Exploring bias in platelet P2Y1 signalling: Host defence versus haemostasis.
Platelets are necessary for maintaining haemostasis. Separately, platelets are important for the propagation of inflammation during the host immune response against infection. The activation of platelets also causes inappropriate inflammation in various disease pathologies, often in the absence of changes to haemostasis. The separate functions of platelets during inflammation compared with haemostasis are therefore varied and this will be reflected in distinct pathways of activation. The activation of platelets by the nucleotide adenosine diphosphate (ADP) acting on P2Y1 and P2Y12 receptors is important for the development of platelet thrombi during haemostasis. However, P2Y1 stimulation of platelets is also important during the inflammatory response and paradoxically in scenarios where no changes to haemostasis and platelet aggregation occur. In these events, Rho-GTPase signalling, rather than the canonical phospholipase Cβ (PLCβ) signalling pathway, is necessary. We describe our current understanding of these differences, reflecting on recent advances in knowledge of P2Y1 structure, and the possibility of biased agonism occurring from activation via other endogenous nucleotides compared with ADP. Knowledge arising from these different pathways of P2Y1 stimulation of platelets during inflammation compared with haemostasis may help therapeutic control of platelet function during inflammation or infection, while preserving essential haemostasis.


[Carl Ferdinand von Graefe (1787-1840) and his relevance to ophthalmology].
This paper gives a short biography of Carl Ferdinand von Graefe, father of the most famous German oculist Albrecht von Graefe (1828-1870). On the occasion of his 200th birthday his work, in particular in the field of ophthalmology (cataract operations, prescription formulae, and therapeutic procedures, publications) is given due recognition. Although C.F. von Graefe was first and foremost a surgeon and the creator of plastic surgery of the face, he may also be considered one of the pioneers of ophthalmology, which, in the first third of the last century, had not yet achieved the status of an independent specialty.


MOEBIUS SYNDROME: CHALLENGES OF AIRWAY MANAGEMENT.
Moebius syndrome is a rare nonprogressive congenital neurological disorder with a wide range of severity and variability of symptoms. This diversity is a consequence of dysfunction of different cranial nerves (most often facial and abducens nerves), accompanying orofacial abnormalities, musculoskeletal malformations, congenital cardiac diseases, as well as specific associations of Moebius and other syndromes. The authors present anesthesia and airway management during the multiple tooth extraction surgery in a 10-year-old girl with Moebius syndrome associated with Poland and trigeminal trophic syndromes.


The Pattern of Psychiatric Morbidity in an Outpatient Child Psychiatry Clinic: A Cross-sectional, Descriptive Study from a Tertiary Care Hospital in Kashmir, North India.
Psychiatric disorders are ubiquitous and affect not only adults but also children and adolescents. The age factor plays an important role in the pattern of these psychiatric disorders. The objective of our study was to find the pattern of psychiatric morbidity in children and adolescents at the child and adolescent outpatient service of a tertiary care hospital. A semi-structured questionnaire was used to record the sociodemographic status. The state of mental health and psychiatric morbidity was assessed after a thorough clinical assessment. Intelligence quotient was assessed by a clinical psychologist as and when needed. All the diagnoses were made on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. A total of 529 patients were included. Most patients belonged to the age group of 6-16 years (70.5%). Boys (67.9%) outnumbered girls. Most of the patients were from rural background (56.7%) and from nuclear families (53%). Attention-deficit hyperactivity disorder (31%) and mental retardation (29%) were the most frequent diagnoses, followed by pervasive developmental disorders (10%). Comorbidity was present in about 18% of our patients. The child psychiatry is gaining acceptance, and children and adolescents with minor mental health issues are being identified and referred for specialized services.


Improving drug safety with a systems pharmacology approach.
Systems pharmacology is used to mechanistically analyze drug-adverse drug reaction (ADRs) pairs and is a promising solution to the complex problem of understanding mechanisms of toxicity. In this research, we have explored the feasibility of retrospectively mapping population-level adverse events from the FDA Adverse Event Reporting System (FAERS) to chemical and biological databases to identify drug safety signals and the underlying molecular mechanisms. We used an analytic platform - Molecular Analysis of Side Effects (MASE™). For this purpose, we selected the adverse event of severe and potentially fatal cutaneous reactions (SCARs) that are associated with acetaminophen (APAP). SCARs encompass the continuum between Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). We found a statistically significant association between APAP and TEN, the most severe form of SCARs. We also explored the influence of APAP on other classes of drugs commonly associated with SCARs. We found that APAP significantly reduced the risk of SCARs commonly associated with carbamazepine (CBZ). We used molecular docking simulations to propose a mechanism for APAP's reduction in CBZ-induced SCARs which is competitive inhibition of the binding of CBZ to HLA-B*15:02. We conclude that systems pharmacology can complement established surveillance methodologies by providing a means to undertake an independent investigation and review of the mechanisms by which drugs cause adverse events.


Parvovirus Infection Leading to Severe Anemia in an Adult Patient With HIV Disease.
Individuals with human immunodeficiency virus (HIV) disease frequently suffer from anemia. The causes include anemia of chronic disease, vitamin B12 and iron deficiency, opportunistic infections (Mycobacterium tuberculosis, Pneumocystis jiroveci), HIV-related bone marrow suppression, AIDS-associated malignancies, and antiretroviral therapy (ART), specifically zidovudine. In HIV patients with advanced immunodeficiency, failure to produce neutralizing antibodies can lead to chronic parvovirus B19 (B19) infection. Normally, in persons with intact immunity, the progression of B19 is self-limited. However, in chronic B19 infection, it can lead to pure red cell aplasia (PRCA) and chronic anemia. In human immunodeficiency virus (HIV)-infected patients, B19-related anemia is rare and underdiagnosed. It has a great response to intravenous immunoglobulin (IVIG) therapy. Hence, early diagnosis and prompt treatment can significantly reduce mortality. In this article, we described the case of a 25-year-old male with HIV infection who presented with a headache. He had severe normocytic anemia with a low reticulocyte count. The workup for blood loss, hemolysis, hemoglobinopathy, and iron deficiency was negative. Because of extremely low reticulocytopenia with severe anemia, the investigations favored multiple myeloma, parvovirus infection, and bone marrow aspiration biopsy. He was tested for parvovirus B19 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) test due to insufficient seroconversion. It turned out to be positive and he was treated with IVIG therapy.


[Studies on long-term irradiated rats using clomiphenedihydrogen citrate, LH and LH-RH].
The influence of clomiphene, LH and LH-RH on vaginal cycle and ovarian function in mature rats, which had been exposed to continuous light in order to block the cyclic sexual centre, was examined by different doses. While ovulation was obtained by administration of LH and LH-RH, clomiphene showed no effect. It may be assumed that the central mode of action of the "ovulation inducing effect" of clomiphene is mediated by stimulation of the cyclic sexual centre in the anterior hypothalamus.


Analysis of the expression of Fas, FasL and Bcl-2 in the pathogenesis of autoimmune thyroid disorders.
To investigate the expression of apoptosis-related protein (Fas, FasL, and Bcl-2) in the pathogenesis of autoimmune thyroid disorders (ATDs), immunohistochemical staining was performed on 20 Hashimoto's thyroiditis (HT), 20 Graves' disease (GD), and 20 thyroid follicular adenoma (TFA, as control). All the cases expressed Fas, mainly on the cell surface and cytoplasm. FasL was found in 17 cases of the TFA. Bcl-2 was detected in 15 cases of HT, 19 of GD and 17 of TFA. In TFA, a moderate Fas expression and a minimal or no FasL expression was detected on follicular cells. In HT, the follicles adjacent to infiltrating lymphocytes showed increased levels of Fas and FasL expression. A weaker staining of Fas and FasL was exhibited on infiltrating lymphocytes than on thyrocytes. In a comparison of GD with HT, thyrocytes and lymphocytes showed similar Fas staining, but for FasL the staining was rather weaker in HT. The expression of Bcl-2 was nearly identical in GD and TFA, but much weaker on the follicular cells in vicinity of lymphocytes and on the lymphocytes located in germinal centers of HT tissues. The expression of Fas, FasL, Bcl-2 in Hashimoto's thyroiditis and Graves' disease were almost same. FasL strong expression and Bcl-2 weak expression on the follicles in HT may induce apoptosis. These results provided evidence for expression of Fas, FasL and Bcl-2 in the pathogenesis of autoimmune thyroid disease. The lymphocytes seem not to be directly engaged in the process via their own FasL, but they may provide some cytokines that, in turn, upregulate Fas and/or FasL expression to induce apoptosis.


The spontaneous remission of cancer: Current insights and therapeutic significance.
Many diseases heal spontaneously. The common cold, for example, remedies itself within a few days in people with an uncompromised immune system. If a disease with a poor prognosis heals in the absence of a targeted therapeutic, many even call it a miracle cure. Such is the case with the spontaneous regression (SR) of malignant neoplasms, a rare but well-documented phenomenon that finds its first mention in the Ebers Papyrus of 1550 BCE. Given the challenges associated with current cancer treatment modalities such as rapidly evolving drug resistance mechanisms, dose-limiting side effects, and a failure to completely eliminate cancer cells, knowledge of how a tumour heals itself would be immensely helpful in developing more effective therapeutic modalities. Although the intricate mechanisms of SR have yet to be fully elucidated, it has been shown that infection-mediated immune system activation, biopsy procedures, and disruptions of the tumour microenvironment play pivotal roles in the self-healing of many tumours. Bacterial and viral infections are especially well-documented in instances of SR. Insights from these findings are paving the way for novel therapeutic strategies. Inspired by bacteria-mediated SR, Bacillus Calmette-Guérin (BCG) has been used as an approved treatment option for non-muscle-invasive bladder cancer (NMIBC). Similarly, Talimogene laherparepvec (T-VEC), the first engineered oncolytic herpes simplex virus (HSV), has been approved by the United States Food and Drug Administration for the treatment of some forms of advanced melanoma. Here we describe the current understanding of SR, explore its therapeutic significance, and offer perspectives on its future.


Incidence of an Aberrant Right Subclavian Artery on Second-Trimester Sonography in an Unselected Population.
The aim of this study was to assess the incidence of an aberrant right subclavian artery (ARSA) among an unselected population during second-trimester sonography and to review the importance of this conotruncal variant as a marker of Down syndrome. The presence or absence of an ARSA was assessed in an unselected population of 1913 second-trimester fetuses. Among the 1913 patients, an ARSA was detected in 20 fetuses (1.04%), all with a normal karyotype. Thirteen of 20 fetuses had an isolated ARSA, and 7 of them were nonisolated. Associated abnormal sonographic findings were an intracardiac echogenic focus (n = 3), a choroid plexus cyst (n = 1), pyelectasis (n = 1) and tetralogy of Fallot (n = 2). One of the cases of tetralogy of Fallot was also associated with a persistent left superior vena cava, a persistent right umbilical vein, hydrocephalus, rhombencephalosynapsis, and unilateral renal agenesis. There were only 2 fetuses with Down syndrome in this group, and both of them had a normal origin of the right subclavian artery. In an unselected population, an ARSA may be seen less frequently than in a high-risk population and may not be related to Down syndrome. An isolated ARSA is not a sufficient indication for karyotype analysis; it can be managed with noninvasive prenatal testing rather than invasive testing.


Improving antibiotic prescribing quality by an intervention embedded in the primary care practice accreditation: the ARTI4 randomized trial.
Antibiotic overprescribing is a significant problem. Multifaceted interventions improved antibiotic prescribing quality; their implementation and sustainability, however, have proved difficult. We analysed the effectiveness of an intervention embedded in the quality cycle of primary care practice accreditation on quantity and quality of antibiotic prescribing for respiratory tract and ear infections (RTIs). This was a pragmatic, cluster-randomized intervention trial in 88 Dutch primary care practices. The intervention (physician education and audit/feedback on antibiotic prescribing quantity and quality) was integrated in practice accreditation by defining an improvement plan with respect to antibiotic prescribing for RTIs. Numbers and types of dispensed antibiotics were analysed from 1 year prior to the intervention to 2 years after the intervention (pharmacy data). Overprescribing, underprescribing and non-first-choice prescribing for RTIs were analysed at baseline and 1 year later (self-registration). There were significant differences between intervention and control practices in the changes in dispensed antibiotics/1000 registered patients (first year: -7.6% versus -0.4%, P = 0.002; second year: -4.3% versus +2%, P = 0.015), which was more pronounced for macrolides and amoxicillin/clavulanate (first year: -12.7% versus +2.9%, P = 0.001; second year: -7.8% versus +6.7%, P = 0.005). Overprescribing for RTIs decreased from 44% of prescriptions to 28% (P < 0.001). Most general practitioners (GPs) envisaged practice accreditation as a tool for guideline implementation. GP education and an audited improvement plan around antibiotics for RTIs as part of primary care practice accreditation sustainably improved antibiotic prescribing. Tools should be sought to further integrate and facilitate education and audit/feedback in practice accreditation.


Nanoscale Titanium Dioxide (nTiO2) Transport in Natural Sediments: Importance of Soil Organic Matter and Fe/Al Oxyhydroxides.
Many engineered nanoparticle (ENP) transport experiments use quartz sand as the transport media; however, sediments are complex in nature, with heterogeneous compositions that may influence transport. Nanoscale titanium dioxide (nTiO2) transport in water-saturated columns of quartz sand and variations of a natural sediment was studied, with the objective of understanding the influence of soil organic matter (SOM) and Fe/Al-oxyhydroxides and identifying the underlying mechanisms. Results indicated nTiO2 transport was strongly influenced by pH and sediment composition. When influent pH was 5, nTiO2 transport was low because positively charged nTiO2 was attracted to negatively charged minerals and SOM. nTiO2 transport was slightly enhanced in sediments with sufficient SOM concentrations due to leached dissolved organic matter (DOM), which adsorbed onto the nTiO2 surface, reversing the zeta potential to negative. When influent pH was 9, nTiO2 transport was generally high because negatively charged medium repelled negatively charged nTiO2. However, in sediments with SOM or amorphous Fe/Al oxyhydroxides depleted, transport was low due to pH buffering by the sediments, causing attraction between nTiO2 and crystalline Fe oxyhydroxides. This was counteracted by DOM adsorbing to nTiO2, stabilizing it in suspension. Our research demonstrates the importance of SOM and Fe/Al oxyhydroxides in governing ENP transport in natural sediments.


Factors Affecting Electroconvulsive Therapy Ictal Outcomes: Duration and Postictal Suppression.
Electroconvulsive therapy (ECT) is an effective and rapid treatment for severe depression, however predictors of therapeutic outcomes remain insufficiently understood. Ictal duration and postictal suppression are two outcomes that may be correlated with patient response, yet patient and treatment variables which may influence these outcomes have not been thoroughly explored. We collected ECT stimulus metrics, EEG parameters, patient demographics, primary diagnosis, and anesthesia type for retrospective ECTs. Univariate and multivariate mixed-effects linear regression models were used to identify variables associated with ictal duration and postictal suppression index. For both outcomes, multivariate models which included all variables resulted in the best fit, reflecting the complex influences of a variety of factors on the ictal response. These results are an important step forward in elucidating patterns in retrospective ECT clinical data which may lead to new clinical knowledge of modifiable factors to optimize ECT treatment outcomes.


Salvianolic acid B inhibits IL-1β-induced inflammatory cytokine production in human osteoarthritis chondrocytes and has a protective effect in a mouse osteoarthritis model.
Osteoarthritis (OA) is a chronic progressive disease that has complicated mechanisms that involve inflammation and cartilage degradation. In this study, we investigated the anti-inflammatory action of Salvianolic acid B (Sal B) in both human OA chondrocytes and a mouse OA model that was induced by destabilization of the medial meniscus. In vitro, chondrocytes were pretreated with Sal B (0, 25, 50, 100μM) for 2h, then incubated with IL-1β (10ng/mL) for 24h. NO production was determined by Griess method and PGE2 was assessed by ELISA. The expression of INOS, COX-2, MMP-13, ADAMTS-5 and NF-κB-related signaling molecules were tested by Western blotting. Immunofluorescence staining was used to detect P65 nuclear translocation. In vivo, the mouse OA model received intraperitoneal-injection of either Sal B (25mg/kg) or saline every other day. Hematoxylin and Eosin, as well as Safranin-O-Fast green staining, were utilized to evaluate the severity of cartilage lesions up to 8weeks following the surgery. Sal B inhibited the over-production of NO and PGE2, while the elevated expression of INOS, COX-2, MMP-13 and ADAMTS-5 were reversed by Sal B in IL-1β-induced chondrocytes. In addition, IL-1β significantly induced phosphorylation of NF-κB signaling, and this phosphorylation response was blocked by Sal B. Immunofluorescence staining demonstrated that Sal B could suppress IL-1β-induced p65 nuclear translocation. In vivo, the cartilage in Sal B-treated mice exhibited less cartilage degradation and lower OARSI scores. Taken together, Sal B possesses great potential value as a therapeutic agent for OA treatment.


Design and implementation of a new autonomous sensor fish to support advanced hydropower development.
Acceleration in development of additional conventional hydropower requires tools and methods to perform laboratory and in-field validation of turbine performance and fish passage claims. The new-generation Sensor Fish has been developed with more capabilities to accommodate a wider range of users over a broader range of turbine designs and operating environments. It provides in situ measurements of three-dimensional (3D) linear accelerations, 3D rotational velocities, 3D orientation, pressure, and temperature at a sampling frequency of 2048 Hz. It also has an automatic floatation system and built-in radio-frequency transmitter for recovery. The relative errors of the pressure, acceleration, and rotational velocity were within ±2%, ±5%, and ±5%, respectively. The accuracy of orientation was within ±4° and accuracy of temperature was ±2 °C. The new-generation Sensor Fish is becoming a major technology and being deployed for evaluating the conditions for fish passage of turbines or other hydraulic structures in both the United States and several other countries.


Study on the relationship between scoliosis and vision problems: A narrative review.
Adolescent scoliosis is one of the most common surgical disorders of the pediatric spine. With timely detection and early treatment, most scoliotic children can avoid major and expensive surgery. Vision problems are also frequently found at an early age and can take a toll on individuals quality of life. However, scoliosis, a severe health hazard to adolescents, is often accompanied by vision problems clinically, including myopia, astigmatism, strabismus, amblyopia, horizontal paralysis, and blindness. And people with genetic defects have a higher probability of suffering both spinal problems and vision problems than those with nongenetic defects. However, many individuals viewed scoliosis and vision problems as 2 irrelevant diseases. This review searched PubMed, China National Knowledge Infrastructure, and Web of Science for studies on adolescent, scoliosis, eye diseases, myopia, strabismus, spinal disorders, and vision problems for almost 3 decades, and thus confirmed the potential relationship between adolescent scoliosis and vision problems.


Synaptic regulation of cellular properties and burst oscillations of neurons in gastric mill system of spiny lobsters, Panulirus interruptus.
The properties of neurons in the stomatogastric ganglion (STG) participating in the pattern generator for the gastric mill rhythm were studied by intracellular current injection under several conditions: during ongoing gastric rhythms, in the nonrhythmic isolated STG, after stimulation of the nerve carrying central nervous system (CNS) inputs to the STG, or under Ba2+ or Sr2+. Slow regenerative depolarizations during ongoing rhythms were demonstrated in the anterior median, cardiopyloric, lateral cardiac, gastropyloric, and continuous inhibitor (AM, CP, LC, GP, and CI) neurons according to criteria such as voltage dependency, burst triggering, and termination by brief current pulses, etc. Experiments showed that regenerative-like behavior was not due to synaptic network interactions. The slow regenerative responses were abolished by isolating the stomatogastric ganglion but could be reestablished by stimulating the input nerve. This indicates that certain CNS inputs synaptically induce the regenerative property in specific gastric neurons. Slow regenerative depolarizations were not demonstrable in gastric mill (GM) motor neurons. Their burst oscillations and firing rate were instead proportional to injected current. CNS inputs evoked a prolonged depolarization in GM motor neurons, apparently by a nonregenerative mechanism. All the gastric cells showed prolonged regenerative potentials under 0.5-1.5 mM Ba2+. We conclude that the gastric neurons of the STG can be divided into three types according to their properties: those with a regenerative capability, a repetitively firing type, and a nonregenerative "proportional" type. The cells are strongly influenced by several types of CNS inputs, including "gastric command fibers."


Mechanisms of weight loss after bariatric surgery.
The surgical treatment of clinically severe obesity is becoming more popular. To date, little has been published concerning the mechanisms by which each of the commonly employed bariatric surgical procedures induces weight loss. This article reviews the physiology of weight loss induced by semi-starvation and other proposed mechanisms of surgically induced weight loss.


Co-expression of anoctamins in cilia of olfactory sensory neurons.
Vertebrates can sense and identify a vast array of chemical cues. The molecular machinery involved in chemodetection and transduction is expressed within the cilia of olfactory sensory neurons. Currently, there is only limited information available on the distribution and density of individual signaling components within the ciliary compartment. Using super-resolution microscopy, we show here that cyclic-nucleotide-gated channels and calcium-activated chloride channels of the anoctamin family are localized to discrete microdomains in the ciliary membrane. In addition to ANO2, a second anoctamin, ANO6, also localizes to ciliary microdomains. This observation, together with the fact that ANO6 and ANO2 co-localize, indicates a role for ANO6 in olfactory signaling. We show that both ANO2 and ANO6 can form heteromultimers and that this heteromerization alters the recombinant channels' physiological properties. Thus, we provide evidence for interaction of ANO2 and ANO6 in olfactory cilia, with possible physiological relevance for olfactory signaling.


[Coccidiosis of rabbits and its control].
The investigations were performed on 6 farm rabbitries in Wrocław district. Average extensiveness of coccidia infection was 95%, while intensity ranged from 50 to 408,700 ocysts/g of faeces. Nine species of coccidia were identified. Eimeria perforans (84.5%) and E. stiedai (73.2%) dominated, E. coecicola was noticed most seldom (20.7%). In young rabbits up to 3 months of life the infections were caused by 5-9 species of coccidia. However, in animals from breeding herd there prevailed infections caused by 1-3 species. Congeneric infections were stated very rarely, i.e. in 5.7% of infected animals only. Dynamic changes in the intensity of coccidia infections in rabbits in the course of one year breeding cycle on one of the farms demonstrated the occurrence of two peaks in females used for reproduction: the first one in the perinatal period and the second one in the period preceding weaning. The letter one, higher than the first one, was caused by keeping young rabbits with mothers for 8-10 weeks. The studies on the effectiveness of anticoccidial drugs were carried out on California White rabbits (age 5-7 weeks), infected naturally with 9 species of coccidia. Rabbits were given for 5 weeks the following anticoccidials: lasalocid (Avatec), maduramycin (Cygro), robenidine (Cycostat), salinomycin (Sacox), monensin (Elancoban), clopidol + methylbenzoquate (Lerbek) and narasin (Monteban). The best results were obtained with salinomycin at the dosages of 35, 50, 25 ppm and maduramycin at 2 and 3 ppm. Equally effective, but characterized by lower production indices, were: clopidol + methylbenzoquate (216.7 ppm), lasalocid (90, 125 ppm) and monensin (20 ppm). Robenidine was very effective against intestinal coccidia at the dose of 66 ppm, however it had weak effect on E. stiedai's infection. Narasin and maduramycin (4.5 ppm) had toxic effect on animals. A field trial (anticoccidials applied for 6 weeks in does and their progeny) confirmed high effectiveness of salinomycin (25 ppm), maduramycin (1.5 ppm) and monensin (20 ppm).


Soluble Triggering Receptor Expressed on Myeloid Cells-1 as a Novel Marker for Abdominal Sepsis.
The aim of the study was to investigate the concentration and diagnostic significance of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in acute abdominal conditions. Plasma specimens were obtained from 68 patients with abdominal sepsis, 60 patients with systemic inflammatory response syndrome (SIRS), and 60 healthy individuals. The sepsis group was divided into the survival and death groups according to the 28-d outcome. Plasma sTREM-1, procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count were measured. A receiver operating characteristic curve (ROC) was used to compare the diagnostic values of sTREM-1, PCT, CRP, and WBC count. In addition, the correlation between plasma sTREM-1 and the Acute Physiology and Chronic Health Evaluation (APACHE) II score in the sepsis group was assessed by Spearman correlation analysis. The plasma concentration of sTREM-1 in the sepsis group was significantly higher than that in the SIRS and healthy groups (both p < 0.001). Also, the plasma concentration of sTREM-1 in the death group was markedly higher than that in the survival group. The ROC for the diagnosis of sepsis vs. SIRS showed that the area under the curve of sTREM-1 (0.82) was greater than that of PCT (0.77), CRP (0.72), and WBC count (0.70). Additionally, in the sepsis group, the plasma sTREM-1 concentration correlated positively with the APACHE II score (r = 0.41; p < 0.05). The plasma concentration of sTREM-1 may be a significantly sensitive and useful indicator for the rapid diagnosis of abdominal sepsis.


Rotablator versus cutting balloon for the treatment of long in-stent restenoses.
Conventional balloon angioplasty of in-stent-restenoses (ISR) will result in 50 70% re-restenoses. In addition to intracoronary brachytherapy, several ablative and non-ablative interventional technologies have been proposed to manage diffuse ISR. This study was designed to retrospectively assess rotational coronary atherectomy (Rotablator , or RA) and the Cutting Balloon (CB) with respect to the rate of restenoses after 6 months, the need for any additional revascularization at the target lesion (TLR), and the frequency of major cardiac events. To compare both techniques, we used the RA to treat 51 consecutive patients with long (> 10 mm) ISR. Subsequently, 76 patients with identical indications were treated with the CB. Both groups were comparable with respect to their coronary morphologies, demographic and clinical data. Re-angiography was performed in 86% of patients in the RA group and in 72% of patients in the CB group. On quantitative coronary angiography (QCA), the rate of restenoses was 63.9% in the RA and 27.3% in the CB group; the difference was statistically significant (p < 0.01). The rate of re-TLR was also significantly lower (18.7%) in the CB than in the RA group (43.2%). The rate of major cardiac events (not requiring TLR) was not different between both groups (CD = 7.3%; RA = 9.1%). Even when the methodological constraints of retrospective studies are taken into account, the study data indicate that treating diffuse ISR with the CB results in an acceptable long-term outcome and a low complication rate, results which make this method appear superior to RA.


Neoplasms and novel gammaherpesviruses in critically endangered captive European minks (Mustela lutreola).
The European mink (Mustela lutreola) is a riparian mustelid, considered one of the most endangered carnivores in the world. Alpha, beta and gammaherpesviruses described in mustelids have been occasionally associated with different pathological processes. However, there is no information about the herpesviruses species infecting European minks. In this study, 141 samples of swabs (oral, conjunctival, anal), faeces and tissues from 23 animals were analysed for herpesvirus (HV) using a pan-HV-PCR assay. Two different, potentially novel, gammaherpesvirus species were identified in 12 samples from four animals (17.3%), and tentatively named Mustelid gammaherpesvirus-2 (MUGHV-2) and MuGHV-3. Gross examination was performed on dead minks (n = 11), while histopathology was performed using available samples from HV-positive individuals (n = 2), identifying several neoplasms, including B-cell lymphoma (identified by immunohistochemistry) with intralesional syncytia and intranuclear inclusion bodies characteristic of HV (n = 1), pulmonary adenocarcinoma (n = 1), and biliary (n = 1) and preputial (n = 1) cystadenomas, as well as other lesions (e.g., axonal vacuolar degeneration [n = 2] and neuritis [n = 1]). Viral particles, consistent with HVs, were observed by electron microscopy in the mink with neural lymphoma and inclusion bodies. This is the first description of neoplasms and concurrent gammaherpesvirus infection in European minks. The pathological, ultrastructural and PCR findings (MuGHV-2) in the European mink with lymphoma strongly suggest a potential role for this novel gammaherpesvirus in its pathogenesis, as it has been reported in other HV-infected species with lymphoma. The occurrence of neural lymphoma with intralesional syncytia and herpesviral inclusions is, however, unique among mammals. Further research is warranted to elucidate the potential oncogenic properties of gammaherpesviruses in European mink and their epidemiology in the wild population.


Antiplasmodial activity of aspidosperma indole alkaloids.
The antiplasmodial activity of twelve alkaloids with an aspidospermane skeleton was estimated in vitro on chloroquine-resistant and sensitive strains of Plasmodium falciparum. Seven tetracyclic alkaloids possessing a free ethyl chain such aspidospermine, showed IC50 after incubation for 72 h between 3.2 and 15.4 microM. Moreover, four pentacyclic alkaloids with ethyl chain included in a tetrahydrofuran, such haplocine, showed a reduced activity, with IC50, after 72 h, between 22.6 and 52.6 microM. According to these results, a chloroquine-potentiating experiment was also performed with two of the most active compounds. Isobolograms were obtained and demonstrated a synergic effect of N-formyl-aspidospermidine and aspidospermine when associated with chloroquine. The cytotoxicity and the selectivity index of some alkaloids were also estimated.


[Role of a virus in hemorrhagic pancreatitis and the therapeutic effect of rhubarb].
The living measles vaccine was injected into both of the main pancreatic duct and the ear vein of the rabbits in the model group. The serum amylase was significantly higher than that of the control saline group (P less than 0.001 after 24h; P less than 0.05 after 48h). The aggregation function of platelets were increased after 24h(P less than 0.01, P less than 0.01) and 48h (P less than 0.01, P less than 0.05) as compared with both two control groups. The blood stasis and hemorrhage of pancreases were observed in the model group. In the treatment group with Rhubarb the increase of serum amylase was much less marked than the control (P less than 0.001 after 24h, P less than 0.05 after 48h). The platelet aggregation reactivity was inhibited (P less than 0.01 after 24h, P less than 0.05 after 48h). The blood stasis and hemorrhage of pancreases were less evident. The results suggested that: (1) the virus may be one of pathogenetic factor of the hemorrhagic pancreatitis; (2) the rhubarb was effective in the treatment of hemorrhagic pancreatitis under our experimental conditions.


Analysing human mobility patterns of hiking activities through complex network theory.
The exploitation of high volume of geolocalized data from social sport tracking applications of outdoor activities can be useful for natural resource planning and to understand the human mobility patterns during leisure activities. This geolocalized data represents the selection of hike activities according to subjective and objective factors such as personal goals, personal abilities, trail conditions or weather conditions. In our approach, human mobility patterns are analysed from trajectories which are generated by hikers. We propose the generation of the trail network identifying special points in the overlap of trajectories. Trail crossings and trailheads define our network and shape topological features. We analyse the trail network of Balearic Islands, as a case of study, using complex weighted network theory. The analysis is divided into the four seasons of the year to observe the impact of weather conditions on the network topology. The number of visited places does not decrease despite the large difference in the number of samples of the two seasons with larger and lower activity. It is in summer season where it is produced the most significant variation in the frequency and localization of activities from inland regions to coastal areas. Finally, we compare our model with other related studies where the network possesses a different purpose. One finding of our approach is the detection of regions with relevant importance where landscape interventions can be applied in function of the communities.


Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell Function.
One of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GCs). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims were to investigate whether GC secretion was abnormal in UC and exists as a long-term effect of chronic inflammation. Colonoids were established from intestinal stem cells of healthy subjects (HS) and patients with UC. Colonoids were maintained as undifferentiated (UD) or induced to differentiate (DF) and studied as three-dimensional or monolayers on Transwell filters. Total RNA was extracted for quantitative real-time polymerase chain reaction analysis. Carbachol and prostaglandin E2 mediated mucin stimulation was examined by MUC2 IF/confocal microscopy and transmission electron microscopy. Colonoids from UC patients can be propagated over many passages; however, they exhibit a reduced rate of growth and transepithelial electrical resistance compared with HS. Differentiated UC colonoid monolayers form a thin and non-continuous mucus layer. UC colonoids have increased expression of secretory lineage markers ATOH1 and SPDEF, along with MUC2 positive GCs, but failed to secrete mucin in response to the cholinergic agonist carbachol and prostaglandin E2, which caused increased secretion in HS. Exposure to tumor necrosis factor α (5 days) reduced the number of GCs, with a greater percentage decrease in UC colonoids compared with HS. Chronic inflammation in UC causes long-term changes in GCs, leading to abnormal mucus secretion. This continued defect in GC mucus secretion may contribute to the recurrence in UC.


[Comparative assessment of treatments for prostate adenoma greater than 100 cm3].
To compare holmium laser enucleation of the prostate (HoLEP) and endovideosurgical (EVS) adenomectomy in the treatment of prostate adenoma. We compared treatment results of 180 patients with prostate adenomas greater than 100 cm3 who underwent EVS adenomectomy (n=90) and laser enucleation of the prostate (n=90). The analysis included the following parameters: duration of catheterization, length of postoperative hospital stay, I-PSS score, maximum urinary flow rate measured by uroflowmetry and complications according to Clavien-Dindo grading systems. There were no significant differences in patient age, preoperative prostate size, glandular tissue weight, and operative time. The duration of catheterization (p=0.0008) and length of postoperative hospital stay (p<0.0001) were significantly shorter in the HoLEP group. Both groups showed a statistically significant improvement in functional performance at three months post-surgery. Complications in the HoLEP and EVS adenomectomy group occurred in 18 (20%) and 23 (25.55%) patients, respectively (p>0.99). The two methods mentioned above are widely used in the treatment of prostate adenoma. However, holmium laser enucleation of the prostate shows similar short-term functional results and complication rates compared with EVS adenomectomy for prostate adenomas greater than 100 cm3. The patients of the HoLEP group had better results regarding the duration of catheterization and length of postoperative hospital stay. Therefore, laser enucleation is the preferred surgical modality for prostate adenomas greater than 100 cm3.


Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors.
The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain.


Gastrointestinal manifestations in COVID-19.
Coronavirus disease 2019 (COVID-19), a respiratory viral infection, has affected more than 78 million individuals worldwide as of the end of December 2020. Previous studies reported that severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome-related coronavirus infections may affect the gastrointestinal (GI) system. In this review we outline the important GI manifestations of COVID-19 and discuss the possible underlying pathophysiological mechanisms and their diagnosis and management. GI manifestations are reported in 11.4-61.1% of individuals with COVID-19, with variable onset and severity. The majority of COVID-19-associated GI symptoms are mild and self-limiting and include anorexia, diarrhoea, nausea, vomiting and abdominal pain/discomfort. A minority of patients present with an acute abdomen with aetiologies such as acute pancreatitis, acute appendicitis, intestinal obstruction, bowel ischaemia, haemoperitoneum or abdominal compartment syndrome. Severe acute respiratory syndrome coronavirus 2 RNA has been found in biopsies from all parts of the alimentary canal. Involvement of the GI tract may be due to direct viral injury and/or an inflammatory immune response and may lead to malabsorption, an imbalance in intestinal secretions and gut mucosal integrity and activation of the enteric nervous system. Supportive and symptomatic care is the mainstay of therapy. However, a minority may require surgical or endoscopic treatment for acute abdomen and GI bleeding.


Phosphorylation of JAK2 in thrombin-stimulated human platelets.
We show the presence of the tyrosine kinase JAK2 in human platelets and demonstrate that it undergoes phosphorylation on tyrosine residues on challenge with the G protein receptor stimulus, thrombin, or the tyrosine phosphatase inhibitor, peroxovanadate. Thrombin-induced phosphorylation of JAK2 is inhibited by two structurally distinct inhibitors of tyrosine kinases, staurosporine and the tyrphostin ST271. The protein kinase C (PKC) inhibitor, Ro 31-8220, and intracellular Ca2+ chelator, BAPTA-AM, also inhibit thrombin-induced phosphorylation of JAK2, while the phorbol ester, phorbol dibutyrate (PDBu), and Ca2+ ionophore, A23187, induce tyrosine phosphorylation of JAK2. These results suggest that tyrosine phosphorylation of JAK2 stimulated by thrombin may be mediated downstream of phosphoinositide metabolism.


Neuropsychiatric Symptoms and Their Association With Sex, Age, and Enzyme Replacement Therapy in Fabry Disease: A Systematic Review.
Patients suffering from Fabry disease (FD) have an increased risk of developing neuropsychiatric symptoms (NPS), mostly impairment in cognitive performance and depression. Single cases of psychosis have been reported, however, their association with FD can be coincidental. Furthermore, deficits in social functioning and adaptation as well as specific coping styles in FD patients were observed. Recent studies focused on a longitudinal course of the disease and identified risk factors associated with specific NPS. Since 2001, enzyme replacement therapy (ERT) has been available and in preliminary studies seems to improve cognitive impairment and adaptive skills. In this systematic review, we analyze the available literature on the NPS in FD and investigate if there are any differences in their distribution between males and females, children/adolescents and adults, and individuals treated with ERT and untreated. We discuss the role of the psychological, environmental, and molecular alterations and their correlation to psychiatric manifestations in FD. Finally, we would like to increase awareness of the spectrum of NPS in FD.


An amino acid diet supporting superior growth in mice.
A diet containing, as a source of nitrogen, a mixture of purified L-amino acids simulating the amino acid composition of a successful diet containing vegetable and milk proteins was fed to mice in a 3% agar gel. This diet, at 17% amino acids, supported better growth of young male animals during a 21-day period than did the same assortment of amino acids at 23% of the diet, a commercial mouse food or the same basic diet containing a different assortment of amino acids from a published diet developed for rats. Cystine was removed from the diet, which contained 0.317% methionine and no choline, and this diet, fed for 52 days, continued to support growth and produced no microscopic evidence of fatty liver.


Variations in household microclimate affect outdoor-biting behaviour of malaria vectors.
Background: Mosquito behaviours including the degree to which they bite inside houses or outside is a crucial determinant of human exposure to malaria. Whilst seasonality in mosquito vector abundance is well documented, much less is known about the impact of climate on mosquito behaviour. We investigated how variations in household microclimate affect outdoor-biting by malaria vectors, Anopheles arabiensis and Anopheles funestus. Methods: Mosquitoes were sampled indoors and outdoors weekly using human landing catches at eight households in four villages in south-eastern Tanzania, resulting in 616 trap-nights over 12 months. Daily temperature, relative humidity and rainfall were recorded. Generalized additive mixed models (GAMMs) were used to test associations between mosquito abundance and the microclimatic conditions. Generalized linear mixed models (GLMMs) were used to investigate the influence of microclimatic conditions on the tendency of vectors to bite outdoors (proportion of outdoor biting). Results: An. arabiensis abundance peaked during high rainfall months (February-May), whilst An. funestus density remained stable into the dry season (May-August) . Across the range of observed household temperatures, a rise of 1 ºC marginally increased nightly An. arabiensis abundance (~11%), but more prominently increased An. funestus abundance (~66%). The abundance of An. arabiensis and An. funestus showed strong positive associations with time-lagged rainfall (2-3 and 3-4 weeks before sampling). The degree of outdoor biting in An. arabiensis was significantly associated with the relative temperature difference between indoor and outdoor environments, with exophily increasing as temperature inside houses became relatively warmer. The exophily of An. funestus did not vary with temperature differences. Conclusions: This study demonstrates that malaria vector An. arabiensis shifts the location of its biting from indoors to outdoors in association with relative differences in microclimatic conditions. These environmental impacts could give rise to seasonal variation in mosquito biting behaviour and degree of protection provided by indoor-based vector control strategies.


Intramolecular charge-transfer process of jet-cooled (p-cyanophenyl)pentamethyldisilane: roles of the torsional motion and the Si-Si bond change.
To investigate the intramolecular charge-transfer (ICT) process of (p-cyanophenyl)pentamethyldisilane (CPDS), laser-induced fluorescence, dispersed fluorescence, and two-color resonance enhanced two-photon ionization spectra were measured in a jet-cooled isolated condition. Dual fluorescence of CPDS was observed from a ground vibrational level in the locally excited pipi state. Similar to an emission from the charge-transfer (CT) state in solution, one of the dual emissions of the isolated molecule in the jet was assigned as the CT emission. A significant vibrational dependence on the ICT process was found as exciting vibronic levels of the molecule. It was identified that the promoting mode of the ICT process is a torsional motion of the disilanyl group with respect to the phenyl ring. It was also revealed that an effective appearance energy of the CPDS cation via the CT state is much lower than that via the locally excited pipi state suggesting that the electronic configuration of the CT state is similar to that of the cation. On the basis of an electronic configuration of the cationic state, that of the CT state was suggested to be of the (sigma(Si)(-)(Si), 2ppi) type.


Novel psychoactive substances: how to understand the acute toxicity associated with the use of these substances.
Since the turn of the 21st century, there has been an increase in the availability and use of novel psychoactive substances (also known as "legal highs") across Europe. Currently, there is limited information available on the potential acute toxicity (harms) associated with the use of these novel psychoactive substances. There are a number of potential data sources that can provide information on the acute toxicity associated with their use: (1) user reports on Internet discussion fora; (2) subpopulation level surveys of self-reported harms/unwanted effects (3) regional or national poisons information service accesses for support on presentations to healthcare facilities relating to acute toxicity; (4) case reports/series based on self-reported use or analytically confirmed use; and (5) human volunteer studies assessing potential acute toxicological effects. Each of these data sources has its own limitations, particularly those that are based on self-reported use because there are a number of European studies that show that there is inconsistency in the substance(s) in the "drug" that an individual uses. However, by using a multilayered approach of combining different sources, it is possible to reduce the overall impact of the limitations of any one individual data source. In this review article, we will combine information from these different data sources to describe the pattern of acute toxicity associated with 4 novel psychoactive substances: 1-benzylpiperazine, mephedrone (4-methylmethcathinone), synthetic cannabinoid receptor agonists, and methoxetamine.


The effect of postoperative electromagnetic pulsing on canine posterior spinal fusions.
An experimental canine study was devised to evaluate the efficacy of a noninvasive adjunct to improve the rate and quality of the posterior fusion mass over the standard surgical technique. Ten large adult mongrel dogs underwent a three-level lumbar spinal fusion. Bone excised from the spinous processes was packed in removed facet joints and over the decorticated laminae. To insure rigid internal fixation, custom-made distraction instrumentation was placed bilaterally under the laminae of the vertebrae above and below the three fused vertebrae. Five dogs underwent electromagnetic pulsing, and five dogs acted as controls. Two dogs were sacrificed at 4, 6, 9, 12, and 15 weeks to assess the radiographic and histologic status of the fusion mass. Preoperative and preautopsy hematologic studies as well as gross and histologic autopsy specimens revealed no abnormalities attributable to the electromagnetic pulsing. High-resolution radiography and histologic studies showed earlier incorporation of the graft, improved new bone formation, and better organization of the fusion mass in the 4-, 6-, and 9-week stimulated specimens. However, by 12 and 15 weeks there did not appear to be any histologic or radiographic differences between the stimulated and control dogs. Although electromagnetic pulsing appears to produce an early accelerated osteogenic response, it does not appear to improve the overall results of primary canine spinal fusions.


Optical-transparent metasurface for flexible manipulation and analog information modulation.
Recently, optically-transparent metasurface based on indium tin oxide (ITO) film has attracted wide attention due to its remarkable optical and electromagnetic characteristics. However, most previous researches on the ITO film mainly focus on the absorption because of its prominent loss-resistance property, but neglecting the further exploration on programmable functions. Here, we present a programmable metasurface based on an optically-transparent ITO glass, on which varactors are integrated to achieve flexible amplitude manipulation range of about 25 dB. More importantly, the presented programmable design can be applied for direct modulation on the carrier incident wave with the desired pre-designed analog wave-form. Within the 10 MHz modulation speed, both programmable amplitude manipulation and analog information modulation are demonstrated in the measurements, showing good agreement with theoretical analysis and simulations. Combining both optical transparency and programmable modulation capability, the presented metasurface will promote the potential applications in wireless communication, internet of things and other smart scenarios.


[Water exchange in human crystalline lens studied by combined dispersion confocal microspectroscopy].
We have employed the technique of the confocal Raman microspectroscopy to monitor water exchange in human eye lens in vitro. Heavy water (D2O) was used as a marker of the exchange. Raman spectra in the high frequency range (2200-3500 cm-1) were successively recorded at several locations inside the lens in order to register dynamics of the replacement of H2O by D2O. The intensities of the Raman peaks at 2450 cm-1 (OD stretch) and 3390 cm-1 (OH stretch) were used as indicators of H2O/D2O exchange, whereas the Raman peak at 2935 cm-1 (CH stretch of protein) served as an internal standard. The ratios of the Raman intensities I2450/I2935 and I3390/I2935 determined the relative concentrations of D2O and H2O, respectively. For the quantitative description of the exchange, we proposed a diffusion model assuming a constant diffusion coefficient over the volume of the lens. We report the results of experiments performed on four fresh and one fixed lenses. The diffusion coefficient of D2O in the human eye lens was estimated using the least-squares fit of the experimental data.


Improving accuracy and completeness in the collaborative staging system for stomach cancer in South Korea.
Cancer staging enables planning for the best treatments, evaluation of prognosis, and predictions for survival. The Collaborative Stage (CS) system makes it possible to significantly reduce the proportion of patients labeled at an "unknown" stage as well as discrepancies among different staging systems. This study aims to analyze the factors that influence the accuracy and validity of CS data. Data were randomly selected (233 cases) from stomach cancer cases enrolled for CS survey at the Korea Central Cancer Registry. Two questionnaires were used to assess CS values for each case and to review the cancer registration environment for each hospital. Data were analyzed in terms of the relationships between the time spent for acquisition and registration of CS information, environments relating to cancer registration in the hospitals, and document sources of CS information for each item. The time for extracting and registering data was found to be shorter when the hospitals had prior experience gained from participating in a CS pilot study and when they were equipped with full-time cancer registrars. Evaluation of the CS information according to medical record sources found that the percentage of items missing for Site Specific Factor (SSF) was 30% higher than for other CS variables. Errors in CS coding were found in variables such as "CS Extension," "CS Lymph Nodes," "CS Metastasis at Diagnosis," and "SSF25 Involvement of Cardia and Distance from Esophagogastric Junction (EGJ)." To build CS system data that are reliable for cancer registration and clinical research, the following components are required: 1) training programs for medical records administrators; 2) supporting materials to promote active participation; and 3) format development to improve registration validity.


Dynamic Properties of Adsorption Layers of κ-Casein Fibrils.
The dynamic surface properties of native κ-casein solutions and aqueous dispersions of its fibrils differ significantly from the corresponding properties of the systems with globular proteins. The dependence of the dynamic surface elasticity of κ-casein solutions on surface pressure has a local maximum, indicating partial displacement of macromolecules from the proximal region of the surface layer to the distal one. This dependence becomes monotonic for fibril dispersions, similar to the results for dispersions of globular protein fibrils, but unlike the latter case, the surface elasticity close to the steady state reaches values that are approximately four times higher than the data for native protein solutions at the same concentrations.


Delta(9)-Tetrahydrocannabinol-induced desensitization of cannabinoid-mediated inhibition of synaptic transmission between hippocampal neurons in culture.
Prolonged exposure to cannabinoids results in desensitization of cannabinoid receptors. Here, we compared the desensitization produced by the partial agonist, Delta(9)-tetrahydrocannabinol (THC) to that produced by the full agonist Win55,212-2 on cannabinoid-mediated inhibition of glutamatergic synaptic transmission. Synaptic activity between rat hippocampal neurons was determined from network-driven increases in the intracellular Ca(2+) concentration ([Ca(2+)](i) spikes). To assess the effects of prolonged treatment, cultures were incubated with cannabinoids, washed in 0.5% fatty-acid-free bovine serum albumin to ensure the removal of the lipophilic drug and then tested for inhibition of [Ca(2+)](i) spiking by Win55,212-2. In control experiments, 0.1 microM Win55,212-2 inhibited [Ca(2+)](i) spiking by 93 +/- 5%. Win55,212-2 produced significantly less inhibition of [Ca(2+)](i) spiking following 18-24h treatment with 1 microM THC (48 +/- 5%) or treatment with 1 microM Win55,212-2 (29 +/- 6%). Thus, THC produced significantly less functional desensitization than Win55,212-2. The desensitization produced by THC was maximal at 0.3 microM, remained stable between 1 and 7 days of preincubation and shifted the EC(50) of acute inhibition by Win55,212-2 from 27 to 251 nM. Differences in the long-term effects of cannabinoid receptor agonists on synaptic transmission may prove important for evaluating their therapeutic and abuse potential.


Sialic Acids on Tumor Cells Modulate IgA Therapy by Neutrophils via Inhibitory Receptors Siglec-7 and Siglec-9.
Immunotherapy with targeted therapeutic antibodies is often ineffective in long-term responses in cancer patients due to resistance mechanisms such as overexpression of checkpoint molecules. Similar to T lymphocytes, myeloid immune cells express inhibitory checkpoint receptors that interact with ligands overexpressed on cancer cells, contributing to treatment resistance. While CD47/SIRPα-axis inhibitors in combination with IgA therapy have shown promise, complete tumor eradication remains a challenge, indicating the presence of other checkpoints. We investigated hypersialylation on the tumor cell surface as a potential myeloid checkpoint and found that hypersialylated cancer cells inhibit neutrophil-mediated tumor killing through interactions with sialic acid-binding immunoglobulin-like lectins (Siglecs). To enhance antibody-dependent cellular cytotoxicity (ADCC) using IgA as therapeutic, we explored strategies to disrupt the interaction between tumor cell sialoglycans and Siglecs expressed on neutrophils. We identified Siglec-9 as the primary inhibitory receptor, with Siglec-7 also playing a role to a lesser extent. Blocking Siglec-9 enhanced IgA-mediated ADCC by neutrophils. Concurrent expression of multiple checkpoint ligands necessitated a multi-checkpoint-blocking approach. In certain cancer cell lines, combining CD47 blockade with desialylation improved IgA-mediated ADCC, effectively overcoming resistance that remained when blocking only one checkpoint interaction. Our findings suggest that a combination of CD47 blockade and desialylation may be necessary to optimize cancer immunotherapy, considering the upregulation of checkpoint molecules by tumor cells to evade immune surveillance.


Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?
Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.


A retrospective chart review of intramuscular ziprasidone for agitation in children and adolescents on psychiatric units: prospective studies are needed.
Our primary objective was to evaluate the effectiveness and tolerability of intramuscular ziprasidone for impulsivity and agitation in psychiatrically hospitalized children and adolescents. Our secondary objective was to examine demographic and clinical factors associated with treatment response. We conducted a retrospective chart review of children and adolescents admitted to Cincinnati Children's Hospital Medical Center (CCHMC) psychiatric units between January 1, 2002, and July 11, 2005, who received intramuscular ziprasidone. Medical records were reviewed to determine demographic and clinical information as well as tolerability and effectiveness of ziprasidone. The Behavioral Activity Rating Scale (BARS) was used retrospectively to assess clinical response. Regression analyses were performed to evaluate the effect of demographic factors (age, gender, and ethnicity) and primary psychiatric diagnoses on treatment response. Electrocardiogram (ECG) data was inadequate. Fifty nine children and adolescents received a total of 77 injections of intramuscular ziprasidone for acute agitation. The mean +/- SD BARS score decreased from 6.5 +/- 0.7 to 3.1 +/- 1.3. The most common side effect was drowsiness or falling asleep (n = 46, 60%). Three (4%) could not be roused after the injection. Intramuscular ziprasidone may be helpful for agitation but often caused oversedation. Safety data, including ECGs, is needed in controlled prospective studies.


Spontaneous Amino-yne Click Polymerization: A Powerful Tool toward Regio- and Stereospecific Poly(β-aminoacrylate)s.
Efficient synthesis of poly(enamine)s has been a great challenge because of their poor stability, poor solubility, and low molecular weights. In this work, a spontaneous amino-yne click polymerization for the efficient preparation of poly(enamine)s was established, which could proceed with 100% atom efficiency under very mild conditions without any external catalyst. Through systematic optimization of the reaction conditions, several soluble and thermally stable poly(β-aminoacrylate)s with high molecular weights (Mw up to 64400) and well-defined structures were obtained in excellent yields (up to 99%). Moreover, the polymerization can perform in a regio- and stereospecific fashion. Nuclear magnetic resonance spectra analysis revealed that solely anti-Markovnikov additive products with 100% E-isomer were obtained. The reaction mechanism was well demonstrated with the assistance of density functional theory calculations. In addition, by introducing the tetraphenylethene moiety, the resulting polymers exhibit unique aggregation-induced emission characteristics and could be applied in explosives detection and bioimaging. This polyhydroamination is a new type of click polymerization and opens up enormous opportunities for preparing functional polymeric materials.


Polyamines in Eukaryotes, Bacteria, and Archaea.
Polyamines are primordial polycations found in most cells and perform different functions in different organisms. Although polyamines are mainly known for their essential roles in cell growth and proliferation, their functions range from a critical role in cellular translation in eukaryotes and archaea, to bacterial biofilm formation and specialized roles in natural product biosynthesis. At first glance, the diversity of polyamine structures in different organisms appears chaotic; however, biosynthetic flexibility and evolutionary and ecological processes largely explain this heterogeneity. In this review, I discuss the biosynthetic, evolutionary, and physiological processes that constrain or expand polyamine structural and functional diversity.


Mavacamten: A Novel Disease-Specific Treatment for Hypertrophic Cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal thickening of the myocardium, leading to left ventricular outflow tract obstruction. Current treatments for HCM include non-disease-specific medications such as beta blockers or invasive interventions. Mavacamten has been studied for its effects on adenosine triphosphatase, myocardial-specific sarcomeric proteins, and myocardial tissue calcium sensitivity. Given these properties, mavacamten could be used as a disease-specific treatment for HCM. Clinical trials of mavacamten have shown improvements in left ventricular outflow tract obstruction among other favorable improvements in biochemical markers and the clinical symptoms of the disease. While trials to date have been relatively small, mavacamten shows promise as a future disease-specific treatment for HCM.


Risk Factors for Mortality in Children with Congenital Heart Disease Delivered at a Brazilian Tertiary Center.
This study aims to investigate the incidence of postnatal diagnosis of congenital heart disease (CHD) and the predictive factors for hospital mortality. This retrospective cohort study was conducted at a Brazilian tertiary center, and data were collected from medical records with inclusion criteria defined as any newborn with CHD diagnosed in the postnatal period delivered between 2015 and 2017. Univariate and multivariate analyses were performed to determine the potential risk factors for mortality. During the 3-year period, 119 (5.3%) children of the 2215 children delivered at our institution were diagnosed with CHD. We considered birth weight (P=0.005), 1st min Apgar score (P=0.001), and CHD complexity (P=0.013) as independent risk factors for in-hospital mortality. The most common CHD was ventricular septal defect. Indeed, 60.5% cases were considered as "complex" or "significant" CHDs. Heart surgeries were performed on 38.9% children, 15 of whom had "complex" or "significant" CHD. A mortality rate of 42% was observed in this cohort, with 28% occurring within the initial 24 h after delivery and 38% occurring in patients admitted for heart surgery. The postnatal incidence of CHD at our service was 5.3%. Low 1st min Apgar score, low birth weight, and CHD complexity were the independent factors that affected the hospital outcome.


Challenges involved in the Salmonella Saintpaul outbreak and lessons learned.
A 2008 multistate food-borne outbreak of Salmonella Saintpaul caused more than 1 400 illnesses in the United States. Although initial investigations suggested tomatoes as the potential vehicle, jalapeño and serrano peppers were subsequently found positive for the outbreak strain. The uncertainty associated with this incident caused government, industry, and the public to question the efficacy of the US food safety system. Examination of the response to this incident exposed breakdowns in several areas. Communication at all levels was lacking, leading to an absence of coordinated actions and conflicting risk communication messages. Variations in resources between local and state health departments created delays in gathering accurate information for epidemiological investigations. Although new laws required increased documentation, rapid and thorough traceback of products remained elusive. Three factors contributed to the difficulty in the Salmonella Saintpaul outbreak, including (1) delayed response due to discrepancies in available resources and expertise at state and local levels, (2) inadequate communication between stakeholders and agencies, and (3) poor traceability capabilities. Future responses to food-borne illness outbreaks may be improved by addressing these three factors.


Telemonitoring and Care Program for Left Ventricular Assist Device Patients During COVID-19 Outbreak: A European Experience.
Coronavirus disease 2019 (COVID-19) radically modified the organization of healthcare systems with shutdown of routine activities and outpatient clinics. Herein, we report our institutional experience with a Telemonitoring and Care Program (TC-Program) to monitor and support left ventricular assist device (LVAD) patients during COVID-19 outbreak. This single-arm cohort study analyzed 156 patients who entered the TC-Program at our institution between April and August 2020. The TC-Program was based on routine phone calls to patients and a 24/7 emergency line. In November 2020, patients were asked for feedback on the TC-Program and checked for survival, transplant, or explant. The primary endpoint was the rate of TC-Program-driven interventions. Patients (males: 82.8%) were 61 years old (interquartile range [IQR]: 53.0-67.5) and on LVAD support for 1,266 days (IQR: 475-2,211). Patients were included in the TC-Program for a median time of 99 days (min:15, max:120) and received a median number of six phone calls (min:1, max:14). Twenty-three patients (14.7%) were referred for clinical evaluation after phone contact. Two patients (1.27%) were diagnosed with COVID-19: one of them died after intensive care, and one remained paucisymptomatic and recovered. Three patients asked to exit the program considering it not useful while the others gave high rates in terms of usefulness (median: 9, IQR: 8-10), information (median: 9, IQR: 8-10), good medical care (median: 9, IQR: 8-10), and psychologic support (median: 8, IQR: 7-10). A TC-Program based on the four ICSA principles (Inform, Care, Support, and Adapt) is feasible in LVAD patients and can be rapidly implemented during the COVID-19 pandemic.


Patient perceptions of oral health care following stroke: a qualitative study.
Stroke is a serious cerebrovascular disease and is one of the world's leading causes of disability. Maintaining good oral health is a challenge among those hospitalised after stroke. A multidisciplinary approach to oral care involving non-dental professionals can be beneficial in improving oral health outcomes for patients. The aim of this study was to understand the perceptions of stroke survivors regarding oral healthcare across acute and rehabilitation settings. A descriptive qualitative approach was used. Face-to-face semi-structured interviews were conducted. A framework analysis was employed to analyse the data. Patients who had recently experienced a stroke were purposively recruited across both acute and rehabilitation settings, at two metropolitan hospitals in Sydney, Australia. In total, 11 patients were interviewed. Although participants recognised the importance of oral health, few understood the link between oral and general health. Regular oral hygiene practices varied since having stroke, with a few receiving oral care assistance from nurses. Time, cost and lack of information were some barriers to accessing dental services, while supportive measures such as coordination of oral care, financial subsidy and nurse assistance were strategies proposed to support oral care practices amongst stroke survivors. There is scope to improve current models of oral care in stroke. While stroke survivors understand the importance of oral care, an integrated oral health model with a multidisciplinary approach could improve health outcomes.


Association between stillbirth and severe maternal morbidity.
Severe maternal morbidity has been increasing in the past few decades. Few studies have examined the risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries. This study aimed to examine the prevalence and risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries during delivery hospitalization as a primary outcome and during the postpartum period as a secondary outcome. This was a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from California (2008-2018), Michigan (2008-2020), Missouri (2008-2014), Pennsylvania (2008-2014), and South Carolina (2008-2020). Relative risk regression analysis was used to examine the crude and adjusted relative risks of severe maternal morbidity along with 95% confidence intervals among individuals with stillbirths vs individuals with live-birth deliveries, adjusting for birth year, state of residence, maternal sociodemographic characteristics, and the obstetric comorbidity index. Of the 8,694,912 deliveries, 35,012 (0.40%) were stillbirths. Compared with individuals with live-birth deliveries, those with stillbirths were more likely to be non-Hispanic Black (10.8% vs 20.5%); have Medicaid (46.5% vs 52.0%); have pregnancy complications, including preexisting diabetes mellitus (1.1% vs 4.3%), preexisting hypertension (2.3% vs 6.2%), and preeclampsia (4.4% vs 8.4%); have multiple pregnancies (1.6% vs 6.2%); and reside in South Carolina (7.4% vs 11.6%). During delivery hospitalization, the prevalence rates of severe maternal morbidity were 791 cases per 10,000 deliveries for stillbirths and 154 cases per 10,000 deliveries for live-birth deliveries, whereas the prevalence rates for nontransfusion severe maternal morbidity were 502 cases per 10,000 deliveries for stillbirths and 68 cases per 10,000 deliveries for live-birth deliveries. The crude relative risk for severe maternal morbidity was 5.1 (95% confidence interval, 4.9-5.3), whereas the adjusted relative risk was 1.6 (95% confidence interval, 1.5-1.8). For nontransfusion severe maternal morbidity among stillbirths vs live-birth deliveries, the crude relative risk was 7.4 (95% confidence interval, 7.0-7.7), whereas the adjusted relative risk was 2.0 (95% confidence interval, 1.8-2.3). This risk was not only elevated among individuals with stillbirth during the delivery hospitalization but also through 1 year after delivery (severe maternal morbidity adjusted relative risk, 1.3; 95% confidence interval, 1.1-1.4; nontransfusion severe maternal morbidity adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). Stillbirth was found to be an important contributor to severe maternal morbidity.


Laser-induced backward transfer of gold nanodroplets.
It is demonstrated that femtosecond laser-induced processes can be applied for controllable transfer of spherical gold nanodroplets from a thin gold film towards a glass substrate. The size of the transferred droplets depends on the volume of laser-molten gold and can be varied by changing the laser beam focus on the sample surface and the film thickness. Single- and multi-pulse fabrication of microstructures consisting of spherical gold nanodroplets is demonstrated. Mechanisms of these laser-induced backward transfer processes are discussed.


Suicide and the selfish gene.
The application of an evolutionary perspective to human behaviour generates philosophical, political and scientific controversy. Modern human symbolic consciousness is not the cumulation of the long trend that natural selection would predict. The new archaeological data suggested the anatomical and behavioural innovation has been episodic and rare separated by long periods of stagnate. New behavioural mode and the new skeletal structure of modem human arose as an incidental exaptation. Additionally the genetic basis dysfunction connected with suicide behaviour and growing statistic suicide among teenager is contradictory to the theory that our behaviour are programmed in any detail by selfish genes. In this cases genetically determined suicidal behaviour should be rapidly eliminated by natural selection.


Preventive and reverse effects of nifedipine on human bronchoconstriction "in vitro".
The effects of nifedipine, a calcium channel blocking agent, on human bronchoconstriction induced by acetylcholine and histamine were studied in vitro. Bronchial preparations were obtained from 13 patients undergoing surgery for bronchial carcinoma. Bronchial strips were mounted for continuous isometric tension recording. Acetylcholine and histamine caused bronchoconstrictions, but the constrictive effects were inhibited by 2.9 X 10(-6) M nifedipine. At a concentration of 2.9 X 10(-6) M nifedipine increased by 22-fold the concentration of acetylcholine required to produce a 50% of maximal contraction of bronchial strips, and by 160-fold the concentration of histamine required. Nifedipine also reversed already established bronchoconstrictions by acetylcholine and histamine. The percentage of contraction at 20 min after 2.9 X 10(-6) M nifedipine was 7 +/- 11.1% (mean +/- SEM) and - 21 +/- 20.0% of the control maximal response by 10(-3) M acetylcholine and 10(-3) M histamine, respectively. Thus, nifedipine clearly prevented and reversed pharmacologically-induced bronchoconstriction in humans. These results suggest that it is valuable to administer nifedipine to prevent and treat asthma attack.


Effect of rosuvastatin on ROCK activity, endothelial function, and inflammation in Asian patients with atherosclerosis.
HMG-CoA reductase inhibitors (statins) inhibit cholesterol biosynthesis, and also decrease the formation of isoprenoid intermediates required for the activation of Rho kinase (ROCK) pathway. ROCK pathway plays pivotal roles in cardiovascular diseases including arteriosclerosis. It has been implicated that inhibition of ROCK can reverse vascular dysfunction in humans with atherosclerosis. However, it is not clear whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis. We treated 40 subjects with stable atherosclerosis with rosuvastatin 10 mg/day, or rosuvastatin 40 mg/day for 28 days in a randomized, double-blinded study. We assessed the change in the lipid levels, C-reactive protein (CRP), ROCK activity, and flow-mediated dilation (FMD) of the brachial artery before and after statins therapy. Treatment with rosuvastatin 10 mg and 40 mg significantly reduced LDL cholesterol by 43.2% to 55.9% and increased FMD by 29.3% to 42.5% (p<0.05 for both compared with baselines). Both doses inhibited ROCK activity (p<0.05), and the extent of inhibition was greater with rosuvastatin 40 mg compared with 10 mg (p<0.05). Only rosuvastatin 40 mg significantly reduced hsCRP (p<0.05).There was no correlation between changes in ROCK activity and changes in low-density lipoprotein cholesterol (r=0.37, p>0.05 vs. r=0.41, p>0.05) among patients randomized to rosuvastatin 10 mg group or 40 mg group. There was a correlation between ROCK inhibition and change in FMD among patients with rosuvastatin 10 mg therapy (r=0.43, p<0.05), and 40 mg therapy (r=0.54, p<0.05). Correlation was found between changes in ROCK inhibition and changes in CRP in rosuvastatin 40 mg/day group (r=0.47, p<0.05). These results demonstrate that high dose rosuvastatin exerts greater effects on LDL-C, ROCK activity, and CRP than low dose rosuvastatin. These findings provide clinical evidence that statins are effective in improving endothelium dysfunction by a cholesterol-independent mechanism in patients with atherosclerosis.


Recognizing laboratory cross-contamination: two false-positive cultures of Mycobacterium tuberculosis--Oklahoma, 2011.
Mycobacterium tuberculosis (MTB) isolation from clinical specimens is the standard for TB diagnosis. Positive MTB cultures are rarely questioned, but false-positive culture rates range from 2% to 4%. In December 2011, two smear-negative, culture-positive TB cases were reported to the Oklahoma State Department of Health (OSDH) in people without TB signs or symptoms. OSDH TB control officers interviewed physicians and laboratory personnel, reviewed patient charts, traced epidemiologic links, and performed microbiologic studies to determine if these were true TB cases. Both specimens were found to have been processed on the same day, at the same laboratory, under the same hood, and by the same technician sequentially after a strongly smear-positive TB specimen. No epidemiologic links were identified among the three patients. Spoligotyping and 24-locus mycobacterial interspersed repetitive unit typing of the three specimens were identical. Only liquid media grew MTB in the two questionable specimens. A laboratory splash incident was suspected, whereby all three liquid media sample lids were open during inoculation rather than being opened one at a time, causing cross-contamination. Also, the two specimens were incubated for 2-3 weeks longer than standard protocol before MTB growth was observed. Patient 1 was not treated for TB because her physician doubted the culture result. Patient 2, an organ transplant recipient, began four-drug anti-TB therapy, and an investigation was initiated for transplant-associated TB. Adherence to strict laboratory techniques and recognizing the possibility of false-positive MTB cultures, especially when inconsistent with clinical data, are essential in preventing erroneous TB diagnoses.


Thyroid hormone binding by human serum prealbumin (TBPA). Electrophoretic studies of triiodothyronine-TBPA interaction.
Thyroxine-binding prealbumin (TBPA) in normal human serum has been shown in a polyacrylamide gel electrophoresis system to bind 7-9% of tracer level purified [(125)I]triiodothyronine (T3), and more than 30% of T3 in serum deficient in thyroxinebinding globulin (TBG). The T3-TBPA interaction has been confirmed at pH 9.0 and pH 7.4 in this electrophoretic demonstration of TBPA binding of T3 in serum. Purified human TBPA has also been shown to bind T3. Progressive additions of unlabeled thyroxine (T4) to serum containing tracer [(125)I]T3 displace T3 from TBG, its principal carrier, to TBPA and albumin; however, T4 loading does not lead to significant T3 displacement from TBPA even at T4 levels known to saturate TBPA. Loading of serum with unlabeled T3 results in displacement of more than 50% of [(125)I]T3 from TBPA, as well as from TBG, to albumin. Studies carried out with serum containing diphenylhydantoin (DPH) or MK-185, known inhibitors of T4 binding by TBG, also showed T3 displacement from TBG to TBPA and albumin. Although salicylate and tetraiodothyroacetic acid (TETRAC) displace T4 from sites on TBPA, they have only minimal effects on T3-TBPA interaction.


[Evolution of sebaceous hamartoma: prospective pathologic study illustrated with a voluminous ear location].
After an exeresis of a sebaceous hamartoma of retroauricular area, histologic examination showed a trichoblastoma mimicking a basal cell carcinoma. So we realized a retrospective study with histologic examination of 24 cases of basal cell carcinoma after hamartoma. On 24 cases, 19 were not basal cell carcinoma, but trichoblastoma. So the study goes in the same direction of the world literature: hamartoma have a minimal risk of basal cell carcinoma transformation. Exeresis is indicated because of the risk of evolution to a hypertrophic tumour.


A benzodiazepine activator locks Kv7.1 channels open by electro-mechanical uncoupling.
Loss-of-function mutations in Kv7.1 often lead to long QT syndrome (LQTS), a cardiac repolarization disorder associated with arrhythmia and subsequent sudden cardiac death. The discovery of agonistic IKs modulators may offer a new potential strategy in pharmacological treatment of this disorder. The benzodiazepine derivative (R)-L3 potently activates Kv7.1 channels and shortens action potential duration, thus may represent a starting point for drug development. However, the molecular mechanisms underlying modulation by (R)-L3 are still unknown. By combining alanine scanning mutagenesis, non-canonical amino acid incorporation, voltage-clamp electrophysiology and fluorometry, and in silico protein modelling, we show that (R)-L3 not only stimulates currents by allosteric modulation of the pore domain but also alters the kinetics independently from the pore domain effects. We identify novel (R)-L3-interacting key residues in the lower S4-segment of Kv7.1 and observed an uncoupling of the outer S4 segment with the inner S5, S6 and selectivity filter segments.


Horner's syndrome in childhood.
During a 36-month period, seven cases of Horner's syndrome were encountered in a general pediatric hospital. The most common site of involvement was the ipsilateral sympathetic chain, although multiple sites were involved. Several causes of Horner's syndrome in childhood that have received little previous attention are reported-internal carotid artery thrombosis, subclavian artery aneurysm, and nasopharyngeal tumor. Suggestions for routine evaluation are given. Angiography and x-rays of the temporal and sphenoid bones are valuable in the diagnosis of intracranial lesions causing Horner's syndrome. Horner's syndrome is not rare in childhood and is associated with serious underlying disease.


Infrared matrix isolation and theoretical studies of reactions of ozone with bicyclic alkenes: α-pinene, norbornene, and norbornadiene.
The reactions of ozone with three bicyclic alkenes, α-pinene, norbornene, and norbornadiene, were studied by low-temperature (14 K), argon matrix isolation infrared spectroscopy including (18)O isotope-labeling studies. Theoretical calculations of some of the proposed reaction intermediates and products were carried out using the Gaussian 09 suite of programs, applying density functional theory (DFT), the B3LYP functional, and the 6-311G++(d,2p) basis set. In the α-pinene/ozone system, the thermal reaction between α-pinene and ozone was too slow to observe under the twin-jet or merged-jet deposition conditions of these experiments. However, red light (λ ≥ 600 nm) irradiation of the argon matrixes containing α-pinene and ozone caused new infrared peaks to appear that could be readily assigned to reaction products of α-pinene with O((3)P) resulting from ozone photolysis: α-pinene oxide (with an epoxide ring) and two isomeric ketones. Norbornene and norbornadiene were both found to react with ozone in the gas phase during twin-jet or merged-jet deposition of these mixtures with argon. New peaks observed in the infrared spectra were assigned to the primary ozonides, Criegee intermediates, and secondary ozonides of norbornene and norbornadiene, indicating that the bulk of these reactions proceeded via the "classic" Criegee mechanism for ozonolysis of alkenes. Calculated infrared frequencies and molecular energies support these conclusions. Ultraviolet irradiation of these mixtures resulted in complete decomposition of the early intermediates and the formation of acids, aldehydes, alcohols, carbon dioxide, and carbon monoxide. In any case, no evidence for "unusual" chemistry, prompted by the bicyclic nature of the reactants, was observed.


Synthesis and Characterization of Functionalized [12]Cycloparaphenylenes Containing Four Alternating Biphenyl and Naphthyl Units.
Functionalized [12]cycloparaphenylenes ([12]CPPs) containing four alternating biphenyl and naphthyl units were synthesized. A macrocyclic furan-containing CPP precursor was used for the Diels-Alder reaction with the parent benzyne or 3,6-dimethoxybenzyne to form the corresponding macrocyclic carbon frameworks. The subsequent reductive deoxygenation of the Diels-Alder adducts with Fe2(CO)9 followed by oxidative aromatization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone produced the functionalized [12]CPPs. The effect of macrocyclic ring size on the reaction rate of oxidative aromatization was investigated.


Characterization of conjugated linoleic acid production by Bifidobacterium breve LMC 520.
This study was performed to characterize the CLA production ability of a bacterial strain, Bifidobacterium breve LMC 520, which can actively convert linoleic acid (LA) to cis-9,trans-11 conjugated linoleic acid (CLA), a major isomer derived from microbial enzymatic conversion. The culture conditions were optimized to improve CLA production under the aerobic conditions. B. breve LMC 520 was tested with different amounts of LA in varied culture conditions, such as air, additives, and pH. A maximal level of CLA production (up to 90% of substrate) was obtained after 24 h of incubation in culture medium containing 1 mM LA at pH 5.5 and under anaerobic conditions. There was no decline in the CLA level with prolonged incubation until 48 h. When the effect of pre-incubation with LA on CLA production was tested, there was no significant difference between the CLA-producing activity of pre-incubated and untreated bacteria at the third passage but there was a significant reduction in CLA production by the pre-incubated cells after the fourth passage. These results demonstrate that the CLA-producing activity of B. breve LMC 520 could be maximized by numerous environmental factors. The data also indicate its potential for increasing CLA accumulation in dairy products when B. breve LMC 520 is used as a functional starter culture.


DNA oxidative damage of neoplastic rat liver lesions.
Hepatic lesions, experimentally-induced in Fisher 344 (F344) and Brown Norway (BN) rats, respectively, susceptible and resistant to liver carcinogenesis, progress differently to hepatocellular carcinoma (HCC). The mechanisms responsible for the acquisition of the resistant phenotype are not completely clear. Herein, we show that in F344 rats subjected to carcinogenic treatment, angiogenesis and DNA oxidation markers increase in preneoplastic and neoplastic liver lesions. On the contrary, in the HCCs of treated BN rats, angiogenesis and a minor DNA oxidation are accompanied by an attempt of tissue remodelling. This study suggests that DNA oxidation might be an important factor in the initiation and promotion of the events of hepatocarcinogenesis. On the other hand, the enhancement of GSH levels and the down-regulation of superoxide dismutase (SOD) expression in both rat strains suggest that antioxidant response is not involved in the acquisition of resistant phenotype.


Non-line-of-sight optical camera communications based on CPWM and a convolutional neural network.
Non-line-of-sight (NLOS) optical camera communications (OCC) exhibit greater link availability and mobility than line-of-sight links, which are more susceptible to blocking and shadowing. In this work, we propose an NLOS OCC system, where the data signal is mapped into color pulse width modulation (CPWM) symbols prior to transmission using a red-, green-, and blue light-emitting diode. A convolutional-neural-network-based receiver is used to demodulate the CPWM signal. Based on experimental results, the proposed scheme effectively mitigates the effects of diffuse reflection induced intersymbol interference, resulting in an increased data transmission rate to 7.2 kbps over a link span of more than 2 m, which is typical for indoor applications.


Temperature but not season affects the transplantation immunity of anuran amphibians.
The effects of ambient temperature (22 degrees C/10 degrees C) and season (summer/winter) on anuran skin allograft and xenograft rejection was tested in frogs (Rana temporaria and R. esculenta) and toads (Bufo bufo, Bombina variegata, and Bombina bombina). Mean graft survival times were significantly prolonged at the low temperature in a species-specific manner, the edible frog (R. esculenta) being the most sensitive and the common toad (Bufo bufo) relatively resistant. Allografts were more temperature-dependent than xenografts; in the latter case, temperature sensitivity was specific to each donor-host combination. Rejection of second-set grafts in R. esculenta was accelerated both in warmth and in cold, but second-set grafts were less temperature-sensitive than sensitizing ones. Both in summer and in winter, R. esculenta rejected allografts promptly at 22 degrees C but slowly at 10 degrees C. In both seasons, Bombina variegata kept at 22 degrees C rejected allografts in a chronic manner. This indicates that amphibian transplantation immunity depends on the donor-host genetic disparity and ambient temperature but is independent of season.


Macrodontia of a mandibular second premolar: a case report.
Localized macrodontia is very rare. The majority of cases have been reported in mandibular second premolars. This paper describes the dental management of a child who presented with macrodontia of a mandibular right second premolar.


Multiple myeloma developing in a patient with immune thrombocytopenia.
A female diagnosed as having immune thrombocytopenic purpura (ITP) was found to be simultaneously suffering from monoclonal gammopathy of undetermined significance (IgGλ). Urine Bence-Jones protein was negative. During the course, plasma cells accounted for 21.6% of the bone marrow. Based on these clinical features in our case, the second disease was diagnosed as multiple myeloma (MM). Both ITP and MM were successfully treated with corticosteroids, bortezomib, lenalidomide with dexamethasone and eltrombopag olamine. MM with ITP may show the following features: 1) the great majority are IgG types, 2) λ chain types show marked light chain predominance when these two diseases appear simultaneously, 3) κ chain types are predominant in the cases with MM followed by ITP, and 4) MM cases with ITP are more often seen in Japan.


Compensation of spatial system response in SPECT with conjugate gradient reconstruction technique.
A procedure for the determination of the system matrix in single photon emission tomography (SPECT) is described which uses the conjugate gradient reconstruction technique in order to take into account the variable system resolution of a camera equipped with parallel-hole collimators. The procedure involves the acquisition of the system line spread functions (LSF) in the region occupied by the object to be studied. Those data are used to generate a set of weighting factors based on the assumption that the LSFs of the collimated camera are of Gaussian shape with the full width at half maximum (FWHM) linearly dependent on the source depth in the span of image space. The factors are stored on a disc file for subsequent use in the reconstruction process. Afterwards the reconstruction is performed using the conjugate gradient method with the system matrix modified by the incorporation of these precalculated factors in order to take into account the variable geometrical system response. The set of weighting factors is regenerated whenever the acquisition conditions are changed (collimator, radius of rotation). In the case of an ultra high resolution (UHR) collimator 2000 weighting factors need to be calculated. The modification of the system matrix for the geometrical response allows the number of iterations to increase, considerably improving image definition without the appearance of noise artifacts. Moreover, phantom studies show that the number of iterations is less critical because of improved stability in the convergence to the solution. For brain studies of patients 10-15 iterations are usually performed. Studies with a single line source give a value between 7 and 8 mm for the FWHM of the point spread function (PSF) when the conjugate gradient method with modified system matrix is used on data acquired with a UHR collimator, whereas without the modification of the system matrix the result is 9 mm FWHM, if filtered backprojection (FBP) is used with the same filter as in the clinical studies the result is 15 mm FWHM. The results of this work show that proper definition of the system matrix using conjugate gradients influences the quality of the reconstruction remarkably. Nevertheless, further work has to be done in order to assess to what extent the system matrix is ill-conditioned and, eventually, to define a suitable regularization technique.