Infectious Angiogenesis-Different Pathways, the Same Goal.
Infectious angiogenesis is the biological response of neoangiogenesis induced by infectious organisms. The authors present 3 exemplary entities which show paradigmatic clinico-pathological settings of infectious angiogenesis: Bacillary angiomatosis, Orf (ecthyma contagiosum), and Kaposi sarcoma. The authors review the literature and elucidate etiopathogenetic pathways leading to the phenomenon of neovascularization stimulated by infectious organisms. The authors describe the clinical and histological pictures, interactions between microorganisms and host cells, and changes that occur within cellular structures, as well as angiogenic factors that underpin infectious angiogenesis. The importance of chronic inflammation and tumor angiogenesis is emphasized.


Bone marrow transplant for the haemoglobinopathies: past, present and future.
Bone marrow transplantation (BMT) is the only treatment currently available which can cure thalassaemia and sickle cell anaemia. However, it is not without risk and the complications of graft failure, GVHD, veno-occlusive disease, interstitial pneumonitis and infections, together with the toxicity of the conditioning therapy result in a transplant-related mortality in children of 10-20%. For the survivors, long-term sequelae include chronic GVHD, endocrinopathies and an increased incidence of secondary malignancies. The decision to offer BMT to a patient with a haemoglobinopathy must be based on a knowledge of the relative risks of transplant and conventional therapy. However, in sickle cell anaemia, a subset of patients with particularly severe disease can be identified at an early age when the risks associated with BMT are at their lowest. In thalassaemia, chelation therapy can delay the onset of organ damage due to hypertransfusion but is unlikely to prevent it entirely. The results of BMT in children without organ impairment are excellent and BMT must now be considered a real alternative to conventional treatment. Gene therapy is an exciting prospect for the future but recent progress in retroviral gene transfer has been hindered by poor infection efficiencies and expression levels in the target cells. The identification of the positive regulatory elements of both the alpha- and beta-globin genes may resolve some of these problems. Finally, alternative gene delivery systems are being investigated, but the introduction of gene therapy for the haemoglobinopathies into clinical practice may need to await successful gene targeting and replacement.


Nursing care in the chronic phase of COPD: a call for innovative disciplinary research.
The literature on nursing care in nurse clinics that focus on chronic management of chronic obstructive pulmonary disease (COPD) is analysed and synthesised with the purpose of advancing research of practice in nurse clinics. Along with the rising prevalence of COPD and a growing recognition of long-lasting, comprehensive and complex healthcare needs of people with COPD and their families, nurses are challenged to restructure their practice. An integrated review was conducted. The databases searched were NCBI's PubMed database, Scopus, CINAHL and Web of Science from 1996 to 2006. Terms searched were 'COPD' and 'nurse managed clinic' with all subheadings. A nurse had to be primary in managing and providing the services and the methodological approach was inclusive. Of 385 potentially relevant papers, 20 papers reporting 16 studies met the inclusion criteria. The methodological approach was diverse with randomised controlled trials being most common. Significant benefits from experimental treatments were seldom demonstrated. Nursing care in the chronic phase of COPD has mainly been conceptualised as: home-based respiratory care; self-management educational programmes and telephone service with influences of specialisation in respiratory nursing care on patients' outcomes as an emphasis as well. Family focus was not found in any of the studies. Research on nurse clinics that focus on the chronic phase of COPD is in its infancy. Innovative research that addresses the structure and content of the nursing care is essential. Nursing care in nurse clinics that focus on the chronic phase of COPD needs to be based on nursing knowledge, evidence based, comprehensive, family-centred, focused on health and the health experience and be situated within the service system. Diversity, creativity and nursing values should prevail when developing nurse clinics for the purpose of creating possibilities to attend to the whole of patients' and their families' needs and experiences.


The DNA database search controversy revisited: bridging the Bayesian-frequentist gap.
Two different quantities have been suggested for quantification of evidence in cases where a suspect is found by a search through a database of DNA profiles. The likelihood ratio, typically motivated from a Bayesian setting, is preferred by most experts in the field. The so-called np rule has been suggested through frequentist arguments and has been suggested by the American National Research Council and Stockmarr (1999, Biometrics55, 671-677). The two quantities differ substantially and have given rise to the DNA database search controversy. Although several authors have criticized the different approaches, a full explanation of why these differences appear is still lacking. In this article we show that a P-value in a frequentist hypothesis setting is approximately equal to the result of the np rule. We argue, however, that a more reasonable procedure in this case is to use conditional testing, in which case a P-value directly related to posterior probabilities and the likelihood ratio is obtained. This way of viewing the problem bridges the gap between the Bayesian and frequentist approaches. At the same time it indicates that the np rule should not be used to quantify evidence.


Diarrhea: a new risk factor for neural tube defects?
Neural tube defects (NTDs) affect approximately 4000 US pregnancies annually. Folic acid supplementation taken before conception protects against the occurrence of NTDs. Adequate levels of vitamin B12 also appear to play a significant role. Gastrointestinal disturbances, such as those caused by diarrhea, might negatively affect the availability of these vitamins, thereby increasing the risk of these birth defects. To determine whether periconceptional diarrhea increases the risk of NTD-affected pregnancies, a population-based case-control study was conducted in the 14 Texas-Mexico border counties. Information on diarrhea and other risk factors was ascertained by in-person interview. Study subjects were Mexican-American women who resided and delivered in any border county during 1995-2000. Case women, identified through active surveillance, had liveborn or stillborn infants or fetuses diagnosed with anencephalus, spina bifida, or encephalocele. Control women were randomly selected from women delivering normal live births in study area health facilities. One or more episodes of periconceptional diarrhea were associated with increased risk of NTD-affected pregnancies compared to no episodes of diarrhea (OR = 3.7, 95% CI = 1.8-7.6). This association was independent of fever, obesity, maternal age, maternal birthplace, income, prior unproductive pregnancy, and dietary plus multivitamin folate intake, known risk factors for NTDs. Confirmation of this new risk factor might have public health implications due to the feasibility of modifying exposure.


The 'Amoeboid Predator-Fungal Animal Virulence' Hypothesis.
The observation that some aspects of amoeba-fungal interactions resemble animal phagocytic cell-fungal interactions, together with the finding that amoeba passage can enhance the virulence of some pathogenic fungi, has stimulated interest in the amoeba as a model system for the study of fungal virulence. Amoeba provide a relatively easy and cheap model system where multiple variables can be controlled for the study of fungi-protozoal (amoeba) interactions. Consequently, there have been significant efforts to study fungal⁻amoeba interactions in the laboratory, which have already provided new insights into the origin of fungal virulence as well as suggested new avenues for experimentation. In this essay we review the available literature, which highlights the varied nature of amoeba-fungal interactions and suggests some unsolved questions that are potential areas for future investigation. Overall, results from multiple independent groups support the 'amoeboid predator⁻fungal animal virulence hypothesis', which posits that fungal cell predation by amoeba can select for traits that also function during animal infection to promote their survival and thus contribute to virulence.


Lipocalin-2 Promotes Endoplasmic Reticulum Stress and Proliferation by Augmenting Intracellular Iron in Human Pulmonary Arterial Smooth Muscle Cells.
Endoplasmic reticulum (ER) stress, a feature of many conditions associated with pulmonary hypertension (PH), is increasingly recognized as a common response to promote proliferation in the walls of pulmonary arteries. Increased expression of Lipocalin-2 in PH led us to test the hypothesis that Lipocalin-2, a protein known to sequester iron and regulate it intracellularly, might facilitate the ER stress and proliferation in pulmonary arterial smooth muscle cells (PASMCs). In this study, we observed greatly increased Lcn2 expression accompanied with increased ATF6 cleavage in a standard rat model of pulmonary hypertension induced by monocrotaline. In cultured human PASMCs, Lcn2 significantly promoted ER stress (determined by augmented cleavage and nuclear localization of ATF6, up-regulated transcription of GRP78 and NOGO, increased expression of SOD2, and mild augmented mitochondrial membrane potential) and proliferation (assessed by Ki67 staining and BrdU incorporation). Lcn2 promoted ER stress accompanied with augmented intracellular iron levels in human PASMCs. Treatment human PASMCs with FeSO4 induced the similar ER stress and proliferation response and iron chelator (deferoxamine) abrogated the ER stress and proliferation induced by Lcn2 in cultured human PASMCs. In conclusion, Lcn2 significantly promoted human PASMC ER stress and proliferation by augmenting intracellular iron. The up-regulation of Lcn2 probably involved in the pathogenesis and progression of PH.


Neuropathic pain--recent trends in management.
Injury to central or peripheral nervous system causes neuropathic pain. Initially it affects the sensory nerves, then the motor nerves. In crush or traumatic injuries the sensory or motor nerves are affected simultaneously and the symptoms develop simultaneously. Spontaneous pain, abnormal evoked pains and paroxysmal evoked pain are the pesenting symptoms. Types of neuropathies are: Peripheral nerve lesion, spinal or ganglionic lesion and spinal cord lesion. Diabetic neuropathy, postherpetic neuralgia and painful polyneuropathy are the types which should be looked meticulously. The treatment modality can be subdivided into pharmacological pain management and interventional pain management. The following groups of drugs can be used either singularly or in combination in pharmacological pain management: Analgesics, anticonvulsants, antidepressants and miscellaneous group. Interventional pain management can be done by: Neural blockade, electric stimulation and implantable devices.


Investigation on the pH-independent photoluminescence emission from carbon dots impregnated on polymer matrix.
Highly luminescent, polymer nanocomposite films based on poly(vinyl alcohol) (PVA), and monodispersed carbon dots (C-dots) derived from multiwalled carbon nanotubes (MWCNTs), as coatings on substrates as well as free standing ones are obtained via solution-based techniques. The synthesized films exhibit pH-independent photoluminescence (PL) emission, which is an advantageous property compared with the pH-dependent photoluminescence intensity variations, generally observed for the C-dots dispersed in aqueous solution. The synthesized C-dots and the nanocomposite films are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FTIR), ultraviolet (UV) - visible spectroscopy and photoluminescence spectroscopy (PL) techniques. The TEM image provides clear evidence for the formation of C-dots of almost uniform shape and average size of about 8 nm, homogeneously dispersed in aqueous medium. The strong anchoring of C-dots within the polymer matrix can be confirmed from the XRD results. The FTIR spectral studies conclusively establish the presence of oxygen functional groups on the surfaces of the C-dots. The photoluminescence (PL) emission spectra of the nanocomposite films are broad, covering most part of the visible region. The PL spectra do not show any luminescence intensity variations, when the pH of the medium is changed from 1 to 11. The pH-independent luminescence, shown by these films offers ample scope for using them as coatings for designing diagnostic and imaging tools in bio medical applications. The non-toxic nature of these nanocomposite films has been established on the basis of cytotoxicity studies.


Deoxyribonucleotide pools, base pairing, and sequence configuration affecting bromodeoxyuridine- and 2-aminopurine-induced mutagenesis.
Despite recent experiments showing that BrdUrd-induced mutagenesis can be independent of the level of bromouracil (BrUra) substitution [Kaufman, E.R. & Davidson, R.L. (1978) Proc. Natl. Acad. Sci. USA 75, 4982-4986; Aebersold, P.M. (1976) Mutat. Res. 36, 357-362], BrUra.G base mispairs are a major determinant of mutagenesis. We propose that the experiments cited above are sensitive predominantly to G . C leads to A . T transitions driven by the immeasurably small but highly mutagenic substitution of BrUra for cytosine and not by the gross substitution of BrUra for thymine in DNA. More generally, we show how accumulated evidence suggests that both BrdUrd and 2-aminopurine have two mutagenic effects intracellularly: perturbation of normal deoxyribonucleoside triphosphate pools and analogue mispairs in DNA. We propose a molecular basis for various observations of normal exogenous deoxyribonucleosides as synergists and counteragents to base analogue mutagenesis. A model is proposed to explain the antipolarity of BrdUrd and 2-aminopurine mutagenesis--i.e., why mutants at hot spots for induction by one base analogue are usually hot spots for reversion by the other. It is concluded that the configuration of the neighboring nucleotides surrounding the base analogue mispair, and not the base analogue's preference for inducing A . T leads to G . C or G . C leads to A . T errors, is responsible for the antipolarity of BrdUrd and 2-aminopurine mutagenesis.


Different neural frequency bands integrate faces and voices differently in the superior temporal sulcus.
The integration of auditory and visual information is required for the default mode of speech-face-to-face communication. As revealed by functional magnetic resonance imaging and electrophysiological studies, the regions in and around the superior temporal sulcus (STS) are implicated in this process. To provide greater insights into the network-level dynamics of the STS during audiovisual integration, we used a macaque model system to analyze the different frequency bands of local field potential (LFP) responses to the auditory and visual components of vocalizations. These vocalizations (like human speech) have a natural time delay between the onset of visible mouth movements and the onset of the voice (the "time-to-voice" or TTV). We show that the LFP responses to faces and voices elicit distinct bands of activity in the theta (4-8 Hz), alpha (8-14 Hz), and gamma (>40 Hz) frequency ranges. Along with single neuron responses, the gamma band activity was greater for face stimuli than voice stimuli. Surprisingly, the opposite was true for the low-frequency bands-auditory responses were of a greater magnitude. Furthermore, gamma band responses in STS were sustained for dynamic faces but not so for voices (the opposite is true for auditory cortex). These data suggest that visual and auditory stimuli are processed in fundamentally different ways in the STS. Finally, we show that the three bands integrate faces and voices differently: theta band activity showed weak multisensory behavior regardless of TTV, the alpha band activity was enhanced for calls with short TTVs but showed little integration for longer TTVs, and finally, the gamma band activity was consistently enhanced for all TTVs. These data demonstrate that LFP activity from the STS can be segregated into distinct frequency bands which integrate audiovisual communication signals in an independent manner. These different bands may reflect different spatial scales of network processing during face-to-face communication.


[Screening for spinal muscular atrophy mutation carriers among 4931 pregnant women from Liuzhou region of Guangxi].
To screen for carriers of SMN1 gene mutation, which underlies spinal muscular atrophy (SMA), in 4931 pregnant women from Liuzhou region of Guangxi, and to determine the carrier rate. Combined denaturing high-performance liquid chromatography (DHPLC) and multiple PCR techniques were used to detect the copy number of SMN1 gene. The carrier frequency was calculated. The spouse of the carrier was also screened, and prenatal diagnosis was provided to the couples who were both positive. Among the 4931 pregnant women, 61 were found to harbor only one copy of the SMN1 gene, which yielded a carrier rate of 1.2%. Subsequent testing has identified 1 fetus carrying homozygous deletions of the SMN1 gene. The carrier rate of SMA mutation in Liuzhou region is slightly lower than that of other regions of southern China. DHPLC can effectively screen the carriers of SMA mutation and provide a basis for genetic counseling and prenatal diagnosis.


Sedative and Analgesic Drug Rotation Protocol in Critically Ill Children With Prolonged Sedation: Evaluation of Implementation and Efficacy to Reduce Withdrawal Syndrome.
The first aim of this study was to assess the implementation of a sedative and analgesic drug rotation protocol in a PICU. The second aim was to analyze the incidence of withdrawal syndrome, drug doses, and time of sedative or analgesic drug infusion in children after the implementation of the new protocol. Prospective observational study. PICU of a tertiary care hospital between June 2012 and June 2016. All patients between 1 month and 16 years old admitted to the PICU who received continuous IV infusion of sedative or analgesic drugs for more than 4 days were included in the study. A sedative and analgesic drug rotation protocol was designed. The level of sedation, analgesia, and withdrawal syndrome were monitored with validated scales. The relationship between compliance with the protocol and the incidence of withdrawal syndrome was studied. One-hundred pediatric patients were included in the study. The protocol was followed properly in 35% of patients. Sixty-seven percent of the overall cohort presented with withdrawal syndrome. There was a lower incidence rate of withdrawal syndrome (34.3% vs 84.6%; p < 0.001), shorter PICU length of stay (median 16 vs 25 d; p = 0.003), less time of opioid infusion (median 5 vs 7 d for fentanyl; p = 0.004), benzodiazepines (median 5 vs 9 d; p = 0.001), and propofol (median 4 vs 8 d; p = 0.001) in the cohort of children in which the protocol was followed correctly. Our results show that compliance with the drug rotation protocol in critically ill children requiring prolonged sedation may reduce the appearance of withdrawal syndrome without increasing the risk of adverse effects. Furthermore, it may reduce the time of continuous IV infusions for most sedative and analgesic drugs and the length of stay in PICU.


Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity.
The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential.


Statistical approach to quantum chaotic ratchets.
The quantum ratchet effect in fully chaotic systems is approached by studying statistical properties of the ratchet current over well-defined sets of initial states. Natural initial states in a semiclassical regime are those that are phase-space uniform with the maximal possible resolution of one Planck cell. General arguments in this regime, for quantum-resonance values of a scaled Planck constant variant Planck's over 2pi , predict that the distribution of the current over all such states is a zero-mean Gaussian with variance approximately Dvariant Planck's over 2pi2/(2pi2) , where D is the chaotic-diffusion coefficient. This prediction is well supported by extensive numerical evidence. The average strength of the effect, measured by the variance above, is significantly larger than that for the usual momentum states and other states. Such strong effects should be experimentally observable.


Influence of age and physical activity on the primary in vivo antibody and T cell-mediated responses in men.
The aging immune system is characterized by the progressive decline in the antibody and T cell-mediated responses to antigen. Little is known, however, about the benefits of exercise in aging on the generation of a primary immune response to antigen and the subsequent antibody and memory T cell-mediated response. Most in vivo immune research to date has utilized vaccines or recall antigens to elicit an immune response. Therefore, the purpose of this experiment was to examine the association of aging and physical activity on the primary antibody and T cell response to the novel protein antigen keyhole-limpet hemocyanin (KLH). Forty-six physically active and sedentary, young (20-35 yr) and older (60-79 yr) men were recruited. Subjects were intramuscularly immunized with 100 microg of KLH, and blood samples were collected at days 0, 7, 14, 21, and 28. Samples were measured for anti-KLH IgM, IgG, IgG1, and IgG2 by ELISA. On day 21 after intramuscular KLH administration, subjects received an intradermal injection with 1 microg of KLH of inflammation recorded at 24, 48, 72, 96, and 120 h to assess anti-KLH delayed-type hypersensitivity response. There was a significant reduction in all anti-KLH measures with aging except for anti-KLH IgG2. The physically active older group had significantly higher anti-KLH IgM, IgG, IgG1, and delayed-type hypersensitivity responses, but not IgG2 compared with the sedentary older group. In conclusion, regular physical activity in older men is associated with a more robust immune response to novel antigenic challenge.


Growth rate of lung function in healthy preterm infants.
It remains unclear whether premature birth, in the absence of neonatal respiratory disease, results in abnormal growth and development of the lung. We previously reported that a group of healthy infants born at 32-34 weeks' gestation and without respiratory complications had decreased forced expiratory flows and normal forced vital capacities at 2 months of age. Our current study evaluated whether these healthy infants born prematurely exhibited improvement or "catch-up" in their lung function during the second year of life. Longitudinal measurements of forced expiratory flows by the raised volume rapid thoracic compression technique were obtained in the first and the second years of life for infants born prematurely at 32.7 (range, 30-34) weeks' gestation (n = 26) and infants born at full term (n = 24). Healthy infants born prematurely demonstrate decreased forced expiratory flows and normal forced vital capacities in the first and second years of life. In addition, the increases in lung function with growth were similar to full-term infants. Persistently reduced flows in the presence of normal forced vital capacity and the absence of catch-up growth in airway function suggest that premature birth is associated with altered lung development.


Physiologic variance of corticotropin affects diagnosis in adrenal vein sampling.
Differentiating unilateral form from bilateral is a critical diagnostic step in primary aldosteronism (PA), for which adrenal vein sampling (AVS) is accepted to be the most reliable. However, variance of corticotropin could affect the diagnosis in AVS. We conducted simultaneous bilateral AVS on ten biochemically diagnosed PA cases, and used the aldosterone-to-cortisol ratio (A/C) of the samples for the diagnosis. The diagnosis by AVS after a low-dose (0.1 microg) ACTH stimulation, which can provoke maximum-physiologic corticotropic response, was compared with those before the stimulation and after the standard-dose (250 microg) ACTH stimulation. In half of the cases, the low-dose pre-stimulation affected the diagnosis. In four out of ten cases, the side-to-side ratios of A/C were changed in the basal/low-dose/standard-dose AVS as 6.62/2.46/0.63, 2.13/0.41/0.14, 1.88/2.38/2.40, and 1.96/2.27/1.90 respectively. In three out of ten cases, the adrenal vein to the matching inferior vena cava ratio of A/C was also changed across 1, the cut-off to indicate suppression of aldosterone secretion. Additionally, the confirmation of successful sampling was difficult in five out of ten and two out of ten cases of the basal and low-dose AVS respectively, whereas it was easy in all the cases of the standard-dose AVS. The diagnosis in the basal AVS could be affected by the physiologic fluctuation of ACTH at relatively high prevalence. The basal AVS would be unreliable to differentiate two forms of PA.


Extended-release naltrexone versus buprenorphine-naloxone to treat opioid use disorder among black adults.
Few studies examine the effectiveness of treatments for opioid use disorder (OUD) among Black individuals despite recent evidence suggesting opioid overdose death rates are, in some cases, highest and increasing at a faster rate among Black people compared to other racial/ethnic groups. This secondary analysis study investigated treatment preference, retention, and relapse rates amongst a subgroup of 73 Black participants with OUD (81% male, mean age 39.05, SD = 11.80) participating in a 24-week multisite randomized clinical trial ("X:BOT") comparing the effectiveness of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) between 2014 and 2017. Chi-square analyses were used to investigate treatment preference assessed at baseline, and logistic regression analyses were used to investigate differences in the odds of retention and relapse assessed over the 24-week course of treatment between treatment groups. Our findings suggest no differences in preference for XR-NTX versus BUP-NX. However, similar to the parent trial, there was an induction hurdle such that only 59.5% of those randomized to XR-NTX successfully initiated medication compared to 91.6% of those randomized to BUP-NX (OR = 0.13, 95% CI = 0.04, 0.52). No significant differences were found in treatment retention (intention-to-treat: OR = 1.19, 95% CI = 0.43, 3.28; per-protocol [i.e., those who initiated medication]: OR = 0.60, 95% CI = 0.20, 1.82) or relapse rates between treatment groups (intention-to-treat: OR = 1.53, 95% CI = 0.57, 4.13; per-protocol: OR = 0.69, 95% CI = 0.23, 2.06). Although there is a significant initiation hurdle with XR-NTX, once inducted, both medications appear similar in effectiveness, but as in the main study, dropout rates were high. Future research is needed on how to improve adherence.


Effects of probiotic-supplemented diets on growth performance and intestinal immune characteristics of broiler chickens.
This study was conducted to investigate the effects of a probiotic product incorporating Lactobacillus fermentum and Saccharomyces cerevisiae on the growth performance and intestinal immune status in broiler chickens. A total of six hundred ninety-six 1-d-old male Cobb broilers were randomly allotted by BW in 1 of 4 treatments for 6-wk trial. The dietary treatments included the basal diet (NC), and the basal diets supplemented with an antibiotic (100 mg of chlortetracycline/kg of diet; PC), 0.1%, or 0.2% probiotic product (containing 1 × 10(7) cfu/g of Lactobacillus fermentum JS and 2 × 10(6) cfu/g of Saccharomyces cerevisiae). Each treatment had 6 replicates with 29 broilers each. The ADG and feed efficiency were improved (P < 0.05) in broilers fed the probiotic diet compared with NC, and were similar to the PC group during 1 to 21 d. However, there were no significant differences in growth performance of broilers during 22 to 42 d among different dietary treatments. Chicks fed probiotics had higher proportions of CD3+, CD4+, and CD8+ T-lymphocytes, whereas the antibiotic diet decreased the proportion of CD8+ T-lymphocytes in the foregut of broilers at 21 and 42 d compared with the NC group. No significant difference was observed in the mRNA expression level of chicken B-cell marker chB6 (Bu-1) in the foregut of chickens among different treatments. Probiotic-supplemented diets increased (P < 0.05) the mRNA expression levels of Toll-like receptor (TLR) 2 and TLR 4 at 21 d, and only the TLR2 mRNA level at 42 d in the foregut of chickens, but did not change (P > 0.05) TLR7 mRNA expression compared with NC or PC. There was no significant difference in the above TLR mRNA levels in the intestine of broilers between PC and NC. These results indicated that the probiotic product incorporating Lactobacillus fermentum and Saccharomyces cerevisiae could stimulate intestinal T-cell immune system without decreasing growth performance in broilers during 1 to 21 d.


Crystallization and preliminary crystallographic studies of both components of the staphylococcal LukE-LukD leukotoxin.
Soluble forms of recombinant LukE protein (expressed in Escherichia coli) and of wild-type LukD protein (expressed in Staphylococcus aureus), which together form the staphylococcal LukE-LukD leukotoxin, were purified to homogeneity and crystallized using the sitting-drop vapour-diffusion method. The crystals of LukE belonged to space group I4, with unit-cell parameters a = b = 134.50, c = 64.43 Å, and diffracted X-rays to 1.6 Å resolution. The crystals of LukD belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 48.04, b = 50.99, c = 137.40 Å, and diffracted to 1.9 Å resolution. Molecular replacement using the LukF-PV structure (PDB entry 1pvl) as a template model allowed the identification of an initial structure solution for the LukD data. In the case of LukE, a solution comprising only a single copy of the search model (LukS-PV; PDB entry 1t5r) was found, although the unit-cell parameters indicated that up to three molecules could be accommodated in the asymmetric unit.


Growth control and neoplastic transformation in the brain.
For many scientists it is often difficult to predict which meetings, among the plethora convening each year, will be the most rewarding. A particular strength of the Zülch symposium was the lively exchange of novel findings and ideas among researchers tackling problems as diverse as photoreceptor cell development in Drosophila and the molecular basis of tumor metastasis. It is these small focused meetings which draw together molecular biologists, clinicians, and pathologists that bear the key to success. Both of us felt strongly that all participants took ideas back home. What else could we ask for? If Zülch had been granted the opportunity to come to Goslar, he would have enjoyed this symposium very much.


Do valsartan and losartan have the same effects in the treatment of coronary artery disease?
Many angiotensin II type 1 receptor blockers (ARBs) are available for clinical use, but because they do not all have the same effects, the present study investigated whether all benefits conferred by ARBs are class effects. Study 1 was a case-control study of patients with coronary artery disease, which showed that a non-depressor dose of valsartan significantly decreased the rate of target lesion revascularization at 6 months after stenting compared with the control group without ARB treatment. In Study 2, 44 patients with acute myocardial infarction who randomly received an initial lower dose of either valsartan or losartan after stenting were evaluated. The late loss and decrease in %diameter stenosis in the valsartan group were significantly lower than those in the losartan group as assessed by quantitative coronary angiography after 6 months. In addition, the valsartan group showed a significantly lower expression of intracellular adhesion molecule-1 and L-selectin. A non-depressor dose of ARB may have beneficial effects on coronary restenosis that are associated with the regulation of adhesion molecules, and these effects might not be a class effect of ARBs.


Artesunate Alleviates Chronic Hyperoxia-induced Bronchopulmonary Dysplasia by Suppressing NF-κB Pathway in Neonatal Mice.
Bronchopulmonary dysplasia (BPD) is a chronic lung condition that occurs in premature infants who undergo prolonged mechanical ventilation and oxygen therapy. Existing treatment methods have shown limited efficacy, highlighting the urgent need for new therapeutic strategies. Artesunate (AS) is a compound known for its potential anti-inflammatory properties, and studies have shown its protective effects against acute lung injury. However, its impact on BPD and the underlying mechanisms remain unclear. To investigate the effect and underlying mechanism of AS on chronic hyperoxiainduced BPD in neonatal mice. Full-term C57BL/6J mice were randomly assigned to the Air+lactate Ringer's solution (L/R) group, O2 + L/R group, and O2 + AS group. Analysis was performed using assay methods such as ELISA, RT-qPCR, hematoxylin-eosin staining, and Western blotting. Compared with the O2+L/R group, the expression of inflammatory factors in the serum, tissue, and BALF of the O2+AS group was significantly reduced, the lung function of the mice was improved, and the inflammatory infiltrates were significantly alleviated. AS inhibited the mRNA expression of inflammatory factors in mice. We found that the expression of nuclear p65 and cytoplasmic p-IκBα in the NF-κB pathway was inhibited after adding AS. AS ameliorated chronic hyperoxia-induced BPD in neonatal mice probably by inhibiting the expression of NF-κB pathway and inflammatory factors.


Delayed intratumoral hemorrhage after drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma.
Transarterial chemoembolization (TACE) using a drug-eluting bead (DEB-TACE) for hepatocellular carcinoma (HCC) is a new treatment method. We report on a case of delayed intratumoral hemorrhage after DEB-TACE. An 81-year-old male with hepatitis C virus-related cirrhosis was diagnosed with a HCC of 35 mm in diameter in S5 detected by dynamic computed tomography (CT) and contrast-enhanced ultrasonography (CEUS). DEB-TACE with DC Bead (®) and epirubicin hydrochloride was performed because the patient declined to undergo surgical resection. The treatment was completed, and the course after DEB-TACE was favorable. However, right hypochondriac pain suddenly developed about 1 month after DEB-TACE. Unenhanced CT showed an increase of the tumor diameter and intratumoral high-intensity area, which was not enhanced in the arterial phase. CEUS performed at the time of right hypochondriac pain (5 weeks after DEB-TACE) showed nonenhancement of almost the entire tumor in the vascular phase. The cause of the symptom may have been DEB-TACE-associated intratumoral hemorrhage. Tumor hemorrhage has been reported after DEB-TACE with tumors >5 cm in diameter, and the tumor locations were subcapsular in all previous reports. There has been no case of a tumor with a diameter <5 cm distinct from the subcapsular, as was observed in our patient. Incomplete embolization might be the cause of the intratumoral hemorrhage experienced by this case presenting a few risks. To obtain the therapeutic effect of DEB-TACE while preventing the adverse events, it may be important to understand the characteristics of the beads and to apply the appropriate embolization to each individual case.


Capacitating epistasis--detection and role in the genetic architecture of complex traits.
Here, we discuss the potential role of capacitating epistasis in the genetic architecture of complex traits. Two alternative methods for identifying such gene-gene interactions in genetic association studies-mapping of variance controlling loci and the variance plane ratio (VPR) method-are introduced. An overview of the theoretical foundation of the methods is presented together with a discussion on their implementation and available software for performing these analyses. We conclude by highlighting a few examples of capacitating epistasis described in the literature and its potential impacts on the genetics of complex traits.


High-symmetry polarization domains in low-symmetry ferroelectrics.
We present experimental evidence for polygonal domain faceting in the ferroelectric polymer poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) films with the lower orthorhombic crystallographic symmetry. It is proposed that this effect can arise from purely electrostatic depolarizing forces. We show that, in contrast to magnetic bubble shape domains, where such type of deformation instability has a predominantly elliptical character, the emergence of more symmetrical circular harmonics is favored in ferroelectrics with high dielectric constants.


Absence of cilia and basal bodies with predominance of brush cells in the respiratory mucosa from a patient with immotile cilia syndrome.
his report describes the ultrastructural alterations observed in the tracheal epithelium of a 13-year-old male with a history of recurrent pneumonia, chronic bronchitis, chronic otitis media, and situs inversus. The epithelium consisted of globlet and basal cells with many columnar cells that lacked cilia and basal bodies. The surface of these cells had regular microvilli and cytoplasmic features typical of brush cells.


Arsenic exposure and its impact on health in Chile.
The problem of arsenic in Chile was reviewed. In Chile, the population is exposed to arsenic naturally via drinking-water and by air pollution resulted from mining activities. The sources of arsenic were identified to estimate the exposure of population to arsenic through air, water, and food. Health effects, particularly early effects, observed in children and adults, such as vascular diseases (premature cardiac infarct), respiratory illnesses (bronchiectasis), and skin lesions have been described. Chronic effects, such as lung and bladder cancers, were reported 20 years after peak exposure and persisted 27 years after mitigation measures for removing arsenic from drinking surface water were initiated. Although the effects of arsenic are similar in different ethnic and cultural groups (e.g. Japanese, Chinese, Indian, Bangladeshi, American, and Taiwanese), variations could be explained by age at exposure, the dose received, smoking, and nutrition. Since health effects were observed at arsenic levels of 50 microg/L in drinking-water, it is advised that Chile follows the World Health Organization's recommendation of 10 microg/L. The Chilean experience in removal of arsenic suggests that it is feasible to reach this level using the conventional coagulation process.


Protein Citrullination: A Proposed Mechanism for Pathology in Traumatic Brain Injury.
Protein citrullination is a calcium-driven post-translational modification proposed to play a causative role in the neurodegenerative disorders of Alzheimer's disease, multiple sclerosis (MS), and prion disease. Citrullination can result in the formation of antigenic epitopes that underlie pathogenic autoimmune responses. This phenomenon, which is best understood in rheumatoid arthritis, may play a role in the chronic dysfunction following traumatic brain injury (TBI). Despite substantial evidence of aberrations in calcium signaling following TBI, there is little understanding of how TBI alters citrullination in the brain. The present investigation addressed this gap by examining the effects of TBI on the distribution of protein citrullination and on the specific cell types involved. Immunofluorescence revealed that controlled cortical impact in rats profoundly up--regulated protein citrullination in the cerebral cortex, external capsule, and hippocampus. This response was exclusively seen in astrocytes; no such effects were observed on the status of protein citrullination in neurons, oligodendrocytes or microglia. Further, proteomic analyses demonstrated that the effects of TBI on citrullination were confined to a relatively small subset of neural proteins. Proteins most notably affected were those also reported to be citrullinated in other disorders, including prion disease and MS. In vivo findings were extended in an in vitro model of simulated TBI employing normal human astrocytes. Pharmacologically induced calcium excitotoxicity was shown to activate the citrullination and breakdown of glial fibrillary acidic protein, producing a novel candidate TBI biomarker and potential target for autoimmune recognition. In summary, these findings demonstrate that the effects of TBI on protein citrullination are selective with respect to brain region, cell type, and proteins modified, and may contribute to a role for autoimmune dysfunction in chronic pathology following TBI.


Prevalence and predictors of disability for Māori 24 months after injury.
To investigate post-injury disability prevalence and identify pre-injury and injury-related predictors 24 months post-injury among Māori Prospective Outcomes of Injury Study participants. Participants were recruited from New Zealand's no-fault injury insurer. Pre-injury and injury-related characteristic information was obtained from participants at three and 24 months post-injury. The World Health Organization Disability Assessment Schedule was used to measure disability. Multivariable models were developed to estimate relative risks of post-injury disability. Of 2,856 participants, 566 were Māori. Analyses were restricted to 374 Māori with pre-injury and 24-month post-injury disability data available. Pre-injury, 9% reported disability compared to 19% 24 months post-injury. Strong predictors of increased risk of disability 24 months post-injury were having ≥2 chronic conditions pre-injury and having trouble accessing healthcare services after injury. Hospitalisation for injury and having inadequate pre-injury household income were other predictors. Māori experience considerable disability 24 months post-injury. Pre-injury socio-demographic, health and psychosocial, and injury-related characteristics independently predict post-injury disability and provide focus for future research and interventions to improve Māori post-injury outcomes. Implications for public health: Despite having had access to services, injured Māori experienced considerable long-term disability. Pre-injury and injury-related factors predict long-term disability and should be the focus to reduce the post-injury disability burden for Māori.


A fast and efficient python library for interfacing with the Biological Magnetic Resonance Data Bank.
The Biological Magnetic Resonance Data Bank (BMRB) is a public repository of Nuclear Magnetic Resonance (NMR) spectroscopic data of biological macromolecules. It is an important resource for many researchers using NMR to study structural, biophysical, and biochemical properties of biological macromolecules. It is primarily maintained and accessed in a flat file ASCII format known as NMR-STAR. While the format is human readable, the size of most BMRB entries makes computer readability and explicit representation a practical requirement for almost any rigorous systematic analysis. To aid in the use of this public resource, we have developed a package called nmrstarlib in the popular open-source programming language Python. The nmrstarlib's implementation is very efficient, both in design and execution. The library has facilities for reading and writing both NMR-STAR version 2.1 and 3.1 formatted files, parsing them into usable Python dictionary- and list-based data structures, making access and manipulation of the experimental data very natural within Python programs (i.e. "saveframe" and "loop" records represented as individual Python dictionary data structures). Another major advantage of this design is that data stored in original NMR-STAR can be easily converted into its equivalent JavaScript Object Notation (JSON) format, a lightweight data interchange format, facilitating data access and manipulation using Python and any other programming language that implements a JSON parser/generator (i.e., all popular programming languages). We have also developed tools to visualize assigned chemical shift values and to convert between NMR-STAR and JSONized NMR-STAR formatted files. Full API Reference Documentation, User Guide and Tutorial with code examples are also available. We have tested this new library on all current BMRB entries: 100% of all entries are parsed without any errors for both NMR-STAR version 2.1 and version 3.1 formatted files. We also compared our software to three currently available Python libraries for parsing NMR-STAR formatted files: PyStarLib, NMRPyStar, and PyNMRSTAR. The nmrstarlib package is a simple, fast, and efficient library for accessing data from the BMRB. The library provides an intuitive dictionary-based interface with which Python programs can read, edit, and write NMR-STAR formatted files and their equivalent JSONized NMR-STAR files. The nmrstarlib package can be used as a library for accessing and manipulating data stored in NMR-STAR files and as a command-line tool to convert from NMR-STAR file format into its equivalent JSON file format and vice versa, and to visualize chemical shift values. Furthermore, the nmrstarlib implementation provides a guide for effectively JSONizing other older scientific formats, improving the FAIRness of data in these formats.


Cartilage recycling in rhinoplasty: polydioxanone foil as an absorbable biomechanical scaffold.
Primary and secondary rhinoplasty often requires multiple cartilage grafts. Polydioxanone foil may be used as a temporary biomechanical scaffold on which routinely discarded cartilage fragments can be assembled to make maximal use of harvested material. The authors performed an outcome analysis of 58 primary and secondary rhinoplasties in which polydioxanone foil was used in combination with autologous cartilage for aesthetic and valvular reconstruction of the nose. Graft performance, complications, and technical points are reported. The temporary scaffold (polydioxanone foil) was used most often to construct columellar struts, septal extension grafts, and alar battens. Other uses included revision septoplasty and upper lateral replacement grafts. Two minor complications occurred: one infection and one partial extrusion. The long-term stability of the nose following this technique was found to be satisfactory (mean follow-up, 18 months), for both structural and aesthetic purposes. This technique is both simple and effective. By making maximal use of otherwise discarded cartilage fragments, it protects other graft harvest sites and decreases the incidence of the "graft-depleted" patient.


Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis.
Rituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of remission period. We searched PubMed and EMBASE for randomized clinical trials (RCTs) and observational studies evaluating immunosuppressive agents in patients with AAV. We defined serious or severe infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study was registered on PROSPERO (CRD42022366269). From 1,265 abstracts, we identified 21 studies (7 RCTs and 14 observational), with relevant data. We included data from 1,284 and 2,938 individuals for assessment in our primary and secondary outcomes, respectively. The overall cumulative incidence of serious infections was 15.99% (CI 95%: 6.95-27.53%) during the total follow-up period (induction and maintenance) and 7.62% (CI 95%: 4.43-11.43%) during the maintenance period. Additionally, we found a 0.49% overall case fatality rate (CI 95%: 0.02-1.37%) and a 0.09% infection-related mortality rate (CI 95%: 0.00-0.51%) during maintenance treatment. Notably, we found a 14.61% (CI 95%: 10.19-19.61%) cumulative incidence of serious infections among patients who received rituximab and a 5.93% (CI 95%: 1.19-13.26%) cumulative incidence of serious infections among patients who received azathioprine during maintenance. Moreover, the cumulative incidence of serious infections during the total follow-up period (induction and maintenance) was 20.81% (CI 95%:4.56-43.70%) for the combination of cyclophosphamide and azathioprine and 14.12% (CI 95%: 5.20-26.00%) for rituximab. The cumulative incidence of serious infections during total follow-up and maintenance was within expected limits, while fatal infections during maintenance treatment were uncommon. Additionally, treatment with rituximab for both induction and maintenance did not exceed the anticipated by previous studies incidence of serious infections. Clinical practice and long-term follow up data are needed to corroborate these findings. Identifier: PROSPERO (CRD42022366269).


The Toxic Symbiont Caedibacter caryophila in the Cytoplasm of Paramecium novaurelia.
Endosymbiotic bacteria were observed to inhabit the cytoplasm of the freshwater ciliate Paramecium novaurelia. Transmission electron microscopy and toxicity tests with sensitive paramecia showed that the endosymbionts belong to the genus Caedibacter. The bacteria conferred a killer trait to their host paramecia. The production of a proteinaceous inclusion body ("R-body") in the bacterial cell makes them toxic to other paramecia after they become enclosed in food vacuoles. R-bodies of Caedibacter sp were associated with phages, which are known in most other Caedibacter species to code for the R-body proteins. The killer-effect of P. novaurelia on sensitive P. caudatum strains was of the "paralysis" type, which is a characteristic of the symbiont species Caedibacter caryophila. Until now C. caryophila was known to inhabit the macronucleus of Paramecium caudatum only. Sequencing of the 16S rRNA-gene proved that Caedibacter sp from the cytoplasm of P. novaurelia belongs to the species C. caryophila as well. The rDNA-sequence of 1695 bp length differed in a total of only 1 bp from the corresponding gene in C. caryophila from the macronucleus of P. caudatum. The results indicate that the infection of specific host cell compartments may depend on host genes, but not on different traits of the infecting symbiont species. The occurrence of killer and sensitive paramecia strains together in one pond is discussed with respect to the competitive advantage of the killer trait.


Biosynthesis of tetrahydrofolate. Stereochemistry of dihydroneopterin aldolase.
7,8-Dihydroneopterin aldolase catalyzes the formation of the tetrahydrofolate precursor, 6-hydroxymethyl-7,8-dihydropterin, and is a potential target for antimicrobial and anti-parasite chemotherapy. The last step of the enzyme-catalyzed reaction is believed to involve the protonation of an enol type intermediate. In order to study the stereochemical course of that reaction step, [1',2',3',6,7-13C5]dihydroneopterin was treated with aldolase in deuterated buffer. The resulting, partially deuterated [6alpha,6,7-13C3]6-hydroxymethyl-7,8-dihydropterin was converted to partially deuterated 6-(R)-[6,7,9,11-13C4]5,10-methylenetetrahydropteroate by a sequence of three enzyme-catalyzed reactions followed by treatment with [13C]formaldehyde. The product was analyzed by multinuclear NMR spectroscopy. The data show that the carbinol group of enzymatically formed 6-hydroxymethyl-dihydropterin contained 2H predominantly in the pro-S position.


RNA in polysomes is an inhibitor of manganese superoxide dismutase RNA-binding protein activity.
A redox-sensitive protein in rat lung binds to the 3'-untranslated region (3'-UTR) of manganese superoxide dismutase (Mn-SOD) mRNA; the activity of this Mn-SOD RNA-binding protein (Mn-SOD-BP) is greater in 12,000-g supernatant fractions (S12) from neonates than in S12 from adults (H. Fazzone, A. Wangner, and L. B. Clerch. J. Clin. Invest. 92: 1278-1281, 1993). To determine the mechanism underlying this developmental difference, lung subcellular fractions were tested for their effect on Mn-SOD-BP activity. Protein in the 130,000-g supernatant (S130) of lung extracts bound the 3'-UTR. However, the developmental difference in binding was not present in S130. The 130,000-g pellet (P130) did not bind the 3'-UTR; rather, it contained an inhibitor of Mn-SOD-BP activity. Addition of P130 to S130 decreased RNA binding in a dose-dependent manner. Furthermore, adult P130 was a more potent inhibitor of RNA-binding activity than neonatal P130. These data indicate that the developmental difference in Mn-SOD-BP activity is due, in part, to an inhibitor in P130. Biochemical characterization revealed that the inhibitor is an RNA that may participate in the posttranscriptional control of Mn-SOD gene expression.


Rapid prototyping of compliant human aortic roots for assessment of valved stents.
Adequate in-vitro training in valved stents deployment as well as testing of the latter devices requires compliant real-size models of the human aortic root. The casting methods utilized up to now are multi-step, time consuming and complicated. We pursued a goal of building a flexible 3D model in a single-step procedure. We created a precise 3D CAD model of a human aortic root using previously published anatomical and geometrical data and printed it using a novel rapid prototyping system developed by the Fab@Home project. As a material for 3D fabrication we used common house-hold silicone and afterwards dip-coated several models with dispersion silicone one or two times. To assess the production precision we compared the size of the final product with the CAD model. Compliance of the models was measured and compared with native porcine aortic root. Total fabrication time was 3 h and 20 min. Dip-coating one or two times with dispersion silicone if applied took one or two extra days, respectively. The error in dimensions of non-coated aortic root model compared to the CAD design was <3.0% along X, Y-axes and 4.1% along Z-axis. Compliance of a non-coated model as judged by the changes of radius values in the radial direction by 16.39% is significantly different (P<0.001) from native aortic tissue--23.54% at the pressure of 80-100 mmHg. Rapid prototyping of compliant, life-size anatomical models with the Fab@Home 3D printer is feasible--it is very quick compared to previous casting methods.


Discrepancies in Gender Representation Between Integrated and Independent Plastic Surgery Programs.
Despite increasing female representation in integrated plastic surgery training programs, independent programs have lower representation and slow improvement in female enrollment. Self-reported resident data were used to investigate trends of female representation in integrated and independent programs. Data were collected from Accreditation Council of Graduate Medical Education resources of active residents' characteristics. Self-reported gender data were collected for integrated, independent, and general surgery programs from annual reports since 2009. χ2 analysis was conducted to compare female enrollment of integrated programs, independent programs, general surgery programs, and general surgery programs with matriculation-year adjustment. In 2008, 89 independent programs had nearly identical percentage of female enrollment with 30 integrated programs at 23.8% and 23.1%, respectively. Differences in representation between independent and integrated programs became significant in 2012, with independent programs demonstrating 25.1% female enrollment compared with 30.5% in integrated programs. This trend of higher female representation in integrated programs has persisted since 2012. To correct for preexisting disparity in general surgery programs, we compared female enrollment of independent programs with female enrollment of that class' general surgery matriculation-year 5 years earlier. In all examined years, general surgery still had proportionally higher female enrollment compared with independent programs, even with conservative 5-year matriculation adjustment. Dramatic differences in female enrollment were found between integrated and independent programs, with representation in integrated programs rising more quickly. Adjustments for previous rates of female enrollment in general surgery did not yield explanation for low independent program enrollment. Increasing female representation in independent training models will continue to create a more diverse workforce.


How do I analyze thee? Let me count the ways: considering empathy in couple relationships using self and partner ratings.
In this article we describe some of the benefits and challenges of using self ratings and ratings of the partner to measure empathy and similar terms in couple research. If both members of the dyad are assessed, there will be four measures of the same variable. How to use these 4 measures in research and clinical work is a central question in this paper. We demonstrate 3 different latent models that can be used to analyze these ratings based on different theoretical premises. Using empathy as the independent variable with a longitudinal sample of 275 couples, structural equation models are used to evaluate the strength of these models in predicting relationship satisfaction. The findings indicate that the model that is consistent with the social constructionist perspective that focuses on the perceptions within the same person is a good fit to the data. Other models that compare ratings between members of the dyad do not fit the data well. The results demonstrate that perceptions of empathy do have a significant influence on relationship satisfaction across time, especially for females. However, it is largely males' perceptions of empathy of the self and the partner that influence relationship satisfaction for females.


No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene and polycystic ovary syndrome.
Ghrelin plays a role in regulating glucose metabolism and energy balance. Polymorphisms in preproghrelin and ghrelin gene could be responsible for obesity, insulin resistance and low ghrelin levels observed in some individuals. The objective of this study was to evaluate the influence of two single-nucleotide polymorphisms (SNPs) of ghrelin gene on the clinical, the hormonal and metabolic features in women with polycystic ovary syndrome (PCOS) in a Chinese population. A large sample of Chinese PCOS (n = 271) women and a control group (n = 296) of healthy women matched for age were studied. Hormone and metabolic profiles were measured and blood samples were collected for genotype and allelic frequency analysis. Non-synonymous SNPs in the coding region (exon 2) of the preproghrelin gene (Arg51Gln (346 G>A) and Leu72Met (408 C>A) were studied using PCR and restriction fragment length polymorphism analysis. The polymorphism Arg51Gln was not found in the cohorts studied. The distribution of Leu72Met was similar in PCOS group and in healthy controls. There was no significant difference in age, BMI, waist-hip-ratio and levels of FSH, LH, estradiol, testosterone and prolactin between PCOS patients with different genotypes, and the level of plasma glucose and insulin was also similar. No association was found between Leu72Met and Arg51Gln polymorphisms in the ghrelin gene and PCOS in Chinese population.


The erosion of health insurance: the unintended consequences of tiered products by health plans.
When properly structured, consumer-driven health care may provide gains to both patients and the delivery system. However, the current approach by health plans could result in real harm to patients and to an already fragile health care delivery system. While health plans are presenting tiered products as a necessary mechanism to control rising hospital expenditures, this paper explores the real drivers of the rising cost of health care, including utilization, increased demand for advanced medication, and new technology. Left unchecked, such benefit designs could have dangerous public policy implications and consequences, including the further erosion of the basic tenets of health insurance.


A joint model of recurrent events and a terminal event with a nonparametric covariate function.
We extend the shared frailty model of recurrent events and a dependent terminal event to allow for a nonparametric covariate function. We include a Gaussian random effect (frailty) in the intensity functions of both the recurrent and terminal events to capture correlation between the two processes. We employ the penalized cubic spline method to describe the nonparametric covariate function in the recurrent events model. We use Laplace approximation to evaluate the marginal penalized partial likelihood without a closed form. We also propose the variance estimates for regression coefficients. Numerical analysis results show that the proposed estimates perform well for both the nonparametric and parametric components. We apply this method to analyze the hospitalization rate of patients with heart failure in the presence of death.


A quarter of a century biomechanical rupture risk assessment of abdominal aortic aneurysms. Achievements, clinical relevance, and ongoing developments.
Abdominal aortic aneurysm (AAA) disease, the local enlargement of the infrarenal aorta, is a serious condition that causes many deaths, especially in men exceeding 65 years of age. Over the past quarter of a century, computational biomechanical models have been developed towards the assessment of AAA risk of rupture, technology that is now on the verge of being integrated within the clinical decision-making process. The modeling of AAA requires a holistic understanding of the clinical problem, in order to set appropriate modeling assumptions and to draw sound conclusions from the simulation results. In this article we summarize and critically discuss the proposed modeling approaches and report the outcome of clinical validation studies for a number of biomechanics-based rupture risk indices. Whilst most of the aspects concerning computational mechanics have already been settled, it is the exploration of the failure properties of the AAA wall and the acquisition of robust input data for simulations that has the greatest potential for the further improvement of this technology.


Double-Step Image Superimposition Technique for Fabricating a Drilling Guide to Access the Abutment Screw in Implant Prostheses.
Limited retrievability is a major disadvantage of cement-retained implant restorations. Despite great progress in locating the abutment screw within crowns, the existing techniques are based on prior data or prefabricated devices and require significant work. This study introduces a new procedure for fabricating a guide template to drill a screw access hole using a double-step superimposition technique that incorporates intraoral optical scanning, cone beam computed tomography, and dental design software. The double-step superimposition technique with computer-aided design/computer-assisted manufacturing technology can enhance the convenience and accuracy of drilling the screw-access hole.


Cathemerality: a key temporal niche.
Given the marked variation in abiotic and biotic conditions between day and night, many species specialise their physical activity to being diurnal or nocturnal, and it was long thought that these strategies were commonly fairly fixed and invariant. The term 'cathemeral', was coined in 1987, when Tattersall noted activity in a Madagascan primate during the hours of both daylight and darkness. Initially thought to be rare, cathemerality is now known to be a quite widespread form of time partitioning amongst arthropods, fish, birds, and mammals. Herein we provide a synthesis of present understanding of cathemeral behaviour, arguing that it should routinely be included alongside diurnal and nocturnal strategies in schemes that distinguish and categorise species across taxa according to temporal niche. This synthesis is particularly timely because (i) the study of animal activity patterns is being revolutionised by new and improved technologies; (ii) it is becoming apparent that cathemerality covers a diverse range of obligate to facultative forms, each with their own common sets of functional traits, geographic ranges and evolutionary history; (iii) daytime and nighttime activity likely plays an important but currently neglected role in temporal niche partitioning and ecosystem functioning; and (iv) cathemerality may have an important role in the ability of species to adapt to human-mediated pressures.


A study of the impact of a simple stimulus on a receiver's imagination in mediated communication.
Mediated communication involves a form of intimate partnership where, as in the case of face-to-face intimate relationships, parties have a strong desire to exchange emotion and ensure a connection by way of receiving and responding to personal messages. So, in mediated communication, although partners have an effective means of conveying a connection, they still are in need of an equally effective means of conveying emotional state; they need a so-called "emotion-related channel." A desire to develop an efficient means of conveying emotion in mediated communication has driven this study. A study was carried out to determine the effects of a simple stimulus on one's imagination when subjects considered the simple stimulus to be a message from an intimate partner. Twenty-one subjects were first subjected to a simple pattern stimulus. They then experienced the same stimulus as a message received from an intimate partner in mediated communication. They subsequently answered questionnaires on their impressions of the stimulus, the emotional states of their imagined partners, and their own emotional states. A statistical analysis was then carried out. From a close examination of the findings, some interesting points were discovered. One important finding is that from the simple stimulus, subjects were able to imagine not only an intimate partner but also the emotional state of that partner. This and other findings lend support to the notion that a simple stimulus could serve as an emotion-related channel, in mediated communication.


An efficient and scalable synthesis of substituted phenanthrenequinones by intramolecular Friedel-Crafts reaction of imidazolides.
An efficient synthesis of 9,10-phenanthrenequinones is described. The two carbonyl groups were introduced by an orthoselective intermolecular Friedel-Crafts reaction of 3-methoxyphenol with ethyl chlorooxoacetate. The formation of a biaryl bond by Suzuki-Miyaura coupling reaction, followed by the hydrolysis of the ester, gave a biaryloxoacetic acid. Treatment of this acid with CDI gave the corresponding imidazolide. The ring closure to the desired phenanthrenequinone was accomplished by intramolecular Friedel-Crafts reaction of the imidazolide promoted by TiCl(4).


Coronary artery bypass grafting in a patient with situs inversus totalis: a case report.
Coronary artery bypass grafting in situs inversus totalis patients has been seldom reported in the literature. A 76-year-old woman visited our hospital for chest pain and dyspnea that had started about 5 years earlier. Coronary angiography revealed triple-vessel disease, and computed tomography showed situs inversus totalis. Coronary artery bypass grafting was performed. In this case, the main operating surgeon stood on the right side of the patient until cardiopulmonary bypass was established and then switched positions to the left side of the patient for anastomosis. CABG was successfully completed in a patient with situs inversus totalis. The position shift helped improve the safety and ease of the surgery.


The Extreme Value Machine.
It is often desirable to be able to recognize when inputs to a recognition function learned in a supervised manner correspond to classes unseen at training time. With this ability, new class labels could be assigned to these inputs by a human operator, allowing them to be incorporated into the recognition function-ideally under an efficient incremental update mechanism. While good algorithms that assume inputs from a fixed set of classes exist, e.g. , artificial neural networks and kernel machines, it is not immediately obvious how to extend them to perform incremental learning in the presence of unknown query classes. Existing algorithms take little to no distributional information into account when learning recognition functions and lack a strong theoretical foundation. We address this gap by formulating a novel, theoretically sound classifier-the Extreme Value Machine (EVM). The EVM has a well-grounded interpretation derived from statistical Extreme Value Theory (EVT), and is the first classifier to be able to perform nonlinear kernel-free variable bandwidth incremental learning. Compared to other classifiers in the same deep network derived feature space, the EVM is accurate and efficient on an established benchmark partition of the ImageNet dataset.


High burden of anemia among pregnant women in Tanzania: a call to address its determinants.
Anemia in pregnancy is behind a significant burden of maternal mortality and poor birth outcomes globally. Efforts to address it need evidence on trends and its pertinent factors as they vary from one area to another. We pooled data of 23,203 women of reproductive age whose hemoglobin levels were measured from two Tanzania Demographic and Health Surveys (TDHS). Of them, 2,194 women were pregnant. Analyses employed descriptive analyses to determine the burden of anemia, its characteristics, and severity; GIS mapping to determine the regional changes of anemia between 2005 and 2015; and logistic regression to determine the remaining determinants of anemia among pregnant women using Stata 15. The burden of anemia among pregnant women in Tanzania has remained unprecedently high, and varies between regions. There was no significant decline of anemia in general between the two periods after adjusting for individual, households, reproductive, and child characteristics [AOR = 0.964, 95% CI = 0.774-1.202, p = 0.747). Anemia is currently prevalent in 57% of pregnant women in Tanzania. The prevalence is more likely to be higher among women aged 15-19 years than those aged between 20-34 years. It is more likely to be prevalent among those within large families, with no formal education, food insecurity, lack of health insurance, had no antimalaria during pregnancy, and had low frequency of ANC attendance. On the other hand, delivery in a health facility may be potentially protective against anemia. Anemia in pregnancy remained persistently high and prevalent among 57% of pregnant women in Tanzania. Efforts to address anemia are crucial and need to be focused in regions with increasing burden of anemia among pregnant women. It is imperative to address important risk factors such as food insecurity, strengthening universal health coverage, empowering women of reproductive age with education and especially nutritional knowledge and advocating for early antenatal booking, attendance, and facility delivery.


Loop Optimization for Tensor Network Renormalization.
We introduce a tensor renormalization group scheme for coarse graining a two-dimensional tensor network that can be successfully applied to both classical and quantum systems on and off criticality. The key innovation in our scheme is to deform a 2D tensor network into small loops and then optimize the tensors on each loop. In this way, we remove short-range entanglement at each iteration step and significantly improve the accuracy and stability of the renormalization flow. We demonstrate our algorithm in the classical Ising model and a frustrated 2D quantum model.


Improving the efficiency of the photoinduced charge-separation process in a rhenium(I)-zinc porphyrin dyad by simple chemical functionalization.
We demonstrate here that, whereas the rhenium(I)-zinc porphyrin dyad fac-[Re(CO)3(bpy)(Zn·4'MPyP)](CF3SO3) [1; 4'MPyP = 5-(4'-pyridyl)-10,15,20-triphenylporphyrin] shows no evidence for photoinduced electron transfer upon excitation in the visible region because the charge-separated state ZnP(+)-Re(-) is almost isoenergetic with the singlet excited state of the zinc porphyrin (ΔG = -0.05 eV), the introduction of electron-withdrawing ethyl ester groups on the bpy ligand significantly improves the thermodynamics of the process (ΔG = -0.42 eV). As a consequence, in the new dyad fac-[Re(CO)3(4,4'-DEC-bpy)(Zn·4'MPyP)](CF3SO3) (4; 4,4'-DEC-bpy = 4,4'-diethoxycarbonyl-2,2'-bipyridine), an efficient and ultrafast intramolecular electron-transfer process occurs from the excited zinc porphyrin to the rhenium unit upon excitation with visible light. Conversely, the introduction of electron-donor tert-butyl groups on the meso-phenyl moieties of the zinc porphyrin has a negligible effect on the photophysics of the system. For dyad 4, the time constants for the charge-separation and charge-recombination processes in solvents of different polarity (PrCN, DCM, and toluene) were measured by an ultrafast time-resolved absorption technique (λ(exc) = 560 nm).


Topography of the oblique vein of the left atrium (vein of Marshall).
The oblique vein of the left atrium is of interest for electrophysiologists working in the field of both basic science and clinical practice. We aimed to examine the topographic anatomy of the oblique vein and to assess the vein's location and relationships with surrounding cardiac structures. A total of 200 autopsied adult human hearts were examined. The oblique vein was observed in 71% of the hearts. Its mean (SD) total length was 30.8 (13.6) mm. In hearts with the oblique vein, a larger distance was observed between the left inferior pulmonary vein (LIPV) and great cardiac vein (mean [SD], 18.6 [5.1] mm vs 16.3 [4.8] mm; P = 0.004), between the left atrial appendage (LAA) and LIPV (mean [SD], 17.8 [6.8] mm vs 15.1 [5.2] mm; P = 0.007), and between the LAA and left superior pulmonary vein (LSPV; mean [SD], 28.5 [7.2] mm vs 21.3 [6.4] mm; P <0.001). Hearts with a classic pattern of left‑sided pulmonary veins were categorized into 4 types based on the length of oblique vein extension. In type I, the vein extended below the level of the LIPV (21.9%); in type II, to the level of the LIPV (47.7%); in type III, to the level of the interpulmonary area (17.2%); and in type IV, to the level of the LSPV (13.3%). In each type, the distance between the oblique vein and LIPV was shorter than that between the oblique vein and LAA Conclusions: The oblique vein had a variable course and differing lengths of extension. The presence of the oblique vein was connected with a greater distance between the left‑sided pulmonary veins and LAA.


[The Sjögren's syndrome and multiple sclerosis: similarity and differences].
Multiple sclerosis (MS) is very similar to the Sjögren's syndrome (SS) by its clinical presentations. Features found in common between the two disorders include symptoms of lesions of the brain, spinal cord and optic tract, the detection of autoantibodies, such as antinuclear, anti-Ro, anti-La and the prevalence of MRI abnormalities such as periventricular and subcortical lesions. Almost all symptoms found in patients with the CNS-SS involvement described above could be attributed to the concomitant presence of MS. Therefore, the differential diagnosis of these diseases is difficult. The paper addresses clinical and biological presentations of similarity of and differences between MS and SS in the diagnostic aspect.


[Clinical study of electroacupuncture on perioperative analgesia in patients with thyroid surgery under cervical plexus block].
To investigate the change trend and correlation between the perioperative pain degree and neuroendocrine hormone levels in the perioperative period on patients with thyroid surgery by electroacupuncture combined with cervical plexus block. Forty patients with elective thyroidectomy were enrolled and divided into a control group and an observation group according to the random number table method, 20 cases in each group. In the control group, cervical plexus block was performed. In the observation group, the cervical plexus block combined with electroacupuncture (EA) were given. After the cervical plexus block was completed, the EA was applied at the bilateral Hegu (LI 4) and Neiguan (PC 6) for 30 min. The visual analog scale (VAS) was used to assess the pain level before anesthesia (T0), 2 h after operation (T1), 12 h after operation (T2), 24 h after operation (T3) and 48 h after operation (T4). Blood samples such as adrenocorticotropic hormone (ACTH), C-reactive protein (CRP) and β-endorphin (β-EP) were collected to measure the level of neuroendocrine hormones, and to analyze the correlation between ACTH, CRP, β-EP and VAS scores. The VAS scores at T1, T2, T3 were higher than those at T0 in the two groups (all P<0.05). The VAS scores T1, T2 and T3 in the observation group were lower than those in the control group (all P<0.05). The ACTH and CRP in the control group at T1, T2 and T3 were significantly higher than those at T0 (all P<0.05). The β-EP in the observation group at T1, T2 and T3 was significantly higher than that at T0 (all P<0.05). The ACTH and CRP in the observation group at T1, T2 and T3 were lower than those in the control group,and the β-EP level was higher than that in the control group (all P<0.05).The VAS score was significantly positively correlated with ACTH and CRP levels, and negatively correlated with β-EP. EA stimulation can inhibit the secretion of ACTH and CRP, promote the release of β-EP, reduce the perioperative pain score, and inhibit the body's stress response.


Complete amino acid sequence of a beta-galactoside-binding lectin from human placenta.
The complete amino acid sequence of a beta-galactoside-binding lectin from human placenta was determined at protein level. The lectin consists of 134 amino acids and its N-terminal alanine is blocked with acetate. The lectin shows about 50% similarity with chick 14K lectin, which was the first vertebrate beta-galactoside-binding lectin completely sequenced. Only 14 residues proved to be different from those of rat lung lectin, the sole mammalian lectin of which the complete sequence has been reported.


Ecological study on the penetration of induction heating cookers and birth outcomes in Japan.
In recent years, equipment that generates intermediate-frequency electromagnetic fields (IF-EMFs) has become increasingly prevalent, and the influence of IF-EMFs on human health is thus attracting increasing attention. The present study was conducted with the aim of analyzing whether there is a relationship between the penetration of induction heating cookers and birth outcomes using an ecological study design at the prefectural level. We created data sets for all 47 prefectures in Japan using previously published statistics. Spontaneous fetal death rate, fetal death rate after 22 weeks of pregnancy, perinatal mortality rate, and proportion of newborns weighing less than 2500 g were used as birth outcomes in correlation analysis. A weak positive association was observed between the penetration of induction heating cookers and the fetal death rate after the 22nd week of pregnancy (r = 0.27, p = 0.07), but it was not statistically significant. In addition, a weak negative association was observed between the penetration of induction heating cookers and the spontaneous fetal death rate (r = -0.27, p = 0.07), but it was not statistically significant. In the present ecological study, no statistically significant association were shown between the penetration of induction heating cookers and birth outcomes. To demonstrate further the safety of induction heating cooker use, observations in epidemiological studies of other designs should be considered.


The latent structure of attention-deficit/hyperactivity disorder in a clinic-referred sample.
The question of whether attention-deficit/hyperactivity disorder (ADHD) represents a continuum of attentional and executive dysfunction or a natural category has yet to be extensively investigated. Subjective report and neuropsychological data from 437 individuals referred for neuropsychological evaluation were analyzed using latent class and taxometric analyses (mean above minus below a cut [MAMBAC], maximum eigenvalue [MAXEIG], and latent mode [LMODE]). Results indicated no significant evidence for a taxonic representation of ADHD across multiple procedures and indicator sets. Similarly, there was no evidence that ADHD subtypes represent a qualitative distinction. These findings may suggest that current diagnostic conceptualizations are inadequate for accurately identifying and characterizing individuals with problems related to attention and executive dysfunction. Alternatively, the null findings may have resulted from inadequate indicator selection. A dimensional model may better facilitate accurate identification of individuals at risk for functional impairment.


Distribution of neurotransmitter binding sites in the cat median eminence.
Receptor autoradiography was used to determine the distribution of binding sites for monoaminergic and cholinergic neurotransmitters in the cat median eminence. Results showed that binding sites were differentially distributed in that [3H]-p-aminoclonidine (an alpha-2-adrenergic ligand) and [3H]pyrilamine (an H1-histaminergic ligand) binding were concentrated in the medial region of the external layer of the median eminence while [3H]lysergic acid diethylamide (a serotonergic ligand) and [3H] quinuclidinyl benzilate (a muscarinic cholinergic ligand) binding were concentrated within the lateral region of the external layer. These patterns are coincident with the differential distribution of hypophysiotropic hormones in the median eminence, suggesting that monoamines and acetylcholine may regulate the release of these hormones at the level of the median eminence.


In vivo confocal microscopy of meibomian glands in primary blepharospasm: A prospective case-control study in a Chinese population.
The aim of the study was to evaluate the morphological changes of meibomian glands (MGs) in primary blepharospasm (PBS) by in vivo laser scanning confocal microscopy (LSCM) and to investigate the correlations between clinical data of PBS and LSCM parameters of MGs. This prospective and case-control study recruited 30 consecutive PBS patients and 30 age- and gender-matched healthy controls. After questionnaire assessments of ocular surface disease index (OSDI), Jankovic rating scale, and blepharospasm disability index, all subjects underwent blink rate evaluation, tear film break-up time (TBUT), corneal fluorescein staining (CFS), Schirmer test, MG expressibility, meibum quality, MG dropout, and LSCM examination of the MGs. The main LSCM outcomes included the mean MG acinar area and density, orifice diameter, meibum secretion reflectivity, acinar irregularity, and inhomogeneity of interstice and acinar wall. The PBS patients had significantly higher blink rate, higher OSDI and CFS scores, lower TBUT and Schirmer test value, and worse MG expressibility than the controls (All P < 0.05), whereas meibum quality showed no difference (P > 0.05). The PBS patients showed lower values of MG acinar area, orifice diameter and meibum secretion reflectivity, and higher scores of acinar irregularity and inhomogeneity of interstices than the controls (All P < 0.05). For the PBS patients, the severity of blepharospasm evaluated by JCR scale was strong correlated with MG acinar area (P < 0.001), orifice diameter (P = 0.002), meibum secretion reflectivity (P = 0.002), and MG acinar irregularity (P = 0.013). The MG expressibility was significantly correlated to MG acinar area (P = 0.039), orifice diameter (P < 0.001), and MG acinar irregularity (P = 0.014). The OSDI score was moderate correlated with MG acinar irregularity (P = 0.016), whereas the TBUT value was positively correlated with MG acinar area (P = 0.045) and negatively correlated to MG acinar irregularity (P = 0.016). The CFS score was negatively correlated to MG orifice diameter (P = 0.008). The LSCM provided a noninvasive tool for in vivo histopathologic studies of MGs in PBS patients. The excessive constriction of lid muscles closely related to MG morphological alterations of PBS, which offered a new research approach to interpret the interactional mechanism between dry eye and PBS.


Uni-compartment total knee replacement.
Twelve patients with uni-compartment total knee replacement were followed for a period of 12 to 30 months with an average follow-up of 19 months. Results in 11 out of 12 patients suggest that this operation is an alternative to high tibial osteotomy or hemiarthroplasty in selected patients. Long term end result studies are necessary to evaluate uni-compartment total knee replacement as a durable procedure for the management of knee arthritis.


[Traumatic rupture of the descending aorta. A report of 21 operated cases (author's transl)].
From 1965 to December 1976, 21 traumatic ruptures of the descending thoracic aorta have been operated; the last 13 cases have been managed in 1975 and 1976. The lesions consisted in 15 recent ruptures (R.R.) and 6 chronic aneurysma (C.A.). Associated injuries were the rule and 6 patients underwent exploratory laparotomy prior to thoracotomy. Surgical repair was consistently due by use of an extracorporeal by-pass (20 times), and resulted in 12 end-to-end aortic sutures (11 R.R., 1 C.A.) and in 9 reconstruction by means of a tubular dacron graft (5 C.A., and 4 R.R.). 4 patients died. 16 of the 17 survivals are healthy and active. Paraplegia developed in one patient.


The use of recombinant factor VIIa in liver diseases.
Recombinant activated factor VII, a bypassing hemostatic agent originally developed for the treatment of hemorrhages in hemophilic patients with inhibitors, is increasingly being employed on a compassionate use basis for the treatment of uncontrolled massive bleeding from various causes. In this review, we present the current knowledge on the use of this agent in patients with severe coagulopathy due to end-stage liver disease. In particular, the role of recombinant activated factor VII for treating gastrointestinal bleeding episodes in patients with decompensated cirrhosis or for prophylaxis before liver surgical or invasive procedures will be addressed. The pathogenesis of complex coagulopathy in chronic liver diseases and the mechanisms by which recombinant activated factor VII might improve coagulation in such patients will also be described. Given the paucity of the published data and the lack of randomized trials, there is not enough evidence to support the extensive use of recombinant activated factor VII in any of the clinical indications analyzed. In conclusion, further large randomized, controlled clinical trials are needed to better define the role of recombinant activated factor VII in the treatment of bleeding complications of liver disorders.


Does Pharmacological Therapy Still Play a Role in Preventing Sudden Death in Surgically Treated Tetralogy of Fallot?
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, with a familial recurrence risk of 3%. Despite performing an optimal surgical repair, TOF patients may feature a poor medium and long-term survival rate: atrial re-entrant tachycardia will develop in more than 30% of patients and high-grade ventricular arrhythmias will be seen in about 10% of patients. These life-threatening arrhythmias and consequent sudden death continue to represent serious complications following TOF repair. Radiofrequency ablation and implantable cardioverter defibrillator are today the most effective therapeutic tools in these subjects, while the administration of antiarrhythmic drugs (Ib agents, beta blockers, and amiodarone), widely prescribed in the past, is now limited to few conditions. However pharmacological therapy still plays a role in the management of those patients who are resistant to the above stated invasive electrophysiological treatments.


miR-19 targets PTEN and mediates high mobility group protein B1(HMGB1)-induced proliferation and migration of human airway smooth muscle cells.
The abnormal proliferation and migration of airway smooth muscle (ASM) cells contributes to airway remodeling during asthma. MiR-19a has been demonstrated to promote cell proliferation and angiogenesis of several cancer types by regulating the PTEN/PI3K/AKT pathway. Our previous study has shown that High-mobility group box protein 1 (HMGB1) is involved in the pathogenesis of airway remodeling using a mouse model of chronic asthma. However, the effects of HMGB1 on proliferation and migration of ASM cells and its underlying mechanisms remain unknown. Human ASM cells were obtained by primary explant techniques. MiR-19a expression was evaluated using qRT-PCR. Cell proliferation and migration were evaluated by the CCK-8 and the transwell migration assays, respectively. Transfection studies of ASM cells were performed to identify the underlying mechanisms. HMGB1 stimulated ASM cell proliferation and migration in a dose-dependent manner. The expression levels of miR-19a and the PTEN and AKT signaling proteins were also modulated by HMGB1. Functional studies indicated that overexpression of miR-19a enhanced the proliferation and migration of ASM cells, whereas inhibition of miR-19a decreased the proliferation and migration of ASM cells. Western blot analysis demonstrated that miR-19a negatively regulated PTEN expression and positively regulated p-AKT expression. MiR-19 only regulates the proliferation of HASM cells induced by HMGB1, but not PDGF, EGF, TGF-β1. Furthermore, we demonstrated that miR-19 contributed to the promoting effects of HMGB1 on ASM cells by targeting PTEN 3'-UTR. Our results demonstrated that HMGB1 induced proliferation and migration of ASM cells via the miR-19a /PTEN/AKT axis and provided direct evidence on the role of HMGB1 in ASM cells proliferation in vitro. The present study further indicated that miR-19a may be explored as a potential novel therapeutic target to reverse proliferation and migration of ASM cells.


Course Review: Yorkshire Microsurgery Course 2023.
Microsurgery is an advanced set of techniques that require a high level of skill to be performed safely. Surgical skills courses offer safe environments for practice in such skills and form a fundamental part of surgical training. The Yorkshire Microsurgery Course is a 3-day course at Bradford Royal Infirmary, United Kingdom. Delivered via short lectures followed by supervised practical sessions, the course aims to provide delegates with the essential knowledge and skills required for microsurgery.We detail an outline and critical evaluation of the February 2023 iteration of the course, with recommendations for improvement.Overall, we found the course excellent. It provided delegates with a solid grounding in the fundamentals of microsurgery and the opportunity for personalized practice supervised by experts. We would recommend this course to colleagues interested in a career in plastic surgery.


Overcoming default categorical bias in spatial memory.
In the present study, we investigated whether a strong default categorical bias can be overcome in spatial memory by using alternative membership information. In three experiments, we tested location memory in a circular space while providing participants with an alternative categorization. We found that visual presentation of the boundaries of the alternative categories (Experiment 1) did not induce the use of the alternative categories in estimation. In contrast, visual cuing of the alternative category membership of a target (Experiment 2) and unique target feature information associated with each alternative category (Experiment 3) successfully led to the use of the alternative categories in estimation. Taken together, the results indicate that default categorical bias in spatial memory can be overcome when appropriate cues are provided. We discuss how these findings expand the category adjustment model (Huttenlocher, Hedges, & Duncan, 1991) in spatial memory by proposing a retrieval-based category adjustment (RCA) model.


Forebrain activation induced by postoral nutritive substances in rats.
Recent studies have shown the nutrient-sensing systems transmitting nutritive information from the gut to the brain. However neural activity evoked by ingested dietary nutrients has not been investigated adequately. Using functional magnetic resonance imaging, we demonstrated that rat forebrain responded to intragastric administration of glucose, L-glutamate, and NaCl. These dietary nutrients led to a significant activation in the forebrain regions including nucleus accumbens, hypothalamic area, and limbic system with different timings. These data indicate that several forebrain regions have important roles on perception and process of postingestive nutrient information.


Drug migration during drying of tablet granulations I: effect of particle size of major diluent.
Migration of a water-soluble drug, propoxyphene hydrochloride, during drying of tablet granulations was studied. Wet granulations of the drug were prepared using lactose as the major diluent and corn starch as a disintegrant. Particle-size fractions of lactose ranging from 53 to 177 micron in diameter were employed in different granulations to examine the effect of particle size of the major diluent on drug migration. Determination of drug concentration at various depths in a dried granulation bed was accomplished by using a drying cell consisting of four layers. A numerical coefficient of migration was developed to compare the extent of drug migration in the various lactose granulations. Migration increased with decreasing particle size of the major diluent, lactose. Two factors that may contribute to increased migration with smaller particles are increased entry suction due to decreased intragranular capillary size and increased intergranular contact area.


Determination of Dechlorane Plus and related compounds (dechlorane 602, 603 and 604) in fish and vegetable oils.
Dechlorane Plus (DP) is a flame retardant used as a substitute of Mirex since 1970s, but it was not detected in the environment until 2006. Since then, this compound and its main relatives, Dechlorane 602, 603 and 604, have been mainly studied in environmental matrices for monitoring purposes, but the dietary exposure to them has been hardly investigated so far. In the present study, we determined this family of compounds in fish and vegetable oil samples from Catalonia (Spain), most of them used as health supplements. Determination was carried out by gas chromatography-high resolution mass spectrometry (GC-HRMS), after a clean up in a multilayer silica column and preparative high performance liquid chromatography (HPLC) equipped with a pyrenyl(ethyl) column. Concentrations of Dechlorane compounds were between below the limit of detection and 384.2 pg g(-1). Although there are only few studies about the presence of these pollutants in food or feed, concentrations obtained indicated that these compounds are in the same order in fish and vegetable oil health supplements as the few other food and feed studies.