Balancing the benefits and detriments among women targeted by the Norwegian Breast Cancer Screening Program.
To compute a ratio between the estimated numbers of lives saved from breast cancer death and the number of women diagnosed with a breast cancer that never would have been diagnosed during the woman's lifetime had she not attended screening (epidemiologic over-diagnosis) in the Norwegian Breast Cancer Screening Program. The Norwegian Breast Cancer Screening Program invites women aged 50-69 to biennial mammographic screening. Results from published studies using individual level data from the programme for estimating breast cancer mortality and epidemiologic over-diagnosis comprised the basis for the ratio. The mortality reduction varied from 36.8% to 43% among screened women, while estimates on epidemiologic over-diagnosis ranged from 7% to 19.6%. We computed the average estimates for both values. The benefit-detriment ratio, number of lives saved, and number of women over-diagnosed were computed for different scenarios of reduction in breast cancer mortality and epidemiologic over-diagnosis. For every 10,000 biennially screened women, followed until age 79, we estimated that 53-61 (average 57) women were saved from breast cancer death, and 45-126 (average 82) were over-diagnosed. The benefit-detriment ratio using average estimates was 1:1.4, indicating that the programme saved about one life per 1-2 women with epidemiologic over-diagnosis. The benefit-detriment ratio estimates of the Norwegian Breast Cancer Screening Program, expressed as lives saved from breast cancer death and epidemiologic over-diagnosis, should be interpreted with care due to substantial uncertainties in the estimates, and the differences in the scale of values of the events compared.


Lack of correlation between transformed characteristics in culture and tumorigenicity of mouse mammary tumour cells.
Androgen responsive and unresponsive Shionogi 115 mouse mammary carcinoma cells have been examined for anchorage-independent growth and tumorigenicity in nude mice. The two cell types exhibit transformed and normal growth characteristics respectively, but both give rise to tumours in nude mice. No correlation between tumorigenicity and transformed characteristics including anchorage-independent growth could be demonstrated.


Consistent diel activity patterns of forest mammals among tropical regions.
An animal's daily use of time (their "diel activity") reflects their adaptations, requirements, and interactions, yet we know little about the underlying processes governing diel activity within and among communities. Here we examine whether community-level activity patterns differ among biogeographic regions, and explore the roles of top-down versus bottom-up processes and thermoregulatory constraints. Using data from systematic camera-trap networks in 16 protected forests across the tropics, we examine the relationships of mammals' diel activity to body mass and trophic guild. Also, we assess the activity relationships within and among guilds. Apart from Neotropical insectivores, guilds exhibited consistent cross-regional activity in relation to body mass. Results indicate that thermoregulation constrains herbivore and insectivore activity (e.g., larger Afrotropical herbivores are ~7 times more likely to be nocturnal than smaller herbivores), while bottom-up processes constrain the activity of carnivores in relation to herbivores, and top-down processes constrain the activity of small omnivores and insectivores in relation to large carnivores' activity. Overall, diel activity of tropical mammal communities appears shaped by similar processes and constraints among regions reflecting body mass and trophic guilds.


Reliability of routine anthropometric measurements to estimate body composition in term infants.
Birth weight percentiles provide limited information on qualitative infant growth. Body composition provides estimates of fat mass, fat-free mass, and body fat percentage (adiposity). We sought to implement assessment of body composition at birth into clinical practice using a validated anthropometric equation and to evaluate measurement reliability. Body composition was incorporated into newborn nursery admission procedure. Body fat percentage derived from skinfold measurements performed by clinical nurses were compared to a historical database of similar measurements performed on newborns by experienced research staff. Body Mass Index (BMI) and Ponderal Index (PI) were used as surrogates for adiposity. Comparison of correlations between groups assessed measurement reliability. P < 0.05 was considered significant. Nine hundred and ninety-one infants had body composition evaluated. Correlations were similar between BMI and %BF for measurements performed by research and clinical nurses (r2 = 0.82 versus r2 = 0.80; P = 0.142 for the difference between correlation coefficients) demonstrating good reliability. Similar results were found using PI (r2 = 0.58 versus r2 0.53; P = 0.105). Body composition can be assessed at birth using a validated anthropometric equation. Measurements performed by clinical RNs were found to be reliable, allowing for a qualitative measure of growth beyond birth weight. Assessment of neonatal body composition at birth can be implemented into routine clinical practice using an anthropometric equation to estimate fat free-mass, fat mass, and percentage body fat. It provides a detailed, reproducible protocol to incorporate into routine practice. Assessment of fat mass, fat-free mass, and adiposity at birth allows for a qualitative measure of intrauterine growth beyond birth weight. Routine assessment of body composition provides a foundation for longitudinal follow-up of metabolic health in infancy and childhood.


Health care use and cost of treatment for adolescents and young adults with opioid use disorder.
Few studies have examined the cost of medication for opioid use disorder (MOUD) with counseling for the adolescent and young adult population. This study calculated the health care utilization and cost of MOUD treatment, other substance use disorder treatment, and general health care for adolescents and young adults receiving treatment for opioid use disorder. The study randomized youth ages 15 to 21 (N = 288) equally into the two study conditions: extended-release naltrexone (XR-NTX) or treatment as usual (TAU). While participants committed to treatment based on randomization the study observed considerable nonadherence to both randomized conditions. Instead of using the randomly assigned study conditions, we present descriptive costs by the type of MOUD treatment received: XR-NTX only, buprenorphine only, any other combination of MOUD treatments, and no MOUD. Health care use was aggregated over the 6-month period for each participant, and we calculated average/participant utilization for each treatment group. To determine participant costs, we multiplied the unit costs of health care services obtained from the literature by the reported amount of health care utilization for each participant. We then calculated the mean, standard error, median and IQR for MOUD costs, other substance use disorder treatment costs and general healthcare cost from the health care sector perspective. On average, participants in the XR-NTX only group received 2.6 doses of XR-NTX (equivalent to approximately 78 days of treatment). The buprenorphine only group had an average of 97 days of buprenorphine treatment. The XR-NTX only group had higher/patient costs compared to participants in the buprenorphine only group ($10,491 vs. $8765) and higher XR-NTX utilization would further increase costs. Participants in the any other MOUD combination group had the highest total costs ($14,627) while participants in the no MOUD group at the lowest ($3453). Our cost analysis calculates the real-world cost of MOUD treatment and, while not generalizable, provides policy makers an estimate of costs for adolescents and young adults. We found that participants in the XR-NTX only group received fewer days of medication compared to the buprenorphine only group, but their medication costs were higher due to the cost of XR-NTX injections. While the buprenorphine only group had the highest number of days of medication utilization of all the groups, the average number of days of medication utilization was considerably shorter than the six-month treatment period.


Bifunctional asymmetric catalysis: a tandem nucleophile/Lewis acid promoted synthesis of beta-lactams.
[reaction: see text]. We describe a superior procedure for the catalytic, asymmetric synthesis of beta-lactams using a bifunctional catalyst system consisting of a chiral nucleophile and an achiral Lewis acid.


Oxytocin influences avoidant reactions to social threat in adults with borderline personality disorder.
Borderline personality disorder (BPD) is characterized by interpersonal dysfunction, emotional instability, impulsivity, and risk-taking behavior. Recent research has focused on the role of oxytocin in BPD, with mixed results as regards the processing of social stimuli. In a double-blind randomized placebo-controlled study, 13 BPD patients and 13 controls performed a dot probe task to examine attentional biases to happy and angry faces after intranasal application of oxytocin or placebo. Childhood trauma was examined using the childhood trauma questionnaire. In the placebo condition, patients with BPD (but not controls) showed an avoidant reaction to angry faces (but not happy faces). The strength of the avoidant reaction correlated with the severity of childhood trauma. This behavioral response (as well as the correlation) was abolished in the oxytocin condition. Adult patients with BPD show an avoidant response to social threat, a reaction that is linked with traumatic experiences during childhood. This response pattern is altered by oxytocin, possibly by reducing stress and inhibiting social withdrawal from distressing social stimuli.


Enhancement of phenytoin elimination by multiple-dose activated charcoal.
The effect of multiple-dose activated charcoal on the elimination of intravenously administered phenytoin was studied. Seven normal volunteers received phenytoin sodium 15 mg/kg IV with and without activated charcoal. During the charcoal phase, a total dose of 300 g was administered in repeated doses over 48 hours with sufficient sorbitol to produce one to two bowel movements per day. Serum phenytoin concentrations were determined from one to 72 hours after the infusions and were fitted to a one-compartment linear elimination model. The administration of multiple-dose activated charcoal reduced the phenytoin half-life from 44.5 to 22.3 hours. In addition, phenytoin area under the curve was decreased and the elimination rate was increased. Multiple-dose activated charcoal is effective in enhancing the elimination of phenytoin in normal volunteers. Although future studies are needed to determine its role in treating patients with phenytoin toxicity, multiple-dose activated charcoal may provide a readily available, inexpensive therapeutic intervention.


Genome-wide association study in Chinese Holstein cows reveal two candidate genes for somatic cell score as an indicator for mastitis susceptibility.
Bovine mastitis is a typical inflammatory disease causing seriously economic loss. Genome-wide association study (GWAS) can be a powerful method to promote marker assistant selection of this kind of complex disease. The present study aimed to analyze and identify single nucleotide polymorphisms (SNPs) and candidate genes that associated with mastitis susceptibility traits in Chinese Holstein. Forty eight SNPs were identified significantly associated with mastitis resistance traits in Chinese Holstein cows, which are mainly located on the BTA 14. A total of 41 significant SNPs were linked to 31 annotated bovine genes. Gene Ontology and pathway enrichment revealed 5 genes involved in 32 pathways, in which, TRAPPC9 and ARHGAP39 genes participate cell differentiation and developmental pathway together. The six common genome-wide significant SNPs are found located within TRAPPC9 and flanking ARHGAP39 genes. Our data identified the six SNPs significantly associated with SCS EBVs, which suggest that their linked two genes (TRAPPC9 and ARHGAP39) are novel candidate genes of mastitis susceptibility in Holsteins.


Evidence for separate allocentric and egocentric space processing in neglect patients.
Spatial orientation was investigated in two different conditions: (a) when the shape of the enclosure was the only available information; (b) when a clearly perceivable visual cue was added. Three groups of subjects were investigated: normal controls, right brain-damaged patients without and with hemispatial neglect. The performance of the first two groups clearly demonstrated the capacity to use the geometric properties of the environment and to integrate this information with an additional visual cue. Considered as a group, patients with hemispatial neglect were able to use the shape of the environment and, to a lesser extent, the additional visual cue. However, individual differences suggest two opposite performance patterns: two patients responded randomly when the shape of the environment was the only available information, and they improved considerably when the cue was offered; two other patients showed normal competence in dealing with the geometrical properties of the environment, but were unable to take advantage of the cue. The different lesion site in these two types of patients suggests a possible dissociation of processing based upon allocentric or egocentric coding of space in humans as well as in animals.


Clarification of the molecular pathway of Taiwan local pomegranate fruit juice underlying the inhibition of urinary bladder urothelial carcinoma cell by proteomics strategy.
Pomegranate fruit has been shown to exhibit the inhibitory activity against prostate cancer and lung cancer in vitro and in vivo, which might be a resource for chemoprevention and chemotherapy of cancer. Our previous documented findings indicated that treatment of urinary bladder urothelial carcinoma cell with the ethanol extract isolated from the juice of pomegranate fruit grown in Taiwan could inhibit tumor cell. In this study we intended to uncover the molecular pathway underlying anti-cancer efficacy of Taiwan pomegranate fruit juice against urinary bladder urothelial carcinoma. We exploited two-dimensional gel electrophoresis coupled with tandem mass spectrometry to find the de-regulated proteins. Western immunoblotting was used to confirm the results collected from proteomics study. Comparative proteomics indicated that 20 proteins were differentially expressed in ethanol extract-treated T24 cells with 19 up-regulated and 1 down-regulated proteins. These de-regulated proteins were involved in apoptosis, cytoskeleton regulation, cell proliferation, proteasome activity and aerobic glycolysis. Further studies on signaling pathway demonstrated that ethanol extract treatment might inhibit urinary bladder urothelial carcinoma cell proliferation through restriction of PTEN/AKT/mTORC1 pathway via profilin 1 up-regulation. It also might evoke cell apoptosis through Diablo over-expression. The results of this study provide a global picture to further investigate the anticancer molecular mechanism of pomegranate fruit.


Social capital and disaster preparedness in Oromia, Ethiopia: An evaluation of the "Women Empowered" approach.
Ethiopia is faced with challenges posed by natural disasters, especially drought. Integrated approaches to disaster risk reduction are necessary to improve the lives and livelihoods of those most vulnerable to disaster. The Women Empowered (WE) approach provides economic and social opportunities for women to build resilience to respond to disasters. This study examines the association between WE group membership and disaster preparedness and whether this relationship is mediated by social capital. We used a multi-stage random cluster sampling strategy to select and interview 589 female respondents from Lage Hidha district (298 from the intervention area and 291 in the comparison area). Using Stata 14.0, we employed Poisson regression analysis to study the mechanisms through which WE groups are associated with disaster preparedness. After controlling for clustering and confounding factors, we found that different components of social capital mediate the relationship between WE group membership and disaster preparedness. Specifically, taking action to prepare for a disaster is primarily mediated by emotional support from the group and perceived preparedness for a disaster is mediated by social network support, emotional support from the group, collective action, and trust. This study suggests that the association between WE groups and disaster preparedness operates through social capital in drought-prone areas of Ethiopia. Future research is needed to determine which forms of social capital have the greatest potential to help families prepare for and respond to a variety of humanitarian crises.


Enhanced analysis of bacteria susceptibility in connected biofilms.
A common method for visualizing bacterial biofilms is through confocal laser scanning microscopy images. Current software packages separate connected-biofilm bacteria from unconnected bacteria, such as planktonic or dispersed bacteria, but do not save both image sequences, making interpretation of the two bacterial populations difficult. Thus we report the development of an algorithm to save separate image sequences and enable qualitative and quantitative evaluation of each bacterial population. To improve bacterial viability assessment using a membrane integrity dye, a colocalization algorithm was also developed. This assigns colocalized pixels to the dead bacteria population, rather than to both the live and dead bacteria groups. Visually, this makes it clearer to distinguish a green live bacteria pixel from a yellow colocalized dead bacteria pixel. This algorithm also aids in the quantification of viability for connected-biofilm bacteria and unconnected bacteria to investigate susceptibility of each population to antimicrobials. The utility of these algorithms was demonstrated with Pseudomonas aeruginosa biofilms treated with ciprofloxacin hydrochloride. Results from this study indicate that quantification with colocalization adjustment can prevent underestimation of dead bacteria. These improvements in image processing will enable researchers to visually differentiate connected-biofilm and unconnected bacteria in a single image and to quantify these populations independently for viability without double counting the colocalized image pixels.


Perceived social support in pregnant women with gestational diabetes attending hospitals in western Iran compared to healthy controls and its relationship with perceived anxiety.
Due to the importance of social support in pregnant women, especially those with gestational diabetes that cause anxiety and stress in them and requires effective and enough attention, this study aims to assess perceived social support of pregnant women with gestational diabetes in western Iran compared to healthy controls and its relationship with their perceived anxiety. This is a descriptive/analytical study with a cross-sectional design conducted on 180 pregnant women with gestational diabetes (n = 89) and without gestational diabetes (n = 91) referred to the obstetrics and gynecology clinics of two hospitals (Asalian and Shahid Rahimi) in Khorramabad, western Iran. Data collection tools were a demographic checklist, the Multidimensional Scale of Perceived Social Support (MSPSS), and the Beck Anxiety Inventory (BAI). Collected data were analyzed in SPSS v.20 software using chi square test, independent t-test, one-way ANOVA, and Pearson correlation test. The difference between the two groups was significant in terms of perceived support from family (p = 0.001), perceived support from friends (p = 0.006), and anxiety (p = 0.047). Pearson correlation test results showed a significant negative relationship between the scores of MSPSS and BAI in patients (r= -0.329, p = 0.001) and controls (r=-0.204, p = 0.006). There was a significant difference in the MSPSS score among diabetic women in terms of having fetal macrosomia (p = 0.005), occupation (p = 0.003), education (p = 0.001), and frequency of pregnancy (p = 0.010). The perceived social support level is higher in diabetic pregnant women compared to healthy peers in western Iran. Improvement of social support from family and friends can reduce the anxiety of pregnant women with/without diabetes.


Identification of regions in which positive selection may operate in S-RNase of Rosaceae: implication for S-allele-specific recognition sites in S-RNase.
A stylar S-RNase is associated with gametophytic self-incompatibility in the Rosaceae, Solanaceae, and Scrophulariaceae. This S-RNase is responsible for S-allele-specific recognition in the self-incompatible reaction, but how it functions in specific discrimination is not clear. Window analysis of the numbers of synonymous (dS) and non-synonymous (dN) substitutions in rosaceous S-RNases detected four regions with an excess of dN over dS in which positive selection may operate (PS regions). The topology of the secondary structure of the S-RNases predicted by the PHD method is very similar to that of fungal RNase Rh whose tertiary structure is known. When the sequences of S-RNases are aligned with the sequence of RNase Rh based on the predicted secondary structures, the four PS regions correspond to two surface sites on the tertiary structure of RNase Rh. These findings suggest that in S-RNases the PS regions also form two sites and are candidates for the recognition sites for S-allele-specific discrimination.


Microwave Heating of Crystals with Gold Nanoparticles and Synovial Fluid under Synthetic Skin Patches.
Gout is a disease with elusive treatment options. Reduction of the size of l-alanine crystals as a model crystal for gouty tophi with the use of a monomode solid-state microwave was examined as a possible therapeutic aid. The effect of microwave heating on l-alanine crystals in the presence of gold nanoparticles (Au NPs) in solution and synovial fluid (SF) in a plastic pouch through a synthetic skin patch was investigated. In this regard, three experimental paradigms were employed: Paradigm 1 includes the effect of variable microwave power (5-10 W) and variable heating time (5-60 s) and Au NPs in water (20 nm size, volume of 10 μL) in a plastic pouch (1 × 2 cm2 in size). Paradigm 2 includes the effect of a variable volume of 20 nm Au NPs in a variable volume of SF up to 100 μL in a plastic pouch at a constant microwave power (10 W) for 30 s. Paradigm 3 includes the effect of constant microwave power (10 W) and microwave heating time (30 s), constant volume of Au NPs (100 μL), and variable size of Au NPs (20-200 nm) placed in a plastic pouch through a synthetic skin patch. In these experiments, an average of 60-100% reduction in the size of an l-alanine crystal (initial size = 450 μm) without damage to the synthetic skin or increasing the temperature of the samples beyond the physiological range was reported.


The Biomechanical E-Staging: In Vivo Biomechanics in Keratoconus.
Belin's ABCD keratoconus classification system allows keratoconus staging based on the criteria of anterior (A) and posterior (B) corneal curvature, thinnest corneal thickness (C), and best spectacle-corrected visual acuity (D). These parameters also provide a progression assessment, but do not take corneal biomechanics into account. The analysis of corneal biomechanics by the Corvis ST (Oculus, Wetzlar, Germany) allows for separation of healthy and keratoconus corneas, based on the Corvis Biomechanical Index (CBI) and the Tomographic Biomechanical Index (TBI). As Corvis ST measurements are highly reliable and are independent of keratoconus severity, a biomechanical parameter was developed for keratoconus corneas based on the linear term of the CBI. This provides biomechanical keratoconus staging. The Corvis Biomechanical Factor (CBiF) is the basis for the introduction of the biomechanical E-staging, which augments the ABCD classification to the ABCDE classification, thus including the cornerstone of corneal biomechanics. This article highlights strengths and limitations of the ABCDE classification. "Unilateral keratoconus" supposedly turns out to be mostly a snapshot of a highly asymmetric keratectasia. Regular astigmatism is sometimes an important differential diagnosis to keratectasia and may be difficult to differentiate from it. Furthermore, the use of the biomechanical E-staging in daily practice for progression assessment of keratoconus and after its treatment by corneal cross-linking or implantation of intracorneal ring segments will be demonstrated and discussed.


Survival of Campylobacter jejuni on beef trimmings during freezing and frozen storage.
To investigate the survival of two animal isolates of Campylobacter jejuni on beef trimmings during freezing and frozen storage. Meat packs inoculated with 10(3) or 10(6) cfu g(-1) of either strain of C. jejuni were frozen to -18 degrees C, and sampled at regular intervals over 112 d storage to determine Campylobacter numbers and sublethal injury. For both strains and inoculation levels the numbers of Campylobacter decreased in the first 7 d of storage by ca. 0.6-2.2 log cfu g(-1) and then remaining constant over the remainder of the storage trial, with neither isolate exhibiting sublethal injury. Despite an initially significant decrease in number, these pathogens were able to survive standard freezing conditions in meat, but did not exhibit sublethal injury. Strict hygiene and/or the implementation of decontamination technologies are recommended as a means to assure the safety of meat with respect to this pathogen.


Separation of peptides on the basis of the difference in positive charge: simultaneous isolation of C-terminal and blocked N-terminal peptides from tryptic digests.
The microscale separation of peptides based on the difference in positive charge was examined with tryptic digests of apomyoglobin and calmodulin. By this separation method, C-terminal and blocked N-terminal peptides could be selectively isolated in the same fraction without any chemical modifications. Separated peptides, including internal peptides, were further purified by reversed phase high performance liquid chromatography, and the purified peptides could be directly subjected to sequence and amino acid analyses. The N-terminal peptides of calcium-activated neutral protease were successfully isolated by this method.


Immunological evaluation of 15 children with non-Hodgkin lymphoma.
In the present study, 15 children with non-Hodgkin lymphoma have been immunologically evaluated by the following parameters on peripheral blood (PB) lymphocytes: phytohemagglutinin responsiveness (PHA-r); non-immune rosette formation with sheep red blood cells (RF-L) as T-cell marker; presence of surface immunoglobulins (sIg-L) as B-cell marker; serum immunoglobulins levels (IgA, IgM, IgG). Our patients (pts) have been divided in two groups: the first one includes 10 children without PB involvement; the second one includes 5 pts with bone-marrow and PB invasion. From our data it appears that: 1) the majority of pts of the first group presented normal values of membrane markers; PHA-r was impaired in 4/8 pts; 2) in pts with PB invasion absolute number of B and "null" cells was always abnormal and PHA-r altered; 3) in the second group of pts, a "null" cell origin can be suggested by the high percentage and absolute number of cells without surface markers. In our opinion, the high incidence of "null" cells represents the most relevant question: whether they are cells deprived of specific markers, or endowed with markers not identifiable by our current techniques, remains to be established.


Trends in aspirin, paracetamol and non-steroidal anti-inflammatory drug use in children between 1981 and 1992 in France.
Antipyretic/analgesic drugs (AADs) are among the most commonly used drugs in children. Their efficacy and adverse effects have often been debated and new AADs have been introduced over the past few years. The aim of this study was to assess the characteristics of the use of AADs in children in France, and their trends. Two surveys on household health care consumption were undertaken in France, in 1981 and in 1992. They included 5060 and 4841 children, respectively. The AADs studied were aspirin, paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). The proportion of children exposed to AADs increased significantly between 1981 and 1992 (+28% in 11 years). Among them, the percentage of subjects treated with aspirin decreased (-27%). In contrast, the percentage increased for paracetamol (+ 19%) and for NSAIDs (+179%). Aspirin was the AAD most used in 1981 (57.4%) and it was replaced by paracetamol in 1992 (71.6%). Nasopharyngitis was the main reason for AAD prescription under the age of 11 years; for older children it was influenza-like syndrome, irrespective of the study year. A change in AAD choice occurred in nasopharyngitis, acute bronchitis and influenza-like syndrome irrespective of the age group, and in otitis/sinusitis between 4 and 10 years. In all these cases aspirin prescription decreased, in contrast with paracetamol and NSAIDs. Self-medication of AAD was uncommon (8.3% for aspirin and 10.3% for paracetamol in 1992) and decreased (-29% and -33%). It was used principally for nasopharyngitis, influenza-like syndrome and pain. The consumption of AADs in children is high and is increasing. Paracetamol and NSAIDs tend to replace aspirin prescription in children and physicians have played the main role in this change.


Structural basis for cytokinin recognition by Arabidopsis thaliana histidine kinase 4.
Cytokinins are classic hormones that orchestrate plant growth and development and the integrity of stem cell populations. Cytokinin receptors are eukaryotic sensor histidine kinases that are activated by both naturally occurring adenine-type cytokinins and urea-based synthetic compounds. Crystal structures of the Arabidopsis thaliana histidine kinase 4 sensor domain in complex with different cytokinin ligands now rationalize the hormone-binding specificity of the receptor and may spur the design of new cytokinin ligands.


Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies.
Chemotherapy-induced neutropenia (CIN) may increase infection risk for cancer patients; however, there is limited understanding on the quantitative relationships between severity and duration of CIN and infection risk. This study combined individual data from adult cancer patients receiving no granulocyte colony-stimulating factor during the first chemotherapy cycle in six trials. We used area over the curve (AOC) of absolute neutrophil count (ANC) time-response curve (below different thresholds) to measure the combined effect of severity and duration of CIN. Time-dependent Cox proportional hazards models quantified the hazard of first infection associated with duration of grade 4 or grade 3/4 CIN and the hazard associated with AOC. We analyzed data from 271 patients who had small cell lung cancer, non-Hodgkin's lymphoma, head and neck cancer, or breast cancer; 63.8 % of the patients had advanced cancer, and 77.5 % received chemotherapy regimens with high risk of febrile neutropenia. In the first cycle, 18.8 % of the patients had infection-related hospitalizations. Each additional day patients had grade 3/4 or grade 4 CIN was associated with 28 % (95 % CI 7, 51 %) and 30 % (95 % CI 10, 54 %) increased risk of infection-related hospitalization, respectively. Each unit increase in AOC (day × 10(9)/L ANC), with threshold of ANC < 0.5 × 10(9)/L, was associated with a significantly increased risk of infection-related hospitalization (hazard ratio 1.98; 95 % CI 1.35, 2.90). Infection risk increases dramatically with each additional day of grade 3 or 4 CIN. Interventions limiting CIN severity and duration are of critical importance to reduce infection risk in cancer patients receiving chemotherapy.


Flow Cytometry Phenotyping of Bone Marrow-Derived Macrophages from Wild-Type and Mif-/- Mice.
Phenotyping cells by flow cytometry is a powerful way to identify cell type and any morphological changes during cell culture. The staining procedure used in this chapter enables the characterization of mouse macrophages by a flow cytometry antibody panel which can be used for both bone marrow-derived macrophages (BMM) and macrophages derived from other tissues, such as the mouse spleen or peritoneal cavity. The surface and intracellular staining methods are versatile and can be applied to flow cytometry staining of several different cell types by changing the surface markers used with knowledge of which receptors are expressed on different cell types.


Experimental implantation of adipose tissue fragments.
The healing of small adipose tissue implants was evaluated in experimental studies on rats. Adipose tissue of approximately 0.5 ml volume was obtained by resection of parauterine fat pads. The tissue was divided into fragments that were 1-3 mm in size and implanted under the dorsal skin. The implantation of adipose tissue in fragments offered no biological advantage and the healing process terminated in extensive necrosis of fat cells. The results are analysed and considered in relation to the implantation of adipose tissue fragments obtained by liposuction.


Effects of 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB8) on rat atrial muscle.
Rat atria loaded in vitro with the dye INDO-1 produced fluorescence signals indicative of changes in cytoplasmic calcium ion concentration ([Ca2+]c). Such atria showed systolic/diastolic fluctuations in fluorescence indicative of a systolic rise and a diastolic fall in [Ca2+] while being superfused with a solution containing a normal Ca2+ concentration. Some atria were then exposed to a low [Ca2+] in the superfusate. This caused negative inotropism and fluorescence changes indicative of a decline in [Ca2+]c. Both of these responses were reversed by adding 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB8; 2 microM) to the superfusate. Some atria were exposed instead either to a low [K+] in the superfusate or to an ouabain-containing superfusate. These atria developed a contracture, associated with fluorescence changes indicative of a rise in [Ca2+]c. The addition of TMB8 (2 microM) now relaxed the contracture, and this was associated with fluorescence changes indicative of a decline in [Ca2+]c. Atria that were exposed for 15 min to a low [Na+] in the superfusate developed a period of positive inotropism, followed by a brief period of negative inotropism on return to the normal superfusate. The period of positive inotropism was associated with fluorescence changes indicative of a rise in [Ca2+]c and the period of negative inotropism with a decline in [Ca2+]c to below baseline levels. All of these responses were less marked in atria exposed throughout to superfusates containing TMB8 (2 microM). Some atria were loaded with the dye SNARF-1. This emits fluorescence signals indicative of changes in cytoplasmic pH (pHc). These atria showed no systolic/diastolic fluctuation of fluorescence, but when superfused with a bicarbonate-free solution they displayed a change in fluorescence indicative of a decline in pHc in response to the addition of either ouabain or TMB8. Similarities were found between the effects produced by TMB8 and those produced by amiloride or dichlorobenzyl amiloride, suggesting that all three agents inhibit plasmalemmal Na+/Ca2+ and Na+/H+ exchange.


Oral immunization with a novel attenuated Salmonella Gallinarum encoding infectious bronchitis virus spike protein induces protective immune responses against fowl typhoid and infectious bronchitis in chickens.
Fowl typhoid (FT), a septicemic disease caused by Salmonella Gallinarum (SG), and infectious bronchitis (IB) are two economically important avian diseases that affect poultry industry worldwide. Herein, we exploited a live attenuated SG mutant, JOL967, to deliver spike (S) protein 1 of IB virus (V) to elicit protective immunity against both FT and IB in chickens. The codon optimized S1 nucleotide sequence was cloned in-frame into a prokaryotic constitutive expression vector, pJHL65. Subsequently, empty pJHL65 or recombinant pJHL65-S1 plasmid was electroporated into JOL967 and the resultant clones were designated as JOL2068 and JOL2077, respectively. Our results demonstrated that the chickens vaccinated once orally with JOL2077 elicited significantly (p < 0.05) higher IBV-specific humoral and cell-mediated immunity compared to JOL2068 and PBS control groups. Consequently, on challenge with the virulent IBV strain at 28th day post-vaccination, JOL2077 vaccinated birds displayed significantly (p < 0.05) lower inflammatory lesions in virus-targeted tissues compared to control groups. Furthermore, 33.3% (2 of 6) of birds vaccinated with JOL2077 vaccine had shown virus recovery from tracheal tissues compared to 100% (6 of 6) recovery obtained in both the control groups. Against wild-type SG lethal challenge, both JOL2077 and JOL2068 vaccinated groups exhibited only 10% mortality compared to 80% mortality observed in PBS control group. In conclusion, we show that JOL2077 can induce efficient IBV- and carrier-specific protective immunity and can act as a bivalent vaccine against FT and IB. Further studies are warranted to investigate the potential of JOL2077 vaccine in broiler and young layer birds.


Melanotic freckle of Hutchinson: treatment of macular and nodular phases with cryotherapy.
Fourteen cases of Hutchinson's lentigo maligna and eight further cases with nodular invasive areas in whom liquid nitrogen spray has been curative are reported. We suggest that in view of its simplicity and efficacy, cryotherapy is the treatment of choice for the macular phase and possibly also for the nodular invasive stage.


Surgical indications and techniques for posterior pharyngeal flap revision.
Twenty-four patients underwent surgical revision of posterior pharyngeal flaps for correction of abnormal vocal resonance, nasal air escape, or sleep apnea. Anatomical findings upon operation are correlated with preoperative symptoms, and an operative approach is outlined. Overall, 67% of the total group (16 patients) were improved after revision, with the most marked improvement seen in those with preoperative hypernasality or airway obstruction.


Comparison of different methodologies for estimating gold thickness in multilayer samples using XRF spectra.
A detailed comparison of methodologies for assessing gold leaf thickness in multilayer samples using the XRF technique was performed. Standard three-layer samples and six methods of analysis were used: two-line ratio of one or two elements, de Boer's analytical procedure, multivariate PLS analysis and percentage concentration of elements in the layers. The accuracy of each method and the consistency among the results of the methods emerged. The PLS method and the analytical approach might be preferred because they are faster.


"Tricks and tips for home mechanical ventilation" Home mechanical ventilation: set-up and monitoring protocols.
In this part of the review series "Tricks and tips for home mechanical ventilation", we will discuss the evidence with regard to the place and manner of home mechanical ventilation initiation and follow-up. Outsourcing more and more of this chronic care to the home situation is a big challenge for the future: especially for the home situation, monitoring has to be non-invasive, reliable and easy to use, data security needs to be ensured, signals need to be integrated and preferably automatically processed and algorithms need to be developed based on clinically relevant outcomes.


Craniofrontonasal syndrome in a male due to chromosomal mosaicism involving EFNB1: further insights into a genetic paradox.
Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by inactivating mutations in the gene for ephrin-B1 (EFNB1). Paradoxically it shows a more severe phenotype in females than in males. As a result of X inactivation cell populations with and without EFNB1 expression are found in EFNB1+/- females. This is thought to initiate a process termed cellular interference which may be responsible for the phenotype in females. We present a boy with severe clinical features of CFNS. In ∼42% of his blood cells we found a supernumerary ring X chromosome containing EFNB1 but lacking XIST. Mosaicism for cell populations with different levels of EFNB1 expression can explain the severe phenotype of this patient. In vitro experiments in Xenopus tissue showed that cells overexpress ephrinB1 cluster and sort out from wild-type cells. Our report provides further evidence that cellular interference contributes to the paradoxical inheritance pattern of CFNS.


Inhibitory actions of synthetic actin peptides and 2,3-butanedion monoxime on actomyosin system.
Interaction of myosin and actin has been studied in the presence of inhibitors in order to identify and characterize sites essential for the motor function. Acidic amino acid cluster of actin at the amino terminal region is known to interact with basic residue around 50K-20K connecting loop of the myosin heavy chain. In this study, an amino terminal peptide region of actin without the initial four acidic residue cluster is also shown to have important role in the interaction with myosin in the presence of ATP. A set of peptides corresponding to actin sequences from Leu8 to Arg28 or to Gly36 were synthesized. In the absence of actin, neither activation nor inhibition of MgATPase activity of S1 alone has been observed with both types of peptide. In the presence of actin, however, the longer peptide (L8G36) at 50 microM shows about 50% inactivation of the control value of actoS1 Mg2+ATPase activity. The shorter one (L8R28) has been a non competitive and weaker inhibitor. The inhibition could be interpreted as a results of impairing of one of the interactions necessary for normal progression of actomyosin ATPase reaction. Moreover, these results indicate a contribution of amino terminal sequence of actin without initial four acidic residues for the acto myosin interaction. Examination of the inhibitory mechanism of BDM has shown that the effect may not be due to lowering the binding affinity between actin and myosin.


Explaining leak states in the proton pump of heme-copper oxidases observed in single-molecule experiments.
Heme-copper oxidases couple the exergonic oxygen reduction with the endergonic proton translocation. Redox-linked structural changes have been localized in deeply buried regions of the protein, near the low-potential heme. How these movements can modulate distant gating events along the intramolecular proton path, where the entry (exit) of pumped proton occurs, is a major concern for the proton pump models. Generally, these models associate, more or less directly, all translocation events with redox transitions. Although they can account for many phenomenological aspects of the pump, evidences from single-molecules experiments about leak states of the pump represent a formidable challenge. Disconnecting the redox-linked pKa shifts of the proton loading site from the external barriers, we obtain a simple stochastic mechanism which behaves similarly to the real enzyme, able to reverse the flow of the proton transfer.


Flock-level case-control study of slaughter-lamb pneumonia in New Zealand.
Subclinical pneumonia is common in production lambs, and causes reductions in growth rate. We selected farms from meat-inspection records of three New Zealand abattoirs from December 2000 to May 2001 to study risk factors for flocks having >or=3% of their lambs with >or=10% of the lung surface with lesions, compared to flocks with a zero lamb-level prevalence of such pneumonia. A questionnaire of management practices was mailed to participating managers of case and control farms and we received responses from 132/192 (69%) cases and 181/300 (60%) in control farms. Risk factors for case farms were shearing lambs on the day of weaning (OR 6.4), breeding ewe replacements on-farm (OR 4.0), and the percentage of lambs sold between March and May (OR 1.0 for <23% sold (reference category), OR 3.9 for 23-42% sold, OR 2.7 for 43-64% sold, OR 4.3 for >64% sold). Protective factors included: grazing lambs at a fixed stocking rate after weaning (OR 0.4), injecting lambs with vitamin B12 at the time of docking (OR 0.4), and at the time of weaning (OR 0.3). Path analysis was used to show important associations between risk and protective factors differentiated according to time (e.g. before and after birth, at weaning and during growth on pasture). Flocks breeding their own ewe replacements were more likely to shear lambs at weaning, were less likely to buy lambs post-weaning and more likely to have ill-thrift present in >5% of lambs post-weaning. The purchase of lambs post-weaning was indirectly associated with greater odds of pneumonia at slaughter.


Mature teratoma of the cisterna magna in an adult patient.
Teratomas are a rare subgroup of CNS germ cell tumors and are histologically classified into mature teratomas, immature teratomas, and teratomas with malignant transformation. CNS teratomas are infrequently found in the posterior fossa and pure mature teratomas of posterior fossa are rare especially in adults. We present a case of a young adult female with a mature teratoma in the cisterna magna. A 26-year-old female presented to the neurosurgery clinic with headache, nausea and vomiting for the past 1 year. She was found to have dysdiadochokinesia on neurological examination. Brain magnetic resonance imaging scan showed a-well defined lesion, hyperintense on T1 and hypointense on T2-weighted sequences located within the cisterna magna. She underwent a suboccipital craniotomy with resection of lesion. Histopathology confirmed the diagnosis of mature cystic teratoma. Mature teratomas located in the posterior fossa among adults are rare in the literature. We report the second case of mature teratoma in the cisterna magna of an adult patient.


Cryopreservation of rat MSCs by use of a programmed freezer with magnetic field.
Mesenchymal stem cells (MSCs) can be used for the regeneration of various tissues and cryopreservation of MSCs is so important for regenerative medicine. The purpose of this study was to evaluate the influences of cryopreservation on MSCs by use of a programmed freezer with a magnetic field (CAS freezer). MSCs were isolated from bone marrow of rat femora. The cells were frozen by a CAS freezer with 10% dimethyl sulfoxide (Me2SO) and cryopreserved for 7 days at a temperature of -150 °C. Immediately after thawing, the number of survived cells was counted. The cell proliferation also examined after 48 h culture. Next, MSCs were frozen by two different freezers; CAS freezer and a conventional programmed freezer without magnetic field. Then, osteogenic and adipogenic differentiations of cryopreserved cells were examined. As a result, survival and proliferation rates of MSCs were significantly higher in CAS freezer than in the non-magnetic freezer. Alizarin positive reaction, large amount of calcium quantification, and greater alkaline phosphatase activity were shown in both the non-cryopreserved and CAS groups after osteogenic differentiation. Moreover, Oil Red O staining positive reaction and high amount of PPARγ and FABP4 mRNAs were shown in both the non-cryopreserved and CAS groups after adipogenic differentiation. From these findings, it is shown that a CAS freezer can maintain high survival and proliferation rates of MSCs and maintain both adipogenic and osteogenic differentiation abilities. It is thus concluded that CAS freezer is available for cryopreservation of MSCs, which can be applied to various tissue regeneration.


Phenolic compounds and antioxidant activity in vitro and in vivo of Butia and Opuntia fruits.
Despite the consumption recommendations and the potential health benefits, Brazilian biodiversity has a large number of fruit species that are still unexplored, such as Butia catarinensis (Butiá da Praia), Butia eriospatha (Butiá da Serra) and Opuntia elata (Arumbeva). The phenolic compounds of these fruits were determined by HPLC-DAD-MS/MS. Morever, in vitro assays of antioxidant capacity on hydroethanolic extracts against hydrogen peroxide (H2O2), hydroxyl (OH), peroxyl (ROO) and ABTS radicals were evaluated. In vivo assays evaluating the survival of worms and reactive oxygen species (ROS) generation were performed using the nematode Caenorhabditis elegans. Eighteen, twenty-eight and seventeen phenolic compounds were identified in Butiá da Praia, Butiá da Serra and Arumbeva, respectively. The main groups of phenolic compounds found in the fruits were hydroxybenzoic acids (60.5, 26.5 and 96.1% of the total phenolic compounds for Butiá da Praia, Butiá da Serra and Arumbeva, respectively), flavan-3-ols (23.6 and 61.2% of the total phenolic compounds for Butiá da Praia and Butiá da Serra) and flavonols (2.6% of the total phenolic compounds for Arumbeva). The hydroethanolic extracts of these fruits were free radical scavenger, sources of phenolic compounds and did not cause toxic effects in vivo. In hydroethanolic extracts of Butiá da Praia and Arumbeva, the total phenolic content increased by around 67% and 35%, respectively. Besides the health benefits, these proved to be promising sources of natural antioxidants, with phenolic composition variating among species and collection site. The obtained results enable future applications of studied fruits extracts in food and/or pharmaceutical products, encouraging and valuing the sustainable use of biodiversity.


Tibia plateau fracture mapping and its influence on fracture fixation.
Tibial plateau fracture classifications are based on anteroposterior radiographs. Precontoured locking plates are commonly used to treat such fractures. The aims of this study are to: (1) describe tibial plateau fracture anatomy in the axial plane and (2) assess whether current plating systems allow screws to be placed suitably. A graphical tibial plateau template was developed. One hundred twenty-five tibial plateau fractures (four bilateral) were reviewed (80 men, 41 women; average age 45.5 years, range 21-77.7 years). The axial computed tomography (CT) slice 0.3-0.5 mm below the medial articular surface was reviewed in all cases. Fracture lines were drawn on the template. Four lateral locking plates were placed against a cadaveric adult tibia. Based on the projected screw directions, suitable fracture patterns were identified. Fractures were considered "suitable" if the screws passed 90 ± 22° to the fracture line. Two hundred sixty-one different fracture lines were identified. One hundred thirty-four fractures involved the lateral plateau; 96 were suitable for lateral plating. Ninety fractures involved the medial plateau, 82 were treatable using the various plate positions on medial-posterior aspect of the medial plateau. Thirty-seven fractures were bicondylar; 20 were treatable with a posteromedial plate. Tibial plateau fractures follow consistent patterns, with most lateral and medial plateau fracture lines being in the sagittal plane, although there is greater variation medially. Positioning of modern locking plates will deal effectively with 72 % of all lateral plateau fractures and 91 % of medial plateau fractures. Level 3.


PCDDs, PCDFs, and coplanar PCBs in wild terrestrial mammals from Japan: congener specific accumulation and hepatic sequestration.
The present study determined the contamination levels and congener-specific accumulation features of dioxins and related compounds (DRCs) in wild terrestrial mammals such as large Japanese field mice (LJFM), lesser Japanese moles (LJMs), and raccoon dogs (RDs) collected from Kanto region in Japan during 2001. The toxic equivalent quantity (TEQ) levels in the carcasses or adipose tissues were in the order of RDs > or = LJMs > LJFM. Comparison of DRC congener profiles in the three species and principal component analysis (PCA) demonstrated a higher contribution of OCDD, T4CB77, and P5CB118 in LJMs. Analysis of liver-adipose distribution of DRC congeners in RDs showed that livers contained significantly higher TEQs than adipose tissues, indicating that liver is a depository organ and critical for determining the toxicokinetics of DRCs. As for most T4, P5, H6CDD/DFs and for P5CB126, H6CB169 and mono-ortho PCB congeners, their liver/adipose concentration ratios in RDs revealed a tendency to increase with hepatic TEQ levels, suggesting TEQ-dependent hepatic sequestration.


Tolerance to ethanol in the rat vas deferens. Effect of a calcium channel antagonist.
Previous research from this laboratory indicated that ethanol dose-dependently depressed vas deferens contractions. The experiments described here examine the role calcium plays in the inhibitory action of ethanol in this tissue. Rat vas deferens tissues obtained from control (dextrin maltose) or chronically ethanol-treated animals were stimulated in the absence and then in the presence of 181 mM ethanol and/or a calcium channel blocker. Increasing the extracellular calcium concentration from 2.1 to 5.0 mM decreased ethanol's in vitro inhibitory effect on contractions induced by norepinephrine, KCl or electrical stimulation. Following chronic in vivo ethanol administration, increasing the calcium concentration to 5 mM blocked this inhibition. Nifedipine, a calcium channel antagonist inhibited vas deferens contractions. In the presence of nifedipine, in vitro ethanol further depressed vas deferens contractions stimulated by norepinephrine, K+ and by electrical stimulation. In vivo ethanol treatment attenuated ethanol's inhibition in vitro, and reduced the blocking effect of the calcium antagonist on mechanical responses of the vas in ethanol-free medium. These data suggest that changes in calcium mobilization are involved in both the acute action of ethanol and the development of tolerance.


Protein kinase C activity, protein phosphorylation and germinal vesicle breakdown in Spisula oocytes.
To test the possible role of protein kinase C (C-kinase) in regulating germinal vesicle breakdown (GVBD) in Spisula oocytes, we studied the effects of phorbol esters and antagonists of C-kinase on GVBD and protein phosphorylation. Responses to these agents were compared to those elicited by fertilization or increased extracellular K+. The tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent agonist of C-kinase, elicited GVBD with half-maximal stimulation at 20 nM. By contrast, 4 alpha-phorbol-12,13-didecanoate, a phorbol ester which does not stimulate C-kinase, did not trigger GVBD. TPA accelerated GVBD when induced by excess K+, but it did not affect the time course of the process when initiated by fertilization. Three structurally different antagonists of C-kinase (W-7, H-7, and retinol) all blocked GVBD when induced by fertilization or TPA. When oocytes were preincubated with [32P]orthophosphate and then stimulated to undergo GVBD by fertilization, TPA, or 45 mM K+, protein phosphorylation was greatly increased, especially for a polypeptide(s) of about 45 kDa. Phosphorylation increased prior to GVBD. Retinol inhibited phosphorylation in activated eggs. C-kinase activity was demonstrated in oocyte extracts. These results strongly suggest that protein phosphorylation by C-kinase is involved in the pathway that regulates GVBD in Spisula oocytes.


Study on Hematological and Biochemical Characters of Cloned Duroc Pigs and Their Progeny.
To increase public understanding in cloned animals produced by somatic cell nuclear transfer technology, our previous study investigated the carcass trait and meat quality of the clones (paper accepted), and this study we further evaluate differences by investigating the blood parameters in cloned pigs and their progeny. We collected blood samples from the clones and conventionally bred non-clones and their progeny, and investigated their hematological and blood biochemical characters. Our results supported the hypothesis that there was no significant difference between clones and non-clones, or their progeny. Taken together, the data demonstrated that the clones or their progeny were similar with their controls in terms of blood parameters, although there were still other kinds of disorders, such as abnormal DNA methylation or histone modifications that needs further investigation. The data in this study agreed that cloning technique could be used to preserve and enlarge the genetics of the superior boars in pig breeding industry, especially in facing of the deadly threat of African Swine fever happened in China.


Coupling AAA protein function to regulated gene expression.
AAA proteins (ATPases Associated with various cellular Activities) are involved in almost all essential cellular processes ranging from DNA replication, transcription regulation to protein degradation. One class of AAA proteins has evolved to adapt to the specific task of coupling ATPase activity to activating transcription. These upstream promoter DNA bound AAA activator proteins contact their target substrate, the σ(54)-RNA polymerase holoenzyme, through DNA looping, reminiscent of the eukaryotic enhance binding proteins. These specialised macromolecular machines remodel their substrates through ATP hydrolysis that ultimately leads to transcriptional activation. We will discuss how AAA proteins are specialised for this specific task.


Iatrogenic injury of the intrathoracic esophagus sustained during a gastric banding procedure.
The wide diffusion of laparoscopic adjustable gastric banding as a common surgical procedure for the treatment of morbidly obese patients can be attributed not only to the easy surgical technique, the ability to caliber the stoma, and the potential for reversibility, but also to the fact that this procedure is associated with a low rate of immediate postoperative complications compared to other more complex bariatric procedures. Herein reported is the case of a 63-year-old morbidly obese woman who sustained an iatrogenic injury of the intrathoracic esophagus during a laparoscopic adjustable gastric banding procedure. The putative mechanism of this previously unreported complication of laparoscopic adjustable gastric banding and the therapeutic options are discussed. The patient was initially treated with left pleural cavity drainage, antibiotics and the placement of an endoscopic silicone covered stent to cover the esophageal tear. Nine days later she underwent surgery through left thoracotomy due to the persistence of the esophageal leak. Esophageal perforation is a potentially life- threatening complication that may occur during a laparoscopic gastric banding procedure. The conservative treatment with an endoscopic stent should be reserved to patients with no signs of progressive systemic inflammation and include the drainage of the pleural cavity and the mediastinum, the endoscopic lavage and debridement. Standard surgical treatment with direct repair should not be retarded in case of persistence of the leak.


Protective effects of a culture supernatant of Lactobacillus acidophilus and antioxidants on ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug.
Ileal ulcers and thiobarbituric acid (TBA)-reactive substances in the ileal mucosa were induced in rats treated with a nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene (BFMeT), at a dose of 1,000 mg/kg administered with tap water as drinking water. However, the formation of ileal ulcers and TBA-reactive substances in the ileal mucosa was repressed by giving the animals a culture supernatant of Lactobacillus acidophilus as drinking water. We measured the antioxidative activity of the culture supernatant and found that the supernatant inhibited the formation of t-butyl hydroperoxide-induced TBA-reactive substances in erythrocyte membrane ghosts. Therefore, the effects of various known antioxidative compounds on the ileal ulcer formation induced by BFMeT were investigated. While alpha-tocopherol, t-butyl-1,4-hydroxyanisole and allopurinol did not repress ulcer formation after BFMeT treatment, ascorbic acid, dimethyl sulfoxide, glutathione and beta-carotene significantly inhibited formation. Among these compounds, ascorbic acid was the most effective. Accumulation of TBA-reactive substances in the ileal mucosa after BFMeT treatment also decreased significantly in rats treated with ascorbic acid. In addition, the percentage of gram-negative rods in the ileal contents of rats treated with BFMeT and tap water was dramatically increased, but it was not increased in rats treated with BFMeT and these antioxidants. A positive correlation between the percentage of gram-negative rods and the number of ileal ulcers was also observed. These results suggest that lipid peroxidation mediated by oxygen radicals plays an important role in the induction of ileal ulcers by BFMeT in rats, and that lipopolysaccharide-activated neutrophils probably produce highly reactive hypochlorous acid and hydrogen peroxide, which are inactivated by ascorbic acid and glutathione, respectively.


Plasma cell leukemia: Clinicopathologic, immunophenotypic and cytogenetic characteristics of 4 cases.
Plasma cell leukemia (PCL) is a rare hematologic malignancy with very poor outcome. It is defined by the presence of >2 × 10(9)/L plasma cells or >20% plasmacytosis of the differential white cell count in the peripheral blood. Primary PCL is first diagnosed in the leukemic phase, while secondary PCL corresponds to the leukemic transformation of a previously diagnosed multiple myeloma (MM). The incidence of PCL ranges between 2-4% of patients with MM and 0.9% of patients with acute leukemia. In this case series, we describe the clinicopathologic, immunophenotypic, and cytogenetic findings of four patients diagnosed with PCL within a ten-year period (2002-2012) at King Faisal Specialist Hospital and Research Centre (General Organization), Riyadh, Saudi Arabia.


A Comparative Photophysical Study of Structural Modifications of Thioflavin T-Inspired Fluorophores.
The benzothiazolium salt, Thioflavin T (ThT), has been widely adopted as the "gold-standard" fluorescent reporter of amyloid in vitro. Its properties as a molecular rotor result in a large-scale (∼1000-fold) fluorescence turn-on upon binding to β-sheets in amyloidogenic proteins. However, the complex photophysics of ThT combined with the intricate and varied nature of the amyloid binding motif means these interactions are poorly understood. To study this important class of fluorophores, we present a detailed photophysical characterization and comparison of a novel library of 12 ThT-inspired fluorescent probes for amyloid protein (PAPs), where both the charge and donor capacity of the heterocyclic and aminobenzene components have been interrogated, respectively. This enables direct photophysical juxtaposition of two structural groups: the neutral "PAP" (class 1) and the charged "mPAP" fluorophores (class 2). We quantify binding and optical properties at both the bulk and single-aggregate levels with some derivatives showing higher aggregate affinity and brightness than ThT. Finally, we demonstrate their abilities to perform super-resolution imaging of α-synuclein fibrils with localization precisions of ∼16 nm. The properties of the derivatives provide new insights into the relationship between chemical structure and function of benzothiazole probes.


Effects of hypothyroidism on the estrous cycle and reproductive hormones in mature female rat.
The present study was undertaken to examine the systemic role of thyroid hormones by analyzing changes in reproductive functions in hypothyroid female rats. Serum concentrations of triiodo-thyronine (T3) significantly decreased 1 week after the initiation of propyl-thiouracil treatment or thyroidectomy. The estrous cycle became irregular 3 and 2 weeks after the initiation of propyl-thiouracil treatment and thyroidectomy, respectively. Serum luteinizing hormone (LH) levels significantly reduced in both groups on the day of diestrus-1 about 1 month later. Hypothyroid rat shows the high progesterone and low testosterone levels. No significant changes in inhibin and estradiol levels were detected. The serum levels of FSH decreased in the thyroidectomy group. The irregular estrous cycle and the above changes in hormone levels were recovered by administration of T4. Compensatory secretions of FSH and LH induced by ovariectomy were enhanced by thyroidectomy and suppressed by T4 treatment. These results suggest that thyroid hormones play a role in the regulation of reproductive hormones secretion in the cyclic rat ovary.


Screening and verification for proteins that interact with leucine aminopeptidase of Taenia pisiformis using a yeast two-hybrid system.
Leucine aminopeptidase of Taenia pisiformis (TpLAP) belonging to the M17 peptidase family has been implicated as a stage-differentially expressed protein in the adult stage of T. pisiformis. In order to further dissect the biological functions of TpLAP in the growth and development of adult worms, TpLAP-interacting partners were investigated. In this study, a yeast two-hybrid (Y2H) cDNA library from adult T. pisiformis was constructed. Using pGBKT7-TpLAP as bait, proteins interacting with TpLAP were screened by Y2H system and positive preys were sequenced and analyzed using the Basic Local Alignment Search Tool (BLAST). Our results showed that six genuine TpLAP-interacting proteins, including LAP, dynein light chain (DLC), SUMO-conjugating enzyme (UBC9), histone-lysine n-methyltransferase, trans-acting transcriptional, and one unknown protein, were identified via Y2H assay. Furthermore, the interaction between TpLAP and UBC9 of T. pisiformis (TpUBC9), an important protein involved in SUMOylation pathway, was further validated by one-to-one Y2H assay, co-immunoprecipitation, and confocal analysis. These findings provide a deeper understanding of the biological functions of TpLAP and offer the first clue that TpLAP may act as a novel SUMOylated substrate, suggesting that the SUMO modification pathway plays an important role in regulation of adult worm growth and development.


B cells and CD4-CD8- T cells are key regulators of the severity of reactivation histoplasmosis.
The fungus, Histoplasma capsulatum, produces a persistent infection. Reactivation histoplasmosis is largely a result of impaired immunity, but the perturbations associated with escape of the fungus from host defenses remain ill-defined. We analyzed a murine model of reactivation to elucidate the host defects that permit reactivation. C57BL/6 mice were infected intranasally and, 42 days later, they were depleted of CD4(+) and CD8(+) cells. Elimination of these cells, but not either alone, produced a persistent infection over several weeks. Neutralization of IFN-gamma, TNF-alpha, or both did not induce reactivation. Endogenous IL-10 exacerbated reactivation. Depletion of T cells in B cell(-/-) mice induced a markedly higher burden in organs when compared with wild type. However, the infection remained persistent. Elimination of CD4(+) cells alone or neutralization of cytokines increased the fungal load. The persistent infection was not dependent on gammadelta T cells or NK cells. Elimination of Thy-1.2(+) cells in mice given mAb to CD4 and CD8 transformed reactivation into a progressive, lethal infection in B cell(-/-) and wild-type mice, but the tempo of progression was accelerated in the former. The data reveal the complex control by the host to prevent reactivation of this fungus.


CD spectra of isoionic DNA solutions.
The ion-exchange transition of Na-DNA----H-DNA in concentrated salt-free solutions is accompanied by strong variations in CD spectra. The rotational force of the negative band magnitude of delta epsilon 249 decreases when going to H-DNA by about 4 times, and the value of delta epsilon 279, by 1.2 times. These changes are irreversible to a considerable extent, which is evident because the spectra of Na-DNA obtained by neutralizing isoionic H-DNA solutions with NaOH or by the ion-exchange method significantly differ from those of Na-DNA taken by dissolving solid Na-DNA in deionized water. It has been shown that additions of NaCl to an isoionic solution of DNA leads to variations of spectra, typical for deprotonation processes as well as for an increase in DNA hydration.


Inositol pyrophosphates activate the vacuolar transport chaperone complex in yeast by disrupting a homotypic SPX domain interaction.
Many proteins involved in eukaryotic phosphate homeostasis are regulated by SPX domains. In yeast, the vacuolar transporter chaperone (VTC) complex contains two such domains, but mechanistic details of its regulation are not well understood. Here, we show at the atomic level how inositol pyrophosphates interact with SPX domains of subunits Vtc2 and Vtc3 to control the activity of the VTC complex. Vtc2 inhibits the catalytically active VTC subunit Vtc4 by homotypic SPX-SPX interactions via the conserved helix α1 and the previously undescribed helix α7. Binding of inositol pyrophosphates to Vtc2 abrogates this interaction, thus activating the VTC complex. Accordingly, VTC activation is also achieved by site-specific point mutations that disrupt the SPX-SPX interface. Structural data suggest that ligand binding induces reorientation of helix α1 and exposes the modifiable helix α7, which might facilitate its post-translational modification in vivo. The variable composition of these regions within the SPX domain family might contribute to the diversified SPX functions in eukaryotic phosphate homeostasis.


The chain conformational order of ergosterol- or cholesterol-containing DPPC bilayers as modulated by Amphotericin B: a FTIR study.
Amphotericin B (AmB) is the most widely used antibiotic to treat systemic fungal infections. However, the molecular mechanism of its activity is still not completely understood. In the present work we have used FTIR spectroscopy to investigate the conformational state of the aliphatic chains of DPPC liposomes using the 2850 cm(-1) band, associated with the methylene symmetric stretching mode. The liposomes were either binary mixtures of the lipid with AmB, cholesterol or ergosterol, or ternary systems of these constituents. The two sterols contribute to an ordering of the aliphatic chains of the lipid, this ordering being slightly more important with ergosterol. In the gel state, AmB does not change the conformational order of DPPC even at high concentration. In the fluid phase, however, the drug clearly structures its lipid environment. Our results show that AmB can initiate a redistribution of the ergosterol in the plane of the membrane, but not of the cholesterol molecules, which might constitute an additional mechanism to explain the activity of the antibiotic.


Promoting activity of the herbicide dicamba (2-methoxy-3, 6-dichlorobenzoic acid) in two stage hepatocarcinogenesis.
Our goal was to examine whether dicamba, a widely-used broad leaf herbicide, has promoting activity in two-stage hepatocarcinogenesis. Female Sprague Dawley rats were given a single dose of diethylnitrosamine and then diets containing dicamba, or phenobarbital, or both for six months. The number and volume of placental glutathione-S-transferase-positive, glucose-6-phosphatase-negative or ATPase-negative foci were quantified in the liver. Dicamba alone did not increase the number or volume of these altered hepatic foci. Dicamba did, however, show a significant effect on the number or volume of certain markers in animals also treated with phenobarbital. These data show that dicamba in combination with other promoters may have weak promoting activity in two-stage hepatocarcinogenesis in the rat.


Antioxidant peptides generated from chicken feet protein hydrolysates.
As major industrial poultry by-products, chicken feet are considered as notable sources of several bioactive molecules. The current work covers the processing of chicken feet proteins as substrates to be hydrolysed by combinations of three commercial enzymes (Alcalase®, Flavourzyme® and Protana® Prime) during different hydrolysis periods and the evaluation of the identified peptides having antioxidant activity after simulated gastrointestinal digestion. Enzymatic hydrolysis with Alcalase® and Protana® Prime combination for 4 h resulted in the highest activities. Reversed-phase high-performance liquid chromatographic separation of the purified hydrolysate yielded three active fractions that were further identified by nano-liquid chromatography-tandem mass spectrometry. The bioactivities of over 230 identified peptide sequences were estimated after simulated gastrointestinal digestion, and those peptides with the highest chance of exerting antioxidant activity were selected to be further synthesised and tested. In this sense, the synthesised dipeptides CF and GY showed the highest antioxidant capacity. CF presented IC50 values of 69.63 and 145.41 μmol L-1 in 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and oxygen radical absorbance capacity (ORAC) assays, respectively. In contrast, GY IC50 values were 15.27 and 10.06 μmol L-1 in ABTS and ORAC assays, respectively. Significant differences (P < 0.05) were registered between peptides in the same antioxidant assays. Overall, the findings emphasised the favourable impact of enzymatic hydrolysis with the obtaining of antioxidant peptides from poultry by-products that could be evaluated as a safe and economical source to retard oxidation in food systems. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Age-related loss of function of alloactivated interleukin 2-propagated human primed lymphocyte typing clones.
Human lymphocytes alloactivated in vitro were cloned by limiting dilution in the presence of filler cells and interleukin 2 (IL 2)-containing supernatants of phytohaemagglutinin-stimulated lymphocytes. Clones with allospecific proliferative reactivity (PLT clones), measured by tritiated thymidine (3H-TdR) incorporation, were selected for extensive IL 2-dependent expansion. The cloned lines had finite lifespans, ranging from an estimated minimum of 28 to greater than 65 doublings. Function as PLT reagents, however, was retained in all cases for only an estimated 30 cell doublings. This apparent cessation of function was not caused by loss of the ability to metabolize thymidine, since lines continuing to grow for greater than 30 doublings still incorporated 3H-TdR in the presence of IL 2. An altered requirement for stimulating antigen (number of stimulating cells), or altered response kinetics, did not contribute to loss of PLT function. Exogenous IL 2 added during restimulation to responders previously 'rested' overnight without IL 2 did not restore the response. Thus, under present experimental conditions, functional lifespans of cloned PLT reagents appear fixed at approximately 30 cell doublings.


[Available resources for the management of chronic obstructive pulmonary disease exacerbations in Spain].
Chronic obstructive pulmonary disease exacerbations (COPDE) lead to a high use of healthcare resources. This study assesses the healthcare and organisational resources of Spanish health care centres for the management of COPDE at different care levels (Primary Care (PC), Respiratory Diseases, Internal Medicine, and Emergency Departments), and compare with current recommendations. An observational study was carried out through telephone interviews to General Practitioners, Chest Diseases, Internal Medicine, and Emergency Department doctors. A total of 284 doctors were interviewed. According to their responses, at PC centres there is a high availability of pulse oximetry (98.9%) and electrocardiograph (100%), and a low availability of Chest X-Ray (19.1%), or urgent laboratory tests (17.0%) in sites. In hospital wards, non-invasive mechanical ventilation (NIV) availability was 76.1%, with only a 69.7% of nursing staff properly trained in its use. Respiratory intermediate care units (RICUs) were available in 18.3% of public hospitals versus 41.7% of private hospitals. Specific training for COPDE management was received by 47.9% of Emergency Department doctors in the previous year. Only 31.9% of PC centres had specific protocols for referring patients to specialists. More than 35% of PC centres and hospitals do not have their electronic medical records integrated with other healthcare levels. In general terms, there are sufficient resources available in Spanish healthcare centres. However, several areas of improvement were identified, such as an insufficient level of electronic medical record integration between healthcare levels, limited implementation of RICUs in public hospitals, and deficiencies related to specific training in NIV management.


A uniformity correction method to reduce scan time for 7T sodium imaging of brain tumors.
Sodium imaging shows great potential for the characterization of brain tumors. Intensity correction is required but the additional scan time is costly. Recent developments can halve the time but were optimized in normal brains and may not be applicable in brain tumor imaging. We aim to develop an individualized uniformity correction for sodium imaging optimized for brain tumor patients that reduces scan time but provides high-resolution images for clinical practice. Two-, 4-, and 6-mm iso-cubic voxel resolution birdcage coil images were used to calculate the 2-mm iso-cubic voxel individual sensitivity maps in healthy subjects (n = 3). Cut profiles were compared to determine the optimal approach. In addition, a 3-dimensional phantom was developed to test a generalized uniformity correction approach in both healthy subjects (n = 3) and tumor patients (n = 3). The cut profiles showed that the average correlation coefficient between 2- and 4-mm birdcage image correction results was r = .9937, and r = .9876 for 2- and 6-mm birdcage images. The correlation result between individual map correction and phantom map correction was r = .9817. The 4 mm birdcage coil image provided the optimal approach for both as a compromise between the time-savings effect and image quality. This method allows for a 2-mm iso-cubic voxel resolution clinical sodium scan within 12 minutes. We also presented prescanned phantom sensitivity map results, which were designed to cover all patient head sizes. This approach provides an alternative solution in more time-sensitive cases.


Nearly five-year continuous atmospheric measurements of black carbon over a suburban area in central France.
Atmospheric black carbon (BC) concentration over a nearly 5 year period (mid-2017-2021) was continuously monitored over a suburban area of Orléans city (France). Annual mean atmospheric BC concentration were 0.75 ± 0.65, 0.58 ± 0.44, 0.54 ± 0.64, 0.48 ± 0.46 and 0.50 ± 0.72 μg m-3, respectively, for the year of 2017, 2018, 2019, 2020 and 2021. Seasonal pattern was also observed with maximum concentration (0.70 ± 0.18 μg m-3) in winter and minimum concentration (0.38 ± 0.04 μg m-3) in summer. We found a different diurnal pattern between cold (winter and fall) and warm (spring and summer) seasons. Further, fossil fuel burning contributed >90 % of atmospheric BC in the summer and biomass burning had a contribution equivalent to that of the fossil fuel in the winter. Significant week days effect on BC concentrations was observed, indicating the important role of local emissions such as car exhaust in BC level at this site. The behavior of atmospheric BC level with COVID-19 lockdown was also analyzed. We found that during the lockdown in warm season (first lockdown: 27 March-10 May 2020 and third lockdown 17 March-3 May 2021) BC concentration were lower than in cold season (second lockdown: 29 October-15 December 2020), which could be mainly related to the BC emission from biomass burning for heating. This study provides a long-term BC measurement database input for air quality and climate models. The analysis of especially weekend and lockdown effect showed implications on future policymaking toward improving local and regional air quality as well.


Correlation Between Pain, Fear of Falling and Disability in Low Back Pain.
To ascertain if there is a correlation between low back pain (LBP), fear of falling, and disability so that the patients with LBP are aware of the fact that other problems may occur with LBP. Hence, steps can be taken for decreasing the fear of falling and disability in order to improve the condition of patients. A sample size of 100 patients with low back pain, with a range of ages from 40 to 73 years, participated in the study. The Falls Efficacy Scale was used to assess the fear of falling and the Oswestry Disability Index was used to assess the disability and pain in LBP individuals. The Pearson correlation analysis signifies the relationship between pain, fear of falling, and disability in LBP. First, LBP increases the fear of falling. Second, LBP can result in a person becoming disabled. Third, the fear of falling and disability are correlated with each other.


Davunetide: a review of safety and efficacy data with a focus on neurodegenerative diseases.
Davunetide is the first neuroprotective peptide in its class, and has preclinical evidence for neuroprotective, neurotrophic and cognitive protective properties. Davunetide has also been shown to prevent apoptosis or programmed-cell death in a range of in vitro and in vivo models by promoting microtubule stabilization. Potential clinical uses of davunetide include neurodegenerative disorders such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD) or cognitive impairment in other diseases such as schizophrenia where microtubule structure and function is known to be impaired. The nonclinical and clinical safety of davunetide is reviewed here in detail. Pre-clinical toxicology studies in rats and dogs using the maximum feasible dose of davunetide provide strong evidence that davunetide is well-tolerated. Similarly, data from 10 separate clinical trials of davunetide, investigating safety and efficacy provide evidence that davunetide is generally safe and well-tolerated, and has shown some signs of clinical efficacy.


Consequences of hyperthyroidism in male and female fertility: pathophysiology and current management.
Thyroid hormone acts on the oocytes, sperm and embryo during fertilization, implantation and placentation. Both hypothyroidism and hyperthyroidism may influence fertility. However, evidence of the association of hyperthyroidism with infertility is scarce and sometimes conflicting. Thyroid hormone influences human reproduction via a variety of mechanisms at both the central and the peripheral level. Infertility may occur in hyperthyroid men and women, but it is usually reversible upon restoration of euthyroidism. This review aims to summarize the available data on the association of hyperthyroidism and infertility in both men and women and to provide practical suggestions for the management of these patients.


A functional eEF2K-eEF2 pathway in the NAc is critical for the expression of cocaine-induced psychomotor sensitisation and conditioned place preference.
Recent evidence links synaptic plasticity and mRNA translation, via the eukaryotic elongation factor 2 kinase (eEF2K) and its only known substrate, eEF2. However, the involvement of the eEF2 pathway in cocaine-induced neuroadaptations and cocaine-induced behaviours is not known. Knock-in (KI) mice and shRNA were used to globally and specifically reduce eEF2K expression. Cocaine psychomotor sensitization and conditioned place preference were used to evaluate behavioural outcome. Changes in eEF2 phosphorylation were determined by western blot analyses. No effect was observed on the AMPA/NMDA receptor current ratio in the ventral tegmental area, 24 h after cocaine injection in eEF2K-KI mice compared with WT. However, development and expression of cocaine psychomotor sensitization were decreased in KI mice. Phosphorylated eEF2 was decreased one day after psychomotor sensitization and returned to baseline at seven days in the nucleus accumbens (NAc) of WT mice, but not in eEF2K-KI mice. However, one day following cocaine challenge, phosphorylated eEF2 decreased in WT but not KI mice. Importantly, specific targeting of eEF2K expression by shRNA in the NAc decreased cocaine condition place preference. These results suggest that the eEF2 pathway play a role in cocaine-induced locomotor sensitization and conditioned place preference.


Expression of carbamoyl-phosphate synthetase I mRNA in Reuber hepatoma H-35 cells. Regulation by glucocorticoid and insulin.
Reuber hepatoma H-35 cells actively synthesize the urea cycle enzyme, carbamoyl-phosphate synthetase I. Treatment of H-35 cells with dexamethasone (0.14 microM), however, enhanced synthesis of the enzyme (as measured by incorporation of [35S]methionine) by 4-5-fold. Insulin (0.18 microM) completely inhibited dexamethasone-dependent stimulation of enzyme synthesis. In vitro translation and cDNA hybridization assays were employed to measure effects of dexamethasone plus or minus insulin on levels of mRNA encoding the biosynthetic precursor of carbamoyl-phosphate synthetase I (pCPS) in Reuber H-35 cells. Both measurements yielded similar results: dexamethasone increased pCPS mRNA levels by 4-5-fold and insulin suppressed this response, but only by 50%. Specific cDNA hybridization assays also demonstrated that Reuber H-35 cells, even after hormone treatments, contain only very low levels of albumin mRNA, and no detectable ornithine carbamoyl-transferase mRNA.


What Are Optimal Blood Pressure Targets for Patients with Hypertension and Chronic Kidney Disease?
To maximize the risk benefit ratio of blood pressure control in people with chronic kidney diseases (CKD), a number of guidelines provide recommendations on optimal blood pressure (BP) targets in CKD. This review examines these guidelines, their supporting evidence base, and generalizability and limitations of current standards of care. Over the years, the BP targets are liberalized. They now focus on the usual BP target of <140/90 mmHg. In the elderly, where guidelines call for a target of <150/90 mmHg in the general population, the recommendations provide room for the clinician to tailor therapy. Among those with albuminuria of >300 mg/g creatinine, low-quality evidence suggests targeting BP to <130/90 mmHg. Individualization of BP lowering is a key based on comorbid conditions, response to treatment, and level of kidney function. Consideration of out of clinic BP monitoring either implemented by home BP recordings or ambulatory BP measurements may enhance BP control.


Topographic description of an alternative insertion technique for percutaneous approach of cricopharyngeus muscle electromyography: a cadaveric and clinical study.
Cricopharyngeus is the only muscle for which electromyography is used in the differential diagnosis of swallowing disorders. Because of some practical difficulties, electrophysiologic tests for this muscle are not performed routinely. Thus we aimed to describe an alternative topographic way to reach the muscle easily. On 10 cadavers, a spinal needle (20 G) and on 37 patients a concentric needle electrode (26 G) were used. The needle was inserted percutaneous at the level of the superior border of the cricoid cartilage, anterior to the anterior border of the sternocleidomastoid muscle at 60 degrees angle to the frontal plane in the posteromedial direction. We reached the muscle in all cadavers. In all of the patients, the needle entered the muscle on the first attempt; that was confirmed by electromyographic responses. Our results show that this method can be useful for the practical application of cricopharyngeus muscle electromyography.


Role of telemedicine during COVID-19 pandemic in type 2 diabetes outpatients: The AMD annals initiative.
Telemedicine is advocated as a fundamental tool in modern clinical management. However, data on the effects of telemedicine vs face-to-face consultation on clinical outcomes in type 2 diabetes (T2DM) are still uncertain. This paper describes the use of telemedicine during the 2020 COVID-19 emergency and compares volume activity and quality indicators of diabetes care between face-to-face vs telemedicine counseling in the large cohort of T2DM patients from the AMD Annals Initiative. Demographic and clinical characteristics, including laboratory parameters, rate of the screening of long-term complications, current therapies and the Q-score, a validated score that measures the overall quality of care, were compared between 364,898 patients attending face-to-face consultation and 46,424 on telemedicine, during the COVID-19 pandemic. Patients on telemedicine showed lower HbA1c levels (7.1 ± 1.2 % vs 7.3 ± 1.3 %, p < 0.0001), and they were less frequently treated with metformin, GLP1-RAs and SGLT2i and more frequently with DPP4i. The telemedicine group showed reduced monitoring of the various parameters considered as process indicators, especially, eye and foot examination. The proportion of patients with a good quality of care (Q score > 25) was higher among those receiving face-to-face consultation. Moreover, in the telemedicine group, all major clinical outcomes remained stable when further compared to those collected in the year 2019, when the same patients underwent a regular face-to-face consultation, suggesting that the care provided through telemedicine did not negatively affect the most important parameters. During the COVID-19 pandemic, telemedicine provided an acceptable quality of diabetes care, comparable to that of patients attending face-to-face consultation, although a less frequent screening of complications seems to have occurred in subjects consulted by telemedicine.


Operationally defined mercury (Hg) species can delineate Hg bioaccumulation in mangrove sediment systems: A case study.
This study investigated the linkage between mercury (Hg) speciation in the surficial sediments from a mangrove ecosystem of the Zuari Estuary, west coast of India, with Hg bioaccumulation in gastropods collected from the same area. Multiple operationally defined protocols and methods were used for determination of Hg speciation study in the mangrove sediments. Moderately low concentrations of Hg were observed in the sediments, ranging from 37.3 ± 1.9 to 79.6 ± 4.0 µg/kg. Geochemical fractionation showed that a significant part of sedimentary Hg was present within the structure of the sediment (residual fraction) and not bioavailable. Non-residual Hg was primarily associated with oxidizable (sedimentary organic matter (SOM) or sulfide) binding phase of the sediments, and ranged from 9.2 ± 0.3 to 78.5 ± 3.9 µg/kg. Concentration of methylmercury (MeHg) (a neurotoxin) in the sediments varied from 1.7 ± 0.1 to 4.4 ± 0.1 µg/kg. l-Cysteine, a suitable complexing ligand, extractable Hg concentration in the sediments ranged from 4.3 ± 0.1 to 15.9 ± 0.3 µg/kg. Statistical analysis suggested that MeHg was adsorbed on Fe/Mn oxyhydroxide phases in the sediments. l-Cysteine was found to extract sedimentary MeHg and thermodynamically less stable Hg-SOM complexes from the sediments. Concentrations of bioaccumulated Hg in soft tissues of the gastropod, Pirenella cingulata, ranged from 57.6 ± 4.4 to 224.4 ± 7.2 µg/kg. Positive correlations existed between the concentration of bioaccumulated Hg in the gastropods and the concentrations of Hg associated with the oxidizable phase, sedimentary MeHg and l-Cysteine extracted Hg in the sediments. This study indicated that operationally defined Hg species can be useful in estimating bioavailable Hg to obligatory deposit feeder in tropical mangrove systems.


A rationalization of the effects of anti-oestrogens and oestrogens on uterine RNA synthesis in the immature rat.
A series of oestrogens and anti-oestrogens have been compared with respect to their effects on RNA synthesis in the uterus of immature rats. The normal transcriptional response to oestrogen is a biphasic stimulation of transcription. The first phase is a sharp stimulation of RNA synthesis, 2-4 h after hormone administration which peaks at 7-11-fold unstimulated controls but which rapidly falls to near control levels by 8 h after injection. The second phase is a broad peak of RNA synthesis, typically lasting from 12-32 h after hormone administration and accompanied to a much greater extent than the first phase by increases in precursor pool sizes. Oestradiol-17 beta does not show the second phase of this response. This is presumably due to rapid metabolism as derivatives with a longer tissue half life induce the complete response. The first phase of the response is not induced by tamoxifen but is by monohydroxy tamoxifen.


An electrochemical immunosensor for aflatoxin M1 determination in milk using screen-printed electrodes.
The production and assembling of disposable electrochemical AFM1 immunosensors, which can combine the high selectivity of immunoanalysis with the ease of the electrochemical probes, has been carried out. Firstly immunoassay parameters such as amounts of antibody and labelled antigen, buffer and pH, length of time and temperature of each steps (precoating, coating, binding and competition steps) were evaluated and optimised in order to set up a spectrophotometric enzyme-linked immunosorbent assay (ELISA) procedure. This assay exhibited a working range between 30 and 160 ppt in a direct competitive format. Then electrochemical immunosensors were fabricated by immobilising the antibodies directly on the surface of screen-printed electrodes (SPEs), and allowing the competition to occur between free AFM1 and that conjugated with peroxidase (HRP) enzyme. The electrochemical technique chosen was the chronoamperometry, performed at -100 mV. Furthermore, studies of interference and matrix effects have been performed to evaluate the suitability of the developed immunosensors for the analysis of aflatoxin M1 directly in milk. Results have shown that using screen-printed electrodes aflatoxin M1 can be measured with a detection limit of 25 ppt and with a working range between 30 and 160 ppt. A comparison between the spectrophotometric and electrochemical procedure showed that a better detection limit and shorter analysis time could be achieved using electrochemical detection.


Incidence of malignant neoplasms among HIV-infected persons in Scotland.
Among 2574 persons diagnosed with HIV throughout Scotland and observed over the period 1981-1996, cancer incidence compared to the general population was 11 times higher overall; among homosexual/bisexual males, it was 21 times higher and among injecting drug users, haemophiliacs and heterosexuals it was five times higher, mostly due to AIDS-defining neoplasms. However, liver, lung and skin cancers (all non-AIDS-defining) were also significantly increased.


Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog. IV. Energy mechanisms during very early ischemia.
Tissue energy metabolism was examined in posterior (ischemic) and anterior ("control") regions of canine ventricles after 5 and 10 minutes of left circumflex coronary artery occlusion. When compared to identical regions of normal hearts, the following changes were found: (1) decreases in glycogen and phosphorylase activity in the anterior and posterior regions, (2) depressed state 3 rates of oxygen consumption of isolated mitochondria in both anterior and posterior regions, (3) shifts in optimum substrate concentrations for palmityl-CoA (+ carnitine) oxidation by mitochondria in the anterior and posterior regions, and (4) decreases in the apparent zero order and first order rates of mitochondrial palmitylcarnitine production. These changes correlated with a marked decrease in developed tension in the posterior regions. Depression in tension development in the posterior regions of the heart still was present after 30--60 minutes of reperfusion following a 10-minute period of occlusion. Glycogen content in the reperfused areas was significantly decreased after 60 minutes of reperfusion when compared to normal areas and to control hearts perfused for 70 minutes. After reperfusion, mitochondrial function appeared to return toward "normal." However, the slow restoration of contraction of the ischemic area suggests that cellular mechanisms operative in vivo to restore pump function still might be abnormal.


Experimental infection of domestic pigs with the virus of peste des petits ruminants.
Pigs could be subclinically infected with PPRV by inoculation or contact with infected goats. There was no evidence that the virus could spread to uninfected pigs or goats and pigs are not considered important in the epidemiology of PPRV.


Meta-analysis of pre-clinical studies on the effects of opioid receptor ligands on food intake, motivation, and choice.
The opioid receptors (OR) regulate food intake. Still, despite extensive pre-clinical research, the overall effects and individual contribution of the mu (MOR), kappa (KOR), and delta (DOR) OR subtypes to feeding behaviors and food intake remain unclear. To address this, we conducted a pre-registered systematic search and meta-analysis of rodent dose-response studies to evaluate the impact of central and peripheral administration of non-selective and selective OR ligands on intake, motivation, and choice of food. All studies had a high bias risk. Still, the meta-analysis confirmed the overall orexigenic and anorexigenic effects of OR agonists and antagonists, respectively. Our results support a larger orexigenic role for central MOR agonists among OR subtypes and that peripheral OR antagonists reduce motivation for and intake of preferred foods. In binary food choice studies, peripheral OR agonists selectively increase the intake of fat-preferred foods; in contrast, they did not increase the intake of sweet carbohydrate-preferred foods. Overall, these data support that OR regulation of intake, motivation, and choice is influenced by food macronutrient composition.