Ascorbic acid glycation: the reactions of L-threose in lens tissue.
L-Threose is a significant degradation product of ascorbic acid at pH 7.0 in the presence of oxygen. When compared to several other ascorbate-derived degradation products, it had the greatest ability to glycate and crosslink lens proteins in vitro. To determine whether L-threose was formed in the lens, the sugars in a TCA-soluble extract from human lenses were reduced to polyols with NaBH4, acetylated and analysed by gas-liquid chromatography. The threitol levels measured were 3.4 +/- 0.8 micrograms per lens (n = 4). GC-MS measurements made after reduction with NaBD4 indicated that threitol, but little or no threose, was originally present in the human lens. Rat lenses were incubated with [1-13C]D-threose for 24 hr, and considerable D-threitol formation was seen by NMR spectroscopy. Analysis of the lenses after medium removal showed that only [1-13C]threitol was present within the lenses indicating a rapid reduction of threose within the lens, presumably by aldose reductase. Assays with human recombinant aldose reductase and with human lens cortical and nuclear extracts all exhibited sorbinil-inhibitable aldose reductase activity with L-threose as substrate. This was confirmed by incubating a preparation of [1-14C]L-tetrose (a mixture of 40% L-threose and 45% L-erythrose) with both the pure aldose reductase and crude lens extracts followed by the subsequent identification of the [1-14C]L-threitol formed by thin layer chromatography. L-Threose degrades very slowly in 0.1 M phosphate buffer at pH 7.0, but the addition of a four-fold excess of N alpha-acetyl-L-lysine accelerated the rate of disappearance of threose 30-fold, indicating a rapid glycation reaction. When [1-14C]L-tetrose was incubated with a complete bovine lens homogenate, a linear incorporation into protein was observed over a 24 hr period. Increasing levels of lens extract exhibited increasing incorporation into protein. These data confirm a rapid reactivity of L-threose with lens protein and argue that glycation would occur in vivo in spite of the presence of aldose reductase.


Oestrogen conjugates of human late-pregnancy urine.
1. The separation of the oestrogen conjugates in late-pregnancy urine into two groups, peaks I and II, by gel filtration on Sephadex G-25 (Beling, 1963) has been shown to be affected by the presence of urate, which delays the elution of peak II conjugates. 2. By reapplication to a Sephadex column, peak I conjugates have been further separated into two groups (peaks IA and IB) and the metabolites in urine effecting this separation have been studied. 3. Further analysis of the mixed conjugates in the main groups IA, IB and II by ion-exchange and partition chromatography has led to the identification of some of the conjugates present. 4. Oestriol 3-sulphate 16alpha-glucuronide and 16alpha-hydroxyoestrone 3-sulphate 16alpha-glucuronide have been identified in peak IA. 5. The main components of peak IB have been identified as oestrone 3-glucuronide and oestriol 3-glucuronide. 6. The major conjugate in peak II was oestriol 16alpha-glucuronide and no oestriol 17beta-glucuronide was found; small amounts of the ring-d monoglucuronides oestradiol 17beta-glucuronide, 16-epioestriol 16beta-glucuronide and 16alpha-hydroxyoestrone 16alpha-glucuronide were found in this fraction. 7. The behaviour of synthetic oestrogen monoglucuronides has been used as a guide in separation.


Interferon Signature's Members, a Novel Altered Correlation upon Interferon-β Treatment in Multiple Sclerosis Patients.
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system and is characterized by extensive brain damage and neurodegeneration. Immunological, genetic, and histological analyses of MS patients provide data in support of the concept that autoimmunity plays a crucial role in the condition's course. It has been proposed that MS may be treated with interferon (IFN)-β and other members of the type I family. Low levels of type I IFN in MS patients may affect immunological control, establish the threshold for an IFN therapeutic response, and be"primed" or "fixed" by IFN therapy. This study was conducted as a cross-sectional study. qRT-PCR was used to examine the expression of two critical IFN regulatory genes, IFI44 and MX1, in MS patients receiving IFN-β treatment. The findings demonstrated a considerable rise in the expression of both genes in MS patients treated with IFN-β compared to those newly diagnosed with the illness. In addition, IFI44 and MX1 might be positively associated with their expression after IFN-β therapy and be regarded as IFN-β responsiveness indicators. The IFI44/MX1 axis could act as one of the crucial regulators of the disease following IFN-β treatment.


Complement factor H-deficient mice develop spontaneous hepatic tumors.
Hepatocellular carcinoma (HCC) is difficult to detect, carries a poor prognosis, and is one of few cancers with an increasing yearly incidence. Molecular defects in complement factor H (CFH), a critical regulatory protein of the complement alternative pathway (AP), are typically associated with inflammatory diseases of the eye and kidney. Little is known regarding the role of CFH in controlling complement activation within the liver. While studying aging CFH-deficient (fH-/-) mice, we observed spontaneous hepatic tumor formation in more than 50% of aged fH-/- males. Examination of fH-/- livers (3-24 months) for evidence of complement-mediated inflammation revealed widespread deposition of complement-activation fragments throughout the sinusoids, elevated transaminase levels, increased hepatic CD8+ and F4/80+ cells, overexpression of hepatic mRNA associated with inflammatory signaling pathways, steatosis, and increased collagen deposition. Immunostaining of human HCC biopsies revealed extensive deposition of complement fragments within the tumors. Investigating the Cancer Genome Atlas also revealed that increased CFH mRNA expression is associated with improved survival in patients with HCC, whereas mutations are associated with worse survival. These results indicate that CFH is critical for controlling complement activation in the liver, and in its absence, AP activation leads to chronic inflammation and promotes hepatic carcinogenesis.


Application of co-processed excipients for developing fast disintegrating tablets: A review.
The introduction of tablet dosage forms has brought a revolution in the pharmaceutical drug delivery system. Different forms of tablets have been developed based on the target site, the onset of action, and therapeutic drug delivery methods. Fast-disintegrating tablets (FDTs) are the most promising pharmaceutical dosage form, especially for pediatric and geriatric patients having difficulty swallowing. The key feature of FDTs is quick drug release soon after their administration through the oral cavity. With innovations in the formulation of FDTs, the demand for excipients with better functionalities, particularly in terms of flow and compression characteristics, has increased. Co-processed excipients are a mixture of 2 or more conventional excipients that provides significant benefits over the individual excipients while minimizing their shortcomings. Such multifunctional co-processed excipients minimize the number of excipients that are to be incorporated into tablets during the manufacturing process. The present review discusses FTDs formulated from co-processed excipients, their manufacturing techniques, and the latest research, patents and commercially available co-processed FDTs.


Landscape changes in the Mullica River basin of the Pinelands National Reserve, New Jersey, USA.
In 1979, the Pinelands Commission was established as a regional land-use planning and regulatory agency charged with the implementation of a Comprehensive Management Plan (CMP) for the Pinelands National Reserve (New Jersey, USA). The CMP was created to balance land preservation and development interests in the Reserve. Because water-quality degradation from developed and agricultural landscapes is associated with changes in the composition of biological communities, monitoring landscape changes provides one of the most direct measures of the impact of land-use policies on the Pinelands ecosystem. In this study, we prepared detailed, land-cover maps within randomly selected aerial-photograph plots for a major watershed in the Reserve. We used these land-cover maps to quantify changes in landscape composition and structure (i.e., patch size, patch area, and number of patches) and characterize land-cover transitions in the basin between 1979 and 1991. Because the study period represented the first 12 years of the regional-planning effort in the Reserve, we evaluated the relationship between land-cover transitions and Commission management-area designations which permit different land-use intensities. Although the landscape composition was similar in 1979 and 1991, we found an increase in the total area and number of developed-land, managed-grassland, and barren-land patches. An increase in the number of patches and a decrease in the total area and median and third-quartile patch sizes for forest land and for all patches regardless of cover type indicated that fragmentation of forest land and the landscape as a whole occurred during the study period. The major land-cover transitions that occurred during the period were the loss of forest land to development and associated cover types and the conversion of one agricultural type to another. Overall, land-cover transitions during the period were found to be consistent with the Commission management-area designations, which indicated that the regional-planning effort has been successful in directing human activities to appropriate areas of the basin.


Current Evidence on Computer-Aided Diagnosis of Celiac Disease: Systematic Review.
Celiac disease (CD) is a chronic autoimmune disease that occurs in genetically predisposed individuals in whom the ingestion of gluten leads to damage of the small bowel. It is estimated to affect 1 in 100 people worldwide, but is severely underdiagnosed. Currently available guidelines require CD-specific serology and atrophic histology in duodenal biopsy samples for the diagnosis of adult CD. In pediatric CD, but in recent years in adults also, nonbioptic diagnostic strategies have become increasingly popular. In this setting, in order to increase the diagnostic rate of this pathology, endoscopy itself has been thought of as a case finding strategy by use of digital image processing techniques. Research focused on computer aided decision support used as database video capsule, endoscopy and even biopsy duodenal images. Early automated methods for diagnosis of celiac disease used feature extraction methods like spatial domain features, transform domain features, scale-invariant features and spatio-temporal features. Recent artificial intelligence (AI) techniques using deep learning (DL) methods such as convolutional neural network (CNN), support vector machines (SVM) or Bayesian inference have emerged as a breakthrough computer technology which can be used for computer aided diagnosis of celiac disease. In the current review we summarize methods used in clinical studies for classification of CD from feature extraction methods to AI techniques.


Temporal plasticity in annelid development--ontogeny of Phyllodoce groenlandica (Phyllodocidae, Annelida) reveals heterochronous patterns.
The variety of annelid larval types and developmental modes reflects the high diversity and variability within these lophotrochozoans. However, our knowledge of pattern formation and tissue development in annelids and allies is scarce. In order to gain more data concerning neurogenesis and myogenesis in annelid trochophores, we analyzed different larval stages of Phyllodoce groenlandica using immunohistochemical staining techniques and subsequent confocal laser scanning microscopy (clsm). Focusing on pre-metamorphic stages, we reconstruct the process of tissue and body formation within planktonic polychaetous trochophore larvae. Our investigations revealed detailed knowledge of general developmental modes in Annelida and exhibit ontogenetic heterochrony of tissue development between two closely related annelid species. As such, P. groenlandica shows a delayed onset of nervous system development when compared with P. maculata. In contrast to the latter species, we were not able to detect the posterior sensory organ in larval P. groenlandica. We draw conclusions concerning general development of annelid trochophores and provide data showing new insights into the plasticity of body plans in Annelida.


Age of onset of cannabis use is associated with age of onset of high-risk symptoms for psychosis.
Increasing interest in the prodromal stage of schizophrenia over the past decade led us to perform our study to monitor people at high risk for developing a psychosis. We hypothesized that cannabis use or a cannabis use disorder at a younger age relates to high-risk symptoms at a younger age. People referred to the Academic Medical Centre in Amsterdam, the Netherlands, with an ultra-high risk (UHR) for psychosis were interviewed with the Composite International Diagnostic Interview to assess their cannabis consumption. The Interview for the Retrospective Assessment of the Onset of Schizophrenia was used to collect data about age of onset of high-risk or prodromal symptoms. Nine high-risk symptoms were selected and clustered because of their known relation with cannabis use. Among the 68 included participants, 35 had used cannabis (51.5%), of whom 15 had used recently. Twenty-two participants had been cannabis abusers or cannabis-dependent (32.4%) in the past. Younger age at onset of cannabis use was related to younger age of onset of the cluster of symptoms (rho = 0.48, P = 0.003) and also to 6 symptoms individually (rho = 0.47 to 0.90, P < 0.001 to 0.04). Younger age at onset of a cannabis use disorder was related to younger age of onset of the cluster of symptoms (rho = 0.67, P = 0.001) and also to 6 symptoms individually (rho = 0.50 to 0.93, P = 0.007 to 0.03). Cannabis use or a cannabis use disorder at a younger age in a group with an UHR for transition to psychosis is related to onset of high-risk symptoms for psychosis at a younger age.


[Crime and psychopathology].
Crime does not necessarily involve the existence of a psychopathologic disorder. However, some psychiatric disorders as, for example, delirious psychosis, paranoia, melancholy or obsessional neurosis, might predispose to crime. Violence can lead the victim, by the way of stress or trauma, to develop some psychic trouble as neurosis or traumatic psychosis. Children in particular, while constructing, are very vulnerable victims, especially when their aggressor is also a member of their family. Therapy for the aggressors, as well as for the victims, is based on the assertion that both the aggressors and the victims are subject to law.


Immunosuppressive components from an Ascomycete, Diplogelasinospora grovesii.
Two known fungal metabolites, macrophin and colletodiol, and a new stereoisomer of colletodiol named 10-epi-colletodiol, were isolated as immunosuppressive principles from an Ascomycete, Diplogelasinospora grovesii. The IC50 values of the major active component among them, macrophin, were calculated to be 0.4 and 0.3 microgram/ml against concanavalin A- and lipopolysaccharide-induced proliferations of mouse spleen lymphocytes, respectively. A new natural product, 4,8-dimethyl-1,5-dioxacyclooctane-2,6-dione, and a known fungal metabolite, isosclerone, which showed no immunosuppressive activity, were also isolated from this fungus.


Scanning probe microscopy beyond imaging: a general tool for quantitative analysis.
A simple, fast and general approach for quantitative analysis of scanning probe microscopy (SPM) images is reported. As a proof of concept it is used to determine with a high degree of precision the value of observables such as 1) the height, 2) the flowing current and 3) the corresponding surface potential (SP) of flat nanostructures such as gold electrodes, organic semiconductor architectures and graphenic sheets. Despite histogram analysis, or frequency count (Fc), being the most common mathematical tool used to analyse SPM images, the analytical approach is still lacking. By using the mathematical relationship between Fc and the collected data, the proposed method allows quantitative information on observable values close to the noise level to be gained. For instance, the thickness of nanostructures deposited on very rough substrates can be quantified, and this makes it possible to distinguish the contribution of an adsorbed nanostructure from that of the underlying substrate. Being non-numerical, this versatile analytical approach is a useful and general tool for quantitative analysis of the Fc that enables all signals acquired and recorded by an SPM data array to be studied with high precision.


Osteoarthritis of the trapezioscaphoid joint.
Isolated osteoarthritis (OA) of the trapezioscaphoid (TS) joint is little recognized. Nine cases that were examined clinically and radiologically are described. Of these 4 had isolated TS OA, 3 also had generalized OA, and 2 also had rheumatoid arthritis. Symptoms and signs, including pain in the wrist and thumb base, radial and volar swelling, and tenderness over the scaphoid, allowed distinction from other causes of pain at the thumb base. A wrist-working splint was beneficial in relieving pain.


Generalization of the time-to-event continual reassessment method to bivariate outcomes.
This article considers the problem of designing Phase I-II clinical trials with delayed toxicity and efficacy outcomes. The proposed design is motivated by a Phase I-II study evaluating all-trans retinoic acid (ATRA) in combination with a fixed dose of daratumumab in the treatment of relapsed or refractory multiple myeloma. The primary objective of the study is to identify a dose that maximizes efficacy and has an acceptable level of toxicity. The toxicity endpoint is observed in one cycle of therapy (i.e., 4 weeks) while the efficacy endpoint is assessed after 8 weeks of treatment. The difference in endpoint observation windows causes logistical challenges in conducting the trial, since it is not practical to wait until both outcomes for each patient have been fully observed before sequentially assigning the dose of a newly eligible patient. In order to avoid delays in treatment for newly enrolled patients and to accelerate trial progress, we generalize the time-to-event continual reassessment method (TITE-CRM) to bivariate outcomes. Simulation studies are conducted to evaluate the proposed method, and we found that the proposed design is able to accurately select doses that maximize efficacy and have acceptable toxicity, while using all available information in allocating patients at the time of dose assignment. We compare the proposed methodology to two existing methods in the area.


Anabel: An Online Tool for the Real-Time Kinetic Analysis of Binding Events.
Anabel (Analysis of binding events + l) is an open source online software tool (www.skscience.org/anabel) for the convenient analysis of molecular binding interactions. Currently, exported datasets from Biacore (surface plasmon resonance [SPR]), FortéBio (biolayer interference [BLI]), and Biametrics (single color reflectometry [SCORE]) can be uploaded and evaluated in Anabel using 2 different evaluation methods. Moreover, a universal data template format is provided to upload any other binding dataset to Anabel. This enables an easier comparison of different analysis methods for all users. Furthermore, a guide was established in Anabel to help inexperienced users to obtain optimal results. In addition, expert features can be used to optimize and control the fit of the binding model to the measured data. We tried to make the process of fitting and evaluating as easy as possible through the use of an intuitive user interface. At the end of every analysis, a single excel file, containing all results and graphs of the performed analysis, can be downloaded.


Applications of Artificial Intelligence in Myopia: Current and Future Directions.
With the continuous development of computer technology, big data acquisition and imaging methods, the application of artificial intelligence (AI) in medical fields is expanding. The use of machine learning and deep learning in the diagnosis and treatment of ophthalmic diseases is becoming more widespread. As one of the main causes of visual impairment, myopia has a high global prevalence. Early screening or diagnosis of myopia, combined with other effective therapeutic interventions, is very important to maintain a patient's visual function and quality of life. Through the training of fundus photography, optical coherence tomography, and slit lamp images and through platforms provided by telemedicine, AI shows great application potential in the detection, diagnosis, progression prediction and treatment of myopia. In addition, AI models and wearable devices based on other forms of data also perform well in the behavioral intervention of myopia patients. Admittedly, there are still some challenges in the practical application of AI in myopia, such as the standardization of datasets; acceptance attitudes of users; and ethical, legal and regulatory issues. This paper reviews the clinical application status, potential challenges and future directions of AI in myopia and proposes that the establishment of an AI-integrated telemedicine platform will be a new direction for myopia management in the post-COVID-19 period.


Mechanisms underlying the lack of endogenous processing and CLIP-mediated binding of the invariant chain by HLA-DP84Gly.
While the principles of classical antigen presentation via MHC class II are well-established, the mechanisms for the many routes of cross-presentation by which endogenous antigens become associated with class II molecules are not fully understood. We have recently demonstrated that the single amino acid polymorphism HLA-DPβ84Gly (DP84Gly) is critical to abrogate class II invariant chain associated peptide (CLIP) region-mediated binding of invariant chain (Ii) to DP, allowing endoplasmic reticulum (ER)-resident endogenous antigens to constitutively associate with DP84Gly such as DP4. In this study, we demonstrate that both the CLIP and N-terminal non-CLIP Ii regions cooperatively generate an Ii conformation that cannot associate with DP84Gly via the CLIP region. We also demonstrate the ability of DP4 to efficiently process and present antigens encoded in place of CLIP in a chimeric Ii, regardless of wild type Ii and HLA-DM expression. These data highlight the complex interplay between DP polymorphisms and the multiple Ii regions that cooperatively regulate this association, ultimately controlling the presentation of endogenous antigens on DP molecules. These results may also offer a mechanistic explanation for recent studies identifying the differential effects between DP84Gly and DP84Asp as clinically relevant in human disease.


The Impact of Audio-Visual, Visual and Auditory Cues on Multiple Object Tracking Performance in Children with Autism.
Previous studies have documented differences in processing multisensory information by children with autism compared to typically developing children. Furthermore, children with autism have been found to track fewer multiple objects on a screen than those without autism, suggesting reduced attentional control. In the present study, we investigated whether children with autism (n = 33) and children without autism (n = 33) were able to track four target objects moving amongst four indistinguishable distractor objects while sensory cues were presented. During tracking, we presented various types of cues - auditory, visual, or audio-visual or no cues while target objects bounced off the inner boundary of a centralized circle. We found that children with autism tracked fewer targets than children without autism. Furthermore, children without autism showed improved tracking performance in the presence of visual cues, whereas children with autism did not benefit from sensory cues. Whereas multiple object tracking performance improved with increasing age in children without autism, especially when using audio-visual cues, children with autism did not show age-related improvement in tracking. These results are in line with the hypothesis that attention and the ability to integrate sensory cues during tracking are reduced in children with autism. Our findings could contribute valuable insights for designing interventions that incorporate multisensory information.


Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal-Mild Endometriosis.
Endometriosis, characterized by the presence of endometrial-like tissue at extrauterine sites, is a common, chronic, estrogen-dependent, inflammatory condition associated with pelvic pain, subfertility, dysmenorrhea, and dyspareunia, affecting about 10% of reproductive-age women in any population. The diagnosis of endometriosis is usually delayed on an average by 8 to 11 years leading to significant consequences in terms of disease progression. The current study was aimed to validate enzyme-linked immunosorbent assay based on the epitopes of stomatin-like protein 2, tropomodulin 3 (TMOD3), and tropomyosin 3 (TPM3) for diagnosis of minimal-mild endometriosis (revised American Fertility Society Classification (rAFS) stage I-II) and to compare the performance with the reported markers: cancer antigen (CA) 125, CA19-9, α-enolase, Serine/threonine-protein kinase (PDIK1L), and syntaxin 5. This was a cross-sectional, multicenter study conducted during the year 2012 to 2015. Women with minimal-mild endometriosis (rAFS stage I-II [n = 133]) and healthy controls (n = 104) were screened for 11 novel autoimmune markers and reported markers α-enolase, PDIK1L, syntaxin 5, CA-125, and CA19-9. The sensitivity and diagnostic accuracy of serum antibodies against all the 11 epitopes were higher than that of CA-125, CA19-9, α-enolase, PDIK1L, and syntaxin 5 for diagnosis of rAFS stage I to II endometriosis. The sensitivity of 6 biomarkers (anti-TMOD3b-autoAb, anti-TMOD3c-autoAb, anti-TMOD3d-autoAb, anti-TPM3a-autoAb, anti-TPM3c-autoAb, and anti-TPM3d-autoAb) was higher at the specificity of ≥80% for diagnosis of rAFS stage I to II endometriosis as well as ultrasound-negative endometriosis. Further, logistic regression models of this panel of biomarkers showed increase in sensitivity, specificity, and diagnostic accuracy than individual biomarkers. The panel of 6 autoimmune biomarkers could be useful in setting up of noninvasive diagnostic test for detection of minimal-mild endometriosis.


Case Report: Is Pneumoperitoneum the Only Indication for Surgery in Necrotizing Enterocolitis?
Objective: This study aims to explore whether pneumoperitoneum is the only surgical indication for neonates with necrotizing enterocolitis (NEC) and to analyze when early surgical intervention should be considered. Methods: A retrospective case series study was conducted including six neonates with stage 2a-2b NEC who received surgeries without absolute indication but with failed conservative treatment. In the meantime, seven infants who received surgery due to pneumoperitoneum and 32 infants treated with conservative treatment were also included for comparison. Results: Our results indicated that the six infants who received surgical treatment without pneumoperitoneum had a better prognosis compared to the seven infants who underwent surgical treatment after the onset of pneumoperitoneum. None of the infants who received early surgical treatment developed short bowel syndrome or neurodevelopmental impairment, while four out of six infants exhibited growth retardation. On the other hand, a total of five out of the seven infants who received surgical treatment after pneumoperitoneum forfeited further treatment, two developed short bowel syndrome, and one experienced neurodevelopmental impairment. Lower gestational age and birth weight, fetal growth restriction (FGR), perinatal asphyxia, postnatal steroid and vascular active drug use, blood transfusion, and hemodynamic significant patent ductus arteriosus were identified as risk factors associated with surgical repair for infants with NEC. In a laboratory test, infants who needed surgeries had a lower platelet count and a higher C-reactive protein value. Conclusion: Aggressive surgical treatment should be considered in infants with severe necrotizing enterocolitis before the onset of pneumoperitoneum. Lower gestational age and birth weight, FGR, perinatal asphyxia, postnatal steroid and vascular active drug use, blood transfusion, and hsPDA may be associated with surgical repair for infants with NEC.


Systemic fungal infections: diagnosis and treatment. I. Blastomycosis.
Blastomycosis is a rare systemic fungal infection caused by Blastomyces dermatitidis, which is often difficult to diagnose because of its spectrum of manifestations, varying severity, and unusual occurrence in most geographic areas. Because routine serologic methods and skin tests are not reliable for this pathogen, diagnosis is made by visualization of the organism in tissue, sputum, or exudate, or by culture. Once blastomycosis is diagnosed, therapeutic options include treatment with amphotericin B or ketoconazole, or simple observation if spontaneous resolution is anticipated. The purpose of this discussion is to review the features of blastomycosis that relate to the clinical practice of medicine.


Understanding community-based processes for research ethics review: a national study.
Institutional review boards (IRBs), designed to protect individual study participants, do not routinely assess community consent, risks, and benefits. Community groups are establishing ethics review processes to determine whether and how research is conducted in their communities. To strengthen the ethics review of community-engaged research, we sought to identify and describe these processes. In 2008 we conducted an online survey of US-based community groups and community-institutional partnerships involved in human-participants research. We identified 109 respondents who met participation criteria and had ethics review processes in place. The respondents' processes mainly functioned through community-institutional partnerships, community-based organizations, community health centers, and tribal organizations. These processes had been created primarily to ensure that the involved communities were engaged in and directly benefited from research and were protected from research harms. The primary process benefits included giving communities a voice in determining which studies were conducted and ensuring that studies were relevant and feasible, and that they built community capacity. The primary process challenges were the time and resources needed to support the process. Community-based processes for ethics review consider community-level ethical issues that institution-based IRBs often do not.


Evaluation of cardiovascular parameters by continuous 24 hour monitoring in diabetic hypertensive patients with autonomic neuropathies.
Correlations between scores of autonomic neuropathy severity in diabetic hypertensive subjects and behaviour of cardiovascular parameters detected by continuous 24 hour monitoring were investigated in order to reveal any alterations hat indicated onset and progression of disautonomy. R-R and Q-T patterns, circadian pressure rhythm and ECG Holter over 24 hours were analysed in 30 patients divided into various groups (age, duration of disease, treatment) and 10 controls. Three autonomic tests (deep breathing, postural hypotension, lying to standing) were performed and the relative Ewing scores recorded. Data obtained were analysed using Pearson's correlation test and simple linear regression. The results not only confirm circadian rhythm demodulation of arterial pressure, but also show progressive correlation between the scores obtained and modified cardiovascular parameters. According to the authors, detection of these intermediate alterations may be useful in forecasting possible onset or evolution of dysautonomic pathologies.


Effect of smoke inhalation injury on fluid requirement in burn resuscitation.
The effect of smoke inhalation injury on fluid requirement was assessed retrospectively. A total of 131 burn patients were classified into two groups: burn patients with smoke inhalation injury (Group IB: 73 patients) and burn patients without inhalation injury (Group B: 58 patients). Fluid resuscitation was commenced according to the Parkland formula and the infusion rate was modified to meet the main resuscitation goal of an hourly urine output of 1.0 to 2.0 ml/kg. Regression analyses were performed on the volume of fluid administered during the initial 24 hours after injury by burn size for each group. The linear equations obtained were Y (ml/kg/24 hrs) = 71.0 + 5.08 x %TBSA (Group IB) and Y = 39.7 + 5.14 x %TBSA (Group B). A substantial effect of inhalation injury on fluid requirement was speculated to be reflected in a y intercept difference of about 30 ml/kg/24 hrs. Thus, an increase in the fluid requirement related to the presence of inhalation injury was found to be independent and additional to burn injury.


Atrial fibrillation and mortality in an elderly population.
Prospective data from Busselton, Western Australia, collected during triennial surveys from 1966-81 with follow-up of subjects to 1983, showed that atrial fibrillation (AF) was frequent in elderly people and associated with increased mortality. Of 1770 people aged over 60 years, 40 were in atrial fibrillation when first seen and a further 47 developed it during follow-up. Atrial fibrillation was positively associated with angina, history of a myocardial infarction and left bundle branch block. Relative mortality in those with atrial fibrillation compared with those without it, was 1.92 for all causes, 1.82 for death from cardiovascular causes (excluding stroke) and 3.78 for deaths from stroke, after adjustment by proportional hazards regression for confounding effects of age, sex, history of a myocardial infarction, an abnormal electrocardiogram, angina, cholesterol level systolic blood pressure and Quetelet's Index (weight/height2). The excess relative mortality declined with increasing age for both women and men. This raised relative mortality remained constant with time from the first detection of AF for all causes and cardiovascular causes but appeared to increase with time from detection for stroke death. The risk of death from stroke was greatest in the younger women. The observed risk of death from stroke in patients with AF suggests that anticoagulant use should be considered in selected patients.


Cellulolytic potential under environmental changes in microbial communities from grassland litter.
In many ecosystems, global changes are likely to profoundly affect microorganisms. In Southern California, changes in precipitation and nitrogen deposition may influence the composition and functional potential of microbial communities and their resulting ability to degrade plant material. To test whether such environmental changes impact the distribution of functional groups involved in leaf litter degradation, we determined how the genomic diversity of microbial communities in a semi-arid grassland ecosystem changed under reduced precipitation or increased N deposition. We monitored communities seasonally over a period of 2 years to place environmental change responses into the context of natural variation. Fungal and bacterial communities displayed strong seasonal patterns, Fungi being mostly detected during the dry season whereas Bacteria were common during wet periods. Most putative cellulose degraders were associated with 33 bacterial genera and predicted to constitute 18% of the microbial community. Precipitation reduction reduced bacterial abundance and cellulolytic potential whereas nitrogen addition did not affect the cellulolytic potential of the microbial community. Finally, we detected a strong correlation between the frequencies of genera of putative cellulose degraders and cellulase genes. Thus, microbial taxonomic composition was predictive of cellulolytic potential. This work provides a framework for how environmental changes affect microorganisms responsible for plant litter deconstruction.


Absorption, distribution, excretion, and pharmacokinetics of 14C-pyronaridine tetraphosphate in male and female Sprague-Dawley rats.
The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) of 14C-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards. 14C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion of 14C-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that the C(max), AUC (0-inf), and T(max) values were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.


Selection for simple major surface protein 2 variants during Anaplasma marginale transmission to immunologically naïve animals.
Anaplasma marginale, a rickettsial pathogen, evades clearance in the animal host by antigenic variation. Under immune selection, A. marginale expresses complex major surface protein 2 mosaics, derived from multiple donor sequences. However, these mosaics have a selective advantage only in the presence of adaptive immunity and are rapidly replaced by simple variants following transmission.


The consumption of omega-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: a systematic evaluation.
This study was aimed to systematically evaluate results of trials examining the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption on body weight, lean body mass, resting energy expenditure, and overall survival in pancreatic cancer patients. We searched Medline, Pubmed, Embase, and Cochrane databases. We selected randomized controlled trials of n-3 PUFA vs. conventional nutrition in unresectable pancreatic cancer patients. We analyzed our data using the Cochrane statistical package RevMan 5.1. Eleven trials met our inclusion criteria. There was a significant increase in body weight [weighted mean difference (WMD) = 0.62; 95% confidence interval (CI), 0.54-0.69, P < 0.00001) and lean body mass (WMD = 0.96; 95% CI, 0.86-1.06, P < 0.00001), a significant decrease in resting energy expenditure (WMD = -29.74; 95% CI, -55.89-3.59, P = 0.03), and an increase in overall survival (130-259 days vs. 63-130 days) in unresectable pancreatic cancer patients who consumed an oral nutrition supplement enriched with n-3 PUFAs compared to those who consumed conventional nutrition. This preliminary study suggests that n-3 PUFAs are safe and have a positive effect on clinical outcomes and survival in pancreatic cancer patients.


Encystment-specific mRNA is accumulated in the resting cysts of the ciliate Colpoda inflata.
From a random amplified polymorphism cDNA study using vegetative, precystic and mature resting cysts of the ciliate Colpoda inflata, a stage-specific fragment was isolated from the resting cyst cDNA population. This fragment was used as an encystment probe to study the corresponding mRNA expression during this eukaryotic cell differentiation process. This transcript is accumulated in the resting cyst of this ciliate, and it is the first time that accumulation of specific mRNA molecules associated with the ciliate cryptobiosis process is reported. The meaning of this stored mRNA in microbial cryptobiotic stages is discussed.


[Specific dilated myocardiopathy. Chronic chagasic cardiopathy at the National Institute of Cardiology Ignacio Chávez].
Cardiomyopathies are a heterogenous group of heart ailments. Some of them are primary myocardial diseases and are classified as dilated, hypertrophic, restrictive and arryhithmogenic. Dilated cardiomyopathies (DCs) are the most common. Sometimes it is possible to identify an etiologic agent, in that case we talk about a specific dilated cardiomyopathy. Here in, we review one of these specific DCs, the so called Chronic Chagasic Cardiopathy (CCC) from the point of view of our personal experience at the Instituto Nacional de Cardiología "Ignacio Chávez". Chagas' disease is present in Mexico, therefore CCC is also present. We estimate that 5,000 people, suffer CCC with severe symptoms. In Mexico, Chagas' disease occurs below the Tropic of Cancer and between 2,000-2,500 m above sea level, in this area there is a real risk for vectorial infection, mainly in rural villages. Clinical diagnosis should be supported by epidemiological and seroepidemiological confirmatory data. There is not appropriate therapy yet for this condition.


Effects of Teriparatide and Sequential Minodronate on Lumbar Spine Bone Mineral Density and Microarchitecture in Osteoporosis.
The trabecular bone score (TBS) is a new surrogate for trabecular bone microarchitecture assessment, independent of bone mineral density (BMD), calculated from pixel gray-level variations in the lumbar spine (LS) dual-energy X-ray absorptiometry (DXA) image. Although Teriparatide (TPTD) increased LS-BMD as well as TBS in 2 years, the precise time-course of these parameters was not well known. The aim of this study was to determine the changes in LS-BMD and the TBS in osteoporotic patients treated with TPTD, followed by minodronate (MINO). Primary osteoporotic patients with a low LS-BMD (T-score < -2.5) and/or at least one vertebral fracture were treated with TPTD subcutaneously at 20 µg/day for 12-24 months, followed by MINO (orally at 50 mg/once monthly) for 12 months. LS-BMD and the TBS were measured at 0, 3, 6, 12, and 24 months after the initiation of TPTD treatment, and 12 months after the initiation of MINO. The increments of LS-BMD, significant at 6 months, increased until 12 months, whereas the increments of TBS, significant at 3 months (0.035 ± 0.011; p = 0.045 vs. the baseline), stabilized until 12 months. TPTD treatment, followed by 12 months of MINO, maintained both BMD and the TBS. Comparing the increments of the TBS to those of LS-BMD, our results indicate that TPTD treatment improved trabecular microarchitecture faster than mineralization. TPTD treatment, followed by MINO, can maintain both BMD and the TBS.


[Follow-up study, using dynamic transcutaneous oximetry in 17 patients with stage II Leriche and Fontaine occlusive arterial disease of the lower limbs].
We evaluated the value of dynamic transcutaneous oxygen pressure measurement (TcPO2) in 17 patients with stage II occlusive arterial disease of the lower limbs treated with exercise only. We studied 17 patients (15 men, two women) with an average age of 63 years (range 39-80 years). Claudication perimeter and dynamic TcPO2 were evaluated before and after 6 month walking exercise and tabac stopping. Four different sites of TcPO2 were studied: precordium (reference probe), thigh, calf and foot in the dorsal recumbent position after 30 minutes rest, during a standardised exercise stress test at 50 watts and during the recovery phase. The results were expressed as ratio of tissue oxygenation (RTO): thigh, calf or foot TcPO2/precordial TcPO2 x 100 in order to take into account the patients cardiorespiratory status and adaptation to exercise. Claudication perimeter was 255 m +/- 221 before 6 months exercise and 835 m +/- 539 after (P < 0.01). The duration of significative ischemia was significantly reduced after 6 months exercise (P = 0.02 calf, P < 0.01 foot). Dynamic transcutaneous oxymetry would therefore seem to be a useful method of assessing stage II occlusive peripheral arterial disease and the topography of tissue hypoxia. It could be valuable in orientating treatment and the first method to provide and objective evaluation of the efficacy of medical or surgical treatment.


Ex vivo expansion of human UC blood primitive hematopoietic progenitors and transplantable stem cells using human primary BM stromal cells and human AB serum.
In vitro maintenance and expansion of human hematopoietic stem cells is crucial for many clinical applications, and investigators have been using xenogeneic, especially murine, stromal cells for stem-cell expansion. In addition, many such culture systems utilize FCS-containing medium or serum-free medium that contains human- or animal-derived proteins. However, the possible transmission of infectious diseases has led to a debate about the safety of the delivery of grafts expanded in culture using cells and proteins of allogeneic or xenogeneic origin. Using primary human BM stromal cells, we have established an AB serum-based co-culture system to expand human primitive progenitors and transplantable stem cells. Cord blood CD34+ cells were cultured on a monolayer of human BM-derived primary stromal cells with thrombopoietin (TPO), stem-cell factor (SCF) and flt3/flk2 ligand (FL) in the presence of either FCS or AB serum. One to three weeks later, cells were examined for total cells, CD34+ cells, CD34+ CD38- cells, and clonogenic progenitors. SCID mouse reconstituting cell (SRC) activity was also studied. Three weeks of culture with TPO, SCF, and FL supported more than a 250-fold expansion of CD34+ cells, CD34+ CD38- cells and CFU-C, regardless of the kind of serum used. SRC assay revealed that transplantable stem cells were moderately expanded as well. This ex vivo expansion system should prove valuable in clinical settings in which stromal cells and serum are available from recipients or stem-cell donors.


[Evaluation and treatment of children's laryngeal clefts].
Objectives: To provide the experience about the diagnostic process and following management, and to discuss the outcome and predictors in children with laryngeal cleft (LC). Methods: A retrospective case study was conducted at an academic children's hospital. Thirty children were diagnosed as laryngeal cleft between January 2016 and April 2017.Airway evaluations were performed using both flexible and rigid endoscopy, and swallowing evaluations were performed using fiberoptic endoscopic examination of swallowing or modified barium swallow. Results: Of 30 cases, 18 were male and 12 were female, ranging in age from birth to 8 years. Two cases were diagnosed as type 0 LC, and they were offered thickened liquid without medication. Throughout follow-up, they remained asymptomatic and showed no respiratory complications. Nineteen children were diagnosed as type Ⅰ LC. Six of them were significantly improved by anti-reflux therapy and feeding instructions. Four children were concomitant with swallowing dysfunction and/or neuromuscular disorders, and they were given a tracheotomy and routine management. Another 4 children were submitted surgical repair when routine treatment failed, and their symptoms were relieved. Five children were concomitant with larygomalacia, and their symptoms were totally ameliorated by supraglottoplasty. Three children were diagnosed as type Ⅱ LC. Two of them received surgical repair and clinically improved, and the rest one was treated by anti-reflux therapy and still under follow-up. Three children were diagnosed as type Ⅲ LC. One of them was underwent surgical repair and clinically improved. Two children were tracheotomized and treated by anti-reflux therapy. Three cases were diagnosed as type Ⅳ LC at birth and no one survived. Conclusions: Laryngeal cleft is a rare congenital anomaly manifesting with a variety of symptoms, including swallowing disorder, aspirations, dyspnea, stridor and hoarseness. Diagnosis and treatment of laryngeal clefts is a challenge. The best way to evaluate the LC is FEES by laryngeal endoscopy combined with MLB. Cases with type 0-Ⅰ mostly were significantly improved by anti-reflux therapy and feeding instructions. When routine treatment failed, surgical repair is needed. All the cases with LC type Ⅱ-Ⅲ need surgical repair as soon as possible. For type Ⅳ cases, early diagnosis, appropriate treatment and management help to reduce mortality and morbidity.


Clinical efficacy and safety of rosuvastatin in Japanese patients with heterozygous familial hypercholesterolemia.
Rosuvastatin is a new statin that has been shown to produce substantial dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western and Japanese hypercholesterolemic patients. Rosuvastatin efficacy and safety were assessed in an open-label, dose-titration trial of 37 Japanese patients with heterozygous familial hypercholesterolemia. After an 8-week dietary lead-in period, patients received rosuvastatin on the following schedule: 10 mg/day during weeks 0-6; 20 mg/day during weeks 6-12, and 40 mg/day for weeks 12-18. Mean percentage reductions from baseline in LDL-C (49.2-56.7%), total cholesterol (39.4-45.4%), and non-high-density lipoprotein cholesterol (non-HDL-C) (46.7-54.3%) were highly significant at each dose (p < 0.0001). Similar significant reductions in triglycerides (18.2-25.0%; p < 0.006) and increases in HDL-C (9.6-13.6%; p < 0.005) were observed. Rosuvastatin was well tolerated. Two patients withdrew from the study because of adverse events unrelated to the study treatment. No patients had clinically significant elevations in liver transaminases. Two patients exhibited a single increase in creatine kinase (one unrelated to study treatment, the other possibly related) with no muscle symptoms. Rosuvastatin produced significant beneficial changes in all lipid parameters in Japanese patients with heterozygous familial hypercholesterolemia and was well tolerated.


Bifunctional charge transfer operated fluorescent probes with acceptor and donor receptors. 1. Biphenyl-type sensor molecules with protonation-induced anti-energy gap rule behavior.
On the basis of biphenyl (b) type molecules bpb-R substituted with a 2,2':6',2' '-terpyridine acceptor (bp) and either amino-type donor receptors (R = dimethylamino (DMA), A15C5 = monoaza-15-crown-5) or nonbinding substituents (R = CF(3), H, OMe) of various donor strengths, we developed a family of charge transfer (CT) operated monofunctional and bifunctional fluorescent sensors for protons and metal ions. These molecules are designed to communicate the interaction of an analyte with the acceptor and the donor receptor differing in basicity and cation selectivity by clearly distinguishable spectral shifts and intensity modulations in absorption and in emission as well as in fluorescence lifetime. From the dependence of the fluorescence spectra, fluorescence quantum yields, and fluorescence lifetimes of bpb-R on solvent polarity and proton concentration, the photophysics of bpb-R and their protonated analogues can be shown to be governed by the relaxation to a CT state of forbidden nature and by the switching between anti-energy and energy gap law type behaviors. This provides the basis for analytically favorable red shifted emission spectra in combination with comparatively high fluorescence quantum yields. Accordingly, bpb-H and bpb-OMe are capable of ratiometric emission signaling of protons. bpb-DMA reveals a protonation-induced ON-OFF-ON switching of its emission.


Systemic mastocytosis associated with presence of rheumatoid factor.
We encountered a case of systemic mast cell disease associated with rheumatoid factor; to our knowledge, this has not been reported in the literature. Rheumatoid arthritis as an unrelated second disease cannot be excluded, but there is support for a relation between joint symptoms, rheumatoid factor, and the mast cell disease.


Understanding the Independent Predictors of Dysphagia-Related Quality of Life in Stroke Survivors.
It is important to pinpoint modifiable factors contributing to reduced dysphagia-related quality of life (QoL) in order to improve treatment outcomes and patient health given that a large proportion of stroke survivors experience dysphagia. The purpose of this exploratory study was to identify the independent predictors of dysphagia-related QoL in community-dwelling stroke survivors. A sample of 31 adult stroke survivors with dysphagia (M age = 62 years; 23 males) and their partners (M age = 57 years; seven males) participated in the study. Survivors were > 3 months poststroke and living with their partner. Backward regression analysis methods were employed to determine independent predictors of dysphagia-related QoL using scores from the Swallowing-Related Quality of Life questionnaire. Independent variables tested included age, employment status, receiving dysphagia treatment, number of medical conditions, level of diet modification, Stroke Impact Scale (SIS) scores, relationship with partner, partner age, partner employment status, partner burden, and partner depression. Results indicated that number of survivor medical conditions, degree of diet modification, SIS emotional subscale score, and partner employment status significantly predicted dysphagia-related QoL (p < .001). More specifically, stroke survivors with more medical conditions or a partner who worked outside of the home had worse dysphagia-related QoL, and those with better mental health or a less modified diet had better dysphagia-related QoL. Factors related to dysphagia-related QoL are multifactorial and include both survivor and spousal variables. The results of this exploratory study highlight the need for clinicians and researchers to consider patient function and needs more wholistically to maximize perceived QoL.


Ultrafast Transverse Modulation of Free Electrons by Interaction with Shaped Optical Fields.
Spatiotemporal electron-beam shaping is a bold frontier of electron microscopy. Over the past decade, shaping methods evolved from static phase plates to low-speed electrostatic and magnetostatic displays. Recently, a swift change of paradigm utilizing light to control free electrons has emerged. Here, we experimentally demonstrate arbitrary transverse modulation of electron beams without complicated electron-optics elements or material nanostructures, but rather using shaped light beams. On-demand spatial modulation of electron wavepackets is obtained via inelastic interaction with transversely shaped ultrafast light fields controlled by an external spatial light modulator. We illustrate this method for the cases of Hermite-Gaussian and Laguerre-Gaussian modulation and discuss their use in enhancing microscope sensitivity. Our approach dramatically widens the range of patterns that can be imprinted on the electron profile and greatly facilitates tailored electron-beam shaping.


A Cohort Comparison of Lifespan After Age 100 in Denmark and Sweden: Are Only the Oldest Getting Older?
Although Denmark and Sweden have close cultural and historical ties, lifespans for Danes have generally been lower than those of Swedes. Recent improvements in Danish mortality after a period of stagnation have led to the suspicion that there may be positive trends at the very high ages at death within that population and that these trends could be quite different from those observed in Sweden. Although the mean ages at death for Danish and Swedish centenarians have been relatively constant at about 102 years for the cohorts born 1870-1904, the oldest-old in Denmark have been getting older, but no evidence has suggested any increase in lifespan for Swedes. Using quantile regression, we show that Danish centenarian lifespans in the 90th percentile have been lengthening, with those in 94th percentile (6 % longest-lived individuals) having a trend that is statistically significant at the 5 % level. We demonstrate that the increase observed is not due to the increasing sizes of birth cohorts and thus must be due to improving survival among this select top tier. We postulate that this super-select group in Denmark is best able to take advantage of the factors driving mortality reduction, whereas the majority of centenarians are not.


Asymptomatic and symptomatic urethral gonorrhoea in men who have sex with men attending a sexual health service.
Guidelines regarding whether men who have sex with men (MSM) without symptoms of urethritis should be screened for urethral gonorrhoea differ between countries. We examined the rate of asymptomatic urethral gonorrhoea in MSM using sensitive nucleic acid amplification testing. This study was conducted on consecutive MSM attending the Melbourne Sexual Health Centre between July 2015 and May 2016 for sexually transmitted infections screening. Gonorrhoea testing with the Aptima Combo 2 (AC2) assay was performed on all urine specimens obtained from MSM, whether symptoms of urethritis were present or not. Men were classified as having: typical discharge if they reported symptoms suggesting purulent discharge; other symptoms if they reported other symptoms of urethritis; and no symptoms if they reported no urethral symptoms. During the study period, there were 7941 clinic visits by 5947 individual MSM with 7090 urine specimens obtained from 5497 individual MSM tested with the AC2 assay. Urethral gonorrhoea was detected in 242 urine specimens from 228 individual MSM. The majority (189/242, 78%, 95% CI 73-83) reported typical discharge, 27/242 (11%, 95% CI 8-16) reported other urethral symptoms, and 26/242 (11%, 95% CI 7-15) reported no symptoms on the day of presentation and testing. Among men with urethral gonorrhoea, the proportions with concurrent pharyngeal or rectal gonorrhoea were 32% (134/210) and 64% (74/235), respectively. The mean interval between last reported sexual contact and onset of typical urethral discharge, where present, was 3.9 days. The findings from our study lend support to guidelines that recommend screening asymptomatic MSM for urethral gonorrhoea.


Depletion makes the heart grow less helpful: helping as a function of self-regulatory energy and genetic relatedness.
Often people are faced with conflict between prosocial motivations for helping and selfish impulses that favor not helping. Three studies tested the hypothesis that self-regulation is useful for managing such motivational conflicts. In each study, depleted self-regulatory energy reduced willingness to help others. Participants who broke a habit, relative to participants who followed a habit, later reported reduced willingness to help in hypothetical scenarios (e.g., donating food or money; Studies 1 and 3). Controlling attention while watching a video, relative to watching it normally, reduced volunteering efforts to help a victim of a recent tragedy- but drinking a glucose drink undid this effect (Study 2). Depleted energy reduced helping toward strangers but it did not reduce helping toward family members (Study 3). Helping requires self-regulatory energy to manage conflict between selfish and prosocial motivations-a metabolically expensive process-and thus depleted energy reduces helping and increased energy (glucose) increases helping.


Predictors of abnormal heart rate recovery in patients with heart failure reduced and preserved ejection fraction.
Heart rate recovery (HRR) is becoming an important prognostic maker in heart failure (HF), but very little is known about the underlying mechanisms responsible for its clinical efficacy. Therefore, we examined echocardiographic and exercise (submaximal and maximal) characteristics to gain a better appreciation of HRR and factors responsible for the development of abnormal HRR in patients with both heart failure reduced ejection fraction (HFrEF) and heart failure preserved ejection fraction (HFpEF). Cardiopulmonary exercise testing (CPX), a 6-minute walk test (6MWT), and resting 2D echocardiography were randomly performed in 240 HF patients (200 HFrEF, 40 HFpEF) after which HRR was measured. HRR was defined as the difference between heart rate at peak exercise and 1 minute following test termination. Bivariate correlation analyses found significant relationships among most CPX and 6MWT measurements with the highest correlations between 6MWT HRR and 6MWT peak HR (r = 0.65; p < 0.001) and CPX HRR and CPX HRreserve (r = 0.63; p < 0.001). The relationship between 6MWT HRR and CPX HRR was very good (r = 0.91; p < 001). Multivariate logistic regression of submaximal and maximal exercise found 6MWT peak HR and exercise oscillatory ventilation (EOV), respectively, were the strongest predictors (p < 0.001) of abnormal HRR. The E/E' was a significant predictor (p < 0.001) of abnormal HRR, but EOV was the strongest predictor of abnormal HRR (OR = 6.5). HRR after both CPX and the 6MWT is significantly related to many exercise and echocardiographic measures with the most significant predictors of abnormal HRR being related to indices of cardiorespiratory performance in patients with HFrEF and HFpEF.


Clinical anatomy of the periocular region.
The aims of this article are twofold: (1) to provide the facial plastic surgeon with a comprehensive and up-to-date overview of periocular anatomy including the brow, midface, and temporal region and (2) to highlight important anatomical relationships that must be appreciated in order to achieve the best possible functional and aesthetic surgical outcomes.


Finding commonalities: social information processing and domain theory in the study of aggression.
The Arsenio and Lemerise (this issue) proposal integrating social information processing (SIP) and domain theory to study children's aggression is evaluated from a domain theory perspective. Basic tenets of domain theory rendering it compatible with SIP are discussed as well as points of divergence. Focus is directed to the proposition that domains constitute latent structures of SIP. Latent structures are described as cogenerative elements of online processing rather than cumulative stores of social information. Microgenetic studies of the reciprocal role of productive systems described within SIP and latent structures attributed to domain theory are proposed as important to the study of children' aggression. Domain theory studies of social exclusion and bullying are proposed as rich contexts for future research.


Effects of working postures on low back pain.
The prevalence of back pain in a sample of 100 employees in a clothes factory was studied and predisposing factors especially working postures were analyzed. The employee's ages were 17-40 years (mean 28 years). Durations of employment were between 1 month to 21 years (mean 9.4 years). Working time per day was 8 h. The subjects included 18 males and 82 females. The prevalence of back pain was 38%. Working activities like lifting, pulling and pushing, bending and sitting were highly associated with low back pain. Standing and walking were also associated but with a lower prevalence.


Usefulness of molecular diagnosis in egg allergic children.
Egg allergy is one of the most common food allergies in children. Egg white, including ovomucoid (OVM or Gal d 1) and ovalbumin (OVA or Gal d 2), is the major source of allergens. The aim of this study was to assess the role of Gal d 1 and Gal d 2 in predicting the risk of anaphylaxis caused by eggs in children, and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. One hundred and forty-eight children were divided into 2 groups according to a positive (group A, 33 children) or negative (group B, 115 children) history of anaphylaxis after ingestion/contact with eggs. All patients underwent an allergological evaluation by measurements of specific IgE against egg white: Gal d 1 and Gal d 2. Higher levels of Gal d 1, Gal d 2 and IgE against egg white were detected in group A compared to group B (p < 0.001). Although the area under the curve was similar for Gal d 1 and Gal d 2, egg white specific IgE showed a better sensitivity (85%) for a cut-off value ≥ 0.975 kUA/l, while Gal d 1 and Gal d 2 demonstrated a better specificity (90% and 80%, respectively) for cut-off values ≥ 1.460 kUA/l and ≥ 2.310 kUA/l, respectively. Egg white specific IgE showed a similar ability as Gal d 1 and Gal d 2 in differentiating children at risk for egg anaphylaxis, although Gal d 1 and Gal d 2 showed a better specificity.


Selective DNAM-1 expression on small peritoneal macrophages contributes to CD4+ T cell costimulation.
Mouse peritoneal macrophages consist of two subsets: large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), defined as CD11bhiF4/80hi and CD11b+F4/80lo cells, respectively. We reveal that SPMs, but not LPMs, have the ability to present antigens to naïve CD4+ T cells. Coculture of SPMs with naïve ovalbumin (OVA) specific CD4+ T cells (OT-II) in the presence of OVA peptide effectively induced CD4+ T cells priming. SPMs, but not LPMs, strongly express DNAM-1, an activating immunoreceptor. Although antigen uptake and processing were comparable between WT and DNAM-1-deficient SPMs, deficiency of DNAM-1 on SPMs or blockade of DNAM-1 and its ligand interaction impaired CD4+ T cells priming by SPMs. Furthermore, T and B cell responses in mediastinal lymph nodes of mice intraperitoneally immunized with trinitrophenyl (TNP)-OVA protein in Alum adjuvant were enhanced by intraperitoneally transferred wild-type, but not DNAM-1-deficient, SPMs. We propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays a costimulatory role in antigen presentation by SPMs.


A videotape to improve parental knowledge of lead poisoning.
Disadvantaged children are at high risk for lead poisoning. Their parents often have poor knowledge of lead poisoning and do not know how to prevent lead poisoning in their child. To assess an educational videotape's impact on parental knowledge and behavior about lead poisoning. Prospective study by self-administered parental survey immediately before (pretest) and after (posttest 1) well visits and mailed 2-4 weeks later (posttest 2). The intervention group watched the videotape immediately after the pretest. Pediatric clinic in tertiary care hospital. Consecutive sample of parents of 6-month-old to 6-year-old children (n = 146). Survey included demographic questions, the shortened Chicago Lead Knowledge Test (sCLKT), and questions about parental behaviors. Mean pretest scores were 5.8 (SD, 2.8) and 5.3 (SD, 2.2), posttest 1 scores were 6.0 (SD, 2.6) and 10.6 (SD, 2.1), and posttest 2 scores were 6.1 (SD, 2.8) and 9.5 (SD, 2.8) of 14 in the control and intervention groups, respectively. Control and intervention group posttest 1 and posttest 2 score differences were statistically significant (P <.05). Intervention group parents reported more frequent washing of their child's hands (P <.05) and windows, walls, or floors at study completion (P <.05). The videotape significantly increased sCLKT scores and behaviors that may decrease children's risk of developing lead poisoning. Improvement persisted throughout the study period.


[Therapeutic considerations in maxillofacial neuralgia].
In the presence of idiopathic and neuralgiform pain in the trigeminal area, differential diagnosis will have to eliminate sinus disturbances, toothache, TMJ trouble and neuromuscular spasms derived thereof. Neuralgias unconnected to these causes are treated by electrobiological testing of the neurotoxins. Symptomatic immediate treatment was formerly done by enneural injection. Now, a special technique of auriculoacupuncture has been successful for some time.


Early hospital experience with fluphenazine decanoate.
Naturalistic data are reported concerning the first year of hospital use of fluphenazine decanoate. Observations revealed that staff psychiatrists were cautious in their initial use of this product, consistently reserving it for those patients who were very uncooperative about taking oral medications. Outcome of treatment was regarded as satisfactory in only 38% of the patients and a number of unusually severe and prolonged side effects were encountered. A conservative position about the use of depot medications in the treatment of schizophrenia is advocated until further studies of specific target areas for such treatment can be accomplished.


A novel triterpenoid induces transforming growth factor beta production by intraepithelial lymphocytes to prevent ileitis.
The loss of homeostasis is a hallmark of inflammatory bowel disease. Oral infection of susceptible mice with Toxoplasma gondii results in an acute lethal ileitis characterized by increased interferon gamma, tumor necrosis factor alpha, and inducible nitric oxide synthase; homeostasis results from transforming growth factor beta production by intraepithelial lymphocytes. The synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) is a potent anti-inflammatory molecule previously shown in vitro to suppress the de novo synthesis of inducible nitric oxide synthase and to induce the transcription and activation of genes from the transforming growth factor beta signaling pathway. We evaluated the immune response in the small intestine and by intraepithelial lymphocytes after a single intraperitoneal dose of CDDO at the time of T. gondii oral infection. We abrogated the homeostatic effects of CDDO by blocking transforming growth factor beta in vivo. CDDO acid prevented ileitis development through the global down-regulation of inflammatory cytokines and chemokines. Total transforming growth factor beta(1) production by the intraepithelial lymphocytes increased, as did Smad2 expression. Blocking transforming growth factor beta reversed CDDO-induced protection and prevented the up-regulation of Smad2 in the small intestine. CDDO acid is a novel anti-inflammatory molecule capable of preventing ileitis by activating the transforming growth factor beta signaling pathway in a pathogen-driven ileitis model. This could represent a new treatment of inflammatory bowel disease.


Strain tuning of the photocurrent spectrum in single-wall carbon nanotubes.
The effect of uniaxial strain on the photocurrent spectrum of semiconducting single-wall carbon nanotubes is measured. The energy of the lowest-lying free electron transition is observed to shift with strain as predicted by a simple noninteracting model. The higher-order transitions also shift with strain, but being excitonic, their strain dependence differs from the predictions for the free carrier states. An anomalous photocurrent increase is also observed near the ground-state transition and is attributed to the formation of optically active defect states within the nanotube band gap.


A review of the evidence of zolpidem efficacy in neurological disability after brain damage due to stroke, trauma and hypoxia: A justification of further clinical trials.
During 15 years, 23 clinical reports and 6 studies have demonstrated associations between sub-sedative doses of zolpidem and recoveries from brain damage due to strokes, trauma and hypoxia. Clinical findings include unexpected awakenings from vegetative states and regressions of stroke symptoms after dosing that disappear during elimination and reappear on repeat dosing. Initially single-photon emission computed tomography scans showed improved perfusion within, around and distant from infarctions. Then positron emission tomography scans and electroencephalography detected renewed metabolic and neuronal activity. Placebo or a similar, gamma-aminobutyric acid (GABA)-ergic, sedative zopiclone has no such effect. The effect appears only several months after the injury, reflecting recent evidence in mice of substantial differences between the states of GABA receptors in acute and chronic repair phases of recovery. Zolpidem's good safety record and rapid absorption further indicate a need for more clinical trials. List of acronyms: BOLD, Blood-Oxygen-Level Dependent contrast imaging in MRI; CRS, Coma Recovery Scale; CRS-R, Coma Recovery Scale Revised; CSI, Cerebral State Index; CSM, Cerebral State Monitor; DOC, Disorder of Consciousness; EEG, Electro Encephalography; FDG-PET, FluoroDeoxyGlucose-Positron Emission Tomography; FTD, Frontotemporal dementia; GABA, Gamma-Aminobutyric Acid; MCS, Minimally Conscious State; M-EEG, Magneto-Encephalography; MRI, Magnetic Resonance Image; MSN, Median Spiny Neurones; PET, Positron Emission Tomography; PVS, Persistent Vegetative Sate; RLAC, Rancho Los Amigos Cognitive scores; SPECT, Single-photon emission computed tomography; TFES, Tinetti Falls Efficacy Scale; 99mTc HMPAO, Technetium hexamethylpropyleneamine oxime.


In-vitro controlled release of doxorubicin from silica xerogels.
This study aimed at the development of a novel silica xerogel matrix as a delivery tool for an anti-cancer drug. Doxorubicin was incorporated as a hydrochloride salt during hydrolysis and polycondensation of tetraethylorthosilicate (TEOS) in the sol-gel process. The effect of sol-gel synthesis parameters (drug concentration, size of the device and lyophilizing process) on the release rate of the drug were investigated. In addition, dissolution rate, as well as weight loss of silica xerogel, was evaluated. In general, both the lyophilizing process of xerogels and the increase in size of non-lyophilizing device significantly decrease both the rate of drug release and the rate of dissolution of matrix. The overall release process was found to be governed by diffusion control and simultaneous zero-order dissolution of the xerogel.


[ZIKA FEVER: CLINICAL, EPIDEMIOLOGICAL, LABORATORY, AND DIAGNOSTIC ASPECTS].
The authors overview data on the prevalence of Zika fever with reference to biological properties of the causative agent, epidemiological process, pathogenesis, and clinical symptoms of the disease. Special attention is given to the identification of the virus in pregnant women, microcephaly in the babies born by Zika-infected women, algorithm of laboratory diagnostics, and measures needed to prevent and control mosquitoes that spread viruses.


The Montreal Imaging Stress Task: using functional imaging to investigate the effects of perceiving and processing psychosocial stress in the human brain.
We developed a protocol for inducing moderate psychologic stress in a functional imaging setting and evaluated the effects of stress on physiology and brain activation. The Montreal Imaging Stress Task (MIST), derived from the Trier Mental Challenge Test, consists of a series of computerized mental arithmetic challenges, along with social evaluative threat components that are built into the program or presented by the investigator. To allow the effects of stress and mental arithmetic to be investigated separately, the MIST has 3 test conditions (rest, control and experimental), which can be presented in either a block or an event-related design, for use with functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). In the rest condition, subjects look at a static computer screen on which no tasks are shown. In the control condition, a series of mental arithmetic tasks are displayed on the computer screen, and subjects submit their answers by means of a response interface. In the experimental condition, the difficulty and time limit of the tasks are manipulated to be just beyond the individual's mental capacity. In addition, in this condition the presentation of the mental arithmetic tasks is supplemented by a display of information on individual and average performance, as well as expected performance. Upon completion of each task, the program presents a performance evaluation to further increase the social evaluative threat of the situation. In 2 independent studies using PET and a third independent study using fMRI, with a total of 42 subjects, levels of salivary free cortisol for the whole group were significantly increased under the experimental condition, relative to the control and rest conditions. Performing mental arithmetic was linked to activation of motor and visual association cortices, as well as brain structures involved in the performance of these tasks (e.g., the angular gyrus). We propose the MIST as a tool for investigating the effects of perceiving and processing psychosocial stress in functional imaging studies.


Left ventricular outflow tract after Kawashima intraventricular rerouting.
Left ventricular outflow tract obstruction is a concern in the long term after Kawashima intraventricular rerouting for Taussig-Bing anomaly. This study assessed the late results and left ventricular outflow tract dimensions after intraventricular rerouting for Taussig-Bing anomaly in 6 children. Age at operation ranged from 8 months to 7 years. The shortest distance from the tricuspid valve to the pulmonary valve ranged from 8 to 18 mm, which was 79%-139% of the normal aortic annulus diameter. All patients survived the operation, but one died of chronic heart failure 4 months after repair. Three patients had no left ventricular outflow tract obstruction 15 to 31 years after repair, and 2 had significant obstruction at 9 and 14 years. One patient underwent successful revision of the intraventricular baffle; the distance between the tricuspid and pulmonary valves was 16 mm (108% of the normal aortic annulus) although it had been 8 mm (79%) at the initial repair. Late results of intraventricular rerouting were considered favorable.


Inhibition of bacterial quorum sensing by extracts from aquatic fungi: first report from marine endophytes.
In our search for quorum-sensing (QS) disrupting molecules, 75 fungal isolates were recovered from reef organisms (endophytes), saline lakes and mangrove rhizosphere. Their QS inhibitory activity was evaluated in Chromobacterium violaceum CVO26. Four strains of endophytic fungi stood out for their potent activity at concentrations from 500 to 50 μg mL-1. The molecular characterization, based on the internal transcribed spacer (ITS) region sequences (ITS1, 5.8S and ITS2) between the rRNA of 18S and 28S, identified these strains as belonging to four genera: Sarocladium (LAEE06), Fusarium (LAEE13), Epicoccum (LAEE14), and Khuskia (LAEE21). Interestingly, three came from coral species and two of them came from the same organism, the coral Diploria strigosa. Metabolic profiles obtained by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) suggest that a combination of fungal secondary metabolites and fatty acids could be the responsible for the observed activities. The LC-HRMS analysis also revealed the presence of potentially new secondary metabolites. This is, to the best of our knowledge, the first report of QS inhibition by marine endophytic fungi.


Reduced Systemic Corticosteroid Use among Pediatric Patients With Inflammatory Bowel Disease in a Large Learning Health System.
Corticosteroids have long been used to treat inflammatory bowel disease. However, cumulative corticosteroid exposure is associated with adverse effects, particularly in growing children. Professional guidelines recommend steroid-sparing strategies. It remains unknown whether corticosteroid use has decreased in children with inflammatory bowel disease. We performed retrospective cohort study using data from 2007 to 2018 from the international multi-center ImproveCareNow Network, a pediatric inflammatory bowel disease quality improvement collaborative. Pediatric patients diagnosed with inflammatory bowel disease were included. Patients with missing diagnosis or corticosteroid use data were excluded. We performed serial cross-sectional analyses of period prevalence and used multivariate regression models. 27,321 patients were included (65% Crohn disease, 28% ulcerative colitis, 7% indeterminate colitis). Corticosteroids were used in 10,206 (37%). Corticosteroid use decreased from 28% (2007) to 12% (2018). Black patients received corticosteroids more commonly than white patients. This disparity improved as corticosteroid use decreased in both groups. Most corticosteroid use occurred <120 days after diagnosis. Corticosteroid or 5-aminosalicylate use <120 days after diagnosis predicted later corticosteroid use. Anti-tumor necrosis factor-alpha medication use <120 days after diagnosis was associated with a reduction in corticosteroid use. As corticosteroid use decreased, steroid-sparing therapy use increased and height and weight z scores improved, particularly among children with Crohn disease. Despite improvement across the network, variation in corticosteroid usage remains. Corticosteroid use among pediatric patients with inflammatory bowel disease in the ImproveCareNow Network has decreased over time. Racial disparities in corticosteroid use were found, but gradually improved.


Colloidal charge reversal: Dependence on the ionic size and the electrolyte concentration.
Extensive Monte Carlo simulations and scaling arguments are used to study the colloidal charge reversal. The critical colloidal surface charge density sigma(c) at which the reversal first appears is found to depend strongly on the ionic size. We find that sigma(c) has an inflection point as a function of the electrolyte concentration. The width of the plateau region in the vicinity of the inflection point depends on the temperature and the ionic radius a. In agreement with the theoretical predictions it is found that the critical colloidal charge above which the electrophoretic mobility becomes reversed diverges as Z(c) approximately 1/a(2) in the limit a-->0.


Clinical importance of bronchoalveolar lavage fluid and blood cytokines, surfactant protein D, and Kerbs von Lungren 6 antigen in idiopathic pulmonary alveolar proteinosis.
To investigate the clinical importance of cytokines, surfactant protein D (SFTPD, formerly SP-D), and Kerbs von Lungren 6 antigen (KL-6) in bronchoalveolar lavage fluid (BALF) and blood in patients with idiopathic pulmonary alveolar proteinosis (iPAP). Patients with iPAP diagnosed by characteristic cytopathologic examination of BALF and pathologic examination of transbronchial lung biopsy specimens or open lung biopsy specimens were enrolled in the study from January 1, 1995, through June 30, 2005. To investigate the clinical importance of cytokines, SFTPD, and KL-6 in iPAP, we measured tumor necrosis factor superfamily, member 2 (TNF, formerly TNF-alpha) and interleukin (IL) 1beta in BALF and IL-6, IL-10, IL-8, chemokine (C-C motif) ligand 4 (CCL4, formerly MIP-1beta), chemokine (C-C motif) ligand 2 (CCL2, formerly MCP-1), SFTPD, and KL-6 in both BALF and blood in 15 patients with iPAP and 48 patients with interstitial lung diseases (diseased controls) (including 20 with interstitial pneumonitis associated with collagen vascular diseases, 13 with idiopathic pulmonary fibrosis, and 15 with sarcoidosis) and 20 individuals without pulmonary diseases (lung controls). Patients with iPAP had significantly higher levels of TNF, IL-6, IL-8, CCL4, CCL2, SFTPD, and KL-6 in BALF than did lung controls and had significantly higher levels of CCL4, CCL2, SFTPD, and KL-6 levels in BALF than did diseased controls. Patients with iPAP had significantly higher levels of IL-10, IL-8, CCL2, SFTPD, and KL-6 in blood than did lung controls and significantly higher levels of KL-6 in blood than did diseased controls. Levels of KL-6 both in BALF and blood were significantly correlated with serum lactate dehydrogenase level, arterial oxygen tension, and alveolar-arterial gradient in partial pressure of oxygen, the severity markers for iPAP, and were significantly higher in patients with iPAP who required subsequent therapeutic lung lavage. Patients with iPAP had elevated levels of SFTPD, KL-6, and cytokines in both BALF and blood. Elevated levels of KL-6 in both BALF and blood may be valuable in reflecting disease severity of patients with iPAP and in determining the need for therapeutic lung lavage.


Evolving Management of Acute Mastoiditis: Analysis of the Pediatric Health Information System Database.
The optimal management of acute mastoiditis remains controversial. Most existing studies are retrospective single-institutional experiences with small cohorts. Our objectives were to analyze the treatment of acute mastoiditis by pediatric centers across the United States and changes in management over time. Retrospective analysis. Administrative database study using Pediatric Health Information System. Patients ≤18 years of age who were admitted with a principal diagnosis of acute mastoiditis from January 1, 2010 to December 31, 2019 were included. Trends were assessed by Cochran-Armitage Trend Test. χ2 and Wilcoxon rank sum tests were used to compare outcomes between the surgical and nonsurgical groups. A total of 2170 patients met the inclusion criteria, with 1248 (57.5%) requiring surgical management. The rate of surgical procedures decreased significantly over time. The rate of myringotomy decreased from 64% in 2010 to 47% in 2019 (p < .001), and mastoidectomy decreased from 22% in 2010 to 10% in 2019 (p < .001). On admission, 29% of the cohort presented with mastoiditis-related complications. Patients treated surgically were younger (p < .001), more likely to present with complications (37.5% vs 17.5%, p < .001), required longer length of stay (3.7 vs 2.3 days, p < .001), and had higher intensive care unit utilization (8.6% vs 2.2%, p < .001). However, the rate of 30-day readmission, emergency department return, and in-hospital mortality were all similar. Acute mastoiditis has been successfully treated with declining rates of a surgery over time. Younger patients who present with complications are more likely to be managed surgically, and the overall outcomes remain excellent.


Facioscapulohumeral muscular dystrophy: a prospective study of weakness and functional impairment.
Only isolated prospective studies have attempted to chart the natural history of facioascapulohumeral muscular dystrophy (FSHD), a benign myopathy with notoriously variable clinical manifestations and progression. This 10-year prospective study was performed to document by simple clinical methods the natural history of 16 patients with moderately advanced FSHD. Limb strength was evaluated by the bedside manual muscle test. Global weakness was documented as a composite average muscle score (AMS). Limb function was evaluated by a non-linear grading system of important functional milestones. A scale of activities of daily living (ADL) was used to assess disability across multiple functional domains in a home environment. Six-monthly evaluations determined a linear deterioration of the mean AMS that reached statistical significance from baseline at the 5-year interval. Half of patients showed a functional decline of the arms by one grade. All patients maintained useful hand function. Three quarters of patients suffered functional decline of the legs, commonly by one grade. All patients remained ambulant. Interval analyses showed a linear deterioration of the mean ADL score that reached statistical significance from baseline at the 5-year interval. Functional deterioration was mostly due to impaired shoulder girdle activities. This study of a relatively homogeneous subgroup of FSHD patients showed a predictable rate of clinical progression in a muscle disease with a notoriously variable clinical presentation and outcome. Natural history data obtained in this study could serve as positive controls for future therapeutic trials in this patient population. The chosen clinical parameters proved useful tools for charting clinical disease progression. Functional tests proved advantageous, because decline was based partly on patient self-reports, thereby improving time and cost effectiveness.


Effect of seven fluoroquinolones on the determination of serum creatinine by the picric acid and enzymatic methods.
To investigate in vitro the interaction of seven fluoroquinolone antibiotics with the determination of serum creatinine by the picric acid and enzymatic methods. This blind, in vitro study assayed duplicate serum samples for creatinine by the picric acid and enzymatic methods with averaged spiked concentrations of 2.71, 13.56, 27.12, and 108.47 mumol/L of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, 1-ofloxacin, sparfloxacin, and temafloxacin. Cefoxitin (in concentrations of 233.9, 1169.6, 1754.4, and 2339.2 mumol/L) was used as a positive control for the picric acid assay. University-affiliated hospital, Department of Pharmaceutical Services and Clinical Chemistry section of the Department of Pathology. The serum creatinine samples spiked with the seven substituted fluoroquinolones and cefoxitin were assayed by both the picric acid and enzymatic assays. Statistical analysis compared the spiked samples with blank serum by Student's t-test and concentration ranges were compared by analysis of variance. A statistically significant interference with serum creatinine was p < 0.05. None of the substituted fluoroquinolones interfered significantly with the determination of serum creatinine by either method. Cefoxitin significantly interfered with the determination of serum creatinine by the picric acid method. Fluoroquinolones do not interfere with the determination of serum creatinine by either the picric acid or enzymatic method.


A non-starch-fermenting variant of Corynebacterium ulcerans.
Recently a non-starch-fermenting strain of C. ulcerans was isolated and a strain which did not hydrolyse urea when first isolated has also been discovered. For full identification of C. ulcerans both intradermal and subcutaneous tests in guinea-pigs are required, and it is recommended that these tests should be carried out with all organisms which culturally and morphologically resemble diphtheria bacilli.


Minor salivary gland secretion rates and immunoglobulin A in adults and the elderly.
Previously published data are conflicting about the effect of various factors on secretions from minor salivary glands. The aim of the present study was to investigate the secretion rate from palatal, buccal, and labial glands, and to analyze the immunoglobulin A (IgA) concentrations in relation to age, gender, circulatory disease, diabetes, medication, smoking, and pregnancy. Resting and stimulated whole-saliva secretion rates, as well as IgA concentration in stimulated whole saliva, were also examined. One-hundred and forty two individuals (96 women and 46 men), 18-82 yr of age, participated. The results did not suggest any effect of aging on the secretion capacity of minor salivary glands, but the IgA concentration seemed to increase with age. Women had lower buccal and labial saliva secretion rates, and lower levels of IgA in buccal saliva, than men. For whole saliva, resting, but not stimulated, saliva secretion rates were reduced with age, and the secretion rate of stimulated whole saliva was lower in women than in men. The IgA concentration in buccal saliva showed a positive correlation with IgA in stimulated whole saliva, and the IgA concentration decreased with increased flow rate in both salivas.


Arginyl-tRNA synthetase from Escherichia coli, purification by affinity chromatography, properties, and steady-state kinetics.
A Blue Sephadex G-150 affinity column adsorbs the arginyl-tRNA synthetase of Escherichia coli K12 and purifies it with high efficiency. The relatively low enzyme content was conveniently purified by DEAE-cellulose chromatography, affinity chromatography, and fast protein liquid chromatography to a preparation with high activity capable of catalyzing the esterification of about 23,000 nmol of arginine to the cognate tRNA per milligram of enzyme within 1 min, at 37 degrees C, pH 7.4. The turnover number is about 27 s-1. The purification was about 1200-fold, and the overall yield was more than 30%. The enzyme has a single polypeptide chain of about Mr 70,000 and binds arginine and tRNA with 1:1 stoichiometry. For the aminoacylation reaction, the Km values at pH 7.4, 37 degrees C, for various substrates were determined: 12 microM, 0.9 mM, and 2.5 microM for arginine, ATP, and tRNA, respectively. The Km value for cognate tRNA is higher than those of most of the aminoacyl-tRNA synthetase systems so far reported. The ATP-PPi exchange reaction proceeds only in the presence of arginine-specific tRNA. The Km values of the exchange at pH 7.2, 37 degrees C, are 0.11 mM, 2.9 mM, and 0.5 mM for arginine, ATP, and PPi, respectively, with a turnover number of 40 s-1. The pH dependence shows that the reaction is favored toward slightly acidic conditions where the aminoacylation is relatively depressed.


Outcomes and complications of hydrogel scleral explant removal.
To report symptoms of extrusion of hydrogel explants after retinal detachment (RD) repair and the outcomes and complications following removal. All 23 patients had previous RD repair by episcleral buckle with hydrogel explant. Signs and symptoms of scleral buckle (SB) extrusion were analyzed. Main outcomes measured were redetachment of the retina, persistent diplopia, and decreased postoperative visual acuity (VA). Mean time between RD repair and removal of extruded SB was 16.2 years (range: 11 to 21 years). Fifteen patients (65%) received encircling SB and 8 had segmental SB. SB was combined with vitrectomy in 12 patients and 3 received silicone oil. Common complaints included limited ocular motility, presence of a palpable mass under the eyelid, pain and discomfort, diplopia, visible SB under eroded conjunctiva, complete immobility, and signs of infection. Two eyes were phthisical. No scleral perforations occurred during removal of explants. After SB removal, RD recurred in 2 patients and diplopia persisted in 4. VA was not affected by SB removal. Deterioration may occur after implantation for 10 years or longer. This is due to microstructural change of the hydrogel material. The most common problems are motility disturbance and presence of a tumor-like, palpable mass under the eyelid. Removal of the implant can alleviate some ocular problems. However, RD can recur and diplopia may persist after removal of the SB. Vision usually is not affected.


Difficulty in inserting left double-lumen endobronchial tubes at the cricoid level in small-statured women: A retrospective study.
Left double-lumen endobronchial tube (DLT) sizes are selected using tracheal diameters and left mainstem bronchial diameters (LMBDs) determined from chest radiographs or computed tomography (CT) scans. In Western women, 35-Fr or 37-Fr DLTs are often selected. However, difficulties can be encountered when inserting 32-Fr or 35-Fr DLTs in Japanese women. We investigated success rates for 32-Fr or 35-Fr DLT insertion in Japanese women and determined the causes of unsuccessful DLT insertion. We searched anaesthesia records of Japanese women aged ≥20 years who underwent thoracic surgery with 32-Fr or 35-Fr DLTs between April 2010 and March 2015 in our hospital. In the successful group (SG), patients were intubated using the initially selected DLTs. By contrast, in the unsuccessful group (UG), the DLT size had to be changed. The Mann-Whitney U-test and Fisher's exact test were used to compare groups. The SG included 149 (96.1%) of 155 cases of 32-Fr DLT use and 119 (95.2%) of 125 cases of 35-Fr DLT use. Patient height was significantly lower in the UG than in the SG for the 35-Fr DLT (P = 0.0036). In seven of 12 UG patients (three for 32-Fr and four for 35-Fr), the transverse diameters of cricoid cartilages were smaller than the DLTs' tracheal diameters, thereby preventing passage through the cricoid cartilages. Along with LMBDs, transverse diameters of cricoid cartilages based on CT scans or ultrasonogram findings may help in selecting the appropriate left DLT size.


Polyphenols as NLRP3 inflammasome modulators in cardiometabolic diseases: a review of in vivo studies.
The nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs) are components of the innate immune system, important in coordinating the inflammatory response. Among them, NLRP3 can form inflammasomes, multiprotein complexes activating the inflammatory caspase-1 and leading, through a cell death-mediated signaling cascade, to the release of several proinflammatory cytokines. Dietary polyphenols, plant secondary metabolites, have been reported to exhibit anti-inflammatory properties, although studies have focused most on their effect on the expression of the final circulating cytokines rather than on the upstream signals activating the NLRP3 inflammasome. The present review explores current knowledge on the potential of dietary polyphenols to regulate the whole NLRP3 inflammasome pathway, in the context of cardiometabolic pathologies (obesity, cardiovascular diseases, type 2 diabetes and non-alcoholic fatty liver disease), based on in vivo studies. A clear tendency towards a decrease in the expression of the whole NLRP3 inflammasome signaling pathway when several animal models were supplemented with polyphenols was observed, commonly showing a dose-response effect; these modifications were concomitant with clinical improvements in the pathologies. Nevertheless, the diversity of doses used, the disparity in polyphenol structures tested and, particularly, the scarce clinical trials and exploration of mechanisms of action show the need to develop further research on the topic.


Photooxidation of pterin in aqueous solutions: biological and biomedical implications.
Studies of the photochemical reactivity of pterin (= 2-aminopteridin-4(3H)-one; PT) in acidic (pH 5.0-6.0) and alkaline (pH 10.2-10.8) aqueous solutions have been performed. The photochemical reactions were followed by UV/VIS spectrophotometry, thin layer chromatography (TLC), high-performance liquid chromatography (HPLC), and an enzymatic method for H2O2 determination. PT is not light-sensitive in the absence of molecular oxygen, but it undergoes photooxidation in the presence of O2, yielding several nonpteridinic products. The quantum yields for PT disappearance were found to be 8.2 (+/-0.6) x 10(-4) and 1.2 (+/-0.2) x 10(-3) in acidic and alkaline media, respectively. H2O2 was detected and quantified in irradiated solutions of PT; and its importance from a biomedical point of view is discussed. The rate constant of the chemical reaction between singlet oxygen ((1)O2) and PT was determined to be 2.5 (+/-0.2) x 10(5) l mol(-1) s(-1) in alkaline medium, and the role of (1)O2 in the photooxidation of pterin was evaluated.