[Research advancement of lumbar inter-spinous process non-fusion techniques].
To elucidate the new development, structural features and application of the lumbar inter-spinous process non-fusion techniques. With the review of the development course and important research works in the field of the lumbar inter-spinous process non-fusion techniques, the regularity summary, science induction, and prospect were carried out. The lumbar inter-spinous process non-fusion technique was a part of non-fusion insert of spinal division posterior surface. According to the design, it could be divided into two major categories: dynamic and static systems. The dynamic system included Coeflex and device for intervertebral assisted motion; the static system included X-STOP, ExtenSure and Wallis. The lumbar inter-spinous process non-fusion technique was a new technique of spinal division, it could reserve the integrated function of intervertebral disc and zygapophysial joint, maintain or recover the segmental movement to a normal level, and have no adverse effect on the neighboring segments. A lot of basic and clinical researches indicated that lumbar inter-spinous process insert had extensive application to curation retrogression lumbar spinal stenosis, discogenic low back pain, articular process syndrome, lumbar intervertebral disc protrusion and lumbar instability and so on. With the matures of lumbar inter-spinous process non-fusion techniques and the increased study of various types of internal fixation devices, it will greatly facilitate the development of treatment of lumbar degenerative disease. But long-term follow-up is needed to investigating the long-term efficacy and perfect operation indication.


Metabolism and Immune Modulation in Patients with Solid Tumors: Systematic Review of Preclinical and Clinical Evidence.
Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available immunotherapies. It is therefore of paramount importance to identify the prognostic and predictive factors of tumor response/resistance and to design effective therapeutic strategies to overcome primary resistance and improve the efficacy of immunotherapy. The aim of this review is to underline the influence of the tumor and host metabolism on the antitumor immune response and to discuss possible strategies to improve the efficacy of available treatments by targeting the specific metabolic pathways in tumors or immune cells and by modifying patients' nutritional statuses. A systematic search of the Medline and EMBASE databases was carried out to identify scientific papers published until February 2020, which reported original research articles on the influence of tumor or host metabolism on antitumor immune response. The literature data showed the key role of glycolysis and mitochondrial oxidative phosphorylation, arginine, tryptophan, glutamine, lipid metabolism and microbiome on immune cell function. Moreover, specific nutritional behaviors, such as a low dietary intake of vitamin C, low glycemic index and alpha-linolenic acid, eicosapentenoic acid, docosahexaenoic acid, ornithine ketoglutarate, tryptophan and probiotic supplementation were associated with the potential clinical benefits from the currently available immunotherapies.


Rickettsia spp. and coinfections with other pathogenic microorganisms in hard ticks from northern Germany.
Rickettsia species are the causative agent of different forms of spotted fever and thus, monitored in a number of prevalence studies. The current study examined the status of ticks from the city of Hanover, Northern Germany, regarding the presence of Rickettsia spp. and coinfections with Borrelia burgdorferi sensu lato (sl) and Anaplasma phagocytophilum. In total, 1,089 questing Ixodes ricinus L. ticks were analyzed using quantitative real time polymerase chain reaction. A duplex quantitative real time polymerase chain reaction for simultaneous detection of Rickettsia spp. and Ixodes spp.-DNA as positive control for successful DNA-isolation was established. Rickettsia spp. were detected in 363 (33.3%) of the 1,089 investigated ticks. Quantification of Rickettsia showed that larvae contained up to 50,000 bacteria, nymphs up to 85 million and adults up to 200 million per tick. Species differentiation was possible in 178 out of 363 Rickettsia positive samples and resulted in a predominant occurrence of R. helvetica (98.9%, 176/178), whereas R. monacensis was rarely found (1.1%, 2/178). Besides detection of Rickettsia, positive ticks were compared with results from previous studies to examine coinfections with B. burgdorferi sl and A. phagocytophilum. The resulting coinfection rates were 9.1% (99/1,089) for B. burgdorferi sl and 2.8% (11/391) for A. phagocytophilum. Triple-infection with Rickettsia spp., B. burgdorferi sl, and A. phagocytophilum occurred in 5 (1.3%) out of 391 ticks. The current study is the first presenting quantitative data concerning the load of Ixodes ticks with Rickettsia individuals.


Back pain-clinical assessment.
Low back pain accounts for approximately 5% of all general practice consultations. Although the majority of patients will have somatic low back pain of musculoskeletal origin, vigilance in excluding 'red flag' conditions is paramount. The identification of 'yellow flags', ie. psychosocial stress factors, becomes important in patients not making a rapid recovery, and these factors need to be identified and rectified early, lest they lead to chronic pain and disability. This article presents a simple examination of the lower back designed with general practice in mind. It is based on the 'look, move, feel' paradigm of clinical orthopaedic examination. A thorough and conscientious physical examination is not time consuming. It reassures the patient that the practitioner is interested and concerned about their problem. In acute low back pain, this is the springboard to a simple effective management program and improved outcomes. It also confirms the site of pain, and is important in monitoring disability. However, there are no clinical signs, either singly or in multiples, which allow a valid anatomico-pathological diagnosis to be made.


Against intimacy: focusing on the task in hand in PhD supervision.
Worldwide, more nurses are undertaking doctoral studies now than at any other time. However, there is little high-quality evidence focused on investigating successful completion of such studies. Instead there is considerable literature dedicated to untested assumptions about the nature of the supervisory relationship. This article reflects on three critical incidents to show that the key to successful PhD completion may have much less to do with the supervisory relationship than this literature assumes. Success is rather grounded in clear understanding of how all the pertinent tasks fit together. A free online interactive resource is introduced as one method of facilitating this clarity within the supervisory relationship. The effectiveness of this resource could be tested, thereby generating meaningful data for PhD students and their supervisors.


Episodic hemorrhage during honeybee venom anaphylaxis: potential mechanisms.
Episodic hemorrhage is not a typical symptom of anaphylactic reaction to insect stings. Cases of reactions to honeybee (HB) sting or venom immunotherapy in which the uterus is the main target organ are very rare. Hemorrhage can be induced by HB venom components, especially melittin, which interfere with complement cleavage and bradykinin release. Both mechanisms are directly or indirectly associated with coagulation, thrombolysis, hemolysis, and smooth muscle tone. Induction of episodic hemorrhage through pathway destabilization in a defective bradykinin system or vulnerable organ may not be compensated by appropriate regulatory mechanisms. The pathological role of effectors is generally offset by the interaction of various regulatory systems, and the probability of hemorrhage is minimized thanks to this compensatory capability. In endometrial bleeding, the uterus becomes more vulnerable as a result of postmenstrual vascular fragility and additional induction of anaphylaxis-related uterine contractions. Episodic hemorrhage, especially metrorrhagia, as a consequence of HB venom activity may be suspected by an allergologist, but not by a physician. Melittin-free or recombinant allergens of HB venom, as well as modulators of the biochemical systems involved, could help to reduce the likelihood of hemorrhage. However, further investigation is required before these strategies can be introduced in clinical practice.


Introducing community integrated nursing teams: How one Clinical Commissioning Group applied an evidence-based approach.
The present day collection of financial and demographic challenges confronted by health and social care mean that integrated services are undoubtedly essential to sustain adequate care. However, the impact of integrated care upon healthcare staff and patients as well as new ways of working will need to be demonstrated, with collaboration and engagement throughout any transition. This paper provides an overview of the evidence relating to the delivery of effective, integrated out-of-hospital care, with a discussion of the literature. It also considers how one Clinical Commissioning Group has begun the process of integration with the focus on community nursing services for the provision of better care for patients with an evidence-based approach.


Rational automatic search method for stable docking models of protein and ligand.
An efficient automatic method has been developed for docking a ligand molecule to a protein molecule. The method can construct energetically favorable docking models, considering specific interactions between the two molecules and conformational flexibility in the ligand. In the first stage of docking, likely binding modes are searched and estimated effectively in terms of hydrogen bonds, together with conformations in part of the ligand structure that includes hydrogen bonding groups. After that part is placed in the protein cavity and is optimized, conformations in the remaining part are also examined systematically. Finally, several stable docking models are obtained after optimization of the position, orientation and conformation of the whole ligand molecule. In all the screening processes, the total potential energy including intra- and intermolecular interaction energy, consisting of van der Waals, electrostatic and hydrogen bonding energies, is used as the index. The characteristics of our docking method are high accuracy of the results, fully automatic generation of models and short computational time. The efficiency of the method was confirmed by four docking trials using two enzyme systems. In two attempts to dock methotrexate to dihydrofolate reductase and 2'-GMP to ribonuclease T1, the exact structures of complexes in crystals were reproduced as the most stable docking models, without any assumptions concerning the binding modes and ligand conformations. The most stable docking models of dihydrofolate and trimethoprim, respectively, to dihydrofolate reductase were also in good agreement with those suggested by experiment. In all test cases, it was shown that our method can accurately predict the correct docking structures, discriminating the correct model from incorrect ones. The efficiency of our method was further tested from the viewpoint of ability to predict the relative stability of the docking structures of two triazine derivatives to dihydrofolate reductase. Our docking method provides a useful tool for rational drug design and investigations of biochemical reaction mechanisms.


Elevated Hb F associated with beta-thalassaemia trait: haemoglobin synthesis in reticulocytes and in blood BFU-E.
The red cells of a patient heterozygous for beta-thalassaemia contained 19% fetal Hb. Study of his family suggested that the proband had inherited the Swiss type of hereditary persistence of fetal Hb (HPFH) from his mother who is not thalassaemic and possessed 1.37% of Hb and 11% F-cells. Studies of globin synthesis showed a similar imbalance in the heterocellular HPFH-beta-thalassaemia compound heterozygotes and in the heterozygous beta-thalassaemic members of the family. Age stratification of the red cells showed a slight enrichment in Hb F and a decreased Hb A2 level in the older cell populations. Hb F production in the BFU-E colonies of the proband was higher than that found in vivo and in other beta-thalassaemic heterozygotes in culture. Study of single erythroid burst colonies showed a marked heterogeneity in Hb F synthesis from one colony to another, while the pool of free alpha-chains remained of similar magnitude. It is suggested that in the proband, the HPFH gene, which is in trans with respect to the beta-thal-gene, increases the size of the F-cell population and its activity is carried on at the expense of the normal beta A gene.


Design, Development, and Evaluation of an Injury Surveillance App for Cricket: Protocol and Qualitative Study.
Injury surveillance and workload monitoring are important aspects of professional sports, including cricket. However, at the community level, there is a dearth of accessible and intelligent surveillance tools. Mobile apps are an accessible tool for monitoring cricket-related injuries at all levels. The objective of this paper is to share the novel methods associated with the development of the free TeamDoc app and provide evidence from an evaluation of the user experience and perception of the app regarding its functionality, utility, and design. TeamDoc mobile app for Android and Apple smartphones was developed using 3 languages: C++, Qt Modeling Language, and JavaScript. For the server-side connectivity, Hypertext Preprocessor (PHP) was used as it is a commonly used cross-platform language. PHP includes components that interact with popular database management systems, allowing for secure interaction with databases on a server level. The app was evaluated by administrating a modified user version of the Mobile App Rating Scale (uMARS; maximum score: 5). TeamDoc is the first complementary, standalone mobile app that records cricket injuries through a smartphone. It can also record cricketing workloads, which is a known risk factor for injury. The app can be used without the need for supplementary computer devices for synchronization. The uMARS scores showed user satisfaction (overall mean score 3.6 [SD 0.5]), which demonstrates its acceptability by cricketers. Electronic injury surveillance systems have been shown to improve data collection during competitive sports. Therefore, TeamDoc may assist in improving injury reporting and may also act as a monitoring system for coaching staff to adjust individual training workloads. The methods described in this paper provide a template for researchers to develop similar apps for other sports.


The possibility of the native alcoholic drugs as etiological factor of the acquired prothrombin complex deficiency syndrome.
This study was attempted to determine whether the native alcoholic drugs had any significant role in the pathogenesis of the APCD syndrome. The native alcoholic drugs, breast milk and maternal serum were analysed for vitamin K antagonists (dicoumarol, warfarin and coumarin). No vitamin K antagonists were detected from 14 commercial native alcoholic drugs, but one of the two homemade samples had a positive test of coumarin but not dicoumarol and warfarin. Seven breast milk and serum samples from the mothers of APCD infants showed no detectable amount of vitamin K antagonists. Negative results were found in 35 postpartum women who did not consume the drugs and 22 postpartum women who took the drugs. The results suggested that the native alcoholic drugs are unlikely to be the etiological factor of APCD syndrome.


Family-centered maternity units--fact or fiction?
The author describes discrepancies between nursing education and institutional practices in the area of family-centered maternity care, and questions current limitations in FCMC. The maternity nurse is urged to implement changes which will result in a rewarding childbirth experience in a medically safe environment.


Case report of successful low-dose, ultra-slow infusion thrombolysis of prosthetic mitral valve thrombosis in a high risk patient after redo-mitral valve replacement.
An increase in transvalvular pressure gradient of prosthetic valve should always raise suspicion for obstructive valve thrombosis. A multimodality diagnostic approach including transthoracic echocardiography, transoesophageal echocardiography (TOE), cinefluoroscopy, or computed tomography (CT) is necessary for a prompt diagnosis. The management of mechanical prosthetic valve thrombosis (PVT) is high risk in any therapeutic option taken. Emergency valve replacement is recommended for critically ill patients. Fibrinolysis is an alternative for patients with contraindication to surgery or if surgery is not immediately available. A 52-year-old woman presented with symptoms and signs of cardiac congestion. On laboratory, brain natriuretic peptide was elevated and international normalized ratio (INR) was in subtherapeutic range. She underwent a mitral valve replacement with mechanical prosthesis 7 months before, because of a significant residual regurgitation after repair on the same year. TOE revealed severe stenosis of the prosthesis with immobile anterior disc but there was no mass present. CT revealed a minor lesion at the hinge points of the prosthesis without involvement of the ring, suggestive for thrombus. The initial fruitless management with intravenous (i.v) heparin in high therapeutic range was followed by a successful 'low-dose, ultra-slow' fibrinolysis. CT may help differentiate thrombus vs. pannus. The acute onset of symptoms, inadequate anticoagulation, and restricted leaflet motion increased the suspicion for PVT. The current European guidelines propose normal dose fibrinolysis. We performed 'low-dose, ultra-slow' fibrinolysis due to lower bleeding risk with successful results. Low dose should be considered as alternative to normal dose fibrinolysis or urgent surgery.


Association Between Diabetic Microangiopathies and Glycemic Variability Assessed by Continuous Glucose Monitoring.
The aim of this retrospective study was to elucidate the association between glucose profile using the continuous glucose monitoring system (CGMS) and microvascular complications in patients with type 2 diabetes mellitus (T2DM). The subjects were 160 inpatients with T2DM. The mean blood glucose (MBG) level, percentage of time in a 24-hour period spent with blood glucose level higher than 180 mg/dl (time at >180 mg/dl), standard deviation (SD), and mean amplitude of glycemic excursions (MAGE) were measured continuously over 48 hours using the CGMS. The primary outcome was the association between microvascular complications and glycemic variability. The secondary outcome was the association between microangiopathies and MBG. The SD and MAGE were not associated with presence of microangiopathies or number of complications. There were also no associations between abnormal vibratory sensation in the bilateral lower extremities, coefficient of variation of the R-R interval (CVRR), retinopathy stage, nephropathy stage, or microalbuminuria. MBG was associated, however, with retinopathy, retinopathy stage, and number of complications. Time at >180 mg/dl correlated with abnormal vibratory sensation in the bilateral lower extremities and presence or stage of retinopathy. MBG and time at >180 mg/dl were not associated with presence or stage of nephropathy. Our findings suggest that broad glycemic variability was not associated with microvascular complications, the number of which increased in patients with a high mean glucose level and long time spent with hyperglycemia. It is important, therefore, to reduce the mean glucose level and time spent with hyperglycemia to prevent future microangiopathies.


An Omics Perspective on Molecular Biomarkers for Diagnosis, Prognosis, and Therapeutics of Cholangiocarcinoma.
Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy arising from the epithelial bile duct. The lack of early diagnostic biomarkers as well as therapeutic measures results in severe outcomes and poor prognosis. Thus, effective early diagnostic, prognostic, and therapeutic biomarkers are required to improve the prognosis and prolong survival rates in CCA patients. Recent advancement in omics technologies combined with the integrative experimental and clinical validations has provided an insight into the underlying mechanism of CCA initiation and progression as well as clues towards novel biomarkers. This work highlights the discovery and validation of molecular markers in CCA identified through omics approaches. The possible roles of these molecules in various cellular pathways, which render CCA carcinogenesis and progression, will also be discussed. This paper can serve as a reference point for further investigations to yield deeper understanding in the complex feature of this disease, potentially leading to better approaches for diagnosis, prognosis, and therapeutics.


Modulation of Titin-Based Stiffness in Hypertrophic Cardiomyopathy via Protein Kinase D.
The giant protein titin performs structure-preserving functions in the sarcomere and is important for the passive stiffness (Fpassive) of cardiomyocytes. Protein kinase D (PKD) enzymes play crucial roles in regulating myocardial contraction, hypertrophy, and remodeling. PKD phosphorylates myofilament proteins, but it is not known whether the giant protein titin is also a PKD substrate. Here, we aimed to determine whether PKD phosphorylates titin and thereby modulates cardiomyocyte Fpassive in normal and failing myocardium. The phosphorylation of titin was assessed in cardiomyocyte-specific PKD knock-out mice (cKO) and human hearts using immunoblotting with a phosphoserine/threonine and a phosphosite-specific titin antibody. PKD-dependent site-specific titin phosphorylation in vivo was quantified by mass spectrometry using stable isotope labeling by amino acids in cell culture (SILAC) of SILAC-labeled mouse heart protein lysates that were mixed with lysates isolated from hearts of either wild-type control (WT) or cKO mice. Fpassive of single permeabilized cardiomyocytes was recorded before and after PKD and HSP27 administration. All-titin phosphorylation was reduced in cKO compared to WT hearts. Multiple conserved PKD-dependent phosphosites were identified within the Z-disk, A-band and M-band regions of titin by quantitative mass spectrometry, and many PKD-dependent phosphosites detected in the elastic titin I-band region were significantly decreased in cKO. Analysis of titin site-specific phosphorylation showed unaltered or upregulated phosphorylation in cKO compared to matched WT hearts. Fpassive was elevated in cKO compared to WT cardiomyocytes and PKD administration lowered Fpassive of WT and cKO cardiomyocytes. Cardiomyocytes from hypertrophic cardiomyopathy (HCM) patients showed higher Fpassive compared to control hearts and significantly lower Fpassive after PKD treatment. In addition, we found higher phosphorylation at CaMKII-dependent titin sites in HCM compared to control hearts. Expression and phosphorylation of HSP27, a substrate of PKD, were elevated in HCM hearts, which was associated with increased PKD expression and phosphorylation. The relocalization of HSP27 in HCM away from the sarcomeric Z-disk and I-band suggested that HSP27 failed to exert its protective action on titin extensibility. This protection could, however, be restored by administration of HSP27, which significantly reduced Fpassive in HCM cardiomyocytes. These findings establish a previously unknown role for PKDin regulating diastolic passive properties of healthy and diseased hearts.


Gastroschisis: can sonography of the fetal bowel accurately predict postnatal outcome?
To determine whether prenatal sonographic features of the small bowel can accurately predict postnatal outcome in fetuses with gastroschisis, the sonograms of 24 fetuses with prenatally detected gastroschisis were retrospectively reviewed for fetal bowel features including small bowel dilatation and bowel wall thickening. To identify a relationship between the sonographic features and neonatal outcome, each feature was analyzed against eight adverse clinical outcome measures including bowel obstruction or atresia, necrosis, and need for bowel resection, using chi-square analysis and Kendall's taub correlation. When a relationship was identified, the sensitivity and specificity of the sonographic feature for predicting adverse outcome were determined. Only maximum small bowel diameter was related to postnatal bowel complications. Significantly more fetuses with a maximum small bowel diameter of greater than 11 mm (7/12) had bowel complications than did fetuses with MBD 11 mm or less (2/12) P < 0.05). Using a cutoff point of greater than 11 mm for maximum small bowel diameter, the sensitivity was 78%, specificity 66%, and positive predictive value 71% for predicting postnatal bowel complications. However, in only seven of 24 cases did the two observers make the same maximum small bowel diameter measurement, and in 14 of 24 cases their measurements differed by 2 mm or more. The observers varied sufficiently in their measurements to shift three fetuses (13%) between categories (< or = 11 mm or > 11 mm). Although a maximum small bowel diameter of 11 mm stratified our fetuses, this measurement may not be clinically meaningful.


Type 2 Diabetes and Heart Failure: Challenges and Solutions.
Increasing numbers of older patients with type 2 diabetes, and their improved survival from cardiovascular events is seeing a massive increase in patients with both diabetes and heart failure. Already, at least a third of all patients with heart failure have diabetes. This close association is partly because all the major risk factors for heart failure also cluster in patients with type 2 diabetes, including obesity, hypertension, advanced age, sleep apnoea, dyslipidaemia, anaemia, chronic kidney disease, and coronary heart disease. However, diabetes may also cause cardiac dysfunction in the absence of overt macrovascular disease, as well as complicate the response to therapy. Current management is focused on targeting modifiable risk factors for heart failure including hyperglycaemia, dyslipidaemia, hypertension, obesity and anemia. But although these are important risk markers, none of these interventions substantially prevents heart failure or improves its outcomes. Much more needs to be done to focus on this issue, including the inclusion of hospital admission for heart failure as a pre-specified component of the primary composite cardiovascular outcomes and new trials in heart failure management specifically in the context of diabetes.


Should psychiatrists write fiction?
This paper looks at the relationship between fiction and psychiatry. Specifically, the idea of psychiatrists as fiction writers is explored, and reference is made to various fictional texts to illustrate the problems of stigma and negative imagery. These two main areas of focus are highlighted as ones that the practice of writing fiction might address, and some potential pitfalls are discussed. The paper suggests how psychiatrists might ameliorate the present problems by incorporating their unique clinical skills and knowledge into fictional narratives. Declaration of interest None.


Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma: U.S. Myeloma Immunotherapy Consortium real world experience.
While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted CAR T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤ 3 months after CAR T infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤ 3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤ 3 months of infusion (p < 0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (p < 0.001; median PFS for ≥ 3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T who may benefit from specific interventions pre and post CAR T to improve outcomes.


Inhibition of human platelet aggregation by eosinophils.
The relationship between the activity of eosinophils and platelets has been observed in recent decades by many scientists. These observations include increased numbers of eosinophils associated with platelet disorders, including changes in the coagulation cascade and platelet aggregation. Based on these observations, the interaction between eosinophils and platelets in platelet aggregation was analyze. Human platelets were incubated with eosinophil cytosolic fraction, promyelocytic human HL-60 clone 15 cell lineage, and eosinophil cationic protein (ECP). Platelet rich plasma (PRP) aggregation was induced by adenosine diphosphate, platelet activating factor, arachidonic acid, and collagen, and washed platelets (WP) were activated by thrombin. Aggregation induced by all agonists was dose dependently inhibited by eosinophil cytosolic fraction. This inhibition was only partially reversed by previous incubation of the eosinophils with l-Nitro-Arginine-Methyl-Ester (l-NAME). Previous incubation with indomethacin did not prevent the cytosolic fraction induced inhibition. The separation of eosinophil cytosolic fraction by gel filtration on Sephadex G-75 showed that the inhibitory activity was concentrated in the lower molecular weight fraction. HL-60 clone 15 cells differentiated into eosinophils for 5 and 7 day were able to inhibit platelet aggregation. The ECP protein inhibited the platelet aggregation on PRP and WP. This inhibition was more evident in WP, and the citotoxicity MTT assay proved the viability of tested platelets, showing that the observed inhibition by the ECP protein does not occur simply by cell death. Our results indicate that eosinophils play a fundamental role in platelet aggregation inhibition.


The pregnant adolescent. A review of nutritional research and programs.
Avialable nutritional research on pregnant adolescents shows that suboptimal food intake is common. Multiple social, psychologic, and economic problems may mitigate against attainment of adequate nutritional status. Use of supplements will raise the level of some nutrients, but in reported studies, their use by girls was erratic, and routine use is not favored by many practitioners. Results of nutritional counseling are mixed. Multidisciplinary programs, usually providing comprehensive prenatal care while enabling girls to continue their education, have been instituted in many areas, reflecting a changed attiude of school officials toward the pregnant adolescent. Most of these programs include the nutrition classes, counseling, or services valuable to mother and child; however, they do not reach all pregnant adolescents and are not a panacea guaranteeing adequate nutrition for them. More research and a national policy to provide optimal nutrition for all pregnant women, including the adolescent, are needed.


Natural occurrence of organofluorine and other constituents from Streptomyces sp. TC1.
Antioxidant-directed fractionation of an ethyl acetate extract of Streptomyces sp. TC1 resulted in the isolation of a novel secondary metabolite with an aromatic organofluorine scaffold (1), an atypical tripod-type triallyl phenol (2), and a leucine residue comprised polyamine (3). Their structures were established by comprehensive spectroscopic analysis of 1D and 2D NMR data, and compound 1 was confirmed by (19)F NMR and single-crystal X-ray diffraction studies. The absolute configuration of compound 3 was assigned by comparison of its ECD spectra and quantum chemical ECD calculations. Of these, compound 1 displayed antioxidant and DNA and protein binding properties.


Triterpene glycosides from the sea cucumber Cladolabes schmeltzii. II. Structure and biological action of cladolosides A1-A6 .
Six new triterpene glycosides, cladolosides Al-A6 (1-6), have been isolated from the Vietnamese sea cucumber Cladolabes schmeltzii (Cladolabinae, Sclerodactylidae, Dendrochirotida). Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS. All the glycosides have nonsulfated tetrasaccharide linear carbohydrate moieties. Glycoside 6 has a glucose residue as the third monosaccharide unit, while the rest of the compounds comprise a xylose in this postion of the carbohydrate chain. Glycosides 1-6 differ from each other in the structures of their holostane aglycones. Cytotoxic activities of glycosides 1-6 were studied against mouse spleenocytes, along with hemolytic activities against mouse erythrocytes. All the compounds, except cladoloside A5 (5) posessing a hydroxy-group in the aglycone side chain, demonstrated rather strong cytotoxic and hemolytic effects. The most active glycosides were cladolosides A1 (1) and A2 (2) having two O-acetic groups and the xylose residue in the third position of the sugar chain.


Clinical and vascular anatomical study of distally based sural flap.
The distally based sural flap has been useful for reconstruction of the distal third portion of the lower leg. We retrospectively review in this report the clinical outcomes. Moreover, we studied the vascular anatomy surrounding the sural nerve using preserved cadavers. Twenty-eight consecutive cases of distally based sural flap transfer were reviewed retrospectively. All flaps were harvested with the deep fascia and lesser saphenous vein, but the sural nerve was excluded in all cases to prevent paresthesia. The sural nerve can be easily detached from the flap by meticulous dissection from the deep fascia without causing significant bleeding. In the vascular anatomic study, barium was injected through the femoral artery after elevating the flap in 20 legs of preserved cadavers. Subsequently, tissue specimens were harvested from the upper, middle, and lower sites of the flap for histologic analyses. Clinically, 22 of 28 flaps survived completely. Distal partial necrosis was observed in 5 flaps, and total necrosis was observed in 1 flap. Causes of total or partial necrosis have been suggested to be dependent on flap shape, pedicle length, and complicating diseases. Anatomic angiography revealed that small extrinsic vessels around the sural nerve and the lesser saphenous vein are important, especially in distally-based sural flap transfer; those around the sural nerve seem to have the most important impact on flap survival. The sural nerve has fewer intrinsic vessels than the extrinsic vessels of the sural nerve and lesser saphenous vein. The distally based sural flap was useful for reconstruction of the distal third portion of the lower leg. Moreover, these clinical and anatomic findings suggest that the sural nerve can be preserved to prevent surgically induced paresthesia.


Emotion dysregulation and smoking outcome expectancies among Spanish-speaking Latinx adult cigarette smokers in the United States.
Although smoking expectancies are associated with numerous aspects of smoking among non-Latinx Whites, far less is known about how individual differences in emotion dysregulation relate to smoking expectancies among Latinx smokers. The present investigation therefore evaluated the role of emotion dysregulation in smoking outcome expectancies among Latinx adult smokers. Participants were 363 Spanish-speaking Latinx daily smokers (58.7% female, Mage = 33.3 years, SD = 9.81). Emotion dysregulation was significantly related to both negative reinforcement and negative personal consequences for smoking. These effects were moderate in magnitude and evident after adjusting for the variance associated with a wide range of factors. Unexpectedly, emotion dysregulation was also related to expectancies of appetite control and positive reinforcement. This study provides the first empirical evidence that emotion dysregulation is associated with a broad range of smoking outcome expectancies among Latinx smokers. Emotion dysregulation may be an important, yet underrecognized, smoking-cessation treatment target for Latinx smokers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Immunocytochemical analysis of tissue kallikrein and the kinin moiety in rheumatoid synovial fluid neutrophils.
Polymorphonuclear leucocytes (PMNs) from the synovial fluid of patients with rheumatoid arthritis (RA) showed reduced tissue kallikrein and kinin immunoreactivity in comparison with blood PMNs from healthy individuals as judged visually using confocal microscopy. Similarly, synovial fluid PMNs exhibited reduced tissue kallikrein immunoreactivity as compared with blood PMNs from the same RA patients. Blood PMNs stimulated to degranulate in vitro also displayed less immunostaining for tissue kallikrein and kinin than non-stimulated PMNs. By contrast, no difference in kininogen immunostaining was detected between RA synovial fluid PMNs and blood PMNs from healthy people. It is considered that the results support the hypothesis that tissue kallikrein, released from the granules of RA synovial fluid PMNs, cleaves the kinin moiety from multifunctional kininogen protein on the surface of the PMNs.


Unraveling the interaction between the LPS O-antigen of Burkholderia anthina and the 5D8 monoclonal antibody by using a multidisciplinary chemical approach, with synthesis, NMR, and molecular modeling methods.
The interaction between the O-chain from the lipopolysaccharide from Burkholderia anthina and a lipopolysaccharide-specific monoclonal antibody (5D8) has been studied at high resolution by NMR spectroscopy. In particular, the 5D8-bound epitope of the saccharide entity has been unraveled by a combination of saturation transfer difference (STD) and transferred NOESY (tr-NOESY) experiments performed on the 5D8/polysaccharide complex. To dissect the fine details of the molecular recognition events, further experiments with simpler carbohydrate ligands were carried out. Thus, experiments were also performed with ad hoc synthesized trisaccharide and hexasaccharide O-antigen repeating units. By using this multidisciplinary approach (chemical synthesis, NMR spectroscopy and molecular dynamics simulation), determination of the binding epitope and the contribution to the binding of the sugar units composing the O-chain have been determined.


Ultrafast photodissociation dynamics of 1,4-diiodobenzene.
The photodissociation dynamics of 1,4-diiodobenzene is investigated using ultrafast time-resolved photoelectron spectroscopy. Following excitation by laser pulses at 271 nm, the excited-state dynamics is probed by resonance-enhanced multiphoton ionization with 405 nm probe pulses. A progression of Rydberg states, which come into resonance sequentially, provide a fingerprint of the dissociation dynamics of the molecule. The initial excitation decays with a lifetime of 33 ± 4 fs, in good agreement with a previous study. The spectrum is interpreted by reference to ab initio calculations at the CASPT2(18,14) level, including spin-orbit coupling. We propose that both the 5B1 and 6B1 states are excited initially, and based on the calculations, we identify diabatic spin-orbit coupled states corresponding to the main dissociation pathways.


Field trial of Abate and Teknar for Simulium (Diptera: Simuliidae) control in India.
Simulium breeding was eliminated in a river up to 30 km with 0.1 ppm Abate (temephos) for 30 min exposure. Teknar (Bacillus thuringiensis var. israelensis) at 10 ppm for 10 min exposure resulted in 98.4% and 87.9% reduction up to 20 m in 2 sections of a small stream.


Stressors, locus of control, and social support as consequences of affective psychological well-being.
Tests of the influence of affective psychological well-being on stressors, locus of control, and social support in a 1-month follow-up study of 210 male and 34 female British accountants is reported. There was a marginally significant association between the level of psychological symptoms and subsequent reports of intensity of quantitative workload stressors. A significant interaction between psychological symptoms and a measure of depression-enthusiasm was found to predict subsequent locus of control. The results indicate a differential pattern of associations between aspects of affective well-being and subsequent reports of social support. The results also indicate that initially more frequent stressors are associated with subsequently less intense stressors of the same type. The findings highlight the dynamic and reciprocal nature of the occupational stress process.


Joint Local and Nonlocal Progressive Prediction for Versatile Video Coding.
In the latest video coding standard, namely Versatile Video Coding (VVC), more directional intra modes and reference lines have been utilized to improve prediction efficiency. However, complex content still cannot be predicted well with only the adjacent reference samples. Although nonlocal prediction has been proposed to further improve the prediction efficiency in existing algorithms, explicit signalling or matching error potentially limits the coding efficiency. To address these issues, we propose a joint local and nonlocal progressive prediction scheme, targeting at improving nonlocal prediction accuracy without additional signalling. Specifically, template matching based prediction (TMP) is conducted firstly to derive an initial nonlocal predictor. Based on the first prediction and previously decoded reconstruction information, a local template, including inner textures and neighboring reconstruction, is carefully designed. With the local template involved in nonlocal matching process, a more accurate nonlocal predictor can be found progressively in the second prediction. Finally, the coefficients from the two predictions are fused and transmitted in bitstreams. In this way, more accurate nonlocal predictor can be derived implicitly with local information instead of being explicitly signalled. Experimental results on the reference software VTM-9.0 of VVC show that the method achieves 1.02% BD-Rate reduction for natural sequences and 2.31% BD-Rate reduction for screen content videos under all intra (AI) configuration.


Adopted youth and sleep difficulties.
Sleep is a critical component of healthy development for youth, with cascading effects on youth's biological growth, psychological well-being, and overall functioning. Increased sleep difficulties are one of many disruptions that adopted youth may face throughout the adoption process. Sleep difficulties have been frequently cited as a major concern by adoptive parents and hypothesized in the literature as a problem that may affect multiple areas of development and functioning in adopted youth. However, there is limited research exploring this relationship. Using a biopsychosocial framework, this paper reviews the extant literature to explore the development, maintenance, and impact of sleep difficulties in adopted youth. Finally, implications for future research and clinical interventions are outlined.


The effect of N-acetylcysteine in a combined antibiofilm treatment against antibiotic-resistant Staphylococcus aureus.
The WHO declared Staphylococcus aureus as a 'pathogen of high importance' in 2017. One-fifth of all bloodstream-related infections in Australia and 12 000 cases of bacteraemia in the UK (2017-18) were caused by the MRSA variant. To address the need for novel therapies, we investigated several permutations of an innovative combination therapy containing N-acetylcysteine (NAC), an antibiotic and an enzyme of choice in eradicating MRSA and MSSA biofilms. Biofilm viability (resazurin assay) and colony count methods were used to investigate the effect of NAC, antibiotics and enzymes on S. aureus biofilm disruption and killing. The effects of NAC and enzymes on the polysaccharide content of biofilm matrices were analysed using the phenol/sulphuric acid method and the effect of NAC on DNA cleavage was determined using the Qubit fluorometer technique. Changes in biofilm architecture when subjected to NAC and enzymes were visualized using confocal laser scanning microscopy (CLSM). NAC alone displayed bacteriostatic effects when tested on planktonic bacterial growth. Combination treatments containing 30 mM NAC resulted in ≥90% disruption of biofilms across all MRSA and MSSA strains with a 2-3 log10 decrease in cfu/mL in treated biofilms. CLSM showed that NAC treatment drastically disrupted S. aureus biofilm architecture. There was also reduced polysaccharide production in MRSA biofilms in the presence of NAC. Our results indicate that inclusion of NAC in a combination treatment is a promising strategy for S. aureus biofilm eradication. The intrinsic acidity of NAC was identified as key to maximum biofilm disruption and degradation of matrix components.


The inflammatory phase of fracture healing is influenced by oestrogen status in mice.
Fracture healing is known to be delayed in postmenopausal, osteoporotic females under oestrogen-deficient conditions. Confirming this, experimental studies demonstrated impaired callus formation in ovariectomised animals. Oestrogen-deficiency is known to affect the immune system and the inflammatory response during wound healing. Because a balanced immune response is required for proper bone healing, we were interested to ascertain whether the early immune response after facture is affected by oestrogen depletion. To address the above question, female mice received either a bilateral ovariectomy (OVX) or were sham-operated, and femur osteotomy was performed 8 weeks after OVX/sham operation. The effects of OVX on the presence of immune cells and pro-inflammatory cytokines were evaluated by flow cytometry and immunohistochemistry of the fracture calli on days 1 and 3 after fracture. One day after fracture, immune cell numbers and populations in the fracture haematoma did not differ between OVX- and sham-mice. However, on day 3 after fracture, OVX-mice displayed significantly greater numbers of neutrophils. Local expression of the oestrogen-responsive and pro-inflammatory cytokine midkine (Mdk) and interleukin-6 (IL-6) expression in the fracture callus were increased in OVX-mice on day 3 after fracture compared with sham-mice, indicating that both factors might be involved in the increased presence of neutrophils. Confirming this, Mdk-antibody treatment decreased the number of neutrophils in the fracture callus and reduced local IL-6 expression in OVX-mice. These data indicate that oestrogen-deficiency influences the early inflammatory phase after fracture. This may contribute to delayed fracture healing after oestrogen depletion.


Advanced hepatocellular carcinoma associated with cystic fibrosis.
Advances in the treatment of the respiratory complications of cystic fibrosis, including the availability of lung transplantation have led to a greater awareness of the manifestations of liver disease in up to 40% of patients with Cystic Fibrosis (CF). We report the case of an 18 year old female with CF who presented with advanced hepatocellular carcinoma and no prior clinical evidence of chronic liver disease. Hepatocellular carcinoma is usually the most severe manifestation of advanced cirrhosis although its development in non-cirrhotic cases of chronic liver disease has been reported. With the increasing life expectancy of CF patients it is likely that more unusual hepatic complications of this disease may be identified. Greater awareness may perhaps lead to earlier diagnosis in those at risk.


Accelerated Chronic Lymphocytic Leukemia and Richter Transformation in the Era of Novel Agents.
Tremendous developments in the field of Chronic Lymphocytic leukemia (CLL) in recent years has led to a revolutionary change in the treatment approach, which today is based on targeted treatments with a good response and optimal prognosis. Nevertheless, CLL can present or progress to "accelerated CLL" (A-CLL) or to "Richter transformation" (RT) and these two entities have a more aggressive course and are still characterized by challenges in the fields of diagnosis, and therapy. In the current review we summarized the latest knowledge in terms of diagnostic approaches to A-CLL, available treatments and clinical trials, for both A-CLL and RT which still pose an unmet need and require additional basic and clinical investigations. A-CLL is a rare and underdiagnosed entity, that probably stands in the "grey zone" between CLL and RT, generally holding an intermediate prognosis. Its diagnosis is mainly based on histological findings including expanded proliferation centers, increased mitotic activity, and/or high Ki-67 index. Due to its rarity, its treatment approach has still not been defined, but it seems that novel agents, especially Bruton tyrosine kinase inhibitors (BTKi) are effective. As for RT, the standard therapy still consists of chemo-immunotherapy followed by stem-cell transplantation for fit responders with a dismal prognosis. New approaches are recently adopted including B-cell inhibition via novel agents (BTKi, venetoclax), T-cell engagers (checkpoint inhibitors, bispecific antibodies (BiTe) or the Chimeric Antigen Receptor (CAR) technology), antibody-drug conjugates, or drug combinations. Although both CAR-T and BiTe seem promising, especially when combined with BTKi, evidence is still insufficient, and patients should generally be recruited in clinical trials. The field of CLL has been a subject of major advances in recent years, but A-CLL and RT remain topics of "unmet need" and require further studies to identify the best diagnostic approach and more effective treatment.


Computer-based Training in Medicine and Learning Theories.
Computer-based training (CBT) systems can efficiently support modern teaching and learning environments. In this paper, we demonstrate on the basis of the case-based CBT system CAMPUS that current learning theories and design principles (Bloom's Taxonomy and practice fields) are (i) relevant to CBT and (ii) are feasible to implement using computer-based training and adequate learning environments. Not all design principles can be fulfilled by the system alone, the integration of the system in adequate teaching and learning environments therefore is essential. Adequately integrated, CBT programs become valuable means to build or support practice fields for learners that build domain knowledge and problem-solving skills. Learning theories and their design principles can support in designing these systems as well as in assessing their value.


Importance of ERK1/2 in upregulation of endothelin type B receptors in cerebral arteries.
This study examines the importance of mitogen-activated protein kinases (MAPKs) in upregulation of endothelin type B (ETB) receptors. Rat middle cerebral arteries (MCAs) were incubated for 24 h with or without kinase inhibitors. Vessel segments were mounted in myographs and the contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and sarafotoxin 6c (S6c; ETB receptor agonist) were studied. We used real-time PCR to measure the receptor mRNA levels. An ELISA assay showed the activation of ERK1/2 kinases after 3 h. Immunohistochemistry revealed the presence of ETB receptors on the vessels. After organ culture, S6c induced vasoconstriction. Incubation with the MEK/ERK inhibitors U0126 and SB386023 diminished the contractile response to S6c. The p38 MAPK inhibitor SB239063 did not affect the S6c-induced contraction. The ET-1-induced vasoconstriction was increased after incubation with SB386023 or SB239063, while unaffected by U0126. The ETB receptor mRNA levels were diminished by SB386023 and U0126. The ETA receptor mRNA levels were unaffected. The levels of activated ERK1/2 kinases were significantly higher after 3 h of organ culture as compared to fresh vessels. The level of ETB receptor protein on the smooth muscle cells of the MCA, visualised by immunohistochemistry, was somewhat diminished by SB386023. Our results show that the ERK1/2 MAPK is important in the upregulation of contractile ETB receptors in MCA after organ culture. Since there is a similar upregulation in models of focal ischaemia and subarachnoid haemorrhage, this may be an important pathophysiological event.


Enhancement human cytomegalovirus replication in a human lung fibroblast cell line by interleukin-8.
We examined the effects of interleukin-8 (IL-8) on cytomegalovirus (CMV) replication in human fibroblasts. Exposure of fibroblasts to IL-8 augmented both infectious virus production and replication of CMV, with concomitant increases in the levels of both the transcript of the CMV pp71 genome and the synthesis of the CMV late antigen. We also found that CMV selectively induced transcripts of the IL-8 type 1 receptor in fibroblasts. These results suggest that IL-8 also contributes to inflammatory diseases by enhancing CMV replication and that CMV regulates its production through induction of IL-8 receptor.


Self-healing pseudocancers of the skin.
It is believed that a group of self-healing tumors which clinically and microscopically may be confused with squamous cell carcinomas are all variants of one entity, although there are certain differences between the members of the group. The clinical, as well as the histologic evaluation of these tumors is necessary to differentiate them from true squamous cell carcinomas. Some should be treated for cosmetic purposes since the scars following self-healing may be more unsightly than those caused by treatment.


[Swarming phenomenon of an aeromonas spec (author's transl)].
A genuine swarming phenomenon, such as has previously been known to occur in Proteus, Bacillus and Clostridium species only, was observed in an Aeromonas species. Fig. 1 shows the terraced swarming zones of the Aeromonas species on nutrient agar. The swarming rate, expressed as the growth of the swarming zone per time unit, was measured to be 70-120 mum/min on blood agar at 30 degrees C. The swarming could be inhibited by incubation at 37 degrees C (Table 2), by low saline concentrations (Table 3) as well as by addition of 4-nitro-phenylglycerol to the medium (Table 4). A DIENES-phenomenon between the swarming zones of Proteus strains and that of the Aeromonas species could not be observed (Fig. 2). The manner of swarming as seen in phase contrast microscopy was the same kind as that of Proteus. Furthermore, it could be shown by means of light- and electronmicroscopical investigations that the swarming phenomenon is connected with changes in the cell morphology and the form of flagellation (Figs. 4 and 5). Whereas in broth cultures (Fig. 3) as well as in the centre of colonies on solid media (Fig. 5a) the cells appeared as cocoid rods with polar flagellation, they developed elongated forms at the edge of the swarming zone, which - either in addition to or devoid of the polar flagella - were peritrichously populated with thin, flagella-like filaments (Figs. tb, 6, 7 and 8). The discussion deals with the various forms of bacterial surface translocation and investigates into the role of peritrichous flagella or fimbriae in the swarming phenomenon.


Introducing a stroke service in a general hospital setting.
A stroke service was begun at a private general hospital in Florida that consisted of a weekly spouse group meeting, and included treatment services already in existence, that is, occupational therapy, physical therapy, speech therapy, and social work. The five major objectives of this program were early identification of stroke patients who had rehabilitation potential, support for families of stroke patients, coordinated discharge planning as well as better communication among the professional services, and increased discharge of patients to the home setting. This project demonstrates a means of introducing change in a general hospital setting.


IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes.
Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months. The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV1%predicted and the tissue maturation biomarker Pro-collagen 3. IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD. Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.


SRM/MRM targeted proteomics as a tool for biomarker validation and absolute quantification in human urine.
Urine has always been one of the most suitable body fluids for clinical applications. Absolute quantification of disease protein biomarkers in body fluids such as urine is a key step in the biomarker development pipeline. Nevertheless, identification of groups of proteins in complex biological samples is challenging. Traditional affinity-based methodologies such as ELISA are used to verify the presence of biomarkers in clinical samples. More recently, targeted mass spectrometry-based strategies have been developed for biomarker validation, offering an alternative. The great advantage of targeted mass spectrometry-based methodologies is that they allow accurate and specific simultaneous quantification of several biomarkers (multiplexing). Peptides are used as protein surrogates, measured using triple quadrupole instruments in selected reaction monitoring/multiple reaction monitoring mode. In this review, the workflow of selected reaction monitoring/multiple reaction monitoring for disease biomarker validation in urine is presented and assay performance in the latest studies is described.


A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice.
The commensal microbiota has an important impact on host health, which is only beginning to be elucidated. Despite the presence of fungal, archaeal, and viral members, most studies have focused solely on the bacterial microbiota. Antibodies against the yeast Saccharomyces cerevisiae are found in some patients with Crohn's disease (CD), suggesting that the mycobiota may contribute to disease severity. We report that S. cerevisiae exacerbated intestinal disease in a mouse model of colitis and increased gut barrier permeability. Transcriptome analysis of colon tissue from germ-free mice inoculated with S. cerevisiae or another fungus, Rhodotorula aurantiaca, revealed that S. cerevisiae colonization affected the intestinal barrier and host metabolism. A fecal metabolomics screen of germ-free animals demonstrated that S. cerevisiae colonization enhanced host purine metabolism, leading to an increase in uric acid production. Treatment with uric acid alone worsened disease and increased gut permeability. Allopurinol, a clinical drug used to reduce uric acid, ameliorated colitis induced by S. cerevisiae in mice. In addition, we found a positive correlation between elevated uric acid and anti-yeast antibodies in human sera. Thus, yeast in the gut may be able to potentiate metabolite production that negatively affects the course of inflammatory bowel disease.


Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design.
Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1) The selection of the active pharmaceutical ingredient. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic) pain. 2) Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base) are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s) to be delivered. 3) Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4) Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes), enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects.


Peculiar aspects of reading and writing performances in patients with olivopontocerebellar atrophy.
Olivopontocerebellar atrophy (OPCA) is a still debated condition, of which motor disruption is the most common feature. A high incidence of associated mood disorders may exist, but there are few studies on concomitant cognitive impairment. Our aim was to assess whether there is reading and writing disruption in olivopontocerebellar atrophy (OPCA). 6 patients were administered different reading and writing tasks. Scores were then compared to those obtained by healthy volunteers. There was an evident impairment in reading and writing execution in our patients compared to those of the control group. On the contrary, no difference could be found in abstraction, problem-solving, and memory tasks. We discuss the results, debating the role of the cerebellum in the conscious process of cognition or in ocular movement control (necessary for reading and writing fluidity and effective execution) and in the dynamic activation of all the cerebral cortex mediated by the diffuse projection to the reticular system.


Genomic evidence and virulence properties decipher the extra-host origin of Bordetella bronchiseptica.
Until recently, members of the classical Bordetella species comprised only pathogenic bacteria that were thought to live exclusively in warm-blooded animals. The close phylogenetic relationship of Bordetella with Achromobacter and Alcaligenes, which include primarily environmental bacteria, suggests that the ancestral Bordetellae were probably free-living. Eventually, the Bordetella species evolved to infect and live within warm-blooded animals. The modern history of pathogens related to the genus Bordetella started towards the end of the 19th century when it was discovered in the infected respiratory epithelium of mammals, including humans. The first identified member was Bordetella pertussis, which causes whooping cough, a fatal disease in young children. In due course, B. bronchiseptica was recovered from the trachea and bronchi of dogs with distemper. Later, a second closely related human pathogen, B. parapertussis, was described as causing milder whooping cough. The classical Bordetellae are strictly host-associated pathogens transmitted via the host-to-host aerosol route. Recently, the B. bronchiseptica strain HT200 has been reported from a thermal spring exhibiting unique genomic features that were not previously observed in clinical strains. Therefore, it advocates that members of classical Bordetella species have evolved from environmental sources. This organism can be transmitted via environmental reservoirs as it can survive nutrient-limiting conditions and possesses a motile flagellum. This study aims to review the molecular basis of origin and virulence properties of obligate host-restricted and environmental strains of classical Bordetella.


The problem of echocardiographic detection of mitral valve prolapse and determination of its true prevalence.
The prevalence of mitral valve prolapse and the frequency of associated complications is currently still not known with certainty. In post-mortem studies, myxomatous changes of the mitral valve are found in less than 5%. The relationship between characteristic auscultatory findings, detectable in 6 to 18% of young asymptomatic subjects, and angiographic criteria for mitral valve prolapse, observed in up to 30% and more of those undergoing routine cardiac catheterization, is similarly unclear. Establishing the diagnosis based on M-mode echocardiographic criteria has yielded problems, in particular, a frequency too high for apparently healthy subjects. By means of two-dimensional echocardiography, displacement of a mitral leaflet could be detected more frequently in the four-chamber view than in the parasternal long-axis view, a finding which renders both the diagnostic comparability and the assumption of a planar mitral annulus questionable. Accordingly, a saddle-shaped mitral annulus has been postulated. The hypothesis of the saddle-shaped form has been repeatedly tested and confirmed: on a valve model, in patients without mitral valve disease by means of two-dimensional echocardiography as well as by means of three-dimensional reconstruction of two-dimensional echocardiographic images and, lastly, in animal experiments with surgical implantation of radioopaque markers with fluoroscopic observation. Patients can be divided into one of three categories according to the position of the leaflet with respect to the highest or lowest point of the mitral annulus: level of coaptation of the leaflets beneath, completely within or above the highest and lowest points of the annulus. A subgroup of patients in the latter category can be regarded as abnormal.(ABSTRACT TRUNCATED AT 250 WORDS)


The route of inoculation dictates the replication patterns of the infectious laryngotracheitis virus (ILTV) pathogenic strain and chicken embryo origin (CEO) vaccine.
Infectious laryngotracheitis virus (ILTV) has a high proclivity to replicate in the larynx and trachea of chickens causing severe lesions. There is a lack of knowledge on the ability of ILTV to replicate in other respiratory associated tissues apart from in the trachea. The objective of this study was to investigate how tissues that first encounter the virus dictate further sites of viral replication during the lytic stage of infection. Replication patterns of the pathogenic strain 63140 and the chicken embryo origin (CEO) vaccine in the conjunctiva, the Harderian gland, nasal cavity and trachea were evaluated after ocular, oral, intranasal or intratracheal inoculation of specific pathogen-free chickens. Viral replication was assessed by detection of microscopic cytolytic lesions, detection of viral antigen and viral genome load. The route of viral entry greatly influenced virus replication of both strain 63140 and CEO vaccine in the conjunctiva and trachea, while replication in the nasal cavity was not affected. In the Harderian gland, independently of the route of viral entry, microscopic lesions characteristic of lytic replication were absent, whereas viral antigen and viral genomes for either virus were detected, suggesting that the Harderian gland may be a key site of antigen uptake. Findings from this study suggest that interactions of the virus with the epithelial-lymphoid tissues of the nasal cavity, conjunctiva and the Harderian gland dictate patterns of ILTV lytic replication.


Anisotropic in-plane thermal conductivity of black phosphorus nanoribbons at temperatures higher than 100 K.
Black phosphorus attracts enormous attention as a promising layered material for electronic, optoelectronic and thermoelectric applications. Here we report large anisotropy in in-plane thermal conductivity of single-crystal black phosphorus nanoribbons along the zigzag and armchair lattice directions at variable temperatures. Thermal conductivity measurements were carried out under the condition of steady-state longitudinal heat flow using suspended-pad micro-devices. We discovered increasing thermal conductivity anisotropy, up to a factor of two, with temperatures above 100 K. A size effect in thermal conductivity was also observed in which thinner nanoribbons show lower thermal conductivity. Analysed with the relaxation time approximation model using phonon dispersions obtained based on density function perturbation theory, the high anisotropy is attributed mainly to direction-dependent phonon dispersion and partially to phonon-phonon scattering. Our results revealing the intrinsic, orientation-dependent thermal conductivity of black phosphorus are useful for designing devices, as well as understanding fundamental physical properties of layered materials.


Ultrafast electron microscopy integrated with a direct electron detection camera.
In the past decade, we have witnessed the rapid growth of the field of ultrafast electron microscopy (UEM), which provides intuitive means to watch atomic and molecular motions of matter. Yet, because of the limited current of the pulsed electron beam resulting from space-charge effects, observations have been mainly made to periodic motions of the crystalline structure of hundreds of nanometers or higher by stroboscopic imaging at high repetition rates. Here, we develop an advanced UEM with robust capabilities for circumventing the present limitations by integrating a direct electron detection camera for the first time which allows for imaging at low repetition rates. This approach is expected to promote UEM to a more powerful platform to visualize molecular and collective motions and dissect fundamental physical, chemical, and materials phenomena in space and time.


Antibodies to heterologous proteins in hemophilia A patients receiving recombinant factor VIII (Recombinate).
As a consequence of the manufacturing process, trace quantities of Chinese hamster ovary cell protein, bovine serum albumin and murine immunoglobulin G are present in Recombinate recombinant human factor VIII (rhFVIII). The development of antibodies (Abs) to these heterologous proteins was evaluated during long-term rhFVIII therapy of hemophilia A in 68 previously treated and 73 previously untreated patients. Ab prevalence was also assessed in 157 non-hemophilic subjects. Abs against heterologous proteins could be detected in varying percentages of patients and non-hemophilic subjects. Abs arose in patients sporadically, and levels were typically low. There were no adverse events associated with development or presence of anti-heterologous protein Abs. These data indicate that sustained immune responses to trace levels of heterologous proteins are very infrequent during long-term rhFVIII therapy.


Sarafotoxin 6c (S6c) reduces infarct size and preserves mRNA for the ETB receptor in the ischemic/reperfused myocardium of anesthetized rats.
The aims of this study were to determine if the ETB receptor agonist, sarafotoxin 6c (S6c) reduces myocardial infarct size following myocardial ischemia and reperfusion and to investigate whether any changes in mRNA for endothelin receptors in the injured myocardium were modified by S6c pretreatment. Hypnorm/Hypnovel anesthetized rats were subjected to occlusion of the left main coronary artery for 30 minutes, followed by 120 minutes reperfusion. Animals were administered a bolus dose of S6c (0.24 nmol kg-1 i.v., n = 10) or saline (n = 15) 5 minutes prior to occlusion. At the end of reperfusion, hearts were stained with Evan's Blue dye to delineate area at risk. A 1.5- to 2.0-mm thick slice was cut transmurally 1 mm below the site of ligation for assessment of infarct size by triphenyltetrazolium chloride. A further transmural slice (2.5-3-mm thick) was cut for assessment of receptor mRNA levels by RTPCR. Administration of S6c caused a transient fall in mean arterial blood pressure (MABP) prior to occlusion and attenuated the fall in MABP induced by coronary occlusion. S6c significantly reduced infarct size (13 +/- 4% of area of slice at risk) compared with control hearts (35 +/- 5%; P < 0.05). In control hearts, there was a marked reduction in mRNA content for both ETA (50% reduction) and ETB (70% reduction) receptors in the ischemic zone, compared with non-ischemic tissue. In hearts pre-treated with S6c there was a reduction in ETA, but not ETB receptor mRNA in the ischemic zone. This study has shown that S6c reduces myocardial infarct size and results in preservation of ETB receptor mRNA in ischemic/reperfused tissue.


Chronic alcohol consumption does not cause hippocampal neuron loss in humans.
High alcohol consumption for long periods of time causes significant hippocampal neurodegeneration in rodents. A single study using neuronal density measures has reported similar findings in humans. The present study aims to substantiate these findings in human alcoholics using unbiased stereological techniques. Both amnesic (n = 5) and nonamnesic (n = 7) chronic alcoholics were selected and compared with nonalcoholic controls (n = 8) and patients with marked memory loss and hippocampal neurodegeneration caused by Alzheimer's disease (n = 4). Hippocampal volume was significantly reduced in the alcoholics and in patients with Alzheimer's disease. However, in alcoholics the volume reduction occurred exclusively in the white matter, whereas both the gray and white matter were reduced in the patients with Alzheimer's disease. Neuron loss occurred exclusively from the CA1 and subiculum subregions of the hippocampus in Alzheimer's disease. No neuron loss occurred from any subregion of the hippocampus in alcoholics. There were no correlations with age and any of the volume or neuron number measures. Hippocampal volume correlated with brain volume and with the regional gray and white matter volumes within the hippocampus. In addition, hippocampal gray matter volume correlated with the number of CA1 pyramidal neurons. These results do not support the theory that chronic alcohol consumption is neurotoxic to hippocampal pyramidal neurons in humans. Further, the present results suggest that changes observed in rodent models of alcoholism do not parallel those observed in humans, questioning the validity of such models.


Radiophobia Overreaction: College of Chiropractors of British Columbia Revoke Full X-Ray Rights Based on Flawed Study and Radiation Fear-Mongering.
Fears over radiation have created irrational pressures to dissuade radiography use within chiropractic. Recently, the regulatory body for chiropractors practicing in British Columbia, Canada, the College of Chiropractors of British Columbia (CCBC), contracted Pierre Côté to review the clinical use of X-rays within the chiropractic profession. A "rapid review" was performed and published quickly and included only 9 papers, the most recent dating from 2005; they concluded, "Given the inherent risks of radiation, we recommend that chiropractors do not use radiographs for the routine and repeat evaluation of the structure and function of the spine." The CCBC then launched an immediate review of the use of X-rays by chiropractors in their jurisdiction. Member and public opinion were gathered but not presented to their members. On February 4, 2021, the College announced amendments to their Professional Conduct Handbook that revoked X-ray rights for routine/repeat assessment and management of patients with spine disorders. Here, we highlight current and historical evidence that substantiates that X-rays are not a public health threat. We also point out critical and insurmountable flaws in the single paper used to support irrational and unscientific policy that discriminates against chiropractors who practice certain forms of evidence-based X-ray-guided methods.


A2B6O9F2 (A = NH4, K): new members of A2B6O9F2 family with deep-UV cutoff edges and moderate birefringence.
The fluorooxoborate A2B6O9F2 family (A = alkali metal) has attracted much attention because of its diverse structures and properties. Herein, two new members of this family, (NH4)2B6O9F2 and K2B6O9F2, have been synthesized which exhibit different two-dimensional [B6O9F2]∞ layered structures. Millimeter-sized crystals of (NH4)2B6O9F2 have been grown with NH4F as the flux. The transmittance spectrum indicates that it has a wide UV transparency window with a cutoff edge lower than 180 nm. First-principles calculations show that both (NH4)2B6O9F2 and K2B6O9F2 have deep-UV cutoff edges and moderate birefringence. The contributions of the constituent structural groups to the optical properties are discussed.


Grain-size effect on the structure and antiobesity activity of konjac flour.
The effect of high-frequency oscillatory type ball-mill treatment on the structure and antiobesity activity of konjac flour was investigated. The grain size of konjac flour changed from 657.3 microm (d(50)) to 23.7 microm (d(50)) after 4 h of treatment. The structural change of the konjac flour with different grain size was characterized by using X-ray diffraction (XRD) differential scanning calorimetry (DSC). The results indicated that the crystallinity decreased and the diffraction peak drifted not only by when the crystallization region was reduced but also when the crystalline structure was changed. With the decrease of the grain size and crystallinity, the konjac flour grain, especially the 4 h milled konjac flour, swelled more rapidly and led to the improvement of the antiobesity effect. Compared with the native konjac flour, the 4 h milled konjac flour could significantly decrease the body weight and total wet weight of fat of nutritional obese rats (P < 0.05) and also decreased the contents of triglyceride, glucose, and high-density lipoprotein in blood of nutritional obese rat significantly (P < 0.05), which meant the grain-size effect of konjac flour improved its antiobesity activity notably.


[Treatment of early-stage upper and/or middle thoracic esophageal cancer with a new muscle-sparing thoracotomy].
To evaluate the feasibility of performing muscle-sparing thoracotomy and intercostal sutures in the treatment of upper and/or middle thoracic esophageal cancer for the purpose of tumor control and postoperative quality of life improvement. Seven patients with esophageal cancer were treated with vertical muscle-sparing thoracotomy and Mckeown esophagectomy. Detailed clinic data were summarized and analyzed with patient follow-up information. Of the 7 patients, five were still alive with a 71.4% five-year survival rate. There were no deaths resulting from the operation in this group. The mean length of thoracic incision was 11 cm. The range of hospital stays was 14 to 25 days, with a mean length of 18 days. No patients complained of impaired shoulder action, and the incision pain was hardly perceived without external stimulation 1 month after operation. Performing the muscle-sparing thoracotomy in the treatment of early-stage esophageal cancer located in the upper and /or middle thoracic segment yields a satisfactory long-term survival rate with an improved life quality in terms of incision pain relief and shoulder function.


SLEEP TENDENCIES: EFFECTS OF BAROMETRIC PRESSURE.
For two samples of naval aviation cadets, curvilinear relationships were obtained between barometric pressure readings and the occurrence of signs of the onset of sleep on electroencephalograms obtained during routine EEG examinations. High and low barometric pressures relative to the prevailing average pressures were associated with increased proportions of subjects showing signs of onset of sleep.


Prostaglandins stimulate the secretion of inhibin from human placental cells.
In this study, the effects of prostaglandins (PGs) on inhibin secretion were investigated in primary culture of human placental cells. Isolated trophoblast cells were cultured for 2-5 days with PGE1, PGE2, 6-keto-PGF1 alpha, PGF2 alpha, and thromboxane B2. Inhibin levels in the culture medium were measured by immunoenzymatic assay. PGs significantly stimulated inhibin secretion in the cell culture. The addition of PGs (1 nM to 10 microM) to the culture resulted in dose-dependent increases in inhibin levels in the medium. At a dose of 10 microM, inhibin levels in the medium were increased by 35.2-172.5% compared to the control value. Compared with the efficacies of these PGs, PGE2 and PGF2 alpha enhanced inhibin secretion more potently than other tested PGs. A close correlation between the effects of PGs and the number of trophoblasts seeded in the culture was observed, with an optimal response of the cells to PGs at 1.0-2.0 x 10(6) cells/well. Time-course studies showed that a significant increment in inhibin levels in the PG-treated culture occurred after 48-120 h, but not during the first 24 h, of the culture, indicating a possible involvement of PGs in inhibin biosynthesis in the cells. Epidermal growth factor (EGF) could enhance PG-stimulated inhibin releases in the cell culture. Treatment with EGF (100 ng/mL) increased inhibin in the medium by 83.3% (ED50) in the presence of PGE2 or by 70.3% (ED50) in the presence of PGF2 alpha compared to the control values. The addition of 8-bromo-cAMP (100 microM) and cholera toxin (1000 ng/mL) to the culture also enhanced basal and PG-induced inhibin secretion, but the addition of the 4-bromo-calcium ionophore A23187 (1 microM) did not alter inhibin releases, suggesting that the stimulatory effects of PGs on inhibin secretion in placental cells may be mediated through the cAMP pathway. In the cell cultures treated with PGE and PGF2 alpha, there was no change in cell growth or intracellular DNA content, as measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assay and DNA determination with fluorescence spectrophotometry. Morphological studies showed that PGE2 alpha (1 microM), alone or combined with EGF (100 ng/mL), significantly accelerated the process of differentiation from cytotrophoblasts to syncytiotrophoblasts, indicating that the actions of PGs may be related to their effects on syncytial transformation, rather than cellular proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)


Educating teachers of nursing: the attitudes of students.
One hundred and twenty-four experienced registered nurses representing four status categories (nurse managers, full-time student teachers of nursing, first year part-time student teachers of nursing, and second year part-time teachers of nursing) participated in a study to investigate the nature of their social attitudes. Oliver's Survey of Opinions about Education was used as a measure of social attitudes. The overall conclusion was that the social attitudes of the subjects in the study were more similar than dissimilar. Significant differences were found between the managers and the full time teachers (t = -2.03, P less than 0.05) on radicalism. The teachers were found to be more radical. Significant differences were found between the managers and the first year part-time teachers (t = 2.55, P less than 0.05) on tender-mindedness. The teachers were found to be more tender-minded. Significant differences were also found on tender-mindedness between the managers and the second year part-time teachers (t = -2.37, P less than 0.05). Again, the teachers were found to be more tender-minded than the managers. Apart from these differences, the social attitudes of the subjects were found to be well balanced. When the findings of the present study are compared with other studies relating to the social attitudes of nurses, the pattern which emerges in a more balanced one. However, previous studies mainly used subjects in the 18-21-year age group. The difference in the ages of the subjects is likely to be an important factor on their social attitudes, but further research would be required to determine whether factors other than a difference in ages play a part.


Psychiatric emergencies (part III): psychiatric symptoms resulting from organic diseases.
An exhaustive review on the organic illnesses presenting with psychiatric manifestations, properly defined pseudopsychiatric emergencies, is presented. A systematic classification of the numerous organic causes of psychiatric disorders, based on authors' experience and literature revision, is carefully analysed, and their suitable diagnostic management in emergency setting is proposed. Moreover, the role of bedside ultrasonography in Emergency Department is emphasized. The underlying pathogenetic mechanisms are separately discussed. A particular significance is given to "neuropsychological studies", displaying the complex connection between the central nervous system and the endocrine system. The role of immune system in influencing the central nervous system, explaining the model of "sickness behaviour" in inflammatory disease, is also described, according to recent reports of "psychoneuroimmunology". Moreover, the immune-mediated mechanism explaining how neoplasm can influence brain function in the "paraneoplastic syndromes" is shown. In order to facilitate the teaching method, organic illnesses presenting with acute psychic manifestations or mimicking specific psychiatric disorders are subdivided into three groups: (1) Endocrine and metabolic disorders and deficiency states; (2) Internal diseases; (3) Neurologic disorders.


Event-Based Media Enrichment Using an Adaptive Probabilistic Hypergraph Model.
Nowadays, with the continual development of digital capture technologies and social media services, a vast number of media documents are captured and shared online to help attendees record their experience during events. In this paper, we present a method combining semantic inference and multimodal analysis for automatically finding media content to illustrate events using an adaptive probabilistic hypergraph model. In this model, media items are taken as vertices in the weighted hypergraph and the task of enriching media to illustrate events is formulated as a ranking problem. In our method, each hyperedge is constructed using the K-nearest neighbors of a given media document. We also employ a probabilistic representation, which assigns each vertex to a hyperedge in a probabilistic way, to further exploit the correlation among media data. Furthermore, we optimize the hypergraph weights in a regularization framework, which is solved as a second-order cone problem. The approach is initiated by seed media and then used to rank the media documents using a transductive inference process. The results obtained from validating the approach on an event dataset collected from EventMedia demonstrate the effectiveness of the proposed approach.


A novel nonenzymatic pathway for the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-arginine.
Nitric oxide (NO) is a biologically active molecule known to be enzymatically synthesized from L-arginine in the presence of NO synthetase (NOS). In this study, we demonstrate a novel non-enzymatic pathway for NO synthesis involving hydrogen peroxide and D- or L-arginine. We employed two measures of NO generation. The first consists in the demonstration of the oxidative metabolites of NO (NO2 + NO3 = NOx) and the second is the confirmatory finding of chemiluminescence derived from NO. The results show that NOx increases in the incubation mixture containing hydrogen peroxide coupled with D-arginine, L-arginine, L-canavanine, and even the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). However, chemiluminescence was detected only from the reactions of hydrogen peroxide and D- or L-arginine and was diminished by the addition of carboxy-2-phenyl-4, 4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO), a specific scavenger of NO, confirming NO generation in the reaction.


Role of collateral ventilation in ventilation-perfusion balance.
Species with collateral ventilation have an auxiliary respiratory mechanism that could protect them, under certain circumstances, from regional alveolar hypoxia. Species without collateral ventilation may have a greater potential for routinely experiencing regional hypoxia; to maintain ventilation-perfusion balance they would have to rely on pulmonary vasoconstriction. We tested these ideas by ventilating a sublobar region of pig lung (no collateral ventilation) with 13% O2 while the rest of the lung was ventilated with 30% O2. Blood flow, as measured by radioactive microsphere distribution to the sublobar region, was reduced 50% during hypoxia. The hypoxia-induced vasoconstriction effectively defended arterial PO2. When a vasodilator was infused, regional blood flow increased to control levels; shunt fraction rose, and arterial PO2 fell. In dogs (collateral ventilation present) the same experimental maneuvers had no significant effect on regional end-tidal gases or on microsphere distribution, indicating that collateral ventilation was able to maintain ventilation-perfusion balance. When regional hypoxia was created in dogs by overcoming collateral ventilation with slightly positive airway pressure in the sublobar region, the dog acted like the pig and used hypoxic vasoconstriction to shift approximately 30% of the blood flow away from the hypoxic alveoli.


[Non-pharmacological therapeutic possibilities in gastroesophageal reflux dyspepsia].
New knowledge concerning the pathophysiology of gastroesophageal reflux gives an opportunity for updating measures of conservative antireflux treatment. There are only few controlled trials, and it is uncertain whether the requirement for pharmacological treatment may hereby be diminished. General advice such as eating small meals, reducing the fat intake, avoiding food intake for three hours before bedtime are recommended to all, while advice on more specific foods should be individualized according to actual food related symptoms. Patients with annoying symptoms of reflux are advised not to consume alcohol every day, while the consumption of tobacco seems to be of minor importance. Advising weight loss isn't well founded, but ought to be given to obese patients. Elevation of the head of the bed is suggested to patients with nocturnal symptoms of reflux, which usually coincide with the presence of a hiatal hernia. If possible, revision of other current pharmacotherapy should be done. Theophylline, calcium channel blockers, benzodiazepines and nonsteroidal antiinflammatory drugs, seem in particular to be able to provoke or aggravate reflux. Patient support groups with medical supervision might be useful and reduce the number of consultations. The non-pharmacological measures should still be the basis of treatment and it might be sufficient in mild cases. It is recommended that the advise be individualized to each patient in such a way that no unfounded changes of life style are recommended that impair the quality of life. Gastroesophageal reflux, nonpharmacological treatment, food advices, alcohol, tobacco, overweight, hiatal hernia, drugs, patient education.


Comparative study of cell culture and purification methods to obtain highly enriched cultures of proliferating adult rat Schwann cells.
We present here a fast protocol that could be used to obtain highly purified cultures of maximal proliferating adult rat Schwann cells. These adult rat Schwann cells can be transfected in a nonbiological way using the physical transfection method of electroporation. Schwann cells are decisive in recovery of peripheral nerves after injury. In a clinical context, the use of enriched adult Schwann cells is necessary for autologous cell transplantation within nerve transplants for peripheral nerve repair. Different parameters such as tissue preparation, culture conditions, and protocols for enrichment, elevation of proliferation rates, and transfection were evaluated in cell cultures harvested from adult rat peripheral nerves. Cell preparation from in vivo predegenerated adult rat sciatic nerves combined with the use of melanocyte growth medium supplemented with forskolin, fibroblast growth factor (FGF)-2, and pituitary extract as a selective, serum-free culture medium, with a secondary cell-enrichment step using specific detachment, resulted in highly enriched cultures of adult rat Schwann cells (>90%) with enhanced proliferation rates (>or=40%). About 20% of these adult Schwann cells could be modified genetically using an optimized electroporation protocol.


Identification of Candidate Functional Elements in the Genome from ChIP-seq Data.
ChIP-seq datasets provide a wealth of information for the identification of candidate regulatory elements in the genome. For this potential to be fully realized, methods for evaluating data quality and for distinguishing reproducible signal from technical and biological noise are necessary. Here, the computational methods for addressing these challenges developed by the ENCODE Consortium are described and the key considerations for analyzing and interpreting ChIP-seq data are discussed.


PI(3)Kgamma has an important context-dependent role in neutrophil chemokinesis.
The directional movement of cells in a gradient of external stimulus is termed chemotaxis and is important in many aspects of development and differentiated cell function. Phophoinositide 3-kinases (PI(3)Ks) are thought to have critical roles within the gradient-sensing machinery of a variety of highly motile cells, such as mammalian phagocytes, allowing these cells to respond quickly and efficiently to shallow gradients of soluble stimuli. Our analysis of mammalian neutrophil migration towards ligands such as fMLP shows that, although PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) accumulate in a PI(3)Kgamma-dependent fashion at the up-gradient leading-edge, this signal is not required for efficient gradient-sensing and gradient-biased movement. PI(3)Kgamma activity is however, a critical determinant of the proportion of cells that can move, that is, respond chemokinetically, in reaction to fMLP. Furthermore, this dependence of chemokinesis on PI(3)Kgamma activity is context dependent, both with respect to the state of priming of the neutrophils and the type of surface on which they are migrating. We propose this effect of PI(3)Kgamma is through roles in the regulation of some aspects of neutrophil polarization that are relevant to movement, such as integrin-based adhesion and the accumulation of polymerized (F)-actin at the leading-edge.


Resonance coupling in the fourth OH-stretching overtone spectrum of formic acid.
The room-temperature vibrational overtone spectra of the formic acid isotopomers HCOOH and DCOOH have been recorded in the third and fourth OH-stretching overtone regions with intracavity laser photoacoustic spectroscopy. Resonance coupling between the OH- and CH-stretching vibrations in HCOOH is clearly identified in the fourth overtone region. This is an example of strong coupling across bonds. In the third overtone region, no resonance is observed. Vibrational energies and intensities of the OH- and CH-stretching overtones and combination bands have been calculated with an anharmonic oscillator local mode model. The pure OH-stretching bright state carries almost all the intensity prior to resonance coupling.


[Chronic migraine treatment: multidisciplinary approach. Case report].
We described clinical case of chronic migraine and such comorbid disorders as insomnia and panic disorder. The influence of anxiety, insomnia, painkillers overuse on the chronicity of migraine has been shown. Multidisciplinary program was made for treatment of patient with chronic migraine, insomnia and panic disorder. Multidisciplinary program included education, detoxification therapy, cognitive-behavioral therapy and pharmacotherapy. Patient's mistaken ideas about disorders was changed by using of cognitive-behavioral therapy. Also techniques of cognitive-behavioral therapy were needed for education of patient about effective skills to overcome pain, insomnia and anxiety. The transformation of migraine from chronic to episodic, improved sleep, improved emotional state and functional activity were noted after 3 months of treatment. Follow-up of the patient for 12 months showed long lasting positive effect of treatment for chronic migraine, insomnia and panic disorder.