A family practice breastfeeding education pilot program: an observational, descriptive study.
The United States Preventive Services Task Force found that effective interventions for extending breastfeeding duration are generally begun during the prenatal period, provide ongoing support for patients and combine information with face-to-face guidance. A 2001 literature review had similar findings but also found that employing a lactation consultant in the clinical setting may increase breastfeeding duration rates. Thus, a program was developed at a family practice office that employed a lactation consultant and followed the American Academy of Pediatrics' "Ten Steps to Support Parents' Choice to Breastfeed Their Baby." The program distributed handouts at each prenatal and well-child visit (up to one year). Using questionnaires, a small audit project evaluated the program's impact on breastfeeding goals, duration, in-hospital exclusivity and maternal perception of success. Mothers completed goal surveys at baseline and post-intervention, usually while waiting for prenatal clinic visits. Duration was assessed by surveys completed during well-infant visits, postal mailings or telephone interviews at breastfeeding cessation, 6 months and 1 year. The outcomes measured were increases in goals, maternal perception of success, duration and in-hospital exclusivity. Participants included 33 women: 48% had a bachelor's or master's degree, 61% were non-Hispanic white, and 67% reported incomes of US$75,000 or higher. At baseline 5/31 planned to exclusively breastfeed for 4-6 months and 5/33 planned to breastfeed for 6-12 months. Post-intervention there was a 200% increase (15/31) in the exclusively breastfeeding 4-6 month group and a 160% increase (13/33) in the 6-12 month duration group. Actual in-hospital exclusivity rates were 61%, 6-month duration rates were 73%, and 12-month rates were 33%. Over 75% of mothers reported feeling successful. This small pilot educational program may have significant impacts on breastfeeding goals. Setting and meeting goals may increase duration and in-hospital exclusivity rates as well as enhance maternal self-perception and empowerment due to succeeding at their breastfeeding goals and/or experiencing a fulfilling breastfeeding relationship.


User-centered virtual environment design for virtual rehabilitation.
As physical and cognitive rehabilitation protocols utilizing virtual environments transition from single applications to comprehensive rehabilitation programs there is a need for a new design cycle methodology. Current human-computer interaction designs focus on usability without benchmarking technology within a user-in-the-loop design cycle. The field of virtual rehabilitation is unique in that determining the efficacy of this genre of computer-aided therapies requires prior knowledge of technology issues that may confound patient outcome measures. Benchmarking the technology (e.g., displays or data gloves) using healthy controls may provide a means of characterizing the "normal" performance range of the virtual rehabilitation system. This standard not only allows therapists to select appropriate technology for use with their patient populations, it also allows them to account for technology limitations when assessing treatment efficacy. An overview of the proposed user-centered design cycle is given. Comparisons of two optical see-through head-worn displays provide an example of benchmarking techniques. Benchmarks were obtained using a novel vision test capable of measuring a user's stereoacuity while wearing different types of head-worn displays. Results from healthy participants who performed both virtual and real-world versions of the stereoacuity test are discussed with respect to virtual rehabilitation design. The user-centered design cycle argues for benchmarking to precede virtual environment construction, especially for therapeutic applications. Results from real-world testing illustrate the general limitations in stereoacuity attained when viewing content using a head-worn display. Further, the stereoacuity vision benchmark test highlights differences in user performance when utilizing a similar style of head-worn display. These results support the need for including benchmarks as a means of better understanding user outcomes, especially for patient populations. The stereoacuity testing confirms that without benchmarking in the design cycle poor user performance could be misconstrued as resulting from the participant's injury state. Thus, a user-centered design cycle that includes benchmarking for the different sensory modalities is recommended for accurate interpretation of the efficacy of the virtual environment based rehabilitation programs.


Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation.
Declines in immune function are well described in the elderly and are considered to contribute significantly to the disease burden in this population. Regulatory T cells (T(regs)), a CD4(+) T cell subset usually characterized by high CD25 expression, control the intensity of immune responses both in rodents and humans. However, because CD25 expression does not define all T(regs), especially in aged hosts, we characterized T(regs) by the expression of FOXP3, a transcription factor crucial for T(reg) differentiation and function. The proportion of FOXP3(+)CD4(+) T(regs) increased in the blood of the elderly and the lymphoid tissues of aged mice. The expression of functional markers, such as CTLA-4 and GITR, was either preserved or increased on FOXP3(+) T(regs) from aged hosts, depending on the tissue analyzed. In vitro depletion of peripheral T(regs) from elderly humans improves effector T cell responses in most subjects. Importantly, T(regs) from old FoxP3-GFP knock-in mice were suppressive, exhibiting a higher level of suppression per cell than young T(regs). The increased proportion of T(regs) in aged mice was associated with the spontaneous reactivation of chronic Leishmania major infection in old mice, likely because old T(regs) efficiently suppressed the production of IFN-gamma by effector T cells. Finally, in vivo depletion of T(regs) in old mice attenuated disease severity. Accumulation of functional T(regs) in aged hosts could therefore play an important role in the frequent reactivation of chronic infections that occurs in aging. Manipulation of T(reg) numbers and/or activity may be envisioned to enhance the control of infectious diseases in this fragile population.


Cytotoxicity and Genotoxicity of Azobenzene-Based Polymeric Nanocarriers for Phototriggered Drug Release and Biomedical Applications.
Drug nanoencapsulation increases the availability, pharmacokinetics, and concentration efficiency for therapeutic regimes. Azobenzene light-responsive molecules experience a hydrophobicity change from a polar to an apolar tendency by trans-cis photoisomerization upon UV irradiation. Polymeric photoresponse nanoparticles (PPNPs) based on azobenzene compounds and biopolymers such as chitosan derivatives show prospects of photodelivering drugs into cells with accelerated kinetics, enhancing their therapeutic effect. PPNP biocompatibility studies detect the safe concentrations for their administration and reduce the chance of side effects, improving the effectiveness of a potential treatment. Here, we report on a PPNP biocompatibility evaluation of viability and the first genotoxicity study of azobenzene-based PPNPs. Cell line models from human ventricular cardiomyocytes (RL14), as well as mouse fibroblasts (NIH3T3) as proof of concept, were exposed to different concentrations of azobenzene-based PPNPs and their precursors to evaluate the consequences on mitochondrial metabolism (MTT assay), the number of viable cells (trypan blue exclusion test), and deoxyribonucleic acid (DNA) damage (comet assay). Lethal concentrations of 50 (LC50) of the PPNPs and their precursors were higher than the required drug release and synthesis concentrations. The PPNPs affected the cell membrane at concentrations higher than 2 mg/mL, and lower concentrations exhibited lesser damage to cellular genetic material. An azobenzene derivative functionalized with a biopolymer to assemble PPNPs demonstrated biocompatibility with the evaluated cell lines. The PPNPs encapsulated Nile red and dofetilide separately as model and antiarrhythmic drugs, respectively, and delivered upon UV irradiation, proving the phototriggered drug release concept. Biocompatible PPNPs are a promising technology for fast drug release with high cell interaction opening new opportunities for azobenzene biomedical applications.


Chemical Stability of Proteins in Foods: Oxidation and the Maillard Reaction.
Protein is a major nutrient present in foods along with carbohydrates and lipids. Food proteins undergo a wide range of modifications during food production, processing, and storage. In this review, we discuss two major reactions, oxidation and the Maillard reaction, involved in chemical modifications of food proteins. Protein oxidation in foods is initiated by metal-, enzyme-, or light-induced processes. Food protein oxidation results in the loss of thiol groups and the formation of protein carbonyls and specific oxidation products of cysteine, tyrosine, tryptophan, phenylalanine, and methionine residues, such as disulfides, dityrosine, kynurenine, m-tyrosine, and methionine sulfoxide. The Maillard reaction involves the reaction of nucleophilic amino acid residues with reducing sugars, which yields numerous heterogeneous compounds such as α-dicarbonyls, furans, Strecker aldehydes, advanced glycation end-products, and melanoidins. Both protein oxidation and the Maillard reaction result in the loss of essential amino acids but may positively or negatively impact food structure and flavor.


Intelligent machines, care work and the nature of practical reasoning.
The debate over the ethical implications of care robots has raised a range of concerns, including the possibility that such technologies could disrupt caregiving as a core human moral activity. At the same time, academics in information ethics have argued that we should extend our ideas of moral agency and rights to include intelligent machines. This article explores issues of the moral status and limitations of machines in the context of care. A conceptual argument is developed, through a four-part scheme derived from the work of Alasdair MacIntyre. No empirical data are used. No primary data were gathered for this study. Secondary sources and authorship have been acknowledged throughout. Certain kinds of social experience, including the narrative unity of a life, and the giving and receiving of care, are essential for moral development. Machines, no matter how advanced, cannot participate in such experiences in key respects, and thus cannot develop as practical reasoners. It follows that they cannot be moral agents and that they cannot care. There are, it seems, no such things as care robots. In view of the institutional power of tech companies and commissioning bodies, care practitioners need to take more of a lead in developing new assistive technologies which are appropriate to their practice.


Enhancing insulin-use safety in hospitals: Practical recommendations from an ASHP Foundation expert consensus panel.
Consensus recommendations to help ensure safe insulin use in hospitalized patients are presented. Insulin products are frequently involved in medication errors in hospitals, and insulin is classified as a high-alert medication when used in inpatient settings. In an initiative to promote safer insulin use, the American Society of Health-System Pharmacists (ASHP) Research and Education Foundation convened a 21-member panel representing the fields of pharmacy, medicine, and nursing and consumer advocacy groups for a three-stage consensus-building initiative. The panel's consensus recommendations include the following: development of protocol-driven insulin order sets, elimination of the routine use of correction/sliding-scale insulin doses for management of hyperglycemia, restrictions on the types of insulin products stored in patient care areas, and policies to restrict the preparation of insulin bolus doses and i.v. infusions to the pharmacy department. In addition, the panelists recommended that hospitals better coordinate insulin use with meal intake and glucose testing, prospectively monitor the coordination of insulin delivery and rates of hypoglycemia and hyperglycemia, and provide standardized education and competency assessment for all hospital-based health care professionals responsible for insulin use. A 21-member expert panel convened by the ASHP Foundation identified 10 recommendations for enhancing insulin-use safety across the medication-use process in hospitals. Professional organizations, accrediting bodies, and consumer groups can play a critical role in the translation of these recommendations into practice. Rigorous research studies and program evaluations are needed to study the impact of implementation of these recommendations.


Forecasting the Risk of Heart Failure Hospitalization After Acute Coronary Syndromes: the CORALYS HF Score.
The present study aimed to identify patients at a higher risk of hospitalization for heart failure (HF) in a population of patients with acute coronary syndrome (ACS) treated with percutaneous coronary revascularization without a history of HF or reduced left ventricular (LV) ejection fraction before the index admission. We performed a Cox regression multivariable analysis with competitive risk and machine learning models on the incideNce and predictOrs of heaRt fAiLure After Acute coronarY Syndrome (CORALYS) registry (NCT04895176), an international and multicenter study including consecutive patients admitted for ACS in 16 European Centers from 2015 to 2020. Of 14,699 patients, 593 (4.0%) were admitted for the development of HF up to 1 year after the index ACS presentation. A total of 2 different data sets were randomly created, 1 for the derivative cohort including 11,626 patients (80%) and 1 for the validation cohort including 3,073 patients (20%). On the Cox regression multivariable analysis, several variables were associated with the risk of HF hospitalization, with reduced renal function, complete revascularization, and LV ejection fraction as the most relevant ones. The area under the curve at 1 year was 0.75 (0.72 to 0.78) in the derivative cohort, whereas on validation, it was 0.72 (0.67 to 0.77). The machine learning analysis showed a slightly inferior performance. In conclusion, in a large cohort of patients with ACS without a history of HF or LV dysfunction before the index event, the CORALYS HF score identified patients at a higher risk of hospitalization for HF using variables easily accessible at discharge. Further approaches to tackle HF development in this high-risk subset of patients are needed.


Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.
Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses1,2 and can function as bona fide antigens that facilitate tumour rejection3. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma4-6, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load1,7 and an immunologically 'cold' tumour microenvironment8. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.


Determinants of volumetric breast density in Chilean premenopausal women.
High mammographic breast density (BD) is a strong risk factor of breast cancer; however, little is known in women under 40 years of age. Recently, dual-energy X-ray Absorptiometry (DXA) has been developed as a low-dose method to measure BD in young populations. Thus, our aims were to describe BD in relation to risk factors in Chilean women under 40 years old and to explore the equivalence of DXA to mammography for the measurement of BD. We selected 192 premenopausal Chilean female participants of the DERCAM study for whom we have anthropometric, sociodemographic, and gyneco-obstetric data. The subjects received both digital mammograms (Hologic) and breast DXA scans (GE iDXA). Mammographic BD was estimated using a fully automated commercial method (VOLPARA®) and BI-RADS. Breast DXA scans were performed using a standardized protocol and the % fibroglandular volume (%FGV) was estimated considering a two-compartment model of adipose and fibroglandular tissue. The mean age was 37 years (SD = 6.5) and 31.6% of the subjects were obese. The median %FGV and absolute FGV (AFGV) measured by DXA were 9% and 198.1 cm3 and for VOLPARA®, 8.6% and 58.0 cm3, respectively. The precision for %FGV after reposition was 2.8%. The correlation coefficients for %FGV, AFGV, and breast volume between DXA and mammography were over 0.7. Age and body mass index (BMI) were inversely associated with %FGV, and BMI was positively related to AFGV as estimated with DXA or mammography. We did not observe an association with gyneco-obstetric characteristics, education, and %FGV and AFGV; smoking was only associated with AFGV as measured by VOLPARA®. DXA is an alternative method to measure volumetric BD; thus, it could be used to continuously monitor BD in adult women in follow-up studies or to assess BD in young women.


A High-Accuracy Detection System: Based on Transfer Learning for Apical Lesions on Periapical Radiograph.
Apical Lesions, one of the most common oral diseases, can be effectively detected in daily dental examinations by a periapical radiograph (PA). In the current popular endodontic treatment, most dentists spend a lot of time manually marking the lesion area. In order to reduce the burden on dentists, this paper proposes a convolutional neural network (CNN)-based regional analysis model for spical lesions for periapical radiographs. In this study, the database was provided by dentists with more than three years of practical experience, meeting the criteria for clinical practical application. The contributions of this work are (1) an advanced adaptive threshold preprocessing technique for image segmentation, which can achieve an accuracy rate of more than 96%; (2) a better and more intuitive apical lesions symptom enhancement technique; and (3) a model for apical lesions detection with an accuracy as high as 96.21%. Compared with existing state-of-the-art technology, the proposed model has improved the accuracy by more than 5%. The proposed model has successfully improved the automatic diagnosis of apical lesions. With the help of automation, dentists can focus more on technical and medical diagnoses, such as treatment, tooth cleaning, or medical communication. This proposal has been certified by the Institutional Review Board (IRB) with the certification number 202002030B0.


The natural history of aortic root aneurysms.
The aortic root has a different embryologic origin from all other segments of the human aorta, a feature that likely confers unique susceptibilities, anatomical patterns, and clinical behavior of aneurysm disease in this vital location. In this manuscript, we review the natural history of ascending aortic aneurysm, with a specific focus on the aortic root. The specific central message is that root dilatation is more malignant than ascending dilatation.


A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway.
S100A9 (S100 calcium-binding protein A9) is a calcium-binding protein of the S100 family, and its differential expression has been associated with acute and chronic inflammation and several human cancers. Our previous work showed that S100A9 was severely down-regulated in human ESCC (oesophageal squamous cell carcinoma). To further investigate the transcriptional regulation of S100A9, we analysed the S100A9 promoter region and found several putative p53BS (p53-binding sites). Luciferase reporter assays showed that constructs carrying the p53BS exhibited enhanced luciferase activity in response to wild-type p53 activation. Further study demonstrated that S100A9 mRNA and protein expression could be positively regulated in a p53-dependent manner and p53 could bind to p53BS on the S100A9 promoter. Overexpression of S100A9 could induce cellular apoptosis, and this was partly p53-dependent. Knockdown of S100A9 impaired the apoptosis induced by p53. Thus we conclude that a gene down-regulated in ESCC, S100A9, is a novel p53 transcriptional target, induces cellular apoptosis in a partly p53-dependent manner and mediates the p53 apoptosis pathway.


Professionalism and community psychiatric nursing: a case study of four mental health teams.
In this paper I report on a 2-year study of the professional status of 10 psychiatric nurses, working in four community mental health teams. The focus of the research was directed towards identifying the levels of clinical autonomy experienced by psychiatric nurses working in these teams. Diary-interview schedules were used to record how new clients were processed by the psychiatric nurse. The other members of the teams were interviewed (as were the managers to whom the nurses were accountable), using focused-interview schedules. The quantitative data from the diary-interview schedules were analysed using the Statistical Package for the Social Sciences. An adapted form of the technique advocated by Burnard was used to analyse qualitative data extracted from the diary-interview schedules and the focused-interviews. Conclusions from the research indicated that the nurses experienced a high degree of de facto clinical autonomy, which was characterized by unsupervized and arbitrary decision-making processes. In order to protect the user of mental health services, it is recommended that the espoused occupational strategy of professionalization for community psychiatric nurses is reconsidered.


Network analysis of a community-wide teenage pregnancy prevention initiative.
Although US teenage birth rates substantially decreased over the past two decades, it still remains the highest in the developed world. More innovative, community-wide initiatives are needed to combat the issue. In Oklahoma County, Oklahoma, the Central Oklahoma Teen Pregnancy Prevention Collaboration is utilizing the collective impact model to convene multiple organizations with the goal of making systems-level changes related to teenage pregnancy within the community. This study used an interorganizational network analysis to evaluate the current strength of relationships between organizations in the Collaboration. An interorganizational network survey assessed collaborative relationships (e.g. information sharing and joint planning) within the network. Using R software, network diagrams were developed to depict partner relationships, and network measures, including node-, group- and network-level measures, were calculated. The network depiction (n = 23) revealed that the network core was composed of organizations from multiple sectors, and the backbone organization served as the most central organization for most centrality measures. This study provides insight into how organizational relationships can be assessed in order to increase community capacity to address teenage pregnancy. Continuous monitoring of the strength of relationships is important to ensure success in achieving goals as well as collective impact.


[Correlation between survival time and severity of injuries in fatal injuries in traffic accidents].
In forensic pathology, only trauma systems based on disintegration of anatomic structure of organs and tissues, could be used for objectivization, comparison and establishing of severity of injuries. Trauma systems based on pathophysiological values are useless. The Abbreviated Injury Scale (AIS) and its derivate Injury Severity Score (ISS) are the most common. AIS coded injuries are divided into six body regions and injuries are assigned a six-digit score in relation to their severity. ISS results the sum of the squares of the highest AIS values from the three most severely injured body regions. In this way, the ISS values are discontinued and vary from 0 (absence of injuries) to 75 (incompatible-with-life injury). The purpose of this paper is to establish the correlation degree between outliving period and trauma severity in persons fatally injured in traffic accidents, and according to this finding to point out the ISS value of critical injury. A retrospective autopsy study was performed; it included the material of the Institute of Forensic Medicine in Belgrade of 1998. The autopsy reports and accessible clinical medical data were analyzed for persons over the age of 18, fatally injured in traffic accidents who survived trauma less than 15 days. The sample was statistically prepared (chi 2-test, t-test, correlation coefficient, regression line). The sample included 272 persons: 193 males and 79 females. The proportion of men was more significant (chi 2 = 4.76; 0.01 < p < 0.05). Average age was 51.08 years (SD = 18.08): males 49.84 +/- 17.41 and females 54.09 +/- 19.38. The most frequently injured persons in our sample were pedestrians (134). The authors combined the autopsy and accessible clinical data in order to obtain the ISS value for each case. They considered that all persons found dead on the spot or died ante portam did not outlive trauma. The sample distribution by ISS values showed three peaks: for ISS--75, 41-50 and 26-35. Peaks indicated the number of the injured body regions and trauma severity in these persons. In 87 persons who did not survive, the ISS value was 75. There were 73 persons without outliving period with ISS values less than 75: their mean ISS value was 31.87 (SD = 11.30). In 112 cases the mean outliving period was 4.79 days (SD = 3.77) and their mean ISS value was 18.05 (SD = 15.33), which was a statistically significant lower ISS value than in previous group (t = 7.015; p < 0.001). A weak negative correlation between outliving period and ISS values in our sample was noted (coefficient of linear correlation r = -0.452). Our sample is representative (t = 8.37). Coefficient of a determination (r2 = 0.20), pointed to the fact that direct correlation outliving period-trauma severity was only about 20% and the rest of correlation i.e. 80% depended on other factors (e.g. effective emergency medical system and triage, prompt and correct diagnosis, adequate medical treatment and care, etc.). The calculated linear regression was as follows: outliving period approximately 52-3 ISS. This regression pointed out that critical and potentially fatal injury, in our sample, was injury with ISS of 17. There were 22 persons with ISS < or = 7. Six of them died on the spot as car passengers; they died due to mechanical asphyxia (thoracoabdominal pressure) or respiratory and/or circulation failure due to critical chest injury (flail chest, contusions and rupture of the lungs with consequent haemopneumothorax). The rest of 16 persons survived trauma in an average of 8.56 days (SD = 3.88), and the causes of death were pneumonia, thrombus and fat embolism, sepsis, etc. By anaylzing our sample of fatally injured persons in traffic accidents (unpenetrated blunt trauma), there was a negative weak correlation between the outliving period and severity of injury based on ISS. This correlation was partly direct but mostly depended on other factors (e.g. effective emergency medical system and triage, prompt and correct diagnosis, adequate medical treatment and care, etc.). Establishment of these factors could be possible through state medical projects in big medical trauma centres. Prospect registration, evaluation and scoring of all injuries in hospitals and dissecting rooms, and comparison of the obtained results, can give valid data on mortality of injured people, bad diagnosis, and appropriate medical treatment. The autopsy of injured persons dead on the spot can point out what kind of injuries are incompatible with life, as well as with their severity. The autopsy of injured persons who survived trauma can point to the most frequent injury complications, clinical diagnosis and preventable deaths. According to this paper, the critical injury by ISS is 17. In such cases, the forensic pathologist must answer the following questions: whether the death was due to trauma; whether the precipitated cause of death was the consequence or complication of injury; what were the mechanism and mode of dying; whether the death was preventable; if there were possible malpractice and negligence, etc.


Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid-aspirin complex: results of a randomized, crossover, bioequivalence study.
Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid formulation of a novel pharmaceutical lipid-aspirin complex (PL-ASA) was designed to prevent this disruption. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with immediate release aspirin (IR-ASA). In this active-control crossover study, 32 healthy volunteers were randomized to receive 1 of 2 dose levels (a single dose of 325 mg or 650 mg) of either PL-ASA or IR-ASA. After a 2-week washout period between treatment assignments, subjects received a single dose of the alternative treatment, at the same dose level. The primary objectives of the study were to assess, for PL-ASA and IR-ASA at 325 mg and 650 mg dose levels, PK and PD bioequivalence, and safety, over a 24-h period after administration of both drugs. PK parameters were similar for PL-ASA and IR-ASA, and met FDA-criteria for bioequivalence. Regarding PD, both drugs also showed Cmin TxB2 values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) and > 99% inhibition of serum TxB2 ( ≥ 95% inhibition represents the cut-off for aspirin responders) along with similar results in several secondary PK/PD parameters. There were no serious adverse events or changes from baseline in vital signs or laboratory values in either of the 2 treatment groups. PL-ASA's novel liquid formulation has similar PK and PD performance compared with IR-ASA, supporting functional and clinical equivalence. These data coupled with the improved gastric safety of PL-ASA suggest that this novel formulation may exhibit an improved benefit-risk profile, warranting evaluation in future trials.Clinical trial registration: http://www.clinicaltrials.gov . Unique Identifier: NCT04008979.


Demography of the human sex ratio in some Latin American countries, 1967-1986.
A sample based on hospital births recorded for the Latin American Collaborative Study on Congenital Malformations (ECLAMC) program was used in the present study to determine sex ratios for live births and for stillbirths. Sixty-four cities and 147 hospitals in 11 countries (Uruguay, Chile, Argentina, Brazil, Bolivia, Peru, Paraguay, Ecuador, Venezuela, Colombia, and Costa Rica) were included in the present analyses. The number of live births was 1,886,653 in the period 1967-1986, and the number of stillbirths was 24,818 in the period 1978-1986. The sex ratio for the total sample was 0.5112 for live births and 0.5477 for stillbirths. The sex ratio as a whole is decreasing with time in a parabolic fashion. Each country in our study behaved differently. Except for Peru and Uruguay, the countries experienced a significant decrease in the sex ratio after 1978 for live births; only Brazil did not show a temporal trend for the sex ratio for stillbirths.


Building Clinical Leadership Competencies When Caring for Hospitalized Adults Experiencing Dementia.
Attempting to improve the experience of hospitalized adults with dementia and reduce patient attendant costs, we addressed hospital nursing staff confidence managing responsive behaviors through education, mentorship, and individualized patient care planning for adults with dementia.Responsive behaviors (such as pacing, calling out) is a term used to describe behaviors demonstrated by a person with dementia as a way of responding to something negative, frustrating, or confusing in their social and physical environment. Under time restraints, we performed a rapid environmental scan and developed internal clinical resources and a learning strategy that informed a quality improvement initiative that focused on dementia care of hospitalized patients. Using quantitative and qualitative evaluation methods, the interventions increased confidence, competency, and leadership in clinical nursing leaders and improved person-centered care planning practices. The cost of patient attendant usage for this patient population decreased by 28% in 1 year. This intervention, which was not a copyrighted program associated with administration costs, improved hospital-based dementia care and staff confidence in dementia care and reduced annual costs associated with patient attendant useage.


Impact of background and modulation on parameter estimation using fractional Fourier transform and its solutions.
Analysis of closed-fringe patterns with quadratic phase that are often encountered plays an important role in optical interferometry. But because the frequency spectra of the two exponential signals that compose closed-fringe patterns overlap in the Fourier domain while one is clearly distinct from the other in the fractional Fourier domain, fractional Fourier transform (FRFT) is a useful method for analyzing the images to provide parameter estimation. However, when the fringe pattern has varying background and/or modulation due to non-uniform illumination, parameter estimation accuracy based on FRFT is affected, which lacks theoretical justification. Thus, the impact of varying background and/or modulation on the FRFT is studied with theoretic analysis and presented in this paper. Key factors that contribute to the optimal results are discussed when employing three kinds of fringe normalization methods to eliminate the impact. Here, the fringe pattern is first processed by the normalization technique. Then the cosine-only term is used to estimate parameter by use of the FRFT-based method. Physical quantities are then obtained by parameter estimation. In comparison with our previous method based on FRFT, more accurate results are achieved. The feasibility and applicability of the proposed approach are demonstrated using simulation and experimental results.


alpha1-Antitrypsin deficiency and skin abnormalities.
A 19-year-old Moroccan male was found to have total absence of serum alpha1-antitrypsin, a major inhibitor of elastase. This patient had chronic obstructive lung disease, hyperextensibility of the skin over the cheeks and wrists, and hyperlaxity of the hand joints. Microscopic sections of the skin revealed a thickened dermis with shortened and rarefied elastic fibers. Ultrastructural study showed collagen fibers with variable and irregular diameters. Elastic fibers were scarce and their relatively poor matrix was surrounded by numberous microfibrils. The outline of the fibers was irregular with deep recesses filled with microfibrils. The ergastoplasm of the fibroblasts was well developed. The differential diagnosis with other connective dystrophies showed the original characteristic of this case. Clinically and histopathologically, the skin abnormalities are probably related to the deficiency in elastase inhibitor.


The sign of Leser-Trélat. Report of a case with adenocarcinoma of the duodenum.
The sign of Leser-Trélat is a rare cutaneous manifestation of internal malignancy. Although adenocarcinoma is the most common malignant neoplasm associated with the sign of Leser-Trélat, we report what we believe to be the first case of adenocarcinoma of the duodenum associated with this sign. Because of the location of the tumor, we considered the possibility that the skin changes may be due to increased levels of epidermal growth factor (EGF) in this patient. However, no alteration in urine EGF levels was found.


Overexpression of insulin receptors in fibroblast and ovary cells induces a ligand-mediated transformed phenotype.
To investigate whether overexpression of the insulin receptor results in altered cell growth we used NIH 3T3 cells transfected with a bovine papilloma virus/insulin receptor cDNA construct (3T3/HIR). These cells expressed high numbers of insulin receptors (mean +/- sd, 631.0 +/- 16.7 ng receptors/10(6) cells). Insulin significantly stimulated the growth of 3T3/HIR cells maintained in serum-free medium. Moreover, in these cells, insulin induced marked phenotypic changes, including alterations in cell shape, loss of contact inhibition, and focal growth. In contrast to 3T3/HIR cells, insulin was without effect in either wild-type 3T3 cells (3T3/wt), 3T3 cells transfected with the neomycin resistance gene (3T3/NEO), or the bovine papilloma virus (3T3/BPV). To assess the presence of anchorage-independent growth, cells were seeded in soft agar and inspected for colony formation. 3T3/HIR cells showed absent or minimal colony growth in the absence of insulin. However, there was a dose-dependent insulin-stimulated increase in both colony size and number. Insulin-stimulated colony formation was specifically inhibited by an insulin antagonist, monoclonal antibody MA-10. In the presence of 100 nM insulin, about 3% of cells formed large colonies. Insulin neither stimulated growth nor induced colony formation in 3T3/wt cells or 3T3/NEO cells. Insulin also stimulated colony formation in CHO cells transfected with an insulin receptor cDNA construct. In conclusion, overexpression of normal insulin receptors induces a ligand-dependent transformed phenotype. This phenomenon may have clinical relevance by conferring a selective growth advantage to tumor cells with high numbers of insulin receptors.


Visualizing water clearance in the lung with MRI.
Current indirect measurements of alveolar fluid clearance (AFC) suggest that the rate of fluid clearance correlates with morbidity and mortality in patients with pulmonary edema. In a traditional AFC-measurement, fluid laced with a tracer macromolecule is instilled into the lung and thereafter repeated samples of the instilled fluid are extracted from the lung's fluid-filled airspaces. The change in concentration of the tracer molecule indicates the AFC-rate. In this work, a new MRI technique was developed to image lung water clearance by adding Gadolinium-DTPA to the instilled fluid. As fluid is absorbed by the animal, the concentration of gadolinium will increase, reducing the T(1) relaxation time. By repeatedly measuring the T(1) relaxation time, the AFC can be tracked over time with high spatial resolution. The new technique was tested both in phantoms and 10 Yorkshire piglets.


Retroviral Transduction of Human Primary T Cells Followed by Real-Time T-Cell-Mediated Cancer Cell Cytolysis Analysis.
Retroviral transduction is a highly useful tool to genetically engineer hard-to-transfect human primary cells. Here, we transduce human primary T cells with a tumor-specific T cell receptor. This creates a useful tool to analyze T cell-cancer cell interactions, such as cytolysis analysis using xCELLigence technology.


Variability in patients with glaucomatous visual field damage is reduced using size V stimuli.
To test the hypothesis that variability of conventional automated perimetry can be reduced using size V stimuli for patients with glaucomatous visual field damage. Ten patients with glaucoma and five age-matched control volunteers were tested with the Humphrey Field Analyzer program 24-2 or 30-2, after which the method of constant stimuli was used to measure frequency-of-seeing curves. This was done by controlling the perimeter with a custom program run by a personal computer. At two widely separated visual field locations on the program 24-2 or 30-2 grid, stimuli were presented in 2 dB intervals to at least 10 dB on either side of the estimated program 24-2 or 30-2 threshold. This protocol was performed for each of three stimulus sizes (Goldmann sizes I, III, and V). For the patients with glaucoma, one test location was chosen in an area of normal visual field sensitivity, the other in an area of 10 to 20 dB loss. Control subjects were tested at the (3 degrees, 3 degrees) and (-21 degrees, -9 degrees) test locations. Fifteen repetitions were performed at each intensity. Repeated measures analysis of variance showed that variability, as measured by the standard deviation of the cumulative Gaussian function of the fitted frequency-of-seeing curves, was lowest at the abnormal sensitivity test location in the subjects with glaucoma using a size V stimulus. Differences between the results from the V to III and V to I stimuli were statistically significant (size V = 2.9 dB, III = 10.1 dB, I = 10.1 dB). The same trend in estimated standard deviations was present in tests of the area of normal sensitivity (size V = 1.1 dB, III = 1.7 dB, I = 2.0 dB) in subjects with glaucoma and for the control subjects' peripheral test locations, but not for the central location. The smaller reduction in variability between estimated standard deviations of the size I and size III stimuli was not statistically significant at any test location. Use of size V stimuli in conventional automated perimetry reduces variability in tests of moderately damaged and normal sensitivity test locations in subjects with glaucoma.


Pharmacokinetics and CNS pharmacodynamics of the 5-HT1A agonist buspirone in humans following acute L-tryptophan depletion challenge.
This study was designed to evaluate the relationship between the pharmacokinetic(s) (PK) and CNS pharmacodynamic(s) (PD) of buspirone, an antidepressant/anxiolytic, in 6 healthy male volunteers placed on an acute L-tryptophan deficient (ATD) diet. The study was a randomized, double-blind, placebo-controlled, four-period, three-way crossover study. The first study period was a single-blind familiarization period in which all subjects received placebo. During the remaining three study periods, subjects received either placebo, 10 mg or 30 mg oral buspirone. Subjects were administered the ATD diets 5 h prior to buspirone/placebo administration during each study period. All subjects underwent serial measurements of resting electroencephalography (REEG) and vigilance electroence-phalography (VEEG), cognitive tests, subjective rating scales, and blood was sampled for determination of unbound plasma L-tryptophan, serum prolactin, serum cortisol and plasma buspirone and its active metabolite, 1-pyrimdylpiperazine (1-PP). The ATD diet reduced the unbound plasma L-tryptophan concentrations to 20% of their baseline values. The intraindividual and interindividual variability in the unbound L-tryptophan concentration drop was less than 10% and 15%, respectively. Peak L-tryptophan depletion occurred 5 h after ATD diet was administered; L-tryptophan depletion lasted for approximately 11 h, and L-tryptophan concentrations recovered to baseline values approximately 13 h after administration of the ATD diet. PK-PD analysis for buspirone showed that: 1) peak plasma concentration (Cmax) and total area under the plasma concentration-time curve (AUC infinity) for buspirone following the 10 mg dose in this study were higher than those reported previously in the literature; 2) there was a transient response in the neuroendocrine measures, subjective rating scales and the EEG, but no changes in the cognitive tests with increasing doses of buspirone; 3) the PD measures were correlated with the doses of buspirone, but not with plasma concentrations of buspirone and 1-PP; and 4) the subjective rating scales were the most sensitive indicators of buspirone's CNS effects. This study provides evidence that ATD diet is a simple, specific and non-toxic experimental method to lower plasma L-tryptophan concentrations and thereby (indirectly) deplete brain tryptophan and serotonin (5-HT) concentrations. The ATD challenge may serve as a model of depression in healthy volunteers because of its ability to induce transient symptoms of the disease. Comparison of the results from this study to those reported in the literature suggests that the use of the ATD diet decreases the buspirone-induced neuroendocrine response, increases the buspirone-induced changes in subjective rating scales and, at the same time, increases the systemic exposure to buspirone and 1-PP.


DNA methylation in haematological malignancies: the role of decitabine.
Normal cell development and function is dependent upon controlled gene expression. DNA methylation is an epigenetic modification that can play an important role in the control of gene expression. DNA methylation at cytosine residues in gene promoter CpG sequences is known to inhibit gene transcription. Inappropriate inhibition of the transcription of tumour suppressor genes, genes that inhibit angiogenesis and metastasis and genes involved in DNA repair by uncontrolled methylation, can lead to unregulated growth and proliferation of a cell and carcinogenesis. Promoter hypermethylation affecting the p16 gene, resulting in gene silencing, has been shown to occur in many human solid tumours and a 'hypermethylation profile' in some leukaemias has been defined. The molecular mechanisms by which aberrant DNA methylation takes place during carcinogenesis are still not clear. However, the large number of target genes (involved in tumorigenesis) that are silenced by aberrant methylation suggests that inhibition of this process may have potential as cancer therapy. Decitabine (NSC-127716, Dacogen; SuperGen) is a potent and specific hypomethylating agent and an inhibitor of the DNA methyltransferase activity that mediates DNA methylation. Decitabine has been shown to have a broad range of antineoplastic activity in preclinical studies. This agent has exhibited significant activity in the treatment of patients with myelodysplastic syndrome, chronic myeloid leukaemia and acute myeloid leukaemia, although clinical Phase I and II studies with solid tumours have not been very promising. Phase II and III studies are currently ongoing to evaluate decitabine, both alone and in combination, in various stages of these haematological malignancies.


Expression of Glut-1 in Normal Endometrium and Endometrial Lesions: Analysis of 336 Cases.
Glucose transporter-1 (Glut-1) is a membrane glycoprotein that is, together with other glucose transporters, responsible for the regulation of glucose uptake. An increased expression of this protein seems to be a general feature of several malignant tumors that are able to reprogram their metabolism and switch from oxidative phosphorylation to aerobic glycolysis. We performed comprehensive immunohistochemical analysis of Glut-1 expression in 336 endometrial samples, including tumors, nontumor lesions, and normal tissues. Expression of Glut-1 was found in 87% of endometrioid carcinomas (160/184 cases), 100% of serous carcinomas (29/29 cases), 100% of clear cell carcinomas (17/17 cases), 50% of polyps with atypical hyperplasia (8/16 cases), 12.5% of polyps with non-atypical hyperplasia (3/24 cases), 77% of hyperplasias with atypias (10/13 cases), 9% of hyperplasias without atypias (1/11 cases), 87% of secretory endometrium samples (13/15 cases), and in none of the nonsecretory endometrium samples (0/27 cases). In endometrioid carcinomas, Glut-1 was expressed in a marked geographical pattern. In nontumor lesions, its expression was more common in atypical hyperplasia and polyps with atypical hyperplasia compared with polyps with non-atypical hyperplasia and hyperplasias without atypia ( P = .00032). Our study confirms the high expression of Glut-1 not only in endometrioid carcinomas but also in other carcinomas of endometrium including clear cell and serous types. Glut-1 expression can be used as a surrogate marker in differential diagnosis between hyperplasia with and without atypia. Because of common Glut-1 expression in malignant tumors, therapeutic strategies influencing this protein or its signaling pathways can be beneficial.


Human insulin receptor substrate-2: gene organization and promoter characterization.
Insulin receptor substrate-2 (IRS-2) belongs to a family of cytoplasmic adaptor proteins, which link insulin, IGF-1, and cytokine receptor tyrosine kinases to signaling pathways regulating metabolism, growth, and differentiation (1-3). IRS-2-deficient mice display all characteristics of type 2 diabetes, suggesting that dysfunction of the IRS-2 gene may contribute to the pathogenesis of human type 2 diabetes (4). Based on its progesterone inducibility, we have recently cloned and sequenced a full-length human IRS-2 cDNA containing an open reading frame (ORF) of 4,014 bp and 5'- and 3'-untranslated regions (UTRs) of 516 and 2,466 bp (5). Although the IRS-2 gene has previously been thought to lack introns within the coding region (6,7), the amino acid sequence predicted from our cDNA sequence differed at its very COOH-terminal end from an IRS-2 protein sequence derived from genomic IRS-2 sequences. Therefore, we carefully analyzed the genomic structure of the IRS-2 gene and found that the IRS-2 gene contains an intron that disrupts the ORF. Characterization of promoter and 5'-flanking regions of IRS-2 by sequencing, reporter gene assays, and chromatin structure analysis suggests that elements conferring progesterone inducibility are not located immediately upstream of the gene promoter.


Vesicopsoas hitch: a versatile procedure.
The vesicoposoas hitch is an ideal operation for the management of lower ureteral injury and disease requiring replacement of varying lengths of ureter. It is safe and easy to perform, complications are minimal and the success rate is high. In combination with the Boari flap and downward mobilization of the kidney, up to 70% of the ureter may be replaced by this technique. The authors describe their experience between 1970 and 1980 with 52 patients treated by the vesicopsoas hitch, with and without the Boari flap.


Four-year-olds in a new suburb: the need for medical and social care.
The standardized Swedish health examination of 4-year-olds was performed in a residential suburb of Stockholm with a high percentage of young families and immigrants. Emphasis was placed on identifying children in need of pedagogic and psychological measures. Psychological problems were identified by: a structured interview with the parents, and an examination of the child, including developmental screening tests and the parents' assessment of the child's behaviour at home. We have placed more emphasis on the findings and evaluation at the examination than on interview data when arriving at a psychological diagnosis. The somatic part of the examination revealed only minor problems, confirming previous studies on four-year-olds in Sweden. Twelve percent of the 257 children were referred for further psychological investigation, and 16% were recommended early admittance to preschool because of psychological problems. Among the 46 immigrant children who did not have any Swedish parent, more than 50% did not speak Swedish and were recommended early admittance to preschool. In the whole material, 41% needed or were already (17%) in preschool or day nurseries. This indicates unfulfilled demands on such services within the community. The mother's perception of her lack of social contacts in the neighbourhood correlated with the presence of psychological problems and the need for subsequent measures for her child.


High-Throughput Genotyping of CRISPR/Cas Edited Cells in 96-Well Plates.
The emergence in recent years of DNA editing technologies-Zinc finger nucleases (ZFNs), transcription activator-like effector (TALE) guided nucleases (TALENs), clustered regularly interspaced short palindromic repeats (CRISPR)/Cas family enzymes, and Base-Editors-have greatly increased our ability to generate hundreds of edited cells carrying an array of alleles, including single-nucleotide substitutions. However, the infrequency of homology-dependent repair (HDR) in generating these substitutions in general requires the screening of large numbers of edited cells to isolate the sequence change of interest. Here we present a high-throughput method for the amplification and barcoding of edited loci in a 96-well plate format. After barcoding, plates are indexed as pools which permits multiplexed sequencing of hundreds of clones simultaneously. This protocol works at high success rate with more than 94% of clones successfully genotyped following analysis.


[Phosphodiesterase of cyclic nucleotides].
Problems are considered on form multiplicity, purification and molecular weight of cyclic nucleotides phosphodiesterase. A supposition is made that the molecular weight of the catalytic subunit of the enzyme for most studied objects is about 60000. The catalytic subunit may form di- and trimers and be associated with regulatory proteins of different type. The problem of phosphodiesterase regulation is analyzed on the basis of potentialities of the equilibrium shift between the protein subunits of the enzyme; the role of cyclic nucleotides as well as of triphosphonucleotides are shown to influence the regulation of the enzymic activity. In some cases the mechanism of changes in the activity of phosphodiesterase bound with the receptor is shown to be similar to that for adenylate cyclase. In particular, the role of GTP and one of the protein subunits of phosphodiesterase in this process is stated.


Opioid regulation of pallidal enkephalin release: bimodal effects of locally administered mu and delta opioid agonists in freely moving rats.
The globus pallidus and ventral pallidum receive dense enkephalinergic innervation from the dorsal and ventral striatum, respectively. A previous study demonstrated peripheral morphine administration to increase pallidal enkephalin release. To determine whether such opioid stimulatory effects may be mediated directly in the pallidum, in vivo microdialysis was used to study the effects of local administration of several concentrations of the mu receptor agonists morphine and morphine-6-glucuronide (M6G) as well as the the delta receptor agonist SNC80 on pallidal enkephalin release in freely moving rats. Low concentrations of morphine or M6G (1-10 nM) enhanced the release of enkephalins, an effect that was reversed by coadministration of the mu receptor antagonist beta-funaltrexamine (beta-FNA). A similar stimulatory effect was observed with a low concentration of SNC80 (50 nM), an effect that was blocked by the delta antagonist naltrindole (NTD). High concentrations of morphine (100 nM to 100 microM) had little or no effect, whereas M6G (10 microM) suppressed enkephalin release, an effect that was reversed by beta-FNA. Similarly, a high concentration (5 microM) of SNC80 suppressed enkephalin release. However, this effect was not blocked by NTD but was attenuated by beta-FNA, suggesting a mu receptor-mediated action. These results offer in vivo evidence of bimodal (i.e., stimulatory and inhibitory) effects of mu and delta opioid agonists on enkephalin release in the pallidum.


Association of mid-pregnancy antioxidative vitamin and oxidative stress levels with infant growth during the first 3 years of life.
Numerous studies have revealed the impacts of maternal nutritional status on subsequent birth outcome, but much less is known about the long-term impacts on infant growth after birth. We investigated the association between maternal micronutrient levels/oxidative stress status in pregnancy and infant growth during the first 3 years of life. Prospective cohort study. The Ewha Birth & Growth Cohort study was constructed for women who had been recruited between 24 and 28 weeks' gestation and their offspring at Ewha Womans University Hospital. Maternal serum vitamin and urinary oxidative stress levels were measured, and infant weight, height, and head circumference were measured repeatedly at birth and at 6, 12, 18, 24, and 36 months of age. Maternal vitamins A and C were positively associated with infant head circumference and infant weight, respectively, during the first 3 years of life, even after controlling for potential confounding factors. But, maternal oxidative stress was not related to infant growth. The effects of maternal vitamin levels on subsequent infant growth during the first 3 years of life necessitate interventions to supplement antioxidative vitamins during pregnancy.


Preoperative scintigraphic and intraoperative scintimetric localization of parathyroid adenoma with cationic Tc-99m complexes and a hand-held gamma-probe.
The aim of our study was to evaluate the possibility of intraoperative scintimetric detection of parathyroid adenomas with Tc-99m labelled tracers for its usefulness in dystropic or ectopic adenomas. 12 women with biochemically confirmed hyperparathyroidism were included in our study. After injection of 370 MBq Tc-99m tetrofosmin e.g. sestamibi, preoperative scintigraphy (double phase study and SPECT) was performed and T/NT ratios were evaluated for early, delayed and SPECT images. Surgery was performed using a hand-held gamma-probe after preoperative injection of 555-925 MBq Tc-99m tetrofosmin e.g. sestamibi. Count rates (cts/10 sec) were measured and used for calculating in situ- and ex situ-T/NT ratios. In 9 out of 12 patients, adenoma could be detected on static images. Mean T/NT ratios for Tc-99m tetrofosmin were 1.29 for early and 1.23 for delayed images, respectively 1.39 and 1.23 for early and delayed Tc-99m sestamibi scan. Three cases could only be detected with SPECT reconstruction, 11 of 12 parathyroid adenomas could be confirmed intra-operatively. SPECT with Tc-99m labelled cationic complexes showed advantages in detection, precise localization and contrast over static scintigraphy and should therefore be performed at least in cases with poor or no uptake on static images to avoid failures in detection of deeply sited, dislocated glands or adenomas with low uptake. Intraoperative localization and confirmation of parathyroid adenoma with Tc-99m labelled cationic complexes and a gamma probe is possible an 1 may be useful in case of dys- or ectopic adenoma by influencing surgical approach and operating time.


[Detection by a computer program of drug interactions in chronic patients. Its practical usefulness in a health center].
To evaluate a computer programme which was used to detect drug interactions (DI) from the Long Treatment Cards (LTC) and to analyse the factors possibly linked to these interactions. An observational, descriptive study. Primary Health Care: an urban Health Centre. The reference context was 1,640 chronic patients being cared for at a nursing clinic. We selected 141 cases at random by taking 10 LTCs from each list. (Alpha risk = 0.05; Confidence Interval = 0.05). The sample was mainly feminine (2:1), with an average age of 67. The most common diagnosis was Diabetes or AHT. 55% had accumulated 4 or more medicines per card, with multiple medication most common among men. The programme enabled 58 drug interactions, affecting 34% of the LTCs, to be identified. Special attention should be paid to the LTCs with 7 or more drugs prescribed because of their association with DI and NIV. The programme's efficacy would increase, both if the DIs were more accurately defined and if the programme could be computerised and applied massively to chronic treatments.


Role of bowel ultrasound as a predictor of surgical recurrence of Crohn's disease.
In Crohn's disease natural history, about 80% of the patients require surgery, which is not curative: unfortunately, the disease recurs in many patients. To investigate the role of intestinal ultrasound to predict the risk of post-operative surgical recurrence in Crohn's disease. A total of 196 patients, with ileal or ileocolonic Crohn's disease, undergoing intestinal resection, were retrospectively enrolled. All patients underwent bowel ultrasonography 6-15 months after resection. Wall thickness at the anastomosis level was measured, and thickening >3 mm was evaluated as risk factor of long-term need for reoperation. Patients who have a bowel wall thickness >3 mm have an risk ratio (RR) of surgical recurrence = 2.1 [95% confidence interval (CI) = 1.12-3.74] higher than those with a thickness of ≤3 mm. The absolute incidence of new surgical intervention is 13% in patients with thickness of 3 mm, 28% in patients with thickness >3 mm, 29,1% with thickness >4 mm, 34% with thickness >5 mm, and 40% with thickness >6 mm. Bowel wall thickness >3 mm at ultrasound may be a non-invasive predictor of early surgical recurrence after ileo-colonic resection.


Lymphopenia in Sjögren's syndrome with rheumatoid arthritis: relationship to lymphocytotoxic antibodies, cryoglobulinemia, and impaired mitogen responsiveness.
Lymphocyte subpopulation studies in 21 patients with Sjögren's syndrome and rheumatoid arthritis revealed an absolute lymphopenia and a normal percentage of T- and SIg-cells. In one patient, a large percentage of lymphocytes bore both IgG and IgM; after cell trypsinization only IgM was resynthesized. This surface IgM was capable of binding human IgG, suggesting that the presence of multiple classes of immunoglobulins on the surface of these lymphocytes was due to surface rheumatoid factor activity. Profound lymphopenia was associated with high concentrations of cryoglobulins and the presence of lymphocytotoxic antibodies. These antibodies were broadly reactive, causing cytotoxicity of T- and SIg-cells from normal subjects, from viral and lymphoproliferative disease subjects, from different organs, and SIg-cells from human lymphoblastoid cell lines. Lymphocyte transformation after phytohemagglutinin and pokeweed mitogen stimulation was impaired in comparison to normal subjects. Warm washing of the lymphocytes and purification to greater than 80 per cent T-cells did not restore mitogen responsiveness to normal, suggesting that cell coating by an antibody and diminished responder cell number were inadequate explanations for the impaired transformation.


[Morpho-biophysical research of erythrocytes of intact and vagotomized rats in various terms after the acute hemorrhage].
The acute massive hemorrhage (35-37% of the blood volume) at rats is accompanied by changes of morphological (diameter, the area, polarizations, the form-factor, integrated and specific absorbency) and biophysical (a relief of a surface and microviscosity of a lipid phase of plasmolemma) characteristics of erythrocytes. Thus character and dynamics of response of erythron initially intact and vagotomized (14 days after operation) animals essentially differ: the former demonstrate significant changes in 3-10 h and 240 h and the latter--in 0.5 h and 96 h.


Clinical characteristics associated with conjunctival inflammation in allergic rhinoconjunctivitis.
Allergic rhinitis affects up to 30% of the general population worldwide and is increasing in prevalence. Among several comorbidities, conjunctivitis is probably the most common and occurs so frequently with allergic rhinitis that the term allergic rhinoconjunctivitis (ARC) has been coined. The cytological characteristics of conjunctival inflammation in patients with ARC were assessed and then correlated to clinical characteristics. Fifty-one patients with clinically diagnosed ARC (23 men; 32.4 ± 13.5 years old) underwent a detailed clinical history and standard diagnostic allergy workup as well as nasal and conjunctival scraping for cytological analysis. Patients were subdivided into 3 groups on the basis of cytological phenotype: (1) nasal and conjunctival inflammation, (2) nasal inflammation only, and (3) no mucosal inflammation. Group 1 patients reported significantly higher eye itching scores (5.8 ± 2.9 on a 0-10 scale) than did patients in group 2 (3.8 ± 2.8; P = .06) or 3 (2.6 ± 2.9; P = .018) and were mostly men (81.8%). Male sex (odds ratio, 8.4; P = .005) and eye itching (odds ratio, 1.3; P = .019) significantly correlated with conjunctival inflammation. The odds of exhibiting conjunctival inflammation, at multivariate analysis, increased 13-fold for men and 1.5-fold for each point on the eye itching scale. A cutoff value of 3 or more for eye itching effectively identified patients with conjunctival inflammation. Our study demonstrates that some clinical manifestations of ARC correlate well with conjunctival inflammation.


Magnetic resonance spectroscopy in preterm infants: association with neurodevelopmental outcomes.
To compare magnetic resonance spectroscopy (MRS) metabolite ratios in preterm infants at term-equivalent age with those in term infants and to evaluate the association between MRS metabolites and neurodevelopmental outcomes at 18 months corrected age in preterm infants. We studied infants born at a gestational age <37 weeks and weighing <1500 g during 2009-2013 using MRS at term-equivalent age. Infants with major brain abnormalities were excluded. The ratios of N-acetylaspartate (NAA) to creatine (Cre), NAA to choline-containing compounds (Cho) and Cho to Cre in the frontal white matter and thalamus were measured using multivoxel point-resolved proton spectroscopy sequence. Neurodevelopmental outcomes were assessed at 18 months corrected age. Thirty-three preterm infants and 16 term infants were enrolled in this study. Preterm infants with normal development at 18 months showed significantly lower NAA/Cho ratios in the frontal white matter than term infants. There were no differences in the Cre/Cho ratios between preterm and term infants. At 18 months corrected age, 9 preterm infants with a mild developmental delay showed significantly lower NAA/Cho ratios in the thalamus than 24 preterm infants with normal development. Preterm infants at term-equivalent age showed reduced MRS metabolites (NAA/Cho) compared with term infants. Decreased NAA/Cho ratios in the thalamus were associated with neurodevelopmental delay at 18 months corrected age in preterm infants.


Pyrethroid exposure alters internal and cuticle surface bacterial communities in Anopheles albimanus.
A deeper understanding of the mechanisms underlying insecticide resistance is needed to mitigate its threat to malaria vector control. Following previously identified associations between mosquito microbiota and insecticide resistance, we demonstrate for the first time, the effects of pyrethroid exposure on the microbiota of F1 progeny of field-collected Anopheles albimanus. Larval and adult mosquitoes were exposed to the pyrethroids alphacypermethrin (only adults), permethrin, and deltamethrin. While there were no significant differences in bacterial composition between insecticide-resistant and insecticide-susceptible mosquitoes, bacterial composition between insecticide-exposed and non-exposed mosquitoes was significantly different for alphacypermethrin and permethrin exposure. Along with other bacterial taxa not identified to species, Pantoea agglomerans (a known insecticide-degrading bacterial species) and Pseudomonas fragi were more abundant in insecticide-exposed compared to non-exposed adults, demonstrating that insecticide exposure can alter mosquito bacterial communities. We also show for the first time that the cuticle surfaces of both larval and adult An. albimanus harbor more diverse bacterial communities than their internal microbial niches. Together, these findings demonstrate how insecticide pressure could be selecting for certain bacteria within mosquitoes, especially insecticide-metabolizing bacteria, thus potentially contributing to insecticide resistance.


Ex vivo spermine dialdehyde treatment prevents lethal GVHD in a murine bone marrow transplantation model.
Spermine dialdehyde (SDA), an oxidized product of spermine which irreversibly suppresses T cell and NK cell activities, was evaluated as an ex vivo purging agent in the prevention of graft-versus-host disease (GVHD) in mice transplanted with SDA-treated allogeneic bone marrow. In this model, lethally irradiated C3H (H-2k) mice received BALB/c (H-2d) bone marrow and spleen cell mixtures which had been treated ex vivo for 10 min with SDA. Mice receiving SDA-treated cells survived past 100 days whereas mice in the control group died between days 25-35 suffering from severe GVHD. Surviving mice from the SDA-treated groups exhibited full chimerism at day 120. In vitro assays indicated that SDA inhibited T cell and NK cell activities at concentrations that spared myeloid cell growth. When a minimum number of bone marrow cells were used for reconstitution, SDA-treated marrow reconstituted lethally irradiated mice as effectively as control marrow suggesting that SDA had little impact on early myeloid cells which are required for engraftment. SDA may have clinical application as a purging agent in allogeneic bone marrow transplantation.


Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly expresses EBNA3A with conserved CD8 T-cell epitopes.
Post-transplantation lymphoproliferative disorders (PTLD) arise in the immunosuppressed and are frequently Epstein-Barr virus (EBV) associated. The most common PTLD histological sub-type is diffuse large B-cell lymphoma (EBV+DLBCL-PTLD). Restoration of EBV-specific T-cell immunity can induce EBV+DLBCL-PTLD regression. The most frequent B-cell lymphoma in the immunocompetent is also DLBCL. 'EBV-positive DLBCL of the elderly' (EBV+DLBCL) is a rare but well-recognized DLBCL entity that occurs in the overtly immunocompetent, that has an adverse outcome relative to EBV-negative DLBCL. Unlike PTLD (which is classified as viral latency III), literature suggests EBV+DLBCL is typically latency II, i.e. expression is limited to the immuno-subdominant EBNA1, LMP1 and LMP2 EBV-proteins. If correct, this would be a major impediment for T-cell immunotherapeutic strategies. Unexpectedly we observed EBV+DLBCL-PTLD and EBV+DLBCL both shared features consistent with type III EBV-latency, including expression of the immuno-dominant EBNA3A protein. Extensive analysis showed frequent polymorphisms in EB-NA1 and LMP1 functionally defined CD8+ T-cell epitope encoding regions, whereas EBNA3A polymorphisms were very rare making this an attractive immunotherapy target. As with EBV+DLBCL-PTLD, the antigen presenting machinery within lymphomatous nodes was intact. EBV+DLBCL express EBNA3A suggesting it is amenable to immunotherapeutic strategies.


Hearing with an atympanic ear: good vibration and poor sound-pressure detection in the royal python, Python regius.
Snakes lack both an outer ear and a tympanic middle ear, which in most tetrapods provide impedance matching between the air and inner ear fluids and hence improve pressure hearing in air. Snakes would therefore be expected to have very poor pressure hearing and generally be insensitive to airborne sound, whereas the connection of the middle ear bone to the jaw bones in snakes should confer acute sensitivity to substrate vibrations. Some studies have nevertheless claimed that snakes are quite sensitive to both vibration and sound pressure. Here we test the two hypotheses that: (1) snakes are sensitive to sound pressure and (2) snakes are sensitive to vibrations, but cannot hear the sound pressure per se. Vibration and sound-pressure sensitivities were quantified by measuring brainstem evoked potentials in 11 royal pythons, Python regius. Vibrograms and audiograms showed greatest sensitivity at low frequencies of 80-160 Hz, with sensitivities of -54 dB re. 1 m s(-2) and 78 dB re. 20 μPa, respectively. To investigate whether pythons detect sound pressure or sound-induced head vibrations, we measured the sound-induced head vibrations in three dimensions when snakes were exposed to sound pressure at threshold levels. In general, head vibrations induced by threshold-level sound pressure were equal to or greater than those induced by threshold-level vibrations, and therefore sound-pressure sensitivity can be explained by sound-induced head vibration. From this we conclude that pythons, and possibly all snakes, lost effective pressure hearing with the complete reduction of a functional outer and middle ear, but have an acute vibration sensitivity that may be used for communication and detection of predators and prey.


Assessment of the feed additive consisting of sodium benzoate (Protural®) for weaned piglets for the renewal of its authorisation and the extension of use to other growing Suidae (Taminco Finland Oy).
Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Protural® (sodium benzoate) when used as a zootechnical additive in feed for weaned piglets and other growing Suidae at 4,000 mg/kg feedingstuff. Protural® consists of sodium benzoate without any carrier materials and is currently authorised for use in weaned piglets. This opinion concerns the renewal of the authorisation of Protural® for weaned piglets and the evaluation of the new use in other growing Suidae. The applicant provided evidence that the additive currently in the market complies with the existing conditions of authorisation. The FEEDAP Panel concluded that Protural® is safe under the current conditions of authorisation for the target species, consumers of products from animals fed the additive and the environment. Protural® was not considered as irritant to skin and eyes but a skin sensitiser. Based on dusting potential data, the FEEDAP Panel considered that the powder formulation of the additive represented a risk by inhalation. There was no need for assessing the efficacy of Protural® in the context of the renewal of the authorisation for weaned piglets. The efficacy data previously evaluated allowed the FEEDAP Panel to conclude that the additive has the potential to be efficacious at the level of 4,000 mg/kg feedingstuff in other growing Suidae. A conclusion cannot be reached for the efficacy in pigs for fattening.


A Comparative Study of Efficacy and Safety of Eberconazole versus Terbinafine in Patients of Tinea Versicolor.
Tinea versicolor (TV) is characterised by the appearance of maculosquamous lesions sometimes associated with mild erythema and pruritus in characteristic areas of the body. Eberconazole and terbinafine though drugs of different classes provide both mycological and clinical cure. This study aims to compare the efficacy and safety of eberconazole versus terbinafine in patients of TV. An open-label, randomised, comparative clinical trial was conducted on 60 patients. The patients were randomly divided into two study groups. Group A: Eberconazole 1% cream once daily and Group B: Terbinafine 1% cream once daily for 2 weeks. Efficacy assessment was done by observing signs and symptoms, i.e., Physician assessment 4-point scale, microscopic KOH examination, Wood's lamp examination, global clinical response assessment, and patient's assessment on visual analog scale at the end of 2 weeks and subsequently patients were reassessed at the end of 4 and 8 weeks to check any relapse. Safety assessment was also done. There was a significant improvement in all the parameters in both groups over a period of 2 weeks. Both the treatment groups, i.e., eberconazole and terbinafine were found to be safe and efficacious at the end of 2 weeks, and no statistically significant difference was observed between the two groups regarding complete cure, i.e., mycological and clinical cure (80% vs. 63.33%), respectively. However, early response (at the end of week 1) was observed with eberconazole. No relapse was seen with eberconazole, but one patient had relapse at 8 weeks with terbinafine. Both drugs had similar safety profile. Although both the drugs cured the disease, eberconazole showed better response as clinical cure and mycological cure were observed earlier and no patient relapsed in the follow-up.


Illicit Cigarette Consumption and Government Revenue Loss in Vietnam: Evidence from a Primary Data Approach.
This article provides the first comprehensive picture and independent estimates of both illicit cigarette consumption and the resulting government tax revenue loss in Vietnam using data from a representative survey of cigarette smokers in 12 Vietnamese provinces. The survey consisted of face-to-face interviews and on-site cigarette pack examinations. We find that more than 720 million illicit cigarette packs, or 20.7% of total cigarette consumption, circulated in Vietnam in 2012. Consequently, government tax revenue loss due to illicit trade ranged from US $223 to 295 million. Our estimates also indicate that 1) the most popular illicit brands were Jet and Hero, both were sold at higher prices than the average legal brand; 2) the average price of illicit cigarettes was 51% higher than the average price of legal cigarettes; and 3) majority of illicit cigarettes were sold at convenience stores, which were registered and licensed businesses. Our findings suggest that prices are not a driver of illicit cigarette consumption in Vietnam, and this illicit trade is at least partially a consequence of weak market control enforcement.


Emodin-induced apoptosis in human breast cancer BCap-37 cells through the mitochondrial signaling pathway.
Emodin, a natural anthraquinone compound isolated from the rhizome of rhubarb, is reported to suppress the growth of tumor in many clinical situations. In this study, we focused on the effect of emodin in human breast cancer BCap-37 cells and further understand the underlying molecular mechanism in treating breast cancer. Using MTT assay and flow cytometry, we demonstrated the critical role of emodin in the suppression of the proliferation of BCap-37 cells based on a concentration-and time-dependent manner. The increase of apoptotic rate was also observed after incubation of BCap-37 cells on emodin at 20 microM and 50 microM for 48 h. The cells exhibited typical apoptotic features including cellular morphological change, chromatin condensation and membrane blebbing. The results of the study further showed that Bcl-2 level decreased, while Bax and cytosolic cytochrome c levels in sample cells increased after the emodin treatment by using Western blot. The decline in the Bcl-2/Bax ratio and the increase of cytosolic cytochrome c concentration were consistent with the increase of the apoptotic ratio. The results strongly suggest that the disruption of the mitochondrial signaling pathway was involved in emodin-induced apoptosis in BCap-37 cells.


Cytosolic protein concentration is the primary volume signal in dog red cells.
It is not known whether the activation of Na/H exchange by shrinkage in dog red cells is due to the packing of cell contents or a change in cell configuration. To make this distinction we prepared resealed ghosts that resembled intact cells in hemoglobin concentration and surface area, but had one-third their volume. A shrinkage-induced, amiloride-sensitive Na flux in the ghosts was activated at a much smaller volume in the ghosts than in the intact cells, but at the same concentration (by weight) of dry solids in both preparations. Na/H exchange in ghosts containing a mixture of 40% albumin and 60% hemoglobin (weight/weight) was activated by osmotic shrinkage at a dry solid concentration similar to that of intact cells or of ghosts containing only hemoglobin. We conclude that the process of Na/H exchange activation by cell shrinkage originates with an increase in the concentration of intracellular protein and not with a change in membrane configuration or tension. The macromolecular crowding that accompanies the reduction in cell volume probably alters the activities of key enzymes that in turn modulate the Na/H exchanger.


The psychological impact of sarcoma on affected patients.
Sarcoma diagnosis and its treatment trajectory may deeply affect the somatopsychic balance of patients and their caregivers. This systematic review aimed at deepening the understanding of sarcoma's impact on the entire family unit involved in the illness experience on a physical (e.g. fatigue), psychological (e.g. mental health, affective regulation, defense mechanisms), and interpersonal (e.g. social isolation, loneliness) level. The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The literature search led to the identification and subsequent inclusion of 44 articles focused on sarcoma patients. Results were classified into seven categories: Quality of Life, worries and distress, anxiety and depression, suicide ideation, financial and occupational consequences, unmet needs, and coping strategies. Our search identified only one study focusing on informal caregivers, thus we could not perform a systematic review on these results. Our findings underlined the traumatic impact of the sarcoma diagnosis. Patients can experience an impoverished emotional life, somatization, social withdrawal, difficulty in decision-making, increased feelings of discouragement and demoralization, and profound experiences of helplessness and vulnerability. Moreover, they seemed to display anxiety and depression and might present a higher suicide incidence than the general population. Our review highlighted that the psychosocial aftermath of sarcoma patients should guide institutions and healthcare professionals toward the design of assessment and intervention models that could contemplate the different dimensions of their suffering. Furthermore, it points out that there is still a lack of evidence regarding the psychosocial impact affecting sarcoma patients' caregivers.


Hyperoxia may be beneficial.
The current practice of mechanical ventilation comprises the use of the least inspiratory O2 fraction associated with an arterial O2 tension of 55 to 80 mm Hg or an arterial hemoglobin O2 saturation of 88% to 95%. Early goal-directed therapy for septic shock, however, attempts to balance O2 delivery and demand by optimizing cardiac function and hemoglobin concentration, without making use of hyperoxia. Clearly, it has been well-established for more than a century that long-term exposure to pure O2 results in pulmonary and, under hyperbaric conditions, central nervous O2 toxicity. Nevertheless, several arguments support the use of ventilation with 100% O2 as a supportive measure during the first 12 to 24 hrs of septic shock. In contrast to patients without lung disease undergoing anesthesia, ventilation with 100% O2 does not worsen intrapulmonary shunt under conditions of hyperinflammation, particularly when low tidal volume-high positive end-expiratory pressure ventilation is used. In healthy volunteers and experimental animals, exposure to hyperoxia may cause pulmonary inflammation, enhanced oxidative stress, and tissue apoptosis. This, however, requires long-term exposure or injurious tidal volumes. In contrast, within the timeframe of a perioperative administration, direct O2 toxicity only plays a negligible role. Pure O2 ventilation induces peripheral vasoconstriction and thus may counteract shock-induced hypotension and reduce vasopressor requirements. Furthermore, in experimental animals, a redistribution of cardiac output toward the kidney and the hepato-splanchnic organs was observed. Hyperoxia not only reverses the anesthesia-related impairment of the host defense but also is an antibiotic. In fact, perioperative hyperoxia significantly reduced wound infections, and this effect was directly related to the tissue O2 tension. Therefore, we advocate mechanical ventilation with 100% O2 during the first 12 to 24 hrs of septic shock. However, controlled clinical trials are mandatory to test the safety and efficacy of this approach.


Vascular remodelling in the pathogenesis of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrosing interstitial pneumonia of unknown aetiology that usually leads to respiratory failure and death within 5 years of diagnosis. Alveolar epithelial cell injury, disruption of alveolar capillary membrane integrity and abnormal vascular repair and remodelling have all been proposed as possible pathogenic mechanisms. This review summarizes our current knowledge of the abnormalities in vascular remodelling observed in IPF and highlights several of the cytokines thought to play a pathogenic role, which may ultimately prove to be future therapeutic targets.


Activity Recognition for IoT Devices Using Fuzzy Spatio-Temporal Features as Environmental Sensor Fusion.
The IoT describes a development field where new approaches and trends are in constant change. In this scenario, new devices and sensors are offering higher precision in everyday life in an increasingly less invasive way. In this work, we propose the use of spatial-temporal features by means of fuzzy logic as a general descriptor for heterogeneous sensors. This fuzzy sensor representation is highly efficient and enables devices with low computing power to develop learning and evaluation tasks in activity recognition using light and efficient classifiers. To show the methodology's potential in real applications, we deploy an intelligent environment where new UWB location devices, inertial objects, wearable devices, and binary sensors are connected with each other and describe daily human activities. We then apply the proposed fuzzy logic-based methodology to obtain spatial-temporal features to fuse the data from the heterogeneous sensor devices. A case study developed in the UJAmISmart Lab of the University of Jaen (Jaen, Spain) shows the encouraging performance of the methodology when recognizing the activity of an inhabitant using efficient classifiers.


Gait assessment in dairy cattle.
Lameness is one of the most important dairy cow welfare issues and has inspired a growing body of literature on gait assessment. Validation studies have shown that several methods of gait assessment are able to successfully distinguish cows with and without painful pathologies. While subjective methods provide an immediate, on-site assessment and require no technical equipment, they show variation in observer reliability. On the other hand, objective methods of gait assessment provide accurate and reliable data, but typically require sophisticated technology, limiting their use on farms. In this critical review, we evaluate gait assessment methods, discuss the reliability and validity of measures used to date, and point to areas where new research is needed. We show how gait can be affected by hoof and leg pathologies, treatment of these ailments and the pain associated with lameness. We also discuss how cow (e.g. conformation, size and udder fill) and environmental features (e.g. flooring) contribute to variation in the way cows walk. An understanding of all these factors is important to avoid misclassifying of cows and confounding comparisons between herds.


Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis.
There is a need to assess the laminar inflammatory response in a laminitis model that more closely resembles clinical cases of sepsis-related laminitis than the black walnut extract (BWE) model. To determine if a similar pattern of laminar inflammation, characterised by proinflammatory cytokine expression, occurs in the CHO model of laminitis as has been previously reported for the BWE model. Sixteen horses administered 17.6 g of starch (85% corn starch/15% wood flour)/kg bwt via nasogastric (NG) tube were anaesthetised either after developing a temperature>38.9°C (DEV group, n=8) or at onset of Obel grade 1 lameness (OG1 group, n=8). Control horses (CON group, n=8) were anaesthetised 24 h after NG administration of 6 l of deionised water. Laminar tissue was collected from horses while under anaesthesia, followed by humane euthanasia. Real time-quantitative PCR was used to assess laminar mRNA concentrations of genes involved in inflammatory signalling. Increased mRNA concentrations (P<0.05) for IL-1β, IL-6, IL-12p35, COX-2, E-selectin and ICAM-1 were present in laminae from horses with OG1 lameness but not at the DEV time, when compared to the CON horses. No differences between the groups were found for IL-2, IL-4, IL-10, TNF-α, IFN-γ or COX-1 at either the DEV or OG1 time points. There was a notable difference in the temporal pattern of inflammatory events between the BWE and CHO models, with the majority of laminar inflammatory events appearing to occur at or near the onset of lameness in the CHO model, whereas many of these events peak earlier in the developmental stages in the BWE model. This suggests that, in addition to circulating inflammatory molecules, there may be a local phenomenon in the CHO model resulting in the simultaneous onset of multiple laminar events including endothelial activation, leucocyte emigration and proinflammatory cytokine expression. The similar (although somewhat delayed) inflammatory response in the CHO model of laminitis indicates that inflammatory signalling is a consistent entity in the pathophysiology of laminitis.


Pulmonary Tuberculosis: Decreased Activation of T lymphocyte Subsets in vitro.
Protection against M. tuberculosis depends on T cells of the CD4(+) or CD8(+) phenotype. The definition of cellular response and target molecules are important to understand pathological immune mechanisms in tuberculosis. In this report we have analyzed the expression of activation markers (CD25, CD71, HLA DR) on CD4(+), CD8(+) subsets in patients with pulmonary tuberculosis by dual color flow cytometry. We investigated 19 patients with newly diagnosed severe active untreated pulmonary tuberculosis. Previously it was shown, that in the above form of pulmonary tuberculosis amidst CD4(+) and CD8(+) T cells there were a significant decrease in quantity of CD45RA(+) lymphocytes and increase in CD25(+), HLA DR(+) activated cells. To estimate the functional significance of these differences, peripheral blood mononuclear cells were stimulated with polyclonal mitogen phytoheamaglutin in vitro. Since the decreased mitogen response could reflect a difference in the ability of T cell subsets to proliferate, the phenotype of the T cells after stimulation with PHA was determined. Although the patients with PT demonstrated a decreased number of all the T cell subsets (CD25(+), CD71(+), HLA DR(+) after 72 h of PHA-stimulation compared to control, the most pronounced decrease was in CD8(+) cells. Differential analysis of the activation markers in dependence on the flow cytometry gates for PHA-stimulated lymphocytes revealed some defect in the expression of activation markers at the level of small blasts that arrested CD4(+), CD8(+) cells on the early activation stages. Taken together these results suggest that investigated clinical form of pulmonary tuberculosis seems to be directly associated with a defect in reactivity of T lymphocyte subsets at the early activation steps.


Analysis of antibiotics by CE and CEC and their use as chiral selectors: An update.
Natural, synthetic or semisynthetic antibiotics are highly used to prevent or treat diseases in humans and animals, and to promote animal growth. This fact makes that antibiotics residues or their transformation products may be present in food or in the environment after human or animal excretion. For this reason, it is imperative to develop reliable and sensitive analytical methodologies for their analysis. The main aim of this work is to present and discuss the most recent applications of capillary electromigration methods for the analysis of antibiotics, including the developments and applications of their use as chiral selectors in CE. The literature published from June 2015 to June 2017 is included following the previous review by Domínguez-Vega et al. (Electrophoresis, 2016, 37, 189-211). Information about the use of different detection systems, off-line and on-line strategies to improve sensitivity, and microchip devices for the analysis of antibiotics is provided and properly discussed.


Crystal structure of the bacterial cell-division protein FtsZ.
Bacterial cell division ends with septation, the constriction of the cell wall and cell membranes that leads to the formation of two daughter cells. During septation, FtsZ, a protein of relative molecular mass 40,000 which is ubiquitous in eubacteria and is also found in archaea and chloroplasts, localizes early at the division site to form a ring-shaped septum. This septum is required for the mechanochemical process of membrane constriction. FtsZ is a GTPase with weak sequence homology to tubulins. The nature of FtsZ polymers in vivo is unknown, but FtsZ can form tubules, sheets and minirings in vitro. Here we report the crystal structure at 2.8 A resolution of recombinant FtsZ from the hyperthermophilic methanogen Methanococcus jannaschii. FtsZ has two domains, one of which is a GTPase domain with a fold related to one found in the proteins p21ras and elongation factor EF-Tu. The carboxy-terminal domain, whose function is unknown, is a four-stranded beta-sheet tilted by 90 degrees against the beta-sheet of the GTPase domain. The two domains are arranged around a central helix. GDP binding is different from that typically found in GTPases and involves four phosphate-binding loops and a sugar-binding loop in the first domain, with guanine being recognized by residues in the central connecting helix. The three-dimensional structure of FtsZ is similar to the structure of alpha- and beta-tubulin.


Indications for pedicled pectoralis major flap in a free tissue transfer practice.
The pedicled pectoralis major myocutaneous flap (PMMF) was highly used over the last 3 decades. The current era of free tissue transfer has gradually relegated the PMMF to a secondary role. In a retrospective review of all patients undergoing pedicled PMMF from 2002 to now, we sought to determine the current role and assess the outcomes of the PMMF in a primary microvascular head and neck reconstructive center. Fifty-five PMMFs were performed in 53 patients (24 myocutaneous and 31 myofascial); group 1 consisted of 20 patients (38%) who underwent a secondary PMMF after a free flap complication (flap failure 9/20, fistula 5/20, wound breakdown with great vessel exposure 3/20, loss of soft tissue skin paddle 2/20, and delayed hematoma in 1/20); group 2 included 18 patients (33%) who had a simultaneous free flap with a PMMF for dead space filler or cervical skin/great vessel coverage reconstruction, whereas the remaining 15 patients (29%) in group 3 underwent primary PMMF for reconstruction of cervical skin defect, great vessel coverage, pharyngocutaneous fistula, infection, and dead space filler. Complications of PMMF included 3 hematomas, 2 partial dehiscences, 1 chest wall abscess, and 1 case of mastitis. Because of cervical tethering, 14 of 53 patients underwent secondary pectoralis myectomy with cervical contracture release at a mean of 10.3 months after initial surgery. The pedicled PMMF continues to serve an important role in head and neck reconstruction in the microvascular era with notable uses for free flap rescue, with simultaneous free flap reconstruction and for primary reconstruction in select circumstances with an overall acceptable short- and long-term morbidity profile.


Possible horizontal transfer of Drosophila genes by the mite Proctolaelaps regalis.
There is strong inferential evidence for recent horizontal gene transfer of the P (mobile) element to Drosophila melanogaster from a species of the Drosophila willistoni group. One potential vector of this transfer is a semiparasitic mite, Proctolaelaps regalis DeLeon, whose morphology, behavior, and co-occurrence with Drosophila are consistent with the properties necessary for such a vector. Southern blot hybridization, polymerase chain reaction (PCR) amplification, and DNA sequencing showed that samples of P. regalis associated with a P strain of D. melanogaster carried P element sequences. Similarly, Drosophila ribosomal DNA sequences were identified in P. regalis samples that had been associated with Drosophila cultures. These results have potentially important evolutionary implications, not only for understanding the mechanisms by which genes may be transferred between reproductively isolated species, but also for improved detection of some host-parasite and predator-prey relationships.