Protein modification by short-chain fatty acid metabolites in sepsis: a comprehensive review.
Sepsis is a major life-threatening syndrome of organ dysfunction caused by a dysregulated host response due to infection. Dysregulated immunometabolism is fundamental to the onset of sepsis. Particularly, short-chain fatty acids (SCFAs) are gut microbes derived metabolites serving to drive the communication between gut microbes and the immune system, thereby exerting a profound influence on the pathophysiology of sepsis. Protein post-translational modifications (PTMs) have emerged as key players in shaping protein function, offering novel insights into the intricate connections between metabolism and phenotype regulation that characterize sepsis. Accumulating evidence from recent studies suggests that SCFAs can mediate various PTM-dependent mechanisms, modulating protein activity and influencing cellular signaling events in sepsis. This comprehensive review discusses the roles of SCFAs metabolism in sepsis associated inflammatory and immunosuppressive disorders while highlights recent advancements in SCFAs-mediated lysine acylation modifications, such as substrate supplement and enzyme regulation, which may provide new pharmacological targets for the treatment of sepsis.


Intra- and interexaminer reliability of anthropometric measurements of term infants.
The reliability of anthropometric measurements of term infants has not been studied sufficiently to determine if these measurements are reliable enough to be used in clinical practice and research. This study described the intra- and interexaminer reliability of the following anthropometric measurements: weight (WT), head circumference (HC), chest circumference (CC), abdominal circumference (AC), mid-arm circumference (MAC), and length. A convenience sample of 50 clinically stable term infants was studied. Two examiners obtained the six measurements twice using blank tape measures. The order of examiners was randomized and the examiners were masked to their own and the other examiners' measurements. The intraexaminer mean absolute differences were as follows: WT = 1.88, 3.28 g; HC = 0.29, 0.29 cm; CC = 0.50, 0.78 cm; AC = 0.71, 0.77 cm; MAC = 0.36, 0.39 cm; length = 0.92, 1.18 cm. The interexaminer mean absolute differences were as follows: WT = 1.94, 1.66 g; HC = 0.37, 0.36 cm; CC = 0.59, 0.72 cm; AC = 0.99, 0.77 cm; MAC = 0.41, 0.57 cm; length = 1.57, 1.47 cm. These findings indicate that intraexaminer differences tended to be smaller than interexaminer differences for all measures except weight, which remained stable for intra- and interexaminer comparisons. These findings also suggest that weight and head circumference were the most reliable measures, whereas length and mid-arm circumference were the least reliable measures.


Nurses and Psychologists Advancing the Patient-Centered Medical Home Model.
As America experiences the largest health care revolution of the past 50 years, clinicians and administrators are refocusing their attention on the goals of the Quadruple Aim. Motivation and capabilities among stakeholders vary as practical tools and an adequate workforce remain elusive. At the same time, the patient-centered medical home (PCMH) model is spreading rapidly but demonstrating variable results. Positive PCMH outcomes seem to reflect high-quality teamwork. A primary care physician shortage is looming, and increasing numbers of health professionals are being pushed into the PCMH, mandated to provide "integrated" care. Even now, the majority of our Graduate Medical Education programs do not train clinicians in team-based workflow models and interaction skills. Consequently, PCMH teams will only optimize and realize the model's true potential if they learn to coordinate, communicate, and collaborate effectively. This means all PCMH staff members achieve solid teamwork skills and work at the top of their license. The authors discuss resources for improving coordination, communication, and collaboration among members of PCMH teams, and strategies for including other professionals.


[Research Progress in Black Queen Cell Virus Causing Disease].
In nature, honeybees are the most important pollinators. They play a vital role in both protecting the diversity of natural ecosystems, and maintaining the yield-improving effects of agroecosystems. But in recent years, epidemic disease in bees has caused huge losses. Black Queen Cell Virus (BQCV) is a bee pathogen that was first reported in 1955. It mainly infects bee larvae and pupae, making their bodies turn dark and black, and causing a massive decrease in the bee population. More specifically, the virus makes the exterior of the cell walls in the larvae and pupae turn black. BQCV is a seasonal epidemic, spread by means horizontal and vertical transmission, and is often unapparent. BQCV not only infects a variety of bee species, but also spiders, centipedes and other arthropods. It can also be coinfected with other honeybee viruses. In recent years, research has shown that the Nosema intestinal parasite plays an important role in BQCV transmission and bees carrying Nosema that become infected with BQCV have increased mortality. Here we summarize current research on the incidence, prevalence, geographical distribution and transmission of BQCV.


[Screening and management of coronary artery disease in diabetic patients].
Diabetes represents as independent risk factor for coronary artery disease (CAD) and the prognosis in term of survival rates is worse for diabetic patients who have CAD with report to those with CAD but no diabetes. The coronary artery disease in diabetes has specificities and, in particular, more extensive atherosclerosis. Diabetic patients are also more frequently asymptomatic. Due to the extreme complexity of ischemic vascular disease in patients with diabetes, an optimal therapeutic strategy is based on the correction of elevated blood glucose and lipid levels, of blood pressure, of platelet and coagulation abnormalities. Diabetic patients benefit from secondary prevention by drug therapy(aspirin, lipid lowering with statines, beta blocker and ACE inhibitors) to the same extent as, or more than, non-diabetic patients. Both percutaneous and surgical myocardial revascularization have been proved equally effective for CAD treatment in diabetes. A recent randomized trial has shown a significantly improved outcome after surgical revascularization. But, the effects of drug-eluting stents, which dramatically decrease the incidence of re-stenosis, seem promising.


A bispecific antibody enhances the fibrinolytic potency of single-chain urokinase.
A monoclonal antibody specific for an epitope at the amino terminus of the beta chain of fibrin and a monoclonal antibody that binds both one- and two-chain high molecular weight urokinase were chemically cross-linked [using N-succinimidyl 3-(2-pyridyldithio)propionate and 2-iminothiolane]. The chemically modified material was heterogeneous, ranging in molecular size from tetramers to monomers and containing the two antibodies in various ratios. Nevertheless, fractions of a molecular size larger than a monomer were capable of binding fibrin and urokinase simultaneously in a radioimmunoassay. These fractions also enhanced fibrinolysis by high molecular weight single-chain urokinase (scuPA) by 50-fold and plasma clot lysis by 5-fold. Whereas scuPA significantly decreased the concentration of fibrinogen in plasma clot assay supernatants, scuPA in association with the bispecific antibody did not.


Association between periodontal disease and polycystic ovary syndrome: a systematic review.
The purpose of the present study was to review systematically the association between periodontal diseases (PDs) and polycystic ovary syndrome (PCOS). To address the focused question, 'Is there a relationship between PD and PCOS?' indexed databases were searched up to October 2016 without time or language restrictions using different combinations of the following key words: PCOS, ovarian cysts, PD, periodontitis, gingival diseases and gingivitis. Letters to the Editor, commentaries, historic reviews, case-report, unpublished articles and animal/experimental studies were excluded. Seven case-control studies were included. The number of study participants ranged between 52 and 196 females aged between 15 and 45 years. In three and three studies, proinflammatory cytokines were assessed in gingival crevicular fluid and saliva samples, respectively. In one study, salivary microbes were investigated. All studies reported that a positive association exists between PD and PCOS. In conclusion, there is a positive association between PD and PCOS; however, further well-designed longitudinal controlled clinical trials are needed in this regard. It is recommended that physicians should refer patients with PCOS to oral health-care providers for comprehensive oral evaluation and treatment.


Optimization of a tri-drug treatment against lung cancer using orthogonal design in preclinical studies.
A growing body of evidence suggests that anesthetics impact the outcome of patients with cancer after surgical intervention. However, the optimal dose and underlying mechanisms of co-administered anesthetics in lung tumor therapy have been poorly studied. Here, we aimed to investigate the role of combined anesthetics propofol, sufentanil, and rocuronium in treating lung cancer using an orthogonal experimental design and to explore the optimal combination of anesthetics. First, we evaluated the effects of the three anesthetics on the proliferation and invasion of A-549 cells using Cell Counting Kit 8 and Transwell migration and invasion assays. Subsequently, we applied the orthogonal experimental design (OED) method to screen the appropriate concentrations of the combined anesthetics with the most effective antitumor activity. We found that all three agents inhibited the proliferation of A-549 cells in a dose- and time-dependent manner when applied individually or in combination, with the highest differences in the magnitude of inhibition occurring 24 h after combined drug exposure. The optimal combination of the three anesthetics that achieved the strongest reduction in cell viability was 1.4 µmol/L propofol, 2 nmol/L sufentanil, and 7.83 µmol/L rocuronium. This optimal 3-drug combination produced a more beneficial result at 24 h than either single drug. Our results provide a theoretical basis for improving the efficacy of lung tumor treatment and optimizing anesthetic strategies.


[Leukomalacia and periventricular echogenicity in very low birth weight premature infants].
Cystic periventricular leukomalacia (c-PVL) and persistent periventricular echogenicity (PPVE) are white matter injuries of multifactorial etiology, high incidence in premature infants and with harmful effect in neurodevelopment. To determine PPVE and c-PVL incidence, and to assess potential predictors. Cohort of 164 very low birth weight premature infants (< 1,500 g and with gestational age equal or below 32 weeks), admitted to the Neonatal Care Unit of Hospital Clinico Regional de Valdivia, Chile. Cerebral ultrasound within the first week, at day 15 and day 30 of life was performed, and diagnosis of the lesions was made according Volpe's classification. The association of PPVE and c-PVL with several perinatal factors was evaluated by univariate risk estimation -relative risk (RR), and 95% confidence interval (95% CI)-, and then, multivariate analysis through multiple logistic regression -adjusted odds ratio (OR)--was carried out. The incidence of PPVE and c-PVL was 13.4 and 23.8%, respectively. 66.7% of c-PVL cases were observed in infants lower than 28 weeks (RR = 4.83; 95% CI = 2.72-8.58). The risk of c-PVL was lower with gestational age for each additional week (OR = 0.5; 95% CI = 0.38-0.65) and maternal hypertension (OR = 0.27; 95% CI = 0.08-0.87). A significant decrease of PPVE risk was found with better Apgar score after 1 minute and male sex. No association was found with either chorioamnionitis, antenatal corticosteroids nor other perinatal factors. This study confirms high incidence of white matter lesions, being gestational age a strong predictor of c-PVL. Studies are needed to clarify maternal hypertension effect on c-PVL development.


Cell death-based treatments of melanoma:conventional treatments and new therapeutic strategies.
The incidence of malignant melanoma has continued to rise during the past decades. However, in the last few years, treatment protocols have significantly been improved thanks to a better understanding of the key oncogenes and signaling pathways involved in its pathogenesis and progression. Anticancer therapy would either kill tumor cells by triggering apoptosis or permanently arrest them in the G1 phase of the cell cycle. Unfortunately, melanoma is often refractory to commonly used anticancer drugs. More recently, however, some new anticancer strategies have been developed that are "external" to cancer cells, for example stimulating the immune system's response or inhibiting angiogenesis. In fact, the increasing knowledge of melanoma pathogenetic mechanisms, in particular the discovery of genetic mutations activating specific oncogenes, stimulated the development of molecularly targeted therapies, a form of treatment in which a drug (chemical or biological) is developed with the goal of exclusively destroying cancer cells by interfering with specific molecules that drive growth and spreading of the tumor. Again, after the initial exciting results associated with targeted therapy, tumor resistance and/or relapse of the melanoma lesion have been observed. Hence, very recently, new therapeutic strategies based on the modulation of the immune system function have been developed. Since cancer cells are known to be capable of evading immune-mediated surveillance, i.e., to block the immune system cell activity, a series of molecular strategies, including monoclonal antibodies, have been developed in order to "release the brakes" on the immune system igniting immune reactivation and hindering metastatic melanoma cell growth. In this review we analyze the various biological strategies underlying conventional chemotherapy as well as the most recently developed targeted therapies and immunotherapies, pointing at the molecular mechanisms of cell injury and death engaged by the different classes of therapeutic agents.


Formalin use in anatomical and histological science in the 19th and 20th centuries.
The introduction of formalin, a formaldehyde solution, as a disinfectant and fixative was an essential improvement in anatomical and histological science. This paper is an outline of the historical use of formalin based on primary source texts and historical studies. We describe how the discovery of acetaldehyde in the 18th century led to the development of formalin as the most common ingredient in embalming fluids in the 20th century and is still used today. Particularly important contributions to this process were made by Justus von Liebig, Alexander Butlerow and August Wilhelm Hofmann in the development of anatomical and histological preparation techniques, and by Ferdinand Blum, Ferdinand Julius Cohn, Frederick C. Kenyon and Victor Wehr in the practical uses of formaldehyde solutions in preservation and fixation of soft tissues. However, formalin is not without its drawbacks and as its toxicity became more understood, method to mitigate its effects were demanded. Eventually safer preparation techniques were developed, including Hagens' plastination and Thiel Embalming Method. These techniques may someday largely replace high-concentration formalin solutions but they both still require at least small quantities of formaldehyde to preserve tissues for study.


Clinical evaluation of a new cosmetic cream containing PEPHA®-TIGHT on the skin of childbearing women.
The purpose of this study is to evaluate the efficacy of daily application of a new cosmetic cream on the skin of childbearing women. Fifty-two childbearing women were evaluated and each subject was initially (T0) prepared using an hydration and sebometry test. A quantity of 50 ml of cosmetic cream was applied for 1 month on each patient. At the end of the month (T1), the tests were repeated. At the end of the study, all enrolled women showed an improvement of facial skin hydration and sebum normalization and reduction of skin aging. The present study shows that the cosmetic preparations containing PEPHA®-TIGHT and other moisturizing agents are able to improve skin hydration and reduce skin aging, according to several published clinical trials. The absence of a control group and the short observation time limits this study.


The Metabolic Plant Feedback Hypothesis: How Plant Secondary Metabolites Nonspecifically Impact Human Health.
Humans can ingest gram amounts of plant secondary metabolites daily through diet. Many of these phytochemicals are bioactive beyond our current understanding because they act through weak negative biological feedback mechanisms, undetectable in vitro. Homeostatic-type assessments shed light on the evolutionary implications of the human diet from plants, giving rise to the metabolic plant feedback hypothesis. The hypothesis states that ancient diets rich in carbohydrates coincide with bulk dietary phytochemicals that act as nonspecific inhibitors of metabolic and inflammatory processes. Consequently, food-derived phytochemicals are likely to be equally effective as herbal medicines for these indications. In addition to the ubiquitous flavonoids, terpenoids, and fatty acids in the diet, the likely impact of chronic chlorophyll ingestion on human health is discussed, and data on its modulation of blood glucose levels are presented. A major deduction of this hypothesis is that starchy diets lacking plant secondary metabolites are associated with multimorbidity (lifestyle diseases) including obesity, type 2 diabetes, and cardiovascular disease. It is proposed that the intake of leafy vegetables, spices, and herbal remedies rich in phytochemicals matches the transition and genetic adaptation to early agriculture, playing a compensatory role in the mismatch of old genes and new diets.


Technical nuances for the resection of cervical dumbbell schwannomas.
The majority of spinal nerve sheath tumors are within the intradural/extramedullary compartment. A subset of these tumors develop extraforaminal components that gradually expand into potential spaces. Herein, the authors provide a 2D video demonstrating the technical nuances concerning resection of cervical dumbbell schwannomas with extraspinal extension. Although nerve sheath tumors with large extraforaminal extension are often associated with complications and pose unique challenges to surgeons, circumferential exposure with intradural exploration allows for gross-total resection and nerve root preservation, without need for adjuvant treatments. The use of intraoperative ultrasound, neurophysiological monitoring, Doppler imaging, and meticulous surgical techniques aided to circumvent complications.


Effects of classwide curriculum-based measurement and peer tutoring: a collaborative researcher-practitioner interview study.
Recent research and development has integrated computer-managed classwide curriculum-based measurement (CBM) and peer tutoring (PT) to help general educators adapt instruction to address the diverse needs of their students. The purpose of this study was to gain insight into the teachers' perspective on the advantages and disadvantages of these methods. Twenty general education teachers participating in a project that combined CBM and PT were interviewed regarding (a) ways in which the project had affected their students and their instruction, (b) their level of satisfaction with the project, and (c) shortcomings of the project. An unusual feature of this study was that in attempting to take advantage of the insider information possessed by the educators, we involved the teachers in developing the actual interview questions. Teachers specified a large number of academic, social, and instructional benefits of the methods, and they identified several weaknesses that should be addressed. Implications are discussed in terms of the development of other educational innovations and the use of CBM and PT in general education classrooms that include students with learning disabilities.


Implementing the Collaborative Chronic Care Model in Mental Health Clinics: Achieving and Sustaining Clinical Effects.
Collaborative chronic care models (CCMs) were established with implementation support in nine mental health clinics. This study sought to determine whether their clinical impact was maintained after implementation support ceased. Posttrial data were analyzed from a randomized stepped-wedge CCM implementation trial in general mental health clinics in nine Department of Veterans Affairs medical centers. Sites received 1 year of implementation support, which was associated with reduced mental health hospitalization rates compared with non-CCM clinics in the same medical centers. Hospitalization rates for the year after implementation support were analyzed by using repeated measures logistic regression comparing the same clinics. Hospitalization rates for the postsupport year did not differ from comparison clinics either in the population that initially showed the difference or the population active in the clinics at the end of the year of implementation support. Clinical effects of the CCM may wane after cessation of active implementation support.


Antagonism of bradykinin B2 receptor prevents inflammatory responses in human endothelial cells by quenching the NF-kB pathway activation.
Bradykinin (BK) induces angiogenesis by promoting vessel permeability, growth and remodeling. This study aimed to demonstrate that the B2R antagonist, fasitibant, inhibits the BK pro-angiogenic effects. We assesed the ability of fasibitant to antagonize the BK stimulation of cultured human cells (HUVEC) and circulating pro-angiogenic cells (PACs), in producing cell permeability (paracellular flux), migration and pseocapillary formation. The latter parameter was studied in vitro (matrigel assay) and in vivo in mice (matrigel plug) and in rat model of experimental osteoarthritis (OA). We also evaluated NF-κB activation in cultured cells by measuring its nuclear translocation and its downstream effectors such as the proangiogenic ciclooxygenase-2 (COX-2), prostaglandin E-2 and vascular endothelial growth factor (VEGF). HUVEC, exposed to BK (1-10 µM), showed increased permeability, disassembly of adherens and tight-junction, increased cell migration, and pseudocapillaries formation. We observed a significant increase of vessel density in the matrigel assay in mice and in rats OA model. Importantly, B2R stimulation elicited, both in HUVEC and PACs, NF-κB activation, leading to COX-2 overexpression, enhanced prostaglandin E-2 production. and VEGF output. The BK/NF-κB axis, and the ensuing amplification of inflammatory/angiogenic responses were fully prevented by fasitibant as well as by IKK VII, an NF-κB. Inhibitor. This work illustrates the role of the endothelium in the inflammation provoked by the BK/NF-κB axis. It also demonstates that B2R blockade by the antaogonist fasibitant, abolishes both the initial stimulus and its amplification, strongly attenuating the propagation of inflammation.


Geometrical optics analysis of the structural imperfection of retroreflection corner cubes with a nonlinear conjugate gradient method.
Geometrical optics analysis of the structural imperfection of retroreflection corner cubes is described. In the analysis, a geometrical optics model of six-beam reflection patterns generated by an imperfect retroreflection corner cube is developed, and its structural error extraction is formulated as a nonlinear optimization problem. The nonlinear conjugate gradient method is employed for solving the nonlinear optimization problem, and its detailed implementation is described. The proposed method of analysis is a mathematical basis for the nondestructive optical inspection of imperfectly fabricated retroreflection corner cubes.


A density functional theory study of atomic oxygen and nitrogen adsorption over alpha-alumina (0001).
The interaction of atomic oxygen and nitrogen on the (0001) surface of corundum (alpha-alumina) is investigated from first-principles by means of periodic density functional calculations within the generalized gradient approximation. A large Al(2)O(3) slab model (18 layers relaxing 10) ended with the most stable aluminium layer is used throughout the study. Geometries, adsorption energies and vibrational frequencies are calculated for several stationary points for two spin states at different sites over an 1 x 1 unit cell. Two stable adsorption minima over Al or in a bridge between Al and O surface atoms are found for oxygen and nitrogen, without activation energies. The oxygen adsorption (e.g., E(ad) = 2.30 eV) seems to be much more important than for nitrogen (e.g., E(ad) = 1.23 eV). Transition states for oxygen surface diffusion are characterized and present not very high-energy barriers. The computed geometries and adsorption energies are consistent with similar adsorption theoretical studies and related experimental data for O, N or alpha-alumina. The present results along with our previous results for beta-cristobalite do not support the assumption of an equal E(ad) for O and N over similar oxides, which is commonly used in some kinetic models to derive catalytic atomic recombination coefficients for atomic oxygen and nitrogen. The magnitude of O and N adsorption energies imply that Eley-Rideal and Langmuir-Hinshelwood reactions with these species will be exothermic, contrary to what happens for beta-cristobalite.


Average daily quantities: a tool for measuring prescribing volume in England.
No perfect unit exists for measuring prescribing volume, because of the limitations of the prescription item and the Defined Daily Dose system. A specific English and easily understandable unit was thought desirable to allow discussions in the field with doctors about aspects of their prescribing. An expert group was therefore established to produce appropriate volume units (Average Daily Quantities, ADQs) for important drug groups, based on DDDs, average prescribed daily doses, and any available information on therapeutic equivalence. This system will be a useful tool for discussions with doctors concerning their prescribing. It is of some value for researchers performing drug utilization studies and studies on prescribing in England. The ADQ values will be reviewed regularly to ensure that changes in licensed doses, actual prescribing patterns, and DDDs are reflected, and that new drugs can be included. Copyright (c) 2000 John Wiley & Sons, Ltd.


Maxillary shape at the end of puberty in operated unilateral cleft lip and palate: A geometric morphometric assessment using computer tomography.
Cleft lip and palate (CLP) surgery interferes with maxillary growth and contributes to transversal and sagittal growth impairment. Our retrospective descriptive study aimed to evaluate maxillary bone shape in a homogenous unilateral CLP patient group using geometric morphometrics based on CT-scan data. We included all patients with available CT-scans at the end of pubertal growth and operated on at Smile House of Milan, according to the standard protocol, involving two surgical steps: (1) primary closure of the lip and soft palate at 6 months of age and (2) early secondary gingivoalveoloplasty (GAP) associated with hard palate repair at 18-36 months. Shape differences between CLP and an age-matched control group were characterized using geometric morphometrics based on 15 3D landmarks. We included 16 unilateral CLP patients and 20 age-matched controls. Principal component and canonical variate analyses showed that the maxillary shape in CLP was significantly different from controls but that this difference was limited. Linear and angular measurements confirmed these differences. Early secondary GAP results in satisfactory maxillary shape, with significant but limited differences relative to controls.


[Evaluation of the reactogenicity and immunogenic potency of combined vaccine "Bubo-Kok" in the immunization of children against diphtheria, tetanus, pertussis and viral hepatitis B].
Combined vaccine "Bubo-Kok" is characterized by safety and high immunological activity. The number of postvaccinal reactions in children aged 1 and 2 years, immunized with vaccine "Bubo-Kok", was not statistically different from those in groups of children immunized with adsorbed DPT vaccine, as well with such vaccine in combination with vaccine against hepatitis B. After the completion of the primary course of immunization 100% of children had protective antibody titers against diphtheria, tetanus and hepatitis B. Antibody titers against pertussis, equal to or exceeding protective titers, were found in more than 70% of immunized children. The immunogenic potency of vaccine "Bubo-Kok" with respect to all its components was not inferior to that of adsorbed DPT vaccine and vaccine against hepatitis B, when introduced simultaneously in different areas of the body. Vaccine "Bubo-Kok" successfully passed state trials and was recommended for registration.


The zona incerta modulates spontaneous spike-wave discharges in the rat.
The contribution of the zona incerta (ZI) of the thalamus on spike-wave discharges (SWDs) was investigated. Chronic recordings of bilateral cortices, bilateral vibrissa muscle, and unilateral ZI were performed in Long-Evans rats to examine the functional role of SWDs. Rhythmic ZI activity appeared at the beginning of SWD and was accompanied by higher-oscillation frequencies and larger spike magnitudes. Bilateral lidocaine injections into the mystacial pads led to a decreased oscillation frequency of SWDs, but the phenomenon of ZI-related spike magnitude enhancement was preserved. Moreover, 800-Hz ZI microstimulation terminates most of the SWDs and whisker twitching (WT; >80%). In contrast, 200-Hz ZI microstimulation selectively stops WTs but not SWDs. Stimulation of the thalamic ventroposteriomedial nucleus showed no obvious effect on terminating SWDs. A unilateral ZI lesion resulted in a significant reduction of 7- to 12-Hz power of both the ipsilateral cortical and contralateral vibrissae muscle activities during SWDs. Intraincertal microinfusion of muscimol showed a significant inhibition on SWDs. Our present data suggest that the ZI actively modulates the SWD magnitude and WT behavior.


Clinical outcomes in patients with acute myocardial infarction treated with primary percutaneous coronary intervention stratified according to duration of pain-to-balloon time and type of myocardial infarction.
Based on the clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), treated with primary percutaneous coronary intervention (pPCI), this study intended to assess mortality and major adverse cardiac and cerebrovascular event (MACCE) rates according to duration of pain-to-balloon (PTB) time and type of MI. This is a retrospective cohort study based on the prospectively collected ORPKI registry which covers PCIs performed in Poland chosen between January 2014 and December 2017. Under assessment were 1,994 STEMI and 923 NSTEMI patients. Study endpoints included mortality and MACCE rates (in-hospital, 30-day, 12- and 36-month). Predictors of all-cause mortality in the overall group, STEMI and NSTEMI were assessed by multivariable analysis. Kaplan-Meier survival curve analysis did not reveal significant differences between the STEMI and NSTEMI group for all-cause mortality or MACCE at the 36-month follow-up. While in the long PTB time group, MACCE rate was significantly greater in STEMI patients when compared to NSTEMI (p = 0.004). Among STEMI patients, the short, medium and long PTB time groups differed significantly in the rate of all-cause mortality (p = 0.006) and MACCE (p = 0.04) at 1,095 days of follow-up, which were the greatest in the long PTB time group. Before considering the length of PTB time, there were no statistically significant differences in mortality or MACCE frequency between the STEMI and NSTEMI group at 36-month follow-up. Longer PTB times are related to significantly greater mortality at the 36-month follow-up in the STEMI, but not in the NSTEMI group.


Learning to smell the roses: experience-dependent neural plasticity in human piriform and orbitofrontal cortices.
It is widely presumed that odor quality is a direct outcome of odorant structure, but human studies indicate that molecular knowledge of an odorant is not always sufficient to predict odor quality. Indeed, the same olfactory input may generate different odor percepts depending on prior learning and experience. Combining functional magnetic resonance imaging with an olfactory paradigm of perceptual learning, we examined how sensory experience modifies odor perception and odor quality coding in the human brain. Prolonged exposure to a target odorant enhanced perceptual differentiation for odorants related in odor quality or functional group, an effect that was paralleled by learning-induced response increases in piriform cortex and orbitofrontal cortex (OFC). Critically, the magnitude of OFC activation predicted subsequent improvement in behavioral differentiation. Our findings suggest that neural representations of odor quality can be rapidly updated through mere perceptual experience, a mechanism that may underlie the development of odor perception.


The universal growth rate behavior and regime transition in adherent cell colonies.
In this work, we used five cell lineages, cultivated in vitro, to show they follow a common functional form to the growth rate: a sigmoidal curve, suggesting that competition and cooperation (usual mechanisms for systems with this behavior) might be present. Both theoretical and experimental investigations, on the causes of this behavior, are challenging for the research field; since the sigmoidal form to the growth rate seems to absorb important properties of such systems, e.g., cell deformation and statistical interactions. We shed some light on this subject by showing how cell spreading affects the radius behavior of the growing colonies. Doing numerical time derivatives of the experimental data, we obtained the growth rates. Using reduced variables for the time and rates, we obtained the collapse of all colonies growth rates onto one curve with sigmoidal shape. This suggests a universal-type behavior, with regime transition related to a morphological transition of adherent cell colonies.


[Protective effect of LR-90 on articular cartilage in rabbit model of osteoarthritis].
To investigate the protective effect of LR-90 on articular cartilage in rabbit model of osteoarthritis. The cultured rabbits chondrocytes were assigned to be treated with IL-1β (10ng/ml) or IL-1β (10ng/ml)+LR-90 (50 mg/L). The mRNA expression of MMP-13, ADAMTS-5, aggrecan and collagen II in chondrocytes were assessed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Twenty male New Zealand white rabbits underwent bilateral anterior cruciate ligament transection (ACLT) to establish a animal model of osteoarthritis. Four weeks after model established, on the basis of randomization one knee of each rabbit was treated with 50 mg/L LR-90 in normal saline (NS) (experimental group) and the other knee was treated with same volume of NS (control group), 1/week × 5. Nine weeks after ACLT all rabbits were sacrificed and the knee joints were evaluated by gross morphology and histology. The mRNA expression of IL-1β, MMP-13, ADAMTS-5, aggrecan and collagen Ⅱ in articular cartilage was analyzed by RT-PCR. Gross morphology and Mankin histological evaluation showed that the extent and grade of cartilage damage in the experimental group were less severe than those in the control group.Compared to IL-1β group, LR-90 treatment suppressed the mRNA expression of MMP-13 and ADAMTS-5, and enhanced aggrecan and collagen Ⅱ mRNA expression. Consistent with the in vitro results, the intraarticular LR-90 administration suppressed the mRNA expression of IL-1β,MMP-13 and ADAMTS-5 (all P<0.01), while enhanced mRNA expression of aggrecan and collagen Ⅱ in cartilage (all P<0.01). LR-90 protects against cartilage degradation and inhibits the progression of osteoarthritis in rabbit mode1 of osteoarthritis, which is associated with the suppressing IL-1β, MMP-13, ADAMTS-5 and promoting aggrecan and collagen Ⅱ mRNA expression in cartilage.


Portal venous arterialization resulting in increased portal inflow and portal vein wall thickness in rats.
To explore the influence of portal vein hemo-dynamic changes after portal venous arterialization (PVA) on peribiliary vascular plexus (PVP) morphological structure and hepatic pathology, and to establish a theoretical basis for the clinical application of PVA. Sprague-Dawley rats were randomly divided into control and PVA groups. After PVA, hemodynamic changes of the portal vein and morphological structure of hepatohilar PVP were observed using Doppler ultrasound, liver function tests, ink perfusion transparency management and three-dimensional reconstruction of computer microvisualization, and pathological examination was performed on tissue from the bile duct wall and the liver. After PVA, the cross-sectional area and blood flow of the portal vein were increased, and the increase became more significant over time, in a certain range. If the measure to limit the flow in PVA was not adopted, the high blood flow would lead to dilatation of intrahepatic portal vein and its branches, increase in collagen and fiber degeneration in tunica intima. Except glutamic pyruvic transaminase (GPT), other liver function tests were normal. Blood with a certain flow and oxygen content is important for filling the PVP and meeting the oxygen requirement of the bile duct wall. After PVA, It is the anatomic basis to maintain normal morphology of hepatohilar bile duct wall that the blood with high oxygen content and high flow in arterialized portal vein may fill PVP by collateral vessel reflux. A adequate measure to limit blood flow is necessary in PVA.


FGF19 is a target for FOXC1 regulation in ciliary body-derived cells.
The forkhead C1 (FOXC1) transcription factor is involved in the development and regulation of several organs, including the eye, where FOXC1 alterations cause iris, trabecular meshwork and corneal anomalies. Using nickel agarose chromatin enrichment with human anterior segment cells, we previously identified the fibroblast growth factor 19 (FGF19) locus as a gene potentially regulated by FOXC1. Here, we demonstrate that FGF19 is a direct target of FOXC1 in the eye. FOXC1 positively regulates FGF19 expression in corneal and periocular mesenchymal cells in cell culture and in zebrafish embryos. Through the FGFR4 tyrosine kinase, FGF19 promotes MAPK phosphorylation in the developing and mature cornea. During development, loss of either FOXC1 or FGF19 results in complementary, but distinct, anterior segment dysgeneses. This study reveals an important role for FOXC1 in the direct regulation of the FGF19-FGFR4-MAPK pathway to promote both the development and maintenance of anterior segment structures within the eye.


Age-related changes in mastication are not improved by tongue exercise in a rat model.
Aging results in progressive changes in deglutitive functions, which may be due in part to alterations in muscle morphology and physiology. Mastication is a critical component of bolus formation and swallowing, but aging effects on masticatory function have not been well studied. The purpose of this study was to 1) quantify the effects of aging on mastication, and 2) determine the effects of tongue exercise on mastication in young adult and old rats. We hypothesized that there would be significant differences in mastication characteristics (number of bites, interval between bites, time to eat) as a function of age, and that tongue exercise would resolve preexercise differences between age groups. We expanded the established model of progressive, 8-week tongue exercise to include a mastication measurement: acoustic recordings of vermicelli pasta biting from 17 old and 17 young adult rats, randomized into exercise and control groups. We found the following: 1) Mastication characteristics were impacted by age. Specifically in older rats, there was an increase in time to eat and number of bites and intervals between bites decreased, suggesting increased oral motor-processing requirements for bolus formation. 2) tongue exercise did not impact mastication behaviors in young adult or old rats. Tongue exercise may not have been specific enough to result in behavioral changes in mastication or exercise dose may not have been sufficient. Nevertheless, results were noteworthy in expanding the established rat model of aging and have relevant clinical implications for future translation to human populations. NA Laryngoscope, 127:E29-E34, 2017.


Psoriasis and eczema are not mutually exclusive diseases.
Some reports have suggested that psoriasis and eczema are seldom found together. Knowledge of disease co-occurrence could lead to improved understanding of shared or opposing pathological mechanisms. We sought to determine whether psoriasis and eczema could exist simultaneously and consecutively in the same individuals. Skin examination data relating to 9,263 British children born during March 3rd to 9th, 1958 (the National Child Development Survey), were analysed for the co-occurrence of eczema and psoriasis. Of 354 children with visible eczema at the ages of 11 or 16 years, 5 (1.4%) were also noted to have visible psoriasis, compared to 89 (1.0%) of 8,909 children who did not have visible eczema at 11 or 16 years. The relative risk of psoriasis in a case of eczema was 1.41, 95% confidence intervals from 0.58 to 3.46. Contrary to some hospital-based studies which have suggested that the two diseases are seldom found together, this study of a large and representative population suggests that eczema and psoriasis may co-occur concurrently and consecutively in the same individual.


Adenosine receptors--the role in modulation of dopamine and glutamate release in the rat striatum.
The aim of present study was to assess the role of activation of adenosine A-1 and A-2a receptors in the modulation of dopamine (DA) and glutamate release in the rat striatum by microdialysis in freely moving animals. Adenosine A-1 receptor agonist N6-cyclopentyladenosine (CPA) and A-2a receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) were administered locally into the striatum through microdialysis probe. CPA (10, 100 and 500 microM) did not affect basal levels of DA or glutamate. In contrast, CGS 21680 at the concentrations of 10, 50 and 100 microM increased in a dose-dependent manner the level of DA and at 100 microM also the level of glutamate. Both agonists at the concentration of 100 microM inhibited KCl-induced (100 mM) DA and glutamate release. The present results suggest, that in physiological conditions only excitatory effects of adenosine may be observed and adenosine A-2a receptors seem to be involved. During depolarization with KCl, adenosine, by inhibiting excessive outflow of neurotransmitters mediated via A-1 and A-2a receptors, manifests its protective role as homeostatic neuromodulator.


Effect of cyclic thermal stress on the fatigue life of teeth restored with gold inlay.
This study aimed to evaluate the stress distribution that results from temperature changes in teeth restored with gold inlay and to predict the fatigue life of the teeth. A thermal load regimen for finite element analysis (FEA) was established in an in vivo experiment, in which participants with gold inlays drank hot and cold water. An extracted human maxillary molar was converted into a 3D FEA model. The tooth models with Class I and II preparations were restored with gold inlay in the experimental groups. The stress distribution was analyzed under the thermal loads. Also, lifetime prediction was conducted using Basquin's formulation. The gold inlay groups showed a higher stress distribution than the preparation-only groups regardless of the type of preparation. The Class II gold inlay group showed the shortest fatigue life of 2.48×1011 cycles, whereas the Class I preparation group showed the longest fatigue life of 4.49×1016 cycles.


Paid carers' understanding and experiences of meaningful involvement in bereavement for people with intellectual disability when a significant other is dying.
Wider communication about death and dying for those with intellectual disabilities has been highlighted as being of key importance. To gain the perspective of paid carers based in residential homes about meaningfully supporting individuals with intellectual disabilities in the bereavement process. Semi-structured interviews were conducted with paid carers working across two residential homes. Four themes were identified: (a) challenges in having conversations about death and dying; (b) meaningful involvement of residents in the bereavement process; (c) the relationship between paid carers and residents (including the impact of a resident's death on paid carers); and (d) the support needs of paid carers. The recommendations from previous research of meaningfully involving people with intellectual disabilities in the bereavement process have not filtered fully into practice. Paid carers still highlight the need for specialist support and advice to help them discuss and increase involvement in death and dying.


Differential effects of fenofibrate or simvastatin treatment of rats on hepatic microsomal overt and latent diacylglycerol acyltransferase activities.
Hepatic triacylglycerol secretion is elevated in insulin-resistant states. Microsomal diacylglycerol acyltransferase (DGAT) catalyzes the final reaction in the synthesis of triacylglycerol (TAG). We have previously described two DGAT activities in rat liver microsomes, one overt (cytosol-facing) and one latent (endoplasmic reticulum lumen-facing) (Owen MR, Corstorphine CG, Zammit VA: Overt and latent activities of diacylglycerol acytransferase in rat liver microsomes: possible roles in very-low-density lipoprotein triacylglycerol secretion. Biochem J 323:17-21, 1977). It was suggested that they are involved in the synthesis of TAG for the cytosolic droplet and VLDL lipidation, respectively. In the present study, we measured the overt and latent DGAT activities in rats fed diets containing one of two hypolipidemic drugs: fenofibrate (a peroxisome proliferator-activated receptor alpha [PPARalpha] agonist) and simvastatin (a 3-hydroxy-3-methylglutaryl [HMG]-CoA reductase inhibitor). We found that the activities of the two DGATs could be varied independently by these treatments. Fenofibrate raised overt DGAT activity but lowered that of latent DGAT. In contrast, simvastatin markedly lowered overt DGAT activity without affecting that of latent DGAT. The increase in overt DGAT activity induced by fenofibrate could not be mimicked by feeding a diet enriched in n-3 polyunsaturated fatty acids (PUFA), which lowered overt DGAT activity but did not affect latent DGAT, suggesting that n-3 PUFA act through a mechanism independent of PPARalpha activation. The fibrate-induced increase in overt DGAT activity and the inhibition of latent DGAT may provide a mechanism through which acyl moieties are retained within the liver for oxidation through the pathways concomitantly upregulated by PPARalpha activation.


[Effect of respiratory care on pulmonary function in patients after cardiopulmonary bypass].
Respiratory failure after cardiopulmonary bypass (CPB) remains one of the major complications after cardiac surgery. This study was designed to evaluate effects of respiratory care after CPB on pulmonary function. Eighteen patients scheduled for cardiac surgery were investigated. Preoperative respiratory functions (%VC, FEV1.0%, V25/Ht, FRC-CC, deltaN2) were measured in all the patients. Both induction and maintenance of anesthesia were performed using propofol, midazolam, fentanyl, and vecuronium bromide. All the patients were ventilated using volume controlled ventilation by setting FIO2 at 0.5, the respiratory frequency at 15 x min(-1), the tidal volume at 6-10 ml x kg(-1) adjusted to maintain PaCO2 between 30 to 40 mmHg, and the peak airway pressures below 40 cmH2O, PEEP of 0 cmH2O. From 1 hour after the operation, the patients were randomly divided into 2 groups: group A, ventilated artificially with PEEP of 5 cmH2O and group B, ventilated with PEEP adjusted to the patient's lower inflection point (LIP) obtained by the pressure-volume curve. PaO2, Qs/Qt and FRC were measured after induction of anesthesia, just after surgery, 1 hour after surgery and 1 hour after artificial ventilation with PEEP. The values of the LIP were obtained from the P-V curves with the constant-flow methods before and after surgery. PaO2 and FRC decreased and Qs/Qt increased significantly after the surgery in all the patients. One hour after artificial ventilation with PEEP, PaO2 increased and Qs/Qt decreased significantly compared with the values after operation. However, there was no significant difference in the magnitude of these changes among the different groups. The changes in PaO2 and Qs/Qt were not correlated with the changes in FRC and preoperative respiratory functions. The LIP tended to increase after surgery in 2 groups. Although pulmonary function deteriorated after CPB. PEEP could improve oxygenation in all the patients. There were no significant differences in the degree of these improvements between patients receiving PEEP of 5 cmH2O and patients with PEEP adjusted to their LIP. There was no significant relationship between preoperative pulmonary function and changes in oxygenation after CPB.


Müllerian inhibiting substance/anti-Müllerian hormone type II receptor protein and mRNA expression in the healthy and cancerous endometria.
Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) is a regulator of the female reproductive system, an indicator of ovarian reserve and a growth inhibitor of Müllerian duct-derived tumors in vivo and in vitro. The objective of the present study was to analyze MIS/AMH type II receptor (MIS/AMHRII) protein and mRNA expression in healthy human endometria compared with patients with endometrial hyperplasia and endometrial cancer, providing a foundation for MIS/AMH as a biological modifier for treatment of endometrial hyperplasia and endometrial cancer. The present study included healthy endometrial tissues (n=20), simple endometrial hyperplasia tissues without atypia (n=17), complex endometrial hyperplasia tissues without atypia (n=24) and endometrial cancer tissues (n=8). The location and variation of MIS/AMHRII protein expression was observed by immunohistochemistry. The expression was graded by two pathologists and was categorized as follows: Negative, weakly positive, moderately positive or strongly positive. Reverse transcription-quantitative polymerase chain reaction was used to quantify MIS/AMHRII mRNA expression. The expression of MIS/AMHRII protein was observed in the cytoplasm of healthy human endometria, endometrial hyperplasia and endometrial cancer cells. The frequency of MIS/AMHRII protein expression was 20.22±10.35% in the proliferative phase of the healthy endometrium and 24.09±11.73% in the secretory phase of the healthy endometrium. However, no differences were observed in the menstrual cycle phases. The frequency was 54.50±16.59% in endometrial hyperplasia without atypia, 55.10±15.87% in endometrial hyperplasia with atypia and 73.88±15.70% in endometrial cancer, indicating that expression was enhanced as the disease progressed from healthy to malignant status. In endometrial hyperplasia, MIS/AMHRII protein expression was significantly associated with histological complexity compared with atypia status. The present study demonstrated that MIS/AMHRII is present in healthy endometria, endometrial hyperplasia and endometrial cancer. The low expression frequency of MIS/AMHRII was not significantly different among normal endometrial tissues, however, the protein expression was elevated in endometrial hyperplasia and endometrial cancer. These findings indicated that the study of bioactive MIS/AMH, as a possible treatment for tumors expressing the MIS/AMH receptor, is essential.


Response of the murine hematopoietic system to chronic infection with Mycobacterium lepraemurium.
Mycobacterium lepraemurium infection of mice produces a chronic lethal disease that is characterized by massive accumulation of macrophages throughout the mononuclear-phagocyte system. We studied the influence of M. lepraemurium infection on the composition and function of the hematopoietic system. Medullary erythropoiesis was virtually abolished, as reflected by a small number of erythroid elements and a decrease in the number and frequency of erythroid progenitors in the bone marrow, together with reduced uptake of 59Fe into bone marrow hemin. On the other hand, erythropoiesis was observed in the spleen, as demonstrated by a large number of erythroid cells, a sixfold increase of 59Fe uptake, and a pronounced increase in the number of erythroid progenitors. A considerable increase of monocyte progenitors was observed in the spleen, and a more modest increase was observed in the bone marrow. This increase may be accounted for, at least in part, by greatly increased levels of macrophage-colony-stimulating factor in the serum of infected mice. Thus, M. lepraemurium infection produces important changes in the hematopoietic system, during the course of which the spleen becomes the major hematopoietic organ.


Salvage surgery for cervical radioiodine refractory 18F-FDG-PET positive recurrence of papillary thyroid cancer.
Five percent of patients with differentiated thyroid cancer are diagnosed with radioiodine refractory relapse in the course of the disease. For isolated or oligometastatic cervical recurrence, resection or another local treatment is recommended. In this study, the impact of surgical treatment of cervical radioiodine refractory 18F-FDG-PET positive relapse of papillary thyroid cancer (PTC) was evaluated. Patients receiving radioiodine therapy between 2005 and 2015 at the University Hospital of Cologne, Germany, for PTC were screened. The subgroup of patients undergoing surgery during the course of disease after recommendation by a multidisciplinary endocrine team for cervical radioiodine refractory 18F-FDG-PET positive recurrence was identified. Demographics, clinic-pathologic characteristics, oncologic treatment, and outcome were analyzed. Thirty (3%) of 969 patients with PTC treated with radioiodine therapy at our institution underwent surgery for radioiodine refractory 18F-FDG-PET positive cervical recurrence during the course of the disease. In eight (26.6%) patients, more than one operation was performed. Sixteen (53%) patients received external beam radiation therapy (EBRT) after surgery. Follow-up was on average, 79.2 ± 61.6 months after the last surgical treatment. Biochemical and radiological cure was seen in 12 (40%) patients. Remission was significantly more frequent in younger patients (P = 0.0001) with lymph node rather than soft tissue tumor recurrence (P = 0.004). Surgical treatment of radioiodine refractory 18F-FDG-PET positive cervical recurrence led to biochemical and radiological cure in about 40% of patients in this study. Further data are needed concerning risk stratification of potential subgroups benefitting of surgical approach and the possible role of EBRT after repetitive surgery.


The evaluation of follow-up strategies of watch-and-wait patients with a complete response after neoadjuvant therapy in rectal cancer.
Many of the current follow-up schedules in a watch-and-wait approach include very frequent MRI and endoscopy examinations to ensure early detection of local regrowth (LR). The aim of this study was to analyse the occurrence and detection of LR in a watch-and-wait cohort and to suggest a more efficient follow-up schedule. Rectal cancer patients with a clinical complete response after neoadjuvant therapy were prospectively and retrospectively included in a multicentre watch-and-wait registry between 2004 and 2018, with the current follow-up schedule with 3-monthly endoscopy and MRI in the first year and 6 monthly thereafter. A theoretical comparison was constructed for the detection of LR in the current follow-up schedule against four other hypothetical schedules. In all, 50/304 (16%) of patients developed a LR. The majority (98%) were detected at ≤2 years, located in the lumen (94%) and were visible on endoscopy (88%). The theoretical comparison of the different hypothetical schedules suggests that the optimal follow-up schedule should focus on the first 2 years with 3-monthly endoscopy and 3-6 monthly MRI. Longer intervals in the first 2 years will cause delays in diagnosis of LR ranging from 0 to 5 months. After 2 years, increasing the interval from 6 to 12 months did not cause important delays. The optimal follow-up schedule for a watch-and-wait policy in patients with a clinical complete response after chemoradiation for rectal cancer should include frequent endoscopy and to a lesser degree MRI in the first 2 years. Longer intervals, up to 12 months, can be considered after 2 years.


An autochthonous case of Echinococcus vogeli Rausch & Bernstein, 1972 polycystic echinococcosis in the state of Rondônia, Brazil.
The present case report refers to a patient from the State of Rondônia, North region of Brazil, attended with clinical suspicion of hepatic echinococcosis. Examination by imaging (ultrasonography and computerized tomography) revealed a conglomerate of cystic lesions, with mobile contents within the cyst. The serology (immunoblot) for Echinococcus sp. was positive (21 and 31 kDa bands). This case is the first reported in Rondônia, suggesting the need to investigate the polycystic echinococcosis in individuals with hepatic cysts from areas of tropical forest and hunting habits where wild life was present as wild dogs, cats and rodents, particularly Agouti paca (paca) and Dasyprocta aguti (agouti).


The role of hydrogen peroxide and RRR-alpha-tocopherol in smooth muscle cell proliferation.
Oxidants can be considered early growth signals, since they have been shown to activate a number of pathways that are also stimulated by growth factors. In particular, H(2)O(2) activates the protein kinase C signal transduction pathway in smooth muscle cells. These events certainly play a role in the activation of the DNA synthesis machinery although it is still unclear whether they can also regulate the lethal response. Evidence exists of an oxidant-mediated increase in tyrosine protein phosphorylation as an early event in the signal transduction cascade of growth factor receptors, leading to augmentation of cell proliferation. Oxidants can also induce transcription of enzymes, such as ornithine decarboxylase and the phosphatase CL-100. CL-100 is the first example of a new class of protein phosphatases responsible for modulating the activation of MAP kinase following exposure of quiescent cells to growth factors and further implicates MAP kinase activation/deactivation in the cellular response to hydrogen peroxide. Moreover H(2)O(2) activates the MAP kinase cascade by stimulating the tyrosine kinase and protein kinase C pathways. JNK1, a relative of the MAP kinase group, is activated by dual phosphorylation at Thr and Tyr during the UV response. RRR-alpha-tocopherol and RRR-beta-tocopherol have different and competing effects on smooth muscle cell proliferation, indicating that they do not act as antioxidants. The earliest event brought by RRR-alpha-tocopherol in the signal transduction cascade contolling receptor mediated cell growth is the inhibition of the transcription factor AP-1, activated by phorbol esters. RRR-beta-tocopherol alone is without effect but in combination with RRR-alpha-tocopherol prevents the AP-1-inhibiting effect of the latter. Protein kinase C is inhibited by RRR-alpha-tocopherol and not by RRR-beta-tocopherol, which also in this case prevented the effect of RRR-alpha-tocopherol. The inhibition of RRR-alpha-tocopherol of protein kinase C is not the consequence of a direct interaction but is due to a diminution, produced by RRR-alpha-tocopherol of the kinase phosphorylation. A tocopherol binding protein appears to be at the basis of the RRR-alpha-tocopherol, that discriminates between RRR-alpha-tocopherol and RRR-beta-tocopherol and initiates a cascade of events at the level of cell signal transduction leading to cell proliferation inhibition.


Klebsiella pneumoniae and Staphylococcus aureus infection in mice: difference in uremia and ammoniagenesis.
Lethal infections by Staphylococcus aureus and Klebsiella pneumoniae were compared for kidney-related effects in mice. K. pneumoniae caused uremia and an increase in blood ammonia that could reach 2.5 times normal. These events did not occur in mice inoculated with S. aureus. Use of germfree animals indicated that most of the increase in ammonia arose from the gut, presumably due to greater availability of urea and ureolysis. Injected ornithine restored blood ammonia to nearly normal levels and extended survival.


Panoramic Background Image Generation for PTZ Cameras.
Being able to cover a wide range of views, pan-tilt-zoom (PTZ) cameras have been widely deployed in visual surveillance systems. To achieve a global-view perception of a surveillance scene, it is necessary to generate its panoramic background image, which can be used for the subsequent applications such as road segmentation, active tracking, and so on. However, few works have been reported on this problem, partially due to the lack of benchmark dataset and the high complexity of panoramic image generation of PTZ cameras. In this paper, we build, for the first time to our best knowledge, a benchmark PTZ camera dataset with multiple views, and derive a complete set of panoramic transformation formulas for PTZ cameras. We further propose a fast multi-band blending method to address the efficiency issue in panoramic image fusion and mosaicing. Some related panoramic transformations are also developed, such as cylindrical and overlooking transformations. Our proposed approach exhibits impressive accuracy and efficiency in PTZ panorama generation as well as panoramic image mosaicing.


Optimized Threshold Inference for Partitioning of Clones From High-Throughput B Cell Repertoire Sequencing Data.
During adaptive immune responses, activated B cells expand and undergo somatic hypermutation of their B cell receptor (BCR), forming a clone of diversified cells that can be related back to a common ancestor. Identification of B cell clones from high-throughput Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) data relies on computational analysis. Recently, we proposed an automated method to partition sequences into clonal groups based on single-linkage hierarchical clustering of the BCR junction region with length-normalized Hamming distance metric. This method could identify clonal sequences with high confidence on several benchmark experimental and simulated data sets. However, determining the threshold to cut the hierarchy, a key step in the method, is computationally expensive for large-scale repertoire sequencing data sets. Moreover, the methodology was unable to provide estimates of accuracy for new data. Here, a new method is presented that addresses this computational bottleneck and also provides a study-specific estimation of performance, including sensitivity and specificity. The method uses a finite mixture model fitting procedure for learning the parameters of two univariate curves which fit the bimodal distribution of the distance vector between pairs of sequences. These distributions are used to estimate the performance of different threshold choices for partitioning sequences into clones. These performance estimates are validated using simulated and experimental data sets. With this method, clones can be identified from AIRR-seq data with sensitivity and specificity profiles that are user-defined based on the overall goals of the study.


Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice.
The production of antimicrobial peptides, such as the cathelicidins, plays a prominent role in the innate immune response against microbial pathogens. Cathelicidins are widely distributed amongst living organisms, and the antimicrobial peptides generated by proteolysis of the precursor forms are typically cationic and α-helical, a structure that facilitates their interaction and insertion into anionic bacterial cell walls and membranes, causing damage and promoting microbial death. Here, we found that mouse cathelicidin (Camp) expression was induced in bone marrow-derived macrophages by infection with Mycobacterium avium in a TLR2- and TNF-dependent manner. However, the endogenous production of the cathelin-related antimicrobial peptide (CRAMP) was not required for the bacteriostasis of M. avium either in primary cultures of macrophages or in vivo, as shown by the use of CRAMP-null mice. In contrast, the lack of Camp led to a transient improvement of M. avium growth control in the spleens of infected mice while at the same time causing an exacerbation of the inflammatory response to infection. Our data highlight the anti-inflammatory effects of CRAMP and suggests that virulent mycobacteria may possess strategies to escape its antimicrobial activity.


Drought Sensitivity of the Carbon Isotope Composition of Leaf Dark-Respired CO2 in C3 (Leymus chinensis) and C4 (Chloris virgata and Hemarthria altissima) Grasses in Northeast China.
Whether photosynthetic pathway differences exist in the amplitude of nighttime variations in the carbon isotope composition of leaf dark-respired CO2 (δ13Cl) and respiratory apparent isotope fractionation relative to biomass (ΔR,biomass) in response to drought stress is unclear. These differences, if present, would be important for the partitioning of C3-C4 mixed ecosystem C fluxes. We measured δ13Cl, the δ13C of biomass and of potential respiratory substrates and leaf gas exchange in one C3 (Leymus chinensis) and two C4 (Chloris virgata and Hemarthria altissima) grasses during a manipulated drought period. For all studied grasses, δ13Cl decreased from 21:00 to 03:00 h. The magnitude of the nighttime shift in δ13Cl decreased with increasing drought stress. The δ13Cl values were correlated with the δ13C of respiratory substrates, whereas the magnitude of the nighttime shift in δ13Cl strongly depended on the daytime carbon assimilation rate and the range of nighttime variations in the respiratory substrate content. The ΔR,biomass in the C3 and C4 grasses varied in opposite directions with the intensification of the drought stress. The contribution of C4 plant-associated carbon flux is likely to be overestimated if carbon isotope signatures are used for the partitioning of ecosystem carbon exchange and the δ13C of biomass is used as a substitute for leaf dark-respired CO2. The detected drought sensitivities in δ13Cl and differences in respiratory apparent isotope fractionation between C3 and C4 grasses have marked implications for isotope partitioning studies at the ecosystem level.


Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases.
To further study the clinicopathologic and immunohistochemical features of ovarian granulosa cell tumors (GCTs). We retrospectively studied all cases of GCTs diagnosed in our laboratory over the last 10-year period. Immunohistochemistry for inhibin, vimentin, cytokeratin, Ki-67 and p53 was performed on archival paraffin blocks. Pathologic and immunohistochemical findings were correlated with the clinical records of the patients. Twenty-one cases (15 of the adult and 6 of the juvenile type) were retrieved. All patients were FIGO Stage I at the time of diagnosis. Recurrent disease was detected in four patients (19%) during a median follow-up of 36 months (range 2-26 years). Pathology revealed a concomitant theca-cell component in three cases, a Sertoli-Leydig component in one case, and a thecoma in one case. Archival tissue material was available in 12 cases. Immunohistochemistry was positive for: beta-inhibin in 12/12 cases (100%), vimentin in 11/12 cases (91.7%), cytokeratin in 3/12 cases (25%), CD34 in 0 cases (0%), and p53 in 2/12 cases (16.7%). The Ki-67 index was < 5% in 12/12 cases (100%). No significant correlations were observed between the pathologic and immunohistochemical parameters examined and the clinical outcome. Despite the relatively indolent nature and favorable prognosis of most GCTs, late recurrences are not a rare event even in Stage I patients, necessitating a close and long-term follow-up. The identification of novel prognostic markers, in addition to our traditional staging parameters such as clinical staging, is needed in order to more accurately predict probabilities of recurrence in these patients.


Image-guided tissue engineering of anatomically shaped implants via MRI and micro-CT using injection molding.
This study demonstrates for the first time the development of engineered tissues based on anatomic geometries derived from widely used medical imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Computer-aided design and tissue injection molding techniques have demonstrated the ability to generate living implants of complex geometry. Due to its complex geometry, the meniscus of the knee was used as an example of this technique's capabilities. MRI and microcomputed tomography (microCT) were used to design custom-printed molds that enabled the generation of anatomically shaped constructs that retained shape throughout 8 weeks of culture. Engineered constructs showed progressive tissue formation indicated by increases in extracellular matrix content and mechanical properties. The paradigm of interfacing tissue injection molding technology can be applied to other medical imaging techniques that render 3D models of anatomy, demonstrating the potential to apply the current technique to engineering of many tissues and organs.


INHIBITION OF SYNTHESIS OF THE CELL WALL OF STAPHYLOCOCCUS AUREUS BY CEPHALOTHIN.
Cephalothin, 7-(thiophene-2-acetamido)-cephalosporanic acid, suppresses synthesis of the cell of Staphylococcus aureus. Exposure to this agent led to a reduction in the degree of incorporation of carbon-14-lysine into the mucopeptide of the cell wall material and to an accumulation of N-acetyl glucosamine in the cell. The intensity of the lesions was comparable to that produced by penicillin.


Differential remodeling of carotid artery in spontaneously hypertensive and hereditary hypertriglyceridemic rats.
High blood pressure, increased level of cholesterol, diabetes, hypertriglyceridemia and obesity are risk factors accompanied metabolic syndrome. The aim of the study was to compare geometry of carotid artery (AC) of 3-week-old (3w) and 52-week-old (52w) hereditary hypertriglyceridemic rats (hHTG) and spontaneously hypertensive rats (SHR) which represent a genetic model of human essential hypertension with age-matched Wistar rats. After sacrificing the rats were perfused with a glutaraldehyde fixative under the pressure 90 mm Hg (3w) and 120 mm Hg (52w) for 10 min via cannula placed into left ventricle. Middle part of AC was excised and processed according to standard electron microscopy procedure. Geometry of AC was evaluated in light microscopy. SHR vs. Wistar rats: BP of 3w did not differ, in 52w it was increased; cardiac hypertrophy was found in both ages; wall thickness (WT) and cross sectional area (CSA) in 3w did not differ, in 52w both were increased; inner diameter (ID) in 3w and 52w was decreased; WT/ID was increased in both ages. Hereditary HTG vs. Wistar rats: BP was increased in both periods; cardiac hypertrophy was observed in 3w; WT in 3w was decreased, in 52w it was increased; CSA and ID were decreased in both ages; WT/ID was increased only in 52w. Discrepancies between development of BP, cardiac hypertrophy in SHR and hHTG rats were observed. Alterations of BP were not in harmony with alterations in geometry of carotid arteries in both SHR and hHTG rats. We suggest that BP is not the main stimuli evoked hemodynamic and structural alterations of cardiovascular system in ontogenic development of SHR and hHTG rats.


Hypoxia-inducible factor-1alpha expression correlates with focal macrophage infiltration, angiogenesis and unfavourable prognosis in urothelial carcinoma.
Hypoxia inducible factor (HIF)-1alpha is a critical regulatory protein of cellular response to hypoxia and is closely related to angiogenic process. To explore the potential role and the prognostic value of HIF-1alpha in urothelial carcinoma (UC). Clinicopathological and follow-up data on 99 UC cases were reviewed and immunostained for HIF-1alpha, CD68, vascular endothelial growth factor (VEGF) and CD34 antigen. Tumour-associated macrophage (TAM) counts and HIF-1alpha expression were compared with clinicopathologic characteristics, overall survival (OS) and disease-free survival rates (DFS). High expression of HIF-1alpha was detected in 55 of 99 (55.6%) tumours. HIF-1alpha expression was correlated with tumour size, histological grade, tumour invasiveness and recurrence. VEGF and microvessel density (MVD) demonstrated their positive correlation with HIF-1alpha overexpression, supporting the correlation of HIF-1alpha up-regulation with tumour angiogenesis. Higher TAM infiltration was identified in high expression of HIF-1alpha cases rather than HIF-1alpha low expression cases (p = 0.002). Kaplan-Meier analysis found that HIF-1alpha overexpression and high TAM count was only associated with worse DFS (p = 0.009, p = 0.023) but was not associated with OS (p = 0.696, p = 0.141). Multivariate analyses indicated only tumour size (p = 0.038) to be an independently significant prognostic factor for OS, in addition, HIF-1alpha expression (p = 0.011), as well as histological grade (p = 0.038), and MVD (p = 0.004), to be independently significant prognostic factors for DFS. Our results indicate that HIF-1alpha is a key regulator of the angiogenic cascade. We show that HIF-1alpha is an independent prognostic factor for disease-free survival.


Serum amyloid-A protein and serum rheumatoid factor as serological surrogate markers for smoking risk factor in Saudi population.
Tobacco smoking represents major national and international health hazard that interferes with wide range of physiological functions and biomarkers. In the current study we have investigated the influence of tobacco smoking on some biological markers such as serum amyloid protein-A, rheumatoid factor, serum glucose level and lipid profile in Saudi population. The fore mentioned parameters were investigated in a total of 275 cases in 3 different age categories (less than 20 years old, 20-40 years old and older than 40 years old). Long term survey was adopted in all cases; yet, lightly smoking and heavily smoking groups were compared to never smoking healthy population. Results obtained showed significant increase in serum amyloid protein-A and rheumatoid factor in correlation to the degree of smoking nonetheless in the age category older than 40 years old. Serum glucose, triglyceride, and total cholesterol was not affected by smoking in all studied age categories; however serum LDL-cholesterol was elevated and serum HDL-cholesterol was depressed in correlation to the degree of smoking in all age categories. In conclusion, tobacco smoking represents major cardiovascular risk factor in Saudi population in all age categories and serum amyloid protein-A and rheumatoid factor might be used as a serological surrogate marker for such risk.


Cellular constituents of clinically normal foal bronchoalveolar lavage fluid during postnatal maturation.
Bronchoalveolar lavage was performed 5 times, sequentially, on 3 healthy foals when each was between 2 and 63 days of age. Total and differential counts were performed on recovered cells. The lungs of foals less than 19 days of age contained few alveolar macrophages recoverable by bronchoalveolar lavage. This number increased sharply during the first 2 to 3 weeks of life, but remained relatively constant subsequently. Approximately 86% of the alveolar cells in the lungs of foals up to 3 weeks of age were alveolar macrophages. During the first 2 months of life, this number decreased to approximately 71%, whereas the relative percentage of lymphocytes increased from 5% to 20%.


[Recent advances in the genetics of respiratory allergies].
The genetics of atopy and asthma is a fascinating area of research which has made tremendous progresses over the last couple of years. It has been known for ages that allergies and asthma are concentrating within families. Modern genetics has pintpointed some gene areas such as 5q31.1, 6p21.3, 11q13, 12q15 and 14q11.1. To do so, a crucial step is the definition of the phenotypes. Once the phenotype is set up (which is not an easy task), familial aggregation and segregation studies can be performed. These familial studies allow molecular genetics and linkage analysis. Both candidate gene approach and genome-wide search have been utilized in the genetic of atopy and asthma. Much of the information available today has been fragmentary and not always confirmed. Alleles at multiple loci are likely to be involved and the ultimate picture is most likely determined by many genetic and environmental factors.


[A comparative study of two imaging techniques for the diagnosis of sagittal fracture of mandible condyle].
To investigate the relationship between fractured fragment and joint disc displacement after sagittal fracture of mandibular condyle (SFMC). based on CT examination, SFMC were classified into fissue, displacement and dislocation type. Based on oblique sagittal MRI examination, the displacement of joint disc was grouped into type A and type B. Abnormal superiorposterior attachment was classified into elongation and avulsion type. CT exmination were taken in 26 patients with 41 SFMC. There were 5 SFMC (12%) with fissue type, 18 SFMC (44%) with displacement type and 18 SFMC (44%) with dislocation type. Both CT and MRI examination were taken in 19 patients with 32 SFMC. There were 27 (84%) SFMC with disc displacement. Five SFMC with type fissue showed no signs of disc displacement. Among 15 SFMC with type displacement, there were 3 cases with type A disc displacement and 12 cases with type B disc displacement. All the dislocated SFMC (12 cases) were type B disc displacement. In term of superiorposterior attachment figures, 4 cases (4/5) of type fissue SFMC showed normal. 14 cases (14/15) of the displacement SFMC showed elongated and all cases with dislocated SFMC showed sign of avulsion. There were 20 cases (63%) showing superior joint effusion. There were 13 cases (13/15) with displaced SFMC and 6 cases with dislocated SFMC showing joint effusion. One case with fissue SFMC showed no sign of joint effusion. Joint effusion, disc displacement and abnormal superiorposterior attachment were related to the displacement of condyle which was involved with SFMC.


Juggling with theory, evidence, practice, and real-world circumstances: Development of a complex community intervention to increase physical activity in inactive adults aged 50 years and older - The Move for Life Study.
Despite well-known benefits of physical activity, in Ireland only 38 % of older adults are sufficiently active. Behavioural interventions are rarely developed systematically and, when reported, inadequate description often becomes a barrier for subsequent replication and scalability. In this article, we describe the development and characteristics of Move for Life, an intervention to reach and help inactive adults aged 50 years and older increase their physical activity. It was designed to fit within existing group-based structured physical activity programmes run by Local Sports Partnerships, thus maximising the likelihood of translation into policy and practice. Constructs from social cognitive theory, self-determination theory, and the conceptual model of group cohesion in exercise informed the conceptual model and the development of behavioural skills, social support, and group cohesion intervention strategies. Physical activity instructors supported by peer mentors, who also contributed to sustaining the intervention, implemented these strategies. Moving away from accounts of intervention development as a relatively simple linear process, we illustrate the complex interplay of theory, evidence, practice, and real-world contextual circumstances that shaped the development of Move for Life. Against this backdrop, we discuss issues relevant to the planning and reporting of behavioural and physical activity interventions in public health.


qPCR multiplex detection of microRNA and messenger RNA in a single reaction.
Reverse Transcription-Quantitative PCR (RT-qPCR) is one of the standards for analytical measurement of different RNA species in biological models. However, current Reverse Transcription (RT) based priming strategies are unable to synthesize differing RNAs and ncRNAs especially miRNAs, within a single tube. We present a new methodology, referred to as RNAmp, that measures in parallel miRNA and mRNA expression. We demonstrate this in various cell lines, then evaluate clinical utility by quantifying several miRNAs and mRNA simultaneously in sera. PCR efficiency in RNAmp was estimated between 1.8 and 1.9 which is comparable to standard miRNA and random primer RT approaches. Furthermore, when using RNAmp to detect selected mRNA and miRNAs, the quantification cycle (Cq) was several cycles lower. This low volume single-tube duplex protocol reduces technical variation and reagent usage and is suitable for uniform analysis of single or multiple miRNAs and/or mRNAs within a single qPCR reaction.


Peripheral arterial disease among children with type 1 diabetes mellitus in a Nigerian teaching hospital.
The study aimed to determine the prevalence of PAD in children with T1DM and to correlate PAD with clinical characteristics in children with T1DM. A comparative cross-sectional study was conducted involving 90 subjects (forty-five with T1DM and 45 apparently healthy comparative subjects that were matched for age and gender). Systolic blood pressure was measured in all limbs using the pocket Doppler machine (Norton Doppler scan machine). Ankle brachial index (ABI) was calculated as a ratio of ankle to arm systolic blood pressure. Peripheral arterial disease was defined as ABI less than 0.9. The prevalence of PAD was significantly higher in children with T1DM than in the matched comparison group (37.8% vs. 6.7%, p<0.001). Average values of waist circumference, hip circumference, weight, height and body mass index were comparable in subjects with TIDM and the comparison group (p>0.05). Subjects with PAD had a poorer glucose control evident by higher average values of glycated haemoglobin than those without PAD (13.47 ± 3.2% vs. 8.16 ± 2.3%, p<0.001). There is a strong negative correlation between ABI scores and glycated haemoglobin among subjects with T1DM (r=-0.626, p<0.001). With these findings, it is recommended that screening for PAD in children who have T1DM and poor glycaemic control should be done early to prevent cardiovascular complications before they arise.


[Application and value of preoperative staging in gastric cancer].
A more differentiated therapy regimen for gastric carcinoma requires more precise preoperative staging. In patients with early gastric cancer (EGC), especially mucosa, endoscopic resection (ER) should be performed to avoid unnecessary surgical procedures. To achieve R0 resection for locally-advanced gastric cancer (AGC), neoadjuvant treatments have been investigated. Clinical staging of gastric cancer has been greatly improved by advance in imaging techniques such as endoscopic ultrasonography (EUS), transabdominal ultrasonography (TAUS), multi-slice spiral CT (MSCT), magnetic resonance imaging (MRI), positron emission tomography (PET), combined PET-CT scans, and laparoscopic staging. This review is to summarize the clinical application and the value of preoperative staging in gastric cancer.


Trends in Injector Deaths in Ireland, as Recorded by the National Drug-Related Deaths Index, 1998-2014.
The purpose of this study was to provide trend analysis on all deaths among drug users who injected at or around the time of their death in Ireland between 1998 and 2014. A review of the data recorded by the National Drug-Related Deaths Index (NDRDI) was conducted to identify individuals who were known to be injecting at or around the time of their death, from 1998 to 2014. Between 1998 and 2014, 16,500 deaths were recorded by the NDRDI. Of these, 792 (5%) people were known to be injecting at or around the time of death; 90% were poisoning deaths (n = 715) and 10% nonpoisoning deaths (n = 77). The majority of those who died while injecting were male (n = 682; 86%). Most people were living in Dublin city or county (n = 550; 69%). One fifth of those who died were homeless (n = 149; 19%). Opioids, specifically heroin, were implicated in the vast majority of injector poisoning deaths (n = 673; 94%), most commonly in association with polydrug use (n = 417; 62%). Single opioid poisoning resulted in 256 deaths (38%), and two fifths of those who died by single opioid poisoning were not alone at the time of death (n = 105; 41%). This study is the first to describe the trends in all deaths among drug users who injected at or around the time of their death in Ireland between 1998 and 2014. The analysis provides empirical evidence that can be used by policy makers to support the ongoing improvement of drug treatment services, harm reduction initiatives, and overdose prevention strategies for people who inject drugs.


The effects of laser light on sperm motility and velocity in vitro.
The effect of Laser light on the motility and the velocity of human spermatozoa were measured by means of multiple exposure photography. Total sperm motility increased after Laser irradiation at 4 J/cm2, 8 J/cm2 and 32 J/cm2 respectively with respect to control. However, no influence on sperm velocity was demonstrated after Laser irradiation. This observation suggests that Laser light stimulates non-motile live spermatozoa.


Immunization of experimental animals with reconstituted glycoprotein mixtures of herpes simplex virus 1 and 2: protection against challenge with virulent virus.
Artificial mixtures of the glycoproteins B, C, D, and E of herpes simplex virus 1 and 2 (HSV-1 and HSV-2), purified individually from infected Vero cell lysates by immunoaffinity to monoclonal antibodies, were bound to an aluminum hydroxide gel and were used to immunize mice, guinea pigs, and owl monkeys (Aotus trivirgatus) once or twice (mice and guinea pigs) to as many as four times (owl monkeys). In all animals tested, low levels of neutralizing antibodies were detected only after two or more immunizations. Lymphocyte transformation tests in owl monkeys suggested low or borderline levels of cellular immunity. The survival of immunized mice after intracerebral challenge was inversely related to the challenge dose. Immunized guinea pigs challenged by intravaginal inoculation showed reduced morbidity at the site of inoculation and were protected from CNS disease. Both immunized and nonimmunized monkeys were highly susceptible and could not be differentiated with respect to morbidity or mortality when challenged with 1,000 pfu of HSV-2 by the intravaginal route.


Genomic strategies for personalized cancer therapy.
Numerous recent studies have demonstrated the use of genomic data, particularly gene expression signatures, as clinical prognostic factors in cancer and other complex diseases. These studies highlight the opportunity for strategies to achieve truly personalized cancer treatment. In particular, the ability to develop gene expression signatures will likely allow us to guide the use of currently available cancer drugs, develop new targeted therapeutics, and provide an opportunity to better match the most effective drug or drugs with the molecular characteristics of the individual patient.


The impact of postoperative cerebrospinal fluid drainage on neurological improvement following thoracic aortic and thoracoabdominal aortic surgery.
Various preventive measures and treatment methods exist to prevent paraplegia during thoracic aortic surgery. Postoperative cerebrospinal fluid drainage (CSFD) is one of the treatment options when paraplegia occurs. This study aimed to evaluate the neurological efficacy of postoperative CSFD in patients undergoing thoracic aortic and thoracoabdominal aortic surgery. We analyzed perioperative data from 85 patients who underwent perioperative CSFD for thoracic and thoracoabdominal aortic surgery between January 2006 and December 2022, focusing on neurological changes. A total of 61 patients (72%) received preoperative CSFD, and 24 patients (28%) received postoperative CSFD. Perioperative neurological data were analyzed with a focus on perioperative changes. In the postoperative CSFD group, the manual muscle test (MMT) score before CSFD was 0.8, that just after CSFD was 2.4, and that at discharge was 3.0. Therefore, postoperative CSFD improved MMT scores compared with preoperative CSFD. The mean time between surgery completion and postoperative CSFD implantation was 9.8 hours. However, 6 (25%) of the patients who developed postoperative paraplegia and underwent early postoperative CSFD remained paraplegic without any improvement. In the preoperative CSFD group, there was only one case (2%) of postoperative paraplegia. Postoperative CSFD improved the neurological prognosis of individuals undergoing thoracic aortic and thoracoabdominal aortic surgery. However, 25% of the patients remained paraplegic despite postoperative CSFD.


A Zebra Diagnosis: A Case of Spontaneous Hematomyelia Associated With COVID-19.
Spontaneous non-traumatic spinal hematomyelia, characterized by intramedullary spinal hematoma, is a rare neurological emergency. Bleeding arteriovenous malformation, coagulopathies, and neoplasms are reported causes of this rare diagnosis. The authors present a case of a previously healthy man who presented with acute paraplegia and was found to have a spontaneous hematomyelia in association with covid infection. He underwent laminectomy and hematoma evacuation but did not recover any neurological function.


Risk factors associated with 30-day hospital readmissions among persons living with HIV in Nantong, China.
To estimate 30-day hospital readmission rates among persons living with HIV (PLWH) at the Nantong Infectious Disease Hospital in China and analyse the related risk factors. A single-centre retrospective cohort study was conducted. There were 894 PLWH records obtained from the electronic medical record (EMR) system at the Nantong Infectious Disease Hospital in China, from October 2013 to February 2018. The 30-day readmission rates were calculated, and the risk factors were analysed by generalised estimating equations (GEEs). A total of 1153 hospitalizations from 894 patients were recorded between October 2013 and February 2018. The median time of 30-day readmissions was 13 days (interquartile range (IQR), 6-23). The reasons for all causes, acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs), and non-AIDS-defining infections (non-ADIs) were 9.08, 13.52, and 7.91%, respectively. The results from the GEE analysis demonstrated that the risk factors associated with 30-days readmissions were as follows: no antiretroviral therapy (ART) prior to hospitalisations (odds ratio (OR) = 1.90, 95% confidence interval (CI): 1.21-3.00), low CD4 counts (OR = 2.17, 95% CI: 1.33-3.54), and multiple comorbidities (OR = 6.45, 95% CI: 1.62-25.73). Early detection of HIV infection and early initiation of ART treatment are the keys to controlling 30-day readmissions.


Dicyano-Substituted Diazaacenes.
Herein, we report the synthesis, spectroscopic, and structural properties of novel 2,3-dicyano-substituted azaacenes containing three to six annelated rings as a framework. The targets were prepared by Pd-catalyzed coupling of diamino-bis(tri-isopropylsilylethynyl)benzene, -naphthalene, and -anthracene with either 4,5-dibromophthalonitrile or 6,7-dibromonaphthalene-2,3-dicarbonitrile into the respective N,N'-dihydrodiazaacenes. Oxidation with MnO2 or PbO2 furnishes the dicyano-substituted diazaacenes in reasonable to good yields. An exception is the diazahexacene, where the N,N'-dihydrodiazaacene is difficult to oxidize. Most of the targets could be crystallized and pack in isolated pairs, stacks, and brick-wall motifs. The n-type behavior of these molecules was illustrated in a proof-of-concept organic field-effect transistor, showing mobilities up to 7×10-3 cm2 V-1 s-1 .


Donor/recipient origin of lung cancer after lung transplantation by DNA short tandem repeat analysis.
Lung cancer is more common in posttransplant recipients than in the general population. The objective of this study was to examine the chimerism donor/recipient cell origin of graft cancer in recipients of lung transplant. A retrospective chart review was conducted at Foch Hospital for all lung transplantations from 1989 to 2020. Short tandem repeat PCR (STR-PCR) analysis, the gold standard technique for chimerism quantification, was used to determine the donor/recipient cell origin of lung cancers in transplant patients. Fourteen (1.4%) of the 1,026 patients were found to have graft lung cancer after lung transplantation, and one developed two different lung tumors in the same lobe. Among the 15 lung tumors, 10 (67%) presented with adenocarcinoma, four (27%) with squamous cell carcinoma and one with small cell lung cancer. STR analysis showed that the origin of the cancer was the donor in 10 patients (71%), the recipient in three patients (21%), and was undetermined in one patient. Median time to diagnosis was 62 months. The prevalence of lung cancer in lung transplant recipients is very low. However, the results of our study showed heterogeneity of genetic alterations, with 21% being of recipient origin. Our results highlight the importance of donor selection and medical supervision after lung transplantation.


Binary Ni-Fe layered double hydroxide on flexible nickel foam for the wide-range voltammetric detection of fibrinogen in simulated body fluid.
Fibrinogen, a circulating glycoprotein in the blood, is a potential biomarker of various health conditions. This work reports a flexible electrochemical sensor based on Ni-Fe layered double hydroxide (Ni-Fe LDH) coated on Nickel foam (Ni-Fe LDH/NF) to detect fibrinogen in simulated human body fluid (or blood plasma). The nanoflakes like morphology and hexagonal crystal structure of LDH, synthesized via urea hydrolysis assisted precipitation technique, are revealed by scanning electron microscopy (SEM) and powder x-ray diffraction (PXRD) techniques, respectively. The fabricated sensor exhibits linearity in a wide dynamic range covering the physiological concentration, from 1 ng ml-1to 10 mg ml-1, with a sensitivity of 0.0914 mA (ng/ml)-1(cm)-2. This LDH-based sensor is found to have a limit of detection (LOD) of 0.097 ng ml-1and a limit of quantification (LOQ) of 0.294 ng ml-1(S/N = 3.3). The higher selectivity of the sensor towards fibrinogen protein is verified in the presence of various interfering analytes such as dopamine, epinephrine, serotonin, glucose, potassium, chloride, and magnesium ions. The sensor is successful in the trace-level detection of fibrinogen in simulated body fluid with excellent recovery percentages ranging from 99.5% to 102.5%, proving the synergetic combination of 2D Ni-Fe layered double hydroxide and 3D nickel foam as a promising platform for electrochemical sensing that has immense potential in clinical applications.


Novel Amorphous-Wollastonitic Low-Calcium Hydraulic Binders: A State-of-the-Art Review.
Because of the severe environmental impact of the CO2 emissions associated with the production of ordinary Portland cement (OPC) and the increasing demand for this commodity material, the development of alternative products has become a global concern. One alternative to OPC, or alitic-based clinkers, are amorphous-wollastonitic low-calcium hydraulic binders (AWLCs). This new class of hydraulic binders, described in the literature for the first time in 2015, may significantly reduce the CO2 emissions associated with its production, resulting from its lower calcium content, but also from the fact that its production technology can be fully electrified. In this paper, a state-of-the-art review is presented, providing a comprehensive description of the latest research, summarizing both the physicochemical and mechanical characteristics of this type of hydraulic binder, as well as possible routes for its production at an industrial scale.


Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee.
We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p<0.05), osteophyte formation and subchondral sclerotic bone (p<0.05). Using sectional cartilage area, modified Mankin scoring system as well as thickness of calcified and un-calcified cartilage analysis, the results showed that articular cartilage damage was ameliorated and T+F(M) group had the most protection as compared with other locations (p<0.05). Detectable cartilage surface damage and proteoglycan loss were measured and T+F(M) group showed the smallest lesion score among other groups (p<0.05). Micro-CT revealed significantly improved in subchondral bone repair in all ESWT groups compared to OA group (p<0.05). There were no significantly differences in bone remodeling after ESWT groups except F(M) group. In the immunohistochemical analysis, T+F(M) group significant reduced TUNEL activity, promoted cartilage proliferation by observation of PCNA marker and reduced vascular invasion through observation of CD31 marker for angiogenesis compared to OA group (P<0.001). Overall the data suggested that the order of the effective site of ESWT was T+F(M) ≧ T(M) > T(M+L) > F(M) in OA rat knees.