Effect of endurance training on coronary artery size and function in healthy men: an invasive followup study.
In eight healthy male volunteers (cardiologists; age 36 +/- 5 yr), bicycle spiroergometry, Doppler echocardiography, and quantitative coronary angiography with intracoronary Doppler measurements before and after completion of a physical endurance exercise program of >5 mo duration were performed. Maximum oxygen uptake increased from 46 +/- 6 to 54 +/- 5 ml x kg(-1) x min(-1) (P = 0.04), maximum ergometric workload changed from 3.8 +/- 0.3 to 4.4 +/- 0.3 W/kg (P = 0.001), and left ventricular mass index increased from 82 +/- 18 to 108 +/- 29 g/m(2) (P = 0.001). The right, left main, and left anterior descending coronary artery cross-sectional area increased significantly in response to exercise. Before versus at the end of the exercise program, flow-induced left anterior descending coronary artery cross-sectional area was 10.1 +/- 3.5 and 11.0 +/- 3.9 mm(2), respectively (P = 0.03), nitroglycerin-induced left coronary calibers increased significantly, and coronary flow velocity reserve changed from 3.8 +/- 0.8 to 4.5 +/- 0.7 (P = 0.001). Left coronary artery correlated significantly with ventricular mass and maximum oxygen uptake, and coronary flow velocity reserve was significantly associated with maximum workload.


Backward Double Integration is a Valid Method to Calculate Maximal and Sub-Maximal Jump Height.
The backward double integration method uses one force plate and could calculate jump height for countermovement jumping, squat jumping and drop jumping by analysing the landing phase instead of the push-off phase. This study compared the accuracy and variability of the forward double integration (FDI), backwards double integration (BDI) and Flight Time + Constant (FT+C) methods, against the marker-based rigid-body modelling method. It was hypothesised that the jump height calculated using the BDI method would be equivalent to the FDI method, while the FT+C method would have reduced accuracy and increased variability during sub-maximal jumping compared to maximal jumping. Twenty-four volunteers performed five maximal and five sub-maximal countermovement jumps, while force plate and motion capture data were collected. The BDI method calculated equivalent mean jump heights compared to the FDI method, with only slightly higher variability (2-3 mm), and therefore can be used in situations where FDI cannot be employed. The FT+C method was able to account for reduced heel-lift distance, despite employing an anthropometrically scaled heel-lift constant. However, across both sub-maximal and maximal jumping, it had increased variability (1.1 cm) compared to FDI and BDI and should not be used when alternate methods are available.


Effect of cigarette smoking upon reproductive hormones in women of reproductive age: a retrospective analysis.
There is continuing debate concerning the relationship between cigarette smoking and premature ovarian failure. The aim of this retrospective data analysis was to investigate whether smoking has a measurable effect on early follicular serum concentrations of inhibin B hormone, FSH and anti-Müllerian hormone (AMH) in women of reproductive age. A database containing data on age, smoking status and serum concentrations of inhibin B, FSH and AMH was analysed. Pearson's correlation coefficient was calculated to determine the correlation between hormone concentrations and age. One-way analysis of variance was used to determine any significant difference in age between smoking categories and a univariate general linear model was used to compare geometric means and geometric mean ratios of hormone concentrations in relation to smoking status. Serum concentrations of inhibin B were significantly lower in women who had ever smoked cigarettes: F(2,332) = 3.371, P = 0.036. There was no statistically significant difference in FSH or AMH concentrations although a trend towards lower AMH concentrations in smokers was observed. This analysis provides evidence of an advancement of ovarian ageing in women who smoke cigarettes and is relevant to women of childbearing age who wish to avoid premature decline in fertility.


Challenges in Healing Wound: Role of Complementary and Alternative Medicine.
Although the word wound sounds like a simple injury to tissue, individual's health status and other inherent factors may make it very complicated. Hence, wound healing has gained major attention in the healthcare. The biology wound healing is precise and highly programmed, through phases of hemostasis, inflammation, proliferation and remodeling. Current options for wound healing which includes, use of anti-microbial agents, healing promoters along with application of herbal and natural products. However, there is no efficient evidence-based therapy available for specific chronic wounds that can result in definitive clinical outcomes. Under co-morbid conditions, chronic would poses numerous challenges. Use of Complementary and Alternative Medicines (CAMs) in health care sector is increasing and its applications in wound management remains like to "separate the diamonds from ore." Attempts have been made to understand the wound at the molecular level, mainly through the analysis of signature genes and the influence of several synthetic and natural molecules on these. We have outlined a review of challenges in chronic wound healing and the role of CAMs in chronic wound management. The main focus is on the applications and limitations of currently available treatment options for a non-healing wound and the best possible alternates to consider. This information generates broader knowledge on challenges in chronic wound healing, which can be further addressed using multidisciplinary approach and combination therapies.


[Establishment of a rabbit model of small diameter vascular graft replacement].
To establish an rabbit model that mimics the hemodynamics of the bypass graft after coronary artery bypass surgery. Sixteen New Zealand rabbits were randomly divided into two groups for abdominal aortic artery replacement using a 3-cm-long ePTFE graft with an inner diameter 4 mm through an incision at 1/3 from the middle to the lower part of the abdomen (group A) or in the lower abdomen (group B). The general conditions of the rabbits, operative time, number of collateral vessels that needed to be ligated, rate of massive intraoperative bleeding, fluctuation of vascular anastomosis after surgery, patency rate of the graft on day 7 after the operation were compared between the two groups. The two groups of rabbits had similar body weight, diameter of the abdominal aortic artery, intraoperative bleeding rate and occlusion rate of the vascular graft at 7 days after the procedure. The operative time was longer in group A, but the difference was not statistically significant. In group A, the number of the vascular branches that needed to be ligated was smaller and the rate normal femoral artery pulsation was higher than those in group B. It is feasible to establish models of small diameter vascular graft replacement in rabbits, and the patency rate of the graft can be monitored by observation of the general condition and ultrasound examination of the rabbits.


Cytomorphologic differentiation of Hodgkin's lymphoma and Ki-1+ anaplastic large cell lymphoma in fine needle aspirates.
To cytomorphologically differentiate Hodgkin's lymphoma (HL) from Ki-1+ anaplastic large cell lymphoma (ALCL) in fine needle aspirates. We blindly reviewed 63 fine needle aspiration (FNA) smears from histologically and immunophenotypically proven cases of ALCL (n = 15) and HL (n = 48). The smears were reviewed for the following criteria: (1) estimated percentages of abnormal cells, (2) pattern of the smears (polymorphous vs. dimorphous), and (3) presence or absence of multilobated cells. All cases were phenotyped by immunohistochemistry for CD3, CD15, CD20, CD30 and CD45, with flow cytometric immunophenotpyping in 41 cases. Flow cytometric phenotyping was not successful in any of the cases. The smears were polymorphous in all 15 cases of ALCL and in 1 case of HL (2%). The percentage of abnormal cells ranged from 10% to 90% in cases of ALCL (median, 30%) whereas it ranged from 1% to 25% in HL (median 3%; P = .0003). Three cases of HL showed abnormal cells constituting > or = 20% of the smears. They were all grade 2 disease. Multilobated cells were identified in 14 of the 15 cases of ALCL (93%) and in 3 of the 48 cases of HL (6.25%; P = .0008). Our findings indicate that the differentiation of ALCL from HL can be achieved in FNA smears through identification of abnormal cells representing > 30% of the population, a spectrum of abnormal cells and the presence of multilobated nuclei. Rare cases of grade 2 HL may be difficult to differentiate from ALCL.


Encoder: a connectionist model of how learning to visually encode fixated text images improves reading fluency.
This article proposes that visual encoding learning improves reading fluency by widening the span over which letters are recognized from a fixated text image so that fewer fixations are needed to cover a text line. Encoder is a connectionist model that learns to convert images like the fixated text images human readers encode into the corresponding letter sequences. The computational theory of classification learning predicts that fixated text-image size makes this learning difficult but that reducing image variability and biasing learning should help. Encoder confirms these predictions. It fails to learn as image size increases but achieves humanlike visual encoding accuracy when image variability is reduced by regularities in fixation positions and letter sequences and when learning is biased to discover mapping functions based on the sequential, componential structure of text. After training, Encoder exhibits many humanlike text familiarity effects.


Preparation for NCLEX-RN: an innovative course. National Council Licensure Examination.
In summary, a course with a content review format is frustrating to both students and faculty because an attempt is made to cover all nursing clinical disciplines in a short time period. The preparation for NCLEX-RN course format was changed from a primarily content review to a test-taking approach. The student is given a Decision-Making Model for eliminating response choices for questions to which they do not already know the answer. This was found to be a positive change for both students and faculty. This innovative approach to the NCLEX-RN review would be beneficial for other state board review courses.


Comparison of surface iodination methods by electron microscopic autoradiography applied in vitro to different life-stages of Dipetalonema viteae (Filarioidea).
Different states of Dipetalonema viteae (males, females, microfilariae, and 3rd-stage larvae) have been iodinated in vitro under physiological conditions by chloroglycoluril, lactoperoxidase or chloramine T. The concentrations of the catalysts were correlated with the viability of the worms. Localization of the label with the different iodination methods had been visualized by electro microscopical autoradiography. Chloroglycoluril-mediated iodination is predominantly localized on the filarial cuticle. Lactoperoxidase-catalysed iodination is less specific and chloramine T catalyses iodination in a gradient decreasing from the cuticle to inner structures. It is necessary to visualize the labelling by electron microscopical autoradiography prior to biochemical and immunological experiments to avoid the extraction of structures iodinated by leakage of the catalyst into sub-cuticular regions.


[Posterior reversible encephalopathy syndrome: Report of a fatal case and analysis of predictive factors of a poor prognosis].
Posterior reversible encephalopathy syndrome is an illness with multiple causes and distinctive clinicalradiological characteristics that should be known by intensivists and emergency room physicians for a timely diagnosis and treatment. A fatal case of posterior reversible encephalopathy syndrome is presented, and the risk factors related to the outcome are identified.A 60-year-old man without a relevant medical history arrived at the emergency room presenting with depressed consciousness, seizures, and high blood pressure. Tomographic images revealed a posterior cerebellar hematoma. Resonance images showed ischemic zones, vasogenic edema from the thalamus to the brain stem, middle cerebellar peduncles, deep white matter of the cerebral hemispheres, and zones of hemorrhagic transformation. Despite medical-surgical management, the patient died. The risk factors described as the cause of the fatal outcome were identified. This case demonstrates that posterior reversible encephalopathy syndrome can occur without triggering risk factors and highlights the need for early recognition to establish an appropriate intervention to avoid injury or a fatal outcome. Cases of posterior reversible encephalopathy syndrome provide opportunities to investigate the susceptibility for the development of this condition and to establish appropriate preventive measures.


[Absence of nephro-protective effect of acetylcysteine in patients with chronic renal failure investigated by coronary angiography].
Recent studies have suggested that an oral dose of acetylcysteine could play a prophylactic role in the prevention of nephrotoxicity from iodine contrast media in patients affected by chronic renal failure. Between June 2001 and September 2002 we selected 120 patients with a basal plasma creatinine level greater than 1.36 mg/dl investigated by coronary angiography. The treatment group included 60 patients who received 600 mg of acetylcysteine in the morning and evening before the day of the examination together with intravenous saline hydration. The control group patients received hydration alone. The clinical characteristics of the groups were comparable as well as the basal plasma creatinine level: 2.01+/-1.1 mg/dl in the acetylcysteine group and 1.81+/-0.69 in the control group. The plasma creatinine level was measured 24 and 48 hours after coronary angiography. The respective changes in plasma creatinine level at 24 and 48 hours were 0.12+/-0.29 and 0.02+/-0.29 mg/dl in the acetylcysteine group and 0.06+/-0.29 and 0.07+/-0.43 mg/dl in the control group (NS). Acute renal failure caused by the contrast medium, defined by an increase of 25% in the plasma creatinine level compared to the basal value, occurred in 3 patients from the acetylcysteine group and 2 patients from the control group. The only predictive factor for acute renal failure was the quantity of contrast medium (316+/-141 vs 173+/-115 ml, p<0.05). In conclusion, acute renal failure caused by contrast medium is rare in sufficiently hydrated patients with moderate chronic renal failure when a low dose of contrast medium is used. Our study does not confirm a prophylactic effect of acetylcysteine in the prevention of nephrotoxicity from contrast media following coronary angiography in patients with moderate chronic renal failure.


Mature miRNAs form secondary structure, which suggests their function beyond RISC.
The generally accepted model of the miRNA-guided RNA down-regulation suggests that mature miRNA targets mRNA in a nucleotide sequence-specific manner. However, we have shown that the nucleotide sequence of miRNA is not the only determinant of miRNA specificity. Using specific nucleases, T1, V1 and S1 as well as NMR, UV/Vis and CD spectroscopies, we found that miR-21, miR-93 and miR-296 can adopt hairpin and/or homoduplex structures. The secondary structure of those miRNAs in solution is a function of RNA concentration and ionic conditions. Additionally, we have shown that a formation of miRNA hairpin is facilitated by cellular environment.Looking for functional consequences of this observation, we have perceived that structure of these miRNAs resemble RNA aptamers, short oligonucleotides forming a stable 3D structures with a high affinity and specificity for their targets. We compared structures of anti-tenascin C (anti-Tn-C) aptamers, which inhibit brain tumor glioblastoma multiforme (GBM, WHO IV) and selected miRNA. A strong overexpression of miR-21, miR-93 as well Tn-C in GBM may imply some connections between them. The structural similarity of these miRNA hairpins and anti-Tn-C aptamers indicates that miRNAs may function also beyond RISC and are even more sophisticated regulators, that it was previously expected. We think that the knowledge of the miRNA structure may give a new insight into miRNA-dependent gene regulation mechanism and be a step forward in the understanding their function and involvement in cancerogenesis. This may improve design process of anti-miRNA therapeutics.


Epidemiology of community-acquired methicillin-resistant Staphylococcus aureus skin infections among healthcare workers in an outpatient clinic.
We describe an investigation of soft-tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains in 2 healthcare workers employed in an outpatient clinic for patients with human immunodeficiency virus infection. Cultures of environmental samples from multiple surfaces in the clinic grew toxin-producing CA-MRSA strains, suggesting fomites may play a role in the transmission of these strains of MRSA.


A Study of Vicon System Positioning Performance.
Motion capture setups are used in numerous fields. Studies based on motion capture data can be found in biomechanical, sport or animal science. Clinical science studies include gait analysis as well as balance, posture and motor control. Robotic applications encompass object tracking. Today's life applications includes entertainment or augmented reality. Still, few studies investigate the positioning performance of motion capture setups. In this paper, we study the positioning performance of one player in the optoelectronic motion capture based on markers: Vicon system. Our protocol includes evaluations of static and dynamic performances. Mean error as well as positioning variabilities are studied with calibrated ground truth setups that are not based on other motion capture modalities. We introduce a new setup that enables directly estimating the absolute positioning accuracy for dynamic experiments contrary to state-of-the art works that rely on inter-marker distances. The system performs well on static experiments with a mean absolute error of 0.15 mm and a variability lower than 0.025 mm. Our dynamic experiments were carried out at speeds found in real applications. Our work suggests that the system error is less than 2 mm. We also found that marker size and Vicon sampling rate must be carefully chosen with respect to the speed encountered in the application in order to reach optimal positioning performance that can go to 0.3 mm for our dynamic study.


Therapeutic approaches in the treatment of gout.
Gout is a disease in which the metabolic condition hyperuricemia leads to the formation of monosodium urate crystals, which provoke acute and chronic inflammatory responses through activation of the innate immune system. Recent advances in our knowledge of gout pathogenesis have emphasized the role of the kidneys in urate handling, the evolutionary loss of uricase as a necessary precondition for hyperuricemia, and the central role of IL-1ß in the pathogenesis of gouty inflammation. These, and other advances, have shaped our current strategies for managing gout. Here, we review the most current, evidence-based gout management approaches, including treating acute flares, addressing gout through the long-term regulation of serum urate, and prophylaxis against gouty flares during urate lowering.


[Traumatic rupture of the pericardium--the source of massive haemothorax, a case report].
Extensive traumatic haemothorax is a life-threatening condition that requires the surgeon's resolute approach. Massive bleeding may first lead to hypovoleamic shock, then to haemorrhagic shock. The most common sources are bleeding from the chest wall (intercostal artery), bleeding when the lung parenchyma or major intrathoracic vessels are injured. The case report describes a rare case of massive right-sided haemothorax in pericardial rupture with cardiac herniation in a patient with polytrauma when the source of bleeding was artery pericardium. The report draws attention to the treacherousness of the diagnosis in a polytraumatised patient; the report retrospectively evaluates the interpretation of imaging examinations that were carried out


[Two allelic genes of human p53 code for proteins differing with respect to amino acid sequence].
Two allelic p53 genes were investigated. The allelic gene with BgIII site in the first intron codes for faster p53 protein variant, the other allelic gene coding for slower p53 protein variant (according to the mobility in SDS-PAAG). Exons and flanked regions of introns were sequenced. In coding regions allelic genes only differ by second nucleotides of codon 72 (G----C), which leads to the change in amino acid sequence (Arg----Pro). The relationship of these changes and the function of p53 is discussed.


[Monoclonal analysis of immunoglobulin heavy chain and T-cell receptor gamma chain gene rearrangements in paraffin-embedded tissues from non-Hodgkin lymphoma patients].
Gene rearrangement is an important diagnostic marker of malignant lymphoma, and rearrangements of the immunoglobulin heavy chain (IgH) and T-cell receptor gamma chain (TCRgamma) genes are useful markers for Band T-cell lymphoma, respectively. A polymerase chain reaction (PCR) can be used to analyze clonality in formalin-fixed paraffin-embedded specimens. We performed 73 monoclonal analyses of such specimens of lymphoma tissues and examined the ability to diagnose malignant lymphoma by this method. Monoclonality of lymphoma cells was found in 71.9% and 78.9% of specimens with IgH and TCRgamma gene rearrangements, respectively. Therefore, in diagnosing cases of non-Hodgkin lymphoma in which neoplasms and reactive lymphoid tissues are difficult to identify by morphological and immunohistochemical findings, PCR-based monoclonal analysis may allow confirmation of a pathological diagnosis of malignant lymphoma.


Transcription Factor CREM Mediates High Glucose Response in Cardiomyocytes and in a Male Mouse Model of Prolonged Hyperglycemia.
This study aims at investigating the epigenetic landscape of cardiomyocytes exposed to elevated glucose levels. High glucose (30 mM) for 72 hours determined some epigenetic changes in mouse HL-1 and rat differentiated H9C2 cardiomyocytes including upregulation of class I and III histone deacetylase protein levels and activity, inhibition of histone acetylase p300 activity, increase in histone H3 lysine 27 trimethylation, and reduction in H3 lysine 9 acetylation. Gene expression analysis focused on cardiotoxicity revealed that high glucose induced markers associated with tissue damage, fibrosis, and cardiac remodeling such as Nexilin (NEXN), versican, cyclic adenosine 5'-monophosphate-responsive element modulator (CREM), and adrenoceptor α2A (ADRA2). Notably, the transcription factor CREM was found to be important in the regulation of cardiotoxicity-associated genes as assessed by specific small interfering RNA and chromatin immunoprecipitation experiments. In CD1 mice, made hyperglycemic by streptozotoicin (STZ) injection, cardiac structural alterations were evident at 6 months after STZ treatment and were associated with a significant increase of H3 lysine 27 trimethylation and reduction of H3 lysine 9 acetylation. Consistently, NEXN, CREM, and ADRA2 expression was significantly induced at the RNA and protein levels. Confocal microscopy analysis of NEXN localization showed this protein irregularly distributed along the sarcomeres in the heart of hyperglycemic mice. This evidence suggested a structural alteration of cardiac Z-disk with potential consequences on contractility. In conclusion, high glucose may alter the epigenetic landscape of cardiac cells. Sildenafil, restoring guanosine 3', 5'-cyclic monophosphate levels, counteracted the increase of CREM and NEXN, providing a protective effect in the presence of hyperglycemia.


[Retinal imaging in hereditary chorioretinal dystrophies].
The paper presents retinal imaging (color and red-free photografs, fluorescein angiograms and optical coherence tomography) of the most common hereditary chorioretinal dystrophies: retinitis pigmentosa, Stargardt's disease, choroideremia, cone dystrophy vitteliform dystrophy. Retinal imaging has an important role in the diagnosis and the follow-up of these diseases, but genetic investigations are frequently necessary.


Sampling Lasioderma serricorne (Coleoptera: Anobiidae) in 2 coffee bean warehouses in New Jersey.
Cigarette beetle, Lasioderma serricorne (F.), is one of the most common stored-product pests. We monitored their population dynamics and distribution in two coffee bean warehouses in New Jersey, USA, using pheromone traps and sticky traps during September 2018-October 2020, and light traps in 2020. The two warehouses only implemented treatment procedures for controlling Indian meal moth (Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae)) during the study period. The first L. serricorne adult appeared on pheromone traps from late May to early June when temperature reached 21-22 °C, and the last L. serricorne adult appeared on pheromone traps from late October to mid-November when temperature dropped to 10-14 °C. The majority of L. serricorne was caught during July-October. Light traps caught 5.5- and 2.2-times more L. serricorne per trap than pheromone traps in Warehouse 1 and 2, respectively. Warehouse 1 had a significantly higher density of L. serricorne than Warehouse 2. The L. serricorne activity peaks were not always clear and varied between year and the two warehouses. Zero to 3 hot spots, where had the largest numbers of L. serricorne, were identified from July to October in each warehouse based on pheromone traps, and their locations were similar through the months both in 2019 and 2020. The L. serricorne counts from pheromone traps placed inside warehouse were at least 2.3-times more than those placed outside. Also, the L. serricorne active period outside of the warehouses was shorter than that from inside of the warehouses.


Validation of Acoustic Wave Induced Traumatic Brain Injury in Rats.
This study looked to validate the acoustic wave technology of the Storz-D-Actor that inflicted a consistent closed-head, traumatic brain injury (TBI) in rats. We studied a range of single pulse pressures administered to the rats and observed the resulting decline in motor skills and memory. Histology was observed to measure and confirm the injury insult. Four different acoustic wave pressures were studied using a single pulse: 0, 3.4, 4.2 and 5.0 bar (n = 10 rats per treatment group). The pulse was administered to the left frontal cortex. Rotarod tests were used to monitor the rats' motor skills while the water maze test was used to monitor memory deficits. The rats were then sacrificed ten days post-treatment for histological analysis of TBI infarct size. The behavioral tests showed that acoustic wave technology administered an effective insult causing significant decreases in motor abilities and memory. Histology showed dose-dependent damage to the cortex infarct areas only. This study illustrates that the Storz D-Actor effectively induces a repeatable TBI infarct, avoiding the invasive procedure of a craniotomy often used in TBI research.


Infant Feeding Pattern Clusters Are Associated with Childhood Health Outcomes.
(1) Background: Feeding behavior habits have a pattern with a certain tendency during infancy. We aimed to identify the associations between feeding patterns in infancy and the subsequent 10-year childhood disease burden. (2) Methods: Data from 236,372 infants were obtained from the national health insurance and screening program records in South Korea. Parent-administered questionnaires during infancy provided details on the feeding type and types/frequency of complementary food for analyzing feeding patterns. The outcomes were all-cause hospitalization and the development of 15 representative childhood diseases until the age of 10 years. Anthropometric measurements obtained at 6 years of age were analyzed. To estimate outcome risks while considering multiple risk factors, we employed a Cox proportional hazard and modified Poisson regression. (3) Results: Three clusters were identified: high prevalence of breastfeeding with regular exposure to a variety of solid foods (n = 116,372, cluster 1), similar prevalence of breastfeeding and formula feeding with less exposure to solid foods (n = 108,189, cluster 2), and similar prevalence of breastfeeding and formula feeding with the least exposure to solid foods in infancy (n = 11,811, cluster 3). Compared with cluster 1, children in clusters 2 and 3 had increased risks of all-cause hospitalization (hazard ratio (HR), (95% confidence interval (CI)), 1.04 (1.03-1.06) and 1.08 (1.05-1.11), respectively). Children in clusters 2 and 3 had an increased risk of upper respiratory infection, pneumonia, and gastroenteritis, as well as neurobehavioral diseases. Overweight/obesity at the age of 6 years was associated with clusters 2 and 3. (4) Conclusions: Feeding patterns in infancy were associated with an increased risk of childhood disease burden.


Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations.
We investigated radiation exposure of patients undergoing whole-body 18F-FDG PET/CT examinations at 4 hospitals equipped with different tomographs. Patient doses were estimated by using established dose coefficients for 18F-FDG and from thermoluminescent measurements performed on an anthropomorphic whole-body phantom. The most relevant difference between the protocols examined was the incorporation of CT as part of the combined PET/CT examination: Separate low-dose CT scans were acquired at 2 hospitals for attenuation correction of emission data in addition to a contrast-enhanced CT scan for diagnostic evaluation, whereas, at the other sites, contrast-enhanced CT scans were used for both purposes. Nevertheless, the effective dose per PET/CT examination was similar, about 25 mSv. The dosimetric concepts presented in this study provide a valuable tool for the optimization of whole-body 18F-FDG PET/CT protocols. Further reduction of patient exposure can be achieved by modifications to the existing hardware and software of PET/CT systems.


Loss of Langerhans cells from gingival tissue maintained in organ culture.
Changes occurring in a population of Langerhans cells (LC) were investigated using human gingival epithelium maintained in organ culture. The enzyme adenosine-5'-triphosphatase together with the surface antigens HLA-DR and T6 were used to identify and quantitate these cells. An exponential fall in the expression of each of these markers was seen to occur with increasing incubation time, suggesting that a true loss of these cells is in fact occurring. HLA-DR antigen is shed from LC at a rate significantly greater than that at which LC are lost. A mathematical model which simulates the behaviour of LC within organ culture is presented, and several implications and possible explanations proposed.


The E2F-1 transcription factor promotes caspase-8 and bid expression, and enhances Fas signaling in T cells.
The immune system depends on the extensive proliferation of rare Ag-specific precursor T lymphocytes, followed by their differentiation, the delivery of effector function, and finally death by apoptosis. T cells that lack the E2F-1 transcription factor, which is activated as cells pass the restriction point and enter S phase, show defects in activation-induced cell death. We now report that E2F-1 increases the activity of an apoptotic pathway that is important in murine primary T cells. Thus, E2F-1 promotes the transcription of Bid, a molecule that links death receptor signaling to the activation of apoptotic mechanisms in mitochondria. It also promotes the transcription of caspase-8, the enzyme that cleaves and activates Bid. Enforced expression of Bid can partially restore apoptosis in E2F-1-deficient T cells. Thus, E2F-1 integrates cell cycle progression with apoptosis.


Rapid and Programmable Protein Mutagenesis Using Plasmid Recombineering.
Comprehensive and programmable protein mutagenesis is critical for understanding structure-function relationships and improving protein function. There is thus a need for robust and unbiased molecular biological approaches for the construction of the requisite comprehensive protein libraries. Here we demonstrate that plasmid recombineering is a simple and robust in vivo method for the generation of protein mutants for both comprehensive library generation as well as programmable targeting of sequence space. Using the fluorescent protein iLOV as a model target, we build a complete mutagenesis library and find it to be specific and comprehensive, detecting 99.8% of our intended mutations. We then develop a thermostability screen and utilize our comprehensive mutation data to rapidly construct a targeted and multiplexed library that identifies significantly improved variants, thus demonstrating rapid protein engineering in a simple protocol.


YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.
Myelination is essential for nervous system function. Schwann cells interact with neurons and the basal lamina to myelinate axons using known receptors, signals and transcription factors. In contrast, the transcriptional control of axonal sorting and the role of mechanotransduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. We describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice, we show that Taz is required in Schwann cells for radial sorting and myelination and that Yap is redundant with Taz. Yap and Taz are activated in Schwann cells by mechanical stimuli and regulate Schwann cell proliferation and transcription of basal lamina receptor genes, both necessary for radial sorting of axons and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.


Sharing Patient-Generated Data in Clinical Practices: An Interview Study.
Patients are tracking and generating an increasingly large volume of personal health data outside the clinic due to an explosion of wearable sensing and mobile health (mHealth) apps. The potential usefulness of these data is enormous as they can provide good measures of everyday behavior and lifestyle. However, how we can fully leverage patient-generated data (PGD) and integrate them in clinical practice is less clear. In this interview study, we aim to understand how patients and clinicians currently share patient-generated data in clinical care practice. From the study, we identified technical, social, and organizational challenges in sharing and fully leveraging patient-generated data in clinical practices. Our findings can provide researchers potential avenues for enablers and barriers in sharing patient-generated data in clinical settings.


Androgen deprivation therapy for advanced prostate cancer: why does it fail and can its effects be prolonged?
Androgen deprivation therapy (ADT) has been the cornerstone of treatment for advanced prostate cancer for over 65 years. Although there can be worrisome side effects, data will be presented that for men with metastatic prostate cancer, immediate ADT can reduce the likelihood of developing the rare but catastrophic sequellae of metastatic disease, although it is unlikely to prolong survival compared with waiting for symptoms before initiating ADT. Additionally, for patients with extremely high risk prostate cancer that is not distantly metastatic (e.g. have a life expectancy from prostate cancer less than 10 years with all other available treatments except immediate ADT) and, whose life expectancy from non-prostate cancer diseases is excellent during this period, early ADT both alone and in conjunction with definitive local treatment prolongs survival. Moreover, ADT seems to be most effective when the cancer volume is low. However, eventually most men receiving ADT experience disease progression. The biological mechanisms explaining how prostate cancer escapes from ADT's control include: 1) Alterations in the androgen receptor (AR) and in the AR co-factors (which modify the responsiveness of the AR to androgens) allow molecules and medications which are not normally AR agonists to act as agonists. 2) The human prostate gland, and particularly prostate cancer, may be able to synthesize androgens from both cholesterol and adrenal androgens. This may occur because prostate cancer tissue has higher concentrations of androgens than does the serum in patients receiving ADT. Thus, castrated men may not be starving their prostate cancers of androgens. 3) The AR in prostatic stroma far more strongly stimulates both malignant and benign prostatic epithelial growth than the epithelial AR does. Indeed, the epithelial AR, particularly in advanced prostate cancer, may have anti-proliferative and anti-tumor progression properties. That is, the AR in the prostatic epithelial cells, particularly malignant ones, may act as a tumor suppressor. Thus, by inhibiting the epithelial AR, its protective effects may be abrogated. The controversial nature of these concepts, as well as the clinical and experimental data which support and question them, will be presented. Additionally, strategies for addressing each of these escape mechanisms, which may be able to prolong responsiveness to ADT, will be discussed.


Performance of Children and Adolescents With Brain Injury on the Lebby-Asbell Neurocognitive Screening Examination for Children and Adolescents.
Traumatic brain injuries are one of the leading causes of deaths and disabilities in children and adolescents. There is a need for clinicians to quickly screen for disrupted cognitive functioning to appropriately refer to specialists. The Lebby-Asbell Neurocognitive Screening Examination for Children and Lebby-Asbell Neurocognitive Screening Examination for Adolescents were developed to fill a gap in available measures and create a screening tool to quickly identify impaired neurocognitive functioning. A series of statistical analyses were conducted to determine their clinical utility. A multivariate analysis of variance found a statistically significant difference between those with brain injury (n = 59) from noninjured (n = 190) on the combined dependent variables, F(14, 234) = 46.530, P < .001; Wilks Lambda = .264; partial η(2) = .763. The Lebby-Asbell Neurocognitive Screening Examinations for Children and Adolescents are effective neurocognitive screening measures for children and adolescents in identifying brain injury.


Histological, Immunological, and Genetic Analysis of Feline Chronic Gingivostomatitis.
Feline chronic gingivostomatitis (FCGS) is an immune-mediated inflammatory condition affecting the oral mucosa that results in substantial pain and suffering. The goal of this study was to complete an in-depth immunohistochemistry analysis of affected FCGS mucosa, to perform and compare immune cell phenotypes in the blood of FCGS and healthy controls cats, and to determine a transcriptomic profile of the affected and normal oral mucosa of FCGS cats. We hypothesized that cats with FCGS would have circulating activated CD8+ T cells and that tissues would be infiltrated with activated B and T cells with a highly proinflammatory transcriptome. We found that oral mucosal tissues from cats with FCGS have high tissue infiltration of B cells and that T cells include both CD4+ and CD8+ lymphocytes. Cells positive for CD25 (IL2 receptor, indicative of lymphocyte activation) and FOXP3 (indicative of regulatory T cells) were scattered throughout the mucosa. Compared to healthy individuals, cats with FCGS had high circulating CD8+ effector memory cells with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L-). Gene expression in the affected tissues was enriched for genes associated with T-cell signaling, cell adhesion molecules, leukocyte migration, inflammatory signaling pathways, extracellular matrix-receptor interactions, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity, among others. These data are essential to understand disease pathogenesis, to inform mechanism of action studies for future and current therapies, and to help select prognostic biomarkers and potency assays for stem cell treatment of FCGS.


Expanding surgical treatment of pancreatic cancer: the role of regional chemotherapy.
Pancreatic cancer is a lethal disease that offers little chance of long-term survival for patients with unresectable tumors. Surgery remains the most effective means of attaining prolonged survival, yet its role remains limited. Regional chemotherapy has been described for patients with pancreatic cancer, including reports of objective tumor regression allowing for tumor resection in previously unresectable cases. However, comprehensive data have not been reviewed to date. A review of the literature from 1995 to 2010 was performed to analyze the results of regional chemotherapy administered to patients with advanced pancreatic cancer. Reports of individual cases, postoperative regional therapy, and treatment of mixed tumor types were excluded. Twenty-one reports of 895 total patients with pancreatic cancer were reviewed. Greater than 95% of the patients had stage III or IV adenocarcinoma. Objective response rates ranged from nil to 58%, with associated median survivals of 4 to 22 months. Low-grade gastrointestinal and hematologic toxicities were not uncommon. Regional chemotherapy can be administered safely to patients with pancreatic cancer but with unclear benefit. Advanced pancreatic tumors converted to resectable status by the use of regional chemotherapy may improve patient survival.


POPULATION DIVERGENCE IN SEXUAL ORNAMENTS: THE WHITE FOREHEAD PATCH OF NORWEGIAN PIED FLYCATCHERS IS SMALL AND UNSEXY.
Models of sexual selection suggest that populations may easily diverge in male secondary sexual characters. Studies of a Spanish population of the pied flycatcher, Ficedula hypoleuca, and a Swedish population of the closely related collared flycatcher, F. albicollis, have indicated that the white forehead patch of males is a sexually selected trait. We studied the white forehead patch of male pied flycatchers (n = 487) in a Norwegian population over seven years. Males with large forehead patches were in general more brightly colored, but patch height was not correlated to body mass, body size, or parasite loads. Conditions during the nestling period did not seem to influence patch height as an adult. Patch height increased slightly from the first to the second year as adults, but then remained relatively constant at higher ages. Patch height was not related to survival. Year-to-year changes showed that males who increased in patch height also increased in body mass, suggesting that expression of the forehead patch may be partly condition dependent. However, changes in body mass explained only a small proportion of the variance in patch height between males. Thus, patch height would not be a good indicator of male quality. Furthermore, patch size was also not related to male ability to feed nestlings, indicating that females would not obtain direct benefits by choosing males with large patches. However, patch height could be a Fisher trait, but this requires heritability and there was no significant father-son resemblance in patch height. Comparisons of the males visited by each female during the mate sampling period indicated that chosen males did not have larger forehead patches than rejected males. Experimental manipulation of patch height did not affect male mating success. These results indicate that females do not use patch size as a mate choice cue. Finally, patch height did not predict the outcome of male contests for nestboxes, suggesting that the forehead patch is not an intrasexually selected cue of status. Norwegian pied flycatchers have smaller forehead patches than both Spanish pied flycatchers and Swedish collared flycatchers. We suggest that this pattern may be explained by the lack of sexual selection on the forehead patch in the Norwegian population as compared to the other populations, where the patch is apparently sexually selected. We discuss possible reasons for these population divergences, such as female choice on an alternative secondary sexual character (general plumage color) and speciation among Ficedula flycatchers.


Zinc and gastrointestinal disease.
This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases.


The MicroRNA-21 in Autoimmune Diseases.
MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease.


NHC-Catalyzed Generation of α,β-Unsaturated Acylazoliums for the Enantioselective Synthesis of Heterocycles and Carbocycles.
This Account is aimed at highlighting the recent developments in the N-heterocyclic carbene (NHC)-catalyzed generation of α,β-unsaturated acylazolium intermediates and their subsequent reactivity with (bis)nucleophiles thereby shedding light on the power of this NHC-bound intermediate in organocatalysis. This key intermediate can be generated by the addition of NHCs to α,β-unsaturated aldehyde or acid derivatives. A wide variety of bisnucleophiles can add across the α,β-unsaturated acylazoliums to form various five and six-membered heterocycles and carbocycles. Moreover, suitably substituted nucleophiles can add to this intermediate and result in valuable products following cascade processes. Employing chiral NHCs in the process can result in the enantioselective synthesis of valuable compounds. In 2013, we developed a unified strategy for the enantioselective synthesis of dihydropyranones and dihydropyridinones by the NHC-catalyzed formal [3 + 3] annulation of 2-bromoenals with readily available 1,3-dicarbonyl compounds or primary vinylogous amides. This reaction takes place under mild conditions with low catalyst loading. Interestingly, employing enolizable aldehydes as the bisnucleophiles in this annulation afforded chiral 4,5-disubstituted dihydropyranones in spite of the competing benzoin/Stetter pathways. Moreover, the use of cyclic 1,3-dicarbonyl compounds such as 4-hydroxy coumarin/pyrazolone afforded the coumarin/pyrazole-fused dihydropyranones. In addition, a [3 + 2] annulation for the synthesis of spiro γ-butyrolactones was demonstrated using 3-hydroxy oxindoles as the bisnucleophile. The interception of α,β-unsaturated acylazolium intermediates with malonic ester derivatives having a γ-benzoyl group resulted in the enantioselective synthesis of functionalized cyclopentenes via a cascade process involving a Michael-intramolecular aldol-β-lactonization-decarboxylation sequence. The use of cyclic β-ketoamides as the coupling partner for catalytically generated α,β-unsaturated acylazoliums resulted in the enantioselective synthesis of spiro-glutarimide and the reaction proceeds in a Michael addition-intramolecular amidation pathway. We have recently demonstrated the enantioselective synthesis of tricyclic δ-lactones with three contiguous stereocenters by the reaction of enals with dinitrotoluene derivatives bearing electron-withdrawing groups, under oxidative conditions. This atom-economic cascade reaction proceeds in a Michael/Michael/lactonization sequence tolerating a range of functional groups. This technique was also used for the N-H functionalization of indoles for the enantioselective synthesis of pyrroloquinolines following the aza-Michael/Michael/lactonization sequence. The use of α-arylidene pyrazolinones as the bisnucleophiles for the tandem generation of dienolate/enolates combined with the NHC-catalyzed generation of α,β-unsaturated acylazoliums resulted in the enantioselective synthesis of pyrazolone-fused spirocyclohexadienones. This formal [3 + 3] annulation proceeds via the vinylogous Michael/spiroannulation/dehydrogenation sequence to afford spirocyclic compounds with an all-carbon quaternary stereocenter. It is reasonable to believe that the chemistry of α,β-unsaturated acylazoliums, catalytically generated through NHCs, will continue to flourish and will lead to amazing results. Future challenges in this area include the applications of this key intermediate in the synthesis of biologically active natural products and drugs.


Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy.
A substantial number of patients will develop further biochemical progression after radical prostatectomy (RP) and salvage radiotherapy (sRT). Recently published data using prostate-specific membrane antigen ligand positron emission tomography (PSMA - PET) for re-staging suggest that those recurrences are often located outside the prostate fossa and most of the patients have a limited number of metastases, making them amenable to metastasis-directed treatment (MDT). We analyzed 78 patients with biochemical progression after RP and sRT from a retrospective European multicenter database and assessed the biochemical recurrence-free survival (bRFS; PSA < nadir + 0.2 ng/ml or no PSA decline) as well as the androgen deprivation therapy- free survival (ADT-FS) using Kaplan-Meier curves. Log-rank test and multivariate analysis was performed to determine influencing factors. A total of 185 PSMA - PET positive metastases were detected and all lesions were treated with radiotherapy (RT). Concurrent ADT was prescribed in 16.7% (13/78) of patients. The median PSA level before RT was 1.90 ng/mL (range, 0.1-22.1) and decreased statistically significantly to a median PSA nadir level of 0.26 ng/mL (range, 0.0-12.25; p < 0.001). The median PSA level of 0.88 ng/mL (range, 0.0-25.8) at the last follow-up was also statistically significantly lower (p = 0.008) than the median PSA level of 1.9 ng/mL (range, 0.1-22.1) before RT. The median bRFS was 17.0 months (95% CI, 14.2-19.8). After 12 months, 55.3% of patients were free of biochemical progression. Multivariate analyses showed that concurrent ADT was the most important independent factor for bRFS (p = 0.01). The median ADT-FS was not reached and exploratory statistical analyses estimated a median ADT-FS of 34.0 months (95% CI, 16.3-51.7). Multivariate analyses revealed no significant parameters for ADT-FS. RT as MDT based on PSMA - PET of all metastases of recurrent prostate cancer after RP and sRT represents a viable treatment option for well-informed and well-selected patients.


Benchmarking of pluck lesions at slaughter as a health monitoring tool for pigs slaughtered at 170kg (heavy pigs).
Abattoir post-mortem inspections offer a useful tool for the development and monitoring of animal health plans and a source of data for epidemiological investigation. The aim of the present work was to develop an abattoir benchmarking system which provides feedback on the prevalence and severity of lesions of the pluck (lung, pleura and liver) in batches of pigs to inform individual producers and their veterinarians of the occurrence of pathological conditions affecting their herds. The weekly collection of data throughout a year (from September 2014 to September 2015) supported the further aim of providing benchmark values for the prevalence of lesions and their seasonality in Italian heavy pig production. Finally, correlations and redundancies among different lesions were evaluated. In total, 727 batches of heavy pigs (around 165kg live weight and 9 months of age) derived from 272 intensive commercial farms located in Northern Italy were monitored. Within each batch, an average number of 100 plucks was individually scored, assigning a value for lesions of lungs (0-24), pleura (0-4) and liver (1-3). Presence of lung scars, abscesses, consolidations, lobular/chessboard pattern lesions and pleural sequestra was also recorded. Statistical analysis showed a strong farm effect (36-68% of variation depending of the lesion) and a seasonal effect on all lesions. Winter showed the lowest percentage of severe lung and pleural lesions (P<0.001 and P=0.005), whereas lung scars from older lesions (P=0.003), as well as severe hepatic lesions (P<0.001), were reduced in autumn. In order to allow effective benchmarking of each farm in a determined health class, scores for each quartile of the population are reported. Whilst such a benchmarking scheme provides useful data for herd health management, challenges of repeatability of scoring and cost of implementation need to be overcome.


Why seek treatment for temporomandibular disorder pain complaints? A study based on semi-structured interviews.
To identify potential predictors of self-reported sleep bruxism (SB) within children's family and school environments. A Aims: To assess possible differences between care seekers and non-care seekers with temporomandibular disorder (TMD) pain complaints, by using semi-structured interviews. Semi-structured interviews were held with 16 subjects who had TMD- pain complaints: 8 care seekers and 8 non-care seekers, matched for age, sex, pain intensity, and fear of movement. Subjects were selected from a previously held survey study, with their consent. The interviews were audiotaped, transcribed verbatim, and analyzed according to qualitative content analysis. From the analysis, seven themes differentiating care seekers from non-care seekers were identified: catastrophizing, pain management, assertiveness, critical attitude towards health care, confidence in medical care, recognition, and adequate referral. Aspects upon which care seekers differed from non-care seekers were mainly person-related characteristics. Next to these characteristics, it appeared that inadequate referrals may play a role in care seeking. The use of semi-structured interviews may further improve insights into processes that determine care seeking among people with TMD pain complaints.


Selection of an empiric antibiotic regimen for hospital-acquired pneumonia using a unit and culture-type specific antibiogram.
The objective of this retrospective study was to determine the optimal initial antibiotic regimen for hospital-acquired pneumonia using the frequency and sensitivity of Gram negative microorganisms found in sputum cultures. An antibiogram was constructed and compared with the hospital intensive care unit (ICU) antibiogram. The results yielded 191 microorganisms. The study-generated antibiogram showed that the highest percent susceptible antibiotics for all Gram-negative microorganisms were imipenem (75%) and amikacin (84%). Considering only Pseudomonas aeruginosa, the study-generated antibiogram and the hospital ICU antibiogram showed similar results, piperacillin and amikacin (86% and 82%, respectively, vs 91% and 85%, P = nonsignificant for both). The optimal empiric antibiotic regimen in the surgical ICU is different if directed against all possible microorganisms as opposed to the most prevalent microorganism P aeruginosa. Determining initial empiric antibiotic therapy using an ICU and culture-type specific antibiogram would result in a greater likelihood that more patients would receive adequate initial antibiotic therapy.


Shear Viscosity and Heterogeneous Structure of Alkylaminoethanol-Based CO2 Absorbents.
Shear viscosity of concentrated aqueous solutions of alkylaminoethanols was determined with changing the length of the alkyl chain and the concentration of dissolved CO2. The viscosity increased with increasing the CO2 loading, reflecting the strengthening of the intermolecular electrostatic interaction. The dependence of the viscosity on both temperature and CO2 loading was described by a modified version of Vogel-Fulchar-Tammann equation. Compared at the same volume concentration of CO2, the viscosity increased with increasing the alkyl chain lengths, and the dependence on the alkyl chain length increased with the CO2 loading. At the same time, small-angle X-ray scattering profiles exhibited the presence of a prepeak when the alkyl chain was long, and the prepeak grew with the CO2 loading. It suggests that the presence of the heterogeneous structure increases the shear viscosity of the CO2 absorbents when the alkyl chain is long.


Cardiovascular effects of positive end-expiratory pressure during acute left ventricular failure in dogs.
Haemodynamic and metabolic effects of ventilation with positive end-expiratory pressure (PEEP) were studied in closed-chest dogs anaesthetized with sodium pentobarbital during normal cardiac function and during acute left ventricular (LV) failure. LV failure was induced by embolizing the left coronary bed with 50 micron plastic microspheres causing a marked depression of LV function. End-expiratory pressure was set to 0, 5, 10 and 15 cm H2O both before and after coronary embolization. During normal cardiac function PEEP above 5 cm H2O depressed cardiac output (CO) significantly. However, following coronary embolization after which LV function was seriously impaired, CO was maintained as PEEP was applied. This is attributed to reduced sensitivity to the LV pre-load reductions induced by PEEP during LV failure. PEEP reduced MBF both during normal and impaired LV function. This did not result in ischaemic myocardial metabolism assessed by lactate extraction either in normal hearts or following coronary embolization. The reduced MBF was, however, associated with reduced MVO2 both during normal cardiac function and during LV failure. It is suggested that the reduced MBF is mainly due to reduced myocardial oxygen demand probably caused by reduced LV wall tension during PEEP ventilation.


Off-label use of mycophenolate mofetil in the treatment of rare and complex rheumatic connective tissue diseases.
We aimed to investigate the clinical off-label use of mycophenolate mofetil (MMF), including its safety and efficacy in patients with rare and complex rheumatic connective tissue diseases (rCTDs). A survey was distributed across experts from ERN-ReCONNET reference centres in order to assess the experience with MMF off-label use. Patient-level data of patients with rCTDs under treatment with MMF was also collected for analysis of safety and efficacy. Twelve experts from eleven centres distributed throughout Europe (7 countries) answered the survey. The experience was concordant in that, despite of its off-label use, experts reported opting frequently for this therapeutic alternative with robust confidence on its efficacy and safety. The analysis of 108 patients with rCTDs under MMF revealed a good safety profile, as well as good clinical outcomes, especially for systemic lupus erythematosus and idiopathic inflammatory myopathies. The presence of interstitial lung disease was, as expected, associated with a worse clinical outcome despite use of MMF. MMF is widely used in reference centres for rCTDs. Its safety profile and efficacy seem to be recognised by experts and demonstrated with patient-level analysis. While selected rCTDs will likely remain an off-label indication for MMF, robust data seem to support this therapy as an appropriate alternative for safely and effectively treating many manifestations of rCTDs.


Tomographic inversion techniques incorporating physical constraints for line integrated spectroscopy in stellarators and tokamaks.
Accurate tomographic inversion is important for diagnostic systems on stellarators and tokamaks which rely on measurements of line integrated emission spectra. A tomographic inversion technique based on spline optimization with enforcement of constraints is described that can produce unique and physically relevant inversions even in situations with noisy or incomplete input data. This inversion technique is routinely used in the analysis of data from the x-ray imaging crystal spectrometer (XICS) installed at the Large Helical Device. The XICS diagnostic records a 1D image of line integrated emission spectra from impurities in the plasma. Through the use of Doppler spectroscopy and tomographic inversion, XICS can provide profile measurements of the local emissivity, temperature, and plasma flow. Tomographic inversion requires the assumption that these measured quantities are flux surface functions, and that a known plasma equilibrium reconstruction is available. In the case of low signal levels or partial spatial coverage of the plasma cross-section, standard inversion techniques utilizing matrix inversion and linear-regularization often cannot produce unique and physically relevant solutions. The addition of physical constraints, such as parameter ranges, derivative directions, and boundary conditions, allow for unique solutions to be reliably found. The constrained inversion technique described here utilizes a modified Levenberg-Marquardt optimization scheme, which introduces a condition avoidance mechanism by selective reduction of search directions. The constrained inversion technique also allows for the addition of more complicated parameter dependencies, for example, geometrical dependence of the emissivity due to asymmetries in the plasma density arising from fast rotation. The accuracy of this constrained inversion technique is discussed, with an emphasis on its applicability to systems with limited plasma coverage.


Systemic hyperfibrinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma.
Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. Blood samples were collected in the field or at emergency department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), "eufibrinolytic" (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins. HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 and fold change of concentrations of 0.75-1.3). HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times, or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs. Prognostic, level III.


Use of a live attenuated Salmonella typhimurium vaccine to protect hens against Salmonella enteritidis infection while undergoing molt.
Previous studies demonstrated that Salmonella enteritidis infections in hens undergoing molt via feed withdrawal were more severe than in full fed hens. We conducted two trials to determine if immunizing specific-pathogen-free, Salmonella-culture-negative hens via aerosol exposure to MeganVacl, a commercially available attenuated Salmonella typhimurium vaccine, would reduce transmission of S. enteritidis from infected hens to uninfected but contact-exposed hens during a molt. In trial 1, one group of hens received two aerosol doses of vaccine 2 wk apart whereas a second group of hens remained nonvaccinated. In trial 2, the vaccinated group received only one dose of vaccine. Two weeks after the final immunization, feed was removed from all the hens, and on day 4, the center hen in rows of 11 hens received a dose of 3 x 10(5) (trial 1) or 1.3 x 10(6) (trial 2). Transmission to the unchallenged hens was followed 3, 10, 17, and 24 days later. Vaccination reduced the horizontal spread of S. enteritidis in vaccinated hens compared with their nonvaccinated counterparts, with vaccinated hens shedding significantly less S. enteritidis on day 10 postchallenge in trial 1 and on days 3, 10, 17, and 24 in trial 2. Recovery of S. enteritidis from ovaries was significantly reduced in the vaccinated hens in trial 1 and from livers/spleens, ovaries, and cecum in trial 2. These studies indicate that immunization of hens with a live S. typhimurium vaccine could help reduce S. enteritidis problems during a molt situation.


Body composition - what is measurable?
In 1878 Behnke noted that 'nothing is measured with greater error than the human body'. Over the intervening period measurement techniques have been developed which range from the relatively simple anthropometric methods to those based on sophisticated radiation and nuclear physics technologies. Nevertheless, despite the undoubted progress, it is important that we ask ourselves whether Behnke's observation might still have some validity. Many reviews have concentrated on the problems and limitations of given techniques with particular emphasis on achievable precision (because precision is easy to measure). However a straight-forward analysis of published data, especially of that relating to indirect techniques, shows that measurement precision is frequently small in magnitude compared to biological precision, the latter being simply a reflection of Nature's refusal to conform to imposed regression relationships. In this paper the body composition technologies are reviewed in the context of achievable accuracy and precision.


Stretch-mediated activation of cardiac renin gene.
This study was designed to quantitate cardiac mRNA levels encoding components of the local renin-angiotensin system during the development of volume overload-induced cardiac hypertrophy. Changes in cardiac renin mRNA levels were measured in relation to renin activity in the left ventricle (LV) and in plasma after acute passive stretch of the heart caused by an aortovenocaval shunt in the rat. A quantitative reverse-transcriptase polymerase chain reaction method with competitive internal standards was used to measure mRNA levels in total RNA derived from cardiac tissues after shunt. Seven days after shunt surgery, LV weight was increased by 23%. Renin activities were elevated four- and twofold in plasma and LV, respectively. LV angiotensinogen mRNAs were not significantly increased by shunt surgery; they were twofold higher than phosphoglycerate kinase mRNA from the housekeeping gene PGK-1. By day 7, LV levels for renin mRNA were significantly increased from well below 0.25% to approximately 1% of PGK-1 mRNA. Identity between renin polymerase chain reaction products from kidney and heart cDNAs and absence of "reninlike" amplification products were supported by Southern blotting. Volume overload caused increased expression of the renin gene in the stretched myocardium. This finding is consistent with the concept of a myocardial renin-angiotensin system that can be activated by locally produced renin and contributes to the hypertrophy of cardiac muscle.


Distinct responses in feed sorting, chewing behavior, and ruminal acidosis risk between primiparous and multiparous Simmental cows fed diets differing in forage and starch levels.
During early lactation, both primiparous (PP) and multiparous (MP) cows are commonly fed diets rich in starch and low in forages to support their high energy requirements. Yet, the PP cows experience this dietary challenge for the first time, which might result in higher odds for them to develop rumen and systemic health disorders. The primary objective of this study was to evaluate the effect of decreasing the amount of forages in the diet on chewing and sorting behaviors and rumen and systemic health variables in PP and MP dairy cows. Twenty-four lactating Simmental cows [8 PP, average dry matter intake (DMI) of 19.1 ± 1.1 kg/d; 16 MP, average DMI of 22.5 ± 1.1 kg/d] with a body weight of 737 ± 90 kg and 50 ± 22 days in milk were used in this study. Cows were first fed a total mixed ration with 60% forage and 40% concentrate [on a dry matter (DM) basis] considered marginal in forages for 2 wk. Then, cows were switched to a diet low in forages with 40% forage and 60% concentrate (on a DM basis) for 4 wk. Reticular pH was measured continuously with wireless pH-sensors inserted into the reticulum to calculate the subacute ruminal acidosis (SARA) index. Chewing activity was measured with noseband-sensor halters, and feed sorting was measured weekly. Blood samples were collected weekly and analyzed for metabolic and inflammation markers. Switching PP and MP cows from a marginal to low-forage diet decreased the time spent eating and ruminating per kilogram of DM. Primiparous cows chewed longer per kilogram of DMI than MP cows. Also, the PP cows sorted more pronounced for longer particles and against fine particles than MP cows did. Despite higher rumination activity per kilogram of DMI and the adaptive sorting behavior, the PP cows spent on average 4.6 h/d longer below a pH of 5.8 and had a higher SARA index (i.e., area pH <5.8/DMI) than MP cows, especially during the first week of the low-forage diet (9.5 vs. 4.8). The concentration of liver enzymes increased with the low-forage diet, which was especially pronounced in the PP cows. In conclusion, this study demonstrated greater susceptibility of PP cows to SARA and liver damage than MP cows fed the same diets. Although PP cows demonstrated greater chewing and ruminating activity per kilogram of DMI, as well as adapted sorting behavior in favor of large particles during the low-forage high-starch feeding, they developed more severe signs of SARA. This suggests higher forage fiber requirements for PP cows and the need for improved feeding strategies to mitigate rumen fermentation disorders during early lactation in these cows.


The pain pathway in the rat following noxious thermal stimulation: effect of morphine on pERK1/2 and TRPV1 at the dorsal horn level, and on hyperalgesia.
The aim of the present study was to investigate the phosphorylation of ERK1/2 in the lumbar dorsal horn of the rat by fluorescence immunohistochemistry following a noxious thermal stimulation of the hind paw. The protein level of TRPV1 in the dorsal spinal cord and the development of a heat hyperalgesia after the acute noxious thermal stimulation were also measured. The protein content of TRPV1 was determined by Western blot and heat hyperalgesia by the plantar test. At 2 and 10 min after the thermal stimulation a 4-fold increase in pERK1/2 immunoreactivity was observed in cells of lamina I/II of the L3-L5 dorsal horn. A pretreatment with the opioid analgesic morphine markedly attenuated ERK1/2 phosphorylation. The protein content of TRPV1 in the lumbar dorsal spinal cord was not significantly altered at 1 and 4 h after the thermal hind paw stimulation and by the morphine pretreatment. Heat hyperalgesia in the plantar test was observed at 8 h, but not at 24 h after the noxious stimulation. This temporary hyperalgesia was prevented by the morphine pretreatment. The present findings indicate that ERK1/2 activation in dorsal horn nociceptive neurons may be linked to the development of hyperalgesia, and that opioid analgesics are effective agents to prevent sensitization in the pain pathway at spinal level.


The Burden of Opioid-Related Adverse Drug Events on Hospitalized Previously Opioid-Free Surgical Patients.
Opioid analgesics are a mainstay for acute pain management, but postoperative opioid administration has risks. We examined the prevalence, risk factors, and consequences of opioid-related adverse drug events (ORADEs) in a previously opioid-free surgical population. A retrospective, observational, cohort study using administrative, billing, clinical, and medication administration data from two hospitals. Data were collected for all adult patients who were opioid-free at admission, underwent surgery between October 1, 2015, and September 30, 2016, and received postoperative opioids. Potential ORADEs were determined based on inpatient billing codes or postoperative administration of naloxone. We determined independent predictors of ORADE development using multivariable logistic regression. We measured adjusted inpatient mortality, hospital costs, length of hospital stay, discharge destination, and readmission within 30 days for patients with and without ORADEs. Among 13,389 hospitalizations where opioid-free patients had a single qualifying surgery, 12,218 (91%) received postoperative opioids and comprised the study cohort. Of these, we identified 1111 (9.1%) with a potential ORADE. Independent predictors of ORADEs included older age, several markers of disease severity, longer surgeries, and concurrent benzodiazepine use. Opioid-related adverse drug events were strongly associated with the route and duration of opioids administered postoperatively: 18% increased odds per day on intravenous opioids. In analyses adjusted for several covariates, presence of an ORADE was associated with 32% higher costs of hospitalization, 45% longer postoperative length of stay, 36% lower odds of discharge home, and 2.2 times the odds of death. We demonstrate a high rate and severe consequences of potential ORADEs in previously opioid-free patients receiving postoperative opioids. Knowledge of risk factors and predictors of ORADEs can help develop targeted interventions to minimize the development of these potentially dangerous and costly events.


The prevalence of polycystic ovaries in thin oligomenorrhoeic, anovulatory women.
Seventeen thin oligomenorrhoeic, anovulatory women were investigated with high resolution ovarian ultrasound, laparoscopy and biochemical parameters. Nine (53%) had ultrasound, laparoscopic and biochemical evidence of polycystic ovaries (PCO), 2 (12%) had multicystic ovaries (MCO) and 6 (35%) had morphologically normal ovaries. Three patients had biochemical evidence of thyroid disease and one patient had elevated gonadotrophins. Overall, 12 (71%) of these thin oligomenorrhoeic women had an explanation in addition to their low body mass to explain their menstrual disorder.


Template-controlled assembly of ditopic catechol phosphines: a strategy for the generation of complexes of bidentate phosphines with different bite angles.
A rational approach to the synthesis of heterobi- or -trimetallic complexes based upon self-assembly of a flexible ditopic catechol-phosphine ligand with [(cod)PdCl(2)] and simple metal halides such as GaCl(3), BiCl(3), SnCl(4), or ZrCl(4) is described. All products were characterized by spectroscopic and analytical data and single-crystal X-ray diffraction studies. The molecular structures can be described in terms of cis-configured palladium complexes with supramolecular bisphosphine ligands that are formed by the assembly of two phosphine catecholate fragments on a main group/transition metal template. Of particular interest are the distinct decreases in P-Pd-P bite angles and P...P distances between the ligating atoms with increasing covalent radii of the templates. The range of these variations is of a magnitude similar to that of the geometrical changes in known families of complexes containing molecular bidentate ligands. Solution NMR studies give further evidence that in several cases the mu(2)-bridging coordination of two of the catechol oxygen atoms in the template complexes is broken under the influence of donor solvents, thus allowing the supramolecular ligand to be switched between tetradentate -O(2)P(2) and bidentate -P(2) coordination modes.


Chondrocyte senescence and telomere regulation: implications in cartilage aging and cancer (a brief review).
Recent studies on osteoarthritis and the cartilage aging in our laboratory demonstrate that chronologic age correlates with molecular changes in human chondrocytes that affect cell cycle control and replicative life span. These findings indicate that age-related changes in chondrocytes may explain the heightened risk for development of primary osteoarthritis (OA) with increasing age. Concomitant studies of human chondrosarcoma suggest that these aging mechanisms may also play a role in preventing the malignant transformation of chondrocytes. The convergence at the molecular level of these seemingly dissimilar biologic processes provides an excellent opportunity to deepen our understanding of the fundamental processes underlying cartilage neoplasia, cartilage aging, and osteoarthritis.


Semitendinosus muscle architecture during maximum isometric contractions in individuals with anterior cruciate ligament reconstruction and controls.
The most widely used graft as a replacement in anterior cruciate ligament (ACL) reconstruction is the semitendinosus (ST) tendon graft. After harvesting for ACL reconstruction, the hamstring tendon regenerates in most people and becomes similar to normal. The effect of graft harvest on muscle morphology and function remains unclear. The present study aimed to examine the morphology of the ST during isometric contraction after harvesting the ST tendon for ACL reconstruction. Maximal isometric contractions of the knee flexors from two angular positions were performed by 8 participants, at least 1 year after ACL reconstruction with an ST tendon graft and 8 matched controls. Ultrasonographic images were used to measure the pennation angle and muscle thickness of the ST muscle. There was not a statistically significant difference in pennation angle values between the control group and the group who underwent ACL reconstruction (p >0.05). Muscle thickness was significantly higher in the ACLR group compared with controls (p< 0.05). Individuals who underwent ACL reconstruction display a higher ST muscle thickness but similar pennation angle compared with controls. This indicates that ACL reconstruction has an effect on ST muscle belly but effect on force generation capacity is rather limited. IIb.


Body composition and physical activity patterns of Indonesian elderly with low body mass index.
Body composition and physical activity of institutionalised elderly were studied. Forty elderly subjects were divided into two groups according to their body mass index (BMI). One group (n=20) had BMI < 17 kg/m2 (low BMI) and was defined as having chronic energy deficiency (CED), and the other group (n=20) had BMI values between 22.0 to 25.0 kg/m2 (BMIs generally regarded as healthy). Body composition was measured using skinfold thicknesses and bioelectrical impedance analysis (BIA). The Durnin and Womersley1 equation was used to estimate fat mass (FM) from the sum of four skinfold thicknesses, namely biceps, triceps, subscapular and suprailiac. With BIA, two formulae were adopted to calculate fat free mass (FFM); they were the Lukaski2 and Deurenberg3 equations. These three formulae were compared. The physical activity level (PAL) was estimated on the basis of recorded daily physical activity patterns, and calculation of energy expenditure was based on a report by FAO/WHO/UNU4. Skinfold assessment provided the highest value for FM estimation, and BIA using Deurenberg's3 equation (BIA-H) gave the lowest value. The average of FM obtained by the three methods in elderly with low and normal BMI were 4.9 ± 2.5 kg and 16.7 ± 3.2 kg, respectively. The discrepancy between Lukaski2 and Deurenberg3 equations was less as FM increased. The elderly with low BMIs had very low fat mass. Nevertheless, thin elderly had the same level of physical activity (1.3 x BMR) as those with apparently healthy BMIs. The BMI cut off point to define CED was not sensitive enough to detect any physical consequences of low BMI in Indonesian elderly as this may reflect PALs which are overall very low. Comparable investigation of non-institutionalised elderly is needed. This study is the first to assess the functional significance of BMI in Southeast Asian elderly.


Comparison of transabdominal and transvaginal pelvic ultrasonography for ovarian follicle assessment in in vitro fertilisation.
The emergence of transvaginal ultrasound-guided oocyte retrieval provided an opportunity to review and improve the traditional transabdominal ultrasonic approach for follicular tracking in in vitro fertilisation (IVF). This technique requires a full bladder, which may cause extreme discomfort. Hence, to provide both effective and comfortable monitoring, we instituted a study comparing transabdominal and transvaginal ultrasonography, with regard to patient preference and follicular number, size and dominance, in patients undergoing IVF and gamete intrafallopian transfer (GIFT). Commencing usually on day 9 of the treatment cycle, 45 patients were scanned on 55 occasions, initially abdominally (with a full bladder) and subsequently vaginally, using a transvaginal 7.5 MHz sector transducer. Follicular number was identical in 78% of cases, with the majority of the remaining patients showing an extra follicle on vaginal assessment. There were no significant differences in overall or dominant follicular diameters with either technique. Overall, 85% unashamedly preferred the vaginal approach. We believe that tracking follicular development in IVF treatment cycles is efficient and popular using the vaginal sector transducer and accordingly have ceased all assessments using the abdominal probe. Subsequently, 450 follicle scans have been performed with virtually the unanimous approval of our patients.


Clinical features and outcomes following bilateral lower limb amputation in Korea.
The objectives of this study were to evaluate the clinical features and outcomes of 43 bilateral lower limb amputees. The clinical features obtained included the causes of amputation, level of amputation, concurrent medical problems, and stump condition. Outcome measures were obtained using the activities of daily living (ADL) index, the Frenchay Activities Index (FAI), and mobility grading with prostheses or wheelchair. Of 33 amputees who were prosthetic ambulators, 22 (67%), mainly bilateral trans-tibial (TT) amputees, were community ambulators, and participated in activities which included stair-walking, and six of 11 household ambulators were combination trans-femoral (TF) and TT amputees. Of 10 amputees who were wheelchair ambulators, only one was able to perform wheelchair transfers independently and five were independent wheelchair ambulators. Using the ADL index and FAI, there was no significant difference in scores according to the level of amputation (p > 0.05), but the scores of community prosthetic ambulators were significantly higher than those of wheelchair ambulators (p < 0.05). Age was found to be negatively correlated with ADL index and FAI scores (r = -0.518 vs. r = -0.550) (p < 0.01). This study concludes that overall independence in ADL after bilateral lower limb amputation improved with young age and prosthetic mobility.


Prognostic Nomogram for Disease-Specific Survival in Patients with Non-metastatic Ampullary Carcinoma After Surgery.
The aim of this study was to establish and validate an individualized nomogram for predicting disease-specific survival (DSS) in patients with non-metastatic ampullary carcinoma after surgery. The nomogram was prepared using retrospective data from the Surveillance, Epidemiology, and End Results database, and included 2022 patients (training dataset: 1276; validation dataset: 746 patients) with non-metastatic ampullary carcinoma who were surgically treated between 2004 and 2014. Cox multivariate regression was performed to identify independent risk factors. The predictive accuracy was determined using the concordance index (C-index) and calibration curves. Results were validated internally using bootstrap resampling, and externally against the validation dataset. The median follow-up for the training dataset was 25.5 months (range 1-143), the median survival time was 52 months [95% confidence interval (CI) 41.67-62.33], and the postoperative 1-, 3-, and 5-year DSS rates were 86.7%, 57.3%, and 47.2%, respectively. Univariate and multivariate regression analysis demonstrated that age, grade, tumor size, lymph node ratio, extension range, and histology were independent risk factors for DSS. The C-index of the internal validation dataset for predicting DSS was 0.70 (95% CI 0.68-0.72), which was superior to that of the American Joint Committee on Cancer staging, i.e. 0.64 (95% CI 0.62-0.66; p < 0.001). The 5-year DSS and median DSS time for the low-risk group were significantly greater than those for the high-risk group (p < 0.001). Our nomogram reliably and accurately predicted DSS in patients with non-metastatic ampullary carcinoma after surgery. This model may help clinicians in their decision making.


Improving the Blast Resistance of Large Steel Gates-Numerical Study.
Blast resistant gates/doors are essential for sensitive infrastructure, such as embassies, ministries, or parliaments. Lightweight gates equipped with 'energy absorbing systems' have better operational performance than the traditional costly and bulky design. Graded auxetic structures have not yet been used as potential passive damping systems in the supporting frame of blast resistant gates. Consequently, this study tries to test if a uniaxial graded auxetic damper (UGAD) proposed by the authors in a recent article, namely the development of a new shock absorbing UGAD, could maintain a 3000 × 4500 mm steel gate operable after high blast peak reflected overpressure of 6.6 MPa, from 100 kg TNT at 5 m stand-off distance. The blast-induced response of the gate was assessed, with and without the proposed UGAD, using Abaqus/Explicit solver. Results showed that the attachment of the proposed UGAD to the gate led to a dramatic decrease in permanent deformations (a critical factor for gate operability after a blast event). Hence, a lighter, more economical gate (with 50% reduction in mass) was required to satisfy the operability condition. In addition, 49% of peak reaction forces were diminished, that have a direct impact on the supporting frame. Moreover, the results revealed that, in the numerical model, 56% of the achieved plastic dissipation energy was from the UGADs, and 44% from the gate. The outcomes of this research may have a positive impact on other sectors beyond academia, such as industry, economy, and public safety.


Sexual Dimorphism in the Age-Induced Insulin Resistance, Liver Steatosis, and Adipose Tissue Function in Rats.
Age-linked metabolic disturbances, such as liver steatosis and insulin resistance, show greater prevalence in men than in women. Thus, our aim was to analyze these sex-related differences in male and female Wistar rats (aged 26 days and 3, 7, and 14 months), and to assess their potential relationship with alterations in the capacity of adipose tissue expansion and the dysregulation of the main adipokines produced by the adipose tissue, leptin and adiponectin. Adiposity-related parameters, blood parameters, the expression of genes related to expandability and inflammation (WAT), lipid metabolism (liver), and leptin and insulin signaling (both tissues) were measured. In females, adiposity index and WAT DNA content gradually increased with age, whereas males peaked at 7 months. A similar sex-dependent pattern was observed for leptin expression in WAT, while Mest expression levels decreased with age in males but not in females. Females also showed increased expression of the proliferation marker PCNA in the inguinal WAT compared to males. In males, leptin/adiponectin ratio greatly increased from 7 to 14 months in a more acute manner than in females, along with an increase in HOMA-IR index and hepatic triacylglyceride content, while no changes were observed in females. In liver, 14-month-old males displayed decreased mRNA levels of Insr, Ampkα2, and Cpt1a compared with levels at 7 months. Males also showed decreased mRNA levels of Obrb (both tissues), and increased expression levels of Cd68 and Emr1 (WAT) with age. In conclusion, females are more protected from age-related metabolic disturbances, such as insulin resistance, hepatic lipid deposition, and WAT inflammation compared to males. This may be related to their greater capacity for WAT expansion-reflected by a greater Mest/leptin mRNA ratio-and to their ability to maintain adiponectin levels and preserve leptin sensitivity with aging.


Circadian Patterns of Heart Rate Turbulence, Heart Rate Variability and Their Relationship.
Heart rate variability (HRV) is an established tool for studying cardiac autonomic activity over time, while heart rate turbulence (HRT) is a recent method used to assess autonomic dysfunction. However, there are different autonomic tones at different times of a day. This study aimed to examine the effect of circadian change of autonomic tone on heart rate turbulence and variability, and determine any relationship between them based on circadian variations. Twenty-four-hour Holter recordings from 35 subjects with structurally normal heart were done, and HRV and HRT parameters of turbulence onset (TO) and turbulence slope (TS) were calculated. The 24-hour circadian patterns of these parameters and correlation analysis between them were performed. There were conspicuous diurnal oscillations in TS and HRV parameters, with less prominent variation in TO. TS and high frequency power (HF) shared the similar oscillation patterns in a day. Comparing HRT and HRV based on circadian variation, TS showed positive correlations with HF and low frequency power (LF) to a reasonable degree, while there was an inverse correlation between TS and LF/HF. Circadian change of TS values throughout the day is more prominent than TO. It also presents as an autonomic activity more than TO. The relationships between HRV and HRT persist independently on the time of a day.


Laparoscopic assisted vaginal hysterectomy of the large uterus using ultrasonic dissection.
Laparoscopic assisted vaginal hysterectomy (LAVH) is a procedure gaining in popularity over abdominal hysterectomy, for a number of different indications. According to a recent study by Wilcox, et al., over 1.7 million women underwent a hysterectomy procedure in the U.S. from 1988 through 1990, and two-thirds of the procedures for benign disease were performed for leiomyomata or endometriosis, indications typically afflicting women of child-bearing age. Seventy-five percent of the procedures included in the Wilcox study were abdominal hysterectomies, the remainder being vaginal hysterectomies. National Hospital Discharge Summary data reveal that 562,000 hysterectomies were performed in 1993, rendering hysterectomy second only to cesarean section in volume of annual Ob/Gyn surgical procedures performed.


Early Neonatal SARS-CoV-2 Infection Manifesting With Hypoxemia Requiring Respiratory Support.
We describe a case of neonatal SARS-CoV-2 infection, in an infant diagnosed 3 days after birth, and manifesting with silent hypoxemia, requiring respiratory support.


Attracting Views and Going Viral: How Message Features and News-Sharing Channels Affect Health News Diffusion.
This study examined how intrinsic as well as perceived message features affect the extent to which online health news stories prompt audience selections and social retransmissions, and how news-sharing channels (e-mail vs. social media) shape what goes viral. The study analyzed actual behavioral data on audience viewing and sharing of New York Times health news articles, and associated article content and context data. News articles with high informational utility and positive sentiment invited more frequent selections and retransmissions. Articles were also more frequently selected when they presented controversial, emotionally evocative, and familiar content. Informational utility and novelty had stronger positive associations with e-mail-specific virality, while emotional evocativeness, content familiarity, and exemplification played a larger role in triggering social media-based retransmissions.


Neonatal Sepsis.
Neonatal sepsis is associated with severe morbidity and mortality in the neonatal period. Clinical manifestations range from subclinical infection to severe local or systemic infection. Neonatal sepsis is divided into three groups as early-onset neonatal sepsis, late-onset neonatal sepsis and very late-onset neonatal sepsis according to the time of the onset. It was observed that the incidence of early-onset neonatal sepsis decreased with intrapartum antibiotic treatment. However, the incidence of late-onset neonatal sepsis has increased with the increase in the survival rate of preterm and very low weight babies. The source of the causative pathogen may be acquisition from the intrauterine origin but may also acquisition from maternal flora, hospital or community. Prematurity, low birth weight, chorioamnionitis, premature prolonged rupture of membranes, resuscitation, low APGAR score, inability to breastfeed, prolonged hospital stay and invasive procedures are among the risk factors. This article reviews current information on the definition, classification, epidemiology, risk factors, pathogenesis, clinical symptoms, diagnostic methods and treatment of neonatal sepsis.


Impact of Graft Velocity on Saphenous Vein Graft Atherosclerosis after Coronary Artery Bypass Grafting.
Saphenous vein grafts (SVGs) sometimes occur as vein graft stenosis or failure in coronary artery bypass grafting. The purpose of this study was to detect the factors affecting vein graft atherosclerosis. We performed two analysis. In the first analysis, we enrolled 120 grafts using conventionally harvested saphenous vein graft (C-SVG) and followed-up with multiple coronary computed tomography angiography (CCTA). We examined the factors that contribute to the graft atherosclerosis defined by graft failure at subsequent CCTA or substantial progression of graft stenosis (a decrease of ≥0.6 mm in diameter). In the second analysis, 66 grafts using no-touch harvested saphenous vein graft (N-SVG) were compared with those in the first analysis using C-SVG, focusing on the differences in intraoperative factors using propensity score-matched analysis. In the first analysis, graft atherosclerosis+ group comprised 27 grafts, which had a larger SVG diameter, lower graft velocity, and higher graft/native ratio in diameter than the graft atherosclerosis- group. In the multivariable analysis, slow graft velocity and graft/native ≥2 in diameter were independently associated with the graft atherosclerosis. In the second analysis, the N-SVG group had a much greater graft velocity than the C-SVG group. Lower graft velocity and higher graft/native ratio in diameter were associated with the graft atherosclerosis. The N-SVG group had increased graft velocity, which may contribute to prevent the graft atherosclerosis.(Trial registration: UMIN Clinical Trial Registry no. UMIN000050482. Registered 3 March 2023, retrospectively registered.).


Repellent Effect of Volatile Fatty Acids on Lesser Mealworm (Alphitobius diaperinus).
Volatile fatty acids (VFAs) are a group of common metabolites and semiochemicals mediating information transfer between higher organisms and bacteria, either from microbiome or external environment. VFAs commonly occur among various insect orders. There are numerous studies exploring their influence on the behavior of different insect species. In relation to the papers published by J. E. McFarlane in 1985, we assessed the effects of formic, acetic, propionic, butyric and valeric acids on the spatial preference of the lesser mealworm (Alphitobius diaperinus), a common pest of stored food grain products and the poultry industry. The main aim of the presented study was to provide new angles in VFA research, recreating the classical study both with new methods and on economically significant pest species. This paper presents a novel method of continuous, simultaneous assessment of site preference and the travelled distance in a constant-flow olfactometer. All the tested VFAs, except valeric acid, had a significant repellent effect, with formic acid being effective even at the lowest used concentration. Additionally, the VFAs significantly altered the distance travelled by the insects. The obtained results indicate a potential role for VFAs in the olfactory guided behavior of A. diaperinus. It is suspected that the reaction to the presence of VFAs may deviate from the specificity of species' original habitat.