), as well as the functionality of the repair and signaling pathways of the DNA double-strand breaks (DSBs) in three skin fibroblasts derived from USH1 patients. The clonogenic cell survival, the micronuclei, the nuclear foci formed by the phosphorylated forms of the X variant of the H2A histone (ɣH2AX), the phosphorylated forms of the ATM protein (pATM), and the meiotic recombination 11 nuclease (MRE11) were used as cellular and molecular endpoints. The interaction between the ATM and USH1 proteins was also examined by proximity ligation assay. The results showed that USH1 fibroblasts were associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired DSB recognition but normal DSB repair, likely caused by a delayed RIANS, suggesting a possible sequestration of ATM by some USH1 proteins overexpressed in the cytoplasm. To our knowledge, this report is the first radiobiological characterization of cells from USH1 patients at both molecular and cellular scales.


Usefulness of vacuum-assisted closure after stoma closure with purse string suturing: a retrospective trial.
Surgical site infection (SSI) is a problematic complication after stoma closure. The purse string suture (PSS) technique eliminates this problem, but the area takes longer to heal. The present retrospective study was performed to evaluate the usefulness of a vacuum-assisted closure (VAC) system for the promotion of wound healing after stoma closure. Consecutive patients undergoing stoma closure with the PSS technique were divided into two groups: those treated with and without use of the VAC system. The volume of dead space and the size of the wound were measured after stoma closure in both groups. The same measurements were performed on days 3 and 7 after closure. The time needed for wound closure was also examined in both groups. Outcomes were also evaluated according to age, body mass index, operative time, bleeding volume, wound consistency, patient satisfaction, perioperative inflammatory response, occurrence of SSI, and hospitalization days. The VAC group comprised 31 patients, and the non-VAC group comprised 34 patients. The volume of dead space on days 3 and 7 after closure was significantly smaller in the VAC group than in the non-VAC group (P=0.006 and P<0.001, respectively). The number of SSIs was significantly lower in the VAC group than in the non-VAC group (P=0.014). The dead space volume on days 3 and 7 after stoma closure with PSS significantly decreased by using the VAC system. The incidence of SSI after stoma closure also significantly decreased by using the VAC system.


Fabrication of Porous Spherical Beads from Corn Starch by Using a 3D Food Printing System.
This study introduces a 3D food printing approach to fabricate spherical starch beads with small sizes and high porosity for the first time. The results illustrated that 3D food printing could generate starch beads in different sizes depending on the nozzle diameter, printing pressure, and ink viscosity. The 3D-printed beads were characterized for their morphology, crystallinity, and textural properties, while the starch-based ink was analyzed for its rheological properties. A suitable printing was attained when viscosity was in the range of 1000-1200 Pa.s at a low shear rate (˂0.1 s-1). Among the starch concentrations (10-15%, w/w) investigated, 15% starch concentration provided the best control over the shape of the beads due to its high storage modulus (8947 Pa), indicating higher gel strength. At this condition, the starch beads revealed an average size of ~650 µm, which was significantly smaller than the beads produced with other starch concentrations (10 and 12.5%), and had a density of 0.23 g/cm3. However, at lower starch concentrations (10%), the beads were not able to retain their spherical shape, resulting in larger beads (812-3501 µm). Starch crystallinity decreased by gelatinization, and the starch beads exhibited a porous structure, as observed from their SEM images. Overall, 3D food printing can be an alternative approach to preparing porous beads for the delivery of bioactive compounds with high precision.


Presentation of the Therapy Program for Management of Chronic Cough.
To present a proposal for speech-language pathology rehabilitation called the Therapy Program for Management of Chronic Cough (TMCC) for the treatment of refractory chronic cough. TMCC was developed based on two stages: literature and clinical analysis. The literature analysis stage was carried out through the following procedures: electronic and manual search for articles and books published until June 2019 that included adult participants with chronic cough and intervention with speech-language pathology therapy; selection of sources; analysis of articles and books included; and, preparation of the initial version of the therapy program. The initial version of the therapy program resulting from literature analysis stage was submitted to clinical analysis stage through the following procedures: analysis by three judges; revision of the proposal by the authors; judges' re-analysis; elaboration of the final version called the Therapy Program for Management of Chronic Cough (TMCC). TMCC synthesizes scientific knowledge and current clinical experience on the behavioral management of refractory chronic cough into a program with three main components, each one with specific objectives and strategies. TMCC consists of four sessions, with weekly frequency and duration between 30-45 minutes per session, executed in hierarchical phases, with specific objectives and strategies per session. TMCC is a program structured to offer global cough rehabilitation. To obtain scientific evidence about its effectiveness is necessary, so that it can be used in clinical practice.


Tractography optimization using quantitative T1 mapping in the human optic radiation.
Diffusion MRI tractography is essential for reconstructing white-matter projections in the living human brain. Yet tractography results miss some projections and falsely identify others. A challenging example is the optic radiation (OR) that connects the thalamus and the primary visual cortex. Here, we tested whether OR tractography can be optimized using quantitative T1 mapping. Based on histology, we proposed that myelin-sensitive T1 values along the OR should remain consistently low compared with adjacent white matter. We found that complementary information from the T1 map allows for increasing the specificity of the reconstructed OR tract by eliminating falsely identified projections. This T1-filtering outperforms other, diffusion-based tractography filters. These results provide evidence that the smooth microstructural signature along the tract can be used as constructive input for tractography. Finally, we demonstrate that this approach can be applied in a case of multiple sclerosis, and generalized to the HCP-available MRI measurements. We conclude that multimodal MRI microstructural information can be used to eliminate spurious tractography results in the case of the OR.


"You Killed the Hospital, They Have No Place Left": The Experience of Nursing Home Multidisciplinary Staff in Israel during the COVID-19 Pandemic.
The purpose of the present study is to examine how multidisciplinary staffs experienced and coped with the COVID-19 pandemic crisis in nursing homes. The research included six in-depth online focus groups consisting of 21 multidisciplinary staff members from 14 Israeli nursing homes. The qualitative analysis was encoded in stages with repeated comparisons between individual participants and within groups and led to four main themes: (a) Multidisciplinary staff perceptions of nursing home management's performance in relation to them, which was experienced as insufficient appreciation and feelings of abandonment among the non-medical staff; (b) Multidisciplinary staff perceptions of the Ministry of Health's performance, which was experienced as chaotic and disconnected albeit supportive on the personal level; (c)The nursing home multidisciplinary staff experience during the COVID-19 pandemic, in terms of perceived stress and burnout, as well as development of a routine; (d) The multidisciplinary staff's coping strategies, which included commitment to work despite risk, redefinition of their role, and staff insights about the need to take responsibility for their role and not rely on outside help. The findings indicate the importance of relationships that promote support and mutual communication between multidisciplinary staff, and both nursing home management and Ministry of Health.KEY POINTS Nursing home multidisciplinary staff experienced disconnection from and abandonment by nursing home management and Ministry of Health during the Covid-19 pandemic.Nursing home multidisciplinary staff experienced stress and burnout but also developed a routine.Despite intensified negative emotional feelings, multidisciplinary staff also underwent processes of redefining their role and gaining greater independence.Findings indicate the importance of creating a climate that facilitates mutual sharing, listening and learning.


Commentary: Three Ideas about "Post-Vention".
When presented with the opportunity to provide a commentary on this Special Issue of Healthcare Quarterly on patient safety, we thought it would be particularly powerful to bring together those with intimate lived experience of patient safety incidents. As such, this submission is being brought to you by two patients whose lives have been irrevocably altered by medical mishaps, along with a physician who has spent a considerable portion of his career advancing and integrating the patient voice on patient safety issues.


Prevalence of Depression and Associated Factors in Non-institutionalized Older Adults With a Previous History of Falling.
The purpose of this paper was to estimate the prevalence of depression and associated factors in people aged 65 or older with a history of falling in the last 12months. A cross-sectional descriptive study was performed involving a random sample of 213 participants from two social centers for older adults in the city of Zaragoza (Spain). The mean age of the participants was 77.3years (SD±7.0). Our findings reveal a prevalence of depression of 28.2% in the study sample, with older adults who were at a high risk of falling being more susceptible to developing depression. In conclusion, one in three elderly people who were at risk of suffering a fall in the 12months prior to data collection had symptoms of depression. This is in agreement with the results from previous studies, which confirm that there is a high prevalence of depression in elderly patients with a previous history of falls.


Opening up safely: public health system requirements for ongoing COVID-19 management based on evaluation of Australia's surveillance system performance.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community transmission was eliminated in Australia from 1/11/2020 to 30/6/2021, allowing evaluation of surveillance system performance in detecting novel outbreaks, including against variants of concern (VoCs). This paper aims to define system requirements for coronavirus disease 2019 (COVID-19) surveillance under future transmission and response scenarios, based on surveillance system performance to date. This study described and evaluated surveillance systems and epidemiological characteristics of novel outbreaks based on publicly available data, and assessed surveillance system sensitivity and timeliness in outbreak detection. These findings were integrated with analysis of other critical COVID-19 public health measures to establish future COVID-19 management requirements. Twenty-five epidemiologically distinct outbreaks and five distinct clusters were identified in the study period, all linked through genomic sequencing to novel introductions from international travellers. Seventy percent (21/30) were detected through community testing of people with acute respiratory illness, and 30% (9/30) through quarantine screening. On average, 2.07% of the State population was tested in the week preceding detection for those identified through community surveillance. From 17/30 with publicly available data, the average time from seeding to detection was 4.9 days. One outbreak was preceded by unexpected positive wastewater results. Twenty of the 24 outbreaks in 2021 had publicly available sequencing data, all of which identified VoCs. A surveillance strategy for future VoCs similar to that used for detecting SARS-CoV-2 would require a 100-1000-fold increase in genomic sequencing capacity compared to the study period. Other essential requirements are maintaining outbreak response capacity and developing capacity to rapidly engineer, manufacture, and distribute variant vaccines at scale. Australia's surveillance systems performed well in detecting novel introduction of SARS-CoV-2 while community transmission was eliminated; introductions were infrequent and case numbers were low. Detection relied on quarantine screening and community surveillance in symptomatic members of the general population, supported by comprehensive genomic sequencing. Once vaccine coverage is maximised, future COVID-19 control should shift to detection of SARS-CoV-2 VoCs, requiring maintenance of surveillance systems and testing all international arrivals, alongside greatly increased genomic sequencing capacity. Effective government support of localised public health response mechanisms and engagement of all sectors of the community is crucial to current and future COVID-19 management.


Influence of the forms and levels of dietary selenium on antioxidant status and oxidative stress-related parameters in rainbow trout (Oncorhynchus mykiss) fry.
Se is an essential micronutrient required for normal growth, development and antioxidant defence. The objective of the present study was to assess the impact of dietary Se sources and levels on the antioxidant status of rainbow trout (Oncorhynchus mykiss) fry. First-feeding fry (initial body weight: 91 mg) were fed either a plant- or fishmeal-based diet containing 0·5 or 1·2 mg Se/kg diet supplemented or not with 0·3 mg Se/kg diet supplied as Se-enriched yeast or sodium selenite for 12 weeks at 17°C. Growth and survival of rainbow trout fry were not significantly affected by dietary Se sources and levels. Whole-body Se was raised by both Se sources and to a greater extent by Se-yeast. The reduced:oxidised glutathione ratio was raised by Se-yeast, whereas other lipid peroxidation markers were not affected by dietary Se. Whole-body Se-dependent glutathione peroxidase (GPX) activity was enhanced in fish fed Se-yeast compared to fish fed sodium selenite or non-supplemented diets. Activity and gene expression of this enzyme as well as gene expression of selenoprotein P (SelP) were reduced in fish fed the non-supplemented plant-based diet. Catalase, glutamate-cysteine ligase and nuclear factor-erythroid 2-related factor 2 (Nrf2) gene expressions were reduced by Se-yeast. These results suggest the necessity to supplement plant-based diets with Se for rainbow trout fry, and highlight the superiority of organic form of Se to fulfil the dietary Se requirement and sustain the antioxidant status of fish. GPX and SelP expression proved to be good markers of Se status in fish.


Quantitative Reconstructions of 3D Chemical Nanostructures in Nanowires.
Energy dispersive X-ray spectrometry is used to extract a quantitative 3D composition profile of heterostructured nanowires. The analysis of hypermaps recorded along a limited number of projections, with a preliminary calibration of the signal associated with each element, is compared to the intensity profiles calculated for a model structure with successive shells of circular, elliptic, or faceted cross sections. This discrete tomographic technique is applied to II-VI nanowires grown by molecular beam epitaxy, incorporating ZnTe and CdTe and their alloys with Mn and Mg, with typical size down to a few nanometers and Mn or Mg content as low as 10%.


A randomized clinical 1-year trial comparing two types of non-submerged dental implants.
This study compared the implant stability and clinical outcomes obtained with two types of non-submerged dental implants that have different thread designs and surface treatments. A randomized clinical trial with 1 year of follow-up was performed on 56 participants with 75 implants (control group, 36 implants in 28 subjects; experimental group, 39 implants in 28 subjects). The experimental group received the Osstem SSII Implant system; the control group received the Standard Straumann Dental Implant System. The diameter and length of the fixture were uniform at 4.1 mm and 10 mm and all the implants restored the unilateral loss of one or two molars from the mandible. To compare implant stability, the peak insertion torque, implant stability quotient (ISQ), and periotest value (PTV) were evaluated during surgery, and at 4 and 10 weeks after surgery. To compare marginal bone loss, standard periapical radiographs were obtained during surgery, and at 10 weeks and 1 year after surgery. This study showed statistically significant differences between the two groups in peak insertion torque (P=0.009) and ISQ (P=0.003) but not in PTV (P=0.097) at surgery. In contrast, there was no statistically significant difference in the pattern of change of ISQ during the 10 weeks after surgery (P=0.339). For marginal bone loss, no significant difference was observed between the control and the experimental groups before functional loading (P=0.624), but after 1 year of follow-up, a borderline difference was observed (P=0.048). The success rate after 1 year of follow-up was 100% for both implant system despite the presence of a significant difference in implant stability during surgery. There was a borderline difference in marginal bone loss after 1 year of follow-up.


MicroRNA expression signature of human sarcomas.
MicroRNAs (miRNAs) are approximately 22 nucleotide-long noncoding RNAs involved in several biological processes including development, differentiation and proliferation. Recent studies suggest that knowledge of miRNA expression patterns in cancer may have substantial value for diagnostic and prognostic determinations as well as for eventual therapeutic intervention. We performed comprehensive analysis of miRNA expression profiles of 27 sarcomas, 5 normal smooth muscle and 2 normal skeletal muscle tissues using microarray technology and/or small RNA cloning approaches. The miRNA expression profiles are distinct among the tumor types as demonstrated by an unsupervised hierarchical clustering, and unique miRNA expression signatures were identified in each tumor class. Remarkably, the miRNA expression patterns suggested that two of the sarcomas had been misdiagnosed and this was confirmed by reevaluation of the tumors using histopathologic and molecular analyses. Using the cloning approach, we also identified 31 novel miRNAs or other small RNA effectors in the sarcomas and normal skeletal muscle tissues examined. Our data show that different histological types of sarcoma have distinct miRNA expression patterns, reflecting the apparent lineage and differentiation status of the tumors. The identification of unique miRNA signatures in each tumor type may indicate their role in tumorigenesis and may aid in diagnosis of soft tissue sarcomas.


Indicated preterm birth for placenta accreta.
The purpose of this article is to review the risks and benefits of scheduled preterm delivery in patients with placenta accreta, increta, and percreta and to provide guidance regarding timing of delivery in such cases. Relevant documents for this opinion were identified through a search of the English literature for publications, including one or more of the keywords "accreta" or "increta" or "percreta" and "preterm" and "delivery time" by the use of PubMed (U.S. National Library Of Medicine, January 1990-January 2010), with results limited to studies involving humans. Additional information was obtained from references identified from within selected articles, from additional review articles, and from guidelines by organizations, including the American College of Obstetricians & Gynecologists. Each included article was evaluated according to study design and quality in accordance with scheme outlined by the U.S. Preventative Services Task Force, and final recommendations are provided based on the level of published evidence. On the basis of this search, we found that abnormal placentation, encompassing placenta accreta, increta, and percreta, is increasingly common. We also found that randomized controlled trials and well-controlled observational studies that can be used to define best practice in delivery time are lacking. Optimal delivery time must be determined from available case series, retrospective reviews and decision analysis studies. Given the best-available evidence, optimal time for delivery is believed to be between 34 and 35 weeks in most cases.


Detection of antibodies to varicella-zoster virus using a latex agglutination assay.
There is a clinical need to have a rapid and sensitive means to identify persons with immunity to varicella-zoster virus (VZV). We evaluated a simple-to-perform assay for detecting antibodies to VZV using a commercial latex agglutination (LA) test, in which dilutions of test sera were added to latex particles that had been coated with VZV glycoprotein antigens. Sera obtained from patients, including recipients of varicella vaccine, whose clinical immune status to VZV was known, were tested by LA and the results compared to those obtained by a standard indirect immunofluorescence assay (FAMA). Using the LA test, long-term persistence of antibodies in leukemic and adult recipients of varicella vaccine were determined. The LA test compared favorably with FAMA in varicella susceptibles and immunes. 741 acute sera were negative and 741 convalescent varicella sera were positive by LA. Antibodies to VZV were found to persist for as long as 11 years in most recipients of varicella vaccine (n = 145). Geometric mean titers were higher by LA than FAMA. Prozone phenomena were noted in about 5% of antibody-positive sera. Results from this test are available in less than an hour, and no special equipment is required. This assay is rapid, simple to perform, and inexpensive. It is particularly useful for identifying individuals who are immune to varicella, including those who have been immunized in the distant past. The main problem associated with the test is that prozone phenomena can occur; these may be avoided by testing sera at various dilutions.


High-Efficiency Production of Graphene by Supercritical CO2 Exfoliation with Rapid Expansion.
In this study, direct nonequilibrium molecular dynamics simulations based on the density-functional tight-binding potential were performed to investigate the mechanism of graphite exfoliation by supercritical CO2 in the depressurization process. We found that the graphite peeling rate and the graphene yield depended on the number of inserted CO2 molecules in our simulations, and the appropriate pressure or density of CO2 is a prerequisite to achieve graphite exfoliation. Our theoretical results proposed that the graphite peeling occurred till the pressure or the density of CO2 was larger than 12.2 MPa or 0.21 g/cm3. This is confirmed by the experimental observations. Furthermore, we declared that the essential effect of the pressure or density of CO2 was attributed to the competition between the van der Waals attraction in the graphite interlayer and repulsion of CO2 and graphite, which resulted from the steric hinder effect. The current theoretical observations provide potential scientific evidence to control graphite exfoliation by supercritical CO2.


Kinetic studies of HPr, HPr(H15D), HPr(H15E), and HPr(His approximately P) phosphorylation by the Streptococcus salivarius HPr(Ser) kinase/phosphorylase.
HPr is a central protein of the phosphoenolpyruvate:sugar phosphotransferase transport system (PTS). In streptococci, HPr can be phosphorylated at His(15) at the expense of PEP by enzyme I (EI) of the PTS, producing HPr(His approximately P). HPr can also be phosphorylated at Ser(46) by the ATP-dependent HPr(Ser) kinase/phosphorylase (HprK/P), producing HPr(Ser-P). Lastly, HPr can be phosphorylated on both residues, producing HPr(Ser-P)(His approximately P) (HPr-P2). We report here a study on the phosphorylation of Streptococcus salivarius HPr, HPr(H15D), HPr(H15E), and HPr(His approximately P) by HprK/P to assess the involvement of HprK/P in the synthesis of HPr-P2 in streptococcal cells. We first developed a spectrophotometric method for measuring HprK/P kinase activity. Using this assay, we found that the K(m) of HprK/P for HPr at pH 7.4 and 37 degrees C was approximately 110 muM, with a specificity constant (k(cat)/K(m)) of 1.7 x 10(4) M(-1) s(-1). The specificity constants for HPr(H15D) and HPr(H15E) were approximately 13 times lower. Kinetic studies conducted under conditions where HPr(His approximately P) was stable (i.e., pH 8.6 and 15 degrees C) showed that HPr(His approximately P) was a poorer substrate for HprK/P than HPr(H15D), the k(cat)/K(m) for HPr(H15D) and HPr(His approximately P) being approximately 9 and 26 times lower than that for HPr, respectively. Our results suggested that (i) the inefficiency of the phosphorylation of HPr(His approximately P) by HprK/P results from the presence of a negative charge at position 15 as well as from other structural elements and (ii) the contribution of streptococcal HprK/P to the synthesis of HPr-P2 in vivo is marginal.


Effects of fluid resuscitation methods on burn trauma-induced oxidative stress.
The aim of the study was to analyze the oxidative stress response after severe burn injury. We studied the effect of two methods of fluid resuscitation regimes on the oxidative stress reaction. Sixteen patients were involved in the study. Inclusion criteria were the presence of flame burn injury affecting >20% of BSA and in-hospital fluid resuscitation started within 3 hours after injury. Patients were randomly assigned into two groups. In the first group (n=8), the fluid resuscitation was guided by the hourly urine output and in the second (n=8), by the intrathoracic blood volume index. Blood sample was taken from the patients at admission and on the following five mornings. White blood cell count normalized by the third day in both groups, but the relative number of granulocytes and lymphocytes significantly (P<.05) diverged between hourly urine output and intrathoracic blood volume index groups from the fourth day of trauma. Plasma malondialdehyde level (P<.05 vs control population), reactive oxygen species production in whole blood (P<.05 vs control population), and catalase activity were elevated, whereas glutathione, plasma sulfhydryl groups level (P<.05 vs control population), and superoxide dismutase enzyme activity lowered in both groups. Our results confirmed that burn injury induces pronounced oxidative stress. The main finding is that fluid resuscitation regimes have different impact on prooxidant status, mainly on the granulocyte function but not on the changes in endogenous antioxidants in burned patients.


Presence of two sets of ribosomal genes in phytopathogenic mollicutes.
DNA from 28 strains of phytopathogenic mycoplasmalike organisms that represented five primary taxonomic clusters was digested with restriction endonucleases and hybridized with several ribosomal probes. The results indicate the presence of two sets of ribosomal genes in all strains examined. Restriction maps of the two ribosomal operons for a group of 12 aster yellows mycoplasmalike organisms were constructed.


Binuclear Lanthanide-Radical Complexes Featuring Two Centers with Different Magnetic and Luminescence Properties.
Binuclear complexes with general formula [Ln2(hfac)6(H2O)2(dppnTEMPO)] (LnIII = Gd, Tb, and Dy) have been obtained using the paramagnetic ligand 1-piperidinyl-4-[(diphenylphosphinyl)amino]-2,2,6,6-tetramethyl (dppnTEMPO) as a bridge. One of the lanthanide ions is ferromagnetically coupled with the TEMPO moiety. Two of the complexes (Dy and Tb) show slow relaxation of the magnetization, and the non-magneto-equivalence of the two LnIII ions was clearly observed. The ab initio CASSCF calculations were employed to confirm this behavior, as well as to rationalize the Ln-Rad interaction. The simulations of the magnetic properties were allowed by the insights given by the calculations. The inequivalence of the TbIII ions was also proved by emission spectroscopy.


Cystatin C and cathepsin B production by alveolar macrophages from smokers and nonsmokers.
The capacity of alveolar macrophages (AM) obtained from smokers and nonsmokers to secrete cathepsin B and its inhibitor cystatin C was examined because of the concept that an imbalance in the production of proteolytic enzymes and/or their inhibitors could be responsible for the lung damage seen in smokers. Quantitation of immunoprecipitates on Western blots showed that the amount of total cystatin C secreted into the culture medium by AM of smokers was significantly greater than the amount secreted by cells obtained from nonsmokers, whereas the difference between the amount of cathepsin B secreted by the AM of smokers and that from nonsmokers did not appear significant. The cystatin C found in the medium conditioned by AM of nonsmokers appeared to be more heterogeneous in molecular size, presenting either as a single band of about 14 Kd or as a high-molecular-weight triplet of about 69 Kd, 63 Kd, and 57.3 Kd. Furthermore, in some cases there were single or doublet bands at 14 Kd as well as the high-molecular-weight triplets. In contrast, smokers AM-conditioned medium uniformly possessed both the low-and the high-molecular-weight cystatin C. Cathepsin B was not detected in Western blots at its reported molecular weights but was identified at the exact area occupied by the higher molecular weight cystatin C, i.e., at bands corresponding to 69 Kd, 63 Kd, and 57.3 Kd. Therefore, it is clear that in culture media of AM, cystatin C and cathepsin B are present as proteinase-antiproteinase complexes. The observation also suggests that in smokers an excess of cystatin C may be elaborated, which, if further substantiated, would show for the first time a likely role for this proteinase inhibitor in vivo.


Sudden onset of cauda equina syndrome resulting from posterior migration of lumbar herniated disc without significant previous neurological signs.
While extruded disc fragments are known to migrate anteriorly, posteriorly, or laterally to the theca sac, posterior migration of the fragments is relatively rare and sudden onset of cauda equina syndrome (CES) caused by the migration is extremely rare. The authors experienced a case of CES that was manifested abruptly with sudden paraplegia caused by posterior migration of the lumbar intervertebral disc. A 74-year old man, who had no prior significant neurologic signs or trauma history, visited our emergency center with paraplegia of both lower extremities occurring suddenly when awakened. On magnetic resonance image (MRI) findings, we could detect ruptured disc herniation with severe lumbar stenosis at the L2-3 level. We performed an emergent decompression, and the right posterior migrated disc fragments at L2-3 were intraoperatively observed. The patient was fully recovered himself on the follow up after 3 months of the operation. In conclusion, early operation can result in better outcome in acute paraplegia caused by the posterior migrated disc fragments.


Insulin silences apolipoprotein B mRNA translation by inducing intracellular traffic into cytoplasmic RNA granules.
Insulin is a potent inducer of global mRNA translation and protein synthesis, yet it negatively regulates apolipoprotein B (apoB) mRNA translation, via an unknown mechanism. ApoB mRNA has a long half-life of 16 h, suggesting intracellular storage as mRNPs likely in the form of RNA granules. The availability of apoB mRNA for translation may be regulated by the rate of release from translationally silenced mRNPs within cytoplasmic foci called processing bodies (P bodies). In this report, we directly imaged intracellular apoB mRNA traffic and determined whether insulin silences apoB mRNA translation by entering cytoplasmic P bodies. We assessed the colocalization of apoB mRNA and β-globin mRNA (as a control) with P body (PB) markers using a strong interaction between the bacteriophage capsid protein MS2 and a sequence specific RNA stem-loop structure. We observed statistically significant increases in the localization of apoB mRNA into P bodies 4-16 h after insulin treatment (by 72-89%). The movement of apoB mRNA into cytoplasmic P bodies correlated with reduced translational efficiency as assessed by polysomal profiling and measurement of apoB mRNA abundance. PB localization of β-globin mRNA was insensitive to insulin treatment, suggesting selective regulation of apoB mRNA by insulin. Overall, our data suggest that insulin may specifically silence apoB mRNA translation by reprogramming its mRNA into P bodies and reducing the size of translationally competent mRNA pools. Translational control via traffic into cytoplasmic RNA granules may be an important mechanism for controlling the rate of apoB synthesis and hepatic lipoprotein production.


Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells.
Benzalkonium chloride (BAK) is a cationic detergent with a very slow turnover. Because of its strong antibacterial activities, BAK is widely used especially in dentistry and ophthalmology. It is the most commonly used preservative in topical ophthalmic medications. Due to chronicity and widespread use of such treatments, BAK's side effects are of great importance. BAK toxicity for adherent cells, probably related to its pro-oxidative activities, is time- and dose-dependent. Although lymphocytes often infiltrate superficial eye tissues, the BAK influence on them is yet to be established. The aim of this study was to check BAK cytotoxicity on T lymphocytic Jurkat line cells and to verify the suggestion that BAK can induce G2M cell blocks. A dose- and time-dependent cytotoxic effect of BAK on lymphoid cells in relatively low concentrations was shown in this study. In lower concentrations, it shows a moderate apoptotic and minimal antiproliferative effect on Jurkat cells, while in higher concentrations it shows a rapid necrotic effect. No G2M cell blocks were observed. Our findings could suggest lymphoid dysfunction during intensive, prolonged topical BAK treatment, even at dosages relatively non-toxic to epithelial eye cells.


Effects of photobiomodulation combined with orofacial myofunctional therapy on the quality of life of individuals with temporomandibular disorder.
To analyze the impact of photobiomodulation combined with orofacial myofunctional therapy (OMT) on the oral health quality of life (OHQOL) of individuals with temporomandibular disorder, before and after the treatment. Blind, controlled, randomized clinical trial with 34 volunteers randomly distributed into two groups: G1, who received OMT combined with photobiomodulation, and G2, treated with OMT combined with inactive laser. The subjects were first assessed with a visual analog scale (VAS) to classify them according to the degree of orofacial pain and with the Oral Health Impact Profile - Short Form (OHIP-14) regarding the impact on the OHQOL. The resulting data were statistically analyzed. The significance level was set at 0.05 (95%). "Physical pain", "psychological discomfort", "physical disability", and "psychological disability" were the aspects with the greatest impact on the OHQOL. The G1 subjects responded positively to their treatment, as well as G2 to theirs. There was a strong positive correlation between VAS and total OHIP-14 score in both groups after the treatment. However, the functional recovery in the control group individuals (G2) was the most perceived positive change in the OHQOL in comparison with the experimental group (G1). The people who received photobiomodulation combined with OMT perceived an improvement in the OHQOL, as well as those treated with placebo laser. There was a strong positive correlation in both groups in the improvement of the degree of pain and self-perception of the OHQOL.


[Evaluation of T cell subsets in myasthenia gravis by anti-T cell monoclonal antibodies].
In this paper, T lymphocyte subsets were measured in the peripheral blood of 46 patients with myasthenia gravis (MG) and 86 healthy controls, by using a modified microcytotoxicity assay and OKT monoclonal antibodies. The results showed that the OKT+3, OKT+4, OKT+8 cells of the patients with MG decreased significantly as compared with those of the controls (57.71% versus 66.42%; 34.50% versus 41.65%; 21.23% versus 27.19% respectively, P less than 0.01), and the OKT4/OKT8 ratio increased significantly (2.19 versus 1.64, P less than 0.05). Furthermore, the patients with the ocular type had less OKT+8 cells than those with the general type (14.19% versus 23.47%, P less than 0.05 and had a high OKT4/OKT8 ratio (3.27 versus 1.57, P less than 0.01). No correlating changes of T cell subsets with clinical conditions in that age, sex, and severity showed, and also that there was no difference between the patients whether prednisone was used or not (P greater than 0.05).


Frequency and amplitude estimation of the first peak of head-related transfer functions from individual pinna anthropometry.
The first (lowest) peak of head-related transfer functions (HRTFs) is known to be a concha depth resonance and a spectral cue in human sound localization. However, there is still no established model to estimate its center-frequency F1 and amplitude A1 from pinna anthropometry. Here, with geometries of 38 pinnae measured and their median-plane HRTFs calculated by numerical simulation, linear regression models were evaluated in estimating F1 and A1 from 25 concha depth and aperture measurements. F1 was best estimated (correlation coefficient r = 0.84, mean absolute error MAE = 118 Hz) by lateral distances from the base of the posterior cavum concha to the outer surface of the antitragus and antihelix (longest measures of concha depth). A1 was best estimated (r = 0.83, MAE = 0.84 dB) by the lateral distance from the ear-canal entrance to the side of the cheek near the anterior notch (shortest measure of concha depth) and by the equivalent diameter of the concha aperture. These results suggest that the first resonance's quarter-wavelength corresponds to the longest lateral extent of the concha and that its energy lost to the surrounding air depends on the concha aperture and the cavum concha's shortest lateral depth.


Exposure characteristics of ferric oxide nanoparticles released during activities for manufacturing ferric oxide nanomaterials.
The exposure characteristics of Fe2O3 nanoparticles (NPs) released in a factory were investigated, as exposure data on this type of NP is absent. The nature of the particles was identified in terms of their concentrations [i.e. number concentration (NC(20-1000 nm)), mass concentration (MC(100-1000 nm)), surface area concentration (SAC(10-1000 nm))], size distribution, morphology and elemental composition. The relationships between different exposure metrics were determined through analyses of exposure ranking (ER), concentration ratios (CR), correlation coefficients and shapes of the particle concentration curves. Work activities such as powder screening, material feeding and packaging generated higher levels of NPs as compared to those of background particles (p < 0.01). The airborne Fe2O3 NPs exhibited a unimodal size distribution and a spindle-like morphology and consisted predominantly of the elements O and Fe. Periodic and activity-related characteristics were noticed in the temporal variations in NC(20-1000 nm) and SAC(10-1000 nm). The modal size of the Fe2O3 NPs remained relatively constant (ranging from 10 to 15 nm) during the working periods. The ER, CR values and the shapes of NC(20-1000 nm) and SAC(10-1000 nm) curves were similar; however, these were significantly different from those for MC(100-1000 nm). There was a high correlation between NC(20-1000 nm) and SAC(10-1000 nm), and relatively lower correlations between the two and MC(100-1000 nm). These findings suggest that the work activities during the manufacturing processes generated high levels of primary Fe2O3 NPs. The particle concentrations exhibited periodicity and were activity dependent. The number and SACs were found to be much more relevant metrics for characterizing NPs than was the mass concentration.


Cryptic duplication of the distal segment of 22q due to a translocation (21;22): three case reports and a review of the literature.
Duplications of the proximal segment of chromosome 22q are not uncommon, like Cat-eye syndrome and duplications due to familial (11;22) translocations. However, duplications of the distal long arm of chromosome 22 (22qter) seem to be exceedingly rare. So far, duplications of 22q12 or 22q13 to 22qter have been described in 21 patients, of whom 13 had a pure duplication 22qter. Here we report on three new cases with a pure duplication of the distal part of 22q. The first patient carries a duplication of terminal 22q due to a de novo unbalanced translocation, 46,XX,der(21)t(21;22) (p13;q13.2), detected by NOR-staining, while the other patients have a familial cryptic duplication of terminal 22q due to an unbalanced translocation, 46,XY,der(21)t(21;22)(p10;q13.3). The last two patients were initially thought to have a polymorphic variant of 21p, but additional subtelomeric screening using FISH showed the extra material was derived from chromosome 22. Terminal duplications of 22qter may be more common than generally assumed, but due to its small size, especially when located on an acrocentric chromosome and/or possibly relatively mild phenotype remain undetected thus far.


How cells activate ATR.
ATR is a critical upstream regulator of checkpoint responses to incompletely replicated and damaged DNA. However, it had not been understood how the kinase activity of ATR is switched on during checkpoint responses. TopBP1 and its homologs are necessary for both DNA replication and checkpoint control. A recent report from this laboratory demonstrated that TopBP1 functions as an activator of ATR. It had been known that TopBP1 accumulates at sites of replicative stress and DNA damage. Thus, interaction of ATR with a critical protein at stalled replication forks and sites of DNA damage triggers its activation. This finding helps to explain how aberrant DNA structures in the genome induce ATR-dependent signaling processes.


Treatment of steroid-resistant pediatric nephrotic syndrome.
Children who suffer from steroid-resistant nephrotic syndrome (SRNS) require aggressive treatment to achieve remission. When intravenous high-dose methylprednisolone fails, calcineurin inhibitors, such as cyclosporine and tacrolimus, are used as the first line of treatment. A significant number of patients with SRNS progress to end-stage renal disease if remission is not achieved. For these children, renal replacement therapy can also be problematic; peritoneal dialysis may be accompanied by significant protein loss through the peritoneal membrane, and kidney allograft transplantation may be complicated by recurrence of SRNS. Plasmapheresis and rituximab were initially used for treatment of recurrent SRNS after transplantation; these are now under consideration as rescue therapies for refractory SRNS. Although the prognosis of SRNS is complicated and unfavorable, intensive treatment in the early stages of the disease may achieve remission in more than half of the patients. Therefore, timely referral of pediatric SRNS patients to pediatric nephrology specialists for histological and genetic diagnosis and treatment is highly recommended.


Rectal injuries.
Rectal injuries were often caused by penetrating injuries and usually occurred in male patients. The results of treatment related to many factors. These factors include the mechanisms of injury, the time from wounding to treatment, the severity of associated injuries, and the operative procedures. The important therapeutic procedures are colostomies, presacral drainage, and rectal irrigation. The type of colostomy and repair of the rectal defect played little significant role concerning the outcome of the patients.


A Novel Reconstruction Algorithm with High Performance for Compressed Ultrafast Imaging.
Compressed ultrafast photography (CUP) is a type of two-dimensional (2D) imaging technique to observe ultrafast processes. Intelligence reconstruction methods that influence the imaging quality are an essential part of a CUP system. However, existing reconstruction algorithms mostly rely on image priors and complex parameter spaces. Therefore, it usually takes a lot of time to obtain acceptable reconstruction results, which limits the practical application of the CUP. In this paper, we proposed a novel reconstruction algorithm named PnP-FFDNet, which can provide a high quality and high efficiency compared to previous methods. First, we built a forward model of the CUP and three sub-optimization problems were obtained using the alternating direction multiplier method (ADMM), and the closed-form solution of the first sub-optimization problem was derived. Secondly, inspired by the PnP-ADMM framework, we used an advanced denoising algorithm based on a neural network named FFDNet to solve the second sub-optimization problem. On the real CUP data, PSNR and SSIM are improved by an average of 3 dB and 0.06, respectively, compared with traditional algorithms. Both on the benchmark dataset and on the real CUP data, the proposed method reduces the running time by an average of about 96% over state-of-the-art algorithms, and show comparable visual results, but in a much shorter running time.


Redetermination of the Structure of a Water-Soluble Hypervalent Iodine(V) Reagent AIBX and Its Synthetic Utility in the Oxidation of Alcohols and Synthesis of Isoxazoline N-Oxides.
The structure of a water-soluble hypervalent iodine(V) reagent AIBX is re-examined through its single-crystal X-ray analysis and theoretical calculations including Mayer bond order and localized orbital locator (LOL) and AIBX is believed to be a pseudocyclic iodylarene because of the strong electron-withdrawing nature of the trimethylammonium cation on its phenyl ring, which would decrease the electron density of carboxylic anion and make the ortho-carboxyl oxygen anion incapable to form hypervalent bond with iodine atom. However, the cyclic benziodoxole structure of AIBX could be obtained by adding a Brønsted acid, which was supported by the calculation result including the increase of Mayer bond order and the shortening of the I-O bond length. Moreover, the fact that the system of AIBX and TFA could oxidize various alcohols to their corresponding carbonyl compounds would indicate that AIBX constitutes a cyclic benziodoxole structure under acidic conditions. In addition, an efficient method has been developed for the synthesis of isoxazoline N-oxides via AIBX-induced dehydrogenative cyclization using β-keto esters as substrates and methyl nitroacetate as a nucleophile.


Autoimmune cytopenia in chronic lymphocytic leukemia/small lymphocytic lymphoma: changes in clinical presentation and prognosis.
Improved medical care could have altered the clinical presentation and survival of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) complicated by autoimmune disease cytopenia (AID cytopenia). We reviewed the clinical characteristics, treatment, and outcome of AID cytopenia that was diagnosed in 75 (4.3%) of 1750 patients with CLL seen at a single institution over 10 years. When compared with the historical reported data, our study shows a lower rate of autoimmune hemolytic anemia (2.3%), and similar rates of immune thrombocytopenia (2.0%), and pure red blood cell aplasia (0.5%). AID cytopenia occurred at all stages of CLL, responded well to treatment, did not alter overall survival, and contributed to death in only 6 (12%) patients. We propose that more sensitive and accurate diagnostic methods for CLL have decreased the perceived prevalence of AID cytopenia and that improvements in management could have increased the survival of these patients.


Macrophage-specific targeting of isoniazid through mannosylated gelatin microspheres.
Active targeting of drug molecules can be achieved by effective attachment of suitable ligands to the surface of carriers. The present work was attempted to prepare mannosylated gelatin microspheres (m-GMs) so as to achieve targeted delivery of isoniazid (INH) to alveolar macrophages (AMs) and maintain its therapeutic concentration for prolonged period of time. Microspheres were prepared by emulsification solvent extraction method and evaluated for physicochemical characteristics, drug release, ex vivo drug uptake by AMs and pharmacokinetic characteristics. Fourier transform infrared spectroscopy and nuclear magnetic resonance spectral analysis confirmed that mannosylation took place through Schiff base formation between aldehyde and amino groups of mannose and gelatin, respectively. Prepared microspheres offered suitable physicochemical characteristics for their delivery to AMs. Their average size was about 4 μm and drug entrapment efficiency of 56% was achieved with them. Ex vivo uptake results indicated that in comparison to plain microspheres, m-GMs were selectively uptaken and were found to be associated with phago-lysosomal vesicles of AMs. Pharmacokinetic studies showed the formulation could maintain the therapeutic concentration of INH for prolonged period of time even with a reduced clinical dose. m-GMs were found to be stable in broncheo-alveolar lavage fluid. The study concluded that ligand decorated carriers could be a potential strategy to improve the therapeutic properties of INH.


A potent α/β-peptide analogue of GLP-1 with prolonged action in vivo.
Glucagon-like peptide-1 (GLP-1) is a natural agonist for GLP-1R, a G protein-coupled receptor (GPCR) on the surface of pancreatic β cells. GLP-1R agoinsts are attractive for treatment of type 2 diabetes, but GLP-1 itself is rapidly degraded by peptidases in vivo. We describe a design strategy for retaining GLP-1-like activity while engendering prolonged activity in vivo, based on strategic replacement of native α residues with conformationally constrained β-amino acid residues. This backbone-modification approach may be useful for developing stabilized analogues of other peptide hormones.


Inactivation of cytosol enzymes by a liver membrane protein.
Non-proteolytic inactivation reactions have been suggested to play an important role in determining the relative rates of enzyme degradation within cells. An inactivation factor is present at high specific activity in hepatocyte plasma membrane which inactivates cytosol enzymes at rates roughly proportional to their rates of degradation in vivo. This factor has been purified about 100-fold and has similar catalytic selectivity to the crude factor. The inactivation reaction is accelerated by disulphide compounds and can be partially reversed by thiols. Furthermore, inactivation of enzymes is accompanied by a loss of measurable thiols in the enzymes. From these experiments it is concluded that the inactivation factor carries out a disulphide attack on surface thiol groups in cytosol enzymes leading to the formation of mixed disulphides which have lost catalytic activity. The inactive enzymes may be substrates for lysosomal or non-lysosomal proteolysis.


Emerging Concepts and Therapies for Mucoobstructive Lung Disease.
A spectrum of intrapulmonary airway diseases, for example, cigarette smoke-induced bronchitis, cystic fibrosis, primary ciliary dyskinesia, and non-cystic fibrosis bronchiectasis, can be categorized as "mucoobstructive" airway diseases. A common theme for these diseases appears to be the failure to properly regulate mucus concentration, producing mucus hyperconcentration that slows mucus transport and, importantly, generates plaque/plug adhesion to airway surfaces. These mucus plaques/plugs generate long diffusion distances for oxygen, producing hypoxic niches within adherent airway mucus and subjacent epithelia. Data suggest that concentrated mucus plaques/plugs are proinflammatory, in part mediated by release of IL-1α from hypoxic cells. The infectious component of mucoobstructive diseases may be initiated by anaerobic bacteria that proliferate within the nutrient-rich hypoxic mucus environment. Anaerobes ultimately may condition mucus to provide the environment for a succession to classic airway pathogens, including Staphylococcus aureus, Haemophilus influenzae, and ultimately Pseudomonas aeruginosa. Novel therapies to treat mucoobstructive diseases focus on restoring mucus concentration. Strategies to rehydrate mucus range from the inhalation of osmotically active solutes, designed to draw water into airway surfaces, to strategies designed to manipulate the relative rates of sodium absorption versus chloride secretion to endogenously restore epithelial hydration. Similarly, strategies designed to reduce the mucin burden in the airways, either by reducing mucin production/secretion or by clearing accumulated mucus (e.g., reducing agents), are under development. Thus, the new insights into a unifying process, that is, mucus hyperconcentration, that drives a significant component of the pathogenesis of mucoobstructive diseases promise multiple new therapeutic strategies to aid patients with this syndrome.


Simulation-based architecture of a stable large-area [Formula: see text] atmospheric plasma source.
Unified jet-DBD design, [Formula: see text], proposed in this work presents large-scale plasma in an unbounded region of atmospheric air, without any need for the flow of gas, offering efficient exposure to sizable and complex objects. This is a simulation-based architecture for stable non-thermal plasma source with notable experimental results. [Formula: see text] geometry optimizes the electric field and charge distribution for a diffuse discharge in the steady air by a key design parameter of [Formula: see text]. Teflon insulator with a thickness [Formula: see text] imposes an intense and uniform electric field shaped up at the open area in front of the device and generates radially/axially expanded plasma jet. In the [Formula: see text], phase shift increases by [Formula: see text] and the plasma generates more power than the classical plasma jet. Two distinct states of [Formula: see text] operation indicate the mode-swap at [Formula: see text] and power dissipation. In the reactive [Formula: see text] scheme even small changes in the phase angle effectively improves the electric power.


A second mutant allele (V199I) at the PRKAG3 (RN) locus-II. Effect on colour characteristics of pork loin.
Three alleles at the PRKAG3 (RN) locus that influence the glycogen content of pork were found to be segregating in Hampshire×Landrace crossbred pigs, RN(-), rn(+) as well as second mutant allele V 199I (here denoted rn*). The effect of these three alleles on ultimate pH, pigment content, internal reflectance (FOP), surface colour measured by tristimulus colorimetry (L*, a*, b*) and fractions of deoxymyoglobin (Mb), oxymyoglobin (MbO(2)) and metmyoglobin (MetMb) of pork loin was studied. Moreover, the effect of sex, entire male versus female pigs, on these traits was also analysed. The three PRKAG3 alleles affected ultimate pH, internal reflectance, colour and distribution of myoglobin derivatives of pork loin, while the pigment content was not influenced. Ultimate pH values of loins from the three genotypes were found to be in the order RN(-)/- genotypes <rn(+)/rn(+) genotype <rn(+)/rn* genotype=rn*/rn* genotype. The internal reflectance in the loin was found to be in the order RN(-)/- genotypes >rn(+)/rn(+) genotype=rn(+)/rn* genotype=rn*/rn* genotype. The RN(-) allele was dominant resulting in higher redness (a* value) and yellowness (b* value), while the rn* allele tended to result in lower redness and yellowness compared with the rn* allele. The RN(-) allele was dominant over the rn* allele in lightness (L* value) giving a lighter colour. Surface colour differences were mainly explained by differences in the distribution of the myoglobin derivatives. Finally, surface lightness was higher and pigment content, redness and fraction of MbO(2) lower in loin from entire males compared with females.


Perfusion SPECT and FDG-PET.
Both perfusion SPECT and FDG-PET provide images that closely reflect neuronal activity. There is a characteristic regional impairment in Alzheimer's disease (AD) that involves mainly the temporo-parietal association cortices, mesial temporal structures and to a more variable degree also the frontal association cortex. This pattern of functional impairment can provide a biomarker for diagnosis of AD and other neurodegenerative dementias at the clinical stage of mild cognitive impairment, and for monitoring of progression. FDG-PET is quantitatively more accurate and thus better suited to multicenter studies than perfusion SPECT. Regional metabolic and blood flow changes are closely related to clinical symptoms, and most areas involved in these changes will also develop significant cortical atrophy. FDG-PET is complementary to amyloid PET, which targets a molecular marker that does not have a close relation to current symptoms. Current restrictions in the availability and cost of FDG-PET are being reduced, as oncological FDG-PET is being adopted as a standard clinical service in most countries. Limitations in the availability of trained staff should be overcome by training programs set up by professional organizations. Against the background of the development of new criteria for diagnosing AD before the onset of dementia, FDG-PET is expected to play an increasing role in diagnosing patients at an early stage of AD and in clinical trials of drugs aimed at preventing or delaying the onset of dementia.


Selection for Growth and Precocity Alters Muscle Metabolism in Nellore Cattle.
To clarify the relationship between beef genetic selection for growth and precocity with muscle metabolism and metabolites, we performed metabolomic analysis using Longissimus lumborum (LL) muscle from Nellore cattle with divergent selection for these traits (high growth, HG; low growth, LG; high precocity, HP; low precocity, LP). Genetic potential for growth affected muscle protein and energetic metabolism. HG animals had a high concentration of arginine, carnosine, and leucine compared to LG animals. HP animals presented a high concentration of glutamine, betaine, creatinine, isoleucine, carnitine, acetyl carnitine, and lower levels of glucose compared to LP animals, affecting protein and fatty acid metabolism. Intensity of selection (high or low) was correlated with changes in protein metabolism, and the type of selection (growth or precocity) affected fat metabolism. In conclusion, both HG and HP appear to be correlated with a high concentration of protein metabolites and changes in protein metabolic pathways, while selection for precocity is more correlated with changes in fat metabolism compared to animals selected for growth.


Impact of conditional cash transfers on child nutritional outcomes among sub-Saharan African countries: a systematic review protocol.
The objective of this review is to assess the impact of conditional cash transfers on child nutritional outcomes among sub-Saharan African countries. More specifically, the objectives are to assess the impact of conditional cash transfers on child anthropometry, micro-nutrient, and improvement in dietary diversity of households.


Excitatory effects of hypocretin-1 (orexin-A) in the trigeminal motor nucleus are reversed by NMDA antagonism.
Hypocretin-1 and -2 (Hcrt-1 and -2, also called orexin-A and -B) are newly identified neuropeptides synthesized by hypothalamic neurons. Defects in the Hcrt system underlie the sleep disorder narcolepsy, which is characterized by sleep fragmentation and the involuntary loss of muscle tone called cataplexy. Hcrt neurons project to multiple brain regions including cranial and spinal motor nuclei. In vitro studies suggest that Hcrt application can modulate presynaptic glutamate release. Together these observations suggest that Hcrt can affect motor output and that glutamatergic processes may be involved. We addressed these issues in decerebrate cats by applying Hcrt-1 and -2 into the trigeminal motor nucleus to determine whether these ligands alter masseter muscle activity and by pretreating the trigeminal motor nucleus with a N-methyl-d-aspartate (NMDA) antagonist to determine if glutamatergic pathways are involved in the transduction of the Hcrt signal. We found that Hcrt-1 and -2 microinjections into the trigeminal motor nucleus increased ipsilateral masseter muscle tone in a dose-dependent manner. We also found that Hcrt application into the hypoglossal motor nucleus increases genioglossus muscle activity. Pretreatment with a NMDA antagonist (d-(-)-2-amino-phosphonovaleric acid) abolished the excitatory response of the masseter muscle to Hcrt-1 application; however, pretreatment with methysergide, a serotonin antagonist had no effect. These studies are the first to demonstrate that Hcrt causes the excitation of motoneurons and that functional NMDA receptors are required for this response. We suggest that Hcrt regulates motor control processes and that this regulation is mediated by glutamate release in the trigeminal motor nucleus.


Graphs of protein-water hydrogen bond networks to dissect structural movies of ion-transfer microbial rhodopsins.
Microbial rhodopsins are membrane proteins that use the energy absorbed by the covalently bound retinal chromophore to initiate reaction cycles resulting in ion transport or signal transduction. Thousands of distinct microbial rhodopsins are known and, for many rhodopsins, three-dimensional structures have been solved with structural biology, including as entire sets of structures solved with serial femtosecond crystallography. This sets the stage for comprehensive studies of large datasets of static protein structures to dissect structural elements that provide functional specificity to the various microbial rhodopsins. A challenge, however, is how to analyze efficiently intra-molecular interactions based on large datasets of static protein structures. Our perspective discusses the usefulness of graph-based approaches to dissect structural movies of microbial rhodopsins solved with time-resolved crystallography.


A Randomized, Double-Blind, Placebo-Controlled, Split-Face Study of the Efficacy of Topical Epidermal Growth Factor for the Treatment of Melasma.
Melasma is a condition in which patients develop symmetric, reticulated, hyperpigmented macules and patches on the face which is thought to be the result of ultraviolet (UV) exposure and hormonal influences, although the pathogenesis is not completely understood. The topical application of epidermal growth factor has been used as a whitening agent, moisturizer, and an aid for wound healing. In this study, we explore the efficacy of topical EGF in the treatment of melasma. This was a randomized, double-blind, placebo-controlled, split-face study to determine the efficacy of a topical EGF serum in the treatment of melasma. Fifteen women with a mean age of 44 were randomized to treatment side of the face and applied a topical EGF serum and a placebo twice daily to each designated side of the face for eight weeks. Patient satisfaction was assessed by use of the MelasQoL Questionnaire as well as a patient outcome survey. Subjects were evaluated using the Physician Global Aesthetic Improvement Scale (GAIS) by two board-certified dermatologists. GAIS scores showed an improvement in the melasma in 73.4% of subjects vs 13% improvement for the placebo side. The average MelasQoL questionnaire score decreased from 42 to 33 with 73% of subjects having an improvement in their score. In addition, 73% of subjects reported an improvement in their melasma. No adverse events or side effects were reported with use of the topical serum or placebo. This study suggests that topical EGF is a safe, noninvasive, and effective treatment for melasma. J Drugs Dermatol. 2018;17(6):970-973.


Dopaminergic induction of human adipose-derived mesenchymal stem cells is accompanied by transcriptional activation of autophagy.
Neural differentiation involves drastic morphological alterations, essentially performed by a cell-homeostasis maintaining process known as autophagy. Here, we used the cocktail of choroid plexus epithelial cell-conditioned medium (CPEC-CM) and 15% knockout serum (KS) to induce human adipose-derived mesenchymal stem cells (hASCs) into tyrosine hydroxylase (TH)-positive neuron like cells. We showed that upon this induction, autophagy pathway was transcriptionally triggered. The expression levels of autophagy markers mTOR, BECN1, and MAP1LC3 were evidently changed throughout the dopaminergic (DAergic) differentiation of hASCs, highlighting the critical role of autophagy in this process at the level of transcription.


Transnitrosation of non-mutagenic N-nitrosoproline forms mutagenic N-nitroso-N-methylurea.
N-Nitroso-N-methylurea (NMU) is a potent carcinogen and suspected as a cause of human cancer. In this study, mutagenic NMU was detected by HPLC after the transnitrosation of non-mutagenic N-nitrosoproline (NP) to N-methylurea in the presence of thiourea (TU) under acidic conditions. The structure of NMU was confirmed by comparing (1)H NMR and IR spectra with that of authentic NMU after fractionation by column chromatography. Furthermore, a fraction containing NMU formed by transnitrosation was mutagenic in Salmonella typhimurium TA1535. NMU was formed in the reaction of NP and N-methylurea in the presence of 1,1,3,3-tetramethylthiourea (TTU) or 1,3-dimethylthiourea in place of TU as an accelerator. The reaction rate constants (k) for NMU formation were correlated with their nucleophilicity of sulfur atom in thioureas. The N-methylurea concentration did not affect the NMU formation, whereas the rate of NMU formation correlated linearly with concentrations of NP, TTU and oxonium ion. The observed kinetics suggests a mechanism by which the nitroso group was transferred directly from the protonated NP to the thiourea then to N-methylurea to form NMU. The rate-determining step was the formation of the complex with the protonated NP and thiourea.


Cross-sectional study of area-level disadvantage and glycaemic-related risk in community health service users in the Southern.IML Research (SIMLR) cohort.
Objectives The aim of the present study was to determine the association between area-level socioeconomic disadvantage and glycaemic-related risk in health service users in the Illawarra-Shoalhaven region of New South Wales, Australia. Methods HbA1c values recorded between 2010 and 2012 for non-pregnant individuals aged ≥18 years were extracted from the Southern.IML Research (SIMLR) database. Individuals were assigned quintiles of the Socioeconomic Indices for Australia (SEIFA) Index of Relative Socioeconomic Disadvantage (IRSD) according to their Statistical Area 1 of residence. Glycaemic risk categories were defined as HbA1c 5.0-5.99% (lowest risk), 6.0-7.49% (intermediate risk) and ≥7.5% (highest risk). Logistic regression models were fit with glycaemic risk category as the outcome variable and IRSD as the study variable, adjusting for age and sex. Results Data from 29064 individuals were analysed. Higher disadvantage was associated with belonging to a higher glycaemic risk category in the fully adjusted model (most disadvantaged vs least disadvantaged quintile; odds ratio 1.74, 95% confidence interval 1.58, 1.93; P<0.001). Conclusion In this geocoded clinical dataset, area-level socioeconomic disadvantage was a significant correlate of increased glycaemic-related risk. Geocoded clinical data can inform more targeted use of health service resources, with the potential for improved health care equity and cost-effectiveness. What is known about the topic? The rapid increase in the prevalence of Type 2 diabetes (T2D), both globally and nationally within Australia, is a major concern for the community and public health agencies. Individual socioeconomic disadvantage is a known risk factor for abnormal glucose metabolism (AGM), including T2D. Although small-area-level socioeconomic disadvantage is a known correlate of AGM in Australia, less is known of the association of area-level disadvantage and glycaemic-related risk in individuals with AGM. What does this paper add? This study demonstrates a robust association between small-area-level socioeconomic disadvantage and glycaemic-related risk in regional New South Wales. The study demonstrates that it is feasible to use geocoded, routinely collected clinical data to identify communities at increased health risk. What are the implications for practitioners? The identification of at-risk populations is an essential step towards targeted public health policy and programs aimed at reducing the burden of AGM, its complications and the associated economic costs. Collaboration between primary care and public health in the collection and use of data described in the present study has the potential to enhance the effectiveness of both sectors.


Development of a novel transgenic mouse/SCID-hu mouse system to characterize the in vivo behavior of reservoirs of human immunodeficiency virus type 1-infected cells.
To develop a system in which transgenic and knockout technologies are used to study the in vivo behavior of human immunodeficiency virus type 1 (HIV-1) reservoirs, 2 different mouse models were combined: transgenic mice carrying full-length provirus encoding the monocyte-tropic HIV-1(JR-CSF) isolate (JR-CSF mice) and severe combined immunodeficient mice implanted with human fetal thymus and liver tissues (thy/liv-SCID-hu mice). Extensive HIV-1 infection of human thymic implants occurred after injection of JR-CSF mouse leukocytes into thy/liv-SCID-hu mice, indicating that these cells provide an in vivo source of replication-competent HIV-1. In vivo persistence of transferred JR-CSF mouse leukocytes carrying replication-competent HIV-1 in thy/liv-SCID-hu mice was indicated by the emergence of HIV-1 infection in mice that had no detectable HIV-1 infection until after highly active antiretroviral therapy. Thus, thy/liv-SCID-hu mice populated with JR-CSF mouse leukocytes, a persistent cellular reservoir harboring replication-competent HIV-1, present a new in vivo system for characterizing reservoirs of HIV-1 and evaluating therapeutic strategies designed to eliminate them.


Effects of silver diamine fluoride on dentine carious lesions induced by Streptococcus mutans and Actinomyces naeslundii biofilms.
BACKGROUND. Silver diamine fluoride (SDF) has been shown to be a successful treatment for arresting caries. However, the mechanism of SDF is to be elucidated. AIM. To characterize the effects of SDF on dentine carious induced by Streptococcus mutans and Actinomyces naeslundii. DESIGN. Thirty-two artificially demineralized human dentine blocks were inoculated: 16 with S. mutans and 16 with A. naeslundii. Either SDF or water was applied to eight blocks in each group. Biofilm morphology, microbial kinetics and viability were evaluated by scanning electron microscopy, colony forming units, and confocal microscopy. The crosssection of the dentine carious lesions were assessed by microhardness testing, scanning electron microscopy with energy-dispersive x-ray spectroscopy and Fourier transform infrared spectroscopy. RESULTS. Biofilm counts were reduced in SDF group than control (P < 0.01). Surfaces of carious lesions were harder after SDF application than after water application (P < 0.05), in S. mutans group, Ca and P weight percentage after SDF application than after water application (P < 0.05). Lesions showed a significantly reduced level of matrix to phosphate after SDF treatment (P < 0.05). CONCLUSION. Present study showed that SDF posses an anti-microbial activity against cariogenic biofilm of S. mutans or A. naeslundii formed on dentine surfaces. SDF slowed down demineralization of dentine. This dual activity could be the reason behind clinical success of SDF.


[Research progress on clinical and mechanisms of chronic pruritus with anxiety and depression].
Chronic pruritus seriously affects the quality of life of patients, which is closely related to stress, anxiety and depression. Prolonged and repeated pruritus can induce negative emotions such as anxiety and depression, while continued increased negative emotions can also promote exacerbation of pruritus, which drives the itch scratch cycle, thereby further aggravating skin damage. More and more studies have explored the mechanism of pruritus, anxiety and depression. This article mainly reviews the clinical relationship between pruritus and anxiety, depression and the new progress of its possible mechanism, providing reference for the prevention, control and effective treatment of chronic pruritus, anxiety and depression.


In vitro analysis of T cell-mediated cytotoxicity displayed by rat heart allograft recipients rendered unresponsive by total-lymphoid irradiation and extracted donor antigen.
The addition of 3M KCl-extracted donor antigen (HAg) to immunosuppressive therapy with 16 Gy total lymphoid irradiation produces a significantly higher fraction of Wistar-Furth (WFu) recipients displaying indefinite survival of heterotopic buffalo (BUF) heart allografts, namely 80 versus 20%. The experiments presented herein analyzed the direct activity as well as estimated the potential precursor numbers at 1 and 3 months in treated recipients. At 1 month post-TLI/HAg therapy, recipients showed reduced proliferative responses in mixed lymphocyte reactions (MLR) in a specific pattern toward donor but not third-party stimulators. Both TLI/Graft and TLI/HAg/Graft groups showed a higher frequency of BUF antigen-directed T-cytotoxic cells (fTc) than TLI-treated, but nontransplanted, WFu hosts. In addition, the TLI/HAg group alone displayed alloantigen-specific suppressor cells that suppressed the MLR proliferative responses of normal spleen T cells against donor, but not third-party, alloantigens. At 3 months postirradition, both TLI/Graft and TLI/HAg/Graft groups displayed variable MLR proliferative responses toward donor and third-party alloantigens. Whereas nontransplanted, TLI-treated WFu rats recovered their fTc to normal levels at 3 months, the TLI and TLI/HAg treated recipients bearing functional heart allografts demonstrated significantly decreased splenic fTc. These results show that reduced numbers of cytotoxic cell precursors may afford more reliable indices of prolonged heart allograft survival than MLR responses. The observations suggest that TLI/HAg transplant hosts display both reduced cytotoxic precursors and activated suppressor elements.


Myositis ossificans in tetanus. A rare complication.
Myositis ossificans developing as a complication of tetanus is very rare. There are only nine cases reported so far. We report here a case of a young female who developed myositis ossificans in both the elbow joints as a complication of severe tetanus.


Macrophage takeover and the host-bacilli interplay during tuberculosis.
Macrophages are key type of antigen-presenting cells that arbitrate the first line of defense against various intracellular pathogens. Tuberculosis, both pulmonary and extrapulmonary, is an infectious disease of global concern caused by Mycobacterium tuberculosis. The bacillus is a highly successful pathogen and has acquired various strategies to downregulate critical innate-effector immune responses of macrophages, such as phagosome-lysosome fusion, autophagy, induction of cytokines, generation of reactive oxygen and nitrogen species and antigen presentation. In addition, the bacilli also subvert acquired immunity. In this review, we aim to provide an overview of different antimycobacterial immune functions of macrophage and the strategies adopted by the bacilli to manipulate these functions to favor its survival and replication inside the host.


Suppression of the synaptic localization of a subset of proteins including APP partially ameliorates phenotypes of the Drosophila Alzheimer's disease model.
APP (amyloid precursor protein), the causative molecule of Alzheimer's disease, is synthesized in neuronal cell bodies and subsequently transported to synapses. We previously showed that the yata gene is required for the synaptic transport of the APP orthologue in Drosophila melanogaster. In this study, we examined the effect of a reduction in yata expression in the Drosophila Alzheimer's disease model, in which expression of human mutant APP was induced. The synaptic localization of APP and other synaptic proteins was differentially inhibited by yata knockdown and null mutation. Expression of APP resulted in abnormal synaptic morphology and the premature death of animals. These phenotypes were partially but significantly rescued by yata knockdown, whereas yata knockdown itself caused no abnormality. Moreover, we observed that synaptic transmission accuracy was impaired in our model, and this phenotype was improved by yata knockdown. Thus, our data suggested that the phenotypes caused by APP can be partially prevented by inhibition of the synaptic localization of a subset of synaptic proteins including APP.


Molecular Structure and Antioxidant Properties of Alkali Metal Salts of Rosmarinic Acid. Experimental and DFT Studies.
The molecular structure of alkali metal rosmarinates was studied in comparison to rosmarinic acid using FT-IR, FT-Raman, 1H and 13C NMR spectroscopy, as well as density functional theory (DFT) calculations. The B3LYP/6-311+G(d,p) method was used to calculate optimized geometrical structures of studied compounds, atomic charges, dipole moments, energies, as well as the wavenumbers and intensities of the bands in vibrational and NMR spectra. Theoretical parameters were compared to experimental data. Antioxidant activity was determined using two spectrophotometric methods: (i) Assessing the ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable radical and (ii) assay of antioxidant power of ferric ions reducing (FRAP). The linear correlations were found between HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap and the reducing power expressed as FRAP (R = 0.77) as well as between IC50 values (the ability of quenching DPPH radicals) and Δνas-s(COO) in IR spectra (differences between asymmetric and symmetric stretching vibrations bands) (R = 0.99). Photochemical properties of studied compounds were also evaluated. The influence of alkali metal on the electronic system of the rosmarinic acid molecule was discussed.


Anomalous median nerve associated with persistent median artery.
A right human forearm showed persistence of the median artery in combination with anomalies of the median nerve and of the palmar circulation. The median nerve formed a ring enclosing the median artery, gave off its 3rd palmar digital branch in the forearm, and had a high palmar cutaneous nerve origin and a double thenar supply. The superficial palmar arch was incomplete. The median artery extended into the hand, providing the 2nd common palmar digital artery and the artery to the radial side of the index finger. It anastomosed with the radial artery in the 1st web space.


Plasminogen activator inhibitor-1 levels and polymorphisms.
To review the published evidence of a relationship between levels of plasminogen activator inhibitor-1 (PAI-1) or the 4G/5G polymorphism of the PAI-1 gene and the occurrence of venous thromboembolic disease. Review of the medical literature using computerized databases and a review of secondary sources identified through bibliographies. Plasminogen activator inhibitor-1 is an important inhibitor of the fibrinolytic system, so it is biologically plausible that elevated levels could suppress fibrinolysis and result in an increased risk of thrombosis. Several small studies reported associations between PAI-1 levels and venous thromboembolism, some of which appear to be familial. Problems with these studies include variations in PAI-1 plasma levels due to circadian changes and the acute phase response, as well as alterations due to common comorbid disease states. More recent investigations have focused on genetic polymorphisms, particularly the 4G/5G insertion/deletion in the promoter region, affecting transcription rates. The relation of 4G/5G to venous thrombosis has been investigated primarily in case-control studies, which have produced inconsistent findings. Most studies, however, have reported higher PAI-1 plasma levels in individuals with 4G/4G. The evidence regarding the relationship between an elevated PAI-1 plasma level or PAI-1 genetic polymorphism and the risk of venous thromboembolism is conflicting. There is insufficient information to recommend use of PAI-1 levels or genotype in evaluating thrombophilia.


Staging of acute diverticulitis based on clinical, radiologic, and physiologic parameters.
Acute diverticulitis is a broad spectrum of diseases with highly varying mortality and need for surgery. The aim of this study was to create an accurate staging of diverticulitis, which could be used both preoperatively and intraoperatively to predict outcome and guide treatment. This was a retrospective study of patients treated for diverticulitis in a secondary and tertiary referral center. Multivariate analysis was performed on several clinical, radiologic, and physiologic parameters to find predictors of mortality, need for surgery, need for intensive care, and length of stay. A total of 631 patients were analyzed. Organ dysfunction, peritonitis, and abscess size greater than 6 cm were identified as independent predictors of poor outcome. Pericolic air or no extraluminal air predicted better outcome. Based on these factors, a five-grade staging was created as follows: Stage 1, uncomplicated diverticulitis; Stage 2, complicated diverticulitis with small abscess (<6 cm); Stage 3, complicated diverticulitis with large abscess (≥6 cm) or distant intraperitoneal or retroperitoneal air; Stage 4, Generalized peritonitis without organ dysfunction; Stage 5, generalized peritonitis with organ dysfunction. Mortality was 0, 1%, 3%, 4%, and 32%; need for surgery was 1%, 5%, 46%, 98%, and 100%; and need for intensive care was 0%, 0%, 8%, 11%, and 50%, in Stages 1 to 5, respectively. New staging showed better predictive ability of outcomes compared with earlier classifications in receiver operating characteristic curve analyses. The proposed staging can be used on all patients both preoperatively and intraoperatively. It takes into account organ dysfunction, which has major influence on survival. The new staging may be easily implemented in daily clinical practice and incorporated in clinical trials. Diagnostic study, level II.


Assembly, Release, and Transport of Airway Mucins in Pigs and Humans.
The respiratory system is protected from inhaled particles and microbes by the mucociliary system. This system differs between animal species, where pigs and humans have numerous submucosal glands. The polymer-forming mucin, MUC5B, is packed in a highly organized way in granules of the mucus-secreting cells in the glands. Upon secretion, the packed MUC5B is flushed out by a chloride- and bicarbonate-rich fluid from the cystic fibrosis transmembrane conductance regulator-expressing serosal cells located at the most distal part of the gland. The bicarbonate raises the pH and removes calcium from the N terminus of MUC5B, allowing the mucin to be pulled out into a linear polymer. Thousands of such polymers gather in bundles in the submucosal gland duct, and these bundles appear at the opening of the glands. They are moved by the beating cilia, and sweep over the airway surface and are patchily coated with the MUC5AC mucin from the surface goblet cells. The movement of these bundles is controlled by the MUC5AC mucin attachment/detachment to the goblet cells. Thus, higher animals with submucosal glands and large diameters of the proximal airways are efficiently cleaned by the thick mucus bundles sweeping the airway surface and moving particles and bacteria toward the larynx.


Ertapenem pharmacokinetics and pharmacodynamics during continuous ambulatory peritoneal dialysis.
Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD). The goals of this study were to characterize the PK profile of ertapenem during CAPD, determine the extent of ertapenem penetration into the peritoneal cavity, and quantify the probability of the target attainment (PTA) profile in the serum and peritoneal cavity. A single-dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined the probability that ertapenem at 500 mg intravenously (i.v.) every 24 h (q24h) would achieve concentrations in excess of the MIC for 40% of the dosing interval (40% T>MIC, where T is time) in the serum and peritoneal cavity. Monte Carlo simulation was also used to calculate the peritoneal cavity/serum mean and median penetration ratios by estimating the area under the concentration-time curve in the peritoneal cavity and serum (AUC(Peritoneal) and AUC(Serum), respectively) from zero to infinity after a single simulated dose. The population mean (± standard deviation [SD]) values for the apparent volume in the central compartment, clearance, and apparent volume in the peritoneal cavity were 2.78 (0.62) liters, 0.24 (0.07) liters/hr, and 5.81 (2.05) liters, respectively. The mean (SD) AUC(Peritoneal)/AUC(Serum) ratio was 1.039 (0.861), and the median penetration ratio was 0.801 (interquartile range, 0.486 to 1.317). In both the serum and peritoneal cavity, ertapenem at 500 mg i.v. q24h was very likely (>90%) to achieve the pharmacodynamic target for MICs of ≤2 mg/liter. The simulations suggest that 500 mg of ertapenem i.v. q24h is very likely to achieve the exposure target associated with clinical efficacy in both the serum and peritoneal cavity against the range of MIC values deemed susceptible by the Clinical and Laboratory Standards Institute.