Trajectory Correction and Locomotion Analysis of a Hexapod Walking Robot with Semi-Round Rigid Feet.
Aimed at solving the misplaced body trajectory problem caused by the rolling of semi-round rigid feet when a robot is walking, a legged kinematic trajectory correction methodology based on the Least Squares Support Vector Machine (LS-SVM) is proposed. The concept of ideal foothold is put forward for the three-dimensional kinematic model modification of a robot leg, and the deviation value between the ideal foothold and real foothold is analyzed. The forward/inverse kinematic solutions between the ideal foothold and joint angular vectors are formulated and the problem of direct/inverse kinematic nonlinear mapping is solved by using the LS-SVM. Compared with the previous approximation method, this correction methodology has better accuracy and faster calculation speed with regards to inverse kinematics solutions. Experiments on a leg platform and a hexapod walking robot are conducted with multi-sensors for the analysis of foot tip trajectory, base joint vibration, contact force impact, direction deviation, and power consumption, respectively. The comparative analysis shows that the trajectory correction methodology can effectively correct the joint trajectory, thus eliminating the contact force influence of semi-round rigid feet, significantly improving the locomotion of the walking robot and reducing the total power consumption of the system.


A Fresh Look at Potential Mechanisms of Change in Applied Relaxation for Generalized Anxiety Disorder: A Case Series.
Applied Relaxation (AR), which involves noticing early signs of anxiety and responding with a relaxation response, is an empirically supported treatment for Generalized Anxiety Disorder (GAD). However, research on hypothesized mechanisms of AR (e.g., reduced muscle tension) has been mixed, making it likely that additional mechanisms are contributing to the efficacy of AR. Stemming from more recent conceptualizations of GAD, it is hypothesized that mindfulness, decentering, and acceptance may be potential mechanisms of change in AR. Outcome, mechanism data, and case descriptions from three individuals diagnosed with GAD who received 16 weeks of AR as part of a larger randomized controlled trial are presented to demonstrate the ways that AR may lead to clinical improvement through mindfulness, decentering, and acceptance.


Trauma to the primary dentition and its sequelae.
Trauma to the primary dentition is common. This injury may have an impact on the child and his/her parents. The examining dentist should take appropriate factors into consideration before providing the required treatment. This paper discusses the management of trauma to the primary teeth and describes the sequelae of injury to both the primary and secondary dentitions. In cases of trauma to the primary teeth, diagnosis and appropriate management is necessary to alleviate the pain and discomfort for the child and to decrease the risk of damage to the permanent successor. It is important to prevent inducing fear and dental anxiety in children during the management of this injury.


A case of huge solitary fibrous tumor with hypoglycemia.
We report the case of a 64-year-old man with a huge solitary fibrous pleural tumor who presented with breathlessness and recurrent severe symptomatic hypoglycemia. The tumor was safely removed in toto via a median sternotomy. The patient had an uneventful postoperative recovery and no recurrent hypoglycemia.


Economic assessment of African horse sickness vaccine impact.
African horse sickness (AHS) is endemic in sub-Saharan Africa posing a threat to equine populations in non-endemic regions. Available vaccine technologies have limitations, creating barriers to horse movement, AHS control and, in non-endemic areas or countries, rapid elimination of virus after incursion. The literature lacks an economic assessment of the benefits of bringing a new, more effective AHS vaccine to market. The study assesses the economic impact of AHS and tests the hypothesis that investment in a safer, more effective AHS vaccine would give an economic return. Cost-benefit analysis. Primary and secondary data were collected to populate the cost-benefit analysis model. A literature review was followed by a questionnaire survey and interviews to gather primary data. At-risk populations were defined and qualitative assessment completed to narrow the target populations for quantitative assessment. A deterministic cost-benefit model was developed in Excel and different scenarios tested. Break-even and sensitivity analysis were conducted on key parameters. The economic impact of AHS was estimated to be US$95 million per annum, and this was mainly in endemic regions with domestic equine industries and involved in international trade. Investment required to bring a new AHS vaccine to market was estimated to be up to US$3.5 million, which was very small relative to the benefits estimated in this study. The economic return on investment in bringing a new AHS vaccine to market was predicted to be positive and the analysis demonstrates this result was robust. Data for the analysis were scarce, requiring expert opinion and extrapolation by the authors. Sensitivity analysis with the deterministic modelling structure indicated there was no justification for stochastic modelling, given the robustness of the return on investment. The analysis predicts a strong and robust economic return on the investment in bringing a new AHS vaccine to market. Main economic beneficiaries would be the high value horse sectors, specifically the equine industries in Republic of South Africa (RSA) and in non-endemic countries. In addition, major benefits would be captured in poor communities in sub-Saharan Africa where working equids are of high economic and social importance.


Inhibition of mTORC1 activity by REDD1 induction in myeloma cells resistant to bortezomib cytotoxicity.
The combination of bortezomib and dexamethasone is becoming the reference induction treatment for multiple myeloma patients younger than 65 years. Despite its advantage over vincristin adryamicin dexamethasone induction treatment, bortezomib does not benefit all patients. We hypothesize that heterogeneity of the response experienced by myeloma patients is, at least in part, due to genomic variations in the malignant plasma cells. To test this hypothesis we used gene expression profiling to identify early responsive genes induced by bortezomib in resistant myeloma cells. Our study revealed: (i) a dramatic induction of REDD1, a negative regulator of mammalian target of rapamycin kinase complex 1 (mTORC1) activity, in these cells; (ii) a transient cell size decrease associated with REDD1 overexpression; and (iii) partial restoration of bortezomib sensitivity in REDD1 knockdown bortezomib-resistant myeloma cells. Together, these results identify a possible novel mechanism of bortezomib resistance in myeloma patients mediated by REDD1 overexpression involving inhibition of mTORC1 activity and suggest that the use of mammalian target of rapamycin inhibitors in myeloma patients could be deleterious.


Inner-city hospitals: a call for research.
Inner-city hospitals serve as safety nets for poor and underserved populations. They cope with serious issues of uncompensated care, aging facilities, and inadequate reimbursement. Yet, little research exists on their needs and problems. The authors argue that research on inner-city institutions is necessary to obtain "policy" attention, legitimize demand for resources, reframe inner-city health issues as a delivery problem, and gain insights on better ways to manage inner-city hospitals. They provide data-based illustrations of future research questions related to issues of inefficiency, overstaffing, case severity, and facility renovation that can contribute to better policymaking on inner-city hospitals. The authors recognize systemic barriers to research including the unpopularity of access issues, lack of data, and absence of input from practitioners working in inner-city institutions. To remove such barriers, they suggest creation of a representative forum, original databases, increased linkage with research and policy agencies, and increased cooperation between inner-city professionals and researchers.


Level crossing, spin structure factor and quantum phases of the frustrated spin-1/2 chain with first and second neighbor exchange.
The spin-1/2 chain with isotropic Heisenberg exchange J1, J2 > 0 between first and second neighbors is frustrated for either sign of J1. Its quantum phase diagram has critical points at fixed J1/J2 between gapless phases with nondegenerate ground state (GS) and quasi-long-range order (QLRO) and gapped phases with doubly degenerate GS and spin correlation functions of finite range. In finite chains, exact diagonalization (ED) estimates critical points as level crossing of excited states. GS spin correlations enter in the spin structure factor S(q) that diverges at wave vector qm in QLRO(q(m)) phases with periodicity 2π/q(m) but remains finite in gapped phases. S(q(m)) is evaluated using ED and density matrix renormalization group (DMRG) calculations. Level crossing and the magnitude of S(q(m)) are independent and complementary probes of quantum phases, based respectively on excited and ground states. Both indicate a gapless QLRO(π/2) phase between -1.2 < J1/|J2| < 0.45. Numerical results and field theory agree well for quantum critical points at small frustration J2 but disagree in the sector of weak exchange J1 between Heisenberg antiferromagnetic chains on sublattices of odd and even-numbered sites.


The metabolism of amino acids, peptides, and disulfides in lysosomes of fibroblasts cultured from normal individuals and those with cystinosis.
The metabolism of amino acids, peptides, and disulfides has been investigates in cultured skin fibroblasts from normal individuals and patients with cystinosis. Human fibroblast lysosomes closely resemble the lysosomes of mouse peritoneal macrophages in having an apparent permeability barrier to amino acids and peptides with molecular weights of greater than 220-230. Cystinotic and normal cells behave similarly in this regard. Normal cells do not undergo lysosomal swelling when exposed to cysteine-penicillamine disulfides, while cystinotic cells are prominently vacuolized under these conditions. Normal lysosomes may have a specific mechanism for the disposal of cystine, and deficient activity of this mechanism in cystinotic lysosomes could result in cystine storage therein. The demonstration that human fibroblasts can be used conveniently to study lysosomal metabolism of small substrates may facilitate investigations of these aspects of lysosomal function in a variety of genetic diseases of man.


Pivotal Advance: Bifidobacteria and Gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease.
CD is a chronic inflammatory disorder of the small intestine that presents in genetically predisposed individuals following gluten consumption. In this study, the effects of Bifidobacterium (Bifidobacterium bifidum IATA-ES2 and Bifidobacterium longum ATCC15707) and Gram-negative bacteria (Bacteroides fragilis DSM2451, Escherichia coli CBL2, and Shigella CBD8 isolated from CD patients), alone and in the presence of CD triggers (gliadins and/or IFN-gamma) on surface marker expression and cytokine production by PBMCs, were determined. These effects were also evaluated in cocultures of PBMCs and Caco-2 cells. The Gram-negative bacteria induced higher secretion of Th1-type proinflammatory cytokines (IL-12 and/or IFN-gamma) than the Bifidobacterium strains. Shigella CBD8 and E. coli CBL2 up-regulated mainly HLA-DR and CD40 expression involved in Th1 activation, and Bifidobacterium strains up-regulated CD83 expression. Specific interactions among the studied bacteria, gliadins, and IFN-gamma, which favored the CD immune features, were also detected. Therefore, intestinal bacteria could be additional factors that regulate the ability of monocytes recruited to the mucosa to respond to gliadins and IFN-gamma in CD patients, influencing the course of the disease.


[3-dimensional imaging of temporal bone structures using spiral CT. Initial results in normal temporal bone anatomy].
3D reconstruction of the temporal bone using spiral CT techniques was performed in 51 patients with various otological diseases during routine clinical work evaluation. The 3D display was optimized by a reduced study time and improved detail accuracy by special algorithms. We were able to demonstrate comprehensively in a 3D mode the normal anatomy of the inner ear and adjacent middle ear structures, such as the modiolus of the cochlea, the semicircular canals, the cochlear and vestibular aqueduct and the ossicles. We suggest routine 3D delineation of the substructures of the temporal bone prior to otologic surgery to provide the surgeon with a 3D view of individual anatomy and specific otosurgical sites.


Oxo-Functionalized Graphene as a Cell Membrane Carrier of Nucleic Acid Probes Controlled by Aging.
We applied a fluorescein-containing oligonucleotide (ON) to probe surface properties of oxidized graphene (oxo-G) and observed that graphene-like patches are formed upon aging of oxo-G, indicated by enhanced probe binding and by FTIR spectroscopic analysis. By using a recently developed fluorogenic endoperoxide (EP) probe, we confirmed that during the aging process the amount of EPs on the oxo-G surface is reduced. Furthermore, aging was found to strongly affect cell membrane carrier properties of this material. In particular, freshly prepared oxo-G does not act as a carrier, whereas oxo-G aged for 28 days at 4 °C is an excellent carrier. Based on these data we prepared an optimized oxo-G, which has a low-defect density, binds ONs, is not toxic, and acts as cell membrane carrier. We successfully applied this material to design fluorogenic probes of representative intracellular nucleic acids 28S rRNA and β-actin-mRNA. The results will help to standardize oxidized graphene derivatives for biomedical and bioanalytical applications.


Risk Factors for Retinopathy and DME in Type 2 Diabetes-Results from the German/Austrian DPV Database.
To assess the prevalence and risk factors for early and severe diabetic retinopathy and macular edema in a large cohort of patients with type 2 diabetes Retinopathy grading (any retinopathy, severe retinopathy, diabetic macular edema) and risk factors of 64784 were prospectively recorded between January 2000 and March 2013 and analyzed by Kaplan-Meier analysis and logistic regression. Retinopathy was present in 20.12% of subjects, maculopathy was found in 0.77%. HbA1c > 8%, microalbuminuria, hypertension, BMI > 35 kg/m2 and male sex were significantly associated with any retinopathy, while HbA1c and micro- and macroalbuminuria were the strongest risk predictors for severe retinopathy. Presence of macroalbuminuria increased the risk for DME by 177%. Retinopathy remains a significant clinical problem in patients with type 2 diabetes. Metabolic control and blood pressure are relevant factors amenable to treatment. Concomitant kidney disease identifies high risk patients and should be emphasized in interdisciplinary communication.


Use of reflectance spectrophotometry in the human corticosteroid skin blanching assay.
A reflectance spectrophotometric method for evaluation of the skin blanching response to topical corticosteroids was evaluated. This blanching response is used, for drug development and regulatory purposes, to assess potency and bioequivalence of topical corticosteroid products. The common method involves the use of a human rater to measure blanching response in the skin. This study evaluated an instrumental alternative to the human rater and used this method to measure the differences between a number of brand name and generic topical corticosteroid products (six creams and six ointments). Products were applied to the forearms of normal volunteers and the blanching responses were assessed after 6 and 16 hours in both occluded and non-occluded skin sites. Only the fluocinolone acetonide generic and brand name preparations were different from each other. The spectrophotometric method proved to be equivalent but not superior to the standard human observer method.


The role of salivary cytokines in the etiology and progression of periodontal disease.
Periodontal disease is a common oral disease in all segments of the population, regardless of their systemic health status. The disease is generalized or localized and the severity of lesions can vary at different sites. It is possible to recognize a number of different types of periodontal disease on the basis of clinical and pathological criteria, which include the extent of periodontal destruction, the age of onset and severity of disease, the distribution of lesions, the microflora involved, and the variation in host responses. The ultimate outcome of periodontal disease in adults, whether treated or untreated, depends on patient susceptibility. While periodontopathic bacteria are recognized as the etiologic agents in periodontal disease, their interaction with and modulation of the host immune response is of fundamental importance. An interplay of protection and pathology active in periodontal disease is that of T-lymphocyte cells and the subsequent production of cytokines within the periodontal tissues.


Cryptococcus gattiivgi in a spinner dolphin (Stenella longirostris) from Hawaii.
A spinner dolphin (Stenella longirostris) was found stranded in Hawaii with cutaneous nodules and enlarged lymph nodes. Numerous Cryptococcus gattii VGI yeast were observed in multiple organs with minimal inflammation. This case represents the first reported infection of C. gattii in a dolphin from Hawaii.


Metabolite diffusion in giant muscle fibers of the spiny lobster Panulirus argus.
The time- and orientation-dependence of metabolite diffusion in giant muscle fibers of the lobster Panulirus argus was examined using (31)P- and (1)H-pulsed-field gradient nuclear magnetic resonance. The (31)P resonance for arginine phosphate and the (1)H resonances for betaine, arginine/arginine phosphate and -CH(2)/-CH groups were suitable for measurement of the apparent diffusion coefficient, D. Diffusion was measured axially, D(//), and radially, D( perpendicular ), in fibers over diffusion times of 20 to 300 ms. Diffusion was strongly anisotropic, and D(//) was higher than D( perpendicular ) at all times. Radial diffusion decreased with time until a steady-state value was reached at a diffusion time of approximately 100 ms. Changes in D( perpendicular ) occurred over a time scale that was consistent with previous measurements from fish and mammalian muscle, indicating that diffusion is hindered by the same types of barriers in these diverse muscle types. The time dependence indicated that the sarcoplasmic reticulum is the principal intracellular structure that inhibits mobility in an orientation-dependent manner in skeletal muscle. The abdominal muscles in P. argus are used for anaerobic, burst contractions during an escape maneuver. The fact that these muscle fibers have diameters that may exceed hundreds of microns in diameter, and nearly all of the mitochondria are localized near the sarcolemmal membrane, suggests that barriers that hinder radial diffusion of ATP equivalents may ultimately limit the rate of post-contractile recovery.


[Effects of gonadotropin and estrogen on endogenous growth factor synthesis in the porcine theca].
In order to investigate the effects of FSH, LH and estradiol (E2) on the synthesis of endogenous growth factor from the thecal tissue, porcine thecal tissues obtained from follicles (greater than 3mm) were cultured for 24 hours in serum-free media in the presence of various concentrations of FSH, LH and E2. After the incubation, thecal tissues and thecal conditioned media (CM) were collected. The growth-promoting activity of thecal CM and thecal cytosol of each conditioned group was assayed by measuring 3H-DNA synthesis in mouse BALB/c 3T3 cells. E2 increased the growth-promoting activity of thecal CM significantly in comparison with controls, whereas neither FSH nor LH showed any significant effects. However, the growth promoting activity in the cytosols was almost the same in all conditioned groups. These results indicate that E2 stimulates the synthesis and secretion of thecal growth factor without changing the original properties.


Challenges and opportunities for medical directors in pathology and laboratory medicine: standardization, integration, and innovation.
Because the practice of pathology and laboratory medicine evolves rapidly, laboratory medical directors must constantly introduce new tests and services and continue to provide consistent, reliable results for existing tests. Innovations in laboratory medicine are frequently introduced, and the number of commercial vendors of test kits and reagents increases yearly. These innovations, however, may pose barriers to standardization and integration of laboratories and to interpretation of results generated by different laboratories. We propose a practical framework for medical directors to address the seemingly contradictory challenges of standardizing and integrating while simultaneously providing the flexibility to introduce innovations. We recommend initiating standardization first, then integration, while maintaining flexibility for innovation. As organizations strive to create effective processes to enhance value, the role of the laboratory medical director will become critical in resolving the natural tension between standardization/integration and innovation in laboratory medicine and pathology.


Fake science: The impact of pseudo-psychological demonstrations on people's beliefs in psychological principles.
Magicians use deception to create effects that allow us to experience the impossible. More recently, magicians have started to contextualize these tricks in psychological demonstrations. We investigated whether witnessing a magic demonstration alters people's beliefs in these pseudo-psychological principles. In the classroom, a magician claimed to use psychological skills to read a volunteer's thoughts. After this demonstration, participants reported higher beliefs that an individual can 1) read a person's mind by evaluating micro expressions, psychological profiles and muscle activities, and 2) effectively prime a person's behaviour through subtle suggestions. Whether he was presented as a magician or psychologist did not influence people's beliefs about how the demonstration was achieved, nor did it influence their beliefs in pseudo-psychological principles. Our results demonstrate that pseudo-psychological demonstrations can have a significant impact on perpetuating false beliefs in scientific principles and raise important questions about the wider impact of scientific misinformation.


A highly miniaturized electron and ion energy spectrometer prototype for the rapid analysis of space plasmas.
MEMS (Micro Electro-Mechanical Systems) plasma analyzers are a promising possibility for future space missions but conventional instrument designs are not necessarily well suited to micro-fabrication. Here, a candidate design for a MEMS-based instrument has been prototyped using electron-discharge machining. The device features 10 electrostatic analyzers that, with a single voltage applied to it, allow five different energies of electron and five different energies of positive ion to be simultaneously sampled. It has been simulated using SIMION and the electron response characteristics tested in an instrument calibration chamber. Small deviations found in the electrode spacing of the as-built prototype were found to have some effect on the electron response characteristics but do not significantly impede its performance.


Early childhood psychological problems predict a poor sense of coherence in adolescents: a 15-year follow-up study.
The aim of the present 15-year follow-up was to study the association between childhood psychological symptoms and sense of coherence (SOC) in adolescence. Destructive behaviour at three years, attention problems and thought problems at 12 years, attention problems, anxiety/depression, delinquency and somatic complaints at 15 years predicted a poor SOC at 18 years. Problems reported by adolescents themselves explained a poor SOC much more often than problems reported by parents. The identification of early childhood behavioural problems helps us to identify children at risk of ill-being in adolescence since problems seem to persist unchanged until that period of life.


Prognostic Laboratory Parameters in Placental Abruption: A Retrospective Case-Control Study.
To evaluate routine laboratory parameters in women with and without placental abruption (PA) and in controls, 417 women were included in this retrospective cohort study in a tertiary-care center. 118 women with PA (Group A: 54 without vaginal bleeding and Group B: 64 with bleeding), 130 women without either PA or vaginal bleeding throughout their pregnancy (Group C), 123 women with vaginal bleeding but without PA (Group D), and 46 healthy pregnant women who had undergone a control laboratory evaluation in the second/third trimester for history of previous cytomegalovirus (additional control group) were included. Hemoglobin, leukocytes, thrombocytes, C-reactive protein (CRP), and fibrinogen were obtained within 48 hours before C-section and/or at the time of bleeding onset. Cases (Groups A and B) revealed higher CRP levels than controls (Groups C and D) after multivariate analysis in the sub-analyses of bleeding (0.56 mg/dL, interquartile range (IQR) 0.28–1.24 vs. 0.51 mg/dL, IQR 0.28–0.84; odds ratio (OR) 1.108, p = 0.006) and non-bleeding women (0.64 mg/dL, IQR 0.48–1.08 vs. 0.32 mg/dL, IQR 0.18–0.61; OR 7.454, p < 0.001). The non-bleeding cases (Group A) revealed significantly higher leukocyte (12.01 g/L, IQR 9.41–14.10 vs. 9.21 g/L, IQR 7.95–10.49; OR 1.378, 95% confidence interval (CI): 1.095⁻1.735; p = 0.006) and CRP levels (0.64 mg/dL, IQR 0.48–1.08 vs. 0.33 mg/dL, IQR 0.20–0.50; OR 7.942, 95% CI: 1.435–43.958; p = 0.018) than the additional control group. In cases, none of the laboratory parameters differed between women with and without bleeding. The significantly increased CRP levels found for women with PA and the lack of a difference in CRP between bleeding and non-bleeding cases point toward a chronic process underlying placental abruption. However, this laboratory parameter does not seem clinically relevant for distinguishing between women with and without placental abruption at this point in time.


Intraaortic balloon pump timing discrepancies in adult patients.
The objective of this clinical study was to quantify the incidence and magnitude of intraaortic balloon pump (IABP) inflation and deflation landmark discrepancies associated with the IABP catheter arterial pressure waveform. Cardiac surgery patients with an IABP inserted prior to surgery were recruited. Following cardiac exposure, a high-fidelity pressure catheter was inserted into the aortic root for digital recording. The radial artery pressure signal was simultaneously recorded from the patient monitor along with the arterial pressure and electrocardiogram waveforms from the IABP console while operating at 1:1 and 1:2 synchronization. In selected patients, recordings were obtained with the IABP timed to the high-fidelity aortic root waveform. In all 11 patients, inflation and deflation landmark delays were observed when comparing the aortic root waveforms to the IABP arterial pressure waveforms (inflation delay = 74 ± 29 [23-117] ms; deflation delay = 71 ± 37 [24-141] ms, mean ± standard deviation [min-max]). Delays were greater when compared to the radial artery waveform (inflation delay = 175 ± 50 [100-233] ms; deflation delay = 168 ± 52 [100-274] ms). In all cases, the landmark delays were statistically different from zero (P < 0.001). Diastolic augmentation and afterload reduction varied with waveform source. Conflicting indications of afterload reduction occurred in four patients. Timing to the aortic root waveform resulted in greater diastolic pressure augmentation and afterload reduction but mixed changes in stroke volume. Delay and distortion of the arterial waveform was consistently found when measured through the IABP catheter lumen. These delays can alter IABP efficacy and may be eliminated by using high-fidelity sensing of aortic pressure.


[Allergic alveolitis following inhalation of mould spores from pot plant earth (author's transl)].
Acute exogenous allergic alveolitis with the typical symptoms of unproductive cough, dyspnoea on exertion, fever, loss of weight, headache and limb pains was observed in a 24-year-old bank employee. Leucocytosis was accompanied by raised ESR; pronounced hypoxaemia and marked restrictive ventilatory defects were found. X-ray changes consisted of severely increased fine reticular interstitial shadowing. The differential diagnosis of allergic alveolitis was confirmed by the demonstration of precipitating antibodies in serum against Pullularia pullulans, Trichoderma viride, Cephalosporium acremonium and Aspergillus fumigatus, moulds with an ubiquitous occurrence. Typical changes of alveolitis were found histopathologically and immunohistologically in the lung tissue after a mini-thoracotomy. The source of exposition leading to the disease were pot plant earth and containers in the patient's flat. Moulds could be isolated from these substrates.


Neurophilosophy and the distal hyperuranic world: Fred Previc's space of the gods (and of men).
Unlike the concept handed down by philosophy (and by the philosophy of science), which proposes a univocal, intellectualistic vision of space, Previc's studies have shown that the relationship between consciousness and space is instead managed by a number of modules, making it possible to categorise spatial interaction on four levels which correspond to the different ways in which we project our existence in different practical and cultural scenarios. What emerges as particularly important is the fourth level of the management of spatiality, the one that sees human consciousness dealing with the great distances - the heavens, the house of the gods. This module makes use of a neural pathway involving ventral sensory structures that also manage the relationship with religion and transcendence. But these are also the structures that are activated when populations are forced to set out in search of new lands - the quest for the eternal "Promised Land". In this study of infinite spaces, the path of the gods and of men coincide and they are seen to advance along it together.


[Retinitis due to cytomegalovirus in AIDS].
Clinical course of 4 AIDS patients suffering from CMV retinitis is presented. Two patients were treated with ganciclovir, one died before starting the treatment and one was vitrectomized with silicone oil injection. Of the two patients treated with ganciclovir one improved significantly when the other continued to deteriorate and died after 8 months of follow-up. Early diagnosis and treatment of patients with zone I involvement gives the best chances for improvement. Mean life expectancy in aids patients after diagnosis of CMV retinitis is 7-10 months.


The Impact of Clinical Pharmacist Support on Patients Receiving Multi-drug Therapy for Coronary Heart Disease in China.
The study determined pharmacist support on patients receiving multi-drug therapy for coronary heart disease by evaluating patient self-care ability, quality of life, and drug therapy compliance. In this study, ninety patients were randomly assigned to an experimental group (n=45) and a control group (n=45). The control group received conventional clinical care. The experimental group received clinical care plus pharmacist support that included medication review, patient education, lifestyle management, discharge guidance, and telephone follow-up. Eighty-five patients completed the study. Self-care ability and quality of life were evaluated before hospital discharge. The experimental group understood their condition better than the control group (P<0.05), the differences between the groups in understanding treatment goals, drug regimens, lifestyle modifications, psychogenic disorders, and satisfaction evaluations were more pronounced (P<0.01). At six-month follow-up, the difference between the groups in drug therapy compliance was P<0.01, as was success rate by intention-to-treat (77.8% vs. 48.9%) and per-protocol (81.4% vs. 52.4%). Two adverse drug reactions occurred in the experimental group and three in the control group. Pharmacist support improved self-care ability, quality of life, drug therapy compliance, and treatment success rate in coronary heart disease patients.


[An experimental study on acupoint neiguan-heart short reflex].
It is reported that the dichotomizing afferent fibers supply both the pericardium and the brachium in rat. This finding provides a possible morphological explanation for short reflex which transmits messages only through the connection of peripheral nerve dichotomization. The animals utilized in this study were 15 male or female wistar rats (235-360 g). Rats were anesthetized with 26% urethane (100mg/100g b. wt, i.p.) and then, acute myocardial ischemia (AMI) was produced by pituitrin (1.0-1.5 u/a rat, i.M.). Following anesthetization and AMI, The I lead of electrocardiogram (ECG) was recorded, the superficial electrical resistance and cutaneous temperature of the acupoint Neiguan and Zusali were measured. In order to break off the long reflex which invokes some effects through central nervous system, the dorsal roots were removed of spinal cord segments cervical 6) C6-thoracic 1(T1). In this condition, the AMI can decrease in superficial electrical resistance and cutaneous temperature of the acupoint Neiguan (P less than 0.01). Acupuncture at Neiguan can also influence the superficial electrical resistance of the acupoint Neiguan, improve in the ECG, increase in the heart rate, but acupuncture at Zusali has no these effects. It suggests that acupoint Neiguan and heart can be connected through a short reflex.


Hemostatic safety of the bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion.
The bolus intravenous injection of a novel 8:2 medium-chain triglyceride:fish oil emulsion was recently found to increase within 60 min and for the subsequent 24-48 h the long-chain polyunsaturated omega3 fatty acid content of both leucocyte and platelet phospholipids in 12 normal subjects. The aim of the present report is to document the hemostatic safety of such a procedure in the same 12 subjects. No adverse effect was found when comparing the results obtained after administration of either the fish oil-containing emulsion or a control 5:5 medium-chain triglyceride:soybean triglyceride emulsion, whether in terms of the occlusion time in either an ADP or epinephrine test or in terms of the [CD]42b, [CD]62p, fibrinogen and PAC-1 response to ADP, collagen or thrombin receptor analog peptide 6 in platelets examined by fluorescence activated cell sorting. In conclusion, this novel procedure for the rapid enrichment of cell phospholipid in long-chain polyunsaturated omega3 fatty acids presents the required safety in a hemostatic perspective.


Genetic Consequences of Antiviral Therapy on HIV-1.
A variety of enzyme inhibitors have been developed in combating HIV-1, however the fast evolutionary rate of this virus commonly leads to the emergence of resistance mutations that finally allows the mutant virus to survive. This review explores the main genetic consequences of HIV-1 molecular evolution during antiviral therapies, including the viral genetic diversity and molecular adaptation. The role of recombination in the generation of drug resistance is also analyzed. Besides the investigation and discussion of published works, an evolutionary analysis of protease-coding genes collected from patients before and after treatment with different protease inhibitors was included to validate previous studies. Finally, the review discusses the importance of considering genetic consequences of antiviral therapies in models of HIV-1 evolution that could improve current genotypic resistance testing and treatments design.


Correlation between structural progression in glaucoma and obstructive sleep apnea.
To investigate the correlation between obstructive sleep apnea (OSA) severity and the structural and functional progression in patients with glaucoma. This retrospective comparative cohort study included subjects from the polysomnography database in Chang Gung Memorial Hospital between June 1, 2009, and June 1, 2017, by identifying patients who had received diagnoses of primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), or glaucoma suspect. Patients with follow-up time of <3 years and/or <3 consecutive reliable optical coherence tomography (OCT) or visual field (VF) tests were excluded. Progression of overall peripapillary retinal nerve fiber layer (RNFL) thickness on OCT scans and VF mean deviation (MD) or VF index (VFI) were determined through linear regression trend analysis. Thirty-two patients were included. There was a trend to higher percentage of progression on RNFL thickness and VF in higher OSAS severity. After stratifying patients to no OSA/mild OSA (group 1) and moderate/severe OSA (group 2), group 2 exhibited a significantly higher percentage of RNFL thickness progression than did group 1 (64.7% vs 26.7%, P = 0.042). Multivariate Cox regression analysis showed that severe OSA had an 8.448-fold higher risk of RNFL thickness progression after age, sex, diabetes mellitus, hypertension, hyperlipidemia, and body mass index adjustment (95% confidence interval, 1.464-48.752, P = 0.017). Severe OSA is significantly correlated with a higher risk of structural deterioration in patients with glaucoma.


In vitro Validation of Chimeric β-Galactosylceramidase Enzymes With Improved Enzymatic Activity and Increased Secretion.
Globoid Cell Leukodystrophy (GLD) is a lysosomal storage disease (LSD) caused by inherited defects of the β-galactosylceramidase (GALC) gene. The infantile forms display a rapid and aggressive central and peripheral nervous system (CNS and PNS) dysfunction. No treatments are available for GLD patients. Effective gene therapy (GT) strategies for GLD require a safe and widespread delivery of the functional GALC enzyme to all affected tissues/organs, and particularly to the CNS. The use of chimeric lysosomal enzymes with increased secretion and enhanced transport across the blood-brain barrier (BBB) that boost the efficacy of GT approaches in pre-clinical models of similar neurodegenerative LSDs may benefit GLD as well. Here, we tested the safety and biological efficacy of chimeric GALC enzymes engineered to express an alternative signal peptide (iduronate-2-sulfatase - IDSsp) and the low-density lipoprotein receptor (LDLr)-binding domain from the Apolipoprotein E II (ApoE II) in GLD murine neural and hematopoietic stem/progenitor cells and progeny, which are relevant cells types in the context of in vivo and ex vivo GT platforms. We show that the lentiviral vector-mediated expression of the chimeric GALC enzymes is safe and leads to supranormal enzymatic activity in both neural and hematopoietic cells. The IDSsp.GALC shows enhanced expression and secretion in comparison to the unmodified GALC. The chimeric GALC enzymes produced by LV-transduced cells reduce intracellular galactosylceramide (GalCer) storage and effectively cross-correct GLD murine neurons and glial cells, indicating that the transgenic enzymes are delivered to lysosomes, efficiently secreted, and functional. Of note, the expression of LDLr and LDLr-related proteins in GLD neurons and glial cells supports the exploitation of this system to enhance the GALC supply in affected CNS cells and tissues. These in vitro studies support the use of chimeric GALC enzymes to develop novel and more effective GT approaches for GLD.


Characterizing gene expressions based on their temporal observations.
Temporal gene expression data are of particular interest to researchers as they contain rich information in characterization of gene function and have been widely used in biomedical studies. However, extracting information and identifying efficient treatment effects without loss of temporal information are still in problem. In this paper, we propose a method of classifying temporal gene expression curves in which individual expression trajectory is modeled as longitudinal data with changeable variance and covariance structure. The method, mainly based on generalized mixed model, is illustrated by a dense temporal gene expression data in bacteria. We aimed at evaluating gene effects and treatments. The power and time points of measurements are also characterized via the longitudinal mixed model. The results indicated that the proposed methodology is promising for the analysis of temporal gene expression data, and that it could be generally applicable to other high-throughput temporal gene expression analyses.


Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature.
Rifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug's potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events. We report a bleeding episode after termination of the co-administration of rifampicin and warfarin and detail the challenges related to international normalized ratio (INR) monitoring. A 59-year-old Brazilian woman chronically treated with warfarin for atrial fibrillation (therapeutic INR range: 2.0-3.0) was referred to a multidisciplinary anticoagulation clinic at a university hospital. She showed anticoagulation resistance at the beginning of rifampicin therapy, as demonstrated by repeated subtherapeutic INR values. Three months of sequential increases in the warfarin dosage were necessary to reach a therapeutic INR, and frequent visits to the anticoagulation clinic were needed to educate the patient about her pharmacotherapy and to perform the warfarin dosage adjustments. The warfarin dosage also had to be doubled at the beginning of rifampicin therapy. However, four weeks after rifampicin discontinuation, an excessively high INR was observed (7.22), with three-day macroscopic hematuria and the need for an immediate reduction in the warfarin dosage. A therapeutic and stable INR was eventually attained at 50% of the warfarin dosage used by the patient during tuberculosis therapy. The present case exemplifies the influence of rifampicin therapy on warfarin dosage requirements and the increased risk of bleeding after rifampicin discontinuation. Additionally, this case highlights the need for warfarin weekly monitoring after stopping rifampicin until the maintenance dose of warfarin has decreased to the amount administered before rifampicin use. In particular, patients with cardiovascular diseases and active tuberculosis represent a group with a substantial risk of drug-drug interactions. Learning how to predict and monitor drug-drug interactions may help reduce the incidence of clinically significant adverse drug events.


Yeast silencers create domains of nuclease-resistant chromatin in an SIR4-dependent manner.
Previous analysis of the repression of the silent mating type loci in Saccharomyces cerevisiae has linked the mechanism of silencing to the formation of a chromatin domain at the silenced loci. In this study, a TRP1 reporter gene was used to examine changes in chromatin structure in a neutral environment. This enabled the chromatin structure organized by yeast silencers to be compared directly with changes effected by the yeast alpha2 repressor. It was found that silencers mediate the formation of lengthy nuclease-resistant domains on the DNA, rather than specifically positioning nucleosomes over promoter regions as the alpha2 repressor does. Silencing at the TRP1 reporter gene closely resembled silencing at the HMR and HML loci. Repression of the test gene was optimal when two silencers flanking the reporter gene were used, mimicking the situation at the silent loci. In addition, both repression of the reporter gene and the formation of nuclease-resistant chromatin domains was SIR4 dependent.


Sustainability of an HIV PEP Program for Sexual Assault Survivors: "Lessons Learned" from Health Care Providers.
This study explored challenges to continuing an HIV post-exposure prophylaxis (PEP) program of care provided to sexual assault survivors in the province of Ontario, Canada. Data were collected as part of an implementation and evaluation of a universal offering of HIV PEP (known as the HIV PEP Program) at 24 of 34 provincial hospital-based sexual assault treatment centres. Experienced health care providers were surveyed (n = 132) and interviewed in four focus groups (n = 26) about their perceptions of what, if any, factors threatened their ability to maintain the HIV PEP Program. All focus groups were audio-recorded and the recordings transcribed. The transcriptions and open-ended survey responses were analyzed using content analysis. Administrator, nurse, physician, social worker, and pharmacist respondents perceived important barriers to sustainability of the HIV PEP Program. Eight constructs were identified within four broad themes: resources (inadequate funds, overworked and unacknowledged staff), expertise (insufficient external supports, insufficiently trained and knowledgeable staff), commitment (lack of institutional support, physician resistance to offering HIV PEP), and accommodation (lack of flexibility in addressing specific client and community needs, inaccessibility and lack of clarity of tools). We discuss the implications of these findings and the actions that were taken to address the challenges.


Himar1 Transposon for Efficient Random Mutagenesis in Aggregatibacter actinomycetemcomitans.
Aggregatibacter actinomycetemcomitans is the primary etiological agent of aggressive periodontal disease. Identification of novel virulence factors at the genome-wide level is hindered by lack of efficient genetic tools to perform mutagenesis in this organism. The Himar1 mariner transposon is known to yield a random distribution of insertions in an organism's genome with requirement for only a TA dinucleotide target and is independent of host-specific factors. However, the utility of this system in A. actinomycetemcomitans is unknown. In this study, we found that Himar1 transposon mutagenesis occurs at a high frequency (×10-4), and can be universally applied to wild-type A. actinomycetemcomitans strains of serotypes a, b, and c. The Himar1 transposon inserts were stably inherited in A. actinomycetemcomitans transconjugants in the absence of antibiotics. A library of 16,000 mutant colonies of A. actinomycetemcomitans was screened for reduced biofilm formation. Mutants with transposon inserts in genes encoding pilus, putative ion transporters, multidrug resistant proteins, transcription regulators and enzymes involved in the synthesis of extracellular polymeric substance, bacterial metabolism and stress response were discovered in this screen. Our results demonstrated the utility of the Himar1 mutagenesis system as a novel genetic tool for functional genomic analysis in A. actinomycetemcomitans.


The increase in BIK expression following ERK1/2 pathway inhibition is a consequence of G₁ cell-cycle arrest and not a direct effect on BIK protein stability.
BIK (BCL2-interacting killer) is a pro-apoptotic BH3 (BCL2 homology domain 3)-only protein and a member of the BCL2 protein family. It was proposed recently that BIK abundance is controlled by ERK1/2 (extracellular-signal-regulated kinase 1/2)-catalysed phosphorylation, which targets the protein for proteasome-dependent destruction. In the present study, we examined ERK1/2-dependent regulation of BIK, drawing comparisons with BIM(EL) (BCL2-interacting mediator of cell death; extra long), a well-known target of ERK1/2. In many ERK1/2-dependent tumour cell lines, inhibition of BRAF(V600E) (v-raf murine sarcoma viral oncogene homologue B1, V600E mutation) or MEK1/2 (mitogen-activated protein kinase/ERK kinase 1/2) had very little effect on BIK expression, whereas BIM(EL) was strongly up-regulated. In some cell lines we observed a modest increase in BIK expression; however, this was not apparent until ~16 h or later, whereas BIM(EL) expression increased rapidly within a few hours. Although BIK was degraded by the proteasome, we found no evidence that this was regulated by ERK1/2 signalling. Rather, the delayed increase in BIK expression was prevented by actinomycin D, and was accompanied by increases in BIK mRNA. Finally, the delayed increase in BIK expression following ERK1/2 inhibition was phenocopied by a highly selective CDK4/6 (cyclin-dependent kinases 4 and 6) inhibitor, which caused a strong G₁ cell-cycle arrest without inhibiting ERK1/2 signalling. In contrast, BIM(EL) expression was induced by ERK1/2 inhibition, but not by CDK4/6 inhibition. We conclude that BIK expression is not subject to direct regulation by the ERK1/2 pathway; rather, we propose that BIK expression is cell-cycle-dependent and increases as a consequence of the G₁ cell-cycle arrest which results from inhibition of ERK1/2 signalling.


[Desiccation and nitrate accumulation of apple orchard soil on the Weibei dryland].
The study of apple orchard soil on the Weibei dryland showed that high input and high yield not only resulted in soil desiccation, but also induced nitrate accumulation in the soil profile. Generally, the soil layers with accumulated nitrate located in 40 - 260 cm depths, and the maximum nitrate content was 403.4 mg x kg(-1). Owing to the continuous application of nitrogen fertilizer, the accumulated nitrate could hardly be reused in the future, which might lead to environmental pollution. Because the soil storage water could not adjust the water utilization of apple trees, the yield of orchard was affected by precipitation. Therefore, the nitrogen application rate should be reduced, and actions should be taken to improve soil moisture in apple orchard.


Probiotics promote gut health through stimulation of epithelial innate immunity.
Probiotic formulations are widely available and have a variety of proposed beneficial effects, including promotion of gut health. The mechanisms of action of probiotic bacteria in the intestine are still unclear but are generally attributed to an antiinflammatory effect. Here, we demonstrate that the multiple probiotic formulation VSL#3 prevents the onset of intestinal inflammation by local stimulation of epithelial innate immune responses (i.e., increased production of epithelial-derived TNF-alpha and restoration of epithelial barrier function in vivo). We also demonstrate that probiotic bacteria stimulate epithelial production of TNF-alpha and activate NF-kappaB in vitro. Our results support the hypothesis that probiotics promote gut health through stimulation, rather than suppression, of the innate immune system. Furthermore, our findings provide the perspective that defects in innate immunity may play a critical role in the pathogenesis and progression of intestinal disorders, such as inflammatory bowel disease.


Selection criteria for successful immediate breast reconstruction.
To evaluate the factors leading to success in immediate breast reconstruction after mastectomy, 176 consecutive immediate reconstructions done with implants or expanders over a 5-year period were analyzed. None of these 176 had "complete muscle coverage." There were only five failures: four with implant loss (one involving radiation) and one removed electively. The failures were 1 in 40 regular implants, 4 in 77 temporary expanders, and 0 in 59 long-term expanders. There is no other report in the literature comparing these different types of implants. Various hypotheses for failure are reviewed. It is concluded that failure in immediate reconstruction is not related to use of drains, bilaterality, or lack of "complete muscle coverage." It is concluded that failure is related to implant type, prior radiation, and most of all to suboptimal patient selection. Specific selection criteria and operative techniques are discussed.


Thyroid-stimulating autoantibodies usually contain only lambda-light chains: evidence for the "forbidden clone" theory.
Burnet's "forbidden clone" theory would predict that in patients with Graves' disease the pathogenic thyroid-stimulating autoantibody (TSab)-secreting clones arise by somatic mutation. Because each lymphocyte and its progeny are permanently committed to producing antibodies of a single light chain type, a clone arising by somatic mutation occurring in a single cell would be expected to produce autoantibodies of exclusively kappa or exclusively lambda type in an individual patient. Using affinity chromatographic techniques and monoclonal antibodies, we investigated the light chain type of TSab in 11 patients with Graves' disease. In all patients tested, TSab activity was confined to a single light chain type, confirming the recent work of Zakarija who used affinity chromatography with polyclonal antisera, but contrasting with earlier studies which used immuno-precipitation methods. Furthermore, the light chain type was lambda in 10 of the 11 patients. These observations provide support for the forbidden clone theory. In addition, the marked preponderance of patients producing TSab of the lambda-light chain type indicates that TSab are more likely to arise from the lambda repertoire of clones than from the kappa repertoire and suggests that immunoglobulin light chain V genes may be genetic determinants for susceptibility to Graves' disease.


Comment on "The effect of same-sex marriage laws on different-sex marriage: evidence from the Netherlands".
In the recent Demography article titled "The Effect of Same-Sex Marriage Laws on Different-Sex Marriage: Evidence From the Netherlands," Trandafir attempted to answer the question, Are rates of opposite sex marriage affected by legal recognition of same-sex marriages? The results of his approach to statistical inference-looking for evidence of a difference in rates of opposite-sex marriage-provide an absence of evidence of such effects. However, the validity of his conclusion of no causal relationship between same-sex marriage laws and rates of opposite-sex marriage is threatened by the fact that Trandafir did not also look for equivalence in rates of opposite-sex marriage in order to provide evidence of an absence of such an effect. Equivalence tests in combination with difference tests are introduced and presented in this article as a more valid inferential approach to the substantive question Trandafir attempted to answer.


Occurrence of an Inhibitor of Tissue-Type Plasminogen Activator in Seeds and in Vitro Cultures of Erythrina caffra Thunb.
The level of an inhibitor of tissue-type plasminogen activator (t-PA) increased slowly during the early developmental stage of seeds of Erythrina caffra Thunb. Thereafter, the inhibitor increased exponentially until the seeds reached maturity. At maturity, the t-PA inhibitor levels in the cotyledons were 38 times higher than the levels at the onset of seed development. The t-PA inhibitor accumulated at a faster rate than the storage proteins, which reached a concentration 15 times higher than the protein concentration at the onset of seed development. During the imbibition and germination process, the t-PA inhibitor decreased gradually. The inhibitor kept on decreasing during the growth of the seedlings until the 10th day after imbibition, when it leveled off at 4.1% of that of the initial inhibitor concentration. The inhibitor remained at this level until the cotyledons were shed at day 22. The total protein in the cotyledons decreased at a slower rate than the inhibitor and reached a minimum concentration at day 20 of 3.6% of the initial protein concentration in the cotyledons. Callus cultures of root, shoot, leaf, and cotyledonary tissue was established and maintained on Murashige-Skoog medium supplemented with 3% sucrose, 10 micromolar benzyladenine, and 5 micromolar 2,4-dichlorophenoxyacetic acid. A shoot cell suspension culture was established on Murashige-Skoog medium supplemented with 3% sucrose, 1 micromolar benzyladenine, and 0.5 micromolar 2,4-dichlorophenoxyacetic acid (pH 5.7) and shaken at 60 revolutions per minute. The level of t-PA inhibitor in root, shoot, leaf, and cotyledonary callus was substantially lower than in the corresponding intact tissue. The t-PA inhibitor levels in the linear growth phase was higher than in the lag or stationary growth phases of the cell suspension culture. A hydrolysate of the cell walls of tomato and E. caffra Thunb, as well as polyamines and organic acids, did not increase the concentration of t-PA inhibitor in suspension cultures or intact leaf tissue of E. caffra. The t-PA inhibitor levels of suspension cultures were increased by Na(2)SO(4) but not by I-cysteine in the nutrient medium.


Whole body vibration exposures in forklift operators: comparison of a mechanical and air suspension seat.
Using a repeated measures design, this study compared differences in whole body vibration (WBV) exposures when 12 forklift operators drove the same forklift with a mechanical suspension and an air suspension seat. A portable PDA-based WBV data acquisition system collected and analysed time-weighted and raw WBV data per ISO 2631-1 and 2631-5 WBV measurement standards. Tri-axial measurements of weighted vibration (A(w)), crest factor, vibration dose values, time-weighted average-peak, raw (+) peak, raw (-) peak and static compression dose (S(ed)) were compared between seats. There were significant differences in z-axis WBV exposures with the air suspension seat, yielding lower WBV exposures. In addition, there were differences between seats in how they attenuated WBV exposures based on the driver's weight. In the mechanical suspension seat, WBV exposures were weight-dependent, with lighter drivers having higher WBV exposures, whereas with the air suspension seat, the same trends were not as prevalent. STATEMENT OF RELEVANCE: This study contributes to the understanding of how different seat suspensions can influence WBV transmission and how some components of vibration transmission are dependent on the weight of the driver. Additional systematic studies are needed to quantify how various factors can influence WBV exposures.


Methods for measuring in-vivo percutaneous absorption in humans.
In-vivo human data on percutaneous absorption are scarce, although they are indispensable for health risk assessment of dermal exposure. In addition, they are considered to be the gold standard for the evaluation of in-vitro systems as well as predictive mathematical models. Dermal absorption in vivo can be assessed using different approaches. The most used methods for determination of in-vivo dermal absorption are the measurement of the parent chemical and/or its metabolite level in biological material, the microdialysis technique and stratum corneum tape stripping. Recently, the non-invasive spectrophotometric methods based on infrared and Raman spectroscopy showed themselves as promising tools for studying percutaneous absorption though these approaches are still in their developmental stages and requires further optimization and validation. The aim of this article is to review different methods for determination of percutaneous absorption in vivo in humans. The advantages and limitations are discussed with respect to generating data for comparison with in-vitro or predictive mathematical models or health risk assessment of chemicals. Furthermore, the importance of the volunteer experiments in generating relevant data for human risk assessment as well as for the development and implementation of biological monitoring in occupational settings will be addressed.


Subtyping of phosphoglucomutase locus 1 (PGM1) polymorphism in some populations of Rwanda: description of variant phenotypes, "haplotype" frequencies, and linkage disequilibrium data.
Some populations of Rwanda (South Twa Pygmies, Hutu, and Tutsi) have been analyzed by acid starch gel electrophoresis for the subtyping of PGM1 polymorphism. The new polymorphic third PGM11 allele, the PGM1(1Twa), which we recently detected in Twa Pygmies from North Rwanda, has not been found in this survey, whereas the rare PGM1(6) allele attains subpolymorphic frequencies in all groups. Comparison between the various populations of Rwanda shows that they differ significantly from each other with the exception of South Twa Pygmies and Tutsi. A relatively low frequency (9.6%) of the PGM1(2S) allele appears to be typical of North Twa Pygmies; a low frequency of PGM1(2F) (1.2%-3.6%) has been found in all these groups but not in the Hutu (6.4%); and a particularly high incidence of the PGM1(1F) allele (the highest so far reported) has been observed in the South Twa Pygmies (20%) and in the Tutsi (18%). The PGM1(1Twa) and PGM1(6) enzymes, which in acid starch gel are not distinguishable, can be clearly differentiated by isoelectric focusing. In addition, the same technique has shown that the rare PGM1(7) allele observed in one Hutu is different from that found at polymorphic frequency in the Japanese and from a rare PGM1(7) allele found in Germany. On the very likely hypothesis that the PGM1(1S), PGM1(1F), PGM1(2S), and PGM1(2F) result from variations at two different polymorphic sites, 1/2 and F/S, within the PGM1 structural gene, all the available population data have been analyzed to investigate whether preferential combinations (haplotypes) were identifiable. Whereas Caucasians show a prevalence of 2F and 1S combination with an 8.02% mean value of linkage disequilibrium expressed as % Dmax, from the very few and scattered African data, it is impossible to draw any inference at present.


Relationship between oral health and mortality rate.
Some symptoms of diseases or causes of death are often related to oral health, especially cardiovascular diseases. The purpose of this study was to investigate the relationship between poor oral health and mortality risk, especially when cases of fatal cardiovascular diseases were excluded. An odontological investigation was made on a sample of 1393 individuals, aged 18-65 years, in 1970 in the County of Stockholm with a follow-up in 1997, when the mortality rate and causes of death in the sample during the time period 1971-1996 were registered. Oral health was defined as a sum of scores for number of missing teeth, apical lesions, caries lesions and marginal bone loss. A significant correlation was found between poor oral health and an increased mortality risk even when persons dying from cardiovascular diseases were excluded from the analyses. Poor oral health was found to be a risk indicator of all-cause mortality. The lack of specificity of the associations between oral health and mortality strengthens the hypothesis that the significant correlations could be explained by not identified confounding factors.


Health Patterns among Migrant and Non-Migrant Middle- and Older-Aged Individuals in Europe-Analyses Based on Share 2004-2017.
European populations are becoming older and more diverse. Little is known about the health differences between the migrant and non-migrant elderly in Europe. The aim of this paper was to analyse changes in the health patterns of middle- and older-aged migrant and non-migrant populations in Europe from 2004 to 2017, with a specific focus on differences in age and gender. We analysed changes in the health patterns of older migrants and non-migrants in European countries from 2004 to 2017. Based on data from the Survey of Health, Ageing and Retirement in Europe (6 waves; 2004-2017; n = 233,117) we analysed three health indicators (physical functioning, depressive symptoms, and self-rated health). Logistic regression models for complex samples were calculated. Interaction terms (wave * migrant * gender * age) were used to analyse gender and age differences and the change over time. Middle- and older-aged migrants in Europe showed significantly higher rates of depressive symptoms, lower self-rated health, and a higher proportion of limitations on general activities compared to non-migrants. However, different time trends were observed. An increasing health gap was identified in the physical functioning of older males. Narrowing health gaps over time were observed in women. An increasing health gap in physical functioning in men is evidence of cumulative disadvantage. In women, evidence points towards the hypothesis of aging-as-leveler. These different results highlight the need for specific interventions focused on healthy ageing in elderly migrant men.


The ecology of the parasite population in micro-mammals in the Italian peninsula and islands.
The importance of micro mammals from many points of view, mainly with an ecological approach was stressed. The study of the spatial-temporal distribution of parasites in their hosts may be carried out in several ways. Tests done in collaboration with the Parasitology Laboratory in the Faculty of Chemistry at the University of Barcelona, the NRCS and the Department of Ecological Studies in Cosenza, have contributed to an understanding of the Helminth communities as relating to several intrinsic variables of microteriofauna as well as extrinsic ones, particularly those concerning environment, climate and season. These comparisons were made using statistical means which compared the categorical and dichotomic variables which would highlight risk differences and their effects on the system. Quantitative dependent variables were also considered in relation to the aforementioned qualitative variables. One of the models studied is that of logistic regression, which estimates the function of regression, connecting the probability of the presence of Helminth as a dependent variable, with biological and ecological parameters (independent variables) such as: gender, age, season of capture, bioclimate, biotope and trapping section.


Capacitance measuring circuit for water waves.
A simple, reliable, integrated circuit is described which is used to measure standing water waves of amplitudes ranging from less than 1 mm. The circuit has a high dynamic range and is linear for changes in water depth of several centimeters. The sensitivity of this capacitance measuring device is 38 mV/mm of wave amplitude, enabling small amplitude waves to be readily detected.


Acute pulmonary complications in patients with hematologic malignancies.
Various acute pulmonary complications may occur in patients with hematologic malignancies because they are in an immunocompromised state due to systemic disease or to chemotherapy or hematopoietic stem cell transplantation. Pulmonary complications may arise from other treatment regimens, as well, or from direct pulmonary involvement in the malignant disease process. The differential diagnosis of pulmonary opacities in patients with hematologic malignancies is broad and includes both infectious and noninfectious causes. Pulmonary hemorrhage, edema, leukostasis, and pneumonia are well-known and common acute pulmonary complications. Less common complications are now encountered with increasing frequency because of the increasing complexity of therapeutic regimens for hematologic malignancies, which may include various drugs that are in clinical trials or were recently released to market. These once uncommon acute pulmonary complications include retinoic acid syndrome, tyrosine kinase inhibitor-induced pulmonary complications, engraftment syndrome, and hemophagocytic lymphohistiocytosis. It is often difficult to differentiate between these entities. However, the clinical setting and radiologic imaging findings may provide clues for interpreting imaging findings of abnormal pulmonary opacity in patients with a hematologic malignancy. Pulmonary hemorrhage is characterized by a sudden onset of symptoms and rapid progression of pulmonary imaging abnormalities and usually occurs in patients with impaired coagulation or a predisposition to bleed. Pulmonary edema should be considered when typical findings of hydrostatic pulmonary edema are seen. Pulmonary leukostasis develops in patients with hyperleukocytosis and leads to symptoms such as a cough, fever, and dyspnea. Various types of pneumonia may develop, depending on the degree and duration of immunosuppression in the patient. Retinoic acid syndrome, tyrosine kinase inhibitor-induced pulmonary complications, and engraftment syndrome occur after specific treatments, so a detailed medical history including recent or current treatments may be helpful for diagnosis. Accurate differentiation of these entities allows their appropriate management, with resultant decreases in morbidity and mortality.


Long-term Outcomes of Adalimumab Therapy in Korean Patients with Ulcerative Colitis: A Hospital-Based Cohort Study.
Studies on long-term outcomes of adalimumab therapy in non-Caucasian patients with ulcerative colitis (UC) are lacking. We analyzed long-term outcomes of Korean UC patients treated with adalimumab at the Asan Medical Center, Seoul, Korea. Between July 2013 and October 2018, adalimumab therapy was started in a total of 100 patients with UC (65 males [65.0%]; median age, 39.5 years [interquartile range, 23.3 to 49.8 years]; and median disease duration, 3.0 years [interquartile range, 1.0 to 7.0 years]). The median duration of adalimumab therapy was 13.5 months (interquartile range, 4.0 to 32.0 months). Eight of 100 patients (8.0%) received induction therapy only, four (4.0%) of whom ultimately underwent colectomy. Of 92 patients who received adalimumab maintenance therapy, 30 (30.0%) stopped adalimumab therapy due to loss of response, and one patient (1.0%) was lost to follow-up. Among the 92 patients who received adalimumab maintenance therapy, the cumulative proportions of patients remaining on adalimumab maintenance therapy were 70.0% at 1 year and 48.9% at 5 years. High partial Mayo score after 8 weeks of adalimumab therapy (hazard ratio [HR], 1.217; 95% confidence interval [CI], 1.040 to 1.425; p=0.014) and a history of exposure to two biologic agents before adalimumab therapy (HR, 4.722; CI, 1.033 to 21.586; p=0.045) were predictors of adalimumab discontinuation. Long-term outcomes of adalimumab therapy in Korean UC patients appear to be comparable to those in previously published Western studies. Furthermore, previous exposure to multiple biologic agents before adalimumab therapy and disease activity after 8 weeks of adalimumab therapy were predictors of adalimumab discontinuation.


Cycloheximide stimulation of cyanide-resistant respiration in suspension cultures of senescent pear fruit cells.
Pear fruit cells undergoing a period of senescence in auxin-deprived media develop a substantial cyanide resistant respiration in response to the addition of 0.7 to 3.5 micromolar cycloheximide. The inhibitor does not affect overall cellular repiratory activity and titrations with salicylhydroxamic acid reveal that only a minor portion, about 10%, of the alternate pathway is utilized by the cycloheximide-treated senescent cells. The alternate respiratory pathway appears to be of mitochondrial origin but is not induced by chloramphenicol.


Standardised opt-out testing for HIV.
This article offers a literature review of the benefits of, and problems associated with, a standardised opt-out screening programme for HIV, and the attitudes of healthcare professionals and patients to its potential introduction in emergency departments. There is a lack of research on the subject in the UK and so the article relies on work undertaken in the US and on opt-out testing in antenatal services in the UK. It reviews the potential benefits of such a programme, in particular the opportunities it offers to improve public health and reduced the stigma associated with HIV, and discusses the issue of consent.


Subcellular calcium transport during contractile failure and recovery in heart perfused with Na-free medium.
Perfusion of isolated rat hearts with Na-free medium resulted in an immediate increase in contractile force followed by a decline and complete loss of contractile force within 25 s. The recovery of the contractile force upon reperfusion was only partial if the duration of Na-free perfusions was 10 min or longer. Ca binding and uptake activities of mitochondria obtained from hearts perfused with Na-free medium did not change significantly. However, Ca binding and uptake activities of microsomes were depressed after 5 min of perfusion. The critical concentration of Na in the perfusion medium for inducing these changes was found to be less than 35 mM. The microsomal Ca-ATPase activity was decreased after 10 min of Na-free perfusion. Only partial recovery of microsomal Ca uptake was observed upon reperfusion of hearts preperfused with Na-free medium for 20 min or longer whereas Ca-ATPase activity in these hearts did not recover at all. These results suggest that the defect in the microsomal Ca transport may be secondary to the development of contractile failure and may partially be associated with the inability of Na-depleted hearts to recover fully their contractile force.


An observational study of the acceptability of patient-delivered partner therapy for management of chlamydia.
Partners of heterosexual cases with chlamydia, who were identified as having difficulty in attending the clinic, were offered patient-delivered partner therapy (PDPT). Medication was delivered by the index case after telephone consultation with the partner to assess symptoms and medical history. The opportunity for testing of partners for chlamydia was provided. The PDPT process was evaluated by standardised phone interview with index patients and partners. Telephone consultation enables safe medication prescribing and an opportunity for further contact tracing. Partners were unlikely to seek testing when provided with PDPT. Delivery of medication resulted in a reported rate of treatment of 100%. PDPT was an acceptable treatment option to both index and partner and should be considered if legislation permits.


Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients: a pilot study.
Intravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients, but it also enhances the generation of hydroxyl radicals. Previously we demonstrated that IVIR increases oxidized serum albumin levels in HD patients. However, the effect of IVIR frequencies on the oxidative stress has never been studied before. Therefore, we compared the two IVIR schedules recommended by the Japanese Society for Dialysis Therapy guideline 2004 by measuring oxidized albumin in chronic HD patients. Twenty-two HD patients were divided into two IVIR protocol groups (group I: 40 mg of iron 3 times a week for 4 weeks, group II: 40 mg of iron once a week for 3 months). These protocols differ in IVIR frequency, but receive the same amount of iron (total 520 mg). We compared these two regimens by determining the levels of hemoglobin, serum ferritin, advanced oxidation protein products (AOPP), and oxidized albumin at 0, 4, 8, 12, 16, and 20 weeks. Both patient groups resulted in a similar and significant increase in hemoglobin levels, whereas group I markedly induced AOPP and oxidation of serum albumin than group II at 4 weeks (P<0.05). AOPP and oxidation of serum albumin was also gradually declined by 20 weeks, while the oxidized albumin and AOPP in group II was not significantly changed during the entire experimental period. Transferrin saturation and serum ferritin levels were also increased in group I compared with group II at 4 weeks (P<0.001). In addition, we found a strong positive correlation between oxidized albumin and serum ferritin levels (r=0.615, P<0.05), suggesting the possibility that the accumulation of iron stores has a causative role in the progression of oxidative stress in HD patients treated with IVIR. The results of this study indicate that lower frequency IVIR protocol is recommended to reduce IVIR-induced oxidative stress in HD patients.


Uniconazole (S-3307) strengthens the growth and cadmium accumulation of accumulator plant Malachium aquaticum.
The effects of uniconazole (S-3307) application on the growth and cadmium (Cd) accumulation of accumulator plant Malachium aquaticum (L.) Fries. were studied through a pot experiment. The application of S-3307 increased the biomass and photosynthetic pigment content of M. aquaticum in Cd-contaminated soil, and also improved the superoxide dismutase (SOD) and peroxidase (POD) activities in M. aquaticum. Application of S-3307 increased Cd content in shoots and decreased Cd content in roots of M. aquaticum, but the translocation factor (TF) of M. aquaticum increased with the increase of S-3307 concentration. For phytoextraction, the application of S-3307 increased Cd extractions by roots, shoots and whole plants of M. aquaticum, and the maxima were obtained at 75 mg L-1 S-3307, which increased by 22.07%, 37.79% and 29.07%, respectively, compared with their respective controls. Therefore, S-3307 can be used for enhancing the Cd extraction ability of M. aquaticum, and 75 mg L-1 S-3307 was the optimal dose.


Anderson Localization for Better Thermoelectrics?
Solid-state thermoelectrics are of great interest because they directly convert between thermal and electrical energy. However, wider application of thermoelectrics is dependent upon improving their performance. Anderson localization of charge carriers has been generally perceived as detrimental to thermoelectrics, but in their paper in this issue of ACS Nano, Lee et al. propose a concept of using selective charge Anderson localization for synergetic enhancement of thermoelectric performance. To facilitate discussions and research on Anderson localization to improve thermoelectrics, this Perspective shares potential directions to explore the viability of using Anderson localization or related strategies to drive thermoelectric performance.


The effect of infestation with Diplostomum sp. on growth rate of Siberian sturgeon fry Acipenser baeri brandt.
The objective of the experiment was to compare the growth rate in two groups of Siberian sturgeon fry, one of which was infested with metacercariae of Diplostomum, the infestation degree was from 1 to 160/fish. The fish fed on natural as well as artificial food; the latter was given at the rate sufficient to cover 50% of the fish requirements. The average initial body weight in the control group was 16.8 +/- 1.9g, and in the group with Diplostomum - 28.4 +/- 3.6 g. During the period of favorable temperatures, viz. for about 90 days, the fry was showed satisfactory growth, but the growth rate became inhibited as the temperatures decreased to below 12 degrees C, so that throughout the wintering period the fish weight decreased by some 10%. Fish from the control group showed a higher growth rate than the infested ones, and by the end of the experiment the controls weighted 7.5% more than the infested group in spite of their lower initial weight.


Tigroid cell foci and neoplastic nodules in the liver of rats treated with a single dose of aflatoxin B1.
In rats treated orally with a single dose of aflatoxin B1 (5 mg/kg body weight) characteristic focal and nodular liver lesions developed which differed in their fine structure, enzyme histochemical pattern and growth behaviour from other types of carcinogen-induced hepatic foci and nodules described earlier. The foci were composed of a distinct cell population which showed specific structural changes of the cytoplasm. Typically, unusually large and abundant basophilic bodies consisting of highly ordered stacks of cisternae of the rough endoplasmic reticulum (ER) were arranged in long, striped bands and stood out against an acidophilic background which was due to hypertrophy of the smooth ER. We propose the descriptive terms 'tigroid cells', and 'tigroid cell foci' for this population of altered hepatocytes. Correlative cytochemical investigations on the tigroid cell foci revealed characteristic changes in carbohydrate metabolism, such as a decrease in the activity of glycogen synthetase and glycogen phosphorylase and an increase in the activity of glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The activity of glucose-6-phosphatase and ATPase was normal (or partially reduced) and that of the gamma-glutamyl-transpeptidase was always lacking. A progressive increase in the number and size of the tigroid cell foci and transitions from tigroid cell foci to neoplastic nodules with similar morphological and cytochemical features were observed during the time period of 104 weeks. The mitotic index within tigroid cell foci and nodules was approximately 100 times higher than that of the surrounding hepatic tissue or the liver parenchyma of untreated control animals. The important question whether the tigroid cell foci represent a specific pre-neoplastic or early neoplastic cell population requires further investigations.


A comparison of minimal cross sectional areas, nasal volumes and peak nasal inspiratory flow between patients with obstructive sleep apnea and healthy controls.
The differences in nasal geometry and function between OSA patients and healthy individuals are not known. Our aim was to evaluate the differences in nasal geometry and function using acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF) between an OSA population and healthy controls. The study was designed as a prospective case-control study. Ninety-three OSA patients and 92 controls were enrolled from 2010 to 2015. The minimal cross-sectional area (MCA) and the nasal cavity volume (NCV) in two parts of the nose (MCA0-3/NCV0-3 and MCA3-5.2/NCV3-5.2) and PNIF were measured at baseline and after decongestion. The mean MCA0-3 in the OSA group was 0.49 cm2; compared to 0.55 cm2 in controls. The mean NCV0-3 correspondingly was 2.51 cm3 compared to 2.73 cm3 in controls. PNIF measured 105 litres/minute in the OSA group and 117 litres/minute in the controls. OSA patients have a lower minimum cross-sectional area, nasal cavity volume and peak inspiratory flow compared to controls. Our study supports the view that changes in the nasal cavity may contribute to development of OSA.


3AE8: monoclonal antibody defining inflammatory macrophages in three species.
A mouse monoclonal antibody (MAb 3AE8) of the IgG1 isotype was prepared against rabbit splenocytes and was found by indirect immunofluorescence and direct binding assays to react, in the rabbit, primarily with oil-induced peritoneal exudate macrophages (PEM phi). This MAb did not bind to rabbit T cells, B cells, polymorphonuclear leukocytes, or resident alveolar or peritoneal M phi but it did bind to a subpopulation of rabbit splenocytes with surface characteristics of null cells. The antibody also recognized mouse and rat PEM phi as well as the murine M phi cell lines P388D1 and IC-21. Consistent with findings in the rabbit, it did not bind to M phi obtained from the peritoneal cavities of rats or mice. The addition of MAb 3AE8 to mouse PEM phi caused a marked enhancement in the phagocytic uptake of erythrocyte target cells sensitized with a mouse antierythrocyte antiserum.


Toxicity studies of a gum guggul extract formulation administered by gavage to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice.
Gum guggul extracts (GGEs) are botanical preparations derived from the oleoresin of the Commiphora mukul tree. The preparations are traditionally used in Ayurvedic medicine to treat hyperlipidemia, obesity, diabetes, atherosclerosis, and inflammatory conditions such as arthritis. In the United States, GGEs are marketed as dietary supplements. GGE toxicity was evaluated due to widespread human exposure through increasing dietary supplement use, demonstrated metabolic and hormone-altering effects, and a lack of available information to adequately assess safe use in humans. Male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice were administered a GGE formulation in corn oil by gavage for 28 days or 3 months. Oral gavage was chosen as the route of exposure for these studies because human exposure primarily occurs by ingestion of encapsulated GGE supplements. (Abstract Abridged).


The Roles of Regional Organisations in Strengthening Health Research Systems in Africa: Activities, Gaps, and Future Perspectives.
Regional cooperation on health in Africa is not new. The institutional landscape of regional cooperation for health and health research, however, has seen important changes. Recent health emergencies have focussed regional bodies' attention on supporting aspects of national health preparedness and response. The state of national health research systems is a key element of capacity to plan and respond to health needs - raising questions about the roles African regional bodies can or should play in strengthening health research systems. We mapped regional organisations involved in health research across Africa and conducted 18 interviews with informants from 15 regional organisations. We investigated the roles, challenges, and opportunities of these bodies in strengthening health research. We deductively coded interview data using themes from established pillars of health research systems - governance, creating resources, research production and use, and financing. We analysed organisations' relevant activities in these areas, how they do this work, and where they perceive impact. Regional organisations with technical foci on health or higher education (versus economic or political remits) were involved in all four areas. Most organisations reported activities in governance and research use. Involvement in governance centred mainly around agenda-setting and policy harmonisation. For organisations involved in creating resources, activities focused on strengthening human resources, but few reported developing research institutions, networks, or infrastructure. Organisations reported more involvement in disseminating than producing research. Generally, few have directly contributed to financing health research. Informants reported gaps in research coordination, infrastructure, and advocacy at regional level. Finally, we found regional bodies' mandates, authority, and collaborations influence their activities in supporting national health research systems. Continued strengthening of health research on the African continent requires strategic thinking about the roles, comparative advantages, and capability of regional organisations to facilitate capacity and growth of health research systems.


The effects of aging on the human sense of smell and its relationship to food choice.
Olfaction plays a significant role in the perception of foods. For the most part, taste is limited to sweet, sour, bitter, and salty. The sensory experiences during consumption of complex foods and drinks cannot be constructed from these units. Indeed, much of the taste of a meal derives from olfactory stimulation. Hence, factors that influence olfactory perception should affect treatment of food-related odors. This article initially reviews previously published observations on the effects of age on olfaction and food preferences and then presents the results of original analyses of data derived from a substantial database formed as a result of the National Geographic Smell Survey. Included in the Survey form were topics relevant to the present article. They include the following question: Would you eat something that smelled like this? Two of the odors in the Survey were food related and two were fragrance related. Hence, in addition, we assessed responses to the following question: Would you apply something that smelled like this to your body? Answers were affected in part by the age and gender of the respondent and by the perceived pleasantness and intensity of the odor.


Reflex effects on gamma fusimotor neurones of chemically induced discharges in small-diameter muscle afferents in decerebrate cats.
The effects on fusimotor discharge rate of algesic agents (bradykinin, potassium chloride, histamine, 5-hydroxytryptamine) and lactic acid, applied by close arterial injection into triceps surae muscles, were investigated in decerebrate cats. Fusimotor discharge was recorded from filaments dissected free from otherwise intact nerves to the triceps muscles. The substances applied induced an increase in discharge rate of spontaneously active gamma fusimotor neurones as well as a recruitment of previously silent ones. Skeletomotor discharges and/or muscle tension changes occurred only occasionally. The increase in fusimotor discharge rate was not always completely abolished by severing the nerves to triceps. What remained was a short-lasting burst at the very onset of blood-pressure fall. It was concluded that the increase in fusimotor discharge rate was mainly, but not solely, elicited reflexly by discharges from Group III and/or IV muscle afferents sensitive to algesic agents. An elevated fusimotor activity might be expected to accompany muscle inflammation and/or trauma when these agents are liberated in muscle tissue. The increase in fusimotor discharge rate elicited by lactic acid injections indicates that the fusimotor system might also be involved in neural processes of muscular fatigue.


Isostreptazolin and sannaphenol, two new metabolites from Streptomyces sannanensis.
Two new compounds, isostreptazolin (1) and sannaphenol (2), were isolated from the culture broth of Streptomyces sannanensis and their structures elucidated on the basis of 1D and 2D NMR as well as MS, IR and UV spectroscopic data analysis. The cytotoxic activity of 1 and 2 were evaluated. Both compounds were inactive against H460 and HeLa cell lines at 100 mM.


Cardiac autonomic control in individuals with Down syndrome.
Our goal in this study was to compare cardiac autonomic control at rest between 50 individuals with Down syndrome and 24 control participants without disabilities. Resting autonomic function was assessed using analysis of heart rate variability. Participants with Down syndrome had reduced total heart rate variability, which indicates possible autonomic dysfunction in this population. Their VO2 peak and BMI were not significantly correlated with resting cardiac autonomic control. This may suggest that fitness level and obesity differentially affect cardiac autonomic control in persons with Down syndrome compared to their healthy, nondisabled peers.


Tumor-infiltrating lymphocytes in the immunotherapy era.
The clinical success of cancer immune checkpoint blockade (ICB) has refocused attention on tumor-infiltrating lymphocytes (TILs) across cancer types. The outcome of immune checkpoint inhibitor therapy in cancer patients has been linked to the quality and magnitude of T cell, NK cell, and more recently, B cell responses within the tumor microenvironment. State-of-the-art single-cell analysis of TIL gene expression profiles and clonality has revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune activation and exhaustion. Many of these states are conserved across tumor types, in line with the broad responses observed clinically. Despite this homology, not all cancer types with similar TIL landscapes respond similarly to immunotherapy, highlighting the complexity of the underlying tumor-immune interactions. This observation is further confounded by the strong prognostic benefit of TILs observed for tumor types that have so far respond poorly to immunotherapy. Thus, while a holistic view of lymphocyte infiltration and dysfunction on a single-cell level is emerging, the search for response and prognostic biomarkers is just beginning. Within this review, we discuss recent advances in the understanding of TIL biology, their prognostic benefit, and their predictive value for therapy.


The pattern of bowel dysfunction in patients with rectal cancer following the multimodal treatment: anorectal manometric measurements at before and after chemoradiation therapy, and postoperative 1 year.
Bowel dysfunction commonly occurs in patients with locally advanced rectal cancer treated with a multimodal approach of chemoradiation therapy (CRT) combined with sphincter-preserving rectal resection. This study investigated the decline in anorectal function using sequential anorectal manometric measurements obtained before and after the multimodal treatment as well as at a 1-year follow-up. This was a retrospective cohort study conducted in a single center. The study population consisted of patients with locally advanced mid- to low rectal cancer who received the preoperative CRT followed by sphincter-preserving surgery from 2012 to 2016. The anorectal manometric value measured after each treatment modality was compared to demonstrate the degree of decline in anorectal function. A generalized linear model of repeated measures was performed using the manometric values measured pre- and post-CRT, and at 12 months postoperatively. Overall, 100 patients with 3 consecutive manometric data were included in the final analysis. In the overall cohort study, the mean resting and maximal squeezing pressures showed insignificant decrement post-neoadjuvant CRT. At a 1-year postoperative follow-up, the maximal squeezing pressure significantly decreased. The maximal rectal sensory threshold demonstrated significant reduction consecutively after each following treatment (P<0.001). The short-term effect of neoadjuvant CRT on the anal sphincters was relatively trivial. The following sphincter-saving surgery resulted in a profound disruption of the anorectal function. Patients with rectal cancer should be consulted on the consequence of multimodal treatment.


Collection and Identification of Allelopathic Compounds from the Undisturbed Root System of Bigalta Limpograss (Hemarthria altissima).
Collection of allelopathic chemicals from the undisturbed plant root system is difficult because of their low concentrations and the high level of contaminants in growth media such as soil. A new approach for the continuous trapping of quantities of extracellular chemicals from donor plants is described. Bigalta limpograss (Hemarthria altissima), a tropical forage with allelopathic activities, was established in sand culture. Nutrient solution was circulated continuously through the root system and a column containing XAD-4 resin. Extracellular hydrophobic metabolites were selectively adsorbed by the resin, while inorganic nutrients were recycled to sustain plant growth. Columns were eluted with methanol and the eluate separated into neutral, acidic, and basic fractions. Bioassays of trapped root exudates using lettuce seed combined with paper and thin layer chromatography showed that the inhibitors were mainly phenolic compounds. The active neutral fraction was methylated and analyzed by gas chromatography-mass spectrometry. Twelve compounds were identified, with two additional compounds tentatively identified. 3-Hydroxyhydrocinnamic, benzoic, phenylacetic, and hydrocinnamic acids were the major rhizospheric compounds with known growth regulatory activities.Inasmuch as the root system was undisturbed and the recovery of exudates was highly efficient compared to conventional solvent extraction methods, this trapping system should be useful for a wide range of studies that relate to the chemistry of the rhizosphere.


Fabrication of Micro-Groove on the Surface of CFRP to Enhance the Connection Strength of Composite Part.
Carbon fiber-reinforced plastic (CFRP) has the advantages of being light weight, high strength, and corrosion resistant. At present, it is widely used in the lightweight design of automobile parts. The manufacturing of lightweight parts inevitably involves the connection between CFRP and the polymer material. The connection strength between CFRP and the polymer material significantly affects the service life of the composite parts. Taking CFRP and polyamide 6 (PA6) injection-molded composite parts as an example, this paper proposed a technological method to enhance the connection strength between CFRP and PA6. The proposed method was to fabricate micro-groove structures on the CFRP surface by compression molding. These micro-groove structures effectively increased the injection-molding area of the composite parts, thus enhancing the connection strength between CFRP and PA6. This paper presented a detailed study on the compression-molding process of micro-grooves on the CFRP surface, and successfully obtained the appropriate parameters. Finally, PA6 was used for injection molding on the CFRP with micro-grooves at an injection pressure of 8 MPa, an injection temperature of 240 °C, a holding pressure of 5 MPa, and a holding time of 2.5 s. The experimental results show that the micro-groove array structures on the CFRP surface could effectively improve the tensile strength of the connection interface in the composite parts. Compared with the composite part without micro-grooves, the tensile strength of the composite part with micro-grooves was increased by 80.93%. The composite parts prepared in this paper are mainly used in automobile interiors and the research results of this paper meet the actual needs of the enterprise.