Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.
Sulfur mustard (HD) is a vesicating and alkylating agent widely used on the battlefield during World War I and more recently in the Iran-Iraq War. It targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function; early acute effects lead to long-term consequences. However, it is the effects on the lungs that drive morbidity and eventual mortality. The temporal postexposure response to HD within lung tissue raises the question of whether toxicity is driven by the alkylating properties of HD on critical homeostatic pathways. We have established an anesthetized swine model of inhaled HD vapor exposure to investigate the toxic effects of HD 12 h postexposure. Large white female swine were anesthetized and instrumented prior to exposure to air, 60 (sublethal) or 100 μg·kg-1 (∼LD40) doses of HD (10 min). Physiological parameters were continuously assessed. Data indicate that exposure to 100 μg·kg-1 HD lowered arterial blood oxygenation and increased shunt fraction and lavage protein compared with those of air-exposed controls and the 60 μg·kg-1 dose of HD. Histopathology showed an increased total pathology score between the 100 μg·kg-1 HD group and air-exposed controls. Principal component analysis of differentially expressed genes demonstrated a distinct and separable response of inhaled HD between air-exposed controls and the 60 and 100 μg·kg-1 doses of HD. Canonical pathway analysis demonstrated changes in acute phase response signaling, aryl hydrocarbon receptor signaling, NRF-2 mediated oxidative stress, and zymosterol biosynthesis in the 60 and 100 μg·kg-1 HD dose group. Transcriptional changes also indicated alterations in immune response, cancer, and cell signaling and metabolism canonical pathways. The 100 μg·kg-1 dose group also showed significant changes in cholesterol biosynthesis. Taken together, exposure to inhaled HD had a significant effect on physiological responses coinciding with acute changes in gene expression and lung histopathology. In addition, transcriptomics support the observed beneficial effects of N-acetyl-l-cysteine for treatment of acute inhalation HD exposure.


[Photoaggravated contact allergy and contact photoallergy caused by ketoprofen: 19 cases].
Between September 1994 and September 1999, we observed 19 cases of photoaggraved contact allergy or contact photoallergy to ketoprofen (non steroidal anti-inflammatory derived from arylpropionic acid). We present a clinical and photobiological retrospective study of these 19 cases with investigation of cross-reactivity between benzophenone-containing molecules. On clinical level, we investigated the type of eruption, the delay of appearance, the initial area of eruption and areas of diffusion. Phototesting included patchtests and photopatchtests performed with the gel containing ketoprofen (17 patients), ketoprofen 2 p. 100 petrolatum (14 patients), fenofibrate 10 p. 100 petrolatum and 10 p. 100 water (15 patients), 3 benzophenones (19 patients): oxybenzone 10 p. 100 petrolatum, mexenone 2 p. 100 petrolatum, sulisobenzone 10 p. 100 petrolatum and the other arylpropionic derivatives (4 patients). Three identical series were applied: one was irradiated with 3/4 polychromatic minimal erythematosus dose, a second was irradiated with UVA 13 J/cm2 until January 1997, then 5 J/cm2, the third series was not irradiated (control series). Patients were 9 men and 10 women with an average age of 41.2 years. The type of eruption was an eczema. The delay of appearance of the eruption was one day to 3 months. For 10 patients, the delay was between 4 and 18 days. The eruption was localized to the application area in 1 case, to the application area then to the same contralateral area in 3 cases, to the application area then to all photoexposed areas in 13 cases, to the application area then to the photoexposed areas and then to non-sun-exposed areas in 2 cases. Evolution showed prolonged photosensitivity in 3 cases after withdrawal of the contact and the contact photoallergy to ketoprofen was severe. Gel-containing ketoprofen photopatchtests showed 9 photoaggravated contact allergy, 6 contact photoallergy and 2 contact allergy. Ketoprofen photopatchtests showed 12 contact photoallergy and 2 photoaggraved contact allergy. Tiaprofenic acid photopatchtests were positive in all performed cases (4/4), but photopatchtests with the other arylpropionic derivatives, without benzophenone structure, were negative. Fenofibrate photopatchtests were always positive (15/15). Benzophenones photopatchtests only showed 4 cases of contact photoallergy to oxybenzone (4/19). In 68 p. 100 of cases, patients presented a contact allergy or photoallergy to fragrances. This study shows the actual frequency of contact allergy and contact photoallergy to ketoprofen with a higher frequency of contact photoallergy. Thus, photopatchtesting is essential. In cases of contact photoallergy to ketoprofen, ketoprofen, tiaprofenic acid but not the other arylpropionic derivatives, fenofibrate and benzophenones have to be withdrawn.


[Nursing classification systems and their application in care: an integrative literature review].
This study sought for scientific evidences on the use of nursing classification systems in care through an integrative literature review. The following databases were used LILACS and PubMed. The keywords used were classification, nursing, standardized language, system. Thirty-eight articles were selected. Five major classification systems, implemented in the services, were found: nursing diagnosis (North American Nursing Diagnosis Association International), nursing interventions (Nursing Interventions Classification), nursing outcomes (Nursing Outcomes Classification), the International Classificationfor Nursing Practice and the International Classificationfor NursingPractice in Colletive Health. The articles covered aspects related to implementation, assessment continuing education and validation of terms related to classification systems. The use of nursing classification systems provides benefits for care, improving it, the quality of information and service organization.


Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma.
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of hepatocellular carcinoma (HCC) in the United States. Prior data suggest that NAFLD-HCC patients are less likely to receive liver transplantation (LT) and have worse overall survival; however, the reason for this discrepancy is unknown. We conducted a retrospective study of 631 HCC patients listed for LT at a large academic center from 2004 to 2013. Waitlist dropout and LT were analyzed using competing risk regression. Compared with other-HCC patients (n = 589), NAFLD-HCC patients (n = 42, 6.7%) were older (65 versus 58, P < 0.001) with more women (50.0 versus 23.6%, P < 0.001), Hispanic ethnicity (40.5 versus 17.7%, P = 0.001), obesity (69.0 versus 29.9%, P < 0.001), diabetes mellitus (59.5 versus 27.8%, P < 0.01), insulin-dependence (23.8 versus 10.2%, P = 0.007), hyperlipidemia (40.5 versus 10.5, P < 0.001), and statin use (33.3 versus 5.3%, P < 0.001). Cumulative incidence of waitlist dropout at 2 y was 17.4% (95% confidence intervals, 7.7-30.4) for NAFLD HCC and 25.4% (95% confidence intervals, 21.9-29.0) for other HCC (P = 0.28). No difference in waitlist dropout or receipt of LT between NAFLD HCC and other HCC was found on regression analysis. Similarly, NAFLD and obesity, obesity alone, diabetes mellitus, insulin-dependence, hyperlipidemia, and statin use were not associated with waitlist outcomes. Finally, we observed no statistically significant difference in 5-y survival from HCC diagnosis between NAFLD HCC and other HCC (78.5% versus 66.9%, P = 0.9). In our single-center cohort, we observed no difference in waitlist outcomes or survival in NAFLD HCC, although conclusions are limited by the small number of NAFLD-HCC patients. Notably, the inclusion of patients with obesity in the NAFLD-HCC group and stratification by individual metabolic factors also showed no difference in waitlist outcomes.


Improvement of lipoatrophy by switching from efavirenz to lopinavir/ritonavir.
To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors (NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy. Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz (EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir (LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed. Thirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm. Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance.


Novel Genetic Rearrangements Termed "Structural Variation Polymorphisms" Contribute to the Genetic Diversity of Orthohepadnaviruses.
The genetic diversity of orthohepadnaviruses is not yet fully understood. This study was conducted to investigate the role of structural variations (SVs) in their diversity. Genetic sequences of orthohepadnaviruses were retrieved from databases. The positions of sequence gaps were investigated, since they were found to be related to SVs, and they were further used to search for SVs. Then, a combination of pair-wise and multiple alignment analyses was performed to analyze the genomic structure. Unique patterns of SVs were observed; genetic sequences at certain genomic positions could be separated into multiple patterns, such as no SV, SV pattern 1, SV pattern 2, and SV pattern 3, which were observed as polymorphic changes. We provisionally referred to these genetic changes as SV polymorphisms. Our data showed that higher frequency of sequence gaps and lower genetic identity were observed in the pre-S1-S2 region of various types of HBVs. Detailed examination of the genetic structure in the pre-S region by a combination of pair-wise and multiple alignment analyses showed that the genetic diversity of orthohepadnaviruses in the pre-S1 region could have been also induced by SV polymorphisms. Our data showed that novel genetic rearrangements provisionally termed SV polymorphisms were observed in various orthohepadnaviruses.


Congenital cystic adenomatoid malformation of the lung. Analysis of 10 cases and a review of literature.
A series of 10 cases of congenital cystic disease of the lung in the form of various types of cystic adenomatoid malformations has been analyzed retrospectively. The cases were obtained from our own biopsy and autopsy files, and autopsy material consulted in our institution between 1989 and 1998.


Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure.
High lipoprotein(a) (Lp(a)) serum concentrations and the underlying apolipoprotein(a) (apo(a)) phenotypes are risk factors for cardiovascular disease in the general population as well as in patients with renal disease. Lp(a) concentrations are markedly elevated in patients with end-stage renal disease. However, nothing is known about the changes of Lp(a) depending on apo(a) size polymorphism in the earliest stages of renal impairment. In this study, GFR was measured by iohexol technique in 227 non-nephrotic patients with different degrees of renal impairment and was then correlated with Lp(a) serum concentrations stratified according to low (LMW) and high (HMW) molecular weight apo(a) phenotypes. Lp(a) increased significantly with decreasing GFR. Such an increase was dependent on apo(a) phenotype. Only renal patients with HMW apo(a) phenotypes expressed higher median Lp(a) concentrations, i.e., 6.2 mg/dl at GFR >90 ml/min per 1.73 m2, 14.2 at GFR 45 to 90 ml/min per 1.73 m2, and 18.0 mg/dl at GFR <45 ml/min per 1.73 m2. These values were markedly different when compared with apo(a) phenotype-matched control subjects who had a median level of 4.4 mg/dl (ANOVA, linear relationship, P < 0.001). In contrast, no significant differences were observed at different stages of renal function in patients with LMW apo(a) phenotypes when compared with phenotype-matched control subjects. The elevation of Lp(a) was independent of the type of primary renal disease and was not related to the concentration of C-reactive protein. Multiple linear regression analysis found that the apo(a) phenotype and GFR were significantly associated with Lp(a) levels. Non-nephrotic-range proteinuria modified the association between GFR and Lp(a) levels. In summary, an increase of Lp(a) concentrations, compared with apo(a) phenotype-matched control subjects, is seen in non-nephrotic patients with primary renal disease even in the earliest stage when GFR is not yet subnormal. This change is found only in subjects with HMW apo(a) phenotypes, however.


Prevention: conditioning and orthotics.
The hand and wrist of both athletes and musicians are very susceptible to injuries. Proper conditioning of the muscles, tendons, ligaments, and joints of the hand and wrist are crucial for injury prevention. Often, orthotic devices, from simple taping to polyethylene casts, can provide adequate protection and support to allow injuries to heal properly or prevent injuries from recurring in susceptible tissues.


A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells.
We systematically compared cytokine-mediated increases or decreases in proliferation with globin gene and protein expression in adult human erythroblasts. Despite their opposite effects on growth, stem cell factor (SCF) and transforming growth factor beta (TGF-B) had synergistic effects with respect to fetal hemoglobin (HbF): average HbF/HbF + adult hemoglobin (HbA) ratio in erythropoietin (EPO) = 1.4 +/- 1.0%; EPO + TGF-B = 10.8 +/- 1.9%; EPO + SCF = 19.1 +/- 6.2%; and EPO + SCF + TGF-B (EST) = 39.3 +/- 6.3%. Polymerase chain reaction (PCR) revealed significant increases in gamma-globin transcripts that were balanced by reduced beta-globin transcripts. Single-cell quantitative PCR demonstrated a complete reversal of gamma-globin gene silencing with detectable gamma-globin mRNA in more than 95% of the cells. Immunostaining with HbF antibodies also showed a pancellular distribution in EST (96.2 +/- 0.01% HbF positive) compared with a heterocellular distribution in EPO (42.9 +/- 0.01% HbF positive). As shown here for the first time, a robust and pancellular reversal of gamma-globin gene silencing among hemoglobinized erythroblasts from adult humans may be achieved in the absence of hereditary mutation or direct genomic manipulation.


Afferent electrical stimulation of mesenteric nerves inhibits duodenal HCO3- secretion via a spinal reflex activation of the splanchnic nerves in the rat.
The experiments were performed on male Sprague-Dawley rats anaesthetized with chloralose. Duodenal HCO3- secretion was measured in situ by pH-stat titration. The nerves bundles surrounding two randomly chosen mesenteric vessels were electrically stimulated (3 Hz, supramaximal intensity) in the afferent direction. This was done in order to mimic the intestino-intestinal spinal reflex activation of the splanchnic sympathetic fibres. The procedure reduced duodenal HCO3- secretion by 20% together with an increase in mean arterial pressure and heart rate. Duodenal HCO3- secretion decreased similarly in control rats and in those subjected to a cervical cord transection, whereas animals with bilaterally cut splanchnic nerves did not respond to such mesenteric nerve stimulation. Pharmacological pretreatment with guanethidine or yohimbine, but not prazosin, inhibited the reduction in duodenal HCO3- secretion. Thus the data suggest that electrical stimulation of mesenteric afferent nerves inhibits duodenal HCO3- secretion via a spinal reflex activation of splanchnic sympathetic nerve fibres to the duodenum, and that the response is mediated via alpha 2 adrenoceptors.


Connecting temporal identity to mitosis: the regulation of Hunchback in Drosophila neuroblast lineages.
Both in vertebrates and invertebrates, neural stem cells generate different cell types at different times during development. It has been suggested that this process depends on temporal identity transitions of neural progenitors, but the underlying mechanism has not been resolved, yet. Recently, Drosophila neuroblasts (NBs) have been shown to be an excellent model system to investigate this subject. Here, changes in temporal identity are regulated by sequential and transient expression of transcription factors in the NB, such as Hunchback (Hb) and Krüppel (Kr). The temporal expression profile is maintained in the progeny. Hb is expressed first and thus defines the earliest identity in a given lineage. Transition to Kr requires the termination of hb expression, which occurs in response to mitosis, and is mediated by Seven-up (Svp). Recent results provided evidence that the dependency of Svp activity on mitosis could be due to an inhibition of the nuclear export of svp mRNA. Furthermore, the maintenance of hb expression in the GMC is regulated by the activity of Prospero (Pros), a transcription factor which asymmetrically segregates into the GMC during mitosis and inhibits Svp activity on both, the transcriptional and posttranscriptional level. These results give first insights as to how temporal cell fate specification can be correlated with mitosis.


Data collectors' field journals as tools for research.
With rising numbers of families giving care to elderly loved ones, novel methods and sources of data need to be used to obtain comprehensive information about family caregiving patterns. The purpose of this paper is to present the interviewers' reflective journals as a source of rich data. Data collectors interviewed Hispanic family caregivers as part of a quantitative study of caregiving patterns. The stories derived from the personal journals brought to life three themes: caregiving as responsibility; creativity in giving care; and resistance to delegating tasks. Well-written journals have the potential of enhancing the interpretation of data collected by other means and of raising the quality of interviews and data through introspection and cultural understanding of the caregiving reality.


Quantitative aspects of T cell activation--peptide generation and editing by MHC class I molecules.
The number of class I MHC/peptide complexes on the surface of antigen presenting cells crucially influences the activation of T cells. The formation of these complexes depends on selection processes at the level of peptide generation from proteins (predominantly in the cytosol), peptide transport into the ER and binding requirements of individual MHC class I molecules. These individual events have co-evolved to what is called 'antigen processing and presentation' and result in the representative presentation of peptides from every cellular protein by a species-specific combination of MHC class I molecules for recognition by MHC class I-restricted T cells.


Killer Cell Immunoglobulin-Like Receptor-Ligand Matching and Outcomes after Unrelated Cord Blood Transplantation in Acute Myeloid Leukemia.
The effect of killer cell immunoglobulin-like receptor (KIR)-ligand matching on outcomes after unrelated cord blood (CB) transplantation was studied in 461 patients with acute myeloid leukemia, categorizing KIR ligand for HLA-C groups C1 and C2 and Bw4. Donor-recipient HLA matching considered allele-level matching at HLA-A, -B, -C, and -DRB1. Separate analyses were conducted for 6-7/8 HLA-matched and 3-5/8 HLA-matched transplants because HLA matching confounded KIR-ligand matching (ie, KIR-ligand mismatching was less likely with better HLA matching). All patients received single CB unit and myeloablative conditioning. There were no significant differences in nonrelapse mortality (NRM), relapse, and overall mortality by KIR-ligand match status. However, among recipients of 3-5/8 HLA-matched transplants, NRM (HR, 2.26; P = .008) and overall mortality (HR, 1.78; P = .008) but not relapse were higher with KIR-ligand mismatched (host-versus-graft direction) compared with KIR-ligand matched transplants. These data do not support selecting CB units based on KIR-ligand match status for transplants mismatched at 1 or 2 HLA loci. Although transplants mismatched at 3 or more HLA loci are not recommended, avoiding KIR-ligand mismatching in this setting lowers mortality risks.


The activation-induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes but only during transcription.
The activation-induced cytidine deaminase (AID) initiates somatic hypermutation, class-switch recombination, and gene conversion of immunoglobulin genes. In vitro, AID has been shown to target single-stranded DNA, relaxed double-stranded DNA, when transcribed, or supercoiled DNA. To simulate the in vivo situation more closely, we have introduced two copies of a nucleosome positioning sequence, MP2, into a supercoiled AID target plasmid to determine where around the positioned nucleosomes (in the vicinity of an ampicillin resistance gene) cytidine deaminations occur in the absence or presence of transcription. We found that without transcription nucleosomes prevented cytidine deamination by AID. However, with transcription AID readily accessed DNA in nucleosomes on both DNA strands. The experiments also showed that AID targeting any DNA molecule was the limiting step, and they support the conclusion that once targeted to DNA, AID acts processively in naked DNA and DNA organized within transcribed nucleosomes.


Dynamic thermal environment and thermal comfort.
Research has shown that a stable thermal environment with tight temperature control cannot bring occupants more thermal comfort. Instead, such an environment will incur higher energy costs and produce greater CO2 emissions. Furthermore, this may lead to the degeneration of occupants' inherent ability to combat thermal stress, thereby weakening thermal adaptability. Measured data from many field investigations have shown that the human body has a higher acceptance to the thermal environment in free-running buildings than to that in air-conditioned buildings with similar average parameters. In naturally ventilated environments, occupants have reported superior thermal comfort votes and much greater thermal comfort temperature ranges compared to air-conditioned environments. This phenomenon is an integral part of the adaptive thermal comfort model. In addition, climate chamber experiments have proven that people prefer natural wind to mechanical wind in warm conditions; in other words, dynamic airflow can provide a superior cooling effect. However, these findings also indicate that significant questions related to thermal comfort remain unanswered. For example, what is the cause of these phenomena? How we can build a comfortable and healthy indoor environment for human beings? This article summarizes a series of research achievements in recent decades, tries to address some of these unanswered questions, and attempts to summarize certain problems for future research.


FTIR spectroscopy studies on the bioprotective effectiveness of trehalose on human hemoglobin aqueous solutions under 50 Hz electromagnetic field exposure.
The effects of extremely low frequency electromagnetic field on the protein structure of hemoglobin were investigated by means of Fourier transform infrared spectroscopy. Three samples of different hemoglobin aqueous solutions (also in the presence of sucrose and trehalose) were exposed to a 50 Hz electromagnetic field at 1 mT, and FTIR measurements were performed after 3 h of exposure. Quantitative spectral analysis revealed an evident decrease in amide A band intensity for hemoglobin in bidistilled water and sucrose aqueous solutions, but not for hemoglobin in trehalose aqueous solution. In addition a low relative increase of β-sheet in amide I region was detected for hemoglobin in both bidistilled water and sucrose aqueous solutions, whereas no appreciable changes were evidenced in the infrared spectra of hemoglobin in trehalose aqueous solutions. These results led us to conclude that a 50 Hz electromagnetic field can affect the N-H plane bending and C-N stretching vibrations of peptide linkages, suggesting compensatory mechanisms by means of environmental biochemical agents, such as evidenced by a protective effect of trehalose toward a low-frequency electromagnetic field.


Deep Convolutional Neural Networks for the Accurate Identification of High-Amplitude Stereotypic Epileptiform Seizures in the Post-Hypoxic-Ischemic EEG of Preterm Fetal Sheep.
Neonatal seizures after birth may contribute to brain injury after an hypoxic-ischemic (HI) event, impaired brain development and a later life risk for epilepsy. Despite neural immaturity, seizures can also occur in preterm infants. However, surprisingly little is known about their evolution after an HI insult or patterns of expression. An improved understanding of preterm seizures will help facilitate diagnosis and prognosis and the implementation of treatments. This requires improved detection of seizures, including electrographic seizures. We have established a stable preterm fetal sheep model of HI that results in different types of post-HI seizures. These including the expression of epileptiform transients during the latent phase (0-6 h) of cerebral energy recovery, and bursts of high amplitude stereotypic evolving seizures (HAS) during the secondary phase of cerebral energy failure (∼6-72 h). We have previously developed successful automated machine-learning strategies for accurate identification and quantification of the evolving micro-scale EEG patterns (e.g. gamma spikes and sharp waves), during the latent phase. The current paper introduces, for the first time, a real-time approach that employs a 15-layer deep convolutional neural network (CNN) classifier, directly fed with the raw EEG time-series, to identify HAS in the 1024Hz and 256Hz down-sampled data in our preterm fetuses post-HI. The classifier was trained and tested using EEG segments during ∼6 to 48 hours post-HI recordings. The classifier accurately identified HAS with 98.52% accuracy in the 1024Hz and 97.78% in the 256Hz data. Clinical relevance-Results highlight the promising ability of the proposed CNN classifier for accurate identification of HI related seizures in the neonatal preterm brain, if further applied to the current 256Hz clinical recordings, in real-world.


Fish oil stabilisation by microencapsulation with modified cellulose.
Fish oil is the richest dietary source of long-chain omega-3 polyunsaturated fatty acids (PUFA). Stabilisation of omega-3 PUFA against oxidation is an important task in food processing. The ability of modified celluloses to act as microencapsulating agents for fish oil was investigated. Fish oil microcapsules were produced by spray-drying of homogenised emulsions containing modified celluloses and maltodextrin as coating materials. The quality of microcapsules was evaluated by scanning electron microscopy, determination of encapsulation efficiency, peroxide value during storage and solubility in water. Methylocellulose (MC) and hydroxypropyl methylocellulose (HPMC) showed good emulsifying properties. Homogenisation of emulsions resulted in creation of high amount of stable foam. More damage occurred in the powders coated with HPMC. The oil retention level was very high, 98.5% (i.e. up to 400.0 g/kg ready powder). Samples with fish oil content of approximately 500.0 g/kg exhibited more structural damage impairing the stabilisation effect. This study indicates that the use of modified cellulose, especially MC, as a coating material for the preparation of spray-dried fish oil microcapsules improves the stability and the concentration of fish oil in the powder.


[Physician-patient communication and health education].
The aim of the present study was to analyze the content in health education of the patient-physician interview. The study was observational and descriptive. The target population were the patients attending the general practices of the Social Security clinics. With permission of patients and physicians, 53 visits of two general practitioners were recorded on tape. 48 interviews were analyzed with definition of activities (asking, answering, discussing, etc.) and contents (health problems, treatment, health education, etc.). Health education was 10% of the contents, and it was associated with the physician's activity of commenting/instructing and with the patient's activity of commenting/asking.


Plasma insulin concentration increases linearly with body condition in Icelandic horses.
This study investigated the variation in plasma insulin concentration (PIC) in a group of Icelandic horses in training, considered to be healthy and examined possible relationships between PIC and gender, age, body size, body condition score and management factors such as feed allowance and subjective level of fitness. Plasma insulin concentration ranged from 0.2 to 13.9 mU/l, body condition score from 2.3 to 4.0 and concentrate allowance from 0 to 4 kg. There was a significant effect of concentrate allowance (P = 0.0007) and body condition score (P = 0.004) on PIC. For every 1 kg increase in the concentrate allowance, log-PIC increased by 0.26 mU/l. For every 1 unit increase in body condition score, log-PIC increased by 0.45 mU/l. There was no effect of hay allowance, level of fitness, transport time, body size and age on insulin concentration. Owners of Icelandic horses should be aware that increased body condition elevates PIC, and thereby potentially the risk of laminitis. However, in the group of horses studied, the concentrations were within the range considered normal.


Effect of Refined Edible Oils on Neurodegenerative Disorders.
Neurodegenerative diseases are comprise a prominent class of neurological diseases. Generally, neurodegenerative diseases cannot be cured, and the available treatments can only regulate the symptoms or delay the disease progression. Among the several factors which could clarify the possible pathogenesis of neurodegenerative diseases, next to aging as the main risk, the dietary related diseases are the most important. Vegetable oils, which are composed of triacyclglycerols as the main components and several other components in a trace amount, are the main part of our diet. This review aims to study the effect of refined or unrefined vegetable oil consumption as a preventive or aiding strategy to slow or halt the progression of neurodegenerative diseases. In the refining process, owing to the chemical materials or severe temperatures of the refining process, removal of the desirable minor components is sometimes unavoidable and thus a worrisome issue affecting physical and neurological health.


Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs.
The nuclear receptors (NRs) are an evolutionarily related family of transcription factors, which share certain common structural characteristics and regulate the expressions of various genes by recognizing different response elements. NRs play important roles in cell differentiation, proliferation, survival and apoptosis, rendering them indispensable in many physiological activities including growth and metabolism. As a result, dysfunctions of NRs are closely related to a variety of diseases, such as diabetes, obesity, infertility, inflammation, the Alzheimer's disease, cardiovascular diseases, prostate and breast cancers. Meanwhile, small-molecule drugs directly targeting NRs have been widely used in the treatment of above diseases. Here we summarize recent progress in the structural biology studies of NR family proteins. Compared with the dozens of structures of isolated DNA-binding domains (DBDs) and the striking more than a thousand of structures of isolated ligand-binding domains (LBDs) accumulated in the Protein Data Bank (PDB) over thirty years, by now there are only a small number of multi-domain NR complex structures, which reveal the integration of different NR domains capable of the allosteric signal transduction, or the detailed interactions between NR and various coregulator proteins. On the other hand, the structural information about several orphan NRs is still totally unavailable, hindering the further understanding of their functions. The fast development of new technologies in structural biology will certainly help us gain more comprehensive information of NR structures, inspiring the discovery of novel NR-targeting drugs with a new binding site beyond the classic LBD pockets and/or a new mechanism of action.


Hydatid cyst of the pancreas causing portal hypertension.
Pancreatic localization of hydatid cyst is uncommon. We report a case of a 49-year-old woman who presented with abdominal discomfort, nausea and vomiting. The diagnosis of pancreatic cyst with splenomegaly and portal hypertension was supported on ultrasound, CT-scan and endoscopic ultrasound. Surgical treatment confirmed the hydatid cyst, and included distal pancreatectomy and splenectomy. The recovery was uneventful and the patient remained symptoms free.


Test-Retest Reliability of the Coronary Heart Disease Damp Phlegm and Blood Stasis Pattern Questionnaire: Results from a Multicenter Clinical Trial.
Damp phlegm and blood stasis pattern (DPBSP) is the main pattern in coronary heart disease (CHD) patients. To quantify and standardize the diagnosis of DPBSP, questionnaires are usually administered. The CHD Damp Phlegm and Blood Stasis Pattern Questionnaire (CHD-DPBSPQ) is the standard metric for measuring CHD-DPBSP signs and symptoms in practice and clinical research. The CHD-DPBSPQ has moderate diagnostic efficiency, as evidenced by its receiver operating characteristic curves. Furthermore, and high reliability and validity have been shown in some studies but not in a multicenter clinical trial. Our purpose was to evaluate the test-retest reliability of a proprietary CHD-DPBSPQ. The CHD-DPBSPQ uses a standard procedure for measuring symptoms. The (interrater) reliability and validity of this questionnaire have been previously studied. Here, we evaluated the test interval and weighted kappa value of items of test-retest (intrarater) reliability of the CHD-DPBSPQ. The test-retest reliability was evaluated by the intraclass correlation coefficient (ICC) for the total CHD-DPBSPQ score and the phlegm domain and blood stasis domain scores. Weighted kappa statistics were calculated for the individual CHD-DPBSPQ items. Using the CHD-DPBSPQ, 79 patients with late-stage CHD who were participating in a multicenter clinical trial were assessed twice. The ICCs for the CHD-DPBSPQ score were as follows: 0.827 for the total CHD-DPBSPQ, 0.778 for the phlegm domain score, and 0.828 for the blood stasis domain score. The reliability was slightly better in patients whose test interval was ≤14 days. The weighted kappa values of individual items showed moderate consistency. The CHD-DPBSPQ was found to have excellent test-retest reliability in this sample of patients.


Cognitive and demographic determinants of dementia in depressed patients with subjective memory complaints.
Previous studies showed that late-life depression with subjective memory complaints (SMC) may be associated with an increased risk of developing dementia. However, not all such patients have cognitive decline. The aim of this longitudinal study was to identify possible clinical determinants of progressive deterioration in depressed elderly patients with SMC. Forty-one consecutive patients referred to a memory clinic because of persistent SMC were investigated and received an ICD-10 diagnosis of mild to moderate depression. Over a mean follow-up period of 15 months, 9 of them (22%) developed dementia. Statistical analysis included Mann-Whitney U and Fisher's exact tests as well as univariate and multivariate logistic regression analyses to assess the relationship between cognitive decline and clinical, demographical and neuropsychological characteristics at baseline. Age at baseline was associated with subsequent dementia, and performance on immediate verbal prose recall and a visual organization test at the initial assessment were worse in those who showed cognitive decline. In a multivariate model, age and immediate recall predicted 32.7% of the cognitive variability, with an additional 2.4% when a visual organization test was added. There was no correlation between cognitive performance and severity of depression at baseline. The study was limited by a small sample size, the nondistinction of depressive subtypes and the absence of a formal neuropsychological assessment on follow-up. Impairment of the executive component of working memory as well as limited access to visual knowledge may predict cognitive deterioration in depressed patients with subjective memory complaints.


Hierarchical Self-Assembly of Responsive Organoplatinum(II) Metallacycle-TMV Complexes with Turn-On Fluorescence.
Here we report that the rod-like tobacco mosaic virus (TMV), having a negatively charged surface, can be assembled into three-dimensional micrometer-sized bundle-like superstructures via multiple electrostatic interactions with a positively charged molecular "glue", namely, a tetraphenylethylene (TPE)-based discrete organoplatinum(II) metallacycle (TPE-Pt-MC). Due to the nanoconfinement effect in the resultant TMV/TPE-Pt-MC complexes and the aggregation-induced emission (AIE) activity of the TPE units, these hierarchical architectures result in a dramatic fluorescence enhancement that not only provides evidence for the formation of novel metal-organic biohybrid materials but also represents an alternative to turn-on fluorescence. Moreover, the dissociation of these final constructs and subsequent release of individual virus have been achieved by disrupting the TPE-Pt-MC core using tetrabutylammonium bromide (TBAB). This strategy is also compatible with other protein-based nanoparticles such as bacteriophage M13 and ferritin, proving the generality of this approach. Hence, this research will open new routes for the fabrication of functional biohybrid materials involving metal-organic complexes and anisotropically shaped bionanoparticles.


Bcl-xL expression interferes with the effects of L-glutamine supplementation on hybridoma cultures.
While feeding protocols and ectopic expression of anti-apoptotic genes have been used to improve the viability of hybridoma cell lines, the effect of the expression levels of survival genes on the behavior of hybridomas following nutrient supplementation is unknown. In this study, we compared the behavior of the Sp2/0-Ag14 hybridoma (Bcl-xL(low)) and the P3x63-Ag8.653 myeloma (Bcl-xL(high)) following culture supplementation with the amino acid L-glutamine (L-Gln). Our data revealed that L-Gln addition substantially increased Sp2/0-Ag14 cell viability and total cell density, concomitant with a decrease in the rate of cell death. This effect was not seen when other amino acids or D-glucose (D-Glc) replaced L-Gln. The improvement in the culture behavior of Sp2/0-Ag14 cells was attributed to a reduction in the rate of accumulation of apoptotic cells. On the other hand, L-Gln supplementation had only a limited effect on the growth of the P3x63-Ag8.653 cells. Interestingly, Sp2/0-Ag14 cells over-expressing Bcl-xL showed a culture behavior upon L-Gln complementation that was similar to the P3x63-Ag8.653 myeloma. These results suggest that the anti-apoptotic gene expression profile of hybridoma cells can markedly impact on the beneficial effects afforded by nutrient supplementation.


Pharmacist-led academic detailing improves statin therapy prescribing for Malaysian patients with type 2 diabetes: Quasi-experimental design.
Previous reports have highlighted the suboptimal utilization and prescription of statin therapy among patients with type 2 diabetes mellitus (T2DM) in the Malaysian clinical practice. This study aims to test the impact of a pharmacist-led academic detailing program on improving the overall statin therapy prescribing in Malaysian hospital and primary care settings. As a quasi-experimental design with a control group and pre-tests., we examined 1,598 medical records of T2DM subjects in six healthcare facilities in the state of Pahang, Malaysia. In all study sites, there was a pre and post-intervention assessment of the percentage of appropriate statin therapy prescribing that complied with the clinical guidelines with no potential safety issues. The intervention was an academic detailing program offered to the health care providers in three study sites, while the other three sites served as the control group. A comparison of the overall percentage of appropriate statin therapy prescribing before and after the academic detailing was performed in all intervention and control sites. Overall, 797 medical records were examined in the pre-intervention phase, and 801 records were evaluated in the post-intervention phase. The academic detailing program was associated with a statistically significant difference in the proportion of appropriate statin therapy prescribing between the post-intervention phase compared to the pre-intervention phase (n = 246, 61.7% versus n = 188, 47.1%), p = 0.001. Whereas, the appropriate statin therapy prescribing in the control study sites experienced a modest change from 53.8% (214/398) to 56.7% (228/402), p = 0.220. The academic detailing showed significant increases in the proportions of appropriate statin therapy prescribing in both hospital and primary care settings. The academic detailing program was found to be significantly associated with a positive impact on the overall statin therapy prescribing among patients with T2DM in Malaysian hospital and primary care settings.


Are acquired hepatocerebral degeneration and hepatic myelopathy reversible?
Acquired hepatocerebral degeneration (AHD) and hepatic myelopathy (HM) are rare complications of chronic liver disease and are usually resistant to medical therapy. The clinical and laboratory findings of 14 male and 2 female patients with AHD or HM were evaluated. The prevalence of AHD and HM was 2% inpatient case series in the last 10 years. The median age of the patients (5 Child's B and 11 Child's C) was 48.7 years (28 to 66 y), and the mean known duration of the liver disease was 75 months (24 to 194 mo). The median time of onset of neurologic findings after diagnosis of the liver disease was 14.5 months. Eight patients who had marked spastic paraparesis or tetraparesis were included in the HM group and all others had AHD group. Sixty-nine percent of the patients had a spontaneous or surgical portosystemic shunts, and the remaining dense retroperitoneal collaterals. During the follow-up period of median 29 months (4 to 72 mo), 12 patients died while waiting for liver transplantation, and these patients suffered from the several complications of chronic liver disease more than the living patients. A marked improvement was observed in 2 of the patients (1 with AHD and the other with HM) at 6 and 8 months after the liver transplantation, respectively. Our data suggest that liver transplantation had an important effect on the improvement in these patients.


Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis.
Neutrophil apoptosis represents a major mechanism involved in the resolution of acute inflammation. In contrast to the effect of hypoxia observed in many other cell types, oxygen deprivation, as we have shown, causes a profound but reversible delay in the rate of constitutive apoptosis in human neutrophils when aged in vitro. This effect was mimicked by exposing cells to 2 structurally unrelated iron-chelating agents, desferrioxamine (DFO) and hydroxypyridines (CP-94), and it appeared specific for hypoxia in that no modulation of apoptosis was observed with mitochondrial electron transport inhibitors, glucose deprivation, or heat shock. The involvement of chelatable iron in the oxygen-sensing mechanism was confirmed by the abolition of the DFO and CP-94 survival effect by Fe(2+) ions. Although hypoxia inducible factor-1alpha (HIF-1alpha) mRNA was identified in freshly isolated neutrophils, HIF-1alpha protein was only detected in neutrophils incubated under hypoxic conditions or in the presence of DFO. Moreover, studies with cyclohexamide demonstrated that the survival effect of hypoxia was fully dependent on continuing protein synthesis. These results indicate that the neutrophil has a ferroprotein oxygen-sensing mechanism identical to that for erythropoietin regulation and results in HIF-1alpha up-regulation and profound but reversible inhibition of neutrophil apoptosis. This finding may have important implications for the resolution of granulocytic inflammation at sites of low-oxygen tension.


A new method for high-bandwidth servo control of the power ratio between two Raman beams for cold atom interferometer.
Light shift produced by the AC Stark effect is one of the major factors limiting the accuracy and long-term stability of a cold atom interferometer. The first order light shift can be canceled by fixing the power ratio of the Raman beams at a specified value. We report here a new method to stabilize the power ratio of the two Raman lasers with ∼100 kHz locking bandwidth, suppressing the effect of the first order light shift. We first mixed the two Raman lasers (at different optical frequencies) with a reference beam and then used two Schottky diode detectors to extract the corresponding beat note signals for each beam, which are much easier to be manipulated and processed as they are in the microwave band. The stability of the power ratio is improved by three orders of magnitude from 5.84 × 10-3 to 3.51 × 10-6 at 1 s averaging time and reaches 1.59 × 10-7 at 10 000 s integrating time when the servo loop is engaged. This method can be used in other precise quantum measurement based on the stimulated Raman transition and can be applied to compact inertial sensors.


An Antioxidant Davallialactone from Phellinus baumii Enhances Sperm Penetration on In Vitro Fertilization of Pigs.
Davallialactone (DAVA) is a hispidin analogue derived from the medicinal fungus Phellinus baumii. We examined the effect of DAVA on in vitro fertilization (IVF) of pigs. Boar spermatozoa were incubated in fertilization medium with varying concentrations of DAVA, then sperm motility and reactive oxygen species (ROS) level were evaluated. Higher sperm motility was found following the addition of 0.5 or 1 µM DAVA after incubation than addition of other concentrations or controls. ROS level decreased significantly with the addition of DAVA. The rate of normal fertilization was higher in the presence of 1 µM DAVA (65.1%) than were those of other concentrations or controls (45.4~59.4%), and the highest total fertilization rate (mono- and polyspermic oocytes) was observed at 1 µM DAVA (83%). In conclusion, addition of DAVA to fertilization medium improved sperm motility, and reduced ROS level so as to potentially improve sperm-oocyte binding in IVF, suggesting the potential of a compound isolated from mushrooms in assisted reproductive technology for humans and animals.


Genome-Wide Identification and Analysis of MAPK and MAPKK Gene Families in Bread Wheat (Triticum aestivum L.).
The mitogen-activated protein kinase (MAPK) cascade is a universal signal transduction module that plays a vital role in regulating growth and development, as well as environmental stress responses in plants. Wheat is one of the most important crops worldwide. Although the MAPK kinase kinase (MAP3K) family in wheat has been investigated, the MAPK and MAPK kinase (MAP2K) gene families remain unknown at present. Here, 54 MAPK and 18 MAPKK genes were identified in wheat using recent genomic information. Phylogenetic analysis of Triticum aestivum L. MAPKs and MAPKKs (TaMAPKs and TaMAPKKs) together with homologous genes from other species classified them into four groups, and the clustering was consistent with the genomic exon/intron structures. Conserved motif analysis found that MAPK proteins contained a typical TXY phosphorylation site and MAPKK proteins contained an S/T-X5-S/T motif. RNA-seq data mapping analysis showed that MAPK and MAPKK genes in group IV had tissue-specific expression profiles, whereas each group I member showed relatively high expression in all organs. Expression patterns of TaMAPK and TaMAPKK genes under stress conditions were also investigated and stress-responsive candidates were identified. Co-expression network analysis identified 11 TaMAPK genes and 6 TaMAPKK genes involved in the interaction network pathway. Overall, this study provided useful information for evolutionary and functional surveys of MAPK and MAPKK gene families in wheat and beyond.


Understanding the X chromosome inactivation cycle in mice: a comprehensive view provided by nuclear transfer.
During mouse development, imprinted X chromosome inactivation (XCI) is observed in preimplantation embryos and is inherited to the placental lineage, whereas random XCI is initiated in the embryonic proper. Xist RNA, which triggers XCI, is expressed ectopically in cloned embryos produced by somatic cell nuclear transfer (SCNT). To understand these mechanisms, we undertook a large-scale nuclear transfer study using different donor cells throughout the life cycle. The Xist expression patterns in the reconstructed embryos suggested that the nature of imprinted XCI is the maternal Xist-repressing imprint established at the last stage of oogenesis. Contrary to the prevailing model, this maternal imprint is erased in both the embryonic and extraembryonic lineages. The lack of the Xist-repressing imprint in the postimplantation somatic cells clearly explains how the SCNT embryos undergo ectopic Xist expression. Our data provide a comprehensive view of the XCI cycle in mice, which is essential information for future investigations of XCI mechanisms.


[Acquired amegakaryocytic thrombocytopenia: three case reports and a literature review].
Acquired amegakaryocytic thrombocytopenia (AAT) is a rare disease characterized by thrombocytopenia due to selective reduction/absence of bone marrow (BM) megakaryocytes. In the BM culture isolated reduction of colony-forming units-megakaryocyte (CFU-Mk) may occur. BM aspirates and trephine biopsies were obtained from all patients and processed by routine methods. In vitro BM culture and cytogenetic analysis was performed in one patient. This article presents three patients with manifested signs of hemorrhagic syndrome due to severe thrombocytopenia caused by an absence/significant reduction of BM megakaryocytes. Existence of systemic or any other disease was excluded in all patients. BM culture of the second patient showed reduction of all hematopoietic progenitors. In the subsequent course of the disease in this patient, signs of dysplastic erythrocytic series and megakaryocytes were also noted, although there were no positive proofs of evolution into myelodysplastic syndrome. AAT is a disease of hematopoietic stem cells manifesting in a certain period as amegakaryocytic thrombocytopenia which subsequently may progress into aplastic anemia or myelodysplastic syndrome. Patients were treated with corticosteroids, lithium carbonate, androgens, vincristine, immunoglobulins, folic acid, platelet and erythrocyte transfusions along with plasma substitution. The first patient reacted positively to the therapy. In two other patients a minimal, short-term therapeutic effect was achieved, followed by improvement of hemorrhagic syndrome and an insignificant increase in platelet count. In one patient the treatment was stopped after 4 months and the other died of bleeding after 4 months. AAT is a rare disease with unpredictable course. This is a case report of three patients with AAT and different therapeutic effects.


Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation.
Low dose radiation exposure may produce a variety of biological effects that are different in quantity and quality from the effects produced by high radiation doses. Addressing questions related to environmental, occupational and public health safety in a proper and scientifically justified manner heavily relies on the ability to accurately measure the biological effects of low dose pollutants, such as ionizing radiation and chemical substances. DNA damage and repair are the most important early indicators of health risks due to their potential long term consequences, such as cancer. Here we describe a protocol to study the effect of chronic in vivo exposure to low doses of γ- and β-radiation on DNA damage and repair in mouse spleen cells. Using a commonly accepted marker of DNA double-strand breaks, phosphorylated histone H2AX called γH2AX, we demonstrate how it can be used to evaluate not only the levels of DNA damage, but also changes in the DNA repair capacity potentially produced by low dose in vivo exposures. Flow cytometry allows fast, accurate and reliable measurement of immunofluorescently labeled γH2AX in a large number of samples. DNA double-strand break repair can be evaluated by exposing extracted splenocytes to a challenging dose of 2 Gy to produce a sufficient number of DNA breaks to trigger repair and by measuring the induced (1 hr post-irradiation) and residual DNA damage (24 hrs post-irradiation). Residual DNA damage would be indicative of incomplete repair and the risk of long-term genomic instability and cancer. Combined with other assays and end-points that can easily be measured in such in vivo studies (e.g., chromosomal aberrations, micronuclei frequencies in bone marrow reticulocytes, gene expression, etc.), this approach allows an accurate and contextual evaluation of the biological effects of low level stressors.


Upper Gastrointestinal Symptoms Experienced by Users of Low-Dose Aspirin (Acetylsalicylic Acid) [75-325 mg/day] for Primary and Secondary Coronary Artery Disease Prevention: Perspectives from Patient Focus Groups.
: As upper gastrointestinal (GI) symptoms are common with the use of low-dose aspirin (low-dose acetylsalicylic acid [LDASA]; 75-325 mg/day), this exploratory qualitative study evaluated the upper GI symptom experience and attribution of symptoms among patients taking LDASA for coronary artery disease (CAD) or known CAD risk factors. : Focus groups were conducted among patients aged ≥40 years with CAD or known CAD risk factors currently taking daily LDASA. Patients were recruited from primary-care clinical sites, and all had experienced upper GI symptoms the week before inclusion (including heartburn, acid reflux, and stomach or abdominal pain). The focus group discussions were designed to explore the participants' experience with upper GI symptoms, LDASA use, potential adverse effects of treatment, and physician interactions. Content analysis and descriptive statistics were used to analyze the data. : Thirty-three men and women participated in four focus group sessions in France and in the US. All participants recognized the cardioprotective benefits of LDASA and reported a high level of compliance with therapy. Although participants regarded LDASA as a necessary and valuable treatment, many participants had concerns about LDASA use, primarily because of the bleeding risk. Many participants were aware that LDASA may cause GI symptoms. Participants experienced a range of upper GI symptoms, including heartburn, regurgitation, and nausea. Almost half of the participants believed that their GI symptoms were solely due to lifestyle issues such as stress and eating spicy food rather than being caused by medication, where others reported that they were directly related to LDASA use. The GI symptoms experienced by LDASA users were cited as troublesome, causing the participants to change eating habits, avoid stress or employ stress-reduction techniques, change physical activities, and take more medication to treat the symptoms. : Participants were well aware of the potential adverse effects of LDASA use and reported that GI symptoms had a high impact on several areas of their lives. To maintain the cardioprotective benefits of LDASA, participants used several strategies to deal with their upper GI symptoms, including changing their eating habits, avoiding stress, changing their physical activities, and taking medication.


Surgical treatment of acute fingernail injuries.
The fingernail has an important role in hand function, facilitating the pinch and increasing the sensitivity of the fingertip. Therefore, immediate and proper strategy in treating fingernail injuries is essential to avoid aesthetic and functional impairment. Nail-bed and fingertip injuries are considered in this review, including subungual hematoma, wounds, simple lacerations of the nail bed and/or matrix, stellate lacerations, avulsion of the nail bed, ungual matrix defect, nail-bed injuries associated with fractures of the distal phalanx, and associated fingertip injuries. All these injuries require careful initial evaluation and adequate treatment, which is often performed under magnification. Delayed and secondary procedures of fingernail sequelae are possible, but final results are often unpredictable.


[Influence of dipyridamole on expression of PAC-1 and CD62p in patients with malignant lymphoma].
This study was purposed to explore the expressions of platelet-activated markers PAC-1 and CD62p in peripheral blood of malignant lymphoma patients and the influence of dipyridamole on their expression. 32 lymphoma patients were divided into simple chemotherapy group (simple group) and chemotherapy plus dipyridamole group (combined group) randomly, and 15 healthy peoples were selected as control group. The dipyridamole of 100 mg/day was given to the patients in combined group. The expression levels of PAC-1, CD62p and fibrinogen (Fib) were detected by flow cytometry and magnetic bead method on day 0, 3, 7 and 14 of chemotherapy respectively. The results showed that the levels of PAC-1, CD62p and Fib in lymphoma patients were significantly higher than those in control group (p < 0.01, 0.05), moreover there was positive correlation between levels of PAC-1 and Fib (r = 0.549, p < 0.01). PAC-1 expression on day 0 and 3 of chemotherapy in simple group was higher than that on day 14 (p < 0.05, 0.01) and CD62p expression on day 3 of chemotherapy was higher than that on day 0, 7 and 14 (p < 0.05, 0.01). PAC-1 expression in combined group on day 14 of chemotherapy was lower than than on day 0 and 3 (p < 0.05, 0.01), and CD62p on day 14 was lower than that on day 3 of chemotherapy (p < 0.05); PAC-1 and CD62p expressions in combined group on day 3, 7 and 14 of chemotherapy were decreased than those in simple group, but Fib level was not changed significantly. It is concluded that the patients with malignant lymphoma usually accompany with platelet activation and hyperfibrinogenemia in peripheral blood. Applying dipyridamole routine dosage in chemotherapy can efficiently restrain platelet activation.


[Peritoneal tuberculosis in Madagascar, 55 cases at the Soavinandriana Hospital Center in Antananaviro].
This retrospective study conducted in Antananarivo for a 42 months period, from September 1991 to March 1994, allowed to record 55 peritoneal tuberculosis, all of them in malagasy patients. The sex ratio was 0,83 and the mean age 36 years old. Ascites puncture was done each time there was an effusion (44 cases). For all cases. For all cases, the diagnosis based on laparoscopy allowed an investigation of the liver and the peritoneum, and 10 peritoneum biopsies could be done. The tubercular bacillus has been isolated in 2 ascites fluids out of 8 incubations, and in 5 biopsies of peritoneal granulation out of 8. For 8 cases, another tubercular localization has been discovered: 5 pleurisis, 2 evolutive tuberculosis and 1 pericardial effusion. All the patients have been put under antitubercular treatment and have regained health. Peritoneal tuberculosis has become rare in the West but is still a frequent pathology mostly in young women, in Africa and up in Madagascar.


Inappropriate prescription of antibiotics in pediatric practice: Analysis of the prescriptions in primary care.
Misuse of antibiotics is largely responsible for the emergence of bacterial resistance. Children represent a subset of the population who frequently receive antibiotics. The objectives were to calculate the frequency of antibiotic prescriptions that do not comply with best practice recommendations in paediatrics primary care and to examine the thoughts and feelings of physicians and parents about antibiotic prescription and recommendations from the national health authorities. We included children admitted at the paediatric emergency room (PER) of the NANTES university hospital between June 2011 and October 2012 and who were under antibiotic drugs. Two independent experts evaluated the compliance with the national recommendations. Parents and general practitioner (GP) who prescribed the antibiotic before admission to PER were called to collect their thoughts and feeling about antibiotic prescription. The median age of the 88 included children was 2.8 years. The upper respiratory tract infection motivated the prescription of antibiotic in 59%. Seventy-six per cent of the prescriptions analysed were inappropriate, 72% of the antibiotics had a too broad spectrum, and one-third was not indicated. Ninety-one per cent of the interviewed parents thought that the antibiotic prescribed to their child was adequate. Among the 77 prescribing GP who were called, 33% agreed that they lacked time during consultation to explain to parents that no antibiotics were required. Antibiotic prescriptions were too often inadequate in this sample of children admitted in a French PER. Efforts have to be made with physicians and general public to optimize the antibiotic drug use.


The effect of an adhesive external nasal dilator strip on the inspiratory nasal airflow.
We studied the affect of an adhesive external nasal dilator strip (ENDS) on the inspiratory nasal airflow. A prospective study was performed. Twenty-two healthy volunteers were enrolled in the study. All volunteers analyzed the inspiratory nasal sound samples before and while wearing a commercially available ENDS. This nasal sound analysis includes the spectral analysis and average sound intensities in low frequency (Lf), medium frequency (Mf), and high frequency (Hf). In the sound analyses, an increase was found in sound intensity at Hf when the nasal strips were not worn whereas a decrease was found in sound intensity at Hf when the nasal strips were on. Changes in the nasal geometry of the anterior part of the nose by wearing nasal strips affects the pattern of nasal airflow and transforms it into a laminar pattern.


Rehabilitation, case management, and functional outcome: An insurance industry perspective.
Case management of claims by or for an insurer, whether it be a large employer that self-insures its benefits plan or an insurance company, evolved in response to employers' desire for help in controlling escalating costs. In tracking savings for the disability and health case management services it provides to claimants, Northwestern National Life has documented significant savings. Our recent study of 9747 incurred long-term disability claims from January 1987 to December 1993 revealed an average savings of $35 in disability reserves for every dollar spent on rehabilitation services. For health claims, estimated savings produced by NWNL's medical case management program have grown from about $500000 in 1987, the program's first year of operation, to $8.1 million in 1993. From an insurance industry perspective, both health care and disability case management services maintain a strong focus on positive rehabilitation outcomes as well as cost effectiveness. Case managers evaluate rehabilitation plans based on their ability to offer quality care, interdisciplinary cooperation, and promote recovery or returning to a productive work life. The health insurance case manager gets involved in cases where there are alternative service delivery options for the treatment plan. Working closely with the physician, patient, family members and other health care professionals, the case manager looks for highly effective, outcome-based rehabilitation facilities. As treatment goals to improve health and physical functioning are reached, the focus of case management shifts to returning an individual to a productive work life where possible or appropriate. The rehabilitation case manager evaluates return-to-work potential, with a primary goal of getting disabled workers back to the same job.


Functional characterisation and drug target validation of a mitotic kinesin-13 in Trypanosoma brucei.
Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have unusual biochemical properties because they do not transport cargo along microtubules but are able to depolymerise microtubules at their ends, therefore contributing to the regulation of microtubule length. In other eukaryotic genomes sequenced to date, only between one and three Kinesin-13s are present. We have used immunolocalisation, RNAi-mediated protein depletion, biochemical in vitro assays and a mouse model of infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular localisation of all five T. brucei Kinesin-13s revealed distinct distributions, indicating that the expansion of this kinesin family in kinetoplastids is accompanied by functional diversification. Only a single kinesin (TbKif13-1) has a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we experimentally confirm the depolymerising properties of this kinesin. We analyse the biological function of TbKif13-1 by RNAi-mediated protein depletion and show its central role in regulating spindle assembly during mitosis. Absence of the protein leads to abnormally long and bent mitotic spindles, causing chromosome mis-segregation and cell death. RNAi-depletion in a mouse model of infection completely prevents infection with the parasite. Given its essential role in mitosis, proliferation and survival of the parasite and the availability of a simple in vitro activity assay, TbKif13-1 has been identified as an excellent potential drug target.


Optimization of Modulation Methods for Solenoid Valves to Realize an Odor Generation System.
An artificial olfactory system coupled with an odor generation system is herein reported. The artificial olfactory system is composed of four chemical sensors consisting of quartz crystal microbalances (QCMs) coated with room temperature ionic liquids (RTILs). The sensors are interrogated by four vector network analyzers, which are used to measure the series resonant frequency and motional resistance. The odor generation system can generate eight different odors and mix them in any composition. Solenoid valves are used to switch the path and control the concentration of the different odors before blending. Two algorithms to control the solenoid valves, delta-sigma modulator, and simple pulse width modulation (PWM) are studied, optimized, and compared. Finally, the uncertainty of the odor generating system is calculated.


Method for numerically enhancing the resolution of certain types of detection systems.
We present a method for increasing the resolution of detection systems in which the desired information has been convolved with the system instrumental response function and further distorted by the presence of noise. We have written a computer program which can deconvolve the detected signal while treating the noise in a self-consistent manner, allowing to a good degree the reconstruction of the desired signal. We apply this method to reconstruct one component of the ion velocity distribution of a barium plasma. The information is in the form of Doppler-shifted resonance light which is detected and broadened by a Fabry-Perot interferometer. Results are presented and limitations to this method are discussed.


Expression profile analysis of ascorbic acid-related genes in response to temperature stress in the tea plant, Camellia sinensis (L.) O. Kuntze.
Ascorbic acid (AsA), also known as ascorbate or vitamin C, is a natural organic compound in green plants that has antioxidant properties, and is an essential nutrient for humans. The tea plant, Camellia sinensis (L.) O. Kuntze, is an important global economic crop. Here, the expression profiles of genes related to AsA biosynthesis and recycling were analyzed in tea plants in response to temperature stress. Eighteen genes involved in AsA biosynthesis and recycling pathways were identified based on the transcriptome database. The expression levels of CsPGI1 in two varieties of tea plants ('Yingshuang' and 'Huangjinya') increased, peaked at 4 h, and then decreased in response to cold stress. In 'Yingshuang', the genes involved in AsA biosynthesis pathway rapidly responded to heat stress and substantially increased their expression levels at 1 h. The expression levels of CsMDHAR, CsDHAR1, and CsDHAR2 increased sharply at 1 h in response to heat stress in 'Yingshuang'. In contrast, the expression levels of CsMDHAR, CsDHAR1, and CsDHAR2 in 'Huangjinya' gradually increased during heat treatment from 1 to 24 h. The expression trends of two DHAR isoforms differed in 'Huangjinya' during cold stress. The expression patterns of AsA-related genes differed in the different tea plant varieties and depended on temperature. The genes involved in AsA biosynthesis and recycling pathways were induced by heat and cold stress. Our study provides useful data with which to improve the resistance of tea plants to cold and heat stress.


Manganese Supplementation in Deer under Balanced Diet Increases Impact Energy and Contents in Minerals of Antler Bone Tissue.
Bone ash, collagen, Ca and P composition, are considered the main factors affecting mechanical properties in bones. However, a series of studies in bone and antler have shown that some trace minerals, such as manganese, may play a role whose importance exceeds what may be expected considering their low content. A previous study showed that a reduction in manganese in antlers during a year of late winter frosts led to generalized antler breakage in Spain, which included a reduction of 30% of cortical thickness, 27% reduction in impact energy, and 10% reduction in work to peak force. Starting for this observation, we experimentally studied the effects of manganese supplementation in adults and yearling (yearlings) red deer under a balanced diet. Subjects were 29 deer of different age classes (adult n = 19, yearlings n = 10) that were divided in a manganese injected group (n = 14) and a control group (n = 15). Antler content in ashes and minerals, intrinsic mechanical properties and cross section structure were examined at 4 points along the antler beam. A one way ANOVA (mean per antler) showed that in yearlings, manganese supplementation only increased its content and that of Fe. However, in adults, Mn supplementation increased the mean content per antler of Ca, Na, P, B, Co, Cu, K, Mn, Ni, Se (while Si content was reduced), and impact work but not Young's modulus of elasticity, bending strength or work to peak force. A GLM series on characteristics in the uppermost part examined in the antler, often showing physiological exhaustion and depletion of body stores, showed also a 16% increase in work to peak force in the antlers of the treated group. Thus, manganese supplementation altered mineral composition of antler and improved structure and some mechanical properties despite animals having a balanced diet.


The foundation for future health care.
In the March-April issue of Physician Executive, Thomas Ainsworth, MD, provided his view of the current status of health promotion within the health care delivery system. The potential, he wrote, is far greater than the realization to date, and physicians can have a significant role in the development of health promotion programs. In this article, the theory is posited that the prime factor in the failure of health promotion to achieve a more significant position in the health care field is inertia. The forces for the status quo have simply been too great to be overcome. However, consumers, providers, and payers are almost certain to be involved in a health promotion strategy that will revolutionize the health care industry.


Photophysics of fluorinated benzene. II. Quantum dynamics.
Nuclear dynamics in the coupled electronic states of mono-, di-(ortho and meta), and pentafluorobenzene molecules is investigated here. Attempts are specifically made to understand the complexity and broadening of the recorded gas phase electronic absorption spectra of these molecules. Justification is also provided for the low quantum yield of fluorescence emission with increasing number of fluorine substitutions. The nuclear dynamics is simulated from first principles both by time-independent and time-dependent quantum mechanical methods. Potential energy surfaces of the low-lying excited electronic states of these molecules constructed in Paper I [Mondal and Mahapatra, J. Chem. Phys. 133, 084304 (2010)] are employed for the purpose. Theoretical results presented in this paper are compared with the available experimental data and the agreement between the two is found to be excellent. While structured electronic absorption bands are observed for the S(1) state of mono- and difluorobenzene molecules, the same for the pentafluorobenzene is broad and structureless. Occurrence of S(1)-S(2) conical intersections in pentafluorobenzene leads to a nonradiative internal conversion of the S(1) state in approximately 165 fs and contributes to the broadening of the S(1)<--S(0) absorption band and a biexponential decay of its fluorescence emission.


Influence of chemical aging on physico-chemical properties of mineral dust particles: A case study of 2016 dust storms over Delhi.
The physico-chemical properties of dust particles collected During Dust Storm (DDS) and After Dust Storm (ADS) events were studied using Scanning Electron Microscope coupled with Energy Dispersive X-ray Spectroscopy (SEM-EDS), X-ray Fluorescence Spectroscopy (XRF) and X-ray Photoelectron Spectroscopy (XPS). Morphological and compositional change in dust particles were observed as they react with the anthropogenic pollutants present in the urban environment. The calcite rich particles were observed to transform into calcium chloride, calcium nitrate, and calcium sulfate on reacting with the chlorides, nitrates, and sulfates present in the urban atmosphere. The frequency distributions of Aspect Ratio (AR) for the DDS and ADS particles were observed to be bimodal (mode peaks at 1.2 and 1.5) and monomodal (mode peak at 1.1), respectively. The highly irregular shaped solid dust particles were observed to transform into nearly spherical semisolid particles in the urban environment. XPS analysis confirms the high concentration of oxides, nitrates, and chlorides at the surface of ADS samples which show the signatures of mineral dust particles aging. Species with a high value of imaginary part of refractive index (like Cr metal, Fe metal, Cr2O3, FeO, Fe2O3) were observed at the surface of dust particles. At 550 nm wavelength, the light-absorbing potential of the observed species along with black carbon (BC) was found to vary in the order; Cr metal > Fe metal > Cr2O3> FeO > BC > Fe2O3> FeOOH. The presence of the aforementioned species on the surface of ADS particles will tremendously affect the particle optical and radiative properties compared to that of DDS particles. The present work could reduce the uncertainty in the radiation budget estimations of mineral dust and assessment of their climatic impacts over Delhi.


Protein kinase C-independent effects of protein kinase D3 in glucose transport in L6 myotubes.
Protein kinase C (PKC) and protein kinase D (PKD) coordinate and regulate many fundamental cellular processes. In this study, we evaluate the role of classic and novel PKC (c/nPKC) and PKD in glucose transport in L6 myotubes. c/nPKC is either activated by short-term phorbol 12-myristate 13-acetate (PMA) treatment or down-regulated by prolonged PMA treatment at a high dose in L6 myotubes. Our results indicate that PMA treatments have little impact on basal and insulin-stimulated glucose uptake and insulin-induced Akt activation. In contrast, the PKC inhibitors Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo[3,4-c] carbazole], Go6983 [2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide], GF 109203X [bisindolylmaleimide I; 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(1H-indol-3-yl)maleimide], and Ro 31-8220 [bisindolylmaleimide IX; 2-{1-[3-(amidinothio)propyl]-1H-indol3-yl}-3-(1-methylindol-3-yl)maleimide] block basal and insulin-stimulated glucose uptake, and their inhibitory effects persist upon down-regulation of c/nPKC by PMA, implying the presence of PKC-independent effectors in mediating their inhibition of glucose uptake. Go6976, the potent cPKC inhibitor that also effectively inhibits PKD, dose-dependently blocks basal glucose uptake in L6 myotubes, whereas Go6983, the nonselective PKC inhibitor that is ineffective for PKD, has little effect on basal glucose uptake, implying the involvement of PKD in this process. Most prominently, adenoviral gene expression of a dominant-negative PKD isoform, PKD3, primarily inhibits basal glucose uptake and, to a lesser extent, insulin-stimulated glucose uptake, whereas overexpression of wild-type PKD3 significantly enhances basal glucose uptake. Moreover, expression of a PKD3-targeted siRNA significantly inhibits basal glucose uptake. Taken together, our results indicate that PKD, specifically PKD3, directly contributes to insulin-independent basal glucose uptake in L6 skeletal muscle cells.


Prediction of diabetic vascular complications by nerve conduction data.
We performed nerve conduction studies in order to study the ability of nerve conduction data to discriminate between patients with and without a given vascular complication (peripheral vascular disease, coronary disease and retinopathy). All data were processed by discriminant analysis. The nerve conduction studies could discriminate between patients with and without retinopathy, but could not discriminate between those with peripheral vascular disease and those with coronary disease. Our work supports the hypothesis that there is a common pathogenesis of nerve conduction and retinal changes.


The Promise of Big Data and Digital Solutions in Building a Cardiovascular Learning System: Opportunities and Barriers.
The learning health system is a conceptual model for continuous learning and knowledge generation rooted in the daily practice of medicine. While companies such as Google and Amazon use dynamic learning systems that learn iteratively through every customer interaction, this efficiency has not materialized on a comparable scale in health systems. An ideal learning health system would learn from every patient interaction to benefit the care for the next patient. Notable advances include the greater use of data generated in the course of clinical care, Common Data Models, and advanced analytics. However, many remaining barriers limit the most effective use of large and growing health care data assets. In this review, we explore the accomplishments, opportunities, and barriers to realizing the learning health system.


Glyceraldehyde-3-phosphate dehydrogenase is a surface-associated, fibronectin-binding protein of Trichomonas vaginalis.
Trichomonas vaginalis colonizes the urogenital tract of humans and causes trichomonosis, the most prevalent nonviral sexually transmitted disease. We have shown an association of T. vaginalis with basement membrane extracellular matrix components, a property which we hypothesize is important for colonization and persistence. In this study, we identify a fibronectin (FN)-binding protein of T. vaginalis. A monoclonal antibody (MAb) from a library of hybridomas that inhibited the binding of T. vaginalis organisms to immobilized FN was identified. The MAb (called ws1) recognized a 39-kDa protein and was used to screen a cDNA expression library of T. vaginalis. A 1,086-bp reactive cDNA clone that encoded a protein of 362 amino acids with identity to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was obtained. The gapdh gene was cloned, and recombinant GAPDH (rGAPDH) was expressed in Escherichia coli cells. Natural GAPDH and rGAPDH bound to immobilized FN and to plasminogen and collagen but not to laminin. MAb ws1 inhibited binding to FN. GAPDH was detected on the surface of trichomonads and was upregulated in synthesis and surface expression by iron. Higher levels of binding to FN were seen for organisms grown in iron-replete medium than for organisms grown in iron-depleted medium. In addition, decreased synthesis of GAPDH by antisense transfection of T. vaginalis gave lower levels of organisms bound to FN and had no adverse effect on growth kinetics. Finally, GAPDH did not associate with immortalized vaginal epithelial cells (VECs), and neither GAPDH nor MAb ws1 inhibited the adherence of trichomonads to VECs. These results indicate that GAPDH is a surface-associated protein of T. vaginalis with alternative functions.


UV reflection properties of plumage and skin of domesticated turkeys (Meleagris gallopavo f. dom.) as revealed by UV photography.
Reflection and fluorescence properties of feathered and non-feathered body regions of white- and bronze-colored fattening turkeys of various ages were examined by ultraviolet (UV) photography. The examinations were carried out on 20 white-feathered fattening turkeys (B.U.T. 6; 10 males, 10 females) and 20 bronze-feathered fattening turkeys (Grelier 708; 10 males, 10 females) over a period of 21 weeks. The turkeys were photographed once a wk under long-wave UV (UVA) radiation illumination (λ = 344-407 nm) using a digital camera. A bandpass filter was used for UV reflectography to filter out the visible components of the used light source. A longpass filter was used for UV fluorescence photography to avoid blurring in the image due to chromatic aberration as a result of UV illumination. We found that natal down feathers of white-feathered turkeys showed an intense yellowish-green fluorescence under UVA light. UVA fluorescence also was shown by the natal downs of the slightly melanized plumage areas of bronze turkeys. Vaned feathers of white fattening turkeys reflected UVA radiation. Freshly molted feathers were optically distinguishable from the previous feather generation due to their more intense UVA reflection. In bronze turkeys, both the bright end seams of the dark pennaceous feathers and rectrices and the bright banding of primary and secondary remiges reflected UVA radiation. Intense UVA fluorescence was recognizable in day-old chicks of both color variants on the scutellate scales of the legs and toes. In male turkeys of both color variants, UVA-reflecting parts were recognizable with increasing age on the featherless head region. The UVA-fluorescent and UVA-reflective characteristics of the plumage of fattening turkeys were closely related to the plumage color, the feather type, the molting state, and the age of the birds. Further research is needed regarding the UVA-reflecting properties of the turkey plumage and the effects of full-spectrum illumination, including the UVA spectrum, on the behavior and health of fattening turkeys.


Do community scorecards improve utilisation of health services in community clinics: experience from a rural area of Bangladesh.
The government of Bangladesh initiated community clinics (CC) to extend the reach of public health services and these facilities were planned to be run through community participation. However, utilisation of CC services is still very low. Evidence indicates community score card is an effective tool to increase utilisation of services from health facility through regular interface meeting between service providers and beneficiary. We investigated whether community scorecards (CSC) improve utilisation of health services provided by CCs in rural area of Bangladesh. This study was conducted from December 2017 to November 2018. Three intervention and three control CCs were selected from Chakaria, a rural sub-district of Bangladesh. CSC was introduced with the Community Groups and Community Support Groups in intervention CCs between January to October 2018. Data were collected through observation of CCs during operational hours, key informant interviews, focus group discussions, and from DHIS2. Utilisation of CC services was compared between intervention and control areas, pre and post CSC intervention. Post CSC intervention, community awareness about CC services, utilisation of clinic operational hours, and accountability of healthcare providers have increased in the intervention CCs. Utilisation of primary healthcare services including family planning services, antenatal care, postnatal care and basic health services have significantly improved in intervention CCs. CSC is an effective tool to increase the service utilization provided by CCs by ensuring community awareness and participation, and service providers' accountability. Policy makers and concerned authorities may take necessary steps to integrate community scorecard in the health system by incorporating it in CCs.


Kinetic analysis of cardiac compressions during cardiopulmonary resuscitation.
Little is known about the dynamics of cardiac compression during cardiopulmonary resuscitation (CPR). The purpose of this study was to investigate the dynamics of chest compressions by analyzing movement of the right ventricular free wall excursion during CPR. Patients older than 18 years with non-traumatic cardiac arrest who received CPR were enrolled. During CPR, transesophageal echocardiography (TEE) was performed and M-mode tracing was performed at the maximal compression area of the right ventricular free wall to measure the dynamics of cardiac compression. Twenty patients (mean age, 71 years; 14 males) were enrolled. The median compression depth of the right ventricular free wall was 34.4 (IQR 24.5-44.5) mm. The median duration of one compression-relaxation cycle was 0.59 (IQR 0.58-0.60) s, which comprised 0.23 (IQR 0.19-0.27) s of compression and 0.36 (IQR 0.32-0.39) s of relaxation. The median compression velocity was 162 (IQR 95-215) mm/s, and the median relaxation velocity was 93 (IQR 75-121) mm/s. Compression depth was linearly correlated with mean compression velocity (r = 0.882, p < 0.001). Compression velocity had a negative correlation with the ratio of compression-relaxation time (r=-0.711, p < 0.001). Maintaining high compression velocity is helpful in achieving adequate compression depth during CPR.


Challenges to Antimicrobial Stewardship in the Countries of the Arab League: Concerns of Worsening Resistance during the COVID-19 Pandemic and Proposed Solutions.
The COVID-19 pandemic is expected to worsen the global problem of antimicrobial resistance (AMR). There is a heightened interest in understanding this effect and to develop antimicrobial stewardship (AMS) interventions accordingly to curb this threat. Our paper aims to evaluate the potential magnitude of COVID-19 on AMR and AMS with a focus on the countries of the Arab league, given the social, political, and economic environments. We also evaluate obstacles in applying the rational use of antibiotics, monitoring resistance trends in the midst of the pandemic, and evaluating the impact of the economic crisis in some countries. We aim to raise awareness about the potential effects of antibiotic overuse during the pandemic and to propose practical approaches to tackle this issue.


The effects of respiratory sinus arrhythmia biofeedback on heart rate variability and posttraumatic stress disorder symptoms: a pilot study.
Recent studies have found a significant association between PTSD and low heart rate variability (HRV), a biomarker of autonomic dysregulation. Research indicates that respiratory sinus arrhythmia (RSA) biofeedback increases HRV while reducing related pathological symptoms. This controlled pilot study compared RSA biofeedback to progressive muscle relaxation (PMR) as adjunctive interventions for 38 persons with PTSD symptoms in a residential treatment facility for a substance use disorder. Both groups were assessed at pre-intervention and 4-week post-intervention. Group x time interactions revealed significantly greater reductions in depressive symptoms and increases in HRV indices for the RSA group. Both groups significantly reduced PTSD and insomnia symptoms and a statistical trend was observed for reduced substance craving for the RSA group. Increases in HRV were significantly associated with PTSD symptom reduction. Overall, these results provide preliminary support for the efficacy of RSA biofeedback in improving physiological and psychological health for individuals with PTSD.


Addressing maternal medication use during breastfeeding using clinical resources and a novel physiologically based pharmacokinetic model-derived metric: A qualitative study.
Breastfeeding has major benefits to the maternal-infant dyad and yet healthcare providers have expressed uncertainty about advocating breastfeeding when mothers are taking medications. The tendency for some providers to be more cautious in their advising approach is likely a consequence of limited, unfamiliar, and unreliable existing information on medication use during lactation. A novel risk metric termed the Upper Area Under the Curve Ratio (UAR) was developed to overcome existing resource shortcomings. However, the perception and use of the UAR in practice by providers is not known. The aim of this study was to understand existing resource use and potential UAR use in practice, their advantages and disadvantages, and areas of improvement for the UAR. Healthcare providers mainly practicing in California with experience advising on medication use during lactation were recruited. One-on-one semi-structured interviews that included questions on current practices when advising medication use during breastfeeding, and approaches to a given a scenario with and without information about the UAR were conducted. The Framework Method was applied for data analysis to construct themes and codes. Twenty-eight providers representing multiple professions and disciplines were interviewed. Six main themes emerged: (1) Current Practice Approaches, (2) Advantages of Existing Resources, (3) Disadvantages of Existing Resources, (4) Advantages of the UAR, (5) Disadvantages of the UAR, and (6) Strategies to Improve the UAR. Overall, 108 codes were identified that illustrated theme topics ranging from a general lack of metric use to the realities of advising. A workflow describing current practice approaches connected all other themes. Almost all disadvantages of existing resources could be overcome by advantages of other resources and the UAR. Several improvements to the UAR were identified to address its shortcomings. Through interviews with providers who use resources to advise on medication use during breastfeeding, an improved understanding of current practice approaches and accessed resources was ascertained. Ultimately, it was found that the UAR would confer multiple benefits over existing resources, and improvements of the UAR were identified. Future work should focus on implementing the suggested recommendations to ensure optimal uptake of the UAR to improve advising practices.


IFN-gamma inhibits inflammatory cell recruitment and the evolution of bacterial cell wall-induced arthritis.
Localization of streptococcal cell wall Ag (SCW) in the synovial tissue of treated rats induces an influx of leukocytes and a cell-mediated immune response leading to arthritis and joint destruction. Systemic administration of the T cell product, IFN-gamma (10(6) U/kg/day), suppresses the recruitment of leukocytes into the synovium and effectively inhibits the inflammation and pathology characteristic of SCW-induced arthritis (articular index 10.4 +/- 0.6 for SCW vs 2.0 +/- 0.7 for SCW with IFN-gamma, p less than 0.005). Monocyte-macrophages from animals treated with IFN-gamma exhibited defective chemotactic responses when tested in vitro and furthermore, monocytes cultured with IFN-gamma (25 to 500 U/ml) in vitro had significantly suppressed chemotactic responses to the complement fragment C5a (p less than 0.005). The decreased ability to migrate to C5a was associated with decreased binding of fluorochrome-conjugated C5a indicative of reduced expression of C5a receptors. Based on these data, IFN-gamma that induces monocyte maturation as reflected by increased Ia expression conversely inhibits C5a receptor expression. Although locally elevated IFN-gamma levels may serve to inhibit recruitment away from an inflammatory site, systemic exposure to IFN-gamma appears to inhibit leukocyte recruitment to the inflammatory site by its ability to induce premature maturation and concomitant inability to respond to certain chemotactic ligands. Inasmuch as monocyte recruitment to the synovium is pivotal in the development of SCW-induced polyarthritis, the ability of IFN-gamma to inhibit this event effectively inhibits the synovial pathology.


Molecular characterization of serotype A foot-and-mouth disease viruses circulating in Vietnam in 2009.
Foot-and-mouth disease (FMD) is a major cause of endemic outbreaks in Vietnam in recent years. In this work, six serotype A foot-and-mouth disease viruses (FMDV), collected from endemic outbreaks during January and February of 2009 in four different provinces in Vietnam, were genetically characterized for their complete genome sequences. Genetic analysis based on the complete viral genome sequence indicated that they were closely related to each other and shared 99.0-99.8% amino acid (aa) identity. Genetic and deduced aa analysis of the capsid coding gene VP1 showed that the six Vietnamese strains were all classified into the genotype IX from a total of 10 major genotypes worldwide, sharing 98.1-100% aa identity each other. They were most closely related to the type A strains recently isolated in Laos (A/LAO/36/2003, A/LAO/1/2006, A/LAO/6/2006, A/LAO/7/2006, and A/LAO/8/2006), Thailand (A/TAI/2/1997 and A/TAI/118/1987), and Malaysia (A/MAY/2/2002), sharing 88.3-95.5% nucleotide (nt) identities. In contrast, Vietnamese type A strains showed low nt identities with the two old type A FMDVs, isolated in 1960 in Thailand (a15thailand iso43) and in 1975 in the Philippines (aphilippines iso50), ranging from 77.3 to 80.9% nt identity. A multiple alignment based on the deduced amino acid sequences of the capsid VP1 coding gene of type A FMDV revealed three amino acid substitutions between Vietnamese strains and the strains of other Southeast Asian countries (Laos, Thailand, Malaysia, and the Philippines). Alanine was replaced by valine at residue 24, asparagine by arginine at residue 85, and serine by threonine at residue 196. Furthermore, type A FMDV strains recently isolated in Vietnam, Laos, Thailand, and Malaysia all have one amino acid deletion at residue 140 of the capsid VP1 protein compared with the two old type A FMDV strains from Thailand and the Philippines as well as most other type A representatives worldwide. This article is the first to report on the comprehensive genetic characterization of type A FMDV circulating in Vietnam.